PT J
AU Fairén, AG
   Davila, AF
   Gago-Duport, L
   Amils, R
   McKay, CP
AF Fairen, Alberto G.
   Davila, Alfonso F.
   Gago-Duport, Luis
   Amils, Ricardo
   McKay, Christopher P.
TI Stability against freezing of aqueous solutions on early Mars
SO NATURE
LA English
DT Article
ID carbon-dioxide clouds; water; atmospheres; climate; earth
AB Many features of the Martian landscape are thought to have been formed by liquid water flow(1,2) and water-related mineralogies on the surface of Mars are widespread and abundant(3). Several lines of evidence, however, suggest that Mars has been cold with mean global temperatures well below the freezing point of pure water(4). Martian climate modellers(5,6) considering a combination of greenhouse gases at a range of partial pressures find it challenging to simulate global mean Martian surface temperatures above 273 K, and local thermal sources(7,8) cannot account for the widespread distribution of hydrated and evaporitic minerals throughout the Martian landscape(3). Solutes could depress the melting point of water(9,10) in a frozen Martian environment, providing a plausible solution to the early Mars climate paradox. Here we model the freezing and evaporation processes of Martian fluids with a composition resulting from the weathering of basalts, as reflected in the chemical compositions at Mars landing sites. Our results show that a significant fraction of weathering fluids loaded with Si, Fe, S, Mg, Ca, Cl, Na, K and Al remain in the liquid state at temperatures well below 273 K. We tested our model by analysing the mineralogies yielded by the evolution of the solutions: the resulting mineral assemblages are analogous to those actually identified on the Martian surface. This stability against freezing of Martian fluids can explain saline liquid water activity on the surface of Mars at mean global temperatures well below 273 K.
C1 [Fairen, Alberto G.; Davila, Alfonso F.; McKay, Christopher P.] NASA, Ames Res Ctr, Space Sci & Astrobiol Div, Moffett Field, CA 94035 USA.
   [Gago-Duport, Luis] Univ Vigo, Dept Geociencias Marinas, Vigo 36200, Spain.
   [Amils, Ricardo] CSIC INTA, Ctr Astrobiol, Madrid 28850, Spain.
   [Amils, Ricardo] CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain.
C3 National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Universidade de Vigo; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Biologia Molecular Severo Ochoa (CBM)
RP Fairén, AG (corresponding author), NASA, Ames Res Ctr, Space Sci & Astrobiol Div, Moffett Field, CA 94035 USA.
EM alberto.g.fairen@nasa.gov
FU ORAU-NPP
NR 30
TC 108
Z9 117
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2009
VL 459
IS 7245
BP 401
EP 404
DI 10.1038/nature07978
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700040
PM 19458717
DA 2026-03-09
ER

PT J
AU Santiago, J
   Dupeux, F
   Round, A
   Antoni, R
   Park, SY
   Jamin, M
   Cutler, SR
   Rodriguez, PL
   Márquez, JA
AF Santiago, Julia
   Dupeux, Florine
   Round, Adam
   Antoni, Regina
   Park, Sang-Youl
   Jamin, Marc
   Cutler, Sean R.
   Luis Rodriguez, Pedro
   Marquez, Jose Antonio
TI The abscisic acid receptor PYR1 in complex with abscisic acid
SO NATURE
LA English
DT Article
ID protein phosphatases; arabidopsis; binding; start; scattering; program; domain; fold
AB The plant hormone abscisic acid (ABA) has a central role in coordinating the adaptive response in situations of decreased water availability as well as the regulation of plant growth and development. Recently, a 14-member family of intracellular ABA receptors, named PYR/PYL/RCAR(1-3), has been identified. These proteins inhibit in an ABA-dependent manner the activity of a family of key negative regulators of the ABA signalling pathway: the group-A protein phosphatases type 2C (PP2Cs)(4-6). Here we present the crystal structure of Arabidopsis thaliana PYR1, which consists of a dimer in which one of the subunits is bound to ABA. In the ligand-bound subunit, the loops surrounding the entry to the binding cavity fold over the ABA molecule, enclosing it inside, whereas in the empty subunit they form a channel leaving an open access to the cavity, indicating that conformational changes in these loops have a critical role in the stabilization of the hormone-receptor complex. By providing structural details on the ABA-binding pocket, this work paves the way for the development of new small molecules able to activate the plant stress response.
C1 [Dupeux, Florine; Round, Adam; Marquez, Jose Antonio] UJF, EMBL, CNRS, European Mol Biol Lab,Grenoble Outstn, F-38042 Grenoble 9, France.
   [Dupeux, Florine; Round, Adam; Marquez, Jose Antonio] UJF, EMBL, CNRS, Unit Virus Host Cell Interact, F-38042 Grenoble 9, France.
   [Santiago, Julia; Antoni, Regina; Luis Rodriguez, Pedro] Univ Politecn Valencia, CSIC, Inst Biol Mol & Celular Plantas, ES-46022 Valencia, Spain.
   [Park, Sang-Youl; Cutler, Sean R.] Univ Calif Riverside, Ctr Plant Cell Biol, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
   [Jamin, Marc] Univ Grenoble 1, CNRS, EMBL, Virus Host Cell Interact UVHCI UMI 3265, F-38042 Grenoble 9, France.
C3 European Molecular Biology Laboratory (EMBL); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); European Molecular Biology Laboratory (EMBL); Consejo Superior de Investigaciones Cientificas (CSIC); Universitat Politecnica de Valencia; CSIC-UPV - Instituto de Biologia Molecular y Celular de Plantas (IBMCP); University of California System; University of California Riverside; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); European Molecular Biology Laboratory (EMBL)
RP Márquez, JA (corresponding author), UJF, EMBL, CNRS, European Mol Biol Lab,Grenoble Outstn, 6 Rue Jules Horowitz,BP181, F-38042 Grenoble 9, France.
EM marquez@embl.fr
FU Ministerio de Educacion y Ciencia [BIO2008-00221]; Fondo Europeo de Desarrollo Regional; Consejo Superior de Investigaciones Cientificas; European Community-Research Infrastructure Action PCUBE; Direct For Biological Sciences [0820508] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems [0820508] Funding Source: National Science Foundation
NR 23
TC 437
Z9 505
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 DEC 3
PY 2009
VL 462
IS 7273
BP 665
EP U143
DI 10.1038/nature08591
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900044
PM 19898494
DA 2026-03-09
ER

PT J
AU Stine, AR
   Huybers, P
   Fung, IY
AF Stine, A. R.
   Huybers, P.
   Fung, I. Y.
TI Changes in the phase of the annual cycle of surface temperature
SO NATURE
LA English
DT Article
ID soil-moisture; global distribution; semiannual cycles; mean temperature; air-temperature; climate; model; radiation; dataset; seasons
AB The annual cycle in the Earth's surface temperature is extremely large - comparable in magnitude to the glacial - interglacial cycles over most of the planet. Trends in the phase and the amplitude of the annual cycle have been observed, but the causes and significance of these changes remain poorly understood - in part because we lack an understanding of the natural variability. Here we show that the phase of the annual cycle of surface temperature over extratropical land shifted towards earlier seasons by 1.7 days between 1954 and 2007; this change is highly anomalous with respect to earlier variations, which we interpret as being indicative of the natural range. Significant changes in the amplitude of the annual cycle are also observed between 1954 and 2007. These shifts in the annual cycles appear to be related, in part, to changes in the northern annular mode of climate variability, although the land phase shift is significantly larger than that predicted by trends in the northern annular mode alone. Few of the climate models presented by the Intergovernmental Panel on Climate Change reproduce the observed decrease in amplitude and none reproduce the shift towards earlier seasons.
C1 [Stine, A. R.; Fung, I. Y.] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
   [Huybers, P.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 University of California System; University of California Berkeley; Harvard University
RP Stine, AR (corresponding author), Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
EM zan@atmos.berkeley.edu
FU Chancellor's Fellowship; University of California; US National Science Foundation [0645936, 0628278]; Office of Science, US Department of Energy; Directorate For Geosciences; Division Of Ocean Sciences [0645936] Funding Source: National Science Foundation
NR 48
TC 220
Z9 256
U1 5
U2 95
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 22
PY 2009
VL 457
IS 7228
BP 435
EP U1
DI 10.1038/nature07675
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200037
PM 19158790
DA 2026-03-09
ER

PT J
AU Barwick, B
   Flannigan, DJ
   Zewail, AH
AF Barwick, Brett
   Flannigan, David J.
   Zewail, Ahmed H.
TI Photon-induced near-field electron microscopy
SO NATURE
LA English
DT Article
ID diffraction
AB In materials science and biology, optical near-field microscopies enable spatial resolutions beyond the diffraction limit(1,2), but they cannot provide the atomic-scale imaging capabilities of electron microscopy(3). Given the nature of interactions(4-8) between electrons and photons, and considering their connections(9,10) through nanostructures, it should be possible to achieve imaging of evanescent electromagnetic fields with electron pulses when such fields are resolved in both space (nanometre and below) and time (femtosecond) (11-13). Here we report the development of photon-induced near-field electron microscopy (PINEM), and the associated phenomena. We show that the precise spatiotemporal overlap of femtosecond single-electron packets with intense optical pulses at a nanostructure (individual carbon nanotube or silver nanowire in this instance) results in the direct absorption of integer multiples of photon quanta (nh omega) by the relativistic electrons accelerated to 200 keV. By energy-filtering only those electrons resulting from this absorption, it is possible to image directly in space the near-field electric field distribution, obtain the temporal behaviour of the field on the femtosecond timescale, and map its spatial polarization dependence. We believe that the observation of the photon-induced near-field effect in ultrafast electron microscopy demonstrates the potential for many applications, including those of direct space-time imaging of localized fields at interfaces and visualization of phenomena related to photonics, plasmonics and nanostructures.
C1 [Barwick, Brett; Flannigan, David J.; Zewail, Ahmed H.] CALTECH, Arthur Amos Noyes Lab Chem Phys, Phys Biol Ctr Ultrafast Sci & Technol, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Zewail, AH (corresponding author), CALTECH, Arthur Amos Noyes Lab Chem Phys, Phys Biol Ctr Ultrafast Sci & Technol, Pasadena, CA 91125 USA.
EM zewail@caltech.edu
FU National Science Foundation; Air Force Office of Scientific Research in the Gordon; Betty Moore Center for Physical Biology at the California Institute of Technology
NR 30
TC 607
Z9 689
U1 3
U2 242
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 17
PY 2009
VL 462
IS 7275
BP 902
EP 906
DI 10.1038/nature08662
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400039
PM 20016598
DA 2026-03-09
ER

PT J
AU Sreekumar, A
   Poisson, LM
   Rajendiran, TM
   Khan, AP
   Cao, Q
   Yu, JD
   Laxman, B
   Mehra, R
   Lonigro, RJ
   Li, Y
   Nyati, MK
   Ahsan, A
   Kalyana-Sundaram, S
   Han, B
   Cao, XH
   Byun, J
   Omenn, GS
   Ghosh, D
   Pennathur, S
   Alexander, DC
   Berger, A
   Shuster, JR
   Wei, JT
   Varambally, S
   Beecher, C
   Chinnaiyan, AM
AF Sreekumar, Arun
   Poisson, Laila M.
   Rajendiran, Thekkelnaycke M.
   Khan, Amjad P.
   Cao, Qi
   Yu, Jindan
   Laxman, Bharathi
   Mehra, Rohit
   Lonigro, Robert J.
   Li, Yong
   Nyati, Mukesh K.
   Ahsan, Aarif
   Kalyana-Sundaram, Shanker
   Han, Bo
   Cao, Xuhong
   Byun, Jaeman
   Omenn, Gilbert S.
   Ghosh, Debashis
   Pennathur, Subramaniam
   Alexander, Danny C.
   Berger, Alvin
   Shuster, Jeffrey R.
   Wei, John T.
   Varambally, Sooryanarayana
   Beecher, Christopher
   Chinnaiyan, Arul M.
TI Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
SO NATURE
LA English
DT Article
ID molecular-genetics; polycomb; ezh2; expression
AB Multiple, complex molecular events characterize cancer development and progression(1,2). Deciphering the molecular networks that distinguish organ- confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high- throughput liquid- and- gas- chromatography- based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer ( 42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N- methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non- invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine- N- methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.
C1 [Sreekumar, Arun; Rajendiran, Thekkelnaycke M.; Khan, Amjad P.; Cao, Qi; Yu, Jindan; Laxman, Bharathi; Mehra, Rohit; Lonigro, Robert J.; Li, Yong; Kalyana-Sundaram, Shanker; Han, Bo; Cao, Xuhong; Varambally, Sooryanarayana; Beecher, Christopher; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
   [Sreekumar, Arun; Omenn, Gilbert S.; Pennathur, Subramaniam; Beecher, Christopher; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA.
   [Sreekumar, Arun; Rajendiran, Thekkelnaycke M.; Khan, Amjad P.; Cao, Qi; Yu, Jindan; Laxman, Bharathi; Mehra, Rohit; Li, Yong; Kalyana-Sundaram, Shanker; Han, Bo; Cao, Xuhong; Varambally, Sooryanarayana; Beecher, Christopher; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Sreekumar, Arun; Lonigro, Robert J.; Nyati, Mukesh K.; Ghosh, Debashis; Pennathur, Subramaniam; Wei, John T.; Varambally, Sooryanarayana; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
   [Poisson, Laila M.; Ghosh, Debashis] Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Nyati, Mukesh K.; Ahsan, Aarif] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.
   [Byun, Jaeman; Omenn, Gilbert S.; Pennathur, Subramaniam] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Omenn, Gilbert S.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Wei, John T.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA.
   [Varambally, Sooryanarayana] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
   [Ghosh, Debashis] Penn State Univ, Dept Stat, University Pk, PA 16802 USA.
   [Ghosh, Debashis] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA.
   [Alexander, Danny C.; Berger, Alvin; Shuster, Jeffrey R.] Metabolon Inc, Durham, NC 27713 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; 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; 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; Metabolon
RP Chinnaiyan, AM (corresponding author), Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
EM arul@umich.edu
FU Early Detection Research Network; National Institutes of Health; MTTC; Clinical Translational Science Award; Fund for Discovery of the University of Michigan Comprehensive Cancer Center; University of Michigan Cancer Biostatistics Training Grant; Doris Duke Charitable Foundation; National Cancer Institute [T32CA083654] Funding Source: NIH RePORTER
NR 18
TC 1906
Z9 2181
U1 9
U2 876
PU NATURE PUBLISHING 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 12
PY 2009
VL 457
IS 7231
BP 910
EP 914
DI 10.1038/nature07762
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700051
PM 19212411
DA 2026-03-09
ER

PT J
AU Neilsen, J
   Lee, JC
AF Neilsen, Joseph
   Lee, Julia C.
TI Accretion disk winds as the jet suppression mechanism in the microquasar GRS 1915+105
SO NATURE
LA English
DT Article
ID x-ray binary; black-hole; infrared flares; spectral states; radio-emission; grs-1915+105; variability; radiation; galaxy; spectroscopy
AB Stellar-mass black holes with relativistic jets, also known as microquasars, mimic the behaviour of quasars and active galactic nuclei(1). Because timescales around stellar-mass black holes are orders of magnitude smaller than those around more distant supermassive black holes, microquasars are ideal nearby 'laboratories' for studying the evolution of accretion disks and jet formation in black-hole systems(2). Whereas studies of black holes have revealed a complex array of accretion activity, the mechanisms that trigger and suppress jet formation remain a mystery. Here we report the presence of a broad emission line in the faint, hard states and narrow absorption lines in the bright, soft states of the microquasar GRS 1915+105. ('Hard' and 'soft' denote the character of the emitted X-rays.) Because the hard states exhibit prominent radio jets(3), we argue that the broad emission line arises when the jet illuminates the inner accretion disk. The jet is weak or absent during the soft states(4), and we show that the absorption lines originate when the powerful radiation field around the black hole drives a hot wind off the accretion disk(5-7). Our analysis shows that this wind carries enough mass away from the disk to halt the flow of matter into the radio jet.
C1 [Neilsen, Joseph; Lee, Julia C.] Harvard Univ, Dept Astron, Cambridge, MA 02138 USA.
C3 Harvard University
RP Neilsen, J (corresponding author), Harvard Univ, Dept Astron, 60 Garden St,MS-10, Cambridge, MA 02138 USA.
EM jneilsen@cfa.harvard.edu
FU Harvard University Graduate School of Arts and Sciences; Faculty of Arts and Sciences
NR 28
TC 262
Z9 277
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 MAR 26
PY 2009
VL 458
IS 7237
BP 481
EP 484
DI 10.1038/nature07680
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400038
PM 19325629
DA 2026-03-09
ER

PT J
AU Conard, NJ
   Malina, M
   Münzel, SC
AF Conard, Nicholas J.
   Malina, Maria
   Muenzel, Susanne C.
TI New flutes document the earliest musical tradition in southwestern Germany
SO NATURE
LA English
DT Article
ID western eurasia; late middle; cave; aurignacian
AB Considerable debate surrounds claims for early evidence of music in the archaeological record(1-5). Researchers universally accept the existence of complex musical instruments as an indication of fully modern behaviour and advanced symbolic communication(1) but, owing to the scarcity of finds, the archaeological record of the evolution and spread of music remains incomplete. Although arguments have been made for Neanderthal musical traditions and the presence of musical instruments in Middle Palaeolithic assemblages, concrete evidence to support these claims is lacking(1-4). Here we report the discovery of bone and ivory flutes from the early Aurignacian period of southwestern Germany. These finds demonstrate the presence of a well-established musical tradition at the time when modern humans colonized Europe, more than 35,000 calendar years ago. Other than the caves of the Swabian Jura, the earliest secure archaeological evidence for music comes from sites in France and Austria and post-date 30,000 years ago(6-8).
C1 [Muenzel, Susanne C.] Univ Tubingen, Zentrum Nat Wissensch Archaol, D-72070 Tubingen, Germany.
   [Conard, Nicholas J.] Univ Tubingen, Abt Altere Urgeschichte & Quartarokol, Inst Ur & Fruhgeschichte & Archaol Mittelalters, D-72070 Tubingen, Germany.
   [Malina, Maria] Heidelberger Akad Wissensch, Res Project Role Culture Early Expans Humans, D-72070 Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen
RP Conard, NJ (corresponding author), Univ Tubingen, Zentrum Nat Wissensch Archaol, Rumelinstr 23, D-72070 Tubingen, Germany.
EM nicholas.conard@uni-tuebingen.de
NR 27
TC 314
Z9 396
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 AUG 6
PY 2009
VL 460
IS 7256
BP 737
EP 740
DI 10.1038/nature08169
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300038
PM 19553935
DA 2026-03-09
ER

PT J
AU Kerschensteiner, D
   Morgan, JL
   Parker, ED
   Lewis, RM
   Wong, ROL
AF Kerschensteiner, Daniel
   Morgan, Josh L.
   Parker, Edward D.
   Lewis, Renate M.
   Wong, Rachel O. L.
TI Neurotransmission selectively regulates synapse formation in parallel circuits in vivo
SO NATURE
LA English
DT Article
ID retinal ganglion-cells; bipolar cells; mouse retina; mammalian retina; ribbon synapses; competition; expression
AB Activity is thought to guide the patterning of synaptic connections in the developing nervous system. Specifically, differences in the activity of converging inputs are thought to cause the elimination of synapses from less active inputs and increase connectivity with more active inputs(1,2). Here we present findings that challenge the generality of this notion and offer a new view of the role of activity in synapse development. To imbalance neurotransmission from different sets of inputs in vivo, we generated transgenic mice in which ON but not OFF types of bipolar cells in the retina express tetanus toxin ( TeNT). During development, retinal ganglion cells (RGCs) select between ON and OFF bipolar cell inputs ( ON or OFF RGCs) or establish a similar number of synapses with both on separate dendritic arborizations (ON-OFF RGCs). In TeNT retinas, ON RGCs correctly selected the silenced ON bipolar cell inputs over the transmitting OFF bipolar cells, but were connected with them through fewer synapses at maturity. Time-lapse imaging revealed that this was caused by a reduced rate of synapse formation rather than an increase in synapse elimination. Similarly, TeNT-expressing ON bipolar cell axons generated fewer presynaptic active zones. The remaining active zones often recruited multiple, instead of single, synaptic ribbons. ON-OFF RGCs in TeNT mice maintained convergence of ON and OFF bipolar cells inputs and had fewer synapses on their ON arbor without changes to OFF arbor synapses. Our results reveal an unexpected and remarkably selective role for activity in circuit development in vivo, regulating synapse formation but not elimination, affecting synapse number but not dendritic or axonal patterning, and mediating independently the refinement of connections from parallel (ON and OFF) processing streams even where they converge onto the same postsynaptic cell.
C1 [Kerschensteiner, Daniel; Morgan, Josh L.; Lewis, Renate M.; Wong, Rachel O. L.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
   [Kerschensteiner, Daniel; Morgan, Josh L.; Wong, Rachel O. L.] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA.
   [Parker, Edward D.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
C3 Washington University (WUSTL); University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Kerschensteiner, D (corresponding author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
EM KerschensteinerD@vision.wustl.edu; wongr2@u.washington.edu
FU National Institutes of Health [EY10699, T32 EY07031]; McDonnell Foundation at Washington University; National Eye Institute [EY01730]; Deutsche Forschungsgemeinschaft [1466/1-1]; National Eye Institute [R01EY010699, P30EY001730, T32EY007031] Funding Source: NIH RePORTER
NR 28
TC 146
Z9 192
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 1016
EP U103
DI 10.1038/nature08236
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500035
PM 19693082
DA 2026-03-09
ER

PT J
AU Whittington, AG
   Hofmeister, AM
   Nabelek, PI
AF Whittington, Alan G.
   Hofmeister, Anne M.
   Nabelek, Peter I.
TI Temperature-dependent thermal diffusivity of the Earth's crust and implications for magmatism
SO NATURE
LA English
DT Article
ID heat; leukogranites; conductivity; constraints; anatexis; origin; model
AB The thermal evolution of planetary crust and lithosphere is largely governed by the rate of heat transfer by conduction(1-3). The governing physical properties are thermal diffusivity (kappa) and conductivity (k=kappa rho C-P), where rho denotes density and C-P denotes specific heat capacity at constant pressure. Although for crustal rocks both kappa and k decrease above ambient temperature(4,5), most thermal models of the Earth's lithosphere assume constant values for kappa (similar to 1 mm(2) s(-1)) and/or k (similar to 3 to 5 W m(-1) K-1)(6,7) owing to the large experimental uncertainties associated with conventional contact methods at high temperatures. Recent advances in laser-flash analysis(8,9) permit accurate (+/- 2 per cent) measurements on minerals and rocks to geologically relevant temperatures(10). Here we provide data from laser-flash analysis for three different crustal rock types, showing that kappa strongly decreases from 1.5-2.5 mm(2) s(-1) at ambient conditions, approaching 0.5 mm(2) s(-1) at mid-crustal temperatures. The latter value is approximately half that commonly assumed, and hot middle to lower crust is therefore a much more effective thermal insulator than previously thought. Above the quartz alpha-beta phase transition, crustal kappa is nearly independent of temperature, and similar to that of mantle materials(11). Calculated values of k indicate that its negative dependence on temperature is smaller than that of kappa, owing to the increase of C-P with increasing temperature, but k also diminishes by 50 per cent from the surface to the quartz alpha-beta transition. We present models of lithospheric thermal evolution during continental collision and demonstrate that the temperature dependence of kappa and C-P leads to positive feedback between strain heating in shear zones and more efficient thermal insulation, removing the requirement for unusually high radiogenic heat production to achieve crustal melting temperatures. Positive feedback between heating, increased thermal insulation and partial melting is predicted to occur in many tectonic settings, and in both the crust and the mantle, facilitating crustal reworking and planetary differentiation(12).
C1 [Whittington, Alan G.; Nabelek, Peter I.] Univ Missouri, Dept Geol Sci, Columbia, MO 65211 USA.
   [Hofmeister, Anne M.] Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
C3 University of Missouri System; University of Missouri Columbia; Washington University (WUSTL)
RP Whittington, AG (corresponding author), Univ Missouri, Dept Geol Sci, Columbia, MO 65211 USA.
EM whittingtona@missouri.edu
FU US National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0711020] Funding Source: National Science Foundation
NR 30
TC 387
Z9 439
U1 5
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 MAR 19
PY 2009
VL 458
IS 7236
BP 319
EP 321
DI 10.1038/nature07818
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600037
PM 19295606
DA 2026-03-09
ER

PT J
AU Saini, P
   Eyler, DE
   Green, R
   Dever, TE
AF Saini, Preeti
   Eyler, Daniel E.
   Green, Rachel
   Dever, Thomas E.
TI Hypusine-containing protein eIF5A promotes translation elongation
SO NATURE
LA English
DT Article
ID synthesis initiation-factors; yeast; purification; mechanism; binding; cells; gene
AB Translation elongation factors facilitate protein synthesis by the ribosome. Previous studies identified two universally conserved translation elongation factors, EF-Tu in bacteria (known as eEF1A in eukaryotes) and EF-G (eEF2), which deliver aminoacyl-tRNAs to the ribosome and promote ribosomal translocation, respectively(1). The factor eIF5A (encoded by HYP2 and ANB1 in Saccharomyces cerevisiae), the sole protein in eukaryotes and archaea to contain the unusual amino acid hypusine (N-epsilon-(4-amino-2-hydroxybutyl)lysine)(2), was originally identified based on its ability to stimulate the yield (endpoint) of methionylpuromycin synthesis-a model assay for first peptide bond synthesis thought to report on certain aspects of translation initiation(3,4). Hypusine is required for eIF5A to associate with ribosomes(5,6) and to stimulate methionyl-puromycin synthesis(7). Because eIF5A did not stimulate earlier steps of translation initiation(8), and depletion of eIF5A in yeast only modestly impaired protein synthesis(9), it was proposed that eIF5A function was limited to stimulating synthesis of the first peptide bond or that eIF5A functioned on only a subset of cellular messenger RNAs. However, the precise cellular role of eIF5A is unknown, and the protein has also been linked to mRNA decay, including the nonsense-mediated mRNA decay pathway(10,11), and to nucleocytoplasmic transport(12,13). Here we use molecular genetic and biochemical studies to show that eIF5A promotes translation elongation. Depletion or inactivation of eIF5A in the yeast S. cerevisiae resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant eIF5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of eIF5A mimicked the effects of the eEF2 inhibitor sordarin, indicating that eIF5A might function together with eEF2 to promote ribosomal translocation. Because eIF5A is a structural homologue of the bacterial protein EF-P-14,P-15, we propose that eIF5A/EF-P is a universally conserved translation elongation factor.
C1 [Saini, Preeti; Dever, Thomas E.] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
   [Eyler, Daniel E.; Green, Rachel] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
C3 National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Howard Hughes Medical Institute; Johns Hopkins University
RP Dever, TE (corresponding author), NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM tdever@nih.gov
FU HHMI; NIH; NICHD; Eunice Kennedy Shriver National Institute of Child Health and Human Development [ZIAHD001010] Funding Source: NIH RePORTER
NR 35
TC 356
Z9 435
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 MAY 7
PY 2009
VL 459
IS 7243
BP 118
EP U129
DI 10.1038/nature08034
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300041
PM 19424157
DA 2026-03-09
ER

PT J
AU Sankaran, VG
   Xu, J
   Ragoczy, T
   Ippolito, GC
   Walkley, CR
   Maika, SD
   Fujiwara, Y
   Ito, M
   Groudine, M
   Bender, MA
   Tucker, PW
   Orkin, SH
AF Sankaran, Vijay G.
   Xu, Jian
   Ragoczy, Tobias
   Ippolito, Gregory C.
   Walkley, Carl R.
   Maika, Shanna D.
   Fujiwara, Yuko
   Ito, Masafumi
   Groudine, Mark
   Bender, M. A.
   Tucker, Philip W.
   Orkin, Stuart H.
TI Developmental and species-divergent globin switching are driven by BCL11A
SO NATURE
LA English
DT Article
ID yeast artificial chromosome; locus-control region; fetal-hemoglobin; functional-analysis; gene-expression; evo-devo; transcription; differentiation; erythropoiesis; pattern
AB The contribution of changes in cis-regulatory elements or trans-acting factors to interspecies differences in gene expression is not well understood. The mammalian beta-globin loci have served as a model for gene regulation during development. Transgenic mice containing the human beta-globin locus, consisting of the linked embryonic (epsilon), fetal (gamma) and adult (beta) genes, have been used as a system to investigate the temporal switch from fetal to adult haemoglobin, as occurs in humans. Here we show that the human gamma-globin (HBG) genes in these mice behave as murine embryonic globin genes, revealing a limitation of the model and demonstrating that critical differences in the trans-acting milieu have arisen during mammalian evolution. We show that the expression of BCL11A, a repressor of human gamma-globin expression identified by genome-wide association studies, differs between mouse and human. Developmental silencing of the mouse embryonic globin and human gamma-globin genes fails to occur in mice in the absence of BCL11A. Thus, BCL11A is a critical mediator of species-divergent globin switching. By comparing the ontogeny of beta-globin gene regulation in mice and humans, we have shown that alterations in the expression of a trans-acting factor constitute a critical driver of gene expression changes during evolution.
C1 [Sankaran, Vijay G.; Xu, Jian; Walkley, Carl R.; Fujiwara, Yuko; Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA.
   [Sankaran, Vijay G.; Xu, Jian; Walkley, Carl R.; Fujiwara, Yuko; Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Xu, Jian; Fujiwara, Yuko; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Ragoczy, Tobias; Groudine, Mark; Bender, M. A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Ippolito, Gregory C.; Maika, Shanna D.; Tucker, Philip W.] Univ Texas Austin, Inst Mol & Cellular Biol, Austin, TX 78712 USA.
   [Ito, Masafumi] Nagoya First Hosp, Dept Pathol, Nagoya, Aichi, Japan.
   [Groudine, Mark] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA.
   [Bender, M. A.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Howard Hughes Medical Institute; Fred Hutchinson Cancer Center; University of Texas System; University of Texas Austin; Red Cross Nagoya Daiichi Hospital; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Orkin, SH (corresponding author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA.
EM stuart_orkin@dfci.harvard.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); National Cancer Institute; Howard Hughes Medical Institute (HHMI); Leukemia AMP; Lymphoma Society; American Society of Hematology; Helen Hay Whitney Foundation; NCI postdoctoral fellowship; National Heart Lung and Blood Institute [P01HL032262] Funding Source: NIH RePORTER
NR 38
TC 321
Z9 394
U1 0
U2 31
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1093
EP 1097
DI 10.1038/nature08243
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000030
PM 19657335
DA 2026-03-09
ER

PT J
AU Ray, PS
   Jia, J
   Yao, P
   Majumder, M
   Hatzoglou, M
   Fox, PL
AF Ray, Partho Sarothi
   Jia, Jie
   Yao, Peng
   Majumder, Mithu
   Hatzoglou, Maria
   Fox, Paul L.
TI A stress-responsive RNA switch regulates VEGFA expression
SO NATURE
LA English
DT Article
ID endothelial growth-factor; gene-expression; translational control; bacillus-subtilis; messenger-rnas; noncanonical function; leader rna; hypoxia; protein; riboswitches
AB Ligand binding to structural elements in the non- coding regions of messenger RNA modulates gene expression(1,2). Ligands such as free metabolites or other small molecules directly bind and induce conformational changes in regulatory RNA elements known as riboswitches(1-4). Other types of RNA switches are activated by complexed metabolites - for example, RNA- ligated metabolites such as aminoacyl- charged transfer RNA in the T- box system(5), or protein-bound metabolites in the glucose- or amino- acid- stimulated terminator-anti- terminator systems(6,7). All of these switch types are found in bacteria, fungi and plants(8-10). Here we report an RNA switch in human vascular endothelial growth factor- A ( VEGFA, also known as VEGF) mRNA 39 untranslated region ( UTR) that integrates signals from interferon ( IFN)-gamma and hypoxia to regulate VEGFA translation in myeloid cells. Analogous to riboswitches, the VEGFA 3 ' UTR undergoes a binary conformational change in response to environmental signals. However, the VEGFA 3 ' UTR switch is metabolite independent, and the conformational change is dictated by mutually exclusive, stimulus- dependent binding of proteins, namely, the IFN-gamma-activated inhibitor of translation complex(11,12) and heterogeneous
C1 [Ray, Partho Sarothi; Jia, Jie; Yao, Peng; Fox, Paul L.] Cleveland Clin, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44195 USA.
   [Ray, Partho Sarothi] Indian Inst Sci Educ & Res, Dept Biol, Kolkata 700106, India.
   [Majumder, Mithu; Hatzoglou, Maria] Case Western Reserve Univ, Dept Nutr, Cleveland, OH 44106 USA.
C3 Cleveland Clinic Foundation; Indian Institute of Science Education & Research (IISER) - Kolkata; University System of Ohio; Case Western Reserve University
RP Fox, PL (corresponding author), Cleveland Clin, Dept Cell Biol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM foxp@ccf.org
FU National Institutes of Health [P01 HL29582, R01 HL67725, P01 HL76491, R01 DK60596]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK053307, R01DK060596] Funding Source: NIH RePORTER
NR 31
TC 217
Z9 252
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 FEB 12
PY 2009
VL 457
IS 7231
BP 915
EP 919
DI 10.1038/nature07598
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700052
PM 19098893
DA 2026-03-09
ER

PT J
AU Gonzales, EB
   Kawate, T
   Gouaux, E
AF Gonzales, Eric B.
   Kawate, Toshimitsu
   Gouaux, Eric
TI Pore architecture and ion sites in acid-sensing ion channels and P2X receptors
SO NATURE
LA English
DT Article
ID structural motif; sodium; selectivity; neurodegeneration; mutation; desensitization; identification; sensitivity; permeation; proteins
AB Acid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits, and are members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels. These ubiquitous eukaryotic ion channels have essential roles in biological activities as diverse as sodium homeostasis, taste and pain. Despite their crucial roles in biology and their unusual trimeric subunit stoichiometry, there is little knowledge of the structural and chemical principles underlying their ion channel architecture and ion-binding sites. Here we present the structure of a functional acid-sensing ion channel in a desensitized state at 3 angstrom resolution, the location and composition of the similar to 8 angstrom 'thick' desensitization gate, and the trigonal antiprism coordination of caesium ions bound in the extracellular vestibule. Comparison of the acid-sensing ion channel structure with the ATP-gated P2X(4) receptor reveals similarity in pore architecture and aqueous vestibules, suggesting that there are unanticipated yet common structural and mechanistic principles.
C1 [Gonzales, Eric B.; Kawate, Toshimitsu; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Howard Hughes Medical Institute
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU National Institute of General Medical Sciences (NIGMS)-National Research Service Award (NRSA); National Institutes of Health (NIH)
NR 48
TC 369
Z9 421
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 599
EP U62
DI 10.1038/nature08218
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300043
PM 19641589
DA 2026-03-09
ER

PT J
AU Celniker, SE
   Dillon, LAL
   Gerstein, MB
   Gunsalus, KC
   Henikoff, S
   Karpen, GH
   Kellis, M
   Lai, EC
   Lieb, JD
   MacAlpine, DM
   Micklem, G
   Piano, F
   Snyder, M
   Stein, L
   White, KP
   Waterston, RH
AF Celniker, Susan E.
   Dillon, Laura A. L.
   Gerstein, Mark B.
   Gunsalus, Kristin C.
   Henikoff, Steven
   Karpen, Gary H.
   Kellis, Manolis
   Lai, Eric C.
   Lieb, Jason D.
   MacAlpine, David M.
   Micklem, Gos
   Piano, Fabio
   Snyder, Michael
   Stein, Lincoln
   White, Kevin P.
   Waterston, Robert H.
TI Unlocking the secrets of the genome
SO NATURE
LA English
DT Article
ID gene-expression map; functional elements; drosophila; discovery; identification; transcription; evolution; profiles; networks
C1 [Celniker, Susan E.] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Genome Biol, Berkeley, CA 94720 USA.
   [Dillon, Laura A. L.] NHGRI, Div Extramural Res, NIH, Bethesda, MD 20892 USA.
   [Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [Gerstein, Mark B.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Gunsalus, Kristin C.; Piano, Fabio] NYU, Ctr Genom & Syst Biol, New York, NY 10003 USA.
   [Henikoff, Steven] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Karpen, Gary H.] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Mol & Cell Biol, Dept Genome & Computat Biol, Berkeley, CA 94720 USA.
   [Kellis, Manolis] MIT, Broad Inst, Cambridge, MA 02140 USA.
   [Kellis, Manolis] Harvard Univ, Cambridge, MA 02140 USA.
   [Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Lai, Eric C.] Sloan Kettering Inst, New York, NY 10065 USA.
   [Lieb, Jason D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Lieb, Jason D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [MacAlpine, David M.] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Micklem, Gos] Cambridge Syst Biol Ctr, Cambridge CB2 1QR, England.
   [Micklem, Gos] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
   [Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06824 USA.
   [Stein, Lincoln] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11542 USA.
   [White, Kevin P.] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
   [White, Kevin P.] Argonne Natl Lab, Inst Genom & Syst Biol, Argonne, IL 60439 USA.
   [Waterston, Robert H.] Dept Genome Sci, Seattle, WA 98195 USA.
   [Waterston, Robert H.] Univ Washington, Sch Med, Seattle, WA 98195 USA.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Yale University; Yale University; Yale University; New York University; Fred Hutchinson Cancer Center; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Memorial Sloan Kettering Cancer Center; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Duke University; University of Cambridge; University of Cambridge; Yale University; Cold Spring Harbor Laboratory; University of Chicago; United States Department of Energy (DOE); Argonne National Laboratory; University of Washington; University of Washington Seattle
RP Celniker, SE (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Genome Biol, Berkeley, CA 94720 USA.
EM celniker@fruitfly.org
FU NHGRI NIH HHS [U01 HG004258, R01 HG004037, U01 HG004279] Funding Source: Medline; NIGMS NIH HHS [R01 GM066272] Funding Source: Medline
NR 35
TC 629
Z9 824
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 JUN 18
PY 2009
VL 459
IS 7249
BP 927
EP 930
DI 10.1038/459927a
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500031
PM 19536255
DA 2026-03-09
ER

PT J
AU Lavik, G
   Stührmann, T
   Brüchert, V
   Van der Plas, A
   Mohrholz, V
   Lam, P
   Mussmann, M
   Fuchs, BM
   Amann, R
   Lass, U
   Kuypers, MMM
AF Lavik, Gaute
   Stuehrmann, Torben
   Bruechert, Volker
   Van der Plas, Anja
   Mohrholz, Volker
   Lam, Phyllis
   Mussmann, Marc
   Fuchs, Bernhard M.
   Amann, Rudolf
   Lass, Ulrich
   Kuypers, Marcel M. M.
TI Detoxification of sulphidic African shelf waters by blooming chemolithotrophs
SO NATURE
LA English
DT Article
ID sulfide; bacteria; identification; hypoxia; gas; phytoplankton; community; reduction; oxidation; sediment
AB Coastal waters support similar to 90 per cent of global fisheries and are therefore an important food reserve for our planet(1). Eutrophication of these waters, due to human activity, leads to severe oxygen depletion and the episodic occurrence of hydrogen sulphide toxic to multi- cellular life - with disastrous consequences for coastal ecosytems(2-5). Here we show that an area of similar to 7,000 km(2) of African shelf, covered by sulphidic water, was detoxified by blooming bacteria that oxidized the biologically harmful sulphide to environmentally harmless colloidal sulphur and sulphate. Combined chemical analyses, stoichiometric modelling, isotopic incubations, comparative 16S ribosomal RNA, functional gene sequence analyses and fluorescence in situ hybridization indicate that the detoxification proceeded by chemolithotrophic oxidation of sulphide with nitrate and was mainly catalysed by two discrete populations of gamma- and epsilon-proteobacteria. Chemolithotrophic bacteria, accounting for similar to 20 per cent of the bacterioplankton in sulphidic waters, created a buffer zone between the toxic sulphidic subsurface waters and the oxic surface waters, where fish and other nekton live. This is the first time that large- scale detoxification of sulphidic waters by chemolithotrophs has been observed in an open- ocean system. The data suggest that sulphide can be completely consumed by bacteria in the subsurface waters and, thus, can be overlooked by remote sensing or monitoring of shallow coastal waters. Consequently, sulphidic bottom waters on continental shelves may be more common than previously believed, and could therefore have an important but as yet neglected effect on benthic communities.
C1 [Lavik, Gaute; Stuehrmann, Torben; Bruechert, Volker; Lam, Phyllis; Fuchs, Bernhard M.; Amann, Rudolf; Kuypers, Marcel M. M.] Max Planck Inst Microbiol, D-28359 Bremen, Germany.
   [Van der Plas, Anja] Minist Fisheries & Marine Resources, Natl Marine Informat & Res Ctr, Swakopmund, Namibia.
   [Mohrholz, Volker; Lass, Ulrich] Balt Sea Res Inst Warnemunde, D-18119 Rostock, Germany.
   [Mussmann, Marc] Univ Vienna, Dept Microbial Ecol, Vienna Ecol Ctr, A-1090 Vienna, Austria.
C3 Max Planck Society; University of Vienna
RP Kuypers, MMM (corresponding author), Max Planck Inst Microbiol, Celsiusstr 1, D-28359 Bremen, Germany.
EM mkuypers@mpi-bremen.de
FU MPG; BMBF programme Geotechnologien; NAMIBGAS; DFG; BENEFIT; Namibian Ministry of Fisheries and Natural Resources
NR 40
TC 272
Z9 311
U1 2
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 29
PY 2009
VL 457
IS 7229
BP 581
EP U86
DI 10.1038/nature07588
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200041
PM 19078958
DA 2026-03-09
ER

PT J
AU Wiederhecker, GS
   Chen, L
   Gondarenko, A
   Lipson, M
AF Wiederhecker, Gustavo S.
   Chen, Long
   Gondarenko, Alexander
   Lipson, Michal
TI Controlling photonic structures using optical forces
SO NATURE
LA English
DT Article
ID wave-guides; cavity; resonances; chip
AB The use of optical forces to manipulate small objects is well known. Applications include the manipulation of living cells by optical tweezers(1) and optical cooling in atomic physics(2). The miniaturization of optical systems ( to the micro and nanoscale) has resulted in very compliant systems with masses of the order of nanograms, rendering them susceptible to optical forces(3-6). Optical forces have been exploited to demonstrate chaotic quivering of microcavities(7), optical cooling of mechanical modes(8-11), actuation of a tapered-fibre waveguide and excitation of the mechanical modes of silicon nano-beams(12,13). Despite recent progress in this field(14-17), it is challenging to manipulate the optical response of photonic structures using optical forces; this is because of the large forces that are required to induce appreciable changes in the geometry of the structure. Here we implement a resonant structure whose optical response can be efficiently statically controlled using relatively weak attractive and repulsive optical forces. We demonstrate a static mechanical deformation of up to 20 nanometres in a silicon nitride structure, using three milliwatts of continuous optical power. Because of the sensitivity of the optical response to this deformation, such optically induced static displacement introduces resonance shifts spanning 80 times the intrinsic resonance linewidth.
C1 [Wiederhecker, Gustavo S.; Chen, Long; Gondarenko, Alexander; Lipson, Michal] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA.
C3 Cornell University
RP Lipson, M (corresponding author), Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA.
EM ml292@cornell.edu
FU National Science Foundation [00446571]; Cornell University's Center for Nanoscale Systems; National Science Foundation; Cornell University and Industrial
NR 21
TC 311
Z9 359
U1 4
U2 175
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 633
EP U103
DI 10.1038/nature08584
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900037
PM 19915549
DA 2026-03-09
ER

PT J
AU Park, S
   Roelofs, J
   Kim, W
   Robert, J
   Schmidt, M
   Gygi, SP
   Finley, D
AF Park, Soyeon
   Roelofs, Jeroen
   Kim, Woong
   Robert, Jessica
   Schmidt, Marion
   Gygi, Steven P.
   Finley, Daniel
TI Hexameric assembly of the proteasomal ATPases is templated through their C termini
SO NATURE
LA English
DT Article
ID 19s regulatory particle; 26 s-proteasome; 20s proteasm; structural basis; complex; yeast; proteins; subunits; pathway; degradation
AB Substrates of the proteasome are recognized and unfolded by the regulatory particle, and then translocated into the core particle (CP) to be degraded(1). A hetero-hexameric ATPase ring, containing subunits Rpt1-6, is situated within the base subassembly of the regulatory particle(1). The ATPase ring sits atop the CP, with the Rpt carboxy termini inserted into pockets in the CP2-6. Here we identify a previously unknown function of the Rpt proteins in proteasome biogenesis through deleting the C-terminal residue from each Rpt in the yeast Saccharomyces cerevisiae. Our results indicate that assembly of the hexameric ATPase ring is templated on the CP. We have also identified an apparent intermediate in base assembly, BP1, which contains Rpn1, three Rpts and Hsm3, a chaperone for base assembly. The Rpt proteins with the strongest assembly phenotypes, Rpt4 and Rpt6, were absent from BP1. We propose that Rpt4 and Rpt6 form a nucleating complex to initiate base assembly, and that this complex is subsequently joined by BP1 to complete the Rpt ring. Our studies show that assembly of the proteasome base is a rapid yet highly orchestrated process.
C1 [Park, Soyeon; Roelofs, Jeroen; Kim, Woong; Robert, Jessica; Gygi, Steven P.; Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Schmidt, Marion] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA.
C3 Harvard University; Harvard Medical School; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Finley, D (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM daniel_finley@hms.harvard.edu
FU US National Institutes of Health (NIH) [GM043601, GM67945]; EMBO; NIH NRSA [5F32GM75737-2]; National Institute of General Medical Sciences [R01GM067945] Funding Source: NIH RePORTER
NR 30
TC 116
Z9 152
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 866
EP U9
DI 10.1038/nature08065
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500044
PM 19412160
DA 2026-03-09
ER

PT J
AU Colgin, LL
   Denninger, T
   Fyhn, M
   Hafting, T
   Bonnevie, T
   Jensen, O
   Moser, MB
   Moser, EI
AF Colgin, Laura Lee
   Denninger, Tobias
   Fyhn, Marianne
   Hafting, Torkel
   Bonnevie, Tora
   Jensen, Ole
   Moser, May-Britt
   Moser, Edvard I.
TI Frequency of gamma oscillations routes flow of information in the hippocampus
SO NATURE
LA English
DT Article
ID entorhinal cortex; behaving rat; neuronal synchronization; spatial representation; synaptic plasticity; pyramidal cells; theta-rhythm; ca1; memory; modulation
AB Gamma oscillations are thought to transiently link distributed cell assemblies that are processing related information(1,2), a function that is probably important for network processes such as perception(1-3), attentional selection(4) and memory(5,6). This 'binding' mechanism requires that spatially distributed cells fire together with millisecond range precision(7,8); however, it is not clear how such coordinated timing is achieved given that the frequency of gamma oscillations varies substantially across space and time, from similar to 25 to almost 150 Hz(1,9-13). Here we show that gamma oscillations in the CA1 area of the hippocampus split into distinct fast and slow frequency components that differentially couple CA1 to inputs from the medial entorhinal cortex, an area that provides information about the animal's current position(14-17), and CA3, a hippocampal subfield essential for storage of such information(14,18,19). Fast gamma oscillations in CA1 were synchronized with fast gamma in medial entorhinal cortex, and slow gamma oscillations in CA1 were coherent with slow gamma in CA3. Significant proportions of cells in medial entorhinal cortex and CA3 were phase-locked to fast and slow CA1 gamma waves, respectively. The two types of gamma occurred at different phases of the CA1 theta rhythm and mostly on different theta cycles. These results point to routeing of information as a possible function of gamma frequency variations in the brain and provide a mechanism for temporal segregation of potentially interfering information from different sources.
C1 [Colgin, Laura Lee; Denninger, Tobias; Fyhn, Marianne; Hafting, Torkel; Bonnevie, Tora; Moser, May-Britt; Moser, Edvard I.] Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, NO-7489 Trondheim, Norway.
   [Colgin, Laura Lee; Denninger, Tobias; Fyhn, Marianne; Hafting, Torkel; Bonnevie, Tora; Moser, May-Britt; Moser, Edvard I.] Norwegian Univ Sci & Technol, Ctr Biol Memory, MTFS, NO-7489 Trondheim, Norway.
   [Jensen, Ole] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands.
C3 Norwegian University of Science & Technology (NTNU); Norwegian University of Science & Technology (NTNU); Radboud University Nijmegen
RP Colgin, LL (corresponding author), Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, Olav Kyrres Gate 9, NO-7489 Trondheim, Norway.
EM laura.colgin@ntnu.no; edvard.moser@ntnu.no
FU Kavli Foundation; Norwegian Research Council
NR 30
TC 1040
Z9 1277
U1 0
U2 145
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 19
PY 2009
VL 462
IS 7271
BP 353
EP U119
DI 10.1038/nature08573
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300045
PM 19924214
DA 2026-03-09
ER

PT J
AU Elsig, J
   Schmitt, J
   Leuenberger, D
   Schneider, R
   Eyer, M
   Leuenberger, M
   Joos, F
   Fischer, H
   Stocker, TF
AF Elsig, Joachim
   Schmitt, Jochen
   Leuenberger, Daiana
   Schneider, Robert
   Eyer, Marc
   Leuenberger, Markus
   Joos, Fortunat
   Fischer, Hubertus
   Stocker, Thomas F.
TI Stable isotope constraints on Holocene carbon cycle changes from an Antarctic ice core
SO NATURE
LA English
DT Article
ID atmospheric co2; terrestrial; dynamics; record; age; variability; peatlands; dioxide; climate; sink
AB Reconstructions of atmospheric CO2 concentrations based on Antarctic ice cores(1,2) reveal significant changes during the Holocene epoch, but the processes responsible for these changes in CO2 concentrations have not been unambiguously identified. Distinct characteristics in the carbon isotope signatures of the major carbon reservoirs (ocean, biosphere, sediments and atmosphere) constrain variations in the CO2 fluxes between those reservoirs. Here we present a highly resolved atmospheric delta C-13 record for the past 11,000 years from measurements on atmospheric CO2 trapped in an Antarctic ice core. From mass-balance inverse model calculations(3,4) performed with a simplified carbon cycle model, we show that the decrease in atmospheric CO2 of about 5 parts per million by volume (p.p.m.v.). The increase in delta C-13 of about 0.25 parts per thousand during the early Holocene is most probably the result of a combination of carbon uptake of about 290 gigatonnes of carbon by the land biosphere and carbon release from the ocean in response to carbonate compensation of the terrestrial uptake during the termination of the last ice age. The 20 p.p.m.v. increase of atmospheric CO2 and the small decrease in delta C-13 of about 0.05 parts per thousand during the later Holocene can mostly be explained by contributions from carbonate compensation of earlier land-biosphere uptake and coral reef formation, with only a minor contribution from a small decrease of the land-biosphere carbon inventory.
C1 [Elsig, Joachim; Schmitt, Jochen; Leuenberger, Daiana; Schneider, Robert; Eyer, Marc; Leuenberger, Markus; Joos, Fortunat; Fischer, Hubertus; Stocker, Thomas F.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
   [Elsig, Joachim; Schmitt, Jochen; Leuenberger, Daiana; Schneider, Robert; Eyer, Marc; Leuenberger, Markus; Joos, Fortunat; Fischer, Hubertus; Stocker, Thomas F.] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Schmitt, Jochen; Fischer, Hubertus] Alfred Wegener Inst Polar & Marine Res AWI, D-27568 Bremerhaven, Germany.
C3 University of Bern; University of Bern; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research
RP Stocker, TF (corresponding author), Univ Bern, Inst Phys, Sidlerstr 5, CH-3012 Bern, Switzerland.
EM stocker@climate.unibe.ch
FU EU (EPICA-MIS); national contributions from Belgium, Denmark, France, Germany, Italy, the Netherlands, Norway, Sweden, Switzerland and the United Kingdom; Swiss NSF; DFG priority programme INTERDYNAMIK; German climate programme DEKLIM
NR 30
TC 167
Z9 186
U1 0
U2 109
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 24
PY 2009
VL 461
IS 7263
BP 507
EP 510
DI 10.1038/nature08393
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900036
PM 19779448
DA 2026-03-09
ER

PT J
AU Lee, P
   Lee, DJ
   Chan, C
   Chen, SW
   Ch'en, I
   Jamora, C
AF Lee, Pedro
   Lee, Dai-Jen
   Chan, Carol
   Chen, Shih-Wei
   Ch'en, Irene
   Jamora, Colin
TI Dynamic expression of epidermal caspase 8 simulates a wound healing response
SO NATURE
LA English
DT Article
ID inflammatory skin-disease; nf-kappa-b; stem-cells; innate immunity; cutting edge; interleukin-1-alpha; keratinocytes; homeostasis; activation; contribute
AB Tissue homeostasis and regeneration are regulated by an intricate balance of seemingly competing processes-proliferation versus differentiation, and cell death versus survival(1). Here we demonstrate that the loss of epidermal caspase 8, an important mediator of apoptosis(2), recapitulates several phases of a wound healing response in the mouse. The epidermal hyperplasia in the caspase 8 null skin is the culmination of signals exchanged between epidermal keratinocytes, dermal fibroblasts and leukocytic cells. This reciprocal interaction is initiated by the paracrine signalling of interleukin 1 alpha (IL1 alpha), which activates both skin stem cell proliferation and cutaneous inflammation. The non-canonical secretion of IL1a is induced by a p38-MAPK-mediated upregulation of NALP3 (also known as NLRP3), leading to inflammasome assembly and caspase 1 activation. Notably, the increased proliferation of basal keratinocytes is counterbalanced by the growth arrest of suprabasal keratinocytes in the stratified epidermis by IL1 alpha-dependent NF kappa B signalling. Altogether, our findings illustrate how the loss of caspase 8 can affect more than programmed cell death to alter the local microenvironment and elicit processes common to wound repair and many neoplastic skin disorders.
C1 [Lee, Pedro; Lee, Dai-Jen; Chan, Carol; Chen, Shih-Wei; Jamora, Colin] Div Biol Sci, Sect Cell & Dev Biol, La Jolla, CA 92093 USA.
   [Ch'en, Irene] Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
   [Jamora, Colin] Dept Med Dermatol, La Jolla, CA 92093 USA.
RP Jamora, C (corresponding author), Div Biol Sci, Sect Cell & Dev Biol, Nat Sci Bldg,Room 6311,9500 Gilman Dr,MC 0380, La Jolla, CA 92093 USA.
EM cjamora@ucsd.edu
FU National Institutes of Health (NIAMS) [5R01AR053185-03]; American Skin Association; Dermatology Foundation
NR 30
TC 129
Z9 158
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 519
EP U7
DI 10.1038/nature07687
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400047
PM 19204729
DA 2026-03-09
ER

PT J
AU Sancho, D
   Joffre, OP
   Keller, AM
   Rogers, NC
   Martínez, D
   Hernanz-Falcón, P
   Rosewell, I
   Sousa, CRE
AF Sancho, David
   Joffre, Olivier P.
   Keller, Anna M.
   Rogers, Neil C.
   Martinez, Dolores
   Hernanz-Falcon, Patricia
   Rosewell, Ian
   Reis e Sousa, Caetano
TI Identification of a dendritic cell receptor that couples sensing of necrosis to immunity
SO NATURE
LA English
DT Article
ID activation; adjuvants; danger; clec9a; death
AB Injury or impaired clearance of apoptotic cells leads to the pathological accumulation of necrotic corpses, which induce an inflammatory response that initiates tissue repair(1). In addition, antigens present in necrotic cells can sometimes provoke a specific immune response(2-4) and it has been argued that necrosis could explain adaptive immunity in seemingly infection-free situations, such as after allograft transplantation or in spontaneous and therapy-induced tumour rejection(5,6). In the mouse, the CD8 alpha(+) subset of dendritic cells phagocytoses dead cell remnants and cross-primes CD8(+) T cells against cell-associated antigens(7). Here we show that CD8 alpha(+) dendritic cells use CLEC9A (also known as DNGR-1), a recently-characterized C-type lectin(8-10), to recognize a preformed signal that is exposed on necrotic cells. Loss or blockade of CLEC9A does not impair the uptake of necrotic cell material by CD8 alpha(+) dendritic cells, but specifically reduces cross-presentation of dead-cell-associated antigens in vitro and decreases the immunogenicity of necrotic cells in vivo. The function of CLEC9A requires a key tyrosine residue in its intracellular tail that allows the recruitment and activation of the tyrosine kinase SYK, which is also essential for cross-presentation of dead-cell-associated antigens. Thus, CLEC9A functions as a SYK-coupled C-type lectin receptor to mediate sensing of necrosis by the principal dendritic-cell subset involved in regulating cross-priming to cell-associated antigens.
C1 [Sancho, David; Joffre, Olivier P.; Keller, Anna M.; Rogers, Neil C.; Hernanz-Falcon, Patricia; Reis e Sousa, Caetano] Lincolns Inn Fields Labs, Immunobiol Lab, London WC2A 3PX, England.
   [Sancho, David; Joffre, Olivier P.; Keller, Anna M.; Rogers, Neil C.; Hernanz-Falcon, Patricia; Reis e Sousa, Caetano] Lincolns Inn Fields Labs, London Res Inst, Canc Res UK, FACS Lab, London WC2A 3PX, England.
   [Martinez, Dolores; Rosewell, Ian] Imperial Canc Res Fund, Clare Hall Labs, Canc Res UK, Trangen Serv, Potters Bar EN6 3LD, Herts, England.
C3 Cancer Research UK; Cancer Research UK
RP Sousa, CRE (corresponding author), Lincolns Inn Fields Labs, Immunobiol Lab, 44 Lincolns Inn Fields, London WC2A 3PX, England.
EM caetano@cancer.org.uk
FU Cancer Research UK; EMBO [ALTF 336-2004]; European Community [MEIF-CT-2005-009205]
NR 26
TC 595
Z9 698
U1 3
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 16
PY 2009
VL 458
IS 7240
BP 899
EP 903
DI 10.1038/nature07750
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500045
PM 19219027
DA 2026-03-09
ER

PT J
AU Bao, SQ
   Tang, FC
   Li, XH
   Hayashi, K
   Gillich, A
   Lao, KQ
   Surani, MA
AF Bao, Siqin
   Tang, Fuchou
   Li, Xihe
   Hayashi, Katsuhiko
   Gillich, Astrid
   Lao, Kaiqin
   Surani, M. Azim
TI Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells
SO NATURE
LA English
DT Article
ID x-chromosome; germ-cells; mouse; methylation; heterogeneity; establishment; states; lines
AB The pluripotent state, which is first established in the primitive ectoderm cells of blastocysts, is lost progressively and irreversibly during subsequent development(1). For example, development of post-implantation epiblast cells from primitive ectoderm involves significant transcriptional and epigenetic changes, including DNA methylation and X chromosome inactivation(2), which create a robust epigenetic barrier and prevent their reversion to a primitive-ectoderm-like state. Epiblast cells are refractory to leukaemia inhibitory factor (LIF)-STAT3 signalling, but they respond to activin/basic fibroblast growth factor to form self-renewing epiblast stem cells (EpiSCs), which exhibit essential properties of epiblast cells(3,4) and that differ from embryonic stem (ES) cells derived from primitive ectoderm(5). Here we show reprogramming of advanced epiblast cells fromembryonic day 5.5-7.5mouseembryos with uniform expression of N-cadherin and inactive X chromosome to ES-cell-like cells (rESCs) in response to LIF-STAT3 signalling. Cultured epiblast cells overcome the epigenetic barrier progressively as they proceed with the erasure of key properties of epiblast cells, resulting in DNA demethylation, X reactivation and expression of E-cadherin. The accompanying changes in the transcriptome result in a loss of phenotypic and epigenetic memory of epiblast cells. Using this approach, we report reversion of established EpiSCs to rESCs. Moreover, unlike epiblast and EpiSCs, rESCs contribute to somatic tissues and germ cells in chimaeras. Further studies may reveal how signalling-induced epigenetic reprogramming may promote reacquisition of pluripotency.
C1 [Bao, Siqin; Tang, Fuchou; Hayashi, Katsuhiko; Gillich, Astrid; Surani, M. Azim] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England.
   [Li, Xihe] Inner Mongolia Univ, Mengniu RB CO Ltd, Coll Life Sci, Hohhot 010021, Inner Mongolia, Peoples R China.
   [Lao, Kaiqin] Appl Biosyst Inc, Mol Cell Biol, Foster City, CA 94404 USA.
C3 University of Cambridge; Inner Mongolia University; Thermo Fisher Scientific; Applied Biosystems
RP Surani, MA (corresponding author), Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
EM a.surani@gurdon.cam.ac.uk
FU Wellcome Trust; Medical Research Council [G0800784, G0800784B] Funding Source: researchfish; MRC [G0800784] Funding Source: UKRI
NR 31
TC 308
Z9 365
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 29
PY 2009
VL 461
IS 7268
BP 1292
EP 1295
DI 10.1038/nature08534
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800051
PM 19816418
DA 2026-03-09
ER

PT J
AU Matsuoka, T
   Shimizu, K
AF Matsuoka, Takahiro
   Shimizu, Katsuya
TI Direct observation of a pressure-induced metal-to-semiconductor transition in lithium
SO NATURE
LA English
DT Article
ID alkali-metals; dense lithium; gpa; phase; superconductivity; temperature; resistance
AB Lithium, the lightest metal, has long been considered to have a 'simple' electronic structure that can be well explained within the nearly-free-electron model. But lithium does not stay 'simple' under compression: rather than becoming more free-electron-like as pressure is increased, first-principles calculations(1,2) suggest that it transforms into a semi-metal or semiconductor. Experimentally, it has been shown that dense lithium adopts low-symmetry structures(3,4); there is also evidence that its resistivity increases with pressure(5-8). However, the electronic transport properties of lithium have so far not been directly monitored as a function of increasing static pressure. Here we report electrical resistance measurements on lithium in a diamond anvil cell up to pressures of 105 GPa, which reveal a significant increase in electrical resistivity and a change in its temperature dependence near 80 GPa. Our data thus provide unambiguous experimental evidence for a pressure-induced metal-to-semiconductor transition in a 'simple' metallic element.
C1 [Matsuoka, Takahiro; Shimizu, Katsuya] Osaka Univ, Ctr Quantum Sci & Technol Extreme Condit, KYOKUGEN, Osaka 5608531, Japan.
C3 University of Osaka
RP Matsuoka, T (corresponding author), Osaka Univ, Ctr Quantum Sci & Technol Extreme Condit, KYOKUGEN, 1-3 Machikaneyama, Osaka 5608531, Japan.
EM matsuoka@djebel.mp.es.osaka-u.ac.jp
FU Grant-in-Aid for Scientific Research [19104009]; Global COE Program Core Research and Engineering of Advanced Materials-Interdisciplinary Education Center for Materials Science), MEXT, Japan; Grant-in-Aid for JSPS Fellows [19.52753]; Grants-in-Aid for Scientific Research [19104009] Funding Source: KAKEN
NR 22
TC 240
Z9 266
U1 2
U2 114
PU 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 12
PY 2009
VL 458
IS 7235
BP 186
EP 189
DI 10.1038/nature07827
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700039
PM 19279633
DA 2026-03-09
ER

PT J
AU Song, H
   Kim, Y
   Jang, YH
   Jeong, H
   Reed, MA
   Lee, T
AF Song, Hyunwook
   Kim, Youngsang
   Jang, Yun Hee
   Jeong, Heejun
   Reed, Mark A.
   Lee, Takhee
TI Observation of molecular orbital gating
SO NATURE
LA English
DT Article
ID electron-tunneling spectroscopy; single; conductance; transistor; transport; junctions
AB The control of charge transport in an active electronic device depends intimately on the modulation of the internal charge density by an external node(1). For example, a field-effect transistor relies on the gated electrostatic modulation of the channel charge produced by changing the relative position of the conduction and valence bands with respect to the electrodes. In molecular-scale devices(2-10), a longstanding challenge has been to create a true three-terminal device that operates in this manner (that is, by modifying orbital energy). Here we report the observation of such a solid-state molecular device, in which transport current is directly modulated by an external gate voltage. Resonance-enhanced coupling to the nearest molecular orbital is revealed by electron tunnelling spectroscopy, demonstrating direct molecular orbital gating in an electronic device. Our findings demonstrate that true molecular transistors can be created, and so enhance the prospects for molecularly engineered electronic devices.
C1 [Song, Hyunwook; Lee, Takhee] Gwangju Inst Sci & Technol, Dept Nanobio Mat & Elect, Kwangju 500712, South Korea.
   [Song, Hyunwook; Jang, Yun Hee; Lee, Takhee] Gwangju Inst Sci & Technol, Dept Mat Sci & Engn, Kwangju 500712, South Korea.
   [Kim, Youngsang; Jeong, Heejun] Hanyang Univ, Dept Appl Phys, Ansan 426791, South Korea.
   [Reed, Mark A.] Yale Univ, Dept Elect Engn, New Haven, CT 06520 USA.
   [Reed, Mark A.] Yale Univ, Dept Appl Phys, New Haven, CT 06520 USA.
C3 Gwangju Institute of Science & Technology (GIST); Gwangju Institute of Science & Technology (GIST); Hanyang University; Yale University; Yale University
RP Lee, T (corresponding author), Gwangju Inst Sci & Technol, Dept Nanobio Mat & Elect, Kwangju 500712, South Korea.
EM mark.reed@yale.edu; tlee@gist.ac.kr
FU Korean National Research Laboratory programme; Korean National Core Research Center; World Class University programme of the Korean Ministry of Education, Science and Technology; Program for Integrated Molecular System at the Gwangju Institute of Science and Technology; SystemIC2010 project of the Korean Ministry of Knowledge Economy; US Army Research Office [W911NF-08-1-0365]; Canadian Institute for Advanced Research
NR 30
TC 718
Z9 806
U1 5
U2 295
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1039
EP 1043
DI 10.1038/nature08639
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000043
PM 20033044
DA 2026-03-09
ER

PT J
AU Kragl, M
   Knapp, D
   Nacu, E
   Khattak, S
   Maden, M
   Epperlein, HH
   Tanaka, EM
AF Kragl, Martin
   Knapp, Dunja
   Nacu, Eugen
   Khattak, Shahryar
   Maden, Malcolm
   Epperlein, Hans Henning
   Tanaka, Elly M.
TI Cells keep a memory of their tissue origin during axolotl limb regeneration
SO NATURE
LA English
DT Article
ID cdna library; blastema; dedifferentiation; differentiation; thymidine; nerves; stump; skin
AB During limb regeneration adult tissue is converted into a zone of undifferentiated progenitors called the blastema that reforms the diverse tissues of the limb. Previous experiments have led to wide acceptance that limb tissues dedifferentiate to form pluripotent cells. Here we have reexamined this question using an integrated GFP transgene to track the major limb tissues during limb regeneration in the salamander Ambystoma mexicanum (the axolotl). Surprisingly, we find that each tissue produces progenitor cells with restricted potential. Therefore, the blastema is a heterogeneous collection of restricted progenitor cells. On the basis of these findings, we further demonstrate that positional identity is a cell-type-specific property of blastema cells, in which cartilage-derived blastema cells harbour positional identity but Schwann-derived cells do not. Our results show that the complex phenomenon of limb regeneration can be achieved without complete dedifferentiation to a pluripotent state, a conclusion with important implications for regenerative medicine.
C1 [Kragl, Martin; Knapp, Dunja; Nacu, Eugen; Khattak, Shahryar; Tanaka, Elly M.] Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
   [Epperlein, Hans Henning] Tech Univ Dresden, Fac Med, Inst Anat, D-01307 Dresden, Germany.
   [Kragl, Martin; Knapp, Dunja; Nacu, Eugen; Khattak, Shahryar; Tanaka, Elly M.] Tech Univ Dresden, Ctr Regenerat Therapies, D-01307 Dresden, Germany.
   [Maden, Malcolm] Univ Florida, McKnight Brian Inst, Regenerat Project, Gainesville, FL 32611 USA.
C3 Max Planck Society; Technische Universitat Dresden; Technische Universitat Dresden; State University System of Florida; University of Florida
RP Tanaka, EM (corresponding author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
EM elly.tanaka@crt-dresden.de
FU Volkswagen Foundation [I/78 766]; DFG [SFB655, SPP1109, SPP 1356]; BMBF Biofutures program; Max Planck Institute; Center of Regenerative Therapies; Alexander von Humboldt Foundation
NR 41
TC 672
Z9 827
U1 7
U2 278
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 60
EP 65
DI 10.1038/nature08152
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200029
PM 19571878
DA 2026-03-09
ER

PT J
AU Xiu, XA
   Puskar, NL
   Shanata, JAP
   Lester, HA
   Dougherty, DA
AF Xiu, Xinan
   Puskar, Nyssa L.
   Shanata, Jai A. P.
   Lester, Henry A.
   Dougherty, Dennis A.
TI Nicotine binding to brain receptors requires a strong cation-π interaction
SO NATURE
LA English
DT Article
ID acetylcholine-receptors; ion channels; m2 domain; agonists; achbp; site; activation; tolerance; complexes; chemistry
AB Nicotine addiction begins with high-affinity binding of nicotine to acetylcholine (ACh) receptors in the brain. The end result is over 4,000,000 smoking-related deaths annually worldwide and the largest source of preventable mortality in developed countries. Stress reduction, pleasure, improved cognition and other central nervous system effects are strongly associated with smoking. However, if nicotine activated ACh receptors found in muscle as potently as it does brain ACh receptors, smoking would cause intolerable and perhaps fatal muscle contractions. Despite extensive pharmacological, functional and structural studies of ACh receptors, the basis for the differential action of nicotine on brain compared with muscle ACh receptors has not been determined. Here we show that at the alpha 4 beta 2 brain receptors thought to underlie nicotine addiction, the high affinity for nicotine is the result of a strong cation-pi interaction to a specific aromatic amino acid of the receptor, TrpB. In contrast, the low affinity for nicotine at the muscle-type ACh receptor is largely due to the fact that this key interaction is absent, even though the immediate binding site residues, including the key amino acid TrpB, are identical in the brain and muscle receptors. At the same time a hydrogen bond from nicotine to the backbone carbonyl of TrpB is enhanced in the neuronal receptor relative to the muscle type. A point mutation near TrpB that differentiates alpha 4 beta 2 and muscle-type receptors seems to influence the shape of the binding site, allowing nicotine to interact more strongly with TrpB in the neuronal receptor. ACh receptors are established therapeutic targets for Alzheimer's disease, schizophrenia, Parkinson's disease, smoking cessation, pain, attention-deficit hyperactivity disorder, epilepsy, autism and depression(1). Along with solving a chemical mystery in nicotine addiction, our results provide guidance for efforts to develop drugs that target specific types of nicotinic receptors.
C1 [Xiu, Xinan; Puskar, Nyssa L.; Shanata, Jai A. P.; Dougherty, Dennis A.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Lester, Henry A.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
C3 California Institute of Technology; California Institute of Technology
RP Dougherty, DA (corresponding author), CALTECH, Div Chem & Chem Engn, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM dadougherty@caltech.edu
FU NIH [NS 34407, NS 11756]; California Tobacco-Related Disease Research Program of the University of California [16RT-0160]; NRSA
NR 31
TC 311
Z9 390
U1 2
U2 140
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 534
EP U10
DI 10.1038/nature07768
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400050
PM 19252481
DA 2026-03-09
ER

PT J
AU Nakanishi, K
   Bonnefond, L
   Kimura, S
   Suzuki, T
   Ishitani, R
   Nureki, O
AF Nakanishi, Kotaro
   Bonnefond, Luc
   Kimura, Satoshi
   Suzuki, Tsutomu
   Ishitani, Ryuichiro
   Nureki, Osamu
TI Structural basis for translational fidelity ensured by transfer RNA lysidine synthetase
SO NATURE
LA English
DT Article
ID isoleucine transfer-rna; amino-acid specificity; crystal-structure; anticodon; recognition; codon; refinement; resolution; complex; gene
AB Maturation of precursor transfer RNA (pre-tRNA) includes excision of the 5' leader and 3' trailer sequences, removal of introns and addition of the CCA terminus(1-3). Nucleotide modifications are incorporated at different stages of tRNA processing, after the RNA molecule adopts the proper conformation. In bacteria, tRNA(Ile2) lysidine synthetase (TilS) modifies cytidine into lysidine (L; 2-lysyl-cytidine) at the first anticodon of tRNA(Ile2) (refs 4-9). This modification switches tRNA(Ile2) from a methionine-specific to an isoleucine-specific tRNA(9). However, the aminoacylation of tRNA(Ile2) by methionyl-tRNA synthetase (MetRS), before the modification by TilS, might lead to the misincorporation of methionine in response to isoleucine codons. The mechanism used by bacteria to avoid this pitfall is unknown. Here we show that the TilS enzyme specifically recognizes and modifies tRNA(Ile2) in its precursor form, thereby avoiding translation errors. We identified the lysidine modification in pre-tRNA(Ile2) isolated from RNase-Edeficient Escherichia coli and did not detect mature tRNA(Ile2) lacking this modification. Our kinetic analyses revealed that TilS can modify both types of RNA molecule with comparable efficiencies. X-ray crystallography and mutational analyses revealed that TilS specifically recognizes the entire L-shape structure in pre-tRNA(Ile2) through extensive interactions coupled with sequential domain movements. Our results demonstrate how TilS prevents the recognition of tRNA(Ile2) by MetRS and achieves high specificity for its substrate. These two key points form the basis for maintaining the fidelity of isoleucine codon translation in bacteria. Our findings also provide a rationale for the necessity of incorporating specific modifications at the precursor level during tRNA biogenesis.
C1 [Nakanishi, Kotaro; Nureki, Osamu] Tokyo Inst Technol, Dept Biol Informat, Grad Sch Biosci & Biotechnol, Kanagawa 2258501, Japan.
   [Bonnefond, Luc; Ishitani, Ryuichiro; Nureki, Osamu] Univ Tokyo, Inst Med Sci, Dept Basic Med Sci, Minato Ku, Tokyo 1088639, Japan.
   [Kimura, Satoshi; Suzuki, Tsutomu] Univ Tokyo, Grad Sch Engn, Dept Chem & Biotechnol, Bunkyo Ku, Tokyo 1138656, Japan.
C3 Institute of Science Tokyo; Tokyo Institute of Technology; University of Tokyo; University of Tokyo
RP Nureki, O (corresponding author), Tokyo Inst Technol, Dept Biol Informat, Grad Sch Biosci & Biotechnol, Kanagawa 2258501, Japan.
EM nureki@ims.u-tokyo.ac.jp
FU SORST program grant from Japan Science and Technology; Ministry of Education, Culture, Sports, Science and Technology (MEXT); Mitsubishi Foundation; Kurata Memorial Hitachi Science and Technology Foundation; Japan Society for the Promotion of Science
NR 39
TC 60
Z9 69
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1144
EP U249
DI 10.1038/nature08474
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600049
PM 19847269
DA 2026-03-09
ER

PT J
AU Woltjen, K
   Michael, IP
   Mohseni, P
   Desai, R
   Mileikovsky, M
   Hämäläinen, R
   Cowling, R
   Wang, W
   Liu, PT
   Gertsenstein, M
   Kaji, K
   Sung, HK
   Nagy, A
AF Woltjen, Knut
   Michael, Iacovos P.
   Mohseni, Paria
   Desai, Ridham
   Mileikovsky, Maria
   Haemaelaeinen, Riikka
   Cowling, Rebecca
   Wang, Wei
   Liu, Pentao
   Gertsenstein, Marina
   Kaji, Keisuke
   Sung, Hoon-Ki
   Nagy, Andras
TI piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID mammalian-cells; mouse; expression; generation; induction; mice; insertions; vectors; gene
AB Transgenic expression of just four defined transcription factors (c-Myc, Klf4, Oct4 and Sox2) is sufficient to reprogram somatic cells to a pluripotent state(1-4). The resulting induced pluripotent stem (iPS) cells resemble embryonic stem cells in their properties and potential to differentiate into a spectrum of adult cell types. Current reprogramming strategies involve retroviral(1), lentiviral(5), adenoviral(6) and plasmid(7) transfection to deliver reprogramming factor transgenes. Although the latter two methods are transient and minimize the potential for insertion mutagenesis, they are currently limited by diminished reprogramming efficiencies. piggyBac (PB) transposition is host-factor independent, and has recently been demonstrated to be functional in various human and mouse cell lines(8-11). The PB transposon/transposase system requires only the inverted terminal repeats flanking a transgene and transient expression of the transposase enzyme to catalyse insertion or excision events(12). Here we demonstrate successful and efficient reprogramming of murine and human embryonic fibroblasts using doxycycline-inducible transcription factors delivered by PB transposition(13). Stable iPS cells thus generated express characteristic pluripotency markers and succeed in a series of rigorous differentiation assays. By taking advantage of the natural propensity of the PB system for seamless excision(12), we show that the individual PB insertions can be removed from established iPS cell lines, providing an invaluable tool for discovery. In addition, we have demonstrated the traceless removal of reprogramming factors joined with viral 2A sequences(14) delivered by a single transposon from murine iPS lines. We anticipate that the unique properties of this virus-independent simplification of iPS cell production will accelerate this field further towards full exploration of the reprogramming process and future cell-based therapies.
C1 [Woltjen, Knut; Michael, Iacovos P.; Mohseni, Paria; Desai, Ridham; Mileikovsky, Maria; Haemaelaeinen, Riikka; Cowling, Rebecca; Gertsenstein, Marina; Sung, Hoon-Ki; Nagy, Andras] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   [Michael, Iacovos P.; Mohseni, Paria; Desai, Ridham; Nagy, Andras] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Wang, Wei; Liu, Pentao] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
   [Kaji, Keisuke] Univ Edinburgh, Inst Stem Cell Res, Ctr Regenerat Med, MRC, Edinburgh EH9 3JQ, Midlothian, Scotland.
C3 University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; Wellcome Trust Sanger Institute; University of Edinburgh
RP Nagy, A (corresponding author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.
EM nagy@lunenfeld.ca
FU Wellcome Trust; Canadian Stem Cell Network; JDRF; Medical Research Council [G0700672, G0700711B] Funding Source: researchfish; MRC [G0700672] Funding Source: UKRI
NR 29
TC 1372
Z9 1859
U1 2
U2 350
PU NATURE PUBLISHING 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 9
PY 2009
VL 458
IS 7239
BP 766
EP U106
DI 10.1038/nature07863
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600042
PM 19252478
DA 2026-03-09
ER

PT J
AU Oppo, DW
   Rosenthal, Y
   Linsley, BK
AF Oppo, Delia W.
   Rosenthal, Yair
   Linsley, Braddock K.
TI 2,000-year-long temperature and hydrology reconstructions from the Indo-Pacific warm pool
SO NATURE
LA English
DT Article
ID intertropical convergence zone; surface-temperature; climate; monsoon; ocean
AB Northern Hemisphere surface temperature reconstructions suggest that the late twentieth century was warmer than any other time during the past 500 years and possibly any time during the past 1,300 years (refs 1, 2). These temperature reconstructions are based largely on terrestrial records from extra-tropical or high-elevation sites; however, global average surface temperature changes closely follow those of the global tropics(3), which are 75% ocean. In particular, the tropical Indo-Pacific warm pool (IPWP) represents a major heat reservoir that both influences global atmospheric circulation(4) and responds to remote northern high-latitude forcings(5,6). Here we present a decadally resolved continuous sea surface temperature (SST) reconstruction from the IPWP that spans the past two millennia and overlaps the instrumental record, enabling both a direct comparison of proxy data to the instrumental record and an evaluation of past changes in the context of twentieth century trends. Our record from the Makassar Strait, Indonesia, exhibits trends that are similar to a recent Northern Hemisphere temperature reconstruction(2). Reconstructed SST was, however, within error of modern values from about AD 1000 to AD 1250, towards the end of the Medieval Warm Period. SSTs during the Little Ice Age ( approximately AD 1550-1850) were variable, and similar to 0.5 to 1 degrees C colder than modern values during the coldest intervals. A companion reconstruction of delta O-18 of sea water-a sea surface salinity and hydrology indicator-indicates a tight coupling with the East Asian monsoon system and remote control of IPWP hydrology on centennial-millennial timescales, rather than a dominant influence from local SST variation.
C1 [Oppo, Delia W.] Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
   [Rosenthal, Yair] Rutgers State Univ, Inst Marine & Coastal Sci, New Brunswick, NJ 08901 USA.
   [Rosenthal, Yair] Rutgers State Univ, Dept Earth & Planetary Sci, New Brunswick, NJ 08901 USA.
   [Linsley, Braddock K.] SUNY Albany, Dept Atmospher & Environm Sci, Albany, NY 12222 USA.
C3 Woods Hole Oceanographic Institution; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; State University of New York (SUNY) System; University at Albany, SUNY
RP Oppo, DW (corresponding author), Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
EM doppo@whoi.edu
FU US NSF; Ocean Climate Change Institute of WHOI; Division Of Ocean Sciences; Directorate For Geosciences [0902679] Funding Source: National Science Foundation
NR 29
TC 273
Z9 337
U1 1
U2 138
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1113
EP 1116
DI 10.1038/nature08233
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000035
PM 19713927
DA 2026-03-09
ER

PT J
AU Bijl, PK
   Schouten, S
   Sluijs, A
   Reichart, GJ
   Zachos, JC
   Brinkhuis, H
AF Bijl, Peter K.
   Schouten, Stefan
   Sluijs, Appy
   Reichart, Gert-Jan
   Zachos, James C.
   Brinkhuis, Henk
TI Early Palaeogene temperature evolution of the southwest Pacific Ocean
SO NATURE
LA English
DT Article
ID sea-surface temperatures; eocene; climate; middle
AB Relative to the present day, meridional temperature gradients in the Early Eocene age (similar to 56-53 Myr ago) were unusually low, with slightly warmer equatorial regions(1) but with much warmer subtropical Arctic(2) and mid-latitude(3) climates. By the end of the Eocene epoch (similar to 34 Myr ago), the first major Antarctic ice sheets had appeared(4,5), suggesting that major cooling had taken place. Yet the global transition into this icehouse climate remains poorly constrained, as only a few temperature records are available portraying the Cenozoic climatic evolution of the high southern latitudes. Here we present a uniquely continuous and chronostratigraphically well-calibrated TEX86 record of sea surface temperature (SST) from an ocean sediment core in the East Tasman Plateau (palaeolatitude similar to 65 degrees S). We show that southwest Pacific SSTs rose above presentday tropical values (to similar to 34 degrees C) during the Early Eocene age (similar to 53 Myr ago) and had gradually decreased to about 21 degrees C by the early Late Eocene age (similar to 36 Myr ago). Our results imply that there was almost no latitudinal SST gradient between subequatorial and subpolar regions during the Early Eocene age (55-50 Myr ago). Thereafter, the latitudinal gradient markedly increased. In theory, if Eocene cooling was largely driven by a decrease in atmospheric greenhouse gas concentration(6), additional processes are required to explain the relative stability of tropical SSTs given that there was more significant cooling at higher latitudes.
C1 [Bijl, Peter K.; Sluijs, Appy; Brinkhuis, Henk] Univ Utrecht, Palaeobot & Palynol Lab, Fac Sci, Inst Environm Biol, NL-3584 CD Utrecht, Netherlands.
   [Reichart, Gert-Jan] Univ Utrecht, Fac Geosci, Dept Geochem, NL-3584 CD Utrecht, Netherlands.
   [Schouten, Stefan] NIOZ Royal Netherlands Inst Sea Res, Dept Marine Organ Biogeochem, NL-1790 AB Den Burg, Netherlands.
   [Zachos, James C.] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Zachos, James C.] Univ Calif Santa Cruz, Inst Marine Sci, Santa Cruz, CA 95064 USA.
C3 Utrecht University; Utrecht University; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz
RP Bijl, PK (corresponding author), Univ Utrecht, Palaeobot & Palynol Lab, Fac Sci, Inst Environm Biol, Budapestlaan 4, NL-3584 CD Utrecht, Netherlands.
EM p.k.bijl@uu.nl
FU Utrecht University; Netherlands Organisation for Scientific Research; LPP Foundation; US National Science Foundation
NR 30
TC 292
Z9 328
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 OCT 8
PY 2009
VL 461
IS 7265
BP 776
EP 779
DI 10.1038/nature08399
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500032
PM 19812670
DA 2026-03-09
ER

PT J
AU Shen, GJ
   Gao, X
   Gao, B
   Granger, DE
AF Shen, Guanjun
   Gao, Xing
   Gao, Bin
   Granger, Darryl E.
TI Age of Zhoukoudian Homo erectus determined with 26Al/10Be burial dating
SO NATURE
LA English
DT Article
ID middle pleistocene; china; site; calibration; locality-1; chronology; loess
AB The age of Zhoukoudian Homo erectus, commonly known as 'Peking Man', has long been pursued, but has remained problematic owing to the lack of suitable dating methods(1-7). Here we report cosmogenic Al-26/Be-10 burial dating of quartz sediments and artefacts from the lower strata of Locality 1 in the southwestern suburb of Beijing, China, where early representatives of Zhoukoudian Homo erectus were discovered. This study marks the first radioisotopic dating of any early hominin site in China beyond the range of mass spectrometric U-series dating. The weighted mean of six meaningful age measurements, 0.77 +/- 0.08 million years (Myr, mean +/- s.e.m.), provides the best age estimate for lower cultural layers 7-10. Together with previously reported U-series dating of speleothem calcite(3) and palaeomagnetic stratigraphy(4), as well as sedimentological considerations(8,9), these layers may be further correlated to S6-S7 in Chinese loess stratigraphy or marine isotope stages (MIS) 17-19, in the range of similar to 0.68 to 0.78 Myr ago. These ages are substantially older than previously supposed and may imply early hominin's presence at the site in northern China through a relatively mild glacial period corresponding to MIS 18.
C1 [Shen, Guanjun; Gao, Bin] Nanjing Normal Univ, Coll Geog Sci, Nanjing 210046, Jiangsu, Peoples R China.
   [Gao, Xing] Acad Sinica, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
   [Granger, Darryl E.] Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
C3 Nanjing Normal University; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Purdue University System; Purdue University
RP Shen, GJ (corresponding author), Nanjing Normal Univ, Coll Geog Sci, Nanjing 210046, Jiangsu, Peoples R China.
EM gjshen@njnu.edu.cn; dgranger@purdue.edu
FU National Natural Science Foundation of China; Wenner-Gren Foundation; NSF; Division Of Earth Sciences; Directorate For Geosciences [0851981] Funding Source: National Science Foundation
NR 30
TC 175
Z9 236
U1 2
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 198
EP 200
DI 10.1038/nature07741
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700042
PM 19279636
DA 2026-03-09
ER

PT J
AU Marchetti, A
   Parker, MS
   Moccia, LP
   Lin, EO
   Arrieta, AL
   Ribalet, F
   Murphy, MEP
   Maldonado, MT
   Armbrust, EV
AF Marchetti, Adrian
   Parker, Micaela S.
   Moccia, Lauren P.
   Lin, Ellen O.
   Arrieta, Angele L.
   Ribalet, Francois
   Murphy, Michael E. P.
   Maldonado, Maria T.
   Armbrust, E. Virginia
TI Ferritin is used for iron storage in bloom-forming marine pennate diatoms
SO NATURE
LA English
DT Article
ID southern-ocean; phytoplankton; growth; requirements; hydrolysis; limitation; chemistry; evolution; oxidation; pacific
AB Primary productivity in 30 - 40% of the world's oceans is limited by availability of the micronutrient iron(1,2). Regions with chronically low iron concentrations are sporadically pulsed with new iron inputs by way of dust(3) or lateral advection from continental margins(4). Addition of iron to surface waters in these areas induces massive phytoplankton blooms dominated primarily by pennate diatoms(5,6). Here we provide evidence that the bloom- forming pennate diatoms Pseudo- nitzschia and Fragilariopsis use the iron- concentrating protein, ferritin, to safely store iron. Ferritin has not been reported previously in any member of the Stramenopiles, a diverse eukaryotic lineage that includes unicellular algae, macroalgae and plant parasites. Phylogenetic analyses suggest that ferritin may have arisen in this small subset of diatoms through a lateral gene transfer. The crystal structure and functional assays of recombinant ferritin derived from Pseudo- nitzschia multiseries reveal a maxi- ferritin that exhibits ferroxidase activity and binds iron. The protein is predicted to be targeted to the chloroplast to control the distribution and storage of iron for proper functioning of the photosynthetic machinery. Abundance of Pseudo- nitzschia ferritin transcripts is regulated by iron nutritional status, and is closely tied to the loss and recovery of photosynthetic competence. Enhanced iron storage with ferritin allows the oceanic diatom Pseudo- nitzschia granii to undergo several more cell divisions in the absence of iron than the comparably sized, oceanic centric diatom Thalassiosira oceanica. Ferritin in pennate diatoms probably contributes to their success in chronically low- iron regions that receive intermittent iron inputs, and provides an explanation for the importance of these organisms in regulating oceanic CO2 over geological timescales(7,8).
C1 [Marchetti, Adrian; Parker, Micaela S.; Lin, Ellen O.; Ribalet, Francois; Armbrust, E. Virginia] Univ Washington, Sch Oceanog, Seattle, WA 98195 USA.
   [Moccia, Lauren P.; Maldonado, Maria T.] Univ British Columbia, Dept Earth & Ocean Sci, Vancouver, BC V6T 1Z4, Canada.
   [Arrieta, Angele L.; Murphy, Michael E. P.] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada.
C3 University of Washington; University of Washington Seattle; University of British Columbia; University of British Columbia
RP Armbrust, EV (corresponding author), Univ Washington, Sch Oceanog, Box 357940, Seattle, WA 98195 USA.
EM armbrust@ocean.washington.edu
FU Gordon and Betty Moore Foundation Marine Microbiology Investigator Award; National Science Foundation; National Institute of Environmental Health Sciences; National Sciences and Engineering Research Council of Canada; Canadian Institutes of Health Research; Department of Energy, Office of Biological and Environmental Research; National Institutes of Health; National Center for Research Resources; Biomedical Technology Program; National Institute of General Medical Sciences; Division Of Ocean Sciences; Directorate For Geosciences [0910624] Funding Source: National Science Foundation
NR 26
TC 264
Z9 313
U1 4
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 JAN 22
PY 2009
VL 457
IS 7228
BP 467
EP 470
DI 10.1038/nature07539
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200044
PM 19037243
DA 2026-03-09
ER

PT J
AU Kiendler-Scharr, A
   Wildt, J
   Dal Maso, M
   Hohaus, T
   Kleist, E
   Mentel, TF
   Tillmann, R
   Uerlings, R
   Schurr, U
   Wahner, A
AF Kiendler-Scharr, Astrid
   Wildt, Juergen
   Dal Maso, Miikka
   Hohaus, Thorsten
   Kleist, Einhard
   Mentel, Thomas F.
   Tillmann, Ralf
   Uerlings, Ricarda
   Schurr, Uli
   Wahner, Andreas
TI New particle formation in forests inhibited by isoprene emissions
SO NATURE
LA English
DT Article
ID organic aerosol; natural aerosol; sulfuric-acid; oxidation; impact; rates; model
AB It has been suggested that volatile organic compounds (VOCs) are involved in organic aerosol formation, which in turn affects radiative forcing and climate(1). The most abundant VOCs emitted by terrestrial vegetation are isoprene and its derivatives, such as monoterpenes and sesquiterpenes(2). New particle formation in boreal regions is related to monoterpene emissions(3) and causes an estimated negative radiative forcing(4) of about -0.2 to -0.9 W m(-2). The annual variation in aerosol growth rates during particle nucleation events correlates with the seasonality of monoterpene emissions of the local vegetation, with a maximum during summer(5). The frequency of nucleation events peaks, however, in spring and autumn(5). Here we present evidence from simulation experiments conducted in a plant chamber that isoprene can significantly inhibit new particle formation. The process leading to the observed decrease in particle number concentration is linked to the high reactivity of isoprene with the hydroxyl radical (OH). The suppression is stronger with higher concentrations of isoprene, but with little dependence on the specific VOC mixture emitted by trees. A parameterization of the observed suppression factor as a function of isoprene concentration suggests that the number of new particles produced depends on the OH concentration and VOCs involved in the production of new particles undergo three to four steps of oxidation by OH. Our measurements simulate conditions that are typical for forested regions and may explain the observed seasonality in the frequency of aerosol nucleation events, with a lower number of nucleation events during summer compared to autumn and spring(5). Biogenic emissions of isoprene are controlled by temperature and light(2), and if the relative isoprene abundance of biogenic VOC emissions increases in response to climate change or land use change, the new particle formation potential may decrease, thus damping the aerosol negative radiative forcing effect.
C1 [Kiendler-Scharr, Astrid; Dal Maso, Miikka; Hohaus, Thorsten; Mentel, Thomas F.; Tillmann, Ralf; Wahner, Andreas] Forschungszentrum Julich, Inst ICG 2, D-52425 Julich, Germany.
   [Wildt, Juergen; Kleist, Einhard; Uerlings, Ricarda; Schurr, Uli] Forschungszentrum Julich, Inst ICG 3, D-52425 Julich, Germany.
   [Dal Maso, Miikka] Univ Helsinki, Dept Phys, Helsinki 00014, Finland.
C3 Helmholtz Association; Julich Research Centre; Helmholtz Association; Julich Research Centre; University of Helsinki
RP Kiendler-Scharr, A (corresponding author), Forschungszentrum Julich, Inst ICG 2, Postfach 1913, D-52425 Julich, Germany.
EM a.kiendler-scharr@fz-juelich.de
FU European Commission [036833-2]
NR 29
TC 227
Z9 264
U1 7
U2 241
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 381
EP 384
DI 10.1038/nature08292
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100036
PM 19759617
DA 2026-03-09
ER

PT J
AU Smith, GJD
   Vijaykrishna, D
   Bahl, J
   Lycett, SJ
   Worobey, M
   Pybus, OG
   Ma, SK
   Cheung, CL
   Raghwani, J
   Bhatt, S
   Peiris, JSM
   Guan, Y
   Rambaut, A
AF Smith, Gavin J. D.
   Vijaykrishna, Dhanasekaran
   Bahl, Justin
   Lycett, Samantha J.
   Worobey, Michael
   Pybus, Oliver G.
   Ma, Siu Kit
   Cheung, Chung Lam
   Raghwani, Jayna
   Bhatt, Samir
   Peiris, J. S. Malik
   Guan, Yi
   Rambaut, Andrew
TI Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic
SO NATURE
LA English
DT Article
ID multiple sequence alignment; virus; transmission; infection; pigs
AB In March and early April 2009, a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States(1). During the first few weeks of surveillance, the virus spread worldwide to 30 countries (as of May 11) by human-to-human transmission, causing the World Health Organization to raise its pandemic alert to level 5 of 6. This virus has the potential to develop into the first influenza pandemic of the twenty-first century. Here we use evolutionary analysis to estimate the time-scale of the origins and the early development of the S-OIV epidemic. We show that it was derived from several viruses circulating in swine, and that the initial transmission to humans occurred several months before recognition of the outbreak. A phylogenetic estimate of the gaps in genetic surveillance indicates a long period of unsampled ancestry before the S-OIV outbreak, suggesting that the reassortment of swine lineages may have occurred years before emergence in humans, and that the multiple genetic ancestry of S-OIV is not indicative of an artificial origin. Furthermore, the unsampled history of the epidemic means that the nature and location of the genetically closest swine viruses reveal little about the immediate origin of the epidemic, despite the fact that we included a panel of closely related and previously unpublished swine influenza isolates. Our results highlight the need for systematic surveillance of influenza in swine, and provide evidence that the mixing of new genetic elements in swine can result in the emergence of viruses with pandemic potential in humans(2).
C1 [Lycett, Samantha J.; Raghwani, Jayna; Rambaut, Andrew] Univ Edinburgh, Ashworth Labs, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Smith, Gavin J. D.; Vijaykrishna, Dhanasekaran; Bahl, Justin; Ma, Siu Kit; Cheung, Chung Lam; Peiris, J. S. Malik; Guan, Yi] Univ Hong Kong, State Key Lab Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China.
   [Smith, Gavin J. D.; Vijaykrishna, Dhanasekaran; Bahl, Justin; Ma, Siu Kit; Cheung, Chung Lam; Peiris, J. S. Malik; Guan, Yi] Univ Hong Kong, Dept Microbiol, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
   [Worobey, Michael] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85705 USA.
   [Pybus, Oliver G.; Bhatt, Samir] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
C3 University of Edinburgh; University of Hong Kong; University of Hong Kong; University of Arizona; University of Oxford
RP Rambaut, A (corresponding author), Univ Edinburgh, Ashworth Labs, Inst Evolutionary Biol, Kings Bldg, Edinburgh EH9 3JT, Midlothian, Scotland.
EM yguan@hku.hk; a.rambaut@ed.ac.uk
FU The Royal Society of London; National Institute of Allergy and Infectious Diseases ( NIAID); Biotechnology and Biological Sciences Research Council ( BBSRC); David and Lucile Packard Foundation; Interdisciplinary Centre for Human and Avian Influenza Research ( ICHAIR); National Institutes of Health [HHSN266200700005C]; Area of Excellence Scheme of the University Grants Committee of the Hong Kong SAR Government [AoE/M-12/06]; BBSRC [BB/E009670/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/E009670/1] Funding Source: researchfish
NR 29
TC 1738
Z9 2081
U1 7
U2 419
PU NATURE PUBLISHING 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 25
PY 2009
VL 459
IS 7250
BP 1122
EP U107
DI 10.1038/nature08182
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700042
PM 19516283
DA 2026-03-09
ER

PT J
AU Glessner, JT
   Wang, K
   Cai, GQ
   Korvatska, O
   Kim, CE
   Wood, S
   Zhang, HT
   Estes, A
   Brune, CW
   Bradfield, JP
   Imielinski, M
   Frackelton, EC
   Reichert, J
   Crawford, EL
   Munson, J
   Sleiman, PMA
   Chiavacci, R
   Annaiah, K
   Thomas, K
   Hou, CP
   Glaberson, W
   Flory, J
   Otieno, F
   Garris, M
   Soorya, L
   Klei, L
   Piven, J
   Meyer, KJ
   Anagnostou, E
   Sakurai, T
   Game, RM
   Rudd, DS
   Zurawiecki, D
   McDougle, CJ
   Davis, LK
   Miller, J
   Posey, DJ
   Michaels, S
   Kolevzon, A
   Silverman, JM
   Bernier, R
   Levy, SE
   Schultz, RT
   Dawson, G
   Owley, T
   McMahon, WM
   Wassink, TH
   Sweeney, JA
   Nurnberger, JI
   Coon, H
   Sutcliffe, JS
   Minshew, NJ
   Grant, SFA
   Bucan, M
   Cook, EH
   Buxbaum, JD
   Devlin, B
   Schellenberg, GD
   Hakonarson, H
AF Glessner, Joseph T.
   Wang, Kai
   Cai, Guiqing
   Korvatska, Olena
   Kim, Cecilia E.
   Wood, Shawn
   Zhang, Haitao
   Estes, Annette
   Brune, Camille W.
   Bradfield, Jonathan P.
   Imielinski, Marcin
   Frackelton, Edward C.
   Reichert, Jennifer
   Crawford, Emily L.
   Munson, Jeffrey
   Sleiman, Patrick M. A.
   Chiavacci, Rosetta
   Annaiah, Kiran
   Thomas, Kelly
   Hou, Cuiping
   Glaberson, Wendy
   Flory, James
   Otieno, Frederick
   Garris, Maria
   Soorya, Latha
   Klei, Lambertus
   Piven, Joseph
   Meyer, Kacie J.
   Anagnostou, Evdokia
   Sakurai, Takeshi
   Game, Rachel M.
   Rudd, Danielle S.
   Zurawiecki, Danielle
   McDougle, Christopher J.
   Davis, Lea K.
   Miller, Judith
   Posey, David J.
   Michaels, Shana
   Kolevzon, Alexander
   Silverman, Jeremy M.
   Bernier, Raphael
   Levy, Susan E.
   Schultz, Robert T.
   Dawson, Geraldine
   Owley, Thomas
   McMahon, William M.
   Wassink, Thomas H.
   Sweeney, John A.
   Nurnberger, John I., Jr.
   Coon, Hilary
   Sutcliffe, James S.
   Minshew, Nancy J.
   Grant, Struan F. A.
   Bucan, Maja
   Cook, Edwin H., Jr.
   Buxbaum, Joseph D.
   Devlin, Bernie
   Schellenberg, Gerard D.
   Hakonarson, Hakon
TI Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
SO NATURE
LA English
DT Article
ID spectrum disorder; susceptibility gene; mutations; association; neuroligins; migration; linkage
AB Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins(1-4). Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs(5-9). Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with similar to 550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12), several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls (P = 9.5 x 10(-3)). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3.3 x 10(-3)). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 x 10(-6)). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.
C1 [Glessner, Joseph T.; Wang, Kai; Kim, Cecilia E.; Zhang, Haitao; Bradfield, Jonathan P.; Imielinski, Marcin; Frackelton, Edward C.; Sleiman, Patrick M. A.; Chiavacci, Rosetta; Annaiah, Kiran; Thomas, Kelly; Hou, Cuiping; Glaberson, Wendy; Flory, James; Otieno, Frederick; Garris, Maria; Grant, Struan F. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Cai, Guiqing; Reichert, Jennifer; Soorya, Latha; Anagnostou, Evdokia; Sakurai, Takeshi; Zurawiecki, Danielle; Kolevzon, Alexander; Silverman, Jeremy M.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA.
   [Korvatska, Olena; Estes, Annette; Munson, Jeffrey; Bernier, Raphael; Dawson, Geraldine] Univ Washington, Seattle, WA 98105 USA.
   [Wood, Shawn; Klei, Lambertus; Michaels, Shana; Devlin, Bernie] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
   [Wood, Shawn; Klei, Lambertus; Michaels, Shana; Devlin, Bernie] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15260 USA.
   [Brune, Camille W.; Owley, Thomas; Sweeney, John A.; Cook, Edwin H., Jr.] Univ Illinois, Inst Juvenile Res, Chicago, IL 60608 USA.
   [Brune, Camille W.; Owley, Thomas; Sweeney, John A.; Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Chicago, IL 60608 USA.
   [Crawford, Emily L.; Game, Rachel M.; Sutcliffe, James S.] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN 37235 USA.
   [Crawford, Emily L.; Game, Rachel M.; Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37235 USA.
   [Piven, Joseph] Univ N Carolina, Neurodev Disorders Res Ctr, Greensboro, NC 27412 USA.
   [Piven, Joseph] Univ N Carolina, Dept Psychiat, Greensboro, NC 27412 USA.
   [Meyer, Kacie J.; Rudd, Danielle S.; Davis, Lea K.; Wassink, Thomas H.] Univ Iowa, Iowa City, IA 52242 USA.
   [Miller, Judith; McMahon, William M.; Coon, Hilary] Univ Utah, Salt Lake City, UT 84112 USA.
   [McDougle, Christopher J.; Posey, David J.; Nurnberger, John I., Jr.] Indiana Univ, Indianapolis, IN 46202 USA.
   [Levy, Susan E.; Schultz, Robert T.; Grant, Struan F. A.; Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA.
   [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA.
   [Bucan, Maja] Univ Penn, Sch Med, Dept Genet Biol & Biostat, Philadelphia, PA 19104 USA.
   [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
   [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Schellenberg, Gerard D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Icahn School of Medicine at Mount Sinai; University of Washington; University of Washington Seattle; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Vanderbilt University; Vanderbilt University; University of North Carolina; University of North Carolina Greensboro; University of North Carolina; University of North Carolina Greensboro; University of Iowa; Utah System of Higher Education; University of Utah; Indiana University System; Indiana University Indianapolis; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Pennsylvania; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University of Pennsylvania
RP Hakonarson, H (corresponding author), Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
EM gerardsc@mail.med.upenn.edu; hakonarson@chop.edu
FU Children's Hospital of Philadelphia, Autism Speaks; NICHD [HD35476]; National Institute of Mental Health [1U24MH081810]; Margaret Q. Landenberger Foundation [UL1-RR024134-03]; Cotswold Foundation; Beatrice and Stanley A. Seaver Foundation; Department of Veterans Affairs; National Institute of Health [HD055782-01]; Utah Autism Foundation [MH0666730, MH061009, NS049261, HD055751, U10MH66766-02S1, MH69359, M01-RR00064]; Institutional Development Award to the Center for Applied Genomics; Children's Hospital of Philadelphia; Medical Research Council (UK); Health Research Board (Ireland);  [MH64547]; National Institute of General Medical Sciences [T32GM008629] Funding Source: NIH RePORTER
NR 29
TC 1075
Z9 1289
U1 0
U2 128
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 28
PY 2009
VL 459
IS 7246
BP 569
EP 573
DI 10.1038/nature07953
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500039
PM 19404257
DA 2026-03-09
ER

PT J
AU Maeda, S
   Nakagawa, S
   Suga, M
   Yamashita, E
   Oshima, A
   Fujiyoshi, Y
   Tsukihara, T
AF Maeda, Shoji
   Nakagawa, So
   Suga, Michihiro
   Yamashita, Eiki
   Oshima, Atsunori
   Fujiyoshi, Yoshinori
   Tsukihara, Tomitake
TI Structure of the connexin 26 gap junction channel at 3.5 Å resolution
SO NATURE
LA English
DT Article
ID amino-acid-residues; extracellular loop; gating polarity; 3-dimensional structure; charge selectivity; diffraction data; pore; model; identification; terminus
AB Gap junctions consist of arrays of intercellular channels between adjacent cells that permit the exchange of ions and small molecules. Here we report the crystal structure of the gap junction channel formed by human connexin 26 (Cx26, also known as GJB2) at 3.5 angstrom resolution, and discuss structural determinants of solute transport through the channel. The density map showed the two membrane-spanning hemichannels and the arrangement of the four transmembrane helices of the six protomers forming each hemichannel. The hemichannels feature a positively charged cytoplasmic entrance, a funnel, a negatively charged transmembrane pathway, and an extracellular cavity. The pore is narrowed at the funnel, which is formed by the six amino-terminal helices lining the wall of the channel, which thus determines the molecular size restriction at the channel entrance. The structure of the Cx26 gap junction channel also has implications for the gating of the channel by the transjunctional voltage.
C1 [Maeda, Shoji; Nakagawa, So; Suga, Michihiro; Yamashita, Eiki; Tsukihara, Tomitake] Osaka Univ, OLABB, Inst Prot Res, Osaka 5650874, Japan.
   [Oshima, Atsunori; Fujiyoshi, Yoshinori] Kyoto Univ, Grad Sch Sci, Dept Biophys, Sakyo Ku, Kyoto 6068502, Japan.
   [Tsukihara, Tomitake] Univ Hyogo, Grad Sch Life Sci, Picobiol Inst, Akoh, Hyogo 6781297, Japan.
C3 University of Osaka; Kyoto University; University of Hyogo
RP Tsukihara, T (corresponding author), Osaka Univ, OLABB, Inst Prot Res, 6-2-3 Furuedai, Osaka 5650874, Japan.
EM tsuki@protein.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan [10687101, 16087206, 18207006, A-041]; Japan Biological Informatics Consortium; Strategic Japan-UK Cooperation Program of the Japan Science and Technology Agency; New Energy and Industrial Technology Development Organization; Grants-in-Aid for Specially Promoted Research; Grants-in-Aid for Scientific Research [16087206, 18207006] Funding Source: KAKEN
NR 58
TC 603
Z9 703
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 APR 2
PY 2009
VL 458
IS 7238
BP 597
EP U61
DI 10.1038/nature07869
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200033
PM 19340074
DA 2026-03-09
ER

PT J
AU Stickley, CE
   St John, K
   Koç, N
   Jordan, RW
   Passchier, S
   Pearce, RB
   Kearns, LE
AF Stickley, Catherine E.
   St John, Kristen
   Koc, Nalan
   Jordan, Richard W.
   Passchier, Sandra
   Pearce, Richard B.
   Kearns, Lance E.
TI Evidence for middle Eocene Arctic sea ice from diatoms and ice-rafted debris
SO NATURE
LA English
DT Article
ID glaciation; transport; ma
AB Oceanic sediments from long cores drilled on the Lomonosov ridge, in the central Arctic(1), contain ice-rafted debris (IRD) back to the middle Eocene epoch, prompting recent suggestions that ice appeared in the Arctic about 46 million years (Myr) ago(2,3). However, because IRD can be transported by icebergs (derived from land-based ice) and also by sea ice(4), IRD records(2,3) are restricted to providing a history of general ice-rafting only. It is critical to differentiate sea ice from glacial (land-based) ice as climate feedback mechanisms vary and global impacts differ between these systems: sea ice directly affects ocean-atmosphere exchanges(5), whereas land-based ice affects sea level and consequently ocean acidity(6). An earlier report(3) assumed that sea ice was prevalent in the middle Eocene Arctic on the basis of IRD, and although somewhat preliminary supportive evidence exists(2), these data are neither comprehensive nor quantified. Here we show the presence of middle Eocene Arctic sea ice from an extraordinary abundance of a group of sea-ice-dependent fossil diatoms (Synedropsis spp.). Analysis of quartz grain textural characteristics further supports sea ice as the dominant transporter of IRD at this time. Together with new information on cosmopolitan diatoms and existing IRD records(2), our data strongly suggest a two-phase establishment of sea ice: initial episodic formation in marginal shelf areas similar to 47.5 Myr ago, followed similar to 0.5 Myr later by the onset of seasonally paced sea-ice formation in offshore areas of the central Arctic. Our data establish a 2-Myr record of sea ice, documenting the transition from a warm, ice-free(3) environment to one dominated by winter sea ice at the start of the middle Eocene climatic cooling phase(7).
C1 [Stickley, Catherine E.; Koc, Nalan] Univ Tromso, Dept Geol, N-9037 Tromso, Norway.
   [St John, Kristen; Kearns, Lance E.] James Madison Univ, Dept Geog & Environm Sci, Harrisonburg, VA 22807 USA.
   [Stickley, Catherine E.; Koc, Nalan] Polar Environm Ctr, Norwegian Polar Inst, N-9296 Tromso, Norway.
   [Jordan, Richard W.] Yamagata Univ, Dept Earth & Environm Sci, Yamagata 9908560, Japan.
   [Passchier, Sandra] Montclair State Univ, Dept Earth & Environm Studies, Montclair, NJ 07043 USA.
   [Pearce, Richard B.] Univ Southampton, Southampton SO14 3ZH, Hants, England.
   [Pearce, Richard B.] Natl Oceanog Ctr, Southampton, Hants, England.
C3 UiT The Arctic University of Tromso; James Madison University; Norwegian Polar Institute; Yamagata University; Montclair State University; University of Southampton; NERC National Oceanography Centre
RP Stickley, CE (corresponding author), Univ Tromso, Dept Geol, N-9037 Tromso, Norway.
EM catherine.stickley@npolar.no
FU VISTA ( Norwegian Academy of Science and Letters and StatoilHydro); Research Council of Norway
NR 31
TC 142
Z9 159
U1 1
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 376
EP U88
DI 10.1038/nature08163
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000034
PM 19606146
DA 2026-03-09
ER

PT J
AU Yoo, AS
   Staahl, BT
   Chen, L
   Crabtree, GR
AF Yoo, Andrew S.
   Staahl, Brett T.
   Chen, Lei
   Crabtree, Gerald R.
TI MicroRNA-mediated switching of chromatin-remodelling complexes in neural development
SO NATURE
LA English
DT Article
ID mammalian swi/snf complexes; stem-cells; transcription; genes; neurons; mir-124; mouse; rest; identification; embryogenesis
AB One of the most distinctive steps in the development of the vertebrate nervous system occurs at mitotic exit when cells lose multi-potency and begin to develop stable connections that will persist for a lifetime(1,2). This transition is accompanied by a switch in ATP-dependent chromatin-remodelling mechanisms that appears to coincide with the final mitotic division of neurons. This switch involves the exchange of the BAF53a (also known as ACTL6a) and BAF45a (PHF10) subunits within Swi/Snf-like neural-progenitor-specific BAF (npBAF) complexes for the homologous BAF53b (ACTL6b) and BAF45b (DPF1) subunits within neuron-specific BAF (nBAF) complexes in post-mitotic neurons. The subunits of the npBAF complex are essential for neural-progenitor proliferation, and mice with reduced dosage for the genes encoding its subunits have defects in neural-tube closure similar to those in human spina bifida(3), one of the most serious congenital birth defects. In contrast, BAF53b and the nBAF complex are essential for an evolutionarily conserved program of post-mitotic neural development and dendritic morphogenesis(4,5). Here we show that this essential transition is mediated by repression of BAF53a by miR-9* and miR-124. We find that BAF53a repression is mediated by sequences in the 3' untranslated region corresponding to the recognition sites for miR-9* and miR-124, which are selectively expressed in post-mitotic neurons. Mutation of these sites led to persistent expression of BAF53a and defective activity-dependent dendritic outgrowth in neurons. In addition, overexpression of miR-9* and miR-124 in neural progenitors caused reduced proliferation. Previous studies have indicated that miR-9* and miR-124 are repressed by the repressor-element-1-silencing transcription factor (REST, also known as NRSF)(6). Indeed, expression of REST in post-mitotic neurons led to derepression of BAF53a, indicating that REST-mediated repression of microRNAs directs the essential switch of chromatin regulatory complexes.
C1 [Yoo, Andrew S.; Staahl, Brett T.; Chen, Lei; Crabtree, Gerald R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Yoo, Andrew S.; Staahl, Brett T.; Chen, Lei; Crabtree, Gerald R.] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA.
   [Yoo, Andrew S.; Chen, Lei; Crabtree, Gerald R.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
C3 Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University
RP Crabtree, GR (corresponding author), Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
EM crabtree@stanford.edu
FU Helen Hay Whitney Foundation; US National Institutes of Health (NIH) [2 T32 HD007249]; Howard Hughes Medical Institute; NIH [HD55391, AI060037, NS046789]
NR 32
TC 514
Z9 637
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 642
EP U112
DI 10.1038/nature08139
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300053
PM 19561591
DA 2026-03-09
ER

PT J
AU Paterson, AH
   Bowers, JE
   Bruggmann, R
   Dubchak, I
   Grimwood, J
   Gundlach, H
   Haberer, G
   Hellsten, U
   Mitros, T
   Poliakov, A
   Schmutz, J
   Spannagl, M
   Tang, HB
   Wang, XY
   Wicker, T
   Bharti, AK
   Chapman, J
   Feltus, FA
   Gowik, U
   Grigoriev, IV
   Lyons, E
   Maher, CA
   Martis, M
   Narechania, A
   Otillar, RP
   Penning, BW
   Salamov, AA
   Wang, Y
   Zhang, LF
   Carpita, NC
   Freeling, M
   Gingle, AR
   Hash, CT
   Keller, B
   Klein, P
   Kresovich, S
   McCann, MC
   Ming, R
   Peterson, DG
   Mehboob-ur-Rahman
   Ware, D
   Westhoff, P
   Mayer, KFX
   Messing, J
   Rokhsar, DS
AF Paterson, Andrew H.
   Bowers, John E.
   Bruggmann, Remy
   Dubchak, Inna
   Grimwood, Jane
   Gundlach, Heidrun
   Haberer, Georg
   Hellsten, Uffe
   Mitros, Therese
   Poliakov, Alexander
   Schmutz, Jeremy
   Spannagl, Manuel
   Tang, Haibao
   Wang, Xiyin
   Wicker, Thomas
   Bharti, Arvind K.
   Chapman, Jarrod
   Feltus, F. Alex
   Gowik, Udo
   Grigoriev, Igor V.
   Lyons, Eric
   Maher, Christopher A.
   Martis, Mihaela
   Narechania, Apurva
   Otillar, Robert P.
   Penning, Bryan W.
   Salamov, Asaf A.
   Wang, Yu
   Zhang, Lifang
   Carpita, Nicholas C.
   Freeling, Michael
   Gingle, Alan R.
   Hash, C. Thomas
   Keller, Beat
   Klein, Patricia
   Kresovich, Stephen
   McCann, Maureen C.
   Ming, Ray
   Peterson, Daniel G.
   Mehboob-ur-Rahman
   Ware, Doreen
   Westhoff, Peter
   Mayer, Klaus F. X.
   Messing, Joachim
   Rokhsar, Daniel S.
TI The Sorghum bicolor genome and the diversification of grasses
SO NATURE
LA English
DT Article
ID rice genome; wide analysis; maize genome; cell-walls; evolution; sequence; identification; recombination; duplication; reveals
AB Sorghum, an African grass related to sugar cane and maize, is grown for food, feed, fibre and fuel. We present an initial analysis of the similar to 730- megabase Sorghumbicolor ( L.) Moench genome, placing, 98% of genes in their chromosomal context using whole- genome shotgun sequence validated by genetic, physical and syntenic information. Genetic recombination is largely confined to about one- third of the sorghum genome with gene order and density similar to those of rice. Retrotransposon accumulation in recombinationally recalcitrant heterochromatin explains the similar to 75% larger genome size of sorghum compared with rice. Although gene and repetitive DNA distributions have been preserved since palaeopolyploidization similar to 70 million years ago, most duplicated gene sets lost one member before the sorghum - rice divergence. Concerted evolution makes one duplicated chromosomal segment appear to be only a few million years old. About 24% of genes are grass- specific and 7% are sorghum- specific. Recent gene and microRNA duplications may contribute to sorghum's drought tolerance.
C1 [Paterson, Andrew H.; Bowers, John E.; Tang, Haibao; Wang, Xiyin; Feltus, F. Alex; Gingle, Alan R.; Peterson, Daniel G.; Mehboob-ur-Rahman] Univ Georgia, Plant Genome Mapping Lab, Athens, GA 30602 USA.
   [Bruggmann, Remy; Bharti, Arvind K.; Messing, Joachim] Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA.
   [Dubchak, Inna; Hellsten, Uffe; Poliakov, Alexander; Chapman, Jarrod; Grigoriev, Igor V.; Otillar, Robert P.; Salamov, Asaf A.; Rokhsar, Daniel S.] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Grimwood, Jane; Schmutz, Jeremy; Rokhsar, Daniel S.] Stanford Univ, Stanford Human Genome Ctr, Palo Alto, CA 94304 USA.
   [Gundlach, Heidrun; Haberer, Georg; Spannagl, Manuel; Martis, Mihaela; Wang, Yu; Mayer, Klaus F. X.] Helmholtz Zentrum Munchen, MIPS IBIS, D-85764 Neuherberg, Germany.
   [Mitros, Therese] Univ Calif Berkeley, Ctr Integrat Genom, Berkeley, CA 94720 USA.
   [Wang, Xiyin] Hebei Polytech Univ, Coll Sci, Tangshan 063000, Hebei, Peoples R China.
   [Wicker, Thomas; Keller, Beat] Univ Zurich, Inst Plant Biol, CH-8008 Zurich, Switzerland.
   [Feltus, F. Alex] Clemson Univ, Dept Genet & Biochem, Clemson, SC 29631 USA.
   [Gowik, Udo; Westhoff, Peter] Univ Dusseldorf, Inst Entwicklungs & Mol Biol Pflanzen, D-40225 Dusseldorf, Germany.
   [Lyons, Eric; Freeling, Michael] Univ Calif Berkeley, Dept Plant & Microbial Sci, Berkeley, CA 94720 USA.
   [Maher, Christopher A.; Narechania, Apurva; Zhang, Lifang] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Penning, Bryan W.; McCann, Maureen C.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
   [Carpita, Nicholas C.] Purdue Univ, Dept Bot & Plant Pathol, W Lafayette, IN 47907 USA.
   [Hash, C. Thomas] Int Crops Res Inst Semi Arid Trop, Patancheru 502324, Andhra Pradesh, India.
   [Klein, Patricia] Texas A&M Univ, Dept Hort, College Stn, TX 77843 USA.
   [Klein, Patricia] Texas A&M Univ, Inst Plant Genom & Biotechnol, College Stn, TX 77843 USA.
   [Kresovich, Stephen] Cornell Univ, Inst Genom Divers, Ithaca, NY 14853 USA.
   [Ming, Ray] Univ Illinois, Dept Plant Biol, Urbana, IL 61801 USA.
   [Peterson, Daniel G.] Mississippi State Univ, Mississippi Genome Explorat Lab, Starkville, MS 39762 USA.
   [Mehboob-ur-Rahman] NIBGE, Faisalabad, Pakistan.
   [Ware, Doreen] USDA, NAA Robert Holley Ctr Agr & Hlth, Ithaca, NY 14853 USA.
C3 University System of Georgia; University of Georgia; Rutgers University System; Rutgers University New Brunswick; United States Department of Energy (DOE); Stanford University; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of California System; University of California Berkeley; North China University of Science & Technology; University of Zurich; Clemson University; Heinrich Heine University Dusseldorf; University of California System; University of California Berkeley; Cold Spring Harbor Laboratory; Purdue University System; Purdue University; Purdue University System; Purdue University; CGIAR; International Crops Research Institute for the Semi-Arid-Tropics (ICRISAT); Texas A&M University System; Texas A&M University College Station; Texas A&M University System; Texas A&M University College Station; Cornell University; University of Illinois System; University of Illinois Urbana-Champaign; Mississippi State University; Pakistan Institute of Engineering & Applied Science; United States Department of Agriculture (USDA)
RP Paterson, AH (corresponding author), Univ Georgia, Plant Genome Mapping Lab, Athens, GA 30602 USA.
EM paterson@uga.edu
FU US National Science Foundation [DBI-9872649, DBI-0115903, MCB-0450260, DBI-0321467]; International Consortium for Sugarcane Biotechnology; National Sorghum Producers; John Simon Guggenheim Foundation; US Department of Energy [DE-FG05-95ER20194]; German Federal Ministry of Education GABI initiative [0313117, 0314000C]; US Department of Agriculture-Agricultural Research Service
NR 50
TC 2251
Z9 2832
U1 6
U2 453
PU NATURE PUBLISHING 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 29
PY 2009
VL 457
IS 7229
BP 551
EP 556
DI 10.1038/nature07723
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200034
PM 19189423
DA 2026-03-09
ER

PT J
AU Saleh, MC
   Tassetto, M
   van Rij, RP
   Goic, B
   Gausson, V
   Berry, B
   Jacquier, C
   Antoniewski, C
   Andino, R
AF Saleh, Maria-Carla
   Tassetto, Michel
   van Rij, Ronald P.
   Goic, Bertsy
   Gausson, Valerie
   Berry, Bassam
   Jacquier, Caroline
   Antoniewski, Christophe
   Andino, Raul
TI Antiviral immunity in Drosophila requires systemic RNA interference spread
SO NATURE
LA English
DT Article
ID double-stranded-rna; distinct roles; pathway; dsrna; gene; melanogaster; virus; dicer-2; entry
AB Multicellular organisms evolved sophisticated defence systems to confer protection against pathogens. An important characteristic of these immune systems is their ability to act both locally at the site of infection and at distal uninfected locations(1-4). In insects, such as Drosophila melanogaster, RNA interference (RNAi) mediates antiviral immunity(5-7). However, the antiviral RNAi defence in flies seems to be a local, cell-autonomous process, as flies are thought to be unable to generate a systemic RNAi response(8). Here we show that a recently defined double-stranded RNA(dsRNA) uptake pathway(9) is essential for effective antiviral RNAi immunity in adult flies. Mutant flies defective in this dsRNA uptake pathway were hypersensitive to infection with Drosophila C virus and Sindbis virus. Mortality in dsRNA-uptake-defective flies was accompanied by 100-to 10(5)-fold increases in viral titres and higher levels of viral RNA. Furthermore, inoculating naked dsRNA into flies elicited a sequence-specific antiviral immune response that required an intact dsRNA uptake pathway. These findings suggest that spread of dsRNA to uninfected sites is essential for effective antiviral immunity. Notably, infection with green fluorescent protein (GFP)-tagged Sindbis virus suppressed expression of host-encoded GFP at a distal site. Thus, similar to protein-based immunity in vertebrates, the antiviral RNAi response in flies also relies on the systemic spread of a virus-specific immunity signal.
C1 [Saleh, Maria-Carla; Tassetto, Michel; van Rij, Ronald P.; Andino, Raul] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94122 USA.
   [Goic, Bertsy; Gausson, Valerie; Berry, Bassam; Jacquier, Caroline; Antoniewski, Christophe] Inst Pasteur, F-75015 Paris, France.
   [Berry, Bassam; Jacquier, Caroline; Antoniewski, Christophe] CNRS, URA 2578, F-75015 Paris, France.
C3 University of California System; University of California San Francisco; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS)
RP Andino, R (corresponding author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94122 USA.
EM raul.andino@ucsf.edu
FU NIH [AI40085, AI064738]; Institut Pasteur; CNRS; ANR; ARC
NR 24
TC 236
Z9 292
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 19
PY 2009
VL 458
IS 7236
BP 346
EP U109
DI 10.1038/nature07712
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600043
PM 19204732
DA 2026-03-09
ER

PT J
AU Sharon, I
   Alperovitch, A
   Rohwer, F
   Haynes, M
   Glaser, F
   Atamna-Ismaeel, N
   Pinter, RY
   Partensky, F
   Koonin, EV
   Wolf, YI
   Nelson, N
   Béjà, O
AF Sharon, Itai
   Alperovitch, Ariella
   Rohwer, Forest
   Haynes, Matthew
   Glaser, Fabian
   Atamna-Ismaeel, Nof
   Pinter, Ron Y.
   Partensky, Frederic
   Koonin, Eugene V.
   Wolf, Yuri I.
   Nelson, Nathan
   Beja, Oded
TI Photosystem I gene cassettes are present in marine virus genomes
SO NATURE
LA English
DT Article
ID cyanobacterium synechocystis sp; photosynthesis genes; targeted inactivation; electron flow; prochlorococcus; organization; prokaryote
AB Cyanobacteria of the Synechococcus and Prochlorococcus genera are important contributors to photosynthetic productivity in the open oceans(1-3). Recently, core photosystem II (PSII) genes were identified in cyanophages and proposed to function in photosynthesis and in increasing viral fitness by supplementing the host production of these proteins(4-7). Here we show evidence for the presence of photosystem I (PSI) genes in the genomes of viruses that infect these marine cyanobacteria, using pre-existing meta-genomic data from the global ocean sampling expedition(8) as well as from viral biomes(9). The seven cyanobacterial core PSI genes identified in this study, psaA, B, C, D, E, K and a unique J and F fusion, form a cluster in cyanophage genomes, suggestive of selection for a distinct function in the virus life cycle. The existence of this PSI cluster was confirmed with overlapping and long polymerase chain reaction on environmental DNA from the Northern Line Islands. Potentially, the seven proteins encoded by the viral genes are sufficient to form an intact monomeric PSI complex. Projection of viral predicted peptides on the cyanobacterial PSI crystal structure(10) suggested that the viral-PSI components might provide a unique way of funnelling reducing power from respiratory and other electron transfer chains to the PSI.
C1 [Sharon, Itai; Alperovitch, Ariella; Atamna-Ismaeel, Nof; Beja, Oded] Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel.
   [Sharon, Itai; Pinter, Ron Y.] Technion Israel Inst Technol, Fac Comp Sci, IL-32000 Haifa, Israel.
   [Glaser, Fabian] Technion Israel Inst Technol, Bioinformat Knowledge Unit, Lorry I Lokey Interdisciplinary Ctr Life Sci & En, IL-32000 Haifa, Israel.
   [Rohwer, Forest; Haynes, Matthew] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
   [Rohwer, Forest] San Diego State Univ, Ctr Microbial Sci, San Diego, CA 92182 USA.
   [Partensky, Frederic] CNRS, F-29682 Roscoff, France.
   [Partensky, Frederic] UPMC, Biol Stn, UMR 7144, F-29682 Roscoff, France.
   [Koonin, Eugene V.; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
   [Nelson, Nathan] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Biochem, Daniella Rich Inst Struct Biol, IL-69978 Tel Aviv, Israel.
C3 Technion Israel Institute of Technology; Technion Israel Institute of Technology; Technion Israel Institute of Technology; California State University System; San Diego State University; California State University System; San Diego State University; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM); Tel Aviv University
RP Béjà, O (corresponding author), Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel.
EM beja@tx.technion.ac.il
FU Israel Science Foundation [1203/06, 356/06]; Henry Taub Award for Academic Excellence; Technion V. P. R. Fund-Henri Gutwirth Promotion of Research Fund
NR 30
TC 159
Z9 192
U1 0
U2 75
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 10
PY 2009
VL 461
IS 7261
BP 258
EP 262
DI 10.1038/nature08284
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600043
PM 19710652
DA 2026-03-09
ER

PT J
AU Gentile, G
   Famaey, B
   Zhao, HS
   Salucci, P
AF Gentile, Gianfranco
   Famaey, Benoit
   Zhao, HongSheng
   Salucci, Paolo
TI Universality of galactic surface densities within one dark halo scale-length
SO NATURE
LA English
DT Article
ID tully-fisher relation; spiral galaxy; rotation curve; matter distribution; mass; mond
AB It was recently discovered that the mean dark matter surface density within one dark halo scale-length (the radius within which the volume density profile of dark matter remains approximately flat) is constant across a wide range of galaxies(1). This scaling relation holds for galaxies spanning a luminosity range of 14 magnitudes and the whole Hubble sequence(1-3). Here we report that the luminous matter surface density is also constant within one scale-length of the dark halo. This means that the gravitational acceleration generated by the luminous component in galaxies is always the same at this radius. Although the total luminous-to-dark matter ratio is not constant, within one halo scale-length it is constant. Our finding can be interpreted as a close correlation between the enclosed surface densities of luminous and dark matter in galaxies(4).
C1 [Gentile, Gianfranco] Univ Ghent, Sterrenkundig Observatorium, B-9000 Ghent, Belgium.
   [Gentile, Gianfranco; Famaey, Benoit] Univ Libre Bruxelles, Inst Astron & Astrophys, B-1050 Brussels, Belgium.
   [Famaey, Benoit] Univ Strasbourg, CNRS, UMR 7550, Astron Observ, F-67000 Strasbourg, France.
   [Famaey, Benoit] Univ Bonn, AIfA, D-53121 Bonn, Germany.
   [Zhao, HongSheng] Univ St Andrews, Sch Phys & Astron, SUPA, St Andrews KY16 9SS, Fife, Scotland.
   [Zhao, HongSheng] Leiden Univ, Sterrewacht & Inst Lorentz, NL-2333 CA Leiden, Netherlands.
   [Salucci, Paolo] SISSA, Int Sch Adv Studies, I-34151 Trieste, Italy.
C3 Ghent University; Universite Libre de Bruxelles; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Bonn; University of St Andrews; Leiden University - Excl LUMC; Leiden University; International School for Advanced Studies (SISSA)
RP Gentile, G (corresponding author), Univ Ghent, Sterrenkundig Observatorium, Krijgslaan 281, B-9000 Ghent, Belgium.
EM gianfranco.gentile@ugent.be
FU FWO-Vlaanderen (Belgium); Alexander von Humboldt foundation (Germany); FNRS (Belgium),; CNRS (France); STFC [PP/D000890/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/D000890/1] Funding Source: researchfish
NR 16
TC 129
Z9 136
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 1
PY 2009
VL 461
IS 7264
BP 627
EP 628
DI 10.1038/nature08437
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600034
PM 19794488
DA 2026-03-09
ER

PT J
AU Sasaki, E
   Suemizu, H
   Shimada, A
   Hanazawa, K
   Oiwa, R
   Kamioka, M
   Tomioka, I
   Sotomaru, Y
   Hirakawa, R
   Eto, T
   Shiozawa, S
   Maeda, T
   Ito, M
   Ito, R
   Kito, C
   Yagihashi, C
   Kawai, K
   Miyoshi, H
   Tanioka, Y
   Tamaoki, N
   Habu, S
   Okano, H
   Nomura, T
AF Sasaki, Erika
   Suemizu, Hiroshi
   Shimada, Akiko
   Hanazawa, Kisaburo
   Oiwa, Ryo
   Kamioka, Michiko
   Tomioka, Ikuo
   Sotomaru, Yusuke
   Hirakawa, Reiko
   Eto, Tomoo
   Shiozawa, Seiji
   Maeda, Takuji
   Ito, Mamoru
   Ito, Ryoji
   Kito, Chika
   Yagihashi, Chie
   Kawai, Kenji
   Miyoshi, Hiroyuki
   Tanioka, Yoshikuni
   Tamaoki, Norikazu
   Habu, Sonoko
   Okano, Hideyuki
   Nomura, Tatsuji
TI Generation of transgenic non-human primates with germline transmission
SO NATURE
LA English
DT Article
ID lentiviral gene-transfer; pluripotent stem-cells; spinal-cord-injury; marmoset monkey; model; establishment; expression; disease; cattle
AB The common marmoset (Callithrix jacchus) is increasingly attractive for use as a non-human primate animal model in biomedical research. It has a relatively high reproduction rate for a primate, making it potentially suitable for transgenic modification. Although several attempts have been made to produce non-human transgenic primates, transgene expression in the somatic tissues of live infants has not been demonstrated by objective analyses such as polymerase chain reaction with reverse transcription or western blots. Here we show that the injection of a self-inactivating lentiviral vector in sucrose solution into marmoset embryos results in transgenic common marmosets that expressed the transgene in several organs. Notably, we achieved germline transmission of the transgene, and the transgenic offspring developed normally. The successful creation of transgenic marmosets provides a new animal model for human disease that has the great advantage of a close genetic relationship with humans. This model will be valuable to many fields of biomedical research.
C1 [Sasaki, Erika; Suemizu, Hiroshi; Shimada, Akiko; Oiwa, Ryo; Kamioka, Michiko; Tomioka, Ikuo; Hirakawa, Reiko; Eto, Tomoo; Shiozawa, Seiji; Maeda, Takuji; Ito, Mamoru; Ito, Ryoji; Kito, Chika; Yagihashi, Chie; Kawai, Kenji; Tanioka, Yoshikuni; Tamaoki, Norikazu; Nomura, Tatsuji] Cent Inst Expt Anim, Miyamae Ku, Kanagawa 2160001, Japan.
   [Hanazawa, Kisaburo] Juntendo Univ, Nerima Hosp, Dept Urol, Nerima Ku, Tokyo 1778521, Japan.
   [Tomioka, Ikuo; Hirakawa, Reiko] Keio Univ, Sch Med, Ctr Integrated Med Res, Shinjuku Ku, Tokyo 1608582, Japan.
   [Shiozawa, Seiji; Maeda, Takuji; Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, Tokyo 1608582, Japan.
   [Sotomaru, Yusuke] Hiroshima Univ, Nat Sci Ctr Basic Res & Dev, Minami Ku, Hiroshima 7348551, Japan.
   [Miyoshi, Hiroyuki] RIKEN, BioResource Ctr, Subteam Manipulat Cell Fate, Tsukuba, Ibaraki 3050074, Japan.
   [Habu, Sonoko] Tokai Univ, Sch Med, Dept Immunol, Kanagawa 2591193, Japan.
C3 Juntendo University; Keio University; Keio University; Hiroshima University; RIKEN; Tokai University
RP Sasaki, E (corresponding author), Cent Inst Expt Anim, Miyamae Ku, 1430 Nogawa, Kanagawa 2160001, Japan.
EM esasaki@ciea.or.jp; hidokano@sc.itc.keio.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT); Japanese Government to Keio University; Solution-Oriented Research for Science and Technology (SORST) of the Japan Science and Technology Agency; Grants-in-Aid for Scientific Research [21240042] Funding Source: KAKEN
NR 26
TC 577
Z9 631
U1 3
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 28
PY 2009
VL 459
IS 7246
BP 523
EP U50
DI 10.1038/nature08090
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500029
PM 19478777
DA 2026-03-09
ER

PT J
AU Kong, A
   Steinthorsdottir, V
   Masson, G
   Thorleifsson, G
   Sulem, P
   Besenbacher, S
   Jonasdottir, A
   Sigurdsson, A
   Kristinsson, KT
   Jonasdottir, A
   Frigge, ML
   Gylfason, A
   Olason, PI
   Gudjonsson, SA
   Sverrisson, S
   Stacey, SN
   Sigurgeirsson, B
   Benediktsdottir, KR
   Sigurdsson, H
   Jonsson, T
   Benediktsson, R
   Olafsson, JH
   Johannsson, OT
   Hreidarsson, AB
   Sigurdsson, G
   Ferguson-Smith, AC
   Gudbjartsson, DF
   Thorsteinsdottir, U
   Stefansson, K
AF Kong, Augustine
   Steinthorsdottir, Valgerdur
   Masson, Gisli
   Thorleifsson, Gudmar
   Sulem, Patrick
   Besenbacher, Soren
   Jonasdottir, Aslaug
   Sigurdsson, Asgeir
   Kristinsson, Kari Th.
   Jonasdottir, Adalbjorg
   Frigge, Michael L.
   Gylfason, Arnaldur
   Olason, Pall I.
   Gudjonsson, Sigurjon A.
   Sverrisson, Sverrir
   Stacey, Simon N.
   Sigurgeirsson, Bardur
   Benediktsdottir, Kristrun R.
   Sigurdsson, Helgi
   Jonsson, Thorvaldur
   Benediktsson, Rafn
   Olafsson, Jon H.
   Johannsson, Oskar Th.
   Hreidarsson, Astradur B.
   Sigurdsson, Gunnar
   Ferguson-Smith, Anne C.
   Gudbjartsson, Daniel F.
   Thorsteinsdottir, Unnur
   Stefansson, Kari
TI Parental origin of sequence variants associated with complex diseases
SO NATURE
LA English
DT Article
ID genome-wide association; imprinted genes; susceptibility; expression; imputation; kcnq1
AB Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism ( SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.
C1 [Kong, Augustine; Steinthorsdottir, Valgerdur; Masson, Gisli; Thorleifsson, Gudmar; Sulem, Patrick; Besenbacher, Soren; Jonasdottir, Aslaug; Sigurdsson, Asgeir; Jonasdottir, Adalbjorg; Frigge, Michael L.; Gylfason, Arnaldur; Olason, Pall I.; Gudjonsson, Sigurjon A.; Sverrisson, Sverrir; Stacey, Simon N.; Gudbjartsson, Daniel F.; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland.
   [Sigurgeirsson, Bardur; Olafsson, Jon H.] Landspitali Univ Hosp, Dept Dermatol, IS-101 Reykjavik, Iceland.
   [Benediktsdottir, Kristrun R.] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland.
   [Sigurdsson, Helgi; Johannsson, Oskar Th.] Landspitali Univ Hosp, Dept Oncol, IS-101 Reykjavik, Iceland.
   [Jonsson, Thorvaldur] Landspitali Univ Hosp, Dept Surg, IS-101 Reykjavik, Iceland.
   [Benediktsson, Rafn; Hreidarsson, Astradur B.; Sigurdsson, Gunnar] Landspitali Univ Hosp, Dept Endocrinol & Metab, IS-101 Reykjavik, Iceland.
   [Ferguson-Smith, Anne C.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
   [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
C3 Decode Genetics; Landspitali National University Hospital; Landspitali National University Hospital; Landspitali National University Hospital; Landspitali National University Hospital; Landspitali National University Hospital; University of Cambridge; University of Iceland
RP Kong, A (corresponding author), deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.
EM kong@decode.is; kstefans@decode.is
FU FP7-MC-IAPP [218071]; Academy of Finland (AKA) [218071] Funding Source: Academy of Finland (AKA); National Institute of Diabetes and Digestive and Kidney Diseases [R01DK029867] Funding Source: NIH RePORTER; Medical Research Council [MC_U127592696, G9723500, MC_U106179471, MC_U106179474] Funding Source: researchfish; MRC [MC_U106179474, MC_U127592696, G9723500] Funding Source: UKRI
NR 24
TC 438
Z9 490
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 17
PY 2009
VL 462
IS 7275
BP 868
EP U59
DI 10.1038/nature08625
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400032
PM 20016592
DA 2026-03-09
ER

PT J
AU Zofall, M
   Fischer, T
   Zhang, K
   Zhou, M
   Cui, BW
   Veenstra, TD
   Grewal, SIS
AF Zofall, Martin
   Fischer, Tamas
   Zhang, Ke
   Zhou, Ming
   Cui, Bowen
   Veenstra, Timothy D.
   Grewal, Shiv I. S.
TI Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs
SO NATURE
LA English
DT Article
ID fission yeast; quality control; noncoding rnas; variant; transcription; chromatin; genome; drosophila; complex; exosome
AB Eukaryotic transcriptomes are characterized by widespread transcription of noncoding and antisense RNAs(1-3), which is linked to key chromosomal processes, such as chromatin remodelling, gene regulation and heterochromatin assembly(4-7). However, these transcripts can be deleterious, and their accumulation is suppressed by several mechanisms including degradation by the nuclear exosome(8,9). The mechanisms by which cells differentiate coding RNAs from transcripts targeted for degradation are not clear. Here we show that the variant histone H2A.Z, which is loaded preferentially at the 5' ends of genes by the Swr1 complex containing a JmjC domain protein, mediates suppression of antisense transcripts in the fission yeast Schizosaccharomyces pombe genome. H2A.Z is partially redundant in this regard with the Clr4 (known as SUV39H in mammals)-containing heterochromatin silencing complex that is also distributed at euchromatic loci, and with RNA interference component Argonaute (Ago1). Loss of Clr4 or Ago1 alone has little effect on antisense transcript levels, but cells lacking either of these factors and H2A.Z show markedly increased levels of antisense RNAs that are normally degraded by the exosome. These analyses suggest that as well as performing other functions, H2A.Z is a component of a genome indexing mechanism that cooperates with heterochromatin and RNAi factors to suppress read-through antisense transcripts.
C1 [Zofall, Martin; Fischer, Tamas; Zhang, Ke; Cui, Bowen; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Zhou, Ming; Veenstra, Timothy D.] NCI Frederick, SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Science Applications International Corporation (SAIC); SAIC-Frederick
RP Grewal, SIS (corresponding author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
FU National Institutes of Health [N01-CO-12400]; National Cancer Institute; National Cancer Institute [ZIABC011208, ZIABC010523] Funding Source: NIH RePORTER
NR 30
TC 119
Z9 140
U1 1
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 419
EP U120
DI 10.1038/nature08321
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100045
PM 19693008
DA 2026-03-09
ER

PT J
AU Konopka, G
   Bomar, JM
   Winden, K
   Coppola, G
   Jonsson, ZO
   Gao, FY
   Peng, S
   Preuss, TM
   Wohlschlegel, JA
   Geschwind, DH
AF Konopka, Genevieve
   Bomar, Jamee M.
   Winden, Kellen
   Coppola, Giovanni
   Jonsson, Zophonias O.
   Gao, Fuying
   Peng, Sophia
   Preuss, Todd M.
   Wohlschlegel, James A.
   Geschwind, Daniel H.
TI Human-specific transcriptional regulation of CNS development genes by FOXP2
SO NATURE
LA English
DT Article
ID human brain; accelerated evolution; mass-spectrometry; language; speech; expression; identification; mice; mutations; dyspraxia
AB The signalling pathways controlling both the evolution and development of language in the human brain remain unknown. So far, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction(1-3). It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans(4,5). However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans.
C1 [Konopka, Genevieve; Bomar, Jamee M.; Winden, Kellen; Geschwind, Daniel H.] Univ Calif Los Angeles, Program Neurogenet, Los Angeles, CA 90095 USA.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA 90095 USA.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA.
   [Konopka, Genevieve; Bomar, Jamee M.; Winden, Kellen; Coppola, Giovanni; Gao, Fuying; Peng, Sophia; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Wohlschlegel, James A.; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Biol Chem, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [Preuss, Todd M.] Emory Univ, Sch Med, Div Neurosci, Atlanta, GA 30329 USA.
   [Preuss, Todd M.] Emory Univ, Sch Med, Ctr Behav Neurosci, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Preuss, Todd M.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30329 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Emory University; Emory University; Emory University
RP Konopka, G (corresponding author), Univ Calif Los Angeles, Program Neurogenet, Los Angeles, CA 90095 USA.
EM gena@alum.mit.edu; dhg@ucla.edu
FU A. P. Giannini Foundation Medical Research Fellowship; NARSAD; NIH/NCRR [RR00165]; McDonnell Foundation [JSMF 21002093];  [R21MH075028];  [R37MH60233-06A1];  [T32HD007032];  [T32MH073526]
NR 31
TC 291
Z9 357
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 NOV 12
PY 2009
VL 462
IS 7270
BP 213
EP U89
DI 10.1038/nature08549
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100042
PM 19907493
DA 2026-03-09
ER

PT J
AU Bo, S
   Siegert, MJ
   Mudd, SM
   Sugden, D
   Fujita, S
   Cui, XB
   Jiang, YY
   Tang, XY
   Li, YS
AF Bo, Sun
   Siegert, Martin J.
   Mudd, Simon M.
   Sugden, David
   Fujita, Shuji
   Cui Xiangbin
   Jiang Yunyun
   Tang Xueyuan
   Li Yuansheng
TI The Gamburtsev mountains and the origin and early evolution of the Antarctic Ice Sheet
SO NATURE
LA English
DT Article
ID east antarctica; miocene; valley; expansion; history
AB Ice-sheet development in Antarctica was a result of significant and rapid global climate change about 34 million years ago(1). Ice-sheet and climate modelling suggest reductions in atmospheric carbon dioxide ( less than three times the pre-industrial level of 280 parts per million by volume) that, in conjunction with the development of the Antarctic Circumpolar Current, led to cooling and glaciation paced by changes in Earth's orbit(2). Based on the present subglacial topography, numerical models point to ice-sheet genesis on mountain massifs of Antarctica, including the Gamburtsev mountains at Dome A, the centre of the present ice sheet(2,3). Our lack of knowledge of the present-day topography of the Gamburtsev mountains(4) means, however, that the nature of early glaciation and subsequent development of a continental-sized ice sheet are uncertain. Here we present radar information about the base of the ice at Dome A, revealing classic Alpine topography with pre-existing river valleys overdeepened by valley glaciers formed when the mean summer surface temperature was around 3 degrees C. This landscape is likely to have developed during the initial phases of Antarctic glaciation. According to Antarctic climate history (estimated from offshore sediment records) the Gamburtsev mountains are probably older than 34 million years and were the main centre for ice-sheet growth. Moreover, the landscape has most probably been preserved beneath the present ice sheet for around 14 million years.
C1 [Bo, Sun; Cui Xiangbin; Jiang Yunyun; Tang Xueyuan; Li Yuansheng] Polar Res Inst China, Shanghai 200136, Peoples R China.
   [Siegert, Martin J.; Mudd, Simon M.; Sugden, David] Univ Edinburgh, Sch Geosci, Edinburgh EH9 3JW, Midlothian, Scotland.
   [Fujita, Shuji] Natl Inst Polar Res, Res Org Informat & Syst, Itabashi Ku, Tokyo 1738515, Japan.
C3 Polar Research Institute of China; University of Edinburgh; Research Organization of Information & Systems (ROIS); National Institute of Polar Research (NIPR) - Japan
RP Bo, S (corresponding author), Polar Res Inst China, 451 Jinqiao Rd, Shanghai 200136, Peoples R China.
EM sunbo@pric.gov.cn; m.j.siegert@ed.ac.uk
FU National Natural Science Foundation of China [40476005]; Ministry of Science and Technology of China [2006BAB18B03]; UK Natural Environment Research Council [NE/D003733/1]; NERC [NE/E018254/1, NE/F016646/1] Funding Source: UKRI; Natural Environment Research Council [NE/F016646/1, NE/E018254/1] Funding Source: researchfish
NR 30
TC 146
Z9 180
U1 1
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 690
EP 693
DI 10.1038/nature08024
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600041
PM 19494912
DA 2026-03-09
ER

PT J
AU Galloway, JL
   Delgado, I
   Ros, MA
   Tabin, CJ
AF Galloway, Jenna L.
   Delgado, Irene
   Ros, Maria A.
   Tabin, Clifford J.
TI A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning
SO NATURE
LA English
DT Article
ID apical ectodermal ridge; vertebrate limb; chick limb; nitrogen-mustard; sonic-hedgehog; feedback loop; thalidomide; bud; expression; outgrowth
AB Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a marked increase in incidence in the early 1960s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative(1,2). This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation(3-5). Both X-irradiation(5) and thalidomide-induced phocomelia(5,6) have been interpreted as patterning defects in the context of the progress zone model, which states that a cell's proximodistal identity is determined by the length of time spent in a distal limb region termed the 'progress zone'(7). Indeed, studies of X-irradiation-induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the progress zone model. Here, using a combination of molecular analysis and lineage tracing in chick, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. Because skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the aetiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that proximodistal patterning is unaffected after X-irradiation does not support the predictions of the progress zone model.
C1 [Galloway, Jenna L.; Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Delgado, Irene] Univ Cantabria, Dept Anat & Biol Celular, E-39005 Santander, Spain.
   [Ros, Maria A.] CSIC UC IDICAN, Inst Biomed & Biotecnol Cantabria, Santander 39005, Spain.
C3 Harvard University; Harvard Medical School; Universidad de Cantabria; Consejo Superior de Investigaciones Cientificas (CSIC); Universidad de Cantabria; CSIC - Instituto de Biomedicina y Biotecnologia de Cantabria (IBBTEC)
RP Tabin, CJ (corresponding author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM tabin@receptor.med.harvard.edu
FU NIH [R37 HD032443]; National Institute of Child Health and Human Development [F32HD057701]; Spanish Ministry of Science and Innovation [BFU2008-00397]
NR 30
TC 52
Z9 58
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 400
EP U119
DI 10.1038/nature08117
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000040
PM 19553938
DA 2026-03-09
ER

PT J
AU Levine, JM
   HilleRisLambers, J
AF Levine, Jonathan M.
   HilleRisLambers, Janneke
TI The importance of niches for the maintenance of species diversity
SO NATURE
LA English
DT Article
ID coexistence; variability; predation; dynamics; climate
AB Ecological communities characteristically contain a wide diversity of species with important functional, economic and aesthetic value. Ecologists have long questioned how this diversity is maintained(1-3). Classic theory shows that stable coexistence requires competitors to differ in their niches(4-6); this has motivated numerous investigations of ecological differences presumed to maintain diversity(3,6-8). That niche differences are key to coexistence, however, has recently been challenged by the neutral theory of biodiversity, which explains coexistence with the equivalence of competitors(9). The ensuing controversy has motivated calls for a better understanding of the collective importance of niche differences for the diversity observed in ecological communities(10,11). Here we integrate theory and experimentation to show that niche differences collectively stabilize the dynamics of experimental communities of serpentine annual plants. We used field-parameterized population models to develop a null expectation for community dynamics without the stabilizing effects of niche differences. The population growth rates predicted by this null model varied by several orders of magnitude between species, which is sufficient for rapid competitive exclusion. Moreover, after two generations of community change in the field, Shannon diversity was over 50 per cent greater in communities stabilized by niche differences relative to those exhibiting dynamics predicted by the null model. Finally, in an experiment manipulating species' relative abundances, population growth rates increased when species became rare-the demographic signature of niche differences. Our work thus provides strong evidence that species differences have a critical role in stabilizing species diversity.
C1 [Levine, Jonathan M.] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [HilleRisLambers, Janneke] Univ Washington, Dept Biol, Seattle, WA 98195 USA.
C3 University of California System; University of California Santa Barbara; University of Washington; University of Washington Seattle
RP Levine, JM (corresponding author), Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
EM levine@lifesci.ucsb.edu; jhrl@u.washington.edu
FU US National Science Foundation [0743365, 0743183]; David and Lucile Packard Foundation; Division Of Environmental Biology; Direct For Biological Sciences [0743365, 0743183] Funding Source: National Science Foundation
NR 24
TC 490
Z9 540
U1 8
U2 597
PU NATURE PUBLISHING 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 10
PY 2009
VL 461
IS 7261
BP 254
EP U130
DI 10.1038/nature08251
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600042
DA 2026-03-09
ER

PT J
AU Tu, XM
   Manohar, S
   Jagota, A
   Zheng, M
AF Tu, Xiaomin
   Manohar, Suresh
   Jagota, Anand
   Zheng, Ming
TI DNA sequence motifs for structure-specific recognition and separation of carbon nanotubes
SO NATURE
LA English
DT Article
ID single-stranded-dna; molecular-dynamics; hybrids; dispersion; simulation; polymers; energy
AB Single-walled carbon nanotubes (SWNTs) are a family of molecules that have the same cylindrical shape but different chiralities(1). Many fundamental studies and technological applications(2) of SWNTs require a population of tubes with identical chirality that current syntheses cannot provide. The SWNT sorting problem-that is, separation of a synthetic mixture of tubes into individual single-chirality components-has attracted considerable attention in recent years. Intense efforts so far have focused largely on, and resulted in solutions for, a weaker version of the sorting problem: metal/semiconductor separation(3,4). A systematic and general method to purify each and every single-chirality species of the same electronic type from the synthetic mixture of SWNTs is highly desirable, but the task has proven to be insurmountable to date. Here we report such a method, which allows purification of all 12 major single-chirality semiconducting species from a synthetic mixture, with sufficient yield for both fundamental studies and application development. We have designed an effective search of a DNA library of similar to 10(60) in size, and have identified more than 20 short DNA sequences, each of which recognizes and enables chromatographic purification of a particular nanotube species from the synthetic mixture. Recognition sequences exhibit a periodic purine-pyrimidines pattern, which can undergo hydrogen-bonding to form a two-dimensional sheet, and fold selectively on nanotubes into a well-ordered three-dimensional barrel. We propose that the ordered two-dimensional sheet and three-dimensional barrel provide the structural basis for the observed DNA recognition of SWNTs.
C1 [Tu, Xiaomin; Zheng, Ming] DuPont Co Inc, Cent Res & Dev, Wilmington, DE 19880 USA.
   [Manohar, Suresh; Jagota, Anand] Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA.
   [Jagota, Anand] Lehigh Univ, Bioengn Program, Bethlehem, PA 18015 USA.
C3 DuPont; DuPont USA; Lehigh University; Lehigh University
RP Zheng, M (corresponding author), DuPont Co Inc, Cent Res & Dev, Wilmington, DE 19880 USA.
EM ming.zheng@usa.dupont.com
FU US National Science Foundation [CMS-060950]
NR 28
TC 971
Z9 1162
U1 3
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 JUL 9
PY 2009
VL 460
IS 7252
BP 250
EP 253
DI 10.1038/nature08116
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000039
PM 19587767
DA 2026-03-09
ER

PT J
AU Wang, GG
   Song, JK
   Wang, ZX
   Dormann, HL
   Casadio, F
   Li, HT
   Luo, JL
   Patel, DJ
   Allis, CD
AF Wang, Gang G.
   Song, Jikui
   Wang, Zhanxin
   Dormann, Holger L.
   Casadio, Fabio
   Li, Haitao
   Luo, Jun-Li
   Patel, Dinshaw J.
   Allis, C. David
TI Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger
SO NATURE
LA English
DT Article
ID histone h3; developmental regulators; lysine-4 trimethylation; protein structures; plant homeodomain; methylation; transcription; polycomb; differentiation; macrophages
AB Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities(1). The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states(1,2). The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders(3). Here we report that fusing an H3K4-trimethylation (H3K4me3)binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias(4,5), generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.
C1 [Wang, Gang G.; Dormann, Holger L.; Casadio, Fabio; Allis, C. David] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA.
   [Song, Jikui; Wang, Zhanxin; Li, Haitao; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Luo, Jun-Li] Scripps Florida, Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA.
C3 Rockefeller University; Memorial Sloan Kettering Cancer Center; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
RP Allis, CD (corresponding author), Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA.
EM alliscd@rockefeller.edu
FU Leukemia & Lymphoma Society Fellow award; Choh-Hao Li Memorial Fund Scholar award; Boehringer Ingelheim Foundation; National Institutes of Health (NIH); Rockefeller University; Abby RockefellerMauze Trust; Dewitt Wallace and Maloris Foundations; US Department of Defense CDMRP; Starr Foundation Cancer Consortium
NR 53
TC 360
Z9 402
U1 2
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 847
EP U6
DI 10.1038/nature08036
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500040
PM 19430464
DA 2026-03-09
ER

PT J
AU DiCarlo, L
   Chow, JM
   Gambetta, JM
   Bishop, LS
   Johnson, BR
   Schuster, DI
   Majer, J
   Blais, A
   Frunzio, L
   Girvin, SM
   Schoelkopf, RJ
AF DiCarlo, L.
   Chow, J. M.
   Gambetta, J. M.
   Bishop, Lev S.
   Johnson, B. R.
   Schuster, D. I.
   Majer, J.
   Blais, A.
   Frunzio, L.
   Girvin, S. M.
   Schoelkopf, R. J.
TI Demonstration of two-qubit algorithms with a superconducting quantum processor
SO NATURE
LA English
DT Article
ID search algorithm; qubits; state; implementation; entanglement; circuit; photon; cavity; bits
AB Quantum computers, which harness the superposition and entanglement of physical states, could outperform their classical counterparts in solving problems with technological impact-such as factoring large numbers and searching databases(1,2). A quantum processor executes algorithms by applying a programmable sequence of gates to an initialized register of qubits, which coherently evolves into a final state containing the result of the computation. Building a quantum processor is challenging because of the need to meet simultaneously requirements that are in conflict: state preparation, long coherence times, universal gate operations and qubit readout. Processors based on a few qubits have been demonstrated using nuclear magnetic resonance(3-5), cold ion trap(6,7) and optical(8) systems, but a solid-state realization has remained an outstanding challenge. Here we demonstrate a two-qubit superconducting processor and the implementation of the Grover search and Deutsch-Jozsa quantum algorithms(1,2). We use a two-qubit interaction, tunable in strength by two orders of magnitude on nanosecond timescales, which is mediated by a cavity bus in a circuit quantum electrodynamics architecture(9,10). This interaction allows the generation of highly entangled states with concurrence up to 94 per cent. Although this processor constitutes an important step in quantum computing with integrated circuits, continuing efforts to increase qubit coherence times, gate performance and register size will be required to fulfil the promise of a scalable technology.
C1 [DiCarlo, L.; Chow, J. M.; Bishop, Lev S.; Johnson, B. R.; Schuster, D. I.; Frunzio, L.; Girvin, S. M.; Schoelkopf, R. J.] Yale Univ, Dept Phys, New Haven, CT 06511 USA.
   [DiCarlo, L.; Chow, J. M.; Bishop, Lev S.; Johnson, B. R.; Schuster, D. I.; Frunzio, L.; Girvin, S. M.; Schoelkopf, R. J.] Yale Univ, Dept Appl Phys, New Haven, CT 06511 USA.
   [Gambetta, J. M.] Univ Waterloo, Dept Phys & Astron, Waterloo, ON N2L 3G1, Canada.
   [Gambetta, J. M.] Yale Univ, Inst Quantum Comp, New Haven, CT 06511 USA.
   [Majer, J.] TU Wien, Atominst Osterreich Univ, A-1020 Vienna, Austria.
   [Blais, A.] Univ Sherbrooke, Dept Phys, Sherbrooke, PQ J1K 2R1, Canada.
C3 Yale University; Yale University; University of Waterloo; Yale University; Technische Universitat Wien; University of Sherbrooke
RP Schoelkopf, RJ (corresponding author), Yale Univ, Dept Phys, New Haven, CT 06511 USA.
EM robert.schoelkopf@yale.edu
FU LPS/NSA [W911NF-05-1-0365]; NSF [DMR-0653377, DMR-0603369]; CIFAR; MRI; MITACS; NSERC; Alfred P. Sloan Foundation; CNR-Istituto di Cibernetica, Pozzuoli, Italy
NR 30
TC 972
Z9 1188
U1 6
U2 235
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 240
EP 244
DI 10.1038/nature08121
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000037
PM 19561592
DA 2026-03-09
ER

PT J
AU Jiang, QF
   Karata, K
   Woodgate, R
   Cox, MM
   Goodman, MF
AF Jiang, Qingfei
   Karata, Kiyonobu
   Woodgate, Roger
   Cox, Michael M.
   Goodman, Myron F.
TI The active form of DNA polymerase V is UmuD′2C-RecA-ATP
SO NATURE
LA English
DT Article
ID single-stranded-dna; escherichia-coli; reca protein; uv-mutagenesis; replication; deficient; mutations; repair; umuc; purification
AB DNA-damage-induced SOS mutations arise when Escherichia coli DNA polymerase (pol) V, activated by a RecA nucleoprotein filament (RecA*), catalyses translesion DNA synthesis. Here we address two longstanding enigmatic aspects of SOS mutagenesis, the molecular composition of mutagenically active pol V and the role of RecA*. We show that RecA* transfers a single RecA-ATP stoichiometrically from its DNA 39-end to free polV (UmuD'C-2) to form an active mutasome (polV Mut) with the composition UmuD'C-2-RecA-ATP. PolV Mut catalyses TLS in the absence of RecA* and deactivates rapidly upon dissociation from DNA. Deactivation occurs more slowly in the absence of DNA synthesis, while retaining RecA-ATP in the complex. Reactivation of polV Mut is triggered by replacement of RecA-ATP from RecA*. Thus, the principal role of RecA* in SOS mutagenesis is to transfer RecA-ATP to pol V, and thus generate active mutasomal complex for translesion synthesis.
C1 [Jiang, Qingfei; Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
   [Jiang, Qingfei; Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
   [Karata, Kiyonobu; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
   [Cox, Michael M.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
C3 University of Southern California; University of Southern California; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); University of Wisconsin System; University of Wisconsin Madison
RP Goodman, MF (corresponding author), Univ So Calif, Dept Biol Sci, Univ Pk, Los Angeles, CA 90089 USA.
EM mgoodman@usc.edu
FU National Institutes of Health [ES12259, R37GM21422, GM32335]; NICHD/NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development [ZIAHD001500] Funding Source: NIH RePORTER
NR 25
TC 117
Z9 156
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 JUL 16
PY 2009
VL 460
IS 7253
BP 359
EP 363
DI 10.1038/nature08178
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000030
PM 19606142
DA 2026-03-09
ER

PT J
AU Boothroyd, CE
   Dreesen, O
   Leonova, T
   Ly, KI
   Figueiredo, LM
   Cross, GAM
   Papavasiliou, FN
AF Boothroyd, Catharine E.
   Dreesen, Oliver
   Leonova, Tatyana
   Ly, K. Ina
   Figueiredo, Luisa M.
   Cross, George A. M.
   Papavasiliou, F. Nina
TI A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei
SO NATURE
LA English
DT Article
ID vsg expression site; african trypanosm; surface-antigens; gene-expression; transcription; activation; sequences; copy; end
AB Trypanosoma brucei is the causative agent of African sleeping sickness in humans and one of the causes of nagana in cattle. This protozoan parasite evades the host immune system by antigenic variation, a periodic switching of its variant surface glycoprotein (VSG) coat. VSG switching is spontaneous and occurs at a rate of about 10(-2)-10(-3) per population doubling in recent isolates from nature, but at a markedly reduced rate (10(-5)-10(-6)) in laboratory-adapted strains(1-3). VSG switching is thought to occur predominantly through gene conversion, a form of homologous recombination initiated by a DNA lesion that is used by other pathogens (for example, Candida albicans, Borrelia sp. and Neisseria gonorrhoeae) to generate surface protein diversity, and by B lymphocytes of the vertebrate immune system to generate antibody diversity. Very little is known about the molecular mechanism of VSG switching in T. brucei. Here we demonstrate that the introduction of a DNA double-stranded break (DSB) adjacent to the similar to 70-base-pair ( bp) repeats upstream of the transcribed VSG gene increases switching in vitro similar to 250-fold, producing switched clones with a frequency and features similar to those generated early in an infection. We were also able to detect spontaneous DSBs within the 70-bp repeats upstream of the actively transcribed VSG gene, indicating that a DSB is a natural intermediate of VSG gene conversion and that VSG switching is the result of the resolution of this DSB by break-induced replication.
C1 [Boothroyd, Catharine E.; Leonova, Tatyana; Ly, K. Ina; Papavasiliou, F. Nina] Rockefeller Univ, Lab Lymphocyte Biol, New York, NY 10065 USA.
   [Dreesen, Oliver; Figueiredo, Luisa M.; Cross, George A. M.] Rockefeller Univ, Mol Parasitol Lab, New York, NY 10065 USA.
C3 Rockefeller University; Rockefeller University
RP Papavasiliou, FN (corresponding author), Rockefeller Univ, Lab Lymphocyte Biol, New York, NY 10065 USA.
EM papavas@rockefeller.edu
FU the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health [R01AI021729]; C. H. Revson Foundation; German National Academic Foundation; Otto Ritter Foundation; W. M. Keck Foundation; Irma T. Hirschl Foundation
NR 30
TC 117
Z9 130
U1 0
U2 11
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 278
EP U168
DI 10.1038/nature07982
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100047
PM 19369939
DA 2026-03-09
ER

PT J
AU Thybo, H
   Nielsen, CA
AF Thybo, H.
   Nielsen, C. A.
TI Magma-compensated crustal thinning in continental rift zones
SO NATURE
LA English
DT Article
ID kenya rift; lithospheric structure; central-asia; baikal; mongolia; tectonics; intrusion; evolution; atlantic; basalts
AB Continental rift zones are long, narrow tectonic depressions in the Earth's surface where the entire lithosphere has been modified in extension(1). Rifting can eventually lead to rupture of the continental lithosphere and creation of new oceanic lithosphere or, alternatively, lead to formation of wide sedimentary basins around failed rift zones. Conventional models of rift zones include three characteristic features: surface manifestation as an elongated topographic trough, Moho shallowing due to crustal thinning, and reduced seismic velocity in the uppermost mantle due to decompression melting or heating from the Earth's interior(2-4). Here we demonstrate that only the surface manifestation is observed at the Baikal rift zone, whereas the crustal and mantle characteristics can be ruled out by a new seismic profile across southern Lake Baikal in Siberia. Instead we observe a localized zone in the lower crust which has exceptionally high seismic velocity and is highly reflective. We suggest that the expected Moho uplift was compensated by magmatic intrusion into the lower crust, producing the observed high- velocity zone. This finding demonstrates a previously unknown role for magmatism in rifting processes with significant implications for estimation of stretching factors and modelling of sedimentary basins around failed rift structures.
C1 [Thybo, H.; Nielsen, C. A.] Univ Copenhagen, Dept Geog & Geol, Oester Voldgade 10, DK-1350 Copenhagen K, Denmark.
C3 University of Copenhagen
RP Thybo, H (corresponding author), Univ Copenhagen, Dept Geog & Geol, Oester Voldgade 10, DK-1350 Copenhagen K, Denmark.
EM thybo@geo.ku.dk
FU Carlsberg Foundation; Danish Natural Science Research Council; Russian Academy of Sciences; Siberian Branch; Polish Academy of Sciences
NR 32
TC 198
Z9 216
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 12
PY 2009
VL 457
IS 7231
BP 873
EP 876
DI 10.1038/nature07688
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700043
PM 19212408
DA 2026-03-09
ER

PT J
AU Berriman, M
   Haas, BJ
   LoVerde, PT
   Wilson, RA
   Dillon, GP
   Cerqueira, GC
   Mashiyama, ST
   Al-Lazikani, B
   Andrade, LF
   Ashton, PD
   Aslett, MA
   Bartholomeu, DC
   Blandin, G
   Caffrey, CR
   Coghlan, A
   Coulson, R
   Day, TA
   Delcher, A
   DeMarco, R
   Djikeng, A
   Eyre, T
   Gamble, JA
   Ghedin, E
   Gu, Y
   Hertz-Fowler, C
   Hirai, H
   Hirai, Y
   Houston, R
   Ivens, A
   Johnston, DA
   Lacerda, D
   Macedo, CD
   McVeigh, P
   Ning, ZM
   Oliveira, G
   Overington, JP
   Parkhill, J
   Pertea, M
   Pierce, RJ
   Protasio, AV
   Quail, MA
   Rajandream, MA
   Rogers, J
   Sajid, M
   Salzberg, SL
   Stanke, M
   Tivey, AR
   White, O
   Williams, DL
   Wortman, J
   Wu, WJ
   Zamanian, M
   Zerlotini, A
   Fraser-Liggett, CM
   Barrell, BG
   El-Sayed, NM
AF Berriman, Matthew
   Haas, Brian J.
   LoVerde, Philip T.
   Wilson, R. Alan
   Dillon, Gary P.
   Cerqueira, Gustavo C.
   Mashiyama, Susan T.
   Al-Lazikani, Bissan
   Andrade, Luiza F.
   Ashton, Peter D.
   Aslett, Martin A.
   Bartholomeu, Daniella C.
   Blandin, Gaelle
   Caffrey, Conor R.
   Coghlan, Avril
   Coulson, Richard
   Day, Tim A.
   Delcher, Art
   DeMarco, Ricardo
   Djikeng, Appolinaire
   Eyre, Tina
   Gamble, John A.
   Ghedin, Elodie
   Gu, Yong
   Hertz-Fowler, Christiane
   Hirai, Hirohisha
   Hirai, Yuriko
   Houston, Robin
   Ivens, Alasdair
   Johnston, David A.
   Lacerda, Daniela
   Macedo, Camila D.
   McVeigh, Paul
   Ning, Zemin
   Oliveira, Guilherme
   Overington, John P.
   Parkhill, Julian
   Pertea, Mihaela
   Pierce, Raymond J.
   Protasio, Anna V.
   Quail, Michael A.
   Rajandream, Marie-Adele
   Rogers, Jane
   Sajid, Mohammed
   Salzberg, Steven L.
   Stanke, Mario
   Tivey, Adrian R.
   White, Owen
   Williams, David L.
   Wortman, Jennifer
   Wu, Wenjie
   Zamanian, Mostafa
   Zerlotini, Adhemar
   Fraser-Liggett, Claire M.
   Barrell, Barclay G.
   El-Sayed, Najib M.
TI The genome of the blood fluke Schistosoma mansoni
SO NATURE
LA English
DT Article
ID hidden markov model; embryonic-development; trypanosoma-cruzi; gene; database; sequence; retrotransposons; diversity; discovery; alignment
AB Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
C1 [Berriman, Matthew; Aslett, Martin A.; Eyre, Tina; Gamble, John A.; Gu, Yong; Hertz-Fowler, Christiane; Houston, Robin; Ivens, Alasdair; Parkhill, Julian; Protasio, Anna V.; Quail, Michael A.; Rajandream, Marie-Adele; Rogers, Jane; Tivey, Adrian R.; Barrell, Barclay G.] Wellcome Trust Sanger Inst, Cambridge CB10 1SD, England.
   [Coulson, Richard; Overington, John P.] European Bioinformat Inst EMBL, Cambridge CB10 1SD, England.
   [Haas, Brian J.; Bartholomeu, Daniella C.; Blandin, Gaelle; Djikeng, Appolinaire; Ghedin, Elodie; Lacerda, Daniela; White, Owen; Wortman, Jennifer; Fraser-Liggett, Claire M.; El-Sayed, Najib M.] J Craig Venter Inst, Inst Genom Res, Rockville, MD 20850 USA.
   [LoVerde, Philip T.; Ashton, Peter D.; Wu, Wenjie] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
   [LoVerde, Philip T.; Ashton, Peter D.; Wu, Wenjie] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
   [Wilson, R. Alan; Dillon, Gary P.; DeMarco, Ricardo] Univ York, Dept Biol, York YO10 5YW, N Yorkshire, England.
   [Cerqueira, Gustavo C.; Macedo, Camila D.; El-Sayed, Najib M.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
   [Cerqueira, Gustavo C.; Delcher, Art; Pertea, Mihaela; Salzberg, Steven L.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
   [Cerqueira, Gustavo C.; Macedo, Camila D.; Salzberg, Steven L.; El-Sayed, Najib M.] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA.
   [Mashiyama, Susan T.; Caffrey, Conor R.; Sajid, Mohammed] Univ Calif San Francisco, Sandler Ctr Basic Res Parasit Dis, San Francisco, CA 94158 USA.
   [Mashiyama, Susan T.] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94158 USA.
   [Mashiyama, Susan T.] Univ Calif San Francisco, Dept Pharmaceut Chem, Calif Inst Quantitat Biomed Res QB3, San Francisco, CA 94158 USA.
   [Al-Lazikani, Bissan; Zerlotini, Adhemar] Inst Canc Res, Haddow Labs, Canc Res UK Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England.
   [Andrade, Luiza F.; Oliveira, Guilherme] Fiocruz MS, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil.
   [Coghlan, Avril] Natl Univ Ireland Univ Coll Cork, Dept Microbiol, Cork, Ireland.
   [Day, Tim A.; McVeigh, Paul; Zamanian, Mostafa] Iowa State Univ, Dept Biomed Sci, Ames, IA 50011 USA.
   [DeMarco, Ricardo] Univ Sao Paulo, Inst Quim, BR-05508 Sao Paulo, Brazil.
   [DeMarco, Ricardo] Univ Sao Paulo, Inst Fis Sao Carlos, BR-05508 Sao Paulo, Brazil.
   [Hirai, Hirohisha; Hirai, Yuriko] Kyoto Univ, Primate Res Inst, Aichi 4848506, Japan.
   [Johnston, David A.] Nat Hist Museum, Biomed Parasitol Div, London SW7 5BD, England.
   [Pierce, Raymond J.] Univ Lille 2, INSERM, U547, Inst Pasteur Lille,IFR 142, Lille, France.
   [Stanke, Mario] Univ Gottingen, Inst Mikrobiol & Genet, Abt Bioinformat, D-37077 Gottingen, Germany.
   [Williams, David L.] Illinois State Univ, Dept Biol Sci, Normal, IL 61790 USA.
C3 Wellcome Trust Sanger Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; J. Craig Venter Institute; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; University of York - UK; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; 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 London; Institute of Cancer Research - UK; Cancer Research UK; Fundacao Oswaldo Cruz; Fiocruz - Research Center Rene Rachou; University College Cork; Iowa State University; Universidade de Sao Paulo; Universidade de Sao Paulo; Kyoto University; Natural History Museum London; Pasteur Network; Universite de Lille; Institut Pasteur Lille; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Gottingen; Illinois State University
RP Berriman, M (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
EM mb4@sanger.ac.uk; elsayed@umd.edu
FU Wellcome Trust [WT085775/Z/08/Z]; National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) [AI48828]; Oyama Health Foundation; Japan Society for the Promotion of Science [13557021]; Japan's Ministry of Education, Culture, Sports, Science and Technology; Sandler Foundation; NIH-Fogarty [5D43TW006580, 5D43TW007012-03]; NIH [AI054711-01A2]; PhRMA Foundation; Burroughs Wellcome Fund; United Nations Children's Fund (UNICEF)/United Nations Development Program (UNDP)/World bank/World Health Organization (WHO); CAPES; FAPESP;  [FAPEMIG REDE-281/05]; Grants-in-Aid for Scientific Research [13557021] Funding Source: KAKEN
NR 85
TC 851
Z9 947
U1 1
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 JUL 16
PY 2009
VL 460
IS 7253
BP 352
EP U65
DI 10.1038/nature08160
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000029
PM 19606141
DA 2026-03-09
ER

PT J
AU Frei, R
   Gaucher, C
   Poulton, SW
   Canfield, DE
AF Frei, Robert
   Gaucher, Claudio
   Poulton, Simon W.
   Canfield, Don E.
TI Fluctuations in Precambrian atmospheric oxygenation recorded by chromium isotopes
SO NATURE
LA English
DT Article
ID hexavalent chromium; rise; reduction; ediacaran; evolution; oxidation; ratios; earth
AB Geochemical data(1-4) suggest that oxygenation of the Earth's atmosphere occurred in two broad steps. The first rise in atmospheric oxygen is thought to have occurred between similar to 2.45 and 2.2 Gyr ago(1,5), leading to a significant increase in atmospheric oxygen concentrations and concomitant oxygenation of the shallow surface ocean. The second increase in atmospheric oxygen appears to have taken place in distinct stages during the late Neoproterozoic era (similar to 800-542 Myr ago)(3,4), ultimately leading to oxygenation of the deep ocean similar to 580 Myr ago(3), but details of the evolution of atmospheric oxygenation remain uncertain. Here we use chromium (Cr) stable isotopes from banded iron formations (BIFs) to track the presence of Cr(VI) in Precambrian oceans, providing a time-resolved picture of the oxygenation history of the Earth's atmosphere-hydrosphere system. The geochemical behaviour of Cr is highly sensitive to the redox state of the surface environment because oxidative weathering processes produce the oxidized hexavalent [Cr(VI)] form. Oxidation of reduced trivalent [Cr(III)] chromium on land is accompanied by an isotopic fractionation, leading to enrichment of the mobile hexavalent form in the heavier isotope. Our fractionated Cr isotope data indicate the accumulation of Cr(VI) in ocean surface waters similar to 2.8 to 2.6 Gyr ago and a likely transient elevation in atmospheric and surface ocean oxygenation before the first great rise of oxygen 2.45-2.2 Gyr ago ( the Great Oxidation Event)(1,5). In similar to 1.88-Gyr-old BIFs we find that Cr isotopes are not fractionated, indicating a decline in atmospheric oxygen. Our findings suggest that the Great Oxidation Event did not lead to a unidirectional stepwise increase in atmospheric oxygen. In the late Neoproterozoic, we observe strong positive fractionations in Cr isotopes (delta(53) Cr up to +4.9 parts per thousand), providing independent support for increased surface oxygenation at that time, which may have stimulated rapid evolution of macroscopic multicellular life(3,4,6).
C1 [Frei, Robert; Gaucher, Claudio] Univ Copenhagen, Inst Geog & Geol, DK-1350 Copenhagen, Denmark.
   [Frei, Robert; Gaucher, Claudio] Univ Copenhagen, Nord Ctr Earth Evolut, DK-1350 Copenhagen, Denmark.
   [Gaucher, Claudio] Fac Ciencias, Dept Geol, Montevideo 11400, Uruguay.
   [Poulton, Simon W.] Univ Newcastle, Sch Civil Engn & Geosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Canfield, Don E.] Univ So Denmark, Inst Biol, DK-5230 Odense, Denmark.
   [Canfield, Don E.] Nord Ctr Earth Evolut, DK-5230 Odense, Denmark.
C3 University of Copenhagen; University of Copenhagen; Universidad de la Republica, Uruguay; Newcastle University - UK; University of Southern Denmark
RP Frei, R (corresponding author), Univ Copenhagen, Inst Geog & Geol, Oster Voldgade 10, DK-1350 Copenhagen, Denmark.
EM robertf@geo.ku.dk
FU Danish Agency for Science, Technology and Innovation; Danish National Research Foundation
NR 35
TC 512
Z9 592
U1 6
U2 334
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 10
PY 2009
VL 461
IS 7261
BP 250
EP U125
DI 10.1038/nature08266
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600041
PM 19741707
DA 2026-03-09
ER

PT J
AU Vinkovic, D
AF Vinkovic, Dejan
TI Radiation-pressure mixing of large dust grains in protoplanetary disks
SO NATURE
LA English
DT Article
ID solar nebula; evolution; tauri; transport; surface; stars
AB Dusty disks around young stars are formed out of interstellar dust that consists of amorphous, submicrometre grains. Yet the grains found in comets(1) and meteorites(2), and traced in the spectra of young stars(3), include large crystalline grains that must have undergone annealing or condensation at temperatures in excess of 1,000 K, even though they are mixed with surrounding material that never experienced temperatures as high as that(4). This prompted theories of large-scale mixing capable of transporting thermally altered grains from the inner, hot part of accretion disks to outer, colder disk regions(5-7), but all have assumptions that may be problematic(8-12). Here I report that infrared radiation arising from the dusty disk can loft grains bigger than one micrometre out of the inner disk, whereupon they are pushed outwards by stellar radiation pressure while gliding above the disk. Grains re-enter the disk at radii where it is too cold to produce sufficient infrared radiation-pressure support for a given grain size and solid density. Properties of the observed disks suggest that this process might be active in almost all young stellar objects and young brown dwarfs.
C1 Univ Split, Dept Phys, Split 21000, Croatia.
C3 University of Split
RP Vinkovic, D (corresponding author), Univ Split, Dept Phys, Nikole Tesle 12, Split 21000, Croatia.
EM vinkovic@pmfst.hr
NR 30
TC 41
Z9 42
U1 0
U2 5
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 227
EP 229
DI 10.1038/nature08032
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100035
PM 19444210
DA 2026-03-09
ER

PT J
AU Koralek, JD
   Weber, CP
   Orenstein, J
   Bernevig, BA
   Zhang, SC
   Mack, S
   Awschalom, DD
AF Koralek, J. D.
   Weber, C. P.
   Orenstein, J.
   Bernevig, B. A.
   Zhang, Shou-Cheng
   Mack, S.
   Awschalom, D. D.
TI Emergence of the persistent spin helix in semiconductor quantum wells
SO NATURE
LA English
DT Article
AB According to Noether's theorem(1), for every symmetry in nature there is a corresponding conservation law. For example, invariance with respect to spatial translation corresponds to conservation of momentum. In another well-known example, invariance with respect to rotation of the electron's spin, or SU(2) symmetry, leads to conservation of spin polarization. For electrons in a solid, this symmetry is ordinarily broken by spin-orbit coupling, allowing spin angular momentum to flow to orbital angular momentum. However, it has recently been predicted that SU(2) can be achieved in a two-dimensional electron gas, despite the presence of spin-orbit coupling(2). The corresponding conserved quantities include the amplitude and phase of a helical spin density wave termed the 'persistent spin helix'(2). SU(2) is realized, in principle, when the strengths of two dominant spin-orbit interactions, the Rashba(3) (strength parameterized by alpha) and linear Dresselhaus(4) (beta(1)) interactions, are equal. This symmetry is predicted to be robust against all forms of spin-independent scattering, including electron-electron interactions, but is broken by the cubic Dresselhaus term (beta(3)) and spin-dependent scattering. When these terms are negligible, the distance over which spin information can propagate is predicted to diverge as alpha approaches beta(1). Here we report experimental observation of the emergence of the persistent spin helix in GaAs quantum wells by independently tuning alpha and beta(1). Using transient spin-grating spectroscopy(5), we find a spin-lifetime enhancement of two orders of magnitude near the symmetry point. Excellent quantitative agreement with theory across a wide range of sample parameters allows us to obtain an absolute measure of all relevant spin-orbit terms, identifying beta(3) as the main SU(2)violating term in our samples. The tunable suppression of spin relaxation demonstrated in this work is well suited for application to spintronics(6,7).
C1 [Koralek, J. D.; Weber, C. P.; Orenstein, J.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Weber, C. P.] Santa Clara Univ, Dept Phys, Santa Clara, CA 95053 USA.
   [Orenstein, J.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Bernevig, B. A.] Princeton Univ, Princeton Ctr Theoret Sci, Princeton, NJ 08540 USA.
   [Zhang, Shou-Cheng] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Mack, S.; Awschalom, D. D.] Univ Calif Santa Barbara, Ctr Spintron & Quantum Computat, Santa Barbara, CA 93106 USA.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Santa Clara University; University of California System; University of California Berkeley; Princeton University; Stanford University; University of California System; University of California Santa Barbara
RP Koralek, JD (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
EM jdkoralek@lbl.gov
FU US Department of Energy, Office of Basic Energy Science, Materials Science and Engineering Division; US National Science Foundation and Office of Naval Research; Direct For Mathematical & Physical Scien [0801388] Funding Source: National Science Foundation; Division Of Materials Research [0801388] Funding Source: National Science Foundation
NR 27
TC 523
Z9 566
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 2
PY 2009
VL 458
IS 7238
BP 610
EP U73
DI 10.1038/nature07871
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200036
PM 19340077
DA 2026-03-09
ER

PT J
AU Sirotin, YB
   Das, A
AF Sirotin, Yevgeniy B.
   Das, Aniruddha
TI Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity
SO NATURE
LA English
DT Article
ID intrinsic signal; bold fmri; spectroscopy; stimulation; spikes; maps; v1
AB Haemodynamic signals underlying functional brain imaging ( for example, functional magnetic resonance imaging ( fMRI)) are assumed to reflect metabolic demand generated by local neuronal activity, with equal increases in haemodynamic signal implying equal increases in the underlying neuronal activity(1-6). Few studies have compared neuronal and haemodynamic signals in alert animals(7,8) to test for this assumed correspondence. Here we present evidence that brings this assumption into question. Using a dual-wavelength optical imaging technique(9) that independently measures cerebral blood volume and oxygenation, continuously, in alert behaving monkeys, we find two distinct components to the haemodynamic signal in the alert animals' primary visual cortex (V1). One component is reliably predictable from neuronal responses generated by visual input. The other component - of almost comparable strength - is a hither to unknown signal that entrains to task structure independently of visual input or of standard neural predictors of haemodynamics. This latter component shows predictive timing, with increases of cerebral blood volume in anticipation of trial onsets even in darkness. This trial- locked haemodynamic signal could be due to an accompanying V1 arterial pumping mechanism, closely matched in time, with peaks of arterial dilation entrained to predicted trial onsets. These findings ( tested in two animals) challenge the current understanding of the link between brain haemodynamics and local neuronal activity. They also suggest the existence of a novel preparatory mechanism in the brain that brings additional arterial blood to cortex in anticipation of expected tasks.
C1 [Sirotin, Yevgeniy B.; Das, Aniruddha] Columbia Univ, Dept Neurosci, New York, NY 10027 USA.
   [Das, Aniruddha] Columbia Univ, Dept Psychiat, New York, NY 10027 USA.
   [Das, Aniruddha] Columbia Univ, WM Keck Ctr Brain Plastic & Cognit, New York, NY 10027 USA.
   [Das, Aniruddha] Columbia Univ, Mahoney Ctr Brain & Behav, New York, NY 10027 USA.
   [Das, Aniruddha] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.
   [Das, Aniruddha] New York State Psychiat Inst & Hosp, Unit 87, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; New York State Psychiatry Institute
RP Das, A (corresponding author), Columbia Univ, Dept Neurosci, New York, NY 10027 USA.
EM ad2069@columbia.edu
FU Keck foundation; National Institutes of Health; Klingenstein Foundation; Gatsby Initiative in Brain Circuitry; Dana Foundation; National Research Service Award
NR 30
TC 323
Z9 384
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 JAN 22
PY 2009
VL 457
IS 7228
BP 475
EP U6
DI 10.1038/nature07664
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200046
PM 19158795
DA 2026-03-09
ER

PT J
AU Li, H
   Collado, M
   Villasante, A
   Strati, K
   Ortega, S
   Cañamero, M
   Blasco, MA
   Serrano, M
AF Li, Han
   Collado, Manuel
   Villasante, Aranzazu
   Strati, Katerina
   Ortega, Sagrario
   Canamero, Marta
   Blasco, Maria A.
   Serrano, Manuel
TI The Ink4/Arf locus is a barrier for iPS cell reprogramming
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; senescence; expression; ink4a/arf; genes; inhibitors; induction; cancer; p53
AB The mechanisms involved in the reprogramming of differentiated cells into induced pluripotent stem (iPS) cells by the three transcription factors Oct4 (also known as Pou5f1), Klf4 and Sox2 remain poorly understood1. The Ink4/Arf locus comprises the Cdkn2a Cdkn2b genes encoding three potent tumour suppressors, namely p16 Ink4a, p19 Arf and p15 Ink4b, which are basally expressed in differentiated cells and upregulated by aberrant mitogenic signals(2-4). Here we show that the locus is completely silenced in iPS cells, as well as in embryonic stem (ES) cells, acquiring the epigenetic marks of a bivalent chromatin domain, and retaining the ability to be reactivated after differentiation. Cell culture conditions during reprogramming enhance the expression of the Ink4/Arf locus, further highlighting the importance of silencing the locus to allow proliferation and reprogramming. Indeed, the three factors together repress the Ink4/Arf locus soon after their expression and concomitant with the appearance of the first molecular markers of 'stemness'. This downregulation also occurs in cells carrying the oncoprotein large-T, which functionally inactivates the pathways regulated by the Ink4/Arf locus, thus indicating that the silencing of the locus is intrinsic to reprogramming and not the result of a selective process. Genetic inhibition of the Ink4/Arf locus has a profound positive effect on the efficiency of iPS cell generation, increasing both the kinetics of reprogramming and the number of emerging iPS cell colonies. In murine cells, Arf, rather than Ink4a, is the main barrier to reprogramming by activation of p53 (encoded by Trp53) and p21 (encoded by Cdkn1a); whereas, in human fibroblasts, INK4a is more important than ARF. Furthermore, organismal ageing upregulates the Ink4/Arf locus(2,5) and, accordingly, reprogramming is less efficient in cells from old organisms, but this defect can be rescued by inhibiting the locus with a short hairpin RNA. All together, we conclude that the silencing of Ink4/Arf locus is rate-limiting for reprogramming, and its transient inhibition may significantly improve the generation of iPS cells.
C1 [Li, Han; Collado, Manuel; Villasante, Aranzazu; Serrano, Manuel] Spanish Natl Canc Res Ctr CNIO, Tumor Suppress Grp, 3 Melchor Fernandez Almagro St, E-28029 Madrid, Spain.
   [Strati, Katerina; Blasco, Maria A.] Spanish Natl Canc Res Ctr CNIO, Telomeres & Telomerase Grp, E-28029 Madrid, Spain.
   [Ortega, Sagrario] Spanish Natl Canc Res Ctr CNIO, Transgen Mice Unit, E-28029 Madrid, Spain.
   [Canamero, Marta] Spanish Natl Canc Res Ctr CNIO, Comparat Pathol Unit, E-28029 Madrid, Spain.
C3 Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO)
RP Serrano, M (corresponding author), Spanish Natl Canc Res Ctr CNIO, Tumor Suppress Grp, 3 Melchor Fernandez Almagro St, E-28029 Madrid, Spain.
EM mserrano@cnio.es
FU Spanish Ministry of Science (MICINN).; 'Ramon y Cajal' contract (MICINN).; Regional Government of Madrid; European Union; European Research Council (ERC),; 'Marcelino Botin' Foundation
NR 31
TC 784
Z9 915
U1 2
U2 125
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1136
EP 1139
DI 10.1038/nature08290
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000040
PM 19668188
DA 2026-03-09
ER

PT J
AU Malmström, J
   Beck, M
   Schmidt, A
   Lange, V
   Deutsch, EW
   Aebersold, R
AF Malmstroem, Johan
   Beck, Martin
   Schmidt, Alexander
   Lange, Vinzenz
   Deutsch, Eric W.
   Aebersold, Ruedi
TI Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans
SO NATURE
LA English
DT Article
ID tandem mass-spectrometry; electron-microscopy; escherichia-coli; absolute quantification; salmonella-typhimurium; tomography; expression; peptides; complex; ms
AB Mass-spectrometry-based methods for relative proteome quantification have broadly affected life science research. However, important research directions, particularly those involving mathematical modelling and simulation of biological processes, also critically depend on absolutely quantitative data-that is, knowledge of the concentration of the expressed proteins as a function of cellular state. Until now, absolute protein concentration measurements of a considerable fraction of the proteome (73%) have only been derived from genetically altered Saccharomyces cerevisiae cells(1), a technique that is not directly portable from yeast to other species. Here we present a mass-spectrometry-based strategy to determine the absolute quantity, that is, the average number of protein copies per cell in a cell population, for a large fraction of the proteome in genetically unperturbed cells. Applying the technology to the human pathogen Leptospira interrogans, a spirochete responsible for leptospirosis(2), we generated an absolute protein abundance scale for 83% of the mass-spectrometry-detectable proteome, from cells at different states. Taking advantage of the unique cellular dimensions of L. interrogans, we used cryo-electron tomography morphological measurements to verify, at the single-cell level, the average absolute abundance values of selected proteins determined by mass spectrometry on a population of cells. Because the strategy is relatively fast and applicable to any cell type, we expect that it will become a cornerstone of quantitative biology and systems biology.
C1 [Malmstroem, Johan; Beck, Martin; Schmidt, Alexander; Lange, Vinzenz; Aebersold, Ruedi] ETH, Swiss Fed Inst Technol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Schmidt, Alexander; Lange, Vinzenz; Aebersold, Ruedi] Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland.
   [Deutsch, Eric W.; Aebersold, Ruedi] Inst Syst Biol, Seattle, WA 98103 USA.
   [Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Institute for Systems Biology (ISB); University of Zurich
RP Aebersold, R (corresponding author), ETH, Swiss Fed Inst Technol, Inst Mol Syst Biol, Wolfgang Pauli Str 16, CH-8093 Zurich, Switzerland.
EM aebersold@imsb.biol.ethz.ch
FU ETH Zurich; Swiss National Science Foundation [31000-10767]; National Heart, Lung and Blood Institute; National Institutes of Health [N01-HV-28179]; ERC; Swedish Society for Medical Research; European Molecular Biology Organization; Marie Curie fellowship of the European Commission; Competence Center for Systems Physiology and Metabolic Diseases
NR 33
TC 355
Z9 378
U1 1
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 6
PY 2009
VL 460
IS 7256
BP 762
EP U112
DI 10.1038/nature08184
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300044
PM 19606093
DA 2026-03-09
ER

PT J
AU Hren, MT
   Tice, MM
   Chamberlain, CP
AF Hren, M. T.
   Tice, M. M.
   Chamberlain, C. P.
TI Oxygen and hydrogen isotope evidence for a temperate climate 3.42 billion years ago
SO NATURE
LA English
DT Article
ID south-africa; water; evolution; ratios; chert; geochemistry; transvaal; seawater; bearing; origin
AB Stable oxygen isotope ratios (delta O-18) of Precambrian cherts have been used to establish much of our understanding of the early climate history of Earth(1-3) and suggest that ocean temperatures during the Archaean era (similar to 3.5 billion years ago) were between 55 degrees C and 85 degrees C (ref. 2). But, because of uncertainty in the delta O-18 of the primitive ocean, there is considerable debate regarding this conclusion. Examination of modern and ancient cherts indicates that another approach, using a combined analysis of delta O-18 and hydrogen isotopes (delta D) rather than delta O-18 alone, can provide a firmer constraint on formational temperatures without independent knowledge of the isotopic composition of ambient waters(4,5). Here we show that delta O-18 and delta D sampled from 3.42-billion-year-old Buck Reef Chert rocks in South Africa are consistent with formation from waters at varied low temperatures. The most O-18-enriched Buck Reef Chert rocks record the lowest diagenetic temperatures and were formed in equilibrium with waters below similar to 40 degrees C. Geochemical and sedimentary evidence suggests that the Buck Reef Chert was formed in shallow to deep marine conditions, so our results indicate that the Palaeoarchaean ocean was isotopically depleted relative to the modern ocean and far cooler (<= 40 degrees) than previously thought(2).
C1 [Hren, M. T.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06511 USA.
   [Tice, M. M.] Texas A&M Univ, Dept Geol & Geophys, College Stn, TX 77843 USA.
   [Chamberlain, C. P.] Stanford Univ, Dept Environm Earth Syst Sci, Stanford, CA 94305 USA.
C3 Yale University; Texas A&M University System; Texas A&M University College Station; Stanford University
RP Hren, MT (corresponding author), Univ Michigan, Dept Geol Sci, 2534 CC Little Bldg,1100 N Univ Ave, Ann Arbor, MI 48109 USA.
EM mhren@umich.edu; tice@geo.tamu.edu
NR 30
TC 138
Z9 167
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 12
PY 2009
VL 462
IS 7270
BP 205
EP 208
DI 10.1038/nature08518
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100040
PM 19907491
DA 2026-03-09
ER

PT J
AU Reilly, LAO
   Tai, L
   Lee, L
   Kruse, EA
   Grabow, S
   Fairlie, WD
   Haynes, NM
   Tarlinton, DM
   Zhang, JG
   Belz, GT
   Smyth, MJ
   Bouillet, P
   Robb, L
   Strasser, A
AF Reilly, Lorraine A. O'
   Tai, Lin
   Lee, Lily
   Kruse, Elizabeth A.
   Grabow, Stephanie
   Fairlie, W. Douglas
   Haynes, Nicole M.
   Tarlinton, David M.
   Zhang, Jian-Guo
   Belz, Gabrielle T.
   Smyth, Mark J.
   Bouillet, Philippe
   Robb, Lorraine
   Strasser, Andreas
TI Membrane-bound Fas ligand only is essential for Fas-induced apoptosis
SO NATURE
LA English
DT Article
ID autoimmune lymphoproliferative syndrome; dendritic cells; down-regulation; regulators bim; immune-system; mice; gene; expression; death; activation
AB Fas ligand (FasL), an apoptosis-inducing member of the TNF cytokine family, and its receptor Fas are critical for the shutdown of chronic immune responses(1-3) and prevention of autoimmunity(4,5). Accordingly, mutations in their genes cause severe lymphadenopathy and autoimmune disease in mice(6,7) and humans(8,9). FasL function is regulated by deposition in the plasma membrane and metalloprotease-mediated shedding(10,11). Here we generated gene-targeted mice that selectively lack either secreted FasL (sFasL) or membrane-bound FasL (mFasL) to resolve which of these forms is required for cell killing and to explore their hypothesized non-apoptotic activities. Mice lacking sFasL (FasL(Delta s/Delta s)) appeared normal and their T cells readily killed target cells, whereas T cells lacking mFasL (FasL(Delta m/Delta m)) could not kill cells through Fas activation. FasL(Delta m/Delta m) mice developed lymphadenopathy and hypergammaglobulinaemia, similar to FasL(gld/gld) mice, which express a mutant form of FasL that cannot bind Fas, but surprisingly, FasL(Delta m/Delta m) mice (on a C57BL/6 background) succumbed to systemic lupus erythematosus (SLE)-like autoimmune kidney destruction and histiocytic sarcoma, diseases that occur only rarely and much later in FasL(gld/gld) mice. These results demonstrate that mFasL is essential for cytotoxic activity and constitutes the guardian against lymphadenopathy, autoimmunity and cancer, whereas excess sFasL appears to promote autoimmunity and tumorigenesis through nonapoptotic activities.
C1 [Reilly, Lorraine A. O'; Tai, Lin; Lee, Lily; Kruse, Elizabeth A.; Grabow, Stephanie; Fairlie, W. Douglas; Tarlinton, David M.; Zhang, Jian-Guo; Belz, Gabrielle T.; Bouillet, Philippe; Robb, Lorraine; Strasser, Andreas] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Kruse, Elizabeth A.; Grabow, Stephanie] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
   [Haynes, Nicole M.; Smyth, Mark J.] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
C3 Walter & Eliza Hall Institute; University of Melbourne; Peter Maccallum Cancer Center
RP Strasser, A (corresponding author), Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
EM strasser@wehi.edu.au
FU NHMRC [461221, 454569]; IRIISS [361646, 257502]; Victorian State Government; Leukemia and Lymphoma Society [7015]; NIH [CA043540-18, CA80188-6]; JDRF/NHMRC; Association for International Cancer Research; Charles and Sylvia Viertel Charitable Foundation; Leukemia Research Foundation; National Health and Medical Research Council (NHMRC) [454569, 461221] Funding Source: National Health and Medical Research Council (NHMRC)
NR 41
TC 329
Z9 374
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 1
PY 2009
VL 461
IS 7264
BP 659
EP U106
DI 10.1038/nature08402
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600042
PM 19794494
DA 2026-03-09
ER

PT J
AU Fang, C
   Frontiera, RR
   Tran, R
   Mathies, RA
AF Fang, Chong
   Frontiera, Renee R.
   Tran, Rosalie
   Mathies, Richard A.
TI Mapping GFP structure evolution during proton transfer with femtosecond Raman spectroscopy
SO NATURE
LA English
DT Article
ID green fluorescent protein; excited-state dynamics; stimulated raman; molecular-dynamics; aequorea; isomerization; perturbation; vision; light
AB Tracing the transient atomic motions that lie at the heart of chemical reactions requires high-resolution multidimensional structural information on the timescale of molecular vibrations, which commonly range from 10 fs to 1 ps. For simple chemical systems, it has been possible to map out in considerable detail the reactive potential-energy surfaces describing atomic motions and resultant reaction dynamics(1), but such studies remain challenging for complex chemical and biological transformations(2). A case in point is the green fluorescent protein (GFP)(3-5) from the jellyfish Aequorea victoria, which is a widely used gene expression marker owing to its efficient bioluminescence. This feature is known to arise from excited-state proton transfer (ESPT)(6-8), yet the atomistic details of the process are still not fully understood. Here we show that femtosecond stimulated Raman spectroscopy(9,10) provides sufficiently detailed and time-resolved vibrational spectra of the electronically excited chromophore of GFP to reveal skeletal motions involved in the proton transfer that produces the fluorescent form of the protein. In particular, we observe that the frequencies and intensities of two marker bands, the C-O and C=N stretching modes at opposite ends of the conjugated chromophore, oscillate out of phase with a period of 280 fs; we attribute these oscillations to impulsively excited low-frequency phenoxyl-ring motions, which optimize the geometry of the chromophore for ESPT. Our findings illustrate that femtosecond simulated Raman spectroscopy is a powerful approach to revealing the real-time nuclear dynamics that make up a multidimensional polyatomic reaction coordinate.
C1 [Fang, Chong; Frontiera, Renee R.; Tran, Rosalie; Mathies, Richard A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Mathies, RA (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM ramathies@berkeley.edu
FU Mathies Royalty Fund
NR 29
TC 414
Z9 470
U1 3
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 NOV 12
PY 2009
VL 462
IS 7270
BP 200
EP U74
DI 10.1038/nature08527
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100039
PM 19907490
DA 2026-03-09
ER

PT J
AU Hong, H
   Takahashi, K
   Ichisaka, T
   Aoi, T
   Kanagawa, O
   Nakagawa, M
   Okita, K
   Yamanaka, S
AF Hong, Hyenjong
   Takahashi, Kazutoshi
   Ichisaka, Tomoko
   Aoi, Takashi
   Kanagawa, Osami
   Nakagawa, Masato
   Okita, Keisuke
   Yamanaka, Shinya
TI Suppression of induced pluripotent stem cell generation by the p53-p21 pathway
SO NATURE
LA English
DT Article
ID somatic-cells; mouse; p53; fibroblasts; myc
AB Induced pluripotent stem(iPS) cells can be generated from somatic cells by the introduction of Oct3/4 ( also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse(1-4) and in human(5-8). The efficiency of this process, however, is low(9). Pluripotency can be induced without c-Myc, but with even lower efficiency(10,11). A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation(12), but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53-p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation.
C1 [Hong, Hyenjong; Takahashi, Kazutoshi; Ichisaka, Tomoko; Aoi, Takashi; Nakagawa, Masato; Okita, Keisuke; Yamanaka, Shinya] Kyoto Univ, Inst Integrated Cell Mat Sci, Ctr iPS Cell Res & Applicat CiRA, Kyoto 6068507, Japan.
   [Hong, Hyenjong; Nakagawa, Masato; Yamanaka, Shinya] Kyoto Univ, Inst Frontier Med Sci, Dept Stem Cell Biol, Kyoto 6068507, Japan.
   [Ichisaka, Tomoko; Yamanaka, Shinya] Japan Sci & Technol Agcy, Yamanaka iPS Cell Special Project, Kawaguchi, Saitama 3320012, Japan.
   [Kanagawa, Osami] RIKEN Yokohama Inst, RIKEN Ctr Allergy & Immunol, Lab Autoimmune Regulat, Tsurumi Ku, Kanagawa 2300045, Japan.
   [Yamanaka, Shinya] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
C3 Kyoto University; Kyoto University; Japan Science & Technology Agency (JST); RIKEN; University of California System; University of California San Francisco; The J David Gladstone Institutes
RP Yamanaka, S (corresponding author), Kyoto Univ, Inst Integrated Cell Mat Sci, Ctr iPS Cell Res & Applicat CiRA, Kyoto 6068507, Japan.
EM yamanaka@frontier.kyoto-u.ac.jp
FU Leading Project of MEXT; JSPS and MEXT; Program for Promotion of Fundamental Studies in Health Sciences of NIBIO; Japanese Government ( MEXT)
NR 23
TC 1039
Z9 1274
U1 1
U2 290
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1132
EP 1135
DI 10.1038/nature08235
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000039
PM 19668191
DA 2026-03-09
ER

PT J
AU Neugebauer, JM
   Amack, JD
   Peterson, AG
   Bisgrove, BW
   Yost, HJ
AF Neugebauer, Judith M.
   Amack, Jeffrey D.
   Peterson, Annita G.
   Bisgrove, Brent W.
   Yost, H. Joseph
TI FGF signalling during embryo development regulates cilia length in diverse epithelia
SO NATURE
LA English
DT Article
ID left-right asymmetry; left-right axis; zebrafish fin regeneration; kupffers vesicle; leftward flow; cells; specification; inhibition; xenopus; mutant
AB Cilia are cell surface organelles found on most epithelia in vertebrates. Specialized groups of cilia have critical roles in embryonic development, including left-right axis formation. Recently, cilia have been implicated as recipients of cell-cell signalling(1,2). However, little is known about cell-cell signalling pathways that control the length of cilia(3). Here we provide several lines of evidence showing that fibroblast growth factor (FGF) signalling regulates cilia length and function in diverse epithelia during zebrafish and Xenopus development. Morpholino knockdown of FGF receptor 1 (Fgfr1) in zebrafish cell-autonomously reduces cilia length in Kupffer's vesicle and perturbs directional fluid flow required for left-right patterning of the embryo. Expression of a dominant-negative FGF receptor (DN-Fgfr1), treatment with SU5402 ( a pharmacological inhibitor of FGF signalling) or genetic and morpholino reduction of redundant FGF ligands Fgf8 and Fgf24 reproduces this cilia length phenotype. Knockdown of Fgfr1 also results in shorter tethering cilia in the otic vesicle and shorter motile cilia in the pronephric ducts. In Xenopus, expression of a dn-fgfr1 results in shorter monocilia in the gastrocoel roof plate that control left-right patterning(4) and in shorter multicilia in external mucociliary epithelium. Together, these results indicate a fundamental and highly conserved role for FGF signalling in the regulation of cilia length in multiple tissues. Abrogation of Fgfr1 signalling downregulates expression of two ciliogenic transcription factors, foxj1 and rfx2, and of the intraflagellar transport gene ift88 (also known as polaris), indicating that FGF signalling mediates cilia length through an Fgf8/Fgf24-Fgfr1-intraflagellar transport pathway. We propose that a subset of developmental defects and diseases ascribed to FGF signalling are due in part to loss of cilia function.
C1 [Neugebauer, Judith M.; Amack, Jeffrey D.; Peterson, Annita G.; Bisgrove, Brent W.; Yost, H. Joseph] Univ Utah, Sch Med, Dept Neurobiol & Anat, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah
RP Yost, HJ (corresponding author), Univ Utah, Sch Med, Dept Neurobiol & Anat, Eccles Inst Human Genet, Bldg 533,Room 3160,15 North 2030 East, Salt Lake City, UT 84112 USA.
EM jyost@genetics.utah.edu
FU American Heart Association; NRSA Postdoctoral fellowship; NHLBI; NICHD; Primary Children's Medical Foundation
NR 33
TC 207
Z9 248
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 2
PY 2009
VL 458
IS 7238
BP 651
EP U119
DI 10.1038/nature07753
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200045
PM 19242413
DA 2026-03-09
ER

PT J
AU O'Gorman, CM
   Fuller, HT
   Dyer, PS
AF O'Gorman, Celine M.
   Fuller, Hubert T.
   Dyer, Paul S.
TI Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus
SO NATURE
LA English
DT Article
ID polymorphic dna markers; mating-type; sequence; systems; heterothallism; teleomorph; biology
AB Aspergillus fumigatus is a saprotrophic fungus whose spores are ubiquitous in the atmosphere(1). It is also an opportunistic human pathogen in immunocompromised individuals, causing potentially lethal invasive infections(2,3), and is associated with severe asthma and sinusitis(4). The species is only known to reproduce by asexual means(5), but there has been accumulating evidence for recombination and gene flow from population genetic studies(5-8), genome analysis(9,10), the presence of mating- type genes(8,10) and expression of sex- related genes(8) in the fungus. Here we show that A. fumigatus possesses a fully functional sexual reproductive cycle that leads to the production of cleistothecia and ascospores, and the teleomorph Neosartorya fumigata is described. The species has a heterothallic breeding system; isolates of complementary mating types are required for sex to occur. We demonstrate increased genotypic variation resulting from recombination between mating type and DNA fingerprint markers in ascospore progeny from an Irish environmental subpopulation. The ability of A. fumigatus to engage in sexual reproduction is highly significant in understanding the biology and evolution of the species. The presence of a sexual cycle provides an invaluable tool for classical genetic analyses and will facilitate research into the genetic basis of pathogenicity and fungicide resistance in A. fumigatus, with the aim of improving methods for the control of aspergillosis. These results also yield insights into the potential for sexual reproduction in other supposedly 'asexual' fungi.
C1 [O'Gorman, Celine M.; Fuller, Hubert T.] Univ Coll Dublin, Sch Biol & Environm Sci, Dublin 4, Ireland.
   [O'Gorman, Celine M.; Dyer, Paul S.] Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England.
C3 University College Dublin; University of Nottingham
RP O'Gorman, CM (corresponding author), Univ Coll Dublin, Sch Biol & Environm Sci, Dublin 4, Ireland.
EM celine.ogorman@ucd.ie; paul.dyer@nottingham.ac.uk
FU IRCSET Postgraduate Research Scholarship; EC Marie Curie Training Fellowship; British Mycological Society
NR 47
TC 371
Z9 473
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 JAN 22
PY 2009
VL 457
IS 7228
BP 471
EP U5
DI 10.1038/nature07528
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200045
PM 19043401
DA 2026-03-09
ER

PT J
AU Roushan, P
   Seo, J
   Parker, CV
   Hor, YS
   Hsieh, D
   Qian, D
   Richardella, A
   Hasan, MZ
   Cava, RJ
   Yazdani, A
AF Roushan, Pedram
   Seo, Jungpil
   Parker, Colin V.
   Hor, Y. S.
   Hsieh, D.
   Qian, Dong
   Richardella, Anthony
   Hasan, M. Z.
   Cava, R. J.
   Yazdani, Ali
TI Topological surface states protected from backscattering by chiral spin texture
SO NATURE
LA English
DT Article
ID interference; insulator; phase
AB Topological insulators are a new class of insulators in which a bulk gap for electronic excitations is generated because of the strong spin-orbit coupling(1-5) inherent to these systems. These materials are distinguished from ordinary insulators by the presence of gapless metallic surface states, resembling chiral edge modes in quantum Hall systems, but with unconventional spin textures. A key predicted feature of such spin-textured boundary states is their insensitivity to spin-independent scattering, which is thought to protect them from backscattering and localization. Recently, experimental and theoretical efforts have provided strong evidence for the existence of both two-and three-dimensional classes of such topological insulator materials in semiconductor quantum well structures(6-8) and several bismuth-based compounds(9-13), but so far experiments have not probed the sensitivity of these chiral states to scattering. Here we use scanning tunnelling spectroscopy and angle-resolved photoemission spectroscopy to visualize the gapless surface states in the three-dimensional topological insulator Bi1-xSbx, and examine in detail the influence of scattering from disorder caused by random alloying in this compound. We show that, despite strong atomic scale disorder, backscattering between states of opposite momentum and opposite spin is absent. Our observations demonstrate that the chiral nature of these states protects the spin of the carriers. These chiral states are therefore potentially useful for spin-based electronics, in which long spin coherence is critical(14), and also for quantum computing applications, where topological protection can enable fault-tolerant information processing(15,16).
C1 [Roushan, Pedram; Seo, Jungpil; Parker, Colin V.; Hsieh, D.; Qian, Dong; Richardella, Anthony; Hasan, M. Z.; Cava, R. J.; Yazdani, Ali] Princeton Univ, Joseph Henry Labs, Princeton, NJ 08544 USA.
   [Roushan, Pedram; Seo, Jungpil; Parker, Colin V.; Hsieh, D.; Qian, Dong; Richardella, Anthony; Hasan, M. Z.; Cava, R. J.; Yazdani, Ali] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
   [Hor, Y. S.] 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 ONR; ARO; DOE; NSF-DMR; NSF-MRSEC; NSF graduate fellowship; Direct For Mathematical & Physical Scien; Division Of Materials Research [0819860] Funding Source: National Science Foundation
NR 28
TC 925
Z9 1053
U1 8
U2 409
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1106
EP 1109
DI 10.1038/nature08308
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000033
PM 19668187
DA 2026-03-09
ER

PT J
AU Hellier, C
   Anderson, DR
   Cameron, AC
   Gillon, M
   Hebb, L
   Maxted, PFL
   Queloz, D
   Smalley, B
   Triaud, AHMJ
   West, RG
   Wilson, DM
   Bentley, SJ
   Enoch, B
   Horne, K
   Irwin, J
   Lister, TA
   Mayor, M
   Parley, N
   Pepe, F
   Pollacco, DL
   Segransan, D
   Udry, S
   Wheatley, PJ
AF Hellier, Coel
   Anderson, D. R.
   Cameron, A. Collier
   Gillon, M.
   Hebb, L.
   Maxted, P. F. L.
   Queloz, D.
   Smalley, B.
   Triaud, A. H. M. J.
   West, R. G.
   Wilson, D. M.
   Bentley, S. J.
   Enoch, B.
   Horne, K.
   Irwin, J.
   Lister, T. A.
   Mayor, M.
   Parley, N.
   Pepe, F.
   Pollacco, D. L.
   Segransan, D.
   Udry, S.
   Wheatley, P. J.
TI An orbital period of 0.94 days for the hot-Jupiter planet WASP-18b
SO NATURE
LA English
DT Article
ID transiting planet; extrasolar; evolution; candidates
AB The 'hot Jupiters' that abound in lists of known extrasolar planets are thought to have formed far from their host stars, but migrate inwards through interactions with the proto-planetary disk from which they were born(1,2), or by an alternative mechanism such as planet-planet scattering(3). The hot Jupiters closest to their parent stars, at orbital distances of only similar to 0.02 astronomical units, have strong tidal interactions(4,5), and systems such as OGLE-TR-56 have been suggested as tests of tidal dissipation theory(6,7). Here we report the discovery of planet WASP-18b with an orbital period of 0.94 days and a mass of ten Jupiter masses (10 M-Jup), resulting in a tidal interaction an order of magnitude stronger than that of planet OGLE-TR-56b. Under the assumption that the tidal-dissipation parameter Q of the host star is of the order of 10 6, as measured for Solar System bodies and binary stars and as often applied to extrasolar planets, WASP-18b will be spiralling inwards on a timescale less than a thousandth that of the lifetime of its host star. Therefore either WASP-18 is in a rare, exceptionally short-lived state, or the tidal dissipation in this system (and possibly other hot-Jupiter systems) must be much weaker than in the Solar System.
C1 [Hellier, Coel; Anderson, D. R.; Maxted, P. F. L.; Smalley, B.; Wilson, D. M.; Bentley, S. J.] Keele Univ, Astrophys Grp, Keele ST5 5BG, Staffs, England.
   [Anderson, D. R.; Hebb, L.; Enoch, B.; Horne, K.; Parley, N.] Univ St Andrews, Sch Phys & Astron, Haugh KY16 9SS, Fife, Scotland.
   [Gillon, M.; Queloz, D.; Triaud, A. H. M. J.; Mayor, M.; Pepe, F.; Segransan, D.; Udry, S.] Univ Geneva, Observ Geneve, CH-1290 Sauverny, Switzerland.
   [Gillon, M.] Univ Liege, Inst Astrophys & Geophys, Liege 1, Belgium.
   [West, R. G.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Irwin, J.] Harvard Univ, Dept Astron, Cambridge, MA 02138 USA.
   [Lister, T. A.] Las Cumbres Observ, Santa Barbara, CA 93117 USA.
   [Pollacco, D. L.] Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
   [Wheatley, P. J.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
C3 Keele University; University of St Andrews; University of Geneva; University of Liege; University of Leicester; Harvard University; Queens University Belfast; University of Warwick
RP Hellier, C (corresponding author), Keele Univ, Astrophys Grp, Keele ST5 5BG, Staffs, England.
EM ch@astro.keele.ac.uk
FU UK's Science and Technology Facilities Council; STFC [ST/F002599/1, ST/G001987/1, ST/G002355/1, ST/F002270/1, ST/J000035/1, PP/F000081/1, PP/D000890/1, PP/D000955/1, PP/F000057/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/D000890/1, ST/F002599/1, PP/F000057/1, ST/G001987/1, PP/F000081/1, PP/D000955/1, ST/G002355/1, ST/F002270/1] Funding Source: researchfish
NR 27
TC 208
Z9 223
U1 0
U2 14
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1098
EP 1100
DI 10.1038/nature08245
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000031
PM 19713926
DA 2026-03-09
ER

PT J
AU Clemente-Blanco, A
   Mayán-Santos, M
   Schneider, DA
   Machín, F
   Jarmuz, A
   Tschochner, H
   Aragón, L
AF Clemente-Blanco, Andres
   Mayan-Santos, Maria
   Schneider, David A.
   Machin, Felix
   Jarmuz, Adam
   Tschochner, Herbert
   Aragon, Luis
TI Cdc14 inhibits transcription by RNA polymerase I during anaphase
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; budding yeast; chromosome condensation; nucleolar segregation; ribosomal dna; mitotic exit; cell-cycle; rdna; phosphatase; mitosis
AB Chromosome condensation and the global repression of gene transcription(1) are features of mitosis inmost eukaryotes. The logic behind this phenomenon is that chromosome condensation prevents the activity of RNA polymerases. In budding yeast, however, transcription was proposed to be continuous during mitosis(2). Here we show that Cdc14, a protein phosphatase required for nucleolar segregation(3) and mitotic exit(4), inhibits transcription of yeast ribosomal genes (rDNA) during anaphase. The phosphatase activity of Cdc14 is required for RNA polymerase I (Pol I) inhibition in vitro and in vivo. Moreover Cdc14-dependent inhibition involves nucleolar exclusion of Pol I subunits. We demonstrate that transcription inhibition is necessary for complete chromosome disjunction, because ribosomal RNA (rRNA) transcripts block condensin binding to rDNA, and show that bypassing the role of Cdc14 in nucleolar segregation requires in vivo degradation of nascent transcripts. Our results show that transcription interferes with chromosome condensation, not the reverse. We conclude that budding yeast, like most eukaryotes, inhibit Pol I transcription before segregation as a prerequisite for chromosome condensation and faithful genome separation.
C1 [Clemente-Blanco, Andres; Mayan-Santos, Maria; Machin, Felix; Jarmuz, Adam; Aragon, Luis] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, Cell Cycle Grp, London W12 0NN, England.
   [Schneider, David A.] Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
   [Tschochner, Herbert] Univ Regensburg, Inst Biochem Mikrobiol & Genet, Munich, Germany.
C3 Imperial College London; University of Alabama System; University of Alabama Birmingham; University of Regensburg
RP Aragón, L (corresponding author), Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, Cell Cycle Grp, Du Cane Rd, London W12 0NN, England.
EM luis.aragon@csc.mrc.ac.uk
FU Medical Research Council of the UK; UAB HSF-GEF; La Junta de Extremadura; Medical Research Council [MC_U120074328] Funding Source: researchfish; MRC [MC_U120074328] Funding Source: UKRI
NR 30
TC 103
Z9 116
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 219
EP U8
DI 10.1038/nature07652
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700047
PM 19158678
DA 2026-03-09
ER

PT J
AU Douglas, SM
   Dietz, H
   Liedl, T
   Högberg, B
   Graf, F
   Shih, WM
AF Douglas, Shawn M.
   Dietz, Hendrik
   Liedl, Tim
   Hoegberg, Bjoern
   Graf, Franziska
   Shih, William M.
TI Self-assembly of DNA into nanoscale three-dimensional shapes
SO NATURE
LA English
DT Article
ID double-crossover molecules; conductive nanowires; nanostructures; octahedron; nanotubes; complexes; lattices; design
AB Molecular self-assembly offers a 'bottom-up' route to fabrication with subnanometre precision of complex structures from simple components(1). DNA has proved to be a versatile building block(2-5) for programmable construction of such objects, including two-dimensional crystals(6), nanotubes(7-11), and three-dimensional wire-frame nanopolyhedra(12-17). Templated self-assembly of DNA(18) into custom two-dimensional shapes on the megadalton scale has been demonstrated previously with a multiple-kilobase 'scaffold strand' that is folded into a flat array of antiparallel helices by interactions with hundreds of oligonucleotide 'staple strands'(19,20). Here we extend this method to building custom three-dimensional shapes formed as pleated layers of helices constrained to a honeycomb lattice. We demonstrate the design and assembly of nanostructures approximating six shapes-monolith, square nut, railed bridge, genie bottle, stacked cross, slotted cross-with precisely controlled dimensions ranging from 10 to 100 nm. We also show hierarchical assembly of structures such as homomultimeric linear tracks and heterotrimeric wireframe icosahedra. Proper assembly requires week-long folding times and calibrated monovalent and divalent cation concentrations. We anticipate that our strategy for self-assembling custom three-dimensional shapes will provide a general route to the manufacture of sophisticated devices bearing features on the nanometre scale.
C1 [Douglas, Shawn M.; Dietz, Hendrik; Liedl, Tim; Hoegberg, Bjoern; Graf, Franziska; Shih, William M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Douglas, Shawn M.; Dietz, Hendrik; Liedl, Tim; Hoegberg, Bjoern; Graf, Franziska; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Douglas, Shawn M.; Graf, Franziska; Shih, William M.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University
RP Shih, WM (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM william_shih@dfci.harvard.edu
FU Claudia Adams Barr Program Investigator grant; Wyss Institute for Biologically Inspired Engineering; NIH [1DP2OD004641-01]; Humboldt Fellowship; Deutscher Akademischer Austauschdienst (DAAD); Swedish Science Council (Vetenskapsra det)
NR 29
TC 2127
Z9 2616
U1 18
U2 1117
PU NATURE PUBLISHING 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 21
PY 2009
VL 459
IS 7245
BP 414
EP 418
DI 10.1038/nature08016
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700043
PM 19458720
DA 2026-03-09
ER

PT J
AU Mercado, LM
   Bellouin, N
   Sitch, S
   Boucher, O
   Huntingford, C
   Wild, M
   Cox, PM
AF Mercado, Lina M.
   Bellouin, Nicolas
   Sitch, Stephen
   Boucher, Olivier
   Huntingford, Chris
   Wild, Martin
   Cox, Peter M.
TI Impact of changes in diffuse radiation on the global land carbon sink
SO NATURE
LA English
DT Article
ID deciduous forest; co2; photosynthesis; reduction; dioxide; climate; clouds; model
AB Plant photosynthesis tends to increase with irradiance. However, recent theoretical and observational studies have demonstrated that photosynthesis is also more efficient under diffuse light conditions(1-5). Changes in cloud cover or atmospheric aerosol loadings, arising from either volcanic or anthropogenic emissions, alter both the total photosynthetically active radiation reaching the surface and the fraction of this radiation that is diffuse, with uncertain overall effects on global plant productivity and the land carbon sink. Here we estimate the impact of variations in diffuse fraction on the land carbon sink using a global model modified to account for the effects of variations in both direct and diffuse radiation on canopy photosynthesis. We estimate that variations in diffuse fraction, associated largely with the 'global dimming' period(6-8), enhanced the land carbon sink by approximately one-quarter between 1960 and 1999. However, under a climate mitigation scenario for the twenty-first century in which sulphate aerosols decline before atmospheric CO2 is stabilized, this 'diffuse-radiation' fertilization effect declines rapidly to near zero by the end of the twenty-first century.
C1 [Mercado, Lina M.; Huntingford, Chris] Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England.
   [Bellouin, Nicolas; Sitch, Stephen; Boucher, Olivier] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [Wild, Martin] ETH, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
   [Cox, Peter M.] Univ Exeter, Sch Engn Comp Sci & Math, Exeter EX4 4QF, Devon, England.
C3 UK Centre for Ecology & Hydrology (UKCEH); Met Office - UK; Hadley Centre; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Exeter
RP Mercado, LM (corresponding author), Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England.
EM lmme@ceh.ac.uk
FU UK Natural Environment Research Council; UK Department for Environment, Food and Rural Affairs (Defra); UK Ministry of Defence (MoD) [GA01101, CBC/2B/0417_Annex C5]; Swiss NCCR Climate; Natural Environment Research Council [earth010002] Funding Source: researchfish; NERC [earth010002] Funding Source: UKRI
NR 31
TC 826
Z9 926
U1 15
U2 461
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 23
PY 2009
VL 458
IS 7241
BP 1014
EP U87
DI 10.1038/nature07949
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900039
PM 19396143
DA 2026-03-09
ER

PT J
AU Calvo, MR
   Fernández-Rossier, J
   Palacios, JJ
   Jacob, D
   Natelson, D
   Untiedt, C
AF Reyes Calvo, M.
   Fernandez-Rossier, Joaquin
   Jose Palacios, Juan
   Jacob, David
   Natelson, Douglas
   Untiedt, Carlos
TI The Kondo effect in ferromagnetic atomic contacts
SO NATURE
LA English
DT Article
AB Iron, cobalt and nickel are archetypal ferromagnetic metals. In bulk, electronic conduction in these materials takes place mainly through the s and p electrons, whereas the magnetic moments are mostly in the narrow d-electron bands, where they tend to align. This general picture may change at the nanoscale because electrons at the surfaces of materials experience interactions that differ from those in the bulk. Here we show direct evidence for such changes: electronic transport in atomic-scale contacts of pure ferromagnets ( iron, cobalt and nickel), despite their strong bulk ferromagnetism, unexpectedly reveal Kondo physics, that is, the screening of local magnetic moments by the conduction electrons below a characteristic temperature(1). The Kondo effect creates a sharp resonance at the Fermi energy, affecting the electrical properties of the system; this appears as a Fano-Kondo resonance(2) in the conductance characteristics as observed in other artificial nanostructures(3-11). The study of hundreds of contacts shows material-dependent log-normal distributions of the resonance width that arise naturally from Kondo theory(12). These resonances broaden and disappear with increasing temperature, also as in standard Kondo systems(4-7). Our observations, supported by calculations, imply that coordination changes can significantly modify magnetism at the nanoscale. Therefore, in addition to standard micromagnetic physics, strong electronic correlations along with atomic-scale geometry need to be considered when investigating the magnetic properties of magnetic nanostructures.
C1 [Reyes Calvo, M.; Fernandez-Rossier, Joaquin; Jose Palacios, Juan; Untiedt, Carlos] Univ Alicante, Fac Ciencias, Dept Fis Aplicada, E-03790 Alicante, Spain.
   [Jacob, David] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [Natelson, Douglas] Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.
C3 Universitat d'Alacant; Rutgers University System; Rutgers University New Brunswick; Rice University
RP Untiedt, C (corresponding author), Univ Alicante, Fac Ciencias, Dept Fis Aplicada, E-03790 Alicante, Spain.
EM untiedt@ua.es
FU European Union through MolSpinQIP and Spanish MEC [MAT2007-65487, 31099-E, CSD2007-0010]; US National Science Foundation (NSF) [DMR-0528969]; NSF [DMR-0347253]; Lucille Packard Foundation; W. M. Keck Program in Quantum Materials
NR 29
TC 132
Z9 137
U1 1
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 30
PY 2009
VL 458
IS 7242
BP 1150
EP U85
DI 10.1038/nature07878
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600043
PM 19407797
DA 2026-03-09
ER

PT J
AU Pritchard, HD
   Arthern, RJ
   Vaughan, DG
   Edwards, LA
AF Pritchard, Hamish D.
   Arthern, Robert J.
   Vaughan, David G.
   Edwards, Laura A.
TI Extensive dynamic thinning on the margins of the Greenland and Antarctic ice sheets
SO NATURE
LA English
DT Article
ID sea-level rise; mass-balance; acceleration; glaciers
AB Many glaciers along the margins of the Greenland and Antarctic ice sheets are accelerating and, for this reason, contribute increasingly to global sea-level rise(1-7). Globally, ice losses contribute similar to 1.8 mm yr(-1) (ref. 8), but this could increase if the retreat of ice shelves and tidewater glaciers further enhances the loss of grounded ice(9) or initiates the large-scale collapse of vulnerable parts of the ice sheets(10). Ice loss as a result of accelerated flow, known as dynamic thinning, is so poorly understood that its potential contribution to sea level over the twenty-first century remains unpredictable(11). Thinning on the ice-sheet scale has been monitored by using repeat satellite altimetry observations to track small changes in surface elevation, but previous sensors could not resolve most fast-flowing coastal glaciers(12). Here we report the use of high-resolution ICESat (Ice, Cloud and land Elevation Satellite) laser altimetry to map change along the entire grounded margins of the Greenland and Antarctic ice sheets. To isolate the dynamic signal, we compare rates of elevation change from both fast-flowing and slow-flowing ice with those expected from surface mass-balance fluctuations. We find that dynamic thinning of glaciers now reaches all latitudes in Greenland, has intensified on key Antarctic grounding lines, has endured for decades after ice-shelf collapse, penetrates far into the interior of each ice sheet and is spreading as ice shelves thin by ocean-driven melt. In Greenland, glaciers flowing faster than 100 m yr(-1) thinned at an average rate of 0.84 m yr(-1), and in the Amundsen Sea embayment of Antarctica, thinning exceeded 9.0 m yr(-1) for some glaciers. Our results show that the most profound changes in the ice sheets currently result from glacier dynamics at ocean margins.
C1 [Pritchard, Hamish D.; Arthern, Robert J.; Vaughan, David G.] British Antarctic Survey, NERC, Cambridge CB3 0ET, England.
   [Edwards, Laura A.] Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
C3 UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; University of Bristol
RP Pritchard, HD (corresponding author), British Antarctic Survey, NERC, Madingley Rd, Cambridge CB3 0ET, England.
EM hprit@bas.ac.uk
FU UK Natural Environment Research Council; Natural Environment Research Council [earth010003, bas010018] Funding Source: researchfish; NERC [earth010003, bas010018] Funding Source: UKRI
NR 31
TC 748
Z9 893
U1 6
U2 384
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 971
EP 975
DI 10.1038/nature08471
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700045
PM 19776741
DA 2026-03-09
ER

PT J
AU Kawamichi, T
   Haneda, T
   Kawano, M
   Fujita, M
AF Kawamichi, Takehide
   Haneda, Tsuyoshi
   Kawano, Masaki
   Fujita, Makoto
TI X-ray observation of a transient hemiaminal trapped in a porous network
SO NATURE
LA English
DT Article
ID nuclear-magnetic-resonance; coordination networks; frameworks; mechanism; aldolase; pores
AB X-ray crystallography is the method of choice for the direct structural analysis of crystalline compounds(1). Extending its use to the in situ mapping of chemical transformations could provide valuable insights, as illustrated by time-resolved X-ray crystallography studies(2,3); however, the transient nature of unstable reaction intermediates often poses a significant challenge. It has recently been demonstrated that standard chemical reactions can occur within the pores of porous coordination networks(4-6) and that the robust crystallinity of these networks facilitates in situ X-ray analysis of the adducts and products(7-11). Here we show that such systems even enable X-ray observations of reaction intermediates that are usually transient and non-isolable. Our proof-of-concept demonstration examines the simple and ubiquitous reaction between an amine and an aldehyde, which normally form a very short-lived hemiaminal that then yields the Schiff-base product. The mechanism of this reaction has been exhaustively examined, but the hemiaminal intermediate has only rarely been observed(12-16). We first determine the structure of a porous network with an aromatic amine embedded in it, then diffuse an aldehyde substrate into the material to transform the amine into a hemiaminal intermediate that is kinetically trapped and thus amenable to X-ray analysis, and finally raise the temperature of the system to obtain the imine product and determine its structure. These results establish that porous network materials provide a means of obtaining sequential X-ray-based snapshots of the structural transformations that occur during chemical reactions.
C1 [Kawamichi, Takehide; Haneda, Tsuyoshi; Kawano, Masaki; Fujita, Makoto] Univ Tokyo, Sch Engn, Dept Appl Chem, Bunkyo Ku, Tokyo 1138656, Japan.
   [Fujita, Makoto] Japan Sci & Technol Agcy, Bunkyo Ku, Tokyo 1138656, Japan.
C3 University of Tokyo; Japan Science & Technology Agency (JST)
RP Kawano, M (corresponding author), Univ Tokyo, Sch Engn, Dept Appl Chem, Bunkyo Ku, Tokyo 1138656, Japan.
EM mkawano@postech.ac.kr; mfujita@appchem.t.u-tokyo.ac.jp
FU Japan Science and Technology Agency; KAKENHI; Japan Society for the Promotion of Science, the Global COE Program (Chemistry Innovation through Cooperation of Science and Engineering), MEXT, Japan; Koei Chemical Co. Ltd
NR 20
TC 247
Z9 266
U1 4
U2 148
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 1
PY 2009
VL 461
IS 7264
BP 633
EP 635
DI 10.1038/nature08326
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600036
PM 19794489
DA 2026-03-09
ER

PT J
AU Scott, GR
   Gibert, L
AF Scott, Gary R.
   Gibert, Luis
TI The oldest hand-axes in Europe
SO NATURE
LA English
DT Article
ID baza basin; se spain; orce; age; chronology; 40ar/39ar; boundary; africa; record
AB Stone tools are durable reminders of the activities, skills and customs of early humans, and have distinctive morphologies that reflect the development of technological skills during the Pleistocene epoch. In Africa, large cutting tools (hand-axes and bifacial chopping tools) became part of Palaeolithic technology during the Early Pleistocene (similar to 1.5 Myr ago)(1-3). However, in Europe this change had not been documented until the Middle Pleistocene (<0.5 Myr ago)(4,5). Here we report dates for two western Mediterranean hand-axe sites that are nearly twice the age of the supposed earliest Acheulian in western Europe. Palaeomagnetic analysis of these two sites in southeastern Spain found reverse polarity magnetozones, showing that hand-axes were already in Europe as early as 0.9 Myr ago. This expanded antiquity for European hand-axe culture supports a wide geographic distribution of Palaeolithic bifacial technology outside of Africa during the Early Pleistocene.
C1 [Scott, Gary R.; Gibert, Luis] Berkeley Geochronol Ctr, Berkeley, CA 94709 USA.
C3 Berkeley Geochronolgy Center
RP Gibert, L (corresponding author), Berkeley Geochronol Ctr, 2455 Ridge Rd, Berkeley, CA 94709 USA.
EM lgibert@bgc.org
FU Fullbright Scholar Program; Fundacion Espanola para la Ciencia y la Tecnologia; Fundacion Seneca [05584/ARQ/07]; Direccion General de Investigacion [CGL2005-05337BTE]; Earthwatch Institute
NR 29
TC 142
Z9 148
U1 0
U2 35
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 82
EP 85
DI 10.1038/nature08214
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800034
PM 19727198
DA 2026-03-09
ER

PT J
AU Verschuren, D
   Damsté, JSS
   Moernaut, J
   Kristen, I
   Blaauw, M
   Fagot, M
   Haug, GH
AF Verschuren, Dirk
   Damste, Jaap S. Sinninghe
   Moernaut, Jasper
   Kristen, Iris
   Blaauw, Maarten
   Fagot, Maureen
   Haug, Gerald H.
TI Half-precessional dynamics of monsoon rainfall near the East African Equator
SO NATURE
LA English
DT Article
ID atlantic thermohaline circulation; last glacial maximum; millennial-scale; climate; insolation; holocene; collapse; tanzania; record; bp
AB External climate forcings-such as long-term changes in solar insolation-generate different climate responses in tropical and high latitude regions(1). Documenting the spatial and temporal variability of past climates is therefore critical for understanding how such forcings are translated into regional climate variability. In contrast to the data-richmiddle and high latitudes, high-quality climate-proxy records from equatorial regions are relatively few(2-4), especially from regions experiencing the bimodal seasonal rainfall distribution associated with twice-annual passage of the Intertropical Convergence Zone. Here we present a continuous and well-resolved climate-proxy record of hydrological variability during the past 25,000 years from equatorial East Africa. Our results, based on complementary evidence from seismic-reflection stratigraphy and organic biomarker molecules in the sediment record of Lake Challa near Mount Kilimanjaro, reveal that monsoon rainfall in this region varied at half-precessional (similar to 11,500-year) intervals in phase with orbitally controlled insolation forcing. The southeasterly and northeasterly monsoons that advect moisture from the western Indian Ocean were strengthened in alternation when the inter-hemispheric insolation gradient was at a maximum; dry conditions prevailed when neither monsoon was intensified and modest local March or September insolation weakened the rain season that followed. On sub-millennial timescales, the temporal pattern of hydrological change on the East African Equator bears clear high-northern-latitude signatures, but on the orbital timescale it mainly responded to low-latitude insolation forcing. Predominance of low-latitude climate processes in this monsoon region can be attributed to the low-latitude position of its continental regions of surface air flow convergence, and its relative isolation from the Atlantic Ocean, where prominent meridional overturning circulation more tightly couples low-latitude climate regimes to high-latitude boundary conditions.
C1 [Verschuren, Dirk; Fagot, Maureen] Univ Ghent, Dept Biol, Limnol Unit, B-9000 Ghent, Belgium.
   [Damste, Jaap S. Sinninghe] Univ Utrecht, Fac Geosci, NL-3508 TA Utrecht, Netherlands.
   [Damste, Jaap S. Sinninghe] NIOZ Royal Netherlands Inst Sea Res, Dept Marine Organ Biogeochem, NL-1790 AB Den Burg, Netherlands.
   [Moernaut, Jasper] Univ Ghent, Dept Geol & Soil Sci, Renard Ctr Marine Geol, B-9000 Ghent, Belgium.
   [Kristen, Iris] Geoforschungszentrum Potsdam, Sekt Klimadynam & Sedimente 3 3, D-14473 Potsdam, Germany.
   [Blaauw, Maarten] Queens Univ Belfast, Sch Geog Archaeol & Palaeoecol, Belfast BT9 6AX, Antrim, North Ireland.
   [Haug, Gerald H.] ETH, Inst Geol, Dept Earth Sci, CH-8092 Zurich, Switzerland.
   [Haug, Gerald H.] Univ Potsdam, DFG Leibniz Ctr Earth Surface Proc & Climate Stud, D-14476 Potsdam, Germany.
C3 Ghent University; Utrecht University; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); Ghent University; Helmholtz Association; GFZ Helmholtz Centre for Geosciences; Queens University Belfast; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Potsdam
RP Verschuren, D (corresponding author), Univ Ghent, Dept Biol, Limnol Unit, Ledeganckstr 35, B-9000 Ghent, Belgium.
EM dirk.verschuren@UGent.be
FU Belgium (FWO-Vlaanderen); Denmark ( Danish National Research Council), Germany (DFG); The Netherlands (NWO); EuroCLIMATE; Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen); Natural Environment Research Council [nigl010001, bgs04003] Funding Source: researchfish; NERC [bgs04003, nigl010001] Funding Source: UKRI
NR 30
TC 256
Z9 285
U1 0
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 637
EP 641
DI 10.1038/nature08520
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900038
PM 19956257
DA 2026-03-09
ER

PT J
AU Du, X
   Skachko, I
   Duerr, F
   Luican, A
   Andrei, EY
AF Du, Xu
   Skachko, Ivan
   Duerr, Fabian
   Luican, Adina
   Andrei, Eva Y.
TI Fractional quantum Hall effect and insulating phase of Dirac electrons in graphene
SO NATURE
LA English
DT Article
ID magnetic-fields
AB In graphene, which is an atomic layer of crystalline carbon, two of the distinguishing properties of the material are the charge carriers' two-dimensional and relativistic character. The first experimental evidence of the two-dimensional nature of graphene came from the observation of a sequence of plateaus in measurements of its transport properties in the presence of an applied magnetic field(1,2). These are signatures of the so-called integer quantum Hall effect. However, as a consequence of the relativistic character of the charge carriers, the integer quantum Hall effect observed in graphene is qualitatively different from its semiconductor analogue(3). As a third distinguishing feature of graphene, it has been conjectured that interactions and correlations should be important in this material, but surprisingly, evidence of collective behaviour in graphene is lacking. In particular, the quintessential collective quantum behaviour in two dimensions, the fractional quantum Hall effect (FQHE), has so far resisted observation in graphene despite intense efforts and theoretical predictions of its existence(4-9). Here we report the observation of the FQHE in graphene. Our observations are made possible by using suspended graphene devices probed by two-terminal charge transport measurements(10). This allows us to isolate the sample from substrate-induced perturbations that usually obscure the effects of interactions in this system and to avoid effects of finite geometry. At low carrier density, we find a field-induced transition to an insulator that competes with the FQHE, allowing its observation only in the highest quality samples. We believe that these results will open the door to the physics of FQHE and other collective behaviour in graphene.
C1 [Du, Xu; Skachko, Ivan; Duerr, Fabian; Luican, Adina; Andrei, Eva Y.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08855 USA.
C3 Rutgers University System; Rutgers University New Brunswick
RP Andrei, EY (corresponding author), Rutgers State Univ, Dept Phys & Astron, POB 849, Piscataway, NJ 08855 USA.
EM eandrei@physics.rutgers.edu
FU [DE-FG02-99ER45742];  [NSF-DMR-045673]
NR 28
TC 789
Z9 934
U1 3
U2 382
PU NATURE PUBLISHING 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 12
PY 2009
VL 462
IS 7270
BP 192
EP 195
DI 10.1038/nature08522
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100037
PM 19829294
DA 2026-03-09
ER

PT J
AU Rockström, J
   Steffen, W
   Noone, K
   Persson, Å
   Chapin, FS
   Lambin, EF
   Lenton, TM
   Scheffer, M
   Folke, C
   Schellnhuber, HJ
   Nykvist, B
   de Wit, CA
   Hughes, T
   van der Leeuw, S
   Rodhe, H
   Sörlin, S
   Snyder, PK
   Costanza, R
   Svedin, U
   Falkenmark, M
   Karlberg, L
   Corell, RW
   Fabry, VJ
   Hansen, J
   Walker, B
   Liverman, D
   Richardson, K
   Crutzen, P
   Foley, JA
AF Rockstrom, Johan
   Steffen, Will
   Noone, Kevin
   Persson, Asa
   Chapin, F. Stuart, III
   Lambin, Eric F.
   Lenton, Timothy M.
   Scheffer, Marten
   Folke, Carl
   Schellnhuber, Hans Joachim
   Nykvist, Bjorn
   de Wit, Cynthia A.
   Hughes, Terry
   van der Leeuw, Sander
   Rodhe, Henning
   Sorlin, Sverker
   Snyder, Peter K.
   Costanza, Robert
   Svedin, Uno
   Falkenmark, Malin
   Karlberg, Louise
   Corell, Robert W.
   Fabry, Victoria J.
   Hansen, James
   Walker, Brian
   Liverman, Diana
   Richardson, Katherine
   Crutzen, Paul
   Foley, Jonathan A.
TI A safe operating space for humanity
SO NATURE
LA English
DT Article
ID climate; resilience; biodiversity; consequences; perspective; phosphorus; shifts; sea
C1 [Rockstrom, Johan; Steffen, Will; Noone, Kevin; Persson, Asa; Folke, Carl; Nykvist, Bjorn; Sorlin, Sverker; Costanza, Robert; Svedin, Uno; Falkenmark, Malin; Karlberg, Louise; Walker, Brian] Stockholm Univ, Stockholm Resilience Ctr, S-10691 Stockholm, Sweden.
   [Rockstrom, Johan; Persson, Asa; Nykvist, Bjorn; Karlberg, Louise] Stockholm Environm Inst, S-10691 Stockholm, Sweden.
   [Steffen, Will] Australian Natl Univ, ANU Climate Change Inst, Canberra, ACT 0200, Australia.
   [Noone, Kevin; de Wit, Cynthia A.] Stockholm Univ, Dept Appl Environm Sci, S-10691 Stockholm, Sweden.
   [Chapin, F. Stuart, III] Univ Alaska Fairbanks, Inst Arctic Biol, Fairbanks, AK 99775 USA.
   [Lambin, Eric F.] Catholic Univ Louvain, Dept Geog, B-1348 Louvain, Belgium.
   [Lenton, Timothy M.] Univ E Anglia, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
   [Scheffer, Marten] Wageningen Univ, Aquat Ecol & Water Qual Management Grp, NL-6700 HB Wageningen, Netherlands.
   [Folke, Carl] Royal Swedish Acad Sci, Beijer Inst Ecol Econ, S-10405 Stockholm, Sweden.
   [Schellnhuber, Hans Joachim] Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany.
   [Schellnhuber, Hans Joachim] Univ Oxford, Tyndall Ctr, Oxford OX1 3QY, England.
   [Schellnhuber, Hans Joachim; Liverman, Diana] Univ Oxford, Environm Change Inst, Oxford OX1 3QY, England.
   [Hughes, Terry] James Cook Univ, ARC Ctr Excellence Coral Reef Studies, Townsville, Qld 4811, Australia.
   [van der Leeuw, Sander] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
   [Rodhe, Henning] Stockholm Univ, Dept Meteorol, S-10691 Stockholm, Sweden.
   [Sorlin, Sverker] Royal Inst Technol, Div Hist Sci & Technol, S-10044 Stockholm, Sweden.
   [Snyder, Peter K.] Univ Minnesota, Dept Soil Water & Climate, St Paul, MN 55108 USA.
   [Costanza, Robert] Univ Vermont, Gund Inst Ecol Econ, Burlington, VT 05405 USA.
   [Falkenmark, Malin] Stockholm Int Water Inst, S-11151 Stockholm, Sweden.
   [Corell, Robert W.] H John Heinz III Ctr Sci Econ & Environm, Washington, DC 20006 USA.
   [Fabry, Victoria J.] Calif State Univ San Marcos, Dept Biol Sci, San Marcos, CA 92096 USA.
   [Hansen, James] NASA, Goddard Inst Space Studies, New York, NY 10025 USA.
   [Walker, Brian] Commonwealth Sci & Ind Org, Sustainable Ecosyst, Canberra, ACT 2601, Australia.
   [Liverman, Diana] Univ Arizona, Inst Environm, Tucson, AZ 85721 USA.
   [Richardson, Katherine] Fac Nat Sci, DK-2200 Copenhagen N, Denmark.
   [Crutzen, Paul] Max Planck Inst Chem, D-55020 Mainz, Germany.
   [Foley, Jonathan A.] Univ Minnesota, Inst Environm, St Paul, MN 55108 USA.
C3 Stockholm University; Stockholm Environment Institute; Australian National University; Stockholm University; University of Alaska System; University of Alaska Fairbanks; Universite Catholique Louvain; University of East Anglia; Wageningen University & Research; Royal Swedish Academy of Sciences; Beijer Institute of Ecological Economics; Potsdam Institut fur Klimafolgenforschung; University of Oxford; University of Oxford; James Cook University; ARC Centre of Excellence for Coral Reef Studies; Arizona State University; Arizona State University-Tempe; Stockholm University; Royal Institute of Technology; University of Minnesota System; University of Minnesota Twin Cities; University of Vermont; California State University System; California State University San Marcos; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Goddard Institute for Space Studies; Commonwealth Scientific & Industrial Research Organisation (CSIRO); University of Arizona; Max Planck Society; University of Minnesota System; University of Minnesota Twin Cities
RP Rockström, J (corresponding author), Stockholm Univ, Stockholm Resilience Ctr, Kraftriket 2B, S-10691 Stockholm, Sweden.
FU Natural Environment Research Council [tynd10001] Funding Source: researchfish; NERC [tynd10001] Funding Source: UKRI
NR 46
TC 10067
Z9 12273
U1 136
U2 4012
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 24
PY 2009
VL 461
IS 7263
BP 472
EP 475
DI 10.1038/461472a
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900020
PM 19779433
DA 2026-03-09
ER

PT J
AU Shalm, LK
   Adamson, RBA
   Steinberg, AM
AF Shalm, L. K.
   Adamson, R. B. A.
   Steinberg, A. M.
TI Squeezing and over-squeezing of triphotons
SO NATURE
LA English
DT Article
ID quantum limit; state; separability
AB Quantum mechanics places a fundamental limit on the accuracy of measurements. In most circumstances, the measurement uncertainty is distributed equally between pairs of complementary properties; this leads to the 'standard quantumlimit' for measurement resolution. Using a technique known as 'squeezing', it is possible to reduce the uncertainty of one desired property below the standard quantumlimit at the expense of increasing that of the complementary one. Squeezing is already being used to enhance the sensitivity of gravity- wave detectors(1) and may play a critical role in other high precision applications, such as atomic clocks(2) and optical communications(3). Spin squeezing ( the squeezing of angular momentum variables) is a powerful tool, particularly in the context of quantum light - matter interfaces(4-9). Although impressive gains in squeezing have been made, optical spin- squeezed systems are still many orders of magnitude away from the maximum possible squeezing, known as the Heisenberg uncertainty limit. Here we demonstrate how an optical system can be squeezed essentially all the way to this fundamental bound. Weconstruct spin- squeezed states by overlapping three indistinguishable photons in an optical fibre and manipulating their polarization ( spin), resulting in the formation of a squeezed composite particle known as a 'triphoton'. The symmetry properties of polarization imply that the measured triphoton states can be most naturally represented by quasi- probability distributions on the surface of a sphere. In this work we show that the spherical topology of polarization imposes a limit on how much squeezing can occur, leading to the quasi- probability distributions wrapping around the sphere - a phenomenon we term 'oversqueezing'. Our observations of spin- squeezing in the few- photon regime could lead to new quantum resources for enhanced measurement, lithography and information processing that can be precisely engineered photon- by- photon.
C1 [Shalm, L. K.; Adamson, R. B. A.; Steinberg, A. M.] Univ Toronto, Dept Phys, Inst Opt Sci, Ctr Comp Informat & Quantum Control, Toronto, ON M5S 1A7, Canada.
C3 University of Toronto
RP Shalm, LK (corresponding author), Univ Toronto, Dept Phys, Inst Opt Sci, Ctr Comp Informat & Quantum Control, 60 St George St, Toronto, ON M5S 1A7, Canada.
EM lshalm@physics.utoronto.ca
FU Natural Sciences and Engineering Research Council of Canada; Ontario Centres of Excellence; Canadian Institute for Photonic Innovations; Quantum Works; Canadian Institute for Advanced Research.
NR 30
TC 39
Z9 40
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 1
PY 2009
VL 457
IS 7225
BP 67
EP 70
DI 10.1038/nature07624
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900031
PM 19122637
DA 2026-03-09
ER

PT J
AU Smirnova, O
   Mairesse, Y
   Patchkovskii, S
   Dudovich, N
   Villeneuve, D
   Corkum, P
   Ivanov, MY
AF Smirnova, Olga
   Mairesse, Yann
   Patchkovskii, Serguei
   Dudovich, Nirit
   Villeneuve, David
   Corkum, Paul
   Ivanov, Misha Yu.
TI High harmonic interferometry of multi-electron dynamics in molecules
SO NATURE
LA English
DT Article
ID attosecond; interference; generation
AB High harmonic emission occurs when an electron, liberated from a molecule by an incident intense laser field, gains energy from the field and recombines with the parent molecular ion. The emission provides a snapshot of the structure and dynamics of the recombining system, encoded in the amplitudes, phases and polarization of the harmonic light. Here we show with CO2 molecules that high harmonic interferometry can retrieve this structural and dynamic information: by measuring the phases and amplitudes of the harmonic emission, we reveal 'fingerprints' of multiple molecular orbitals participating in the process and decode the underlying attosecond multi-electron dynamics, including the dynamics of electron rearrangement upon ionization. These findings establish high harmonic interferometry as an effective approach to resolving multi-electron dynamics with sub-Angstrom spatial resolution arising from the de Broglie wavelength of the recombining electron, and attosecond temporal resolution arising from the timescale of the recombination event.
C1 [Smirnova, Olga; Mairesse, Yann; Patchkovskii, Serguei; Dudovich, Nirit; Villeneuve, David; Corkum, Paul; Ivanov, Misha Yu.] Natl Res Council Canada, Ottawa, ON K1A 0R6, Canada.
   [Smirnova, Olga] Max Born Inst, D-12489 Berlin, Germany.
   [Mairesse, Yann] Univ Bordeaux 1, CELIA, CNRS, CEA,UMR 5107, F-33405 Talence, France.
   [Dudovich, Nirit] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
   [Ivanov, Misha Yu.] Univ London Imperial Coll Sci Technol & Med, Dept Phys, London SW7 2AZ, England.
C3 National Research Council Canada; Leibniz Association; Max Born Institute for Nonlinear Optics & Short Term Spectroscopy; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); CEA; Weizmann Institute of Science; Imperial College London
RP Smirnova, O (corresponding author), Natl Res Council Canada, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada.
EM olga.smirnova@mbi-berlin.de
FU NSERC SRO; AFOSR; Leibniz SAW award; Alexander von Humboldt foundation
NR 37
TC 992
Z9 1081
U1 7
U2 254
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 972
EP 977
DI 10.1038/nature08253
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500026
PM 19626004
DA 2026-03-09
ER

PT J
AU Bendkowsky, V
   Butscher, B
   Nipper, J
   Shaffer, JP
   Löw, R
   Pfau, T
AF Bendkowsky, Vera
   Butscher, Bjoern
   Nipper, Johannes
   Shaffer, James P.
   Loew, Robert
   Pfau, Tilman
TI Observation of ultralong-range Rydberg molecules
SO NATURE
LA English
DT Article
ID collisions; atoms; states; cs; rb
AB Rydberg atoms have an electron in a state with a very high principal quantum number, and as a result can exhibit unusually long-range interactions. One example is the bonding of two such atoms by multipole forces to form Rydberg-Rydberg molecules with very large internuclear distances(1-3). Notably, bonding interactions can also arise from the low-energy scattering of a Rydberg electron with negative scattering length from a ground-state atom(4,5). In this case, the scattering-induced attractive interaction binds the ground-state atom to the Rydberg atom at a well-localized position within the Rydberg electron wavefunction and thereby yields giant molecules that can have internuclear separations of several thousand Bohr radii(6-8). Here we report the spectroscopic characterization of such exotic molecular states formed by rubidium Rydberg atoms that are in the spherically symmetric s state and have principal quantum numbers, n, between 34 and 40. We find that the spectra of the vibrational ground state and of the first excited state of the Rydberg molecule, the rubidium dimer Rb(5s)-Rb(ns), agree well with simple model predictions. The data allow us to extract the s-wave scattering length for scattering between the Rydberg electron and the ground-state atom, Rb(5s), in the low-energy regime (kinetic energy, <100meV), and to determine the lifetimes and the polarizabilities of the Rydberg molecules. Given our successful characterization of s-wave bound Rydberg states, we anticipate that p-wave bound states(9), trimer states(10) and bound states involving a Rydberg electron with large angular momentum-so-called trilobite molecules(5)-will also be realized and directly probed in the near future.
C1 [Bendkowsky, Vera; Butscher, Bjoern; Nipper, Johannes; Shaffer, James P.; Loew, Robert; Pfau, Tilman] Univ Stuttgart, Phys Inst 5, D-70569 Stuttgart, Germany.
   [Shaffer, James P.] Univ Oklahoma, Homer L Dodge Dept Phys & Astron, Norman, OK 73072 USA.
C3 University of Stuttgart; University of Oklahoma System; University of Oklahoma - Norman
RP Bendkowsky, V (corresponding author), Univ Stuttgart, Phys Inst 5, Pfaffenwaldring 57, D-70569 Stuttgart, Germany.
EM v.bendkowsky@physik.uni-stuttgart.de; t.pfau@physik.uni-stuttgart.de
FU Deutsche Forschungsgemeinschaft [PF 381/4-1]; Landesstiftung Baden-Wurttemberg; Carl Zeiss foundation; Alexander von Humboldt foundation
NR 29
TC 364
Z9 408
U1 1
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 23
PY 2009
VL 458
IS 7241
BP 1005
EP U76
DI 10.1038/nature07945
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900037
PM 19396141
DA 2026-03-09
ER

PT J
AU Liu, J
   Cao, L
   Chen, JC
   Song, SW
   Lee, IH
   Quijano, C
   Liu, HJ
   Keyvanfar, K
   Chen, HQ
   Cao, LY
   Ahn, BH
   Kumar, NG
   Rovira, II
   Xu, XL
   van Lohuizen, M
   Motoyama, N
   Deng, CX
   Finkel, T
AF Liu, Jie
   Cao, Liu
   Chen, Jichun
   Song, Shiwei
   Lee, In Hye
   Quijano, Celia
   Liu, Hongjun
   Keyvanfar, Keyvan
   Chen, Haoqian
   Cao, Long-Yue
   Ahn, Bong-Hyun
   Kumar, Neil G.
   Rovira, Ilsa I.
   Xu, Xiao-Ling
   van Lohuizen, Maarten
   Motoyama, Noboru
   Deng, Chu-Xia
   Finkel, Toren
TI Bmi1 regulates mitochondrial function and the DNA damage response pathway
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; self-renewal; repair; proliferation; senescence; ink4a; mice; p16(ink4a); target; growth
AB Mice deficient in the Polycomb repressor Bmi1 develop numerous abnormalities including a severe defect in stem cell self-renewal, alterations in thymocyte maturation and a shortened lifespan. Previous work has implicated de-repression of the Ink4a/Arf (also known as Cdkn2a) locus as mediating many of the aspects of the Bmi1(-/-) phenotype. Here we demonstrate that cells derived from Bmi1(-/-) mice also have impaired mitochondrial function, a marked increase in the intracellular levels of reactive oxygen species and subsequent engagement of the DNA damage response pathway. Furthermore, many of the deficiencies normally observed in Bmi1(-/-) mice improve after either pharmacological treatment with the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response pathway by Chk2 (also known as Chek2) deletion. These results demonstrate that Bmi1 has an unexpected role in maintaining mitochondrial function and redox homeostasis and indicate that the Polycomb family of proteins can coordinately regulate cellular metabolism with stem and progenitor cell function.
C1 [Liu, Jie; Cao, Liu; Song, Shiwei; Lee, In Hye; Quijano, Celia; Liu, Hongjun; Chen, Haoqian; Cao, Long-Yue; Ahn, Bong-Hyun; Kumar, Neil G.; Rovira, Ilsa I.; Finkel, Toren] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
   [Cao, Liu; Keyvanfar, Keyvan] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
   [Kumar, Neil G.] NIH, Howard Hughes Med Inst, Res Scholar Program, Bethesda, MD 20892 USA.
   [Xu, Xiao-Ling; Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
   [van Lohuizen, Maarten] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands.
   [Motoyama, Noboru] Natl Ctr Geriatr & Gerontol, Natl Inst Longev Sci, Dept Geriatr Med, Aichi 4748522, Japan.
C3 National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; Howard Hughes Medical Institute; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Netherlands Cancer Institute; National Center for Geriatrics & Gerontology
RP Finkel, T (corresponding author), NHLBI, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM Liu.Cao@nih.gov; finkelt@nih.gov
FU National Heart Lung and Blood Institute [ZICHL005906] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NIA NIH HHS [R00 AG032356] Funding Source: Medline; Intramural NIH HHS [Z01 HL005012] Funding Source: Medline
NR 38
TC 408
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U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2009
VL 459
IS 7245
BP 387
EP U100
DI 10.1038/nature08040
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700037
PM 19404261
DA 2026-03-09
ER

PT J
AU Rhyee, JS
   Lee, KH
   Lee, SM
   Cho, E
   Kim, SI
   Lee, E
   Kwon, YS
   Shim, JH
   Kotliar, G
AF Rhyee, Jong-Soo
   Lee, Kyu Hyoung
   Lee, Sang Mock
   Cho, Eunseog
   Kim, Sang Il
   Lee, Eunsung
   Kwon, Yong Seung
   Shim, Ji Hoon
   Kotliar, Gabriel
TI Peierls distortion as a route to high thermoelectric performance in In4Se3-δ crystals
SO NATURE
LA English
DT Article
ID merit
AB Thermoelectric energy harvesting-the transformation of waste heat into useful electricity-is of great interest for energy sustainability. The main obstacle is the low thermoelectric efficiency of materials for converting heat to electricity, quantified by the thermoelectric figure of merit, ZT. The best available n-type materials for use in mid-temperature (500-900K) thermoelectric generators have a relatively low ZT of 1 or less, and so there is much interest in finding avenues for increasing this figure of merit(1). Here we report a binary crystalline n-type material, In4Se3-delta, which achieves the ZT value of 1.48 at 705K-very high for a bulk material. Using high-resolution transmission electron microscopy, electron diffraction, and first-principles calculations, we demonstrate that this material supports a charge density wave instability which is responsible for the large anisotropy observed in the electric and thermal transport. The high ZT value is the result of the high Seebeck coefficient and the low thermal conductivity in the plane of the charge density wave. Our results suggest a new direction in the search for high-performance thermoelectric materials, exploiting intrinsic nanostructural bulk properties induced by charge density waves.
C1 [Rhyee, Jong-Soo; Lee, Kyu Hyoung; Lee, Sang Mock; Cho, Eunseog; Kim, Sang Il; Lee, Eunsung] Samsung Adv Inst Technol, Mat Res Lab, Yongin 446712, South Korea.
   [Kwon, Yong Seung] Sungkyunkwan Univ, Dept Phys, Suwon 440746, South Korea.
   [Shim, Ji Hoon] Pohang Univ Sci & Technol, Dept Chem, Pohang 790784, South Korea.
   [Kotliar, Gabriel] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
C3 Samsung; Sungkyunkwan University (SKKU); Pohang University of Science & Technology (POSTECH); Rutgers University System; Rutgers University New Brunswick
RP Lee, SM (corresponding author), Samsung Adv Inst Technol, Mat Res Lab, Yongin 446712, South Korea.
EM sangmocklee@samsung.com
FU WCU [KOSEF: R32-2008-000-10180-0]
NR 19
TC 503
Z9 563
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 JUN 18
PY 2009
VL 459
IS 7249
BP 965
EP 968
DI 10.1038/nature08088
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500038
PM 19536260
DA 2026-03-09
ER

PT J
AU Rothman, JS
   Cathala, L
   Steuber, V
   Silver, RA
AF Rothman, Jason S.
   Cathala, Laurence
   Steuber, Volker
   Silver, R. Angus
TI Synaptic depression enables neuronal gain control
SO NATURE
LA English
DT Article
ID shunting inhibition; pyramidal neurons; nmda receptors; single; noise; transmission; invariance; synapses; cells; model
AB To act as computational devices, neurons must perform mathematical operations as they transform synaptic and modulatory input into output firing rate(1). Experiments and theory indicate that neuronal firing typically represents the sum of synaptic inputs(1-3), an additive operation, but multiplication of inputs is essential for many computations(1). Multiplication by a constant produces a change in the slope, or gain, of the input - output relationship, amplifying or scaling down the sensitivity of the neuron to changes in its input. Such gain modulation occurs in vivo, during contrast invariance of orientation tuning(4), attentional scaling(5), translation- invariant object recognition(6), auditory processing(7) and coordinate transformations(8,9). Moreover, theoretical studies highlight the necessity of gain modulation in several of these tasks(9-11). Although potential cellular mechanisms for gain modulation have been identified, they often rely on membrane noise and require restrictive conditions to work(3,12-18). Because nonlinear components are used to scale signals in electronics, we examined whether synaptic nonlinearities are involved in neuronal gain modulation. We used synaptic stimulation and the dynamic- clamp technique to investigate gain modulation in granule cells in acute slices of rat cerebellum. Here we show that when excitation is mediated by synapses with short- term depression ( STD), neuronal gain is controlled by an inhibitory conductance in a noise-independent manner, allowing driving and modulatory inputs to be multiplied together. The nonlinearity introduced by STD transforms inhibition- mediated additive shifts in the input - output relationship into multiplicative gain changes. When granule cells were driven with bursts of high- frequency mossy fibre input, as observed in vivo(19,20), larger inhibition- mediated gain changes were observed, as expected with greater STD. Simulations of synaptic integration in more complex neocortical neurons suggest that STD- based gain modulation can also operate in neurons with large dendritic trees. Our results establish that neurons receiving depressing excitatory inputs can act as powerful multiplicative devices even when integration of postsynaptic conductances is linear.
C1 [Rothman, Jason S.; Cathala, Laurence; Steuber, Volker; Silver, R. Angus] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England.
C3 University of London; University College London
RP Silver, RA (corresponding author), UCL, Dept Neurosci Physiol & Pharmacol, Gower St, London WC1E 6BT, England.
EM a.silver@ucl.ac.uk
FU Wellcome Trust; MRC [G0400598]; EU EUSynapse [LSHM-CT-2005-019055]; Wellcome Senior Research Fellowship; BBSRC [BB/F005369/1] Funding Source: UKRI; MRC [G0400598] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/F005369/1] Funding Source: researchfish; Medical Research Council [G0400598] Funding Source: researchfish
NR 44
TC 171
Z9 198
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 FEB 19
PY 2009
VL 457
IS 7232
BP 1015
EP U6
DI 10.1038/nature07604
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400043
PM 19145233
DA 2026-03-09
ER

PT J
AU Kelbert, A
   Schultz, A
   Egbert, G
AF Kelbert, Anna
   Schultz, Adam
   Egbert, Gary
TI Global electromagnetic induction constraints on transition-zone water content variations
SO NATURE
LA English
DT Article
ID upper-mantle beneath; electrical-conductivity; c-responses; mid-mantle; carbonated eclogite; region; wadsleyite; hydrogen; transportation; model
AB Small amounts of water can significantly affect the physical properties of mantle materials, including lowering of the solidus(1), and reducing effective viscosity(2) and seismic velocity(3). The amount and distribution of water within the mantle thus has profound implications for the dynamics and geochemical evolution of the Earth(4,5). Electrical conductivity is also highly sensitive to the presence of hydrogen in mantle minerals(6). The mantle transition zone minerals wadsleyite and ringwoodite in particular have high water solubility(4), and recent high pressure experiments show that the electrical conductivity of these minerals is very sensitive to water content(7-9). Thus estimates of the electrical conductivity of the mantle transition zone derived from electromagnetic induction studies have the potential to constrain the water content of this region. Here we invert long period geomagnetic response functions to derive a global-scale three-dimensional model of electrical conductivity variations in the Earth's mantle, revealing variations in the electrical conductivity of the transition zone of approximately one order of magnitude. Conductivities are high in cold, seismically fast, areas where slabs have subducted into or through the transition zone. Significant variations in water content throughout the transition zone provide a plausible explanation for the observed patterns. Our results support the view(10,11) that at least some of the water in the transition zone has been carried into that region by cold subducting slabs.
C1 [Kelbert, Anna; Schultz, Adam; Egbert, Gary] Oregon State Univ, Coll Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
C3 Oregon State University
RP Kelbert, A (corresponding author), Oregon State Univ, Coll Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
EM anya@coas.oregonstate.edu
FU US National Science Foundation [EAR-0739111]; US National Aeronautics and Space Administration [NNX08AG04G]
NR 44
TC 249
Z9 286
U1 3
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 1003
EP U85
DI 10.1038/nature08257
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500032
PM 19693081
DA 2026-03-09
ER

PT J
AU Loarie, SR
   Duffy, PB
   Hamilton, H
   Asner, GP
   Field, CB
   Ackerly, DD
AF Loarie, Scott R.
   Duffy, Philip B.
   Hamilton, Healy
   Asner, Gregory P.
   Field, Christopher B.
   Ackerly, David D.
TI The velocity of climate change
SO NATURE
LA English
DT Article
ID migration capacity; protected areas; change impacts; dispersal; mountain; systems; forest; shifts; birds; usa
AB The ranges of plants and animals are moving in response to recent changes in climate(1). As temperatures rise, ecosystems with 'nowhere to go', such as mountains, are considered to be more threatened(2,3). However, species survival may depend as much on keeping pace with moving climates as the climate's ultimate persistence(4,5). Here we present a new index of the velocity of temperature change (km yr(-1)), derived from spatial gradients (degrees C km(-1)) and multimodel ensemble forecasts of rates of temperature increase (degrees C yr(-1)) in the twenty-first century. This index represents the instantaneous local velocity along Earth's surface needed to maintain constant temperatures, and has a global mean of 0.42 km yr(-1) (A1B emission scenario). Owing to topographic effects, the velocity of temperature change is lowest in mountainous biomes such as tropical and subtropical coniferous forests (0.08 km yr(-1)), temperate coniferous forest, and montane grasslands. Velocities are highest in flooded grasslands (1.26 km yr(-1)), mangroves and deserts. High velocities suggest that the climates of only 8% of global protected areas have residence times exceeding 100 years. Small protected areas exacerbate the problem in Mediterranean-type and temperate coniferous forest biomes. Large protected areas may mitigate the problem in desert biomes. These results indicate management strategies for minimizing biodiversity loss from climate change. Montane landscapes may effectively shelter many species into the next century. Elsewhere, reduced emissions, a much expanded network of protected areas(6), or efforts to increase species movement may be necessary(7).
C1 [Loarie, Scott R.; Duffy, Philip B.; Asner, Gregory P.; Field, Christopher B.] Carnegie Inst Sci, Dept Global Ecol, Stanford, CA 94305 USA.
   [Duffy, Philip B.] Climate Cent Inc, Palo Alto, CA 94301 USA.
   [Hamilton, Healy] Calif Acad Sci, Ctr Appl Biodivers Informat, San Francisco, CA 94118 USA.
   [Ackerly, David D.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
C3 Carnegie Institution for Science; California Academy of Sciences; University of California System; University of California Berkeley
RP Loarie, SR (corresponding author), Carnegie Inst Sci, Dept Global Ecol, Stanford, CA 94305 USA.
EM loarie@stanford.edu
FU Gordon and Betty Moore Foundation; Stanford University Global Climate and Energy Project
NR 31
TC 1899
Z9 2254
U1 25
U2 1504
PU 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 24
PY 2009
VL 462
IS 7276
BP 1052
EP U111
DI 10.1038/nature08649
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000046
PM 20033047
DA 2026-03-09
ER

PT J
AU Scott, FL
   Stec, B
   Pop, C
   Dobaczewska, MK
   Lee, JJ
   Monosov, E
   Robinson, H
   Salvesen, GS
   Schwarzenbacher, R
   Riedl, SJ
AF Scott, Fiona L.
   Stec, Boguslaw
   Pop, Cristina
   Dobaczewska, Malgorzata K.
   Lee, JeongEun J.
   Monosov, Edward
   Robinson, Howard
   Salvesen, Guy S.
   Schwarzenbacher, Robert
   Riedl, Stefan J.
TI The Fas-FADD death domain complex structure unravels signalling by receptor clustering
SO NATURE
LA English
DT Article
ID cell-death; mutational analysis; apoptosis; cd95; architecture; inflammation; interfaces; spots
AB The death inducing signalling complex ( DISC) formed by Fas receptor, FADD( Fas- associated death domain protein) and caspase 8 is a pivotal trigger of apoptosis(1-3). The Fas - FADD DISC represents a receptor platform, which once assembled initiates the induction of programmed cell death. A highly oligomeric network of homotypic protein interactions comprised of the death domains of Fas and FADD is at the centre of DISC formation(4,5). Thus, characterizing the mechanistic basis for the Fas - FADD interaction is crucial for understanding DISC signalling but has remained unclear largely because of a lack of structural data. We have successfully formed and isolated the human Fas - FADD death domain complex and report the 2.7 angstrom crystal structure. The complex shows a tetrameric arrangement of four FADD death domains bound to four Fas death domains. We show that an opening of the Fas death domain exposes the FADD binding site and simultaneously generates a Fas - Fas bridge. The result is a regulatory Fas - FADD complex bridge governed by weak protein - protein interactions revealing a model where the complex itself functions as a mechanistic switch. This switch prevents accidental DISC assembly, yet allows for highly processive DISC formation and clustering upon a sufficient stimulus. In addition to depicting a previously unknown mode of death domain interactions, these results further uncover a mechanism for receptor signalling solely by oligomerization and clustering events.
C1 [Scott, Fiona L.; Stec, Boguslaw; Pop, Cristina; Dobaczewska, Malgorzata K.; Lee, JeongEun J.; Monosov, Edward; Salvesen, Guy S.; Riedl, Stefan J.] Burnham Inst, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA.
   [Robinson, Howard] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
   [Schwarzenbacher, Robert] Salzburg Univ, Dept Mol Biol, A-5020 Salzburg, Austria.
C3 Sanford Burnham Prebys Medical Discovery Institute; United States Department of Energy (DOE); Brookhaven National Laboratory; Salzburg University
RP Riedl, SJ (corresponding author), Burnham Inst, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA.
EM robert.schwarzenbacher@sbg.ac.at; sriedl@burnham.org
FU cancer center grant [P30 CA030199]; Biological and Environmental Research DOE; National Center for Research Resources NIH; LLS scholarship;  [R01AA017238];  [PO1CA69381];  [MCEXT-033534]; National Cancer Institute [P30CA030199] Funding Source: NIH RePORTER
NR 30
TC 309
Z9 365
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 FEB 19
PY 2009
VL 457
IS 7232
BP 1019
EP 1022
DI 10.1038/nature07606
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400044
PM 19118384
DA 2026-03-09
ER

PT J
AU Yu, YC
   Bultje, RS
   Wang, XQ
   Shi, SH
AF Yu, Yong-Chun
   Bultje, Ronald S.
   Wang, Xiaoqun
   Shi, Song-Hai
TI Specific synapses develop preferentially among sister excitatory neurons in the neocortex
SO NATURE
LA English
DT Article
ID radial glial-cells; cortical-neurons; synaptic connections; cerebral-cortex; visual-cortex; rat; plasticity; circuits; layers; migration
AB Neurons in the mammalian neocortex are organized into functional columns(1,2). Within a column, highly specific synaptic connections are formed to ensure that similar physiological properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly specific(3-8) to allow even adjacent neurons to convey information independently(9-12). How this fine-scale microcircuit is constructed to create a functional columnar architecture at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by in utero intraventricular injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar micro-architectures in the mature neocortex.
C1 [Yu, Yong-Chun; Bultje, Ronald S.; Wang, Xiaoqun; Shi, Song-Hai] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
   [Bultje, Ronald S.] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine
RP Shi, SH (corresponding author), Mem Sloan Kettering Canc Ctr, Dev Biol Program, 1275 York Ave, New York, NY 10065 USA.
EM shis@mskcc.org
FU March of Dimes Foundation; Whitehall Foundation; Klingenstein Foundation; DANA Foundation; Autism Speaks Foundation; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Institutes of Health
NR 30
TC 250
Z9 296
U1 1
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 501
EP U3
DI 10.1038/nature07722
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400043
PM 19204731
DA 2026-03-09
ER

PT J
AU Nakanishi, H
   Bishop, KJM
   Kowalczyk, B
   Nitzan, A
   Weiss, EA
   Tretiakov, KV
   Apodaca, MM
   Klajn, R
   Stoddart, JF
   Grzybowski, BA
AF Nakanishi, Hideyuki
   Bishop, Kyle J. M.
   Kowalczyk, Bartlomiej
   Nitzan, Abraham
   Weiss, Emily A.
   Tretiakov, Konstantin V.
   Apodaca, Mario M.
   Klajn, Rafal
   Stoddart, J. Fraser
   Grzybowski, Bartosz A.
TI Photoconductance and inverse photoconductance in films of functionalized metal nanoparticles
SO NATURE
LA English
DT Article
ID self-assembled monolayers; charge-limited currents; molecular junctions; hydrated electron; alkanethiols; resistance; transport; cells
AB In traditional photoconductors(1-3), the impinging light generates mobile charge carriers in the valence and/or conduction bands, causing the material's conductivity to increase(4). Such positive photoconductance is observed in both bulk and nanostructured(5,6) photoconductors. Here we describe a class of nanoparticle-based materials whose conductivity can either increase or decrease on irradiation with visible light of wavelengths close to the particles' surface plasmon resonance. The remarkable feature of these plasmonic materials is that the sign of the conductivity change and the nature of the electron transport between the nanoparticles depend on the molecules comprising the self-assembled monolayers (SAMs)(7,8) stabilizing the nanoparticles. For SAMs made of electrically neutral (polar and non-polar) molecules, conductivity increases on irradiation. If, however, the SAMs contain electrically charged (either negatively or positively) groups, conductivity decreases. The optical and electrical characteristics of these previously undescribed inverse photoconductors can be engineered flexibly by adjusting the material properties of the nanoparticles and of the coating SAMs. In particular, in films comprising mixtures of different nanoparticles or nanoparticles coated with mixed SAMs, the overall photoconductance is a weighted average of the changes induced by the individual components. These and other observations can be rationalized in terms of light-induced creation of mobile charge carriers whose transport through the charged SAMs is inhibited by carrier trapping in transient polaron-like states(9,10). The nanoparticle-based photoconductors we describe could have uses in chemical sensors and/or in conjunction with flexible substrates.
C1 [Nakanishi, Hideyuki; Kowalczyk, Bartlomiej; Nitzan, Abraham; Weiss, Emily A.; Apodaca, Mario M.; Stoddart, J. Fraser; Grzybowski, Bartosz A.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
   [Nakanishi, Hideyuki; Bishop, Kyle J. M.; Kowalczyk, Bartlomiej; Tretiakov, Konstantin V.; Klajn, Rafal; Grzybowski, Bartosz A.] Northwestern Univ, Dept Biol & Chem Engn, Evanston, IL 60208 USA.
   [Nitzan, Abraham] Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel.
C3 Northwestern University; Northwestern University; Tel Aviv University
RP Grzybowski, BA (corresponding author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM grzybor@northwestern.edu
FU Alfred P. Sloan Fellowship; Dreyfus Teacher-Scholar Award
NR 30
TC 245
Z9 272
U1 2
U2 272
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 371
EP 375
DI 10.1038/nature08131
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000033
PM 19606145
DA 2026-03-09
ER

PT J
AU Gendrel, M
   Rapti, G
   Richmond, JE
   Bessereau, JL
AF Gendrel, Marie
   Rapti, Georgia
   Richmond, Janet E.
   Bessereau, Jean-Louis
TI A secreted complement-control-related protein ensures acetylcholine receptor clustering
SO NATURE
LA English
DT Article
ID elegans neuromuscular-junction; hikaru genki protein; caenorhabditis-elegans; c-elegans; levamisole resistance; glutamate receptors; drosophila; system; genes; trafficking
AB Efficient neurotransmission at chemical synapses relies on spatial congruence between the presynaptic active zone, where synaptic vesicles fuse, and the postsynaptic differentiation, where neurotransmitter receptors concentrate. Diverse molecular systems have evolved to localize receptors at synapses, but in most cases, they rely on scaffolding proteins localized below the plasma membrane(1-3). A few systems have been suggested to control the synaptic localization of neurotransmitter receptors through extracellular interactions, such as the pentraxins that bind AMPA receptors and trigger their aggregation(4). However, it is not yet clear whether these systems have a central role in the organization of postsynaptic domains in vivo or rather provide modulatory functions(5). Here we describe an extracellular scaffold that is necessary to cluster acetylcholine receptors at neuromuscular junctions in the nematode Caenorhabditis elegans. It involves the ectodomain of the previously identified transmembrane protein LEV-10 (ref. 6) and a novel extracellular protein, LEV-9. LEV-9 is secreted by the muscle cells and localizes at cholinergic neuromuscular junctions. Acetylcholine receptors, LEV-9 and LEV-10 are interdependent for proper synaptic localization and physically interact based on biochemical evidence. Notably, the function of LEV-9 relies on eight complement control protein (CCP) domains. These domains, also called 'sushi domains', are usually found in proteins regulating complement activity in the vertebrate immune system(7). Because the complement system does not exist in protostomes, our results suggest that some of the numerous uncharacterized CCP proteins expressed in the mammalian brain might be directly involved in the organization of the synapse, independently from immune functions.
C1 [Gendrel, Marie; Rapti, Georgia; Bessereau, Jean-Louis] ENS, Dept Biol, F-75005 Paris, France.
   [Gendrel, Marie; Rapti, Georgia; Bessereau, Jean-Louis] INSERM, U789, F-75005 Paris, France.
   [Richmond, Janet E.] Univ Illinois, Dept Biol, Chicago, IL 60607 USA.
C3 Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
RP Bessereau, JL (corresponding author), ENS, Dept Biol, F-75005 Paris, France.
EM jlbesse@biologie.ens.fr
FU Ministere de la Recherche; Association Francaise contre les Myopathies; Ministere de la Recherche fellow; INSERM Avenir; Agence Nationale de la Recherche [ANR-07-NEURO-032-01]; NIH [RO1 MH073156]
NR 41
TC 90
Z9 113
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 992
EP U258
DI 10.1038/nature08430
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700050
PM 19794415
DA 2026-03-09
ER

PT J
AU Compagno, M
   Lim, WK
   Grunn, A
   Nandula, SV
   Brahmachary, M
   Shen, Q
   Bertoni, F
   Ponzoni, M
   Scandurra, M
   Califano, A
   Bhagat, G
   Chadburn, A
   Dalla-Favera, R
   Pasqualucci, L
AF Compagno, Mara
   Lim, Wei Keat
   Grunn, Adina
   Nandula, Subhadra V.
   Brahmachary, Manisha
   Shen, Qiong
   Bertoni, Francesco
   Ponzoni, Maurilio
   Scandurra, Marta
   Califano, Andrea
   Bhagat, Govind
   Chadburn, Amy
   Dalla-Favera, Riccardo
   Pasqualucci, Laura
TI Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphoma
SO NATURE
LA English
DT Article
ID hodgkin lymphoma; expression; receptor; cd40; transduction; responses; family; cancer; bcl6; a20
AB Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adulthood, comprises multiple biologically and clinically distinct subtypes including germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL1. Gene expression profile studies have shown that its most aggressive subtype, ABC-DLBCL, is associated with constitutive activation of the NF-kappa B transcription complex(2). However, except for a small fraction of cases(3), it remains unclear whether NF-kappa B activation in these tumours represents an intrinsic program of the tumour cell of origin or a pathogenetic event. Here we show that >50% of ABC-DLBCL and a smaller fraction of GCB- DLBCL carry somatic mutations in multiple genes, including negative (TNFAIP3, also called A20) and positive (CARD11, TRAF2, TRAF5, MAP3K7 (TAK1) and TNFRSF11A ( RANK)) regulators of NF-kappa B. Of these, the A20 gene, which encodes a ubiquitin-modifying enzyme involved in termination of NF-kappa B responses, is most commonly affected, with similar to 30% of patients displaying biallelic inactivation by mutations and/or deletions. When reintroduced in cell lines carrying biallelic inactivation of the gene, A20 induced apoptosis and cell growth arrest, indicating a tumour suppressor role. Less frequently, missense mutations of TRAF2 and CARD11 produce molecules with significantly enhanced ability to activate NF-kappa B. Thus, our results demonstrate that NF-kappa B activation in DLBCL is caused by genetic lesions affecting multiple genes, the loss or activation of which may promote lymphomagenesis by leading to abnormally prolonged NF-kappa B responses.
C1 [Compagno, Mara; Grunn, Adina; Nandula, Subhadra V.; Brahmachary, Manisha; Shen, Qiong; Califano, Andrea; Bhagat, Govind; Dalla-Favera, Riccardo; Pasqualucci, Laura] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA.
   [Compagno, Mara; Grunn, Adina; Nandula, Subhadra V.; Brahmachary, Manisha; Shen, Qiong; Califano, Andrea; Bhagat, Govind; Dalla-Favera, Riccardo; Pasqualucci, Laura] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
   [Lim, Wei Keat; Califano, Andrea] Columbia Univ, Joint Ctr Syst Biol, New York, NY 10032 USA.
   [Nandula, Subhadra V.; Bhagat, Govind; Dalla-Favera, Riccardo; Pasqualucci, Laura] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Bertoni, Francesco; Scandurra, Marta] Oncol Inst So Switzerland IOSI, Expt Oncol Lab, CH-6500 Bellinzona, Switzerland.
   [Bertoni, Francesco; Scandurra, Marta] Oncol Inst So Switzerland IOSI, Lymphoma Unit, CH-6500 Bellinzona, Switzerland.
   [Ponzoni, Maurilio] Ist Sci San Raffaele, Unit Lymphoid Malignancies, Pathol Unit, I-20132 Milan, Italy.
   [Chadburn, Amy] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA.
   [Dalla-Favera, Riccardo] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University; Institute of Oncology Research (IOR); Institute of Oncology Research (IOR); Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Cornell University; Weill Cornell Medicine; Columbia University
RP Pasqualucci, L (corresponding author), Columbia Univ, Inst Canc Genet, New York, NY 10032 USA.
EM lp171@columbia.edu
FU NIH [P01 CA92625-07]; NIAID [R01AI066116]; National Centers for Biomedical Computing NIH Roadmap [U54CA121852]; Leukemia and Lymphoma Society SCOR
NR 35
TC 879
Z9 1014
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 4
PY 2009
VL 459
IS 7247
BP 717
EP U124
DI 10.1038/nature07968
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600047
PM 19412164
DA 2026-03-09
ER

PT J
AU Narteau, C
   Byrdina, S
   Shebalin, P
   Schorlemmer, D
AF Narteau, Clement
   Byrdina, Svetlana
   Shebalin, Peter
   Schorlemmer, Danijel
TI Common dependence on stress for the two fundamental laws of statistical seismology
SO NATURE
LA English
DT Article
ID earthquake catalogs; seismicity; california; aftershocks; magnitude; models; decay
AB Two of the long-standing relationships of statistical seismology are power laws: the Gutenberg-Richter relation(1) describing the earthquake frequency-magnitude distribution, and the Omori-Utsu law(2) characterizing the temporal decay of aftershock rate following a main shock. Recently, the effect of stress on the slope (the b value) of the earthquake frequency-magnitude distribution was determined(3) by investigations of the faulting-style dependence of the b value. In a similar manner, we study here aftershock sequences according to the faulting style of their main shocks. We show that the time delay before the onset of the power-law aftershock decay rate ( the c value) is on average shorter for thrust main shocks than for normal fault earthquakes, taking intermediate values for strike-slip events. These similar dependences on the faulting style indicate that both of the fundamental power laws are governed by the state of stress. Focal mechanisms are known for only 2 per cent of aftershocks. Therefore, c and b values are independent estimates and can be used as new tools to infer the stress field, which remains difficult to measure directly.
C1 [Narteau, Clement; Byrdina, Svetlana; Shebalin, Peter] Univ P7, UMR 7154, CNRS, Inst Phys Globe, F-75252 Paris 05, France.
   [Byrdina, Svetlana] Univ Savoie, IRD, CNRS, Lab Geophys Interne & Tectonophys,UMR 5559, F-73376 Le Bourget Du Lac, France.
   [Shebalin, Peter] Int Inst Earthquake Predict Theory & Math Geophys, Moscow 117997, Russia.
   [Schorlemmer, Danijel] Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite; Universite Savoie Mont Blanc; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Russian Academy of Sciences; Institute of Earthquake Prediction Theory & Mathematical Geophysics; University of Southern California
RP Narteau, C (corresponding author), Univ P7, UMR 7154, CNRS, Inst Phys Globe, 4 Pl Jussieu, F-75252 Paris 05, France.
EM narteau@ipgp.jussieu.fr
NR 29
TC 122
Z9 132
U1 2
U2 39
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 642
EP U113
DI 10.1038/nature08553
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900039
PM 19956258
DA 2026-03-09
ER

PT J
AU Rybczynski, N
   Dawson, MR
   Tedford, RH
AF Rybczynski, Natalia
   Dawson, Mary R.
   Tedford, Richard H.
TI A semi-aquatic Arctic mammalian carnivore from the Miocene epoch and origin of Pinnipedia
SO NATURE
LA English
DT Article
ID phylogeny; impact
AB Modern pinnipeds (seals, sea lions and the walrus) are semi-aquatic, generally marine carnivores the limbs of which have been modified into flippers. Recent phylogenetic studies using morphological and molecular evidence support pinniped monophyly, and suggest a sister relationship with ursoids(1,2) (for example bears) or musteloids(3-7) (the clade that includes skunks, badgers, weasels and otters). Although the position of pinnipeds within modern carnivores appears moderately well resolved, fossil evidence of the morphological steps leading from a terrestrial ancestor to the modern marine forms has been weak or contentious. The earliest well-represented fossil pinniped is Enaliarctos, a marine form with flippers, which had appeared on the northwestern shores of North America by the early Miocene epoch(8,9). Here we report the discovery of a nearly complete skeleton of a new semi-aquatic carnivore from an early Miocene lake deposit in Nunavut, Canada, that represents a morphological link in early pinniped evolution. The new taxon retains a long tail and the proportions of its fore-and hindlimbs are more similar to those of modern terrestrial carnivores than to modern pinnipeds. Morphological traits indicative of semi-aquatic adaptation include a forelimb with a prominent deltopectoral ridge on the humerus, a posterodorsally expanded scapula, a pelvis with relatively short ilium, a shortened femur and flattened phalanges, suggestive of webbing. The new fossil shows evidence of pinniped affinities and similarities to the early Oligocene Amphicticeps from Asia and the late Oligocene and Miocene Potamotherium from Europe. The discovery suggests that the evolution of pinnipeds included a freshwater transitional phase, and may support the hypothesis that the Arctic was an early centre of pinniped evolution.
C1 [Rybczynski, Natalia] Canadian Museum Nat, Ottawa, ON K1P 6P4, Canada.
   [Dawson, Mary R.] Carnegie Museum Nat Hist, Pittsburgh, PA 15213 USA.
   [Tedford, Richard H.] Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA.
C3 American Museum of Natural History (AMNH)
RP Rybczynski, N (corresponding author), Canadian Museum Nat, POB 3443 STN D, Ottawa, ON K1P 6P4, Canada.
EM nrybczynski@mus-nature.ca
NR 30
TC 95
Z9 113
U1 4
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 23
PY 2009
VL 458
IS 7241
BP 1021
EP 1024
DI 10.1038/nature07985
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900041
PM 19396145
DA 2026-03-09
ER

PT J
AU Adams, GB
   Alley, IR
   Chung, U
   Chabner, KT
   Jeanson, NT
   Lo Celso, C
   Marsters, ES
   Chen, M
   Weinstein, LS
   Lin, CP
   Kronenberg, HM
   Scadden, DT
AF Adams, Gregor B.
   Alley, Ian R.
   Chung, Ung-il
   Chabner, Karissa T.
   Jeanson, Nathaniel T.
   Lo Celso, Cristina
   Marsters, Emily S.
   Chen, Min
   Weinstein, Lee S.
   Lin, Charles P.
   Kronenberg, Henry M.
   Scadden, David T.
TI Haematopoietic stem cells depend on Gαs-mediated signalling to engraft bone marrow
SO NATURE
LA English
DT Article
ID in-vivo; cholera-toxin; mice; differentiation; lymphopoiesis; myelopoiesis; migration; selectins; cxcr4
AB Haematopoietic stem and progenitor cells (HSPCs) change location during development(1) and circulate in mammals throughout life(2), moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention(3-5). Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the guanine-nucleotide-binding protein stimulatory a subunit (G alpha(s)). HSPCs from adult mice deficient in G alpha(s) (G alpha(-/-)(s)) differentiate and undergo chemotaxis, but also do not home to or engraft in the bone marrow in adult mice and demonstrate a marked inability to engage the marrow microvasculature. If deleted after engraftment, G alpha(s) deficiency did not lead to lack of retention in the marrow, rather cytokine-induced mobilization into the blood was impaired. Testing whether activation of G alpha(s) affects HSPCs, pharmacological activators enhanced homing and engraftment in vivo. G alpha(s) governs specific aspects of HSPC localization under physiological conditions in vivo and may be pharmacologically targeted to improve transplantation efficiency.
C1 [Adams, Gregor B.; Alley, Ian R.; Chabner, Karissa T.; Jeanson, Nathaniel T.; Lo Celso, Cristina; Marsters, Emily S.; Scadden, David T.] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Chung, Ung-il; Kronenberg, Henry M.] Harvard Univ, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
   [Lin, Charles P.] Harvard Univ, Sch Med, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA.
   [Lin, Charles P.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Adams, Gregor B.; Lo Celso, Cristina; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Scadden, David T.] Harvard Univ, Sch Med, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA.
   [Chen, Min; Weinstein, Lee S.] NIDDKD, Bethesda, MD 20892 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Harvard Medical School; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Scadden, DT (corresponding author), Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
EM dscadden@mgh.harvard.edu
FU Burroughs Wellcome Fund, Doris Duke Charitable Trust; Harvard Stem Cell Institute; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK043313] Funding Source: NIH RePORTER
NR 21
TC 54
Z9 70
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 7
PY 2009
VL 459
IS 7243
BP 103
EP U111
DI 10.1038/nature07859
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300038
PM 19322176
DA 2026-03-09
ER

PT J
AU Oda, T
   Iwasa, M
   Aihara, T
   Maéda, Y
   Narita, A
AF Oda, Toshiro
   Iwasa, Mitsusada
   Aihara, Tomoki
   Maeda, Yuichiro
   Narita, Akihiro
TI The nature of the globular-to fibrous-actin transition
SO NATURE
LA English
DT Article
ID fiber diffraction data; f-actin; crystal-structure; structural basis; monomeric actin; arp2/3 complex; electron cryomicroscopy; molecular-dynamics; normal-modes; yeast actin
AB Actin plays crucial parts in cell motility through a dynamic process driven by polymerization and depolymerization, that is, the globular ( G) to fibrous ( F) actin transition. Although our knowledge about the actin- based cellular functions and the molecules that regulate the G- to F- actin transition is growing, the structural aspects of the transition remain enigmatic. We created a model of F- actin using X- ray fibre diffraction intensities obtained from well oriented sols of rabbit skeletal muscle F- actin to 3.3 A in the radial direction and 5.6 A along the equator. Here we show that the G- to F- actin conformational transition is a simple relative rotation of the two major domains by about 20 degrees. As a result of the domain rotation, the actin molecule in the filament is flat. The flat form is essential for the formation of stable, helical F- actin. Our F- actin structure model provides the basis for understanding actin polymerization as well as its molecular interactions with actin- binding proteins.
C1 [Oda, Toshiro; Aihara, Tomoki] RIKEN, Harima Inst, Xray Struct Anal Res Team, SPring 8 Ctr, Mikazuki, Hyogo 6795148, Japan.
   [Oda, Toshiro; Iwasa, Mitsusada; Maeda, Yuichiro] Japan Sci & Technol Agcy, ERATO Project Actin Filament Dynam, Mikazuki, Hyogo 6795148, Japan.
   [Maeda, Yuichiro; Narita, Akihiro] Nagoya Univ, Grad Sch Sci, Struct Biol Res Ctr, Nagoya, Aichi 4648601, Japan.
   [Maeda, Yuichiro; Narita, Akihiro] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Nagoya, Aichi 4648601, Japan.
C3 Japan Synchrotron Radiation Research Institute; RIKEN; Japan Science & Technology Agency (JST); Nagoya University; Nagoya University
RP Oda, T (corresponding author), RIKEN, Harima Inst, Xray Struct Anal Res Team, SPring 8 Ctr, 1-1-1 Kouto, Mikazuki, Hyogo 6795148, Japan.
EM toda@spring8.or.jp
FU Kazato Research Foundation
NR 50
TC 506
Z9 626
U1 0
U2 101
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 22
PY 2009
VL 457
IS 7228
BP 441
EP 445
DI 10.1038/nature07685
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200038
PM 19158791
DA 2026-03-09
ER

PT J
AU Eldrett, JS
   Greenwood, DR
   Harding, IC
   Huber, M
AF Eldrett, James S.
   Greenwood, David R.
   Harding, Ian C.
   Huber, Matthew
TI Increased seasonality through the Eocene to Oligocene transition in northern high latitudes
SO NATURE
LA English
DT Article
ID carbon-dioxide concentrations; model version-3 ccsm3; eocene/oligocene boundary; calcite compensation; paleoclimatic change; climate sensitivity; bipolar glaciation; greenland; ice; simulation
AB A profound global climate shift took place at the Eocene-Oligocene transition (similar to 33.5 million years ago) when Cretaceous/early Palaeogene greenhouse conditions gave way to icehouse conditions(1-3). During this interval, changes in the Earth's orbit and a long-term drop in atmospheric carbon dioxide concentrations(4-6) resulted in both the growth of Antarctic ice sheets to approximately their modern size(2,3) and the appearance of Northern Hemisphere glacial ice(7,8). However, palaeoclimatic studies of this interval are contradictory: although some analyses indicate no major climatic changes(9,10), others imply cooler temperatures(11), increased seasonality(12,13) and/or aridity(12-15). Climatic conditions in high northern latitudes over this interval are particularly poorly known. Here we present northern high-latitude terrestrial climate estimates for the Eocene to Oligocene interval, based on bioclimatic analysis of terrestrially derived spore and pollen assemblages preserved in marine sediments from the Norwegian-Greenland Sea. Our data indicate a cooling of similar to 5 degrees C in cold-month (winter) mean temperatures to 0-2 degrees C, and a concomitant increased seasonality before the Oi-1 glaciation event. These data indicate that a cooling component is indeed incorporated in the delta 18O isotope shift across the Eocene Oligocene transition. However, the relatively warm summer temperatures at that time mean that continental ice on East Greenland was probably restricted to alpine outlet glaciers.
C1 [Eldrett, James S.] Shell Explorat & Prod UK Ltd, Aberdeen AB12 3FY, Scotland.
   [Greenwood, David R.] Brandon Univ, Dept Biol, Brandon, MB R7A 6A9, Canada.
   [Harding, Ian C.] Univ Southampton, Natl Oceanog Ctr, Sch Ocean & Earth Sci, Southampton SO14 3ZH, Hants, England.
   [Huber, Matthew] Purdue Univ, Dept Earth & Atmospher Sci, Purdue Climate Change Res Ctr, W Lafayette, IN 47906 USA.
C3 Brandon University; University of Southampton; NERC National Oceanography Centre; Purdue University System; Purdue University
RP Eldrett, JS (corresponding author), Shell Explorat & Prod UK Ltd, 1 Altens Farm Rd, Aberdeen AB12 3FY, Scotland.
EM james.eldrett@shell.com
FU US National Science Foundation (NSF); NSERC (Canada)
NR 48
TC 244
Z9 268
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 JUN 18
PY 2009
VL 459
IS 7249
BP 969
EP U91
DI 10.1038/nature08069
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500039
PM 19536261
DA 2026-03-09
ER

PT J
AU Christensen, UR
   Holzwarth, V
   Reiners, A
AF Christensen, Ulrich R.
   Holzwarth, Volkmar
   Reiners, Ansgar
TI Energy flux determines magnetic field strength of planets and stars
SO NATURE
LA English
DT Article
ID core-mantle boundary; t-tauri stars; m dwarfs; mass; dynamos
AB Themagnetic fields of Earth and Jupiter, along with those of rapidly rotating, low- mass stars, are generated by convection- driven dynamos that may operate similarly(1-4) ( the slowly rotating Sun generates its field through a different dynamo mechanism(5)). The field strengths of planets and stars vary over three orders of magnitude, but the critical factor causing that variation has hitherto been unclear(5,6). Here we report an extension of a scaling law derived from geodynamo models(7) to rapidly rotating stars that have strong density stratification. The unifying principle in the scaling law is that the energy flux available for generating the magnetic field sets the field strength. Our scaling law fits the observed field strengths of Earth, Jupiter, young contracting stars and rapidly rotating low-mass stars, despite vast differences in the physical conditions of the objects. We predict that the field strengths of rapidly rotating brown dwarfs and massive extrasolar planets are high enough to make them observable.
C1 [Christensen, Ulrich R.; Holzwarth, Volkmar] Max Planck Inst Sonnensyst Forsch, D-37191 Katlenburg Lindau, Germany.
   [Reiners, Ansgar] Univ Gottingen, Inst Astrophys, D-37077 Gottingen, Germany.
C3 Max Planck Society; University of Gottingen
RP Christensen, UR (corresponding author), Max Planck Inst Sonnensyst Forsch, Max Planck Str 2, D-37191 Katlenburg Lindau, Germany.
EM christensen@mps.mpg.de
NR 30
TC 318
Z9 348
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 8
PY 2009
VL 457
IS 7226
BP 167
EP 169
DI 10.1038/nature07626
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200026
PM 19129842
DA 2026-03-09
ER

PT J
AU Hishida, T
   Kubota, Y
   Carr, AM
   Iwasaki, H
AF Hishida, Takashi
   Kubota, Yoshino
   Carr, Antony M.
   Iwasaki, Hiroshi
TI RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light
SO NATURE
LA English
DT Article
ID dna-damage tolerance; nucleotide excision-repair; saccharomyces-cerevisiae; postreplication repair; budding yeast; replication; checkpoint; protein; mechanisms; ubiquitin
AB In nature, organisms are exposed to chronic low- dose ultraviolet light ( CLUV) as opposed to the acute high doses common to laboratory experiments. Analysis of the cellular response to acute high-dose exposure has delineated the importance of direct DNA repair by the nucleotide excision repair pathway(1) and for checkpoint-induced cell cycle arrest in promoting cell survival(2). Here we examine the response of yeast cells to CLUV and identify a key role for the RAD6-RAD18-RAD5 error- free postreplication repair (RAD6 error-free PRR) pathway(3,4) in promoting cell growth and survival. We show that loss of the RAD6 error- free PRR pathway results in DNA-damage-checkpoint- induced G2 arrest in CLUV-exposed cells, whereas wild-type and nucleotide-excision-repair-deficient cells are largely unaffected. Cell cycle arrest in the absence of the RAD6 error- free PRR pathway was not caused by a repair defect or by the accumulation of ultraviolet-induced photoproducts. Notably, we observed increased replication protein A (RPA) and Rad52 - yellow fluorescent protein foci(5) in the CLUV- exposed rad18 Delta cells and demonstrated that Rad52- mediated homologous recombination is required for the viability of the rad18 Delta cells after release from CLUV- induced G2 arrest. These and other data presented suggest that, in response to environmental levels of ultraviolet exposure, the RAD6 error- free PRR pathway promotes replication of damaged templates without the generation of extensive single- stranded DNA regions. Thus, the error- free PRR pathway is specifically important during chronic low- dose ultraviolet exposure to prevent counter- productive DNA checkpoint activation and allow cells to proliferate normally.
C1 [Hishida, Takashi; Kubota, Yoshino] Osaka Univ, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan.
   [Carr, Antony M.] Univ Sussex, MRC Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
   [Iwasaki, Hiroshi] Yokohama City Univ, Int Grad Sch Arts & Sci, Kanagawa 2300045, Japan.
C3 University of Osaka; University of Sussex; Yokohama City University
RP Hishida, T (corresponding author), Osaka Univ, Res Inst Microbial Dis, 3-1 Yamadaoka, Suita, Osaka 5650871, Japan.
EM hishida@biken.osaka-u.ac.jp
FU Sumitomo foundation; Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; MRC (UK) [G0600233]; Medical Research Council [G0600233, G0300662B] Funding Source: researchfish; MRC [G0600233] Funding Source: UKRI
NR 34
TC 67
Z9 76
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 29
PY 2009
VL 457
IS 7229
BP 612
EP U124
DI 10.1038/nature07580
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200048
PM 19079240
DA 2026-03-09
ER

PT J
AU Alby, K
   Schaefer, D
   Bennett, RJ
AF Alby, Kevin
   Schaefer, Dana
   Bennett, Richard J.
TI Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; cryptococcus-neoformans; sexual reproduction; gene-expression; bar1 gene; pheromone; protein; yeast; identification; infections
AB Candida albicans is the most common fungal pathogen in humans, causing both debilitating mucosal infections and potentially life-threatening systemic infections(1,2). Until recently, C. albicans was thought to be strictly asexual, existing only as an obligate diploid. A cryptic mating cycle has since been uncovered in which diploid a and alpha cells undergo efficient cell and nuclear fusion, resulting in tetraploid a/alpha mating products(3-6). Whereas mating between a and alpha cells has been established (heterothallism), we report here two pathways for same-sex mating (homothallism) in C. albicans. First, unisexual populations of a cells were found to undergo autocrine pheromone signalling and same-sex mating in the absence of the Bar1 protease. In both C. albicans and Saccharomyces cerevisiae, Bar1 is produced by a cells and inactivates mating pheromone alpha, typically secreted by alpha cells(7-10). C. albicans Delta bar1 a cells were shown to secrete both a and alpha mating pheromones; alpha-pheromone activated self-mating in these cells in a process dependent on Ste2, the receptor for alpha-pheromone. In addition, pheromone production by alpha cells was found to promote same-sex mating between wild-type a cells. These results establish that homothallic mating can occur in C. albicans, revealing the potential for genetic exchange even within unisexual populations of the organism. Furthermore, Bar1 protease has an unexpected but pivotal role in determining whether sexual reproduction can potentially be homothallic or is exclusively heterothallic. These findings also have implications for the mode of sexual reproduction in related species that propagate unisexually, and indicate a role for specialized sexual cycles in the survival and adaptation of pathogenic fungi.
C1 [Alby, Kevin; Schaefer, Dana; Bennett, Richard J.] Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA.
C3 Brown University
RP Bennett, RJ (corresponding author), Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA.
EM Richard_Bennett@brown.edu
FU Burroughs Wellcome Fund
NR 34
TC 169
Z9 199
U1 2
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 13
PY 2009
VL 460
IS 7257
BP 890
EP U127
DI 10.1038/nature08252
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300038
PM 19675652
DA 2026-03-09
ER

PT J
AU Dekel, A
   Birnboim, Y
   Engel, G
   Freundlich, J
   Goerdt, T
   Mumcuoglu, M
   Neistein, E
   Pichon, C
   Teyssier, R
   Zinger, E
AF Dekel, A.
   Birnboim, Y.
   Engel, G.
   Freundlich, J.
   Goerdt, T.
   Mumcuoglu, M.
   Neistein, E.
   Pichon, C.
   Teyssier, R.
   Zinger, E.
TI Cold streams in early massive hot haloes as the main mode of galaxy formation
SO NATURE
LA English
DT Article
ID integral field spectroscopy; submillimeter galaxy; major mergers; disk galaxy; dark-matter; to 2; evolution; accretion; z-similar-to-2.3; simulations
AB Massive galaxies in the young Universe, ten billion years ago, formed stars at surprising intensities(1,2). Although this is commonly attributed to violent mergers, the properties of many of these galaxies are incompatible with such events, showing gas- rich, clumpy, extended rotating disks not dominated by spheroids(1-5). Cosmological simulations(6) and clustering theory(6,7) are used to explore how these galaxies acquired their gas. Here we report that they are 'stream- fed galaxies', formed from steady, narrow, cold gas streams that penetrate the shock- heated media of massive dark matter haloes(8,9). A comparison with the observed abundance of star- forming galaxies implies that most of the input gas must rapidly convert to stars. One- third of the stream mass is in gas clumps leading to mergers of mass ratio greater than 1: 10, and the rest is in smoother flows. With a merger duty cycle of 0.1, three- quarters of the galaxies forming stars at a given rate are fed by smooth streams. The rarer, submillimetre galaxies that form stars even more intensely(2,12,13) are largely merger- induced starbursts. Unlike destructive mergers, the streams are likely to keep the rotating disk configuration intact, although turbulent and broken into giant star- forming clumps that merge into a central spheroid(4,10,11). This stream- driven scenario for the formation of discs and spheroids is an alternative to the merger picture.
C1 [Dekel, A.; Birnboim, Y.; Engel, G.; Freundlich, J.; Goerdt, T.; Mumcuoglu, M.; Neistein, E.; Zinger, E.] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Birnboim, Y.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Freundlich, J.] Ecole Normale Super, Dept Phys, F-75231 Paris, France.
   [Neistein, E.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Pichon, C.] Inst Astrophys, F-75014 Paris, France.
   [Pichon, C.] UPMC, F-75014 Paris, France.
   [Teyssier, R.] CEA Saclay, DSM IRFU, UMR AIM, F-91191 Gif Sur Yvette, France.
   [Teyssier, R.] Univ Zurich, Inst Theoret Phys, CH-8057 Zurich, Switzerland.
C3 Hebrew University of Jerusalem; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; Universite PSL; Ecole Normale Superieure (ENS); Max Planck Society; Sorbonne Universite; Sorbonne Universite; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite Paris Saclay; University of Zurich
RP Dekel, A (corresponding author), Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
EM dekel@phys.huji.ac.il
FU France-Israel Teamwork in Sciences; German-Israel Science Foundation; Israel Science Foundation; NASA Theory Program at UCSC; Minerva fellowship
NR 33
TC 1481
Z9 1614
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 22
PY 2009
VL 457
IS 7228
BP 451
EP 454
DI 10.1038/nature07648
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200040
PM 19158792
DA 2026-03-09
ER

PT J
AU Unterreithmeier, QP
   Weig, EM
   Kotthaus, JP
AF Unterreithmeier, Quirin P.
   Weig, Eva M.
   Kotthaus, Joerg P.
TI Universal transduction scheme for nanomechanical systems based on dielectric forces
SO NATURE
LA English
DT Article
ID nanoelectromechanical systems; parametric resonance; motion; actuation; oscillator; noise; nems
AB Any polarizable body placed in an inhomogeneous electric field experiences a dielectric force. This phenomenon is well known from the macroscopic world: a water jet is deflected when approached by a charged object. This fundamental mechanism is exploited in a variety of contexts-for example, trapping microscopic particles in an optical tweezer(1), where the trapping force is controlled via the intensity of a laser beam, or dielectrophoresis(2), where electric fields are used to manipulate particles in liquids. Here we extend the underlying concept to the rapidly evolving field of nanoelectromechanical systems(3,4) (NEMS). A broad range of possible applications are anticipated for these systems(5,6,7), but drive and detection schemes for nanomechanical motion still need to be optimized(8,9). Our approach is based on the application of dielectric gradient forces for the controlled and local transduction of NEMS. Using a set of on-chip electrodes to create an electric field gradient, we polarize a dielectric resonator and subject it to an attractive force that can be modulated at high frequencies. This universal actuation scheme is efficient, broadband and scalable. It also separates the driving scheme from the driven mechanical element, allowing for arbitrary polarizable materials and thus potentially ultralow dissipation NEMS10. In addition, it enables simple voltage tuning of the mechanical resonance over a wide frequency range, because the dielectric force depends strongly on the resonator-electrode separation. We use the modulation of the resonance frequency to demonstrate parametric actuation(11,12). Moreover, we reverse the actuation principle to realize dielectric detection, thus allowing universal transduction of NEMS. We expect this combination to be useful both in the study of fundamental principles and in applications such as signal processing and sensing.
C1 [Unterreithmeier, Quirin P.; Weig, Eva M.; Kotthaus, Joerg P.] Univ Munich, Fak Phys, D-80539 Munich, Germany.
   [Unterreithmeier, Quirin P.; Weig, Eva M.; Kotthaus, Joerg P.] Univ Munich, CeNS, D-80539 Munich, Germany.
C3 University of Munich; University of Munich
RP Kotthaus, JP (corresponding author), Univ Munich, Fak Phys, Geschwister Scholl Pl 1, D-80539 Munich, Germany.
EM kotthaus@lmu.de
FU Deutsche Forschungsgemeinschaft [Ko 416/18]; German Excellence Initiative via the Nanosystems Initiative Munich (NIM); LMUexcellent; LMUinnovativ
NR 30
TC 212
Z9 241
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 23
PY 2009
VL 458
IS 7241
BP 1001
EP 1004
DI 10.1038/nature07932
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900036
PM 19396140
DA 2026-03-09
ER

PT J
AU Maher, CA
   Kumar-Sinha, C
   Cao, XH
   Kalyana-Sundaram, S
   Han, B
   Jing, XJ
   Sam, L
   Barrette, T
   Palanisamy, N
   Chinnaiyan, AM
AF Maher, Christopher A.
   Kumar-Sinha, Chandan
   Cao, Xuhong
   Kalyana-Sundaram, Shanker
   Han, Bo
   Jing, Xiaojun
   Sam, Lee
   Barrette, Terrence
   Palanisamy, Nallasivam
   Chinnaiyan, Arul M.
TI Transcriptome sequencing to detect gene fusions in cancer
SO NATURE
LA English
DT Article
ID somatic mutations; human breast; lung-cancer; identification; aberrations; inhibitor; patterns; efficacy; imatinib; protein
AB Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours(1), have recently been described in common solid tumours(2-9). Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to 're-discover' the BCR-ABL1 (ref. 10) gene fusion in a chronic myelogenous leukaemia cell line and the TMPRSS2-ERG(2,3) gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeric transcripts in cancer cell lines and tumours. Taken together, this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization.
C1 [Maher, Christopher A.; Kumar-Sinha, Chandan; Cao, Xuhong; Kalyana-Sundaram, Shanker; Han, Bo; Jing, Xiaojun; Sam, Lee; Barrette, Terrence; Palanisamy, Nallasivam; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
   [Cao, Xuhong; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
   [Maher, Christopher A.; Kumar-Sinha, Chandan; Kalyana-Sundaram, Shanker; Han, Bo; Jing, Xiaojun; Sam, Lee; Barrette, Terrence; Palanisamy, Nallasivam; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA.
   [Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Howard Hughes Medical Institute; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Chinnaiyan, AM (corresponding author), Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
EM arul@umich.edu
FU National Institutes of Health; Department of Defense; Early Detection Research Network; NCIBI [U54 DA 021519]; American Association of Cancer Research Amgen Fellowship in Clinical/Translational Research; Canary Foundation and American Cancer Society Early Detection Postdoctoral Fellowship
NR 33
TC 665
Z9 875
U1 1
U2 105
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 5
PY 2009
VL 458
IS 7234
BP 97
EP U9
DI 10.1038/nature07638
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000040
PM 19136943
DA 2026-03-09
ER

PT J
AU Dang, WW
   Steffen, KK
   Perry, R
   Dorsey, JA
   Johnson, FB
   Shilatifard, A
   Kaeberlein, M
   Kennedy, BK
   Berger, SL
AF Dang, Weiwei
   Steffen, Kristan K.
   Perry, Rocco
   Dorsey, Jean A.
   Johnson, F. Brad
   Shilatifard, Ali
   Kaeberlein, Matt
   Kennedy, Brian K.
   Berger, Shelley L.
TI Histone H4 lysine 16 acetylation regulates cellular lifespan
SO NATURE
LA English
DT Article
ID block protein fob1; saccharomyces-cerevisiae; calorie restriction; genomic instability; mother cells; yeast; sir2; replication; chromatin; sirtuins
AB Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved NAD(+)-dependent deacetylases or ADP-ribosyltransferases, promote longevity in diverse organisms; however, their molecular mechanisms in ageing regulation remain poorly understood. Yeast Sir2, the first member of the family to be found, establishes and maintains chromatin silencing by removing histone H4 lysine 16 acetylation and bringing in other silencing proteins. Here we report an age-associated decrease in Sir2 protein abundance accompanied by an increase in H4 lysine 16 acetylation and loss of histones at specific subtelomeric regions in replicatively old yeast cells, which results in compromised transcriptional silencing at these loci. Antagonizing activities of Sir2 and Sas2, a histone acetyltransferase, regulate the replicative lifespan through histone H4 lysine 16 at subtelomeric regions. This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin.
C1 [Dang, Weiwei; Perry, Rocco; Dorsey, Jean A.; Berger, Shelley L.] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA.
   [Kaeberlein, Matt] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
   [Steffen, Kristan K.; Kennedy, Brian K.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Johnson, F. Brad] Univ Penn, Sch Med, Dept Pathol & Lab Med, Cell & Mol Biol Grp,Biomed Grad Studies, Philadelphia, PA 19104 USA.
   [Johnson, F. Brad] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA.
   [Shilatifard, Ali] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Berger, Shelley L.] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
C3 The Wistar Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Pennsylvania; University of Pennsylvania; Stowers Institute for Medical Research; University of Pennsylvania
RP Berger, SL (corresponding author), Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA.
EM sberger@mail.med.upenn.edu
FU US National Institutes of Health; American Federation for Aging Research Julie Martin Mid-Career Award in Aging Research
NR 45
TC 518
Z9 622
U1 1
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 802
EP U2
DI 10.1038/nature08085
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500030
PM 19516333
DA 2026-03-09
ER

PT J
AU Visel, A
   Blow, MJ
   Li, ZR
   Zhang, T
   Akiyama, JA
   Holt, A
   Plajzer-Frick, I
   Shoukry, M
   Wright, C
   Chen, F
   Afzal, V
   Ren, B
   Rubin, EM
   Pennacchio, LA
AF Visel, Axel
   Blow, Matthew J.
   Li, Zirong
   Zhang, Tao
   Akiyama, Jennifer A.
   Holt, Amy
   Plajzer-Frick, Ingrid
   Shoukry, Malak
   Wright, Crystal
   Chen, Feng
   Afzal, Veena
   Ren, Bing
   Rubin, Edward M.
   Pennacchio, Len A.
TI ChIP-seq accurately predicts tissue-specific activity of enhancers
SO NATURE
LA English
DT Article
ID genome; chromatin; sequence; vertebrate; constraint; promoters; database; identification; coactivator; recruitment
AB A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant- acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non- coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer- associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue- specific enhancers in human biology and disease on a genome- wide scale.
C1 [Visel, Axel; Blow, Matthew J.; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Afzal, Veena; Rubin, Edward M.; Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA.
   [Blow, Matthew J.; Zhang, Tao; Wright, Crystal; Chen, Feng; Rubin, Edward M.; Pennacchio, Len A.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Li, Zirong; Ren, Bing] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; United States Department of Energy (DOE); Joint Genome Institute - JGI; Joint BioEnergy Institute - JBEI; Ludwig Institute for Cancer Research; University of California System; University of California San Diego
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 Berkeley-PGA; National Heart, Lung, & Blood Institute; National Human Genome Research Institute; American Heart Association; Ludwig Institute for Cancer Research; National Human Genome Research Institute [R01HG003988] Funding Source: NIH RePORTER
NR 53
TC 1301
Z9 1703
U1 0
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 FEB 12
PY 2009
VL 457
IS 7231
BP 854
EP 858
DI 10.1038/nature07730
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700039
PM 19212405
DA 2026-03-09
ER

PT J
AU Wang, YG
   Vera, L
   Fischer, WH
   Montminy, M
AF Wang, Yiguo
   Vera, Liliana
   Fischer, Wolfgang H.
   Montminy, Marc
TI The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum stress; unfolded protein response; transcription factor; insulin; atf6; torc2; proteolysis; obesity; cells; ire1
AB In fasted mammals, circulating pancreatic glucagon stimulates hepatic gluconeogenesis in part through the CREB regulated transcription coactivator 2 (CRTC2, also referred to as TORC2)(1,2). Hepatic glucose production is increased in obesity, reflecting chronic increases in endoplasmic reticulum (ER) stress that promote insulin resistance(3). Whether ER stress also modulates the gluconeogenic program directly, however, is unclear. Here we show that CRTC2 functions as a dual sensor for ER stress and fasting signals. Acute increases in ER stress triggered the dephosphorylation and nuclear entry of CRTC2, which in turn promoted the expression of ER quality control genes through an association with activating transcription factor 6 alpha (ATF6 alpha, also known as ATF6)-an integral branch of the unfolded protein response(4-9). In addition to mediating CRTC2 recruitment to ER stress inducible promoters, ATF6 alpha also reduced hepatic glucose output by disrupting the CREB-CRTC2 interaction and thereby inhibiting CRTC2 occupancy over gluconeogenic genes. Conversely, hepatic glucose output was upregulated when hepatic ATF6 alpha protein amounts were reduced, either by RNA interference (RNAi)-mediated knockdown or as a result of persistent stress in obesity. Because ATF6 alpha overexpression in the livers of obese mice reversed CRTC2 effects on the gluconeogenic program and lowered hepatic glucose output, our results demonstrate how cross-talk between ER stress and fasting pathways at the level of a transcriptional coactivator contributes to glucose homeostasis.
C1 [Wang, Yiguo; Vera, Liliana; Fischer, Wolfgang H.; Montminy, Marc] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA.
C3 Salk Institute
RP Montminy, M (corresponding author), Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM montminy@salk.edu
FU National Institutes of Health; Clayton Foundation for Medical Research; Keickhefer Foundation; Vincent J. Coates Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK083834] Funding Source: NIH RePORTER
NR 18
TC 244
Z9 291
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 23
PY 2009
VL 460
IS 7254
BP 534
EP U116
DI 10.1038/nature08111
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000043
PM 19543265
DA 2026-03-09
ER

PT J
AU Steig, EJ
   Schneider, DP
   Rutherford, SD
   Mann, ME
   Comiso, JC
   Shindell, DT
AF Steig, Eric J.
   Schneider, David P.
   Rutherford, Scott D.
   Mann, Michael E.
   Comiso, Josefino C.
   Shindell, Drew T.
TI Warming of the Antarctic ice-sheet surface since the 1957 International Geophysical Year
SO NATURE
LA English
DT Article
ID southern-hemisphere climate; in-situ; variability; trends; temperatures; simulation; length; season
AB Assessments of Antarctic temperature change have emphasized the contrast between strong warming of the Antarctic Peninsula and slight cooling of the Antarctic continental interior in recent decades(1). This pattern of temperature change has been attributed to the increased strength of the circumpolar westerlies, largely in response to changes in stratospheric ozone(2). This picture, however, is substantially incomplete owing to the sparseness and short duration of the observations. Here we show that significant warming extends well beyond the Antarctic Peninsula to cover most of West Antarctica, an area of warming much larger than previously reported. West Antarctic warming exceeds 0.1 degrees C per decade over the past 50 years, and is strongest in winter and spring. Although this is partly offset by autumn cooling in East Antarctica, the continent- wide average near- surface temperature trend is positive. Simulations using a general circulation model reproduce the essential features of the spatial pattern and the long- term trend, and we suggest that neither can be attributed directly to increases in the strength of the westerlies. Instead, regional changes in atmospheric circulation and associated changes in sea surface temperature and sea ice are required to explain the enhanced warming in West Antarctica.
C1 [Steig, Eric J.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Steig, Eric J.] Univ Washington, Quaternary Res Ctr, Seattle, WA 98195 USA.
   [Schneider, David P.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA.
   [Rutherford, Scott D.] Roger Williams Univ, Dept Environm Sci, Bristol, RI 02809 USA.
   [Mann, Michael E.] Penn State Univ, Dept Meteorol, University Pk, PA 16802 USA.
   [Mann, Michael E.] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [Comiso, Josefino C.] NASA, Goddard Space Flight Ctr, NASA Lab Hydrospher & Biospher Sci, Greenbelt, MD 20771 USA.
   [Shindell, Drew T.] NASA, Goddard Inst Space Studies, New York, NY 10025 USA.
   [Shindell, Drew T.] Columbia Univ, Ctr Climate Syst Res, New York, NY 10025 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; National Center Atmospheric Research (NCAR) - USA; Roger Williams 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; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Goddard Institute for Space Studies; Columbia University
RP Steig, EJ (corresponding author), Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
EM steig@ess.washington.edu
FU US National Science Foundation [OPP-0440414, OPP-0126161, OPP-0125670]; US ITASE
NR 30
TC 567
Z9 658
U1 0
U2 173
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 22
PY 2009
VL 457
IS 7228
BP 459
EP 462
DI 10.1038/nature07669
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200042
PM 19158794
DA 2026-03-09
ER

PT J
AU Mravec, J
   Skupa, P
   Bailly, A
   Hoyerová, K
   Krecek, P
   Bielach, A
   Petrásek, J
   Zhang, J
   Gaykova, V
   Stierhof, YD
   Dobrev, PI
   Schwarzerová, K
   Rolcík, J
   Seifertová, D
   Luschnig, C
   Benková, E
   Zazímalová, E
   Geisler, M
   Friml, J
AF Mravec, Jozef
   Skupa, Petr
   Bailly, Aurelien
   Hoyerova, Klara
   Krecek, Pavel
   Bielach, Agnieszka
   Petrasek, Jan
   Zhang, Jing
   Gaykova, Vassilena
   Stierhof, York-Dieter
   Dobrev, Petre I.
   Schwarzerova, Katerina
   Rolcik, Jakub
   Seifertova, Daniela
   Luschnig, Christian
   Benkova, Eva
   Zazimalova, Eva
   Geisler, Markus
   Friml, Jiri
TI Subcellular homeostasis of phytohormone auxin is mediated by the ER-localized PIN5 transporter
SO NATURE
LA English
DT Article
ID box protein tir1; plasma-membrane; twisted dwarf1; arabidopsis; gradients; land; flow
AB The plant signalling molecule auxin provides positional information in a variety of developmental processes by means of its differential distribution (gradients) within plant tissues(1). Thus, cellular auxin levels often determine the developmental output of auxin signalling. Conceptually, transmembrane transport and metabolic processes regulate the steady-state levels of auxin in any given cell(2,3). In particular, PIN auxin-efflux-carrier-mediated, directional transport between cells is crucial for generating auxin gradients(2,4,5). Here we show that Arabidopsis thaliana PIN5, an atypical member of the PIN gene family, encodes a functional auxin transporter that is required for auxin-mediated development. PIN5 does not have a direct role in cell-to-cell transport but regulates intracellular auxin homeostasis and metabolism. PIN5 localizes, unlike other characterized plasma membrane PIN proteins, to endoplasmic reticulum ( ER), presumably mediating auxin flow from the cytosol to the lumen of the ER. The ER localization of other PIN5-like transporters ( including the moss PIN) indicates that the diversification of PIN protein functions in mediating auxin homeostasis at the ER, and cell-to-cell auxin transport at the plasma membrane, represent an ancient event during the evolution of land plants.
C1 [Mravec, Jozef; Bielach, Agnieszka; Zhang, Jing; Benkova, Eva; Friml, Jiri] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Mravec, Jozef; Bielach, Agnieszka; Zhang, Jing; Benkova, Eva; Friml, Jiri] Univ Ghent, Dept Plant Biotechnol & Genet, B-9052 Ghent, Belgium.
   [Mravec, Jozef; Zhang, Jing; Gaykova, Vassilena; Stierhof, York-Dieter] Univ Tubingen, Ctr Plant Mol Biol ZMBP, D-72076 Tubingen, Germany.
   [Skupa, Petr; Hoyerova, Klara; Krecek, Pavel; Petrasek, Jan; Dobrev, Petre I.; Seifertova, Daniela; Zazimalova, Eva] ASCR, Inst Expt Bot, Prague 16502 6, Czech Republic.
   [Bailly, Aurelien; Geisler, Markus] Univ Zurich, Inst Plant Biol, Zurich Basel Plant Sci Ctr, CH-8008 Zurich, Switzerland.
   [Petrasek, Jan; Schwarzerova, Katerina] Charles Univ Prague, Fac Sci, Dept Plant Physiol, CR-12844 Prague 2, Czech Republic.
   [Rolcik, Jakub] ASCR, Inst Expt Bot, Lab Growth Regulators, Olomouc 78371, Czech Republic.
   [Rolcik, Jakub] Palacky Univ, Fac Sci, Olomouc 78371, Czech Republic.
   [Luschnig, Christian] Univ Nat Resources & Appl Life Sci BOKU, Dept Appl Genet & Cell Biol, A-1190 Vienna, Austria.
   [Friml, Jiri] Masaryk Univ, Fac Sci, Dept Funct Genom & Prote, Brno 62500, Czech Republic.
C3 Flanders Institute for Biotechnology (VIB); Ghent University; Ghent University; Eberhard Karls University of Tubingen; Czech Academy of Sciences; Institute of Experimental Botany of the Czech Academy of Sciences; University of Zurich; Charles University Prague; Czech Academy of Sciences; Institute of Experimental Botany of the Czech Academy of Sciences; Palacky University Olomouc; BOKU University; Masaryk University
RP Friml, J (corresponding author), Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
EM jiri.friml@psb.vib-ugent.be
FU Volkswagenstiftung; Odysseus programme of the FWO [IAA601630703, KJB600380604]; Ministry of Education, Youth and Sports of the Czech Republic [LC06034, MSM6198959216]; European Research Council starting independent research grant; Novartis Foundation; Swiss National Funds; Forschungskredit of the University of Zurich; Austrian Science Fund
NR 46
TC 450
Z9 539
U1 8
U2 206
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1136
EP U127
DI 10.1038/nature08066
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700045
PM 19506555
DA 2026-03-09
ER

PT J
AU De Ridder, J
   Barban, C
   Baudin, F
   Carrier, F
   Hatzes, AP
   Hekker, S
   Kallinger, T
   Weiss, WW
   Baglin, A
   Auvergne, M
   Samadi, R
   Barge, P
   Deleuil, M
AF De Ridder, Joris
   Barban, Caroline
   Baudin, Frederic
   Carrier, Fabien
   Hatzes, Artie P.
   Hekker, Saskia
   Kallinger, Thomas
   Weiss, Werner W.
   Baglin, Annie
   Auvergne, Michel
   Samadi, Reza
   Barge, Pierre
   Deleuil, Magali
TI Non-radial oscillation modes with long lifetimes in giant stars
SO NATURE
LA English
DT Article
ID solar-like oscillations; stellar oscillations; epsilon-ophiuchi; red giants; k-giants; asteroseismology; discovery; arcturus
AB Towards the end of their lives, stars like the Sun greatly expand to become red giant stars. Such evolved stars could provide stringent tests of stellar theory, as many uncertainties of the internal stellar structure accumulate with age. Important examples are convective overshooting and rotational mixing during the central hydrogen-burning phase, which determine the mass of the helium core, but which are not well understood(1). In principle, analysis of radial and non-radial stellar oscillations can be used to constrain the mass of the helium core. Although all giants are expected to oscillate(2), it has hitherto been unclear whether non-radial modes are observable at all in red giants, or whether the oscillation modes have a short or a long mode lifetime(3-7), which determines the observational precision of the frequencies. Here we report the presence of radial and non-radial oscillations in more than 300 giant stars. For at least some of the giants, the mode lifetimes are of the order of a month. We observe giant stars with equally spaced frequency peaks in the Fourier spectrum of the time series, as well as giants for which the spectrum seems to be more complex. No satisfactory theoretical explanation currently exists for our observations.
C1 [De Ridder, Joris; Carrier, Fabien; Hekker, Saskia] Katholieke Univ Leuven, Inst Sterrenkunde, B-3001 Louvain, Belgium.
   [Barban, Caroline; Baglin, Annie; Auvergne, Michel; Samadi, Reza] Univ Paris 07, Univ Paris 06, UMR8109, LESIA,Observ Paris, F-92195 Meudon, France.
   [Baudin, Frederic] Univ Paris 11, CNRS, UMR 8617, Inst Astrophys Spatiale, F-91405 Orsay, France.
   [Hatzes, Artie P.] Thuringer Landessternwarte, D-07778 Tautenburg, Germany.
   [Hekker, Saskia] Observ Royal Belgique, B-1180 Brussels, Belgium.
   [Kallinger, Thomas; Weiss, Werner W.] Univ Vienna, Inst Astron, A-1180 Vienna, Austria.
   [Barge, Pierre; Deleuil, Magali] Univ Aix Marseille, OAMP, Lab Astrophys Marseille, F-13388 Marseille 13, France.
   [Barge, Pierre; Deleuil, Magali] CNRS, F-13388 Marseille 13, France.
C3 KU Leuven; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite; Sorbonne Universite; Universite PSL; Observatoire de Paris; Sorbonne Universite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Vienna; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS)
RP De Ridder, J (corresponding author), Katholieke Univ Leuven, Inst Sterrenkunde, Celestijnenlaan 200D, B-3001 Louvain, Belgium.
EM joris@ster.kuleuven.ac.be
FU Fund for Scientific Research, Flanders; research council of K. U. Leuven; Belgian Federal Science Policy; Deutsches Zentrum fur Luft-und Raumfahrt; Austrian Research Promotion Agency
NR 21
TC 248
Z9 262
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2009
VL 459
IS 7245
BP 398
EP 400
DI 10.1038/nature08022
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700039
PM 19458716
DA 2026-03-09
ER

PT J
AU Schneider, NM
   Burger, MH
   Schaller, EL
   Brown, ME
   Johnson, RE
   Kargel, JS
   Dougherty, MK
   Achilleos, NA
AF Schneider, Nicholas M.
   Burger, Matthew H.
   Schaller, Emily L.
   Brown, Michael E.
   Johnson, Robert E.
   Kargel, Jeffrey S.
   Dougherty, Michele K.
   Achilleos, Nicholas A.
TI No sodium in the vapour plumes of Enceladus
SO NATURE
LA English
DT Article
ID discovery; atmosphere; spectrometer; origin
AB The discovery of water vapour and ice particles erupting from Saturn's moon Enceladus fuelled speculation that an internal ocean was the source(1-3). Alternatively, the source might be ice warmed, melted or crushed by tectonic motions(4). Sodium chloride (that is, salt) is expected to be present in a long-lived ocean in contact with a rocky core. Here we report a ground-based spectroscopic search for atomic sodium near Enceladus that places an upper limit on the mixing ratio in the vapour plumes orders of magnitude below the expected ocean salinity(5). The low sodium content of escaping vapour, together with the small fraction of salt-bearing particles(6), argues against a situation in which a near-surface geyser is fuelled by a salty ocean through cracks in the crust(1). The lack of observable sodium in the vapour is consistent with a wide variety of alternative eruption sources, including a deep ocean(6), a freshwater reservoir, or ice. The existing data may be insufficient to distinguish between these hypotheses.
C1 [Schneider, Nicholas M.] Univ Colorado, Atmospher & Space Phys Lab, Boulder, CO 80309 USA.
   [Burger, Matthew H.] Univ Maryland Baltimore Cty, Greenbelt, MD 20771 USA.
   [Burger, Matthew H.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Schaller, Emily L.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Brown, Michael E.] CALTECH, Pasadena, CA 91125 USA.
   [Johnson, Robert E.] Univ Virginia, Charlottesville, VA 22904 USA.
   [Kargel, Jeffrey S.] Univ Arizona, Tucson, AZ 85721 USA.
   [Dougherty, Michele K.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
   [Achilleos, Nicholas A.] UCL, London WC1E 6BT, England.
C3 University of Colorado System; University of Colorado Boulder; University System of Maryland; University of Maryland Baltimore County; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Hawaii System; California Institute of Technology; University of Virginia; University of Arizona; Imperial College London; University of London; University College London
RP Schneider, NM (corresponding author), Univ Colorado, Atmospher & Space Phys Lab, Campus Box 392, Boulder, CO 80309 USA.
EM nick.schneider@lasp.colorado.edu
FU W. M. Keck Foundation; National Science Foundation's Planetary Astronomy Program; NASA Postdoctoral Program; Science and Technology Facilities Council [PP/E001076/1, PP/D000912/1] Funding Source: researchfish; STFC [PP/D000912/1, PP/E001076/1] Funding Source: UKRI
NR 23
TC 33
Z9 37
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 JUN 25
PY 2009
VL 459
IS 7250
BP 1102
EP 1104
DI 10.1038/nature08070
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700037
PM 19553993
DA 2026-03-09
ER

PT J
AU Wang, K
   Zhang, HT
   Ma, DQ
   Bucan, M
   Glessner, JT
   Abrahams, BS
   Salyakina, D
   Imielinski, M
   Bradfield, JP
   Sleiman, PMA
   Kim, CE
   Hou, CP
   Frackelton, E
   Chiavacci, R
   Takahashi, N
   Sakurai, T
   Rappaport, E
   Lajonchere, CM
   Munson, J
   Estes, A
   Korvatska, O
   Piven, J
   Sonnenblick, LI
   Retuerto, AIA
   Herman, EI
   Dong, HM
   Hutman, T
   Sigman, M
   Ozonoff, S
   Klin, A
   Owley, T
   Sweeney, JA
   Brune, CW
   Cantor, RM
   Bernier, R
   Gilbert, JR
   Cuccaro, ML
   McMahon, WM
   Miller, J
   State, MW
   Wassink, TH
   Coon, H
   Levy, SE
   Schultz, RT
   Nurnberger, JI
   Haines, JL
   Sutcliffe, JS
   Cook, EH
   Minshew, NJ
   Buxbaum, JD
   Dawson, G
   Grant, SFA
   Geschwind, DH
   Pericak-Vance, MA
   Schellenberg, GD
   Hakonarson, H
AF Wang, Kai
   Zhang, Haitao
   Ma, Deqiong
   Bucan, Maja
   Glessner, Joseph T.
   Abrahams, Brett S.
   Salyakina, Daria
   Imielinski, Marcin
   Bradfield, Jonathan P.
   Sleiman, Patrick M. A.
   Kim, Cecilia E.
   Hou, Cuiping
   Frackelton, Edward
   Chiavacci, Rosetta
   Takahashi, Nagahide
   Sakurai, Takeshi
   Rappaport, Eric
   Lajonchere, Clara M.
   Munson, Jeffrey
   Estes, Annette
   Korvatska, Olena
   Piven, Joseph
   Sonnenblick, Lisa I.
   Retuerto, Ana I. Alvarez
   Herman, Edward I.
   Dong, Hongmei
   Hutman, Ted
   Sigman, Marian
   Ozonoff, Sally
   Klin, Ami
   Owley, Thomas
   Sweeney, John A.
   Brune, Camille W.
   Cantor, Rita M.
   Bernier, Raphael
   Gilbert, John R.
   Cuccaro, Michael L.
   McMahon, William M.
   Miller, Judith
   State, Matthew W.
   Wassink, Thomas H.
   Coon, Hilary
   Levy, Susan E.
   Schultz, Robert T.
   Nurnberger, John I., Jr.
   Haines, Jonathan L.
   Sutcliffe, James S.
   Cook, Edwin H.
   Minshew, Nancy J.
   Buxbaum, Joseph D.
   Dawson, Geraldine
   Grant, Struan F. A.
   Geschwind, Daniel H.
   Pericak-Vance, Margaret A.
   Schellenberg, Gerard D.
   Hakonarson, Hakon
TI Common genetic variants on 5p14.1 associate with autism spectrum disorders
SO NATURE
LA English
DT Article
ID genome-wide association; bipolar disorder; familial risk; linkage; loci; underconnectivity; disconnection; expression; identification; chromosome
AB Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell-adhesion molecules-revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 x 10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.
C1 [Wang, Kai; Zhang, Haitao; Glessner, Joseph T.; Imielinski, Marcin; Bradfield, Jonathan P.; Sleiman, Patrick M. A.; Kim, Cecilia E.; Hou, Cuiping; Frackelton, Edward; Chiavacci, Rosetta; Grant, Struan F. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Gen, Philadelphia, PA 19104 USA.
   [Ma, Deqiong; Salyakina, Daria; Gilbert, John R.; Cuccaro, Michael L.; Pericak-Vance, Margaret A.] Univ Miami, Miami Inst Human Genom, Miami, FL 33101 USA.
   [Ma, Deqiong; Salyakina, Daria; Gilbert, John R.; Cuccaro, Michael L.; Pericak-Vance, Margaret A.] Univ Miami, Dept Human Genet, Miami, FL 33101 USA.
   [Bucan, Maja] Univ Penn, Dept Genet, Philadelphia, PA 19014 USA.
   [Abrahams, Brett S.; Sonnenblick, Lisa I.; Retuerto, Ana I. Alvarez; Herman, Edward I.; Dong, Hongmei; Hutman, Ted; Sigman, Marian; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
   [Abrahams, Brett S.; Sonnenblick, Lisa I.; Retuerto, Ana I. Alvarez; Herman, Edward I.; Dong, Hongmei; Hutman, Ted; Sigman, Marian; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA.
   [Takahashi, Nagahide; Sakurai, Takeshi; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA.
   [Rappaport, Eric; Levy, Susan E.; Schultz, Robert T.; Grant, Struan F. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19014 USA.
   [Lajonchere, Clara M.] Univ So Calif & Autism Speaks, Dept Biomed Engn, Los Angeles, CA 90089 USA.
   [Munson, Jeffrey; Estes, Annette; Korvatska, Olena; Bernier, Raphael; Dawson, Geraldine] Univ Washington, Dept Psychiat, Seattle, WA 98105 USA.
   [Piven, Joseph] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
   [Piven, Joseph] Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA.
   [Ozonoff, Sally] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA.
   [Ozonoff, Sally] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA.
   [Klin, Ami; State, Matthew W.] Yale Univ, Dept Genet, New Haven, CT 06520 USA.
   [Klin, Ami; State, Matthew W.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
   [Owley, Thomas; Sweeney, John A.; Brune, Camille W.; Cook, Edwin H.] Univ Illinois, Inst Juvenile Res, Chicago, IL 60608 USA.
   [Owley, Thomas; Sweeney, John A.; Brune, Camille W.; Cook, Edwin H.] Univ Illinois, Dept Psychiat, Chicago, IL 60608 USA.
   [Cantor, Rita M.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [McMahon, William M.; Miller, Judith; Coon, Hilary] Univ Utah, Dept Psychiat, Salt Lake City, UT 84132 USA.
   [Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Iowa City, IA USA.
   [Nurnberger, John I., Jr.] Indiana Univ, Inst Psychiat Res, Indianapolis, IN 46202 USA.
   [Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA.
   [Sutcliffe, James S.] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN 37232 USA.
   [Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA.
   [Minshew, Nancy J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
   [Minshew, Nancy J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
   [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
   [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
   [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Miami; University of Miami; University of Pennsylvania; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Icahn School of Medicine at Mount Sinai; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Washington; University of Washington Seattle; University of North Carolina; University of North Carolina Chapel Hill; University of California System; University of California Davis; University of California System; University of California Davis; Yale University; Yale University; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of California System; University of California Los Angeles; Utah System of Higher Education; University of Utah; University of Iowa; Indiana University System; Indiana University Indianapolis; Vanderbilt University; Vanderbilt University; Vanderbilt University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University of Pennsylvania
RP Hakonarson, H (corresponding author), Childrens Hosp Philadelphia, Ctr Appl Gen, Philadelphia, PA 19104 USA.
EM hakonarson@chop.edu
FU National Institute of Mental Health [1U24MH081810]; National Institute of Child Health and Human Development [NO1-HD-4-3368, NO1-HD-4-3383]; Institutional Development Award; Margaret Q. Landenberger Foundation; Cotswold Foundation [UL1-RR024134-03]; Mental Retardation and Developmental Disability Research Center; Beatrice and Stanley A. Seaver Foundation; Department of Veterans Affairs; NIH [MH64547, HD055782-01, MH0666730, MH061009, NS049261, HD055751, MH69359, M01-RR00064, MH081754, HD055784, NS26630, NS36768, MH080647]; Autism Genome Project Consortium; Autism Speaks; Medical Research Council (UK) and the Health Research Board (Ireland); Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders [P50HD055784] Funding Source: NIH RePORTER
NR 51
TC 747
Z9 894
U1 2
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 28
PY 2009
VL 459
IS 7246
BP 528
EP 533
DI 10.1038/nature07999
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500030
PM 19404256
DA 2026-03-09
ER

PT J
AU Günter, G
   Anappara, AA
   Hees, J
   Sell, A
   Biasiol, G
   Sorba, L
   De Liberato, S
   Ciuti, C
   Tredicucci, A
   Leitenstorfer, A
   Huber, R
AF Guenter, G.
   Anappara, A. A.
   Hees, J.
   Sell, A.
   Biasiol, G.
   Sorba, L.
   De Liberato, S.
   Ciuti, C.
   Tredicucci, A.
   Leitenstorfer, A.
   Huber, R.
TI Sub-cycle switch-on of ultrastrong light-matter interaction
SO NATURE
LA English
DT Article
ID cavity; microcavity; technology; plasma; system
AB Controlling the way light interacts with material excitations is at the heart of cavity quantum electrodynamics (QED). In the strong-coupling regime, quantum emitters in a microresonator absorb and spontaneously re-emit a photon many times before dissipation becomes effective, giving rise to mixed light-matter eigenmodes(1-12). Recent experiments(13) in semiconductor microcavities reached a new limit of ultrastrong coupling(14), where photon exchange occurs on timescales comparable to the oscillation period of light. In this limit, ultrafast modulation of the coupling strength has been suggested to lead to unconventional QED phenomena(14,15). Although sophisticated light-matter coupling has been achieved in all three spatial dimensions, control in the fourth dimension, time, is little developed. Here we use a quantum-well waveguide structure to optically tune light-matter interaction from weak to ultrastrong and turn on maximum coupling within less than one cycle of light. In this regime, a class of extremely non-adiabatic phenomena becomes observable. In particular, we directly monitor how a coherent photon population converts to cavity polaritons during abrupt switching. This system forms a promising laboratory in which to study novel sub-cycle QED effects and represents an efficient room-temperature switching device operating at unprecedented speed.
C1 [Guenter, G.; Anappara, A. A.; Hees, J.; Sell, A.; Leitenstorfer, A.; Huber, R.] Univ Konstanz, Dept Phys, D-78464 Constance, Germany.
   [Guenter, G.; Anappara, A. A.; Hees, J.; Sell, A.; Leitenstorfer, A.; Huber, R.] Univ Konstanz, Ctr Appl Photon, D-78464 Constance, Germany.
   [Anappara, A. A.; Sorba, L.; Tredicucci, A.] CNR, INFM, Lab NEST, I-56127 Pisa, Italy.
   [Anappara, A. A.; Sorba, L.; Tredicucci, A.] Scuola Normale Super Pisa, I-56127 Pisa, Italy.
   [Biasiol, G.; Sorba, L.] INFM, Lab Nazl TASC, CNR, I-34012 Trieste, Italy.
   [De Liberato, S.; Ciuti, C.] Univ Paris 07, Lab Mat & Phenomenes Quant, F-75205 Paris, France.
   [De Liberato, S.] Ecole Normale Super, Lab Pierre Aigrain, UMR 8551, F-75005 Paris, France.
C3 University of Konstanz; University of Konstanz; Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale per la Fisica della Materia (INFM-CNR); Scuola Normale Superiore di Pisa; Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale per la Fisica della Materia (INFM-CNR); Universite Paris Cite; Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Cite; CNRS - Institute of Physics (INP)
RP Huber, R (corresponding author), Univ Konstanz, Dept Phys, Univ Str 10, D-78464 Constance, Germany.
EM rupert.huber@uni-konstanz.de
FU Deutsche Forschungsgemeinschaft through the Emmy Noether Program; SFB767
NR 29
TC 496
Z9 534
U1 0
U2 130
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 178
EP 181
DI 10.1038/nature07838
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700037
PM 19279631
DA 2026-03-09
ER

PT J
AU Seiffert, ER
   Perry, JMG
   Simons, EL
   Boyer, DM
AF Seiffert, Erik R.
   Perry, Jonathan M. G.
   Simons, Elwyn L.
   Boyer, Doug M.
TI Convergent evolution of anthropoid-like adaptations in Eocene adapiform primates
SO NATURE
LA English
DT Article
ID middle eocene; fissure-fillings; molecular-data; egypt; phylogeny; fossil; paleogene; myanmar; africa; china
AB Adapiform or 'adapoid' primates first appear in the fossil record in the earliest Eocene epoch (similar to 55 million years (Myr) ago), and were common components of Palaeogene primate communities in Europe, Asia and North America(1). Adapiforms are commonly referred to as the 'lemur-like' primates of the Eocene epoch, and recent phylogenetic analyses have placed adapiforms as stem members of Strepsirrhini(2-4), a primate suborder whose crown clade includes lemurs, lorises and galagos. An alternative view is that adapiforms are stem anthropoids(5). This debate has recently been rekindled by the description of a largely complete skeleton of the adapiform Darwinius(6), from the middle Eocene of Europe, which has been widely publicised as an important 'link' in the early evolution of Anthropoidea(7). Here we describe the complete dentition and jaw of a large-bodied adapiform (Afradapis gen. nov.) from the earliest late Eocene of Egypt (similar to 37 Myr ago) that exhibits a striking series of derived dental and gnathic features that also occur in younger anthropoid primates-notably the earliest catarrhine ancestors of Old World monkeys and apes. Phylogenetic analysis of 360 morphological features scored across 117 living and extinct primates (including all candidate stem anthropoids) does not place adapiforms as haplorhines (that is, members of a Tarsius-Anthropoidea clade) or as stem anthropoids, but rather as sister taxa of crown Strepsirrhini; Afradapis and Darwinius are placed in a geographically widespread clade of caenopithecine adapiforms that left no known descendants. The specialized morphological features that these adapiforms share with anthropoids are therefore most parsimoniously interpreted as evolutionary convergences. As the largest non-anthropoid primate ever documented in Afro-Arabia, Afradapis nevertheless provides surprising new evidence for prosimian diversity in the Eocene of Africa, and raises the possibility that ecological competition between adapiforms and higher primates might have played an important role during the early evolution of stem and crown Anthropoidea in Afro-Arabia.
C1 [Seiffert, Erik R.] SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA.
   [Perry, Jonathan M. G.] Midwestern Univ, Dept Anat, Downers Grove, IL 60515 USA.
   [Simons, Elwyn L.] Duke Lemur Ctr, Div Fossil Primates, Durham, NC 27705 USA.
   [Boyer, Doug M.] SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA.
C3 State University of New York (SUNY) System; Stony Brook University; Midwestern University; Midwestern University - Downers Grove; State University of New York (SUNY) System; Stony Brook University
RP Seiffert, ER (corresponding author), SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA.
EM erik.seiffert@stonybrook.edu
FU Research Foundation of SUNY; US National Science Foundation; The Leakey Foundation; Duke Lemur Center publication [1155]; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [0819186] Funding Source: National Science Foundation
NR 48
TC 92
Z9 112
U1 0
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1118
EP U214
DI 10.1038/nature08429
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600043
PM 19847263
DA 2026-03-09
ER

PT J
AU Elde, NC
   Child, SJ
   Geballe, AP
   Malik, HS
AF Elde, Nels C.
   Child, Stephanie J.
   Geballe, Adam P.
   Malik, Harmit S.
TI Protein kinase R reveals an evolutionary model for defeating viral mimicry
SO NATURE
LA English
DT Article
ID positive selection; substrate recognition; molecular mimicry; antiviral protein; crystal-structure; pkr; yeast; bacterial; rna; k3l
AB Distinguishing self from non- self is a fundamental biological challenge. Many pathogens exploit the challenge of self discrimination by employing mimicry to subvert key cellular processes including the cell cycle, apoptosis and cytoskeletal dynamics(1-5). Other mimics interfere with immunity(6,7). Poxviruses encode K3L, a mimic of eIF2 alpha, which is the substrate of protein kinase R ( PKR), an important component of innate immunity in vertebrates(8,9). The PKR - K3L interaction exemplifies the conundrum imposed by viral mimicry. To be effective, PKR must recognize a conserved substrate (eIF2 alpha) while avoiding rapidly evolving substrate mimics such as K3L. Using the PKR - K3L system and a combination of phylogenetic and functional analyses, we uncover evolutionary strategies by which host proteins can overcome mimicry. We find that PKR has evolved under intense episodes of positive selection in primates. The ability of PKR to evade viral mimics is partly due to positive selection at sites most intimately involved in eIF2 alpha recognition. We also find that adaptive changes on multiple surfaces of PKR produce combinations of substitutions that increase the odds of defeating mimicry. Thus, although it can seem that pathogens gain insurmountable advantages by mimicking cellular components, host factors such as PKR can compete in molecular 'arms races' with mimics because of evolutionary flexibility at protein interaction interfaces challenged by mimicry.
C1 [Elde, Nels C.; Malik, Harmit S.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Child, Stephanie J.; Geballe, Adam P.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
   [Geballe, Adam P.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
   [Geballe, Adam P.] Univ Washington, Dept Med, Seattle, WA 98115 USA.
   [Geballe, Adam P.] Univ Washington, Dept Microbiol, Seattle, WA 98115 USA.
C3 Fred Hutchinson Cancer Center; Fred Hutchinson Cancer Center; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Malik, HS (corresponding author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
EM hsmalik@fhcrc.org
FU NIH [AI026672]; Searle Scholar; Burroughs Wellcome Investigator Award; Ellison Medical Foundation Fellow of the Life Sciences Research Foundation
NR 39
TC 200
Z9 253
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 JAN 22
PY 2009
VL 457
IS 7228
BP 485
EP U8
DI 10.1038/nature07529
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200048
PM 19043403
DA 2026-03-09
ER

PT J
AU Watts, JM
   Dang, KK
   Gorelick, RJ
   Leonard, CW
   Bess, JW
   Swanstrom, R
   Burch, CL
   Weeks, KM
AF Watts, Joseph M.
   Dang, Kristen K.
   Gorelick, Robert J.
   Leonard, Christopher W.
   Bess, Julian W., Jr.
   Swanstrom, Ronald
   Burch, Christina L.
   Weeks, Kevin M.
TI Architecture and secondary structure of an entire HIV-1 RNA genome
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; selective 2'-hydroxyl acylation; single nucleotide resolution; primer extension shape; context-free grammars; reverse transcription; thermodynamic parameters; structure prediction; protein expression; coding regions
AB Single-stranded RNA viruses encompass broad classes of infectious agents and cause the common cold, cancer, AIDS and other serious health threats. Viral replication is regulated at many levels, including the use of conserved genomic RNA structures. Most potential regulatory elements in viral RNA genomes are uncharacterized. Here we report the structure of an entire HIV-1 genome at single nucleotide resolution using SHAPE, a high-throughput RNA analysis technology. The genome encodes protein structure at two levels. In addition to the correspondence between RNA and protein primary sequences, a correlation exists between high levels of RNA structure and sequences that encode inter-domain loops in HIV proteins. This correlation suggests that RNA structure modulates ribosome elongation to promote native protein folding. Some simple genome elements previously shown to be important, including the ribosomal gag-pol frameshift stem-loop, are components of larger RNA motifs. We also identify organizational principles for unstructured RNA regions, including splice site acceptors and hypervariable regions. These results emphasize that the HIV-1 genome and, potentially, many coding RNAs are punctuated by previously unrecognized regulatory motifs and that extensive RNA structure constitutes an important component of the genetic code.
C1 [Watts, Joseph M.; Leonard, Christopher W.; Weeks, Kevin M.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
   [Dang, Kristen K.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA.
   [Swanstrom, Ronald] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA.
   [Burch, Christina L.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Gorelick, Robert J.; Bess, Julian W., Jr.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Science Applications International Corporation (SAIC); SAIC-Frederick
RP Weeks, KM (corresponding author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA.
EM weeks@unc.edu
FU US National Institutes of Health [AI068462]; National Cancer Institute [N01-CO-12400, HHSN261200800001E]; National Institutes of Health (NIH) [AI44667, T32 AI07419]; National Institute of Allergy and Infectious Diseases [T32AI007419] Funding Source: NIH RePORTER
NR 52
TC 648
Z9 914
U1 2
U2 132
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 6
PY 2009
VL 460
IS 7256
BP 711
EP U87
DI 10.1038/nature08237
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300032
PM 19661910
DA 2026-03-09
ER

PT J
AU Hakoyama, T
   Niimi, K
   Watanabe, H
   Tabata, R
   Matsubara, J
   Sato, S
   Nakamura, Y
   Tabata, S
   Li, JC
   Matsumoto, T
   Tatsumi, K
   Nomura, M
   Tajima, S
   Ishizaka, M
   Yano, K
   Imaizumi-Anraku, H
   Kawaguchi, M
   Kouchi, H
   Suganuma, N
AF Hakoyama, Tsuneo
   Niimi, Kaori
   Watanabe, Hirokazu
   Tabata, Ryohei
   Matsubara, Junichi
   Sato, Shusei
   Nakamura, Yasukazu
   Tabata, Satoshi
   Li Jichun
   Matsumoto, Tsuyoshi
   Tatsumi, Kazuyuki
   Nomura, Mika
   Tajima, Shigeyuki
   Ishizaka, Masumi
   Yano, Koji
   Imaizumi-Anraku, Haruko
   Kawaguchi, Masayoshi
   Kouchi, Hiroshi
   Suganuma, Norio
TI Host plant genome overcomes the lack of a bacterial gene for symbiotic nitrogen fixation
SO NATURE
LA English
DT Article
ID alpha-isopropylmalate synthase; iron-molybdenum cofactor; soybean root-nodules; lotus-japonicus; homocitrate synthase; fixing symbiosis; rhizobium; purification; mutants; legumes
AB Homocitrate is a component of the iron-molybdenum cofactor in nitrogenase, where nitrogen fixation occurs(1,2). NifV, which encodes homocitrate synthase (HCS)(3), has been identified from various diazotrophs but is not present in most rhizobial species that perform efficient nitrogen fixation only in symbiotic association with legumes. Here we show that the FEN1 gene of a model legume, Lotus japonicus, overcomes the lack of NifV in rhizobia for symbiotic nitrogen fixation. A Fix(-) (non-fixing) plant mutant, fen1, forms morphologically normal but ineffective nodules(4,5). The causal gene, FEN1, was shown to encode HCS by its ability to complement a HCS-defective mutant of Saccharomyces cerevisiae. Homocitrate was present abundantly in wild-type nodules but was absent from ineffective fen1 nodules. Inoculation with Mesorhizobium loti carrying FEN1 or Azotobacter vinelandii NifV rescued the defect in nitrogen-fixing activity of the fen1 nodules. Exogenous supply of homocitrate also recovered the nitrogen-fixing activity of the fen1 nodules through de novo nitrogenase synthesis in the rhizobial bacteroids. These results indicate that homocitrate derived from the host plant cells is essential for the efficient and continuing synthesis of the nitrogenase system in endosymbionts, and thus provide a molecular basis for the complementary and indispensable partnership between legumes and rhizobia in symbiotic nitrogen fixation.
C1 [Hakoyama, Tsuneo; Niimi, Kaori; Watanabe, Hirokazu; Tabata, Ryohei; Matsubara, Junichi; Suganuma, Norio] Aichi Univ Educ, Dept Life Sci, Aichi 4488542, Japan.
   [Hakoyama, Tsuneo; Yano, Koji; Imaizumi-Anraku, Haruko; Kouchi, Hiroshi] Natl Inst Agrobiol Sci, Tsukuba, Ibaraki 3058602, Japan.
   [Sato, Shusei; Nakamura, Yasukazu; Tabata, Satoshi] Kazusa DNA Res Inst, Chiba 2920812, Japan.
   [Li Jichun; Matsumoto, Tsuyoshi; Tatsumi, Kazuyuki] Nagoya Univ, Grad Sch Sci, Dept Chem, Aichi 4648602, Japan.
   [Li Jichun; Matsumoto, Tsuyoshi; Tatsumi, Kazuyuki] Nagoya Univ, Res Ctr Mat Sci, Aichi 4648602, Japan.
   [Nomura, Mika; Tajima, Shigeyuki] Kagawa Univ, Fac Agr, Kita Ku, Kagawa 7610795, Japan.
   [Ishizaka, Masumi] Natl Inst Agroenvironm Sci, Tsukuba, Ibaraki 3058604, Japan.
   [Kawaguchi, Masayoshi] Natl Inst Nat Sci, Natl Inst Basic Biol, Okazaki, Aichi 4448585, Japan.
C3 Aichi University Education; National Institute of Agrobiological Sciences - Japan; Kazusa DNA Research Institute; Nagoya University; Nagoya University; Kagawa University; National Institute for Agro-Environmental Sciences (NIAES) Japan; National Institutes of Natural Sciences (NINS) - Japan; National Institute for Basic Biology (NIBB)
RP Suganuma, N (corresponding author), Aichi Univ Educ, Dept Life Sci, Aichi 4488542, Japan.
EM nsuganum@auecc.aichi-edu.ac.jp
FU Japanese Ministry of Education, Culture, Sports, Science and Technology; Grants-in-Aid for Scientific Research [18GS0207] Funding Source: KAKEN
NR 35
TC 91
Z9 106
U1 7
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 NOV 26
PY 2009
VL 462
IS 7272
BP 514
EP U210
DI 10.1038/nature08594
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200046
PM 19940927
DA 2026-03-09
ER

PT J
AU Chan, CKF
   Chen, CC
   Luppen, CA
   Kim, JB
   DeBoer, AT
   Wei, K
   Helms, JA
   Kuo, CJ
   Kraft, DL
   Weissman, IL
AF Chan, Charles K. F.
   Chen, Ching-Cheng
   Luppen, Cynthia A.
   Kim, Jae-Beom
   DeBoer, Anthony T.
   Wei, Kevin
   Helms, Jill A.
   Kuo, Calvin J.
   Kraft, Daniel L.
   Weissman, Irving L.
TI Endochondral ossification is required for haematopoietic stem-cell niche formation
SO NATURE
LA English
DT Article
ID bone-formation; endothelial-cells; c-kit; express; angiogenesis; osterix; mice
AB Little is known about the formation of niches, local micro- environments required for stem- cell maintenance. Here we develop an in vivo assay for adult haematopoietic stem- cell ( HSC) niche formation(1,2). With this assay, we identified a population of progenitor cells with surface markers CD45(-)Tie2(-)alpha(+)(V)CD105(+)Thy1.1(-) (CD105(+)Thy1(-)) that, when sorted from 15.5 days post- coitum fetal bones and transplanted under the adult mouse kidney capsule, could recruit host- derived blood vessels, produce donor- derived ectopic bones through a cartilage intermediate and generate a marrow cavity populated by host- derived long- term reconstituting HSC (LT-HSC). In contrast, CD45(-)Tie2(-)alpha(+)(V)CD105(+)Thy1(+) (CD105(+)Thy1(+)) fetal bone progenitors form bone that does not contain a marrow cavity. Suppressing expression of factors involved in endochondral ossification, such as osterix and vascular endothelial growth factor ( VEGF), inhibited niche generation. CD105(+)Thy1(-) progenitor populations derived from regions of the fetal mandible or calvaria that do not undergo endochondral ossification formed only bone without marrow in our assay. Collectively, our data implicate endochondral ossification, bone formation that proceeds through a cartilage intermediate, as a requirement for adult HSC niche formation.
C1 [Chan, Charles K. F.; Chen, Ching-Cheng; Luppen, Cynthia A.; DeBoer, Anthony T.; Kraft, Daniel L.; Weissman, Irving L.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
   [Chan, Charles K. F.; Chen, Ching-Cheng; Luppen, Cynthia A.; DeBoer, Anthony T.; Kraft, Daniel L.; Weissman, Irving L.] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA.
   [Chan, Charles K. F.; Chen, Ching-Cheng; Luppen, Cynthia A.; DeBoer, Anthony T.; Kraft, Daniel L.; Weissman, Irving L.] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Kim, Jae-Beom; Helms, Jill A.] Stanford Univ, Dept Surg, Div Plast & Reconstruct Surg, Stanford, CA 94305 USA.
   [Wei, Kevin; Kuo, Calvin J.] Stanford Univ, Dept Hematol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Stanford University
RP Chan, CKF (corresponding author), Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
EM chazchan@stanford.edu; c3chen@stanford.edu
FU USPHS National Institutes of Health [2R01HL058770-08, 5R01CA086065-09, 1R01HL074267-01, 1R01NS052830-01]; NIH Pathway to Independence [5K99HL087936-02]; NIH Career Development [K08-HL076335]; Hope Street Kids
NR 29
TC 352
Z9 400
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 22
PY 2009
VL 457
IS 7228
BP 490
EP U9
DI 10.1038/nature07547
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200049
PM 19078959
DA 2026-03-09
ER

PT J
AU Rhee, HJ
   June, YG
   Lee, JS
   Lee, KK
   Ha, JH
   Kim, ZH
   Jeon, SJ
   Cho, MH
AF Rhee, Hanju
   June, Young-Gun
   Lee, Jang-Soo
   Lee, Kyung-Koo
   Ha, Jeong-Hyon
   Kim, Zee Hwan
   Jeon, Seung-Joon
   Cho, Minhaeng
TI Femtosecond characterization of vibrational optical activity of chiral molecules
SO NATURE
LA English
DT Article
ID circular-dichroism; spectroscopy; polypeptides
AB Optical activity(1-3) is the result of chiral molecules interacting differently with left versus right circularly polarized light. Because of this intrinsic link to molecular structure, the determination of optical activity through circular dichroism (CD) spectroscopy has long served as a routine method for obtaining structural information about chemical and biological systems in condensed phases(4-6). A recent development is time-resolved CD spectroscopy, which can in principle map the structural changes associated with biomolecular function(7) and thus lead to mechanistic insights into fundamental biological processes. But implementing time-resolved CD measurements is experimentally challenging because CD is a notoriously weak effect (a factor of 10(-4)-10(-6) smaller than absorption). In fact, this problem has so far prevented time-resolved vibrational CD experiments. Here we show that vibrational CD spectroscopy with femtosecond time resolution can be realized when using heterodyned spectral interferometry to detect(8-10) the phase and amplitude of the infrared optical activity free-induction-decay field in time (much like in a pulsed NMR experiment). We show that we can detect extremely weak signals in the presence of large achiral background contributions, by simultaneously measuring with a femtosecond laser pulse the vibrational CD and optical rotatory dispersion spectra of dissolved chiral limonene molecules. We have so far only targeted molecules in equilibrium, but it would be straightforward to extend the method for the observation of ultrafast structural changes such as those occurring during protein folding or asymmetric chemical reactions. That is, we should now be in a position to produce 'molecular motion pictures'(11) of fundamental molecular processes from a chiral perspective.
C1 [Rhee, Hanju; June, Young-Gun; Lee, Jang-Soo; Lee, Kyung-Koo; Kim, Zee Hwan; Jeon, Seung-Joon; Cho, Minhaeng] Korea Univ, Dept Chem, Seoul 136701, South Korea.
   [Rhee, Hanju; Lee, Jang-Soo; Lee, Kyung-Koo; Cho, Minhaeng] Korea Univ, Ctr Multidimens Spect, Seoul 136701, South Korea.
   [Ha, Jeong-Hyon; Jeon, Seung-Joon; Cho, Minhaeng] Korea Basic Sci Inst, Multidimens Spect Lab, Seoul 136713, South Korea.
C3 Korea University; Korea University; Korea Basic Science Institute (KBSI)
RP Cho, MH (corresponding author), Korea Univ, Dept Chem, Seoul 136701, South Korea.
EM mcho@korea.ac.kr
FU Creative Research Initiatives of MEST/KOSEF; Frontier Research Laboratory Program of KBSI; National Research Foundation of Korea [과09A1514] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
NR 29
TC 165
Z9 179
U1 2
U2 123
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 310
EP 313
DI 10.1038/nature07846
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600035
PM 19295604
DA 2026-03-09
ER

PT J
AU Shank, SS
   Margoliash, D
AF Shank, Sylvan S.
   Margoliash, Daniel
TI Sleep and sensorimotor integration during early vocal learning in a songbird
SO NATURE
LA English
DT Article
ID slow-wave sleep; zebra finches; human hippocampus; memory; sparrows; replay; consolidation; sequences; birdsong; behavior
AB Behavioural studies widely implicate sleep in memory consolidation in the learning of a broad range of behaviours(1-4). During sleep, brain regions are reactivated(5,6), and specific patterns of neural activity are replayed(7-10), consistent with patterns observed in previous waking behaviour. Birdsong learning is a paradigmatic model system for skill learning(11-14). Song development in juvenile zebra finches (Taeniopygia guttata) is characterized by sleep-dependent circadian fluctuations in singing behaviour, with immediate post-sleep deterioration in song structure followed by recovery later in the day(15). In sleeping adult birds, spontaneous bursting activity of forebrain premotor neurons in the robust nucleus of the arcopallium (RA) carries information about daytime singing(16). Here we show that, in juvenile zebra finches, playback during the day of an adult 'tutor' song induced profound and tutor-song-specific changes in bursting activity of RA neurons during the following night of sleep. The night-time neuronal changes preceded tutor-song-induced changes in singing, first observed the following day. Interruption of auditory feedback greatly reduced sleep bursting and prevented the tutor-song-specific neuronal remodelling. Thus, night-time neuronal activity is shaped by the interaction of the song model (sensory template) and auditory feedback, with changes in night-time activity preceding the onset of practice associated with vocal learning. We hypothesize that night-time bursting induces adaptive changes in premotor networks during sleep as part of vocal learning. By this hypothesis, adaptive changes driven by replay of sensory information at night and by evaluation of sensory feedback during the day interact to produce the complex circadian patterns seen early in vocal development.
C1 [Shank, Sylvan S.; Margoliash, Daniel] Univ Chicago, Dept Psychol, Chicago, IL 60637 USA.
   [Margoliash, Daniel] Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Margoliash, D (corresponding author), Univ Chicago, Dept Psychol, Chicago, IL 60637 USA.
EM dan@bigbird.uchicago.edu
FU NIMH NIH HHS [R01 MH059831] Funding Source: Medline
NR 34
TC 136
Z9 162
U1 2
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 MAR 5
PY 2009
VL 458
IS 7234
BP 73
EP U4
DI 10.1038/nature07615
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000035
PM 19079238
DA 2026-03-09
ER

PT J
AU Blosser, TR
   Yang, JG
   Stone, MD
   Narlikar, GJ
   Zhuang, XW
AF Blosser, Timothy R.
   Yang, Janet G.
   Stone, Michael D.
   Narlikar, Geeta J.
   Zhuang, Xiaowei
TI Dynamics of nucleosome remodelling by individual ACF complexes
SO NATURE
LA English
DT Article
ID dna translocation; single-molecule; histone octamer; energy-transfer; core particle; chromatin; iswi; swi/snf; mechanism; catalysis
AB The ATP-dependent chromatin assembly and remodelling factor (ACF) functions to generate regularly spaced nucleosomes, which are required for heritable gene silencing. The mechanism by which ACF mobilizes nucleosomes remains poorly understood. Here we report a single-molecule FRET study that monitors the remodelling of individual nucleosomes by ACF in real time, revealing previously unknown remodelling intermediates and dynamics. In the presence of ACF and ATP, the nucleosomes exhibit gradual translocation along DNA interrupted by well-defined kinetic pauses that occurred after approximately seven or three to four base pairs of translocation. The binding of ACF, translocation of DNA and exiting of translocation pauses are all ATP-dependent, revealing three distinct functional roles of ATP during remodelling. At equilibrium, a continuously bound ACF complex can move the nucleosome back-and-forth many times before dissociation, indicating that ACF is a highly processive and bidirectional nucleosome translocase.
C1 [Blosser, Timothy R.; Stone, Michael D.; Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
   [Blosser, Timothy R.] Harvard Univ, Grad Program Biophys, Cambridge, MA 02138 USA.
   [Yang, Janet G.; Narlikar, Geeta J.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94107 USA.
   [Stone, Michael D.; Zhuang, Xiaowei] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA.
   [Zhuang, Xiaowei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 Harvard University; Howard Hughes Medical Institute; Harvard University; University of California System; University of California San Francisco; Harvard University; Harvard University
RP Zhuang, XW (corresponding author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
EM geeta.narlikar@ucsf.edu; zhuang@chemistry.harvard.edu
FU Howard Hughes Medical Institute; National Institutes of Health [GM073767]; Beckman Foundation
NR 41
TC 161
Z9 208
U1 2
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1022
EP U79
DI 10.1038/nature08627
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000039
PM 20033040
DA 2026-03-09
ER

PT J
AU Colantonio, JR
   Vermot, J
   Wu, D
   Langenbacher, AD
   Fraser, S
   Chen, JN
   Hill, KL
AF Colantonio, Jessica R.
   Vermot, Julien
   Wu, David
   Langenbacher, Adam D.
   Fraser, Scott
   Chen, Jau-Nian
   Hill, Kent L.
TI The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear
SO NATURE
LA English
DT Article
ID trypanosoma-brucei; zebrafish; chlamydomonas; protein; mutations; gas11; components; mechanism; homolog; arms
AB In teleosts, proper balance and hearing depend on mechanical sensors in the inner ear. These sensors include actin- based microvilli and microtubule- based cilia that extend from the surface of sensory hair cells and attach to biomineralized 'ear stones' ( or otoliths)(1). Otolith number, size and placement are under strict developmental control, but the mechanisms that ensure otolith assembly atop specific cells of the sensory epithelium are unclear. Here we demonstrate that cilia motility is required for normal otolith assembly and localization. Using in vivo video microscopy, we show that motile tether cilia at opposite poles of the otic vesicle create fluid vortices that attract otolith precursor particles, thereby biasing an otherwise random distribution to direct localized otolith seeding on tether cilia. Independent knockdown of subunits for the dynein regulatory complex and outer- arm dynein disrupt cilia motility, leading to defective otolith biogenesis. These results demonstrate a requirement for the dynein regulatory complex in vertebrates and show that cilia- driven flow is a key epigenetic factor in controlling otolith biomineralization.
C1 [Colantonio, Jessica R.; Hill, Kent L.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
   [Langenbacher, Adam D.; Chen, Jau-Nian] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Chen, Jau-Nian; Hill, Kent L.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
   [Vermot, Julien; Wu, David; Fraser, Scott] CALTECH, Beckman Inst, Biol Imaging Ctr, Pasadena, CA 91125 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; California Institute of Technology
RP Hill, KL (corresponding author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
EM kenthill@mednet.ucla.edu
FU Human Frontier Science Program; NIH Medical Scientist Training Program at UCLA/Caltech; NIH RSDA [M07185]; Warsaw Fellowship; NSF; NIH [R01 HL081799, R01AI52348]; Beckman Young Investigator Award; National Institute of Allergy and Infectious Diseases [R01AI052348] Funding Source: NIH RePORTER
NR 34
TC 106
Z9 125
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 JAN 8
PY 2009
VL 457
IS 7226
BP 205
EP U102
DI 10.1038/nature07520
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200035
PM 19043402
DA 2026-03-09
ER

PT J
AU Hilf, RJC
   Dutzler, R
AF Hilf, Ricarda J. C.
   Dutzler, Raimund
TI Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel
SO NATURE
LA English
DT Article
ID nicotinic acetylcholine-receptor; charged amino-acids; cys-loop; gating mechanism; mono-valent; binding; selectivity; domain; software; reveals
AB The X- ray structure of a pentameric ligand- gated ion channel from Erwinia chrysanthemi ( ELIC) has recently provided structural insight into this family of ion channels at high resolution(1). The structure shows a homo- pentameric protein with a barrel- stave architecture that defines an ion- conduction pore located on the fivefold axis of symmetry. In this structure, the wide aqueous vestibule that is encircled by the extracellular ligand- binding domains of the five subunits narrows to a discontinuous pore that spans the lipid bilayer. The pore is constricted by bulky hydrophobic residues towards the extracellular side, which probably serve as barriers that prevent the diffusion of ions. This interrupted pore architecture in ELIC thus depicts a non- conducting conformation of a pentameric ligand- gated ion channel, the thermodynamically stable state in the absence of bound ligand. As ligand binding promotes pore opening in these ion channels and the specific ligand for ELIC has not yet been identified, we have turned our attention towards a homologous protein from the cyanobacterium Gloebacter violaceus ( GLIC). GLIC was shown to form proton- gated channels that are activated by a pH decrease on the extracellular side and that do not desensitize after activation(2). Both prokaryotic proteins, ELIC and GLIC form ion channels that are selective for cations over anions with poor discrimination among monovalent cations(1,2), characteristics that resemble the conduction properties of the cation- selective branch of the family that includes acetylcholine and serotonin receptors(3,4). Here we present the X- ray structure of GLIC at 3.1 angstrom resolution. The structure reveals a conformation of the channel that is distinct from ELIC and that probably resembles the open state. In combination, both structures suggest a novel gating mechanism for pentameric ligand- gated ion channels where channel opening proceeds by a change in the tilt of the pore- forming helices.
C1 [Hilf, Ricarda J. C.; Dutzler, Raimund] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland.
C3 University of Zurich
RP Dutzler, R (corresponding author), Univ Zurich, Dept Biochem, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM dutzler@bioc.uzh.ch
FU National Center for Competence in Research; EC FP7
NR 42
TC 481
Z9 541
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 JAN 1
PY 2009
VL 457
IS 7225
BP 115
EP U122
DI 10.1038/nature07461
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900042
PM 18987630
DA 2026-03-09
ER

PT J
AU Sakuno, T
   Tada, K
   Watanabe, Y
AF Sakuno, Takeshi
   Tada, Kenji
   Watanabe, Yoshinori
TI Kinetochore geometry defined by cohesion within the centromere
SO NATURE
LA English
DT Article
ID reductional chromosome segregation; fission yeast centromere; 1st meiotic division; meiosis-i; mitotic spindle; precocious separation; monopolar attachment; sister kinetochores; bi-orientation; budding yeast
AB During cell division microtubules capture chromosomes by binding to the kinetochore assembled in the centromeric region of chromosomes. In mitosis sister chromatids are captured by microtubules emanating from both spindle poles, a process called bipolar attachment, whereas in meiosis I sisters are attached to microtubules originating from one spindle pole, called monopolar attachment. For determining chromosome orientation, kinetochore geometry or structure might be an important target of regulation. However, the molecular basis of this regulation has remained elusive. Here we show the link between kinetochore orientation and cohesion within the centromere in fission yeast Schizosaccharomyces pombe by strategies developed to visualize the concealed cohesion within the centromere, and to introduce artificial tethers that can influence kinetochore geometry. Our data imply that cohesion at the core centromere induces the mono-orientation of kinetochores whereas cohesion at the peri-centromeric region promotes bi-orientation. Our study may reveal a general mechanism for the geometric regulation of kinetochores, which collaborates with previously defined tension-dependent reorientation machinery.
C1 [Sakuno, Takeshi; Tada, Kenji; Watanabe, Yoshinori] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Chromosome Dynam, Tokyo 1130032, Japan.
   [Tada, Kenji; Watanabe, Yoshinori] Univ Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo GRAD SCH SC, Japan.
C3 University of Tokyo; University of Tokyo
RP Watanabe, Y (corresponding author), Univ Tokyo, Inst Mol & Cellular Biosci, Lab Chromosome Dynam, Tokyo 1130032, Japan.
EM ywatanab@iam.u-tokyo.ac.jp
FU Special Coordination Funds for Promoting Science and Technology; MEXT, Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Scientific Research [21000010] Funding Source: KAKEN
NR 50
TC 140
Z9 166
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 16
PY 2009
VL 458
IS 7240
BP 852
EP U1
DI 10.1038/nature07876
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500035
PM 19370027
DA 2026-03-09
ER

PT J
AU de Aguiar, MAM
   Baranger, M
   Baptestini, EM
   Kaufman, L
   Bar-Yam, Y
AF de Aguiar, M. A. M.
   Baranger, M.
   Baptestini, E. M.
   Kaufman, L.
   Bar-Yam, Y.
TI Global patterns of speciation and diversity
SO NATURE
LA English
DT Article
ID adaptive speciation; species abundance; space
AB In recent years, strikingly consistent patterns of biodiversity have been identified over space, time, organism type and geographical region(1,2). A neutral theory (assuming no environmental selection or organismal interactions) has been shown to predict many patterns of ecological biodiversity(2,3). This theory is based on a mechanism by which new species arise similarly to point mutations in a population without sexual reproduction. Here we report the simulation of populations with sexual reproduction, mutation and dispersal. We found simulated time dependence of speciation rates, species-area relationships and species abundance distributions consistent with the behaviours found in nature(1-13). From our results, we predict steady speciation rates, more species in one-dimensional environments than two-dimensional environments, three scaling regimes of species-area relationships and lognormal distributions of species abundance with an excess of rare species and a tail that may be approximated by Fisher's logarithmic series. These are consistent with dependences reported for, among others, global birds(4) and flowering plants(5), marine invertebrate fossils(6), ray-finned fishes(7), British birds(8,9) and moths(10), North American songbirds(11), mammal fossils from Kansas(12) and Panamanian shrubs(13). Quantitative comparisons of specific cases are remarkably successful. Our biodiversity results provide additional evidence that species diversity arises without specific physical barriers(6,11,14). This is similar to heavy traffic flows, where traffic jams can form even without accidents or barriers(15).
C1 [de Aguiar, M. A. M.; Baranger, M.; Kaufman, L.; Bar-Yam, Y.] New England Complex Syst Inst, Cambridge, MA 02138 USA.
   [de Aguiar, M. A. M.; Baptestini, E. M.] Univ Estadual Campinas, BR-13083970 Campinas, SP, Brazil.
   [Baranger, M.] Univ Arizona, Tucson, AZ 85719 USA.
   [Kaufman, L.] Boston Univ, Boston, MA 02215 USA.
C3 Universidade Estadual de Campinas; University of Arizona; Boston University
RP Bar-Yam, Y (corresponding author), New England Complex Syst Inst, Cambridge, MA 02138 USA.
EM yaneer@necsi.edu
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
NR 30
TC 137
Z9 151
U1 0
U2 137
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 384
EP 387
DI 10.1038/nature08168
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000036
PM 19606148
DA 2026-03-09
ER

PT J
AU Verbiscer, AJ
   Skrutskie, MF
   Hamilton, DP
AF Verbiscer, Anne J.
   Skrutskie, Michael F.
   Hamilton, Douglas P.
TI Saturn's largest ring
SO NATURE
LA English
DT Article
ID dark side; iapetus; phoebe; satellites; hyperion; lapetus; dust
AB Most planetary rings in the Solar System lie within a few radii of their host body, because at these distances gravitational accelerations inhibit satellite formation. The best known exceptions are Jupiter's gossamer rings(1) and Saturn's E ring, broad sheets of dust that extend outward until they fade from view at five to ten planetary radii. Source satellites continuously supply the dust, which is subsequently lost in collisions or by radial transport. Here we report that Saturn has an enormous ring associated with its outer moon Phoebe, extending from at least 128R(S) to 207R(S) ( Saturn's radius R(S) is 60,330 km). The ring's vertical thickness of 40R(S) matches the range of vertical motion of Phoebe along its orbit. Dynamical considerations argue that these ring particles span the Saturnian system from the main rings to the edges of interplanetary space. The ring's normal optical depth of similar to 2 x 10(-8) is comparable to that of Jupiter's faintest gossamer ring, although its particle number density is several hundred times smaller. Repeated impacts on Phoebe, from both interplanetary and circumplanetary particle populations, probably keep the ring populated with material. Ring particles smaller than centimetres in size slowly migrate inward(2,3) and many of them ultimately strike the dark leading face of Iapetus.
C1 [Verbiscer, Anne J.; Skrutskie, Michael F.] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Hamilton, Douglas P.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
C3 University of Virginia; University System of Maryland; University of Maryland College Park
RP Verbiscer, AJ (corresponding author), Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
EM verbiscer@virginia.edu
FU NASA through an award issued by JPL/Caltech
NR 16
TC 109
Z9 127
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 22
PY 2009
VL 461
IS 7267
BP 1098
EP 1100
DI 10.1038/nature08515
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600038
PM 19812546
DA 2026-03-09
ER

PT J
AU Reineke, S
   Lindner, F
   Schwartz, G
   Seidler, N
   Walzer, K
   Lüssem, B
   Leo, K
AF Reineke, Sebastian
   Lindner, Frank
   Schwartz, Gregor
   Seidler, Nico
   Walzer, Karsten
   Luessem, Bjoern
   Leo, Karl
TI White organic light-emitting diodes with fluorescent tube efficiency
SO NATURE
LA English
DT Article
ID triplet excitons; devices; emission; carrier; layers
AB The development of white organic light-emitting diodes(1) (OLEDs) holds great promise for the production of highly efficient large-area light sources. High internal quantum efficiencies for the conversion of electrical energy to light have been realized(2-4). Nevertheless, the overall device power efficiencies are still considerably below the 60-70 lumens per watt of fluorescent tubes, which is the current benchmark for novel light sources. Although some reports about highly power-efficient white OLEDs exist(5,6), details about structure and the measurement conditions of these structures have not been fully disclosed: the highest power efficiency reported in the scientific literature is 44 lm W-1 (ref. 7). Here we report an improved OLED structure which reaches fluorescent tube efficiency. By combining a carefully chosen emitter layer with high-refractive-index substrates(8,9), and using a periodic outcoupling structure, we achieve a device power efficiency of 90 lm W-1 at 1,000 candelas per square metre. This efficiency has the potential to be raised to 124 lm W-1 if the light outcoupling can be further improved. Besides approaching internal quantum efficiency values of one, we have also focused on reducing energetic and ohmic losses that occur during electron-photon conversion. We anticipate that our results will be a starting point for further research, leading to white OLEDs having efficiencies beyond 100 lm W-1. This could make white-light OLEDs, with their soft area light and high colour-rendering qualities, the light sources of choice for the future.
C1 [Reineke, Sebastian; Lindner, Frank; Schwartz, Gregor; Seidler, Nico; Walzer, Karsten; Luessem, Bjoern; Leo, Karl] Inst Angew Photophys, D-01062 Dresden, Germany.
C3 Technische Universitat Dresden
RP Leo, K (corresponding author), Inst Angew Photophys, George Bahr Str 1, D-01062 Dresden, Germany.
EM leo@iapp.de
FU European Commission [IST-2002-004607]; Leibniz Prize of the Deutsche Forschungsgemeinschaft
NR 29
TC 3229
Z9 3562
U1 28
U2 2692
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 234
EP U116
DI 10.1038/nature08003
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100037
PM 19444212
DA 2026-03-09
ER

PT J
AU Franzdóttir, SR
   Engelen, D
   Yuva-Aydemir, Y
   Schmidt, I
   Aho, A
   Klämbt, C
AF Franzdottir, Sigridur Rut
   Engelen, Daniel
   Yuva-Aydemir, Yeliz
   Schmidt, Imke
   Aho, Annukka
   Klaembt, Christian
TI Switch in FGF signalling initiates glial differentiation in the Drosophila eye
SO NATURE
LA English
DT Article
ID receptor tyrosine kinase; cell migration; growth-factor; messenger-rna; rap1; activation; mesoderm; embryo; morphogenesis; neuregulin-1
AB The formation of a complex nervous system requires the intricate interaction of neurons and glial cells. Glial cells generally migrate over long distances before they initiate their differentiation, which leads to wrapping and insulation of axonal processes(1,2). The molecular pathways coordinating the switch from glial migration to glial differentiation are largely unknown(3). Here we demonstrate that, within the Drosophila eye imaginal disc, fibroblast growth factor (FGF) signalling coordinates glial proliferation, migration and subsequent axonal wrapping. Glial differentiation in the Drosophila eye disc requires a succession from glia-glia interaction to glia-neuron interaction(4). The neuronal component of the fly eye develops in the peripheral nervous system within the eye-antennal imaginal disc, whereas glial cells originate from a pool of central-nervous-system-derived progenitors and migrate onto the eye imaginal disc(5-8). Initially, glial-derived Pyramus, an FGF8-like ligand, modulates glial cell number and motility. A switch to neuronally expressed Thisbe, a second FGF8-like ligand, then induces glial differentiation. This switch is accompanied by an alteration in the intracellular signalling pathway through which the FGF receptor channels information into the cell. Our findings reveal how a switch from glia-glia interactions to glia-neuron interactions can trigger formation of glial membrane around axonal trajectories. These results disclose an evolutionarily conserved control mechanism of axonal wrapping(2), indicating that Drosophila might serve as a model to understand glial disorders in humans.
C1 [Franzdottir, Sigridur Rut; Engelen, Daniel; Yuva-Aydemir, Yeliz; Schmidt, Imke; Aho, Annukka; Klaembt, Christian] Univ Munster, Inst Neurobiol, D-48149 Munster, Germany.
C3 University of Munster
RP Klämbt, C (corresponding author), Univ Munster, Inst Neurobiol, Badestr 9, D-48149 Munster, Germany.
EM klaembt@uni-muenster.de
FU Deutsche Forschungsgemeinschaft
NR 32
TC 109
Z9 123
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 AUG 6
PY 2009
VL 460
IS 7256
BP 758
EP U106
DI 10.1038/nature08167
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300043
PM 19597479
DA 2026-03-09
ER

PT J
AU Hanna, J
   Saha, K
   Pando, B
   van Zon, J
   Lengner, CJ
   Creyghton, MP
   van Oudenaarden, A
   Jaenisch, R
AF Hanna, Jacob
   Saha, Krishanu
   Pando, Bernardo
   van Zon, Jeroen
   Lengner, Christopher J.
   Creyghton, Menno P.
   van Oudenaarden, Alexander
   Jaenisch, Rudolf
TI Direct cell reprogramming is a stochastic process amenable to acceleration
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; tumor-suppressor; nanog; induction; fibroblasts; expression; generation; circuitry; oct4; klf4
AB Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming by these transcription factors is a continuous stochastic process where almost all mouse donor cells eventually give rise to iPS cells on continued growth and transcription factor expression. Additional inhibition of the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell-division-rate-independent manner. Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency.
C1 [Hanna, Jacob; Saha, Krishanu; Lengner, Christopher J.; Creyghton, Menno P.; Jaenisch, Rudolf] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Pando, Bernardo; van Zon, Jeroen; van Oudenaarden, Alexander] MIT, Dept Phys, Cambridge, MA 02142 USA.
   [van Zon, Jeroen; van Oudenaarden, Alexander; Jaenisch, Rudolf] MIT, Dept Biol, Cambridge, MA 02142 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Jaenisch, R (corresponding author), MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
EM Hanna@wi.mit.edu; Jaenisch@wi.mit.edu
FU NIH [RO1-HDO45022, R37-CA084198, RO1-CA087869]; Helen Hay Whitney Foundation; Society in Science: The Brano- Weiss fellowship; Human Frontiers Science Program; National Cancer Institute [U54CA143874]
NR 46
TC 784
Z9 995
U1 0
U2 131
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 595
EP U63
DI 10.1038/nature08592
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900030
PM 19898493
DA 2026-03-09
ER

PT J
AU Zabolotnyy, VB
   Inosov, DS
   Evtushinsky, DV
   Koitzsch, A
   Kordyuk, AA
   Sun, GL
   Park, JT
   Haug, D
   Hinkov, V
   Boris, AV
   Lin, CT
   Knupfer, M
   Yaresko, AN
   Büchner, B
   Varykhalov, A
   Follath, R
   Borisenko, SV
AF Zabolotnyy, V. B.
   Inosov, D. S.
   Evtushinsky, D. V.
   Koitzsch, A.
   Kordyuk, A. A.
   Sun, G. L.
   Park, J. T.
   Haug, D.
   Hinkov, V.
   Boris, A. V.
   Lin, C. T.
   Knupfer, M.
   Yaresko, A. N.
   Buechner, B.
   Varykhalov, A.
   Follath, R.
   Borisenko, S. V.
TI (π, π) electronic order in iron arsenide superconductors
SO NATURE
LA English
DT Article
ID density-wave
AB The distribution of valence electrons in metals usually follows the symmetry of the underlying ionic lattice. Modulations of this distribution often occur when those electrons are not stable with respect to a new electronic order, such as spin or charge density waves. Electron density waves have been observed in many families of superconductors(1-3), and are often considered to be essential for superconductivity to exist(4). Recent measurements(5-9) seem to show that the properties of the iron pnictides(10,11) are in good agreement with band structure calculations that do not include additional ordering, implying no relation between density waves and superconductivity in these materials(12-15). Here we report that the electronic structure of Ba1-xKxFe2As2 is in sharp disagreement with those band structure calculations(12-15), and instead reveals a reconstruction characterized by a (pi, pi) wavevector. This electronic order coexists with superconductivity and persists up to room temperature (300 K).
C1 [Zabolotnyy, V. B.; Inosov, D. S.; Evtushinsky, D. V.; Koitzsch, A.; Kordyuk, A. A.; Knupfer, M.; Buechner, B.; Borisenko, S. V.] IFW Dresden, Inst Solid State Res, D-01171 Dresden, Germany.
   [Inosov, D. S.; Sun, G. L.; Park, J. T.; Haug, D.; Hinkov, V.; Boris, A. V.; Lin, C. T.; Yaresko, A. N.] Max Planck Inst Solid State Res, D-70569 Stuttgart, Germany.
   [Kordyuk, A. A.] Natl Acad Sci Ukraine, Inst Met Phys, UA-03142 Kiev, Ukraine.
   [Boris, A. V.] Loughborough Univ Technol, Dept Phys, Loughborough LE11 3TU, Leics, England.
   [Varykhalov, A.; Follath, R.] Helmholtz Zentrum Berlin Mat & Energie, Elektronenspeicherring BESSY 2, D-12489 Berlin, Germany.
C3 Leibniz Association; Leibniz Institute for Solid State & Materials Research Dresden; Institute for Integrative Nanosciences (IIN); Max Planck Society; National Academy of Sciences Ukraine; Loughborough University; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB)
RP Borisenko, SV (corresponding author), IFW Dresden, Inst Solid State Res, POB 270116, D-01171 Dresden, Germany.
EM s.borisenko@ifw-dresden.de
FU Deutsche Forschungsgemeinschaft [KN393/4, BO 1912/2-1]
NR 24
TC 174
Z9 187
U1 2
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 29
PY 2009
VL 457
IS 7229
BP 569
EP 572
DI 10.1038/nature07714
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200038
PM 19177126
DA 2026-03-09
ER

PT J
AU Saavedra, S
   Reed-Tsochas, F
   Uzzi, B
AF Saavedra, Serguei
   Reed-Tsochas, Felix
   Uzzi, Brian
TI A simple model of bipartite cooperation for ecological and organizational networks
SO NATURE
LA English
DT Article
ID food; embeddedness; exploitation; patterns; rules
AB In theoretical ecology, simple stochastic models that satisfy two basic conditions about the distribution of niche values and feeding ranges have proved successful in reproducing the overall structural properties of real food webs, using species richness and connectance as the only input parameters(1-4). Recently, more detailed models have incorporated higher levels of constraint in order to reproduce the actual links observed in real food webs(5,6). Here, building on previous stochastic models of consumer - resource interactions between species(1-3), we propose a highly parsimonious model that can reproduce the overall bipartite structure of cooperative partner - partner interactions, as exemplified by plant - animal mutualistic networks(7). Our stochastic model of bipartite cooperation uses simple specialization and interaction rules, and only requires three empirical input parameters. We test the bipartite cooperation model on ten large pollination data sets that have been compiled in the literature, and find that it successfully replicates the degree distribution, nestedness and modularity of the empirical networks. These properties are regarded as key to understanding cooperation in mutualistic networks(8-10). We also apply our model to an extensive data set of two classes of company engaged in joint production in the garment industry. Using the same metrics, we find that the network of manufacturer - contractor interactions exhibits similar structural patterns to plant - animal pollination networks. This surprising correspondence between ecological and organizational networks suggests that the simple rules of cooperation that generate bipartite networks may be generic, and could prove relevant in many different domains, ranging from biological systems to human society(11-14).
C1 [Saavedra, Serguei; Reed-Tsochas, Felix] Univ Oxford, CABDyN Complex Ctr, Oxford OX1 1HP, England.
   [Saavedra, Serguei] Univ Oxford, Corp Reputat Ctr, Oxford OX1 1HP, England.
   [Reed-Tsochas, Felix] Univ Oxford, James Martin Inst, Said Business Sch, Oxford OX1 1HP, England.
   [Saavedra, Serguei] Univ Oxford, Dept Engn Sci, Oxford OX1 3PJ, England.
   [Uzzi, Brian] Northwestern Univ, JL Kellogg Grad Sch Management, Evanston, IL 60208 USA.
   [Uzzi, Brian] Northwestern Univ, NW Inst Complex Syst, Evanston, IL 60208 USA.
   [Uzzi, Brian] Univ Calif Berkeley, Haas Sch Business, Berkeley, CA 94720 USA.
C3 University of Oxford; University of Oxford; University of Oxford; University of Oxford; Northwestern University; Northwestern University; University of California System; University of California Berkeley
RP Reed-Tsochas, F (corresponding author), Univ Oxford, CABDyN Complex Ctr, Oxford OX1 1HP, England.
EM felix.reed-tsochas@sbs.ox.ac.uk
FU European Commission; MMCOMNET; CONACYT; Oxford University Corporate Reputation Centre; CABDyN Complexity Centre
NR 30
TC 141
Z9 153
U1 1
U2 102
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 22
PY 2009
VL 457
IS 7228
BP 463
EP 466
DI 10.1038/nature07532
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200043
PM 19052545
DA 2026-03-09
ER

PT J
AU Neil, H
   Malabat, C
   d'Aubenton-Carafa, Y
   Xu, ZY
   Steinmetz, LM
   Jacquier, A
AF Neil, Helen
   Malabat, Christophe
   d'Aubenton-Carafa, Yves
   Xu, Zhenyu
   Steinmetz, Lars M.
   Jacquier, Alain
TI Widespread bidirectional promoters are the major source of cryptic transcripts in yeast
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; unstable transcripts; rna; genome; gene; termination; expression; pathway; polymerase; initiation
AB Pervasive and hidden transcription is widespread in eukaryotes(1-4), but its global level, the mechanisms from which it originates and its functional significance are unclear. Cryptic unstable transcripts ( CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae(5). These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1 - exosome - TRAMP complexes(6,7). Although CUT degradation mechanisms have been analysed in detail, the genome- wide distribution at the nucleotide resolution and the prevalence of CUTs are unknown. Here we report the first high- resolution genomic map of CUTs in yeast, revealing a class of potentially functional CUTs and the intrinsic bidirectional nature of eukaryotic promoters. An RNA fraction highly enriched in CUTs was analysed by a 3 ' Long- SAGE ( serial analysis of gene expression) approach adapted to deep sequencing. The resulting detailed genomic map of CUTs revealed that they derive from extremely widespread and very well defined transcription units and do not result from unspecific transcriptional noise. Moreover, the transcription of CUTs predominantly arises within nucleosome- free regions, most of which correspond to promoter regions of bona fide genes. Some of the CUTs start upstream from messenger RNAs and overlap their 59 end. Our study of glycolysis genes, as well as recent results from the literature(8-11), indicate that such concurrent transcription is potentially associated with regulatory mechanisms. Our data reveal numerous new CUTs with such a potential regulatory role. However, most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by- products of divergent transcription occurring at many and possibly most promoters. Eukaryotic promoter regions are thus intrinsically bidirectional, a fundamental property that escaped previous analyses because in most cases divergent transcription generates short- lived unstable transcripts present at very low steady- state levels.
C1 [Neil, Helen; Malabat, Christophe; Jacquier, Alain] CNRS, Inst Pasteur, Unite Genet Interact Macromol, URA2171, F-75015 Paris, France.
   [d'Aubenton-Carafa, Yves] CNRS, Ctr Genet Mol, F-91198 Gif Sur Yvette, France.
   [Xu, Zhenyu; Steinmetz, Lars M.] European Mol Biol Lab, D-69117 Heidelberg, Germany.
C3 Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; European Molecular Biology Laboratory (EMBL)
RP Jacquier, A (corresponding author), CNRS, Inst Pasteur, Unite Genet Interact Macromol, URA2171, F-75015 Paris, France.
EM alain.jacquier@pasteur.fr
FU Institut Pasteur; CNRS; ANR (CUT program); European Science Foundation (RNA quality program); National Institutes of Health; Deutsche Forschungsgemeinschaft
NR 25
TC 478
Z9 578
U1 2
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 19
PY 2009
VL 457
IS 7232
BP 1038
EP U8
DI 10.1038/nature07747
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400048
PM 19169244
DA 2026-03-09
ER

PT J
AU Velu, V
   Titanji, K
   Zhu, BG
   Husain, S
   Pladevega, A
   Lai, LL
   Vanderford, TH
   Chennareddi, L
   Silvestri, G
   Freeman, GJ
   Ahmed, R
   Amara, RR
AF Velu, Vijayakumar
   Titanji, Kehmia
   Zhu, Baogong
   Husain, Sajid
   Pladevega, Annette
   Lai, Lilin
   Vanderford, Thomas H.
   Chennareddi, Lakshmi
   Silvestri, Guido
   Freeman, Gordon J.
   Ahmed, Rafi
   Amara, Rama Rao
TI Enhancing SIV-specific immunity in vivo by PD-1 blockade
SO NATURE
LA English
DT Article
ID simian immunodeficiency virus; cd8 t-cells; chronic viral-infection; programmed death-1; effector function; expression; lymphocytes; persistence; exhaustion; mechanisms
AB Chronic immunodeficiency virus infections are characterized by dysfunctional cellular and humoral antiviral immune responses(1-3). As such, immune modulatory therapies that enhance and/or restore the function of virus-specific immunity may protect from disease progression. Here we investigate the safety and immune restoration potential of blockade of the co-inhibitory receptor programmed death 1 (PD-1) 4,5 during chronic simian immunodeficiency virus (SIV) infection in macaques. We demonstrate that PD-1 blockade using an antibody to PD-1 is well tolerated and results in rapid expansion of virus-specific CD8 T cells with improved functional quality. This enhanced T-cell immunity was seen in the blood and also in the gut, a major reservoir of SIV infection. PD-1 blockade also resulted in proliferation of memory B cells and increases in SIV envelope-specific antibody. These improved immune responses were associated with significant reductions in plasma viral load and also prolonged the survival of SIV-infected macaques. Blockade was effective during the early (week 10) as well as late (similar to week 90) phases of chronic infection even under conditions of severe lymphopenia. These results demonstrate enhancement of both cellular and humoral immune responses during a pathogenic immunodeficiency virus infection by blocking a single inhibitory pathway and identify a novel therapeutic approach for control of human immunodeficiency virus infections.
C1 [Velu, Vijayakumar; Titanji, Kehmia; Husain, Sajid; Pladevega, Annette; Lai, Lilin; Chennareddi, Lakshmi; Ahmed, Rafi; Amara, Rama Rao] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Velu, Vijayakumar; Titanji, Kehmia; Husain, Sajid; Pladevega, Annette; Lai, Lilin; Chennareddi, Lakshmi; Amara, Rama Rao] Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Zhu, Baogong; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Zhu, Baogong; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Vanderford, Thomas H.; Silvestri, Guido] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
C3 Emory University; Emory University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; University of Pennsylvania
RP Amara, RR (corresponding author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM ramara@emory.edu
FU NCRR NIH HHS [P51 RR00165, R24 RR016038, P51 RR000165, R24 RR16038] Funding Source: Medline; NIAID NIH HHS [R01 AI074417, R01 AI071852, R01 AI057029, P30 AI050409] Funding Source: Medline; National Heart Lung and Blood Institute; National Cancer Institute; National Institute on Minority Health and Health Disparities; National Institute of Nursing Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; National Institute on Drug Abuse; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research [P30AI050409] Funding Source: NIH RePORTER
NR 30
TC 636
Z9 788
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 206
EP U5
DI 10.1038/nature07662
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700044
PM 19078956
DA 2026-03-09
ER

PT J
AU Clare, DK
   Bakkes, PJ
   van Heerikhuizen, H
   van der Vies, SM
   Saibil, HR
AF Clare, D. K.
   Bakkes, P. J.
   van Heerikhuizen, H.
   van der Vies, S. M.
   Saibil, H. R.
TI Chaperonin complex with a newly folded protein encapsulated in the folding chamber
SO NATURE
LA English
DT Article
ID groel-groes; electron-microscopy; mass-spectrometry; crystal-structure; escherichia-coli; central cavity; head protein; binding; cage; atp
AB A subset of essential cellular proteins requires the assistance of chaperonins (in Escherichia coli, GroEL and GroES), double-ring complexes in which the two rings act alternately to bind, encapsulate and fold a wide range of nascent or stress- denatured proteins(1-5). This process starts by the trapping of a substrate protein on hydrophobic surfaces in the central cavity of a GroEL ring(6-10). Then, binding of ATP and co- chaperonin GroES to that ring ejects the non- native protein from its binding sites, through forced unfolding or other major conformational changes, and encloses it in a hydrophilic chamber for folding(11-15). ATP hydrolysis and subsequent ATP binding to the opposite ring trigger dissociation of the chamber and release of the substrate protein(3). The bacteriophage T4 requires its own version of GroES, gp31, which forms a taller folding chamber, to fold the major viral capsid protein gp23 ( refs 16-20). Polypeptides are known to fold inside the chaperonin complex, but the conformation of an encapsulated protein has not previously been visualized. Here we present structures of gp23-chaperonin complexes, showing both the initial captured state and the final, close-to-native state with gp23 encapsulated in the folding chamber. Although the chamber is expanded, it is still barely large enough to contain the elongated gp23 monomer, explaining why the GroEL-GroES complex is not able to fold gp23 and showing how the chaperonin structure distorts to enclose a large, physiological substrate protein.
C1 [Clare, D. K.; Saibil, H. R.] Univ London Birkbeck Coll, Dept Crystallog, London WC1E 7HX, England.
   [Clare, D. K.; Saibil, H. R.] Univ London Birkbeck Coll, Inst Struct & Mol Biol, London WC1E 7HX, England.
   [Bakkes, P. J.; van Heerikhuizen, H.; van der Vies, S. M.] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands.
C3 University of London; Birkbeck University London; University of London; Birkbeck University London; Vrije Universiteit Amsterdam; Amsterdam University Medical Center
RP Saibil, HR (corresponding author), Univ London Birkbeck Coll, Dept Crystallog, Malet St, London WC1E 7HX, England.
EM vdvies@vumc.nl; h.saibil@mail.cryst.bbk.ac.uk
FU Wellcome Trust programme; EU 3D EM Network of Excellence; 3D Repertoire
NR 36
TC 84
Z9 99
U1 1
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 1
PY 2009
VL 457
IS 7225
BP 107
EP U113
DI 10.1038/nature07479
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900040
PM 19122642
DA 2026-03-09
ER

PT J
AU Kalantry, S
   Purushothaman, S
   Bowen, RB
   Starmer, J
   Magnuson, T
AF Kalantry, Sundeep
   Purushothaman, Sonya
   Bowen, Randall Bryant
   Starmer, Joshua
   Magnuson, Terry
TI Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation
SO NATURE
LA English
DT Article
ID dosage compensation; linked genes; mammalian x; expression; methylation; eed
AB XX female mammals undergo transcriptional silencing of most genes on one of their two X chromosomes to equalize X-linked gene dosage with XY males in a process referred to as X-chromosome inactivation (XCI). XCI is an example of epigenetic regulation(1). Once enacted in individual cells of the early female embryo, XCI is stably transmitted such that most descendant cells maintain silencing of that X chromosome(2). In eutherian mammals, XCI is thought to be triggered by the expression of the non-coding Xist RNA from the future inactive X chromosome (Xi)(3-5); Xist RNA in turn is proposed to recruit protein complexes that bring about heterochromatinization of the Xi(6,7). Here we test whether imprinted XCI, which results in preferential inactivation of the paternal X chromosome (Xp), occurs in mouse embryos inheriting an Xp lacking Xist. We find that silencing of Xp-linked genes can initiate in the absence of paternal Xist; Xist is, however, required to stabilize silencing along the Xp. Xp-linked gene silencing associated with mouse imprinted XCI, therefore, can initiate in the embryo independently of Xist RNA.
C1 [Kalantry, Sundeep; Purushothaman, Sonya; Bowen, Randall Bryant; Starmer, Joshua; Magnuson, Terry] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Kalantry, Sundeep; Purushothaman, Sonya; Bowen, Randall Bryant; Starmer, Joshua; Magnuson, Terry] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Kalantry, Sundeep; Purushothaman, Sonya; Bowen, Randall Bryant; Starmer, Joshua; Magnuson, Terry] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill
RP Magnuson, T (corresponding author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM trm4@med.unc.edu
FU American Cancer Society; US National Institutes of Health
NR 30
TC 111
Z9 142
U1 0
U2 12
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 647
EP 651
DI 10.1038/nature08161
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300054
PM 19571810
DA 2026-03-09
ER

PT J
AU Gick, B
   Derrick, D
AF Gick, Bryan
   Derrick, Donald
TI Aero-tactile integration in speech perception
SO NATURE
LA English
DT Article
ID stimulation; hearing; puffs; still; hand
AB Visual information from a speaker's face can enhance(1) or interfere with(2) accurate auditory perception. This integration of information across auditory and visual streams has been observed in functional imaging studies(3,4), and has typically been attributed to the frequency and robustness with which perceivers jointly encounter event-specific information from these two modalities(5). Adding the tactile modality has long been considered a crucial next step in understanding multisensory integration. However, previous studies have found an influence of tactile input on speech perception only under limited circumstances, either where perceivers were aware of the task(6,7) or where they had received training to establish a cross-modal mapping(8-10). Here we show that perceivers integrate naturalistic tactile information during auditory speech perception without previous training. Drawing on the observation that some speech sounds produce tiny bursts of aspiration (such as English 'p')(11), we applied slight, inaudible air puffs on participants' skin at one of two locations: the right hand or the neck. Syllables heard simultaneously with cutaneous air puffs were more likely to be heard as aspirated ( for example, causing participants to mishear 'b' as 'p'). These results demonstrate that perceivers integrate event-relevant tactile information in auditory perception in much the same way as they do visual information.
C1 [Gick, Bryan; Derrick, Donald] Univ British Columbia, Dept Linguist, Vancouver, BC V6T 1Z4, Canada.
   [Gick, Bryan] Haskins Labs Inc, New Haven, CT 06511 USA.
C3 University of British Columbia; Yale University; Haskins Laboratories
RP Gick, B (corresponding author), Univ British Columbia, Dept Linguist, Vancouver, BC V6T 1Z4, Canada.
EM gick@interchange.ubc.ca
FU Natural Sciences and Engineering Council of Canada; National Institutes of Health [DC-02717]; National Institute on Deafness and Other Communication Disorders [R01DC002717] Funding Source: NIH RePORTER
NR 21
TC 142
Z9 168
U1 7
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 502
EP 504
DI 10.1038/nature08572
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200043
PM 19940925
DA 2026-03-09
ER

PT J
AU Bower, AS
   Lozier, MS
   Gary, SF
   Böning, CW
AF Bower, Amy S.
   Lozier, M. Susan
   Gary, Stefan F.
   Boening, Claus W.
TI Interior pathways of the North Atlantic meridional overturning circulation
SO NATURE
LA English
DT Article
ID labrador sea-water; western boundary current
AB To understand how our global climate will change in response to natural and anthropogenic forcing, it is essential to determine how quickly and by what pathways climate change signals are transported throughout the global ocean, a vast reservoir for heat and carbon dioxide. Labrador Sea Water (LSW), formed by open ocean convection in the subpolar North Atlantic, is a particularly sensitive indicator of climate change on interannual to decadal timescales(1-3). Hydrographic observations made anywhere along the western boundary of the North Atlantic reveal a core of LSW at intermediate depths advected southward within the Deep Western Boundary Current (DWBC)(4-9). These observations have led to the widely held view that the DWBC is the dominant pathway for the export of LSW from its formation site in the northern North Atlantic towards the Equator(10,11). Here we show that most of the recently ventilated LSW entering the subtropics follows interior, not DWBC, pathways. The interior pathways are revealed by trajectories of subsurface RAFOS floats released during the period 2003-2005 that recorded once-daily temperature, pressure and acoustically determined position for two years, and by model-simulated 'e-floats' released in the subpolar DWBC. The evidence points to a few specific locations around the Grand Banks where LSW is most often injected into the interior. These results have implications for deep ocean ventilation and suggest that the interior subtropical gyre should not be ignored when considering the Atlantic meridional overturning circulation.
C1 [Bower, Amy S.] Woods Hole Oceanog Inst, Dept Phys Oceanog, Woods Hole, MA 02540 USA.
   [Lozier, M. Susan; Gary, Stefan F.] Duke Univ, Nicholas Sch Environm, Div Earth & Ocean Sci, Durham, NC 27708 USA.
   [Boening, Claus W.] IFM GEOMAR Leibniz Inst Meereswissensch, D-24105 Kiel, Germany.
C3 Woods Hole Oceanographic Institution; Duke University; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel
RP Bower, AS (corresponding author), Woods Hole Oceanog Inst, Dept Phys Oceanog, Woods Hole, MA 02540 USA.
EM abower@whoi.edu; mslozier@duke.edu
FU US National Science Foundation.; Directorate For Geosciences; Division Of Ocean Sciences [0824652] Funding Source: National Science Foundation
NR 29
TC 222
Z9 252
U1 1
U2 74
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 243
EP U126
DI 10.1038/nature07979
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100039
PM 19444214
DA 2026-03-09
ER

PT J
AU Semmelhack, JL
   Wang, JW
AF Semmelhack, Julia L.
   Wang, Jing W.
TI Select Drosophila glomeruli mediate innate olfactory attraction and aversion
SO NATURE
LA English
DT Article
ID antennal lobe; behavioral-responses; fly brain; neurons; receptors; map; melanogaster; representation; information; channels
AB Fruitflies show robust attraction to food odours, which usually excite several glomeruli. To understand how the representation of such odours leads to behaviour, we used genetic tools to dissect the contribution of each activated glomerulus. Apple cider vinegar triggers robust innate attraction at a relatively low concentration, which activates six glomeruli. By silencing individual glomeruli, here we show that the absence of activity in two glomeruli, DM1 and VA2, markedly reduces attraction. Conversely, when each of these two glomeruli was selectively activated, flies showed as robust an attraction to vinegar as wild-type flies. Notably, a higher concentration of vinegar excites an additional glomerulus and is less attractive to flies. We show that activation of the extra glomerulus is necessary and sufficient to mediate the behavioural switch. Together, these results indicate that individual glomeruli, rather than the entire pattern of active glomeruli, mediate innate behavioural output.
C1 [Semmelhack, Julia L.; Wang, Jing W.] Univ Calif San Diego, Div Biol Sci, Neurobiol Sect, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego
RP Wang, JW (corresponding author), Univ Calif San Diego, Div Biol Sci, Neurobiol Sect, La Jolla, CA 92093 USA.
EM jw800@ucsd.edu
FU Whitehall Foundation; National Institute of Deafness and other Communication Disorders [R01DC009597]
NR 47
TC 265
Z9 326
U1 0
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 MAY 14
PY 2009
VL 459
IS 7244
BP 218
EP U100
DI 10.1038/nature07983
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100033
PM 19396157
DA 2026-03-09
ER

PT J
AU Spencer, SL
   Gaudet, S
   Albeck, JG
   Burke, JM
   Sorger, PK
AF Spencer, Sabrina L.
   Gaudet, Suzanne
   Albeck, John G.
   Burke, John M.
   Sorger, Peter K.
TI Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis
SO NATURE
LA English
DT Article
ID tumor-cell; protein; activation; noise; robustness; expression; family; kill
AB In microorganisms, noise in gene expression gives rise to cell-to-cell variability in protein concentrations(1-7). In mammalian cells, protein levels also vary(8-10) and individual cells differ widely in their responsiveness to uniform physiological stimuli(11-15). In the case of apoptosis mediated by TRAIL (tumour necrosis factor (TNF)related apoptosis-inducing ligand) it is common for some cells in a clonal population to die while others survive-a striking divergence in cell fate. Among cells that die, the time between TRAIL exposure and caspase activation is highly variable. Here we image sister cells expressing reporters of caspase activation and mitochondrial outer membrane permeabilization after exposure to TRAIL. We show that naturally occurring differences in the levels or states of proteins regulating receptor-mediated apoptosis are the primary causes of cell-to-cell variability in the timing and probability of death in human cell lines. Protein state is transmitted from mother to daughter, giving rise to transient heritability in fate, but protein synthesis promotes rapid divergence so that sister cells soon become no more similar to each other than pairs of cells chosen at random. Our results have implications for understanding 'fractional killing' of tumour cells after exposure to chemotherapy, and for variability in mammalian signal transduction in general.
C1 [Spencer, Sabrina L.; Gaudet, Suzanne; Albeck, John G.; Burke, John M.; Sorger, Peter K.] Harvard Univ, Sch Med, Dept Syst Biol, Ctr Cell Decis Proc, Boston, MA 02115 USA.
   [Spencer, Sabrina L.] MIT, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT)
RP Sorger, PK (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Ctr Cell Decis Proc, Boston, MA 02115 USA.
EM peter_sorger@hms.harvard.edu
FU National Institute of Health [GM68762, CA112967]
NR 29
TC 782
Z9 982
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 MAY 21
PY 2009
VL 459
IS 7245
BP 428
EP U144
DI 10.1038/nature08012
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700046
PM 19363473
DA 2026-03-09
ER

PT J
AU Zheng, JP
   Birktoft, JJ
   Chen, Y
   Wang, T
   Sha, RJ
   Constantinou, PE
   Ginell, SL
   Mao, CD
   Seeman, NC
AF Zheng, Jianping
   Birktoft, Jens J.
   Chen, Yi
   Wang, Tong
   Sha, Ruojie
   Constantinou, Pamela E.
   Ginell, Stephan L.
   Mao, Chengde
   Seeman, Nadrian C.
TI From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal
SO NATURE
LA English
DT Article
ID nucleic-acid junctions; holliday junction; crystallization; substrate; triangles
AB We live in a macroscopic three-dimensional (3D) world, but our best description of the structure of matter is at the atomic and molecular scale. Understanding the relationship between the two scales requires a bridge from the molecular world to the macroscopic world. Connecting these two domains with atomic precision is a central goal of the natural sciences, but it requires high spatial control of the 3D structure of matter(1). The simplest practical route to producing precisely designed 3D macroscopic objects is to form a crystalline arrangement by self-assembly, because such a periodic array has only conceptually simple requirements: a motif that has a robust 3D structure, dominant affinity interactions between parts of the motif when it self-associates, and predictable structures for these affinity interactions. Fulfilling these three criteria to produce a 3D periodic system is not easy, but should readily be achieved with well-structured branched DNA motifs tailed by sticky ends(2). Complementary sticky ends associate with each other preferentially and assume the well-known B-DNA structure when they do so(3); the helically repeating nature of DNA facilitates the construction of a periodic array. It is essential that the directions of propagation associated with the sticky ends do not share the same plane, but extend to form a 3D arrangement of matter. Here we report the crystal structure at 4 angstrom resolution of a designed, self-assembled, 3D crystal based on the DNA tensegrity triangle(4). The data demonstrate clearly that it is possible to design and self-assemble a well-ordered macromolecular 3D crystalline lattice with precise control.
C1 [Zheng, Jianping; Birktoft, Jens J.; Wang, Tong; Sha, Ruojie; Constantinou, Pamela E.; Seeman, Nadrian C.] NYU, Dept Chem, New York, NY 10003 USA.
   [Chen, Yi; Mao, Chengde] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
   [Ginell, Stephan L.] Argonne Natl Lab, Struct Biol Ctr, Argonne, IL 60439 USA.
C3 New York University; Purdue University System; Purdue University; United States Department of Energy (DOE); Argonne National Laboratory
RP Seeman, NC (corresponding author), NYU, Dept Chem, New York, NY 10003 USA.
EM mao@purdue.edu; ned.seeman@nyu.edu
FU National Institute of General Medical Sciences; National Science Foundation [CCF-0622093]; Army Research Office; Office of Naval Research; W. M. Keck Foundation; NIH [1R21EB007472]; US Department of Energy [DE-AC02-06CH11357]
NR 24
TC 802
Z9 1044
U1 4
U2 501
PU NATURE PUBLISHING 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 3
PY 2009
VL 461
IS 7260
BP 74
EP 77
DI 10.1038/nature08274
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800032
PM 19727196
DA 2026-03-09
ER

PT J
AU Fielding, EJ
   Lundgren, PR
   Bürgmann, R
   Funning, GJ
AF Fielding, Eric J.
   Lundgren, Paul R.
   Buergmann, Roland
   Funning, Gareth J.
TI Shallow fault-zone dilatancy recovery after the 2003 Bam earthquake in Iran
SO NATURE
LA English
DT Article
ID deformation; parkfield; velocity; damage; slip
AB Earthquakes radiate from slip on discrete faults, but also commonly involve distributed deformation within a broader fault zone, especially near the surface. Variations in rock strain during an earthquake are caused by heterogeneity in the elastic stress before the earthquake, by variable material properties and geometry of the fault zones, and by dynamic processes during the rupture(1,2). Stress changes due to the earthquake slip, both dynamic and static, have long been thought to cause dilatancy in the fault zone that recovers after the earthquake(3-5). Decreases in the velocity of seismic waves passing through the fault zone due to coseismic dilatancy have been observed(6) followed by postseismic seismic velocity increases during healing(5,7,8). Dilatancy and its recovery have not previously been observed geodetically. Here we use interferometric analysis of synthetic aperture radar images to measure postseismic surface deformation after the 2003 Bam, Iran, earthquake and show reversal of coseismic dilatancy in the shallow fault zone that causes subsidence of the surface. This compaction of the fault zone is directly above the patch of greatest coseismic slip at depth. The dilatancy and compaction probably reflects distributed shear and damage to the material during the earthquake that heals afterwards. Coseismic and postseismic deformation spread through a fault zone volume may resolve the paradox of shallow slip deficits for some strike-slip fault ruptures(9).
C1 [Fielding, Eric J.; Lundgren, Paul R.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Buergmann, Roland] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
   [Funning, Gareth J.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
C3 National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of California System; University of California Berkeley; University of California System; University of California Riverside
RP Fielding, EJ (corresponding author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
EM Eric.J.Fielding@jpl.nasa.gov
FU AOE [668]
NR 29
TC 97
Z9 107
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 5
PY 2009
VL 458
IS 7234
BP 64
EP 68
DI 10.1038/nature07817
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000033
PM 19262670
DA 2026-03-09
ER

PT J
AU Mueller, M
   Grauschopf, U
   Maier, T
   Glockshuber, R
   Ban, N
AF Mueller, Marcus
   Grauschopf, Ulla
   Maier, Timm
   Glockshuber, Rudi
   Ban, Nenad
TI The structure of a cytolytic α-helical toxin pore reveals its assembly mechanism
SO NATURE
LA English
DT Article
ID hemolysin-e hlye; escherichia-coli; molecular analysis; crystal-structure; bacterial toxin; clya; protein; shea; software; refinement
AB Pore-forming toxins (PFTs) are a class of potent virulence factors that convert from a soluble form to a membrane-integrated pore(1). They exhibit their toxic effect either by destruction of the membrane permeability barrier or by delivery of toxic components through the pores. Among the group of bacterial PFTs are some of the most dangerous toxins, such as diphtheria and anthrax toxin. Examples of eukaryotic PFTs are perforin and the membrane-attack complex, proteins of the immune system(2). PFTs can be subdivided into two classes, alpha-PFTs and beta-PFTs, depending on the suspected mode of membrane integration, either by alpha-helical or beta-sheet elements(3). The only high-resolution structure of a transmembrane PFT pore is available for a beta-PFT-alpha-haemolysin from Staphylococcus aureus 4. Cytolysin A (ClyA, also known as HlyE), an alpha-PFT, is a cytolytic alpha-helical toxin responsible for the haemolytic phenotype of several Escherichia coli and Salmonella enterica strains(5-8). ClyA is cytotoxic towards cultured mammalian cells, induces apoptosis of macrophages and promotes tissue pervasion(9-11). Electron microscopic reconstructions demonstrated that the soluble monomer of ClyA(12) must undergo large conformational changes to form the transmembrane pore(13,14). Here we report the 3.3 angstrom crystal structure of the 400 kDa dodecameric transmembrane pore formed by ClyA. The tertiary structure of ClyA protomers in the pore is substantially different from that in the soluble monomer. The conversion involves more than half of all residues. It results in large rearrangements, up to 140 angstrom, of parts of the monomer, reorganization of the hydrophobic core, and transitions of beta-sheets and loop regions to alpha-helices. The large extent of interdependent conformational changes indicates a sequential mechanism for membrane insertion and pore formation.
C1 [Mueller, Marcus; Grauschopf, Ulla; Maier, Timm; Glockshuber, Rudi; Ban, Nenad] ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Ban, N (corresponding author), ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
EM ban@mol.biol.ethz.ch
FU Swiss National Science Foundation (SNSF); National Center of Excellence in Research (NCCR); Structural Biology program of the SNSF
NR 47
TC 282
Z9 324
U1 1
U2 74
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 726
EP U135
DI 10.1038/nature08026
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600049
PM 19421192
DA 2026-03-09
ER

PT J
AU Wang, XQ
   Tsai, JW
   Imai, JH
   Lian, WN
   Vallee, RB
   Shi, SH
AF Wang, Xiaoqun
   Tsai, Jin-Wu
   Imai, Janice H.
   Lian, Wei-Nan
   Vallee, Richard B.
   Shi, Song-Hai
TI Asymmetric centrosome inheritance maintains neural progenitors in the neocortex
SO NATURE
LA English
DT Article
ID radial glial-cells; stem-cell; neuronal migration; spindle orientation; cortical-neurons; division; cycle; centrioles; mother; ninein
AB Asymmetric divisions of radial glia progenitors produce self-renewing radial glia and differentiating cells simultaneously in the ventricular zone (VZ) of the developing neocortex. Whereas differentiating cells leave the VZ to constitute the future neocortex, renewing radial glia progenitors stay in the VZ for subsequent divisions. The differential behaviour of progenitors and their differentiating progeny is essential for neocortical development; however, the mechanisms that ensure these behavioural differences are unclear. Here we show that asymmetric centrosome inheritance regulates the differential behaviour of renewing progenitors and their differentiating progeny in the embryonic mouse neocortex. Centrosome duplication in dividing radial glia progenitors generates a pair of centrosomes with differently aged mother centrioles. During peak phases of neurogenesis, the centrosome retaining the old mother centriole stays in the VZ and is preferentially inherited by radial glia progenitors, whereas the centrosome containing the new mother centriole mostly leaves the VZ and is largely associated with differentiating cells. Removal of ninein, a mature centriole-specific protein, disrupts the asymmetric segregation and inheritance of the centrosome and causes premature depletion of progenitors from the VZ. These results indicate that preferential inheritance of the centrosome with the mature older mother centriole is required for maintaining radial glia progenitors in the developing mammalian neocortex.
C1 [Wang, Xiaoqun; Imai, Janice H.; Shi, Song-Hai] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10021 USA.
   [Tsai, Jin-Wu; Lian, Wei-Nan; Vallee, Richard B.] Columbia Univ, Dept Pathol, New York, NY 10032 USA.
   [Tsai, Jin-Wu; Lian, Wei-Nan; Vallee, Richard B.] Columbia Univ, Dept Cell Biol, New York, NY 10032 USA.
   [Imai, Janice H.; Shi, Song-Hai] Weill Cornell Med Coll, BCMB Allied Program, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Columbia University; Columbia University; Cornell University; Weill Cornell Medicine
RP Shi, SH (corresponding author), Mem Sloan Kettering Canc Ctr, Dev Biol Program, 1275 York Ave, New York, NY 10021 USA.
EM shis@mskcc.org
FU March of Dimes Birth Defects Foundation; Whitehall Foundation; Dana Foundation; Autism Speaks Foundation; Klingenstein Foundation; NARSAD; NIH; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 50
TC 363
Z9 430
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 947
EP U206
DI 10.1038/nature08435
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700040
PM 19829375
DA 2026-03-09
ER

PT J
AU Sato, T
   Vries, RG
   Snippert, HJ
   van de Wetering, M
   Barker, N
   Stange, DE
   van Es, JH
   Abo, A
   Kujala, P
   Peters, PJ
   Clevers, H
AF Sato, Toshiro
   Vries, Robert G.
   Snippert, Hugo J.
   van de Wetering, Marc
   Barker, Nick
   Stange, Daniel E.
   van Es, Johan H.
   Abo, Arie
   Kujala, Pekka
   Peters, Peter J.
   Clevers, Hans
TI Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
SO NATURE
LA English
DT Article
ID small-intestine; epithelial-cells; expression; differentiation; proliferation; inhibition; cultures; growth; colon; mice
AB The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr(5+) stem cells at the bottoms of small-intestinal crypts(1). Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr(5+) stem cells can also initiate these crypt-villus organoids. Tracing experiments indicate that the Lgr(5+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal crypt-villus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.
C1 [Sato, Toshiro; Vries, Robert G.; Snippert, Hugo J.; van de Wetering, Marc; Barker, Nick; Stange, Daniel E.; van Es, Johan H.; Clevers, Hans] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
   [Sato, Toshiro; Vries, Robert G.; Snippert, Hugo J.; van de Wetering, Marc; Barker, Nick; Stange, Daniel E.; van Es, Johan H.; Clevers, Hans] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Abo, Arie] Nuvelo Inc, San Carlos, CA 94070 USA.
   [Kujala, Pekka; Peters, Peter J.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
C3 Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Netherlands Cancer Institute
RP Clevers, H (corresponding author), Hubrecht Inst, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
EM h.clevers@niob.knaw.nl
NR 30
TC 5633
Z9 6724
U1 56
U2 1054
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 262
EP U147
DI 10.1038/nature07935
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100043
PM 19329995
DA 2026-03-09
ER

PT J
AU Noginov, MA
   Zhu, G
   Belgrave, AM
   Bakker, R
   Shalaev, VM
   Narimanov, EE
   Stout, S
   Herz, E
   Suteewong, T
   Wiesner, U
AF Noginov, M. A.
   Zhu, G.
   Belgrave, A. M.
   Bakker, R.
   Shalaev, V. M.
   Narimanov, E. E.
   Stout, S.
   Herz, E.
   Suteewong, T.
   Wiesner, U.
TI Demonstration of a spaser-based nanolaser
SO NATURE
LA English
DT Article
ID surface-plasmons; gain; lasers
AB One of the most rapidly growing areas of physics and nanotechnology focuses on plasmonic effects on the nanometre scale, with possible applications ranging from sensing and biomedicine to imaging and information technology(1,2). However, the full development of nanoplasmonics is hindered by the lack of devices that can generate coherent plasmonic fields. It has been proposed(3) that in the same way as a laser generates stimulated emission of coherent photons, a 'spaser' could generate stimulated emission of surface plasmons (oscillations of free electrons in metallic nanostructures) in resonating metallic nanostructures adjacent to a gain medium. But attempts to realize a spaser face the challenge of absorption loss in metal, which is particularly strong at optical frequencies. The suggestion(4-6) to compensate loss by optical gain in localized and propagating surface plasmons has been implemented recently(7-10) and even allowed the amplification of propagating surface plasmons in open paths(11). Still, these experiments and the reported enhancement of the stimulated emission of dye molecules in the presence of metallic nanoparticles(12-14) lack the feedback mechanism present in a spaser. Here we show that 44-nm-diameter nanoparticles with a gold core and dye-doped silica shell allow us to completely overcome the loss of localized surface plasmons by gain and realize a spaser. And in accord with the notion that only surface plasmon resonances are capable of squeezing optical frequency oscillations into a nanoscopic cavity to enable a true nanolaser(15-18), we show that outcoupling of surface plasmon oscillations to photonic modes at a wavelength of 531 nm makes our system the smallest nanolaser reported to date-and to our knowledge the first operating at visible wavelengths. We anticipate that now it has been realized experimentally, the spaser will advance our fundamental understanding of nanoplasmonics and the development of practical applications.
C1 [Noginov, M. A.; Zhu, G.; Belgrave, A. M.; Stout, S.] Norfolk State Univ, Ctr Mat Res, Norfolk, VA 23504 USA.
   [Bakker, R.; Shalaev, V. M.; Narimanov, E. E.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
   [Bakker, R.; Shalaev, V. M.; Narimanov, E. E.] Purdue Univ, Birck Nanotechnol Ctr, W Lafayette, IN 47907 USA.
   [Stout, S.; Herz, E.; Suteewong, T.; Wiesner, U.] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14850 USA.
C3 Norfolk State University; Purdue University System; Purdue University; Purdue University System; Purdue University; Cornell University
RP Noginov, MA (corresponding author), Norfolk State Univ, Ctr Mat Res, Norfolk, VA 23504 USA.
EM mnoginov@nsu.edu
FU NSF PREM [0611430]; NSF NCN [EEC-0228390]; NASA URC [NCC3-1035]; ARO-MURI [50342-PH-MUR]; United States Army award [W911NF-06-C-0124]; Division Of Materials Research; Direct For Mathematical & Physical Scien [0611430] Funding Source: National Science Foundation
NR 30
TC 1878
Z9 2103
U1 4
U2 1022
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1110
EP 1112
DI 10.1038/nature08318
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000034
PM 19684572
DA 2026-03-09
ER

PT J
AU Persson, A
   Gross, E
   Laurent, P
   Busch, KE
   Bretes, H
   de Bono, M
AF Persson, Annelie
   Gross, Einav
   Laurent, Patrick
   Busch, Karl Emanuel
   Bretes, Hugo
   de Bono, Mario
TI Natural variation in a neural globin tunes oxygen sensing in wild Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID nucleotide dissociation inhibitor; c-elegans; human neuroglobin; body-fluid; expression; behavior; neurons; family; aggregation; environment
AB Behaviours evolve by iterations of natural selection, but we have few insights into the molecular and neural mechanisms involved. Here we show that some Caenorhabditis elegans wild strains switch between two foraging behaviours in response to subtle changes in ambient oxygen. This finely tuned switch is conferred by a naturally variable hexacoordinated globin, GLB-5. GLB-5 acts with the atypical soluble guanylate cyclases(1-3), which are a different type of oxygen binding protein, to tune the dynamic range of oxygen-sensing neurons close to atmospheric (21%) concentrations. Calcium imaging indicates that one group of these neurons is activated when oxygen rises towards 21%, and is inhibited as oxygen drops below 21%. The soluble guanylate cyclase GCY-35 is required for high oxygen to activate the neurons; GLB-5 provides inhibitory input when oxygen decreases below 21%. Together, these oxygen binding proteins tune neuronal and behavioural responses to a narrow oxygen concentration range close to atmospheric levels. The effect of the glb-5 gene on oxygen sensing and foraging is modified by the naturally variable neuropeptide receptor npr-1 (refs 4, 5), providing insights into how polygenic variation reshapes neural circuit function.
C1 [Persson, Annelie; Gross, Einav; Laurent, Patrick; Busch, Karl Emanuel; Bretes, Hugo; de Bono, Mario] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
   [Persson, Annelie] Univ Gothenburg, Dept Cell & Mol Biol, S-40530 Gothenburg, Sweden.
C3 MRC Laboratory Molecular Biology; University of Gothenburg
RP de Bono, M (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM debono@mrc-lmb.cam.ac.uk
FU Medical Research Council; EU Marie Curie Actions; European Molecular Biology Organization; Fondation Wiener-Anspach; Medical Research Council [MC_U105178786] Funding Source: researchfish; MRC [MC_U105178786] Funding Source: UKRI
NR 33
TC 112
Z9 133
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 APR 23
PY 2009
VL 458
IS 7241
BP 1030
EP U106
DI 10.1038/nature07820
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900043
PM 19262507
DA 2026-03-09
ER

PT J
AU Wyart, C
   Del Bene, F
   Warp, E
   Scott, EK
   Trauner, D
   Baier, H
   Isacoff, EY
AF Wyart, Claire
   Del Bene, Filippo
   Warp, Erica
   Scott, Ethan K.
   Trauner, Dirk
   Baier, Herwig
   Isacoff, Ehud Y.
TI Optogenetic dissection of a behavioural module in the vertebrate spinal cord
SO NATURE
LA English
DT Article
ID fluid-contacting neurons; ionotropic glutamate-receptor; larval zebrafish; in-vivo; genetic dissection; locomotor network; neural circuits; cells; light; interneurons
AB Locomotion relies on neural networks called central pattern generators (CPGs) that generate periodic motor commands for rhythmic movements(1). In vertebrates, the excitatory synaptic drive for inducing the spinal CPG can originate from either supraspinal glutamatergic inputs or from within the spinal cord(2,3). Here we identify a spinal input to the CPG that drives spontaneous locomotion using a combination of intersectional gene expression and optogenetics(4) in zebrafish larvae. The photo-stimulation of one specific cell type was sufficient to induce a symmetrical tail beating sequence that mimics spontaneous slow forward swimming. This neuron is the Kolmer-Agduhr cell(5), which extends cilia into the central cerebrospinal-fluid-containing canal of the spinal cord and has an ipsilateral ascending axon that terminates in a series of consecutive segments(6). Genetically silencing Kolmer-Agduhr cells reduced the frequency of spontaneous free swimming, indicating that activity of Kolmer-Agduhr cells provides necessary tone for spontaneous forward swimming. Kolmer-Agduhr cells have been known for over 75 years, but their function has been mysterious. Our results reveal that during early development in zebrafish these cells provide a positive drive to the spinal CPG for spontaneous locomotion.
C1 [Wyart, Claire; Warp, Erica; Isacoff, Ehud Y.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
   [Wyart, Claire; Warp, Erica; Isacoff, Ehud Y.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Del Bene, Filippo; Scott, Ethan K.; Baier, Herwig] Univ Calif San Francisco, Dept Physiol, Program Neurosci, San Francisco, CA 94158 USA.
   [Trauner, Dirk] Univ Munich, Dept Chem, Munich, Germany.
   [Isacoff, Ehud Y.] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
   [Isacoff, Ehud Y.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California San Francisco; University of Munich; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Isacoff, EY (corresponding author), Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
EM herwig.baier@ucsf.edu; ehud@berkeley.edu
FU Marie Curie Outgoing International Fellowship [CNRS-UMR5020]; Human Frontier Science Program Long-term Postdoctoral Fellowship; National Institutes of Health Nanomedicine Development Center [5PN2EY018241]; Human Frontiers Science Program [RGP23-2005]; Lawrence Berkeley National Laboratory Directed Research and Development Program [R01 NS053358]; Sandler Opportunity Award
NR 31
TC 321
Z9 380
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 SEP 17
PY 2009
VL 461
IS 7262
BP 407
EP U105
DI 10.1038/nature08323
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100042
PM 19759620
DA 2026-03-09
ER

PT J
AU Fusseis, F
   Regenauer-Lieb, K
   Liu, J
   Hough, RM
   De Carlo, F
AF Fusseis, F.
   Regenauer-Lieb, K.
   Liu, J.
   Hough, R. M.
   De Carlo, F.
TI Creep cavitation can establish a dynamic granular fluid pump in ductile shear zones
SO NATURE
LA English
DT Article
ID deformation; mylonites; rocks; lithosphere; propagation; transition; nucleation; transport; growth; phase
AB The feedback between fluid migration and rock deformation in mid-crustal shear zones is acknowledged as being critical for earthquake nucleation, the initiation of subduction zones and the formation of mineral deposits(1-3). The importance of this poorly understood feedback is further highlighted by evidence for shear-zone-controlled advective flow of fluids in the ductile lower crust(4) and the recognition that deformation-induced grain-scale porosity is a key to large-scale geodynamics(5,6). Fluid migration in the middle crust cannot be explained in terms of classical concepts. The environment is considered too hot for a dynamic fracture-sustained permeability as in the upper crust(7), and fluid pathways are generally too deformed to be controlled by equilibrium wetting angles that apply to hotter, deeper environments(8-10). Here we present evidence that mechanical and chemical potentials control a syndeformational porosity generation in mid-crustal shear zones. High-resolution synchrotron X-ray tomography and scanning electron microscopy observations allow us to formulate a model for fluid migration in shear zones where a permeable porosity is dynamically created by viscous grain-boundary sliding, creep cavitation, dissolution and precipitation. We propose that syndeformational fluid migration in our 'granular fluid pump' model is a self-sustained process controlled by the explicit role of the rate of entropy production of the underlying irreversible mechanical and chemical microprocesses. The model explains fluid transfer through the middle crust, where strain localization in the creep regime is required for plate tectonics, the formation of giant ore deposits, mantle degassing and earthquake nucleation. Our findings provide a key component for the understanding of creep instabilities in the middle crust.
C1 [Fusseis, F.; Regenauer-Lieb, K.] Univ Western Australia, Sch Earth & Environm, Crawley, WA 6009, Australia.
   [Regenauer-Lieb, K.; Liu, J.; Hough, R. M.] CSIRO Explorat & Min, Kensington, WA 6151, Australia.
   [De Carlo, F.] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
C3 University of Western Australia; Commonwealth Scientific & Industrial Research Organisation (CSIRO); United States Department of Energy (DOE); Argonne National Laboratory
RP Fusseis, F (corresponding author), Univ Western Australia, Sch Earth & Environm, 35 Stirling Highway, Crawley, WA 6009, Australia.
EM fusseis@cyllene.uwa.edu.au
FU Commonwealth of Australia; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Western Australian Premier's Research Fellowship; University of Western Australia
NR 30
TC 231
Z9 249
U1 5
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 18
PY 2009
VL 459
IS 7249
BP 974
EP 977
DI 10.1038/nature08051
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500040
PM 19536262
DA 2026-03-09
ER

PT J
AU Ploss, A
   Evans, MJ
   Gaysinskaya, VA
   Panis, M
   You, HN
   de Jong, YP
   Rice, CM
AF Ploss, Alexander
   Evans, Matthew J.
   Gaysinskaya, Valeriya A.
   Panis, Maryline
   You, Hana
   de Jong, Ype P.
   Rice, Charles M.
TI Human occludin is a hepatitis C virus entry factor required for infection of mouse cells
SO NATURE
LA English
DT Article
ID epithelial tight junctions; coxsackievirus entry; replication; cd81; glycoproteins; proteins; culture
AB Hepatitis C virus ( HCV) is a leading cause of liver disease worldwide. The development of much needed specific antiviral therapies and an effective vaccine has been hampered by the lack of a convenient small animal model. The determinants restricting HCV tropism to human and chimpanzee hosts are unknown. Replication of the viral RNA has been demonstrated in mouse cells(1,2), but these cells are not infectable with either lentiviral particles bearing HCV glycoproteins (HCVpp)(3) or HCV produced in cell culture ( HCVcc) ( A. P., M. E. and C. M. R., unpublished observations), suggesting that there is a block at the level of entry. Here we show, using an iterative complementary DNA library screening approach, that human occludin ( OCLN) is an essential HCV cell entry factor that is able to render murine cells infectable with HCVpp. Similarly, OCLN is required for the HCV- susceptibility of human cells, because its overexpression in uninfectable cells specifically enhanced HCVpp uptake, whereas its silencing in permissive cells impaired both HCVpp and HCVcc infection. In addition to OCLN, HCVpp infection of murine cells required expression of the previously identified HCV entry factors CD81 ( ref. 4), scavenger receptor class B type I ( SR- BI, also known as SCARB1) 5 and claudin- 1 (CLDN1)(6). Although the mouse versions of SR- BI and CLDN1 function at least as well as the human proteins in promoting HCV entry, both OCLN and CD81 must be of human origin to allow efficient infection. The species- specific determinants of OCLN were mapped to its second extracellular loop. The identification of OCLN as a new HCV entry factor further highlights the importance of the tight junction complex in the viral entry process, and provides an important advance towards efforts to develop small animal models for HCV.
C1 [Ploss, Alexander; Evans, Matthew J.; Gaysinskaya, Valeriya A.; Panis, Maryline; You, Hana; de Jong, Ype P.; Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10065 USA.
   [de Jong, Ype P.] Mt Sinai Sch Med, Div Gastroenterol, New York, NY 10029 USA.
C3 Rockefeller University; Icahn School of Medicine at Mount Sinai
RP Rice, CM (corresponding author), Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10065 USA.
EM ricec@rockefeller.edu
FU Greenberg Medical Research Institute; Ellison Medical Foundation; Starr Foundation; Ronald A. Shellow Memorial Fund; Richard Salomon Family Foundation; Foundation for the National Institutes of Health; Grand Challenges in Global Health initiative; National Institutes of Health; Ellison Medical Foundation Senior Scholar in Global Infectious Diseases; Kimberly Lawrence-Netter Cancer Research Discovery Fund Award Postdoctoral Fellowships; Charles H. Revson Postdoctoral Fellowship
NR 19
TC 741
Z9 899
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 FEB 12
PY 2009
VL 457
IS 7231
BP 882
EP 886
DI 10.1038/nature07684
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700045
PM 19182773
DA 2026-03-09
ER

PT J
AU Guttman, M
   Amit, I
   Garber, M
   French, C
   Lin, MF
   Feldser, D
   Huarte, M
   Zuk, O
   Carey, BW
   Cassady, JP
   Cabili, MN
   Jaenisch, R
   Mikkelsen, TS
   Jacks, T
   Hacohen, N
   Bernstein, BE
   Kellis, M
   Regev, A
   Rinn, JL
   Lander, ES
AF Guttman, Mitchell
   Amit, Ido
   Garber, Manuel
   French, Courtney
   Lin, Michael F.
   Feldser, David
   Huarte, Maite
   Zuk, Or
   Carey, Bryce W.
   Cassady, John P.
   Cabili, Moran N.
   Jaenisch, Rudolf
   Mikkelsen, Tarjei S.
   Jacks, Tyler
   Hacohen, Nir
   Bernstein, Bradley E.
   Kellis, Manolis
   Regev, Aviv
   Rinn, John L.
   Lander, Eric S.
TI Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
SO NATURE
LA English
DT Article
ID x-inactivation center; transcriptional activity; gene-expression; mouse oocytes; stem-cells; genome; chromosome; interference; sequences; noise
AB There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts(1-4). However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise(5,6). Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified similar to 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NF kappa B, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.
C1 [Guttman, Mitchell; Amit, Ido; Garber, Manuel; French, Courtney; Lin, Michael F.; Huarte, Maite; Zuk, Or; Mikkelsen, Tarjei S.; Hacohen, Nir; Bernstein, Bradley E.; Kellis, Manolis; Regev, Aviv; Rinn, John L.; Lander, Eric S.] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA.
   [Guttman, Mitchell; Carey, Bryce W.; Cassady, John P.; Jaenisch, Rudolf; Jacks, Tyler; Regev, Aviv; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Feldser, David; Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Mikkelsen, Tarjei S.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Huarte, Maite; Rinn, John L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
   [Cabili, Moran N.; Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA.
   [Carey, Bryce W.; Cassady, John P.; Jaenisch, Rudolf; Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
   [Bernstein, Bradley E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.
   [Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
   [Bernstein, Bradley E.; Rinn, John L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
RP Rinn, JL (corresponding author), MIT & Harvard, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA.
EM jrinn@broad.mit.edu
FU Human Frontier Science Program Organization; Beth Israel Deaconess Medical Center; National Human Genome Research Institute; Broad Institute of MIT and Harvard
NR 30
TC 3396
Z9 4086
U1 2
U2 432
PU NATURE PUBLISHING 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 12
PY 2009
VL 458
IS 7235
BP 223
EP 227
DI 10.1038/nature07672
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700048
PM 19182780
DA 2026-03-09
ER

PT J
AU Flames, N
   Hobert, O
AF Flames, Nuria
   Hobert, Oliver
TI Gene regulatory logic of dopamine neuron differentiation
SO NATURE
LA English
DT Article
ID olfactory-bulb interneurons; c-elegans; transcriptional codes; expression; brain; architecture; insights; identity; er81; axon
AB Dopamine signalling regulates a variety of complex behaviours, and defects in dopamine neuron function or survival result in severe human pathologies, such as Parkinson's disease(1). The common denominator of all dopamine neurons is the expression of dopamine pathway genes, which code for a set of phylogenetically conserved proteins involved in dopamine synthesis and transport. Gene regulatory mechanisms that result in the direct activation of dopamine pathway genes and thereby ultimately determine the identity of dopamine neurons are poorly understood in all systems studied so far(2). Here we show that a simple cis-regulatory element, the dopamine (DA) motif, controls the expression of all dopamine pathway genes in all dopaminergic cell types in Caenorhabditis elegans. The DA motif is activated by the ETS transcription factor AST-1. Loss of ast-1 results in the failure of all distinct dopaminergic neuronal subtypes to terminally differentiate. Ectopic expression of ast-1 is sufficient to activate the dopamine pathway in some cellular contexts. Vertebrate dopamine pathway genes also contain phylogenetically conserved DA motifs that can be activated by the mouse ETS transcription factor Etv1 (also known as ER81), and a specific class of dopamine neurons fails to differentiate in mice lacking Etv1. Moreover, ectopic Etv1 expression induces dopaminergic fate marker expression in neuronal primary cultures. Mouse Etv1 can also functionally substitute for ast-1 in C. elegans. Our studies reveal a simple and apparently conserved regulatory logic of dopamine neuron terminal differentiation and may provide new entry points into the diagnosis or therapy of conditions in which dopamine neurons are defective.
C1 [Flames, Nuria; Hobert, Oliver] Columbia Univ, Dept Biochem & Mol Biophys, Med Ctr, Howard Hughes Med Inst, New York, NY 10032 USA.
C3 Howard Hughes Medical Institute; Columbia University
RP Flames, N (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, Med Ctr, Howard Hughes Med Inst, 630 W 168th St, New York, NY 10032 USA.
EM nf2171@columbia.edu; or38@columbia.edu
FU National Institutes of Health [R01NS039996-05, R01NS050266-03]; Howard Hughes Medical Institute; EMBO; Marie Curie Outgoing International fellowship; National Institute of Neurological Disorders and Stroke [R01NS039996] Funding Source: NIH RePORTER
NR 25
TC 191
Z9 256
U1 1
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 16
PY 2009
VL 458
IS 7240
BP 885
EP U7
DI 10.1038/nature07929
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500042
PM 19287374
DA 2026-03-09
ER

PT J
AU Walter, F
   Riechers, D
   Cox, P
   Neri, R
   Carilli, C
   Bertoldi, F
   Weiss, A
   Maiolino, R
AF Walter, Fabian
   Riechers, Dominik
   Cox, Pierre
   Neri, Roberto
   Carilli, Chris
   Bertoldi, Frank
   Weiss, Axel
   Maiolino, Roberto
TI A kiloparsec-scale hyper-starburst in a quasar host less than 1 gigayear after the Big Bang
SO NATURE
LA English
DT Article
ID molecular gas; dust emission; nucleus
AB The host galaxy of the quasar SDSS J114816.641525150.3 ( at redshift z = 6.42, when the Universe was less than a billion years old) has an infrared luminosity of 2.2 x 10(13) times that of the Sun(1,2), presumably significantly powered by a massive burst of star formation(3-6). In local examples of extremely luminous galaxies, such as Arp 220, the burst of star formation is concentrated in a relatively small central region of <100 pc radius(7,8). It is not known on which scales stars are forming in active galaxies in the early Universe, at a time when they are probably undergoing their initial burst of star formation. We do know that at some early time, structures comparable to the spheroidal bulge of the Milky Way must have formed. Here we report a spatially resolved image of [CII] emission of the host galaxy of J114816.641525150.3 that demonstrates that its star- forming gas is distributed over a radius of about 750 pc around the centre. The surface density of the star formation rate averaged over this region is similar to 1,000 M. year(-1) kpc-(2). This surface density is comparable to the peak in Arp 220, although about two orders of magnitude larger in area. This vigorous star- forming event is likely to give rise to a massive spheroidal component in this system.
C1 [Walter, Fabian; Riechers, Dominik] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Riechers, Dominik] CALTECH, Pasadena, CA 91125 USA.
   [Cox, Pierre; Neri, Roberto] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Carilli, Chris] Natl Radio Astron Observ, Socorro, NM 87801 USA.
   [Bertoldi, Frank] Argelander Inst Astron, D-53121 Bonn, Germany.
   [Weiss, Axel] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Maiolino, Roberto] Osserv Astron Roma, Ist Nazl Astrofis, I-00040 Monte Porzio Catone, Italy.
C3 Max Planck Society; California Institute of Technology; National Radio Astronomy Observatory (NRAO); University of Bonn; Max Planck Society; Istituto Nazionale Astrofisica (INAF)
RP Walter, F (corresponding author), Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
EM walter@mpia.de
FU MPG (Germany); INSU/CNRS ( France); IGN (Spain); NASA; Hubble Fellowship; Space Telescope Science Institute; Max-Planck Gesellschaft; Alexander von Humboldt Stiftung; Max-Planck-Forschungspreis
NR 29
TC 210
Z9 219
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 699
EP 701
DI 10.1038/nature07681
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700035
PM 19194445
DA 2026-03-09
ER

PT J
AU Lainey, V
   Arlot, JE
   Karatekin, Ö
   Van Hoolst, T
AF Lainey, Valery
   Arlot, Jean-Eudes
   Karatekin, Oezguer
   Van Hoolst, Tim
TI Strong tidal dissipation in Io and Jupiter from astrometric observations
SO NATURE
LA English
DT Article
ID heat-flow; secular acceleration; viscoelastic models; thermal emission; satellites; evolution
AB Io is the volcanically most active body in the Solar System and has a large surface heat flux(1-3). The geological activity is thought to be the result of tides raised by Jupiter(4), but it is not known whether the current tidal heat production is sufficiently high to generate the observed surface heat flow(5,6). Io's tidal heat comes from the orbital energy of the Io-Jupiter system (resulting in orbital acceleration), whereas dissipation of energy in Jupiter causes Io's orbital motion to decelerate. Here we report a determination of the tidal dissipation in Io and Jupiter through its effect on the orbital motions of the Galilean moons. Our results show that the rate of internal energy dissipation in Io (k(2)/Q = 0.015 +/- 0.003, where k(2) is the Love number and Q is the quality factor) is in good agreement with the observed surface heat flow5,6, and suggest that Io is close to thermal equilibrium. Dissipation in Jupiter (k(2)/Q = (1.102 +/- 0.203) x 10(-5)) is close to the upper bound of its average value expected from the long-term evolution of the system(7), and dissipation in extrasolar planets may be higher than presently assumed(8). The measured secular accelerations indicate that Io is evolving inwards, towards Jupiter, and that the three innermost Galilean moons (Io, Europa and Ganymede) are evolving out of the exact Laplace resonance.
C1 [Lainey, Valery; Arlot, Jean-Eudes] IMCCE Observ Paris, CNRS, UMR 8028, F-75014 Paris, France.
   [Karatekin, Oezguer; Van Hoolst, Tim] Observ Royal Belgique, B-1180 Brussels, Belgium.
C3 Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite PSL; Observatoire de Paris
RP Lainey, V (corresponding author), IMCCE Observ Paris, CNRS, UMR 8028, 77 Ave Denfert Rochereau, F-75014 Paris, France.
EM lainey@imcce.fr
NR 33
TC 319
Z9 343
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 JUN 18
PY 2009
VL 459
IS 7249
BP 957
EP 959
DI 10.1038/nature08108
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500036
PM 19536258
DA 2026-03-09
ER

PT J
AU Yan, H
   Chen, ZH
   Zheng, Y
   Newman, C
   Quinn, JR
   Dötz, F
   Kastler, M
   Facchetti, A
AF Yan, He
   Chen, Zhihua
   Zheng, Yan
   Newman, Christopher
   Quinn, Jordan R.
   Dotz, Florian
   Kastler, Marcel
   Facchetti, Antonio
TI A high-mobility electron-transporting polymer for printed transistors
SO NATURE
LA English
DT Article
ID field-effect transistors; thin-film transistors; organic transistors; charge-transport; gate dielectrics; design; semiconductors; transition; displays; voltage
AB Printed electronics is a revolutionary technology aimed at unconventional electronic device manufacture on plastic foils, and will probably rely on polymeric semiconductors for organic thin- film transistor (OTFT) fabrication. In addition to having excellent charge- transport characteristics in ambient conditions, such materials must meet other key requirements, such as chemical stability, large solubility in common solvents, and inexpensive solution and/or low- temperature processing. Furthermore, compatibility of both p- channel (hole- transporting) and n- channel (electron- transporting) semiconductors with a single combination of gate dielectric and contact materials is highly desirable to enable powerful complementary circuit technologies, where p- and n- channel OTFTs operate in concert. Polymeric complementary circuits operating in ambient conditions are currently difficult to realize: although excellent p- channel polymers are widely available, the achievement of high- performance n- channel polymers is more challenging. Here we report a highly soluble (similar to 60 g l(-1)) and printable n- channel polymer exhibiting unprecedented OTFT characteristics ( electron mobilities up to similar to 0.45 - 0.85 cm(2) V-1 s(-1)) under ambient conditions in combination with Au contacts and various polymeric dielectrics. Several top- gate OTFTs on plastic substrates were fabricated with the semiconductor- dielectric layers deposited by spin- coating as well as by gravure, flexographic and inkjet printing, demonstrating great processing versatility. Finally, all- printed polymeric complementary inverters ( with gain 25-65) have been demonstrated.
C1 [Yan, He; Chen, Zhihua; Zheng, Yan; Newman, Christopher; Quinn, Jordan R.; Facchetti, Antonio] Polyera Corp, Skokie, IL 60077 USA.
   [Dotz, Florian] BASF Global Res Ctr Singapore, Singapore 112575, Singapore.
   [Kastler, Marcel] BASF SE, GKS E B001, D-67056 Ludwigshafen, Germany.
C3 Polyera; BASF; BASF
RP Facchetti, A (corresponding author), Polyera Corp, 8045 Lamon Ave, Skokie, IL 60077 USA.
EM afacchetti@polyera.com
NR 51
TC 2779
Z9 3100
U1 24
U2 1831
PU NATURE PUBLISHING 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 5
PY 2009
VL 457
IS 7230
BP 679
EP U1
DI 10.1038/nature07727
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700032
PM 19158674
DA 2026-03-09
ER

PT J
AU Eichenfield, M
   Chan, J
   Camacho, RM
   Vahala, KJ
   Painter, O
AF Eichenfield, Matt
   Chan, Jasper
   Camacho, Ryan M.
   Vahala, Kerry J.
   Painter, Oskar
TI Optomechanical crystals
SO NATURE
LA English
DT Article
ID wave-guides; band-gap; cavity; light
AB Periodicity in materials yields interesting and useful phenomena. Applied to the propagation of light, periodicity gives rise to photonic crystals(1), which can be precisely engineered for such applications as guiding and dispersing optical beams(2,3), tightly confining and trapping light resonantly(4), and enhancing nonlinear optical interactions(5). Photonic crystals can also be formed into planar lightwave circuits for the integration of optical and electrical microsystems(6). In a photonic crystal, the periodicity of the host medium is used to manipulate the properties of light, whereas a phononic crystal uses periodicity to manipulate mechanical vibrations(7-13). As has been demonstrated in studies of Raman-like scattering in epitaxially grown vertical cavity structures(14) and photonic crystal fibres(15), the simultaneous confinement of mechanical and optical modes in periodic structures can lead to greatly enhanced light-matter interactions. A logical next step is thus to create planar circuits that act as both photonic and phononic crystals(16): optomechanical crystals. Here we describe the design, fabrication and characterization of a planar, silicon-chip-based optomechanical crystal capable of co-localizing and strongly coupling 200-terahertz photons and 2-gigahertz phonons. These planar optomechanical crystals bring the powerful techniques of optics and photonic crystals to bear on phononic crystals, providing exquisitely sensitive (near quantum-limited), optical measurements of mechanical vibrations, while simultaneously providing strong nonlinear interactions for optics in a large and technologically relevant range of frequencies.
C1 [Eichenfield, Matt; Chan, Jasper; Camacho, Ryan M.; Vahala, Kerry J.; Painter, Oskar] CALTECH, Thomas J Watson Sr Lab Appl Phys, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Painter, O (corresponding author), CALTECH, Thomas J Watson Sr Lab Appl Phys, Pasadena, CA 91125 USA.
EM opainter@caltech.edu
FU DARPA [HR0011-08-0002]; National Science Foundation [0622246, DMR-0520565, EEC-0812072]; Division of Computing and Communication Foundations; Direct For Computer & Info Scie & Enginr [0622246] Funding Source: National Science Foundation
NR 30
TC 944
Z9 1100
U1 3
U2 467
PU NATURE PUBLISHING 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 5
PY 2009
VL 462
IS 7269
BP 78
EP 82
DI 10.1038/nature08524
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200035
PM 19838165
DA 2026-03-09
ER

PT J
AU Gal-Yam, A
   Mazzali, P
   Ofek, EO
   Nugent, PE
   Kulkarni, SR
   Kasliwal, MM
   Quimby, RM
   Filippenko, AV
   Cenko, SB
   Chornock, R
   Waldman, R
   Kasen, D
   Sullivan, M
   Beshore, EC
   Drake, AJ
   Thomas, RC
   Bloom, JS
   Poznanski, D
   Miller, AA
   Foley, RJ
   Silverman, JM
   Arcavi, I
   Ellis, RS
   Deng, J
AF Gal-Yam, A.
   Mazzali, P.
   Ofek, E. O.
   Nugent, P. E.
   Kulkarni, S. R.
   Kasliwal, M. M.
   Quimby, R. M.
   Filippenko, A. V.
   Cenko, S. B.
   Chornock, R.
   Waldman, R.
   Kasen, D.
   Sullivan, M.
   Beshore, E. C.
   Drake, A. J.
   Thomas, R. C.
   Bloom, J. S.
   Poznanski, D.
   Miller, A. A.
   Foley, R. J.
   Silverman, J. M.
   Arcavi, I.
   Ellis, R. S.
   Deng, J.
TI Supernova 2007bi as a pair-instability explosion
SO NATURE
LA English
DT Article
ID core-collapse supernovae; spectra; stars
AB Stars with initialmasses such that 10M(circle dot) <= M(initial) <= 100M(circle dot), where M(circle dot) is the solar mass, fuse progressively heavier elements in their centres, until the core is inert iron. The core then gravitationally collapses to a neutron star or a black hole, leading to an explosion-an iron-core-collapse supernova(1,2). By contrast, extremely massive stars with M(initial) >= 140M(circle dot) (if such exist) develop oxygen cores with masses, M(core), that exceed 50M(circle dot), where high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs before oxygen ignition and leads to a violent contraction which triggers a nuclear explosion(3-5) that unbinds the star in a pair-instability supernova. Transitional objects with 100M(circle dot) < M(initial) < 140M(circle dot) may end up as iron-core-collapse supernovae following violent mass ejections, perhaps as a result of brief episodes of pair instability, and may already have been identified(6-8). Here we report observations of supernova SN 2007bi, a luminous, slowly evolving object located within a dwarf galaxy. We estimate the exploding core mass to be M(core) approximate to 100M(circle dot), in which case theory unambiguously predicts a pair-instability supernova. We show that >3M(circle dot) of radioactive (56)Ni was synthesized during the explosion and that our observations are well fitted by models of pair-instability supernovae(9,10). This indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic stellar mass limit(11), which perhaps result from processes similar to those that created the first stars in the Universe.
C1 [Gal-Yam, A.; Arcavi, I.] Weizmann Inst Sci, Fac Phys, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
   [Mazzali, P.] Max Planck Inst Astrophys, D-85748 Garching, Germany.
   [Mazzali, P.] Scuola Normale Super Pisa, I-56127 Pisa, Italy.
   [Ofek, E. O.; Kulkarni, S. R.; Kasliwal, M. M.; Quimby, R. M.; Drake, A. J.; Ellis, R. S.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Nugent, P. E.; Thomas, R. C.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Filippenko, A. V.; Cenko, S. B.; Chornock, R.; Bloom, J. S.; Poznanski, D.; Miller, A. A.; Silverman, J. M.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Waldman, R.] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Kasen, D.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Sullivan, M.] Univ Oxford, Dept Astrophys, Oxford OX1 3RH, England.
   [Beshore, E. C.] Univ Arizona, Dept Planetary Sci, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Foley, R. J.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Deng, J.] Chinese Acad Sci, Natl Astron Observ, Beijing 100012, Peoples R China.
C3 Weizmann Institute of Science; Max Planck Society; Scuola Normale Superiore di Pisa; California Institute of Technology; 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; Hebrew University of Jerusalem; University of California System; University of California Santa Cruz; University of Oxford; University of Arizona; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; Chinese Academy of Sciences; National Astronomical Observatory, CAS
RP Gal-Yam, A (corresponding author), Weizmann Inst Sci, Fac Phys, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
EM avishay.gal-yam@weizmann.ac.il
FU US National Aeronautics and Space Administration ( NASA); Weizmann-Minerva grant; Israeli Science Foundation; European Union Seventh Framework Programme Marie Curie IRG fellowship; Benoziyo Center for Astrophysics; Peter and Patricia Gruber Awards; William Z. and Eda Bess Novick New Scientists Fund; US Department of Energy's Scientific Discovery; US National Science Foundation; US Department of Energy; TABASGO Foundation; Gary and Cynthia Bengier; Richard and Rhoda Goldman Fund; National Natural Science Foundation of China; Chinese 973 Program; W. M. Keck Foundation; NASA; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0909182] Funding Source: National Science Foundation
NR 30
TC 404
Z9 437
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 DEC 3
PY 2009
VL 462
IS 7273
BP 624
EP 627
DI 10.1038/nature08579
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900035
PM 19956255
DA 2026-03-09
ER

PT J
AU Meinshausen, M
   Meinshausen, N
   Hare, W
   Raper, SCB
   Frieler, K
   Knutti, R
   Frame, DJ
   Allen, MR
AF Meinshausen, Malte
   Meinshausen, Nicolai
   Hare, William
   Raper, Sarah C. B.
   Frieler, Katja
   Knutti, Reto
   Frame, David J.
   Allen, Myles R.
TI Greenhouse-gas emission targets for limiting global warming to 2 °C
SO NATURE
LA English
DT Article
ID climate sensitivity; temperature; uncertainty; projections; increase; cycle
AB More than 100 countries have adopted a global warming limit of 2 degrees C or below ( relative to pre-industrial levels) as a guiding principle for mitigation efforts to reduce climate change risks, impacts and damages(1,2). However, the greenhouse gas (GHG) emissions corresponding to a specified maximum warming are poorly known owing to uncertainties in the carbon cycle and the climate response. Here we provide a comprehensive probabilistic analysis aimed at quantifying GHG emission budgets for the 2000-50 period that would limit warming throughout the twenty-first century to below 2 degrees C, based on a combination of published distributions of climate system properties and observational constraints. We show that, for the chosen class of emission scenarios, both cumulative emissions up to 2050 and emission levels in 2050 are robust indicators of the probability that twenty-first century warming will not exceed 2 degrees C relative to pre-industrial temperatures. Limiting cumulative CO2 emissions over 2000-50 to 1,000 Gt CO2 yields a 25% probability of warming exceeding 2 degrees C-and a limit of 1,440 Gt CO2 yields a 50% probability - given a representative estimate of the distribution of climate system properties. As known 2000-06 CO2 emissions(3) were similar to 234 Gt CO2, less than half the proven economically recoverable oil, gas and coal reserves(4-6) can still be emitted up to 2050 to achieve such a goal. Recent G8 Communiques(7) envisage halved global GHG emissions by 2050, for which we estimate a 12-45% probability of exceeding 2 degrees C-assuming 1990 as emission base year and a range of published climate sensitivity distributions. Emissions levels in 2020 are a less robust indicator, but for the scenarios considered, the probability of exceeding 2 degrees C rises to 53-87% if global GHG emissions are still more than 25% above 2000 levels in 2020.
C1 [Meinshausen, Malte; Hare, William; Frieler, Katja] Telegraphenberg, Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany.
   [Meinshausen, Nicolai] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
   [Hare, William] Telegraphenberg, Climate Analyt, D-14412 Potsdam, Germany.
   [Raper, Sarah C. B.] Manchester Metropolitan Univ, Ctr Air Transport & Environm, Manchester M1 5GD, Lancs, England.
   [Knutti, Reto] ETH, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
   [Frame, David J.] Univ Oxford, Smith Sch Enterprise & Environm, Oxford OX1 2BQ, England.
   [Frame, David J.; Allen, Myles R.] Univ Oxford, Dept Phys, Oxford OX1 3PU, England.
C3 Potsdam Institut fur Klimafolgenforschung; University of Oxford; Manchester Metropolitan University; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Oxford; University of Oxford
RP Meinshausen, M (corresponding author), Telegraphenberg, Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany.
EM malte.meinshausen@pik-potsdam.de
FU DAAD; German Ministry of Environment; Natural Environment Research Council [NE/C515747/1] Funding Source: researchfish
NR 44
TC 2088
Z9 2431
U1 26
U2 3894
PU NATURE PUBLISHING 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 30
PY 2009
VL 458
IS 7242
BP 1158
EP U96
DI 10.1038/nature08017
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600045
PM 19407799
DA 2026-03-09
ER

PT J
AU Kee, K
   Angeles, VT
   Flores, M
   Nguyen, HN
   Pera, RAR
AF Kee, Kehkooi
   Angeles, Vanessa T.
   Flores, Martha
   Nguyen, Ha Nam
   Pera, Renee A. Reijo
TI Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation
SO NATURE
LA English
DT Article
ID embryonic stem-cells; in-vitro; protein gene; y-chromosome; derivation; mouse; lineage; spermatogenesis; differentiation; establishment
AB The leading cause of infertility in men and women is quantitative and qualitative defects in human germ-cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ-cell formation and differentiation owing to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages(1-8). Here we used a germ-cell reporter to quantify and isolate primordial germ cells derived from both male and female human embryonic stem cells. By silencing and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ-cell formation and developmental progression. We observed that human DAZL (deleted in azoospermia-like) functions in primordial germ cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.
C1 [Kee, Kehkooi; Angeles, Vanessa T.; Flores, Martha; Nguyen, Ha Nam; Pera, Renee A. Reijo] Stanford Univ, Sch Med,Dept Obstet & Gynecol, Inst Stem Cell Biol & Regenerat Med, Ctr Human Embryon Stem Cell Res & Educ, Palo Alto, CA 94305 USA.
C3 Stanford University
RP Pera, RAR (corresponding author), Stanford Univ, Sch Med,Dept Obstet & Gynecol, Inst Stem Cell Biol & Regenerat Med, Ctr Human Embryon Stem Cell Res & Educ, Palo Alto, CA 94305 USA.
EM reneer@stanford.edu
FU California TRDRP [14RT0159]; National Institutes of Health [RO1HD047721, U54HD055764]; California Institute for Regenerative Medicine [RC1-00137]
NR 33
TC 399
Z9 482
U1 0
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 12
PY 2009
VL 462
IS 7270
BP 222
EP U95
DI 10.1038/nature08562
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100043
PM 19865085
DA 2026-03-09
ER

PT J
AU Koehn, EM
   Fleischmann, T
   Conrad, JA
   Palfey, BA
   Lesley, SA
   Mathews, II
   Kohen, A
AF Koehn, Eric M.
   Fleischmann, Todd
   Conrad, John A.
   Palfey, Bruce A.
   Lesley, Scott A.
   Mathews, Irimpan I.
   Kohen, Amnon
TI An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene
SO NATURE
LA English
DT Article
ID catalytic mechanism; escherichia-coli; active-site; synthase-x; flavin; enzyme; dna
AB Biosynthesis of the DNA base thymine depends on activity of the enzyme thymidylate synthase to catalyse the methylation of the uracil moiety of 2'-deoxyuridine-5'-monophosphate. All known thymidylate synthases rely on an active site residue of the enzyme to activate 2'-deoxyuridine-5'-monophosphate(1,2). This functionality has been demonstrated for classical thymidylate synthases, including human thymidylate synthase, and is instrumental in mechanism-based inhibition of these enzymes. Here we report an example of thymidylate biosynthesis that occurs without an enzymatic nucleophile. This unusual biosynthetic pathway occurs in organisms containing the thyX gene, which codes for a flavin-dependent thymidylate synthase (FDTS), and is present in several human pathogens(3-5). Our findings indicate that the putative active site nucleophile is not required for FDTS catalysis, and no alternative nucleophilic residues capable of serving this function can be identified. Instead, our findings suggest that a hydride equivalent (that is, a proton and two electrons) is transferred from the reduced flavin cofactor directly to the uracil ring, followed by an isomerization of the intermediate to form the product, 2'-deoxythymidine-5'-monophosphate. These observations indicate a very different chemical cascade than that of classical thymidylate synthases or any other known biological methylation. The findings and chemical mechanism proposed here, together with available structural data, suggest that selective inhibition of FDTSs, with little effect on human thymine biosynthesis, should be feasible. Because several human pathogens depend on FDTS for DNA biosynthesis, its unique mechanism makes it an attractive target for antibiotic drugs.
C1 [Koehn, Eric M.; Fleischmann, Todd; Kohen, Amnon] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA.
   [Conrad, John A.; Palfey, Bruce A.] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA.
   [Lesley, Scott A.] Novartis Res Fdn, Genom Inst, Joint Ctr Struct Genom, San Diego, CA 92121 USA.
   [Mathews, Irimpan I.] Stanford Univ, Stanford Synchrotron Radiat Lab, Menlo Pk, CA 94025 USA.
C3 University of Iowa; University of Michigan System; University of Michigan; Novartis; Novartis USA; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory
RP Kohen, A (corresponding author), Univ Iowa, Dept Chem, Iowa City, IA 52242 USA.
EM amnon-kohen@uiowa.edu
FU NIH [R01 GM065368, R01 GM61087, GM08270]; NSF [CHE 0715448]; JCSG [U54GM074898]; DOE; OBER; NCRR; NIGMS
NR 24
TC 78
Z9 96
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 APR 16
PY 2009
VL 458
IS 7240
BP 919
EP U13
DI 10.1038/nature07973
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500049
PM 19370033
DA 2026-03-09
ER

PT J
AU Matsushita, K
   Takeuchi, O
   Standley, DM
   Kumagai, Y
   Kawagoe, T
   Miyake, T
   Satoh, T
   Kato, H
   Tsujimura, T
   Nakamura, H
   Akira, S
AF Matsushita, Kazufumi
   Takeuchi, Osamu
   Standley, Daron M.
   Kumagai, Yutaro
   Kawagoe, Tatsukata
   Miyake, Tohru
   Satoh, Takashi
   Kato, Hiroki
   Tsujimura, Tohru
   Nakamura, Haruki
   Akira, Shizuo
TI Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay
SO NATURE
LA English
DT Article
ID autoimmunity; recognition; activation; cleavage; innate
AB Toll-like receptors (TLRs) recognize microbial components, and evoke inflammation and immune responses(1-3). TLR stimulation activates complex gene expression networks that regulate the magnitude and duration of the immune reaction. Here we identify the TLR-inducible gene Zc3h12a as an immune response modifier that has an essential role in preventing immune disorders. Zc3h12a-deficient mice suffered from severe anaemia, and most died within 12 weeks. Zc3h12a(-/-) mice also showed augmented serum immunoglobulin levels and autoantibody production, together with a greatly increased number of plasma cells, as well as infiltration of plasma cells to the lung. Most Zc3h12a(-/-) splenic T cells showed effector/memory characteristics and produced interferon-gamma in response to T-cell receptor stimulation. Macrophages from Zc3h12a (-/-) mice showed highly increased production of interleukin (IL)-6 and IL-12p40 (also known as IL12b), but not TNF, in response to TLR ligands. Although the activation of TLR signalling pathways was normal, Il6 messenger RNA decay was severely impaired in Zc3h12a (-/-) macrophages. Overexpression of Zc3h12a accelerated Il6 mRNA degradation via its 3'-untranslated region (UTR), and destabilized RNAs with 3'-UTRs for genes including Il6, Il12p40 and the calcitonin receptor gene Calcr. Zc3h12a contains a putative amino-terminal nuclease domain, and the expressed protein had RNase activity, consistent with a role in the decay of Il6 mRNA. Together, these results indicate that Zc3h12a is an essential RNase that prevents immune disorders by directly controlling the stability of a set of inflammatory genes.
C1 [Matsushita, Kazufumi; Takeuchi, Osamu; Kumagai, Yutaro; Kawagoe, Tatsukata; Miyake, Tohru; Satoh, Takashi; Kato, Hiroki; Akira, Shizuo] Osaka Univ, Host Def Lab, Suita, Osaka 5650871, Japan.
   [Standley, Daron M.] Osaka Univ, Lab Syst Immunol, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan.
   [Matsushita, Kazufumi; Takeuchi, Osamu; Kumagai, Yutaro; Kawagoe, Tatsukata; Miyake, Tohru; Satoh, Takashi; Kato, Hiroki; Akira, Shizuo] Osaka Univ, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan.
   [Tsujimura, Tohru] Hyogo Coll Med, Dept Pathol, Nishinomiya, Hyogo 6638501, Japan.
   [Nakamura, Haruki] Osaka Univ, Inst Prot Res, Res Ctr Struct & Funct Prote, Suita, Osaka 5650871, Japan.
C3 University of Osaka; University of Osaka; University of Osaka; Hyogo Medical University; University of Osaka
RP Akira, S (corresponding author), Osaka Univ, Host Def Lab, 3-1 Yamada Oka, Suita, Osaka 5650871, Japan.
EM sakira@biken.osaka-u.ac.jp
FU Japanese Ministry of Education, Culture, Sports, Science and Technology; Ministry of Health, Labour and Welfare in Japan; Global Center of Excellence Program of Japan; NIH [P01 AI070167]; Grants-in-Aid for Scientific Research [20002008] Funding Source: KAKEN
NR 22
TC 577
Z9 645
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 30
PY 2009
VL 458
IS 7242
BP 1185
EP U124
DI 10.1038/nature07924
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600050
PM 19322177
DA 2026-03-09
ER

PT J
AU Gemelke, N
   Zhang, XB
   Hung, CL
   Chin, C
AF Gemelke, Nathan
   Zhang, Xibo
   Hung, Chen-Lung
   Chin, Cheng
TI In situ observation of incompressible Mott-insulating domains in ultracold atomic gases
SO NATURE
LA English
DT Article
ID superfluid; transition
AB The observation of the superfluid to Mott insulator phase transition of ultracold atoms in optical lattices(1) was an enabling discovery in experimental many-body physics, providing the first tangible example of a quantum phase transition (one that occurs even at zero temperature) in an ultracold atomic gas. For a trapped gas, the spatially varying local chemical potential gives rise to multiple quantum phases within a single sample, complicating the interpretation of bulk measurements(1-5). Here we report spatially resolved, in-situ imaging of a two-dimensional ultracold atomic gas as it crosses the superfluid to Mott insulator transition, providing direct access to individual characteristics of the insulating, superfluid and normal phases. We present results for the local compressibility in all phases, observing a strong suppression in the insulator domain and suppressed density fluctuations for the Mott insulator, in accordance with the fluctuation-dissipation theorem. Furthermore, we obtain a direct measure of the finite temperature of the system. Taken together, these methods enable a complete characterization of multiple phases in a strongly correlated Bose gas, and of the interplay between quantum and thermal fluctuations in the quantum critical regime.
C1 [Chin, Cheng] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA.
   Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Chin, C (corresponding author), Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM cchin@uchicago.edu
FU NSF [PHY-0747907, NSF-MRSEC, DMR-0213745]; ARO [W911NF0710576]; DARPA OLE programme; Grainger Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [0747907] Funding Source: National Science Foundation
NR 21
TC 318
Z9 371
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 995
EP U75
DI 10.1038/nature08244
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500030
PM 19693080
DA 2026-03-09
ER

PT J
AU Upadhyay, D
   Scherer, EE
   Mezger, K
AF Upadhyay, Dewashish
   Scherer, Erik E.
   Mezger, Klaus
TI 142Nd evidence for an enriched Hadean reservoir in cratonic roots
SO NATURE
LA English
DT Article
ID early differentiation; magma ocean; mantle; crust; heterogeneity; neodymium; mars; ga; systematics; isotopes
AB The isotope Sm-146 undergoes alpha-decay to Nd-142, with a half-life of 103 million years. Measurable variations in the Nd-142/Nd-144 values of rocks resulting from Sm-Nd fractionation could therefore only have been produced within about 400 million years of the Solar System's formation ( that is, when Sm-146 was extant). The Nd-142/(144) Nd compositions of terrestrial rocks(1-7) are accordingly a sensitive monitor of the main silicate differentiation events that took place in the early Earth. High Nd-142/(144) Nd values measured in some Archaean rocks from Greenland(1-5) hint at the existence of an early incompatible-element-depleted mantle. Here we present measurements of low Nd-142/(144) Nd values in 1.48-gigayear-(Gyr)old lithospheric mantle-derived alkaline rocks from the Khariar nepheline syenite complex in southeastern India(8). These data suggest that a reservoir that was relatively enriched in incompatible elements formed at least 4.2 Gyr ago and traces of its isotopic signature persisted within the lithospheric root of the Bastar craton until at least 1.48 Gyr ago. These low Nd-142/(144) Nd compositions may represent a diluted signature of a Hadean (4 to 4.57 Gyr ago) enriched reservoir that is characterized by even lower values. That no evidence of the early depleted mantle has been observed in rocks younger than 3.6 Gyr (refs 3, 4, 7) implies that such domains had effectively mixed back into the convecting mantle by then. In contrast, some early enriched components apparently escaped this fate. Thus, the mantle sampled by magmatism since 3.6 Gyr ago may be biased towards a depleted composition that would be balanced by relatively more enriched reservoirs that are 'hidden' in Hadean crust(6), the D '' layer(9-11) of the lowermost mantle or, as we propose here, also within the roots of old cratons.
C1 [Upadhyay, Dewashish; Scherer, Erik E.; Mezger, Klaus] Univ Munster, Inst Mineral, Zent Lab Geochronol, D-48149 Munster, Germany.
C3 University of Munster
RP Upadhyay, D (corresponding author), Univ Munster, Inst Mineral, Zent Lab Geochronol, Corrensstr 24, D-48149 Munster, Germany.
EM upadhyay@uni-muenster.de
FU Deutsche Forschungsgemeinschaft [ME1717]
NR 27
TC 43
Z9 47
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 JUN 25
PY 2009
VL 459
IS 7250
BP 1118
EP 1121
DI 10.1038/nature08089
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700041
PM 19553997
DA 2026-03-09
ER

PT J
AU Giljohann, DA
   Mirkin, CA
AF Giljohann, David A.
   Mirkin, Chad A.
TI Drivers of biodiagnostic development
SO NATURE
LA English
DT Article
ID ultrasensitive detection; colorimetric detection; dna; nanoparticles; immunoassay; molecules; proteins
AB The promise of point-of-care medical diagnostics - tests that can be carried out at the site of patient care is enormous, bringing the benefits of fast and reliable testing and allowing rapid decisions on the course of treatment to be made. To this end, much innovation is occurring in technologies for use in biodiagnostic tests. Assays based on nanomaterials, for example, are now beginning to make the transition from the laboratory to the clinic. But the potential for such assays to become part of routine medical testing depends on many scientific factors, including sensitivity, selectivity and versatility, as well as technological, financial and policy factors.
C1 [Giljohann, David A.; Mirkin, Chad A.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
   [Giljohann, David A.; Mirkin, Chad A.] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA.
C3 Northwestern University; Northwestern University
RP Mirkin, CA (corresponding author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM chadnano@northwestern.edu
FU US National Science Foundation; National Cancer Institute; National Institutes of Health
NR 33
TC 669
Z9 795
U1 0
U2 400
PU NATURE PUBLISHING 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 26
PY 2009
VL 462
IS 7272
BP 461
EP 464
DI 10.1038/nature08605
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200034
PM 19940916
DA 2026-03-09
ER

PT J
AU Schacherer, J
   Shapiro, JA
   Ruderfer, DM
   Kruglyak, L
AF Schacherer, Joseph
   Shapiro, Joshua A.
   Ruderfer, Douglas M.
   Kruglyak, Leonid
TI Comprehensive polymorphism survey elucidates population structure of Saccharomyces cerevisiae
SO NATURE
LA English
DT Article
ID quantitative trait; nucleotide resolution; genetic diversity; genome evolution; dna-sequences; yeast; strains; map
AB Comprehensive identification of polymorphisms among individuals within a species is essential both for studying the genetic basis of phenotypic differences and for elucidating the evolutionary history of the species. Large-scale polymorphism surveys have recently been reported for human(1), mouse(2) and Arabidopsis thaliana(3). Here we report a nucleotide-level survey of genomic variation in a diverse collection of 63 Saccharomyces cerevisiae strains sampled from different ecological niches (beer, bread, vineyards, immunocompromised individuals, various fermentations and nature) and from locations on different continents. We hybridized genomic DNA from each strain to whole-genome tiling microarrays and detected 1.89 million single nucleotide polymorphisms, which were grouped into 101,343 distinct segregating sites. We also identified 3,985 deletion events of length >200 base pairs among the surveyed strains. We analysed the genome-wide patterns of nucleotide polymorphism and deletion variants, and measured the extent of linkage disequilibrium in S. cerevisiae. These results and the polymorphism resource we have generated lay the foundation for genome-wide association studies in yeast. We also examined the population structure of S. cerevisiae, providing support for multiple domestication events as well as insight into the origins of pathogenic strains.
C1 [Schacherer, Joseph; Shapiro, Joshua A.; Ruderfer, Douglas M.; Kruglyak, Leonid] Princeton Univ, Lewis Sigler Inst Integrat Gen, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [Schacherer, Joseph; Shapiro, Joshua A.; Ruderfer, Douglas M.; Kruglyak, Leonid] Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
C3 Princeton University; Howard Hughes Medical Institute; Princeton University
RP Kruglyak, L (corresponding author), Princeton Univ, Lewis Sigler Inst Integrat Gen, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM leonid@genomics.princeton.edu
FU NIH [R37 MH059520, GM071508]; James S. McDonnell Foundation Centennial Fellowship
NR 30
TC 356
Z9 417
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 MAR 19
PY 2009
VL 458
IS 7236
BP 342
EP U103
DI 10.1038/nature07670
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600042
PM 19212320
DA 2026-03-09
ER

PT J
AU Cooke, J
   Sullivan, M
   Barton, EJ
   Bullock, JS
   Carlberg, RG
   Gal-Yam, A
   Tollerud, E
AF Cooke, Jeff
   Sullivan, Mark
   Barton, Elizabeth J.
   Bullock, James S.
   Carlberg, Ray G.
   Gal-Yam, Avishay
   Tollerud, Erik
TI Type IIn supernovae at redshift z ≈ 2 from archival data
SO NATURE
LA English
DT Article
ID galaxy; z-similar-to-3; telescope; epoch
AB Supernovae have been confirmed to redshift z approximate to 1.7 (refs 1, 2) for type Ia (thermonuclear detonation of a white dwarf) and to z approximate to 0.7 (refs 1, 3-5) for type II (collapse of the core of the star). The subclass type IIn (ref. 6) supernovae are luminous(7-9) core-collapse explosions of massive stars(8-11) and, unlike other types, are very bright in the ultraviolet(12-15), which should enable them to be found optically at redshifts z approximate to 2 and higher(14,16). In addition, the interaction of the ejecta with circumstellar material creates strong, long-lived emission lines that allow spectroscopic confirmation of many events of this type at z approximate to 2 for 3-5 years after explosion (ref. 14). Here we report three spectroscopically confirmed type IIn supernovae, at redshifts z = 0.808, 2.013 and 2.357, detected in archival data using a method(14) designed to exploit these properties at z approximate to 2. Type IIn supernovae directly probe the formation of massive stars at high redshift. The number found to date is consistent with the expectations of a locally measured(17) stellar initial mass function, but not with an evolving initial mass function proposed(18-20) to explain independent observations at low and high redshift.
C1 [Cooke, Jeff; Barton, Elizabeth J.; Bullock, James S.; Tollerud, Erik] Univ Calif Irvine, Dept Phys & Astron, Ctr Cosmol, Irvine, CA 92697 USA.
   [Sullivan, Mark] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
   [Carlberg, Ray G.] Univ Toronto, Dept Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Gal-Yam, Avishay] Weizmann Inst Sci, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
C3 University of California System; University of California Irvine; University of Oxford; University of Toronto; Weizmann Institute of Science
RP Cooke, J (corresponding author), Univ Calif Irvine, Dept Phys & Astron, Ctr Cosmol, Irvine, CA 92697 USA.
EM cooke@uci.edu
FU NSERC; Royal Society; NSF [AST-0071048]
NR 30
TC 37
Z9 37
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 237
EP 239
DI 10.1038/nature08082
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000036
PM 19587765
DA 2026-03-09
ER

PT J
AU Wollert, T
   Wunder, C
   Lippincott-Schwartz, J
   Hurley, JH
AF Wollert, Thomas
   Wunder, Christian
   Lippincott-Schwartz, Jennifer
   Hurley, James H.
TI Membrane scission by the ESCRT-III complex
SO NATURE
LA English
DT Article
ID multivesicular endosm; structural basis; cell-division; proteins; vps4; recognition; biogenesis; machinery; hiv-1; alix
AB The endosomal sorting complex required for transport (ESCRT) system is essential for multivesicular body biogenesis, in which cargo sorting is coupled to the invagination and scission of intralumenal vesicles. The ESCRTs are also needed for budding of enveloped viruses including human immunodeficiency virus 1, and for membrane abscission in cytokinesis. In Saccharomyces cerevisiae, ESCRT-III consists of Vps20, Snf7, Vps24 and Vps2 (also known as Did4), which assemble in that order and require the ATPase Vps4 for their disassembly. In this study, the ESCRT-III-dependent budding and scission of intralumenal vesicles into giant unilamellar vesicles was reconstituted and visualized by fluorescence microscopy. Here we show that three subunits of ESCRT-III, Vps20, Snf7 and Vps24, are sufficient to detach intralumenal vesicles. Vps2, the ESCRT-III subunit responsible for recruiting Vps4, and the ATPase activity of Vps4 were required for ESCRT-III recycling and supported additional rounds of budding. The minimum set of ESCRT-III and Vps4 proteins capable of multiple cycles of vesicle detachment corresponds to the ancient set of ESCRT proteins conserved from archaea to animals.
C1 [Wollert, Thomas; Hurley, James H.] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
   [Wunder, Christian; Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
RP Hurley, JH (corresponding author), NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [ZICHD008874] Funding Source: NIH RePORTER; Intramural NIH HHS [Z01 DK036123] Funding Source: Medline
NR 38
TC 510
Z9 620
U1 1
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 172
EP U2
DI 10.1038/nature07836
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700036
PM 19234443
DA 2026-03-09
ER

PT J
AU Cook, AG
   Fukuhara, N
   Jinek, M
   Conti, E
AF Cook, Atlanta G.
   Fukuhara, Noemi
   Jinek, Martin
   Conti, Elena
TI Structures of the tRNA export factor in the nuclear and cytosolic states
SO NATURE
LA English
DT Article
ID phenylalanine transfer-rna; crystal-structure; angstrom resolution; transport; complex; protein; receptor; identification; translocation; crm1
AB Transfer RNAs are among the most ubiquitous molecules in cells, central to decoding information from messenger RNAs on translating ribosomes. In eukaryotic cells, tRNAs are actively transported from their site of synthesis in the nucleus to their site of function in the cytosol. This is mediated by a dedicated nucleo-cytoplasmic transport factor of the karyopherin-beta family (Xpot, also known as Los1 in Saccharomyces cerevisiae). Here we report the 3.2 angstrom resolution structure of Schizosaccharomyces pombe Xpot in complex with tRNA and RanGTP, and the 3.1 angstrom structure of unbound Xpot, revealing both nuclear and cytosolic snapshots of this transport factor. Xpot undergoes a large conformational change on binding cargo, wrapping around the tRNA and, in particular, binding to the tRNA 59 and 39 ends. The binding mode explains how Xpot can recognize all mature tRNAs in the cell and yet distinguish them from those that have not been properly processed, thus coupling tRNA export to quality control.
C1 [Cook, Atlanta G.; Conti, Elena] MPI Biochem, D-82152 Martinsried, Germany.
   [Fukuhara, Noemi; Jinek, Martin; Conti, Elena] EMBL, D-69117 Heidelberg, Germany.
C3 Max Planck Society; European Molecular Biology Laboratory (EMBL)
RP Conti, E (corresponding author), MPI Biochem, Am Klopferspitz 18, D-82152 Martinsried, Germany.
EM conti@biochem.mpg.de
FU Max Planck Gesellschaft; European Molecular Biology Laboratory (EMBL); Sonderforschungsbereich SFB646; Deutsche Forschungsgemeinschaft (DFG); EU [LSHG-CT-2005-512028]
NR 53
TC 109
Z9 130
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 60
EP U60
DI 10.1038/nature08394
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800029
PM 19680239
DA 2026-03-09
ER

PT J
AU Jenniskens, P
   Shaddad, MH
   Numan, D
   Elsir, S
   Kudoda, AM
   Zolensky, ME
   Le, L
   Robinson, GA
   Friedrich, JM
   Rumble, D
   Steele, A
   Chesley, SR
   Fitzsimmons, A
   Duddy, S
   Hsieh, HH
   Ramsay, G
   Brown, PG
   Edwards, WN
   Tagliaferri, E
   Boslough, MB
   Spalding, RE
   Dantowitz, R
   Kozubal, M
   Pravec, P
   Borovicka, J
   Charvat, Z
   Vaubaillon, J
   Kuiper, J
   Albers, J
   Bishop, JL
   Mancinelli, RL
   Sandford, SA
   Milam, SN
   Nuevo, M
   Worden, SP
AF Jenniskens, P.
   Shaddad, M. H.
   Numan, D.
   Elsir, S.
   Kudoda, A. M.
   Zolensky, M. E.
   Le, L.
   Robinson, G. A.
   Friedrich, J. M.
   Rumble, D.
   Steele, A.
   Chesley, S. R.
   Fitzsimmons, A.
   Duddy, S.
   Hsieh, H. H.
   Ramsay, G.
   Brown, P. G.
   Edwards, W. N.
   Tagliaferri, E.
   Boslough, M. B.
   Spalding, R. E.
   Dantowitz, R.
   Kozubal, M.
   Pravec, P.
   Borovicka, J.
   Charvat, Z.
   Vaubaillon, J.
   Kuiper, J.
   Albers, J.
   Bishop, J. L.
   Mancinelli, R. L.
   Sandford, S. A.
   Milam, S. N.
   Nuevo, M.
   Worden, S. P.
TI The impact and recovery of asteroid 2008 TC3
SO NATURE
LA English
DT Article
AB In the absence of a firm link between individual meteorites and their asteroidal parent bodies, asteroids are typically characterized only by their light reflection properties, and grouped accordingly into classes(1-3). On 6 October 2008, a small asteroid was discovered with a flat reflectance spectrum in the 554-995nm wavelength range, and designated 2008 TC3 (refs 4-6). It subsequently hit the Earth. Because it exploded at 37km altitude, no macroscopic fragments were expected to survive. Here we report that a dedicated search along the approach trajectory recovered 47 meteorites, fragments of a single body named Almahata Sitta, with a total mass of 3.95 kg. Analysis of one of these meteorites shows it to be an achondrite, a polymict ureilite, anomalous in its class: ultra-fine-grained and porous, with large carbonaceous grains. The combined asteroid and meteorite reflectance spectra identify the asteroid as F class(3), now firmly linked to dark carbon-rich anomalous ureilites, a material so fragile it was not previously represented in meteorite collections.
C1 [Jenniskens, P.; Albers, J.; Bishop, J. L.; Mancinelli, R. L.] Carl Sagan Ctr, SETI Inst, Mountain View, CA 94043 USA.
   [Shaddad, M. H.; Numan, D.; Kudoda, A. M.] Univ Khartoum, Dept Phys, Khartoum 11115, Sudan.
   [Elsir, S.] Juba Univ, Dept Phys, Juba, Sudan.
   [Zolensky, M. E.; Le, L.; Robinson, G. A.] NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA.
   [Le, L.; Robinson, G. A.] Jacobs Technol Engn Sci Contact Grp, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA.
   [Friedrich, J. M.] Fordham Univ, Dept Chem, Bronx, NY 10458 USA.
   [Friedrich, J. M.] Amer Museum Nat Hist, Dept Earth & Planetary Sci, New York, NY 10024 USA.
   [Rumble, D.; Steele, A.] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Chesley, S. R.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Fitzsimmons, A.; Duddy, S.; Hsieh, H. H.] Queens Univ Belfast, Sch Math & Phys, Belfast BT7 1NN, Antrim, North Ireland.
   [Ramsay, G.] Armagh Observ, Armagh BT61 9DG, North Ireland.
   [Brown, P. G.; Edwards, W. N.] Univ Western Ontario, Dept Phys & Astron, London, ON N6A 3K7, Canada.
   [Tagliaferri, E.] ET Space Syst, Camarillo, CA 93012 USA.
   [Boslough, M. B.; Spalding, R. E.] Sandia Natl Labs, Albuquerque, NM 87185 USA.
   [Dantowitz, R.; Kozubal, M.] Dexter Sch, Clay Ctr Observ, Brookline, MA 02445 USA.
   [Dantowitz, R.; Kozubal, M.] Southfield Sch, Clay Ctr Observ, Brookline, MA 02445 USA.
   [Pravec, P.; Borovicka, J.] Acad Sci Czech Republ, Astron Inst, Ondrejov 25165, Czech Republic.
   [Charvat, Z.] Czech Hydrometeorol Inst, Prague 14306 4, Czech Republic.
   [Vaubaillon, J.] Inst Mecan Celeste & Calcul Ephemerides, F-75014 Paris, France.
   [Kuiper, J.] Dutch Meteor Soc, NL-3732 XD De Bilt, Netherlands.
   [Sandford, S. A.; Milam, S. N.; Nuevo, M.; Worden, S. P.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
C3 SETI Institute; University of Khartoum; National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; Fordham University; American Museum of Natural History (AMNH); Carnegie Institution for Science; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); Queens University Belfast; Western University (University of Western Ontario); United States Department of Energy (DOE); Sandia National Laboratories; Czech Academy of Sciences; Astronomical Institute of the Czech Academy of Sciences; Czech Hydrometeorological Institute; Universite PSL; Observatoire de Paris; Sorbonne Universite; National Aeronautics & Space Administration (NASA); NASA Ames Research Center
RP Jenniskens, P (corresponding author), Carl Sagan Ctr, SETI Inst, 515 N Whisman Rd, Mountain View, CA 94043 USA.
EM Petrus.M.Jenniskens@nasa.gov
FU NASA Planetary Astronomy program; NASA's Cosmochemistry program [NNX07AI48G]; STFC [ST/F011016/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/F011016/1] Funding Source: researchfish
NR 27
TC 324
Z9 348
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 MAR 26
PY 2009
VL 458
IS 7237
BP 485
EP 488
DI 10.1038/nature07920
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400039
PM 19325630
DA 2026-03-09
ER

PT J
AU Mosher, RA
   Melnyk, CW
   Kelly, KA
   Dunn, RM
   Studholme, DJ
   Baulcombe, DC
AF Mosher, Rebecca A.
   Melnyk, Charles W.
   Kelly, Krystyna A.
   Dunn, Ruth M.
   Studholme, David J.
   Baulcombe, David C.
TI Uniparental expression of PolIV-dependent siRNAs in developing endosperm of Arabidopsis
SO NATURE
LA English
DT Article
ID rna-polymerase-iv; dna-methylation; gene; medea; transposons; micrornas
AB Most eukaryotes produce small RNA (sRNA) mediators of gene silencing that bind to Argonaute proteins and guide them, by base pairing, to an RNA target. MicroRNAs (miRNAs) that normally target messenger RNAs for degradation or translational arrest are the best-understood class of sRNAs. However, in Arabidopsis thaliana flowers, miRNAs account for only 5% of the sRNA mass and less than 0.1% of the sequence complexity. The remaining sRNAs form a complex population of more than 100,000 different small interfering RNAs (siRNAs) transcribed from thousands of loci(1-5). The biogenesis of most of the siRNAs in Arabidopsis are dependent on RNA polymerase IV (PolIV), a homologue of DNA-dependent RNA polymerase II2,3,6. A subset of these PolIV-dependent (p4)-siRNAs are involved in stress responses, and others are associated with epigenetic modifications to DNA or chromatin; however, the biological role is not known for most of them. Here we show that the predominant phase of p4-siRNA accumulation is initiated in the maternal gametophyte and continues during seed development. Expression of p4-siRNAs in developing endosperm is specifically from maternal chromosomes. Our results provide the first evidence for a link between genomic imprinting and RNA silencing in plants.
C1 [Mosher, Rebecca A.; Melnyk, Charles W.; Kelly, Krystyna A.; Dunn, Ruth M.; Baulcombe, David C.] Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England.
   [Studholme, David J.] Sainsbury Lab, Norwich NR4 7UH, Norfolk, England.
C3 University of Cambridge; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre
RP Baulcombe, DC (corresponding author), Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England.
EM dcb40@cam.ac.uk
FU Gatsby Charitable Foundation; SIROCCO [LSHG-CT-2006-037900]; National Science Foundation; Commonwealth and NSERC Scholarships; Royal Society Research
NR 21
TC 250
Z9 284
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 JUL 9
PY 2009
VL 460
IS 7252
BP 283
EP U151
DI 10.1038/nature08084
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000046
PM 19494814
DA 2026-03-09
ER

PT J
AU Stein, A
   Weber, G
   Wahl, MC
   Jahn, R
AF Stein, Alexander
   Weber, Gert
   Wahl, Markus C.
   Jahn, Reinhard
TI Helical extension of the neuronal SNARE complex into the membrane
SO NATURE
LA English
DT Article
ID juxtamembrane region; synaptic exocytosis; molecular-dynamics; fusion; synaptotagmin; proteins; determinants; mechanisms; endosm; syntaxin
AB Neurotransmission relies on synaptic vesicles fusing with the membrane of nerve cells to release their neurotransmitter content into the synaptic cleft, a process requiring the assembly of several members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family. SNAREs represent an evolutionarily conserved protein family that mediates membrane fusion in the secretory and endocytic pathways of eukaryotic cells(1-3). On membrane contact, these proteins assemble in trans between the membranes as a bundle of four alpha-helices, with the energy released during assembly being thought to drive fusion(4-6). However, it is unclear how the energy is transferred to the membranes and whether assembly is conformationally linked to fusion. Here, we report the X-ray structure of the neuronal SNARE complex, consisting of rat syntaxin 1A, SNAP-25 and synaptobrevin 2, with the carboxy-terminal linkers and transmembrane regions at 3.4 angstrom resolution. The structure shows that assembly proceeds beyond the already known core SNARE complex(7), resulting in a continuous helical bundle that is further stabilized by side-chain interactions in the linker region. Our results suggest that the final phase of SNARE assembly is directly coupled to membrane merger.
C1 [Stein, Alexander; Jahn, Reinhard] Max Planck Inst Biophys Chem, Dept Neurobiol, D-37077 Gottingen, Germany.
   [Weber, Gert; Wahl, Markus C.] Max Planck Inst Biophys Chem, Res Grp Xray Crystallog, D-37077 Gottingen, Germany.
   [Weber, Gert; Wahl, Markus C.] Free Univ Berlin, Fachbereich Biol, Inst Chem & Biochem, AG Strukturbiochem, D-14195 Berlin, Germany.
C3 Max Planck Society; Max Planck Society; Free University of Berlin
RP Jahn, R (corresponding author), Max Planck Inst Biophys Chem, Dept Neurobiol, D-37077 Gottingen, Germany.
EM rjahn@gwdg.de
FU NIGMS NIH HHS [P01 GM072694] Funding Source: Medline; National Institute of General Medical Sciences [P01GM072694] Funding Source: NIH RePORTER
NR 49
TC 338
Z9 415
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 JUL 23
PY 2009
VL 460
IS 7254
BP 525
EP U105
DI 10.1038/nature08156
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000041
PM 19571812
DA 2026-03-09
ER

PT J
AU Huebsch, N
   Mooney, DJ
AF Huebsch, Nathaniel
   Mooney, David J.
TI Inspiration and application in the evolution of biomaterials
SO NATURE
LA English
DT Article
ID mesenchymal stem-cells; progenitor cells; hydrogels; matrices; culture; differentiation; activation; interfaces; nanowires; delivery
AB Biomaterials, traditionally defined as materials used in medical devices, have been used since antiquity, but recently their degree of sophistication has increased significantly. Biomaterials made today are routinely information rich and incorporate biologically active components derived from nature. In the future, biomaterials will assume an even greater role in medicine and will find use in a wide variety of non-medical applications through biologically inspired design and incorporation of dynamic behaviour.
C1 [Huebsch, Nathaniel; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Huebsch, Nathaniel] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Mooney, David J.] Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Massachusetts Institute of Technology (MIT)
RP Mooney, DJ (corresponding author), Harvard Univ, Sch Engn & Appl Sci, 29 Oxford St,319 Pierce Hall, Cambridge, MA 02138 USA.
EM mooneyd@seas.harvard.edu
FU US National Institutes of Health; National Science Foundation
NR 50
TC 654
Z9 800
U1 6
U2 437
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 426
EP 432
DI 10.1038/nature08601
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200030
PM 19940912
DA 2026-03-09
ER

PT J
AU Deng, YB
   Guo, XL
   Ferguson, DO
   Chang, S
AF Deng, Yibin
   Guo, Xiaolan
   Ferguson, David O.
   Chang, Sandy
TI Multiple roles for MRE11 at uncapped telomeres
SO NATURE
LA English
DT Article
ID double-strand break; dna-damage; homologous recombination; dysfunctional telomeres; mammalian telomeres; atm activation; complex; repair; trf2; pot1
AB Progressive telomere attrition or uncapping of the shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks(1). Telomere deprotection activates both ataxia telangiectasia mutated (ATM) and telangiectasia and Rad3-related (ATR) kinase-dependent DNA damage response pathways, and promotes efficient non-homologous end-joining (NHEJ) of dysfunctional telomeres(2-5). The mammalian MRE11-RAD50-NBS1 (MRN; NBS1 is also known as NBN) complex interacts with ATM to sense chromosomal double-strand breaks and coordinate global DNA damage responses(6,7). Although the MRN complex accumulates at dysfunctional telomeres, it is not known whether mammalian MRN promotes repair at these sites. Here we address this question by using mouse alleles that either inactivate the entire MRN complex or eliminate only the nuclease activities of MRE11 (ref. 8). We show that cells lacking MRN do not activate ATM when telomeric repeat binding factor 2 (TRF2) is removed from telomeres, and ligase 4 (LIG4)-dependent chromosome end-to-end fusions are markedly reduced. Residual chromatid fusions involve only telomeres generated by leading strand synthesis. Notably, although cells deficient for MRE11 nuclease activity efficiently activate ATM and recruit 53BP1 (also known as TP53BP1) to deprotected telomeres, the 3' telomeric overhang persists to prevent NHEJ-mediated chromosomal fusions. Removal of shelterin proteins that protect the 3' overhang in the setting of MRE11 nuclease deficiency restores LIG4-dependent chromosome fusions. Our data indicate a critical role for the MRN complex in sensing dysfunctional telomeres, and show that in the absence of TRF2, MRE11 nuclease activity removes the 3' telomeric overhang to promote chromosome fusions. MRE11 can also protect newly replicated leading strand telomeres from NHEJ by promoting 5' strand resection to generate POT1a-TPP1-bound 3' overhangs.
C1 [Deng, Yibin; Guo, Xiaolan; Chang, Sandy] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
   [Chang, Sandy] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA.
   [Guo, Xiaolan] N Sichuan Med Coll, Inst Rheumatol & Immunol, Nanchong 637000, Sichuan, Peoples R China.
   [Ferguson, David O.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; North Sichuan Medical University; University of Michigan System; University of Michigan
RP Chang, S (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Genet, Box 1010,1515 Holcombe Blvd, Houston, TX 77030 USA.
EM schang@mdanderson.org
FU National Institute on Aging (NIA) [RO1 AG028888]; National Cancer Institute (NCI) [RO1 CA129037]; Welch Foundation; Susan G. Koman Race for the Cure Foundation; Abraham and Phyllis Katz Foundation; Michael Kadoorie Cancer Genetic Research Program; NCI Howard Temin Award [K01CA124461]; National Cancer Institute [P30CA046592] Funding Source: NIH RePORTER
NR 30
TC 164
Z9 188
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 AUG 13
PY 2009
VL 460
IS 7257
BP 914
EP U157
DI 10.1038/nature08196
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300043
PM 19633651
DA 2026-03-09
ER

PT J
AU Charpinet, S
   Fontaine, G
   Brassard, P
AF Charpinet, S.
   Fontaine, G.
   Brassard, P.
TI Seismic evidence for the loss of stellar angular momentum before the white-dwarf stage
SO NATURE
LA English
DT Article
ID evolution models; magnetic-fields; rotation; stars; search; pg-1159-035
AB White-dwarf stars represent the final products of the evolution of some 95% of all stars(1). If stars were to keep their angular momentum throughout their evolution, their white-dwarf descendants, owing to their compact nature, should all rotate relatively rapidly, with typical periods of the order of a few seconds. Observations of their photospheres show, in contrast, that they rotate much more slowly, with periods ranging from hours to tens of years(2-5). It is not known, however, whether a white dwarf could 'hide' some of its original angular momentum below the superficial layers, perhaps spinning much more rapidly inside than at its surface. Here we report a determination of the internal rotation profile of a white dwarf using a method based on asteroseismology. We show that the pulsating white dwarf PG 1159-035 rotates as a solid body (encompassing more than 97.5% of its mass) with the relatively long period of 33.61 +/- 0.59 h. This implies that it has lost essentially all of its angular momentum, thus favouring theories which suggest important angular momentum transfer and loss in evolutionary phases before the white-dwarf stage(6,7).
C1 [Fontaine, G.; Brassard, P.] Univ Montreal, Dept Phys, Montreal, PQ H3C 3J7, Canada.
   [Charpinet, S.] Univ Toulouse, CNRS, Lab Astrophys Toulouse Tarbes, F-31400 Toulouse, France.
C3 Universite de Montreal; Universite de Toulouse; Centre National de la Recherche Scientifique (CNRS)
RP Fontaine, G (corresponding author), Univ Montreal, Dept Phys, CP 6128,Succ Ctr Ville, Montreal, PQ H3C 3J7, Canada.
EM fontaine@astro.umontreal.ca
FU NSERC (Canada); FQRNT (Quebec); Canada Research Chair Program
NR 20
TC 64
Z9 65
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 24
PY 2009
VL 461
IS 7263
BP 501
EP 503
DI 10.1038/nature08307
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900034
PM 19779446
DA 2026-03-09
ER

PT J
AU Hofstetter, L
   Csonka, S
   Nygård, J
   Schönenberger, C
AF Hofstetter, L.
   Csonka, S.
   Nygard, J.
   Schoenenberger, C.
TI Cooper pair splitter realized in a two-quantum-dot Y-junction
SO NATURE
LA English
DT Article
ID double-quantum dots; superconductor; entanglement
AB Non-locality is a fundamental property of quantum mechanics that manifests itself as correlations between spatially separated parts of a quantum system. A fundamental route for the exploration of such phenomena is the generation of Einstein-Podolsky-Rosen (EPR) pairs(1) of quantum-entangled objects for the test of so-called Bell inequalities(2). Whereas such experimental tests of non-locality have been successfully conducted with pairwise entangled photons, it has not yet been possible to realize an electronic analogue of it in the solid state, where spin-1/2 mobile electrons are the natural quantum objects(3). The difficulty stems from the fact that electrons are immersed in a macroscopic ground state-the Fermi sea-which prevents the straightforward generation and splitting of entangled pairs of electrons on demand. A superconductor, however, could act as a source of EPR pairs of electrons, because its ground-state is composed of Cooper pairs in a spin-singlet state(4). These Cooper pairs can be extracted from a superconductor by tunnelling, but, to obtain an efficient EPR source of entangled electrons, the splitting of the Cooper pairs into separate electrons has to be enforced. This can be achieved by having the electrons 'repel' each other by Coulomb interaction(5). Controlled Cooper pair splitting can thereby be realized by coupling of the superconductor to two normal metal drain contacts by means of individually tunable quantum dots. Here we demonstrate the first experimental realization of such a tunable Cooper pair splitter, which shows a surprisingly high efficiency. Our findings open a route towards a first test of the EPR paradox and Bell inequalities in the solid state.
C1 [Hofstetter, L.; Csonka, S.; Schoenenberger, C.] Univ Basel, Dept Phys, CH-4056 Basel, Switzerland.
   [Csonka, S.] Budapest Univ Technol & Econ, Dept Phys, H-1111 Budapest, Hungary.
   [Nygard, J.] Univ Copenhagen, Niels Bohr Inst, Nanosci Ctr, DK-2100 Copenhagen, Denmark.
C3 University of Basel; Budapest University of Technology & Economics; University of Copenhagen; Niels Bohr Institute
RP Schönenberger, C (corresponding author), Univ Basel, Dept Phys, Klingelbergstr 82, CH-4056 Basel, Switzerland.
EM csonka@dept.phy.bme.hu; christian.schoenenberger@unibas.ch
FU Swiss National Science Foundation; Swiss National Center of Competence in Research on Nanoscale Science; Danish Natural Science Research Council; Hungarian Scientific Research Fund [NNF 78842]; European Union [41139]
NR 31
TC 469
Z9 486
U1 1
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 960
EP 963
DI 10.1038/nature08432
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700042
PM 19829377
DA 2026-03-09
ER

PT J
AU Baek, KH
   Zaslavsky, A
   Lynch, RC
   Britt, C
   Okada, Y
   Siarey, RJ
   Lensch, MW
   Park, IH
   Yoon, SS
   Minami, T
   Korenberg, JR
   Folkman, J
   Daley, GQ
   Aird, WC
   Galdzicki, Z
   Ryeom, S
AF Baek, Kwan-Hyuck
   Zaslavsky, Alexander
   Lynch, Ryan C.
   Britt, Carmella
   Okada, Yoshiaki
   Siarey, Richard J.
   Lensch, M. William
   Park, In-Hyun
   Yoon, Sam S.
   Minami, Takashi
   Korenberg, Julie R.
   Folkman, Judah
   Daley, George Q.
   Aird, William C.
   Galdzicki, Zygmunt
   Ryeom, Sandra
TI Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1
SO NATURE
LA English
DT Article
ID critical region; endothelial-cells; gene-expression; cyclosporine-a; mouse model; angiogenesis; vegf; target; chromosome-21; regression
AB The incidence of many cancer types is significantly reduced in individuals with Down's syndrome(1-4), and it is thought that this broad cancer protection is conferred by the increased expression of one or more of the 231 supernumerary genes on the extra copy of chromosome 21. One such gene is Down's syndrome candidate region-1 (DSCR1, also known as RCAN1), which encodes a protein that suppresses vascular endothelial growth factor ( VEGF)mediated angiogenic signalling by the calcineurin pathway(5-10). Here we show that DSCR1 is increased in Down's syndrome tissues and in a mouse model of Down's syndrome. Furthermore, we show that the modest increase in expression afforded by a single extra transgenic copy of Dscr1 is sufficient to confer significant suppression of tumour growth in mice, and that such resistance is a consequence of a deficit in tumour angiogenesis arising from suppression of the calcineurin pathway. We also provide evidence that attenuation of calcineurin activity by DSCR1, together with another chromosome 21 gene Dyrk1a, may be sufficient to markedly diminish angiogenesis. These data provide a mechanism for the reduced cancer incidence in Down's syndrome and identify the calcineurin signalling pathway, and its regulators DSCR1 and DYRK1A, as potential therapeutic targets in cancers arising in all individuals.
C1 [Baek, Kwan-Hyuck; Zaslavsky, Alexander; Lynch, Ryan C.; Britt, Carmella; Folkman, Judah; Ryeom, Sandra] Childrens Hosp Boston, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
   [Okada, Yoshiaki; Aird, William C.] Beth Israel Deaconess Med Ctr, Div Mol & Vasc Med, Vasc Biol Res Ctr, Boston, MA 02115 USA.
   [Siarey, Richard J.; Galdzicki, Zygmunt] Uniformed Serv Univ Hlth Serv, Sch Med, Mol & Cellular Biol Program, Dept Anat Physiol & Genet Neurosci, Bethesda, MD 20814 USA.
   [Lensch, M. William; Park, In-Hyun; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Dept Med, Boston, MA 02115 USA.
   [Lensch, M. William; Park, In-Hyun; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA.
   [Minami, Takashi] Univ Tokyo, Adv Sci & Technol Res Ctr, Tokyo 1538904, Japan.
   [Korenberg, Julie R.] Univ Utah, Inst Brain, Salt Lake City, UT 84108 USA.
   [Korenberg, Julie R.] Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Tokyo; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah
RP Ryeom, S (corresponding author), Childrens Hosp Boston, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
EM sandra.ryeom@childrens.harvard.edu
FU Howard Hughes Medical Institute; Harvard Stem Cell Institute; National Institute of Health Director's Pioneer Award; NHLBI; Jerome Lejeune Foundation; USUHS; Smith Family Medical Foundation; Garrett B. Smith Foundation; Annie's Fun Foundation
NR 30
TC 292
Z9 328
U1 2
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1126
EP U113
DI 10.1038/nature08062
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700043
PM 19458618
DA 2026-03-09
ER

PT J
AU Gal-Yam, A
   Leonard, DC
AF Gal-Yam, A.
   Leonard, D. C.
TI A massive hypergiant star as the progenitor of the supernova SN 2005gl
SO NATURE
LA English
DT Article
ID red supergiant progenitor; luminous blue variables
AB Our understanding of the evolution of massive stars before their final explosions as supernovae is incomplete, from both an observational and a theoretical standpoint. A key missing piece in the supernova puzzle is the difficulty of identifying and studying progenitor stars. In only a single case-that of supernova SN 1987A in the Large Magellanic Cloud-has a star been detected at the supernova location before the explosion, and been subsequently shown to have vanished after the supernova event(1). The progenitor of SN 1987A was a blue supergiant, which required a rethink of stellar evolution models(2). The progenitor of supernova SN 2005gl was proposed to be an extremely luminous object(3), but the association was not robustly established (it was not even clear that the putative progenitor was a single luminous star). Here we report that the previously proposed(3) object was indeed the progenitor star of SN 2005gl. This very massive star was likely a luminous blue variable that standard stellar evolution predicts should not have exploded in that state.
C1 [Gal-Yam, A.] Weizmann Inst Sci, Fac Phys, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
   [Leonard, D. C.] San Diego State Univ, Dept Astron, San Diego, CA 92182 USA.
C3 Weizmann Institute of Science; California State University System; San Diego State University
RP Gal-Yam, A (corresponding author), Weizmann Inst Sci, Fac Phys, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
EM avishay.gal-yam@weizmann.ac.il
FU Israeli Science Foundation; EU; Benoziyo Center for Astrophysics; Peter and Patricia Gruber; Weizmann Institute
NR 28
TC 277
Z9 301
U1 0
U2 4
PU NATURE PUBLISHING 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 16
PY 2009
VL 458
IS 7240
BP 865
EP 867
DI 10.1038/nature07934
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500037
PM 19305392
DA 2026-03-09
ER

PT J
AU Andreotti, B
   Fourrière, A
   Ould-Kaddour, F
   Murray, B
   Claudin, P
AF Andreotti, Bruno
   Fourriere, Antoine
   Ould-Kaddour, Fouzia
   Murray, Brad
   Claudin, Philippe
TI Giant aeolian dune size determined by the average depth of the atmospheric boundary layer
SO NATURE
LA English
DT Article
ID sand dunes; air-flow; dynamics; field; simulations; velocity; selection; bedforms; ripples; shapes
AB Depending on the wind regime(1,2), sand dunes exhibit linear(3,4), crescent-shaped or star-like forms(5) resulting from the interaction between dune morphology and sand transport(6-8). Small-scale dunes form by destabilization of the sand bed(9-11) with a wavelength (a few tens of metres) determined by the sand transport saturation length(11-13). The mechanisms controlling the formation of giant dunes, and in particular accounting for their typical time and length scales, have remained unknown. Using a combination of field measurements and aerodynamic calculations, we show here that the growth of aeolian giant dunes, ascribed to the non-linear interaction between small-scale superimposed dunes(4,10,14,15), is limited by the confinement of the flow within the atmospheric boundary layer(16,17). Aeolian giant dunes and river dunes form by similar processes, with the thermal inversion layer that caps the convective boundary layer in the atmosphere(18) acting analogously to the water surface in rivers. In both cases, the bed topography excites surface waves on the interface that in turn modify the near-bed flow velocity. This mechanism is a stabilizing process that prevents the scale of the pattern from coarsening beyond the resonant condition. Our results can explain the mean spacing of aeolian giant dunes ranging from 300m in coastal terrestrial deserts to 3.5 km. We propose that our findings could serve as a starting point for the modelling of long-term evolution of desert landscapes under specific wind regimes.
C1 [Andreotti, Bruno; Fourriere, Antoine; Claudin, Philippe] ESPCI, PMMH, CNRS,UMR 7636, Lab Phys & Mecan Milieux Heterogenes,P6,P7, F-75005 Paris, France.
   [Ould-Kaddour, Fouzia] Univ Abou Bekr Belkaid, Phys Theor Lab, Tilimsen, Algeria.
   [Murray, Brad] Duke Univ, Ctr Nonlinear & Complex Syst, Nicholas Sch Environm & Earth Sci, Durham, NC 27708 USA.
C3 Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Universite Paris Cite; Universite Abou Bekr Belkaid; Duke University
RP Claudin, P (corresponding author), ESPCI, PMMH, CNRS,UMR 7636, Lab Phys & Mecan Milieux Heterogenes,P6,P7, 10 Rue Vanquelin, F-75005 Paris, France.
EM claudin@pmmh.espci.fr
FU ANR
NR 30
TC 125
Z9 133
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 FEB 26
PY 2009
VL 457
IS 7233
BP 1120
EP 1123
DI 10.1038/nature07787
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100038
PM 19242473
DA 2026-03-09
ER

PT J
AU Cella, M
   Fuchs, A
   Vermi, W
   Facchetti, F
   Otero, K
   Lennerz, JKM
   Doherty, JM
   Mills, JC
   Colonna, M
AF Cella, Marina
   Fuchs, Anja
   Vermi, William
   Facchetti, Fabio
   Otero, Karel
   Lennerz, Jochen K. M.
   Doherty, Jason M.
   Mills, Jason C.
   Colonna, Marco
TI A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity
SO NATURE
LA English
DT Article
ID growth-factor-beta; aryl-hydrocarbon receptor; ror-gamma-t; epithelial-cells; host-defense; tgf-beta; differentiation; interleukin-22; inflammation; cytokines
AB Natural killer ( NK) cells are classically viewed as lymphocytes that provide innate surveillance against virally infected cells and tumour cells through the release of cytolytic mediators and interferon ( IFN)-gamma. In humans, blood CD56(dim) NKcells specialize in the lysis of cell targets(1). In the lymph nodes, CD56(bright) NK cells secrete IFN-gamma cooperating with dendritic cells and T cells in the generation of adaptive responses(1,2). Here we report the characterization of a human NK cell subset located in mucosa- associated lymphoid tissues, such as tonsils and Peyer's patches, which is hard- wired to secrete interleukin (IL)- 22, IL- 26 and leukaemia inhibitory factor. TheseNKcells, whichwe refer to as NK- 22 cells, are triggered by acute exposure to IL- 23. In vitro, NK- 22- secreted cytokines stimulate epithelial cells to secrete IL- 10, proliferate and express a variety of mitogenic and anti- apoptotic molecules. NK- 22 cells are also found in mouse mucosa- associated lymphoid tissues and appear in the small intestine lamina propria during bacterial infection, suggesting that NK- 22 cells provide an innate source of IL- 22 that may help constrain inflammation and protect mucosal sites.
C1 [Cella, Marina; Fuchs, Anja; Otero, Karel; Lennerz, Jochen K. M.; Doherty, Jason M.; Mills, Jason C.; Colonna, Marco] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Vermi, William; Facchetti, Fabio] Univ Brescia, Dept Pathol 1, Spedali Civili, I-25123 Brescia, Italy.
C3 Washington University (WUSTL); University of Brescia
RP Colonna, M (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
EM mcolonna@pathology.wustl.edu
FU National Institutes of Health [R01AI056139-05, R21AI067748-02]; National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK079798]
NR 30
TC 1061
Z9 1225
U1 0
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 722
EP 725
DI 10.1038/nature07537
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700041
PM 18978771
DA 2026-03-09
ER

PT J
AU Maida, Y
   Yasukawa, M
   Furuuchi, M
   Lassmann, T
   Possemato, R
   Okamoto, N
   Kasim, V
   Hayashizaki, Y
   Hahn, WC
   Masutomi, K
AF Maida, Yoshiko
   Yasukawa, Mami
   Furuuchi, Miho
   Lassmann, Timo
   Possemato, Richard
   Okamoto, Naoko
   Kasim, Vivi
   Hayashizaki, Yoshihide
   Hahn, William C.
   Masutomi, Kenkichi
TI An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA
SO NATURE
LA English
DT Article
ID small interfering rnas; cartilage-hair-hypoplasia; hepatitis-c virus; human telomerase; catalytic subunit; human-cells; genetic elements; marrow failure; immortal cells; mouse oocytes
AB Constitutive expression of telomerase in human cells prevents the onset of senescence and crisis by maintaining telomere homeostasis. However, accumulating evidence suggests that the human telomerase reverse transcriptase catalytic subunit ( TERT) contributes to cell physiology independently of its ability to elongate telomeres. Here we show that TERT interacts with the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a gene that is mutated in the inherited pleiotropic syndrome cartilage-hair hypoplasia. Human TERT and RMRP form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase (RdRP) activity and produces double- stranded RNAs that can be processed into small interfering RNA in a Dicer ( also known as DICER1)-dependent manner. These observations identify a mammalian RdRP composed of TERT in complex with RMRP.
C1 [Possemato, Richard; Hahn, William C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Possemato, Richard; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Possemato, Richard; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Masutomi, Kenkichi] Japan Sci & Technol Agcy, PREST, Kawaguchi, Saitama 3320012, Japan.
   [Maida, Yoshiko; Yasukawa, Mami; Furuuchi, Miho; Okamoto, Naoko; Kasim, Vivi; Masutomi, Kenkichi] Natl Canc Ctr, Canc Stem Cell Project, Chuo Ku, Tokyo 1040045, Japan.
   [Lassmann, Timo; Hayashizaki, Yoshihide] RIKEN, Yokohama Inst, RIKEN Om Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Japan Science & Technology Agency (JST); National Cancer Center - Japan; RIKEN
RP Hahn, WC (corresponding author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM william_hahn@dfci.harvard.edu; kmasutom@ncc.go.jp
FU NIA NIH HHS [R01 AG023145, R01 AG23145] Funding Source: Medline
NR 49
TC 312
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 10
PY 2009
VL 461
IS 7261
BP 230
EP U104
DI 10.1038/nature08283
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600037
PM 19701182
DA 2026-03-09
ER

PT J
AU Torquato, S
   Jiao, Y
AF Torquato, S.
   Jiao, Y.
TI Dense packings of the Platonic and Archimedean solids
SO NATURE
LA English
DT Article
ID molecular-dynamics simulation; nonspherical hard particles
AB Dense particle packings have served as useful models of the structures of liquid, glassy and crystalline states of matter(1-4), granular media(3,5), heterogeneous materials(3) and biological systems(6-8). Probing the symmetries and other mathematical properties of the densest packings is a problem of interest in discrete geometry and number theory(9-11). Previous work has focused mainly on spherical particles-very little is known about dense polyhedral packings. Here we formulate the generation of dense packings of polyhedra as an optimization problem, using an adaptive fundamental cell subject to periodic boundary conditions (we term this the 'adaptive shrinking cell' scheme). Using a variety of multi-particle initial configurations, we find the densest known packings of the four non-tiling Platonic solids (the tetrahedron, octahedron, dodecahedron and icosahedron) in three-dimensional Euclidean space. The densities are 0.782..., 0.947..., 0.904... and 0.836..., respectively. Unlike the densest tetrahedral packing, which must not be a Bravais lattice packing, the densest packings of the other non-tiling Platonic solids that we obtain are their previously known optimal (Bravais) lattice packings. Combining our simulation results with derived rigorous upper bounds and theoretical arguments leads us to the conjecture that the densest packings of the Platonic and Archimedean solids with central symmetry are given by their corresponding densest lattice packings. This is the analogue of Kepler's sphere conjecture for these solids.
C1 [Torquato, S.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
   [Torquato, S.] Princeton Univ, Princeton Ctr Theoret Sci, Princeton, NJ 08544 USA.
   [Torquato, S.] Princeton Univ, Princeton Inst Sci & Technol Mat, Princeton, NJ 08544 USA.
   [Torquato, S.; Jiao, Y.] Princeton Univ, Dept Mech & Aerosp Engn, Princeton, NJ 08544 USA.
   [Torquato, S.] Inst Adv Study, Sch Nat Sci, Princeton, NJ 08540 USA.
C3 Princeton University; Princeton University; Princeton University; Princeton University; Institute for Advanced Study - USA
RP Torquato, S (corresponding author), Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
EM torquato@princeton.edu
FU National Science Foundation [DMS-0804431, DMR-0820341]
NR 28
TC 363
Z9 430
U1 1
U2 188
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 13
PY 2009
VL 460
IS 7257
BP 876
EP U109
DI 10.1038/nature08239
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300034
PM 19675649
DA 2026-03-09
ER

PT J
AU Wheeler, MJ
   de Graaf, BHJ
   Hadjiosif, N
   Perry, RM
   Poulter, NS
   Osman, K
   Vatovec, S
   Harper, A
   Franklin, FCH
   Franklin-Tong, VE
AF Wheeler, Michael J.
   de Graaf, Barend H. J.
   Hadjiosif, Natalie
   Perry, Ruth M.
   Poulter, Natalie S.
   Osman, Kim
   Vatovec, Sabina
   Harper, Andrea
   Franklin, F. Christopher H.
   Franklin-Tong, Vernonica E.
TI Identification of the pollen self-incompatibility determinant in Papaver rhoeas
SO NATURE
LA English
DT Article
ID programmed cell-death; gene; cloning; actin; depolymerization; polymorphism; locus
AB Higher plants produce seed through pollination, using specific interactions between pollen and pistil. Self-incompatibility is an important mechanism used in many species to prevent inbreeding; it is controlled by a multi-allelic S locus(1,2). 'Self' (incompatible) pollen is discriminated from 'non-self' (compatible) pollen by interaction of pollen and pistil S locus components, and is subsequently inhibited. In Papaver rhoeas, the pistil S locus product is a small protein that interacts with incompatible pollen, triggering a Ca2+-dependent signalling network, resulting in pollen inhibition and programmed cell death(3-7). Here we have cloned three alleles of a highly polymorphic pollen-expressed gene, PrpS (Papaver rhoeas pollen S), from Papaver and provide evidence that this encodes the pollen S locus determinant. PrpS is a single-copy gene linked to the pistil S gene (currently called S, but referred to hereafter as PrsS for Papaver rhoeas stigma S determinant). Sequence analysis indicates that PrsS and PrpS are equally ancient and probably co-evolved. PrpS encodes a novel similar to 20-kDa protein. Consistent with predictions that it is a transmembrane protein, PrpS is associated with the plasma membrane. We show that a predicted extracellular loop segment of PrpS interacts with PrsS and, using PrpS antisense oligonucleotides, we demonstrate that PrpS is involved in S-specific inhibition of incompatible pollen. Identification of PrpS represents a major advance in our understanding of the Papaver self-incompatibility system. As a novel cell-cell recognition determinant it contributes to the available information concerning the origins and evolution of cell-cell recognition systems involved in discrimination between self and non-self, which also include histocompatibility systems in primitive chordates and vertebrates.
C1 [Wheeler, Michael J.; de Graaf, Barend H. J.; Hadjiosif, Natalie; Perry, Ruth M.; Poulter, Natalie S.; Osman, Kim; Vatovec, Sabina; Harper, Andrea; Franklin, F. Christopher H.; Franklin-Tong, Vernonica E.] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England.
C3 University of Birmingham
RP Franklin-Tong, VE (corresponding author), Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England.
EM V.E.Franklin-Tong@bham.ac.uk
FU Biotechnology and Biological Sciences Research Council (BBSRC) [BB/C501325/1]; Biotechnology and Biological Sciences Research Council [BB/C501325/1] Funding Source: researchfish
NR 39
TC 169
Z9 214
U1 2
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 18
PY 2009
VL 459
IS 7249
BP 992
EP U118
DI 10.1038/nature08027
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500044
PM 19483678
DA 2026-03-09
ER

PT J
AU Guan, JS
   Haggarty, SJ
   Giacometti, E
   Dannenberg, JH
   Joseph, N
   Gao, J
   Nieland, TJF
   Zhou, Y
   Wang, XY
   Mazitschek, R
   Bradner, JE
   DePinho, RA
   Jaenisch, R
   Tsai, LH
AF Guan, Ji-Song
   Haggarty, Stephen J.
   Giacometti, Emanuela
   Dannenberg, Jan-Hermen
   Joseph, Nadine
   Gao, Jun
   Nieland, Thomas J. F.
   Zhou, Ying
   Wang, Xinyu
   Mazitschek, Ralph
   Bradner, James E.
   DePinho, Ronald A.
   Jaenisch, Rudolf
   Tsai, Li-Huei
TI HDAC2 negatively regulates memory formation and synaptic plasticity
SO NATURE
LA English
DT Article
ID histone deacetylase inhibitors; gene-expression; mouse model; huntingtons-disease; chromatin; acetylation; mice; modulation; receptors; mechanism
AB Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment.
C1 [Guan, Ji-Song; Joseph, Nadine; Gao, Jun; Zhou, Ying; Wang, Xinyu; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
   [Guan, Ji-Song; Joseph, Nadine; Gao, Jun; Zhou, Ying; Wang, Xinyu; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Guan, Ji-Song; Haggarty, Stephen J.; Joseph, Nadine; Nieland, Thomas J. F.; Mazitschek, Ralph; Bradner, James E.; Tsai, Li-Huei] Harvard Univ, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Guan, Ji-Song; Haggarty, Stephen J.; Joseph, Nadine; Nieland, Thomas J. F.; Mazitschek, Ralph; Bradner, James E.; Tsai, Li-Huei] MIT, Cambridge, MA 02142 USA.
   [Haggarty, Stephen J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA 02142 USA.
   [Giacometti, Emanuela; Jaenisch, Rudolf] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Giacometti, Emanuela; Jaenisch, Rudolf] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Dannenberg, Jan-Hermen; DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA.
   [Dannenberg, Jan-Hermen; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Dannenberg, Jan-Hermen; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Mazitschek, Ralph] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School
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 National Institute of Neurological Disorders and Stroke [2 ROI NS051874]; Stanley Center for Psychiatric Research; National Alliance for Research on Schizophrenia and Depression Foundation; Damon-Runyon Cancer Research Foundation; Dutch Cancer Society; NIH [5-RO1-CA087869, 5-R37-CA084198, 5-RO1-HD0445022]; Robert A. and Renee E. Belfer Institute for Applied Cancer Science
NR 35
TC 1364
Z9 1597
U1 1
U2 166
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 7
PY 2009
VL 459
IS 7243
BP 55
EP U58
DI 10.1038/nature07925
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300027
PM 19424149
DA 2026-03-09
ER

PT J
AU Niethammer, P
   Grabher, C
   Look, AT
   Mitchison, TJ
AF Niethammer, Philipp
   Grabher, Clemens
   Look, A. Thomas
   Mitchison, Timothy J.
TI A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish
SO NATURE
LA English
DT Article
ID tumor-suppressor pten; endothelial-cells; nox inhibitor; dual oxidases; inflammation; chemotaxis; migration; growth; neutrophils; expression
AB Barrier structures (for example, epithelia around tissues and plasma membranes around cells) are required for internal homeostasis and protection from pathogens. Wound detection and healing represent a dormant morphogenetic program that can be rapidly executed to restore barrier integrity and tissue homeostasis. In animals, initial steps include recruitment of leukocytes to the site of injury across distances of hundreds of micrometres within minutes of wounding. The spatial signals that direct this immediate tissue response are unknown. Owing to their fast diffusion and versatile biological activities, reactive oxygen species, including hydrogen peroxide (H2O2), are interesting candidates for wound-to-leukocyte signalling. Here we probe the role of H2O2 during the early events of wound responses in zebrafish larvae expressing a genetically encoded H2O2 sensor(1). This reporter revealed a sustained rise in H2O2 concentration at the wound margin, starting similar to 3 min after wounding and peaking at similar to 20 min, which extended similar to 100-200 mu m into the tail-fin epithelium as a decreasing concentration gradient. Using pharmacological and genetic inhibition, we show that this gradient is created by dual oxidase (Duox), and that it is required for rapid recruitment of leukocytes to the wound. This is the first observation, to our knowledge, of a tissue-scale H2O2 pattern, and the first evidence that H2O2 signals to leukocytes in tissues, in addition to its known antiseptic role.
C1 [Niethammer, Philipp; Mitchison, Timothy J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Grabher, Clemens; Look, A. Thomas] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Look, A. Thomas] Harvard Univ, Sch Med, Dept Pediat,Childrens Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School
RP Niethammer, P (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM Philipp_Niethammer@hms.harvard.edu
FU National Institutes of Health [GM023928]
NR 33
TC 1264
Z9 1492
U1 7
U2 341
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 18
PY 2009
VL 459
IS 7249
BP 996
EP U123
DI 10.1038/nature08119
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500045
PM 19494811
DA 2026-03-09
ER

PT J
AU Netzer, N
   Goodenbour, JM
   David, A
   Dittmar, KA
   Jones, RB
   Schneider, JR
   Boone, D
   Eves, EM
   Rosner, MR
   Gibbs, JS
   Embry, A
   Dolan, B
   Das, S
   Hickman, HD
   Berglund, P
   Bennink, JR
   Yewdell, JW
   Pan, T
AF Netzer, Nir
   Goodenbour, Jeffrey M.
   David, Alexandre
   Dittmar, Kimberly A.
   Jones, Richard B.
   Schneider, Jeffrey R.
   Boone, David
   Eves, Eva M.
   Rosner, Marsha R.
   Gibbs, James S.
   Embry, Alan
   Dolan, Brian
   Das, Suman
   Hickman, Heather D.
   Berglund, Peter
   Bennink, Jack R.
   Yewdell, Jonathan W.
   Pan, Tao
TI Innate immune and chemically triggered oxidative stress modifies translational fidelity
SO NATURE
LA English
DT Article
ID genetic-code; quality-control; cells; evolution; antioxidants; mitochondria; proteins; candida
AB Translational fidelity, essential for protein and cell function, requires accurate transfer RNA (tRNA) aminoacylation. Purified aminoacyl-tRNA synthetases exhibit a fidelity of one error per 10,000 to 100,000 couplings(1,2). The accuracy of tRNA aminoacylation in vivo is uncertain, however, and might be considerably lower(3-6). Here we show that in mammalian cells, approximately 1% of methionine (Met) residues used in protein synthesis are aminoacylated to non-methionyl-tRNAs. Remarkably, Met-misacylation increases up to tenfold upon exposing cells to live or non-infectious viruses, toll-like receptor ligands or chemically induced oxidative stress. Met is misacylated to specific non-methionyl-tRNA families, and these Met-misacylated tRNAs are used in translation. Met-misacylation is blocked by an inhibitor of cellular oxidases, implicating reactive oxygen species (ROS) as the misacylation trigger. Among six amino acids tested, tRNA misacylation occurs exclusively with Met. As Met residues are known to protect proteins against ROS-mediated damage(7), we propose that Met-misacylation functions adaptively to increase Met incorporation into proteins to protect cells against oxidative stress. In demonstrating an unexpected conditional aspect of decoding mRNA, our findings illustrate the importance of considering alternative iterations of the genetic code.
C1 [Netzer, Nir; David, Alexandre; Gibbs, James S.; Embry, Alan; Dolan, Brian; Das, Suman; Hickman, Heather D.; Berglund, Peter; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
   [Goodenbour, Jeffrey M.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Dittmar, Kimberly A.; Pan, Tao] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Jones, Richard B.; Eves, Eva M.; Rosner, Marsha R.] Univ Chicago, Ben May Inst, Chicago, IL 60637 USA.
   [Schneider, Jeffrey R.; Boone, David] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Chicago; University of Chicago; University of Chicago; University of Chicago
RP Yewdell, JW (corresponding author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov; taopan@uchicago.edu
FU Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health; National Institute of Allergy and Infectious Diseases [ZIAAI001014] Funding Source: NIH RePORTER
NR 24
TC 275
Z9 321
U1 0
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 522
EP 526
DI 10.1038/nature08576
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200048
PM 19940929
DA 2026-03-09
ER

PT J
AU Xu, ZY
   Wei, W
   Gagneur, J
   Perocchi, F
   Clauder-Münster, S
   Camblong, J
   Guffanti, E
   Stutz, F
   Huber, W
   Steinmetz, LM
AF Xu, Zhenyu
   Wei, Wu
   Gagneur, Julien
   Perocchi, Fabiana
   Clauder-Muenster, Sandra
   Camblong, Jurgi
   Guffanti, Elisa
   Stutz, Francoise
   Huber, Wolfgang
   Steinmetz, Lars M.
TI Bidirectional promoters generate pervasive transcription in yeast
SO NATURE
LA English
DT Article
ID genome-wide transcription; saccharomyces-cerevisiae; antisense transcription; tiling arrays; identification; resolution; nucleosm; polymerase; landscape; map
AB Genome- wide pervasive transcription has been reported in many eukaryotic organisms(1-7), revealing a highly interleaved transcriptome organization that involves hundreds of previously unknown non- codingRNAs(8). These recently identified transcripts either exist stably in cells ( stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway ( cryptic unstable transcripts, CUTs). One characteristic of pervasive transcription is the extensive overlap of SUTs and CUTs with previously annotated features, which prompts questions regarding how these transcripts are generated, and whether they exert function(9). Single- gene studies have shown that transcription of SUTs and CUTs can be functional, through mechanisms involving the generated RNAs10,11 or their generation itself(12-14). So far, a complete transcriptome architecture including SUTs and CUTs has not been described in any organism. Knowledge about the position and genome- wide arrangement of these transcripts will be instrumental in understanding their function(8,15). Here we provide a comprehensive analysis of these transcripts in the context of multiple conditions, a mutant of the exosome machinery and different strain backgrounds of Saccharomyces cerevisiae. We show that both SUTs and CUTs display distinct patterns of distribution at specific locations. Most of the newly identified transcripts initiate from nucleosome- free regions ( NFRs) associated with the promoters of other transcripts ( mostly protein- coding genes), or from NFRs at the 3 ' ends of protein- coding genes. Likewise, about half of all coding transcripts initiate from NFRs associated with promoters of other transcripts. These data change our view of how a genome is transcribed, indicating that bidirectionality is an inherent feature of promoters. Such an arrangement of divergent and overlapping transcripts may provide a mechanism for local spreading of regulatory signals - that is, coupling the transcriptional regulation of neighbouring genes by means of transcriptional interference or histone modification.
C1 [Xu, Zhenyu; Wei, Wu; Gagneur, Julien; Perocchi, Fabiana; Clauder-Muenster, Sandra; Steinmetz, Lars M.] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Camblong, Jurgi] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
   [Guffanti, Elisa; Stutz, Francoise] Univ Geneva, Dept Cell Biol, CH-1211 Geneva 4, Switzerland.
   [Huber, Wolfgang] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
C3 European Molecular Biology Laboratory (EMBL); University of Oxford; University of Geneva; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute
RP Steinmetz, LM (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM larsms@embl.de
FU National Institutes of Health; Deutsche Forschungsgemeinschaft; SystemsX fellowship; Roche fellowship; SNF; NCCR Frontiers in Genetics
NR 30
TC 736
Z9 900
U1 2
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 19
PY 2009
VL 457
IS 7232
BP 1033
EP U7
DI 10.1038/nature07728
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400047
PM 19169243
DA 2026-03-09
ER

PT J
AU Cyr-Choinière, O
   Daou, R
   Laliberté, F
   LeBoeuf, D
   Doiron-Leyraud, N
   Chang, J
   Yan, JQ
   Cheng, JG
   Zhou, JS
   Goodenough, JB
   Pyon, S
   Takayama, T
   Takagi, H
   Tanaka, Y
   Taillefer, L
AF Cyr-Choiniere, Olivier
   Daou, R.
   Laliberte, Francis
   LeBoeuf, David
   Doiron-Leyraud, Nicolas
   Chang, J.
   Yan, J. -Q.
   Cheng, J. -G.
   Zhou, J. -S.
   Goodenough, J. B.
   Pyon, S.
   Takayama, T.
   Takagi, H.
   Tanaka, Y.
   Taillefer, Louis
TI Enhancement of the Nernst effect by stripe order in a high-Tc superconductor
SO NATURE
LA English
DT Article
ID fermi-surface
AB The Nernst effect in metals is highly sensitive to two kinds of phase transition: superconductivity and density-wave order(1). The large, positive Nernst signal observed in hole-doped high-T-c superconductors(2) above their transition temperature (T-c) has so far been attributed to fluctuating superconductivity(3). Here we report that in some of these materials the large Nernst signal is in fact the result of stripe order, a form of spin/charge modulation(4) that causes a reconstruction of the Fermi surface(5). In La2-xSrxCuO4 (LSCO) doped with Nd or Eu, the onset of stripe order causes the Nernst signal to change from being small and negative to being large and positive, as revealed either by lowering the hole concentration across the quantum critical point in Nd-doped LSCO (refs 6-8) or by lowering the temperature across the ordering temperature in Eu-doped LSCO (refs 9, 10). In the second case, two separate peaks are resolved, respectively associated with the onset of stripe order at high temperature and superconductivity near T-c.
C1 [Cyr-Choiniere, Olivier; Daou, R.; Laliberte, Francis; LeBoeuf, David; Doiron-Leyraud, Nicolas; Chang, J.; Taillefer, Louis] Univ Sherbrooke, Dept Phys, Sherbrooke, PQ J1K 2R1, Canada.
   [Cyr-Choiniere, Olivier; Daou, R.; Laliberte, Francis; LeBoeuf, David; Doiron-Leyraud, Nicolas; Chang, J.; Taillefer, Louis] Univ Sherbrooke, RQMP, Sherbrooke, PQ J1K 2R1, Canada.
   [Yan, J. -Q.; Cheng, J. -G.; Zhou, J. -S.; Goodenough, J. B.] Univ Texas Austin, Texas Mat Inst, Austin, TX 78712 USA.
   [Pyon, S.; Takayama, T.; Takagi, H.; Tanaka, Y.] Univ Tokyo, Dept Adv Mat, Kashiwa, Chiba 2778561, Japan.
   [Takagi, H.] RIKEN, Inst Phys & Chem Res, Wako, Saitama 3510198, Japan.
   [Tanaka, Y.] RIKEN, SPring8 Ctr, Mikazuki, Hyogo 6795148, Japan.
   [Taillefer, Louis] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
C3 University of Sherbrooke; University of Sherbrooke; University of Texas System; University of Texas Austin; University of Tokyo; RIKEN; RIKEN; 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; US National Science Foundation; MEXT Japan; National Science and Engineering Research Council of Canada; Fonds Quebecois de la Recherche sur la Nature et les Technologies and a Canada Research Chair; Direct For Mathematical & Physical Scien; Division Of Materials Research [0904282] Funding Source: National Science Foundation
NR 19
TC 117
Z9 131
U1 0
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 9
PY 2009
VL 458
IS 7239
BP 743
EP 745
DI 10.1038/nature07931
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600036
PM 19360083
DA 2026-03-09
ER

PT J
AU Sanada, M
   Suzuki, T
   Shih, LY
   Otsu, M
   Kato, M
   Yamazaki, S
   Tamura, A
   Honda, H
   Sakata-Yanagimoto, M
   Kumano, K
   Oda, H
   Yamagata, T
   Takita, J
   Gotoh, N
   Nakazaki, K
   Kawamata, N
   Onodera, M
   Nobuyoshi, M
   Hayashi, Y
   Harada, H
   Kurokawa, M
   Chiba, S
   Mori, H
   Ozawa, K
   Omine, M
   Hirai, H
   Nakauchi, H
   Koeffler, HP
   Ogawa, S
AF Sanada, Masashi
   Suzuki, Takahiro
   Shih, Lee-Yung
   Otsu, Makoto
   Kato, Motohiro
   Yamazaki, Satoshi
   Tamura, Azusa
   Honda, Hiroaki
   Sakata-Yanagimoto, Mamiko
   Kumano, Keiki
   Oda, Hideaki
   Yamagata, Tetsuya
   Takita, Junko
   Gotoh, Noriko
   Nakazaki, Kumi
   Kawamata, Norihiko
   Onodera, Masafumi
   Nobuyoshi, Masaharu
   Hayashi, Yasuhide
   Harada, Hiroshi
   Kurokawa, Mineo
   Chiba, Shigeru
   Mori, Hiraku
   Ozawa, Keiya
   Omine, Mitsuhiro
   Hirai, Hisamaru
   Nakauchi, Hiromitsu
   Koeffler, H. Phillip
   Ogawa, Seishi
TI Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; retroviral vector gcdnsap; myelodysplastic syndrm; negative regulation; ubiquitin ligases; v-cbl; mutations; protein; p53; transformation
AB Acquired uniparental disomy(aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes(1), but also with gain-of-function mutations of proto-oncogenes(2). Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases(3-6). Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl(-/-) haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl(+/+) HSPCs, and transduction of C-CBL mutants into c-Cbl(-/-) HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl(-/-) background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some myeloid cancer subsets.
C1 [Sanada, Masashi; Kato, Motohiro; Tamura, Azusa; Takita, Junko; Nakazaki, Kumi; Ogawa, Seishi] Univ Tokyo, Canc Genom Project, Bunkyo Ku, Tokyo 1138655, Japan.
   [Kato, Motohiro; Takita, Junko] Univ Tokyo, Dept Pediat, Bunkyo Ku, Tokyo 1138655, Japan.
   [Kumano, Keiki; Takita, Junko; Nakazaki, Kumi; Kurokawa, Mineo; Hirai, Hisamaru] Univ Tokyo, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan.
   [Sanada, Masashi; Yamazaki, Satoshi; Nakauchi, Hiromitsu; Ogawa, Seishi] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan.
   [Suzuki, Takahiro; Nobuyoshi, Masaharu; Ozawa, Keiya] Jichi Med Univ, Dept Med, Div Hematol, Shimotsuke, Tochigi 3290498, Japan.
   [Shih, Lee-Yung] Chang Gung Univ, Chang Gung Mem Hosp, Dept Internal Med, Div Hematol Oncol, Taipei 105, Taiwan.
   [Otsu, Makoto; Nakauchi, Hiromitsu] Univ Tokyo, Div Stem Cell Therapy, Ctr Stem Cell & Regenerat Med, Minato Ku, Tokyo 1088639, Japan.
   [Gotoh, Noriko] Univ Tokyo, Div Syst Biomed Technol, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan.
   [Honda, Hiroaki] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Dev Biol, Minami Ku, Hiroshima 7348553, Japan.
   [Sakata-Yanagimoto, Mamiko; Chiba, Shigeru] Univ Tsukuba, Inst Clin Med, Dept Clin & Expt Hematol, Tsukuba, Ibaraki 3058571, Japan.
   [Oda, Hideaki] Tokyo Womens Med Univ, Dept Pathol, Shinjuku Ku, Tokyo 1628666, Japan.
   [Yamagata, Tetsuya] Dokkyo Univ, Sch Med, Dept Hematol, Mibu, Tochigi 3210293, Japan.
   [Kawamata, Norihiko; Koeffler, H. Phillip] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   [Onodera, Masafumi] Natl Res Inst Child Hlth & Dev, Dept Genet, Setagaya Ku, Tokyo 1578535, Japan.
   [Hayashi, Yasuhide] Gunma Childrens Med Ctr, Shibukawa, Gunma 3778577, Japan.
   [Harada, Hiroshi; Mori, Hiraku; Omine, Mitsuhiro] Showa Univ, Fujigaoka Hosp, Div Hematol, Aoba Ku, Kanagawa 2278501, Japan.
C3 University of Tokyo; University of Tokyo; University of Tokyo; Japan Science & Technology Agency (JST); Jichi Medical University; Chang Gung University; Chang Gung Memorial Hospital; University of Tokyo; University of Tokyo; Hiroshima University; University of Tsukuba; Tokyo Women's Medical University; Dokkyo Medical University; Cedars Sinai Medical Center; National Center for Child Health & Development - Japan; Gunma Children's Medical Centre; Showa Medical University
RP Ogawa, S (corresponding author), Univ Tokyo, Canc Genom Project, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM sly7012@adm.cgmh.org.tw; sogawa-tky@umin.ac.jp
FU Core Research for Evolutional Science and Technology; Japan Science and Technology Agency; Ministry of Health, Labor and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology; National Health Research Institute, Taiwan [NHRI-EX96-9434SI, NIH-2R01CA026038-30]; Grants-in-Aid for Scientific Research [21390316] Funding Source: KAKEN
NR 36
TC 352
Z9 390
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 13
PY 2009
VL 460
IS 7257
BP 904
EP U145
DI 10.1038/nature08240
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300041
PM 19620960
DA 2026-03-09
ER

PT J
AU Davis, DA
   Hamilton, A
   Yang, JL
   Cremar, LD
   Van Gough, D
   Potisek, SL
   Ong, MT
   Braun, PV
   Martínez, TJ
   White, SR
   Moore, JS
   Sottos, NR
AF Davis, Douglas A.
   Hamilton, Andrew
   Yang, Jinglei
   Cremar, Lee D.
   Van Gough, Dara
   Potisek, Stephanie L.
   Ong, Mitchell T.
   Braun, Paul V.
   Martinez, Todd J.
   White, Scott R.
   Moore, Jeffrey S.
   Sottos, Nancy R.
TI Force-induced activation of covalent bonds in mechanoresponsive polymeric materials
SO NATURE
LA English
DT Article
ID molecular-dynamics; mechanotransduction
AB Mechanochemical transduction enables an extraordinary range of physiological processes such as the sense of touch, hearing, balance, muscle contraction, and the growth and remodelling of tissue and bone(1-6). Although biology is replete with materials systems that actively and functionally respond to mechanical stimuli, the default mechanochemical reaction of bulk polymers to large external stress is the unselective scission of covalent bonds, resulting in damage or failure(7). An alternative to this degradation process is the rational molecular design of synthetic materials such that mechanical stress favourably alters material properties. A few mechanosensitive polymers with this property have been developed(8-14); but their active response is mediated through non-covalent processes, which may limit the extent to which properties can be modified and the long-term stability in structural materials. Previously, we have shown with dissolved polymer strands incorporating mechanically sensitive chemical groups-so-called mechanophores-that the directional nature of mechanical forces can selectively break and re-form covalent bonds(15,16). We now demonstrate that such force-induced covalent-bond activation can also be realized with mechanophore-linked elastomeric and glassy polymers, by using a mechanophore that changes colour as it undergoes a reversible electrocyclic ring-opening reaction under tensile stress and thus allows us to directly and locally visualize the mechanochemical reaction. We find that pronounced changes in colour and fluorescence emerge with the accumulation of plastic deformation, indicating that in these polymeric materials the transduction of mechanical force into the ring-opening reaction is an activated process. We anticipate that force activation of covalent bonds can serve as a general strategy for the development of new mechanophore building blocks that impart polymeric materials with desirable functionalities ranging from damage sensing to fully regenerative self-healing.
C1 [Yang, Jinglei; Braun, Paul V.; Martinez, Todd J.; White, Scott R.; Moore, Jeffrey S.; Sottos, Nancy R.] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA.
   [Davis, Douglas A.; Cremar, Lee D.; Potisek, Stephanie L.; Ong, Mitchell T.; Braun, Paul V.; Martinez, Todd J.; Moore, Jeffrey S.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Hamilton, Andrew] Univ Illinois, Dept Engn Sci & Mech, Urbana, IL 61801 USA.
   [Van Gough, Dara; Braun, Paul V.; Moore, Jeffrey S.; Sottos, Nancy R.] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA.
   [White, Scott R.] Univ Illinois, Dept Aerosp Engn, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Sottos, NR (corresponding author), Univ Illinois, Beckman Inst, Urbana, IL 61801 USA.
EM n-sottos@illinois.edu
FU ARO MURI programme [W911NF-07-1-0409]
NR 27
TC 1542
Z9 1783
U1 29
U2 1464
PU NATURE PUBLISHING 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 7
PY 2009
VL 459
IS 7243
BP 68
EP 72
DI 10.1038/nature07970
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300030
PM 19424152
DA 2026-03-09
ER

PT J
AU Weiss, LA
   Arking, DE
AF Weiss, Lauren A.
   Arking, Dan E.
TI A genome-wide linkage and association scan reveals novel loci for autism
SO NATURE
LA English
DT Article
ID spectrum disorders; genetic variant; expression; gtf2ird1; deficits; cntnap2; cortex; risk
AB Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success(1). Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families ( 1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 ( between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.
C1 [Weiss, Lauren A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Weiss, Lauren A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Weiss, Lauren A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Arking, Dan E.] Johns Hopkins Univ, Ctr Complex Dis Genom, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Johns Hopkins University
RP Weiss, LA (corresponding author), Univ Calif San Francisco, Dept Psychiat, Inst Human Genet, Ctr Neurobiol & Psychiat, San Francisco, CA 94143 USA.
FU National Center for Research Resources [U54 RR020278]; National Institutes of Mental Health [MH60007, MH081754]; Simons Foundation; Autism Consortium of Boston; NIMH [1R01 MH083565, 1K23MH080954]; Nancy Lurie Marks ( NLM) Family Foundation; National Institute of Health [MH52708, MH39437, MH00219, MH00980, MH6454, MH61009, MH55135, MH55284, HD055782, NS042165]; National Health Medical Research Council [0034328]; Scottish Rite; Spunk Fund, Inc.; Rebecca and Solomon Baker Fund; APEX Foundation; National Alliance for Research in Schizophrenia and Affective Disorders ( NARSAD),; Nancy Pritzker Laboratory; Cure Autism Now Foundation; Fundacao Calouste Gulbenkian; INSERM, Fondation de France, Fondation Orange; Fondation pour la Recherche Medicale; Swedish Science Council; The Seaver Foundation; The Children's Medical & Research Foundation; Our Lady's Children's Hospital, Crumlin, Ireland; The Medical Research Council ( MRC); MRC [G0601030] Funding Source: UKRI; Medical Research Council [G0601030] Funding Source: researchfish
NR 42
TC 490
Z9 594
U1 0
U2 67
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 8
PY 2009
VL 461
IS 7265
BP 802
EP U62
DI 10.1038/nature08490
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500038
PM 19812673
DA 2026-03-09
ER

PT J
AU Sessions, OM
   Barrows, NJ
   Souza-Neto, JA
   Robinson, TJ
   Hershey, CL
   Rodgers, MA
   Ramirez, JL
   Dimopoulos, G
   Yang, PL
   Pearson, JL
   Garcia-Blanco, MA
AF Sessions, October M.
   Barrows, Nicholas J.
   Souza-Neto, Jayme A.
   Robinson, Timothy J.
   Hershey, Christine L.
   Rodgers, Mary A.
   Ramirez, Jose L.
   Dimopoulos, George
   Yang, Priscilla L.
   Pearson, James L.
   Garcia-Blanco, Mariano A.
TI Discovery of insect and human dengue virus host factors
SO NATURE
LA English
DT Article
ID west-nile-virus; alpha-glucosidase inhibitors; japanese encephalitis-virus; unfolded protein response; endoplasmic-reticulum; nuclear-localization; endocytic pathway; bafilomycin a1; infected-cells; aedes-aegypti
AB Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection(1). The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat(1,2). Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified(3-10). Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and alpha-glucosidases)(3-5,7,9,10), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.
C1 [Sessions, October M.; Robinson, Timothy J.; Pearson, James L.; Garcia-Blanco, Mariano A.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
   [Sessions, October M.; Barrows, Nicholas J.; Pearson, James L.; Garcia-Blanco, Mariano A.] Duke Univ, Med Ctr, Ctr RNA Biol, Durham, NC 27710 USA.
   [Barrows, Nicholas J.; Pearson, James L.; Garcia-Blanco, Mariano A.] Duke Univ, Med Ctr, Duke RNAi Facil, Durham, NC 27710 USA.
   [Barrows, Nicholas J.] Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27710 USA.
   [Robinson, Timothy J.] Duke Univ, Med Ctr, Med Scientist Training Program, Durham, NC 27710 USA.
   [Robinson, Timothy J.] Duke Univ, Med Ctr, Program Mol Canc Biol, Durham, NC 27710 USA.
   [Souza-Neto, Jayme A.; Ramirez, Jose L.; Dimopoulos, George] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
   [Souza-Neto, Jayme A.; Ramirez, Jose L.; Dimopoulos, George] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD 21205 USA.
   [Hershey, Christine L.; Rodgers, Mary A.; Yang, Priscilla L.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
   [Garcia-Blanco, Mariano A.] Duke NUS Grad Med Sch, Programin Emerging Infect Dis, Singapore 169547, Singapore.
C3 Duke University; Duke University; Duke University; Duke University; Duke University; Duke University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Harvard University; Harvard Medical School; National University of Singapore
RP Pearson, JL (corresponding author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM pears016@mc.duke.edu; garci001@mc.duke.edu
FU National Institutes of Health (NIH) [RO1 GM067761, R21-AI64925, 5U54-AI057157-05S, 1RO1AI076442, 1R01AI061576-01, 1SA0RR024572-1]; American Society of Microbiology; Johns Hopkins Malaria Research Institute; North Carolina Biotechnology Center; Duke Center for RNA Biology; Duke University School of Medicine; Institute of Genome Sciences and Policy; Duke Comprehensive Cancer Center [5P30-CA14236]; National Cancer Institute [P30CA014236] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007417] Funding Source: NIH RePORTER
NR 30
TC 314
Z9 382
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 APR 23
PY 2009
VL 458
IS 7241
BP 1047
EP 1050
DI 10.1038/nature07967
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900047
PM 19396146
DA 2026-03-09
ER

PT J
AU Hearn, EM
   Patel, DR
   Lepore, BW
   Indic, M
   van den Berg, B
AF Hearn, Elizabeth M.
   Patel, Dimki R.
   Lepore, Bryan W.
   Indic, Mridhu
   van den Berg, Bert
TI Transmembrane passage of hydrophobic compounds through a protein channel wall
SO NATURE
LA English
DT Article
ID fatty-acid transport; escherichia-coli; multidrug transporter; membrane-protein; p-glycoprotein; cytoplasmic leaflet; lactococcus-lactis; crystal-structure; plasma-membrane; fadl gene
AB Membrane proteins that transport hydrophobic compounds have important roles in multi-drug resistance(1-3) and can cause a number of diseases(4,5), underscoring the importance of protein-mediated transport of hydrophobic compounds. Hydrophobic compounds readily partition into regular membrane lipid bilayers(6), and their transport through an aqueous protein channel is energetically unfavourable(3). Alternative transport models involving acquisition from the lipid bilayer by lateral diffusion have been proposed for hydrophobic substrates(3,4,7-12). So far, all transport proteins for which a lateral diffusion mechanism has been proposed function as efflux pumps. Here we present the first example of a lateral diffusion mechanism for the uptake of hydrophobic substrates by the Escherichia coli outer membrane long-chain fatty acid transporter FadL. A FadL mutant in which a lateral opening in the barrel wall is constricted, but which is otherwise structurally identical to wild-type FadL, does not transport substrates. A crystal structure of FadL from Pseudomonas aeruginosa shows that the opening in the wall of the beta-barrel is conserved and delineates a long, hydrophobic tunnel that could mediate substrate passage from the extracellular environment, through the polar lipopolysaccharide layer and, by means of the lateral opening in the barrel wall, into the lipid bilayer from where the substrate can diffuse into the periplasm. Because FadL homologues are found in pathogenic and biodegrading bacteria, our results have implications for combating bacterial infections and bioremediating xenobiotics in the environment.
C1 [Hearn, Elizabeth M.; Patel, Dimki R.; Lepore, Bryan W.; Indic, Mridhu; van den Berg, Bert] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester
RP van den Berg, B (corresponding author), Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
EM bert.vandenberg@umassmed.edu
FU National Insitutes of Health; NIH [1R01GM074824]
NR 41
TC 125
Z9 166
U1 0
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 367
EP U134
DI 10.1038/nature07678
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600047
PM 19182779
DA 2026-03-09
ER

PT J
AU Tateishi, K
   Okada, Y
   Kallin, EM
   Zhang, Y
AF Tateishi, Keisuke
   Okada, Yuki
   Kallin, Eric M.
   Zhang, Yi
TI Role of Jhdm2a in regulating metabolic gene expression and obesity resistance
SO NATURE
LA English
DT Article
ID activated receptor-alpha; mitochondrial uncoupling protein; energy-balance; beta; thermogenesis; transcription; methylation; elements; muscle; mice
AB Recent studies indicate that the methylation state of histones can be dynamically regulated by histone methyltransferases and demethylases(1,2). The H3K9-specific demethylase Jhdm2a (also known as Jmjd1a and Kdm3a) has an important role in nuclear hormone receptor-mediated gene activation and male germ cell development(3,4). Through disruption of the Jhdm2a gene in mice, here we demonstrate that Jhdm2a is critically important in regulating the expression of metabolic genes. The loss of Jhdm2a function results in obesity and hyperlipidemia in mice. We provide evidence that the loss of Jhdm2a function disrupts beta-adrenergic-stimulated glycerol release and oxygen consumption in brown fat, and decreases fat oxidation and glycerol release in skeletal muscles. We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression. Furthermore, we demonstrate that beta-adrenergic activation-induced binding of Jhdm2a to the PPAR responsive element (PPRE) of the Ucp1 gene not only decreases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at the PPRE, but also facilitates the recruitment of Ppar gamma and Rxr alpha and their co-activators Pgc1 alpha (also known as Ppargc1a), CBP/p300 (Crebbp) and Src1 (Ncoa1) to the PPRE. Our studies thus demonstrate an essential role for Jhdm2a in regulating metabolic gene expression and normal weight control in mice.
C1 [Tateishi, Keisuke; Okada, Yuki; Kallin, Eric M.; Zhang, Yi] Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA.
   [Tateishi, Keisuke; Okada, Yuki; Kallin, Eric M.; Zhang, Yi] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
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
RP Zhang, Y (corresponding author), Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA.
EM yi_zhang@med.unc.edu
FU UNC Clinical Nutrition Research Unit [DK56350]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056350] Funding Source: NIH RePORTER
NR 23
TC 369
Z9 431
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 APR 9
PY 2009
VL 458
IS 7239
BP 757
EP 761
DI 10.1038/nature07777
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600040
PM 19194461
DA 2026-03-09
ER

PT J
AU Devlin, MJ
   Ade, PAR
   Aretxaga, I
   Bock, JJ
   Chapin, EL
   Griffin, M
   Gundersen, JO
   Halpern, M
   Hargrave, PC
   Hughes, DH
   Klein, J
   Marsden, G
   Martin, PG
   Mauskopf, P
   Moncelsi, L
   Netterfield, CB
   Ngo, H
   Olmi, L
   Pascale, E
   Patanchon, G
   Rex, M
   Scott, D
   Semisch, C
   Thomas, N
   Truch, MDP
   Tucker, C
   Tucker, GS
   Viero, MP
   Wiebe, DV
AF Devlin, Mark J.
   Ade, Peter A. R.
   Aretxaga, Itziar
   Bock, James J.
   Chapin, Edward L.
   Griffin, Matthew
   Gundersen, Joshua O.
   Halpern, Mark
   Hargrave, Peter C.
   Hughes, David H.
   Klein, Jeff
   Marsden, Gaelen
   Martin, Peter G.
   Mauskopf, Philip
   Moncelsi, Lorenzo
   Netterfield, Calvin B.
   Ngo, Henry
   Olmi, Luca
   Pascale, Enzo
   Patanchon, Guillaume
   Rex, Marie
   Scott, Douglas
   Semisch, Christopher
   Thomas, Nicholas
   Truch, Matthew D. P.
   Tucker, Carole
   Tucker, Gregory S.
   Viero, Marco P.
   Wiebe, Donald V.
TI Over half of the far-infrared background light comes from galaxies at z ≥ 1.2
SO NATURE
LA English
DT Article
ID degree extragalactic survey; deep submillimeter survey; field-south survey; number counts; source catalogs; star-formation; high-redshift; lockman hole; spitzer; chandra
AB Submillimetre surveys during the past decade have discovered a population of luminous, high-redshift, dusty starburst galaxies(1-8). In the redshift range 1 <= z <= 4, these massive submillimetre galaxies go through a phase characterized by optically obscured star formation at rates several hundred times that in the local Universe. Half of the starlight from this highly energetic process is absorbed and thermally re-radiated by clouds of dust at temperatures near 30 K with spectral energy distributions peaking at 100 mu m in the rest frame(9). At 1 <= z <= 4, the peak is redshifted to wavelengths between 200 and 500 mu m. The cumulative effect of these galaxies is to yield extragalactic optical and far-infrared backgrounds with approximately equal energy densities. Since the initial detection of the far-infrared background (FIRB)(10), higher-resolution experiments have sought to decompose this integrated radiation into the contributions from individual galaxies. Here we report the results of an extragalactic survey at 250, 350 and 500 mu m. Combining our results at 500 mu m with those at 24 mu m, we determine that all of the FIRB comes from individual galaxies, with galaxies at z >= 1.2 accounting for 70% of it. As expected, at the longest wavelengths the signal is dominated by ultraluminous galaxies at z > 1.
C1 [Devlin, Mark J.; Klein, Jeff; Rex, Marie; Semisch, Christopher; Truch, Matthew D. P.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
   [Ade, Peter A. R.; Griffin, Matthew; Hargrave, Peter C.; Mauskopf, Philip; Moncelsi, Lorenzo; Pascale, Enzo; Tucker, Carole] Cardiff Univ, Sch Phys & Astron, Cardiff CF24 3AA, S Glam, Wales.
   [Aretxaga, Itziar; Hughes, David H.] Inst Nacl Astrofis Opt & Electr, Puebla, Mexico.
   [Bock, James J.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Chapin, Edward L.; Halpern, Mark; Marsden, Gaelen; Ngo, Henry; Scott, Douglas] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Gundersen, Joshua O.; Thomas, Nicholas] Univ Miami, Dept Phys, Coral Gables, FL 33146 USA.
   [Martin, Peter G.] Univ Toronto, Canadian Inst Theoret Astrophys, Toronto, ON M5S 3H8, Canada.
   [Martin, Peter G.; Netterfield, Calvin B.; Viero, Marco P.] Univ Toronto, Dept Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Netterfield, Calvin B.; Wiebe, Donald V.] Univ Toronto, Dept Phys, Toronto, ON M5S 1A7, Canada.
   [Olmi, Luca] Univ Puerto Rico, Dept Phys, Rio Piedras, PR 00931 USA.
   [Olmi, Luca] INAF Osservatorio Astrofis Arcetri, I-50125 Florence, Italy.
   [Patanchon, Guillaume] Univ Paris Diderot, Lab APC, F-75205 Paris, France.
   [Tucker, Gregory S.] Brown Univ, Dept Phys, Providence, RI 02912 USA.
C3 University of Pennsylvania; Cardiff University; Instituto Nacional de Astrofisica, Optica y Electronica; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of British Columbia; University of Miami; University of Toronto; University of Toronto; University of Toronto; University of Puerto Rico; University of Puerto Rico Rio Piedras; Istituto Nazionale Astrofisica (INAF); Universite PSL; Observatoire de Paris; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Brown University
RP Devlin, MJ (corresponding author), Univ Penn, Dept Phys & Astron, 209 S 33rd St, Philadelphia, PA 19104 USA.
EM devlin@physics.upenn.edu
FU NASAUS National Science Foundation Office; Canadian Space Agency; Natural Sciences and Engineering Research Council of Canada; UK Science and Technology Facilities Council; STFC [ST/G002711/1] Funding Source: UKRI
NR 28
TC 155
Z9 179
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 APR 9
PY 2009
VL 458
IS 7239
BP 737
EP 739
DI 10.1038/nature07918
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600034
PM 19360081
DA 2026-03-09
ER

PT J
AU Smirnov, DA
   Morley, M
   Shin, E
   Spielman, RS
   Cheung, VG
AF Smirnov, Denis A.
   Morley, Michael
   Shin, Eunice
   Spielman, Richard S.
   Cheung, Vivian G.
TI Genetic analysis of radiation-induced changes in human gene expression
SO NATURE
LA English
DT Article
ID genome-wide association; cells; linkage; dissection; apoptosis; traits; growth
AB Humans are exposed to radiation through the environment and in medical settings. To deal with radiation-induced damage, cells mount complex responses that rely on changes in gene expression. These gene expression responses differ greatly between individuals(1) and contribute to individual differences in response to radiation(2). Here we identify regulators that influence expression levels of radiation-responsive genes. We treated radiation-induced changes in gene expression as quantitative phenotypes(3,4), and conducted genetic linkage and association studies to map their regulators. For more than 1,200 of these phenotypes there was significant evidence of linkage to specific chromosomal regions. Nearly all of the regulators act in trans to influence the expression of their target genes; there are very few cis-acting regulators. Some of the transacting regulators are transcription factors, but others are genes that were not known to have a regulatory function in radiation response. These results have implications for our basic and clinical understanding of how human cells respond to radiation.
C1 [Smirnov, Denis A.; Cheung, Vivian G.] Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
   [Morley, Michael; Shin, Eunice; Cheung, Vivian G.] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Spielman, Richard S.; Cheung, Vivian G.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
   [Cheung, Vivian G.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Howard Hughes Medical Institute; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Pennsylvania
RP Cheung, VG (corresponding author), Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
EM vcheung@mail.med.upenn.edu
FU National Center for Research Resources; National Institutes of Health; University of Pennsylvania Center for Excellence in Environmental Toxicology; W. W. Smith Endowed Chair; Howard Hughes Medical Institute
NR 30
TC 185
Z9 203
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 28
PY 2009
VL 459
IS 7246
BP 587
EP U120
DI 10.1038/nature07940
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500043
PM 19349959
DA 2026-03-09
ER

PT J
AU Wang, HH
   Isaacs, FJ
   Carr, PA
   Sun, ZZ
   Xu, G
   Forest, CR
   Church, GM
AF Wang, Harris H.
   Isaacs, Farren J.
   Carr, Peter A.
   Sun, Zachary Z.
   Xu, George
   Forest, Craig R.
   Church, George M.
TI Programming cells by multiplex genome engineering and accelerated evolution
SO NATURE
LA English
DT Article
ID escherichia-coli; lycopene biosynthesis; recombination; genes; identification; mutagenesis; improvement; efficiency; bacteria; pathway
AB The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments(1,2). However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales(3). Although in vitro and directed evolution methods(4-9) have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-D-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties.
C1 [Wang, Harris H.; Isaacs, Farren J.; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Wang, Harris H.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA.
   [Wang, Harris H.] MIT, Harvard Mit Div Hlth Sci & Technol, Program Med Engn Med Phys, Cambridge, MA 02139 USA.
   [Carr, Peter A.] MIT, Ctr Bits & Atoms, Cambridge, MA 02139 USA.
   [Carr, Peter A.] MIT, Media Lab, Cambridge, MA 02139 USA.
   [Sun, Zachary Z.; Xu, George] Harvard Univ, Cambridge, MA 02138 USA.
   [Forest, Craig R.] Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; University System of Georgia; Georgia Institute of Technology
RP Wang, HH (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM hhwang@genetics.med.harvard.edu; farren@alumni.upenn.edu
FU NSF; DOE; DARPA; Wyss Institute for Biologically Inspired Engineering; NIH; NDSEG
NR 32
TC 1176
Z9 1643
U1 9
U2 574
PU NATURE PUBLISHING 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 13
PY 2009
VL 460
IS 7257
BP 894
EP U133
DI 10.1038/nature08187
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300039
PM 19633652
DA 2026-03-09
ER

PT J
AU Trabucchi, M
   Briata, P
   Garcia-Mayoral, M
   Haase, AD
   Filipowicz, W
   Ramos, A
   Gherzi, R
   Rosenfeld, MG
AF Trabucchi, Michele
   Briata, Paola
   Garcia-Mayoral, MariaFlor
   Haase, Astrid D.
   Filipowicz, Witold
   Ramos, Andres
   Gherzi, Roberto
   Rosenfeld, Michael G.
TI The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs
SO NATURE
LA English
DT Article
ID posttranscriptional regulation; dicer; expression; mirnas; lin-28; trbp
AB Consistent with the role of microRNAs (miRNAs) in down-regulating gene expression by reducing the translation and/or stability of target messenger RNAs1, the levels of specific miRNAs are important for correct embryonic development and have been linked to several forms of cancer(2-4). However, the regulatory mechanisms by which primary miRNAs (pri-miRNAs) are processed first to precursor miRNAs (pre-miRNAs) and then to mature miRNAs by the multiprotein Drosha and Dicer complexes(5-8), respectively, remain largely unknown. The KH-type splicing regulatory protein (KSRP, also known as KHSRP) interacts with single-strand AU-rich-element-containing mRNAs and is a key mediator of mRNA decay(9,10). Here we show in mammalian cells that KSRP also serves as a component of both Drosha and Dicer complexes and regulates the biogenesis of a subset of miRNAs. KSRP binds with high affinity to the terminal loop of the target miRNA precursors and promotes their maturation. This mechanism is required for specific changes in target mRNA expression that affect specific biological programs, including proliferation, apoptosis and differentiation. These findings reveal an unexpected mechanism that links KSRP to the machinery regulating maturation of a cohort of miRNAs that, in addition to its role in promoting mRNA decay, independently serves to integrate specific regulatory programs of protein expression.
C1 [Trabucchi, Michele; Rosenfeld, Michael G.] Univ Calif San Diego, Howard Hughes Med Inst, Dept & Sch Med, La Jolla, CA 92093 USA.
   [Briata, Paola; Gherzi, Roberto] Ist Nazl Ric Canc IST, I-16132 Genoa, Italy.
   [Garcia-Mayoral, MariaFlor; Ramos, Andres] Natl Inst Med Res, Div Mol Struct, London NW7 1AA, England.
   [Haase, Astrid D.; Filipowicz, Witold] Friedrich Miescher Inst Biomed Res, CH-4002 Basel, Switzerland.
C3 Howard Hughes Medical Institute; University of California System; University of California San Diego; University of Genoa; IRCCS AOU San Martino IST; MRC National Institute for Medical Research; Friedrich Miescher Institute for Biomedical Research
RP Rosenfeld, MG (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, Dept & Sch Med, 9500 Gilman Dr,Room 345, La Jolla, CA 92093 USA.
EM aramos@nimr.mrc.ac.uk; rgherzi@ucsd.edu; mrosenfeld@ucsd.edu
FU Italian ISS [527B/2B/6]; AIRC; CIPE; ISS [526D/39]; EC; NIH [DK018477, DK39949, HL065445]; AICF; Wellcome Trust [WT022088MA]; Novartis Research Foundation; MRC [MC_U117574558, MC_U117533887] Funding Source: UKRI; Medical Research Council [MC_U117533887, MC_U117574558] Funding Source: researchfish; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK039949, R01DK018477] Funding Source: NIH RePORTER; Fondazione Telethon Funding Source: Custom
NR 40
TC 537
Z9 636
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 JUN 18
PY 2009
VL 459
IS 7249
BP 1010
EP U144
DI 10.1038/nature08025
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500048
PM 19458619
DA 2026-03-09
ER

PT J
AU Israelian, G
   Mena, ED
   Santos, NC
   Sousa, SG
   Mayor, M
   Udry, S
   Cerdena, CD
   Rebolo, R
   Randich, S
AF Israelian, Garik
   Mena, Elisa Delgado
   Santos, Nuno C.
   Sousa, Sergio G.
   Mayor, Michel
   Udry, Stephane
   Cerdena, Carolina Dominguez
   Rebolo, Rafael
   Randich, Sofia
TI Enhanced lithium depletion in Sun-like stars with orbiting planets
SO NATURE
LA English
DT Article
ID exoplanet host stars; open clusters; abundances; solar; sample; dwarf; fe/h; ages; ix
AB The surface abundance of lithium on the Sun is 140 times less than the protosolar value(1), yet the temperature at the base of the surface convective zone is not hot enough to burn-and hence deplete-Li (refs 2, 3). A large range of Li abundances is observed(4,5) in solar-type stars of the same age, mass and metallicity as the Sun, but such a range is theoretically difficult to understand(3,6,7). An earlier suggestion(8-10) that Li is more depleted in stars with planets was weakened by the lack of a proper comparison sample of stars without detected planets. Here we report Li abundances for an unbiased sample of solar-analogue stars with and without detected planets. We find that the planet-bearing stars have less than one per cent of the primordial Li abundance, while about 50 per cent of the solar analogues without detected planets have on average ten times more Li. The presence of planets may increase the amount of mixing and deepen the convective zone to such an extent that the Li can be burned.
C1 [Israelian, Garik; Mena, Elisa Delgado; Sousa, Sergio G.; Cerdena, Carolina Dominguez; Rebolo, Rafael] Inst Astrofis Canarias, E-38200 San Cristobal la Laguna, Spain.
   [Israelian, Garik; Mena, Elisa Delgado; Cerdena, Carolina Dominguez; Rebolo, Rafael] Univ La Laguna, Dept Astrofis, E-38205 San Cristobal la Laguna, Spain.
   [Santos, Nuno C.; Sousa, Sergio G.] Univ Porto, Ctr Astrofis, P-4150762 Oporto, Portugal.
   [Santos, Nuno C.; Mayor, Michel; Udry, Stephane] Univ Geneva, Observ Geneva, CH-1290 Versoix, Switzerland.
   [Rebolo, Rafael] CSIC, E-28006 Madrid, Spain.
   [Randich, Sofia] Osserv Astrofis Arcetri, Inst Nazl Astrofis, I-59125 Florence, Italy.
C3 Instituto de Astrofisica de Canarias; Universidad de la Laguna; Universidade do Porto; University of Geneva; Consejo Superior de Investigaciones Cientificas (CSIC); Istituto Nazionale Astrofisica (INAF)
RP Israelian, G (corresponding author), Inst Astrofis Canarias, Via Lactea S-N, E-38200 San Cristobal la Laguna, Spain.
EM gil@iac.es
FU Spanish Ministry of Science and Innovation; Fundacao para a Ciencia e a Tecnologia, Portugal [Ciencia 2007]
NR 30
TC 136
Z9 150
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 NOV 12
PY 2009
VL 462
IS 7270
BP 189
EP 191
DI 10.1038/nature08483
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100036
PM 19907489
DA 2026-03-09
ER

PT J
AU Kohyama, M
   Ise, W
   Edelson, BT
   Wilker, PR
   Hildner, K
   Mejia, C
   Frazier, WA
   Murphy, TL
   Murphy, KM
AF Kohyama, Masako
   Ise, Wataru
   Edelson, Brian T.
   Wilker, Peter R.
   Hildner, Kai
   Mejia, Carlo
   Frazier, William A.
   Murphy, Theresa L.
   Murphy, Kenneth M.
TI Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis
SO NATURE
LA English
DT Article
ID ets protein; in-vivo; b-cells; expression; gene; hemochromatosis; mice; heterogeneity; recognition; receptors
AB Tissue macrophages comprise a heterogeneous group of cell types differing in location, surface markers and function(1). Red pulp macrophages are a distinct splenic subset involved in removing senescent red blood cells(2). Transcription factors such as PU.1 ( also known as Sfpi1) and C/EBPa (Cebpa) have general roles in myelomonocytic development(3,4), but the transcriptional basis for producing tissue macrophage subsets remains unknown. Here we show that Spi-C ( encoded by Spic), a PU.1- related transcription factor, selectively controls the development of red pulp macrophages. Spi-C is highly expressed in red pulp macrophages, but not monocytes, dendritic cells or other tissue macrophages. Spic(-/-) mice have a cell- autonomous defect in the development of red pulp macrophages that is corrected by retroviral Spi- C expression in bone marrow cells, but have normal monocyte and other macrophage subsets. Red pulp macrophages highly express genes involved in capturing circulating haemoglobin and in iron regulation. Spic(-/-) mice show ormal trapping of red blood cells in the spleen, but fail to phagocytose these red blood cells efficiently, and develop an iron overload localized selectively to splenic red pulp. Thus, Spi- C controls development of red pulp macrophages required for red blood cell recycling and iron homeostasis.
C1 [Kohyama, Masako; Ise, Wataru; Edelson, Brian T.; Wilker, Peter R.; Hildner, Kai; Mejia, Carlo; Murphy, Theresa L.; Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Kohyama, Masako; Ise, Wataru; Hildner, Kai; Mejia, Carlo; Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
   [Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Howard Hughes Medical Institute; Washington University (WUSTL); Washington University (WUSTL)
RP Murphy, KM (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM murphy@wustl.edu
FU Howard Hughes Medical Institute; Burroughs Wellcome Fund Career Award for Medical Scientists
NR 30
TC 353
Z9 463
U1 1
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 318
EP 321
DI 10.1038/nature07472
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900040
PM 19037245
DA 2026-03-09
ER

PT J
AU Lin, YJ
   Compton, RL
   Jiménez-García, K
   Porto, JV
   Spielman, IB
AF Lin, Y. -J.
   Compton, R. L.
   Jimenez-Garcia, K.
   Porto, J. V.
   Spielman, I. B.
TI Synthetic magnetic fields for ultracold neutral atoms
SO NATURE
LA English
DT Article
ID quantum; vortices
AB Neutral atomic Bose condensates and degenerate Fermi gases have been used to realize important many-body phenomena in their most simple and essential forms(1-3), without many of the complexities usually associated with material systems. However, the charge neutrality of these systems presents an apparent limitation-a wide range of intriguing phenomena arise from the Lorentz force for charged particles in a magnetic field, such as the fractional quantum Hall effect in two-dimensional electron systems(4,5). The limitation can be circumvented by exploiting the equivalence of the Lorentz force and the Coriolis force to create synthetic magnetic fields in rotating neutral systems. This was demonstrated by the appearance of quantized vortices in pioneering experiments(6-9) on rotating quantum gases, a hallmark of superfluids or superconductors in a magnetic field. However, because of technical issues limiting the maximum rotation velocity, the metastable nature of the rotating state and the difficulty of applying stable rotating optical lattices, rotational approaches are not able to reach the large fields required for quantum Hall physics(10-12). Here we experimentally realize an optically synthesized magnetic field for ultracold neutral atoms, which is evident from the appearance of vortices in our Bose-Einstein condensate. Our approach uses a spatially dependent optical coupling between internal states of the atoms, yielding a Berry's phase(13) sufficient to create large synthetic magnetic fields, and is not subject to the limitations of rotating systems. With a suitable lattice configuration, it should be possible to reach the quantum Hall regime, potentially enabling studies of topological quantum computation.
C1 [Lin, Y. -J.; Compton, R. L.; Jimenez-Garcia, K.; Porto, J. V.; Spielman, I. B.] NIST, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
   [Lin, Y. -J.; Compton, R. L.; Jimenez-Garcia, K.; Porto, J. V.; Spielman, I. B.] Univ Maryland, Gaithersburg, MD 20899 USA.
   [Jimenez-Garcia, K.] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Fis, Mexico City 07360, DF, Mexico.
C3 National Institute of Standards & Technology (NIST) - USA; University System of Maryland; University of Maryland College Park; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; Instituto Politecnico Nacional - Mexico
RP Spielman, IB (corresponding author), NIST, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
EM ian.spielman@nist.gov
FU DARPA OLE programme; NSF through the JQI Physics Frontier Center; NIST/ NRC postdoctoral programme; CONACYT; Direct For Mathematical & Physical Scien; Division Of Physics [0822671] Funding Source: National Science Foundation
NR 30
TC 1175
Z9 1306
U1 4
U2 179
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 628
EP 632
DI 10.1038/nature08609
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900036
PM 19956256
DA 2026-03-09
ER

PT J
AU Liu, JY
   O'Brien, KL
   Lynch, DM
   Simmons, NL
   La Porte, A
   Riggs, AM
   Abbink, P
   Coffey, RT
   Grandpre, LE
   Seaman, MS
   Landucci, G
   Forthal, DN
   Montefiori, DC
   Carville, A
   Mansfield, KG
   Havenga, MJ
   Pau, MG
   Goudsmit, J
   Barouch, DH
AF Liu, Jinyan
   O'Brien, Kara L.
   Lynch, Diana M.
   Simmons, Nathaniel L.
   La Porte, Annalena
   Riggs, Ambryice M.
   Abbink, Peter
   Coffey, Rory T.
   Grandpre, Lauren E.
   Seaman, Michael S.
   Landucci, Gary
   Forthal, Donald N.
   Montefiori, David C.
   Carville, Angela
   Mansfield, Keith G.
   Havenga, Menzo J.
   Pau, Maria G.
   Goudsmit, Jaap
   Barouch, Dan H.
TI Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys
SO NATURE
LA English
DT Article
ID immunodeficiency virus sivmac239; simian-immunodeficiency; adenovirus vectors; replication; infection; memory; immunogenicity; responses; hiv; mamu-a-asterisk-01
AB A recombinant adenovirus serotype 5 ( rAd5) vector- based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans(1,2). Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys ( Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 ( ref. 3). Here we show that an improved T- cell- based vaccine regimen using two serologically distinct adenovirus vectors afforded substantially improved protective efficacy in this challenge model. In particular, a heterologous rAd26 prime/rAd5 boost vaccine regimen expressing SIV Gag elicited cellular immune responses with augmented magnitude, breadth and polyfunctionality as compared with the homologous rAd5 regimen. After SIVMAC251 challenge, monkeys vaccinated with the rAd26/rAd5 regimen showed a 1.4 log reduction of peak and a 2.4 log reduction of setpoint viral loads as well as decreased AIDS- related mortality as compared with control animals. These data demonstrate that durable partial immune control of a pathogenic SIV challenge for more than 500 days can be achieved by a T- cell- based vaccine in Mamu-A*01-negative rhesus monkeys in the absence of a homologous Env antigen. These findings have important implications for the development of next- generation T- cell- based vaccine candidates for HIV- 1.
C1 [Liu, Jinyan; O'Brien, Kara L.; Lynch, Diana M.; Simmons, Nathaniel L.; La Porte, Annalena; Riggs, Ambryice M.; Abbink, Peter; Coffey, Rory T.; Grandpre, Lauren E.; Seaman, Michael S.; Barouch, Dan H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA.
   [Landucci, Gary; Forthal, Donald N.] Univ Calif Irvine, Sch Med, Irvine, CA 92697 USA.
   [Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
   [Carville, Angela; Mansfield, Keith G.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA.
   [Havenga, Menzo J.] TNO Biosci, NL-2301 CE Leiden, Netherlands.
   [Pau, Maria G.; Goudsmit, Jaap] Crucell Holland BV, NL-2301 CA Leiden, Netherlands.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; University of California System; University of California Irvine; Duke University; Netherlands Organization Applied Science Research; Johnson & Johnson; Johnson & Johnson Netherlands
RP Barouch, DH (corresponding author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA.
EM dbarouch@bidmc.harvard.edu
FU NIH [AI066305, AI066924, AI078526, AI030034, RR000168]
NR 30
TC 386
Z9 476
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 1
PY 2009
VL 457
IS 7225
BP 87
EP 91
DI 10.1038/nature07469
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900036
PM 18997770
DA 2026-03-09
ER

PT J
AU Ferraro, FR
   Beccari, G
   Dalessandro, E
   Lanzoni, B
   Sills, A
   Rood, RT
   Pecci, FF
   Karakas, AI
   Miocchi, P
   Bovinelli, S
AF Ferraro, F. R.
   Beccari, G.
   Dalessandro, E.
   Lanzoni, B.
   Sills, A.
   Rood, R. T.
   Pecci, F. Fusi
   Karakas, A. I.
   Miocchi, P.
   Bovinelli, S.
TI Two distinct sequences of blue straggler stars in the globular cluster M 30
SO NATURE
LA English
DT Article
ID stellar collisions; dynamical models; main-sequence; mass-transfer; parameters; catalog; origin
AB Stars in globular clusters are generally believed to have all formed at the same time, early in the Galaxy's history(1). 'Blue stragglers' are stars massive enough(2) that they should have evolved into white dwarfs long ago. Two possible mechanisms have been proposed for their formation: mass transfer between binary companions(3) and stellar mergers resulting from direct collisions between two stars(4). Recently the binary explanation was claimed to be dominant(5). Here we report that there are two distinct parallel sequences of blue stragglers in M 30. This globular cluster is thought to have undergone 'core collapse', during which both the collision rate and the mass transfer activity in binary systems would have been enhanced(6). We suggest that the two observed sequences are a consequence of cluster core collapse, with the bluer population arising from direct stellar collisions and the redder one arising from the evolution of close binaries that are probably still experiencing an active phase of mass transfer.
C1 [Ferraro, F. R.; Dalessandro, E.; Lanzoni, B.; Miocchi, P.; Bovinelli, S.] Univ Bologna, Dept Astron, I-40127 Bologna, Italy.
   [Beccari, G.] European Space Agcy, Dept Space Sci, NL-2200 AG Noordwijk, Netherlands.
   [Sills, A.] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada.
   [Rood, R. T.] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Pecci, F. Fusi] Osservatorio Astron Bologna, INAF, I-40127 Bologna, Italy.
   [Karakas, A. I.] Mt Stromlo & Siding Spring Observ, Res Sch Astron & Astrophys, Weston, ACT 2611, Australia.
C3 University of Bologna; European Space Agency; McMaster University; University of Virginia; Istituto Nazionale Astrofisica (INAF); Australian National University
RP Ferraro, FR (corresponding author), Univ Bologna, Dept Astron, Via Ranzani 1, I-40127 Bologna, Italy.
EM francesco.ferraro3@unibo.it
FU Istituto Nazionale di Astrofisica; Agenzia Spaziale Italiana; Ministero dell'Istruzione, dell'Universita e della Ricerca; European Space Research and Technology Centre Faculty Visiting Scientist Programme; Space Telescope Science Institute
NR 29
TC 164
Z9 176
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1028
EP 1031
DI 10.1038/nature08607
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000040
PM 20033041
DA 2026-03-09
ER

PT J
AU Wang, RH
   Farrona, S
   Vincent, C
   Joecker, A
   Schoof, H
   Turck, F
   Alonso-Blanco, C
   Coupland, G
   Albani, MC
AF Wang, Renhou
   Farrona, Sara
   Vincent, Coral
   Joecker, Anika
   Schoof, Heiko
   Turck, Franziska
   Alonso-Blanco, Carlos
   Coupland, George
   Albani, Maria C.
TI PEP1 regulates perennial flowering in Arabis alpina
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; vernalization; gene; flc; protein; evolution; repressor; trimethylation; brassicaceae; methylation
AB Annual plants complete their life cycle in one year and initiate flowering only once, whereas perennials live for many years and flower repeatedly. How perennials undergo repeated cycles of vegetative growth and flowering that are synchronized to the changing seasons has not been extensively studied(1). Flowering is best understood in annual Arabidopsis thaliana 2,3, but many closely related species, such as Arabis alpina(4,5), are perennials. We identified the A. alpina mutant perpetual flowering 1 (pep1), and showed that PEP1 contributes to three perennial traits. It limits the duration of flowering, facilitating a return to vegetative development, prevents some branches from undergoing the floral transition allowing polycarpic growth habit, and confers a flowering response to winter temperatures that restricts flowering to spring. Here we show that PEP1 is the orthologue of the A. thaliana gene FLOWERING LOCUS C (FLC). The FLC transcription factor inhibits flowering until A. thaliana is exposed to winter temperatures(6,7), which trigger chromatin modifications that stably repress FLC transcription(8-11). In contrast, PEP1 is only transiently repressed by low temperatures, causing repeated seasonal cycles of repression and activation of PEP1 transcription that allow it to carry out functions characteristic of the cyclical life history of perennials. The patterns of chromatin modifications at FLC and PEP1 differ correlating with their distinct expression patterns. Thus we describe a critical mechanism by which flowering regulation differs between related perennial and annual species, and propose that differences in chromatin regulation contribute to this variation.
C1 [Wang, Renhou; Farrona, Sara; Vincent, Coral; Joecker, Anika; Schoof, Heiko; Turck, Franziska; Coupland, George; Albani, Maria C.] Max Planck Inst Plant Breeding Res, D-50829 Cologne, Germany.
   [Alonso-Blanco, Carlos] CSIC, Ctr Nacl Biotecnol, Dept Genet Mol Plantas, E-28049 Madrid, Spain.
C3 Max Planck Society; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB)
RP Coupland, G (corresponding author), Max Planck Inst Plant Breeding Res, Carl von Linne Weg 10, D-50829 Cologne, Germany.
EM coupland@mpiz-koeln.mpg.de; albani@mpiz-koeln.mpg.de
FU Max Planck Society
NR 41
TC 304
Z9 331
U1 1
U2 124
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2009
VL 459
IS 7245
BP 423
EP U138
DI 10.1038/nature07988
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700045
PM 19369938
DA 2026-03-09
ER

PT J
AU Lewis, SL
   Lopez-Gonzalez, G
   Sonké, B
   Affum-Baffoe, K
   Baker, TR
   Ojo, LO
   Phillips, OL
   Reitsma, JM
   White, L
   Comiskey, JA
   Djuikouo, MN
   Ewango, CEN
   Feldpausch, TR
   Hamilton, AC
   Gloor, M
   Hart, T
   Hladik, A
   Lloyd, J
   Lovett, JC
   Makana, JR
   Malhi, Y
   Mbago, FM
   Ndangalasi, HJ
   Peacock, J
   Peh, KSH
   Sheil, D
   Sunderland, T
   Swaine, MD
   Taplin, J
   Taylor, D
   Thomas, SC
   Votere, R
   Wöll, H
AF Lewis, Simon L.
   Lopez-Gonzalez, Gabriela
   Sonke, Bonaventure
   Affum-Baffoe, Kofi
   Baker, Timothy R.
   Ojo, Lucas O.
   Phillips, Oliver L.
   Reitsma, Jan M.
   White, Lee
   Comiskey, James A.
   Djuikouo K., Marie-Noel
   Ewango, Corneille E. N.
   Feldpausch, Ted R.
   Hamilton, Alan C.
   Gloor, Manuel
   Hart, Terese
   Hladik, Annette
   Lloyd, Jon
   Lovett, Jon C.
   Makana, Jean-Remy
   Malhi, Yadvinder
   Mbago, Frank M.
   Ndangalasi, Henry J.
   Peacock, Julie
   Peh, Kelvin S. -H.
   Sheil, Douglas
   Sunderland, Terry
   Swaine, Michael D.
   Taplin, James
   Taylor, David
   Thomas, Sean C.
   Votere, Raymond
   Woell, Hannsjoerg
TI Increasing carbon storage in intact African tropical forests
SO NATURE
LA English
DT Article
ID climate; biomass; impacts; balance; cycle
AB The response of terrestrial vegetation to a globally changing environment is central to predictions of future levels of atmospheric carbon dioxide(1,2). The role of tropical forests is critical because they are carbon- dense and highly productive(3,4). Inventory plots across Amazonia show that old- growth forests have increased in carbon storage over recent decades(5-7), but the response of one- third of the world's tropical forests in Africa(8) is largely unknown owing to an absence of spatially extensive observation networks(9,10). Here we report data from a ten- country network of long- term monitoring plots in African tropical forests. We find that across 79 plots ( 163 ha) above- ground carbon storage in live trees increased by 0.63 Mg C ha(-1) yr(-1) between 1968 and 2007 ( 95% confidence interval ( CI), 0.22 - 0.94; mean interval, 1987 - 96). Extrapolation to unmeasured forest components ( live roots, small trees, necromass) and scaling to the continent implies a total increase in carbon storage in African tropical forest trees of 0.34 Pg C yr(-1) ( CI, 0.15 - 0.43). These reported changes in carbon storage are similar to those reported for Amazonian forests per unit area(6,7), providing evidence that increasing carbon storage in old- growth forests is a pan- tropical phenomenon. Indeed, combining all standardized inventory data from this study and from tropical America and Asia(5,6,11) together yields a comparable figure of 0.49 Mg C ha(-1) yr(-1) (n = 156; 562 ha; CI, 0.29 - 0.66; mean interval, 1987 - 97). This indicates a carbon sink of 1.3 Pg C yr(-1) ( CI, 0.8 - 1.6) across all tropical forests during recent decades. Taxon- specific analyses of African inventory and other data(12) suggest that widespread changes in resource availability, such as increasing atmospheric carbon dioxide concentrations, may be the cause of the increase in carbon stocks(13), as some theory(14) and models(2,10,15) predict.
C1 [Lewis, Simon L.; Lopez-Gonzalez, Gabriela; Baker, Timothy R.; Phillips, Oliver L.; Feldpausch, Ted R.; Gloor, Manuel; Lloyd, Jon; Peacock, Julie; Peh, Kelvin S. -H.] Univ Leeds, Earth & Biosphere Inst, Sch Geog, Leeds LS2 9JT, W Yorkshire, England.
   [Sonke, Bonaventure; Djuikouo K., Marie-Noel] Univ Yaounde I, Plant Systemat & Ecol Lab, Yaounde, Cameroon.
   [Affum-Baffoe, Kofi; Votere, Raymond] Forestry Commiss Ghana, Resource Management Support Ctr, Kumasi, Ghana.
   [Ojo, Lucas O.] Univ Agr, Dept Environm Management & Toxicol, Abeokuta, Ogun, Nigeria.
   [Reitsma, Jan M.] Bur Waardenburg BV, NL-4100 AJ Culemborg, Netherlands.
   [White, Lee] IRET, Libreville, Gabon.
   [Comiskey, James A.; Sunderland, Terry] Smithsonian Inst, SI MAB Biodivers Program, Washington, DC 20560 USA.
   [Ewango, Corneille E. N.] Univ Wageningen & Res Ctr, Dept Environm Sci, Forest Ecol & Management Grp, NL-6700 Wageningen, Netherlands.
   [Hamilton, Alan C.] Plantlife Int, Salisbury SP1 1DX, Wilts, England.
   [Hart, Terese; Makana, Jean-Remy] Wildlife Conservat Soc DRC, Kinshasa, DEM REP CONGO.
   [Hladik, Annette] MNHN, Dept Hommes Nat Soc, F-91800 Brunoy, France.
   [Lovett, Jon C.; Taplin, James] Univ York, Dept Environm, Ctr Ecol Law & Policy, York YO10 5DD, N Yorkshire, England.
   [Malhi, Yadvinder] Univ Oxford, Environm Change Inst, Sch Geog & Environm, Oxford OX1 3QY, England.
   [Mbago, Frank M.; Ndangalasi, Henry J.] Univ Dar Es Salaam, Dept Bot, Dar Es Salaam, Tanzania.
   [Sheil, Douglas] Ctr Int Forestry Res, Bogor 16000, Indonesia.
   [Swaine, Michael D.] Univ Aberdeen, Dept Plant & Soil Sci, Sch Biol Sci, Aberdeen AB24 3UU, Scotland.
   [Taylor, David] Univ Dublin Trinity Coll, Sch Nat Sci, Dept Geog, Dublin 2, Ireland.
   [Thomas, Sean C.] Univ Toronto, Fac Forestry, Toronto, ON M5S 3B3, Canada.
C3 University of Leeds; University of Yaounde I; University of Agriculture, Abeokuta; Smithsonian Institution; Wageningen University & Research; Museum National d'Histoire Naturelle (MNHN); University of York - UK; University of Oxford; University of Dar es Salaam; CGIAR; Center for International Forestry Research (CIFOR); University of Aberdeen; Trinity College Dublin; University of Toronto
RP Lewis, SL (corresponding author), Univ Leeds, Earth & Biosphere Inst, Sch Geog, Leeds LS2 9JT, W Yorkshire, England.
EM s.l.lewis@leeds.ac.uk
FU Royal Society and the Natural Environment Research Council (UK); NERC [NE/D005590/1] Funding Source: UKRI; Natural Environment Research Council [NE/D005590/1, NE/B504630/1, NE/D000300/1, NE/B503384/1] Funding Source: researchfish
NR 30
TC 742
Z9 874
U1 4
U2 410
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 19
PY 2009
VL 457
IS 7232
BP 1003
EP U3
DI 10.1038/nature07771
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400040
PM 19225523
DA 2026-03-09
ER

PT J
AU Hofer, SB
   Mrsic-Flogel, TD
   Bonhoeffer, T
   Hübener, M
AF Hofer, Sonja B.
   Mrsic-Flogel, Thomas D.
   Bonhoeffer, Tobias
   Huebener, Mark
TI Experience leaves a lasting structural trace in cortical circuits
SO NATURE
LA English
DT Article
ID ocular dominance plasticity; mouse visual-cortex; long-term potentiation; neocortex in-vivo; dendritic spines; adult cortex; dependent plasticity; synaptic plasticity; responses; stability
AB Sensory experiences exert a powerful influence on the function and future performance of neuronal circuits in the mammalian neocortex(1-3). Restructuring of synaptic connections is believed to be one mechanism by which cortical circuits store information about the sensory world(4,5). Excitatory synaptic structures, such as dendritic spines, are dynamic entities(6-8) that remain sensitive to alteration of sensory input throughout life(6,9). It remains unclear, however, whether structural changes at the level of dendritic spines can outlast the original experience and thereby provide a morphological basis for long- term information storage. Here we follow spine dynamics on apical dendrites of pyramidal neurons in functionally defined regions of adult mouse visual cortex during plasticity of eye- specific responses induced by repeated closure of one eye ( monocular deprivation). The first monocular deprivation episode doubled the rate of spine formation, thereby increasing spine density. This effect was specific to layer-5 cells located in binocular cortex, where most neurons increase their responsiveness to the non-deprived eye(3,10). Restoring binocular vision returned spine dynamics to baseline levels, but absolute spine density remained elevated and many monocular deprivation-induced spines persisted during this period of functional recovery. However, spine addition did not increase again when the same eye was closed for a second time. This absence of structural plasticity stands out against the robust changes of eye- specific responses that occur even faster after repeated deprivation(3). Thus, spines added during the first monocular deprivation experience may provide a structural basis for subsequent functional shifts. These results provide a strong link between functional plasticity and specific synaptic rearrangements, revealing a mechanism of how prior experiences could be stored in cortical circuits.
C1 [Hofer, Sonja B.; Mrsic-Flogel, Thomas D.; Bonhoeffer, Tobias; Huebener, Mark] Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
C3 Max Planck Society
RP Hübener, M (corresponding author), Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
EM mark@neuro.mpg.de
FU Max Planck Society; Wellcome Trust; Humboldt Foundation
NR 30
TC 405
Z9 491
U1 1
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 313
EP U4
DI 10.1038/nature07487
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900039
PM 19005470
DA 2026-03-09
ER

PT J
AU Rohs, R
   West, SM
   Sosinsky, A
   Liu, P
   Mann, RS
   Honig, B
AF Rohs, Remo
   West, Sean M.
   Sosinsky, Alona
   Liu, Peng
   Mann, Richard S.
   Honig, Barry
TI The role of DNA shape in protein-DNA recognition
SO NATURE
LA English
DT Article
ID crystal-structure; nucleosome core; binding-sites; a-tract; nucleic-acids; minor-groove; sequence; complex; resolution; repressor
AB The recognition of specific DNA sequences by proteins is thought to depend on two types of mechanism: one that involves the formation of hydrogen bonds with specific bases, primarily in the major groove, and one involving sequence-dependent deformations of the DNA helix. By comprehensively analysing the three-dimensional structures of protein-DNA complexes, here we show that the binding of arginine residues to narrow minor grooves is a widely used mode for protein-DNA recognition. This readout mechanism exploits the phenomenon that narrow minor grooves strongly enhance the negative electrostatic potential of the DNA. The nucleosome core particle offers a prominent example of this effect. Minor-groove narrowing is often associated with the presence of A-tracts, AT-rich sequences that exclude the flexible TpA step. These findings indicate that the ability to detect local variations in DNA shape and electrostatic potential is a general mechanism that enables proteins to use information in the minor groove, which otherwise offers few opportunities for the formation of base-specific hydrogen bonds, to achieve DNA-binding specificity.
C1 [Rohs, Remo; West, Sean M.; Sosinsky, Alona; Liu, Peng; Honig, Barry] Columbia Univ, Dept Biochem & Mol Biophys, Ctr Computat Biol & Bioinformat, Howard Hughes Med Inst, New York, NY 10032 USA.
C3 Howard Hughes Medical Institute; Columbia University
RP Honig, B (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, Ctr Computat Biol & Bioinformat, Howard Hughes Med Inst, 1130 St Nicholas Ave, New York, NY 10032 USA.
EM rsm10@columbia.edu; bh6@columbia.edu
FU National Institutes of Health (NIH) [GM54510, U54 CA121852]
NR 49
TC 870
Z9 1056
U1 1
U2 160
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 29
PY 2009
VL 461
IS 7268
BP 1248
EP U81
DI 10.1038/nature08473
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800041
PM 19865164
DA 2026-03-09
ER

PT J
AU Sohal, VS
   Zhang, F
   Yizhar, O
   Deisseroth, K
AF Sohal, Vikaas S.
   Zhang, Feng
   Yizhar, Ofer
   Deisseroth, Karl
TI Parvalbumin neurons and gamma rhythms enhance cortical circuit performance
SO NATURE
LA English
DT Article
ID in-vivo; positive interneurons; neural circuitry; transgenic mice; pyramidal cells; oscillations; synchronization; neocortex; connections; modulation
AB Synchronized oscillations and inhibitory interneurons have important and interconnected roles within cortical microcircuits. In particular, interneurons defined by the fast-spiking phenotype and expression of the calcium-binding protein parvalbumin(1,2) have been suggested to be involved in gamma (30-80 Hz) oscillations(3-7), which are hypothesized to enhance information processing(8,9). However, because parvalbumin interneurons cannot be selectively controlled, definitive tests of their functional significance in gamma oscillations, and quantitative assessment of the impact of parvalbumin interneurons and gamma oscillations on cortical circuits, have been lacking despite potentially enormous significance (for example, abnormalities in parvalbumin interneurons may underlie altered gamma-frequency synchronization and cognition in schizophrenia(10) and autism(11)). Here we use a panel of optogenetic technologies(12-14) in mice to selectively modulate multiple distinct circuit elements in neocortex, alone or in combination. We find that inhibiting parvalbumin interneurons suppresses gamma oscillations in vivo, whereas driving these interneurons (even by means of non-rhythmic principal cell activity) is sufficient to generate emergent gamma-frequency rhythmicity. Moreover, gamma-frequency modulation of excitatory input in turn was found to enhance signal transmission in neocortex by reducing circuit noise and amplifying circuit signals, including inputs to parvalbumin interneurons. As demonstrated here, optogenetics opens the door to a new kind of informational analysis of brain function, permitting quantitative delineation of the functional significance of individual elements in the emergent operation and function of intact neural circuitry.
C1 [Sohal, Vikaas S.; Zhang, Feng; Yizhar, Ofer; Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Dept Bioengn, Stanford, CA 94305 USA.
C3 Stanford University
RP Deisseroth, K (corresponding author), Stanford Univ, Dept Psychiat & Behav Sci, Dept Bioengn, W083 Clark Ctr,318 Campus Dr W, Stanford, CA 94305 USA.
EM deissero@stanford.edu
FU President and Provost of Stanford University; BioX; Bioengineering; NIMH; NIDA; CIRM; NSF; Keck, McKnight and Coulter Foundations; NINDS
NR 30
TC 2030
Z9 2524
U1 2
U2 388
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 698
EP 702
DI 10.1038/nature07991
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600043
PM 19396159
DA 2026-03-09
ER

PT J
AU Goda, K
   Tsia, KK
   Jalali, B
AF Goda, K.
   Tsia, K. K.
   Jalali, B.
TI Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena
SO NATURE
LA English
DT Article
ID microscopy
AB Ultrafast real-time optical imaging is an indispensable tool for studying dynamical events such as shock waves(1,2), chemical dynamics in living cells(3,4), neural activity(5,6), laser surgery(7-9) and microfluidics(10,11). However, conventional CCDs (charge-coupled devices) and their complementary metal-oxide-semiconductor (CMOS) counterparts are incapable of capturing fast dynamical processes with high sensitivity and resolution. This is due in part to a technological limitation-it takes time to read out the data from sensor arrays. Also, there is the fundamental compromise between sensitivity and frame rate; at high frame rates, fewer photons are collected during each frame-a problem that affects nearly all optical imaging systems. Here we report an imaging method that overcomes these limitations and offers frame rates that are at least 1,000 times faster than those of conventional CCDs. Our technique maps a two-dimensional (2D) image into a serial time-domain data stream and simultaneously amplifies the image in the optical domain. We capture an entire 2D image using a single-pixel photodetector and achieve a net image amplification of 25 dB (a factor of 316). This overcomes the compromise between sensitivity and frame rate without resorting to cooling and high-intensity illumination. As a proof of concept, we perform continuous real-time imaging at a frame speed of 163 ns (a frame rate of 6.1 MHz) and a shutter speed of 440 ps. We also demonstrate real-time imaging of microfluidic flow and phase-explosion effects that occur during laser ablation.
C1 [Goda, K.; Tsia, K. K.; Jalali, B.] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles
RP Goda, K (corresponding author), Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA.
EM goda@ee.ucla.edu
FU US Defense Advanced Research Projects Agency; Center for Nanoscience Innovation for Defense
NR 28
TC 631
Z9 756
U1 11
U2 301
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 30
PY 2009
VL 458
IS 7242
BP 1145
EP U80
DI 10.1038/nature07980
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600042
PM 19407796
DA 2026-03-09
ER

PT J
AU Pandey, M
   Syed, S
   Donmez, I
   Patel, G
   Ha, T
   Patel, SS
AF Pandey, Manjula
   Syed, Salman
   Donmez, Ilker
   Patel, Gayatri
   Ha, Taekjip
   Patel, Smita S.
TI Coordinating DNA replication by means of priming loop and differential synthesis rate
SO NATURE
LA English
DT Article
ID lagging-strand synthesis; ring-shaped helicase; escherichia-coli; minicircle substrate; replisome; primase; processivity; deficient; mechanism; template
AB Genomic DNA is replicated by two DNA polymerase molecules, one of which works in close association with the helicase to copy the leading-strand template in a continuous manner while the second copies the already unwound lagging-strand template in a discontinuous manner through the synthesis of Okazaki fragments(1,2). Considering that the lagging-strand polymerase has to recycle after the completion of every Okazaki fragment through the slowsteps of primer synthesis and hand-off to the polymerase(3-5), it is not understood how the two strands are synthesized with the same net rate(6-9). Here we show, using the T7 replication proteins(10,11), that RNA primers are made 'on the fly' during ongoing DNA synthesis and that the leading-strand T7 replisome does not pause during primer synthesis, contrary to previous reports(12,13). Instead, the leading-strand polymerase remains limited by the speed of the helicase(14); it therefore synthesizes DNA more slowly than the lagging-strand polymerase. We show that the primase-helicase T7 gp4 maintains contact with the priming sequence during ongoing DNA synthesis; the nascent lagging-strand template therefore organizes into a priming loop that keeps the primer in physical proximity to the replication complex. Our findings provide three synergistic mechanisms of coordination: first, primers are made concomitantly with DNA synthesis; second, the priming loop ensures efficient primer use and hand-off to the polymerase; and third, the lagging-strand polymerase copies DNA faster, which allows it to keep up with leading-strand DNA synthesis overall.
C1 [Syed, Salman; Ha, Taekjip] Howard Hughes Med Inst, Urbana, IL 61801 USA.
   [Pandey, Manjula; Donmez, Ilker; Patel, Gayatri; Patel, Smita S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA.
   [Ha, Taekjip] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Ha, Taekjip] Univ Illinois, Ctr Phys Living Cells, Urbana, IL 61801 USA.
C3 Howard Hughes Medical Institute; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Ha, T (corresponding author), Howard Hughes Med Inst, Urbana, IL 61801 USA.
EM tjha@illinois.edu; patelss@umdnj.edu
FU NIH [GM55310, GM065367]; NSF [0822613, 0646550]; Direct For Mathematical & Physical Scien; Division Of Physics [0822613] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [0646550] Funding Source: National Science Foundation
NR 31
TC 90
Z9 105
U1 1
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 17
PY 2009
VL 462
IS 7275
BP 940
EP U137
DI 10.1038/nature08611
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400047
PM 19924126
DA 2026-03-09
ER

PT J
AU Thilker, DA
   Donovan, J
   Schiminovich, D
   Bianchi, L
   Boissier, S
   de Paz, AG
   Madore, BF
   Martin, DC
   Seibert, M
AF Thilker, David A.
   Donovan, Jennifer
   Schiminovich, David
   Bianchi, Luciana
   Boissier, Samuel
   Gil de Paz, Armando
   Madore, Barry F.
   Martin, D. Christopher
   Seibert, Mark
TI Massive star formation within the Leo 'primordial' ring
SO NATURE
LA English
DT Article
ID h-i cloud; m96 group; ultraviolet extinction; intergalactic ring; neutral hydrogen; evolution; galaxy; search; resolution; disks
AB Few intergalactic, plausibly primordial clouds of neutral atomic hydrogen ( H I) have been found in the local Universe, suggesting that such structures have either dispersed, become ionized or produced a stellar population on gigayear timescales. The Leo ring(1,2), a massive (M-HI approximate to 1.8 x 10(9) M., M. denoting the solar mass), 200- kpc- wide structure orbiting the galaxies M105 and NGC 3384 with a 4- Gyr period, is a candidate primordial cloud. Despite repeated atttempts(3,4), it has previously been seen only from HI emission, suggesting the absence of a stellar population. Here we report the detection of ultraviolet light from gaseous substructures of the Leo ring, which we attribute to recent massive star formation. The ultraviolet colour of the detected complexes is blue, implying the onset of a burst of star formation or continuous star formation of moderate (similar to 10(8)-yr) duration. Measured ultraviolet visible photometry favours models with low metallicity (Z approximate to Z./ 50-Z./5, Z. denoting the solar metallicity), that is, a low proportion of elements heavier than helium, although spectroscopic confirmation is needed. We speculate that the complexes are dwarf galaxies observed during their formation, but distinguished by their lack of a dark matter component(5). In this regard, they resemble tidal dwarf galaxies, although without the enrichment preceding tidal stripping. If structures like the Leo ring were common in the early Universe, they may have produced a large, yet undetected, population of faint, metal- poor, halo- lacking dwarf galaxies.
C1 [Thilker, David A.; Bianchi, Luciana] Johns Hopkins Univ, Ctr Astrophys Sci, Baltimore, MD 21218 USA.
   [Donovan, Jennifer; Schiminovich, David] Columbia Univ, Pupin Phys Labs, Dept Astron, New York, NY 10027 USA.
   [Boissier, Samuel] Lab Astrophys Marseille, F-13376 Marseille 12, France.
   [Gil de Paz, Armando] Univ Complutense Madrid, Dept Astrofis, Fac Ciencias Fis, E-28040 Madrid, Spain.
   [Madore, Barry F.; Seibert, Mark] Carnegie Inst Washington Observ, Pasadena, CA 91101 USA.
   [Martin, D. Christopher] CALTECH, Pasadena, CA 91125 USA.
C3 Johns Hopkins University; Columbia University; Aix-Marseille Universite; Complutense University of Madrid; Carnegie Institution for Science; California Institute of Technology
RP Thilker, DA (corresponding author), Johns Hopkins Univ, Ctr Astrophys Sci, 3400 N Charles St, Baltimore, MD 21218 USA.
EM dthilker@pha.jhu.edu
NR 29
TC 36
Z9 39
U1 0
U2 4
PU NATURE PUBLISHING 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 19
PY 2009
VL 457
IS 7232
BP 990
EP 993
DI 10.1038/nature07780
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400037
PM 19225520
DA 2026-03-09
ER

PT J
AU Tachibana, M
   Sparman, M
   Sritanaudomchai, H
   Ma, H
   Clepper, L
   Woodward, J
   Li, Y
   Ramsey, C
   Kolotushkina, O
   Mitalipov, S
AF Tachibana, Masahito
   Sparman, Michelle
   Sritanaudomchai, Hathaitip
   Ma, Hong
   Clepper, Lisa
   Woodward, Joy
   Li, Ying
   Ramsey, Cathy
   Kolotushkina, Olena
   Mitalipov, Shoukhrat
TI Mitochondrial gene replacement in primate offspring and embryonic stem cells
SO NATURE
LA English
DT Article
ID neurodegenerative diseases; oxidative stress; dna mutations; ooplasmic transplantation; genotype segregation; nuclear transfer; human oocytes; donor oocyte; dysfunction; mtdna
AB Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.
C1 [Tachibana, Masahito; Sparman, Michelle; Sritanaudomchai, Hathaitip; Ma, Hong; Clepper, Lisa; Woodward, Joy; Li, Ying; Ramsey, Cathy; Kolotushkina, Olena; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
   [Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Oregon Stem Cell Ctr, Beaverton, OR 97006 USA.
   [Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Beaverton, OR 97006 USA.
   [Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Beaverton, OR 97006 USA.
C3 Oregon Health & Science University; Oregon National Primate Research Center; Oregon Health & Science University; Oregon Health & Science University; Oregon Health & Science University
RP Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, 505 NW 185th Ave, Beaverton, OR 97006 USA.
EM mitalipo@ohsu.edu
FU Oregon National Primate Research Center; Oregon Stem Cell Center; National Institutes of Health
NR 35
TC 422
Z9 493
U1 0
U2 149
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 367
EP 372
DI 10.1038/nature08368
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100033
PM 19710649
DA 2026-03-09
ER

PT J
AU Katayama, I
   Hirauchi, H
   Michibayashi, K
   Ando, J
AF Katayama, Ikuo
   Hirauchi, Ken-ichi
   Michibayashi, Katsuyoshi
   Ando, Jun-ichi
TI Trench-parallel anisotropy produced by serpentine deformation in the hydrated mantle wedge
SO NATURE
LA English
DT Article
ID p-wave velocity; seismic anisotropy; northeastern japan; fabric transitions; subduction; olivine; beneath; shear; flow; arc
AB Seismic anisotropy is a powerful tool for detecting the geometry and style of deformation in the Earth's interior, as it primarily reflects the deformation-induced preferred orientation of anisotropic crystals(1,2). Although seismic anisotropy in the uppermantle is generally attributed to the crystal-preferred orientation of olivine(3), the strong trench-parallel anisotropy (delay time of one to two seconds) observed in several subduction systems(4,5) is difficult to explain in terms of olivine anisotropy, even if the entire mantle wedge were to act as an anisotropic source. Here we show that the crystal-preferred orientation of serpentine, the main hydrous mineral in the upper mantle, can produce the strong trench-parallel seismic anisotropy observed in subduction systems. High-pressure deformation experiments reveal that the serpentine c-axis tends to rotate to an orientation normal to the shear plane during deformation; consequently, seismic velocity propagating normal to the shear plane (plate interface) is much slower than that in other directions. The seismic anisotropy estimated for deformed serpentine aggregates is an order of magnitude greater than that for olivine(6), and therefore the alignment of serpentine in the hydrated mantle wedge results in a strong trench-parallel seismic anisotropy in the case of a steeply subducting slab. This hypothesis is also consistent with the presence of a hydrous phase in the mantle wedge, as inferred from anomalously low seismic-wave velocities(7).
C1 [Katayama, Ikuo; Hirauchi, Ken-ichi; Ando, Jun-ichi] Hiroshima Univ, Dept Earth & Planetary Syst Sci, Higashihiroshima 7398526, Japan.
   [Michibayashi, Katsuyoshi] Shizuoka Univ, Inst Geosci, Shizuoka 4228529, Japan.
C3 Hiroshima University; Shizuoka University
RP Katayama, I (corresponding author), Hiroshima Univ, Dept Earth & Planetary Syst Sci, Higashihiroshima 7398526, Japan.
EM katayama@hiroshima-u.ac.jp
FU Japan Society for the Promotion of Science (JSPS)
NR 27
TC 212
Z9 236
U1 2
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1114
EP U209
DI 10.1038/nature08513
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600042
PM 19847262
DA 2026-03-09
ER

PT J
AU Butler, G
   Rasmussen, MD
   Lin, MF
   Santos, MAS
   Sakthikumar, S
   Munro, CA
   Rheinbay, E
   Grabherr, M
   Forche, A
   Reedy, JL
   Agrafioti, I
   Arnaud, MB
   Bates, S
   Brown, AJP
   Brunke, S
   Costanzo, MC
   Fitzpatrick, DA
   de Groot, PWJ
   Harris, D
   Hoyer, LL
   Hube, B
   Klis, FM
   Kodira, C
   Lennard, N
   Logue, ME
   Martin, R
   Neiman, AM
   Nikolaou, E
   Quail, MA
   Quinn, J
   Santos, MC
   Schmitzberger, FF
   Sherlock, G
   Shah, P
   Silverstein, KAT
   Skrzypek, MS
   Soll, D
   Staggs, R
   Stansfield, I
   Stumpf, MPH
   Sudbery, PE
   Srikantha, T
   Zeng, QD
   Berman, J
   Berriman, M
   Heitman, J
   Gow, NAR
   Lorenz, MC
   Birren, BW
   Kellis, M
   Cuomo, CA
AF Butler, Geraldine
   Rasmussen, Matthew D.
   Lin, Michael F.
   Santos, Manuel A. S.
   Sakthikumar, Sharadha
   Munro, Carol A.
   Rheinbay, Esther
   Grabherr, Manfred
   Forche, Anja
   Reedy, Jennifer L.
   Agrafioti, Ino
   Arnaud, Martha B.
   Bates, Steven
   Brown, Alistair J. P.
   Brunke, Sascha
   Costanzo, Maria C.
   Fitzpatrick, David A.
   de Groot, Piet W. J.
   Harris, David
   Hoyer, Lois L.
   Hube, Bernhard
   Klis, Frans M.
   Kodira, Chinnappa
   Lennard, Nicola
   Logue, Mary E.
   Martin, Ronny
   Neiman, Aaron M.
   Nikolaou, Elissavet
   Quail, Michael A.
   Quinn, Janet
   Santos, Maria C.
   Schmitzberger, Florian F.
   Sherlock, Gavin
   Shah, Prachi
   Silverstein, Kevin A. T.
   Skrzypek, Marek S.
   Soll, David
   Staggs, Rodney
   Stansfield, Ian
   Stumpf, Michael P. H.
   Sudbery, Peter E.
   Srikantha, Thyagarajan
   Zeng, Qiandong
   Berman, Judith
   Berriman, Matthew
   Heitman, Joseph
   Gow, Neil A. R.
   Lorenz, Michael C.
   Birren, Bruce W.
   Kellis, Manolis
   Cuomo, Christina A.
TI Evolution of pathogenicity and sexual reproduction in eight Candida genomes
SO NATURE
LA English
DT Article
ID albicans genome; mating-type; sequence; yeasts; virulence; lodderomyces; parapsilosis; meiosis; family; codon
AB Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the alpha 1/alpha 2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
C1 [Lin, Michael F.; Sakthikumar, Sharadha; Grabherr, Manfred; Kodira, Chinnappa; Zeng, Qiandong; Birren, Bruce W.; Kellis, Manolis; Cuomo, Christina A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Butler, Geraldine; Fitzpatrick, David A.; Logue, Mary E.] Univ Coll Dublin, Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland.
   [Rasmussen, Matthew D.; Lin, Michael F.; Rheinbay, Esther; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Santos, Manuel A. S.; Santos, Maria C.] Univ Aveiro, Dept Biol, P-3810193 Aveiro, Portugal.
   [Santos, Manuel A. S.; Santos, Maria C.] Univ Aveiro, CESAM, P-3810193 Aveiro, Portugal.
   [Munro, Carol A.; Brown, Alistair J. P.; Nikolaou, Elissavet; Stansfield, Ian; Gow, Neil A. R.] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen AB25 2ZD, Scotland.
   [Rheinbay, Esther] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
   [Forche, Anja; Berman, Judith] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
   [Reedy, Jennifer L.; Heitman, Joseph] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
   [Agrafioti, Ino; Stumpf, Michael P. H.] Univ London Imperial Coll Sci Technol & Med, Ctr Bioinformat, London SW7 2AY, England.
   [Arnaud, Martha B.; Costanzo, Maria C.; Schmitzberger, Florian F.; Sherlock, Gavin; Shah, Prachi; Skrzypek, Marek S.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
   [Bates, Steven] Univ Exeter, Sch Biosci, Exeter EX4 4QD, Devon, England.
   [Brunke, Sascha; Hube, Bernhard; Martin, Ronny] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Microbial Pathogen Mech, D-07745 Jena, Germany.
   [de Groot, Piet W. J.; Klis, Frans M.] Univ Amsterdam, Swammerdam Inst Life Sci, NL-1090 GB Amsterdam, Netherlands.
   [Harris, David; Lennard, Nicola; Quail, Michael A.; Berriman, Matthew] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Hoyer, Lois L.] Univ Illinois, Dept Pathobiol, Urbana, IL 61802 USA.
   [Neiman, Aaron M.] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA.
   [Quinn, Janet] Univ Newcastle, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Silverstein, Kevin A. T.; Staggs, Rodney] Univ Minnesota, Mason Canc Ctr, Biostat & Bioinformat Grp, Minneapolis, MN 55455 USA.
   [Soll, David; Srikantha, Thyagarajan] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA.
   [Sudbery, Peter E.] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England.
   [Lorenz, Michael C.] Univ Texas Hlth Sci Ctr Houston, Dept Microbiol & Mol Genet, Houston, TX 77030 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University College Dublin; Massachusetts Institute of Technology (MIT); Universidade de Aveiro; Universidade de Aveiro; University of Aberdeen; Boston University; University of Minnesota System; University of Minnesota Twin Cities; Duke University; Imperial College London; Stanford University; University of Exeter; Leibniz Association; Hans Knoll Institute (HKI); University of Amsterdam; Wellcome Trust Sanger Institute; University of Illinois System; University of Illinois Urbana-Champaign; State University of New York (SUNY) System; Stony Brook University; Newcastle University - UK; University of Minnesota System; University of Minnesota Twin Cities; University of Iowa; University of Sheffield; University of Texas System; University of Texas Health Science Center Houston
RP Cuomo, CA (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM geraldine.butler@ucd.ie; manoli@mit.edu; cuomo@broad.mit.edu
FU US National Human Genome Research Institute (NHGRI); Fungal Genome Initiative at the Broad Institute; Wellcome Trust; NHGRI; National Institute of Allergy and Infectious Disease; US National Institutes of Health (NIH); Department of Health and Human Services; Science Foundation Ireland; NIH; US National Science Foundation; Sloan Foundation; Biotechnology and Biological Sciences Research Council [BB/F007892/1, BB/F013566/1, BB/F00513X/1] Funding Source: researchfish; Medical Research Council [G0400284] Funding Source: researchfish; BBSRC [BB/F00513X/1, BB/F007892/1, BB/F013566/1] Funding Source: UKRI; MRC [G0400284] Funding Source: UKRI; National Institute of Allergy and Infectious Diseases [R01AI050113] Funding Source: NIH RePORTER
NR 40
TC 842
Z9 1693
U1 2
U2 145
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 657
EP 662
DI 10.1038/nature08064
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600034
PM 19465905
DA 2026-03-09
ER

PT J
AU Cardone, G
   Purdy, JG
   Cheng, NQ
   Craven, RC
   Steven, AC
AF Cardone, Giovanni
   Purdy, John G.
   Cheng, Naiqian
   Craven, Rebecca C.
   Steven, Alasdair C.
TI Visualization of a missing link in retrovirus capsid assembly
SO NATURE
LA English
DT Article
ID rous-sarcoma-virus; amino-terminal domain; 3-dimensional structure; dimerization domain; ca protein; hiv-1 core; resolution; reconstructions; organization; models
AB For a retrovirus such as HIV to be infectious, a properly formed capsid is needed; however, unusually among viruses, retrovirus capsids are highly variable in structure. According to the fullerene conjecture, they are composed of hexamers and pentamers of capsid protein (CA), with the shape of a capsid varying according to how the twelve pentamers are distributed and its size depending on the number of hexamers. Hexamers have been studied in planar and tubular arrays, but the predicted pentamers have not been observed. Here we report cryo- electron microscopic analyses of two in- vitro- assembled capsids of Rous sarcoma virus. Both are icosahedrally symmetric: one is composed of 12 pentamers, and the other of 12 pentamers and 20 hexamers. Fitting of atomic models of the two CA domains into the reconstructions shows three distinct inter- subunit interactions. These observations substantiate the fullerene conjecture, show how pentamers are accommodated at vertices, support the inference that nucleation is a crucial morphologic determinant, and imply that electrostatic interactions govern the differential assembly of pentamers and hexamers.
C1 [Cardone, Giovanni; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Purdy, John G.; Craven, Rebecca C.] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Penn State Health
RP Steven, AC (corresponding author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
EM rcc6@psu.edu; stevena@mail.nih.gov
FU Intramural Research Program of NIAMS; IATAP Program; NIH [CA100322]; Pennsylvania Department of Health; Penn State Cancer Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIAAR027002, ZIAAR041166] Funding Source: NIH RePORTER
NR 43
TC 83
Z9 94
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 694
EP U3
DI 10.1038/nature07724
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700034
PM 19194444
DA 2026-03-09
ER

PT J
AU Gouridis, G
   Karamanou, S
   Gelis, I
   Kalodimos, CG
   Economou, A
AF Gouridis, Giorgos
   Karamanou, Spyridoula
   Gelis, Ioannis
   Kalodimos, Charalampos G.
   Economou, Anastassios
TI Signal peptides are allosteric activators of the protein translocase
SO NATURE
LA English
DT Article
ID escherichia-coli; preprotein translocase; sequence recognition; secy complex; secretion; membrane; channel; motor; mutations; domains
AB Extra-cytoplasmic polypeptides are usually synthesized as 'preproteins' carrying amino-terminal, cleavable signal peptides(1) and secreted across membranes by translocases. The main bacterial translocase comprises the SecYEG protein-conducting channel and the peripheral ATPase motor SecA(2,3). Most proteins destined for the periplasm and beyond are exported post-translationally by SecA(2,3). Preprotein targeting to SecA is thought to involve signal peptides(4) and chaperones like SecB(5,6). Here we show that signal peptides have a new role beyond targeting: they are essential allosteric activators of the translocase. On docking on their binding groove on SecA, signal peptides act in trans to drive three successive states: first, 'triggering' that drives the translocase to a lower activation energy state; second, 'trapping' that engages non-native preprotein mature domains docked with high affinity on the secretion apparatus; and third, 'secretion' during which trapped mature domains undergo several turnovers of translocation in segments(7). A significant contribution by mature domains renders signal peptides less critical in bacterial secretory protein targeting than currently assumed. Rather, it is their function as allosteric activators of the translocase that renders signal peptides essential for protein secretion. A role for signal peptides and targeting sequences as allosteric activators may be universal in protein translocases.
C1 [Gouridis, Giorgos; Karamanou, Spyridoula; Economou, Anastassios] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece.
   [Gouridis, Giorgos; Economou, Anastassios] Univ Crete, Dept Biol, Iraklion 71409, Crete, Greece.
   [Gelis, Ioannis; Kalodimos, Charalampos G.] Rutgers State Univ, Piscataway, NJ 08854 USA.
C3 Foundation for Research & Technology - Hellas (FORTH); University of Crete; Rutgers University System; Rutgers University New Brunswick
RP Economou, A (corresponding author), Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece.
EM aeconomo@imbb.forth.gr
FU European Community [LSHC-CT-2006-037834/Streptomics]; Greek General Secretariat of Research and the European Regional Development Fund [PENED03ED623]; US National Institutes of Health [GM73854]; American Heart Association; Onassis Foundation
NR 30
TC 117
Z9 142
U1 0
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 19
PY 2009
VL 462
IS 7271
BP 363
EP U132
DI 10.1038/nature08559
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300047
PM 19924216
DA 2026-03-09
ER

PT J
AU Crawford, JM
   Korman, TP
   Labonte, JW
   Vagstad, AL
   Hill, EA
   Kamari-Bidkorpeh, O
   Tsai, SC
   Townsend, CA
AF Crawford, Jason M.
   Korman, Tyler P.
   Labonte, Jason W.
   Vagstad, Anna L.
   Hill, Eric A.
   Kamari-Bidkorpeh, Oliver
   Tsai, Shiou-Chuan
   Townsend, Craig A.
TI Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization
SO NATURE
LA English
DT Article
ID crystal-structure; crystallography
AB Polyketides are a class of natural products with diverse structures and biological activities. The structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS group of IPKSs) results from regiospecific cyclizations of reactive poly-beta-keto intermediates(1-3). How poly-beta-keto species are synthesized and stabilized, how their chain lengths are determined, and, in particular, how specific cyclization patterns are controlled have been largely inaccessible and functionally unknown until recently(4). A product template (PT) domain is responsible for controlling specific aldol cyclization and aromatization of these mature polyketide precursors, but the mechanistic basis is unknown. Here we present the 1.8 angstrom crystal structure and mutational studies of a dissected PT monodomain from PksA, the NR-PKS that initiates the biosynthesis of the potent hepatocarcinogen aflatoxin B-1 in Aspergillus parasiticus. Despite having minimal sequence similarity to known enzymes, the structure displays a distinct `double hot dog' (DHD) fold. Co-crystal structures with palmitate or a bicyclic substrate mimic illustrate that PT can bind both linear and bicyclic polyketides. Docking and mutagenesis studies reveal residues important for substrate binding and catalysis, and identify a phosphopantetheine localization channel and a deep two-part interior binding pocket and reaction chamber. Sequence similarity and extensive conservation of active site residues in PT domains suggest that the mechanistic insights gleaned from these studies will prove general for this class of IPKSs, and lay a foundation for defining the molecular rules controlling NR-PKS cyclization specificity.
C1 [Crawford, Jason M.; Labonte, Jason W.; Vagstad, Anna L.; Hill, Eric A.; Townsend, Craig A.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA.
   [Townsend, Craig A.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
   [Townsend, Craig A.] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA.
   [Korman, Tyler P.; Tsai, Shiou-Chuan] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
   [Kamari-Bidkorpeh, Oliver; Tsai, Shiou-Chuan] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA.
   [Tsai, Shiou-Chuan] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA 92697 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine
RP Townsend, CA (corresponding author), Johns Hopkins Univ, Dept Chem, Charles & 34Th St, Baltimore, MD 21218 USA.
EM sctsai@uci.edu; ctownsend@jhu.edu
FU US National Institutes of Health [ES001670]; Pew Foundation; Stanford Synchrotron Radiation Laboratory (SSRL); Stanford University on behalf of the US Department of Energy, Office of Basic Energy Sciences; Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; Damon Runyon Cancer Research Foundation [DRG-2002-09]; National Institute of Environmental Health Sciences [R01ES001670] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM080189] Funding Source: NIH RePORTER
NR 30
TC 151
Z9 192
U1 0
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1139
EP U243
DI 10.1038/nature08475
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600048
PM 19847268
DA 2026-03-09
ER

PT J
AU Keiser, MJ
   Setola, V
   Irwin, JJ
   Laggner, C
   Abbas, AI
   Hufeisen, SJ
   Jensen, NH
   Kuijer, MB
   Matos, RC
   Tran, TB
   Whaley, R
   Glennon, RA
   Hert, J
   Thomas, KLH
   Edwards, DD
   Shoichet, BK
   Roth, BL
AF Keiser, Michael J.
   Setola, Vincent
   Irwin, John J.
   Laggner, Christian
   Abbas, Atheir I.
   Hufeisen, Sandra J.
   Jensen, Niels H.
   Kuijer, Michael B.
   Matos, Roberto C.
   Tran, Thuy B.
   Whaley, Ryan
   Glennon, Richard A.
   Hert, Jerome
   Thomas, Kelan L. H.
   Edwards, Douglas D.
   Shoichet, Brian K.
   Roth, Bryan L.
TI Predicting new molecular targets for known drugs
SO NATURE
LA English
DT Article
ID serotonin receptors; reuptake inhibitor; chemical biology; double-blind; agonist; n,n-dimethyltryptamine; hallucinogen; pharmacology; promiscuity; mechanism
AB Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug-target combinations exist, it would be useful to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the beta(1) receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H-4 receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug-target associations were confirmed, five of which were potent (<100 nM). The physiological relevance of one, the drug N,N-dimethyltryptamine (DMT) on serotonergic receptors, was confirmed in a knockout mouse. The chemical similarity approach is systematic and comprehensive, and may suggest side-effects and new indications for many drugs.
C1 [Keiser, Michael J.; Irwin, John J.; Laggner, Christian; Hert, Jerome; Thomas, Kelan L. H.; Edwards, Douglas D.; Shoichet, Brian K.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA.
   [Keiser, Michael J.] Univ Calif San Francisco, Grad Grp Bioinformat, San Francisco, CA 94143 USA.
   [Setola, Vincent; Kuijer, Michael B.; Matos, Roberto C.; Tran, Thuy B.; Whaley, Ryan; Roth, Bryan L.] Case Western Reserve Univ, Sch Med, Dept Pharmacol, NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA.
   [Abbas, Atheir I.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA.
   [Hufeisen, Sandra J.; Jensen, Niels H.; Roth, Bryan L.] Univ N Carolina, Chapel Hill Sch Med, Div Med Chem & Nat Prod, Chapel Hill, NC 27759 USA.
   [Hufeisen, Sandra J.; Jensen, Niels H.; Roth, Bryan L.] Univ N Carolina, Chapel Hill Sch Med, Dept Pharmacol, Chapel Hill, NC 27759 USA.
   [Glennon, Richard A.] Virginia Commonwealth Univ, Dept Med Chem, Sch Pharm, Med Coll Virginia Campus, Richmond, VA 23298 USA.
   [Thomas, Kelan L. H.] Univ Michigan Hlth Syst, Ann Arbor, MI 48109 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Virginia Commonwealth University; University of Michigan System; University of Michigan
RP Shoichet, BK (corresponding author), Univ Calif San Francisco, Dept Pharmaceut Chem, 1700 4th St, San Francisco, CA 94143 USA.
EM shoichet@cgl.ucsf.edu; bryan_roth@med.unc.edu
FU National Institutes of Health (NIH); National Science Foundation; European Commission; Max Kade Foundation; NARSAD; Michael Hooker Chair; National Institute of General Medical Sciences [T32GM007250] Funding Source: NIH RePORTER
NR 53
TC 1330
Z9 1493
U1 4
U2 255
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 12
PY 2009
VL 462
IS 7270
BP 175
EP U48
DI 10.1038/nature08506
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100034
PM 19881490
DA 2026-03-09
ER

PT J
AU Owusu-Ansah, E
   Banerjee, U
AF Owusu-Ansah, Edward
   Banerjee, Utpal
TI Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation
SO NATURE
LA English
DT Article
ID oxidative stress; feedback-regulation; signaling center; cell; jnk; insulin; growth; blood; foxo; activation
AB Reactive oxygen species (ROS), produced during various electron transfer reactions in vivo, are generally considered to be deleterious to cells(1). In the mammalian haematopoietic system, haematopoietic stem cells contain low levels of ROS. However, unexpectedly, the common myeloid progenitors (CMPs) produce significantly increased levels of ROS2. The functional significance of this difference in ROS level in the two progenitor types remains unresolved(2,3). Here we show that Drosophila multipotent haematopoietic progenitors, which are largely akin to the mammalian myeloid progenitors(4), display increased levels of ROS under in vivo physiological conditions, which are downregulated on differentiation. Scavenging the ROS from these haematopoietic progenitors by using in vivo genetic tools retards their differentiation into mature blood cells. Conversely, increasing the haematopoietic progenitor ROS beyond their basal level triggers precocious differentiation into all three mature blood cell types found in Drosophila, through a signalling pathway that involves JNK and FoxO activation as well as Polycomb downregulation. We conclude that the developmentally regulated, moderately high ROS level in the progenitor population sensitizes them to differentiation, and establishes a signalling role for ROS in the regulation of haematopoietic cell fate. Our results lead to a model that could be extended to reveal a probable signalling role for ROS in the differentiation of CMPs in mammalian haematopoietic development and oxidative stress response.
C1 [Owusu-Ansah, Edward; Banerjee, Utpal] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Banerjee, Utpal] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
   [Banerjee, Utpal] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA.
   [Banerjee, Utpal] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, 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 Banerjee, U (corresponding author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
EM banerjee@mbi.ucla.edu
FU US National Institutes of Health [R01HL067395]; T32 institutional postdoctoral fellowship [T32-HL069766]; National Heart Lung and Blood Institute [R01HL067395, T32HL069766] Funding Source: NIH RePORTER
NR 26
TC 609
Z9 738
U1 2
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 SEP 24
PY 2009
VL 461
IS 7263
BP 537
EP U109
DI 10.1038/nature08313
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900043
PM 19727075
DA 2026-03-09
ER

PT J
AU Gilfillan, SMV
   Lollar, BS
   Holland, G
   Blagburn, D
   Stevens, S
   Schoell, M
   Cassidy, M
   Ding, ZJ
   Zhou, Z
   Lacrampe-Couloume, G
   Ballentine, CJ
AF Gilfillan, Stuart M. V.
   Lollar, Barbara Sherwood
   Holland, Greg
   Blagburn, Dave
   Stevens, Scott
   Schoell, Martin
   Cassidy, Martin
   Ding, Zhenju
   Zhou, Zheng
   Lacrampe-Couloume, Georges
   Ballentine, Chris J.
TI Solubility trapping in formation water as dominant CO2 sink in natural gas fields
SO NATURE
LA English
DT Article
ID rock interactions; noble-gases; carbon; basin; groundwater; reservoirs
AB Injecting CO2 into deep geological strata is proposed as a safe and economically favourable means of storing CO2 captured from industrial point sources(1-3). It is difficult, however, to assess the long-term consequences of CO2 flooding in the subsurface from decadal observations of existing disposal sites(1,2). Both the site design and long-term safety modelling critically depend on how and where CO2 will be stored in the site over its lifetime(2-4). Within a geological storage site, the injected CO2 can dissolve in solution or precipitate as carbonate minerals. Here we identify and quantify the principal mechanism of CO2 fluid phase removal in nine natural gas fields in North America, China and Europe, using noble gas and carbon isotope tracers. The natural gas fields investigated in our study are dominated by a CO2 phase and provide a natural analogue for assessing the geological storage of anthropogenic CO2 over millennial timescales(1,2,5,6). We find that in seven gas fields with siliciclastic or carbonate-dominated reservoir lithologies, dissolution in formation water at a pH of 5-5.8 is the sole major sink for CO2. In two fields with siliciclastic reservoir lithologies, some CO2 loss through precipitation as carbonate minerals cannot be ruled out, but can account for a maximum of 18 per cent of the loss of emplaced CO2. In view of our findings that geological mineral fixation is a minor CO2 trapping mechanism in natural gas fields, we suggest that long-term anthropogenic CO2 storage models in similar geological systems should focus on the potential mobility of CO2 dissolved in water.
C1 [Gilfillan, Stuart M. V.; Holland, Greg; Blagburn, Dave; Ding, Zhenju; Zhou, Zheng; Ballentine, Chris J.] Univ Manchester, Sch Earth Atmospher & Environm Sci, Manchester M13 9PL, Lancs, England.
   [Gilfillan, Stuart M. V.] Univ Edinburgh, Grant Inst, Sch Geosci, Scottish Ctr Carbon Storage, Edinburgh EH9 3JW, Midlothian, Scotland.
   [Lollar, Barbara Sherwood; Lacrampe-Couloume, Georges] Univ Toronto, Dept Geol, Toronto, ON M5S 3B1, Canada.
   [Stevens, Scott] Adv Resources Int, Arlington, VA 22203 USA.
   [Schoell, Martin] GasConsult Int, Berkeley, CA 94703 USA.
   [Cassidy, Martin] Univ Houston, Dept Earth & Atmospher Sci, Houston, TX 77204 USA.
   [Ding, Zhenju] China Univ Geosci, Wuhan 430074, Peoples R China.
C3 University of Manchester; University of Edinburgh; University of Toronto; University of Houston System; University of Houston; China University of Geosciences
RP Gilfillan, SMV (corresponding author), Univ Manchester, Sch Earth Atmospher & Environm Sci, Oxford Rd, Manchester M13 9PL, Lancs, England.
EM stuart.gilfillan@ed.ac.uk
FU Natural Environmental Research Council (NERC); NERC [NE/C516479/1, NE/D004292, NE/F002823]; UK Energy Research Centre [NE/C513169/1]; Natural Sciences and Engineering Research Council of Canada Discovery grant; EPSRC [EP/H022961/1, DT/F007744/1] Funding Source: UKRI; NERC [NE/G015163/1, NE/F004699/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/H022961/1, DT/F007744/1] Funding Source: researchfish; Natural Environment Research Council [NE/F004699/1, NE/G015163/1, NE/C513169/1, NE/C516401/1] Funding Source: researchfish
NR 29
TC 411
Z9 465
U1 14
U2 250
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 2
PY 2009
VL 458
IS 7238
BP 614
EP 618
DI 10.1038/nature07852
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200037
PM 19340078
DA 2026-03-09
ER

PT J
AU Heuer, D
   Lipinski, AR
   Machuy, N
   Karlas, A
   Wehrens, A
   Siedler, F
   Brinkmann, V
   Meyer, TF
AF Heuer, Dagmar
   Lipinski, Anette Rejman
   Machuy, Nikolaus
   Karlas, Alexander
   Wehrens, Andrea
   Siedler, Frank
   Brinkmann, Volker
   Meyer, Thomas F.
TI Chlamydia causes fragmentation of the Golgi compartment to ensure reproduction
SO NATURE
LA English
DT Article
ID host-cell; endoplasmic-reticulum; trachomatis inclusion; apoptosis; apparatus; sphingolipids; inheritance; inhibition; pneumoniae; activation
AB The obligate intracellular bacterium Chlamydia trachomatis survives and replicates within a membrane- bound vacuole, termed the inclusion, which intercepts host exocytic pathways to obtain nutrients(1-3). Like many other intracellular pathogens, C. trachomatis has a marked requirement for host cell lipids, such as sphingolipids and cholesterol, produced in the endoplasmic reticulum and the Golgi apparatus(4-6). However, the mechanisms by which intracellular pathogens acquire host cell lipids are not well understood(1-3). In particular, no host cell protein responsible for transporting Golgi-derived lipids to the chlamydial inclusions has yet been identified. Here we show that Chlamydia infection in human epithelial cells induces Golgi fragmentation to generate Golgi ministacks surrounding the bacterial inclusion. Ministack formation is triggered by the proteolytic cleavage of the Golgimatrix protein golgin-84. Inhibition of golgin-84 truncation prevents Golgi fragmentation, causing a block in lipid acquisition and maturation of C. trachomatis. Golgi fragmentation by means of RNA- interference- mediated knockdown of distinct Golgi matrix proteins before infection enhances bacterial maturation. Our data functionally connect bacteria- induced golgin-84 cleavage, Golgi ministack formation, lipid acquisition and intracellular pathogen growth. We show that C. trachomatis subverts the structure and function of an entire host cell organelle for its own advantage.
C1 [Heuer, Dagmar; Lipinski, Anette Rejman; Machuy, Nikolaus; Karlas, Alexander; Wehrens, Andrea; Meyer, Thomas F.] Max Planck Inst Infect Biol, Dept Mol Biol, D-10117 Berlin, Germany.
   [Brinkmann, Volker] Max Planck Inst Infect Biol, Microscopy Core Facil, D-10117 Berlin, Germany.
   [Siedler, Frank] Max Planck Inst Biochem, Dept Membrane Biochem, D-82152 Martinsried, Germany.
C3 Max Planck Society; Max Planck Society; Max Planck Society
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 Senate of Berlin; BMBF
NR 25
TC 232
Z9 291
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 731
EP U8
DI 10.1038/nature07578
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700043
PM 19060882
DA 2026-03-09
ER

PT J
AU Macosko, EZ
   Pokala, N
   Feinberg, EH
   Chalasani, SH
   Butcher, RA
   Clardy, J
   Bargmann, CI
AF Macosko, Evan Z.
   Pokala, Navin
   Feinberg, Evan H.
   Chalasani, Sreekanth H.
   Butcher, Rebecca A.
   Clardy, Jon
   Bargmann, Cornelia I.
TI A hub-and-spoke circuit drives pheromone attraction and social behaviour in C-elegans
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; natural variation; chemosensory neurons; chemical repellents; neuropeptide-y; gene; chemotaxis; inhibition; modulation; expression
AB Innate social behaviours emerge from neuronal circuits that interpret sensory information on the basis of an individual's own genotype, sex and experience. The regulated aggregation behaviour of the nematode Caenorhabditis elegans, a simple animal with only 302 neurons, is an attractive system to analyse these circuits. Wild social strains of C. elegans aggregate in the presence of specific sensory cues, but solitary strains do not(1-4). Here we identify the RMG inter/motor neuron as the hub of a regulated circuit that controls aggregation and related behaviours. RMG is the central site of action of the neuropeptide receptor gene npr-1, which distinguishes solitary strains (high npr-1 activity) from wild social strains (low npr-1 activity); high RMG activity is essential for all aspects of social behaviour. Anatomical gap junctions connect RMG to several classes of sensory neurons known to promote aggregation, and to ASK sensory neurons, which are implicated in male attraction to hermaphrodite pheromones(5). We find that ASK neurons respond directly to pheromones, and that high RMG activity enhances ASK responses in social strains, causing hermaphrodite attraction to pheromones at concentrations that repel solitary hermaphrodites. The coordination of social behaviours by RMG suggests an anatomical hub-and-spoke model for sensory integration in aggregation, and points to functions for related circuit motifs in the C. elegans wiring diagram.
C1 [Macosko, Evan Z.; Pokala, Navin; Feinberg, Evan H.; Chalasani, Sreekanth H.; Bargmann, Cornelia I.] Rockefeller Univ, Howard Hughes Med Inst, Lab Neural Circuits & Behav, New York, NY 10065 USA.
   [Butcher, Rebecca A.; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Rockefeller University; Harvard University; Harvard Medical School
RP Bargmann, CI (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, Lab Neural Circuits & Behav, 1230 York Ave, New York, NY 10065 USA.
EM cori@rockefeller.edu
FU Howard Hughes Medical Institute; Harold and Leila Y Mathers Charitable Foundation; Jensam Foundation; National Institute of Health [GM07739, CA24487, GM077943]; National Institute of General Medical Sciences [T32GM007739] Funding Source: NIH RePORTER
NR 40
TC 363
Z9 460
U1 3
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 30
PY 2009
VL 458
IS 7242
BP 1171
EP U110
DI 10.1038/nature07886
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600048
PM 19349961
DA 2026-03-09
ER

PT J
AU Ishii, M
   Egen, JG
   Klauschen, F
   Meier-Schellersheim, M
   Saeki, Y
   Vacher, J
   Proia, RL
   Germain, RN
AF Ishii, Masaru
   Egen, Jackson G.
   Klauschen, Frederick
   Meier-Schellersheim, Martin
   Saeki, Yukihiko
   Vacher, Jean
   Proia, Richard L.
   Germain, Ronald N.
TI Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis
SO NATURE
LA English
DT Article
ID protein-coupled receptor; sphingosine 1-phosphate; cell-migration; vascular maturation; lymphoid organs; transgenic mice; t-cells; marrow; expression; collagen
AB Osteoclasts are the only somatic cells with bone-resorbing capacity and, as such, they have a critical role not only in normal bone homeostasis (called 'bone remodelling') but also in the pathogenesis of bone destructive disorders such as rheumatoid arthritis and osteoporosis(1). A major focus of research in the field has been on gene regulation by osteoclastogenic cytokines such as receptor activator of NF-kappa B-ligand (RANKL, also known as TNFSF11) and TNF-alpha, both of which have been well documented to contribute to osteoclast terminal differentiation(2,3). A crucial process that has been less well studied is the trafficking of osteoclast precursors to and from the bone surface, where they undergo cell fusion to form the fully differentiated multinucleated cells that mediate bone resorption. Here we report that sphingosine-1-phosphate (S1P), a lipid mediator enriched in blood(4,5), induces chemotaxis and regulates the migration of osteoclast precursors not only in culture but also in vivo, contributing to the dynamic control of bone mineral homeostasis. Cells with the properties of osteoclast precursors express functional S1P(1) receptors and exhibit positive chemotaxis along an S1P gradient in vitro. Intravital two-photon imaging of bone tissues showed that a potent S1P(1) agonist, SEW2871, stimulated motility of osteoclast precursor-containing monocytoid populations in vivo. Osteoclast/monocyte (CD11b, also known as ITGAM) lineage-specific conditional S1P(1) knockout mice showed osteoporotic changes due to increased osteoclast attachment to the bone surface. Furthermore, treatment with the S1P(1) agonist FTY720 relieved ovariectomy-induced osteoporosis in mice by reducing the number of mature osteoclasts attached to the bone surface. Together, these data provide evidence that S1P controls the migratory behaviour of osteoclast precursors, dynamically regulating bone mineral homeostasis, and identifies a critical control point in osteoclastogenesis that may have potential as a therapeutic target.
C1 [Ishii, Masaru; Egen, Jackson G.; Germain, Ronald N.] NIDDK, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Klauschen, Frederick; Meier-Schellersheim, Martin; Germain, Ronald N.] NIDDK, Program Syst Immunol & Infect Dis Modeling, NIAID, NIH, Bethesda, MD 20892 USA.
   [Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
   [Ishii, Masaru] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Biol Imaging, Suita, Osaka 5650871, Japan.
   [Ishii, Masaru; Saeki, Yukihiko] Natl Osaka Minami Med Ctr, Dept Clin Res, Osaka 5868521, Japan.
   [Vacher, Jean] Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); University of Osaka; Universite de Montreal; Institut de Recherche Clinique de Montreal (IRCM)
RP Germain, RN (corresponding author), NIDDK, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM rgermain@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases; NIH; US Department of Health and Human Services; International Human Frontier Science Program; National Institute of Allergy and Infectious Diseases [ZIAAI000545] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK056015, ZIADK056014] Funding Source: NIH RePORTER
NR 29
TC 423
Z9 474
U1 3
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 524
EP U8
DI 10.1038/nature07713
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400048
PM 19204730
DA 2026-03-09
ER

PT J
AU Wild, G
   Gardner, A
   West, SA
AF Wild, Geoff
   Gardner, Andy
   West, Stuart A.
TI Adaptation and the evolution of parasite virulence in a connected world
SO NATURE
LA English
DT Article
ID inclusive fitness; group selection; social semantics; models; cooperation; behaviour; altruism
AB Adaptation is conventionally regarded as occurring at the level of the individual organism, where it functions to maximize the individual's inclusive fitness(1-3). However, it has recently been argued that empirical studies on the evolution of parasite virulence in spatial populations show otherwise(4-7). In particular, it has been claimed that the evolution of lower virulence in response to limited parasite dispersal(8,9) provides proof of Wynne-Edwards's(10) idea of adaptation at the group level. Although previous theoretical work has shown that limited dispersal can favour lower virulence, it has not clarified why, with five different suggestions having been given(6,8,11-15). Here we show that the effect of dispersal on parasite virulence can be understood entirely within the framework of inclusive fitness theory. Limited parasite dispersal favours lower parasite growth rates and, hence, reduced virulence because it (1) decreases the direct benefit of producing offspring(dispersers are worth more than non-dispersers, because they can go to patches with no or fewer parasites), and (2) increases the competition for hosts experienced by both the focal individual ('self-shading') and their relatives ('kin shading'). This demonstrates that reduced virulence can be understood as an individual-level adaptation by the parasite to maximize its inclusive fitness, and clarifies the links with virulence theory more generally(16).
C1 [Wild, Geoff] Univ Western Ontario, Dept Appl Math, London, ON N6A 5B7, Canada.
   [Gardner, Andy] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
   [West, Stuart A.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
C3 Western University (University of Western Ontario); University of Edinburgh; University of Oxford
RP Wild, G (corresponding author), Univ Western Ontario, Dept Appl Math, London, ON N6A 5B7, Canada.
EM gwild@uwo.ca
FU Natural Sciences and Engineering Research Council of Canada; UK Natural Environmental Research Council; Royal Society; Leverhulme Trust; European Research Council
NR 30
TC 111
Z9 123
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 JUN 18
PY 2009
VL 459
IS 7249
BP 983
EP 986
DI 10.1038/nature08071
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500042
PM 19474791
DA 2026-03-09
ER

PT J
AU Postberg, F
   Kempf, S
   Schmidt, J
   Brilliantov, N
   Beinsen, A
   Abel, B
   Buck, U
   Srama, R
AF Postberg, F.
   Kempf, S.
   Schmidt, J.
   Brilliantov, N.
   Beinsen, A.
   Abel, B.
   Buck, U.
   Srama, R.
TI Sodium salts in E-ring ice grains from an ocean below the surface of Enceladus
SO NATURE
LA English
DT Article
ID water; origin; dust; vicinity; plume; life
AB Saturn's moon Enceladus emits plumes of water vapour and ice particles from fractures near its south pole(1-5), suggesting the possibility of a subsurface ocean(5-7). These plume particles are the dominant source of Saturn's E ring(7,8). A previous in situ analysis(9) of these particles concluded that the minor organic or siliceous components, identified in many ice grains, could be evidence for interaction between Enceladus' rocky core and liquid water(9,10). It was not clear, however, whether the liquid is still present today or whether it has frozen. Here we report the identification of a population of E-ring grains that are rich in sodium salts (similar to 0.5-2% by mass), which can arise only if the plumes originate from liquid water. The abundance of various salt components in these particles, as well as the inferred basic pH, exhibit a compelling similarity to the predicted composition of a subsurface Enceladus ocean in contact with its rock core(11). The plume vapour is expected to be free of atomic sodium. Thus, the absence of sodium from optical spectra(12) is in good agreement with our results. In the E ring the upper limit for spectroscopy(12) is insufficiently sensitive to detect the concentrations we found.
C1 [Postberg, F.] Heidelberg Univ, Inst Geowissensch, D-69120 Heidelberg, Germany.
   [Postberg, F.; Kempf, S.; Srama, R.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Kempf, S.] Tech Univ Carolo Wilhelmina Braunschweig, IGEP, D-38106 Braunschweig, Germany.
   [Schmidt, J.] Univ Potsdam, D-14476 Potsdam, Germany.
   [Brilliantov, N.] Univ Leicester, Dept Math, Leicester LE1 7RH, Leics, England.
   [Brilliantov, N.] Moscow MV Lomonosov State Univ, Dept Phys, Moscow 119991, Russia.
   [Beinsen, A.; Abel, B.] Univ Gottingen, Inst Phys Chem, D-37077 Gottingen, Germany.
   [Abel, B.] Univ Leipzig, Wilhelm Oswald Inst Phys & Theoret Chem, D-04103 Leipzig, Germany.
   [Buck, U.] Max Planck Inst Dynam & Selbstorg, D-37073 Gottingen, Germany.
C3 Ruprecht Karls University Heidelberg; Max Planck Society; Braunschweig University of Technology; University of Potsdam; University of Leicester; Lomonosov Moscow State University; University of Gottingen; Leipzig University; Max Planck Society
RP Postberg, F (corresponding author), Heidelberg Univ, Inst Geowissensch, D-69120 Heidelberg, Germany.
EM frank.postberg@mpi-hd.mpg.de
FU DLR; DFG; Frontier programme of the University of Heidelberg.
NR 27
TC 477
Z9 532
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 JUN 25
PY 2009
VL 459
IS 7250
BP 1098
EP 1101
DI 10.1038/nature08046
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700036
PM 19553992
DA 2026-03-09
ER

PT J
AU Kim, JB
   Greber, B
   Araúzo-Bravo, MJ
   Meyer, J
   Park, KI
   Zaehres, H
   Schöler, HR
AF Kim, Jeong Beom
   Greber, Boris
   Arauzo-Bravo, Marcos J.
   Meyer, Johann
   Park, Kook In
   Zaehres, Holm
   Schoeler, Hans R.
TI Direct reprogramming of human neural stem cells by OCT4
SO NATURE
LA English
DT Article
ID human fibroblasts; generation; mouse; pluripotency; induction; myc
AB Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4)(1-7). We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells(8). Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.
C1 [Kim, Jeong Beom; Greber, Boris; Arauzo-Bravo, Marcos J.; Zaehres, Holm; Schoeler, Hans R.] Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, NRW, Germany.
   [Meyer, Johann] Hannover Med Sch, Dept Expt Hematol, D-30625 Hannover, Germany.
   [Park, Kook In] Yonsei Univ, Coll Med, Dept Pediat, Project Med Sci BK21, Seoul 120752, South Korea.
C3 Max Planck Society; Hannover Medical School; Yonsei University; Yonsei University Health System
RP Schöler, HR (corresponding author), Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, Rontgenstr 20, D-48149 Munster, NRW, Germany.
EM office@mpi-muenster.mpg.de
FU German Federal Ministry of Education and Research BMBF [01GN0811]; Deutsche Forschungsgemeinschaft DFG [SCHO 340/4-1]
NR 25
TC 531
Z9 675
U1 0
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 1
PY 2009
VL 461
IS 7264
BP 649
EP U93
DI 10.1038/nature08436
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600040
PM 19718018
DA 2026-03-09
ER

PT J
AU Sena, G
   Wang, XN
   Liu, HY
   Hofhuis, H
   Birnbaum, KD
AF Sena, Giovanni
   Wang, Xiaoning
   Liu, Hsiao-Yun
   Hofhuis, Hugo
   Birnbaum, Kenneth D.
TI Organ regeneration does not require a functional stem cell niche in plants
SO NATURE
LA English
DT Article
ID root; expression; scarecrow; polarity
AB Plants rely on the maintenance of stem cell niches at their apices for the continuous growth of roots and shoots. However, although the developmental plasticity of plant cells has been demonstrated(1), it is not known whether the stem cell niche is required for organogenesis. Here we explore the capacity of a broad range of differentiating cells to regenerate an organ without the activity of a stem cell niche. Using a root-tip regeneration system in Arabidopsis thaliana to track the molecular and functional recovery of cell fates, we show that respecification of lost cell identities begins within hours of excision and that the function of specialized cells is restored within one day. Critically, regeneration proceeds in plants with mutations that fail to maintain the stem cell niche. These results show that stem-cell-like properties that mediate complete organ regeneration are dispersed in plant meristems and are not restricted to niches, which nonetheless seem to be necessary for indeterminate growth. This regenerative reprogramming of an entire organ without transition to a stereotypical stem cell environment has intriguing parallels to recent reports of induced transdifferentiation of specific cell types in the adult organs of animals(2,3).
C1 [Sena, Giovanni; Wang, Xiaoning; Liu, Hsiao-Yun; Birnbaum, Kenneth D.] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA.
   [Hofhuis, Hugo] Univ Utrecht, Fac Sci, Dept Biol, NL-3584 CH Utrecht, Netherlands.
C3 New York University; Utrecht University
RP Birnbaum, KD (corresponding author), NYU, Dept Biol, Ctr Genom & Syst Biol, Silver Bldg,100 Washington Sq E, New York, NY 10003 USA.
EM ken.birnbaum@nyu.edu
FU National Institutes of Health [5R01GM078279]
NR 25
TC 207
Z9 231
U1 1
U2 61
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 26
PY 2009
VL 457
IS 7233
BP 1150
EP U110
DI 10.1038/nature07597
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100045
PM 19182776
DA 2026-03-09
ER

PT J
AU Wang, JH
   Gostissa, M
   Yan, CT
   Goff, P
   Hickernell, T
   Hansen, E
   Difilippantonio, S
   Wesemann, DR
   Zarrin, AA
   Rajewsky, K
   Nussenzweig, A
   Alt, FW
AF Wang, Jing H.
   Gostissa, Monica
   Yan, Catherine T.
   Goff, Peter
   Hickernell, Thomas
   Hansen, Erica
   Difilippantonio, Simone
   Wesemann, Duane R.
   Zarrin, Ali A.
   Rajewsky, Klaus
   Nussenzweig, Andre
   Alt, Frederick W.
TI Mechanisms promoting translocations in editing and switching peripheral B cells
SO NATURE
LA English
DT Article
ID end-joining pathway; chromosomal translocations; v(d)j recombination; receptor revision; bone-marrow; dna breaks; lymphocyte development; gene-regulation; aid; expression
AB Variable, diversity and joining gene segment (V(D) J) recombination assembles immunoglobulin heavy or light chain (IgH or IgL) variable region exons in developing bone marrow B cells, whereas class switch recombination (CSR) exchanges IgH constant region exons in peripheral B cells. Both processes use directed DNA double-strand breaks (DSBs) repaired by non-homologous end-joining (NHEJ). Errors in either V(D) J recombination or CSR can initiate chromosomal translocations, including oncogenic IgH locus (Igh) to c-myc (also known as Myc) translocations of peripheral B cell lymphomas. Collaboration between these processes has also been proposed to initiate translocations. However, the occurrence of V(D) J recombination in peripheral B cells is controversial. Here we show that activated NHEJ-deficient splenic B cells accumulate V(D) J-recombination-associated breaks at the lambda IgL locus (Igl), as well as CSR-associated Igh breaks, often in the same cell. Moreover, Igl and Igh breaks are frequently joined to form translocations, a phenomenon associated with specific Igh-Igl co-localization. Igh and c-myc also co-localize in these cells; correspondingly, the introduction of frequent c-myc DSBs robustly promotes Igh-c-myc translocations. Our studies show peripheral B cells that attempt secondary V(D) J recombination, and determine a role for mechanistic factors in promoting recurrent translocations in tumours.
C1 [Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
   [Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Rajewsky, Klaus; Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
   [Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Difilippantonio, Simone; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Wesemann, Duane R.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Alt, FW (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
FU National Insitutes of Health (NIH) [5P01CA92625]; Leukemia and Lymphoma Society of America (LLS) SCORE; NCI
NR 50
TC 101
Z9 127
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 JUL 9
PY 2009
VL 460
IS 7252
BP 231
EP U94
DI 10.1038/nature08159
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000035
PM 19587764
DA 2026-03-09
ER

PT J
AU Gaspar-Maia, A
   Alajem, A
   Polesso, F
   Sridharan, R
   Mason, MJ
   Heidersbach, A
   Ramalho-Santos, J
   McManus, MT
   Plath, K
   Meshorer, E
   Ramalho-Santos, M
AF Gaspar-Maia, Alexandre
   Alajem, Adi
   Polesso, Fanny
   Sridharan, Rupa
   Mason, Mike J.
   Heidersbach, Amy
   Ramalho-Santos, Joao
   McManus, Michael T.
   Plath, Kathrin
   Meshorer, Eran
   Ramalho-Santos, Miguel
TI Chd1 regulates open chromatin and pluripotency of embryonic stem cells
SO NATURE
LA English
DT Article
ID self-renewal; expression; transcription; differentiation; fibroblasts; generation; lysine-4; protein
AB An open chromatin largely devoid of heterochromatin is a hallmark of stem cells. It remains unknown whether an open chromatin is necessary for the differentiation potential of stem cells, and which molecules are needed to maintain open chromatin. Here we show that the chromatin remodelling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells. Chd1 is a euchromatin protein that associates with the promoters of active genes, and downregulation of Chd1 leads to accumulation of heterochromatin. Chd1-deficient embryonic stem cells are no longer pluripotent, because they are incapable of giving rise to primitive endoderm and have a high propensity for neural differentiation. Furthermore, Chd1 is required for efficient reprogramming of fibroblasts to the pluripotent stem cell state. Our results indicate that Chd1 is essential for open chromatin and pluripotency of embryonic stem cells, and for somatic cell reprogramming to the pluripotent state.
C1 [Gaspar-Maia, Alexandre; Polesso, Fanny; Ramalho-Santos, Miguel] Univ Calif San Francisco, Dept Ob Gyn, San Francisco, CA 94143 USA.
   [Gaspar-Maia, Alexandre; Polesso, Fanny; Ramalho-Santos, Miguel] Univ Calif San Francisco, Dept Pathol, Ctr Reprod Sci, San Francisco, CA 94143 USA.
   [Gaspar-Maia, Alexandre; Polesso, Fanny; Ramalho-Santos, Miguel] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Gaspar-Maia, Alexandre; Polesso, Fanny; Heidersbach, Amy; McManus, Michael T.; Ramalho-Santos, Miguel] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
   [Gaspar-Maia, Alexandre] Univ Coimbra, PhD Programme Biomed & Expt Biol, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal.
   [Alajem, Adi; Meshorer, Eran] Hebrew Univ Jerusalem, Dept Genet, Inst Life Sci, IL-91904 Jerusalem, Israel.
   [Sridharan, Rupa; Mason, Mike J.; Plath, Kathrin] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA.
   [Sridharan, Rupa; Mason, Mike J.; Plath, Kathrin] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 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; Universidade de Coimbra; Hebrew University of Jerusalem; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Ramalho-Santos, M (corresponding author), Univ Calif San Francisco, Dept Ob Gyn, 513 Parnassus Ave, San Francisco, CA 94143 USA.
EM mrsantos@diabetes.ucsf.edu
FU Sandler Family; CIRM Young Investigator Award; NIH Director's New Innovator Award; Israel Science Foundation [ISF 215/07]; European Union [IRG-206872]; Alon Fellowship; California Institute for Regenerative Medicine; Juvenile Diabetes Research Foundation
NR 39
TC 402
Z9 494
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 AUG 13
PY 2009
VL 460
IS 7257
BP 863
EP U97
DI 10.1038/nature08212
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300031
PM 19587682
DA 2026-03-09
ER

PT J
AU Hanada, R
   Leibbrandt, A
   Hanada, T
   Kitaoka, S
   Furuyashiki, T
   Fujihara, H
   Trichereau, J
   Paolino, M
   Qadri, F
   Plehm, R
   Klaere, S
   Komnenovic, V
   Mimata, H
   Yoshimatsu, H
   Takahashi, N
   von Haeseler, A
   Bader, M
   Kilic, SS
   Ueta, Y
   Pifl, C
   Narumiya, S
   Penninger, JM
AF Hanada, Reiko
   Leibbrandt, Andreas
   Hanada, Toshikatsu
   Kitaoka, Shiho
   Furuyashiki, Tomoyuki
   Fujihara, Hiroaki
   Trichereau, Jean
   Paolino, Magdalena
   Qadri, Fatimunnisa
   Plehm, Ralph
   Klaere, Steffen
   Komnenovic, Vukoslav
   Mimata, Hiromitsu
   Yoshimatsu, Hironobu
   Takahashi, Naoyuki
   von Haeseler, Arndt
   Bader, Michael
   Kilic, Sara Sebnem
   Ueta, Yoichi
   Pifl, Christian
   Narumiya, Shuh
   Penninger, Josef M.
TI Central control of fever and female body temperature by RANKL/RANK
SO NATURE
LA English
DT Article
ID osteoclast differentiation factor; febrile response; mice lacking; c-fos; receptor; inflammation; mechanisms; denosumab; protein; ligand
AB Receptor-activator of NF-kappa B ligand (TNFSF11, also known as RANKL, OPGL, TRANCE and ODF) and its tumour necrosis factor (TNF)-family receptor RANK are essential regulators of bone remodelling, lymph node organogenesis and formation of a lactating mammary gland(1-4). RANKL and RANK are also expressed in the central nervous system(5,6). However, the functional relevance of RANKL/RANK in the brain was entirely unknown. Here we report that RANKL and RANK have an essential role in the brain. In both mice and rats, central RANKL injections trigger severe fever. Using tissue-specific Nestin-Cre and GFAP-Cre rank(floxed) deleter mice, the function of RANK in the fever response was genetically mapped to astrocytes. Importantly, Nestin-Cre and GFAP-Cre rank(floxed) deleter mice are resistant to lipopolysaccharide-induced fever as well as fever in response to the key inflammatory cytokines IL-1 beta and TNF alpha. Mechanistically, RANKL activates brain regions involved in thermoregulation and induces fever via the COX2-PGE(2)/EP3R pathway. Moreover, female Nestin-Cre and GFAP-Cre rank(floxed) mice exhibit increased basal body temperatures, suggesting that RANKL and RANK control thermoregulation during normal female physiology. We also show that two children with RANK mutations exhibit impaired fever during pneumonia. These data identify an entirely novel and unexpected function for the key osteoclast differentiation factors RANKL/RANK in female thermoregulation and the central fever response in inflammation.
C1 [Hanada, Reiko; Leibbrandt, Andreas; Hanada, Toshikatsu; Trichereau, Jean; Paolino, Magdalena; Komnenovic, Vukoslav; Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
   [Kitaoka, Shiho; Furuyashiki, Tomoyuki; Narumiya, Shuh] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan.
   [Fujihara, Hiroaki; Ueta, Yoichi] Univ Occupat & Environm Hlth, Sch Med, Dept Physiol, Kitakyushu, Fukuoka 8078555, Japan.
   [Qadri, Fatimunnisa; Plehm, Ralph; Bader, Michael] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Klaere, Steffen; von Haeseler, Arndt] Ctr Integrated Bioinformat, Max F Perutz Labs, A-1030 Vienna, Austria.
   [Mimata, Hiromitsu; Yoshimatsu, Hironobu] Oita Univ, Fac Med, Oita 8795593, Japan.
   [Takahashi, Naoyuki] Matsumoto Dent Univ, Inst Oral Sci, Nagano 3990781, Japan.
   [Kilic, Sara Sebnem] Uludag Univ, Fac Med, TR-16059 Bursa, Turkey.
   [Pifl, Christian] Med Univ Vienna, Ctr Brain Res, A-1090 Vienna, Austria.
C3 Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Austrian Academy of Sciences; Kyoto University; University of Occupational & Environmental Health - Japan; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL); Oita University; Matsumoto Dental University; Uludag University; Medical University of Vienna
RP Penninger, JM (corresponding author), Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
EM josef.penninger@imba.oeaw.ac.at
FU UEHARA Foundation; Japan Foundation for Applied Enzymology; Austrian Ministry for Science and Research; Wiener Wissenschafts-, Forschungs- und Technologiefonds (WWTF); IMBA; Austrian Ministry of Sciences; Austrian Academy of Sciences; GEN-AU ( AustroMouse); EU Marie Curie Excellence; EU ERC; Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF)
NR 22
TC 205
Z9 226
U1 2
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 505
EP 509
DI 10.1038/nature08596
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200044
PM 19940926
DA 2026-03-09
ER

PT J
AU Laskar, J
   Gastineau, M
AF Laskar, J.
   Gastineau, M.
TI Existence of collisional trajectories of Mercury, Mars and Venus with the Earth
SO NATURE
LA English
DT Article
ID long-term integrations; insolation quantity; evolution; stability
AB It has been established that, owing to the proximity of a resonance with Jupiter, Mercury's eccentricity can be pumped to values large enough to allow collision with Venus within 5 Gyr (refs 1-3). This conclusion, however, was established either with averaged equations(1,2) that are not appropriate near the collisions or with non-relativistic models in which the resonance effect is greatly enhanced by a decrease of the perihelion velocity of Mercury(2,3). In these previous studies, the Earth's orbit was essentially unaffected. Here we report numerical simulations of the evolution of the Solar System over 5 Gyr, including contributions from the Moon and general relativity. In a set of 2,501 orbits with initial conditions that are in agreement with our present knowledge of the parameters of the Solar System, we found, as in previous studies(2), that one per cent of the solutions lead to a large increase in Mercury's eccentricity-an increase large enough to allow collisions with Venus or the Sun. More surprisingly, in one of these high-eccentricity solutions, a subsequent decrease in Mercury's eccentricity induces a transfer of angular momentum from the giant planets that destabilizes all the terrestrial planets similar to 3.34 Gyr from now, with possible collisions of Mercury, Mars or Venus with the Earth.
C1 [Laskar, J.; Gastineau, M.] UPMC, Observ Paris, IMCCE CNRS, UMR8028, F-75014 Paris, France.
C3 Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite PSL; Observatoire de Paris
RP Laskar, J (corresponding author), UPMC, Observ Paris, IMCCE CNRS, UMR8028, 77 Ave Denfert Rochereau, F-75014 Paris, France.
EM laskar@imcce.fr
FU French National Research Centre; Paris Observatory; National Research Agency
NR 20
TC 169
Z9 191
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 JUN 11
PY 2009
VL 459
IS 7248
BP 817
EP 819
DI 10.1038/nature08096
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500033
PM 19516336
DA 2026-03-09
ER

PT J
AU Guydosh, NR
   Block, SM
AF Guydosh, Nicholas R.
   Block, Steven M.
TI Direct observation of the binding state of the kinesin head to the microtubule
SO NATURE
LA English
DT Article
ID optical force clamp; hand-over-hand; single-molecule; atp; resolution; mechanism; strain; steps; cycle
AB The dimeric motor protein kinesin-1 converts chemical energy from ATP hydrolysis into mechanical work used to transport cargo along microtubules(1,2). Cargo attached to the kinesin stalk moves processively in 8-nm increments(3) as its twin motor domains (heads) carry out an asymmetric, 'hand-over-hand' walk(4-7). The extent of individual head interactions with the microtubule during stepping, however, remains controversial(4,8-14). A major experimental limitation has been the lack of a means to monitor the attachment of an individual head to the microtubule during movement, necessitating indirect approaches. Here we report the development of a single-molecule assay that can directly report head binding in a walking kinesin molecule, and show that only a single head is bound to the microtubule between steps at low ATP concentrations. A bead was linked to one of the two kinesin heads by means of a short DNA tether and used to apply rapidly alternating hindering and assisting loads with an optical trap. The time-dependent difference between forwards and backwards displacements of the bead alternated between two discrete values during stepping, corresponding to those intervals when the linked head adopted a bound or an unbound state. The linked head could only rebind the microtubule once ATP had become bound to its partner head.
C1 [Block, Steven M.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Block, Steven M.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Guydosh, Nicholas R.] Stanford Univ, Biophys Program, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University
RP Block, SM (corresponding author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
EM sblock@stanford.edu
FU US National Institutes of Health [GM51453]
NR 31
TC 85
Z9 110
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 SEP 3
PY 2009
VL 461
IS 7260
BP 125
EP U137
DI 10.1038/nature08259
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800043
PM 19693012
DA 2026-03-09
ER

PT J
AU Kim, M
   Ogawa, M
   Fujita, Y
   Yoshikawa, Y
   Nagai, T
   Koyama, T
   Nagai, S
   Lange, A
   Fässler, R
   Sasakawa, C
AF Kim, Minsoo
   Ogawa, Michinaga
   Fujita, Yukihiro
   Yoshikawa, Yuko
   Nagai, Takeshi
   Koyama, Tomohiro
   Nagai, Shinya
   Lange, Anika
   Faessler, Reinhard
   Sasakawa, Chihiro
TI Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment
SO NATURE
LA English
DT Article
ID iii secretion system; escherichia-coli; shigella-flexneri; protein-kinase; ilk; pathogenicity; repertoire; expression; mechanism; virulence
AB The rapid turnover and exfoliation of mucosal epithelial cells provides an innate defence system against bacterial infection(1,2). Nevertheless, many pathogenic bacteria, including Shigella, are able to surmount exfoliation and colonize the epithelium efficiently(3,4). Here we show that the Shigella flexneri effector OspE(5,6) (consisting of OspE1 and OspE2 proteins), which is highly conserved among enteropathogenic Escherichia coli, enterohaemorrhagic E. coli, Citrobacter rodentium and Salmonella strains(7), reinforces host cell adherence to the basement membrane by interacting with integrin-linked kinase (ILK)(8). The number of focal adhesions was augmented along with membrane fraction ILK by ILK-OspE binding. The interaction between ILK and OspE increased cell surface levels of beta 1 integrin and suppressed phosphorylation of focal adhesion kinase and paxillin, which are required for rapid turnover of focal adhesion in cell motility(9). Nocodazole-washout-induced focal adhesion disassembly was blocked by expression of OspE. Polarized epithelial cells infected with a Shigella mutant lacking the ospE gene underwent more rapid cell detachment than cells infected with wild-type Shigella. Infection of guinea pig colons with Shigella corroborated the pivotal role of the OspE-ILK interaction in suppressing epithelial detachment, increasing bacterial cell-to-cell spreading, and promoting bacterial colonization. These results indicate that Shigella sustain their infectious foothold by using special tactics to prevent detachment of infected cells.
C1 [Kim, Minsoo; Sasakawa, Chihiro] Univ Tokyo, Int Res Ctr Infect Dis, Dept Infect Dis Control, Minato Ku, Tokyo 1088639, Japan.
   [Ogawa, Michinaga; Fujita, Yukihiro; Yoshikawa, Yuko; Nagai, Takeshi; Sasakawa, Chihiro] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Minato Ku, Tokyo 1088639, Japan.
   [Kim, Minsoo; Ogawa, Michinaga; Fujita, Yukihiro; Yoshikawa, Yuko; Nagai, Takeshi; Sasakawa, Chihiro] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
   [Koyama, Tomohiro; Nagai, Shinya] Nippon Inst Biol Sci, Tokyo 1980024, Japan.
   [Lange, Anika; Faessler, Reinhard] Max Planck Inst Biochem, Dept Mol Med, D-82151 Martinsried, Germany.
C3 University of Tokyo; University of Tokyo; Japan Science & Technology Agency (JST); Max Planck Society
RP Sasakawa, C (corresponding author), Univ Tokyo, Int Res Ctr Infect Dis, Dept Infect Dis Control, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan.
EM sasakawa@ims.u-tokyo.ac.jp
FU Deutsche Forschungsgemeinschaft [SFB576]; Max Planck Society; Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); Japan Science and Technology Agency (JSTA)
NR 37
TC 142
Z9 167
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 MAY 28
PY 2009
VL 459
IS 7246
BP 578
EP U109
DI 10.1038/nature07952
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500041
PM 19489119
DA 2026-03-09
ER

PT J
AU Bakr, WS
   Gillen, JI
   Peng, A
   Fölling, S
   Greiner, M
AF Bakr, Waseem S.
   Gillen, Jonathon I.
   Peng, Amy
   Foelling, Simon
   Greiner, Markus
TI A quantum gas microscope for detecting single atoms in a Hubbard-regime optical lattice
SO NATURE
LA English
DT Article
ID ultracold atoms; mott insulator
AB Recent years have seen tremendous progress in creating complex atomicmany-body quantum systems. One approach is to use macroscopic, effectively thermodynamic ensembles of ultracold atoms to create quantum gases and strongly correlated states of matter, and to analyse the bulk properties of the ensemble. For example, bosonic and fermionic atoms in a Hubbard-regime optical lattice(1-5) can be used for quantum simulations of solid-state models(6). The opposite approach is to build up microscopic quantum systems atom-by-atom, with complete control over all degrees of freedom(7-9). The atoms or ions act as qubits and allow the realization of quantum gates, with the goal of creating highly controllable quantum information systems. Until now, the macroscopic and microscopic strategies have been fairly disconnected. Here we present a quantum gas 'microscope' that bridges the two approaches, realizing a system in which atoms of a macroscopic ensemble are detected individually and a complete set of degrees of freedom for each of them is determined through preparation and measurement. By implementing a high-resolution optical imaging system, single atoms are detected with near-unity fidelity on individual sites of a Hubbard-regime optical lattice. The lattice itself is generated by projecting a holographic mask through the imaging system. It has an arbitrary geometry, chosen to support both strong tunnel coupling between lattice sites and strong on-site confinement. Our approach can be used to directly detect strongly correlated states of matter; in the context of condensed matter simulation, this corresponds to the detection of individual electrons in the simulated crystal. Also, the quantum gas microscope may enable addressing and read-out of large-scale quantum information systems based on ultracold atoms.
C1 [Bakr, Waseem S.; Gillen, Jonathon I.; Peng, Amy; Foelling, Simon; Greiner, Markus] Harvard Univ, Harvard MIT Ctr Ultracold Atoms, Cambridge, MA 02138 USA.
   [Bakr, Waseem S.; Gillen, Jonathon I.; Peng, Amy; Foelling, Simon; Greiner, Markus] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University
RP Greiner, M (corresponding author), Harvard Univ, Harvard MIT Ctr Ultracold Atoms, Cambridge, MA 02138 USA.
EM greiner@physics.harvard.edu
FU NSF; AFOSR MURI; DARPA; Alfred P. Sloan Fellowship
NR 30
TC 1234
Z9 1449
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 NOV 5
PY 2009
VL 462
IS 7269
BP 74
EP U80
DI 10.1038/nature08482
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200034
PM 19890326
DA 2026-03-09
ER

PT J
AU Mammoto, A
   Connor, KM
   Mammoto, T
   Yung, CW
   Huh, D
   Aderman, CM
   Mostoslavsky, G
   Smith, LEH
   Ingber, DE
AF Mammoto, Akiko
   Connor, Kip M.
   Mammoto, Tadanori
   Yung, Chong Wing
   Huh, Dongeun
   Aderman, Christopher M.
   Mostoslavsky, Gustavo
   Smith, Lois E. H.
   Ingber, Donald E.
TI A mechanosensitive transcriptional mechanism that controls angiogenesis
SO NATURE
LA English
DT Article
ID endothelial growth-factor; cell-shape; extracellular-matrix; retinal neovascularization; lineage specification; cytoskeletal tension; regulatory networks; geometric control; tfii-i; vegf
AB Angiogenesis is controlled by physical interactions between cells and extracellular matrix as well as soluble angiogenic factors, such as VEGF. However, the mechanism by which mechanical signals integrate with other microenvironmental cues to regulate neovascularization remains unknown. Here we show that the Rho inhibitor, p190RhoGAP (also known as GRLF1), controls capillary network formation in vitro in human microvascular endothelial cells and retinal angiogenesis in vivo by modulating the balance of activities between two antagonistic transcription factors, TFII-I (also known as GTF2I) and GATA2, that govern gene expression of the VEGF receptor VEGFR2 (also known as KDR). Moreover, this new angiogenesis signalling pathway is sensitive to extracellular matrix elasticity as well as soluble VEGF. This is, to our knowledge, the first known functional cross-antagonism between transcription factors that controls tissue morphogenesis, and that responds to both mechanical and chemical cues.
C1 [Mammoto, Akiko; Mammoto, Tadanori; Yung, Chong Wing; Huh, Dongeun; Ingber, Donald E.] Childrens Hosp, Dept Pathol, Vasc Biol Program, Boston, MA 02115 USA.
   [Mammoto, Akiko; Mammoto, Tadanori; Yung, Chong Wing; Huh, Dongeun; Ingber, Donald E.] Childrens Hosp, Dept Pathol, Dept Surg, Boston, MA 02115 USA.
   [Connor, Kip M.; Aderman, Christopher M.; Smith, Lois E. H.] Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
   [Mostoslavsky, Gustavo] Harvard Univ, Sch Med, Harvard Inst Med, Dept Genet, Boston, MA 02115 USA.
   [Ingber, Donald E.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Ingber, Donald E.] Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University
RP Ingber, DE (corresponding author), Childrens Hosp, Dept Pathol, Vasc Biol Program, Boston, MA 02115 USA.
EM donald.ingber@childrens.harvard.edu
FU NIH; V. Kann Rasmussen Foundation; Children's Hospital Mental Retardation and Developmental Disabilities Research Center; Research to Prevent Blindness Lew Wasserman Merit Award; American Heart Association; Children's Hospital House Officer Development Award; DoD Breast Cancer Innovator Award
NR 47
TC 437
Z9 575
U1 0
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 26
PY 2009
VL 457
IS 7233
BP 1103
EP U57
DI 10.1038/nature07765
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100034
PM 19242469
DA 2026-03-09
ER

PT J
AU Jovanovic-Talisman, T
   Tetenbaum-Novatt, J
   McKenney, AS
   Zilman, A
   Peters, R
   Rout, MP
   Chait, BT
AF Jovanovic-Talisman, Tijana
   Tetenbaum-Novatt, Jaclyn
   McKenney, Anna Sophia
   Zilman, Anton
   Peters, Reiner
   Rout, Michael P.
   Chait, Brian T.
TI Artificial nanopores that mimic the transport selectivity of the nuclear pore complex
SO NATURE
LA English
DT Article
ID nucleocytoplasmic transport; importin-beta; nucleoporins; permeability; architecture; mechanism; membranes; reveals; regions; sites
AB Nuclear pore complexes ( NPCs) act as effective and robust gateways between the nucleus and the cytoplasm, selecting for the passage of particular macromolecules across the nuclear envelope. NPCs comprise an elaborate scaffold that defines a similar to 30 nm diameter passageway connecting the nucleus and the cytoplasm. This scaffold anchors proteins termed 'phenylalanine- glycine' ( FG)- nucleoporins, the natively disordered domains of which line the passageway and extend into its lumen(1). Passive diffusion through this lined passageway is hindered in a size- dependent manner. However, transport factors and their cargo- bound complexes overcome this restriction by transient binding to the FG-nucleoporins(2-10). To test whether a simple passageway and a lining of transport- factor- binding FG- nucleoporins are sufficient for selective transport, we designed a functionalized membrane that incorporates just these two elements. Here we demonstrate that this membrane functions as a nanoselective filter, efficiently passing transport factors and transport- factor - cargo complexes that specifically bind FG- nucleoporins, while significantly inhibiting the passage of proteins that do not. This inhibition is greatly enhanced when transport factor is present. Determinants of selectivity include the passageway diameter, the length of the nanopore region coated with FG- nucleoporins, the binding strength to FG-nucleoporins, and the antagonistic effect of transport factors on the passage of proteins that do not specifically bind FG- nucleoporins. We show that this artificial system faithfully reproduces key features of trafficking through the NPC, including transport-factor-mediated cargo import.
C1 [Jovanovic-Talisman, Tijana; Chait, Brian T.] Rockefeller Univ, Lab Mass Spect & Gaseous Ion Chem, New York, NY 10065 USA.
   [Tetenbaum-Novatt, Jaclyn; McKenney, Anna Sophia; Rout, Michael P.] Rockefeller Univ, Lab Cellular & Struct Biol, New York, NY 10065 USA.
   [Zilman, Anton] Los Alamos Natl Lab, Div Theoret, Theoret Biol & Biophys Grp, Los Alamos, NM 87545 USA.
   [Zilman, Anton] Los Alamos Natl Lab, Div Theoret, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA.
   [Peters, Reiner] Univ Munster, Inst Med Phys & Biophys, D-48149 Munster, Germany.
   [Peters, Reiner] Univ Munster, Ctr Nanotechnol CeNTech, D-48149 Munster, Germany.
C3 Rockefeller University; Rockefeller University; United States Department of Energy (DOE); Los Alamos National Laboratory; United States Department of Energy (DOE); Los Alamos National Laboratory; University of Munster; University of Munster
RP Chait, BT (corresponding author), Rockefeller Univ, Lab Mass Spect & Gaseous Ion Chem, 1230 York Ave, New York, NY 10065 USA.
EM chait@rockefeller.edu
FU NIH; DoE; National Institute of General Medical Sciences [T32GM007739] Funding Source: NIH RePORTER
NR 29
TC 242
Z9 278
U1 4
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 FEB 19
PY 2009
VL 457
IS 7232
BP 1023
EP 1027
DI 10.1038/nature07600
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400045
PM 19098896
DA 2026-03-09
ER

PT J
AU Mathieu, RD
   Geller, AM
AF Mathieu, Robert D.
   Geller, Aaron M.
TI A binary star fraction of 76 per cent and unusual orbit parameters for the blue stragglers of NGC 188
SO NATURE
LA English
DT Article
ID wiyn open cluster; solar-type stars; spectroscopic binary; tidal circularization; m67; ngc-188; triple; populations; evolution; systems
AB Blue straggler stars lie on or near the main sequences of star clusters (all members of which formed around the same time), but typically are more luminous than the turn-off stars and therefore long ago should have evolved off the main sequence to become giants and white dwarfs. They are thought to derive from normal main-sequence stars that have undergone a recent increase in mass. Statistical evidence indicates that in globular star clusters the blue stragglers probably form from binary stars(1). The specific formation processes, such as mass transfer, mergers or stellar collisions during dynamical encounters of binary stars, remain unresolved. Here we report that 16 of the 21 blue stragglers ( 76 per cent) in the old (7-Gyr; ref. 2) open cluster NGC188 are currently in binary systems, a frequency three times that found among normal solar-type main-sequence stars. These blue straggler binaries have a remarkable period-eccentricity distribution, with all but three having orbital periods of similar to 1,000 days. Moreover, these stars are rotating faster than normal main-sequence stars of the same surface temperatures. These data show that most, and possibly all, blue stragglers derive from multiple-star systems, and indicate that the several formation processes operate simultaneously. We suggest that rapid rotation of blue stragglers may place upper limits on their ages.
C1 [Mathieu, Robert D.; Geller, Aaron M.] Univ Wisconsin, Dept Astron, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison
RP Mathieu, RD (corresponding author), Univ Wisconsin, Dept Astron, 475 N Charter St, Madison, WI 53706 USA.
EM mathieu@astro.wisc.edu
FU US National Science Foundation [AST-0406615]; Wisconsin Space Grant Consortium
NR 26
TC 125
Z9 136
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 DEC 24
PY 2009
VL 462
IS 7276
BP 1032
EP 1035
DI 10.1038/nature08568
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000041
PM 20033042
DA 2026-03-09
ER

PT J
AU Xiao, A
   Li, HT
   Shechter, D
   Ahn, SH
   Fabrizio, LA
   Erdjument-Bromage, H
   Ishibe-Murakami, S
   Wang, B
   Tempst, P
   Hofmann, K
   Patel, DJ
   Elledge, SJ
   Allis, CD
AF Xiao, Andrew
   Li, Haitao
   Shechter, David
   Ahn, Sung Hee
   Fabrizio, Laura A.
   Erdjument-Bromage, Hediye
   Ishibe-Murakami, Satoko
   Wang, Bin
   Tempst, Paul
   Hofmann, Kay
   Patel, Dinshaw J.
   Elledge, Stephen J.
   Allis, C. David
TI WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity
SO NATURE
LA English
DT Article
ID double-strand breaks; mass-spectrometry; genomic stability; histone h2ax; chromatin; mdc1; complex; iswi; atm; phosphorylation
AB DNA double- stranded breaks present a serious challenge for eukaryotic cells. The inability to repair breaks leads to genomic instability, carcinogenesis and cell death. During the double- strand break response, mammalian chromatin undergoes reorganization demarcated by H2A.X Ser 139 phosphorylation (gamma-H2A.X). However, the regulation of gamma-H2A.X phosphorylation and its precise role in chromatin remodelling during the repair process remain unclear. Here we report a new regulatory mechanism mediated by WSTF ( Williams - Beuren syndrome transcription factor, also known as BAZ1B) - a component of the WICH complex (WSTF-ISWI ATP- dependent chromatin- remodelling complex). We show that WSTF has intrinsic tyrosine kinase activity by means of a domain that shares no sequence homology to any known kinase fold. We show that WSTF phosphorylates Tyr 142 of H2A.X, and that WSTF activity has an important role in regulating several events that are critical for the DNA damage response. Our work demonstrates a new mechanism that regulates the DNA damage response and expands our knowledge of domains that contain intrinsic tyrosine kinase activity.
C1 [Xiao, Andrew; Shechter, David; Ahn, Sung Hee; Allis, C. David] Rockefeller Univ, Lab Chromatin Biol, New York, NY 10065 USA.
   [Li, Haitao; Ishibe-Murakami, Satoko; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Fabrizio, Laura A.; Erdjument-Bromage, Hediye; Tempst, Paul] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA.
   [Wang, Bin; Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA.
   [Hofmann, Kay] Miltenyi Biotec GmbH, D-50829 Cologne, Germany.
C3 Rockefeller University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Miltenyi Biotec
RP Allis, CD (corresponding author), Rockefeller Univ, Lab Chromatin Biol, New York, NY 10065 USA.
EM alliscd@rockefeller.edu
FU Susan G. Komen Breast Cancer Foundation; Abby Rockefeller Mauze Trust; Starr Foundation; The Dewitt Wallace and Maloris Foundations; The Irma T. Hirschl Trust; NCI Cancer Center Support Grant [P30 CA08748]; National Institutes of Health; The Rockefeller University; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM040922] Funding Source: NIH RePORTER
NR 48
TC 332
Z9 413
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 JAN 1
PY 2009
VL 457
IS 7225
BP 57
EP U57
DI 10.1038/nature07668
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900029
PM 19092802
DA 2026-03-09
ER

PT J
AU Cheng, N
   Tsunenari, T
   Yau, KW
AF Cheng, Ning
   Tsunenari, Takashi
   Yau, King-Wai
TI Intrinsic light response of retinal horizontal cells of teleosts
SO NATURE
LA English
DT Article
ID sustained calcium current; gamma-aminobutyric-acid; ganglion-cells; melanopsin; opsin; modulation; receptors; zebrafish; goldfish; tissue
AB The discovery of intrinsically photosensitive retinal ganglion cells has overthrown the long-held belief that rods and cones are the exclusive retinal photoreceptors(1,2). Intrinsically photosensitive retinal ganglion cells use melanopsin(3) as the photopigment, and mediate non-image-forming visual functions such as circadian photoentrainment. In fish, in situ hybridization studies indicated that melanopsin is present in retinal horizontal cells(4-6)-lateral association neurons critical for creating the centre-surround receptive fields of visual neurons. This raises the question of whether fish horizontal cells are intrinsically photosensitive. This notion was examined previously in flat-mount roach retina, but all horizontal-cell light response disappeared after synaptic transmission was blocked(6), making any conclusion difficult to reach. To examine this question directly, we have now recorded from single, acutely dissociated horizontal cells from catfish and goldfish. We found that light induced a response in catfish cone horizontal cells, but not rod horizontal cells, consisting of a modulation of the nifedipine-sensitive, voltage-gated calcium current. The light response was extremely slow, lasting for many minutes. Similar light responses were observed in a high percentage of goldfish horizontal cells. We have cloned two melanopsin genes and one vertebrate ancient (VA) opsin gene from catfish. In situ hybridization indicated that melanopsin, but less likely VA opsin, was expressed in the horizontal-cell layer of catfish retina. This intrinsic light response may serve to modulate, over a long time-scale, lateral inhibition mediated by these cells. Thus, at least in some vertebrates, there are retinal non-rod/non-cone photoreceptors involved primarily in image-forming vision.
C1 [Cheng, Ning; Tsunenari, Takashi; Yau, King-Wai] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Cheng, Ning; Tsunenari, Takashi; Yau, King-Wai] Johns Hopkins Univ, Sch Med, Ctr Sensory Biol, Baltimore, MD 21205 USA.
   [Yau, King-Wai] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University
RP Cheng, N (corresponding author), NINDS, Unit Dev Neural Plast, NIH, Bethesda, MD 20892 USA.
EM chengn2@mail.nih.gov; kwyau@mail.jhmi.edu
FU NIH; Antonio Champalimaud Vision Award (Portugal); National Eye Institute [R01EY014596] Funding Source: NIH RePORTER
NR 30
TC 42
Z9 51
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 13
PY 2009
VL 460
IS 7257
BP 899
EP U139
DI 10.1038/nature08175
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300040
PM 19633653
DA 2026-03-09
ER

PT J
AU Grandison, RC
   Piper, MDW
   Partridge, L
AF Grandison, Richard C.
   Piper, Matthew D. W.
   Partridge, Linda
TI Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila
SO NATURE
LA English
DT Article
ID natural-selection; reproduction; food; melanogaster; longevity; survival; growth
AB Dietary restriction extends healthy lifespan in diverse organisms and reduces fecundity(1,2). It is widely assumed to induce adaptive reallocation of nutrients from reproduction to somatic maintenance, aiding survival of food shortages in nature(3-6). If this were the case, long life under dietary restriction and high fecundity under full feeding would be mutually exclusive, through competition for the same limiting nutrients. Here we report a test of this idea in which we identified the nutrients producing the responses of lifespan and fecundity to dietary restriction in Drosophila. Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction. Lifespan was decreased by the addition of amino acids, with an interaction between methionine and other essential amino acids having a key role. Hence, an imbalance in dietary amino acids away from the ratio optimal for reproduction shortens lifespan during full feeding and limits fecundity during dietary restriction. Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms(7), and we find that it also protects against the shortening of lifespan with full feeding. In other organisms, including mammals, it may be possible to obtain the benefits to lifespan of dietary restriction without incurring a reduction in fecundity, through a suitable balance of nutrients in the diet.
C1 [Grandison, Richard C.; Piper, Matthew D. W.; Partridge, Linda] UCL, Inst Healthy Ageing, Dept Genet Evolut & Environm, London WC1E 6BT, England.
C3 University of London; University College London
RP Partridge, L (corresponding author), UCL, Inst Healthy Ageing, Dept Genet Evolut & Environm, Gower St, London WC1E 6BT, England.
EM l.partridge@ucl.ac.uk
FU Wellcome Trust Strategic Award; Research into Ageing
NR 36
TC 621
Z9 737
U1 0
U2 194
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1061
EP U121
DI 10.1038/nature08619
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000048
PM 19956092
DA 2026-03-09
ER

PT J
AU Ishikawa, H
   Ma, Z
   Barber, GN
AF Ishikawa, Hiroki
   Ma, Zhe
   Barber, Glen N.
TI STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
SO NATURE
LA English
DT Article
ID hepatitis-c virus; rig-i; adapter protein; cytoplasmic dna; cytosolic dna; kappa-b; recognition; rna; inflammasome; activation
AB The innate immune system is critical for the early detection of invading pathogens and for initiating cellular host defence countermeasures, which include the production of type I interferon (IFN) 1-3. However, little is known about how the innate immune system is galvanized to respond to DNA-based microbes. Here we show that STING (stimulator of interferon genes) is critical for the induction of IFN by non-CpG intracellular DNA species produced by various DNA pathogens after infection(4). Murine embryonic fibroblasts, as well as antigen presenting cells such as macrophages and dendritic cells (exposed to intracellular B-form DNA, the DNA virus herpes simplex virus 1 (HSV-1) or bacteria Listeria monocytogenes), were found to require STING to initiate effective IFN production. Accordingly, Sting-knockout mice were susceptible to lethal infection after exposure to HSV-1. The importance of STING in facilitating DNA-mediated innate immune responses was further evident because cytotoxic T-cell responses induced by plasmid DNA vaccination were reduced in Sting-deficient animals. In the presence of intracellular DNA, STING relocalized with TANK-binding kinase 1 (TBK1) from the endoplasmic reticulum to perinuclear vesicles containing the exocystcomponent Sec5 (also known as EXOC2). Collectively, our studies indicate that STING is essential for host defence against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines.
C1 [Barber, Glen N.] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
   Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
C3 University of Miami; University of Miami
RP Barber, GN (corresponding author), Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
EM gbarber@med.miami.edu
FU NIH [AI079336]
NR 30
TC 2263
Z9 2647
U1 5
U2 420
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 8
PY 2009
VL 461
IS 7265
BP 788
EP U40
DI 10.1038/nature08476
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500035
PM 19776740
DA 2026-03-09
ER

PT J
AU Leidel, S
   Pedrioli, PGA
   Bucher, T
   Brost, R
   Costanzo, M
   Schmidt, A
   Aebersold, R
   Boone, C
   Hofmann, K
   Peter, M
AF Leidel, Sebastian
   Pedrioli, Patrick G. A.
   Bucher, Tamara
   Brost, Renee
   Costanzo, Michael
   Schmidt, Alexander
   Aebersold, Ruedi
   Boone, Charles
   Hofmann, Kay
   Peter, Matthias
TI Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA
SO NATURE
LA English
DT Article
ID protein conjugation; statistical-model; mass-spectrometry; escherichia-coli; biosynthesis; yeast; identification; thiamin; tandem; genes
AB Ubiquitin-like proteins (UBLs) can change protein function, localization or turnover by covalent attachment to lysine residues(1). Although UBLs achieve this conjugation through an intricate enzymatic cascade, their bacterial counterparts MoaD and ThiS function as sulphur carrier proteins(2,3). Here we show that Urm1p, the most ancient UBL3, acts as a sulphur carrier in the process of eukaryotic transfer RNA ( tRNA) modification, providing a possible evolutionary link between UBL and sulphur transfer. Moreover, we identify Uba4p, Ncs2p, Ncs6p and Yor251cp as components of this conserved pathway. Using in vitro assays, we show that Ncs6p binds to tRNA, whereas Uba4p first adenylates and then directly transfers sulphur onto Urm1p. Finally, functional analysis reveals that the thiolation function of Urm1p is critical to regulate cellular responses to nutrient starvation and oxidative stress conditions, most likely by increasing translation fidelity.
C1 [Leidel, Sebastian; Pedrioli, Patrick G. A.; Bucher, Tamara; Peter, Matthias] ETH, Inst Biochem, CH-8093 Zurich, Switzerland.
   [Brost, Renee; Costanzo, Michael; Boone, Charles] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
   [Brost, Renee; Costanzo, Michael; Boone, Charles] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.
   [Schmidt, Alexander; Aebersold, Ruedi] ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland.
   [Aebersold, Ruedi] Inst Syst Biol, Seattle, WA 98103 USA.
   [Schmidt, Alexander; Aebersold, Ruedi; Peter, Matthias] Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland.
   [Hofmann, Kay] Miltenyi Biotec GmbH, Bioinformat Grp, D-51429 Bergisch Gladbach, Germany.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Toronto; University of Toronto; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich; Institute for Systems Biology (ISB); Miltenyi Biotec
RP Peter, M (corresponding author), ETH, Inst Biochem, Schafmattstr 18, CH-8093 Zurich, Switzerland.
EM kay.hofmann@miltenyibiotec.de; matthias.peter@bc.biol.ethz.ch
FU EuroDyna; Roche Research Foundation; ETHZ; SNF; Canadian Institutes of Health Research; Genome Canada through the Ontario Genomics Institute
NR 49
TC 239
Z9 274
U1 1
U2 44
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 228
EP U9
DI 10.1038/nature07643
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700049
PM 19145231
DA 2026-03-09
ER

PT J
AU Pallé, E
   Osorio, MRZ
   Barrena, R
   Montañés-Rodríguez, P
   Martín, EL
AF Palle, Enric
   Zapatero Osorio, Maria Rosa
   Barrena, Rafael
   Montanes-Rodriguez, Pilar
   Martin, Eduardo L.
TI Earth's transmission spectrum from lunar eclipse observations
SO NATURE
LA English
DT Article
ID extrasolar planet; super-earths; water-vapor; atmosphere; search; ionosphere; mission
AB Of the 342 planets so far discovered(1) orbiting other stars, 58 'transit' the stellar disk, meaning that they can be detected through a periodic decrease in the flux of starlight(2). The light from the star passes through the atmosphere of the planet, and in a few cases the basic atmospheric composition of the planet can be estimated(3-5). As we get closer to finding analogues of Earth(6-8), an important consideration for the characterization of extrasolar planetary atmospheres is what the transmission spectrum of our planet looks like. Here we report the optical and near-infrared transmission spectrum of the Earth, obtained during a lunar eclipse. Some biologically relevant atmospheric features that are weak in the reflection spectrum(9) (such as ozone, molecular oxygen, water, carbon dioxide and methane) are much stronger in the transmission spectrum, and indeed stronger than predicted by modelling(10,11). We also find the 'fingerprints' of the Earth's ionosphere and of the major atmospheric constituent, molecular nitrogen (N(2)), which are missing in the reflection spectrum.
C1 [Palle, Enric; Zapatero Osorio, Maria Rosa; Barrena, Rafael; Montanes-Rodriguez, Pilar; Martin, Eduardo L.] Inst Astrofis Canarias, E-38205 Tenerife, Spain.
   [Martin, Eduardo L.] Univ Cent Florida, Dept Phys, Orlando, FL 32816 USA.
C3 Instituto de Astrofisica de Canarias; State University System of Florida; University of Central Florida
RP Pallé, E (corresponding author), Inst Astrofis Canarias, Via Lactea S-N, E-38205 Tenerife, Spain.
EM epalle@iac.es
FU Spanish Ministry of Science via the Ramon y Cajal [AYA2007-67458]
NR 29
TC 113
Z9 120
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 814
EP 816
DI 10.1038/nature08050
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500032
PM 19516335
DA 2026-03-09
ER

PT J
AU Kim, JI
   Ju, YS
   Park, H
   Kim, S
   Lee, S
   Yi, JH
   Mudge, J
   Miller, NA
   Hong, D
   Bell, CJ
   Kim, HS
   Chung, IS
   Lee, WC
   Lee, JS
   Seo, SH
   Yun, JY
   Woo, HN
   Lee, H
   Suh, D
   Lee, S
   Kim, HJ
   Yavartanoo, M
   Kwak, M
   Zheng, Y
   Lee, MK
   Park, H
   Kim, JY
   Gokcumen, O
   Mills, RE
   Zaranek, AW
   Thakuria, J
   Wu, X
   Kim, RW
   Huntley, JJ
   Luo, S
   Schroth, GP
   Wu, TD
   Kim, H
   Yang, KS
   Park, WY
   Kim, H
   Church, GM
   Lee, C
   Kingsmore, SF
   Seo, JS
AF Kim, Jong-Il
   Ju, Young Seok
   Park, Hansoo
   Kim, Sheehyun
   Lee, Seonwook
   Yi, Jae-Hyuk
   Mudge, Joann
   Miller, Neil A.
   Hong, Dongwan
   Bell, Callum J.
   Kim, Hye-Sun
   Chung, In-Soon
   Lee, Woo-Chung
   Lee, Ji-Sun
   Seo, Seung-Hyun
   Yun, Ji-Young
   Woo, Hyun Nyun
   Lee, Heewook
   Suh, Dongwhan
   Lee, Seungbok
   Kim, Hyun-Jin
   Yavartanoo, Maryam
   Kwak, Minhye
   Zheng, Ying
   Lee, Mi Kyeong
   Park, Hyunjun
   Kim, Jeong Yeon
   Gokcumen, Omer
   Mills, Ryan E.
   Zaranek, Alexander Wait
   Thakuria, Joseph
   Wu, Xiaodi
   Kim, Ryan W.
   Huntley, Jim J.
   Luo, Shujun
   Schroth, Gary P.
   Wu, Thomas D.
   Kim, HyeRan
   Yang, Kap-Seok
   Park, Woong-Yang
   Kim, Hyungtae
   Church, George M.
   Lee, Charles
   Kingsmore, Stephen F.
   Seo, Jeong-Sun
TI A highly annotated whole-genome sequence of a Korean individual
SO NATURE
LA English
DT Article
ID messenger-rna
AB Recent advances in sequencing technologies have initiated an era of personal genome sequences. To date, human genome sequences have been reported for individuals with ancestry in three distinct geographical regions: a Yoruba African, two individuals of northwest European origin, and a person from China(1-4). Here we provide a highly annotated, whole-genome sequence for a Korean individual, known as AK1. The genome of AK1 was determined by an exacting, combined approach that included whole-genome shot-gun sequencing (27.8x coverage), targeted bacterial artificial chromosome sequencing, and high-resolution comparative genomic hybridization using custom microarrays featuring more than 24 million probes. Alignment to the NCBI reference, a composite of several ethnic clades(5,6), disclosed nearly 3.45 million single nucleotide polymorphisms ( SNPs), including 10,162 non-synonymous SNPs, and 170,202 deletion or insertion polymorphisms (indels). SNP and indel densities were strongly correlated genome-wide. Applying very conservative criteria yielded highly reliable copy number variants for clinical considerations. Potential medical phenotypes were annotated for non-synonymous SNPs, coding domain indels, and structural variants. The integration of several human whole-genome sequences derived from several ethnic groups will assist in understanding genetic ancestry, migration patterns and population bottlenecks.
C1 [Kim, Jong-Il; Ju, Young Seok; Park, Hansoo; Yi, Jae-Hyuk; Hong, Dongwan; Suh, Dongwhan; Lee, Seungbok; Kim, Hyun-Jin; Yavartanoo, Maryam; Kwak, Minhye; Zheng, Ying; Park, Hyunjun; Kim, Jeong Yeon; Park, Woong-Yang; Seo, Jeong-Sun] Seoul Natl Univ, Med Res Ctr, Genom Med Inst, Seoul 110799, South Korea.
   [Kim, Jong-Il; Ju, Young Seok; Suh, Dongwhan; Lee, Seungbok; Yavartanoo, Maryam; Kwak, Minhye; Zheng, Ying; Park, Woong-Yang; Seo, Jeong-Sun] Seoul Natl Univ, Grad Sch, Coll Med, Dept Biochem & Mol Biol, Seoul 110799, South Korea.
   [Suh, Dongwhan; Lee, Seungbok; Kim, Hyun-Jin; Park, Woong-Yang; Seo, Jeong-Sun] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 110799, South Korea.
   [Kim, Jong-Il; Kim, Sheehyun; Lee, Seonwook; Kim, Hye-Sun; Chung, In-Soon; Lee, Woo-Chung; Lee, Ji-Sun; Woo, Hyun Nyun; Lee, Heewook; Kim, HyeRan; Yang, Kap-Seok; Kim, Hyungtae; Seo, Jeong-Sun] Macrogen Inc, Seoul 153023, South Korea.
   [Kim, Jong-Il; Park, Hansoo; Seo, Seung-Hyun; Yun, Ji-Young; Lee, Mi Kyeong; Seo, Jeong-Sun] Psoma Therapeut Inc, Seoul 110799, South Korea.
   [Mudge, Joann; Miller, Neil A.; Bell, Callum J.; Mills, Ryan E.; Kingsmore, Stephen F.] Natl Ctr Genome Resources, Santa Fe, NM 87505 USA.
   [Gokcumen, Omer; Mills, Ryan E.; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Zaranek, Alexander Wait; Thakuria, Joseph; Wu, Xiaodi; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Huntley, Jim J.; Luo, Shujun; Schroth, Gary P.] Illumina Inc, Hayward, CA 94545 USA.
   [Wu, Thomas D.] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA.
C3 Seoul National University (SNU); Seoul National University (SNU); Seoul National University (SNU); Macrogen, Inc.; National Center for Genome Resources (NCGR); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Illumina; Roche Holding; Roche Holding USA; Genentech
RP Seo, JS (corresponding author), Seoul Natl Univ, Med Res Ctr, Genom Med Inst, Seoul 110799, South Korea.
EM jeongsun@snu.ac.kr
FU Korean Ministry of Education, Science, and Technology [M10305030000]; Green Cross Therapeutics [0411-20080023]; Macrogen Inc. [MG2009001]; National Institutes of Health (NIH) [RR016480, HG004221]
NR 22
TC 251
Z9 311
U1 0
U2 22
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 1011
EP U96
DI 10.1038/nature08211
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500034
PM 19587683
DA 2026-03-09
ER

PT J
AU Quigley, DA
   To, MD
   Pérez-Losada, J
   Pelorosso, FG
   Mao, JH
   Nagase, H
   Ginzinger, DG
   Balmain, A
AF Quigley, David A.
   To, Minh D.
   Perez-Losada, Jesus
   Pelorosso, Facundo G.
   Mao, Jian-Hua
   Nagase, Hiroki
   Ginzinger, David G.
   Balmain, Allan
TI Genetic architecture of mouse skin inflammation and tumour susceptibility
SO NATURE
LA English
DT Article
ID atopic-dermatitis; linkage analysis; innate immunity; stem-cells; disease; cancer; identification; expression; psoriasis; networks
AB Germline polymorphisms in model organisms and humans influence susceptibility to complex trait diseases such as inflammation and cancer(1-4). Mice of the Mus spretus species are resistant to tumour development, and crosses between M. spretus and susceptible Mus musculus strains have been used to map locations of genetic variants that contribute to skin cancer susceptibility(4-6). We have integrated germline polymorphisms with gene expression in normal skin from a M. musculus 3 M. spretus backcross to generate a network view of the gene expression architecture of mouse skin. Here we demonstrate how this approach identifies expression motifs that contribute to tissue organization and biological functions related to inflammation, haematopoiesis, cell cycle control and tumour susceptibility. Motifs associated with inflammation, epidermal barrier function and proliferation are differentially regulated in backcross mice susceptible or resistant to tumour development. The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of the hair follicle, and the vitamin D receptor (Vdr) is linked to coordinated control of epidermal barrier function, inflammation and tumour susceptibility.
C1 [Quigley, David A.; To, Minh D.; Pelorosso, Facundo G.; Mao, Jian-Hua; Ginzinger, David G.; Balmain, Allan] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA.
   [To, Minh D.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94115 USA.
   [Perez-Losada, Jesus] Univ Salamanca, Fac Med, Dept Med, Salamanca 37007, Spain.
   [Mao, Jian-Hua] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
   [Nagase, Hiroki] Nihon Univ, Adv Res Inst Sci & Humanities, Tokyo, Japan.
   [Nagase, Hiroki] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA.
C3 University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of California System; University of California San Francisco; University of Salamanca; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Nihon University; Roswell Park Comprehensive Cancer Center
RP Balmain, A (corresponding author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA.
EM abalmain@cc.ucsf.edu
FU National Cancer Institute; Barbara Bass Bakar Chair of Cancer Genetics; Sandler Foundation; Spanish 'Ministerio de Educacion y Ciencia'; European Community; Fondo de Investigaciones Sanitarias; Junta de Castilla y Leon
NR 29
TC 109
Z9 126
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 26
PY 2009
VL 458
IS 7237
BP 505
EP 508
DI 10.1038/nature07683
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400044
PM 19136944
DA 2026-03-09
ER

PT J
AU Wang, Y
   Huang, YJ
   Wang, JW
   Cheng, C
   Huang, WJ
   Lu, PL
   Xu, YN
   Wang, PY
   Yan, N
   Shi, YG
AF Wang, Yi
   Huang, Yongjian
   Wang, Jiawei
   Cheng, Chao
   Huang, Weijiao
   Lu, Peilong
   Xu, Ya-Nan
   Wang, Pengye
   Yan, Nieng
   Shi, Yigong
TI Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel
SO NATURE
LA English
DT Article
ID escherichia-coli; protein; nitrate; glycerol; naru; identification; reconstitution; software; family; nirc
AB FocA is a representative member of the formate-nitrite transporter family, which transports short-chain acids in bacteria, archaea, fungi, algae and parasites. The structure and transport mechanism of the formate-nitrite transporter family remain unknown. Here we report the crystal structure of Escherichia coli FocA at 2.25 angstrom resolution. FocA forms a symmetric pentamer, with each protomer consisting of six transmembrane segments. Despite a lack of sequence homology, the overall structure of the FocA protomer closely resembles that of aquaporin and strongly argues that FocA is a channel, rather than a transporter. Structural analysis identifies potentially important channel residues, defines the channel path and reveals two constriction sites. Unlike aquaporin, FocA is impermeable to water but allows the passage of formate. A structural and biochemical investigation provides mechanistic insights into the channel activity of FocA.
C1 [Huang, Yongjian; Wang, Jiawei; Cheng, Chao; Huang, Weijiao; Yan, Nieng] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
   [Huang, Yongjian; Wang, Jiawei; Cheng, Chao; Huang, Weijiao; Yan, Nieng] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Wang, Yi; Lu, Peilong; Shi, Yigong] Tsinghua Univ, Minist Educ Prot Sci Lab, Beijing 100084, Peoples R China.
   [Xu, Ya-Nan; Wang, Pengye] Chinese Acad Sci, Inst Phys, Beijing Natl Lab Condensed Matter Phys, Beijing 100190, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Chinese Academy of Sciences; Institute of Physics, CAS
RP Yan, N (corresponding author), Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
EM nyan@tsinghua.edu.cn; shi-lab@tsinghua.edu.cn
FU Ministry of Science and Technology of China [2009CB918801, 2009CB918802]; National Natural Science Foundation of China [30888001]; Beijing Municipal Commissions of Education and Science and Technology; Yuyuan Foundation; Li's Foundation
NR 38
TC 150
Z9 171
U1 0
U2 186
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 467
EP U158
DI 10.1038/nature08610
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200035
PM 19940917
DA 2026-03-09
ER

PT J
AU Zhou, WJ
   Ercan, D
   Chen, L
   Yun, CH
   Li, DN
   Capelletti, M
   Cortot, AB
   Chirieac, L
   Iacob, RE
   Padera, R
   Engen, JR
   Wong, KK
   Eck, MJ
   Gray, NS
   Jänne, PA
AF Zhou, Wenjun
   Ercan, Dalia
   Chen, Liang
   Yun, Cai-Hong
   Li, Danan
   Capelletti, Marzia
   Cortot, Alexis B.
   Chirieac, Lucian
   Iacob, Roxana E.
   Padera, Robert
   Engen, John R.
   Wong, Kwok-Kin
   Eck, Michael J.
   Gray, Nathanael S.
   Jaenne, Pasi A.
TI Novel mutant-selective EGFR kinase inhibitors against EGFR T790M
SO NATURE
LA English
DT Article
ID pan-erbb inhibitor; cell lung-cancer; tyrosine kinase; resistance; mutation; gefitinib; sensitivity; nilotinib; imatinib; hki-272
AB The clinical efficacy of epidermal growth factor receptor ( EGFR) kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the development of drug-resistance mutations, including the gatekeeper T790M mutation(1-3). Strategies targeting EGFR T790M with irreversible inhibitors have had limited success and are associated with toxicity due to concurrent inhibition of wild-type EGFR(4,5). All current EGFR inhibitors possess a structurally related quinazoline-based core scaffold and were identified as ATP-competitive inhibitors of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by screening an irreversible kinase inhibitor library specifically against EGFR T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wildtype EGFR, than quinazoline-based EGFR inhibitors in vitro. They are also effective in murine models of lung cancer driven by EGFR T790M. Co-crystallization studies reveal a structural basis for the increased potency and mutant selectivity of these agents. These mutant-selective irreversible EGFR kinase inhibitors may be clinically more effective and better tolerated than quinazoline-based inhibitors. Our findings demonstrate that functional pharmacological screens against clinically important mutant kinases represent a powerful strategy to identify new classes of mutant-selective kinase inhibitors.
C1 [Zhou, Wenjun; Yun, Cai-Hong; Eck, Michael J.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Zhou, Wenjun; Yun, Cai-Hong; Eck, Michael J.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Ercan, Dalia; Chen, Liang; Li, Danan; Capelletti, Marzia; Cortot, Alexis B.; Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
   [Ercan, Dalia; Chen, Liang; Li, Danan; Capelletti, Marzia; Cortot, Alexis B.; Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Chirieac, Lucian; Padera, Robert] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Iacob, Roxana E.; Engen, John R.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA.
   [Iacob, Roxana E.; Engen, John R.] Northeastern Univ, Dept Chem & Biol Chem, Boston, MA 02115 USA.
   [Wong, Kwok-Kin; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Wong, Kwok-Kin; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, 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 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; Northeastern University; Northeastern University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Gray, NS (corresponding author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM Nathanael_Gray@dfci.harvard.edu; pjanne@partners.org
FU National Institutes of Health [RO1CA11446, R01CA135257, R01CA080942, R01CA130876-02, R01CA116020, R01AG2400401, R01 CA122794, R01GM070590]; National Cancer Institute Lung SPORE [P50CA090578]; Cecily and Robert Harris Foundation; Uniting Against Lung Cancer; Flight Attendant Medical Research Institute; Hazel and Samuel Bellin Research Fund; Damon Runyon Foundation Cancer Innovation Award; National Cancer Institute [R01CA116020] Funding Source: NIH RePORTER
NR 28
TC 880
Z9 1100
U1 4
U2 220
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1070
EP 1074
DI 10.1038/nature08622
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000050
PM 20033049
DA 2026-03-09
ER

PT J
AU Tanvir, NR
   Fox, DB
   Levan, AJ
   Berger, E
   Wiersema, K
   Fynbo, JPU
   Cucchiara, A
   Krühler, T
   Gehrels, N
   Bloom, JS
   Greiner, J
   Evans, PA
   Rol, E
   Olivares, F
   Hjorth, J
   Jakobsson, P
   Farihi, J
   Willingale, R
   Starling, RLC
   Cenko, SB
   Perley, D
   Maund, JR
   Duke, J
   Wijers, RAMJ
   Adamson, AJ
   Allan, A
   Bremer, MN
   Burrows, DN
   Castro-Tirado, AJ
   Cavanagh, B
   Postigo, AD
   Dopita, MA
   Fatkhullin, TA
   Fruchter, AS
   Foley, RJ
   Gorosabel, J
   Kennea, J
   Kerr, T
   Klose, S
   Krimm, HA
   Komarova, VN
   Kulkarni, SR
   Moskvitin, AS
   Mundell, CG
   Naylor, T
   Page, K
   Penprase, BE
   Perri, M
   Podsiadlowski, P
   Roth, K
   Rutledge, RE
   Sakamoto, T
   Schady, P
   Schmidt, BP
   Soderberg, AM
   Sollerman, J
   Stephens, AW
   Stratta, G
   Ukwatta, TN
   Watson, D
   Westra, E
   Wold, T
   Wolf, C
AF Tanvir, N. R.
   Fox, D. B.
   Levan, A. J.
   Berger, E.
   Wiersema, K.
   Fynbo, J. P. U.
   Cucchiara, A.
   Kruehler, T.
   Gehrels, N.
   Bloom, J. S.
   Greiner, J.
   Evans, P. A.
   Rol, E.
   Olivares, F.
   Hjorth, J.
   Jakobsson, P.
   Farihi, J.
   Willingale, R.
   Starling, R. L. C.
   Cenko, S. B.
   Perley, D.
   Maund, J. R.
   Duke, J.
   Wijers, R. A. M. J.
   Adamson, A. J.
   Allan, A.
   Bremer, M. N.
   Burrows, D. N.
   Castro-Tirado, A. J.
   Cavanagh, B.
   de Ugarte Postigo, A.
   Dopita, M. A.
   Fatkhullin, T. A.
   Fruchter, A. S.
   Foley, R. J.
   Gorosabel, J.
   Kennea, J.
   Kerr, T.
   Klose, S.
   Krimm, H. A.
   Komarova, V. N.
   Kulkarni, S. R.
   Moskvitin, A. S.
   Mundell, C. G.
   Naylor, T.
   Page, K.
   Penprase, B. E.
   Perri, M.
   Podsiadlowski, P.
   Roth, K.
   Rutledge, R. E.
   Sakamoto, T.
   Schady, P.
   Schmidt, B. P.
   Soderberg, A. M.
   Sollerman, J.
   Stephens, A. W.
   Stratta, G.
   Ukwatta, T. N.
   Watson, D.
   Westra, E.
   Wold, T.
   Wolf, C.
TI A γ-ray burst at a redshift of z ≈ 8.2
SO NATURE
LA English
DT Article
ID reionization; afterglow; evolution; fraction; galaxy; probe; grbs
AB Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars(1), and some are bright enough that they should be observable out to redshifts of z > 20 using current technology(2-4). Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy(5). Here we report that GRB 090423 lies at a redshift of z approximate to 8.2, implying that massive stars were being produced and dying as GRBs similar to 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.
C1 [Tanvir, N. R.; Wiersema, K.; Evans, P. A.; Farihi, J.; Willingale, R.; Starling, R. L. C.; Duke, J.; Page, K.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Fox, D. B.; Cucchiara, A.; Burrows, D. N.; Kennea, J.] Penn State Univ, Dept Astron & Astrophys, University Pk, PA 16802 USA.
   [Levan, A. J.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Berger, E.; Foley, R. J.; Soderberg, A. M.; Westra, E.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Fynbo, J. P. U.; Hjorth, J.; Maund, J. R.; Sollerman, J.; Watson, D.] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen, Denmark.
   [Kruehler, T.; Greiner, J.; Olivares, F.] Max Planck Inst Extraterr Phys, D-85740 Garching, Germany.
   [Kruehler, T.] Tech Univ Munich, D-85748 Garching, Germany.
   [Gehrels, N.; Krimm, H. A.; Sakamoto, T.; Ukwatta, T. N.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Bloom, J. S.; Cenko, S. B.; Perley, D.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Rol, E.; Wijers, R. A. M. J.] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1090 GE Amsterdam, Netherlands.
   [Jakobsson, P.] Univ Iceland, Inst Sci, Ctr Astrophys & Cosmol, IS-107 Reykjavik, Iceland.
   [Adamson, A. J.; Cavanagh, B.; Kerr, T.; Wold, T.] Joint Astron Ctr, Hilo, HI 96720 USA.
   [Allan, A.; Naylor, T.] Univ Exeter, Sch Phys, Exeter EX4 4QL, Devon, England.
   [Bremer, M. N.] Univ Bristol, HH Wills Phys Lab, Bristol BS8 1TL, Avon, England.
   [Castro-Tirado, A. J.; Gorosabel, J.] CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain.
   [de Ugarte Postigo, A.] European So Observ, Santiago 19, Chile.
   [Dopita, M. A.; Schmidt, B. P.] Australian Natl Univ, Res Sch Astron & Astrophys, Weston, ACT 2611, Australia.
   [Fatkhullin, T. A.; Komarova, V. N.; Moskvitin, A. S.] Special Astrophys Observ, Nizhnii Arkhyz 369167, Russia.
   [Fruchter, A. S.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Klose, S.] Thuringer Landessternwarte Tautenburg, D-07778 Tautenburg, Germany.
   [Krimm, H. A.; Sakamoto, T.] CRESST, Greenbelt, MD 20771 USA.
   [Krimm, H. A.] Univ Space Res Assoc, Columbia, MD 21044 USA.
   [Kulkarni, S. R.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Mundell, C. G.] Liverpool John Moores Univ, Astrophys Res Inst, Birkenhead CH41 1LD, Merseyside, England.
   [Penprase, B. E.] Pomona Coll, Dept Phys & Astron, Claremont, CA 91711 USA.
   [Perri, M.; Stratta, G.] ASI Sci Data Ctr, I-00044 Frascati, Italy.
   [Podsiadlowski, P.; Wolf, C.] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
   [Roth, K.; Stephens, A. W.] Gemini Observ, Hilo, HI 96720 USA.
   [Rutledge, R. E.] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
   [Schady, P.] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Sollerman, J.] Stockholm Univ, Dept Astron, Oskar Klein Ctr, S-10691 Stockholm, Sweden.
   [Ukwatta, T. N.] George Washington Univ, Washington, DC 20052 USA.
C3 University of Leicester; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Warwick; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; University of Copenhagen; Niels Bohr Institute; Max Planck Society; Technical University of Munich; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of California System; University of California Berkeley; University of Amsterdam; University of Iceland; University of Exeter; University of Bristol; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); European Southern Observatory; Australian National University; Russian Academy of Sciences; Special Astrophysics Observatory of the Russian Academy of Sciences; Space Telescope Science Institute; Universities Space Research Association (USRA); California Institute of Technology; Liverpool John Moores University; Claremont Colleges; Pomona College; Agenzia Spaziale Italiana (ASI); University of Oxford; McGill University; University of London; University College London; Oskar Klein Centre; Stockholm University; George Washington University
RP Tanvir, NR (corresponding author), Univ Leicester, Dept Phys & Astron, Univ Rd, Leicester LE1 7RH, Leics, England.
EM nrt3@star.le.ac.uk
FU Clay Fellowship; STFC [ST/F002742/1, ST/F002599/1, PP/E002137/1, ST/G001049/1, ST/F003277/1, PP/E001149/1, PP/E002064/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/F003277/1, ST/G001049/1, PP/E002137/1, PP/E001149/1, ST/F002599/1, PP/E002064/1, ST/F002742/1] Funding Source: researchfish; UK Space Agency [ST/G008655/1] Funding Source: researchfish
NR 27
TC 542
Z9 587
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 29
PY 2009
VL 461
IS 7268
BP 1254
EP 1257
DI 10.1038/nature08459
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800042
PM 19865165
DA 2026-03-09
ER

PT J
AU Shi, JX
   Levinson, DF
   Duan, JB
   Sanders, AR
   Zheng, YL
   Pe'er, I
   Dudbridge, F
   Holmans, PA
   Whittemore, AS
   Mowry, BJ
   Olincy, A
   Amin, F
   Cloninger, CR
   Silverman, JM
   Buccola, NG
   Byerley, WF
   Black, DW
   Crowe, RR
   Oksenberg, JR
   Mirel, DB
   Kendler, KS
   Freedman, R
   Gejman, PV
AF Shi, Jianxin
   Levinson, Douglas F.
   Duan, Jubao
   Sanders, Alan R.
   Zheng, Yonglan
   Pe'er, Itsik
   Dudbridge, Frank
   Holmans, Peter A.
   Whittemore, Alice S.
   Mowry, Bryan J.
   Olincy, Ann
   Amin, Farooq
   Cloninger, C. Robert
   Silverman, Jeremy M.
   Buccola, Nancy G.
   Byerley, William F.
   Black, Donald W.
   Crowe, Raymond R.
   Oksenberg, Jorge R.
   Mirel, Daniel B.
   Kendler, Kenneth S.
   Freedman, Robert
   Gejman, Pablo V.
TI Common variants on chromosome 6p22.1 are associated with schizophrenia
SO NATURE
LA English
DT Article
ID genetics
AB Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5-1%, with high heritability (80-85%) and complex transmission(1). Recent studies implicate rare, large, high-penetrance copy number variants in some cases(2), but the genes or biological mechanisms that underlie susceptibility are not known. Here we show that schizophrenia is significantly associated with single nucleotide polymorphisms (SNPs) in the extended major histocompatibility complex region on chromosome 6. We carried out a genome-wide association study of common SNPs in the Molecular Genetics of Schizophrenia (MGS) case-control sample, and then a meta-analysis of data from the MGS, International Schizophrenia Consortium and SGENE data sets. No MGS finding achieved genome-wide statistical significance. In the meta-analysis of European-ancestry subjects (8,008 cases, 19,077 controls), significant association with schizophrenia was observed in a region of linkage disequilibrium on chromosome 6p22.1 (P = 9.54 x 10(-9)). This region includes a histone gene cluster and several immunity-related genes-possibly implicating aetiological mechanisms involving chromatin modification, transcriptional regulation, autoimmunity and/or infection. These results demonstrate that common schizophrenia susceptibility alleles can be detected. The characterization of these signals will suggest important directions for research on susceptibility mechanisms.
C1 [Duan, Jubao; Sanders, Alan R.; Zheng, Yonglan; Gejman, Pablo V.] NorthShore Univ HealthSyst, Res Inst, Ctr Psychiat Genet, Evanston, IL 60201 USA.
   [Shi, Jianxin; Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94304 USA.
   [Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA.
   [Dudbridge, Frank] MRC, Biostat Unit, Inst Publ Hlth, Cambridge CB2 2SR, England.
   [Holmans, Peter A.] MRC, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Sch Med, Cardiff CF23 6BQ, Wales.
   [Whittemore, Alice S.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94304 USA.
   [Mowry, Bryan J.] Queensland Ctr Mental Hlth Res, Brisbane, Qld 4072, Australia.
   [Mowry, Bryan J.] Queensland Inst Med Res, Brisbane, Qld 4072, Australia.
   [Olincy, Ann; Freedman, Robert] Univ Colorado Denver, Dept Psychiat, Aurora, CO 80045 USA.
   [Amin, Farooq] Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
   [Amin, Farooq] Emory Univ, Atlanta, GA 30322 USA.
   [Cloninger, C. Robert] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA.
   [Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
   [Buccola, Nancy G.] Louisiana State Univ, Hlth Sci Ctr, Sch Nursing, New Orleans, LA 70112 USA.
   [Byerley, William F.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
   [Black, Donald W.; Crowe, Raymond R.] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA.
   [Black, Donald W.; Crowe, Raymond R.] Univ Iowa, Carver Coll Med, Mental Hlth Clin Res Ctr, Iowa City, IA 52242 USA.
   [Oksenberg, Jorge R.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA.
   [Mirel, Daniel B.] MIT, Broad Inst, Ctr Genotyping & Anal, Cambridge, MA 02142 USA.
   [Mirel, Daniel B.] Harvard Univ, Cambridge, MA 02142 USA.
   [Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA.
   [Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA.
C3 NorthShore University Health System; Stanford University; Columbia University; MRC Biostatistics Unit; University of Cambridge; Stanford University; Queensland Centre for Mental Health Research; QIMR Berghofer Medical Research Institute; University of Colorado System; University of Colorado Anschutz Medical Campus; Children's Hospital Colorado; US Department of Veterans Affairs; Veterans Health Administration (VHA); Atlanta VA Health Care System; Emory University; Washington University (WUSTL); Icahn School of Medicine at Mount Sinai; Louisiana State University System; Louisiana State University Health Sciences Center New Orleans; University of California System; University of California San Francisco; University of Iowa; University of Iowa; University of California System; University of California San Francisco; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Virginia Commonwealth University; Virginia Commonwealth University
RP Gejman, PV (corresponding author), NorthShore Univ HealthSyst, Res Inst, Ctr Psychiat Genet, Evanston, IL 60201 USA.
EM pgejman@mac.com
FU National Institute of Mental Health (USA); National Alliance for Research on Schizophrenia and Depression; Genetic Association Information Network (GAIN); Paul Michael Donovan Charitable Foundation; National Center for Research Resources (USA); MRC [G0801418, MC_U105292688] Funding Source: UKRI; Medical Research Council [G0801418, MC_U105292688] Funding Source: researchfish
NR 12
TC 920
Z9 1082
U1 0
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 6
PY 2009
VL 460
IS 7256
BP 753
EP 757
DI 10.1038/nature08192
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300042
PM 19571809
DA 2026-03-09
ER

PT J
AU Reyes, N
   Ginter, C
   Boudker, O
AF Reyes, Nicolas
   Ginter, Christopher
   Boudker, Olga
TI Transport mechanism of a bacterial homologue of glutamate transporters
SO NATURE
LA English
DT Article
ID extracellular gate; sulfhydryl modification; membrane-transport; permeation pathway; crystal-structure; cysteine mutants; substrate; protein; reveals; binding
AB Glutamate transporters are integral membrane proteins that catalyse a thermodynamically uphill uptake of the neurotransmitter glutamate from the synaptic cleft into the cytoplasm of glia and neuronal cells by harnessing the energy of pre-existing electrochemical gradients of ions. Crucial to the reaction is the conformational transition of the transporters between outward and inward facing states, in which the substrate binding sites are accessible from the extracellular space and the cytoplasm, respectively. Here we describe the crystal structure of a double cysteine mutant of a glutamate transporter homologue from Pyrococcus horikoshii, Glt(Ph), which is trapped in the inward facing state by cysteine crosslinking. Together with the previously determined crystal structures of Glt(Ph) in the outward facing state, the structure of the crosslinked mutant allows us to propose a molecular mechanism by which Glt(Ph) and, by analogy, mammalian glutamate transporters mediate sodium-coupled substrate uptake.
C1 [Reyes, Nicolas; Ginter, Christopher; Boudker, Olga] Weill Cornell Med Coll, Dept Physiol & Biophys, 1300 York Ave,Box 75, New York, NY 10065 USA.
C3 Cornell University; Weill Cornell Medicine
RP Boudker, O (corresponding author), Weill Cornell Med Coll, Dept Physiol & Biophys, 1300 York Ave,Box 75, New York, NY 10065 USA.
EM olb2003@med.cornell.edu
FU National Institute of Health; Jane Coffin Childs Memorial Fund
NR 51
TC 366
Z9 438
U1 2
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 DEC 17
PY 2009
VL 462
IS 7275
BP 880
EP 885
DI 10.1038/nature08616
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400034
PM 19924125
DA 2026-03-09
ER

PT J
AU Weisswange, I
   Newsome, TP
   Schleich, S
   Way, M
AF Weisswange, Ina
   Newsome, Timothy P.
   Schleich, Sibylle
   Way, Michael
TI The rate of N-WASP exchange limits the extent of ARP2/3-complex-dependent actin-based motility
SO NATURE
LA English
DT Article
ID vaccinia virus; inhibition; membranes; pathways; kinases; complex
AB Understanding cell motility will require detailed knowledge not only of the localization of signalling networks regulating actin polymerization, but also of their dynamics. Unfortunately, many signalling networks are not amenable to such analysis, as they are frequently transient and dispersed. By contrast, the signalling pathways used by pathogens undergoing actin-based motility are highly localized and operate in a constitutive fashion(1-5). Taking advantage of this, we have analysed the dynamics of neuronal Wiskott-Aldrich syndrome protein (N-WASP), WASP-interacting protein (WIP), GRB2 and NCK, which are required to stimulate actin-related protein (ARP) 2/3-complex-dependent actin-based motility of vaccinia virus(6-9), using fluorescence recovery after photobleaching. Here we show that all four proteins are rapidly exchanging, albeit at different rates, and that the turnover of N-WASP depends on its ability to stimulate ARP2/3-complex-mediated actin polymerization. Conversely, disruption of the interaction of N-WASP with GRB2 and/or the barbed ends of actin filaments increases its exchange rate and results in a faster rate of virus movement. We suggest that the exchange rate of N-WASP controls the rate of ARP2/3-complex-dependent actin-based motility by regulating the extent of actin polymerization by antagonizing filament capping.
C1 [Weisswange, Ina; Newsome, Timothy P.; Schleich, Sibylle; Way, Michael] London Res Inst, Canc Res UK, Cell Motil Lab, London WC2A 3PX, England.
C3 Cancer Research UK
RP Way, M (corresponding author), London Res Inst, Canc Res UK, Cell Motil Lab, 44 Lincolns Inn Fields, London WC2A 3PX, England.
EM michael.way@cancer.org.uk
FU Human Frontier Science Program (HFSP); Cancer Research UK
NR 24
TC 115
Z9 131
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 5
PY 2009
VL 458
IS 7234
BP 87
EP U6
DI 10.1038/nature07773
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000038
PM 19262673
DA 2026-03-09
ER

PT J
AU Okabe, Y
   Sano, T
   Nagata, S
AF Okabe, Yasutaka
   Sano, Teruyuki
   Nagata, Shigekazu
TI Regulation of the innate immune response by threonine-phosphatase of Eyes absent
SO NATURE
LA English
DT Article
ID pattern-recognition receptors; protein-tyrosine-phosphatase; nf-kappa-b; branchiootorenal syndrome; antiviral pathway; virus-infection; mammalian dna; gene; transcription; activation
AB Innate immunity is stimulated not only by viral or bacterial components, but also by non-microbial danger signals (damage-associated molecular patterns)(1). One of the damage-associated molecular patterns is chromosomal DNA that escapes degradation. In programmed cell death and erythropoiesis, DNA from dead cells or nuclei expelled from erythroblasts is digested by DNase II in the macrophages after they are engulfed. DNase II-/- (also known as Dnase2a(-/-)) mice suffer from severe anaemia or chronic arthritis due to interferon-beta (IFN-beta) and tumour necrosis factor-alpha (TNF-alpha) produced from the macrophages carrying undigested DNA(2,3) in a Toll-like receptor (TLR)-independent mechanism(4). Here we show that Eyes absent 4 (EYA4), originally identified as a co-transcription factor, stimulates the expression of IFN-beta and CXCL10 in response to the undigested DNA of apoptotic cells. EYA4 enhanced the innate immune response against viruses (Newcastle disease virus and vesicular stomatitis virus), and could associate with signalling molecules (IPS-1 (also known as MAVS), STING (TMEM173) and NLRX1). Three groups have previously shown that EYA has phosphatase activity(5-7). We found that mouse EYA family members act as a phosphatase for both phosphotyrosine and phosphothreonine. The haloacid dehalogenase domain at the carboxy terminus contained the tyrosine-phosphatase, and the amino-terminal half carried the threonine-phosphatase. Mutations of the threonine-phosphatase, but not the tyrosine-phosphatase, abolished the ability of EYA4 to enhance the innate immune response, suggesting that EYA regulates the innate immune response by modulating the phosphorylation state of signal transducers for the intracellular pathogens.
C1 [Okabe, Yasutaka; Sano, Teruyuki; Nagata, Shigekazu] Kyoto Univ, Grad Sch Med, Dept Med Chem, Kyoto 6068501, Japan.
   [Okabe, Yasutaka; Nagata, Shigekazu] Japan Sci & Technol Corp, Kyoto 6068501, Japan.
C3 Kyoto University; Japan Science & Technology Agency (JST)
RP Nagata, S (corresponding author), Kyoto Univ, Grad Sch Med, Dept Med Chem, Kyoto 6068501, Japan.
EM snagata@mfour.med.kyoto-u.ac.jp
FU Ministry of Education, Science, Sports, and Culture in Japan
NR 47
TC 136
Z9 172
U1 2
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 JUL 23
PY 2009
VL 460
IS 7254
BP 520
EP U99
DI 10.1038/nature08138
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000040
PM 19561593
DA 2026-03-09
ER

PT J
AU Pecho-Vrieseling, E
   Sigrist, M
   Yoshida, Y
   Jessell, TM
   Arber, S
AF Pecho-Vrieseling, Eline
   Sigrist, Markus
   Yoshida, Yutaka
   Jessell, Thomas M.
   Arber, Silvia
TI Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition
SO NATURE
LA English
DT Article
ID synaptic connections; spinal-cord; motoneurons; afferents; neurons; proteins; axons; pea3
AB Spinal reflexes are mediated by synaptic connections between sensory afferents and motor neurons(1-3). The organization of these circuits shows several levels of specificity. Only certain classes of proprioceptive sensory neurons make direct, monosynaptic connections with motor neurons(4). Those that do are bound by rules of motor pool specificity: they form strong connections with motor neurons supplying the same muscle, but avoid motor pools supplying antagonistic muscles(1,5-7). This pattern of connectivity is initially accurate and is maintained in the absence of activity(8), implying that wiring specificity relies on the matching of recognition molecules on the surface of sensory and motor neurons. However, determinants of fine synaptic specificity here, as in most regions of the central nervous system, have yet to be defined. To address the origins of synaptic specificity in these reflex circuits we have used molecular genetic methods to manipulate recognition proteins expressed by subsets of sensory and motor neurons. We show here that a recognition system involving expression of the class 3 semaphorin Sema3e by selected motor neuron pools, and its high-affinity receptor plexin D1 (Plxnd1) by proprioceptive sensory neurons, is a critical determinant of synaptic specificity in sensory-motor circuits in mice. Changing the profile of Sema3e-Plxnd1 signalling in sensory or motor neurons results in functional and anatomical rewiring of monosynaptic connections, but does not alter motor pool specificity. Our findings indicate that patterns of monosynaptic connectivity in this prototypic central nervous system circuit are constructed through a recognition program based on repellent signalling.
C1 [Pecho-Vrieseling, Eline; Sigrist, Markus; Arber, Silvia] Univ Basel, Dept Cell Biol, Biozentrum, CH-4056 Basel, Switzerland.
   [Pecho-Vrieseling, Eline; Sigrist, Markus; Arber, Silvia] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Yoshida, Yutaka; Jessell, Thomas M.] Columbia Univ, Howard Hughes Med Inst, Dept Neurosci, Kavli Inst Brain Sci, New York, NY 10032 USA.
   [Yoshida, Yutaka; Jessell, Thomas M.] Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, Kavli Inst Brain Sci, New York, NY 10032 USA.
   [Yoshida, Yutaka] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
C3 University of Basel; Friedrich Miescher Institute for Biomedical Research; Howard Hughes Medical Institute; Columbia University; Howard Hughes Medical Institute; Columbia University; Cincinnati Children's Hospital Medical Center
RP Arber, S (corresponding author), Univ Basel, Dept Cell Biol, Biozentrum, CH-4056 Basel, Switzerland.
EM tmj1@columbia.edu; silvia.arber@unibas.ch
FU Swiss National Science Foundation; NCCR Frontiers in Genetics; Kanton Basel-Stadt; EU Framework Program 7; Novartis Research Foundation; NIH [RO1NS065048]; NINDS; Harold and Leila Mathers Foundation; Wellcome Trust
NR 30
TC 145
Z9 180
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 JUN 11
PY 2009
VL 459
IS 7248
BP 842
EP 846
DI 10.1038/nature08000
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500039
PM 19421194
DA 2026-03-09
ER

PT J
AU Hsieh, D
   Xia, Y
   Qian, D
   Wray, L
   Dil, JH
   Meier, F
   Osterwalder, J
   Patthey, L
   Checkelsky, JG
   Ong, NP
   Fedorov, AV
   Lin, H
   Bansil, A
   Grauer, D
   Hor, YS
   Cava, RJ
   Hasan, MZ
AF Hsieh, D.
   Xia, Y.
   Qian, D.
   Wray, L.
   Dil, J. H.
   Meier, F.
   Osterwalder, J.
   Patthey, L.
   Checkelsky, J. G.
   Ong, N. P.
   Fedorov, A. V.
   Lin, H.
   Bansil, A.
   Grauer, D.
   Hor, Y. S.
   Cava, R. J.
   Hasan, M. Z.
TI A tunable topological insulator in the spin helical Dirac transport regime
SO NATURE
LA English
DT Article
ID electronic-structure; bi2te3; cone
AB Helical Dirac fermions-charge carriers that behave as massless relativistic particles with an intrinsic angular momentum (spin) locked to its translational momentum-are proposed to be the key to realizing fundamentally new phenomena in condensed matter physics(1-9). Prominent examples include the anomalous quantization of magneto-electric coupling(4-6), half-fermion states that are their own antiparticle(7,8), and charge fractionalization in a Bose-Einstein condensate(9), all of which are not possible with conventional Dirac fermions of the graphene variety(10). Helical Dirac fermions have so far remained elusive owing to the lack of necessary spin-sensitive measurements and because such fermions are forbidden to exist in conventional materials harbouring relativistic electrons, such as graphene(10) or bismuth(11). It has recently been proposed that helical Dirac fermions may exist at the edges of certain types of topologically ordered insulators(3,4,12)-materials with a bulk insulating gap of spin-orbit origin and surface states protected against scattering by time-reversal symmetry-and that their peculiar properties may be accessed provided the insulator is tuned into the so-called topological transport regime(3-9). However, helical Dirac fermions have not been observed in existing topological insulators(13-18). Here we report the realization and characterization of a tunable topological insulator in a bismuth-based class of material by combining spin-imaging and momentum-resolved spectroscopies, bulk charge compensation, Hall transport measurements and surface quantum control. Our results reveal a spin-momentum locked Dirac cone carrying a non-trivial Berry's phase that is nearly 100 per cent spin-polarized, which exhibits a tunable topological fermion density in the vicinity of the Kramers point and can be driven to the long-sought topological spin transport regime. The observed topological nodal state is shown to be protected even up to 300 K. Our demonstration of room-temperature topological order and non-trivial spin-texture in stoichiometric Bi2Se3.M-x (M-x indicates surface doping or gating control) paves the way for future graphene-like studies of topological insulators, and applications of the observed spin-polarized edge channels in spintronic and computing technologies possibly at room temperature.
C1 [Hsieh, D.; Xia, Y.; Qian, D.; Wray, L.; Checkelsky, J. G.; Ong, N. P.; Hasan, M. Z.] Princeton Univ, Joseph Henry Labs Phys, Dept Phys, Princeton, NJ 08544 USA.
   [Grauer, D.; Hor, Y. S.; Cava, R. J.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
   [Hasan, M. Z.] Princeton Univ, Princeton Ctr Complex Mat, Princeton, NJ 08544 USA.
   [Hasan, M. Z.] Princeton Univ, Princeton Inst Sci & Technol Mat, Princeton, NJ 08544 USA.
   [Qian, D.] Shanghai Jiao Tong Univ, Dept Phys, Shanghai 200030, Peoples R China.
   [Dil, J. H.; Meier, F.; Patthey, L.] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Dil, J. H.; Meier, F.; Osterwalder, J.] Univ Zurich Irchel, Inst Phys, CH-8057 Zurich, Switzerland.
   [Fedorov, A. V.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Lin, H.; Bansil, A.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
C3 Princeton University; Princeton University; Princeton University; Princeton University; Shanghai Jiao Tong University; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; University of Zurich; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Northeastern University
RP Hasan, MZ (corresponding author), Princeton Univ, Joseph Henry Labs Phys, Dept Phys, Princeton, NJ 08544 USA.
EM mzhasan@Princeton.edu
FU Basic Energy Sciences of the US Department of Energy [DE-FG-02-05ER46200, AC03-76SF00098, DE-FG02-07ER46352]; Swiss Light Source, Paul Scherrer Institute; NSF through the Princeton Center for Complex Materials [DMR-0819860]; Princeton University; A. P. Sloan Foundation; R. H. Dicke; Kavli Institute of Theoretical Physics at Santa Barbara; Division Of Materials Research; Direct For Mathematical & Physical Scien [0819860] Funding Source: National Science Foundation
NR 35
TC 1742
Z9 1985
U1 4
U2 911
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1101
EP 1105
DI 10.1038/nature08234
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000032
PM 19620959
DA 2026-03-09
ER

PT J
AU Nimura, K
   Ura, K
   Shiratori, H
   Ikawa, M
   Okabe, M
   Schwartz, RJ
   Kaneda, Y
AF Nimura, Keisuke
   Ura, Kiyoe
   Shiratori, Hidetaka
   Ikawa, Masato
   Okabe, Masaru
   Schwartz, Robert J.
   Kaneda, Yasufumi
TI A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome
SO NATURE
LA English
DT Article
ID chromatin; gene; methylation; protein; heart; sall4; set2; tbx5; methyltransferase; purification
AB Diverse histone modifications are catalysed and recognized by various specific proteins, establishing unique modification patterns that act as transcription signals(1,2). In particular, histone H3 trimethylation at lysine 36 (H3K36me3) is associated with actively transcribed regions and has been proposed to provide landmarks for continuing transcription(3,4); however, the control mechanisms and functions of H3K36me3 in higher eukaryotes are unknown. Here we show that the H3K36me3-specific histone methyltransferase (HMTase) Wolf-Hirschhorn syndrome candidate 1 (WHSC1, also known as NSD2 or MMSET) functions in transcriptional regulation together with developmental transcription factors whose defects overlap with the human disease Wolf Hirschhorn syndrome (WHS)(5,6). We found that mouse Whsc1, one of five putative Set2 homologues(2,7,8), governed H3K36me3 along euchromatin by associating with the cell-type-specific transcription factors Sall1, Sall4 and Nanog in embryonic stem cells, and Nkx2-5 in embryonic hearts, regulating the expression of their target genes. Whsc1-deficient mice showed growth retardation and various WHS-like midline defects, including congenital cardiovascular anomalies. The effects of Whsc1 haploin sufficiency were increased in Nkx2-5 heterozygous mutant hearts, indicating their functional link. We propose that WHSC1 functions together with developmental transcription factors to prevent the inappropriate transcription that can lead to various pathophysiologies.
C1 [Nimura, Keisuke; Ura, Kiyoe; Kaneda, Yasufumi] Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Suita, Osaka 5650871, Japan.
   [Shiratori, Hidetaka] Osaka Univ, Grad Sch Frontier Biosci, Dev Genet Grp, Suita, Osaka 5650871, Japan.
   [Ikawa, Masato; Okabe, Masaru] Osaka Univ, Genome Informat Res Ctr, Suita, Osaka 5650871, Japan.
   [Schwartz, Robert J.] Ctr Mol Dev & Dis, Inst Biosci & Technol, Houston, TX 77030 USA.
C3 University of Osaka; University of Osaka; University of Osaka
RP Ura, K (corresponding author), Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, 2-2 Yamada Oka, Suita, Osaka 5650871, Japan.
EM kiyoeura@gts.med.osaka-u.ac.jp; kaneday@gts.med.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT); Naito Foundation; Osaka University
NR 38
TC 320
Z9 391
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 JUL 9
PY 2009
VL 460
IS 7252
BP 287
EP U157
DI 10.1038/nature08086
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000047
PM 19483677
DA 2026-03-09
ER

PT J
AU Long, JA
   Trinajstic, K
   Johanson, Z
AF Long, John A.
   Trinajstic, Kate
   Johanson, Zerina
TI Devonian arthrodire embryos and the origin of internal fertilization in vertebrates
SO NATURE
LA English
DT Article
ID live birth; fishes; viviparity; phylogeny; australia; evolution; fossil
AB Evidence of reproductive biology is extremely rare in the fossil record. Recently the first known embryos were discovered within the Placodermi(1), an extinct class of armoured fish, indicating a viviparous mode of reproduction in a vertebrate group outside the crown-group Gnathostomata (Chondrichthyes and Osteichthyes). These embryos were found in ptyctodontids, a small group of placoderms phylogenetically basal to the largest group, the Arthrodira(2,3). Here we report the discovery of embryos in the Arthrodira inside specimens of Incisoscutum ritchiei from the Upper Devonian Gogo Formation of Western Australia(4) (approximately 380 million years ago), providing the first evidence, to our knowledge, for reproduction using internal fertilization in this diverse group. We show that Incisoscutum and some phyllolepid arthrodires possessed pelvic girdles with long basipterygia that articulated distally with an additional cartilaginous element or series, as in chondrichthyans, indicating that the pelvic fin was used in copulation. As homology between similar pelvic girdle skeletal structures in ptyctodontids, arthrodires and chondrichthyans is difficult to reconcile in the light of current phylogenies of lower gnathostomes(2,3,5), we explain these similarities as being most likely due to convergence (homoplasy). These new finds confirm that reproduction by internal fertilization and viviparity was much more widespread in the earliest gnathostomes than had been previously appreciated.
C1 [Long, John A.] Victoria & Albert Museum, Melbourne, Vic 3001, Australia.
   [Long, John A.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 2600, Australia.
   [Long, John A.] Monash Univ, Sch Geosci, Clayton, Vic 3800, Australia.
   [Trinajstic, Kate] Univ Western Australia, Sch Earth & Geog Sci, Perth, WA 6009, Australia.
   [Johanson, Zerina] Nat Hist Museum, London SW7 5BD, England.
C3 Australian National University; Monash University; University of Western Australia; Natural History Museum London
RP Long, JA (corresponding author), Victoria & Albert Museum, POB 666, Melbourne, Vic 3001, Australia.
EM jlong@museum.vic.gov.au
FU Australian Research Council
NR 27
TC 65
Z9 70
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 FEB 26
PY 2009
VL 457
IS 7233
BP 1124
EP 1127
DI 10.1038/nature07732
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100039
PM 19242474
DA 2026-03-09
ER

PT J
AU Araki, K
   Turner, AP
   Shaffer, VO
   Gangappa, S
   Keller, SA
   Bachmann, MF
   Larsen, CP
   Ahmed, R
AF Araki, Koichi
   Turner, Alexandra P.
   Shaffer, Virginia Oliva
   Gangappa, Shivaprakash
   Keller, Susanne A.
   Bachmann, Martin F.
   Larsen, Christian P.
   Ahmed, Rafi
TI mTOR regulates memory CD8 T-cell differentiation
SO NATURE
LA English
DT Article
ID selective expression; dendritic cells; viral-infection; effector; receptor; rapamycin; subsets; homeostasis; pathway; target
AB Memory CD8 T cells are a critical component of protective immunity, and inducing effective memory T-cell responses is a major goal of vaccines against chronic infections and tumours(1-3). Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T cells(4). Here we show that mTOR (mammalian target of rapamycin(5), also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-like particles. In addition, rapamycin treatment also enhanced memory T-cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-cell differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-cell differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine-or infection-induced memory T cells.
C1 [Araki, Koichi; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Araki, Koichi; Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
   [Turner, Alexandra P.; Shaffer, Virginia Oliva; Gangappa, Shivaprakash; Larsen, Christian P.] Emory Univ, Sch Med, Emory Transplant Ctr, Atlanta, GA 30322 USA.
   [Turner, Alexandra P.; Shaffer, Virginia Oliva; Gangappa, Shivaprakash; Larsen, Christian P.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA.
   [Keller, Susanne A.; Bachmann, Martin F.] Cytos Biotechnol AG, CH-8952 Zurich, Switzerland.
C3 Emory University; Emory University; Emory University; Emory University; Cytos Biotechnology AG
RP Ahmed, R (corresponding author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM rahmed@emory.edu
FU NIH [AI030048, N01-AI-50025, AI040519]; National Institute of Allergy and Infectious Diseases [R01AI073707, R01AI030048] Funding Source: NIH RePORTER
NR 24
TC 1332
Z9 1596
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 JUL 2
PY 2009
VL 460
IS 7251
BP 108
EP U124
DI 10.1038/nature08155
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200039
PM 19543266
DA 2026-03-09
ER

PT J
AU Tigges, M
   Marquez-Lago, TT
   Stelling, J
   Fussenegger, M
AF Tigges, Marcel
   Marquez-Lago, Tatiana T.
   Stelling, Joerg
   Fussenegger, Martin
TI A tunable synthetic mammalian oscillator
SO NATURE
LA English
DT Article
ID circadian gene-expression; clock
AB Autonomous and self- sustained oscillator circuits mediating the periodic induction of specific target genes are minimal genetic time- keeping devices found in the central and peripheral circadian clocks(1,2). They have attracted significant attention because of their intriguing dynamics and their importance in controlling critical repair(3), metabolic(4) and signalling pathways(5). The precise molecular mechanism and expression dynamics of this mammalian circadian clock are still not fully understood. Here we describe a synthetic mammalian oscillator based on an auto- regulated sense - antisense transcription control circuit encoding a positive and a time- delayed negative feedback loop, enabling autonomous, self- sustained and tunable oscillatory gene expression. After detailed systems design with experimental analyses and mathematical modelling, we monitored oscillating concentrations of green fluorescent protein with tunable frequency and amplitude by time- lapse microscopy in real time in individual Chinese hamster ovary cells. The synthetic mammalian clock may provide an insight into the dynamics of natural periodic processes and foster advances in the design of prosthetic networks in future gene and cell therapies.
C1 [Tigges, Marcel; Marquez-Lago, Tatiana T.; Stelling, Joerg; Fussenegger, Martin] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland.
   [Marquez-Lago, Tatiana T.; Stelling, Joerg] ETH, Inst Computat Sci, CH-8092 Zurich, Switzerland.
   [Marquez-Lago, Tatiana T.; Stelling, Joerg] ETH, Swiss Inst Bioinformat, CH-8092 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Institute of Bioinformatics; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Fussenegger, M (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland.
EM joerg.stelling@bsse.ethz.ch; fussenegger@bsse.ethz.ch
FU Swiss National Science Foundation; EC Framework 6 (COBIOS)
NR 29
TC 450
Z9 576
U1 2
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 309
EP 312
DI 10.1038/nature07616
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900038
PM 19148099
DA 2026-03-09
ER

PT J
AU Eichenfield, M
   Camacho, R
   Chan, J
   Vahala, KJ
   Painter, O
AF Eichenfield, Matt
   Camacho, Ryan
   Chan, Jasper
   Vahala, Kerry J.
   Painter, Oskar
TI A picogram- and nanometre-scale photonic-crystal optomechanical cavity
SO NATURE
LA English
DT Article
ID nanocavity; design
AB The dynamic back-action caused by electromagnetic forces (radiation pressure) in optical(1-6) and microwave(7) cavities is of growing interest(8). Back-action cooling, for example, is being pursued as a means of achieving the quantum ground state of macroscopic mechanical oscillators. Work in the optical domain has revolved around millimetre-or micrometre-scale structures using the radiation pressure force. By comparison, in microwave devices, low-loss superconducting structures have been used for gradient-force-mediated coupling to a nanomechanical oscillator of picogram mass(7). Here we describe measurements of an optical system consisting of a pair of specially patterned nanoscale beams in which optical and mechanical energies are simultaneously localized to a cubic-micron-scale volume, and for which large perphoton optical gradient forces are realized. The resulting scale of the per-photon force and the mass of the structure enable the exploration of cavity optomechanical regimes in which, for example, the mechanical rigidity of the structure is dominantly provided by the internal light field itself. In addition to precision measurement and sensitive force detection(9), nano-optomechanics may find application in reconfigurable and tunable photonic systems(10), light-based radio-frequency communication(11) and the generation of giant optical nonlinearities for wavelength conversion and optical buffering(12).
C1 [Eichenfield, Matt; Camacho, Ryan; Chan, Jasper; Vahala, Kerry J.; Painter, Oskar] CALTECH, Sr Lab Appl Phys, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Painter, O (corresponding author), CALTECH, Sr Lab Appl Phys, Pasadena, CA 91125 USA.
EM opainter@caltech.edu
FU US Defense Advanced Research Projects Agency; US National Science Foundation
NR 30
TC 609
Z9 707
U1 4
U2 267
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 28
PY 2009
VL 459
IS 7246
BP 550
EP U79
DI 10.1038/nature08061
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500035
PM 19489118
DA 2026-03-09
ER

PT J
AU Martin, SG
   Berthelot-Grosjean, M
AF Martin, Sophie G.
   Berthelot-Grosjean, Martine
TI Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle
SO NATURE
LA English
DT Article
ID nim1/cdr1 mitotic inducer; dual-specificity kinase; fission yeast; protein-kinase; schizosaccharomyces-pombe; negative regulation; division plane; growth; wee1; phosphorylation
AB Cells normally grow to a certain size before they enter mitosis and divide. Entry into mitosis depends on the activity of Cdk1, which is inhibited by the Wee1 kinase and activated by the Cdc25 phosphatase(1). However, how cells sense their size for mitotic commitment remains unknown. Here we show that an intracellular gradient of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) Pom1, which emanates from the ends of rod-shaped Schizosaccharomyces pombe cells, serves to measure cell length and control mitotic entry. Pom1 provides positional information both for polarized growth and to inhibit cell division at cell ends(2-5). We discovered that Pom1 is also a dose-dependent G2-M inhibitor. Genetic analyses indicate that Pom1 negatively regulates Cdr1 and Cdr2, two previously described Wee1 inhibitors of the SAD kinase family(6-10). This inhibition may be direct, because in vivo and in vitro evidence suggest that Pom1 phosphorylates Cdr2. Whereas Cdr1 and Cdr2 localize to a medial cortical region, Pom1 forms concentration gradients from cell tips that overlap with Cdr1 and Cdr2 in short cells, but not in long cells. Disturbing these Pom1 gradients leads to Cdr2 phosphorylation and imposes a G2 delay. In short cells, Pom1 prevents precocious M-phase entry, suggesting that the higher medial Pom1 levels inhibit Cdr2 and promote a G2 delay. Thus, gradients of Pom1 from cell ends provide a measure of cell length to regulate M-phase entry.
C1 [Martin, Sophie G.; Berthelot-Grosjean, Martine] Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
C3 University of Lausanne
RP Martin, SG (corresponding author), Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, Genopode Bldg, CH-1015 Lausanne, Switzerland.
EM Sophie.Martin@unil.ch
FU Swiss National Science Foundation Professorship [PP00A-114936]; Human Frontiers Science Program Career Development Award [CDA0016/2008]
NR 32
TC 243
Z9 298
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 JUN 11
PY 2009
VL 459
IS 7248
BP 852
EP U7
DI 10.1038/nature08054
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500041
PM 19474792
DA 2026-03-09
ER

PT J
AU van Dokkum, PG
   Kriek, M
   Franx, M
AF van Dokkum, Pieter G.
   Kriek, Mariska
   Franx, Marijn
TI A high stellar velocity dispersion for a compact massive galaxy at redshift z=2.186
SO NATURE
LA English
DT Article
ID star-formation; quycent galaxy; fundamental plane; elliptic galaxy; size evolution; z-similar-to-2.3; red; co; form
AB Recent studies have found that the oldest and most luminous galaxies in the early Universe are surprisingly compact(1-7), having stellar masses similar to present-day elliptical galaxies but much smaller sizes. This finding has attracted considerable attention(8-13), as it suggests that massive galaxies have grown in size by a factor of about five over the past ten billion years (10 Gyr). A key test of these results is a determination of the stellar kinematics of one of the compact galaxies: if the sizes of these objects are as extreme as has been claimed, their stars are expected to have much higher velocities than those in present-day galaxies of the same mass. Here we report a measurement of the stellar velocity dispersion of a massive compact galaxy at redshift z = 2.186, corresponding to a look-back time of 10.7 Gyr. The velocity dispersion is very high at 510(-95)(+165) km s(-1), consistent with the mass and compactness of the galaxy inferred from photometric data. This would indicate significant recent structural and dynamical evolution of massive galaxies over the past 10 Gyr. The uncertainty in the dispersion was determined from simulations that include the effects of noise and template mismatch. However, we cannot exclude the possibility that some subtle systematic effect may have influenced the analysis, given the low signal-to-noise ratio of our spectrum.
C1 [van Dokkum, Pieter G.] Yale Univ, Dept Astron, New Haven, CT 06511 USA.
   [Kriek, Mariska] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Franx, Marijn] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
C3 Yale University; Princeton University; Leiden University - Excl LUMC; Leiden University
RP van Dokkum, PG (corresponding author), Yale Univ, Dept Astron, 260 Whitney Ave, New Haven, CT 06511 USA.
EM pieter.vandokkum@yale.edu
FU NASA; NSF
NR 28
TC 162
Z9 167
U1 1
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 AUG 6
PY 2009
VL 460
IS 7256
BP 717
EP 719
DI 10.1038/nature08220
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300033
PM 19661911
DA 2026-03-09
ER

PT J
AU Minton, DA
   Malhotra, R
AF Minton, David A.
   Malhotra, Renu
TI A record of planet migration in the main asteroid belt
SO NATURE
LA English
DT Article
ID late heavy bombardment; solar-system; origin; neptune; uranus; orbit
AB The main asteroid belt lies between the orbits of Mars and Jupiter, but the region is not uniformly filled with asteroids. There are gaps, known as the Kirkwood gaps, in distinct locations that are associated with orbital resonances with the giant planets(1); asteroids placed in these locations will follow chaotic orbits and be removed(2). Here we show that the observed distribution of main belt asteroids does not fill uniformly even those regions that are dynamically stable over the age of the Solar System. We find a pattern of excess depletion of asteroids, particularly just outward of the Kirkwood gaps associated with the 5:2, the 7:3 and the 2:1 Jovian resonances. These features are not accounted for by planetary perturbations in the current structure of the Solar System, but are consistent with dynamical ejection of asteroids by the sweeping of gravitational resonances during the migration of Jupiter and Saturn similar to 4 Gyr ago.
C1 [Minton, David A.; Malhotra, Renu] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85716 USA.
C3 University of Arizona
RP Minton, DA (corresponding author), Univ Arizona, Lunar & Planetary Lab, 1629 E Univ Blvd, Tucson, AZ 85716 USA.
EM daminton@lpl.arizona.edu
FU NASA; NSF
NR 20
TC 117
Z9 129
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 FEB 26
PY 2009
VL 457
IS 7233
BP 1109
EP 1111
DI 10.1038/nature07778
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100035
PM 19242470
DA 2026-03-09
ER

PT J
AU Hammoud, SS
   Nix, DA
   Zhang, HY
   Purwar, J
   Carrell, DT
   Cairns, BR
AF Hammoud, Saher Sue
   Nix, David A.
   Zhang, Haiying
   Purwar, Jahnvi
   Carrell, Douglas T.
   Cairns, Bradley R.
TI Distinctive chromatin in human sperm packages genes for embryo development
SO NATURE
LA English
DT Article
ID stem-cells; dna methylation; histone h3; polycomb targets; genome; organization; fibroblasts; expression; drosophila; complex
AB Because nucleosomes are widely replaced by protamine in mature human sperm, the epigenetic contributions of sperm chromatin to embryo development have been considered highly limited. Here we show that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signalling factors. Notably, histone modifications localize to particular developmental loci. Dimethylated lysine 4 on histone H3 (H3K4me2) is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain noncoding RNAs, and generally to paternally expressed imprinted loci, but not paternally repressed loci. Notably, trimethylated H3K27 (H3K27me3) is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells. Furthermore, developmental promoters are generally DNA hypomethylated in sperm, but acquire methylation during differentiation. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.
C1 [Hammoud, Saher Sue; Carrell, Douglas T.] Univ Utah, Sch Med, IVF & Androl Labs, Dept Surg, Salt Lake City, UT 84112 USA.
   [Hammoud, Saher Sue; Carrell, Douglas T.] Univ Utah, Sch Med, IVF & Androl Labs, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA.
   [Hammoud, Saher Sue; Carrell, Douglas T.] Univ Utah, Sch Med, IVF & Androl Labs, Dept Physiol, Salt Lake City, UT 84112 USA.
   [Hammoud, Saher Sue; Zhang, Haiying; Purwar, Jahnvi; Cairns, Bradley R.] Univ Utah, Sch Med, Howard Hughes Med Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA.
   [Nix, David A.] Univ Utah, Sch Med, Huntsman Canc Inst, Res Informat & Bioinformat Core Facil, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Howard Hughes Medical Institute; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Huntsman Cancer Institute
RP Carrell, DT (corresponding author), Univ Utah, Sch Med, IVF & Androl Labs, Dept Surg, Salt Lake City, UT 84112 USA.
EM douglas.carrell@hsc.utah.edu; brad.cairns@hci.utah.edu
FU National Cancer Institute [P30CA016056] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [P30 CA016056, CA16056, CA24014] Funding Source: Medline
NR 39
TC 1031
Z9 1195
U1 1
U2 105
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 473
EP U47
DI 10.1038/nature08162
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000030
PM 19525931
DA 2026-03-09
ER

PT J
AU Ahlberg, P
   Trinajstic, K
   Johanson, Z
   Long, J
AF Ahlberg, Per
   Trinajstic, Kate
   Johanson, Zerina
   Long, John
TI Pelvic claspers confirm chondrichthyan-like internal fertilization in arthrodires
SO NATURE
LA English
DT Article
AB Recent finds(1,2) demonstrate that internal fertilization and viviparity (live birth) were more widespread in the Placodermi, an extinct group of armoured fishes, than was previously realized. Placoderms represent the sister group of the crown group jawed vertebrates (Gnathostomata)(3,4), making their mode(s) of reproduction potentially informative about primitive gnathostome conditions. An ossified pelvic fin basipterygium discovered in the arthrodire Incisoscutum ritchiei was hypothesized to be identical in males and females, with males presumed to have an additional cartilaginous element or series forming a clasper. Here we report the discovery of a completely ossified pelvic clasper in Incisoscutum ritchiei (WAM 03.3.28) which shows that this interpretation was incorrect: the basipterygium described previously(1) is in fact unique to females. The male clasper is a slender rod attached to a square basal plate that articulates directly with the pelvis. It carries a small cap of dermal bone covered in denticles and small hooks that may be homologous with the much larger dermal component of the ptyctodont clasper.
C1 [Trinajstic, Kate] Curtin Univ, Dept Appl Chem, Western Australian Organ & Isotope Geochem Ctr, Perth, WA 6102, Australia.
   [Ahlberg, Per] Uppsala Univ, Dept Physiol & Dev Biol, Subdept Evolutionary Organismal Biol, S-75236 Uppsala, Sweden.
   [Trinajstic, Kate] Western Australian Museum, Perth, WA 6000, Australia.
   [Trinajstic, Kate] Univ Western Australia, Sch Earth & Environm, Perth, WA 6009, Australia.
   [Johanson, Zerina] Nat Hist Museum, Dept Palaeontol, London SW7 5BD, England.
   [Long, John] Museum Victoria, Melbourne, Vic 3001, Australia.
   [Long, John] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 2600, Australia.
   [Long, John] Monash Univ, Sch Geosci, Clayton, Vic 3800, Australia.
C3 Curtin University; Uppsala University; Western Australian Museum; University of Western Australia; Natural History Museum London; Museum Victoria; Australian National University; Monash University
RP Trinajstic, K (corresponding author), Curtin Univ, Dept Appl Chem, Western Australian Organ & Isotope Geochem Ctr, Perth, WA 6102, Australia.
EM ktrinajs@bigpond.net.au
FU Australian Research Council Discovery grants; Australian Geographic grant; Swedish Research Council
NR 7
TC 38
Z9 40
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 AUG 13
PY 2009
VL 460
IS 7257
BP 888
EP 889
DI 10.1038/nature08176
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300037
PM 19597477
DA 2026-03-09
ER

PT J
AU Liu, CC
   Linde, AT
   Sacks, IS
AF Liu, ChiChing
   Linde, Alan T.
   Sacks, I. Selwyn
TI Slow earthquakes triggered by typhoons
SO NATURE
LA English
DT Article
ID episodic tremor; japan; slip; seismicity; subduction; taiwan; alaska; fault
AB The first reports(1,2) on a slow earthquake were for an event in the Izu peninsula, Japan, on an intraplate, seismically active fault. Since then, many slow earthquakes have been detected(3-8). It has been suggested(9) that the slow events may trigger ordinary earthquakes (in a context supported by numerical modelling(10)), but their broader significance in terms of earthquake occurrence remains unclear. Triggering of earthquakes has received much attention: strain diffusion from large regional earthquakes has been shown to influence large earthquake activity(11,12), and earthquakes may be triggered during the passage of teleseismic waves(13), a phenomenon now recognized as being common(14-17). Here we show that, in eastern Taiwan, slow earthquakes can be triggered by typhoons. We model the largest of these earthquakes as repeated episodes of slow slip on a reverse fault just under land and dipping to the west; the characteristics of all events are sufficiently similar that they can be modelled with minor variations of the model parameters. Lower pressure results in a very small unclamping of the fault that must be close to the failure condition for the typhoon to act as a trigger. This area experiences very high compressional deformation but has a paucity of large earthquakes; repeating slow events may be segmenting the stressed area and thus inhibiting large earthquakes, which require a long, continuous seismic rupture.
C1 [Liu, ChiChing] Acad Sinica, Inst Earth Sci, Taipei 115, Taiwan.
   [Linde, Alan T.; Sacks, I. Selwyn] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
C3 Academia Sinica - Taiwan; Carnegie Institution for Science
RP Liu, CC (corresponding author), Acad Sinica, Inst Earth Sci, 128 Sinica Rd,Sec 2, Taipei 115, Taiwan.
EM liucc@sinica.edu.tw
NR 30
TC 102
Z9 136
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 JUN 11
PY 2009
VL 459
IS 7248
BP 833
EP 836
DI 10.1038/nature08042
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500037
PM 19516339
DA 2026-03-09
ER

PT J
AU Petreanu, L
   Mao, TY
   Sternson, SM
   Svoboda, K
AF Petreanu, Leopoldo
   Mao, Tianyi
   Sternson, Scott M.
   Svoboda, Karel
TI The subcellular organization of neocortical excitatory connections
SO NATURE
LA English
DT Article
ID rat barrel cortex; phaseolus-vulgaris-leukoagglutinin; pyramidal neurons; synaptic connectivity; visual-cortex; motor cortex; dendrites; circuit; channelrhodopsin-2; projections
AB Understanding cortical circuits will require mapping the connections between specific populations of neurons(1), as well as determining the dendritic locations where the synapses occur(2). The dendrites of individual cortical neurons overlap with numerous types of local and long-range excitatory axons, but axodendritic overlap is not always a good predictor of actual connection strength(3-5). Here we developed an efficient channelrhodopsin-2 (ChR2)-assisted method(6-8) to map the spatial distribution of synaptic inputs, defined by presynaptic ChR2 expression, within the dendritic arborizations of recorded neurons. We expressed ChR2 in two thalamic nuclei, the whisker motor cortex and local excitatory neurons and mapped their synapses with pyramidal neurons in layers 3, 5A and 5B (L3, L5A and L5B) in the mouse barrel cortex. Within the dendritic arborizations of L3 cells, individual inputs impinged onto distinct single domains. These domains were arrayed in an orderly, monotonic pattern along the apical axis: axons from more central origins targeted progressively higher regions of the apical dendrites. In L5 arborizations, different inputs targeted separate basal and apical domains. Input to L3 and L5 dendrites in L1 was related to whisker movement and position, suggesting that these signals have a role in controlling the gain of their target neurons(9). Our experiments reveal high specificity in the subcellular organization of excitatory circuits.
C1 [Petreanu, Leopoldo; Mao, Tianyi; Sternson, Scott M.; Svoboda, Karel] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 Howard Hughes Medical Institute
RP Svoboda, K (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
EM svobodak@janelia.hhmi.org
FU Howard Hughes Medical Institute Funding Source: Medline
NR 34
TC 797
Z9 962
U1 3
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 26
PY 2009
VL 457
IS 7233
BP 1142
EP U100
DI 10.1038/nature07709
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100043
PM 19151697
DA 2026-03-09
ER

PT J
AU Waite, JH
   Lewis, WS
   Magee, BA
   Lunine, JI
   McKinnon, WB
   Glein, CR
   Mousis, O
   Young, DT
   Brockwell, T
   Westlake, J
   Nguyen, MJ
   Teolis, BD
   Niemann, B
   McNutt, RL
   Perry, M
   Ip, WH
AF Waite, J. H., Jr.
   Lewis, W. S.
   Magee, B. A.
   Lunine, J. I.
   McKinnon, W. B.
   Glein, C. R.
   Mousis, O.
   Young, D. T.
   Brockwell, T.
   Westlake, J.
   Nguyen, M. -J.
   Teolis, B. D.
   Niemann, B.
   McNutt, R. L., Jr.
   Perry, M.
   Ip, W. -H.
TI Liquid water on Enceladus from observations of ammonia and 40Ar in the plume
SO NATURE
LA English
DT Article
ID neutral mass-spectrometer; cassini ion; south-pole; origin; abundances; atmosphere; volatiles; deuterium; reservoir; surface
AB Jets of water ice from surface fractures near the south pole(1) of Saturn's icy moon Enceladus produce a plume of gas and particles(2-5). The source of the jets may be a liquid water region under the ice shell-as suggested most recently by the discovery of salts in E-ring particles derived from the plume(6)-or warm ice that is heated, causing dissociation of clathrate hydrates(7). Here we report that ammonia is present in the plume, along with various organic compounds, deuterium and, very probably, Ar-40. The presence of ammonia provides strong evidence for the existence of at least some liquid water, given that temperatures in excess of 180 K have been measured near the fractures from which the jets emanate(8). We conclude, from the overall composition of the material, that the plume derives from both a liquid reservoir (or from ice that in recent geological time has been in contact with such a reservoir) as well as from degassing, volatile-charged ice.
C1 [Waite, J. H., Jr.; Lewis, W. S.; Magee, B. A.; Young, D. T.; Brockwell, T.; Westlake, J.; Nguyen, M. -J.; Teolis, B. D.] SW Res Inst, San Antonio, TX 78228 USA.
   [Lunine, J. I.; Mousis, O.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [McKinnon, W. B.] Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
   [Glein, C. R.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Mousis, O.] Observ Besancon, Inst UTINAM, CNRS, UMR 6213, F-25010 Besancon, France.
   [Niemann, B.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [McNutt, R. L., Jr.; Perry, M.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Ip, W. -H.] Natl Cent Univ, Inst Astron, Chungli 32054, Taiwan.
   [Ip, W. -H.] Natl Cent Univ, Inst Space Sci, Chungli 32054, Taiwan.
C3 Southwest Research Institute; University of Arizona; Washington University (WUSTL); Arizona State University; Arizona State University-Tempe; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Marie et Louis Pasteur; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; National Central University; National Central University
RP Lewis, WS (corresponding author), SW Res Inst, 6220 Culebra Rd, San Antonio, TX 78228 USA.
EM wlewis@swri.edu
FU Cassini Project; Southwest Research Institute
NR 30
TC 459
Z9 510
U1 1
U2 139
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 487
EP 490
DI 10.1038/nature08153
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000032
DA 2026-03-09
ER

PT J
AU Kawate, T
   Michel, JC
   Birdsong, WT
   Gouaux, E
AF Kawate, Toshimitsu
   Michel, Jennifer Carlisle
   Birdsong, William T.
   Gouaux, Eric
TI Crystal structure of the ATP-gated P2X4 ion channel in the closed state
SO NATURE
LA English
DT Article
ID cysteine residues; binding-site; amino-acids; receptor; identification; cloning; release; pain; expression; ectodomain
AB P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X(4) receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit-subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in beta-strands, have large acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the 'gate' is defined by an similar to 8 angstrom slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit rearrangement and ion channel opening.
C1 [Kawate, Toshimitsu; Michel, Jennifer Carlisle; Birdsong, William T.; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Howard Hughes Medical Institute
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU National Institutes of Health (NIH); American Asthma Foundation; Howard Hughes Medical Institute
NR 50
TC 622
Z9 703
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 JUL 30
PY 2009
VL 460
IS 7255
BP 592
EP U55
DI 10.1038/nature08198
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300042
PM 19641588
DA 2026-03-09
ER

PT J
AU Toledo-Arana, A
   Dussurget, O
   Nikitas, G
   Sesto, N
   Guet-Revillet, H
   Balestrino, D
   Loh, E
   Gripenland, J
   Tiensuu, T
   Vaitkevicius, K
   Barthelemy, M
   Vergassola, M
   Nahori, MA
   Soubigou, G
   Régnault, B
   Coppée, JY
   Lecuit, M
   Johansson, J
   Cossart, P
AF Toledo-Arana, Alejandro
   Dussurget, Olivier
   Nikitas, Georgios
   Sesto, Nina
   Guet-Revillet, Helene
   Balestrino, Damien
   Loh, Edmund
   Gripenland, Jonas
   Tiensuu, Teresa
   Vaitkevicius, Karolis
   Barthelemy, Mathieu
   Vergassola, Massimo
   Nahori, Marie-Anne
   Soubigou, Guillaume
   Regnault, Beatrice
   Coppee, Jean-Yves
   Lecuit, Marc
   Johansson, Joergen
   Cossart, Pascale
TI The Listeria transcriptional landscape from saprophytism to virulence
SO NATURE
LA English
DT Article
ID small noncoding rnas; monocytogenes virulence; identification; genome; expression; gene; infection; model; riboswitches; targets
AB The bacterium Listeria monocytogenes is ubiquitous in the environment and can lead to severe food-borne infections. It has recently emerged as a multifaceted model in pathogenesis. However, how this bacterium switches from a saprophyte to a pathogen is largely unknown. Here, using tiling arrays and RNAs from wild-type and mutant bacteria grown in vitro, ex vivo and in vivo, we have analysed the transcription of its entire genome. We provide the complete Listeria operon map and have uncovered far more diverse types of RNAs than expected: in addition to 50 small RNAs (<500 nucleotides), at least two of which are involved in virulence in mice, we have identified antisense RNAs covering several open-reading frames and long overlapping 59 and 39 untranslated regions. We discovered that riboswitches can act as terminators for upstream genes. When Listeria reaches the host intestinal lumen, an extensive transcriptional reshaping occurs with a SigB-mediated activation of virulence genes. In contrast, in the blood, PrfA controls transcription of virulence genes. Remarkably, several non-coding RNAs absent in the non-pathogenic species Listeria innocua exhibit the same expression patterns as the virulence genes. Together, our data unravel successive and coordinated global transcriptional changes during infection and point to previously unknown regulatory mechanisms in bacteria.
C1 [Toledo-Arana, Alejandro; Dussurget, Olivier; Sesto, Nina; Guet-Revillet, Helene; Balestrino, Damien; Nahori, Marie-Anne; Cossart, Pascale] Inst Pasteur, Unite Interact Bacteries Cellules, F-75015 Paris, France.
   [Toledo-Arana, Alejandro; Dussurget, Olivier; Nikitas, Georgios; Sesto, Nina; Guet-Revillet, Helene; Balestrino, Damien; Nahori, Marie-Anne; Lecuit, Marc; Cossart, Pascale] INSERM, U604, F-75015 Paris, France.
   [Toledo-Arana, Alejandro; Dussurget, Olivier; Sesto, Nina; Guet-Revillet, Helene; Balestrino, Damien; Nahori, Marie-Anne; Cossart, Pascale] INRA, USC2020, F-75015 Paris, France.
   [Nikitas, Georgios; Lecuit, Marc] Inst Pasteur, Microorganismes & Barrieres Hote G5, F-75015 Paris, France.
   [Nikitas, Georgios; Lecuit, Marc] INSERM, U604, F-75015 Paris, France.
   [Loh, Edmund; Gripenland, Jonas; Tiensuu, Teresa; Vaitkevicius, Karolis; Johansson, Joergen] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden.
   [Loh, Edmund; Gripenland, Jonas; Tiensuu, Teresa; Vaitkevicius, Karolis; Johansson, Joergen] Umea Univ, Lab Mol Infect Med Sweden MIMS, S-90187 Umea, Sweden.
   [Barthelemy, Mathieu; Soubigou, Guillaume; Regnault, Beatrice; Coppee, Jean-Yves] Inst Pasteur, F-75015 Paris, France.
   [Vergassola, Massimo] Inst Pasteur, UP Genet Sil, F-75015 Paris, France.
   [Vergassola, Massimo] CNRS, URA2171, F-75015 Paris, France.
   [Lecuit, Marc] Univ Paris 05, Hop Necker Enfants Malad, AP HP, F-75015 Paris, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); INRAE; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); Umea University; Umea University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP
RP Cossart, P (corresponding author), Inst Pasteur, Unite Interact Bacteries Cellules, F-75015 Paris, France.
EM pascale.cossart@pasteur.fr
FU Swedish Research Council [K2008-58X-15144-05-3, 621-2006-4450]; EU [Nu 018618, 2005-018618]; Institut Pasteur [GPH 9]; Inserm; INRA; ANR [ANR-05-MIIM-026-01]; ERC [233348]; Howard Hughes Medical Institute; European Research Council (ERC) [233348] Funding Source: European Research Council (ERC)
NR 37
TC 718
Z9 826
U1 0
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 18
PY 2009
VL 459
IS 7249
BP 950
EP 956
DI 10.1038/nature08080
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500035
PM 19448609
DA 2026-03-09
ER

PT J
AU Stephens, PJ
   McBride, DJ
   Lin, ML
   Varela, I
   Pleasance, ED
   Simpson, JT
   Stebbings, LA
   Leroy, C
   Edkins, S
   Mudie, LJ
   Greenman, CD
   Jia, MM
   Latimer, C
   Teague, JW
   Lau, KW
   Burton, J
   Quail, MA
   Swerdlow, H
   Churcher, C
   Natrajan, R
   Sieuwerts, AM
   Martens, JWM
   Silver, DP
   Langerod, A
   Russnes, HEG
   Foekens, JA
   Reis-Filho, JS
   van't Veer, L
   Richardson, AL
   Borresen-Dale, AL
   Campbell, PJ
   Futreal, PA
   Stratton, MR
AF Stephens, Philip J.
   McBride, David J.
   Lin, Meng-Lay
   Varela, Ignacio
   Pleasance, Erin D.
   Simpson, Jared T.
   Stebbings, Lucy A.
   Leroy, Catherine
   Edkins, Sarah
   Mudie, Laura J.
   Greenman, Chris D.
   Jia, Mingming
   Latimer, Calli
   Teague, Jon W.
   Lau, King Wai
   Burton, John
   Quail, Michael A.
   Swerdlow, Harold
   Churcher, Carol
   Natrajan, Rachael
   Sieuwerts, Anieta M.
   Martens, John W. M.
   Silver, Daniel P.
   Langerod, Anita
   Russnes, Hege E. G.
   Foekens, John A.
   Reis-Filho, Jorge S.
   van't Veer, Laura
   Richardson, Andrea L.
   Borresen-Dale, Anne-Lise
   Campbell, Peter J.
   Futreal, P. Andrew
   Stratton, Michael R.
TI Complex landscapes of somatic rearrangement in human breast cancer genomes
SO NATURE
LA English
DT Article
ID tandem duplication; myeloid-leukemia; copy number; fusion gene; patterns; translocations; identification; aberrations; etv6-ntrk3; mutation
AB Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.
C1 [Stephens, Philip J.; McBride, David J.; Lin, Meng-Lay; Varela, Ignacio; Pleasance, Erin D.; Simpson, Jared T.; Stebbings, Lucy A.; Leroy, Catherine; Edkins, Sarah; Mudie, Laura J.; Greenman, Chris D.; Jia, Mingming; Latimer, Calli; Teague, Jon W.; Lau, King Wai; Burton, John; Quail, Michael A.; Swerdlow, Harold; Churcher, Carol; Futreal, P. Andrew; Stratton, Michael R.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Natrajan, Rachael; Reis-Filho, Jorge S.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Mol Pathol Lab, London SW3 6JB, England.
   [Sieuwerts, Anieta M.; Martens, John W. M.; Foekens, John A.] Erasmus Univ, Med Ctr, Josephine Nefkens Inst, Dept Med Oncol, NL-3000 CA Rotterdam, Netherlands.
   [Silver, Daniel P.; Richardson, Andrea L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Langerod, Anita; Russnes, Hege E. G.; Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway.
   [van't Veer, Laura] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
   [Richardson, Andrea L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Borresen-Dale, Anne-Lise] Oslo Univ Hosp Radiumhosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway.
   [Stratton, Michael R.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
C3 Wellcome Trust Sanger Institute; University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; Erasmus University Rotterdam; Erasmus MC; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Oslo; Netherlands Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; University of Oslo; 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 Kay Kendall Leukaemia Fund [KKL282]; Human Frontiers [LT000561/2009-L]; NCI [CA089393]; Breakthrough Breast Cancer; Research Council of Norway [155218, 175240]; Wellcome Trust [077012/Z/05/Z]
NR 37
TC 654
Z9 789
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 DEC 24
PY 2009
VL 462
IS 7276
BP 1005
EP U60
DI 10.1038/nature08645
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000036
PM 20033038
DA 2026-03-09
ER

PT J
AU Park, JI
   Venteicher, AS
   Hong, JY
   Choi, J
   Jun, S
   Shkreli, M
   Chang, W
   Meng, ZJ
   Cheung, P
   Ji, H
   McLaughlin, M
   Veenstra, TD
   Nusse, R
   McCrea, PD
   Artandi, SE
AF Park, Jae-Il
   Venteicher, Andrew S.
   Hong, Ji Yeon
   Choi, Jinkuk
   Jun, Sohee
   Shkreli, Marina
   Chang, Woody
   Meng, Zhaojing
   Cheung, Peggie
   Ji, Hong
   McLaughlin, Margaret
   Veenstra, Timothy D.
   Nusse, Roel
   McCrea, Pierre D.
   Artandi, Steven E.
TI Telomerase modulates Wnt signalling by association with target gene chromatin
SO NATURE
LA English
DT Article
ID beta-catenin; reverse-transcriptase; anteroposterior axis; transient activation; growth; proliferation; expression; overexpression; dysfunction; regulators
AB Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/beta-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase exerts these effects are not understood. Here we show that telomerase directly modulates Wnt/beta-catenin signalling by serving as a cofactor in a beta-catenin transcriptional complex. The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in vivo. TERT serves an essential role in formation of the anterior-posterior axis in Xenopus laevis embryos, and this defect in Wnt signalling manifests as homeotic transformations in the vertebrae of Tert(-/-) mice. Chromatin immunoprecipitation of the endogenous TERT protein from mouse gastrointestinal tract shows that TERT physically occupies gene promoters of Wnt-dependent genes. These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/beta-catenin signalling pathway.
C1 [Park, Jae-Il; Venteicher, Andrew S.; Choi, Jinkuk; Jun, Sohee; Shkreli, Marina; Chang, Woody; Cheung, Peggie; Artandi, Steven E.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
   [Venteicher, Andrew S.; Artandi, Steven E.] Stanford Univ, Sch Med, Biophys Program, Stanford, CA 94305 USA.
   [Choi, Jinkuk; Artandi, Steven E.] Stanford Univ, Sch Med, Canc Biol Program, Stanford, CA 94305 USA.
   [Hong, Ji Yeon; Ji, Hong; McCrea, Pierre D.] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Meng, Zhaojing; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [McLaughlin, Margaret] MIT, Koch Inst Integrat Canc Biol, Cambridge, MA 02139 USA.
   [McLaughlin, Margaret] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Nusse, Roel] Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Dev Biol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; University of Texas System; UTMD Anderson Cancer Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Science Applications International Corporation (SAIC); SAIC-Frederick; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Stanford University; Howard Hughes Medical Institute
RP Artandi, SE (corresponding author), Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
EM sartandi@stanford.edu
FU Stanford Comprehensive Cancer Center Fellowship; NCI [CA111691, CA125453]; California Breast Cancer Research Program; National Cancer Institute [P30CA124435] Funding Source: NIH RePORTER
NR 50
TC 572
Z9 686
U1 0
U2 70
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 66
EP U77
DI 10.1038/nature08137
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200030
PM 19571879
DA 2026-03-09
ER

PT J
AU Albrecht, S
   Reffert, S
   Snellen, IAG
   Winn, JN
AF Albrecht, Simon
   Reffert, Sabine
   Snellen, Ignas A. G.
   Winn, Joshua N.
TI Misaligned spin and orbital axes cause the anomalous precession of DI Herculis
SO NATURE
LA English
DT Article
ID apsidal motion; binary; system; alignment; stars
AB The orbits of binary stars precess as a result of general relativistic effects, forces arising from the asphericity of the stars, and forces from any additional stars or planets in the system. For most binaries, the theoretical and observed precession rates are in agreement(1). One system, however-DI Herculis-has resisted explanation for 30 years(2-4). The observed precession rate is a factor of four slower than the theoretical rate, a disagreement that once was interpreted as evidence for a failure of general relativity(5). Among the contemporary explanations are the existence of a circumbinary planet(6) and a large tilt of the stellar spin axes with respect to the orbit(7,8). Here we report that both stars of DI Herculis rotate with their spin axes nearly perpendicular to the orbital axis (contrary to the usual assumption for close binary stars). The rotationally induced stellar oblateness causes precession in the direction opposite to that of relativistic precession, thereby reconciling the theoretical and observed rates.
C1 [Albrecht, Simon; Snellen, Ignas A. G.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Albrecht, Simon; Winn, Joshua N.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Albrecht, Simon; Winn, Joshua N.] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Reffert, Sabine] Zent Astrophys Heidelberg, D-69117 Heidelberg, Germany.
C3 Leiden University - Excl LUMC; Leiden University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Ruprecht Karls University Heidelberg
RP Albrecht, S (corresponding author), Leiden Univ, Leiden Observ, Postbus 9513, NL-2300 RA Leiden, Netherlands.
EM albrecht@space.mit.edu
FU Netherlands Organisation for Scientific Research (NWO); NASA [NNX09AD36G]; Optical Infrared Coordination network (OPTICON); NASA [120361, NNX09AD36G] Funding Source: Federal RePORTER
NR 26
TC 112
Z9 121
U1 0
U2 2
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 373
EP 376
DI 10.1038/nature08408
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100034
PM 19759615
DA 2026-03-09
ER

PT J
AU Cardin, JA
   Carlén, M
   Meletis, K
   Knoblich, U
   Zhang, F
   Deisseroth, K
   Tsai, LH
   Moore, CI
AF Cardin, Jessica A.
   Carlen, Marie
   Meletis, Konstantinos
   Knoblich, Ulf
   Zhang, Feng
   Deisseroth, Karl
   Tsai, Li-Huei
   Moore, Christopher I.
TI Driving fast-spiking cells induces gamma rhythm and controls sensory responses
SO NATURE
LA English
DT Article
ID neuronal synchronization; electrical synapses; cortical networks; fast oscillations; cortex; interneurons; brain; schizophrenia; generation; attention
AB Cortical gamma oscillations (20-80 Hz) predict increases in focused attention, and failure in gamma regulation is a hallmark of neurological and psychiatric disease. Current theory predicts that gamma oscillations are generated by synchronous activity of fast-spiking inhibitory interneurons, with the resulting rhythmic inhibition producing neural ensemble synchrony by generating a narrow window for effective excitation. We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons at varied frequencies (8-200 Hz) selectively amplifies gamma oscillations. In contrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.
C1 [Cardin, Jessica A.; Knoblich, Ulf; Moore, Christopher I.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
   [Cardin, Jessica A.] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA.
   [Carlen, Marie; Meletis, Konstantinos; Tsai, Li-Huei] MIT, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Carlen, Marie; Meletis, Konstantinos; Tsai, Li-Huei] Broad Inst Harvard & Massachusetts Inst Technol, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA.
   [Zhang, Feng; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Tsai, Li-Huei] Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); University of Pennsylvania; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Stanford University; Howard Hughes Medical Institute
RP Moore, CI (corresponding author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM deissero@stanford.edu; lhtsai@mit.edu; cim@mit.edu
FU NIH/NEI; Knut och Alice Wallenberg Foundation; NARSAD Young Investigator Award; NIH NRSA; Tom F. Petersen; NIH; NSF; Simons Foundation Autism Research Initiative; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [0848469, 0848804] Funding Source: National Science Foundation
NR 33
TC 2024
Z9 2511
U1 5
U2 288
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 663
EP U63
DI 10.1038/nature08002
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600035
PM 19396156
DA 2026-03-09
ER

PT J
AU Margueron, R
   Justin, N
   Ohno, K
   Sharpe, ML
   Son, J
   Drury, WJ
   Voigt, P
   Martin, SR
   Taylor, WR
   De Marco, V
   Pirrotta, V
   Reinberg, D
   Gamblin, SJ
AF Margueron, Raphael
   Justin, Neil
   Ohno, Katsuhito
   Sharpe, Miriam L.
   Son, Jinsook
   Drury, William J., III
   Voigt, Philipp
   Martin, Stephen R.
   Taylor, William R.
   De Marco, Valeria
   Pirrotta, Vincenzo
   Reinberg, Danny
   Gamblin, Steven J.
TI Role of the polycomb protein EED in the propagation of repressive histone marks
SO NATURE
LA English
DT Article
ID methyltransferase activity; structural basis; drosophila; recognition; h3; trimethylation; esc; methylation; complexes; chromatin
AB Polycomb group proteins have an essential role in the epigenetic maintenance of repressive chromatin states. The gene-silencing activity of the Polycomb repressive complex 2 (PRC2) depends on its ability to trimethylate lysine 27 of histone H3 (H3K27) by the catalytic SET domain of the EZH2 subunit, and at least two other subunits of the complex: SUZ12 and EED. Here we show that the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and that this leads to the allosteric activation of the methyltransferase activity of PRC2. Mutations in EED that prevent it from recognizing repressive trimethyl-lysine marks abolish the activation of PRC2 in vitro and, in Drosophila, reduce global methylation and disrupt development. These findings suggest a model for the propagation of the H3K27me3 mark that accounts for the maintenance of repressive chromatin domains and for the transmission of a histone modification from mother to daughter cells.
C1 [Ohno, Katsuhito; Pirrotta, Vincenzo] Rutgers State Univ, Dept Mol Biol & Biochem, Nelson Labs, Piscataway, NJ 08854 USA.
   [Margueron, Raphael; Son, Jinsook; Drury, William J., III; Voigt, Philipp; Reinberg, Danny] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
   [Margueron, Raphael; Son, Jinsook; Drury, William J., III; Voigt, Philipp; Reinberg, Danny] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA.
   [Justin, Neil; Sharpe, Miriam L.; Martin, Stephen R.; Taylor, William R.; De Marco, Valeria; Gamblin, Steven J.] MRC Natl Inst Med Res, London NW7 1AA, England.
C3 Rutgers University System; Rutgers University New Brunswick; Howard Hughes Medical Institute; New York University; New York University; MRC National Institute for Medical Research
RP Pirrotta, V (corresponding author), Rutgers State Univ, Dept Mol Biol & Biochem, Nelson Labs, 604 Allison Rd, Piscataway, NJ 08854 USA.
EM pirrotta@biology.rutgers.edu; reinbd01@med.nyu.edu; sgambli@nimr.mrc.ac.uk
FU Deutsche Akademie der Naturforscher Leopoldina [LPDS 2009-5]; NIH [GM064844, GM37120]; HHMI; MRC; Division of Life Sciences of Rutgers University; MRC [MC_U117584222] Funding Source: UKRI; Medical Research Council [MC_U117584222] Funding Source: researchfish
NR 40
TC 950
Z9 1209
U1 0
U2 100
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 8
PY 2009
VL 461
IS 7265
BP 762
EP U11
DI 10.1038/nature08398
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500029
PM 19767730
DA 2026-03-09
ER

PT J
AU Fischer, TP
   Burnard, P
   Marty, B
   Hilton, DR
   Füri, E
   Palhol, F
   Sharp, ZD
   Mangasini, F
AF Fischer, T. P.
   Burnard, P.
   Marty, B.
   Hilton, D. R.
   Fueri, E.
   Palhol, F.
   Sharp, Z. D.
   Mangasini, F.
TI Upper-mantle volatile chemistry at Oldoinyo Lengai volcano and the origin of carbonatites
SO NATURE
LA English
DT Article
ID midocean ridge; noble-gases; subduction; co2; he; fractionation; geochemistry; systematics; solubility; insights
AB Carbonatite lavas are highly unusual in that they contain almost no SiO2 and are >50 per cent carbonate minerals. Although carbonatite magmatism has occurred throughout Earth's history, Oldoinyo Lengai, in Tanzania, is the only currently active volcano producing these exotic rocks(1). Here we show that volcanic gases captured during an eruptive episode at Oldoinyo Lengai are indistinguishable from those emitted along mid-ocean ridges, despite the fact that Oldoinyo Lengai carbonatites occur in a setting far removed from oceanic spreading centres. In contrast to lithophile trace elements, which are highly fractionated by the immiscible phase separation that produces these carbonatites, volatiles (CO2, He, N-2 and Ar) are little affected by this process. Our results demonstrate that a globally homogenous reservoir exists in the upper mantle and supplies volatiles to both mid-ocean ridges and continental rifts. This argues against an unusually C-rich mantle being responsible for the genesis of Na-rich carbonatite and its nephelinite source magma at Oldoinyo Lengai. Rather, these carbonatites are formed in the shallow crust by immiscibility from silicate magmas (nephelinite), and are stable under eruption conditions as a result of their high Na contents.
C1 [Fischer, T. P.; Sharp, Z. D.] Univ New Mexico, Dept Earth & Planetary Sci, Albuquerque, NM 87131 USA.
   [Burnard, P.; Marty, B.; Palhol, F.] Nancy Univ, CNRS, INSU, Ctr Rech Petrog & Geochim, F-54501 Vandoeuvre Les Nancy, France.
   [Hilton, D. R.; Fueri, E.] Univ Calif San Diego, Scripps Inst Oceanog, Geosci Res Div, La Jolla, CA 92093 USA.
   [Mangasini, F.] Univ Dar Es Salaam, Dept Min & Mineral Proc Engn, Dar Es Salaam, Tanzania.
C3 University of New Mexico; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Lorraine; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Dar es Salaam
RP Fischer, TP (corresponding author), Univ New Mexico, Dept Earth & Planetary Sci, MSC03 2040,1 Univ New Mexico, Albuquerque, NM 87131 USA.
EM fischer@unm.edu
FU CNRS-INSU; US National Science Foundation [EAR-0439122]; University of New Mexico [EAR-0537618, EAR-0827352]; Tanzania Commission for Science and Technology [2005-217-NA-2005-74]; Directorate For Geosciences; Division Of Earth Sciences [0827352] Funding Source: National Science Foundation
NR 33
TC 134
Z9 147
U1 4
U2 80
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 7
PY 2009
VL 459
IS 7243
BP 77
EP 80
DI 10.1038/nature07977
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300032
PM 19424154
DA 2026-03-09
ER

PT J
AU Wu, DY
   Hugenholtz, P
   Mavromatis, K
   Pukall, R
   Dalin, E
   Ivanova, NN
   Kunin, V
   Goodwin, L
   Wu, M
   Tindall, BJ
   Hooper, SD
   Pati, A
   Lykidis, A
   Spring, S
   Anderson, IJ
   D'haeseleer, P
   Zemla, A
   Singer, M
   Lapidus, A
   Nolan, M
   Copeland, A
   Han, C
   Chen, F
   Cheng, JF
   Lucas, S
   Kerfeld, C
   Lang, E
   Gronow, S
   Chain, P
   Bruce, D
   Rubin, EM
   Kyrpides, NC
   Klenk, HP
   Eisen, JA
AF Wu, Dongying
   Hugenholtz, Philip
   Mavromatis, Konstantinos
   Pukall, Ruediger
   Dalin, Eileen
   Ivanova, Natalia N.
   Kunin, Victor
   Goodwin, Lynne
   Wu, Martin
   Tindall, Brian J.
   Hooper, Sean D.
   Pati, Amrita
   Lykidis, Athanasios
   Spring, Stefan
   Anderson, Iain J.
   D'haeseleer, Patrik
   Zemla, Adam
   Singer, Mitchell
   Lapidus, Alla
   Nolan, Matt
   Copeland, Alex
   Han, Cliff
   Chen, Feng
   Cheng, Jan-Fang
   Lucas, Susan
   Kerfeld, Cheryl
   Lang, Elke
   Gronow, Sabine
   Chain, Patrick
   Bruce, David
   Rubin, Edward M.
   Kyrpides, Nikos C.
   Klenk, Hans-Peter
   Eisen, Jonathan A.
TI A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea
SO NATURE
LA English
DT Article
ID microbial diversity; protein family; database gold; projects; sequence
AB Sequencing of bacterial and archaeal genomes has revolutionized our understanding of the many roles played by microorganisms(1). There are now nearly 1,000 completed bacterial and archaeal genomes available(2), most of which were chosen for sequencing on the basis of their physiology. As a result, the perspective provided by the currently available genomes is limited by a highly biased phylogenetic distribution(3-5). To explore the value added by choosing microbial genomes for sequencing on the basis of their evolutionary relationships, we have sequenced and analysed the genomes of 56 culturable species of Bacteria and Archaea selected to maximize phylogenetic coverage. Analysis of these genomes demonstrated pronounced benefits ( compared to an equivalent set of genomes randomly selected from the existing database) in diverse areas including the reconstruction of phylogenetic history, the discovery of new protein families and biological properties, and the prediction of functions for known genes from other organisms. Our results strongly support the need for systematic 'phylogenomic' efforts to compile a phylogeny-driven 'Genomic Encyclopedia of Bacteria and Archaea' in order to derive maximum knowledge from existing microbial genome data as well as from genome sequences to come.
C1 [Wu, Dongying; Hugenholtz, Philip; Mavromatis, Konstantinos; Dalin, Eileen; Ivanova, Natalia N.; Kunin, Victor; Hooper, Sean D.; Pati, Amrita; Lykidis, Athanasios; Anderson, Iain J.; D'haeseleer, Patrik; Lapidus, Alla; Nolan, Matt; Copeland, Alex; Chen, Feng; Cheng, Jan-Fang; Lucas, Susan; Kerfeld, Cheryl; Chain, Patrick; Rubin, Edward M.; Kyrpides, Nikos C.; Eisen, Jonathan A.] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Wu, Dongying; Singer, Mitchell; Eisen, Jonathan A.] Univ Calif Davis, Davis, CA 95616 USA.
   [Pukall, Ruediger; Tindall, Brian J.; Spring, Stefan; Lang, Elke; Gronow, Sabine; Klenk, Hans-Peter] Deutsch Sammlung Mikroorganism Zellkultur GmbH, German Collect Microorganisms & Cell Cultures, D-38124 Braunschweig, Germany.
   [Goodwin, Lynne; Han, Cliff; Chain, Patrick; Bruce, David] Los Alamos Natl Lab, DOE Joint Genome Inst, Los Alamos, NM 87545 USA.
   [D'haeseleer, Patrik; Zemla, Adam] Univ Virginia, Charlottesville, VA 22904 USA.
   [Wu, Martin] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
C3 United States Department of Energy (DOE); University of California System; University of California Davis; Leibniz Association; Leibniz Institut fur Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ); United States Department of Energy (DOE); Los Alamos National Laboratory; University of Virginia; United States Department of Energy (DOE); Lawrence Livermore National Laboratory
RP Eisen, JA (corresponding author), DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
EM jaeisen@ucdavis.edu
FU US Department of Energy's Office of Science, Biological and Environmental Research Program; University of California, Lawrence Berkeley National Laboratory [DE-AC02-05CH11231]; Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; Los Alamos National Laboratory [DE-AC02-06NA25396]; Gordon and Betty Moore Foundation [1660]; DFG INST [599/1-1]
NR 30
TC 731
Z9 822
U1 0
U2 146
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1056
EP 1060
DI 10.1038/nature08656
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000047
PM 20033048
DA 2026-03-09
ER

PT J
AU Garcia-Castellanos, D
   Estrada, F
   Jiménez-Munt, I
   Gorini, C
   Fernàndez, M
   Vergés, J
   De Vicente, R
AF Garcia-Castellanos, D.
   Estrada, F.
   Jimenez-Munt, I.
   Gorini, C.
   Fernandez, M.
   Verges, J.
   De Vicente, R.
TI Catastrophic flood of the Mediterranean after the Messinian salinity crisis
SO NATURE
LA English
DT Article
ID alboran sea; gibraltar strait; late miocene; incision; basin; desiccation; evolution; boundary; channel; origin
AB The Mediterranean Sea became disconnected from the world's oceans and mostly desiccated by evaporation about 5.6 million years ago during the Messinian salinity crisis(1-3). The Atlantic waters found a way through the present Gibraltar Strait and rapidly refilled the Mediterranean 5.33 million years ago in an event known as the Zanclean flood(4). The nature, abruptness and evolution of this flood remain poorly constrained(4-6). Borehole and seismic data show incisions over 250 m deep on both sides of the Gibraltar Strait that have previously been attributed to fluvial erosion during the desiccation(4,7). Here we show the continuity of this 200-km-long channel across the strait and explain its morphology as the result of erosion by the flooding waters, adopting an incision model validated in mountain rivers. This model in turn allows us to estimate the duration of the flood. Although the available data are limited, our findings suggest that the feedback between water flow and incision in the early stages of flooding imply discharges of about 10(8) m(3) s(-1) (three orders of magnitude larger than the present Amazon River) and incision rates above 0.4 m per day. Although the flood started at low water discharges that may have lasted for up to several thousand years, our results suggest that 90 per cent of the water was transferred in a short period ranging from a few months to two years. This extremely abrupt flood may have involved peak rates of sea level rise in the Mediterranean of more than ten metres per day.
C1 [Garcia-Castellanos, D.; Jimenez-Munt, I.; Fernandez, M.; Verges, J.; De Vicente, R.] CSIC, Inst Ciencies Terra Jaume Almera, Barcelona, Spain.
   [Estrada, F.] CSIC, Inst Ciencies Mar, Barcelona, Spain.
   [Gorini, C.] Univ Paris 06, F-75005 Paris, France.
   [Gorini, C.] CNRS, ISTEP, UMR 7193, F-75005 Paris, France.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Geociencias Barcelona (GEO3BCN); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Mediterraneo de Investigaciones Marinas y Ambientales (CMIMA); CSIC - Instituto de Ciencias del Mar (ICM); Sorbonne Universite; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU)
RP Garcia-Castellanos, D (corresponding author), CSIC, Inst Ciencies Terra Jaume Almera, Sole & Sabaris S-N, Barcelona, Spain.
EM danielgc@ictja.csic.es
FU Spanish Government [CGL2006-05493]
NR 36
TC 369
Z9 417
U1 2
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 778
EP U96
DI 10.1038/nature08555
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900036
PM 20010684
DA 2026-03-09
ER

PT J
AU Marques-Bonet, T
   Kidd, JM
   Ventura, M
   Graves, TA
   Cheng, Z
   Hillier, LW
   Jiang, ZS
   Baker, C
   Malfavon-Borja, R
   Fulton, LA
   Alkan, C
   Aksay, G
   Girirajan, S
   Siswara, P
   Chen, L
   Cardone, MF
   Navarro, A
   Mardis, ER
   Wilson, RK
   Eichler, EE
AF Marques-Bonet, Tomas
   Kidd, Jeffrey M.
   Ventura, Mario
   Graves, Tina A.
   Cheng, Ze
   Hillier, LaDeana W.
   Jiang, Zhaoshi
   Baker, Carl
   Malfavon-Borja, Ray
   Fulton, Lucinda A.
   Alkan, Can
   Aksay, Gozde
   Girirajan, Santhosh
   Siswara, Priscillia
   Chen, Lin
   Cardone, Maria Francesca
   Navarro, Arcadi
   Mardis, Elaine R.
   Wilson, Richard K.
   Eichler, Evan E.
TI A burst of segmental duplications in the genome of the African great ape ancestor
SO NATURE
LA English
DT Article
ID copy number variation; structural variation; evolution
AB It is generally accepted that the extent of phenotypic change between human and great apes is dissonant with the rate of molecular change(1). Between these two groups, proteins are virtually identical(1,2), cytogenetically there are few rearrangements that distinguish ape - human chromosomes(3), and rates of single- base- pair change(4-7) and retrotransposon activity(8-10) have slowed particularly within hominid lineages when compared to rodents or monkeys. Studies of gene family evolution indicate that gene loss and gain are enriched within the primate lineage(11,12). Here, we perform a systematic analysis of duplication content of four primate genomes ( macaque, orang- utan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of base pairs and in terms of events. This duplication acceleration within the ancestral species is significant when compared to lineage- specific rate estimates even after accounting for copy- number polymorphism and homoplasy. We discover striking examples of recurrent and independent gene- containing duplications within the gorilla and chimpanzee that are absent in the human lineage. Our results suggest that the evolutionary properties of copy- number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single- base- pair mutations, there has been a genomic burst of duplication activity at this period during human evolution.
C1 [Marques-Bonet, Tomas; Kidd, Jeffrey M.; Cheng, Ze; Jiang, Zhaoshi; Baker, Carl; Malfavon-Borja, Ray; Alkan, Can; Aksay, Gozde; Girirajan, Santhosh; Siswara, Priscillia; Chen, Lin; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Marques-Bonet, Tomas; Kidd, Jeffrey M.; Cheng, Ze; Jiang, Zhaoshi; Baker, Carl; Malfavon-Borja, Ray; Alkan, Can; Aksay, Gozde; Girirajan, Santhosh; Siswara, Priscillia; Chen, Lin; Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Marques-Bonet, Tomas; Navarro, Arcadi] UPF CSIC, Inst Biol Evolut, Barcelona 08003, Spain.
   [Ventura, Mario; Cardone, Maria Francesca] Univ Bari, Sez Genet, Dipartimento Anat Patol & Genet, I-70125 Bari, Italy.
   [Graves, Tina A.; Hillier, LaDeana W.; Fulton, Lucinda A.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA.
   [Navarro, Arcadi] ICREA, Barcelona 08003, Spain.
   [Navarro, Arcadi] INB, Barcelona 08003, Spain.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); Universita degli Studi di Bari Aldo Moro; Washington University (WUSTL); ICREA
RP Eichler, EE (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM eee@gs.washington.edu
FU NIH [HG002385, U54 HG003079]; Marie Curie fellowship; Departament d'Educacio i Universitats de la Generalitat de Catalunya; National Human Genome Research Institute [R01HG002385] Funding Source: NIH RePORTER; ICREA Funding Source: Custom
NR 30
TC 186
Z9 228
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 12
PY 2009
VL 457
IS 7231
BP 877
EP 881
DI 10.1038/nature07744
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700044
PM 19212409
DA 2026-03-09
ER

PT J
AU Wang, LG
   Sigworth, FJ
AF Wang, Liguo
   Sigworth, Fred J.
TI Structure of the BK potassium channel in a lipid membrane from electron cryomicroscopy
SO NATURE
LA English
DT Article
ID dependent k+ channel; high-conductance; voltage sensor; cryo-em; streptavidin; environment; refinement; activation; mechanism; proteins
AB A long-sought goal in structural biology has been the imaging of membrane proteins in their membrane environments. This goal has been achieved with electron crystallography(1) in those special cases where a protein forms highly ordered arrays in lipid bilayers. It has also been achieved by NMR methods(1) in proteins up to 50 kilodaltons (kDa) in size, although milligram quantities of protein and isotopic labelling are required. For structural analysis of large soluble proteins in microgram quantities, an increasingly powerful method that does not require crystallization is single-particle reconstruction from electron microscopy of cryogenically cooled samples (electron cryomicroscopy (cryo-EM))(2). Here we report the first single-particle cryo-EM study of a membrane protein, the human large-conductance calcium-and voltage-activated potassium channel(3) (BK), in a lipid environment. The new method is called random spherically constrained (RSC) single-particle reconstruction. BK channels, members of the six-transmembrane segment (6TM) ion channel family, were reconstituted at low density into lipid vesicles (liposomes), and their function was verified by a potassium flux assay. Vesicles were also frozen in vitreous ice and imaged in an electron microscope. From images of 8,400 individual protein particles, a three-dimensional (3D) reconstruction of the BK channel and its membrane environment was obtained at a resolution of 1.7-2.0 nm. Not requiring the formation of crystals, the RSC approach promises to be useful in the structural study of many other membrane proteins as well.
C1 [Wang, Liguo; Sigworth, Fred J.] Yale Univ, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA.
C3 Yale University
RP Sigworth, FJ (corresponding author), Yale Univ, Dept Cellular & Mol Physiol, 333 Cedar St, New Haven, CT 06520 USA.
EM fred.sigworth@yale.edu
FU NCRR NIH HHS [S10 RR014739] Funding Source: Medline; NIGMS NIH HHS [P01 GM062580] Funding Source: Medline; NINDS NIH HHS [R01 NS021501] Funding Source: Medline; National Institute of Neurological Disorders and Stroke [R01NS021501] Funding Source: NIH RePORTER
NR 30
TC 166
Z9 198
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 10
PY 2009
VL 461
IS 7261
BP 292
EP U177
DI 10.1038/nature08291
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600050
PM 19718020
DA 2026-03-09
ER

PT J
AU Houghton, AM
   Hartzell, WO
   Robbins, CS
   Gomis-Rüth, FX
   Shapiro, SD
AF Houghton, A. McGarry
   Hartzell, William O.
   Robbins, Clinton S.
   Xavier Gomis-Rueth, F.
   Shapiro, Steven D.
TI Macrophage elastase kills bacteria within murine macrophages
SO NATURE
LA English
DT Article
ID neutrophil elastase; matrix metalloproteinases; host-defense; gelatinase-a; mice; cleavage; angiogenesis; degradation; activation; mechanisms
AB Macrophages are aptly positioned to function as the primary line of defence against invading pathogens in many organs, including the lung and peritoneum. Their ability to phagocytose and clear microorganisms has been well documented(1,2). Macrophages possess several substances with which they can kill bacteria, including reactive oxygen species, nitric oxide, and antimicrobial proteins(3-9). We proposed that macrophage-derived proteinases may contribute to the antimicrobial properties of macrophages. Macrophage elastase (also known as matrix metalloproteinase 12 or MMP12) is an enzyme predominantly expressed in mature tissue macrophages(10) and is implicated in several disease processes, including emphysema(11). Physiological functions for MMP12 have not been described. Here we show that Mmp12(-/-) mice exhibit impaired bacterial clearance and increased mortality when challenged with both Gram-negative and Gram-positive bacteria at macrophage-rich portals of entry, such as the peritoneum and lung. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The antimicrobial properties of MMP12 do not reside within its catalytic domain, but rather within the carboxyterminal domain. This domain contains a unique four amino acid sequence on an exposed beta loop of the protein that is required for the observed antimicrobial activity. The present study represents, to our knowledge, the first report of direct antimicrobial activity by a matrix metallopeptidase, and describes a new antimicrobial peptide that is sequentially and structurally unique in nature.
C1 [Houghton, A. McGarry; Robbins, Clinton S.; Shapiro, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
   [Hartzell, William O.] Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA.
   [Xavier Gomis-Rueth, F.] CSIC, Mol Biol Inst Barcelona, Proteolysis Lab, E-08028 Barcelona, Spain.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Biologia Molecular de Barcelona (IBMB)
RP Houghton, AM (corresponding author), Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
EM houghtonm@dom.pitt.edu
FU National Institutes of Health (NIH); National Heart, Lung and Blood Institute (NHLBI); Spanish and European public agencies
NR 30
TC 142
Z9 161
U1 3
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 637
EP U106
DI 10.1038/nature08181
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300052
PM 19536155
DA 2026-03-09
ER

PT J
AU Do, MTH
   Kang, SH
   Xue, T
   Zhong, HN
   Liao, HW
   Bergles, DE
   Yau, KW
AF Do, Michael Tri H.
   Kang, Shin H.
   Xue, Tian
   Zhong, Haining
   Liao, Hsi-Wen
   Bergles, Dwight E.
   Yau, King-Wai
TI Photon capture and signalling by melanopsin retinal ganglion cells
SO NATURE
LA English
DT Article
ID cone photoreceptors; light responses; mice; photopigment; reflex; expression; rods; set
AB A subset of retinal ganglion cells has recently been discovered to be intrinsically photosensitive, with melanopsin as the pigment. These cells project primarily to brain centres for non- image- forming visual functions such as the pupillary light reflex and circadian photoentrainment. How well they signal intrinsic light absorption to drive behaviour remains unclear. Here we report fundamental parameters governing their intrinsic light responses and associated spike generation. The membrane density of melanopsin is 10(4)-fold lower than that of rod and cone pigments, resulting in a very low photon catch and a phototransducing role only in relatively bright light. Nonetheless, each captured photon elicits a large and extraordinarily prolonged response, with a unique shape among known photoreceptors. Notably, like rods, these cells are capable of signalling single- photon absorption. A flash causing a few hundred isomerized melanopsin molecules in a retina is sufficient for reaching threshold for the pupillary light reflex.
C1 [Do, Michael Tri H.; Kang, Shin H.; Xue, Tian; Zhong, Haining; Liao, Hsi-Wen; Bergles, Dwight E.; Yau, King-Wai] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Yau, King-Wai] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Do, Michael Tri H.; Xue, Tian; Yau, King-Wai] Johns Hopkins Univ, Sch Med, Ctr Sensory Biol, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University
RP Do, MTH (corresponding author), Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
EM mdo@jhmi.edu; kwyau@mail.jhmi.edu
FU NRSA; VNTP Training Grant; NIH; National Eye Institute [R01EY014596] Funding Source: NIH RePORTER
NR 50
TC 231
Z9 286
U1 0
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 281
EP U2
DI 10.1038/nature07682
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900032
PM 19118382
DA 2026-03-09
ER

PT J
AU Fullwood, MJ
   Liu, MH
   Pan, YF
   Liu, J
   Xu, H
   Bin Mohamed, Y
   Orlov, YL
   Velkov, S
   Ho, A
   Mei, PH
   Chew, EGY
   Huang, PYH
   Welboren, WJ
   Han, YY
   Ooi, HS
   Ariyaratne, PN
   Vega, VB
   Luo, YQ
   Tan, PY
   Choy, PY
   Wansa, KDSA
   Zhao, B
   Lim, KS
   Leow, SC
   Yow, JS
   Joseph, R
   Li, HX
   Desai, KV
   Thomsen, JS
   Lee, YK
   Karuturi, RKM
   Herve, T
   Bourque, G
   Stunnenberg, HG
   Ruan, XL
   Cacheux-Rataboul, V
   Sung, WK
   Liu, ET
   Wei, CL
   Cheung, E
   Ruan, YJ
AF Fullwood, Melissa J.
   Liu, Mei Hui
   Pan, You Fu
   Liu, Jun
   Xu, Han
   Bin Mohamed, Yusoff
   Orlov, Yuriy L.
   Velkov, Stoyan
   Ho, Andrea
   Mei, Poh Huay
   Chew, Elaine G. Y.
   Huang, Phillips Yao Hui
   Welboren, Willem-Jan
   Han, Yuyuan
   Ooi, Hong Sain
   Ariyaratne, Pramila N.
   Vega, Vinsensius B.
   Luo, Yanquan
   Tan, Peck Yean
   Choy, Pei Ye
   Wansa, K. D. Senali Abayratna
   Zhao, Bing
   Lim, Kar Sian
   Leow, Shi Chi
   Yow, Jit Sin
   Joseph, Roy
   Li, Haixia
   Desai, Kartiki V.
   Thomsen, Jane S.
   Lee, Yew Kok
   Karuturi, R. Krishna Murthy
   Herve, Thoreau
   Bourque, Guillaume
   Stunnenberg, Hendrik G.
   Ruan, Xiaoan
   Cacheux-Rataboul, Valere
   Sung, Wing-Kin
   Liu, Edison T.
   Wei, Chia-Lin
   Cheung, Edwin
   Ruan, Yijun
TI An oestrogen-receptor-α-bound human chromatin interactome
SO NATURE
LA English
DT Article
ID chromosome conformation; binding-sites; human genome; transcription; genes; foxa1; chip; elements; reveals; defines
AB Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor alpha (ER-alpha) in the human genome. We found that most high-confidence remote ER-alpha-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-alpha functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.
C1 [Fullwood, Melissa J.; Liu, Mei Hui; Pan, You Fu; Liu, Jun; Xu, Han; Bin Mohamed, Yusoff; Orlov, Yuriy L.; Velkov, Stoyan; Ho, Andrea; Mei, Poh Huay; Chew, Elaine G. Y.; Huang, Phillips Yao Hui; Han, Yuyuan; Ooi, Hong Sain; Ariyaratne, Pramila N.; Vega, Vinsensius B.; Luo, Yanquan; Tan, Peck Yean; Choy, Pei Ye; Wansa, K. D. Senali Abayratna; Zhao, Bing; Lim, Kar Sian; Leow, Shi Chi; Yow, Jit Sin; Joseph, Roy; Li, Haixia; Desai, Kartiki V.; Thomsen, Jane S.; Lee, Yew Kok; Karuturi, R. Krishna Murthy; Herve, Thoreau; Bourque, Guillaume; Ruan, Xiaoan; Cacheux-Rataboul, Valere; Sung, Wing-Kin; Liu, Edison T.; Wei, Chia-Lin; Cheung, Edwin; Ruan, Yijun] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore.
   [Welboren, Willem-Jan; Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Dept Mol Biol, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands.
   [Sung, Wing-Kin] Natl Univ Singapore, Sch Comp, Dept Comp Sci, Singapore 117543, Singapore.
   [Cheung, Edwin; Ruan, Yijun] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore.
   [Cheung, Edwin] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore.
C3 Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Radboud University Nijmegen; National University of Singapore; National University of Singapore; Nanyang Technological University
RP Ruan, YJ (corresponding author), Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore.
EM cheungcwe@gis.a-star.edu.sg; ruanyj@gis.a-star.edu.sg
FU L'Oreal-UNESCO; A*STAR of Singapore; NIH [R01 HG004456-01, R01HG003521-01, 1U54HG004557-01]
NR 31
TC 1358
Z9 1704
U1 2
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 5
PY 2009
VL 462
IS 7269
BP 58
EP 64
DI 10.1038/nature08497
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200031
PM 19890323
DA 2026-03-09
ER

PT J
AU Dorrepaal, E
   Toet, S
   van Logtestijn, RSP
   Swart, E
   van de Weg, MJ
   Callaghan, TV
   Aerts, R
AF Dorrepaal, Ellen
   Toet, Sylvia
   van Logtestijn, Richard S. P.
   Swart, Elferra
   van de Weg, Martine J.
   Callaghan, Terry V.
   Aerts, Rien
TI Carbon respiration from subsurface peat accelerated by climate warming in the subarctic
SO NATURE
LA English
DT Article
ID soil co2 efflux; water-table; temperature sensitivity; natural-abundance; ecosystem; bog; decomposition; growth; cycle; mineralization
AB Among the largest uncertainties in current projections of future climate is the feedback between the terrestrial carbon cycle and climate(1). Northern peatlands contain one-third of the world's soil organic carbon, equivalent to more than half the amount of carbon in the atmosphere(2). Climate-warming-induced acceleration of carbon dioxide (CO(2)) emissions through enhanced respiration of thick peat deposits, centuries to millennia old, may form a strong positive carbon cycle-climate feedback. The long-term temperature sensitivity of carbon in peatlands, especially at depth, remains uncertain, however, because of the short duration or correlative nature of field studies(3-5) and the disturbance associated with respiration measurements below the surface in situ or during laboratory incubations(6,7). Here we combine non-disturbing in situ measurements of CO(2) respiration rates and isotopic ((13)C) composition of respired CO(2) in two whole-ecosystem climate-manipulation experiments in a subarctic peatland. We show that approximately 1 degrees C warming accelerated total ecosystem respiration rates on average by 60% in spring and by 52% in summer and that this effect was sustained for at least eight years. While warming stimulated both short-term (plant-related) and longer-term (peat soil-related) carbon respiration processes, we find that at least 69% of the increase in respiration rate originated from carbon in peat towards the bottom (25-50 cm) of the active layer above the permafrost. Climate warming therefore accelerates respiration of the extensive, subsurface carbon reservoirs in peatlands to a much larger extent than was previously thought(6,7). Assuming that our data from a single site are indicative of the direct response to warming of northern peatland soils on a global scale, we estimate that climate warming of about 1 degrees C over the next few decades could induce a global increase in heterotrophic respiration of 38-100 megatonnes of C per year. Our findings suggest a large, long-lasting, positive feedback of carbon stored in northern peatlands to the global climate system.
C1 [Dorrepaal, Ellen; Toet, Sylvia; van Logtestijn, Richard S. P.; Swart, Elferra; van de Weg, Martine J.; Aerts, Rien] Vrije Univ Amsterdam, Inst Ecol Sci, Dept Syst Ecol, NL-1081 HV Amsterdam, Netherlands.
   [Callaghan, Terry V.] Royal Swedish Acad Sci, Abisko Naturvetenskapliga Stn, SE-98107 Abisko, Sweden.
   [Callaghan, Terry V.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield Ctr Arctic Ecol, Sheffield S10 5BR, S Yorkshire, England.
C3 Vrije Universiteit Amsterdam; Royal Swedish Academy of Sciences; University of Sheffield
RP Dorrepaal, E (corresponding author), Vrije Univ Amsterdam, Inst Ecol Sci, Dept Syst Ecol, Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands.
EM ellen.dorrepaal@ecology.falw.vu.nl
FU USF [98.24]; ALW-NWO [854.00.019]; EU-ATANS [Fp6 506004]
NR 34
TC 593
Z9 692
U1 11
U2 661
PU 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 30
PY 2009
VL 460
IS 7255
BP 616
EP U79
DI 10.1038/nature08216
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300047
DA 2026-03-09
ER

PT J
AU Thomas, DL
   Thio, CL
   Martin, MP
   Qi, Y
   Ge, D
   O'hUigin, C
   Kidd, J
   Kidd, K
   Khakoo, SI
   Alexander, G
   Goedert, JJ
   Kirk, GD
   Donfield, SM
   Rosen, HR
   Tobler, LH
   Busch, MP
   McHutchison, JG
   Goldstein, DB
   Carrington, M
AF Thomas, David L.
   Thio, Chloe L.
   Martin, Maureen P.
   Qi, Ying
   Ge, Dongliang
   O'hUigin, Colm
   Kidd, Judith
   Kidd, Kenneth
   Khakoo, Salim I.
   Alexander, Graeme
   Goedert, James J.
   Kirk, Gregory D.
   Donfield, Sharyne M.
   Rosen, Hugo R.
   Tobler, Leslie H.
   Busch, Michael P.
   McHutchison, John G.
   Goldstein, David B.
   Carrington, Mary
TI Genetic variation in IL28B and spontaneous clearance of hepatitis C virus
SO NATURE
LA English
DT Article
ID natural-history; infection; alpha-2a; host
AB Hepatitis C virus (HCV) infection is the most common bloodborne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide(1). Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma(2). Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance(3,4). Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-lambda 3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment(5). To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (n = 388) or had persistent infection (n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.
C1 [Martin, Maureen P.; Qi, Ying; O'hUigin, Colm; Carrington, Mary] NCI Frederick, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
   [Thomas, David L.; Thio, Chloe L.] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA.
   [Martin, Maureen P.; Qi, Ying; O'hUigin, Colm; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA.
   [Martin, Maureen P.; Qi, Ying; O'hUigin, Colm; Carrington, Mary] Harvard Univ, Boston, MA 02114 USA.
   [Ge, Dongliang; Goldstein, David B.] Duke Univ, Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC 27708 USA.
   [Kidd, Judith; Kidd, Kenneth] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
   [Alexander, Graeme] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England.
   [Khakoo, Salim I.] Univ London Imperial Coll Sci Technol & Med, Div Med, London W2 1NY, England.
   [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
   [Kirk, Gregory D.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
   [Donfield, Sharyne M.] Rho Inc, Chapel Hill, NC 27517 USA.
   [Rosen, Hugo R.] Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Aurora, CO 80045 USA.
   [Tobler, Leslie H.] Blood Syst Res Inst, San Francisco, CA 94118 USA.
   [Busch, Michael P.] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA.
   [McHutchison, John G.] Duke Univ, Sch Med, Div Gastroenterol, Durham, NC 27705 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Science Applications International Corporation (SAIC); SAIC-Frederick; Johns Hopkins University; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Duke University; Yale University; University of Cambridge; Imperial College London; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Rho; University of Colorado System; University of Colorado Anschutz Medical Campus; Vitalant; Vitalant Research Institute; Duke University; Duke University
RP Carrington, M (corresponding author), NCI Frederick, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM carringm@mail.nih.gov
FU National Cancer Institute; National Institutes of Health [HHSN261200800001E, R01DA013324, R01DA004334, R01HL076902, R01DK60590, R01HD41224]; Wellcome Trust Senior Clinical Fellow; National Cancer Institute [ZIACP010214, ZIABC010791, ZICBC011237] Funding Source: NIH RePORTER
NR 24
TC 1737
Z9 1912
U1 3
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 8
PY 2009
VL 461
IS 7265
BP 798
EP U52
DI 10.1038/nature08463
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500037
PM 19759533
DA 2026-03-09
ER

PT J
AU Lauchle, JO
   Kim, D
   Le, DT
   Akagi, K
   Crone, M
   Krisman, K
   Warner, K
   Bonifas, JM
   Li, Q
   Coakley, KM
   Diaz-Flores, E
   Gorman, M
   Przybranowski, S
   Tran, M
   Kogan, SC
   Roose, JP
   Copeland, NG
   Jenkins, NA
   Parada, L
   Wolff, L
   Sebolt-Leopold, J
   Shannon, K
AF Lauchle, Jennifer O.
   Kim, Doris
   Le, Doan T.
   Akagi, Keiko
   Crone, Michael
   Krisman, Kimberly
   Warner, Kegan
   Bonifas, Jeannette M.
   Li, Qing
   Coakley, Kristen M.
   Diaz-Flores, Ernesto
   Gorman, Matthew
   Przybranowski, Sally
   Tran, Mary
   Kogan, Scott C.
   Roose, Jeroen P.
   Copeland, Neal G.
   Jenkins, Nancy A.
   Parada, Luis
   Wolff, Linda
   Sebolt-Leopold, Judith
   Shannon, Kevin
TI Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras
SO NATURE
LA English
DT Article
ID acute lymphoblastic-leukemia; malignant myeloid disorders; bcr-abl; hematopoietic-cells; kinase inhibitors; tyrosine kinase; blast crisis; bone-marrow; children; pathway
AB The cascade comprising Raf, mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) is a therapeutic target in human cancers with deregulated Ras signalling, which includes tumours that have inactivated the Nf1 tumour suppressor(1,2). Nf1 encodes neurofibromin, a GTPase-activating protein that terminates Ras signalling by stimulating hydrolysis of Ras-GTP. We compared the effects of inhibitors of MEK in a myeloproliferative disorder (MPD) initiated by inactivating Nf1 in mouse bone marrow and in acute myeloid leukaemias (AMLs) in which cooperating mutations were induced by retroviral insertional mutagenesis. Here we show that MEK inhibitors are ineffective in MPD, but induce objective regression of many Nf1-deficient AMLs. Drug resistance developed because of outgrowth of AML clones that were present before treatment. We cloned clone-specific retroviral integrations to identify candidate resistance genes including Rasgrp1, Rasgrp4 and Mapk14, which encodes p38 alpha. Functional analysis implicated increased RasGRP1 levels and reduced p38 kinase activity in resistance to MEK inhibitors. This approach represents a robust strategy for identifying genes and pathways that modulate how primary cancer cells respond to targeted therapeutics and for probing mechanisms of de novo and acquired resistance.
C1 [Lauchle, Jennifer O.; Kim, Doris; Le, Doan T.; Crone, Michael; Krisman, Kimberly; Warner, Kegan; Bonifas, Jeannette M.; Diaz-Flores, Ernesto; Gorman, Matthew; Tran, Mary; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
   [Li, Qing] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
   [Coakley, Kristen M.; Roose, Jeroen P.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
   [Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
   [Akagi, Keiko] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
   [Przybranowski, Sally; Sebolt-Leopold, Judith] Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA.
   [Copeland, Neal G.; Jenkins, Nancy A.] Inst Mol & Cell Biol, Singapore 138673, Singapore.
   [Parada, Luis] Univ Texas SW, Dallas, TX 75235 USA.
   [Wolff, Linda] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 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; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Pfizer; Pfizer USA; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); University of Texas System; University of Texas Southwestern Medical Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Shannon, K (corresponding author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
EM shannonk@peds.ucsf.edu
FU National Institutes of Health [U01 CA84221, R37 CA72614, T32 CA09043, T32 HD044331, K08 CA119105]; Leukemia and Lymphoma Society [LLS 7019-04]; US Army Neurofibromatosis Research Program [DAMD 17-02-1-0638]; Ronald McDonald House Charities of Southern California/Couples Against Leukemia; Jeffrey and Karen Peterson Family Foundation; Frank A. Campini Foundation; National Cancer Institute [T32CA128583] Funding Source: NIH RePORTER
NR 25
TC 118
Z9 130
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 SEP 17
PY 2009
VL 461
IS 7262
BP 411
EP U110
DI 10.1038/nature08279
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100043
PM 19727076
DA 2026-03-09
ER

PT J
AU Hauser, MD
AF Hauser, Marc D.
TI The possibility of impossible cultures
SO NATURE
LA English
DT Article
ID grammar; evolution; linguistics; language
C1 [Hauser, Marc D.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
   [Hauser, Marc D.] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
   [Hauser, Marc D.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Harvard University
RP Hauser, MD (corresponding author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA.
EM mdh102559@gmail.com
FU US National Science Foundation
NR 80
TC 49
Z9 55
U1 1
U2 32
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 190
EP 196
DI 10.1038/460190a
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000028
PM 19587759
DA 2026-03-09
ER

PT J
AU Mukhtasimova, N
   Lee, WY
   Wang, HL
   Sine, SM
AF Mukhtasimova, Nuriya
   Lee, Won Yong
   Wang, Hai-Long
   Sine, Steven M.
TI Detection and trapping of intermediate states priming nicotinic receptor channel opening
SO NATURE
LA English
DT Article
ID single-channel; agonist binding; acetylcholine-receptors; bc3h-1 cells; ion channels; end-plate; activation; kinetics; mutation; subunit
AB In the course of synaptic transmission in the brain and periphery, acetylcholine receptors (AChRs) rapidly transduce a chemical signal into an electrical impulse. The speed of transduction is facilitated by rapid ACh association and dissociation, suggesting a binding site relatively non-selective for small cations. Selective transduction has been thought to originate from the ability of ACh, over that of other organic cations, to trigger the subsequent channel-opening step. However, transitions to and from the open state were shown to be similar for agonists with widely different efficacies(1-3). By studying mutant AChRs, we show here that the ultimate closed-to-open transition is agonist-independent and preceded by two primed closed states; the first primed state elicits brief openings, whereas the second elicits long-lived openings. Long-lived openings and the associated primed state are detected in the absence and presence of an agonist, and exhibit the same kinetic signatures under both conditions. By covalently locking the agonist-binding sites in the bound conformation, we find that each site initiates a priming step. Thus, a change in binding-site conformation primes the AChR for channel opening in a process that enables selective activation by ACh while maximizing the speed and efficiency of the biological response.
C1 [Mukhtasimova, Nuriya; Lee, Won Yong; Wang, Hai-Long; Sine, Steven M.] Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Receptor Biol Lab, Rochester, MN 55905 USA.
   [Sine, Steven M.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN 55905 USA.
C3 Mayo Clinic; Mayo Clinic
RP Sine, SM (corresponding author), Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Receptor Biol Lab, Rochester, MN 55905 USA.
EM sine@mayo.edu
FU National Institutes of Health [NS031744]; National Institute of Neurological Disorders and Stroke [R01NS031744] Funding Source: NIH RePORTER
NR 25
TC 186
Z9 206
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 MAY 21
PY 2009
VL 459
IS 7245
BP 451
EP U172
DI 10.1038/nature07923
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700051
PM 19339970
DA 2026-03-09
ER

PT J
AU Abbott, BP
   Abbott, R
   Acernese, F
   Adhikari, R
   Ajith, P
   Allen, B
   Allen, G
   Alshourbagy, M
   Amin, RS
   Anderson, SB
   Anderson, WG
   Antonucci, F
   Aoudia, S
   Arain, MA
   Araya, M
   Armandula, H
   Armor, P
   Arun, KG
   Aso, Y
   Aston, S
   Astone, P
   Aufmuth, P
   Aulbert, C
   Babak, S
   Baker, P
   Ballardin, G
   Ballmer, S
   Barker, C
   Barker, D
   Barone, F
   Barr, B
   Barriga, P
   Barsotti, L
   Barsuglia, M
   Barton, MA
   Bartos, I
   Bassiri, R
   Bastarrika, M
   Bauer, TS
   Behnke, B
   Beker, M
   Benacquista, M
   Betzwieser, J
   Beyersdorf, PT
   Bigotta, S
   Bilenko, IA
   Billingsley, G
   Birindelli, S
   Biswas, R
   Bizouard, MA
   Black, E
   Blackburn, JK
   Blackburn, L
   Blair, D
   Bland, B
   Boccara, C
   Bodiya, TP
   Bogue, L
   Bondu, F
   Bonelli, L
   Bork, R
   Boschi, V
   Bose, S
   Bosi, L
   Braccini, S
   Bradaschia, C
   Brady, PR
   Braginsky, VB
   van den Brand, JFJ
   Brau, JE
   Bridges, DO
   Brillet, A
   Brinkmann, M
   Brisson, V
   Van Den Broeck, C
   Brooks, AF
   Brown, DA
   Brummit, A
   Brunet, G
   Bullington, A
   Bulten, HJ
   Buonanno, A
   Burmeister, O
   Buskulic, D
   Byer, RL
   Cadonati, L
   Cagnoli, G
   Calloni, E
   Camp, JB
   Campagna, E
   Cannizzo, J
   Cannon, KC
   Canuel, B
   Cao, J
   Carbognani, F
   Cardenas, L
   Caride, S
   Castaldi, G
   Caudill, S
   Cavaglià, M
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   Cavalieri, R
   Cella, G
   Cepeda, C
   Cesarini, E
   Chalermsongsak, T
   Chalkley, E
   Charlton, P
   Chassande-Mottin, E
   Chatterji, S
   Chelkowski, S
   Chen, Y
   Christensen, N
   Chung, CTY
   Clark, D
   Clark, J
   Clayton, JH
   Cleva, F
   Coccia, E
   Cokelaer, T
   Colacino, CN
   Colas, J
   Colla, A
   Colombini, M
   Conte, R
   Cook, D
   Corbitt, TRC
   Corda, C
   Cornish, N
   Corsi, A
   Coulon, JP
   Coward, D
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   Creighton, JDE
   Creighton, TD
   Cruise, AM
   Culter, RM
   Cumming, A
   Cunningham, L
   Cuoco, E
   Danilishin, SL
   D'Antonio, S
   Danzmann, K
   Dari, A
   Dattilo, V
   Daudert, B
   Davier, M
   Davies, G
   Daw, EJ
   Day, R
   De Rosa, R
   Debra, D
   Degallaix, J
   del Prete, M
   Dergachev, V
   Desai, S
   DeSalvo, R
   Dhurandhar, S
   Di Fiore, L
   Di Lieto, A
   Emilio, MD
   Di Virgilio, A
   Díaz, M
   Dietz, A
   Donovan, F
   Dooley, KL
   Doomes, EE
   Drago, M
   Drever, RWP
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   Edgar, M
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   Espinoza, E
   Etzel, T
   Evans, T
   Fafone, V
   Fairhurst, S
   Faltas, Y
   Fan, Y
   Fazi, D
   Fehrmann, H
   Ferrante, I
   Fidecaro, F
   Finn, LS
   Fiori, I
   Flaminio, R
   Flasch, K
   Foley, S
   Forrest, C
   Fotopoulos, N
   Fournier, JD
   Franc, J
   Franzen, A
   Frasca, S
   Frasconi, F
   Frede, M
   Frei, M
   Frei, Z
   Freise, A
   Frey, R
   Fricke, T
   Fritschel, P
   Frolov, VV
   Fyffe, M
   Galdi, V
   Gammaitoni, L
   Garofoli, JA
   Garufi, F
   Genin, E
   Gennai, A
   Gholami, I
   Giaime, JA
   Giampanis, S
   Giardina, KD
   Giazotto, A
   Goda, K
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   Gosser, S
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   Gretarsson, AM
   Greverie, C
   Grimaldi, F
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   Grunewald, S
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   Guidi, G
   Gustafson, EK
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   Hallam, JM
   Hammer, D
   Hammond, GD
   Hanna, C
   Hanson, J
   Harms, J
   Harry, GM
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   Harstad, ED
   Haughian, K
   Hayama, K
   Heefner, J
   Heitmann, H
   Hello, P
   Heng, IS
   Heptonstall, A
   Hewitson, M
   Hild, S
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   Hoak, D
   Hodge, KA
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AF Abbott, B. P.
   Abbott, R.
   Acernese, F.
   Adhikari, R.
   Ajith, P.
   Allen, B.
   Allen, G.
   Alshourbagy, M.
   Amin, R. S.
   Anderson, S. B.
   Anderson, W. G.
   Antonucci, F.
   Aoudia, S.
   Arain, M. A.
   Araya, M.
   Armandula, H.
   Armor, P.
   Arun, K. G.
   Aso, Y.
   Aston, S.
   Astone, P.
   Aufmuth, P.
   Aulbert, C.
   Babak, S.
   Baker, P.
   Ballardin, G.
   Ballmer, S.
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   Barker, D.
   Barone, F.
   Barr, B.
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   Barsotti, L.
   Barsuglia, M.
   Barton, M. A.
   Bartos, I.
   Bassiri, R.
   Bastarrika, M.
   Bauer, Th. S.
   Behnke, B.
   Beker, M.
   Benacquista, M.
   Betzwieser, J.
   Beyersdorf, P. T.
   Bigotta, S.
   Bilenko, I. A.
   Billingsley, G.
   Birindelli, S.
   Biswas, R.
   Bizouard, M. A.
   Black, E.
   Blackburn, J. K.
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   Blair, D.
   Bland, B.
   Boccara, C.
   Bodiya, T. P.
   Bogue, L.
   Bondu, F.
   Bonelli, L.
   Bork, R.
   Boschi, V.
   Bose, S.
   Bosi, L.
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   Bradaschia, C.
   Brady, P. R.
   Braginsky, V. B.
   van den Brand, J. F. J.
   Brau, J. E.
   Bridges, D. O.
   Brillet, A.
   Brinkmann, M.
   Brisson, V.
   Van Den Broeck, C.
   Brooks, A. F.
   Brown, D. A.
   Brummit, A.
   Brunet, G.
   Bullington, A.
   Bulten, H. J.
   Buonanno, A.
   Burmeister, O.
   Buskulic, D.
   Byer, R. L.
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   Cagnoli, G.
   Calloni, E.
   Camp, J. B.
   Campagna, E.
   Cannizzo, J.
   Cannon, K. C.
   Canuel, B.
   Cao, J.
   Carbognani, F.
   Cardenas, L.
   Caride, S.
   Castaldi, G.
   Caudill, S.
   Cavaglia, M.
   Cavalier, F.
   Cavalieri, R.
   Cella, G.
   Cepeda, C.
   Cesarini, E.
   Chalermsongsak, T.
   Chalkley, E.
   Charlton, P.
   Chassande-Mottin, E.
   Chatterji, S.
   Chelkowski, S.
   Chen, Y.
   Christensen, N.
   Chung, C. T. Y.
   Clark, D.
   Clark, J.
   Clayton, J. H.
   Cleva, F.
   Coccia, E.
   Cokelaer, T.
   Colacino, C. N.
   Colas, J.
   Colla, A.
   Colombini, M.
   Conte, R.
   Cook, D.
   Corbitt, T. R. C.
   Corda, C.
   Cornish, N.
   Corsi, A.
   Coulon, J. -P.
   Coward, D.
   Coyne, D. C.
   Creighton, J. D. E.
   Creighton, T. D.
   Cruise, A. M.
   Culter, R. M.
   Cumming, A.
   Cunningham, L.
   Cuoco, E.
   Danilishin, S. L.
   D'Antonio, S.
   Danzmann, K.
   Dari, A.
   Dattilo, V.
   Daudert, B.
   Davier, M.
   Davies, G.
   Daw, E. J.
   Day, R.
   De Rosa, R.
   Debra, D.
   Degallaix, J.
   del Prete, M.
   Dergachev, V.
   Desai, S.
   DeSalvo, R.
   Dhurandhar, S.
   Di Fiore, L.
   Di Lieto, A.
   Emilio, M. Di Paolo
   Di Virgilio, A.
   Diaz, M.
   Dietz, A.
   Donovan, F.
   Dooley, K. L.
   Doomes, E. E.
   Drago, M.
   Drever, R. W. P.
   Dueck, J.
   Duke, I.
   Dumas, J. -C.
   Dwyer, J. G.
   Echols, C.
   Edgar, M.
   Effler, A.
   Ehrens, P.
   Ely, G.
   Espinoza, E.
   Etzel, T.
   Evans, T.
   Fafone, V.
   Fairhurst, S.
   Faltas, Y.
   Fan, Y.
   Fazi, D.
   Fehrmann, H.
   Ferrante, I.
   Fidecaro, F.
   Finn, L. S.
   Fiori, I.
   Flaminio, R.
   Flasch, K.
   Foley, S.
   Forrest, C.
   Fotopoulos, N.
   Fournier, J. -D.
   Franc, J.
   Franzen, A.
   Frasca, S.
   Frasconi, F.
   Frede, M.
   Frei, M.
   Frei, Z.
   Freise, A.
   Frey, R.
   Fricke, T.
   Fritschel, P.
   Frolov, V. V.
   Fyffe, M.
   Galdi, V.
   Gammaitoni, L.
   Garofoli, J. A.
   Garufi, F.
   Genin, E.
   Gennai, A.
   Gholami, I.
   Giaime, J. A.
   Giampanis, S.
   Giardina, K. D.
   Giazotto, A.
   Goda, K.
   Goetz, E.
   Goggin, L. M.
   Gonzalez, G.
   Gorodetsky, M. L.
   Gosser, S.
   Gouaty, R.
   Granata, M.
   Granata, V.
   Grant, A.
   Gras, S.
   Gray, C.
   Gray, M.
   Greenhalgh, R. J. S.
   Gretarsson, A. M.
   Greverie, C.
   Grimaldi, F.
   Grosso, R.
   Grote, H.
   Grunewald, S.
   Guenther, M.
   Guidi, G.
   Gustafson, E. K.
   Gustafson, R.
   Hage, B.
   Hallam, J. M.
   Hammer, D.
   Hammond, G. D.
   Hanna, C.
   Hanson, J.
   Harms, J.
   Harry, G. M.
   Harry, I. W.
   Harstad, E. D.
   Haughian, K.
   Hayama, K.
   Heefner, J.
   Heitmann, H.
   Hello, P.
   Heng, I. S.
   Heptonstall, A.
   Hewitson, M.
   Hild, S.
   Hirose, E.
   Hoak, D.
   Hodge, K. A.
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TI An upper limit on the stochastic gravitational-wave background of cosmological origin
SO NATURE
LA English
DT Article
ID spectrum
AB A stochastic background of gravitational waves is expected to arise from a superposition of a large number of unresolved gravitational-wave sources of astrophysical and cosmological origin. It should carry unique signatures from the earliest epochs in the evolution of the Universe, inaccessible to standard astrophysical observations(1). Direct measurements of the amplitude of this background are therefore of fundamental importance for understanding the evolution of the Universe when it was younger than one minute. Here we report limits on the amplitude of the stochastic gravitational-wave background using the data from a two-year science run of the Laser Interferometer Gravitational-wave Observatory(2) (LIGO). Our result constrains the energy density of the stochastic gravitational-wave background normalized by the critical energy density of the Universe, in the frequency band around 100 Hz, to be <6.9 X 10(-6) at 95% confidence. The data rule out models of early Universe evolution with relatively large equation-of-state parameter(3), as well as cosmic (super) string models with relatively small string tension(4) that are favoured in some string theory models(5). This search for the stochastic background improves on the indirect limits from Big Bang nucleosynthesis(1,6) and cosmic microwave background(7) at 100Hz.
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   [Buskulic, D.; Granata, V.; Letendre, N.; Marion, F.; Masserot, A.; Mours, B.; Rolland, L.; Tournefier, E.; Trummer, J.; Verkindt, D.; Yvert, M.] Univ Savoie, CNRS, IN2P3, LAPP, F-74941 Annecy Le Vieux, France.
   [Cadonati, L.; Mohapatra, S. R. P.] Univ Massachusetts, Amherst, MA 01003 USA.
   [Cagnoli, G.; Campagna, E.; Cesarini, E.; Guidi, G.; Lorenzini, M.; Losurdo, G.; Martelli, F.; Piergiovanni, F.; Sturani, R.; Terenzi, R.; Vetrano, F.; Vicere, A.] Ist Nazl Fis Nucl, Sez Firenze, I-50019 Sesto Fiorentino, Italy.
   Univ Florence, I-50121 Florence, Italy.
   [Campagna, E.; Cesarini, E.; Guidi, G.; Martelli, F.; Piergiovanni, F.; Sturani, R.; Terenzi, R.; Vetrano, F.; Vicere, A.] Univ Urbino Carlo Bo, I-61029 Urbino, Italy.
   [Camp, J. B.; Cannizzo, J.; Numata, K.; Stroeer, A.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Caride, S.; Dergachev, V.; Goetz, E.; Gustafson, R.; Riles, K.; Zhang, J.] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Castaldi, G.; Galdi, V.; Longo, M.; Pierro, V.; Pinto, I. M.; Principe, M.] Univ Sannio Benevento, I-82100 Benevento, Italy.
   [Cavaglia, M.] Univ Mississippi, University, MS 38677 USA.
   [Charlton, P.] Charles Sturt Univ, Wagga Wagga, NSW 2678, Australia.
   [Chen, Y.; Li, C.; Mino, Y.; Savov, P.; Somiya, K.; Thorne, K. S.; Vallisneri, M.; Wen, L.] CALTECH CaRT, Pasadena, CA 91125 USA.
   [Christensen, N.; Ely, G.; Isogai, T.] Carleton Coll, Northfield, MN 55057 USA.
   [Chung, C. T. Y.; Melatos, A.] Univ Melbourne, Parkville, Vic 3010, Australia.
   [Coccia, E.; D'Antonio, S.; Emilio, M. Di Paolo; Minenkov, Y.; Morgia, A.; Pagliaroli, G.; Rocchi, A.; Terenzi, R.] Ist Nazl Fis Nucl, Sez Roma Tor Vergata, I-00133 Rome, Italy.
   [Coccia, E.; Morgia, A.; Pagliaroli, G.] Univ Roma Tor Vergata, I-00133 Rome, Italy.
   [Terenzi, R.] IFSI, I-00133 Rome, Italy.
   [Emilio, M. Di Paolo] Univ Aquila, I-67100 Laquila, Italy.
   [Colacino, C. N.; Frei, Z.; Raffai, P.; Szokoly, G. P.] Eotvos Lorand Univ, ELTE, H-1053 Budapest, Hungary.
   [Conte, R.; Postiglione, F.] Univ Salerno, I-84084 Salerno, Italy.
   [Daw, E. J.] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England.
   [Desai, S.; Finn, L. S.; Kopparapu, R.; Menendez, D. F.; Minelli, J.; O'Shaughnessy, R.; Owen, B. J.; Williams, H. R.] Penn State Univ, University Pk, PA 16802 USA.
   [Dhurandhar, S.; Mukhopadhyay, H.] Inter Univ Ctr Astron & Astrophys, Pune 411007, Maharashtra, India.
   [Doomes, E. E.; McGuire, S. C.] Southern Univ, Baton Rouge, LA 70813 USA.
   [Doomes, E. E.; McGuire, S. C.] A&M Coll, Baton Rouge, LA 70813 USA.
   [Prodi, G. A.; Re, V.; Salemi, F.] Ist Nazl Fis Nucl, Grp Coll Trento, I-38050 Trento, Italy.
   [Prodi, G. A.; Re, V.; Salemi, F.] Univ Trent, I-38050 Trento, Italy.
   [Drago, M.; Vedovato, G.] Ist Nazl Fis Nucl, Sez Padova, I-35131 Padua, Italy.
   [Drago, M.] Univ Padua, I-35131 Padua, Italy.
   [Flaminio, R.; Franc, J.; Mackowski, J. -M.; Michel, C.; Morgado, N.; Pinard, L.; Sassolas, B.] CNRS, IN2P3, LMA, F-69622 Villeurbanne, France.
   [Forrest, C.; Melissinos, A. C.] Univ Rochester, Rochester, NY 14627 USA.
   [Frei, M.; Matzner, R. A.] Univ Texas Austin, Austin, TX 78712 USA.
   [Gray, M.; Lam, P. K.; McClelland, D. E.; McKenzie, K.; MowLowry, C.; Mullavey, A.; Satterthwaite, M.; Scott, S. M.; Slagmolen, B. J. J.; Wette, K.] Australian Natl Univ, Canberra, ACT 0200, Australia.
   [Gretarsson, A. M.; Zanolin, M.] Embry Riddle Aeronaut Univ, Prescott, AZ 86301 USA.
   [Hosken, D. J.; Munch, J.; Ottaway, D. J.; Veitch, P.] Univ Adelaide, Adelaide, SA 5005, Australia.
   [Jones, D. I.] Univ Southampton, Southampton SO17 1BJ, Hants, England.
   [Sancho de la Jordana, L.; Sintes, A. M.; Trias, M.] Univ Illes Balears, Dept Fis, E-07122 Palma de Mallorca, Spain.
   [Kalogera, V.; Mandel, I.; Raymond, V.; van der Sluys, M. V.] Northwestern Univ, Evanston, IL 60208 USA.
   [Kawamura, S.; Kokeyama, K.; Morioka, T.; Nishizawa, A.; Sakata, S.; Sato, S.] Natl Astron Observ Japan, Tokyo 1818588, Japan.
   [Khazanov, E.; Sergeev, A.] Inst Appl Phys, Nizhnii Novgorod 603950, Russia.
   [Lockerbie, N. A.] Univ Strathclyde, Glasgow G1 1XQ, Lanark, Scotland.
   [McHugh, M.] Tulane Univ, New Orleans, LA 70118 USA.
   [Penn, S.] Hobart & William Smith Coll, Geneva, NY 14456 USA.
   [Reed, T.; Scanlan, M.; Zotov, N.] Louisiana Tech Univ, Ruston, LA 71272 USA.
   [Roberts, P.; Summerscales, T. Z.] Andrews Univ, Berrien Springs, MI 49104 USA.
   [Saraf, S.] Sonoma State Univ, Rohnert Pk, CA 94928 USA.
   [Ugolini, D.] Trinity Univ, San Antonio, TX 78712 USA.
   [Whelan, J. T.] Rochester Inst Technol, Rochester, NY 14623 USA.
   [Yoshida, S.] SE Louisiana Univ, Hammond, LA 70402 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; California Institute of Technology; Istituto Nazionale di Fisica Nucleare (INFN); University of Naples Federico II; University of Salerno; Max Planck Society; University of Wisconsin System; University of Wisconsin Milwaukee; Stanford University; Louisiana State University System; Louisiana State University; State University System of Florida; University of Florida; Universite Cote d'Azur; Observatoire de la Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); University of Birmingham; Leibniz University Hannover; Max Planck Society; Montana State University System; Montana State University Bozeman; University of Glasgow; University of Western Australia; Massachusetts Institute of Technology (MIT); Universite PSL; Observatoire de Paris; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Istituto Nazionale di Fisica Nucleare (INFN); University of Pisa; University of Siena; Istituto Nazionale di Fisica Nucleare (INFN); Sapienza University Rome; Columbia University; FOM National Institute for Subatomic Physics; Vrije Universiteit Amsterdam; University of Texas System; University of Texas Rio Grande Valley; California State University System; San Jose State University; Lomonosov Moscow State University; Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Centre National de la Recherche Scientifique (CNRS); Washington State University; Istituto Nazionale di Fisica Nucleare (INFN); University of Perugia; University of Camerino; University of Oregon; Cardiff University; Syracuse University; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; University System of Maryland; University of Maryland College Park; Centre National de la Recherche Scientifique (CNRS); Universite Savoie Mont Blanc; CNRS - National Institute of Nuclear and Particle Physics (IN2P3); University of Massachusetts System; University of Massachusetts Amherst; Istituto Nazionale di Fisica Nucleare (INFN); University of Florence; University of Urbino; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Michigan System; University of Michigan; University of Sannio; University of Mississippi; Charles Sturt University; California Institute of Technology; Carleton College; University of Melbourne; Istituto Nazionale di Fisica Nucleare (INFN); University of Rome Tor Vergata; Istituto Nazionale Astrofisica (INAF); University of L'Aquila; Eotvos Lorand University; University of Salerno; University of Sheffield; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Inter-University Centre for Astronomy & Astrophysics; Southern University System; Southern University & A&M College; Louisiana State University System; Louisiana State University; Istituto Nazionale di Fisica Nucleare (INFN); University of Trento; Istituto Nazionale di Fisica Nucleare (INFN); University of Padua; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); University of Rochester; University of Texas System; University of Texas Austin; Australian National University; Embry-Riddle Aeronautical University; Adelaide University; University of Adelaide; University of Southampton; Universitat de les Illes Balears; Northwestern University; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); Institute of Applied Physics of the Russian Academy of Sciences; University of Strathclyde; Tulane University; Hobart & William Smith Colleges; University of Louisiana System; Louisiana Technical University; Andrews University; California State University System; Sonoma State University; Trinity University; Rochester Institute of Technology; University of Louisiana System; Southeastern Louisiana University
RP Mandic, V (corresponding author), Univ Minnesota, Minneapolis, MN 55455 USA.
EM mandic@physics.umn.edu
FU United States National Science Foundation; Science and Technology Facilities Council of the United Kingdom; Max Planck Society; State of Niedersachsen/Germany [GEO600]; Italian Istituto Nazionale di Fisica Nucleare; French Centre National de la Recherche Scientifique; Australian Research Council; Council of Scientific and Industrial Research of India; Istituto Nazionale di Fisica Nucleare of Italy; Spanish Ministerio de Educacion y Ciencia; Conselleria d'Economia Hisenda i Innovacio of the Govern de les Illes Balears; Royal Society; Scottish Funding Council; Scottish Universities Physics Alliance; The National Aeronautics and Space Administration; Carnegie Trust; Leverhulme Trust; David and Lucile Packard Foundation; Research Corporation; Alfred P. Sloan Foundation; Science and Technology Facilities Council [PP/F001096/1, ST/F01032X/1, PP/F00110X/1, ST/G504284/1, PP/E001203/1, PP/F001118/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Physics [0758036, 0854812, 0855313, 0855679] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [0757058] Funding Source: National Science Foundation; STFC [PP/F001118/1, PP/F001096/1, PP/E001203/1, PP/F00110X/1, ST/F01032X/1, ST/G504284/1] Funding Source: UKRI
NR 30
TC 299
Z9 337
U1 0
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 990
EP 994
DI 10.1038/nature08278
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500029
PM 19693079
DA 2026-03-09
ER

PT J
AU Munday, JN
   Capasso, F
   Parsegian, VA
AF Munday, J. N.
   Capasso, Federico
   Parsegian, V. Adrian
TI Measured long-range repulsive Casimir-Lifshitz forces
SO NATURE
LA English
DT Article
ID der-waals forces; mu-m; attraction; physics; solids; silica
AB Quantum fluctuations create intermolecular forces that pervade macroscopic bodies(1-3). At molecular separations of a few nanometres or less, these interactions are the familiar van der Waals forces(4). However, as recognized in the theories of Casimir, Polder and Lifshitz(5-7), at larger distances and between macroscopic condensed media they reveal retardation effects associated with the finite speed of light. Although these long- range forces exist within all matter, only attractive interactions have so far been measured between material bodies(8-11). Here we show experimentally that, in accord with theoretical prediction(12), the sign of the force can be changed from attractive to repulsive by suitable choice of interacting materials immersed in a fluid. The measured repulsive interaction is found to be weaker than the attractive. However, in both cases the magnitude of the force increases with decreasing surface separation. Repulsive Casimir - Lifshitz forces could allow quantum levitation of objects in a fluid and lead to a new class of switchable nanoscale devices with ultra-low static friction(13-15).
C1 [Capasso, Federico] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Munday, J. N.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Parsegian, V. Adrian] NIH, Bethesda, MD 20892 USA.
C3 Harvard University; Harvard University; National Institutes of Health (NIH) - USA
RP Capasso, F (corresponding author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM capasso@seas.harvard.edu
FU Center for Nanoscale Systems at Harvard University; Intramural Research Program of the NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NSF
NR 30
TC 564
Z9 640
U1 4
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 8
PY 2009
VL 457
IS 7226
BP 170
EP 173
DI 10.1038/nature07610
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200027
PM 19129843
DA 2026-03-09
ER

PT J
AU Love, GD
   Grosjean, E
   Stalvies, C
   Fike, DA
   Grotzinger, JP
   Bradley, AS
   Kelly, AE
   Bhatia, M
   Meredith, W
   Snape, CE
   Bowring, SA
   Condon, DJ
   Summons, RE
AF Love, Gordon D.
   Grosjean, Emmanuelle
   Stalvies, Charlotte
   Fike, David A.
   Grotzinger, John P.
   Bradley, Alexander S.
   Kelly, Amy E.
   Bhatia, Maya
   Meredith, William
   Snape, Colin E.
   Bowring, Samuel A.
   Condon, Daniel J.
   Summons, Roger E.
TI Fossil steroids record the appearance of Demospongiae during the Cryogenian period
SO NATURE
LA English
DT Article
ID biomarkers; sponges; marine; origin; classification; bilaterians; oxidation; embryos; oils
AB The Neoproterozoic era ( 1,000 - 542 Myr ago) was an era of climatic extremes and biological evolutionary developments culminating in the emergence of animals ( Metazoa) and new ecosystems(1). Here we show that abundant sedimentary 24- isopropylcholestanes, the hydrocarbon remains of C-30 sterols produced by marine demosponges, record the presence of Metazoa in the geological record before the end of the Marinoan glaciation ( similar to 635 Myr ago). These sterane biomarkers are abundant in all formations of the Huqf Supergroup, South Oman Salt Basin, and, based on a new high-precision geochronology(2), constitute a continuous 100- Myr- long chemical fossil record of demosponges through the terminal Neoproterozoic and into the Early Cambrian epoch. The demosponge steranes occur in strata that underlie the Marinoan cap carbonate ( > 635 Myr ago). They currently represent the oldest evidence for animals in the fossil record, and are evidence for animals pre- dating the termination of the Marinoan glaciation. This suggests that shallow shelf waters in some late Cryogenian ocean basins (> 635 Myr ago) contained dissolved oxygen in concentrations sufficient to support basal metazoan life at least 100 Myr before the rapid diversification of bilaterians during the Cambrian explosion. Biomarker analysis has yet to reveal any convincing evidence for ancient sponges pre- dating the first globally extensive Neoproterozoic glacial episode ( the Sturtian, similar to 713 Myr ago in Oman(2)).
C1 [Love, Gordon D.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Love, Gordon D.; Bradley, Alexander S.; Kelly, Amy E.; Bhatia, Maya; Bowring, Samuel A.; Condon, Daniel J.; Summons, Roger E.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 01239 USA.
   [Grosjean, Emmanuelle] Geosci Australia, Petr & Marine Div, Canberra, ACT 2601, Australia.
   [Stalvies, Charlotte] Newcastle Univ, Sch Civil Engn & Geosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Fike, David A.; Grotzinger, John P.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Meredith, William; Snape, Colin E.] Univ Nottingham, Sch Chem Environm & Min Engn, Nottingham NG7 2RD, England.
C3 University of California System; University of California Riverside; Massachusetts Institute of Technology (MIT); Geoscience Australia; Newcastle University - UK; California Institute of Technology; University of Nottingham
RP Love, GD (corresponding author), Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
EM glove@ucr.edu
FU Petroleum Development Oman (PDO); NASA Exobiology Program; NSF EAR Program; Agouron Institute; NASA Astrobiology Institute; NERC [bgs04003] Funding Source: UKRI; Natural Environment Research Council [bgs04003, NE/C517909/1] Funding Source: researchfish
NR 30
TC 560
Z9 666
U1 0
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 FEB 5
PY 2009
VL 457
IS 7230
BP 718
EP U5
DI 10.1038/nature07673
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700040
PM 19194449
DA 2026-03-09
ER

PT J
AU Nolen, BJ
   Tomasevic, N
   Russell, A
   Pierce, DW
   Jia, Z
   McCormick, CD
   Hartman, J
   Sakowicz, R
   Pollard, TD
AF Nolen, B. J.
   Tomasevic, N.
   Russell, A.
   Pierce, D. W.
   Jia, Z.
   McCormick, C. D.
   Hartman, J.
   Sakowicz, R.
   Pollard, T. D.
TI Characterization of two classes of small molecule inhibitors of Arp2/3 complex
SO NATURE
LA English
DT Article
ID actin-filament; protein; crystallography; polymerization; association; nucleation; wasp; adp; atp
AB Polymerization of actin filaments directed by the actin-related protein (Arp)2/3 complex supports many types of cellular movements(1). However, questions remain regarding the relative contributions of Arp2/3 complex versus other mechanisms of actin filament nucleation to processes such as path finding by neuronal growth cones; this is because of the lack of simple methods to inhibit Arp2/3 complex reversibly in living cells. Here we describe two classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes. Two inhibitors with different mechanisms of action provide a powerful approach for studying the Arp2/3 complex in living cells.
C1 [Nolen, B. J.; Pollard, T. D.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Nolen, B. J.; Pollard, T. D.] Yale Univ, Dept Cell Biol, New Haven, CT 06520 USA.
   [Nolen, B. J.; McCormick, C. D.; Pollard, T. D.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Tomasevic, N.; Russell, A.; Pierce, D. W.; Jia, Z.; Hartman, J.; Sakowicz, R.] Cytokinetics Inc, San Francisco, CA 94080 USA.
C3 Yale University; Yale University; Yale University; Cytokinetics, Inc.
RP Pollard, TD (corresponding author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
EM thomas.pollard@yale.edu
FU Cytokinetics, Inc.; NIH [GM-066311]; NSF; Ruth Kirschstein postdoctoral fellowship [GM074374-02]
NR 24
TC 424
Z9 507
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 AUG 20
PY 2009
VL 460
IS 7258
BP 1031
EP U121
DI 10.1038/nature08231
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500038
PM 19648907
DA 2026-03-09
ER

PT J
AU Carrano, AC
   Liu, Z
   Dillin, A
   Hunter, T
AF Carrano, Andrea C.
   Liu, Zheng
   Dillin, Andrew
   Hunter, Tony
TI A conserved ubiquitination pathway determines longevity in response to diet restriction
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; c-elegans; life-span; pharyngeal development; transcription factor; genetics; daf-16; ligase; insulin/igf-1; degradation
AB Dietary restriction extends longevity in diverse species, suggesting that there is a conserved mechanism for nutrient regulation and prosurvival responses(1). Here we show a role for the HECT (homologous to E6AP carboxy terminus) E3 ubiquitin ligase WWP-1 as a positive regulator of lifespan in Caenorhabditis elegans in response to dietary restriction. We find that overexpression of wwp-1 in worms extends lifespan by up to 20% under conditions of ad libitum feeding. This extension is dependent on the FOXA transcription factor pha-4, and independent of the FOXO transcription factor daf-16. Reduction of wwp-1 completely suppresses the extended longevity of diet-restricted animals. However, the loss of wwp-1 does not affect the long lifespan of animals with compromised mitochondrial function or reduced insulin/IGF-1 signalling. Overexpression of a mutant form of WWP-1 lacking catalytic activity suppresses the increased lifespan of diet-restricted animals, indicating that WWP-1 ubiquitin ligase activity is essential for longevity. Furthermore, we find that the E2 ubiquitin conjugating enzyme, UBC-18, is essential and specific for diet-restriction-induced longevity. UBC-18 interacts with WWP-1 and is required for the ubiquitin ligase activity of WWP-1 and the extended longevity of worms overexpressing wwp-1. Taken together, our results indicate that WWP-1 and UBC-18 function to ubiquitinate substrates that regulate diet-restriction-induced longevity.
C1 [Carrano, Andrea C.; Liu, Zheng; Dillin, Andrew; Hunter, Tony] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
   [Liu, Zheng; Dillin, Andrew] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Liu, Zheng; Dillin, Andrew] Glenn Ctr Aging Res, La Jolla, CA 92037 USA.
C3 Salk Institute; Howard Hughes Medical Institute; Salk Institute
RP Dillin, A (corresponding author), Salk Inst Biol Studies, Mol & Cell Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM Dillin@salk.edu
FU National Institutes of Health (NIH) National Center for Research Resources (NCRR); National Cancer Institute [CA 14195, CA 54418, CA 82683]; National Institute of Diabetes and Digestive and Kidney Diseases [DK 070696]; National Institute on Aging [AG 027463, AG 032560]; Ellison Medical and Glenn Medical Foundations; American Cancer Society; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER
NR 38
TC 104
Z9 131
U1 0
U2 46
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 396
EP U113
DI 10.1038/nature08130
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000039
PM 19553937
DA 2026-03-09
ER

PT J
AU Moseley, JB
   Mayeux, A
   Paoletti, A
   Nurse, P
AF Moseley, James B.
   Mayeux, Adeline
   Paoletti, Anne
   Nurse, Paul
TI A spatial gradient coordinates cell size and mitotic entry in fission yeast
SO NATURE
LA English
DT Article
ID protein-kinase; schizosaccharomyces-pombe; contractile ring; genetic-control; division plane; cytokinesis; mitosis; mid1p; inducer; growth
AB Many eukaryotic cell types undergo size-dependent cell cycle transitions controlled by the ubiquitous cyclin-dependent kinase Cdk1 (refs 1-4). The proteins that control Cdk1 activity are well described but their links with mechanisms monitoring cell size remain elusive. In the fission yeast Schizosaccharomyces pombe, cells enter mitosis and divide at a defined and reproducible size owing to the regulated activity of Cdk1 (refs 2, 3). Here we show that the cell polarity protein kinase Pom1, which localizes to cell ends(5), regulates a signalling network that contributes to the control of mitotic entry. This network is located at cortical nodes in the middle of interphase cells, and these nodes contain the Cdk1 inhibitor Wee1, the Wee1-inhibitory kinases Cdr1 (also known as Nim1) and Cdr2, and the anillin-like protein Mid1. Cdr2 establishes the hierarchical localization of other proteins in the nodes, and receives negative regulatory signals from Pom1. Pom1 forms a polar gradient extending from the cell ends towards the cell middle and acts as a dose-dependent inhibitor of mitotic entry, working through the Cdr2 pathway. As cells elongate, Pom1 levels decrease at the cell middle, leading to mitotic entry. We propose that the Pom1 polar gradient and the medial cortical nodes generate information about cell size and coordinate this with mitotic entry by regulating Cdk1 through Pom1, Cdr2, Cdr1 and Wee1.
C1 [Moseley, James B.; Nurse, Paul] Rockefeller Univ, New York, NY 10065 USA.
   [Mayeux, Adeline; Paoletti, Anne] CNRS, UMR144, F-75248 Paris 05, France.
   [Mayeux, Adeline; Paoletti, Anne] Ctr Rech, Inst Curie, F-75248 Paris 05, France.
C3 Rockefeller University; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite PSL; UNICANCER; Institut Curie; Sorbonne Universite; UNICANCER; Universite PSL; Institut Curie
RP Moseley, JB (corresponding author), Rockefeller Univ, New York, NY 10065 USA.
EM jmoseley@rockefeller.edu
FU American Cancer Society [PF-07-129-01-MBC]; ANR [BLAN06-3_135468]; ARC [4934]; FRM [INE20071110973]; Breast Cancer Research Foundation; Rockefeller University
NR 29
TC 286
Z9 360
U1 0
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 857
EP U8
DI 10.1038/nature08074
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500042
PM 19474789
DA 2026-03-09
ER

PT J
AU Zinzen, RP
   Girardot, C
   Gagneur, J
   Braun, M
   Furlong, EEM
AF Zinzen, Robert P.
   Girardot, Charles
   Gagneur, Julien
   Braun, Martina
   Furlong, Eileen E. M.
TI Combinatorial binding predicts spatio-temporal cis-regulatory activity
SO NATURE
LA English
DT Article
ID transcription factor-binding; muscle-cell lineages; genome-wide analysis; mesoderm development; gene mef2; drosophila; integration; elements; tinman; twist
AB Development requires the establishment of precise patterns of gene expression, which are primarily controlled by transcription factors binding to cis-regulatory modules. Although transcription factor occupancy can now be identified at genome-wide scales, decoding this regulatory landscape remains a daunting challenge. Here we used a novel approach to predict spatio-temporal cis-regulatory activity based only on in vivo transcription factor binding and enhancer activity data. We generated a high-resolution atlas of cis-regulatory modules describing their temporal and combinatorial occupancy during Drosophila mesoderm development. The binding profiles of cis-regulatory modules with characterized expression were used to train support vector machines to predict five spatio-temporal expression patterns. In vivo transgenic reporter assays demonstrate the high accuracy of these predictions and reveal an unanticipated plasticity in transcription factor binding leading to similar expression. This data-driven approach does not require previous knowledge of transcription factor sequence affinity, function or expression, making it widely applicable.
C1 [Zinzen, Robert P.; Girardot, Charles; Gagneur, Julien; Braun, Martina; Furlong, Eileen E. M.] European Mol Biol Lab, D-69117 Heidelberg, Germany.
C3 European Molecular Biology Laboratory (EMBL)
RP Furlong, EEM (corresponding author), European Mol Biol Lab, D-69117 Heidelberg, Germany.
EM furlong@embl.de
FU Human Frontiers Science Program
NR 57
TC 318
Z9 387
U1 1
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 5
PY 2009
VL 462
IS 7269
BP 65
EP U72
DI 10.1038/nature08531
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200032
PM 19890324
DA 2026-03-09
ER

PT J
AU Min, W
   Lu, SJ
   Chong, SS
   Roy, R
   Holtom, GR
   Xie, XS
AF Min, Wei
   Lu, Sijia
   Chong, Shasha
   Roy, Rahul
   Holtom, Gary R.
   Xie, X. Sunney
TI Imaging chromophores with undetectable fluorescence by stimulated emission microscopy
SO NATURE
LA English
DT Article
ID raman-scattering microscopy; toluidine blue; spectroscopy; biology; cells
AB Fluorescence, that is, spontaneous emission, is generally more sensitive than absorption measurement, and is widely used in optical imaging(1,2). However, many chromophores, such as haemoglobin and cytochromes, absorb but have undetectable fluorescence because the spontaneous emission is dominated by their fast non-radiative decay(3). Yet the detection of their absorption is difficult under a microscope. Here we use stimulated emission, which competes effectively with the nonradiative decay, to make the chromophores detectable, and report a new contrast mechanism for optical microscopy. In a pump-probe experiment, on photoexcitation by a pump pulse, the sample is stimulated down to the ground state by a time-delayed probe pulse, the intensity of which is concurrently increased. We extract the miniscule intensity increase with shot-noise-limited sensitivity by using a lock-in amplifier and intensity modulation of the pump beam at a high megahertz frequency. The signal is generated only at the laser foci owing to the nonlinear dependence on the input intensities, providing intrinsic three-dimensional optical sectioning capability. In contrast, conventional one-beam absorption measurement exhibits low sensitivity, lack of three-dimensional sectioning capability, and complication by linear scattering of heterogeneous samples. We demonstrate a variety of applications of stimulated emission microscopy, such as visualizing chromoproteins, non-fluorescent variants of the green fluorescent protein, monitoring lacZ gene expression with a chromogenic reporter, mapping transdermal drug distributions without histological sectioning, and label-free microvascular imaging based on endogenous contrast of haemoglobin. For all these applications, sensitivity is orders of magnitude higher than for spontaneous emission or absorption contrast, permitting non-fluorescent reporters for molecular imaging.
C1 [Min, Wei; Lu, Sijia; Chong, Shasha; Roy, Rahul; Holtom, Gary R.; Xie, X. Sunney] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
C3 Harvard University
RP Xie, XS (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
EM xie@chemistry.harvard.edu
FU National Science Foundation [CHE-0634788]; US Department of Energy's Basic Energy Sciences Program [DE-FG02-07ER15875]
NR 29
TC 242
Z9 280
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 OCT 22
PY 2009
VL 461
IS 7267
BP 1105
EP 1109
DI 10.1038/nature08438
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600040
PM 19847261
DA 2026-03-09
ER

PT J
AU Gu, YY
   Harley, ITW
   Henderson, LB
   Aronow, BJ
   Vietor, I
   Huber, LA
   Harley, JB
   Kilpatrick, JR
   Langefeld, CD
   Williams, AH
   Jegga, AG
   Chen, J
   Wills-Karp, M
   Arshad, SH
   Ewart, SL
   Thio, CL
   Flick, LM
   Filippi, MD
   Grimes, HL
   Drumm, ML
   Cutting, GR
   Knowles, MR
   Karp, CL
AF Gu, YuanYuan
   Harley, Isaac T. W.
   Henderson, Lindsay B.
   Aronow, Bruce J.
   Vietor, Ilja
   Huber, Lukas A.
   Harley, John B.
   Kilpatrick, Jeffrey R.
   Langefeld, Carl D.
   Williams, Adrienne H.
   Jegga, Anil G.
   Chen, Jing
   Wills-Karp, Marsha
   Arshad, S. Hasan
   Ewart, Susan L.
   Thio, Chloe L.
   Flick, Leah M.
   Filippi, Marie-Dominique
   Grimes, H. Leighton
   Drumm, Mitchell L.
   Cutting, Garry R.
   Knowles, Michael R.
   Karp, Christopher L.
TI Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease
SO NATURE
LA English
DT Article
ID genome-wide association; epithelial-cells; nadph oxidase; differentiation; tis7; mice; regeneration; neutrophils; severity; defects
AB Lung disease is the major cause of morbidity and mortality in cystic fibrosis, an autosomal recessive disease caused by mutations in CFTR. In cystic fibrosis, chronic infection and dysregulated neutrophilic inflammation lead to progressive airway destruction. The severity of cystic fibrosis lung disease has considerable heritability, independent of CFTR genotype(1). To identify genetic modifiers, here we performed a genome-wide single nucleotide polymorphism scan in one cohort of cystic fibrosis patients, replicating top candidates in an independent cohort. This approach identified IFRD1 as a modifier of cystic fibrosis lung disease severity. IFRD1 is a histone-deacetylase-dependent transcriptional co-regulator expressed during terminal neutrophil differentiation. Neutrophils, but not macrophages, from Ifrd1-deficient mice showed blunted effector function, associated with decreased NF-kappa B p65 transactivation. In vivo, IFRD1 deficiency caused delayed bacterial clearance from the airway, but also less inflammation and disease-a phenotype primarily dependent on haematopoietic cell expression, or lack of expression, of IFRD1. In humans, IFRD1 polymorphisms were significantly associated with variation in neutrophil effector function. These data indicate that IFRD1 modulates the pathogenesis of cystic fibrosis lung disease through the regulation of neutrophil effector function.
C1 [Gu, YuanYuan; Harley, Isaac T. W.; Flick, Leah M.; Karp, Christopher L.] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA.
   [Aronow, Bruce J.; Jegga, Anil G.; Chen, Jing] Cincinnati Childrens Hosp Res Fdn, Div Biomed Informat, Cincinnati, OH 45229 USA.
   [Wills-Karp, Marsha; Grimes, H. Leighton] Cincinnati Childrens Hosp Res Fdn, Div Immunobiol, Cincinnati, OH 45229 USA.
   [Filippi, Marie-Dominique] Cincinnati Childrens Hosp Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
   Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA.
   [Thio, Chloe L.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
   [Henderson, Lindsay B.; Cutting, Garry R.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Vietor, Ilja; Huber, Lukas A.] Innsbruck Med Univ, Div Cell Biol, Bioctr, A-6020 Innsbruck, Austria.
   [Harley, John B.; Kilpatrick, Jeffrey R.] Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA.
   [Harley, John B.; Kilpatrick, Jeffrey R.] JK Autoimmun Inc, Oklahoma City, OK 73104 USA.
   [Langefeld, Carl D.] Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA.
   [Arshad, S. Hasan] David Hide Asthma & Allergy Res Ctr, Newport PO30 5TG, Isle of Wight, England.
   [Ewart, Susan L.] Michigan State Univ, Coll Vet Med, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA.
   [Drumm, Mitchell L.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
   [Drumm, Mitchell L.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
   [Knowles, Michael R.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA.
C3 University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Research Foundation; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Research Foundation; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Research Foundation; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Research Foundation; University System of Ohio; University of Cincinnati; Johns Hopkins University; Johns Hopkins University; Medical University of Innsbruck; Oklahoma Medical Research Foundation; Wake Forest University; Michigan State University; University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; University of North Carolina; University of North Carolina Chapel Hill
RP Karp, CL (corresponding author), Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA.
EM chris.karp@chmcc.org
FU National Institute of Allergy and Infectious Diseases [R01AI024717] Funding Source: NIH RePORTER; NHLBI NIH HHS [R01 HL068927, R01 HL068890, R01 HL079312] Funding Source: Medline; NIAID NIH HHS [R01 AI024717, R37 AI024717] Funding Source: Medline
NR 34
TC 107
Z9 127
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 23
PY 2009
VL 458
IS 7241
BP 1039
EP U119
DI 10.1038/nature07811
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900045
PM 19242412
DA 2026-03-09
ER

PT J
AU Mateja, A
   Szlachcic, A
   Downing, ME
   Dobosz, M
   Mariappan, M
   Hegde, RS
   Keenan, RJ
AF Mateja, Agnieszka
   Szlachcic, Anna
   Downing, Maureen E.
   Dobosz, Malgorzata
   Mariappan, Malaiyalam
   Hegde, Ramanujan S.
   Keenan, Robert J.
TI The structural basis of tail-anchored membrane protein recognition by Get3
SO NATURE
LA English
DT Article
ID mitochondrial outer-membrane; arsa-atpase; crystallographic structure; endoplasmic-reticulum; crystal-structure; escherichia-coli; signal; particle; insertion; binding
AB Targeting of newly synthesized membrane proteins to the endoplasmic reticulum is an essential cellular process. Most membrane proteins are recognized and targeted co-translationally by the signal recognition particle. However, nearly 5% of membrane proteins are 'tail-anchored' by a single carboxy-terminal transmembrane domain that cannot access the co-translational pathway. Instead, tail-anchored proteins are targeted post-translationally by a conserved ATPase termed Get3. The mechanistic basis for tail-anchored protein recognition or targeting by Get3 is not known. Here we present crystal structures of yeast Get3 in 'open' (nucleotide-free) and 'closed' (ADP center dot AlF4--bound) dimer states. In the closed state, the dimer interface of Get3 contains an enormous hydrophobic groove implicated by mutational analyses in tail-anchored protein binding. In the open state, Get3 undergoes a striking rearrangement that disrupts the groove and shields its hydrophobic surfaces. These data provide a molecular mechanism for nucleotide-regulated binding and release of tail-anchored proteins during their membrane targeting by Get3.
C1 [Mateja, Agnieszka; Szlachcic, Anna; Downing, Maureen E.; Dobosz, Malgorzata; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA.
   [Mariappan, Malaiyalam; Hegde, Ramanujan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
   [Szlachcic, Anna] Univ Wroclaw, Fac Biotechnol, Dept Prot Engn, PL-50137 Wroclaw, Poland.
   [Dobosz, Malgorzata] Jagiellonian Univ, Fac Chem, PL-30060 Krakow, Poland.
C3 University of Chicago; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); University of Wroclaw; Jagiellonian University
RP Keenan, RJ (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Room W238,920 E 57th St, Chicago, IL 60637 USA.
EM bkeenan@uchicago.edu
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Edward Mallinckrodt, Jr. Foundation; National Institutes of Health; National Institute of General Medical Sciences [R01GM086487] Funding Source: NIH RePORTER
NR 40
TC 152
Z9 189
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 17
PY 2009
VL 461
IS 7262
BP 361
EP U58
DI 10.1038/nature08319
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100032
PM 19675567
DA 2026-03-09
ER

PT J
AU Schaller, EL
   Roe, HG
   Schneider, T
   Brown, ME
AF Schaller, E. L.
   Roe, H. G.
   Schneider, T.
   Brown, M. E.
TI Storms in the tropics of Titan
SO NATURE
LA English
DT Article
ID clouds
AB Methane clouds, lakes and most fluvial features on Saturn's moon Titan have been observed in the moist high latitudes(1-6), while the tropics have been nearly devoid of convective clouds and have shown an abundance of wind-carved surface features like dunes(7,8). The presence of small-scale channels and dry riverbeds near the equator observed by the Huygens probe(9) at latitudes thought incapable of supporting convection(10-12) (and thus strong rain) has been suggested to be due to geological seepage or other mechanisms not related to precipitation(13). Here we report the presence of bright, transient, tropospheric clouds in tropical latitudes. We find that the initial pulse of cloud activity generated planetary waves that instigated cloud activity at other latitudes across Titan that had been cloud-free for at least several years. These observations show that convective pulses at one latitude can trigger short-term convection at other latitudes, even those not generally considered capable of supporting convection, and may also explain the presence of methane-carved rivers and channels near the Huygens landing site.
C1 [Schaller, E. L.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Roe, H. G.] Lowell Observ, Flagstaff, AZ 86001 USA.
   [Schneider, T.; Brown, M. E.] CALTECH, Pasadena, CA 91125 USA.
C3 University of Hawaii System; California Institute of Technology
RP Schaller, EL (corresponding author), Univ Hawaii, Inst Astron, 2680 Woodlawn Dr, Honolulu, HI 96822 USA.
EM schaller@ifa.hawaii.edu
FU Hubble Postdoctoral Fellowship; NASA Planetary Astronomy Program; NSF Planetary Astronomy grant
NR 29
TC 79
Z9 89
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 13
PY 2009
VL 460
IS 7257
BP 873
EP 875
DI 10.1038/nature08193
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300033
PM 19675648
DA 2026-03-09
ER

PT J
AU Vinther, BM
   Buchardt, SL
   Clausen, HB
   Dahl-Jensen, D
   Johnsen, SJ
   Fisher, DA
   Koerner, RM
   Raynaud, D
   Lipenkov, V
   Andersen, KK
   Blunier, T
   Rasmussen, SO
   Steffensen, JP
   Svensson, AM
AF Vinther, B. M.
   Buchardt, S. L.
   Clausen, H. B.
   Dahl-Jensen, D.
   Johnsen, S. J.
   Fisher, D. A.
   Koerner, R. M.
   Raynaud, D.
   Lipenkov, V.
   Andersen, K. K.
   Blunier, T.
   Rasmussen, S. O.
   Steffensen, J. P.
   Svensson, A. M.
TI Holocene thinning of the Greenland ice sheet
SO NATURE
LA English
DT Article
ID sea-level changes; temperature; elevation; record; core
AB On entering an era of global warming, the stability of the Greenland ice sheet (GIS) is an important concern(1), especially in the light of new evidence of rapidly changing flow and melt conditions at the GIS margins(2). Studying the response of the GIS to past climatic change may help to advance our understanding of GIS dynamics. The previous interpretation of evidence from stable isotopes (delta O-18) in water from GIS ice cores was that Holocene climate variability on the GIS differed spatially(3) and that a consistent Holocene climate optimum-the unusually warm period from about 9,000 to 6,000 years ago found in many northern-latitude palaeoclimate records(4)-did not exist. Here we extract both the Greenland Holocene temperature history and the evolution of GIS surface elevation at four GIS locations. We achieve this by comparing delta O-18 from GIS ice cores(3,5) with delta O-18 from ice cores from small marginal icecaps. Contrary to the earlier interpretation of delta O-18 evidence from ice cores(3,6), our new temperature history reveals a pronounced Holocene climatic optimum in Greenland coinciding with maximum thinning near the GIS margins. Our delta O-18-based results are corroborated by the air content of ice cores, a proxy for surface elevation(7). State-of-the-art ice sheet models are generally found to be underestimating the extent and changes in GIS elevation and area; our findings may help to improve the ability of models to reproduce the GIS response to Holocene climate.
C1 [Vinther, B. M.; Buchardt, S. L.; Clausen, H. B.; Dahl-Jensen, D.; Johnsen, S. J.; Andersen, K. K.; Blunier, T.; Rasmussen, S. O.; Steffensen, J. P.; Svensson, A. M.] Univ Copenhagen, Niels Bohr Inst, Ctr Ice & Climate, DK-2100 Copenhagen, Denmark.
   [Fisher, D. A.; Koerner, R. M.] Geol Survey Canada, Terrain Sci Div, Glaciol Sect, Ottawa, ON K1A 0E8, Canada.
   [Raynaud, D.] UJF, CNRS, Lab Glaciol & Geophys Environm, F-38402 St Martin Dheres, France.
   [Lipenkov, V.] Arctic & Antarctic Res Inst, St Petersburg 199397, Russia.
C3 University of Copenhagen; Niels Bohr Institute; Natural Resources Canada; Lands & Minerals Sector - Natural Resources Canada; Geological Survey of Canada; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Arctic & Antarctic Research Institute
RP Vinther, BM (corresponding author), Univ Copenhagen, Niels Bohr Inst, Ctr Ice & Climate, Juliane Maries Vej 30, DK-2100 Copenhagen, Denmark.
EM bo@gfy.ku.dk
FU Carlsberg Foundation; Groupement de Recherche Europeen (GDRE) Vostok (Institut national des sciences de l'Univers (INSU)/Centre national de la recherche scientifique (CNRS); Russian Foundation for Basic Research (RFBR)-CNRS [05-05-66801]
NR 30
TC 366
Z9 417
U1 2
U2 186
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 385
EP 388
DI 10.1038/nature08355
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100037
PM 19759618
DA 2026-03-09
ER

PT J
AU Gao, P
   Tchernyshyov, I
   Chang, TC
   Lee, YS
   Kita, K
   Ochi, T
   Zeller, KI
   De Marzo, AM
   Van Eyk, JE
   Mendell, JT
   Dang, CV
AF Gao, Ping
   Tchernyshyov, Irina
   Chang, Tsung-Cheng
   Lee, Yun-Sil
   Kita, Kayoko
   Ochi, Takafumi
   Zeller, Karen I.
   De Marzo, Angelo M.
   Van Eyk, Jennifer E.
   Mendell, Joshua T.
   Dang, Chi V.
TI c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism
SO NATURE
LA English
DT Article
ID tumor-cells; protein; growth; inhibition; apoptosis; database; genes; acid
AB Altered glucose metabolism in cancer cells is termed the Warburg effect, which describes the propensity of most cancer cells to take up glucose avidly and convert it primarily to lactate, despite available oxygen(1,2). Notwithstanding the renewed interest in the Warburg effect, cancer cells also depend on continued mitochondrial function for metabolism, specifically glutaminolysis that catabolizes glutamine to generate ATP and lactate(3). Glutamine, which is highly transported into proliferating cells(4,5), is a major source of energy and nitrogen for biosynthesis, and a carbon substrate for anabolic processes in cancer cells, but the regulation of glutamine metabolism is not well understood(1,6). Here we report that the c-Myc (hereafter referred to as Myc) oncogenic transcription factor, which is known to regulate microRNAs(7,8) and stimulate cell proliferation(9), transcriptionally represses miR-23a and miR-23b, resulting in greater expression of their target protein, mitochondrial glutaminase, in human P-493 B lymphoma cells and PC3 prostate cancer cells. This leads to upregulation of glutamine catabolism(10). Glutaminase converts glutamine to glutamate, which is further catabolized through the tricarboxylic acid cycle for the production of ATP or serves as substrate for glutathione synthesis(11). The unique means by which Myc regulates glutaminase uncovers a previously unsuspected link between Myc regulation of miRNAs, glutamine metabolism, and energy and reactive oxygen species homeostasis.
C1 [Gao, Ping; Zeller, Karen I.; Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA.
   [Tchernyshyov, Irina; Van Eyk, Jennifer E.] Johns Hopkins Univ, Sch Med, Div Cardiol, Dept Med, Baltimore, MD 21205 USA.
   [Chang, Tsung-Cheng; Lee, Yun-Sil; Mendell, Joshua T.; Dang, Chi V.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Mendell, Joshua T.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
   [Mendell, Joshua T.; Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
   [De Marzo, Angelo M.; Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [De Marzo, Angelo M.; Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
   [De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA.
   [Van Eyk, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
   [Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA.
   [Kita, Kayoko; Ochi, Takafumi] Teikyo Univ, Fac Pharmaceut Sci, Toxicol Lab, Kanagawa 2290195, Japan.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Teikyo University
RP Dang, CV (corresponding author), Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA.
EM pgao2@jhmi.edu; cvdang@jhmi.edu
FU NIH [NHLBI NO1-HV-28180, NCI R01CA051497, NCI R01CA57341, NCI R01CA120185, NCI P50CA58236]; Rita Allen Foundation; Leukemia and Lymphoma Society; Sol Goldman Center for Pancreatic Cancer Research; National Cancer Institute [R01CA057341, R01CA051497] Funding Source: NIH RePORTER
NR 30
TC 1780
Z9 2083
U1 6
U2 251
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 9
PY 2009
VL 458
IS 7239
BP 762
EP U100
DI 10.1038/nature07823
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600041
PM 19219026
DA 2026-03-09
ER

PT J
AU Snijder, B
   Sacher, R
   Rämö, P
   Damm, EM
   Liberali, P
   Pelkmans, L
AF Snijder, Berend
   Sacher, Raphael
   Raemoe, Pauli
   Damm, Eva-Maria
   Liberali, Prisca
   Pelkmans, Lucas
TI Population context determines cell-to-cell variability in endocytosis and virus infection
SO NATURE
LA English
DT Article
ID stochastic gene-expression; mediated endocytosis; gm1 ganglioside; single-cell; systems; entry; kinases
AB Single-cell heterogeneity in cell populations arises from a combination of intrinsic and extrinsic factors(1-3). This heterogeneity has been measured for gene transcription, phosphorylation, cell morphology and drug perturbations, and used to explain various aspects of cellular physiology(4-6). In all cases, however, the causes of heterogeneity were not studied. Here we analyse, for the first time, the heterogeneous patterns of related cellular activities, namely virus infection, endocytosis and membrane lipid composition in adherent human cells. We reveal correlations with specific cellular states that are defined by the population context of a cell, and we derive probabilistic models that can explain and predict most cellular heterogeneity of these activities, solely on the basis of each cell's population context. We find that accounting for population-determined heterogeneity is essential for interpreting differences between the activity levels of cell populations. Finally, we reveal that synergy between two molecular components, focal adhesion kinase and the sphingolipid GM1, enhances the population-determined pattern of simian virus 40 (SV40) infection. Our findings provide an explanation for the origin of heterogeneity patterns of cellular activities in adherent cell populations.
C1 [Snijder, Berend; Sacher, Raphael; Raemoe, Pauli; Damm, Eva-Maria; Liberali, Prisca; Pelkmans, Lucas] Swiss Fed Inst Technol, Swiss Fed Inst Technol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Snijder, Berend; Sacher, Raphael] Zurich PhD Program Mol Life Sci, Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Pelkmans, L (corresponding author), Swiss Fed Inst Technol, Swiss Fed Inst Technol, Inst Mol Syst Biol, Wolfgang Pauli Str 16, CH-8093 Zurich, Switzerland.
EM pelkmans@imsb.biol.ethz.ch
FU European Molecular Biology Organisation; Human Frontiers Science Program; Oncosuisse; Federation of European Biochemical Societies; ETH Zurich; SystemsX.ch; Swiss National Science Foundation; European Union
NR 29
TC 336
Z9 395
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 SEP 24
PY 2009
VL 461
IS 7263
BP 520
EP 523
DI 10.1038/nature08282
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900039
PM 19710653
DA 2026-03-09
ER

PT J
AU Barker, N
   Ridgway, RA
   van Es, JH
   van de Wetering, M
   Begthel, H
   van den Born, M
   Danenberg, E
   Clarke, AR
   Sansom, OJ
   Clevers, H
AF Barker, Nick
   Ridgway, Rachel A.
   van Es, Johan H.
   van de Wetering, Marc
   Begthel, Harry
   van den Born, Maaike
   Danenberg, Esther
   Clarke, Alan R.
   Sansom, Owen J.
   Clevers, Hans
TI Crypt stem cells as the cells-of-origin of intestinal cancer
SO NATURE
LA English
DT Article
ID mouse small intestine; beta-catenin; colorectal-cancer; paneth cells; in-vivo; gene; apc; differentiation; epithelium; colon
AB Intestinal cancer is initiated by Wnt- pathway- activating mutations in genes such as adenomatous polyposis coli ( APC). As in most cancers, the cell of origin has remained elusive. In a previously established Lgr5 ( leucine- rich- repeat containing G- protein-coupled receptor 5) knockin mouse model, a tamoxifen- inducible Cre recombinase is expressed in long- lived intestinal stem cells(1). Here we show that deletion of Apc in these stem cells leads to their transformation within days. Transformed stem cells remain located at crypt bottoms, while fuelling a growing microadenoma. These microadenomas show unimpeded growth and develop into macroscopic adenomas within 3-5 weeks. The distribution of Lgr5(+) cells within stem- cell- derived adenomas indicates that a stem cell/ progenitor cell hierarchy is maintained in early neoplastic lesions. When Apc is deleted in short- lived transit- amplifying cells using a different cre mouse, the growth of the induced microadenomas rapidly stalls. Even after 30 weeks, large adenomas are very rare in these mice. We conclude that stem- cell- specific loss of Apc results in progressively growing neoplasia.
C1 [Barker, Nick; van Es, Johan H.; van de Wetering, Marc; Begthel, Harry; van den Born, Maaike; Danenberg, Esther; Clevers, Hans] Hubrecht Inst Dev Biol & Stem Cell Res, NL-3584 CT Utrecht, Netherlands.
   Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Ridgway, Rachel A.; Sansom, Owen J.] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
   [Clarke, Alan R.] Cardiff Sch Biosci, Cardiff CF10 3US, Wales.
C3 Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Beatson Institute; Cardiff University
RP Clevers, H (corresponding author), Hubrecht Inst Dev Biol & Stem Cell Res, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
EM h.clevers@niob.knaw.nl
FU Cancer Research UK; KWF program [PF-HUBR-2007-3956]; MRC [G0301154] Funding Source: UKRI; Medical Research Council [G0301154] Funding Source: researchfish
NR 30
TC 1742
Z9 2062
U1 5
U2 226
PU NATURE PUBLISHING 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 29
PY 2009
VL 457
IS 7229
BP 608
EP U119
DI 10.1038/nature07602
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200047
PM 19092804
DA 2026-03-09
ER

PT J
AU Martin, A
   Troadec, C
   Boualem, A
   Rajab, M
   Fernandez, R
   Morin, H
   Pitrat, M
   Dogimont, C
   Bendahmane, A
AF Martin, Antoine
   Troadec, Christelle
   Boualem, Adnane
   Rajab, Mazen
   Fernandez, Ronan
   Morin, Halima
   Pitrat, Michel
   Dogimont, Catherine
   Bendahmane, Abdelhafid
TI A transposon-induced epigenetic change leads to sex determination in melon
SO NATURE
LA English
DT Article
ID dna methylation; arabidopsis-thaliana; mutation; plants; gene; cis
AB Sex determination in plants leads to the development of unisexual flowers from an originally bisexual floral meristem(1,2). This mechanism results in the enhancement of outcrossing and promotes genetic variability, the consequences of which are advantageous to the evolution of a species(3). In melon, sexual forms are controlled by identity of the alleles at the andromonoecious (a) and gynoecious (g) loci(4). We previously showed that the a gene encodes an ethylene biosynthesis enzyme, CmACS-7, that represses stamen development in female flowers(5). Here we show that the transition from male to female flowers in gynoecious lines results from epigenetic changes in the promoter of a transcription factor, CmWIP1. This natural and heritable epigenetic change resulted from the insertion of a transposon, which is required for initiation and maintenance of the spreading of DNA methylation to the CmWIP1 promoter. Expression of CmWIP1 leads to carpel abortion, resulting in the development of unisexual male flowers. Moreover, we show that CmWIP1 indirectly represses the expression of the andromonoecious gene, CmACS-7, to allow stamen development. Together our data indicate a model in which CmACS-7 and CmWIP1 interact to control the development of male, female and hermaphrodite flowers in melon.
C1 [Martin, Antoine; Troadec, Christelle; Boualem, Adnane; Rajab, Mazen; Fernandez, Ronan; Bendahmane, Abdelhafid] INRA, CNRS, UMR1165, Unite Rech Genom Vegetale, F-91057 Evry, France.
   [Morin, Halima] INRA, Inst Jean Pierre Bourgin, F-78026 Versailles, France.
   [Pitrat, Michel; Dogimont, Catherine] INRA, UR 1052, Unite Genet & Ameliorat Fruits & Legumes, F-84143 Montfavet, France.
C3 INRAE; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Universite Paris Saclay; INRAE; INRAE
RP Bendahmane, A (corresponding author), INRA, CNRS, UMR1165, Unite Rech Genom Vegetale, 2 Rue Gaston Cremieux, F-91057 Evry, France.
EM bendahm@evry.inra.fr
FU GAP department
NR 27
TC 516
Z9 607
U1 11
U2 281
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1135
EP U237
DI 10.1038/nature08498
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600047
PM 19847267
DA 2026-03-09
ER

PT J
AU Pierce, NW
   Kleiger, G
   Shan, SO
   Deshaies, RJ
AF Pierce, Nathan W.
   Kleiger, Gary
   Shan, Shu-ou
   Deshaies, Raymond J.
TI Detection of sequential polyubiquitylation on a millisecond timescale
SO NATURE
LA English
DT Article
ID substrate ubiquitination; conjugating enzyme; complex; scf; mechanism; recognition
AB The pathway by which ubiquitin chains are generated on substrate through a cascade of enzymes consisting of an E1, E2 and E3 remains unclear. Multiple distinct models involving chain assembly on E2 or substrate have been proposed. However, the speed and complexity of the reaction have precluded direct experimental tests to distinguish between potential pathways. Here we introduce new theoretical and experimental methodologies to address both limitations. A quantitative framework based on product distribution predicts that the really interesting new gene (RING) E3 enzymes SCFCdc4 and SCF beta-TrCP work with the E2 Cdc34 to build polyubiquitin chains on substrates by sequential transfers of single ubiquitins. Measurements with millisecond time resolution directly demonstrate that substrate polyubiquitylation proceeds sequentially. Our results present an unprecedented glimpse into the mechanism of RING ubiquitin ligases and illuminate the quantitative parameters that underlie the rate and pattern of ubiquitin chain assembly.
C1 [Pierce, Nathan W.; Kleiger, Gary; Deshaies, Raymond J.] CALTECH, Howard Hughes Med Inst, Div Biol, Pasadena, CA 91125 USA.
   [Shan, Shu-ou] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
C3 Howard Hughes Medical Institute; California Institute of Technology; California Institute of Technology
RP Deshaies, RJ (corresponding author), CALTECH, Howard Hughes Med Inst, Div Biol, MC 156-29,1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM deshaies@caltech.edu
FU Gordon Ross Fellowship; National Institutes of Health [GM065997]; Howard Hughes Medical Institute
NR 22
TC 196
Z9 253
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 3
PY 2009
VL 462
IS 7273
BP 615
EP U85
DI 10.1038/nature08595
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900033
PM 19956254
DA 2026-03-09
ER

PT J
AU Grigoryan, G
   Reinke, AW
   Keating, AE
AF Grigoryan, Gevorg
   Reinke, Aaron W.
   Keating, Amy E.
TI Design of protein-interaction specificity gives selective bZIP-binding peptides
SO NATURE
LA English
DT Article
ID coiled-coil; pdz domain; computational redesign; prediction; stability; interfaces; affinity; energy
AB Interaction specificity is a required feature of biological networks and a necessary characteristic of protein or small-molecule reagents and therapeutics. The ability to alter or inhibit protein interactions selectively would advance basic and applied molecular science. Assessing or modelling interaction specificity requires treating multiple competing complexes, which presents computational and experimental challenges. Here we present a computational framework for designing protein-interaction specificity and use it to identify specific peptide partners for human basic-region leucine zipper (bZIP) transcription factors. Protein microarrays were used to characterize designed, synthetic ligands for all but one of 20 bZIP families. The bZIP proteins share strong sequence and structural similarities and thus are challenging targets to bind specifically. Nevertheless, many of the designs, including examples that bind the oncoproteins c-Jun, c-Fos and c-Maf (also called JUN, FOS and MAF, respectively), were selective for their targets over all 19 other families. Collectively, the designs exhibit a wide range of interaction profiles and demonstrate that human bZIPs have only sparsely sampled the possible interaction space accessible to them. Our computational method provides a way to systematically analyse trade-offs between stability and specificity and is suitable for use with many types of structure-scoring functions; thus, it may prove broadly useful as a tool for protein design.
C1 [Grigoryan, Gevorg; Reinke, Aaron W.; Keating, Amy E.] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Keating, AE (corresponding author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM keating@mit.edu
FU NIH [GM67681]; NSF [0216437]; Direct For Biological Sciences; Div Of Biological Infrastructure [0216437] Funding Source: National Science Foundation
NR 38
TC 295
Z9 377
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 16
PY 2009
VL 458
IS 7240
BP 859
EP U2
DI 10.1038/nature07885
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500036
PM 19370028
DA 2026-03-09
ER

PT J
AU Sakakibara, D
   Sasaki, A
   Ikeya, T
   Hamatsu, J
   Hanashima, T
   Mishima, M
   Yoshimasu, M
   Hayashi, N
   Mikawa, T
   Wälchli, M
   Smith, BO
   Shirakawa, M
   Güntert, P
   Ito, Y
AF Sakakibara, Daisuke
   Sasaki, Atsuko
   Ikeya, Teppei
   Hamatsu, Junpei
   Hanashima, Tomomi
   Mishima, Masaki
   Yoshimasu, Masatoshi
   Hayashi, Nobuhiro
   Mikawa, Tsutomu
   Waelchli, Markus
   Smith, Brian O.
   Shirakawa, Masahiro
   Guentert, Peter
   Ito, Yutaka
TI Protein structure determination in living cells by in-cell NMR spectroscopy
SO NATURE
LA English
DT Article
ID triple-resonance spectra; torsion angle dynamics; subcellular-localization; escherichia-coli; signal peptides; prediction; assignment; resolution; program; domain
AB Investigating proteins 'at work' in a living environment at atomic resolution is a major goal of molecular biology, which has not been achieved even though methods for the three-dimensional (3D) structure determination of purified proteins in single crystals or in solution are widely used. Recent developments in NMR hardware and methodology have enabled the measurement of high-resolution heteronuclear multi-dimensional NMR spectra of macromolecules in living cells (in-cell NMR)(1-5). Various intracellular events such as conformational changes, dynamics and binding events have been investigated by this method. However, the low sensitivity and the short lifetime of the samples have so far prevented the acquisition of sufficient structural information to determine protein structures by in-cell NMR. Here we show the first, to our knowledge, 3D protein structure calculated exclusively on the basis of information obtained in living cells. The structure of the putative heavy-metal binding protein TTHA1718 from Thermus thermophilus HB8 overexpressed in Escherichia coli cells was solved by in-cell NMR. Rapid measurement of the 3D NMR spectra by nonlinear sampling of the indirectly acquired dimensions was used to overcome problems caused by the instability and low sensitivity of living E. coli samples. Almost all of the expected backbone NMR resonances and most of the side-chain NMR resonances were observed and assigned, enabling high quality (0.96 angstrom backbone root mean squared deviation) structures to be calculated that are very similar to the in vitro structure of TTHA1718 determined independently. The in-cell NMR approach can thus provide accurate high-resolution structures of proteins in living environments.
C1 [Sakakibara, Daisuke; Sasaki, Atsuko; Ikeya, Teppei; Hamatsu, Junpei; Hanashima, Tomomi; Mishima, Masaki; Guentert, Peter; Ito, Yutaka] Tokyo Metropolitan Univ, Dept Chem, Tokyo 1920397, Japan.
   [Sakakibara, Daisuke; Sasaki, Atsuko; Hamatsu, Junpei; Mishima, Masaki; Shirakawa, Masahiro; Ito, Yutaka] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
   [Ikeya, Teppei; Guentert, Peter] Goethe Univ Frankfurt, Inst Biophys Chem, D-60438 Frankfurt, Germany.
   [Ikeya, Teppei; Guentert, Peter] Goethe Univ Frankfurt, Ctr Biomol Magnet Resonance, D-60438 Frankfurt, Germany.
   [Yoshimasu, Masatoshi] RIKEN, Cellular & Mol Biol Lab, Wako, Saitama 3510198, Japan.
   [Hayashi, Nobuhiro] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Biomed Polymer Sci, Toyoake, Aichi 4701192, Japan.
   [Mikawa, Tsutomu; Ito, Yutaka] RIKEN, Res Grp Biosupramol Struct Funct, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Waelchli, Markus] Bruker BioSpin, Tsukuba, Ibaraki 3050051, Japan.
   [Smith, Brian O.] Univ Glasgow, Fac Biomed & Life Sci, Div Mol & Cellular Biol, Glasgow G12 8QQ, Lanark, Scotland.
   [Shirakawa, Masahiro] Kyoto Univ, Grad Sch Engn, Dept Mol Engn, Nishikyo Ku, Kyoto 6158510, Japan.
   [Guentert, Peter] Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany.
C3 Tokyo Metropolitan University; Japan Science & Technology Agency (JST); Goethe University Frankfurt; Goethe University Frankfurt; RIKEN; Fujita Health University; RIKEN; Bruker Corporation; Bruker BioSpin GmbH; University of Glasgow; Kyoto University
RP Ito, Y (corresponding author), Tokyo Metropolitan Univ, Dept Chem, 1-1 Minami Osawa, Tokyo 1920397, Japan.
EM ito-yutaka@tmu.ac.jp
FU CREST, Japan Science and Technology Agency (JST); Molecular Ensemble Program, RIKEN; Japanese Ministry of Education, Sports, Culture, Science, and Technology; Volkswagen Foundation;  [TTHA1718]
NR 37
TC 315
Z9 385
U1 1
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 5
PY 2009
VL 458
IS 7234
BP 102
EP U10
DI 10.1038/nature07814
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000041
PM 19262674
DA 2026-03-09
ER

PT J
AU Sun, JC
   Beilke, JN
   Lanier, LL
AF Sun, Joseph C.
   Beilke, Joshua N.
   Lanier, Lewis L.
TI Adaptive immune features of natural killer cells
SO NATURE
LA English
DT Article
ID cd8(+) t-cells; murine cytomegalovirus; activation receptor; viral-infection; nk cells; in-vivo; memory; effector; recognition; antigen
AB In an adaptive immune response, naive T cells proliferate during infection and generate long- lived memory cells that undergo secondary expansion after a repeat encounter with the same pathogen. Although natural killer (NK) cells have traditionally been classified as cells of the innate immune system, they share many similarities with cytotoxic T lymphocytes. We use a mouse model of cytomegalovirus infection to show that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100-fold in the spleen and 1,000- fold in the liver after infection. After a contraction phase, Ly49H- positive NK cells reside in lymphoid and non- lymphoid organs for several months. These self- renewing 'memory' NK cells rapidly degranulate and produce cytokines on reactivation. Adoptive transfer of these NK cells into naive animals followed by viral challenge results in a robust secondary expansion and protective immunity. These findings reveal properties of NK cells that were previously attributed only to cells of the adaptive immune system.
C1 [Sun, Joseph C.; Beilke, Joshua N.; Lanier, Lewis L.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Sun, Joseph C.; Beilke, Joshua N.; Lanier, Lewis L.] Univ Calif San Francisco, Inst Canc Res, 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 Lanier, LL (corresponding author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
EM lewis.lanier@ucsf.edu
FU National Institutes of Health [AI068129]; Irvington Institute for Immunological Research; Juvenile Diabetes Research Foundation
NR 36
TC 1307
Z9 1580
U1 2
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 29
PY 2009
VL 457
IS 7229
BP 557
EP 561
DI 10.1038/nature07665
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200035
PM 19136945
DA 2026-03-09
ER

PT J
AU Gröblacher, S
   Hammerer, K
   Vanner, MR
   Aspelmeyer, M
AF Groeblacher, Simon
   Hammerer, Klemens
   Vanner, Michael R.
   Aspelmeyer, Markus
TI Observation of strong coupling between a micromechanical resonator and an optical cavity field
SO NATURE
LA English
DT Article
ID single quantum-dot; radiation-pressure; atom; electrodynamics; micromirror; microcavity; forces; photon
AB Achieving coherent quantum control over massive mechanical resonators is a current research goal. Nano-and micromechanical devices can be coupled to a variety of systems, for example to single electrons by electrostatic(1,2) or magnetic coupling(3,4), and to photons by radiation pressure(5-9) or optical dipole forces(10,11). So far, all such experiments have operated in a regime of weak coupling, in which reversible energy exchange between the mechanical device and its coupled partner is suppressed by fast decoherence of the individual systems to their local environments. Controlled quantum experiments are in principle not possible in such a regime, but instead require strong coupling. So far, this has been demonstrated only between microscopic quantum systems, such as atoms and photons (in the context of cavity quantum electrodynamics(12)) or solid state qubits and photons(13,14). Strong coupling is an essential requirement for the preparation of mechanical quantum states, such as squeezed or entangled states(15-18), and also for using mechanical resonators in the context of quantum information processing, for example, as quantum transducers. Here we report the observation of optomechanical normal mode splitting(19,20), which provides unambiguous evidence for strong coupling of cavity photons to a mechanical resonator. This paves the way towards full quantum optical control of nano-and micromechanical devices.
C1 [Groeblacher, Simon; Vanner, Michael R.; Aspelmeyer, Markus] Austrian Acad Sci, IQOQI, A-1090 Vienna, Austria.
   [Groeblacher, Simon; Vanner, Michael R.] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
   [Hammerer, Klemens] Austrian Acad Sci, IQOQI, A-6020 Innsbruck, Austria.
   [Hammerer, Klemens] Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
C3 Austrian Academy of Sciences; University of Vienna; Austrian Academy of Sciences; University of Innsbruck
RP Aspelmeyer, M (corresponding author), Austrian Acad Sci, IQOQI, Boltzmanngasse 3, A-1090 Vienna, Austria.
EM markus.aspelmeyer@quantum.at
FU Austrian Science Fund FWF; European Commission; Foundational Questions Institute; Austrian Academy of Sciences; Austrian Science Fund (FWF) [Y 414] Funding Source: researchfish
NR 30
TC 884
Z9 960
U1 4
U2 220
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 6
PY 2009
VL 460
IS 7256
BP 724
EP 727
DI 10.1038/nature08171
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300035
PM 19661913
DA 2026-03-09
ER

PT J
AU Tokuriki, N
   Tawfik, DS
AF Tokuriki, Nobuhiko
   Tawfik, Dan S.
TI Chaperonin overexpression promotes genetic variation and enzyme evolution
SO NATURE
LA English
DT Article
ID carbonic-anhydrase-ii; escherichia-coli; directed evolution; deleterious mutations; protein mutations; groel; stability; hsp90; evolvability; expression
AB Most protein mutations, and mutations that alter protein functions in particular, undermine stability and are therefore deleterious. Chaperones, or heat-shock proteins, are often implicated in buffering mutations, and could thus facilitate the acquisition of neutral genetic diversity and the rate of adaptation. We examined the ability of the Escherichia coli GroEL/GroES chaperonins to buffer destabilizing and adaptive mutations. Here we show that mutational drifts performed in vitro with four different enzymes indicated that GroEL/GroES overexpression doubled the number of accumulating mutations, and promoted the folding of enzyme variants carrying mutations in the protein core and/or mutations with higher destabilizing effects (destabilization energies of >3.5 kcal mol(-1), on average, versus, similar to 1 kcal mol(-1) in the absence of GroEL/GroES). The divergence of modified enzymatic specificity occurred much faster under GroEL/GroES overexpression, in terms of the number of adapted variants (>= 2-fold) and their improved specificity and activity (>= 10-fold). These results indicate that protein stability is a major constraint in protein evolution, and buffering mechanisms such as chaperonins are key in alleviating this constraint.
C1 [Tokuriki, Nobuhiko; Tawfik, Dan S.] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science
RP Tawfik, DS (corresponding author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
EM tawfik@weizmann.ac.il
FU NIH [W81XWH-07-2-0020]; Israel Science Foundation; EU
NR 45
TC 282
Z9 327
U1 0
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 668
EP U71
DI 10.1038/nature08009
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600036
PM 19494908
DA 2026-03-09
ER

PT J
AU Ozsolak, F
   Platt, AR
   Jones, DR
   Reifenberger, JG
   Sass, LE
   McInerney, P
   Thompson, JF
   Bowers, J
   Jarosz, M
   Milos, PM
AF Ozsolak, Fatih
   Platt, Adam R.
   Jones, Dan R.
   Reifenberger, Jeffrey G.
   Sass, Lauryn E.
   McInerney, Peter
   Thompson, John F.
   Bowers, Jayson
   Jarosz, Mirna
   Milos, Patrice M.
TI Direct RNA sequencing
SO NATURE
LA English
DT Article
ID 2nd-strand cdna synthesis; dna; transcriptome; polyadenylation; expression; snorna
AB Our understanding of human biology and disease is ultimately dependent on a complete understanding of the genome and its functions. The recent application of microarray and sequencing technologies to transcriptomics has changed the simplistic view of transcriptomes to a more complicated view of genome-wide transcription where a large fraction of transcripts emanates from unannotated parts of genomes(1-7), and underlined our limited knowledge of the dynamic state of transcription. Most of this broad body of knowledge was obtained indirectly because current transcriptome analysis methods typically require RNA to be converted to complementary DNA ( cDNA) before measurements, even though the cDNA synthesis step introduces multiple biases and artefacts that interfere with both the proper characterization and quantification of transcripts(8-18). Furthermore, cDNA synthesis is not particularly suitable for the analysis of short, degraded and/or small quantity RNA samples. Here we report direct single molecule RNA sequencing without prior conversion of RNA to cDNA. We applied this technology to sequence femtomole quantities of poly(A)(+) Saccharomyces cerevisiae RNA using a surface coated with poly(dT) oligonucleotides to capture the RNAs at their natural poly(A) tails and initiate sequencing by synthesis. We observed transcript 3' end heterogeneity and polyadenylated small nucleolar RNAs. This study provides a path to high-throughput and low-cost direct RNA sequencing and achieving the ultimate goal of a comprehensive and bias-free understanding of transcriptomes.
C1 [Ozsolak, Fatih; Platt, Adam R.; Jones, Dan R.; Reifenberger, Jeffrey G.; Sass, Lauryn E.; McInerney, Peter; Thompson, John F.; Bowers, Jayson; Jarosz, Mirna; Milos, Patrice M.] Helicos BioSci Corp, Cambridge, MA 02139 USA.
RP Ozsolak, F (corresponding author), Helicos BioSci Corp, 1 Kendall Sq, Cambridge, MA 02139 USA.
EM fatihozsolak@gmail.com; pmilos@helicosbio.com
FU NHGRI NIH HHS [R01 HG005230] Funding Source: Medline
NR 30
TC 305
Z9 438
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 OCT 8
PY 2009
VL 461
IS 7265
BP 814
EP U73
DI 10.1038/nature08390
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500040
PM 19776739
DA 2026-03-09
ER

PT J
AU Chatterjee, S
   Grosshans, H
AF Chatterjee, Saibal
   Grosshans, Helge
TI Active turnover modulates mature microRNA activity in Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID target messenger-rna; c-elegans; let-7 microrna; saccharomyces-cerevisiae; human-cells; interference; purification; degradation; maturation; proteins
AB MicroRNAs (miRNAs) constitute a large class of regulatory RNAs that repress target messenger RNAs to control various biological processes(1). Accordingly, miRNA biogenesis is highly regulated, controlled at both transcriptional and post-transcriptional levels(2), and overexpression and underexpression of miRNAs are linked to various human diseases, particularly cancers(1,3). As RNA concentrations are generally a function of biogenesis and turnover, active miRNA degradation might also modulate miRNA accumulation, and the plant 3'-> 5' exonuclease SDN1 has been implicated in miRNA turnover(4). Here we report that degradation of mature miRNAs in the nematode Caenorhabditis elegans, mediated by the 5'-> 3' exoribonuclease XRN-2, affects functional miRNA homeostasis in vivo. We recapitulate XRN-2-dependent miRNA turnover in larval lysates, where processing of precursor-miRNA (pre-miRNA) by Dicer, unannealing of the miRNA duplex and loading of the mature miRNA into the Argonaute protein of the miRNA-induced silencing complex (miRISC) are coupled processes that precede degradation of the mature miRNA. Although Argonaute: miRNA complexes are highly resistant to salt, larval lysate promotes efficient release of the miRNA, exposing it to degradation by XRN-2. Release and degradation can both be blocked by the addition of miRNA target RNA. Our results therefore suggest the presence of an additional layer of regulation of animal miRNA activity that might be important for rapid changes of miRNA expression profiles during developmental transitions and for the maintenance of steady-state concentrations of miRNAs. This pathway might represent a potential target for therapeutic intervention on miRNA expression.
C1 [Chatterjee, Saibal; Grosshans, Helge] Friedrich Miescher Inst Biomed Res, CH-4002 Basel, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research
RP Grosshans, H (corresponding author), Friedrich Miescher Inst Biomed Res, POB 2543, CH-4002 Basel, Switzerland.
EM helge.grosshans@fmi.ch
FU Marie Curie; EMBO
NR 37
TC 282
Z9 377
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 24
PY 2009
VL 461
IS 7263
BP 546
EP U120
DI 10.1038/nature08349
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900045
PM 19734881
DA 2026-03-09
ER

PT J
AU Nozawa, K
   O'Donoghue, P
   Gundllapalli, S
   Araiso, Y
   Ishitani, R
   Umehara, T
   Söll, D
   Nureki, O
AF Nozawa, Kayo
   O'Donoghue, Patrick
   Gundllapalli, Sarath
   Araiso, Yuhei
   Ishitani, Ryuichiro
   Umehara, Takuya
   Soell, Dieter
   Nureki, Osamu
TI Pyrrolysyl-tRNA synthetase-tRNAPyl structure reveals the molecular basis of orthogonality
SO NATURE
LA English
DT Article
ID crystal-structure; active-site; escherichia-coli; genetic-code; in-vitro; synthetases; recognition; trna(phe); proteins; archaea
AB Pyrrolysine (Pyl), the 22nd natural amino acid, is genetically encoded by UAG and inserted into proteins by the unique suppressor tRNA(Pyl) (ref.1). The Methanosarcinaceae produce Pyl and express Pyl-containing methyltransferases that allow growth on methylamines(2). Homologous methyltransferases and the Pyl biosynthetic and coding machinery are also found in two bacterial species(1,3). Pyl coding is maintained by pyrrolysyl-tRNA synthetase (PylRS), which catalyses the formation of Pyl-tRNA(Pyl) (refs 4, 5). Pyl is not a recent addition to the genetic code. PylRS was already present in the last universal common ancestor(6); it then persisted in organisms that utilize methylamines as energy sources. Recent protein engineering efforts added non-canonical amino acids to the genetic code(7,8). This technology relies on the directed evolution of an 'orthogonal' tRNA synthetase-tRNA pair in which an engineered aminoacyl-tRNA synthetase (aaRS) specifically and exclusively acylates the orthogonal tRNA with a non-canonical amino acid. For Pyl the natural evolutionary process developed such a system some 3 billion years ago. When transformed into Escherichia coli, Methanosarcina barkeri PylRS and tRNA(Pyl) function as an orthogonal pair in vivo(5,9). Here we show that Desulfitobacterium hafniense PylRS-tRNA(Pyl) is an orthogonal pair in vitro and in vivo, and present the crystal structure of this orthogonal pair. The ancient emergence of PylRS tRNA(Pyl) allowed the evolution of unique structural features in both the protein and the tRNA. These structural elements manifest an intricate, specialized aaRS-tRNA interaction surface that is highly distinct from those observed in any other known aaRS-tRNA complex; it is this general property that underlies the molecular basis of orthogonality.
C1 [O'Donoghue, Patrick; Gundllapalli, Sarath; Umehara, Takuya; Soell, Dieter] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Soell, Dieter] Yale Univ, Dept Chem, New Haven, CT 06520 USA.
   [Nozawa, Kayo; Araiso, Yuhei; Nureki, Osamu] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Informat, Midori Ku, Yokohama, Kanagawa 2268501, Japan.
   [Ishitani, Ryuichiro; Nureki, Osamu] Univ Tokyo, Inst Med Sci, Dept Basic Med Sci, Minato Ku, Tokyo 1088639, Japan.
C3 Yale University; Yale University; Institute of Science Tokyo; Tokyo Institute of Technology; University of Tokyo
RP Söll, D (corresponding author), Yale Univ, Dept Mol Biophys & Biochem, POB 6666, New Haven, CT 06520 USA.
EM dieter.soll@yale.edu; nureki@ims.u-tokyo.ac.jp
FU National Science Foundation; Japan Science and Technology Agency; Ministry of Education, Culture, Sports, Science and Technology; Mitsubishi Foundation; Kurata Memorial Hitachi Science and Technology Foundation; National Institute of General Medical Sciences; Department of Energy
NR 35
TC 163
Z9 228
U1 3
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 26
PY 2009
VL 457
IS 7233
BP 1163
EP U127
DI 10.1038/nature07611
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100048
PM 19118381
DA 2026-03-09
ER

PT J
AU Bartholomäus, I
   Kawakami, N
   Odoardi, F
   Schläger, C
   Miljkovic, D
   Ellwart, JW
   Klinkert, WEF
   Flügel-Koch, C
   Issekutz, TB
   Wekerle, H
   Flügel, A
AF Bartholomaeus, Ingo
   Kawakami, Naoto
   Odoardi, Francesca
   Schlaeger, Christian
   Miljkovic, Djordje
   Ellwart, Joachim W.
   Klinkert, Wolfgang E. F.
   Fluegel-Koch, Cassandra
   Issekutz, Thomas B.
   Wekerle, Hartmut
   Fluegel, Alexander
TI Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions
SO NATURE
LA English
DT Article
ID experimental allergic encephalomyelitis; central-nervous-system; germline transmission; dendritic cells; choroid-plexus; antigen; protein; lymphocytes; brain; extravasation
AB The tissues of the central nervous system are effectively shielded from the blood circulation by specialized vessels that are impermeable not only to cells, but also to most macromolecules circulating in the blood. Despite this seemingly absolute seclusion, central nervous system tissues are subject to immune surveillance and are vulnerable to autoimmune attacks(1). Using intravital two-photon imaging in a Lewis rat model of experimental autoimmune encephalomyelitis, here we present in real-time the interactive processes between effector T cells and cerebral structures from their first arrival to manifest autoimmune disease. We observed that incoming effector T cells successively scanned three planes. The T cells got arrested to leptomeningeal vessels and immediately monitored the luminal surface, crawling preferentially against the blood flow. After diapedesis, the cells continued their scan on the abluminal vascular surface and the underlying leptomeningeal (pial) membrane. There, the T cells encountered phagocytes that effectively present antigens, foreign as well as myelin proteins. These contacts stimulated the effector T cells to produce pro-inflammatory mediators, and provided a trigger to tissue invasion and the formation of inflammatory infiltrations.
C1 [Bartholomaeus, Ingo; Kawakami, Naoto; Odoardi, Francesca; Schlaeger, Christian; Miljkovic, Djordje; Klinkert, Wolfgang E. F.; Wekerle, Hartmut; Fluegel, Alexander] Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
   [Odoardi, Francesca; Schlaeger, Christian; Fluegel, Alexander] Inst Multiple Sclerosis Res, Dept Neuroimmunol, Gemeinnutzige Hertie Stiftung, D-37073 Gottingen, Germany.
   [Odoardi, Francesca; Schlaeger, Christian; Fluegel, Alexander] Univ Med Ctr Gottingen, D-37073 Gottingen, Germany.
   [Odoardi, Francesca; Fluegel, Alexander] Univ Munich, Inst Immunol, D-80336 Munich, Germany.
   [Ellwart, Joachim W.] Helmholtz Ctr, Inst Expt Hematol, D-81377 Munich, Germany.
   [Fluegel-Koch, Cassandra] Univ Erlangen Nurnberg, Inst Anat 2, D-91054 Erlangen, Germany.
   [Issekutz, Thomas B.] Dalhousie Univ, Dept Pediat, Div Immunol, Halifax, NS B3K 6R8, Canada.
C3 Max Planck Society; University of Gottingen; University of Gottingen Hospital; University of Munich; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Erlangen Nuremberg; Dalhousie University
RP Flügel, A (corresponding author), Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
EM hwekerle@neuro.mpg.de; Fluegel@med.uni-goettingen.de
FU Deutsche Forschungsgemeinschaft [SFB455 A8, SFB571 C6]; Hertie foundation [1.01.1/04/010]
NR 36
TC 550
Z9 628
U1 1
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 5
PY 2009
VL 462
IS 7269
BP 94
EP U104
DI 10.1038/nature08478
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200039
PM 19829296
DA 2026-03-09
ER

PT J
AU Barker, S
   Diz, P
   Vautravers, MJ
   Pike, J
   Knorr, G
   Hall, IR
   Broecker, WS
AF Barker, Stephen
   Diz, Paula
   Vautravers, Maryline J.
   Pike, Jennifer
   Knorr, Gregor
   Hall, Ian R.
   Broecker, Wallace S.
TI Interhemispheric Atlantic seesaw response during the last deglaciation
SO NATURE
LA English
DT Article
ID sea-surface temperature; planktonic-foraminifera; age calibration; bipolar seesaw; south atlantic; ocean; circulation; greenland; events; resumption
AB The asynchronous relationship between millennial-scale temperature changes over Greenland and Antarctica during the last glacial period has led to the notion of a bipolar seesaw which acts to redistribute heat depending on the state of meridional overturning circulation within the Atlantic Ocean. Here we present new records from the South Atlantic that show rapid changes during the last deglaciation that were instantaneous (within dating uncertainty) and of opposite sign to those observed in the North Atlantic. Our results demonstrate a direct link between the abrupt changes associated with variations in the Atlantic meridional overturning circulation and the more gradual adjustments characteristic of the Southern Ocean. These results emphasize the importance of the Southern Ocean for the development and transmission of millennial-scale climate variability and highlight its role in deglacial climate change and the associated rise in atmospheric carbon dioxide.
C1 [Barker, Stephen; Diz, Paula; Pike, Jennifer; Knorr, Gregor; Hall, Ian R.] Cardiff Univ, Sch Earth & Ocean Sci, Cardiff CF10 3YE, S Glam, Wales.
   [Vautravers, Maryline J.] British Antarctic Survey, Cambridge CB3 0ET, England.
   [Broecker, Wallace S.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
C3 Cardiff University; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; Columbia University
RP Barker, S (corresponding author), Cardiff Univ, Sch Earth & Ocean Sci, Cardiff CF10 3YE, S Glam, Wales.
EM barkers3@cf.ac.uk
FU US National Science Foundation [OCE00-02380]; Office of Naval Research [N00014-02-1-0073]; National Science Foundation [OCE-0435703]; NERC [bas010019] Funding Source: UKRI; Natural Environment Research Council [bas010019] Funding Source: researchfish
NR 57
TC 426
Z9 499
U1 2
U2 174
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 26
PY 2009
VL 457
IS 7233
BP 1097
EP U50
DI 10.1038/nature07770
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100033
PM 19242468
DA 2026-03-09
ER

PT J
AU Weisz, C
   Glowatzki, E
   Fuchs, P
AF Weisz, Catherine
   Glowatzki, Elisabeth
   Fuchs, Paul
TI The postsynaptic function of type II cochlear afferents
SO NATURE
LA English
DT Article
ID outer hair-cells; guinea-pig cochlea; spiral ganglion neurons; ribbon synapse; rat cochlea; horseradish-peroxidase; transmitter release; receptor subunits; innervation; fibers
AB The mammalian cochlea is innervated by two classes of sensory neurons. Type I neurons make up 90-95% of the cochlear nerve and contact single inner hair cells to provide acoustic analysis as we know it. In contrast, the far less numerous type II neurons arborize extensively among outer hair cells (OHCs)(1,2) and supporting cells(3,4). Their scarcity and smaller calibre axons have made them the subject of much speculation, but little experimental progress for the past 50 years. Here we record from type II fibres near their terminal arbors under OHCs to show that they receive excitatory glutamatergic synaptic input. The type II peripheral arbor conducts action potentials, but the small and infrequent glutamatergic excitation indicates a requirement for strong acoustic stimulation. Furthermore, we show that type II neurons are excited by ATP. Exogenous ATP depolarized type II neurons, both directly and by evoking glutamatergic synaptic input(5). These results prove that type II neurons function as cochlear afferents, and can be modulated by ATP. The lesser magnitude of synaptic drive dictates a fundamentally different role in auditory signalling from that of type I afferents.
C1 [Weisz, Catherine; Glowatzki, Elisabeth; Fuchs, Paul] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
   [Glowatzki, Elisabeth; Fuchs, Paul] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Ctr Hearing & Balance, Baltimore, MD 21205 USA.
   [Glowatzki, Elisabeth; Fuchs, Paul] Johns Hopkins Univ, Sch Med, Ctr Sensory Biol, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University
RP Fuchs, P (corresponding author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
EM pfuchs1@jhmi.edu
FU NIDCD [R01 DC000276, R01 DC006476, T32 DC000023]; Blaustein Pain Foundation of Johns Hopkins; National Institute on Deafness and Other Communication Disorders [R01DC006476, T32DC000023] Funding Source: NIH RePORTER
NR 30
TC 123
Z9 145
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 22
PY 2009
VL 461
IS 7267
BP 1126
EP U226
DI 10.1038/nature08487
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600045
PM 19847265
DA 2026-03-09
ER

PT J
AU Ho, WCG
   Heinke, CO
AF Ho, Wynn C. G.
   Heinke, Craig O.
TI A neutron star with a carbon atmosphere in the Cassiopeia A supernova remnant
SO NATURE
LA English
DT Article
ID evolution; hydrogen; object
AB The surface of hot neutron stars is covered by a thin atmosphere. If there is accretion after neutron-star formation, the atmosphere could be composed of light elements (H or He); if no accretion takes place or if thermonuclear reactions occur after accretion, heavy elements (for example, Fe) are expected. Despite detailed searches, observations have been unable to confirm the atmospheric composition of isolated neutron stars(1). Here we report an analysis of archival observations of the compact X-ray source in the centre of the Cassiopeia A supernova remnant. We show that a carbon atmosphere neutron star (with low magnetic field) produces a good fit to the spectrum. Our emission model, in contrast with others(2-4), implies an emission size consistent with theoretical predictions for the radius of neutron stars. This result suggests that there is nuclear burning in the surface layers(5,6) and also identifies the compact source as a very young (similar to 330-year-old) neutron star.
C1 [Ho, Wynn C. G.] Univ Southampton, Sch Math, Southampton SO17 1BJ, Hants, England.
   [Heinke, Craig O.] Univ Alberta, Dept Phys, Edmonton, AB T6G 2G7, Canada.
C3 University of Southampton; University of Alberta
RP Ho, WCG (corresponding author), Univ Southampton, Sch Math, Southampton SO17 1BJ, Hants, England.
EM wynnho@slac.stanford.edu; cheinke@phys.ualberta.ca
FU Science and Technology Facilities Council (STFC) in the United Kingdom; Natural Sciences and Engineering Research Council (NSERC) of Canada; STFC [PP/E001025/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/E001025/1] Funding Source: researchfish
NR 30
TC 214
Z9 226
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 5
PY 2009
VL 462
IS 7269
BP 71
EP 73
DI 10.1038/nature08525
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200033
PM 19890325
DA 2026-03-09
ER

PT J
AU Kostrewa, D
   Zeller, ME
   Armache, KJ
   Seizl, M
   Leike, K
   Thomm, M
   Cramer, P
AF Kostrewa, Dirk
   Zeller, Mirijam E.
   Armache, Karim-Jean
   Seizl, Martin
   Leike, Kristin
   Thomm, Michael
   Cramer, Patrick
TI RNA polymerase II-TFIIB structure and mechanism of transcription initiation
SO NATURE
LA English
DT Article
ID start site selection; n-terminal region; preinitiation complex; angstrom resolution; elongation complex; crystal-structure; saccharomyces-cerevisiae; zinc ribbon; yeast; dna
AB To initiate gene transcription, RNA polymerase II (Pol II) requires the transcription factor IIB (B). Here we present the crystal structure of the complete Pol II-B complex at 4.3 angstrom resolution, and complementary functional data. The results indicate the mechanism of transcription initiation, including the transition to RNA elongation. Promoter DNA is positioned over the Pol II active centre cleft with the 'B-core' domain that binds the wall at the end of the cleft. DNA is then opened with the help of the 'B-linker' that binds the Pol II rudder and clamp coiled-coil at the edge of the cleft. The DNA template strand slips into the cleft and is scanned for the transcription start site with the help of the 'B-reader' that approaches the active site. Synthesis of the RNA chain and rewinding of upstream DNA displace the B-reader and B-linker, respectively, to trigger B release and elongation complex formation.
C1 [Kostrewa, Dirk; Armache, Karim-Jean; Seizl, Martin; Leike, Kristin; Cramer, Patrick] Univ Munich, Gene Ctr Munich, D-81377 Munich, Germany.
   [Kostrewa, Dirk; Armache, Karim-Jean; Seizl, Martin; Leike, Kristin; Cramer, Patrick] Univ Munich, Dept Chem & Biochem, CIPSM, D-81377 Munich, Germany.
   [Zeller, Mirijam E.; Thomm, Michael] Univ Regensburg, Inst Biochem Genet & Mikrobiol, D-93053 Regensburg, Germany.
C3 University of Munich; University of Munich; University of Regensburg
RP Cramer, P (corresponding author), Univ Munich, Gene Ctr Munich, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM cramer@lmb.uni-muenchen.de
FU Deutsche Forschungsgemeinschaft; Sonderforschungsbereich [SFB646]; Transregio 5; Forschergruppe 'Regulation und Mechanismen der Ribosomen-Biogenese'; Nanosystems Initiative Munich (NIM); Ernst-Jung-Stiftung; Fonds der chemischen Industrie; Boehringer-Ingelheim-Fonds and Elitenetzwerk Bayern; DFG Forschergruppe 'Regulation und Mechanismen der Ribosomenbiogenese'
NR 50
TC 249
Z9 312
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 19
PY 2009
VL 462
IS 7271
BP 323
EP 330
DI 10.1038/nature08548
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300038
PM 19820686
DA 2026-03-09
ER

PT J
AU Niwa, H
   Ogawa, K
   Shimosato, D
   Adachi, K
AF Niwa, Hitoshi
   Ogawa, Kazuya
   Shimosato, Daisuke
   Adachi, Kenjiro
TI A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells
SO NATURE
LA English
DT Article
ID embryonic stem-cells; transcription factor klf4; self-renewal; nanog expression; differentiation; activation; sox2; identification; sufficient; promoter
AB The cytokine leukaemia inhibitory factor (LIF) integrates signals into mouse embryonic stem (ES) cells to maintain pluripotency. Although the Jak-Stat3 pathway is essential and sufficient to mediate LIF signals(1,2), it is still unclear how these signals are linked to the core circuitry of pluripotency-associated transcription factors, consisting of Oct3/4 (also called Pou5f1), Sox2 and Nanog(3,4). Here we show that two LIF signalling pathways are each connected to the core circuitry via different transcription factors. In mouse ES cells, Klf4 is mainly activated by the Jak-Stat3 pathway and preferentially activates Sox2, whereas Tbx3 is preferentially regulated by the phosphatidylinositol-3-OH kinase-Akt and mitogen-activated protein kinase pathways and predominantly stimulates Nanog. In the absence of LIF, artificial expression of Klf4 or Tbx3 is sufficient to maintain pluripotency while maintaining the expression of Oct3/4. Notably, overexpression of Nanog supports LIF-independent self-renewal of mouse ES cells in the absence of Klf4 and Tbx3 activity. Therefore, Klf4 and Tbx3 are involved in mediating LIF signalling to the core circuitry but are not directly associated with the maintenance of pluripotency, because ES cells keep pluripotency without their expression in the particular context.
C1 [Niwa, Hitoshi; Ogawa, Kazuya; Shimosato, Daisuke; Adachi, Kenjiro] RIKEN Ctr Dev Biol, Lab Pluripotent Cell Studies, Chuo Ku, Kobe, Hyogo 6500047, Japan.
   [Niwa, Hitoshi; Shimosato, Daisuke] Kobe Univ, Grad Sch Med, Lab Dev & Regenerat Med, Chuo Ku, Kobe, Hyogo 6500017, Japan.
   [Niwa, Hitoshi] JST, CREST, Chiyoda Ku, Tokyo 1020075, Japan.
C3 RIKEN; Kobe University; Japan Science & Technology Agency (JST)
RP Niwa, H (corresponding author), RIKEN Ctr Dev Biol, Lab Pluripotent Cell Studies, Chuo Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan.
EM niwa@cdb.riken.jp
NR 30
TC 695
Z9 836
U1 1
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 118
EP 122
DI 10.1038/nature08113
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200041
PM 19571885
DA 2026-03-09
ER

PT J
AU TaufiqUrRahman
   Skupin, A
   Falcke, M
   Taylor, CW
AF TaufiqUrRahman
   Skupin, Alexander
   Falcke, Martin
   Taylor, Colin W.
TI Clustering of InsP3 receptors by InsP3 retunes their regulation by InsP3 and Ca2+
SO NATURE
LA English
DT Article
ID inositol trisphosphate receptor; channels ryanodine receptors; calcium-release channels; ip3 receptors; spatial-distribution; xenopus oocytes; inactivation; membrane; patterns; kinetics
AB The versatility of Ca2+ signals derives from their spatio-temporal organization(1,2). For Ca2+ signals initiated by inositol-1,4,5-trisphosphate (InsP(3)), this requires local interactions between InsP(3) receptors (InsP(3)Rs)(3,4) mediated by their rapid stimulation and slower inhibition(4) by cytosolic Ca2+. This allows hierarchical recruitment of Ca2+ release events as the InsP(3) concentration increases(5). Single InsP(3)Rs respond first, then clustered InsP(3)Rs open together giving a local 'Ca2+ puff', and as puffs become more frequent they ignite regenerative Ca2+ waves(1,5-9). Using nuclear patch-clamp recording(10), here we demonstrate that InsP(3)Rs are initially randomly distributed with an estimated separation of similar to 1 mu m. Low concentrations of InsP(3) cause InsP(3)Rs to aggregate rapidly and reversibly into small clusters of about four closely associated InsP(3)Rs. At resting cytosolic [Ca2+], clustered InsP(3)Rs open independently, but with lower open probability, shorter open time, and less InsP(3) sensitivity than lone InsP(3)Rs. Increasing cytosolic [Ca2+] reverses the inhibition caused by clustering, InsP(3)R gating becomes coupled, and the duration of multiple openings is prolonged. Clustering both exposes InsP(3)Rs to local Ca2+ rises and increases the effects of Ca2+. Dynamic regulation of clustering by InsP(3) retunes InsP(3)R sensitivity to InsP(3) and Ca2+, facilitating hierarchical recruitment of the elementary events that underlie all InsP(3)-evoked Ca2+ signals(3,5).
C1 [TaufiqUrRahman; Taylor, Colin W.] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England.
   [Skupin, Alexander; Falcke, Martin] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
   [Falcke, Martin] Helmholtz Ctr Berlin Mat & Energy, D-14109 Berlin, Germany.
C3 University of Cambridge; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB)
RP Taylor, CW (corresponding author), Univ Cambridge, Dept Pharmacol, Tennis Court Rd, Cambridge CB2 1PD, England.
EM cwt1000@cam.ac.uk
FU The Wellcome Trust; The Biotechnology and Biological Sciences Research Council; Jameel Family Trust; IRTG 'Genomics and Systems Biology of Molecular Networks' of the Deutsche Forschungsgemeinschaft
NR 26
TC 115
Z9 128
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 2
PY 2009
VL 458
IS 7238
BP 655
EP 659
DI 10.1038/nature07763
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200046
PM 19348050
DA 2026-03-09
ER

PT J
AU Tavani, M
   Bulgarelli, A
   Piano, G
   Sabatini, S
   Striani, E
   Evangelista, Y
   Trois, A
   Pooley, G
   Trushkin, S
   Nizhelskij, NA
   McCollough, M
   Koljonen, KII
   Pucella, G
   Giuliani, A
   Chen, AW
   Costa, E
   Vittorini, V
   Trifoglio, M
   Gianotti, F
   Argan, A
   Barbiellini, G
   Caraveo, P
   Cattaneo, PW
   Cocco, V
   Contessi, T
   D'Ammando, F
   Del Monte, E
   De Paris, G
   Di Cocco, G
   Di Persio, G
   Donnarumma, I
   Feroci, M
   Ferrari, A
   Fuschino, F
   Galli, M
   Labanti, C
   Lapshov, I
   Lazzarotto, F
   Lipari, P
   Longo, F
   Mattaini, E
   Marisaldi, M
   Mastropietro, M
   Mauri, A
   Mereghetti, S
   Morelli, E
   Morselli, A
   Pacciani, L
   Pellizzoni, A
   Perotti, F
   Picozza, P
   Pilia, M
   Prest, M
   Rapisarda, M
   Rappoldi, A
   Rossi, E
   Rubini, A
   Scalise, E
   Soffitta, P
   Vallazza, E
   Vercellone, S
   Zambra, A
   Zanello, D
   Pittori, C
   Verrecchia, F
   Giommi, P
   Colafrancesco, S
   Santolamazza, P
   Antonelli, A
   Salotti, L
AF Tavani, M.
   Bulgarelli, A.
   Piano, G.
   Sabatini, S.
   Striani, E.
   Evangelista, Y.
   Trois, A.
   Pooley, G.
   Trushkin, S.
   Nizhelskij, N. A.
   McCollough, M.
   Koljonen, K. I. I.
   Pucella, G.
   Giuliani, A.
   Chen, A. W.
   Costa, E.
   Vittorini, V.
   Trifoglio, M.
   Gianotti, F.
   Argan, A.
   Barbiellini, G.
   Caraveo, P.
   Cattaneo, P. W.
   Cocco, V.
   Contessi, T.
   D'Ammando, F.
   Del Monte, E.
   De Paris, G.
   Di Cocco, G.
   Di Persio, G.
   Donnarumma, I.
   Feroci, M.
   Ferrari, A.
   Fuschino, F.
   Galli, M.
   Labanti, C.
   Lapshov, I.
   Lazzarotto, F.
   Lipari, P.
   Longo, F.
   Mattaini, E.
   Marisaldi, M.
   Mastropietro, M.
   Mauri, A.
   Mereghetti, S.
   Morelli, E.
   Morselli, A.
   Pacciani, L.
   Pellizzoni, A.
   Perotti, F.
   Picozza, P.
   Pilia, M.
   Prest, M.
   Rapisarda, M.
   Rappoldi, A.
   Rossi, E.
   Rubini, A.
   Scalise, E.
   Soffitta, P.
   Vallazza, E.
   Vercellone, S.
   Zambra, A.
   Zanello, D.
   Pittori, C.
   Verrecchia, F.
   Giommi, P.
   Colafrancesco, S.
   Santolamazza, P.
   Antonelli, A.
   Salotti, L.
TI Extreme particle acceleration in the microquasar Cygnus X-3
SO NATURE
LA English
DT Article
ID false-discovery rate; x-ray; emission-lines; radio; jet
AB Super-massive black holes in active galaxies can accelerate particles to relativistic energies(1), producing jets with associated c-ray emission. Galactic 'microquasars', which are binary systems consisting of a neutron star or stellar-mass black hole accreting gas from a companion star, also produce relativistic jets, generally together with radio flares(2). Apart from an isolated event detected(3) in Cygnus X-1, there has hitherto been no systematic evidence for the acceleration of particles to gigaelectronvolt or higher energies in a microquasar, with the consequence that we are as yet unsure about the mechanism of jet energization. Here we report four gamma-ray flares with energies above 100 MeV from the microquasar Cygnus X-3 (an exceptional X-ray binary(4-6) that sporadically produces radio jets(7-9)). There is a clear pattern of temporal correlations between the c-ray flares and transitional spectral states of the radio-frequency and X-ray emission. Particle acceleration occurred a few days before radio-jet ejections for two of the four flares, meaning that the process of jet formation implies the production of very energetic particles. In Cygnus X-3, particle energies during the flares can be thousands of times higher than during quiescent states.
C1 [Tavani, M.; Piano, G.; Evangelista, Y.; Trois, A.; Costa, E.; Vittorini, V.; Argan, A.; D'Ammando, F.; Del Monte, E.; De Paris, G.; Di Persio, G.; Donnarumma, I.; Feroci, M.; Lazzarotto, F.; Pacciani, L.; Rubini, A.; Scalise, E.; Soffitta, P.] INAF IASF Roma, I-00133 Rome, Italy.
   [Tavani, M.; Sabatini, S.; Striani, E.; Cocco, V.; D'Ammando, F.; Picozza, P.] Univ Roma Tor Vergata, Dipartimento Fis, I-00133 Rome, Italy.
   [Tavani, M.; Chen, A. W.; Vittorini, V.; Barbiellini, G.; Ferrari, A.; Zambra, A.] Consorzio Interuniv Fis Spaziale, I-10133 Turin, Italy.
   [Tavani, M.; Piano, G.; Sabatini, S.; Striani, E.; Morselli, A.; Picozza, P.] INFN Roma Tor Vergata, I-00133 Rome, Italy.
   [Bulgarelli, A.; Trifoglio, M.; Gianotti, F.; Di Cocco, G.; Fuschino, F.; Labanti, C.; Marisaldi, M.; Mauri, A.; Morelli, E.] INAF IASF Bologna, I-40129 Bologna, Italy.
   [Pooley, G.] Univ Cambridge, Cavendish Lab, Astrophys Grp, Cambridge CB3 0HE, England.
   [Trushkin, S.; Nizhelskij, N. A.] RAS, Special Astrophys Observ, Nizhnii Arkhyz 36916, Russia.
   [McCollough, M.] Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Koljonen, K. I. I.] TKK Metsahovi Radio Observ, Kylmala 02540, Finland.
   [Pucella, G.; Rapisarda, M.] ENEA Frascati, I-00044 Frascati, RM, Italy.
   [Giuliani, A.; Chen, A. W.; Caraveo, P.; Contessi, T.; Mereghetti, S.; Perotti, F.; Zambra, A.] INAF IASF Milano, I-20133 Milan, Italy.
   [Barbiellini, G.; Longo, F.] Univ Trieste, Dipartimento Fis, I-34127 Trieste, Italy.
   [Barbiellini, G.; Longo, F.; Vallazza, E.] INFN Trieste, I-34012 Trieste, Italy.
   [Cattaneo, P. W.; Rappoldi, A.] INFN Pavia, I-27100 Pavia, Italy.
   [Ferrari, A.] Univ Turin, Dipartimento Fis, I-10125 Turin, Italy.
   [Galli, M.] ENEA Bologna, I-40128 Bologna, Italy.
   [Lapshov, I.] IKI, Moscow 117997, Russia.
   [Lipari, P.; Zanello, D.] INFN Roma 1, I-00185 Rome, Italy.
   [Lipari, P.; Zanello, D.] Univ Roma La Sapienza, Dipartimento Fis, I-00185 Rome, Italy.
   [Mastropietro, M.] CNR, IMIP, I-00016 Rome, Italy.
   [Pellizzoni, A.; Pilia, M.] INAF Osservatorio Astron Cagliari, I-09012 Cagliari, Italy.
   [Pilia, M.; Prest, M.] Univ Insubria, Dipartimento Fis, I-22100 Como, Italy.
   [Vercellone, S.] INAF IASF Palermo, I-90146 Palermo, Italy.
   [Pittori, C.; Verrecchia, F.; Giommi, P.; Colafrancesco, S.; Santolamazza, P.] ESRIN, ASI Sci Data Ctr, I-00044 Frascati, Italy.
   [Antonelli, A.] Osserv Astron Roma, I-00040 Monte Porzio Catone, Italy.
   [Salotti, L.] Agenzia Spaziale Italiana, I-00198 Rome, Italy.
C3 Istituto Nazionale Astrofisica (INAF); University of Rome Tor Vergata; University of Rome Tor Vergata; Istituto Nazionale Astrofisica (INAF); University of Cambridge; Russian Academy of Sciences; Special Astrophysics Observatory of the Russian Academy of Sciences; Smithsonian Institution; Aalto University; Italian National Agency New Technical Energy & Sustainable Economics Development; Italian National Agency New Technical Energy & Sustainable Economics Development; Istituto Nazionale Astrofisica (INAF); University of Trieste; Istituto Nazionale di Fisica Nucleare (INFN); University of Pavia; Istituto Nazionale di Fisica Nucleare (INFN); University of Turin; Italian National Agency New Technical Energy & Sustainable Economics Development; Italian National Agency New Technical Energy & Sustainable Economics Development; Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences; Istituto Nazionale di Fisica Nucleare (INFN); Sapienza University Rome; Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale Astrofisica (INAF); University of Insubria; Istituto Nazionale Astrofisica (INAF); European Space Agency; European Space Research Institute; Agenzia Spaziale Italiana (ASI); Istituto Nazionale Astrofisica (INAF); Agenzia Spaziale Italiana (ASI)
RP Tavani, M (corresponding author), INAF IASF Roma, Via Fosso Cavaliere 100, I-00133 Rome, Italy.
EM pi.agile@iasf-roma.inaf.it
FU Italian Institute of Astrophysics and the Italian Institute of Nuclear Physics
NR 26
TC 168
Z9 182
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 3
PY 2009
VL 462
IS 7273
BP 620
EP 623
DI 10.1038/nature08578
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900034
PM 19935645
DA 2026-03-09
ER

PT J
AU Chen, MJ
   Yokomizo, T
   Zeigler, BM
   Dzierzak, E
   Speck, NA
AF Chen, Michael J.
   Yokomizo, Tomomasa
   Zeigler, Brandon M.
   Dzierzak, Elaine
   Speck, Nancy A.
TI Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter
SO NATURE
LA English
DT Article
ID stem-cells; mouse embryo; adult hematopoiesis; fetal liver; murine allantois; ve-cadherin; expression; vasculogenesis; circulation; compartment
AB Haematopoietic stem cells ( HSCs) are the founder cells of the adult haematopoietic system, and thus knowledge of the molecular program directing their generation during development is important for regenerative haematopoietic strategies. Runx1 is a pivotal transcription factor required for HSC generation in the vascular regions of the mouse conceptus - the aorta, vitelline and umbilical arteries, yolk sac and placenta(1,2). It is thought that HSCs emerge from vascular endothelial cells through the formation of intra-arterial clusters(3) and that Runx1 functions during the transition from 'haemogenic endothelium' to HSCs4,5. Here we show by conditional deletion that Runx1 activity in vascular- endothelial- cadherin-positive endothelial cells is indeed essential for intra-arterial cluster, haematopoietic progenitor and HSC formation in mice. In contrast, Runx1 is not required in cells expressing Vav1, one of the first pan- haematopoietic genes expressed in HSCs. Collectively these data show that Runx1 function is essential in endothelial cells for haematopoietic progenitor and HSC formation from the vasculature, but its requirement ends once or before Vav is expressed.
C1 [Chen, Michael J.; Zeigler, Brandon M.; Speck, Nancy A.] Dartmouth Med Sch, Dept Biochem, Hanover, NH 03755 USA.
   [Chen, Michael J.] Dartmouth Med Sch, Dept Genet, Hanover, NH 03755 USA.
   [Yokomizo, Tomomasa; Dzierzak, Elaine] Erasmus MC, Dept Cell Biol & Genet, NL-3000 CA Rotterdam, Netherlands.
C3 Dartmouth College; Dartmouth College; Erasmus University Rotterdam; Erasmus MC
RP Speck, NA (corresponding author), Univ Penn, Sch Med, Abramson Family Canc Res Inst, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
EM nancyas@exchange.upenn.edu
FU Norris Cotton Cancer Center [NIH CA23108]; Abramson Family Cancer Research Institute;  [R01HL091724];  [R01DK54077];  [T32 AI-07519]; National Cancer Institute [P30CA023108] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [R01HL091724] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007519] Funding Source: NIH RePORTER
NR 31
TC 815
Z9 1001
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 FEB 12
PY 2009
VL 457
IS 7231
BP 887
EP 891
DI 10.1038/nature07619
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700046
PM 19129762
DA 2026-03-09
ER

PT J
AU Royer, JR
   Evans, DJ
   Oyarte, L
   Guo, Q
   Kapit, E
   Möbius, ME
   Waitukaitis, SR
   Jaeger, HM
AF Royer, John R.
   Evans, Daniel J.
   Oyarte, Loreto
   Guo, Qiti
   Kapit, Eliot
   Moebius, Matthias E.
   Waitukaitis, Scott R.
   Jaeger, Heinrich M.
TI High-speed tracking of rupture and clustering in freely falling granular streams
SO NATURE
LA English
DT Article
ID molecular-dynamics; collision; breakup; spheres
AB Thin streams of liquid commonly break up into characteristic droplet patterns owing to the surface-tension-driven Plateau Rayleigh instability(1-3). Very similar patterns are observed when initially uniform streams of dry granular material break up into clusters of grains(4-6), even though flows of macroscopic particles are considered to lack surface tension(7,8). Recent studies on freely falling granular streams tracked fluctuations in the stream profile(9), but the clustering mechanism remained unresolved because the full evolution of the instability could not be observed. Here we demonstrate that the cluster formation is driven by minute, nanoNewton cohesive forces that arise from a combination of van der Waals interactions and capillary bridges between nanometre-scale surface asperities. Our experiments involve high-speed video imaging of the granular stream in the co-moving frame, control over the properties of the grain surfaces and the use of atomic force microscopy to measure grain-grain interactions. The cohesive forces that we measure correspond to an equivalent surface tension five orders of magnitude below that of ordinary liquids. We find that the shapes of these weakly cohesive, non-thermal clusters of macroscopic particles closely resemble droplets resulting from thermally induced rupture of liquid nanojets(10-12).
C1 [Royer, John R.; Evans, Daniel J.; Oyarte, Loreto; Guo, Qiti; Kapit, Eliot; Moebius, Matthias E.; Waitukaitis, Scott R.; Jaeger, Heinrich M.] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA.
   [Royer, John R.; Evans, Daniel J.; Oyarte, Loreto; Guo, Qiti; Kapit, Eliot; Moebius, Matthias E.; Waitukaitis, Scott R.; Jaeger, Heinrich M.] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Royer, JR (corresponding author), Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM jroyer@uchicago.edu
FU NSF through its MRSEC programme; Inter-American Materials Collaboration Chicago-Chile; Keck Initiative for Ultrafast Imaging at the University of Chicago
NR 30
TC 183
Z9 206
U1 3
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1110
EP 1113
DI 10.1038/nature08115
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700039
PM 19553995
DA 2026-03-09
ER

PT J
AU Koshiba-Takeuchi, K
   Mori, AD
   Kaynak, BL
   Cebra-Thomas, J
   Sukonnik, T
   Georges, RO
   Latham, S
   Beck, L
   Henkelman, RM
   Black, BL
   Olson, EN
   Wade, J
   Takeuchi, JK
   Nemer, M
   Gilbert, SF
   Bruneau, BG
AF Koshiba-Takeuchi, Kazuko
   Mori, Alessandro D.
   Kaynak, Bogac L.
   Cebra-Thomas, Judith
   Sukonnik, Tatyana
   Georges, Romain O.
   Latham, Stephany
   Beck, Laural
   Henkelman, R. Mark
   Black, Brian L.
   Olson, Eric N.
   Wade, Juli
   Takeuchi, Jun K.
   Nemer, Mona
   Gilbert, Scott F.
   Bruneau, Benoit G.
TI Reptilian heart development and the molecular basis of cardiac chamber evolution
SO NATURE
LA English
DT Article
ID ventricular septum; tbx5; expression; phylogeny; turtle; growth; roles
AB The emergence of terrestrial life witnessed the need for more sophisticated circulatory systems. This has evolved in birds, mammals and crocodilians into complete septation of the heart into left and right sides, allowing separate pulmonary and systemic circulatory systems, a key requirement for the evolution of endothermy(1-3). However, the evolution of the amniote heart is poorly understood. Reptilian hearts have been the subject of debate in the context of the evolution of cardiac septation: do they possess a single ventricular chamber or two incompletely septated ventricles(4-7)? Here we examine heart development in the red-eared slider turtle, Trachemys scripta elegans (a chelonian), and the green anole, Anolis carolinensis (a squamate), focusing on gene expression in the developing ventricles. Both reptiles initially form a ventricular chamber that homogenously expresses the T-box transcription factor gene Tbx5. In contrast, in birds and mammals, Tbx5 is restricted to left ventricle precursors(8,9). In later stages, Tbx5 expression in the turtle (but not anole) heart is gradually restricted to a distinct left ventricle, forming a left-right gradient. This suggests that Tbx5 expression was refined during evolution to pattern the ventricles. In support of this hypothesis, we show that loss of Tbx5 in the mouse ventricle results in a single chamber lacking distinct identity, indicating a requirement for Tbx5 in septation. Importantly, misexpression of Tbx5 throughout the developing myocardium to mimic the reptilian expression pattern also results in a single mispatterned ventricular chamber lacking septation. Thus ventricular septation is established by a steep and correctly positioned Tbx5 gradient. Our findings provide a molecular mechanism for the evolution of the amniote ventricle, and support the concept that altered expression of developmental regulators is a key mechanism of vertebrate evolution.
C1 [Koshiba-Takeuchi, Kazuko; Mori, Alessandro D.; Kaynak, Bogac L.; Sukonnik, Tatyana; Bruneau, Benoit G.] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Koshiba-Takeuchi, Kazuko; Mori, Alessandro D.; Kaynak, Bogac L.; Sukonnik, Tatyana; Black, Brian L.; Bruneau, Benoit G.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA.
   [Koshiba-Takeuchi, Kazuko; Mori, Alessandro D.; Kaynak, Bogac L.; Sukonnik, Tatyana; Bruneau, Benoit G.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
   [Koshiba-Takeuchi, Kazuko; Takeuchi, Jun K.] Tokyo Inst Technol, Div Cardiovasc Res, Global Edge Inst, Yokohama, Kanagawa 2268503, Japan.
   [Mori, Alessandro D.; Bruneau, Benoit G.] Hosp Sick Children, Program Stem Cell & Dev Biol, Toronto, ON M5G 1X8, Canada.
   [Mori, Alessandro D.; Bruneau, Benoit G.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Cebra-Thomas, Judith] Millersville Univ Pennsylvania, Dept Biol, Millersville, PA 17551 USA.
   [Georges, Romain O.; Nemer, Mona] Univ Montreal, Programme Biol Mol, Inst Rech Clin Montreal, Montreal, PQ H3C 3J7, Canada.
   [Latham, Stephany; Beck, Laural; Wade, Juli] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA.
   [Latham, Stephany; Beck, Laural; Wade, Juli] Michigan State Univ, Program Neurosci, E Lansing, MI 48824 USA.
   [Henkelman, R. Mark] Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON M5G 1X8, Canada.
   [Henkelman, R. Mark] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada.
   [Black, Brian L.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Olson, Eric N.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Nemer, Mona] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada.
   [Gilbert, Scott F.] Swarthmore Coll, Dept Biol, Swarthmore, PA 19081 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; Institute of Science Tokyo; Tokyo Institute of Technology; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Pennsylvania State System of Higher Education (PASSHE); Millersville University of Pennsylvania; Universite de Montreal; Institut de Recherche Clinique de Montreal (IRCM); Michigan State University; Michigan State University; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of California System; University of California San Francisco; University of Texas System; University of Texas Southwestern Medical Center; University of Ottawa; Swarthmore College
RP Bruneau, BG (corresponding author), Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
EM bbruneau@gladstone.ucsf.edu
FU March of Dimes Birth Defects Foundation; J. David Gladstone Institutes; William H. Younger; National Institutes of Health [P01HL089707]; Natural Sciences and Engineering Research Council of Canada; Heart and Stroke Richard Lewar Centre for Excellence; University of Toronto; Ontario Graduate Scholarship; Fumi Yamamura Memorial Foundation; MEXT; Sumitomo Foundation and Nakajima Foundation; Canada Research Chair in Imaging; Heart and Stroke foundation of Canada and the Canadian Institutes for Health Research; National Science Foundation [RUI-0748508, IOS-0742833]; National Institutes of Health/National Center for Research Resources [C06 RR018928]; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0748508] Funding Source: National Science Foundation
NR 30
TC 119
Z9 147
U1 0
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 95
EP U99
DI 10.1038/nature08324
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800037
PM 19727199
DA 2026-03-09
ER

PT J
AU Schraml, BU
   Hildner, K
   Ise, W
   Lee, WL
   Smith, WAE
   Solomon, B
   Sahota, G
   Sim, J
   Mukasa, R
   Cemerski, S
   Hatton, RD
   Stormo, GD
   Weaver, CT
   Russell, JH
   Murphy, TL
   Murphy, KM
AF Schraml, Barbara U.
   Hildner, Kai
   Ise, Wataru
   Lee, Wan-Ling
   Smith, Whitney A. -E.
   Solomon, Ben
   Sahota, Gurmukh
   Sim, Julia
   Mukasa, Ryuta
   Cemerski, Saso
   Hatton, Robin D.
   Stormo, Gary D.
   Weaver, Casey T.
   Russell, John H.
   Murphy, Theresa L.
   Murphy, Kenneth M.
TI The AP-1 transcription factor Batf controls TH17 differentiation
SO NATURE
LA English
DT Article
ID ror-gamma-t; aryl-hydrocarbon receptor; activator protein-1; cell-differentiation; negative regulator; transgenic mice; th17 cells; in-vitro; b-atf; il-21
AB Activator protein 1 (AP-1, also known as JUN) transcription factors are dimers of JUN, FOS, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains(1). Many AP-1 proteins contain defined transcriptional activation domains, but BATF and the closely related BATF3 (refs 2, 3) contain only a basic region and leucine zipper, and are considered to be inhibitors of AP-1 activity(3-8). Here we show that Batf is required for the differentiation of IL17-producing T helper (T(H)17) cells(9). T(H)17 cells comprise a CD4(+) T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity(10-13). Batf(-/-) mice have normal T(H)1 and T(H)2 differentiation, but show a defect in T(H)17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. Batf(-/-) T cells fail to induce known factors required for T(H)17 differentiation, such as ROR gamma t(11) (encoded by Rorc) and the cytokine IL21 (refs 14-17). Neither the addition of IL21 nor the overexpression of ROR gamma t fully restores IL17 production in Batf(-/-) T cells. The Il17 promoter is BATF-responsive, and after T(H)17 differentiation, BATF binds conserved intergenic elements in the Il17a-Il17f locus and to the Il17, Il21 and Il22 (ref. 18) promoters. These results demonstrate that the AP-1 protein BATF has a critical role in T(H)17 differentiation.
C1 [Schraml, Barbara U.; Hildner, Kai; Ise, Wataru; Lee, Wan-Ling; Smith, Whitney A. -E.; Solomon, Ben; Cemerski, Saso; Murphy, Theresa L.; Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Hildner, Kai; Ise, Wataru; Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
   [Sahota, Gurmukh; Stormo, Gary D.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Sim, Julia; Russell, John H.] Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA.
   [Mukasa, Ryuta; Hatton, Robin D.; Weaver, Casey T.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
C3 Washington University (WUSTL); Howard Hughes Medical Institute; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); University of Alabama System; University of Alabama Birmingham
RP Murphy, KM (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM kmurphy@wustl.edu
FU Howard Hughes Medical Institute; National Institutes of Health [HG00249, GM07200, AI035783, AR049293]; Daiichi-Sankyo Co. Ltd; National Institute of General Medical Sciences [T32GM007200] Funding Source: NIH RePORTER
NR 33
TC 500
Z9 606
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 405
EP U125
DI 10.1038/nature08114
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000041
PM 19578362
DA 2026-03-09
ER

PT J
AU Barbie, DA
   Tamayo, P
   Boehm, JS
   Kim, SY
   Moody, SE
   Dunn, IF
   Schinzel, AC
   Sandy, P
   Meylan, E
   Scholl, C
   Fröhling, S
   Chan, EM
   Sos, ML
   Michel, K
   Mermel, C
   Silver, SJ
   Weir, BA
   Reiling, JH
   Sheng, Q
   Gupta, PB
   Wadlow, RC
   Le, H
   Hoersch, S
   Wittner, BS
   Ramaswamy, S
   Livingston, DM
   Sabatini, DM
   Meyerson, M
   Thomas, RK
   Lander, ES
   Mesirov, JP
   Root, DE
   Gilliland, DG
   Jacks, T
   Hahn, WC
AF Barbie, David A.
   Tamayo, Pablo
   Boehm, Jesse S.
   Kim, So Young
   Moody, Susan E.
   Dunn, Ian F.
   Schinzel, Anna C.
   Sandy, Peter
   Meylan, Etienne
   Scholl, Claudia
   Froehling, Stefan
   Chan, Edmond M.
   Sos, Martin L.
   Michel, Kathrin
   Mermel, Craig
   Silver, Serena J.
   Weir, Barbara A.
   Reiling, Jan H.
   Sheng, Qing
   Gupta, Piyush B.
   Wadlow, Raymond C.
   Le, Hanh
   Hoersch, Sebastian
   Wittner, Ben S.
   Ramaswamy, Sridhar
   Livingston, David M.
   Sabatini, David M.
   Meyerson, Matthew
   Thomas, Roman K.
   Lander, Eric S.
   Mesirov, Jill P.
   Root, David E.
   Gilliland, D. Gary
   Jacks, Tyler
   Hahn, William C.
TI Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
SO NATURE
LA English
DT Article
ID nf-kappa-b; tumor-cell survival; lung adenocarcinoma; essential genes; k-ras; activation; screen; phosphorylation; classification; apoptosis
AB The proto-oncogene KRAS is mutated in a wide array of human cancers, most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. A complementary strategy for targeting KRAS is to identify gene products that, when inhibited, result in cell death only in the presence of an oncogenic allele(1,2). Here we have used systematic RNA interference to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical I kappa B kinase TBK1 was selectively essential in cells that contain mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF-kappa B anti-apoptotic signals involving c-Rel and BCL-XL (also known as BCL2L1) that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations indicate that TBK1 and NF-kappa B signalling are essential in KRAS mutant tumours, and establish a general approach for the rational identification of co-dependent pathways in cancer.
C1 [Barbie, David A.; Kim, So Young; Moody, Susan E.; Dunn, Ian F.; Schinzel, Anna C.; Mermel, Craig; Sheng, Qing; Livingston, David M.; Meyerson, Matthew; Gilliland, D. Gary; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Kim, So Young; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Barbie, David A.; Tamayo, Pablo; Boehm, Jesse S.; Moody, Susan E.; Dunn, Ian F.; Schinzel, Anna C.; Chan, Edmond M.; Mermel, Craig; Silver, Serena J.; Weir, Barbara A.; Gupta, Piyush B.; Wadlow, Raymond C.; Le, Hanh; Wittner, Ben S.; Ramaswamy, Sridhar; Sabatini, David M.; Meyerson, Matthew; Lander, Eric S.; Mesirov, Jill P.; Root, David E.; Gilliland, D. Gary; Jacks, Tyler; Hahn, William C.] Broad Inst Harvard, Cambridge, MA 02142 USA.
   [Barbie, David A.; Tamayo, Pablo; Boehm, Jesse S.; Moody, Susan E.; Dunn, Ian F.; Schinzel, Anna C.; Chan, Edmond M.; Mermel, Craig; Silver, Serena J.; Weir, Barbara A.; Gupta, Piyush B.; Wadlow, Raymond C.; Le, Hanh; Wittner, Ben S.; Ramaswamy, Sridhar; Sabatini, David M.; Meyerson, Matthew; Lander, Eric S.; Mesirov, Jill P.; Root, David E.; Gilliland, D. Gary; Jacks, Tyler; Hahn, William C.] MIT, Cambridge, MA 02142 USA.
   [Barbie, David A.; Wadlow, Raymond C.; Wittner, Ben S.; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
   [Scholl, Claudia; Froehling, Stefan; Gilliland, D. Gary; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Sandy, Peter; Meylan, Etienne; Reiling, Jan H.; Sabatini, David M.; Lander, Eric S.; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Sandy, Peter; Meylan, Etienne; Hoersch, Sebastian; Jacks, Tyler] Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
   [Sos, Martin L.; Michel, Kathrin; Thomas, Roman K.] Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany.
   [Sos, Martin L.; Michel, Kathrin; Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany.
   [Reiling, Jan H.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Sabatini, David M.; Gilliland, D. Gary; Jacks, Tyler] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany.
   [Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany.
   [Thomas, Roman K.] Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Max Planck Society; University of Cologne; Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; University of Cologne; University of Cologne; Max Planck Society
RP Hahn, WC (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM william_hahn@dfci.harvard.edu
FU US National Cancer Institute [R33 CA128625, R01 CA130988]; NIH [T32 CA09172-33]; Starr Cancer Consortium [I1-A11]; Susan Madden Fund; ASCO YIA; Department of Defense Prostate Cancer Postdoctoral Fellowship; Brain Science Foundation Fellowship; Deutsche Krebshilfe [107954]; Fritz-Thyssen-Stiftung [10.08.2.175]; German Ministry of Science and Education [01GS08100]; National Cancer Institute [R01CA129105, T32CA009172] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER; Academy of Finland (AKA) [107954] Funding Source: Academy of Finland (AKA)
NR 31
TC 2914
Z9 3323
U1 6
U2 137
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 5
PY 2009
VL 462
IS 7269
BP 108
EP U122
DI 10.1038/nature08460
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200042
PM 19847166
DA 2026-03-09
ER

PT J
AU Bridgham, JT
   Ortlund, EA
   Thornton, JW
AF Bridgham, Jamie T.
   Ortlund, Eric A.
   Thornton, Joseph W.
TI An epistatic ratchet constrains the direction of glucocorticoid receptor evolution
SO NATURE
LA English
DT Article
ID dollos law; irreversible evolution; reversibility; software; proteins
AB The extent to which evolution is reversible has long fascinated biologists(1-8). Most previous work on the reversibility of morphological and life-history evolution(9-13) has been indecisive, because of uncertainty and bias in the methods used to infer ancestral states for such characters(14,15). Further, despite theoretical work on the factors that could contribute to irreversibility(1,8,16), there is little empirical evidence on its causes, because sufficient understanding of the mechanistic basis for the evolution of new or ancestral phenotypes is seldom available(3,8,17). By studying the reversibility of evolutionary changes in protein structure and function, these limitations can be overcome. Here we show, using the evolution of hormone specificity in the vertebrate glucocorticoid receptor as a case-study, that the evolutionary path by which this protein acquired its new function soon became inaccessible to reverse exploration. Using ancestral gene reconstruction, protein engineering and X-ray crystallography, we demonstrate that five subsequent 'restrictive' mutations, which optimized the new specificity of the glucocorticoid receptor, also destabilized elements of the protein structure that were required to support the ancestral conformation. Unless these ratchet-like epistatic substitutions are restored to their ancestral states, reversing the key function-switching mutations yields a non-functional protein. Reversing the restrictive substitutions first, however, does nothing to enhance the ancestral function. Our findings indicate that even if selection for the ancestral function were imposed, direct reversal would be extremely unlikely, suggesting an important role for historical contingency in protein evolution.
C1 [Bridgham, Jamie T.; Thornton, Joseph W.] Univ Oregon, Ctr Ecol & Evolutionary Biol, Eugene, OR 97403 USA.
   [Thornton, Joseph W.] Univ Oregon, Howard Hughes Med Inst, Eugene, OR 97403 USA.
   [Ortlund, Eric A.] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30332 USA.
C3 University of Oregon; Howard Hughes Medical Institute; University of Oregon; Emory University
RP Thornton, JW (corresponding author), Univ Oregon, Ctr Ecol & Evolutionary Biol, Eugene, OR 97403 USA.
EM joet@uoregon.edu
FU National Science Foundation [IOB-0546906]; National Institutes of Health [R01-GM081592, F32-GM074398]; Sloan Foundation Fellowship
NR 35
TC 322
Z9 397
U1 1
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 24
PY 2009
VL 461
IS 7263
BP 515
EP U78
DI 10.1038/nature08249
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900038
PM 19779450
DA 2026-03-09
ER

PT J
AU Elliott, MR
   Chekeni, FB
   Trampont, PC
   Lazarowski, ER
   Kadl, A
   Walk, SF
   Park, D
   Woodson, RI
   Ostankovich, M
   Sharma, P
   Lysiak, JJ
   Harden, TK
   Leitinger, N
   Ravichandran, KS
AF Elliott, Michael R.
   Chekeni, Faraaz B.
   Trampont, Paul C.
   Lazarowski, Eduardo R.
   Kadl, Alexandra
   Walk, Scott F.
   Park, Daeho
   Woodson, Robin I.
   Ostankovich, Marina
   Sharma, Poonam
   Lysiak, Jeffrey J.
   Harden, T. Kendall
   Leitinger, Norbert
   Ravichandran, Kodi S.
TI Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance
SO NATURE
LA English
DT Article
ID extracellular nucleotides; receptor subtypes; epithelial-cells; inflammation; chemotaxis; engulfment; elegans; thymus; death; utp
AB Phagocytic removal of apoptotic cells occurs efficiently in vivo such that even in tissues with significant apoptosis, very few apoptotic cells are detectable(1). This is thought to be due to the release of 'find-me' signals by apoptotic cells that recruit motile phagocytes such as monocytes, macrophages and dendritic cells, leading to the prompt clearance of the dying cells(2). However, the identity and in vivo relevance of such find-me signals are not well understood. Here, through several lines of evidence, we identify extracellular nucleotides as a critical apoptotic cell find-me signal. We demonstrate the caspase-dependent release of ATP and UTP (in equimolar quantities) during the early stages of apoptosis by primary thymocytes and cell lines. Purified nucleotides at these concentrations were sufficient to induce monocyte recruitment comparable to that of apoptotic cell supernatants. Enzymatic removal of ATP and UTP (by apyrase or the expression of ectopic CD39) abrogated the ability of apoptotic cell supernatants to recruit monocytes in vitro and in vivo. We then identified the ATP/UTP receptor P2Y(2) as a critical sensor of nucleotides released by apoptotic cells using RNA interference-mediated depletion studies in monocytes, and macrophages from P2Y(2)-null mice(3). The relevance of nucleotides in apoptotic cell clearance in vivo was revealed by two approaches. First, in a murine air-pouch model, apoptotic cell supernatants induced a threefold greater recruitment of monocytes and macrophages than supernatants from healthy cells did; this recruitment was abolished by depletion of nucleotides and was significantly decreased in P2Y(2)(-/-) ( also known as P2ry(2)(-/-)) mice. Second, clearance of apoptotic thymocytes was significantly impaired by either depletion of nucleotides or interference with P2Y receptor function ( by pharmacological inhibition or in P2Y(2)(-/-) mice). These results identify nucleotides as a critical find-me cue released by apoptotic cells to promote P2Y(2)-dependent recruitment of phagocytes, and provide evidence for a clear relationship between a find-me signal and efficient corpse clearance in vivo.
C1 [Elliott, Michael R.; Chekeni, Faraaz B.; Trampont, Paul C.; Walk, Scott F.; Park, Daeho; Ravichandran, Kodi S.] Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
   [Elliott, Michael R.; Trampont, Paul C.; Walk, Scott F.; Park, Daeho; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
   [Chekeni, Faraaz B.; Leitinger, Norbert] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA.
   [Kadl, Alexandra; Ostankovich, Marina; Sharma, Poonam; Leitinger, Norbert] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
   [Woodson, Robin I.; Lysiak, Jeffrey J.] Univ Virginia, Dept Urol, Charlottesville, VA 22908 USA.
   [Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
   [Lazarowski, Eduardo R.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA.
   [Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 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; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
RP Ravichandran, KS (corresponding author), Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
EM ravi@virginia.edu
FU National Institutes of Health; American Cancer Society; University of Virginia Farrow Fellowship; National Institute of Allergy and Infectious Diseases [T32AI055432] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007267] Funding Source: NIH RePORTER
NR 30
TC 1341
Z9 1573
U1 2
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 10
PY 2009
VL 461
IS 7261
BP 282
EP U165
DI 10.1038/nature08296
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600048
PM 19741708
DA 2026-03-09
ER

PT J
AU Gostissa, M
   Yan, CT
   Bianco, JM
   Cogné, M
   Pinaud, E
   Alt, FW
AF Gostissa, Monica
   Yan, Catherine T.
   Bianco, Julia M.
   Cogne, Michel
   Pinaud, Eric
   Alt, Frederick W.
TI Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3′ regulatory region
SO NATURE
LA English
DT Article
ID heavy-chain locus; class-switch recombination; b-cell development; chromosomal translocations; v(d)j recombination; gene amplification; transgenic mice; dna breaks; end; mechanism
AB B-cell malignancies, such as human Burkitt's lymphoma, often contain translocations that link c-myc or other proto-oncogenes to the immunoglobulin heavy chain locus (IgH, encoded by Igh)(1). The nature of elements that activate oncogenes within such translocations has been a long-standing question. Translocations within Igh involve DNA double-strand breaks initiated either by the RAG1/2 endonuclease during variable, diversity and joining gene segment (V(D)J) recombination, or by activation-induced cytidine deaminase (AID, also known as AICDA) during class switch recombination (CSR)(2-4). V(D)J recombination in progenitor B (pro-B) cells assembles Igh variable region exons upstream of mu constant region (C mu) exons, which are the first of several sets of CH exons ('C-H genes') within a CH locus that span several hundred kilobases (kb)(5,6). In mature B cells, CSR deletes C mu and replaces it with a downstream C-H gene(6). An intronic enhancer (iE mu) between the variable region exons and C mu promotes V(D)J recombination in developing B cells(7). Furthermore, the Igh 3' regulatory region (Igh3' RR) lies downstream of the C-H locus and modulates CSR by long-range transcriptional enhancement of C-H genes(8-10). Transgenic mice bearing iE mu or Igh3' RR sequences fused to c-myc are predisposed to B lymphomas, demonstrating that such elements can confer oncogenic c-myc expression(11-16). However, in many B-cell lymphomas, Igh-c-myc translocations delete iE mu and place c-myc up to 200 kb upstream of the Igh3' RR1. Here we address the oncogenic role of the Igh3' RR by inactivating it in two distinct mouse models for B-cell lymphoma with Igh-c-myc translocations. We show that the Igh3' RR is dispensable for pro-B-cell lymphomas with V( D) J recombination-initiated translocations, but is required for peripheral B-cell lymphomas with CSR-associated translocations. As the Igh3' RR is not required for CSR-associated Igh breaks or Igh-c-myc translocations in peripheral B-cell lymphoma progenitors, we conclude that this regulatory region confers oncogenic activity by long-range and developmental stage-specific activation of translocated c-myc genes.
C1 [Gostissa, Monica; Yan, Catherine T.; Bianco, Julia M.; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Gostissa, Monica; Yan, Catherine T.; Bianco, Julia M.; Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
   [Gostissa, Monica; Yan, Catherine T.; Bianco, Julia M.; Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
   [Gostissa, Monica; Yan, Catherine T.; Bianco, Julia M.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Cogne, Michel; Pinaud, Eric] Univ Limoges, CNRS, Fac Med, UMR 6101, Limoges, France.
C3 Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School; Centre National de la Recherche Scientifique (CNRS); Universite de Limoges
RP Alt, FW (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
FU National Institutes of Health (NIH) [CA92625]; Leukemia and Lymphoma Society of America (LLS) SCORE; NCI; de Villiers International Achievement Award; Fondation pour la Recherche Medicale; Howard Hughes Medical Institute
NR 30
TC 71
Z9 85
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 803
EP U128
DI 10.1038/nature08633
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900042
PM 20010689
DA 2026-03-09
ER

PT J
AU Soucy, TA
   Smith, PG
   Milhollen, MA
   Berger, AJ
   Gavin, JM
   Adhikari, S
   Brownell, JE
   Burke, KE
   Cardin, DP
   Critchley, S
   Cullis, CA
   Doucette, A
   Garnsey, JJ
   Gaulin, JL
   Gershman, RE
   Lublinsky, AR
   McDonald, A
   Mizutani, H
   Narayanan, U
   Olhava, EJ
   Peluso, S
   Rezaei, M
   Sintchak, MD
   Talreja, T
   Thomas, MP
   Traore, T
   Vyskocil, S
   Weatherhead, GS
   Yu, J
   Zhang, J
   Dick, LR
   Claiborne, CF
   Rolfe, M
   Bolen, JB
   Langston, SP
AF Soucy, Teresa A.
   Smith, Peter G.
   Milhollen, Michael A.
   Berger, Allison J.
   Gavin, James M.
   Adhikari, Sharmila
   Brownell, James E.
   Burke, Kristine E.
   Cardin, David P.
   Critchley, Stephen
   Cullis, Courtney A.
   Doucette, Amanda
   Garnsey, James J.
   Gaulin, Jeffrey L.
   Gershman, Rachel E.
   Lublinsky, Anna R.
   McDonald, Alice
   Mizutani, Hirotake
   Narayanan, Usha
   Olhava, Edward J.
   Peluso, Stephane
   Rezaei, Mansoureh
   Sintchak, Michael D.
   Talreja, Tina
   Thomas, Michael P.
   Traore, Tary
   Vyskocil, Stepan
   Weatherhead, Gabriel S.
   Yu, Jie
   Zhang, Julie
   Dick, Lawrence R.
   Claiborne, Christopher F.
   Rolfe, Mark
   Bolen, Joseph B.
   Langston, Steven P.
TI An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
SO NATURE
LA English
DT Article
ID nedd8 conjugation pathway; kappa-b-alpha; ubiquitin ligase; dna-damage; g(2)/m checkpoint; activating enzyme; cell-cycle; degradation; cdt1; complex
AB The clinical development of an inhibitor of cellular proteasome function suggests that compounds targeting other components of the ubiquitin-proteasome system might prove useful for the treatment of human malignancies. NEDD8-activating enzyme (NAE) is an essential component of the NEDD8 conjugation pathway that controls the activity of the cullin-RING subtype of ubiquitin ligases, thereby regulating the turnover of a subset of proteins upstream of the proteasome. Substrates of cullin-RING ligases have important roles in cellular processes associated with cancer cell growth and survival pathways. Here we describe MLN4924, a potent and selective inhibitor of NAE. MLN4924 disrupts cullin-RING ligase-mediated protein turnover leading to apoptotic death in human tumour cells by a new mechanism of action, the deregulation of S-phase DNA synthesis. MLN4924 suppressed the growth of human tumour xenografts in mice at compound exposures that were well tolerated. Our data suggest that NAE inhibitors may hold promise for the treatment of cancer.
C1 [Soucy, Teresa A.; Smith, Peter G.; Milhollen, Michael A.; Berger, Allison J.; Gavin, James M.; Adhikari, Sharmila; Brownell, James E.; Burke, Kristine E.; Cardin, David P.; Critchley, Stephen; Cullis, Courtney A.; Doucette, Amanda; Garnsey, James J.; Gaulin, Jeffrey L.; Gershman, Rachel E.; Lublinsky, Anna R.; McDonald, Alice; Mizutani, Hirotake; Narayanan, Usha; Olhava, Edward J.; Peluso, Stephane; Rezaei, Mansoureh; Sintchak, Michael D.; Talreja, Tina; Thomas, Michael P.; Traore, Tary; Vyskocil, Stepan; Weatherhead, Gabriel S.; Yu, Jie; Zhang, Julie; Dick, Lawrence R.; Claiborne, Christopher F.; Rolfe, Mark; Bolen, Joseph B.; Langston, Steven P.] Millennium Pharmaceut Inc, Cambridge, MA 02139 USA.
C3 Takeda Pharmaceutical Company Ltd; Millennium Pharmaceuticals
RP Soucy, TA (corresponding author), Millennium Pharmaceut Inc, 40 Landsdowne St, Cambridge, MA 02139 USA.
EM teresa.soucy@mpi.com
NR 46
TC 1702
Z9 1999
U1 2
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 APR 9
PY 2009
VL 458
IS 7239
BP 732
EP U67
DI 10.1038/nature07884
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600033
PM 19360080
DA 2026-03-09
ER

PT J
AU Matsumoto, M
   Hikosaka, O
AF Matsumoto, Masayuki
   Hikosaka, Okihide
TI Two types of dopamine neuron distinctly convey positive and negative motivational signals
SO NATURE
LA English
DT Article
ID saccadic eye-movements; ventral tegmental area; midbrain dopamine; nucleus-accumbens; lateral habenula; aversive stimuli; discharge rate; reward; striatum; primate
AB Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward(1-4). These excitatory responses increase as the reward value increases(5). This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.
C1 [Matsumoto, Masayuki; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
RP Matsumoto, M (corresponding author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM matsumotom@nei.nih.gov
FU Intramural Research Program at the National Institutes of Health, National Eye Institute; National Eye Institute [ZIAEY000415] Funding Source: NIH RePORTER
NR 29
TC 1035
Z9 1276
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 JUN 11
PY 2009
VL 459
IS 7248
BP 837
EP U4
DI 10.1038/nature08028
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500038
PM 19448610
DA 2026-03-09
ER

PT J
AU Belogurov, GA
   Vassylyeva, MN
   Sevostyanova, A
   Appleman, JR
   Xiang, AX
   Lira, R
   Webber, SE
   Klyuyev, S
   Nudler, E
   Artsimovitch, I
   Vassylyev, DG
AF Belogurov, Georgiy A.
   Vassylyeva, Marina N.
   Sevostyanova, Anastasiya
   Appleman, James R.
   Xiang, Alan X.
   Lira, Ricardo
   Webber, Stephen E.
   Klyuyev, Sergiy
   Nudler, Evgeny
   Artsimovitch, Irina
   Vassylyev, Dmitry G.
TI Transcription inactivation through local refolding of the RNA polymerase structure
SO NATURE
LA English
DT Article
ID open complex-formation; electron-density maps; ii elongation complex; angstrom resolution; start site; dna; inhibition; holoenzyme; molscript
AB Structural studies of antibiotics not only provide a shortcut to medicine allowing for rational structure- based drug design, but may also capture snapshots of dynamic intermediates that become 'frozen' after inhibitor binding(1,2). Myxopyronin inhibits bacterial RNA polymerase ( RNAP) by an unknown mechanism(3). Here we report the structure of dMyx - a desmethyl derivative of myxopyronin B-4 - complexed with a Thermus thermophilus RNAP holoenzyme. The antibiotic binds to a pocket deep inside the RNAP clamp head domain, which interacts with the DNA template in the transcription bubble(5,6). Notably, binding of dMyx stabilizes refolding of the beta'-subunit switch- 2 segment, resulting in a configuration that might indirectly compromise binding to, or directly clash with, the melted template DNA strand. Consistently, footprinting data show that the antibiotic binding does not prevent nucleation of the promoter DNA melting but instead blocks its propagation towards the active site. Myxopyronins are thus, to our knowledge, a first structurally characterized class of antibiotics that target formation of the pre- catalytic transcription initiation complex the decisive step in gene expression control. Notably, mutations designed in switch- 2 mimic the dMyx effects on promoter complexes in the absence of antibiotic. Overall, our results indicate a plausible mechanism of the dMyx action and a stepwise pathway of open complex formation in which core enzyme mediates the final stage of DNA melting near the transcription start site, and that switch- 2 might act as a molecular checkpoint for DNA loading in response to regulatory signals or antibiotics. The universally conserved switch- 2 may have the same role in all multisubunit RNAPs.
C1 [Belogurov, Georgiy A.; Sevostyanova, Anastasiya; Artsimovitch, Irina] Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA.
   [Vassylyeva, Marina N.; Klyuyev, Sergiy; Vassylyev, Dmitry G.] Univ Alabama, Sch Med, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
   [Vassylyeva, Marina N.; Klyuyev, Sergiy; Vassylyev, Dmitry G.] Univ Alabama, Sch Dent, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
   [Appleman, James R.; Xiang, Alan X.; Lira, Ricardo; Webber, Stephen E.] Anadys Pharmaceut Inc, San Diego, CA 92121 USA.
   [Nudler, Evgeny] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA.
C3 University System of Ohio; Ohio State University; University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham; Anadys Pharmaceuticals; New York University
RP Artsimovitch, I (corresponding author), Ohio State Univ, Dept Microbiol, 484 W 12Th Ave, Columbus, OH 43210 USA.
EM artsimovitch.1@osu.edu; dmitry@uab.edu
FU US Department of Energy, Office of Energy Research [W-31-109-Eng-38]; National Institutes of Health
NR 31
TC 115
Z9 134
U1 0
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 332
EP U8
DI 10.1038/nature07510
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900043
PM 18946472
DA 2026-03-09
ER

PT J
AU Green, DR
   Kroemer, G
AF Green, Douglas R.
   Kroemer, Guido
TI Cytoplasmic functions of the tumour suppressor p53
SO NATURE
LA English
DT Article
ID mitochondrial-membrane permeabilization; cell-death; bcl-xl; apoptosis; autophagy; activation; translocation; nuclear; absence; genes
AB The principal tumour-suppressor protein, p53, accumulates in cells in response to DNA damage, oncogene activation and other stresses. It acts as a nuclear transcription factor that transactivates genes involved in apoptosis, cell cycle regulation and numerous other processes. An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy. These previously unknown functions contribute to the mission of p53 as a tumour suppressor.
C1 [Green, Douglas R.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Kroemer, Guido] Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, France.
   [Kroemer, Guido] Univ Paris Sud, Paris 11, France.
C3 St Jude Children's Research Hospital; UNICANCER; Gustave Roussy; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay
RP Green, DR (corresponding author), St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA.
EM douglas.green@stjude.org; kroemer@igr.fr
FU NIH; American Lebanese and Syrian Associated Charities; Ligue contre le Cancer; INCa; Canceropole; ANR; ANRS; Active p53; Apo-Sys EU networks; National Institute of Allergy and Infectious Diseases [R01AI040646] Funding Source: NIH RePORTER
NR 40
TC 927
Z9 1121
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 APR 30
PY 2009
VL 458
IS 7242
BP 1127
EP 1130
DI 10.1038/nature07986
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600038
PM 19407794
DA 2026-03-09
ER

PT J
AU Liti, G
   Carter, DM
   Moses, AM
   Warringer, J
   Parts, L
   James, SA
   Davey, RP
   Roberts, IN
   Burt, A
   Koufopanou, V
   Tsai, IJ
   Bergman, CM
   Bensasson, D
   O'Kelly, MJT
   van Oudenaarden, A
   Barton, DBH
   Bailes, E
   Ba, ANN
   Jones, M
   Quail, MA
   Goodhead, I
   Sims, S
   Smith, F
   Blomberg, A
   Durbin, R
   Louis, EJ
AF Liti, Gianni
   Carter, David M.
   Moses, Alan M.
   Warringer, Jonas
   Parts, Leopold
   James, Stephen A.
   Davey, Robert P.
   Roberts, Ian N.
   Burt, Austin
   Koufopanou, Vassiliki
   Tsai, Isheng J.
   Bergman, Casey M.
   Bensasson, Douda
   O'Kelly, Michael J. T.
   van Oudenaarden, Alexander
   Barton, David B. H.
   Bailes, Elizabeth
   Ba, Alex N. Nguyen
   Jones, Matthew
   Quail, Michael A.
   Goodhead, Ian
   Sims, Sarah
   Smith, Frances
   Blomberg, Anders
   Durbin, Richard
   Louis, Edward J.
TI Population genomics of domestic and wild yeasts
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; diversity; evolution; kudriavzevii; life; wine
AB Since the completion of the genome sequence of Saccharomyces cerevisiae in 1996 (refs 1, 2), there has been a large increase in complete genome sequences, accompanied by great advances in our understanding of genome evolution. Although little is known about the natural and life histories of yeasts in the wild, there are an increasing number of studies looking at ecological and geographic distributions(3,4), population structure(5-8) and sexual versus asexual reproduction(9,10). Less well understood at the whole genome level are the evolutionary processes acting within populations and species that lead to adaptation to different environments, phenotypic differences and reproductive isolation. Here we present one- to fourfold or more coverage of the genome sequences of over seventy isolates of the baker's yeast S. cerevisiae and its closest relative, Saccharomyces paradoxus. We examine variation in gene content, single nucleotide polymorphisms, nucleotide insertions and deletions, copy numbers and transposable elements. We find that phenotypic variation broadly correlates with global genome-wide phylogenetic relationships. S. paradoxus populations are well delineated along geographic boundaries, whereas the variation among worldwide S. cerevisiae isolates shows less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of S. cerevisiae consists of a few well-defined, geographically isolated lineages and many different mosaics of these lineages, supporting the idea that human influence provided the opportunity for cross-breeding and production of new combinations of pre-existing variations.
C1 [Carter, David M.; Moses, Alan M.; Parts, Leopold; Jones, Matthew; Quail, Michael A.; Goodhead, Ian; Sims, Sarah; Smith, Frances; Durbin, Richard] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Liti, Gianni; Barton, David B. H.; Bailes, Elizabeth; Louis, Edward J.] Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham NG7 2UH, England.
   [Moses, Alan M.; Ba, Alex N. Nguyen] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 2J4, Canada.
   [Warringer, Jonas; Blomberg, Anders] Univ Gothenburg, Lundberg Lab, Dept Cell & Mol Biol, S-41390 Gothenburg, Sweden.
   [James, Stephen A.; Davey, Robert P.; Roberts, Ian N.] AFRC, Inst Food Res, Natl Collect Yeast Cultures, Norwich NR4 7UA, Norfolk, England.
   [Burt, Austin; Koufopanou, Vassiliki; Tsai, Isheng J.] Univ London Imperial Coll Sci Technol & Med, Div Biol, Ascot SL5 7PY, Berks, England.
   [Bergman, Casey M.; Bensasson, Douda] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
   [O'Kelly, Michael J. T.; van Oudenaarden, Alexander] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 Wellcome Trust Sanger Institute; University of Nottingham; University of Toronto; University of Gothenburg; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; University of East Anglia; Quadram Institute; Imperial College London; University of Manchester; Massachusetts Institute of Technology (MIT)
RP Durbin, R (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1HH, England.
EM rd@sanger.ac.uk; ed.louis@nottingham.ac.uk
FU The Wellcome Trust; Royal Society and the Biotechnology and Biological Sciences Research Council (BBSRC); BBSRC; Swedish Research Council; Swedish Foundation for Strategic Research; National Environment Research Council (NERC); Wellcome Trust; NERC; Canada Foundation for Innovation; National Science Foundation; National Institutes of Health; Hertz fellowship; Biotechnology and Biological Sciences Research Council [BBS/E/F/00042258, BB/F015216/1] Funding Source: researchfish; Natural Environment Research Council [NE/D008824/1] Funding Source: researchfish; BBSRC [BB/F015216/1] Funding Source: UKRI; NERC [NE/D008824/1] Funding Source: UKRI
NR 29
TC 1134
Z9 1339
U1 3
U2 272
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 337
EP 341
DI 10.1038/nature07743
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600041
PM 19212322
DA 2026-03-09
ER

PT J
AU Lee, CF
   Leigh, DA
   Pritchard, RG
   Schultz, D
   Teat, SJ
   Timco, GA
   Winpenny, REP
AF Lee, Chin-Fa
   Leigh, David A.
   Pritchard, Robin G.
   Schultz, David
   Teat, Simon J.
   Timco, Grigore A.
   Winpenny, Richard E. P.
TI Hybrid organic-inorganic rotaxanes and molecular shuttles
SO NATURE
LA English
DT Article
ID wheels; machines; rings
AB The tetravalency of carbon and its ability to form covalent bonds with itself and other elements enables large organic molecules with complex structures, functions and dynamics to be constructed. The varied electronic configurations and bonding patterns of inorganic elements, on the other hand, can impart diverse electronic, magnetic, catalytic and other useful properties to molecular-level structures. Some hybrid organic-inorganic materials that combine features of both chemistries have been developed, most notably metal-organic frameworks(1), dense and extended organic inorganic frameworks(2) and coordination polymers(3). Metal ions have also been incorporated into molecules that contain interlocked subunits, such as rotaxanes(4-7) and catenanes(6,8), and structures in which many inorganic clusters encircle polymer chains have been described(9). Here we report the synthesis of a series of discrete rotaxane molecules in which inorganic and organic structural units are linked together mechanically at the molecular level. Structural units (dialkyammonium groups) in dumb-bell-shaped organic molecules template the assembly of essentially inorganic 'rings' about 'axles' to form rotaxanes consisting of various numbers of rings and axles. One of the rotaxanes behaves as a 'molecular shuttle'(10): the ring moves between two binding sites on the axle in a large-amplitude motion typical of some synthetic molecular machine systems(11-15). The architecture of the rotaxanes ensures that the electronic, magnetic and paramagnetic characteristics of the inorganic rings-properties that could make them suitable as qubits for quantum computers(16-18)-can influence, and potentially be influenced by, the organic portion of the molecule.
C1 [Lee, Chin-Fa; Leigh, David A.; Schultz, David] Univ Edinburgh, Sch Chem, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Pritchard, Robin G.; Timco, Grigore A.; Winpenny, Richard E. P.] Univ Manchester, Sch Chem, Manchester M13 9PL, Lancs, England.
   [Teat, Simon J.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
C3 University of Edinburgh; University of Manchester; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Leigh, DA (corresponding author), Univ Edinburgh, Sch Chem, Kings Bldg,W Mains Rd, Edinburgh EH9 3JJ, Midlothian, Scotland.
EM david.leigh@ed.ac.uk; richard.winpenny@manchester.ac.uk
FU Director, Office of Science; Office of Basic Energy Sciences; the US Department of Energy [DE-AC02-05CH11231]; Swiss National Science Foundation; EPSRC Senior Research Fellow; Royal Society Wolfson Research Merit Award; EPSRC [EP/D05138X/1, EP/D029686/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/C545001/1, GR/S57396/01, GR/T28652/01, EP/D05138X/1, EP/D029686/1] Funding Source: researchfish
NR 29
TC 232
Z9 265
U1 3
U2 230
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 314
EP 318
DI 10.1038/nature07847
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600036
PM 19295605
DA 2026-03-09
ER

PT J
AU Xie, XW
   Li, Y
   Liu, ZQ
   Haruta, M
   Shen, WJ
AF Xie, Xiaowei
   Li, Yong
   Liu, Zhi-Quan
   Haruta, Masatake
   Shen, Wenjie
TI Low-temperature oxidation of CO catalysed by Co3O4 nanorods
SO NATURE
LA English
DT Article
ID carbon-monoxide; oxide catalysts; surface; powders; oxygen; water
AB Low-temperature oxidation of CO, perhaps the most extensively studied reaction in the history of heterogeneous catalysis, is becoming increasingly important in the context of cleaning air and lowering automotive emissions(1,2). Hopcalite catalysts (mixtures of manganese and copper oxides) were originally developed for purifying air in submarines, but they are not especially active at ambient temperatures and are also deactivated by the presence of moisture(3,4). Noble metal catalysts, on the other hand, are water tolerant but usually require temperatures above 100 degrees C for efficient operation(5,6). Gold exhibits high activity at low temperatures and superior stability under moisture, but only when deposited in nanoparticulate form on base transition-metal oxides(7-9). The development of active and stable catalysts without noble metals for low-temperature CO oxidation under an ambient atmosphere remains a significant challenge. Here we report that tricobalt tetraoxide nanorods not only catalyse CO oxidation at temperatures as low as -77 degrees C but also remain stable in a moist stream of normal feed gas. High-resolution transmission electron microscopy demonstrates that the Co3O4 nanorods predominantly expose their {110} planes, favouring the presence of active Co3+ species at the surface. Kinetic analyses reveal that the turnover frequency associated with individual Co3+ sites on the nanorods is similar to that of the conventional nanoparticles of this material, indicating that the significantly higher reaction rate that we have obtained with a nanorod morphology is probably due to the surface richness of active Co3+ sites. These results show the importance of morphology control in the preparation of base transition-metal oxides as highly efficient oxidation catalysts.
C1 [Xie, Xiaowei; Li, Yong; Shen, Wenjie] Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Catalysis, Dalian 116023, Peoples R China.
   [Liu, Zhi-Quan] Chinese Acad Sci, Inst Met Res, Shenyang Natl Lab Mat Sci, Shenyang 110016, Peoples R China.
   [Haruta, Masatake] Tokyo Metropolitan Univ, Grad Sch Urban Environm Sci, Dept Appl Chem, Tokyo 1920397, Japan.
   [Haruta, Masatake] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
C3 Chinese Academy of Sciences; Dalian Institute of Chemical Physics, CAS; Chinese Academy of Sciences; Institute of Metal Research, CAS; Tokyo Metropolitan University; Japan Science & Technology Agency (JST)
RP Shen, WJ (corresponding author), Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Catalysis, Dalian 116023, Peoples R China.
EM shen98@dicp.ac.cn
FU National Natural Science Foundation of China; National Basic Research Program of China
NR 26
TC 2445
Z9 2666
U1 48
U2 3175
PU 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 9
PY 2009
VL 458
IS 7239
BP 746
EP 749
DI 10.1038/nature07877
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600037
PM 19360084
DA 2026-03-09
ER

PT J
AU Fehér, O
   Wang, HB
   Saar, S
   Mitra, PP
   Tchernichovski, O
AF Feher, Olga
   Wang, Haibin
   Saar, Sigal
   Mitra, Partha P.
   Tchernichovski, Ofer
TI De novo establishment of wild-type song culture in the zebra finch
SO NATURE
LA English
DT Article
ID white-crowned sparrow; taeniopygia-guttata; conspecific song; untutored song; bird song; evolution; behavior; selectivity; language; rules
AB Culture is typically viewed as consisting of traits inherited epigenetically, through social learning. However, cultural diversity has species-typical constraints(1), presumably of genetic origin. A celebrated, if contentious, example is whether a universal grammar constrains syntactic diversity in human languages(2). Oscine songbirds exhibit song learning and provide biologically tractable models of culture: members of a species show individual variation in song(3) and geographically separated groups have local song dialects(4,5). Different species exhibit distinct song cultures(6,7), suggestive of genetic constraints(8,9). Without such constraints, innovations and copying errors should cause unbounded variation over multiple generations or geographical distance, contrary to observations(9). Here we report an experiment designed to determine whether wild-type song culture might emerge over multiple generations in an isolated colony founded by isolates, and, if so, how this might happen and what type of social environment is required(10). Zebra finch isolates, unexposed to singing males during development, produce song with characteristics that differ from the wild-type song found in laboratory(11) or natural colonies. In tutoring lineages starting from isolate founders, we quantified alterations in song across tutoring generations in two social environments: tutor-pupil pairs in sound-isolated chambers and an isolated semi-natural colony. In both settings, juveniles imitated the isolate tutors but changed certain characteristics of the songs. These alterations accumulated over learning generations. Consequently, songs evolved towards the wild-type in three to four generations. Thus, species-typical song culture can appear de novo. Our study has parallels with language change and evolution(12-14). In analogy to models in quantitative genetics(15,16), we model song culture as a multigenerational phenotype partly encoded genetically in an isolate founding population, influenced by environmental variables and taking multiple generations to emerge.
C1 [Feher, Olga; Saar, Sigal; Tchernichovski, Ofer] CUNY City Coll, Dept Biol, New York, NY 10031 USA.
   [Wang, Haibin; Mitra, Partha P.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 City University of New York (CUNY) System; City College of New York (CUNY); Cold Spring Harbor Laboratory
RP Fehér, O (corresponding author), CUNY City Coll, Dept Biol, 138Th St & Convent Ave, New York, NY 10031 USA.
EM olcifeher@gmail.com
FU US National Institutes of Health (NIH); NIH Research Centers in Minority Institutions; Crick-Clay Professorship
NR 32
TC 248
Z9 302
U1 2
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 28
PY 2009
VL 459
IS 7246
BP 564
EP U94
DI 10.1038/nature07994
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500038
PM 19412161
DA 2026-03-09
ER

PT J
AU Mann, ME
   Woodruff, JD
   Donnelly, JP
   Zhang, ZH
AF Mann, Michael E.
   Woodruff, Jonathan D.
   Donnelly, Jeffrey P.
   Zhang, Zhihua
TI Atlantic hurricanes and climate over the past 1,500 years
SO NATURE
LA English
DT Article
ID prehistoric landfall frequency; tropical pacific; sedimentological evidence; coast records; new-jersey; sea; reconstruction; oscillation
AB Atlantic tropical cyclone activity, as measured by annual storm counts, reached anomalous levels over the past decade(1). The short nature of the historical record and potential issues with its reliability in earlier decades, however, has prompted an ongoing debate regarding the reality and significance of the recent rise(2-5). Here we place recent activity in a longer-term context by comparing two independent estimates of tropical cyclone activity over the past 1,500 years. The first estimate is based on a composite of regional sedimentary evidence of landfalling hurricanes, while the second estimate uses a previously published statistical model of Atlantic tropical cyclone activity driven by proxy reconstructions of past climate changes. Both approaches yield consistent evidence of a peak in Atlantic tropical cyclone activity during medieval times (around AD 1000) followed by a subsequent lull in activity. The statistical model indicates that the medieval peak, which rivals or even exceeds (within uncertainties) recent levels of activity, results from the reinforcing effects of La-Nina-like climate conditions and relative tropical Atlantic warmth.
C1 [Mann, Michael E.; Zhang, Zhihua] Penn State Univ, Dept Meteorol, University Pk, PA 16802 USA.
   [Mann, Michael E.; Zhang, Zhihua] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [Woodruff, Jonathan D.] Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.
   [Donnelly, Jeffrey P.] Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Massachusetts System; University of Massachusetts Amherst; Woods Hole Oceanographic Institution
RP Mann, ME (corresponding author), Penn State Univ, Dept Meteorol, 503 Walker Bldg, University Pk, PA 16802 USA.
EM mann@psu.edu
FU National Science Foundation [ATM-0542356, EAR-0519118, OCE-0402746]; Directorate For Geosciences; Division Of Ocean Sciences [0902889, 0903020] Funding Source: National Science Foundation
NR 37
TC 187
Z9 240
U1 1
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 13
PY 2009
VL 460
IS 7257
BP 880
EP U115
DI 10.1038/nature08219
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300035
PM 19675650
DA 2026-03-09
ER

PT J
AU Kajimura, S
   Seale, P
   Kubota, K
   Lunsford, E
   Frangioni, JV
   Gygi, SP
   Spiegelman, BM
AF Kajimura, Shingo
   Seale, Patrick
   Kubota, Kazuishi
   Lunsford, Elaine
   Frangioni, John V.
   Gygi, Steven P.
   Spiegelman, Bruce M.
TI Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-β transcriptional complex
SO NATURE
LA English
DT Article
ID adipose-tissue; c/ebp-beta; adipocyte differentiation; mice lacking; protein; expression; gene; white; cells; index
AB Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity(1). PRDM16 (PR domain containing 16) is a 140 kDa zinc finger protein that robustly induces brown fat determination and differentiation(2). Recent data suggests that brown fat cells arise in vivo from a Myf5-positive, myoblastic lineage by the action of PRDM16 (ref. 3); however, the molecular mechanisms responsible for this developmental switch is unclear. Here we show that PRDM16 forms a transcriptional complex with the active form of C/EBP-beta ( also known as LAP), acting as a critical molecular unit that controls the cell fate switch from myoblastic precursors to brown fat cells. Forced expression of PRDM16 and C/EBP-beta is sufficient to induce a fully functional brown fat program in naive fibroblastic cells, including skin fibroblasts from mouse and man. Transplantation of fibroblasts expressing these two factors into mice gives rise to an ectopic fat pad with the morphological and biochemical characteristics of brown fat. Like endogenous brown fat, this synthetic brown fat tissue acts as a sink for glucose uptake, as determined by positron emission tomography with fluorodeoxyglucose. These data indicate that the PRDM16-C/EBP-beta complex initiates brown fat formation from myoblastic precursors, and may provide opportunities for the development of new therapeutics for obesity and type-2 diabetes.
C1 [Kajimura, Shingo; Seale, Patrick; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
   [Kajimura, Shingo; Seale, Patrick; Kubota, Kazuishi; Gygi, Steven P.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Lunsford, Elaine; Frangioni, John V.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
RP Spiegelman, BM (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu
FU AHA [0930125N]; National Institutes of Health ( NIH) [DK081605, HG3456, GM67945]; Picower Foundation [DK31405]; NIH/NCRR [S10-RR-023010]; National Institute of General Medical Sciences [R01GM067945] Funding Source: NIH RePORTER; American Heart Association (AHA) [0930125N] Funding Source: American Heart Association (AHA)
NR 36
TC 601
Z9 750
U1 0
U2 96
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1154
EP 1158
DI 10.1038/nature08262
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000044
PM 19641492
DA 2026-03-09
ER

PT J
AU Ledesma, FC
   El Khamisy, SF
   Zuma, MC
   Osborn, K
   Caldecott, KW
AF Ledesma, Felipe Cortes
   El Khamisy, Sherif F.
   Zuma, Maria C.
   Osborn, Kay
   Caldecott, Keith W.
TI A human 5′-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage
SO NATURE
LA English
DT Article
ID receptor-associated factors; strand break repair; spinocerebellar ataxia; covalent complexes; ttrap; tdp1; protein; enzyme; cd40
AB Topoisomerases regulate DNA topology and are fundamental to many aspects of chromosome metabolism(1,2). Their activity involves the transient cleavage of DNA, which, if it occurs near sites of endogenous DNA damage or in the presence of topoisomerase poisons, can result in abortive topoisomerase-induced DNA strand breaks(3-5). These breaks feature covalent linkage of the enzyme to the DNA termini by a 3'- or 5'-phosphotyrosyl bond and are implicated in hereditary human disease(6-8), chromosomal instability and cancer(4,9), and underlie the clinical efficacy of an important class of anti-tumour poisons(3,9,10). The importance of liberating DNA termini from trapped topoisomerase is illustrated by the progressive neurodegenerative disease observed in individuals containing a mutation in tyrosyl-DNA phosphodiesterase 1 (TDP1), an enzyme that cleaves 3'-phosphotyrosyl bonds(6-8). However, a complementary human enzyme that cleaves 5'-phosphotyrosyl bonds has not been reported, despite the effect of DNA double-strand breaks containing such termini on chromosome instability and cancer(6-8). Here we identify such an enzyme in human cells and show that this activity efficiently restores 5'-phosphate termini at DNA double-strand breaks in preparation for DNA ligation. This enzyme, TTRAP, is a member of the Mg2+/Mn2+-dependent family of phosphodiesterases. Cellular depletion of TTRAP results in increased susceptibility and sensitivity to topoisomerase-II-induced DNA double-strand breaks. TTRAP is, to our knowledge, the first human 5'-tyrosyl DNA phosphodiesterase to be identified, and we suggest that this enzyme is denoted tyrosyl DNA phosphodiesterase-2 (TDP2).
C1 [Ledesma, Felipe Cortes; El Khamisy, Sherif F.; Zuma, Maria C.; Osborn, Kay; Caldecott, Keith W.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
   [El Khamisy, Sherif F.] Ain Shams Univ, Fac Pharm, Dept Biochem, Cairo 11566, Egypt.
C3 University of Sussex; Egyptian Knowledge Bank (EKB); Ain Shams University
RP Caldecott, KW (corresponding author), Univ Sussex, Genome Damage & Stabil Ctr, Sci Pk Rd, Brighton BN1 9RQ, E Sussex, England.
EM fc55@sussex.ac.uk; k.w.caldecott@sussex.ac.uk
FU MRC [G0600776]; BBSRC [BB/C516595/1]; CR-UK [C6563/A10192]; Wellcome Trust [085284]; Marie Curie [2007-2-1-IEF-221222]; EMBO [ALTF 956-2006]; Biotechnology and Biological Sciences Research Council [BB/C516595/1] Funding Source: researchfish; Medical Research Council [G0600776, G0901606] Funding Source: researchfish; MRC [G0600776] Funding Source: UKRI
NR 30
TC 342
Z9 389
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 1
PY 2009
VL 461
IS 7264
BP 674
EP U125
DI 10.1038/nature08444
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600045
PM 19794497
DA 2026-03-09
ER

PT J
AU Morris, JR
   Boutell, C
   Keppler, M
   Densham, R
   Weekes, D
   Alamshah, A
   Butler, L
   Galanty, Y
   Pangon, L
   Kiuchi, T
   Ng, T
   Solomon, E
AF Morris, Joanna R.
   Boutell, Chris
   Keppler, Melanie
   Densham, Ruth
   Weekes, Daniel
   Alamshah, Amin
   Butler, Laura
   Galanty, Yaron
   Pangon, Laurent
   Kiuchi, Tai
   Ng, Tony
   Solomon, Ellen
TI The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress
SO NATURE
LA English
DT Article
ID ubiquitin structures; ligase activity; targets brca1; dna-repair; activation; binding; sumoylation; complex; ubiquitylation; brca1-bard1
AB Mutations in BRCA1 are associated with a high risk of breast and ovarian cancer. BRCA1 participates in the DNA damage response and acts as a ubiquitin ligase. However, its regulation remains poorly understood. Here we report that BRCA1 is modified by small ubiquitin-like modifier ( SUMO) in response to genotoxic stress, and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9. PIAS SUMO E3 ligases co-localize with and modulate SUMO modification of BRCA1, and are required for BRCA1 ubiquitin ligase activity in cells. In vitro SUMO modification of the BRCA1/BARD1 heterodimer greatly increases its ligase activity, identifying it as a SUMO-regulated ubiquitin ligase (SRUbL). Further, PIAS SUMO ligases are required for complete accumulation of double-stranded DNA (dsDNA) damage-repair proteins subsequent to RNF8 accrual, and for proficient double-strand break repair. These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response.
C1 [Morris, Joanna R.; Densham, Ruth; Weekes, Daniel; Alamshah, Amin; Butler, Laura; Pangon, Laurent; Solomon, Ellen] Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England.
   [Boutell, Chris] MRC, Virol Unit, Glasgow G11 5JR, Lanark, Scotland.
   [Keppler, Melanie; Kiuchi, Tai; Ng, Tony] Kings Coll London, Richard Dimbleby Dept Canc Res, Randall Div Cell & Mol Biophys, London SE1 1UL, England.
   [Galanty, Yaron] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England.
   [Galanty, Yaron] Univ Cambridge, Dept Zool, Cambridge CB2 1QN, England.
C3 University of London; King's College London; University of London; King's College London; University of Cambridge; University of Cambridge
RP Morris, JR (corresponding author), Kings Coll London, Dept Med & Mol Genet, Guys Med Sch Campus, London SE1 9RT, England.
EM jo.morris@genetics.kcl.ac.uk
FU Breast Cancer Campaign [SF06, 06NovPHD13Morris]; Cancer Research UK [C8820/A9494]; Medical Research Council [6900577]; Richard Dimbleby Cancer Fund; Breakthrough Breast Cancer; MRC Co-operative Group [G0100152, 56891]; UK Research Councils Basic Technology Research Programme [GR/R87901/01]; Engineering and Physical Sciences Research Council [GR/R87901/01] Funding Source: researchfish; Medical Research Council [G9600577, G0100152] Funding Source: researchfish; MRC [G9600577] Funding Source: UKRI
NR 50
TC 344
Z9 430
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 DEC 17
PY 2009
VL 462
IS 7275
BP 886
EP U77
DI 10.1038/nature08593
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400035
PM 20016594
DA 2026-03-09
ER

PT J
AU Qi, Y
   Spong, MC
   Nam, K
   Banerjee, A
   Jiralerspong, S
   Karplus, M
   Verdine, GL
AF Qi, Yan
   Spong, Marie C.
   Nam, Kwangho
   Banerjee, Anirban
   Jiralerspong, Sao
   Karplus, Martin
   Verdine, Gregory L.
TI Encounter and extrusion of an intrahelical lesion by a DNA repair enzyme
SO NATURE
LA English
DT Article
ID empirical force-field; molecular-dynamics; structural basis; nucleic-acids; fpg protein; damaged dna; free-energy; duplex dna; recognition; 8-oxoguanine
AB How living systems detect the presence of genotoxic damage embedded in a million-fold excess of undamaged DNA is an unresolved question in biology. Here we have captured and structurally elucidated a base-excision DNA repair enzyme, MutM, at the stage of initial encounter with a damaged nucleobase, 8-oxoguanine (oxoG), nested within a DNA duplex. Three structures of intrahelical oxoG-encounter complexes are compared with sequence-matched structures containing a normal G base in place of an oxoG lesion. Although the protein-DNA interfaces in the matched complexes differ by only two atoms-those that distinguish oxoG from G-their pronounced structural differences indicate that MutM can detect a lesion in DNA even at the earliest stages of encounter. All-atom computer simulations show the pathway by which encounter of the enzyme with the lesion causes extrusion from the DNA duplex, and they elucidate the critical free energy difference between oxoG and G along the extrusion pathway.
C1 [Spong, Marie C.; Nam, Kwangho; Banerjee, Anirban; Jiralerspong, Sao; Karplus, Martin; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Qi, Yan; Verdine, Gregory L.] Harvard Univ, Sch Med, Grad Program Biophys, Boston, MA 02115 USA.
   [Verdine, Gregory L.] Dana Farber Canc Inst, Chem Biol Initiat, Boston, MA 02115 USA.
   [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA.
   [Karplus, Martin] Univ Strasbourg, ISIS, F-67000 Strasbourg, France.
C3 Harvard University; Harvard University; Harvard University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg
RP Karplus, M (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
EM marci@tammy.harvard.edu; gregory_verdine@harvard.edu
FU NIH [GM044853, GM047467, CA100742, GM030804]; the National Science Foundation; Howard Hughes Medical Institute; National Cancer Center
NR 47
TC 125
Z9 149
U1 0
U2 38
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 762
EP U79
DI 10.1038/nature08561
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900032
PM 20010681
DA 2026-03-09
ER

PT J
AU Goodman, AA
   Rosolowsky, EW
   Borkin, MA
   Foster, JB
   Halle, M
   Kauffmann, J
   Pineda, JE
AF Goodman, Alyssa A.
   Rosolowsky, Erik W.
   Borkin, Michelle A.
   Foster, Jonathan B.
   Halle, Michael
   Kauffmann, Jens
   Pineda, Jaime E.
TI A role for self-gravity at multiple length scales in the process of star formation
SO NATURE
LA English
DT Article
ID turbulence; clouds
AB Self-gravity plays a decisive role in the final stages of star formation, where dense cores (size similar to 0.1 parsecs) inside molecular clouds collapse to form star- plus- disk systems(1). But self- gravity's role at earlier times ( and on larger length scales, such as similar to 1 parsec) is unclear; some molecular cloud simulations that do not include self- gravity suggest that 'turbulent fragmentation' alone is sufficient to create a mass distribution of dense cores that resembles, and sets, the stellar initial mass function(2). Here we report a 'dendrogram' (hierarchical tree- diagram) analysis that reveals that self- gravity plays a significant role over the full range of possible scales traced by (CO)-C-13 observations in the L1448 molecular cloud, but not everywhere in the observed region. In particular, more than 90 per cent of the compact 'pre- stellar cores' traced by peaks of dust emission(3) are projected on the sky within one of the dendrogram's self- gravitating 'leaves'. As these peaks mark the locations of already- forming stars, or of those probably about to form, a self- gravitating cocoon seems a critical condition for their existence. Turbulent fragmentation simulations without self- gravity even of unmagnetized isothermal material - can yield mass and velocity power spectra very similar to what is observed in clouds like L1448. But a dendrogram of such a simulation(4) shows that nearly all the gas in it ( much more than in the observations) appears to be self- gravitating. A potentially significant role for gravity in ` non- self- gravitating' simulations suggests inconsistency in simulation assumptions and output, and that it is necessary to include self- gravity in any realistic simulation of the star- formation process on subparsec scales.
C1 [Goodman, Alyssa A.; Borkin, Michelle A.; Halle, Michael; Kauffmann, Jens] Harvard Univ, Initiat Innovat Comp, Cambridge, MA 02138 USA.
   [Goodman, Alyssa A.; Rosolowsky, Erik W.; Foster, Jonathan B.; Kauffmann, Jens; Pineda, Jaime E.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Rosolowsky, Erik W.] Univ British Columbia, Dept Phys, Kelowna, BC V1V 1V7, Canada.
   [Halle, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA.
   [Halle, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; University of British Columbia; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School
RP Goodman, AA (corresponding author), Harvard Univ, Initiat Innovat Comp, Cambridge, MA 02138 USA.
EM agoodman@cfa.harvard.edu
FU National Institutes of Health [U54-EB005149]; National Science Foundation [AST-0502605]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908159] Funding Source: National Science Foundation
NR 21
TC 133
Z9 148
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 1
PY 2009
VL 457
IS 7225
BP 63
EP 66
DI 10.1038/nature07609
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900030
PM 19122636
DA 2026-03-09
ER

PT J
AU Castro, JM
   Dingwell, DB
AF Castro, Jonathan M.
   Dingwell, Donald B.
TI Rapid ascent of rhyolitic magma at Chaiten volcano, Chile
SO NATURE
LA English
DT Article
ID rock fracture; 1912 eruption; crystallization; decompression; novarupta; precursor; flow
AB Rhyolite magma has fuelled some of the Earth's largest explosive volcanic eruptions(1). Our understanding of these events is incomplete, however, owing to the previous lack of directly observed eruptions. Chaiten volcano, in Chile's northern Patagonia, erupted rhyolite magma unexpectedly and explosively on 1 May 2008 (ref. 2). Chaiten residents felt earthquakes about 24 hours before ash fell in their town and the eruption escalated into a Plinian column. Although such brief seismic forewarning of a major explosive basaltic eruption has been documented(3), it is unprecedented for silicic magmas. As precursory volcanic unrest relates to magma migration from the storage region to the surface, the very short pre-eruptive warning at Chaiten probably reflects very rapid magma ascent through the sub-volcanic system. Here we present petrological and experimental data that indicate that the hydrous rhyolite magma at Chaiten ascended very rapidly, with velocities of the order of one metre per second. Such rapid ascent implies a transit time from storage depths greater than five kilometres to the near surface in about four hours. This result has implications for hazard mitigation because the rapidity of ascending rhyolite means that future eruptions may provide little warning.
C1 [Castro, Jonathan M.] Univ Orleans, Univ Tours, CNRS, INSU,Inst Sci Terre Orleans,UMR 6113, F-45071 Orleans 2, France.
   [Dingwell, Donald B.] Univ Munich, Dept Earth & Environm Sci, D-80333 Munich, Germany.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Orleans; Universite de Tours; University of Munich
RP Castro, JM (corresponding author), Univ Orleans, Univ Tours, CNRS, INSU,Inst Sci Terre Orleans,UMR 6113, Campus Geosci,1A Rue Ferolleire, F-45071 Orleans 2, France.
EM jonathan.castro@cnrs-orleans.fr
FU Alexander von Humboldt Stiftung; Smithsonian Institution; ERC [202844]; European Research Council (ERC) [202844] Funding Source: European Research Council (ERC)
NR 32
TC 219
Z9 237
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 OCT 8
PY 2009
VL 461
IS 7265
BP 780
EP U29
DI 10.1038/nature08458
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500033
PM 19812671
DA 2026-03-09
ER

PT J
AU Oshima, S
   Turer, EE
   Callahan, JA
   Chai, S
   Advincula, R
   Barrera, J
   Shifrin, N
   Lee, B
   Yen, B
   Woo, T
   Malynn, BA
   Ma, A
AF Oshima, Shigeru
   Turer, Emre E.
   Callahan, Joseph A.
   Chai, Sophia
   Advincula, Rommel
   Barrera, Julio
   Shifrin, Nataliya
   Lee, Bettina
   Yen, Benjamin
   Woo, Tammy
   Malynn, Barbara A.
   Ma, Averil
TI ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development
SO NATURE
LA English
DT Article
ID nf-kappa-b; zinc-finger protein; jnk activation; mice; a20; induction; lethality; apoptosis; responses; requires
AB Proteins that directly regulate tumour necrosis factor receptor ( TNFR) signalling have critical roles in regulating cellular activation and survival. ABIN-1 (A20 binding and inhibitor of NF-kappa B) is a novel protein that is thought to inhibit NF-kappa B signalling(1,2). Here we show that mice deficient for ABIN-1 die during embryogenesis with fetal liver apoptosis, anaemia and hypoplasia. ABIN-1 deficient cells are hypersensitive to tumour necrosis factor (TNF)induced programmed cell death, and TNF deficiency rescues ABIN-1 deficient embryos. ABIN-1 inhibits caspase 8 recruitment to FADD (Fas-associated death domain-containing protein) in TNF-induced signalling complexes, preventing caspase 8 cleavage and programmed cell death. Moreover, ABIN-1 directly binds polyubiquitin chains and this ubiquitin sensing activity is required for ABIN-1's anti-apoptotic activity. These studies provide insights into how ubiquitination and ubiquitin sensing proteins regulate cellular and organismal survival.
C1 [Oshima, Shigeru; Turer, Emre E.; Callahan, Joseph A.; Chai, Sophia; Advincula, Rommel; Barrera, Julio; Shifrin, Nataliya; Lee, Bettina; Yen, Benjamin; Woo, Tammy; Malynn, Barbara A.; Ma, Averil] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco
RP Ma, A (corresponding author), Univ Calif San Francisco, Dept Med, 513 Parnassus Ave,S-1057, San Francisco, CA 94143 USA.
EM averil.ma@ucsf.edu
FU NIH; UCSF Liver Center Pathology and Flow Cytometry Facilities; UCSF Transgenic and Targeted Mutagenesis Core Facility; Crohn's and Colitis Foundation of America; NSF fellowship; Rainin Foundation
NR 24
TC 143
Z9 168
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 12
PY 2009
VL 457
IS 7231
BP 906
EP 909
DI 10.1038/nature07575
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700050
PM 19060883
DA 2026-03-09
ER

PT J
AU Ho, MC
   Ménétret, JF
   Tsuruta, H
   Allen, KN
AF Ho, Meng-Chiao
   Menetret, Jean-Francois
   Tsuruta, Hiro
   Allen, Karen N.
TI The origin of the electrostatic perturbation in acetoacetate decarboxylase
SO NATURE
LA English
DT Article
ID active-site; enzymatic decarboxylation; mechanism; software; lysine; resolution; system; pk(a); model
AB Acetoacetate decarboxylase (AADase) has long been cited as the prototypical example of the marked shifts in the pK(a) values of ionizable groups that can occur in an enzyme active site. In 1966, it was hypothesized that in AADase the origin of the large pK(a) perturbation (-4.5 log units) observed in the nucleophilic Lys 115 results from the proximity of Lys 116, marking the first proposal of microenvironment effects in enzymology. The electrostatic perturbation hypothesis has been demonstrated in a number of enzymes, but never for the enzyme that inspired its conception, owing to the lack of a three-dimensional structure. Here we present the X-ray crystal structures of AADase and of the enamine adduct with the substrate analogue 2,4-pentanedione. Surprisingly, the shift of the pK(a) of Lys 115 is not due to the proximity of Lys 116, the side chain of which is oriented away from the active site. Instead, Lys 116 participates in the structural anchoring of Lys 115 in a long, hydrophobic funnel provided by the novel fold of the enzyme. Thus, AADase perturbs the pK(a) of the nucleophile by means of a desolvation effect by placement of the side chain into the protein core while enforcing the proximity of polar residues, which facilitate decarboxylation through electrostatic and steric effects.
C1 [Ho, Meng-Chiao; Menetret, Jean-Francois; Allen, Karen N.] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA.
   [Tsuruta, Hiro] SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA.
C3 Boston University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory
RP Allen, KN (corresponding author), Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA.
EM drkallen@bu.edu
FU National Science Foundation; Offices of Biological and Environmental Research (BER); Basic Energy Sciences (BES) of the US Department of Energy (DOE); National Center for Research Resources (NCRR) of the National Institutes of Health (NIH)
NR 39
TC 83
Z9 105
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2009
VL 459
IS 7245
BP 393
EP U107
DI 10.1038/nature07938
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700038
PM 19458715
DA 2026-03-09
ER

PT J
AU Opher, M
   Bibi, FA
   Toth, G
   Richardson, JD
   Izmodenov, VV
   Gombosi, TI
AF Opher, M.
   Bibi, F. Alouani
   Toth, G.
   Richardson, J. D.
   Izmodenov, V. V.
   Gombosi, T. I.
TI A strong, highly-tilted interstellar magnetic field near the Solar System
SO NATURE
LA English
DT Article
ID wind; heliosphere; asymmetry; voyager-1; dynamics; plasma
AB Magnetic fields play an important (sometimes dominant) role in the evolution of gas clouds in the Galaxy, but the strength and orientation of the field in the interstellar medium near the heliosphere has been poorly constrained. Previous estimates of the field strength range from 1.8-2.5 mu G and the field was thought to be parallel to the Galactic plane(1) or inclined by 38-60 degrees (ref. 2) or 60-90 degrees (ref. 3) to this plane. These estimates relied either on indirect observational inferences or modelling in which the interstellar neutral hydrogen was not taken into account. Here we report measurements of the deflection of the solar wind plasma flows in the heliosheath(4) to determine the magnetic field strength and orientation in the interstellar medium. We find that the field strength in the local interstellar medium is 3.7-5.5 mu G. The field is tilted similar to 20-30 degrees from the interstellar medium flow direction (resulting from the peculiar motion of the Sun in the Galaxy) and is at an angle of about 30 degrees from the Galactic plane. We conclude that the interstellar medium field is turbulent or has a distortion in the solar vicinity.
C1 [Opher, M.; Bibi, F. Alouani] George Mason Univ, Fairfax, VA 22030 USA.
   [Toth, G.; Gombosi, T. I.] Univ Michigan, Ctr Space Environm Modeling, Ann Arbor, MI 48109 USA.
   [Richardson, J. D.] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Izmodenov, V. V.] Moscow MV Lomonosov State Univ, Space Res Inst IKI, Moscow 117997, Russia.
   [Izmodenov, V. V.] Russian Acad Sci, Inst Problems Mech, Moscow 117997, Russia.
C3 George Mason University; University of Michigan System; University of Michigan; Massachusetts Institute of Technology (MIT); Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences; Lomonosov Moscow State University; Russian Academy of Sciences; Ishlinsky Institute for Problems in Mechanics RAS
RP Opher, M (corresponding author), George Mason Univ, 4400 Univ Dr, Fairfax, VA 22030 USA.
EM mopher@gmu.edu
FU NASA; National Science Foundation; Voyager project.; Russian Agency of Science; Dynastia Foundation
NR 23
TC 130
Z9 139
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1036
EP 1038
DI 10.1038/nature08567
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000042
PM 20033043
DA 2026-03-09
ER

PT J
AU D'Onghia, E
   Besla, G
   Cox, TJ
   Hernquist, L
AF D'Onghia, Elena
   Besla, Gurtina
   Cox, Thomas J.
   Hernquist, Lars
TI Resonant stripping as the origin of dwarf spheroidal galaxies
SO NATURE
LA English
DT Article
ID dark-matter; satellite galaxy; clusters; evolution; draco; gas
AB Dwarf spheroidal galaxies are the most dark-matter-dominated systems in the nearby Universe(1-3) and their origin is one of the outstanding puzzles of how galaxies form. Dwarf spheroidals are poor in gas and stars, making them unusually faint(4-6), and those known as ultra-faint dwarfs(7,8) have by far the lowest measured stellar content of any galaxy(9,10). Previous theories(11) require that dwarf spheroidals orbit near giant galaxies like the Milky Way, but some dwarfs have been observed in the outskirts of the Local Group(12). Here we report simulations of encounters between dwarf disk galaxies and somewhat larger objects. We find that the encounters excite a process, which we term 'resonant stripping', that transforms them into dwarf spheroidals. This effect is distinct from other mechanisms proposed to form dwarf spheroidals, including mergers(13), galaxy galaxy harassment(14), or tidal and ram pressure stripping, because it is driven by gravitational resonances. It may account for some of the observed properties of dwarf spheroidals in the Local Group. Within this framework, dwarf spheroidals should form and interact in pairs, leaving detectable long stellar streams and tails.
C1 [D'Onghia, Elena] Univ Zurich, Inst Theoret Phys, CH-8057 Zurich, Switzerland.
   [D'Onghia, Elena; Besla, Gurtina; Cox, Thomas J.; Hernquist, Lars] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
C3 University of Zurich; Smithsonian Institution; Smithsonian Astrophysical Observatory; Harvard University
RP D'Onghia, E (corresponding author), Univ Zurich, Inst Theoret Phys, CH-8057 Zurich, Switzerland.
EM edonghia@cfa.harvard.edu
FU EU [MEIF-041569]; NSERC
NR 30
TC 95
Z9 105
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 605
EP 607
DI 10.1038/nature08215
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300044
DA 2026-03-09
ER

PT J
AU Perron, JT
   Kirchner, JW
   Dietrich, WE
AF Perron, J. Taylor
   Kirchner, James W.
   Dietrich, William E.
TI Formation of evenly spaced ridges and valleys
SO NATURE
LA English
DT Article
ID drainage-basin evolution; channel initiation; driven theory; model; morphology; density; stability; inception; outlets; climate
AB One of the most striking examples of self-organization in landscapes is the emergence of evenly spaced ridges and valleys(1-6). Despite the prevalence of uniform valley spacing, no theory has been shown to predict this fundamental topographic wavelength. Models of long-term landscape evolution can produce landforms that look realistic(7-9), but few metrics exist to assess the similarity between models and natural landscapes. Here we show that the ridge-valley wavelength can be predicted from erosional mechanics. From equations of mass conservation and sediment transport, we derive a characteristic length scale at which the time-scales for erosion by diffusive soil creep and advective stream incision are equal. This length scale is directly proportional to the valley spacing that emerges in a numerical model of landform evolution, and to the measured valley spacing at five field sites. Our results provide a quantitative explanation for one of the most widely observed characteristics of landscapes. The findings also imply that valley spacing is a fundamental topographic signature that records how material properties and climate regulate erosional processes.
C1 [Perron, J. Taylor] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Kirchner, James W.; Dietrich, William E.] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
   [Kirchner, James W.] Swiss Fed Inst Forest Snow & Landscape Res WSL, Birmensdorf, Switzerland.
   [Kirchner, James W.] Swiss Fed Inst Technol, Dept Environm Sci, Zurich, Switzerland.
C3 Massachusetts Institute of Technology (MIT); University of California System; University of California Berkeley; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Perron, JT (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
EM perron@mit.edu
FU National Science Foundation; Institute for Geophysics and Planetary Physics; NASA; National Center for Earth-surface Dynamics (NCED)
NR 30
TC 220
Z9 259
U1 2
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 JUL 23
PY 2009
VL 460
IS 7254
BP 502
EP 505
DI 10.1038/nature08174
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000036
DA 2026-03-09
ER

PT J
AU Ward, BB
   Devol, AH
   Rich, JJ
   Chang, BX
   Bulow, SE
   Naik, H
   Pratihary, A
   Jayakumar, A
AF Ward, B. B.
   Devol, A. H.
   Rich, J. J.
   Chang, B. X.
   Bulow, S. E.
   Naik, Hema
   Pratihary, Anil
   Jayakumar, A.
TI Denitrification as the dominant nitrogen loss process in the Arabian Sea
SO NATURE
LA English
DT Article
ID anaerobic ammonium oxidation; water column; anammox; bacteria; oxide; n-2; nirs
AB Primary production in over half of the world's oceans is limited by fixed nitrogen availability. The main loss term from the fixed nitrogen inventory is the production of dinitrogen gas (N-2) by heterotrophic denitrification or the more recently discovered autotrophic process, anaerobic ammonia oxidation (anammox). Oceanic oxygen minimum zones (OMZ) are responsible for about 35% of oceanic N-2 production and up to half of that occurs in the Arabian Sea(1). Although denitrification was long thought to be the only loss term, it has recently been argued that anammox alone is responsible for fixed nitrogen loss in the OMZs(2-4). Here we measure denitrification and anammox rates and quantify the abundance of denitrifying and anammox bacteria in the OMZ regions of the Eastern Tropical South Pacific and the Arabian Sea. We find that denitrification rather than anammox dominates the N-2 loss term in the Arabian Sea, the largest and most intense OMZ in the world ocean. In seven of eight experiments in the Arabian Sea denitrification is responsible for 87-99% of the total N-2 production. The dominance of denitrification is reproducible using two independent isotope incubation methods. In contrast, anammox is dominant in the Eastern Tropical South Pacific OMZ, as detected using one of the isotope incubation methods, as previously reported(3,5). The abundance of denitrifying bacteria always exceeded that of anammox bacteria by up to 7- and 19-fold in the Eastern Tropical South Pacific and Arabian Sea, respectively. Geographic and temporal variability in carbon supply may be responsible for the different contributions of denitrification and anammox in these two OMZs. The large contribution of denitrification to N-2 loss in the Arabian Sea indicates the global significance of denitrification to the oceanic nitrogen budget.
C1 [Ward, B. B.; Bulow, S. E.; Jayakumar, A.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
   [Devol, A. H.; Chang, B. X.] Univ Washington, Dept Oceanog, Seattle, WA 98195 USA.
   [Rich, J. J.] Brown Univ, Ctr Environm Studies, Providence, RI 02912 USA.
   [Naik, Hema; Pratihary, Anil] Natl Inst Oceanog, Panaji 403004, Goa, India.
C3 Princeton University; University of Washington; University of Washington Seattle; Brown University; Council of Scientific & Industrial Research (CSIR) - India; CSIR - National Institute of Oceanography (NIO)
RP Ward, BB (corresponding author), Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
EM bbw@princeton.edu
FU NSF
NR 27
TC 421
Z9 497
U1 4
U2 384
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 78
EP U77
DI 10.1038/nature08276
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800033
PM 19727197
DA 2026-03-09
ER

PT J
AU Lee, SJR
   Escobedo-Lozoya, Y
   Szatmari, EM
   Yasuda, R
AF Lee, Seok-Jin R.
   Escobedo-Lozoya, Yasmin
   Szatmari, Erzsebet M.
   Yasuda, Ryohei
TI Activation of CaMKII in single dendritic spines during long-term potentiation
SO NATURE
LA English
DT Article
ID protein-kinase-ii; yellow fluorescent protein; resonance energy-transfer; ca2+ channels; synaptic plasticity; ltp; induction; neurons; ras; phosphorylation
AB Calcium/calmodulin-dependent kinase II (CaMKII) plays a central part in long-term potentiation (LTP), which underlies some forms of learning and memory. Here we monitored the spatiotemporal dynamics of CaMKII activation in individual dendritic spines during LTP using two-photon fluorescence lifetime imaging microscopy, in combination with two-photon glutamate uncaging. Induction of LTP and associated spine enlargement in single spines triggered transient (similar to 1 min) CaMKII activation restricted to the stimulated spines. CaMKII in spines was specifically activated by NMDA receptors and L-type voltage-sensitive calcium channels, presumably by nanodomain Ca2+ near the channels, in response to glutamate uncaging and depolarization, respectively. The high degree of compartmentalization and channel specificity of CaMKII signalling allow stimuli-specific spatiotemporal patterns of CaMKII signalling and may be important for synapse-specificity of synaptic plasticity.
C1 [Lee, Seok-Jin R.; Escobedo-Lozoya, Yasmin; Szatmari, Erzsebet M.; Yasuda, Ryohei] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
C3 Duke University
RP Yasuda, R (corresponding author), Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
EM yasuda@neuro.duke.edu
FU Burroughs Wellcome Fund; Dana Foundation; Alfred P. Sloan Foundation; Autism Speaks; National Alliance of Autism Research; Whitehall Foundation; Alzheimer's Association; National Institute of Mental Health [R01MH08004]; National Science Foundation [0642000]; Duke University Undergraduate Research Support Grants; Howard Hughes Neuroscience Forum Fellowship; Ruth K. Broad Biomedical Research Foundation; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0642000] Funding Source: National Science Foundation; National Institute of Mental Health [R01MH080047] Funding Source: NIH RePORTER
NR 45
TC 527
Z9 646
U1 0
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 299
EP U58
DI 10.1038/nature07842
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600033
PM 19295602
DA 2026-03-09
ER

PT J
AU Lo Celso, C
   Fleming, HE
   Wu, JWW
   Zhao, CX
   Miake-Lye, S
   Fujisaki, J
   Côté, D
   Rowe, DW
   Lin, CP
   Scadden, DT
AF Lo Celso, Cristina
   Fleming, Heather E.
   Wu, Juwell W.
   Zhao, Cher X.
   Miake-Lye, Sam
   Fujisaki, Joji
   Cote, Daniel
   Rowe, David W.
   Lin, Charles P.
   Scadden, David T.
TI Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche
SO NATURE
LA English
DT Article
ID stem-cell; identification; osteopontin; expression; component
AB Stem cells reside in a specialized, regulatory environment termed the niche that dictates how they generate, maintain and repair tissues(1,2). We have previously documented that transplanted haematopoietic stem and progenitor cell populations localize to subdomains of bone- marrow microvessels where the chemokine CXCL12 is particularly abundant(3). Using a combination of high-resolution confocal microscopy and two- photon video imaging of individual haematopoietic cells in the calvarium bone marrow of living mice over time, we examine the relationship of haematopoietic stem and progenitor cells to blood vessels, osteoblasts and endosteal surface as they home and engraft in irradiated and c-Kit-receptor-deficient recipient mice. Osteoblasts were enmeshed in microvessels and relative positioning of stem/ progenitor cells within this complex tissue was nonrandom and dynamic. Both cell autonomous and non- autonomous factors influenced primitive cell localization. Different haematopoietic cell subsets localized to distinct locations according to the stage of differentiation. When physiological challenges drove either engraftment or expansion, bone- marrow stem/ progenitor cells assumed positions in close proximity to bone and osteoblasts. Our analysis permits observing in real time, at a single cell level, processes that previously have been studied only by their long- term outcome at the organismal level.
C1 [Lo Celso, Cristina; Fleming, Heather E.; Zhao, Cher X.; Miake-Lye, Sam; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Wu, Juwell W.; Fujisaki, Joji; Cote, Daniel; Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA.
   [Wu, Juwell W.; Fujisaki, Joji; Cote, Daniel; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
   [Lo Celso, Cristina; Fleming, Heather E.; Wu, Juwell W.; Zhao, Cher X.; Fujisaki, Joji; Lin, Charles P.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Rowe, David W.] Univ Connecticut, Ctr Hlth, Farmington, CT 06030 USA.
   [Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; University of Connecticut; Harvard University
RP Scadden, DT (corresponding author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.
EM lin@helix.mgh.harvard.edu; dscadden@mgh.harvard.edu
FU EMBO; HFSP; National Institutes of Health; Harvard Stem Cell Institute
NR 33
TC 721
Z9 855
U1 1
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 1
PY 2009
VL 457
IS 7225
BP 92
EP U96
DI 10.1038/nature07434
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900037
PM 19052546
DA 2026-03-09
ER

PT J
AU Fischer, J
   Koch, L
   Emmerling, C
   Vierkotten, J
   Peters, T
   Brüning, JC
   Rüther, U
AF Fischer, Julia
   Koch, Linda
   Emmerling, Christian
   Vierkotten, Jeanette
   Peters, Thomas
   Bruening, Jens C.
   Ruether, Ulrich
TI Inactivation of the Fto gene protects from obesity
SO NATURE
LA English
DT Article
ID fused toes ft; genome-wide association; insulin-resistance; hormonal-control; adult obesity; fat mass; adiponectin; weight; humans; mice
AB Several independent, genome-wide association studies have identified a strong correlation between body mass index and polymorphisms in the human FTO gene(1-4). Common variants in the first intron define a risk allele predisposing to obesity, with homozygotes for the risk allele weighing approximately 3 kilograms more than homozygotes for the low risk allele(1). Nevertheless, the functional role of FTO in energy homeostasis remains elusive. Here we show that the loss of Fto in mice leads to postnatal growth retardation and a significant reduction in adipose tissue and lean body mass. The leanness of Fto-deficient mice develops as a consequence of increased energy expenditure and systemic sympathetic activation, despite decreased spontaneous locomotor activity and relative hyperphagia. Taken together, these experiments provide, to our knowledge, the first direct demonstration that Fto is functionally involved in energy homeostasis by the control of energy expenditure.
C1 [Fischer, Julia; Emmerling, Christian; Vierkotten, Jeanette; Peters, Thomas; Ruether, Ulrich] Univ Dusseldorf, Inst Anim Dev & Mol Biol, D-40225 Dusseldorf, Germany.
   [Koch, Linda; Bruening, Jens C.] Univ Cologne, Dept Mouse Genet & Metab, Inst Genet, D-50674 Cologne, Germany.
   [Koch, Linda; Bruening, Jens C.] Univ Cologne, Dept Internal Med 2, D-50674 Cologne, Germany.
   [Koch, Linda; Bruening, Jens C.] Univ Cologne, CMMC, D-50674 Cologne, Germany.
   [Koch, Linda; Bruening, Jens C.] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany.
   [Koch, Linda; Bruening, Jens C.] Max Planck Inst Biol Ageing, D-50674 Cologne, Germany.
C3 Heinrich Heine University Dusseldorf; University of Cologne; University of Cologne; University of Cologne; University of Cologne; Max Planck Society
RP Rüther, U (corresponding author), Univ Dusseldorf, Inst Anim Dev & Mol Biol, Univ Str 1, D-40225 Dusseldorf, Germany.
EM jens.bruening@uni-koeln.de; ruether@uni-duesseldorf.de
FU Deutsche Forschungsgemeinschaft; NGFNplus
NR 30
TC 799
Z9 928
U1 2
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 16
PY 2009
VL 458
IS 7240
BP 894
EP U10
DI 10.1038/nature07848
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500044
PM 19234441
DA 2026-03-09
ER

PT J
AU Roy, K
   Hilliard, GM
   Hamilton, DJ
   Luo, JW
   Ostmann, MM
   Fleckenstein, JM
AF Roy, Koushik
   Hilliard, George M.
   Hamilton, David J.
   Luo, Jiwen
   Ostmann, Marguerite M.
   Fleckenstein, James M.
TI Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells
SO NATURE
LA English
DT Article
ID heat-labile enterotoxin; toll-like receptor-5; 2-partner secretion; epithelial-cells; colonization; virulence; proteins; identification; adherence; filament
AB Adhesion to epithelial cells(1) and flagella- mediated motility are critical virulence traits for many Gram- negative pathogens, including enterotoxigenic Escherichia coli (ETEC)(2), a major cause of diarrhoea in travellers and children in developing countries(3,4). Many flagellated pathogens export putative adhesins belonging to the two- partner secretion ( TPS) family(5). However, the actual function of these adhesins remains largely undefined. Here we demonstrate that EtpA, a TPS exoprotein adhesin of enterotoxigenic E. coli(6), mimics and interacts with highly conserved regions of flagellin, the major subunit of flagella, and that these interactions are critical for adherence and intestinal colonization. Although conserved regions of flagellin are mostly buried in the flagellar shaft(7), our results suggest that they are at least transiently exposed at the tips of flagella where they capture EtpA adhesin molecules for presentation to eukaryotic receptors. Similarity of EtpA to molecules encoded by other motile pathogens suggests a potential common pattern for bacterial adhesion, whereas participation of conserved regions of flagellin in adherence has implications for development of vaccines for Gram- negative pathogens.
C1 [Roy, Koushik; Luo, Jiwen; Fleckenstein, James M.] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA.
   [Hilliard, George M.; Fleckenstein, James M.] Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA.
   [Hamilton, David J.] Univ Tennessee, Ctr Hlth Sci, Dept Comparat Med, Memphis, TN 38163 USA.
   [Ostmann, Marguerite M.] Vet Adm Med Ctr, Res Serv, Memphis, TN 38104 USA.
   [Fleckenstein, James M.] Vet Adm Med Ctr, Med Serv, Memphis, TN 38104 USA.
C3 University of Tennessee System; University of Tennessee Health Science Center; University of Tennessee System; University of Tennessee Health Science Center; University of Tennessee System; University of Tennessee Health Science Center; US Department of Veterans Affairs; Veterans Health Administration (VHA); Memphis VA Medical Center; US Department of Veterans Affairs; Veterans Health Administration (VHA); Memphis VA Medical Center
RP Fleckenstein, JM (corresponding author), Univ Tennessee, Ctr Hlth Sci, Dept Med, 956 Court Ave, Memphis, TN 38163 USA.
EM jflecke1@tennessee.edu
FU National Institutes of Health (National Center for Research Resources) [RR16190-05]; Department of Veterans Affairs; University of Tennessee Microbial Pathogenesis Research Center
NR 29
TC 160
Z9 188
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 29
PY 2009
VL 457
IS 7229
BP 594
EP U103
DI 10.1038/nature07568
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200044
PM 19060885
DA 2026-03-09
ER

PT J
AU Schuur, EAG
   Vogel, JG
   Crummer, KG
   Lee, H
   Sickman, JO
   Osterkamp, TE
AF Schuur, Edward A. G.
   Vogel, Jason G.
   Crummer, Kathryn G.
   Lee, Hanna
   Sickman, James O.
   Osterkamp, T. E.
TI The effect of permafrost thaw on old carbon release and net carbon exchange from tundra
SO NATURE
LA English
DT Article
ID climate-change; soil carbon; dynamics; decomposition; temperature; radiocarbon; ecosystems; feedbacks; sink
AB Permafrost soils in boreal and Arctic ecosystems store almost twice as much carbon(1,2) as is currently present in the atmosphere(3). Permafrost thaw and the microbial decomposition of previously frozen organic carbon is considered one of the most likely positive climate feedbacks from terrestrial ecosystems to the atmosphere in a warmer world(1,2,4-7). The rate of carbon release from permafrost soils is highly uncertain, but it is crucial for predicting the strength and timing of this carbon-cycle feedback effect, and thus how important permafrost thaw will be for climate change this century and beyond(1,2,4-7). Sustained transfers of carbon to the atmosphere that could cause a significant positive feedback to climate change must come from old carbon, which forms the bulk of the permafrost carbon pool that accumulated over thousands of years(8-11). Here we measure net ecosystem carbon exchange and the radiocarbon age of ecosystem respiration in a tundra landscape undergoing permafrost thaw(12) to determine the influence of old carbon loss on ecosystem carbon balance. We find that areas that thawed over the past 15 years had 40 per cent more annual losses of old carbon than minimally thawed areas, but had overall net ecosystem carbon uptake as increased plant growth offset these losses. In contrast, areas that thawed decades earlier lost even more old carbon, a 78 per cent increase over minimally thawed areas; this old carbon loss contributed to overall net ecosystem carbon release despite increased plant growth. Our data document significant losses of soil carbon with permafrost thaw that, over decadal timescales, overwhelms increased plant carbon uptake(13-15) at rates that could make permafrost a large biospheric carbon source in a warmer world.
C1 [Schuur, Edward A. G.; Vogel, Jason G.; Crummer, Kathryn G.; Lee, Hanna] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
   [Sickman, James O.] Univ Calif Riverside, Dept Environm Sci, Riverside, CA 92521 USA.
   [Osterkamp, T. E.] Univ Alaska, Inst Geophys, Fairbanks, AK 99775 USA.
C3 State University System of Florida; University of Florida; University of California System; University of California Riverside; University of Alaska System; University of Alaska Fairbanks
RP Schuur, EAG (corresponding author), Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
EM tschuur@ufl.edu
FU NASA New Investigator Program; NSF Bonanza Creek LTER Program; NSF DEB Ecosystems Program; National Park Service; Office of Polar Programs (OPP); Directorate For Geosciences [0806271] Funding Source: National Science Foundation
NR 30
TC 881
Z9 1063
U1 7
U2 782
PU NATURE PUBLISHING 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 28
PY 2009
VL 459
IS 7246
BP 556
EP 559
DI 10.1038/nature08031
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500036
PM 19478781
DA 2026-03-09
ER

PT J
AU Silva, JP
   von Meyenn, F
   Howell, J
   Thorens, B
   Wolfrum, C
   Stoffel, M
AF Silva, Jose P.
   von Meyenn, Ferdinand
   Howell, Jessica
   Thorens, Bernard
   Wolfrum, Christian
   Stoffel, Markus
TI Regulation of adaptive behaviour during fasting by hypothalamic Foxa2
SO NATURE
LA English
DT Article
ID melanin-concentrating hormone; cardiovascular risk-factors; insulin-resistance; physical-activity; cognitive function; mice; orexin; obesity; population; metabolism
AB The lateral hypothalamic area is considered the classic 'feeding centre', regulating food intake, arousal and motivated behaviour through the actions of orexin and melanin-concentrating hormone (MCH)(1-3). These neuropeptides are inhibited in response to feeding-related signals and are released during fasting. However, the molecular mechanisms that regulate and integrate these signals remain poorly understood. Here we show that the forkhead box transcription factor Foxa2,a downstream target of insulin signalling(4-6), regulates the expression of orexin and MCH. During fasting, Foxa2 binds to MCH and orexin promoters and stimulates their expression. In fed and in hyperinsulinemic obese mice, insulin signalling leads to nuclear exclusion of Foxa2 and reduced expression of MCH and orexin. Constitutive activation of Foxa2 in the brain (Nes-Cre/1; Foxa2T156A(flox/flox) genotype) results in increased neuronal MCH and orexin expression and increased food consumption, metabolism and insulin sensitivity. Spontaneous physical activity of these animals in the fed state is significantly increased and is similar to that in fasted mice. Conditional activation of Foxa2 through the T156A mutation expression in the brain of obese mice also resulted in improved glucose homeostasis, decreased fat and increased lean body mass. Our results demonstrate that Foxa2 can act as a metabolic sensor in neurons of the lateral hypothalamic area to integrate metabolic signals, adaptive behaviour and physiological responses.
C1 [Silva, Jose P.; Howell, Jessica; Stoffel, Markus] Rockefeller Univ, Lab Metab Dis, New York, NY 10021 USA.
   [von Meyenn, Ferdinand; Howell, Jessica; Wolfrum, Christian; Stoffel, Markus] ETH, Swiss Fed Inst Technol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Thorens, Bernard] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
C3 Rockefeller University; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Lausanne
RP Stoffel, M (corresponding author), Rockefeller Univ, Lab Metab Dis, 1230 York Ave, New York, NY 10021 USA.
EM stoffel@imsb.biol.ethz.ch
FU SystemsX; Swiss National Science Foundation
NR 22
TC 61
Z9 73
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 646
EP U119
DI 10.1038/nature08589
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900040
PM 19956259
DA 2026-03-09
ER

PT J
AU Chong, JL
   Wenzel, PL
   Sáenz-Robles, MT
   Nair, V
   Ferrey, A
   Hagan, JP
   Gomez, YM
   Sharma, N
   Chen, HZ
   Ouseph, M
   Wang, SH
   Trikha, P
   Culp, B
   Mezache, L
   Winton, DJ
   Sansom, OJ
   Chen, DN
   Bremner, R
   Cantalupo, PG
   Robinson, ML
   Pipas, JM
   Leone, G
AF Chong, Jean-Leon
   Wenzel, Pamela L.
   Saenz-Robles, M. Teresa
   Nair, Vivek
   Ferrey, Antoney
   Hagan, John P.
   Gomez, Yorman M.
   Sharma, Nidhi
   Chen, Hui-Zi
   Ouseph, Madhu
   Wang, Shu-Huei
   Trikha, Prashant
   Culp, Brian
   Mezache, Louise
   Winton, Douglas J.
   Sansom, Owen J.
   Chen, Danian
   Bremner, Rod
   Cantalupo, Paul G.
   Robinson, Michael L.
   Pipas, James M.
   Leone, Gustavo
TI E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells
SO NATURE
LA English
DT Article
ID intestinal epithelium; cellular proliferation; transcription factors; binding protein; s-phase; expression; e2f3; cycle; roles; mice
AB In the established model of mammalian cell cycle control, the retinoblastoma protein (Rb) functions to restrict cells from entering S phase by binding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate effectors of a transcriptional program that commit cells to enter and progress through S phase(1,2). Using a panel of tissue-specific cre-transgenic mice and conditional E2f alleles we examined the effects of E2f1, E2f2 and E2f3 triple deficiency in murine embryonic stem cells, embryos and small intestines. We show that in normal dividing progenitor cells E2f1-3 function as transcriptional activators, but contrary to the current view, are dispensable for cell division and instead are necessary for cell survival. In differentiating cells E2f1-3 function in a complex with Rb as repressors to silence E2f targets and facilitate exit from the cell cycle. The inactivation of Rb in differentiating cells resulted in a switch of E2f1-3 from repressors to activators, leading to the superactivation of E2f responsive targets and ectopic cell divisions. Loss of E2f1-3 completely suppressed these phenotypes caused by Rb deficiency. This work contextualizes the activator versus repressor functions of E2f1-3 in vivo, revealing distinct roles in dividing versus differentiating cells and in normal versus cancer-like cell cycles.
C1 [Chong, Jean-Leon; Wenzel, Pamela L.; Nair, Vivek; Ferrey, Antoney; Hagan, John P.; Gomez, Yorman M.; Sharma, Nidhi; Chen, Hui-Zi; Ouseph, Madhu; Wang, Shu-Huei; Trikha, Prashant; Culp, Brian; Mezache, Louise; Leone, Gustavo] Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
   [Chong, Jean-Leon; Wenzel, Pamela L.; Nair, Vivek; Ferrey, Antoney; Gomez, Yorman M.; Sharma, Nidhi; Chen, Hui-Zi; Ouseph, Madhu; Wang, Shu-Huei; Trikha, Prashant; Culp, Brian; Mezache, Louise; Leone, Gustavo] Ohio State Univ, Coll Biol Sci, Dept Mol Genet, Columbus, OH 43210 USA.
   [Chong, Jean-Leon; Wenzel, Pamela L.; Nair, Vivek; Ferrey, Antoney; Hagan, John P.; Gomez, Yorman M.; Sharma, Nidhi; Chen, Hui-Zi; Ouseph, Madhu; Wang, Shu-Huei; Trikha, Prashant; Culp, Brian; Mezache, Louise; Leone, Gustavo] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
   [Saenz-Robles, M. Teresa; Cantalupo, Paul G.; Pipas, James M.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
   [Winton, Douglas J.] Li Ka Shing Ctr, Cambridge Res Inst, Cambridge CB2 0RE, England.
   [Sansom, Owen J.] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
   [Chen, Danian; Bremner, Rod] Univ Toronto, Toronto Western Res Inst, Univ Hlth Network, Dept Ophthalmol & Visual Sci, Toronto, ON M5T 2S8, Canada.
   [Chen, Danian; Bremner, Rod] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5T 2S8, Canada.
   [Robinson, Michael L.] Miami Univ, Dept Zool, Oxford, OH 45056 USA.
C3 University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; James Cancer Hospital & Solove Research Institute; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Cambridge; CRUK Cambridge Institute; Beatson Institute; University of Toronto; University Health Network Toronto; University of Toronto; University System of Ohio; Miami University
RP Leone, G (corresponding author), Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
EM Gustavo.Leone@osumc.edu
FU NIH [R01CA85619, R01CA82259, R01HD04470, P01CA097189, CA098956, 5 T32 CA106196-04]; DoD award [BC061730]
NR 30
TC 198
Z9 241
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 17
PY 2009
VL 462
IS 7275
BP 930
EP 934
DI 10.1038/nature08677
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400045
PM 20016602
DA 2026-03-09
ER

PT J
AU Kitano, J
   Ross, JA
   Mori, S
   Kume, M
   Jones, FC
   Chan, YF
   Absher, DM
   Grimwood, J
   Schmutz, J
   Myers, RM
   Kingsley, DM
   Peichel, CL
AF Kitano, Jun
   Ross, Joseph A.
   Mori, Seiichi
   Kume, Manabu
   Jones, Felicity C.
   Chan, Yingguang F.
   Absher, Devin M.
   Grimwood, Jane
   Schmutz, Jeremy
   Myers, Richard M.
   Kingsley, David M.
   Peichel, Catherine L.
TI A role for a neo-sex chromosome in stickleback speciation
SO NATURE
LA English
DT Article
ID reproductive isolation; cichlid fish; threespine sticklebacks; segregation distortion; sympatric speciation; y-chromosome; evolution; drosophila; selection; gasterosteus
AB Sexual antagonism, or conflict between the sexes, has been proposed as a driving force in both sex-chromosome turnover and speciation. Although closely related species often have different sex-chromosome systems, it is unknown whether sex-chromosome turnover contributes to the evolution of reproductive isolation between species. Here we show that a newly evolved sex chromosome contains genes that contribute to speciation in threespine stickleback fish (Gasterosteus aculeatus). We first identified a neo-sex chromosome system found only in one member of a sympatric species pair in Japan. We then performed genetic linkage mapping of male-specific traits important for reproductive isolation between the Japanese species pair. The neo-X chromosome contains loci for male courtship display traits that contribute to behavioural isolation, whereas the ancestral X chromosome contains loci for both behavioural isolation and hybrid male sterility. Our work not only provides strong evidence for a large X-effect on reproductive isolation in a vertebrate system, but also provides direct evidence that a young neo-X chromosome contributes to reproductive isolation between closely related species. Our data indicate that sex-chromosome turnover might have a greater role in speciation than was previously appreciated.
C1 [Kitano, Jun; Ross, Joseph A.; Peichel, Catherine L.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
   [Ross, Joseph A.] Univ Washington, Grad Program Mol & Cellular Biol, Seattle, WA 98195 USA.
   [Mori, Seiichi] Gifu Keizai Univ, Biol Lab, Gifu 5038550, Japan.
   [Kume, Manabu] Publ Works Res Inst, Aqua Restorat Res Ctr, Gifu 5016021, Japan.
   [Jones, Felicity C.; Chan, Yingguang F.; Kingsley, David M.] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA.
   [Jones, Felicity C.; Chan, Yingguang F.; Kingsley, David M.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Absher, Devin M.; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M.] Stanford Univ, Dept Genet, Stanford, CA 94304 USA.
   [Absher, Devin M.; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M.] Stanford Univ, Stanford Human Genome Ctr, Stanford, CA 94304 USA.
C3 Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; PWRI: Public Works Research Institute; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University
RP Peichel, CL (corresponding author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave N, Seattle, WA 98109 USA.
EM cpeichel@fhcrc.org
FU Uehara Memorial Foundation; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Water and People Project of Research Institute for Humanity and Nature; Akkeshi Town Grants-in-Aid for Scientific Research in the Lake Akkeshi-Bekanbeushi Wetland; Burroughs Wellcome Fund Career Award in the Biomedical Sciences; National Institutes of Health [T32 GM07270, R01 GM071854, P50 HG02568]
NR 35
TC 304
Z9 339
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 OCT 22
PY 2009
VL 461
IS 7267
BP 1079
EP 1083
DI 10.1038/nature08441
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600035
PM 19783981
DA 2026-03-09
ER

PT J
AU Van Mooy, BAS
   Fredricks, HF
   Pedler, BE
   Dyhrman, ST
   Karl, DM
   Koblízek, M
   Lomas, MW
   Mincer, TJ
   Moore, LR
   Moutin, T
   Rappé, MS
   Webb, EA
AF Van Mooy, Benjamin A. S.
   Fredricks, Helen F.
   Pedler, Byron E.
   Dyhrman, Sonya T.
   Karl, David M.
   Koblizek, Michal
   Lomas, Michael W.
   Mincer, Tracy J.
   Moore, Lisa R.
   Moutin, Thierry
   Rappe, Michael S.
   Webb, Eric A.
TI Phytoplankton in the ocean use non-phosphorus lipids in response to phosphorus scarcity
SO NATURE
LA English
DT Article
ID nitrogen-fixation; n-p; limitation; phosphate; growth; bacterioplankton; prochlorococcus; trichodesmium; biosynthesis; availability
AB Phosphorus is an obligate requirement for the growth of all organisms; major biochemical reservoirs of phosphorus in marine plankton include nucleic acids and phospholipids(1-3). However, eukaryotic phytoplankton and cyanobacteria (that is, 'phytoplankton' collectively) have the ability to decrease their cellular phosphorus content when phosphorus in their environment is scarce(1,4,5). The biochemical mechanisms that allow phytoplankton to limit their phosphorus demand and still maintain growth are largely unknown. Here we show that phytoplankton, in regions of oligotrophic ocean where phosphate is scarce, reduce their cellular phosphorus requirements by substituting non-phosphorus membrane lipids for phospholipids. In the Sargasso Sea, where phosphate concentrations were less than 10 nmol l(-1), we found that only 1.3 +/- 0.6% of phosphate uptake was used for phospholipid synthesis; in contrast, in the South Pacific subtropical gyre, where phosphate was greater than 100 nmol l(-1), plankton used 17 +/- 6% (ref. 6). Examination of the planktonic membrane lipids at these two locations showed that classes of sulphur- and nitrogen-containing membrane lipids, which are devoid of phosphorus, were more abundant in the Sargasso Sea than in the South Pacific. Furthermore, these non-phosphorus, 'substitute lipids' were dominant in phosphorus-limited cultures of all of the phytoplankton species we examined. In contrast, the marine heterotrophic bacteria we examined contained no substitute lipids and only phospholipids. Thus heterotrophic bacteria, which compete with phytoplankton for nutrients in oligotrophic regions like the Sargasso Sea, appear to have a biochemical phosphorus requirement that phytoplankton avoid by using substitute lipids. Our results suggest that phospholipid substitutions are fundamental biochemical mechanisms that allow phytoplankton to maintain growth in the face of phosphorus limitation.
C1 [Van Mooy, Benjamin A. S.; Fredricks, Helen F.; Pedler, Byron E.; Mincer, Tracy J.] Woods Hole Oceanog Inst, Dept Marine Chem & Geochem, Woods Hole, MA 02543 USA.
   [Dyhrman, Sonya T.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA.
   [Karl, David M.] Univ Hawaii, Dept Oceanog, Honolulu, HI 96822 USA.
   [Koblizek, Michal] Acad Sci Czech Republ, Inst Microbiol, Trebon, Czech Republic.
   [Koblizek, Michal] Univ S Bohemia, Inst Phys Biol, Nove Hrady, Czech Republic.
   [Lomas, Michael W.] Bermuda Inst Ocean Sci, St George, Bermuda.
   [Moore, Lisa R.] Univ So Maine, Dept Biol Sci, Portland, ME 04103 USA.
   [Moutin, Thierry] Aix Marseille Univ, Ctr Oceanol Marseille, Lab Oceanog Phys & Biogeochim, Marseille, France.
   [Rappe, Michael S.] Univ Hawaii, Hawaii Inst Marine Biol, Kaneohe, HI USA.
   [Webb, Eric A.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
C3 Woods Hole Oceanographic Institution; Woods Hole Oceanographic Institution; University of Hawaii System; Czech Academy of Sciences; Institute of Microbiology of the Czech Academy of Sciences; University of South Bohemia Ceske Budejovice; Bermuda Institute of Ocean Sciences; University of Maine System; University of Southern Maine; Aix-Marseille Universite; University of Hawaii System; University of Southern California
RP Van Mooy, BAS (corresponding author), Woods Hole Oceanog Inst, Dept Marine Chem & Geochem, Woods Hole, MA 02543 USA.
EM bvanmooy@whoi.edu
FU National Science Foundation [OCE-0646944, OCE-0451419, OCE-0326616, OCE-0453023, OCE-0453019, DEB-0207085]; Office of Naval Research [N00014-06-1-0134, GAAV-1QS500200570]; Centre National de la Recherche Scientifique; Institut des Sciences de l'Univers; Gordon and Betty Moore Foundation; Center for Microbial Oceanography: Research and Education; Woods Hole Oceanographic Institution Ocean Life Institute; Woods Hole Oceanographic Institution Mary Sears Travel Fund
NR 30
TC 631
Z9 724
U1 18
U2 335
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 5
PY 2009
VL 458
IS 7234
BP 69
EP 72
DI 10.1038/nature07659
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000034
PM 19182781
DA 2026-03-09
ER

PT J
AU Ng, SB
   Turner, EH
   Robertson, PD
   Flygare, SD
   Bigham, AW
   Lee, C
   Shaffer, T
   Wong, M
   Bhattacharjee, A
   Eichler, EE
   Bamshad, M
   Nickerson, DA
   Shendure, J
AF Ng, Sarah B.
   Turner, Emily H.
   Robertson, Peggy D.
   Flygare, Steven D.
   Bigham, Abigail W.
   Lee, Choli
   Shaffer, Tristan
   Wong, Michelle
   Bhattacharjee, Arindam
   Eichler, Evan E.
   Bamshad, Michael
   Nickerson, Deborah A.
   Shendure, Jay
TI Targeted capture and massively parallel sequencing of 12 human exomes
SO NATURE
LA English
DT Article
ID human genome; exon capture; alleles; gene
AB Genome-wide association studies suggest that common genetic variants explain only a modest fraction of heritable risk for common diseases, raising the question of whether rare variants account for a significant fraction of unexplained heritability(1,2). Although DNA sequencing costs have fallen markedly(3), they remain far from what is necessary for rare and novel variants to be routinely identified at a genome-wide scale in large cohorts. We have therefore sought to develop second-generation methods for targeted sequencing of all protein-coding regions ('exomes'), to reduce costs while enriching for discovery of highly penetrant variants. Here we report on the targeted capture and massively parallel sequencing of the exomes of 12 humans. These include eight HapMap individuals representing three populations(4), and four unrelated individuals with a rare dominantly inherited disorder, Freeman-Sheldon syndrome (FSS)(5). We demonstrate the sensitive and specific identification of rare and common variants in over 300 megabases of coding sequence. Using FSS as a proof-of-concept, we show that candidate genes for Mendelian disorders can be identified by exome sequencing of a small number of unrelated, affected individuals. This strategy may be extendable to diseases with more complex genetics through larger sample sizes and appropriate weighting of non-synonymous variants by predicted functional impact.
C1 [Ng, Sarah B.; Turner, Emily H.; Robertson, Peggy D.; Flygare, Steven D.; Lee, Choli; Shaffer, Tristan; Wong, Michelle; Eichler, Evan E.; Nickerson, Deborah A.; Shendure, Jay] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Bigham, Abigail W.; Bamshad, Michael] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
   [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Bhattacharjee, Arindam] Agilent Technol, Santa Clara, CA 95051 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Agilent Technologies
RP Shendure, J (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM sarahng@u.washington.edu; shendure@u.washington.edu
FU National Institutes of Health/National Heart Lung and Blood Institute; National Institutes of Health/National Human Genome Research Institute; National Institutes of Health/National Institute of Child Health and Human Development; Washington Research Foundation; Agency for Science, Technology and Research, Singapore; Howard Hughes Medical Institute
NR 30
TC 1500
Z9 1949
U1 1
U2 187
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 10
PY 2009
VL 461
IS 7261
BP 272
EP U153
DI 10.1038/nature08250
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600046
PM 19684571
DA 2026-03-09
ER

PT J
AU Bowler, C
   Karl, DM
   Colwell, RR
AF Bowler, Chris
   Karl, David M.
   Colwell, Rita R.
TI Microbial oceanography in a sea of opportunity
SO NATURE
LA English
DT Article
ID diatom thalassiosira-pseudonana; gene-expression; deep-sea; ocean; genome; biodiversity; biogeography; biosphere; fixation; atlantic
C1 [Bowler, Chris] Ecole Normale Super, Dept Biol, CNRS, UMR8186, Paris, France.
   [Bowler, Chris] Stn Zool Anton Dohrn, I-80121 Naples, Italy.
   [Karl, David M.] Univ Hawaii, Sch Ocean & Earth Sci & Technol, Ctr Microbial Oceanog Res & Educ, Honolulu, HI 96822 USA.
   [Colwell, Rita R.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
C3 Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Stazione Zoologica Anton Dohrn; University of Hawaii System; University System of Maryland; University of Maryland College Park
RP Bowler, C (corresponding author), Ecole Normale Super, Dept Biol, CNRS, UMR8186, 46 Rue Ulm, Paris, France.
EM cbowler@biologie.ens.fr
FU Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0753659] Funding Source: National Science Foundation; PHS HHS [1R01A139129-01] Funding Source: Medline
NR 39
TC 69
Z9 88
U1 0
U2 87
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 180
EP 184
DI 10.1038/nature08056
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100027
PM 19444203
DA 2026-03-09
ER

PT J
AU Sobolevsky, AI
   Rosconi, MP
   Gouaux, E
AF Sobolevsky, Alexander I.
   Rosconi, Michael P.
   Gouaux, Eric
TI X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor
SO NATURE
LA English
DT Article
ID ligand-binding domain; kainate receptors; nmda receptors; functional expression; allosteric modulators; molecular-mechanisms; subunit composition; crystal-structures; k+ channels; desensitization
AB Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system and function by opening a transmembrane ion channel upon binding of glutamate. Despite their crucial role in neurobiology, the architecture and atomic structure of an intact ionotropic glutamate receptor are unknown. Here we report the crystal structure of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-sensitive, homotetrameric, rat GluA2 receptor at 3.6 angstrom resolution in complex with a competitive antagonist. The receptor harbours an overall axis of two-fold symmetry with the extracellular domains organized as pairs of local dimers and with the ion channel domain exhibiting four-fold symmetry. A symmetry mismatch between the extracellular and ion channel domains is mediated by two pairs of conformationally distinct subunits, A/C and B/D. Therefore, the stereochemical manner in which the A/C subunits are coupled to the ion channel gate is different from the B/D subunits. Guided by the GluA2 structure and site-directed cysteine mutagenesis, we suggest that GluN1 and GluN2A NMDA (N-methyl-D-aspartate) receptors have a similar architecture, with subunits arranged in a 1-2-1-2 pattern. We exploit the GluA2 structure to develop mechanisms of ion channel activation, desensitization and inhibition by non-competitive antagonists and pore blockers.
C1 [Sobolevsky, Alexander I.; Rosconi, Michael P.; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Howard Hughes Medical Institute
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU NIH National Research Service Award; Howard Hughes Medical Institute; National Institute of Neurological Disorders and Stroke [R01NS038631] Funding Source: NIH RePORTER
NR 89
TC 867
Z9 1043
U1 1
U2 125
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 745
EP U66
DI 10.1038/nature08624
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900030
PM 19946266
DA 2026-03-09
ER

PT J
AU Rajakulendran, T
   Sahmi, M
   Lefrançois, M
   Sicheri, F
   Therrien, M
AF Rajakulendran, Thanashan
   Sahmi, Malha
   Lefrancois, Martin
   Sicheri, Frank
   Therrien, Marc
TI A dimerization-dependent mechanism drives RAF catalytic activation
SO NATURE
LA English
DT Article
ID b-raf; signaling pathway; oncogenic braf; human cancer; kinase; protein; heterodimerization; domain; inhibitors; drosophila
AB The ERK (extracellular signal-regulated kinase) pathway is an evolutionarily conserved signal transduction module that controls cellular growth, differentiation and survival(1). Activation of receptor tyrosine kinases (RTKs) by the binding of growth factors initiates GTP loading of RAS, which triggers the initial steps in the activation of the ERK pathway by modulating RAF family kinase function. Once activated, RAF participates in a sequential cascade of phosphorylation events that activate MEK, and in turn ERK. Unbridled signalling through the ERK pathway caused by activating mutations in RTKs, RAS or RAF has been linked to several human cancers(2). Of note, one member of the RAF family, BRAF, is the most frequently mutated oncogene in the kinase superfamily(3). Not surprisingly, there has been a colossal effort to understand the underlying regulation of this family of kinases. In particular, the process by which the RAF kinase domain becomes activated towards its substrate MEK remains of topical interest. Here, using Drosophila Schneider S2 cells, we demonstrate that RAF catalytic function is regulated in response to a specific mode of dimerization of its kinase domain, which we term the side-to-side dimer. Moreover, we find that the RAF-related pseudo-kinase KSR ( kinase suppressor of Ras) also participates in forming side-to-side heterodimers with RAF and can thereby trigger RAF activation. This mechanism provides an elegant explanation for the longstanding conundrumabout RAF catalytic activation, and also provides an explanation for the capacity of KSR, despite lacking catalytic function, to directly mediate RAF activation. We also show that RAF side-to-side dimer formation is essential for aberrant signalling by oncogenic BRAF mutants, and identify an oncogenic mutation that acts specifically by promoting side-to-side dimerization. Together, our data identify the side-to-side dimer interface of RAF as a potential therapeutic target for intervention in BRAF-dependent tumorigenesis.
C1 [Rajakulendran, Thanashan; Sicheri, Frank] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada.
   [Rajakulendran, Thanashan; Sicheri, Frank] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Sahmi, Malha; Lefrancois, Martin; Therrien, Marc] Univ Montreal, Inst Res Immunol & Canc, Lab Intracellular Signaling, Montreal, PQ H3C 3J7, Canada.
   [Therrien, Marc] Univ Montreal, Dept Pathol & Biol Cellular, Montreal, PQ H3C 3J7, Canada.
C3 University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; Universite de Montreal; Universite de Montreal
RP Sicheri, F (corresponding author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.
EM sicheri@lunenfeld.ca; marc.therrien@umontreal.ca
FU Canadian Institutes for Health Research [MOP-36399]; Canadian Cancer Society [018046]; Research Fellow of The Terry Fox Foundation [019684]; National Cancer Institute of Canada Scientist award; Canada Research Chair
NR 25
TC 381
Z9 483
U1 2
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 24
PY 2009
VL 461
IS 7263
BP 542
EP U114
DI 10.1038/nature08314
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900044
PM 19727074
DA 2026-03-09
ER

PT J
AU Oulton, RF
   Sorger, VJ
   Zentgraf, T
   Ma, RM
   Gladden, C
   Dai, L
   Bartal, G
   Zhang, X
AF Oulton, Rupert F.
   Sorger, Volker J.
   Zentgraf, Thomas
   Ma, Ren-Min
   Gladden, Christopher
   Dai, Lun
   Bartal, Guy
   Zhang, Xiang
TI Plasmon lasers at deep subwavelength scale
SO NATURE
LA English
DT Article
ID wave-guide
AB Laser science has been successful in producing increasingly high-powered, faster and smaller coherent light sources(1-9). Examples of recent advances are microscopic lasers that can reach the diffraction limit, based on photonic crystals(3), metal-clad cavities(4) and nanowires(5-7). However, such lasers are restricted, both in optical mode size and physical device dimension, to being larger than half the wavelength of the optical field, and it remains a key fundamental challenge to realize ultracompact lasers that can directly generate coherent optical fields at the nanometre scale, far beyond the diffraction limit(10,11). A way of addressing this issue is to make use of surface plasmons(12,13), which are capable of tightly localizing light, but so far ohmic losses at optical frequencies have inhibited the realization of truly nanometre-scale lasers based on such approaches(14,15). A recent theoretical work predicted that such losses could be significantly reduced while maintaining ultrasmall modes in a hybrid plasmonic waveguide(16). Here we report the experimental demonstration of nanometre-scale plasmonic lasers, generating optical modes a hundred times smaller than the diffraction limit. We realize such lasers using a hybrid plasmonic waveguide consisting of a high-gain cadmium sulphide semiconductor nanowire, separated from a silver surface by a 5-nm thick insulating gap. Direct measurements of the emission lifetime reveal a broad-band enhancement of the nanowire's exciton spontaneous emission rate by up to six times owing to the strong mode confinement(17) and the signature of apparently threshold-less lasing. Because plasmonic modes have no cutoff, we are able to demonstrate downscaling of the lateral dimensions of both the device and the optical mode. Plasmonic lasers thus offer the possibility of exploring extreme interactions between light and matter, opening up new avenues in the fields of active photonic circuits(18), bio-sensing(19) and quantum information technology(20).
C1 [Oulton, Rupert F.; Sorger, Volker J.; Zentgraf, Thomas; Gladden, Christopher; Bartal, Guy; Zhang, Xiang] Univ Calif Berkeley, NSF Nanoscale Sci & Engn Ctr, Berkeley, CA 94720 USA.
   [Zhang, Xiang] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Ma, Ren-Min; Dai, Lun] Peking Univ, Sch Phys, Beijing 100871, Peoples R China.
   [Ma, Ren-Min; Dai, Lun] Peking Univ, State Key Lab Mesoscop Phys, Beijing 100871, Peoples R China.
C3 University of California System; University of California Berkeley; National Science Foundation (NSF); United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Peking University; Peking University
RP Zhang, X (corresponding author), Univ Calif Berkeley, NSF Nanoscale Sci & Engn Ctr, 3112 Etcheverry Hall, Berkeley, CA 94720 USA.
EM xiang@berkeley.edu
FU US Air Force Office of Scientific Research (AFOSR) MURI programme [FA9550-04-1-0434]; National Science Foundation Nano-scale Science and Engineering Center (NSF-NSEC) [CMMI-0751621]; Alexander von Humboldt Foundation; Intel Corporation; National Natural Science Foundation of China [60576037, 10774007]; National Basic Research Program of China [2006CB921607, 2007CB613402]
NR 30
TC 2281
Z9 2552
U1 14
U2 1624
PU NATURE PUBLISHING 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 1
PY 2009
VL 461
IS 7264
BP 629
EP 632
DI 10.1038/nature08364
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600035
PM 19718019
DA 2026-03-09
ER

PT J
AU Carreiras, M
   Seghier, ML
   Baquero, S
   Estévez, A
   Lozano, A
   Devlin, JT
   Price, CJ
AF Carreiras, Manuel
   Seghier, Mohamed L.
   Baquero, Silvia
   Estevez, Adelina
   Lozano, Alfonso
   Devlin, Joseph T.
   Price, Cathy J.
TI An anatomical signature for literacy
SO NATURE
LA English
DT Article
ID brain; morphology; diffusion; dyslexia; children; language; skills; integration; mechanisms; handedness
AB Language is a uniquely human ability that evolved at some point in the roughly 6,000,000 years since human and chimpanzee lines diverged(1,2). Even in the most linguistically impoverished environments, children naturally develop sophisticated language systems(3). In contrast, reading is a learnt skill that does not develop without intensive tuition and practice. Learning to read is likely to involve ontogenic structural brain changes(4-6), but these are nearly impossible to isolate in children owing to concurrent biological, environmental and social maturational changes. In Colombia, guerrillas are re-integrating into mainstream society and learning to read for the first time as adults. This presents a unique opportunity to investigate how literacy changes the brain, without the maturational complications present in children. Here we compare structural brain scans from those who learnt to read as adults (late-literates) with those from a carefully matched set of illiterates. Late-literates had more white matter in the splenium of the corpus callosum and more grey matter in bilateral angular, dorsal occipital, middle temporal, left supramarginal and superior temporal gyri. The importance of these brain regions for skilled reading was investigated in early literates, who learnt to read as children. We found anatomical connections linking the left and right angular and dorsal occipital gyri through the area of the corpus callosum where white matter was higher in late-literates than in illiterates; that reading, relative to object naming, increased the interhemispheric functional connectivity between the left and right angular gyri; and that activation in the left angular gyrus exerts top-down modulation on information flow from the left dorsal occipital gyrus to the left supramarginal gyrus. These findings demonstrate how the regions identified in late-literates interact during reading, relative to object naming, in early literates.
C1 [Carreiras, Manuel] Basque Ctr Cognit Brain & Language, Donostia San Sebastian 20009, Spain.
   [Carreiras, Manuel] Basque Fdn Sci, IKERBASQUE, Bilbao 48011, Spain.
   [Carreiras, Manuel] Univ Basque Country, Dept Filol Vasca, Bilbao 48940, Spain.
   [Carreiras, Manuel; Estevez, Adelina] Univ La Laguna, Tenerife 38055, Spain.
   [Seghier, Mohamed L.; Price, Cathy J.] UCL, Inst Neurol, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England.
   [Baquero, Silvia; Lozano, Alfonso] Univ Nacl Colombia, Bogota 3165000, Colombia.
   [Devlin, Joseph T.] UCL, London WC1E 6BT, England.
C3 Basque Foundation for Science; University of Basque Country; Universidad de la Laguna; University of London; University College London; Universidad Nacional de Colombia; University of London; University College London
RP Carreiras, M (corresponding author), Basque Ctr Cognit Brain & Language, Donostia San Sebastian 20009, Spain.
EM m.carreiras@bcbl.eu; c.price@fil.ion.ucl.ac.uk
FU Spanish Ministry of Education and Science; Wellcome Trust
NR 50
TC 319
Z9 369
U1 2
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 983
EP U245
DI 10.1038/nature08461
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700048
PM 19829380
DA 2026-03-09
ER

PT J
AU Ressl, S
   van Scheltinga, ACT
   Vonrhein, C
   Ott, V
   Ziegler, C
AF Ressl, Susanne
   van Scheltinga, Anke C. Terwisscha
   Vonrhein, Clemens
   Ott, Vera
   Ziegler, Christine
TI Molecular basis of transport and regulation in the Na+/betaine symporter BetP
SO NATURE
LA English
DT Article
ID solutes glycine betaine; renal medullary cells; corynebacterium-glutamicum; compatible solutes; organic osmolytes; neurotransmitter transporters; serotonin transporter; osmotic regulation; crystal-structure; volume regulation
AB Osmoregulated transporters sense intracellular osmotic pressure and respond to hyperosmotic stress by accumulation of osmolytes to restore normal hydration levels. Here we report the determination of the X-ray structure of a member of the family of betaine/choline/carnitine transporters, the Na+-coupled symporter BetP from Corynebacterium glutamicum, which is a highly effective osmoregulated uptake system for glycine betaine. Glycine betaine is bound in a tryptophan box occluded from both sides of the membrane with aromatic side chains lining the transport pathway. BetP has the same overall fold as three unrelated Na+-coupled symporters. Whereas these are crystallized in either the outward-facing or the inward-facing conformation, the BetP structure reveals a unique intermediate conformation in the Na+-coupled transport cycle. The trimeric architecture of BetP and the break in three-fold symmetry by the osmosensing C-terminal helices suggest a regulatory mechanism of Na+-coupled osmolyte transport to counteract osmotic stress.
C1 [Ressl, Susanne; van Scheltinga, Anke C. Terwisscha; Ziegler, Christine] Max Planck Inst Biophys, Dept Biol Struct, D-60438 Frankfurt, Germany.
   [Vonrhein, Clemens] Global Phasing Ltd, Sheraton House, Cambridge CB3 0AX, England.
   [Ott, Vera] Univ Cologne, Inst Biochem, D-50937 Cologne, Germany.
C3 Max Planck Society; Global Phasing Limited; University of Cologne
RP Ziegler, C (corresponding author), Max Planck Inst Biophys, Dept Biol Struct, D-60438 Frankfurt, Germany.
EM christine.ziegler@mpibp-frankfurt.mpg.de
FU German Research Foundation; Collaborative Research Centre 807 'Transport and Communication across Biological Membranes'
NR 59
TC 271
Z9 315
U1 1
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 5
PY 2009
VL 458
IS 7234
BP 47
EP U1
DI 10.1038/nature07819
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000029
PM 19262666
DA 2026-03-09
ER

PT J
AU Racki, LR
   Yang, JG
   Naber, N
   Partensky, PD
   Acevedo, A
   Purcell, TJ
   Cooke, R
   Cheng, YF
   Narlikar, GJ
AF Racki, Lisa R.
   Yang, Janet G.
   Naber, Nariman
   Partensky, Peretz D.
   Acevedo, Ashley
   Purcell, Thomas J.
   Cooke, Roger
   Cheng, Yifan
   Narlikar, Geeta J.
TI The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes
SO NATURE
LA English
DT Article
ID dna translocation; iswi; complex; protein; family; chrac; recognition; disruption; mechanism; helicases
AB Evenly spaced nucleosomes directly correlate with condensed chromatin and gene silencing. The ATP-dependent chromatin assembly factor (ACF) forms such structures in vitro and is required for silencing in vivo. ACF generates and maintains nucleosome spacing by constantly moving a nucleosome towards the longer flanking DNA faster than the shorter flanking DNA. How the enzyme rapidly moves back and forth between both sides of a nucleosome to accomplish bidirectional movement is unknown. Here we show that nucleosome movement depends cooperatively on two ACF molecules, indicating that ACF functions as a dimer of ATPases. Further, the nucleotide state determines whether the dimer closely engages one or both sides of the nucleosome. Three-dimensional reconstruction by single-particle electron microscopy of the ATPase-nucleosome complex in an activated ATP state reveals a dimer architecture in which the two ATPases face each other. Our results indicate a model in which the two ATPases work in a coordinated manner, taking turns to engage either side of a nucleosome, thereby allowing processive bidirectional movement. This novel dimeric motor mechanism differs from that of dimeric motors such as kinesin and dimeric helicases that processively translocate unidirectionally and reflects the unique challenges faced by motors that move nucleosomes.
C1 [Cheng, Yifan; Narlikar, Geeta J.] Univ Calif San Francisco, Dept Biochem & Biophys, WM Keck Adv Microscopy Lab, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco
RP Narlikar, GJ (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, WM Keck Adv Microscopy Lab, 600 16th St, San Francisco, CA 94158 USA.
EM ycheng@ucsf.edu; geeta.narlikar@ucsf.edu
FU Sandler Family Supporting Foundation; UCSF Academic Senate Shared Equipment Grant; National Institutes of Health; Beckman Foundation; US National Science Foundation Graduate Research Fellowships
NR 47
TC 143
Z9 175
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 DEC 24
PY 2009
VL 462
IS 7276
BP 1016
EP 1021
DI 10.1038/nature08621
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000038
PM 20033039
DA 2026-03-09
ER

PT J
AU Curran, SP
   Wu, XY
   Riedel, CG
   Ruvkun, G
AF Curran, Sean P.
   Wu, Xiaoyun
   Riedel, Christian G.
   Ruvkun, Gary
TI A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants
SO NATURE
LA English
DT Article
ID life-span; rna interference; gene-expression; factor skn-1; dna-damage; daf-16; identification; longevity; chromatin; targets
AB Unlike the soma, which ages during the lifespan of multicellular organisms, the germ line traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation towards reproduction at the expense of cellular senescence. Here we show that Caenorhabditis elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germ line. Decreased insulin-like signalling causes the somatic misexpression of the germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. The forkhead boxO1A (FOXO) transcription factor DAF-16, the major transcriptional effector of insulin-like signalling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also causes somatic misexpression of PGL-1. These results indicate that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival.
C1 [Curran, Sean P.; Wu, Xiaoyun; Riedel, Christian G.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Curran, Sean P.; Wu, Xiaoyun; Riedel, Christian G.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
RP Ruvkun, G (corresponding author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM ruvkun@molbio.mgh.harvard.edu
FU National Institutes of Health; National Institute on Aging [F32-AG026207, R01-AG016636]; European Molecular Biology Organization; Human Frontier Science Program; National Institute on Aging [R01AG016636] Funding Source: NIH RePORTER
NR 49
TC 92
Z9 128
U1 0
U2 28
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1079
EP U60
DI 10.1038/nature08106
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700033
PM 19506556
DA 2026-03-09
ER

PT J
AU Vecsey, CG
   Baillie, GS
   Jaganath, D
   Havekes, R
   Daniels, A
   Wimmer, M
   Huang, T
   Brown, KM
   Li, XY
   Descalzi, G
   Kim, SS
   Chen, T
   Shang, YZ
   Zhuo, M
   Houslay, MD
   Abel, T
AF Vecsey, Christopher G.
   Baillie, George S.
   Jaganath, Devan
   Havekes, Robbert
   Daniels, Andrew
   Wimmer, Mathieu
   Huang, Ted
   Brown, Kim M.
   Li, Xiang-Yao
   Descalzi, Giannina
   Kim, Susan S.
   Chen, Tao
   Shang, Yu-Ze
   Zhuo, Min
   Houslay, Miles D.
   Abel, Ted
TI Sleep deprivation impairs cAMP signalling in the hippocampus
SO NATURE
LA English
DT Article
ID long-term potentiation; cyclic-amp phosphodiesterase; synaptic plasticity; protein-kinase; late-phase; insufficient sleep; ca1 region; memory; receptor; activation
AB Millions of people regularly obtain insufficient sleep(1). Given the effect of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to produce memory deficits in learning models that are dependent on the hippocampus(2-5). Here we have identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. Sleep deprivation selectively impaired 3',5'-cyclic AMP (cAMP)- and protein kinase A (PKA)-dependent forms of synaptic plasticity(6) in the mouse hippocampus, reduced cAMP signalling, and increased activity and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of mice with phosphodiesterase inhibitors rescued the sleep-deprivation-induced deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent memory. These findings demonstrate that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signalling through increased PDE4 activity. Thus, drugs that enhance cAMP signalling may provide a new therapeutic approach to counteract the cognitive effects of sleep deprivation.
C1 [Vecsey, Christopher G.; Jaganath, Devan; Havekes, Robbert; Daniels, Andrew; Wimmer, Mathieu; Huang, Ted; Abel, Ted] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Vecsey, Christopher G.; Wimmer, Mathieu; Huang, Ted] Univ Penn, Neurosci Grad Grp, Philadelphia, PA 19104 USA.
   [Baillie, George S.; Brown, Kim M.; Houslay, Miles D.] Univ Glasgow, Fac Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
   [Li, Xiang-Yao; Descalzi, Giannina; Kim, Susan S.; Chen, Tao; Shang, Yu-Ze; Zhuo, Min] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada.
C3 University of Pennsylvania; University of Pennsylvania; University of Glasgow; University of Toronto
RP Abel, T (corresponding author), Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
EM abele@sas.upenn.edu
FU Systems and Integrative Biology Training [GM07517]; NIH; Netherlands Organization for Scientific Research NWO-Rubicon [825.07.029]; National Institutes of Health [AG017628]; SCOR [HL060287]; HFSP [RGSP/2005]; Medical Research Council (UK); European Union [LSHB-CT-2006-037189]; Fondation Leducq [06CVD02, CIHR84256]; UK Engineering and Physical Sciences Research Council; National Heart Lung and Blood Institute [T32HL007953] Funding Source: NIH RePORTER; Medical Research Council [G0600765] Funding Source: researchfish; MRC [G0600765] Funding Source: UKRI
NR 41
TC 350
Z9 418
U1 4
U2 101
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1122
EP U221
DI 10.1038/nature08488
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600044
PM 19847264
DA 2026-03-09
ER

PT J
AU Suzuki, HI
   Yamagata, K
   Sugimoto, K
   Iwamoto, T
   Kato, S
   Miyazono, K
AF Suzuki, Hiroshi I.
   Yamagata, Kaoru
   Sugimoto, Koichi
   Iwamoto, Takashi
   Kato, Shigeaki
   Miyazono, Kohei
TI Modulation of microRNA processing by p53
SO NATURE
LA English
DT Article
ID proline-rich domain; tumor-suppressor; expression; cancer; activation; apoptosis; complex; cells; microprocessor; tumorigenesis
AB MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. Although miRNAs can function as both tumour suppressors and oncogenes in tumour development(1), a widespread downregulation of miRNAs is commonly observed in human cancers and promotes cellular transformation and tumorigenesis(2-4). This indicates an inherent significance of small RNAs in tumour suppression. However, the connection between tumour suppressor networks and miRNA biogenesis machineries has not been investigated in depth. Here we show that a central tumour suppressor, p53, enhances the post-transcriptional maturation of several miRNAs with growth-suppressive function, including miR-16-1, miR-143 and miR-145, in response to DNA damage. In HCT116 cells and human diploid fibroblasts, p53 interacts with the Drosha processing complex through the association with DEAD-box RNA helicase p68 (also known as DDX5) and facilitates the processing of primary miRNAs to precursor miRNAs. We also found that transcriptionally inactive p53 mutants interfere with a functional assembly between Drosha complex and p68, leading to attenuation of miRNA processing activity. These findings suggest that transcription-independent modulation of miRNA biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Our study reveals a previously unrecognized function of p53 in miRNA processing, which may underlie key aspects of cancer biology.
C1 [Suzuki, Hiroshi I.; Miyazono, Kohei] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, Tokyo 1130033, Japan.
   [Yamagata, Kaoru; Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Yamagata, Kaoru; Kato, Shigeaki] Japan Sci & Technol Agcy, ERATO, Kawaguchisi, Saitama 3320012, Japan.
   [Sugimoto, Koichi] Juntendo Univ, Sch Med, Dept Internal Med, Div Hematol,Bunkyo Ku, Tokyo 1138421, Japan.
   [Iwamoto, Takashi] Chubu Univ, Coll Life & Hlth Sci, Dept Biomed Sci, Aichi 4878501, Japan.
   [Iwamoto, Takashi] Chubu Univ, Ctr Educ Lab Anim Res, Aichi 4878501, Japan.
C3 University of Tokyo; University of Tokyo; Japan Science & Technology Agency (JST); Juntendo University; Chubu University; Chubu University
RP Miyazono, K (corresponding author), Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM miyazono@m.u-tokyo.ac.jp
FU KAKENHI [17016011]; Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Society for the Promotion of Science for Young Scientists; Grants-in-Aid for Scientific Research [17016011] Funding Source: KAKEN
NR 37
TC 949
Z9 1107
U1 0
U2 145
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 529
EP U111
DI 10.1038/nature08199
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000042
PM 19626115
DA 2026-03-09
ER

PT J
AU Billeter, JC
   Atallah, J
   Krupp, JJ
   Millar, JG
   Levine, JD
AF Billeter, Jean-Christophe
   Atallah, Jade
   Krupp, Joshua J.
   Millar, Jocelyn G.
   Levine, Joel D.
TI Specialized cells tag sexual and species identity in Drosophila melanogaster
SO NATURE
LA English
DT Article
ID cuticular hydrocarbons; behavioral-responses; genetic-control; courtship; pheromones; subgroup; communication; males
AB Social interactions depend on individuals recognizing each other, and in this context many organisms use chemical signals to indicate species and sex(1). Cuticular hydrocarbon signals are used by insects, including Drosophila melanogaster, to distinguish conspecific individuals from others(1-3). These chemicals also contribute to intraspecific courtship and mating interactions(1-3). However, the possibility that sex and species identification are linked by common chemical signalling mechanisms has not been formally tested. Here we provide direct evidence that a single compound is used to communicate female identity among D. melanogaster, and to define a reproductive isolation barrier between D. melanogaster and sibling species. A transgenic manipulation eliminated cuticular hydrocarbons by ablating the oenocytes, specialized cells required for the expression of these chemical signals. The resulting oenocyte-less (oe(-)) females elicited the normal repertoire of courtship behaviours from males, but were actually preferred over wild-type females by courting males. In addition, wild-type males attempted to copulate with oe(-) males. Thus, flies lacking hydrocarbons are a sexual hyperstimulus. Treatment of virgin females with the aversive male pheromone cis-vaccenyl acetate (cVA) significantly delayed mating of oe(-) females compared to wild-type females. This difference was eliminated when oe(-) females were treated with a blend of cVA and the female aphrodisiac (7Z,11Z)-heptacosadiene (7,11-HD), showing that female aphrodisiac compounds can attenuate the effects of male aversive pheromones. 7,11-HD also was shown to have a crucial role in heterospecific encounters. Specifically, the species barrier was lost because males of other Drosophila species courted oe(-) D. melanogaster females, and D. simulans males consistently mated with them. Treatment of oe(-) females with 7,11-HD restored the species barrier, showing that a single compound can confer species identity. These results identify a common mechanism for sexual and species recognition regulated by cuticular hydrocarbons.
C1 [Billeter, Jean-Christophe; Atallah, Jade; Krupp, Joshua J.; Levine, Joel D.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
   [Millar, Jocelyn G.] Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA.
C3 University of Toronto; University Toronto Mississauga; University of California System; University of California Riverside
RP Levine, JD (corresponding author), Univ Toronto, Dept Biol, 3359 Mississauga Rd, Mississauga, ON L5L 1C6, Canada.
EM joel.levine@utoronto.ca
FU Swiss National Science Foundation; Canadian Institutes of Health Research; Canada Research Chair
NR 30
TC 314
Z9 377
U1 3
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 987
EP U250
DI 10.1038/nature08495
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700049
PM 19829381
DA 2026-03-09
ER

PT J
AU Mattsson, J
   Wyss, HM
   Fernandez-Nieves, A
   Miyazaki, K
   Hu, ZB
   Reichman, DR
   Weitz, DA
AF Mattsson, Johan
   Wyss, Hans M.
   Fernandez-Nieves, Alberto
   Miyazaki, Kunimasa
   Hu, Zhibing
   Reichman, David R.
   Weitz, David A.
TI Soft colloids make strong glasses
SO NATURE
LA English
DT Article
ID dynamic light-scattering; hard-sphere suspensions; forming liquids; amorphous solids; transition; fragility; viscoelasticity; relaxation; dependence; viscosity
AB Glass formation in colloidal suspensions has many of the hallmarks of glass formation in molecular materials(1-5). For hard-sphere colloids, which interact only as a result of excluded volume, phase behaviour is controlled by volume fraction, phi; an increase in phi drives the system towards its glassy state, analogously to a decrease in temperature, T, in molecular systems. When phi increases above phi* approximate to 0.53, the viscosity starts to increase significantly, and the system eventually moves out of equilibrium at the glass transition, phi(g) approximate to 0.58, where particle crowding greatly restricts structural relaxation(1-4). The large particle size makes it possible to study both structure and dynamics with light scattering(1) and imaging(3,4); colloidal suspensions have therefore provided considerable insight into the glass transition. However, hard-sphere colloidal suspensions do not exhibit the same diversity of behaviour as molecular glasses. This is highlighted by the wide variation in behaviour observed for the viscosity or structural relaxation time, tau(alpha), when the glassy state is approached in supercooled molecular liquids(5). This variation is characterized by the unifying concept of fragility(5), which has spurred the search for a 'universal' description of dynamic arrest in glass-forming liquids. For 'fragile' liquids, tau(alpha) is highly sensitive to changes in T, whereas non-fragile, or 'strong', liquids show a much lower T sensitivity. In contrast, hard-sphere colloidal suspensions are restricted to fragile behaviour, as determined by their phi dependence(1,6), ultimately limiting their utility in the study of the glass transition. Here we show that deformable colloidal particles, when studied through their concentration dependence at fixed temperature, do exhibit the same variation in fragility as that observed in the T dependence of molecular liquids at fixed volume. Their fragility is dictated by elastic properties on the scale of individual colloidal particles. Furthermore, we find an equivalent effect in molecular systems, where elasticity directly reflects fragility. Colloidal suspensions may thus provide new insight into glass formation in molecular systems.
C1 [Mattsson, Johan; Wyss, Hans M.; Fernandez-Nieves, Alberto; Weitz, David A.] Harvard Univ, Harvard Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Miyazaki, Kunimasa; Reichman, David R.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
   [Hu, Zhibing] Univ N Texas, Dept Phys, Denton, TX 76203 USA.
   [Mattsson, Johan; Wyss, Hans M.; Fernandez-Nieves, Alberto; Weitz, David A.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 Harvard University; Columbia University; University of North Texas System; University of North Texas Denton; Harvard University
RP Mattsson, J (corresponding author), Chalmers, Dept Appl Phys, SE-41296 Gothenburg, Sweden.
EM johanm@chalmers.se
FU US National Science Foundation; Harvard University's Materials Research Science and Engineering Center; Hans Werthen Foundation; Wenner-Gren Foundation; Knut and Alice Wallenberg Foundation; Royal Society of Arts and Sciences in Goteborg; Ministerio de Ciencia e Innovacion; University of Almeria; KAKENHI; Grants-in-Aid for Scientific Research [21540416] Funding Source: KAKEN
NR 30
TC 479
Z9 538
U1 3
U2 316
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 5
PY 2009
VL 462
IS 7269
BP 83
EP 86
DI 10.1038/nature08457
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200036
PM 19890327
DA 2026-03-09
ER

PT J
AU Gros, J
   Serralbo, O
   Marcelle, C
AF Gros, Jerome
   Serralbo, Olivier
   Marcelle, Christophe
TI WNT11 acts as a directional cue to organize the elongation of early muscle fibres
SO NATURE
LA English
DT Article
ID convergent extension movements; cell polarity; subcellular-localization; signaling pathways; planar polarity; neural-tube; gastrulation; prickle; mediate; chick
AB The early vertebrate skeletal muscle is a well- organized tissue in which the primitive muscle fibres, the myocytes, are all parallel and aligned along the antero- posterior axis of the embryo. How myofibres acquire their orientation during development is unknown. Here we show that during early chick myogenesis WNT11 has an essential role in the oriented elongation of the myocytes. We find that the neural tube, known to drive WNT11 expression in the medial border of somites(1), is necessary and sufficient to orient myocyte elongation. We then show that the specific inhibition of WNT11 function in somites leads to the disorganization of myocytes. We establish that WNT11 mediates this effect through the evolutionary conserved planar cell polarity ( PCP) pathway, downstream of the WNT/beta-catenin-dependent pathway, required to initiate the myogenic program of myocytes and WNT11 expression. Finally, we demonstrate that a localized ectopic source of WNT11 can markedly change the orientation of myocytes, indicating that WNT11 acts as a directional cue in this process. All together, these data show that the sequential action of the WNT/ PCP and the WNT/beta-catenin pathways is necessary for the formation of fully functional embryonic muscle fibres. This study also provides evidence that WNTs can act as instructive cues to regulate the PCP pathway in vertebrates.
C1 [Gros, Jerome; Serralbo, Olivier; Marcelle, Christophe] Univ Aix Marseille 2, CNRS, Dev Biol Inst Marseille Luminy IBDML, UMR 6216, F-13288 Marseille 09, France.
C3 Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS)
RP Marcelle, C (corresponding author), Univ Aix Marseille 2, CNRS, Dev Biol Inst Marseille Luminy IBDML, UMR 6216, Campus Luminy,Case 907, F-13288 Marseille 09, France.
EM marcelle@ibdm.univ-mrs.fr
FU Actions Concertees Incitatives; Agence Nationale de la Recherche; Association Francaise contre les Myopathies; EU 6th Framework Programme Network of Excellence MYORES
NR 35
TC 163
Z9 206
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 29
PY 2009
VL 457
IS 7229
BP 589
EP U97
DI 10.1038/nature07564
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200043
PM 18987628
DA 2026-03-09
ER

PT J
AU Xiang, S
   Cooper-Morgan, A
   Jiao, XF
   Kiledjian, M
   Manley, JL
   Tong, L
AF Xiang, Song
   Cooper-Morgan, Amalene
   Jiao, Xinfu
   Kiledjian, Megerditch
   Manley, James L.
   Tong, Liang
TI Structure and function of the 5′→3′ exoribonuclease Rat1 and its activating partner Rai1
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; messenger-rna; transcription termination; saccharomyces-cerevisiae; macromolecular structures; pin domains; protein; exonuclease; turnover; nuclear
AB The 5'-> 3' exoribonucleases (XRNs) comprise a large family of conserved enzymes in eukaryotes with crucial functions in RNA metabolism and RNA interference(1-5). XRN2, or Rat1 in yeast(6), functions primarily in the nucleus and also has an important role in transcription termination by RNA polymerase II (refs 7-14). Rat1 exoribonuclease activity is stimulated by the protein Rai1 (refs 15, 16). Here we report the crystal structure at 2.2 angstrom resolution of Schizosaccharomyces pombe Rat1 in complex with Rai1, as well as the structures of Rai1 and its murine homologue Dom3Z alone at 2.0 angstrom resolution. The structures reveal the molecular mechanism for the activation of Rat1 by Rai1 and for the exclusive exoribonuclease activity of Rat1. Biochemical studies confirm these observations, and show that Rai1 allows Rat1 to degrade RNAs with stable secondary structure more effectively. There are large differences in the active site landscape of Rat1 compared to related and PIN (PilT N terminus) domain-containing nucleases(17-20). Unexpectedly, we identified a large pocket in Rai1 and Dom3Z that contains highly conserved residues, including three acidic side chains that coordinate a divalent cation. Mutagenesis and biochemical studies demonstrate that Rai1 possesses pyrophosphohydrolase activity towards 5' triphosphorylated RNA. Such an activity is important for messenger RNA degradation in bacteria(21), but this is, to our knowledge, the first demonstration of this activity in eukaryotes and suggests that Rai1/Dom3Z may have additional important functions in RNA metabolism.
C1 [Xiang, Song; Cooper-Morgan, Amalene; Manley, James L.; Tong, Liang] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
   [Jiao, Xinfu; Kiledjian, Megerditch] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA.
C3 Columbia University; Rutgers University System; Rutgers University New Brunswick
RP Tong, L (corresponding author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
EM ltong@columbia.edu
FU NIH [GM077175, GM28983, GM67005]; National Institute of General Medical Sciences [R01GM067005] Funding Source: NIH RePORTER
NR 42
TC 172
Z9 194
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 9
PY 2009
VL 458
IS 7239
BP 784
EP U130
DI 10.1038/nature07731
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600046
PM 19194460
DA 2026-03-09
ER

PT J
AU Hornung, V
   Ablasser, A
   Charrel-Dennis, M
   Bauernfeind, F
   Horvath, G
   Caffrey, DR
   Latz, E
   Fitzgerald, KA
AF Hornung, Veit
   Ablasser, Andrea
   Charrel-Dennis, Marie
   Bauernfeind, Franz
   Horvath, Gabor
   Caffrey, Daniel. R.
   Latz, Eicke
   Fitzgerald, Katherine A.
TI AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
SO NATURE
LA English
DT Article
ID nf-kappa-b; innate immune-response; containing apaf1-like protein; regulates activation; inducible genes; hin-200 family; dna; caspase-1; expression; infection
AB The innate immune system senses nucleic acids by germline-encoded pattern recognition receptors. RNA is sensed by Toll-like receptor members TLR3, TLR7 and TLR8, or by the RNA helicases RIG-I (also known as DDX58) and MDA-5 (IFIH1)(1). Little is known about sensors for cytoplasmic DNA that trigger antiviral and/or inflammatory responses(2-6). The best characterized of these responses involves activation of the TANK-binding kinase (TBK1)-interferon regulatory factor 3 (IRF3) signalling axis to trigger transcriptional induction of type I interferon genes(2,3). A second, less well-defined pathway leads to the activation of an 'inflammasome' that, via caspase-1, controls the catalytic cleavage of the pro-forms of the cytokines IL1 beta and IL18 (refs 6, 7). Using mouse and human cells, here we identify the PYHIN (pyrin and HIN domain-containing protein)(8) family member absent in melanoma 2 (AIM2) as a receptor for cytosolic DNA, which regulates caspase-1. The HIN200 domain of AIM2 binds to DNA, whereas the pyrin domain (but not that of the other PYHIN family members) associates with the adaptor molecule ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain) to activate both NF-kappa B and caspase-1. Knockdown of Aim2 abrogates caspase-1 activation in response to cytoplasmic double-stranded DNA and the double-stranded DNA vaccinia virus. Collectively, these observations identify AIM2 as a new receptor for cytoplasmic DNA, which forms an inflammasome with the ligand and ASC to activate caspase-1.
C1 [Hornung, Veit; Ablasser, Andrea; Charrel-Dennis, Marie; Bauernfeind, Franz; Horvath, Gabor; Latz, Eicke; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA.
   [Caffrey, Daniel. R.] Pfizer, Cambridge, MA 02139 USA.
   [Hornung, Veit; Ablasser, Andrea; Bauernfeind, Franz] Univ Klinikum Bonn, Inst Clin Chem & Pharmacol, D-53127 Bonn, Germany.
C3 University of Massachusetts System; University of Massachusetts Worcester; Pfizer; Pfizer USA; University of Bonn
RP Fitzgerald, KA (corresponding author), Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA.
EM veit.hornung@uni-bonn.de; kate.fitzgerald@umassmed.edu
FU Deutsche Forschungsgemeinschaft [Ho2783/2-1]; National Institutes of Health [AI-065483, AI-067497]; National Institute of Allergy and Infectious Diseases [R37AI067497] Funding Source: NIH RePORTER
NR 29
TC 2147
Z9 2545
U1 5
U2 216
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 514
EP U6
DI 10.1038/nature07725
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400046
PM 19158675
DA 2026-03-09
ER

PT J
AU Bramwell, ST
   Giblin, SR
   Calder, S
   Aldus, R
   Prabhakaran, D
   Fennell, T
AF Bramwell, S. T.
   Giblin, S. R.
   Calder, S.
   Aldus, R.
   Prabhakaran, D.
   Fennell, T.
TI Measurement of the charge and current of magnetic monopoles in spin ice
SO NATURE
LA English
DT Article
ID wien dissociation; frustration; lattice
AB The transport of electrically charged quasiparticles (based on electrons or ions) plays a pivotal role in modern technology as well as in determining the essential functions of biological organisms. In contrast, the transport of magnetic charges has barely been explored experimentally, mainly because magnetic charges, in contrast to electric ones, are generally considered at best to be convenient macroscopic parameters(1,2), rather than well-defined quasiparticles. However, it was recently proposed that magnetic charges can exist in certain materials in the form of emergent excitations that manifest like point charges, or magnetic monopoles(3). Here we address the question of whether such magnetic charges and their associated currents-'magnetricity'-can be measured directly in experiment, without recourse to any material-specific theory. By mapping the problem onto Onsager's theory of electrolytes(4), we show that this is indeed possible, and devise an appropriate method for the measurement of magnetic charges and their dynamics. Using muon spin rotation as a suitable local probe, we apply the method to a real material, the 'spin ice' Dy(2)Ti(2)O(7) (refs 5-8). Our experimental measurements prove that magnetic charges exist in this material, interact via a Coulomb potential, and have measurable currents. We further characterize deviations from Ohm's law, and determine the elementary unit of magnetic charge to be 5 mu(B) angstrom(-1), which is equal to that recently predicted using the microscopic theory of spin ice(3). Our measurement of magnetic charge and magnetic current establishes an instance of a perfect symmetry between electricity and magnetism.
C1 [Bramwell, S. T.; Calder, S.; Aldus, R.] UCL, London Ctr Nanotechnol, London WC1H 0AH, England.
   [Bramwell, S. T.; Calder, S.; Aldus, R.] UCL, Dept Phys & Astron, London WC1H 0AH, England.
   [Giblin, S. R.] Rutherford Appleton Lab, ISIS Facil, Chilton OX11 0QX, Oxon, England.
   [Prabhakaran, D.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
   [Fennell, T.] Inst Max Von Laue Paul Langevin, F-38042 Grenoble, France.
C3 University of London; University College London; University of London; University College London; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; University of Oxford; Institut Laue-Langevin (ILL)
RP Bramwell, ST (corresponding author), UCL, London Ctr Nanotechnol, 17-19 Gordon St, London WC1H 0AH, England.
EM s.t.bramwell@ucl.ac.uk
FU Engineering and Physical Sciences Research Council [EP/C534654/1] Funding Source: researchfish; EPSRC [EP/C534654/1] Funding Source: UKRI
NR 30
TC 310
Z9 345
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 956
EP U211
DI 10.1038/nature08500
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700041
PM 19829376
DA 2026-03-09
ER

PT J
AU Roy, M
   Jordan, TH
   Pederson, J
AF Roy, Mousumi
   Jordan, Thomas H.
   Pederson, Joel
TI Colorado Plateau magmatism and uplift by warming of heterogeneous lithosphere
SO NATURE
LA English
DT Article
ID upper-mantle beneath; ultramafic inclusions; peridotite xenoliths; transition zone; kilbourne-hole; volcanic field; farallon slab; lower crustal; san-carlos; bearing
AB The forces that drove rock uplift of the low-relief, high-elevation, tectonically stable Colorado Plateau are the subject of long-standing debate(1-5). While the adjacent Basin and Range province and Rio Grande rift province underwent Cenozoic shortening followed by extension(6), the plateau experienced similar to 2km of rock uplift(7) without significant internal deformation(2-4). Here we propose that warming of the thicker, more iron-depleted Colorado Plateau lithosphere(8-10) over 35-40 Myr following mid-Cenozoic removal of the Farallon plate from beneath North America(11,12) is the primary mechanism driving rock uplift. In our model, conductive re-equilibration not only explains the rock uplift of the plateau, but also provides a robust geodynamic interpretation of observed contrasts between the Colorado Plateau margins and the plateau interior. In particular, the model matches the encroachment of Cenozoic magmatism from the margins towards the plateau interior at rates of 3-6 km Myr(-1) and is consistent with lower seismic velocities(13) and more negative Bouguer gravity(14) at the margins than in the plateau interior. We suggest that warming of heterogeneous lithosphere is a powerful mechanism for driving epeirogenic rock uplift of the Colorado Plateau and may be of general importance in plate-interior settings.
C1 [Roy, Mousumi] Univ New Mexico, Dept Earth & Planetary Sci, Albuquerque, NM 87131 USA.
   [Jordan, Thomas H.] Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
   [Pederson, Joel] Utah State Univ, Dept Geol, Logan, UT 84322 USA.
C3 University of New Mexico; University of Southern California; Utah System of Higher Education; Utah State University
RP Roy, M (corresponding author), Univ New Mexico, Dept Earth & Planetary Sci, Albuquerque, NM 87131 USA.
EM mroy@unm.edu
FU US National Science Foundation (NSF) [EAR0538022, EAR0408513]; Lamont-Doherty Earth Observatory
NR 55
TC 135
Z9 177
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 JUN 18
PY 2009
VL 459
IS 7249
BP 978
EP U102
DI 10.1038/nature08052
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500041
PM 19536263
DA 2026-03-09
ER

PT J
AU Fejes-Toth, K
   Sotirova, V
   Sachidanandam, R
   Assaf, G
   Hannon, GJ
   Kapranov, P
   Foissac, S
   Willingham, AT
   Duttagupta, R
   Dumais, E
   Gingeras, TR
AF Fejes-Toth, Katalin
   Sotirova, Vihra
   Sachidanandam, Ravi
   Assaf, Gordon
   Hannon, Gregory J.
   Kapranov, Philipp
   Foissac, Sylvain
   Willingham, Aarron T.
   Duttagupta, Radha
   Dumais, Erica
   Gingeras, Thomas R.
TI Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs
SO NATURE
LA English
DT Article
ID gene-expression; human genome; cells; identification; transcription; reveal; maps
AB The transcriptomes of eukaryotic cells are incredibly complex. Individual non- coding RNAs dwarf the number of protein- coding genes, and include classes that are well understood as well as classes for which the nature, extent and functional roles are obscure(1). Deep sequencing of small RNAs (, 200 nucleotides) from human HeLa and HepG2 cells revealed a remarkable breadth of species. These arose both from within annotated genes and from unannotated intergenic regions. Overall, small RNAs tended to align with CAGE ( cap- analysis of gene expression) tags(2), which mark the 5 ' ends of capped, long RNA transcripts. Many small RNAs, including the previously described promoter- associated small RNAs3, appeared to possess cap structures. Members of an extensive class of both small RNAs and CAGE tags were distributed across internal exons of annotated protein coding and noncoding genes, sometimes crossing exon - exon junctions. Here we show that processing of mature mRNAs through an as yet unknown mechanism may generate complex populations of both long and short RNAs whose apparently capped 5 ' ends coincide. Supplying synthetic promoter- associated small RNAs corresponding to the c-MYC transcriptional start site reduced MYC messenger RNA abundance. The studies presented here expand the catalogue of cellular small RNAs and demonstrate a biological impact for at least one class of non- canonical small RNAs.
C1 [Fejes-Toth, Katalin; Sotirova, Vihra; Sachidanandam, Ravi; Assaf, Gordon; Gingeras, Thomas R.] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Fejes-Toth, Katalin; Sotirova, Vihra; Assaf, Gordon; Hannon, Gregory J.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
   [Kapranov, Philipp; Foissac, Sylvain; Willingham, Aarron T.; Duttagupta, Radha; Dumais, Erica; Gingeras, Thomas R.] Affymetrix Inc, Santa Clara, CA 95051 USA.
C3 Cold Spring Harbor Laboratory; Howard Hughes Medical Institute; Cold Spring Harbor Laboratory; Affymetrix
RP Hannon, GJ (corresponding author), Cold Spring Harbor Lab, Watson Sch Biol Sci, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM hannon@cshl.edu; gingeras@cshl.edu
FU Schering Foundation; NIH
NR 20
TC 326
Z9 396
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 19
PY 2009
VL 457
IS 7232
BP 1028
EP 1032
DI 10.1038/nature07759
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400046
PM 19169241
DA 2026-03-09
ER

PT J
AU Kara, P
   Boyd, JD
AF Kara, Prakash
   Boyd, Jamie D.
TI A micro-architecture for binocular disparity and ocular dominance in visual cortex
SO NATURE
LA English
DT Article
ID postnatal-development; horizontal disparity; depth discrimination; striate cortex; primate v1; sensitivity; neurons; organization; mechanisms; stereopsis
AB In invertebrate predators such as the praying mantis and vertebrate predators such as wild cats the ability to detect small differences in inter-ocular retinal disparities is a critical means for accurately determining the depth of moving objects such as prey(1). In mammals, the first neurons along the visual pathway that encode binocular disparities are found in the visual cortex. However, a precise functional architecture for binocular disparity has never been demonstrated in any species, and coarse maps for disparity have been found in only one primate species(2,3). Moreover, the dominant approach for assaying the developmental plasticity of binocular cortical neurons used monocular tests of ocular dominance to infer binocular function(4). The few studies that examined the relationship between ocular dominance and binocular disparity of individual cells used single-unit recordings and have provided conflicting results regarding whether ocular dominance can predict the selectivity or sensitivity to binocular disparity(5-9). We used two-photon calcium imaging to sample the response to monocular and binocular visual stimuli from nearly every adjacent neuron in a small region of the cat visual cortex, area 18. Here we show that local circuits for ocular dominance always have smooth and graded transitions from one apparently monocular functional domain to an adjacent binocular region. Most unexpectedly, we discovered a new map in the cat visual cortex that had a precise functional micro-architecture for binocular disparity selectivity. At the level of single cells, ocular dominance was unrelated to binocular disparity selectivity or sensitivity. When the local maps for ocular dominance and binocular disparity both had measurable gradients at a given cortical site, the two gradient directions were orthogonal to each other. Together, these results indicate that, from the perspective of the spiking activity of individual neurons, ocular dominance cannot predict binocular disparity tuning. However, the precise local arrangement of ocular dominance and binocular disparity maps provide new clues regarding how monocular and binocular depth cues may be combined and decoded.
C1 [Kara, Prakash; Boyd, Jamie D.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
C3 Medical University of South Carolina
RP Kara, P (corresponding author), Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
EM kara@musc.edu
FU NIH; Whitehall; Dana Foundations
NR 30
TC 96
Z9 107
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 APR 2
PY 2009
VL 458
IS 7238
BP 627
EP U93
DI 10.1038/nature07721
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200040
PM 19158677
DA 2026-03-09
ER

PT J
AU Diskin, SJ
   Hou, CP
   Glessner, JT
   Attiyeh, EF
   Laudenslager, M
   Bosse, K
   Cole, K
   Mossé, YP
   Wood, A
   Lynch, JE
   Pecor, K
   Diamond, M
   Winter, C
   Wang, K
   Kim, C
   Geiger, EA
   McGrady, PW
   Blakemore, AIF
   London, WB
   Shaikh, TH
   Bradfield, J
   Grant, SFA
   Li, HZ
   Devoto, M
   Rappaport, ER
   Hakonarson, H
   Maris, JM
AF Diskin, Sharon J.
   Hou, Cuiping
   Glessner, Joseph T.
   Attiyeh, Edward F.
   Laudenslager, Marci
   Bosse, Kristopher
   Cole, Kristina
   Mosse, Yael P.
   Wood, Andrew
   Lynch, Jill E.
   Pecor, Katlyn
   Diamond, Maura
   Winter, Cynthia
   Wang, Kai
   Kim, Cecilia
   Geiger, Elizabeth A.
   McGrady, Patrick W.
   Blakemore, Alexandra I. F.
   London, Wendy B.
   Shaikh, Tamim H.
   Bradfield, Jonathan
   Grant, Struan F. A.
   Li, Hongzhe
   Devoto, Marcella
   Rappaport, Eric R.
   Hakonarson, Hakon
   Maris, John M.
TI Copy number variation at 1q21.1 associated with neuroblastoma
SO NATURE
LA English
DT Article
ID pediatric-oncology-group; gene amplification; genome; schizophrenia; expression; hybridization; duplications; polymorphism; phenotypes; cancer
AB Common copy number variations (CNVs) represent a significant source of genetic diversity, yet their influence on phenotypic variability, including disease susceptibility, remains poorly understood. To address this problem in human cancer, we performed a genome-wide association study of CNVs in the childhood cancer neuroblastoma, a disease in which single nucleotide polymorphism variations are known to influence susceptibility(1,2). We first genotyped 846 Caucasian neuroblastoma patients and 803 healthy Caucasian controls at similar to 550,000 single nucleotide polymorphisms, and performed a CNV-based test for association. We then replicated significant observations in two independent sample sets comprised of a total of 595 cases and 3,357 controls. Here we describe the identification of a common CNV at chromosome 1q21.1 associated with neuroblastoma in the discovery set, which was confirmed in both replication sets. This CNV was validated by quantitative polymerase chain reaction, fluorescent in situ hybridization and analysis of matched tumour specimens, and was shown to be heritable in an independent set of 713 cancer-free parent offspring trios. We identified a previously unknown transcript within the CNV that showed high sequence similarity to several neuroblastoma breakpoint family (NBPF) genes(3,4) and represents a new member of this gene family (NBPF23). This transcript was preferentially expressed in fetal brain and fetal sympathetic nervous tissues, and the expression level was strictly correlated with CNV state in neuroblastoma cells. These data demonstrate that inherited copy number variation at 1q21.1 is associated with neuroblastoma and implicate a previously unknown neuroblastoma breakpoint family gene in early tumorigenesis of this childhood cancer.
C1 [Diskin, Sharon J.; Hou, Cuiping; Attiyeh, Edward F.; Laudenslager, Marci; Bosse, Kristopher; Cole, Kristina; Mosse, Yael P.; Wood, Andrew; Lynch, Jill E.; Pecor, Katlyn; Diamond, Maura; Winter, Cynthia; Rappaport, Eric R.; Maris, John M.] Univ Penn, Sch Med, Div Oncol, Philadelphia, PA 19104 USA.
   [Diskin, Sharon J.; Hou, Cuiping; Attiyeh, Edward F.; Laudenslager, Marci; Bosse, Kristopher; Cole, Kristina; Mosse, Yael P.; Wood, Andrew; Lynch, Jill E.; Pecor, Katlyn; Diamond, Maura; Winter, Cynthia; Rappaport, Eric R.; Maris, John M.] Univ Penn, Sch Med, Ctr Childhood Canc Res, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Hou, Cuiping; Glessner, Joseph T.; Wang, Kai; Kim, Cecilia; Bradfield, Jonathan; Grant, Struan F. A.; Hakonarson, Hakon] Univ Penn, Sch Med, Ctr Appl Genom, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Attiyeh, Edward F.; Mosse, Yael P.; Shaikh, Tamim H.; Grant, Struan F. A.; Devoto, Marcella; Rappaport, Eric R.; Hakonarson, Hakon; Maris, John M.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
   [Maris, John M.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
   [Geiger, Elizabeth A.; Shaikh, Tamim H.; Grant, Struan F. A.; Devoto, Marcella; Hakonarson, Hakon] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA.
   [Li, Hongzhe; Devoto, Marcella] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [McGrady, Patrick W.; London, Wendy B.] Univ Florida, Dept Stat, Gainesville, FL 32611 USA.
   [McGrady, Patrick W.; London, Wendy B.] Childrens Oncol Grp, Gainesville, FL 32611 USA.
   [Blakemore, Alexandra I. F.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
   [Devoto, Marcella] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy.
C3 University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; State University System of Florida; University of Florida; Children's Oncology Group (COG); Imperial College London; Sapienza University Rome
RP Maris, JM (corresponding author), Univ Penn, Sch Med, Div Oncol, Philadelphia, PA 19104 USA.
EM maris@chop.edu
FU Children's Oncology Group [U10-CA98543]; NIH [T32-HG000046, R01-CA87847, R01-CA124709, GM081519]; Giulio D'Angio Endowed Chair; Alex's Lemonade Stand Foundation; Evan Dunbar Foundation; Rally Foundation; Andrew's Army Foundation; Abramson Family Cancer Research Institute; Howard Hughes Medical Institute Medical Research Training Fellowship; Center for Applied Genomics; Joseph Stokes Research Institute of the Children's Hospital of Philadelphia; National Human Genome Research Institute [T32HG000046] Funding Source: NIH RePORTER
NR 31
TC 291
Z9 348
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 JUN 18
PY 2009
VL 459
IS 7249
BP 987
EP U112
DI 10.1038/nature08035
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500043
PM 19536264
DA 2026-03-09
ER

PT J
AU Wang, X
   Kruithof-de Julio, M
   Economides, KD
   Walker, D
   Yu, HL
   Halili, MV
   Hu, YP
   Price, SM
   Abate-Shen, C
   Shen, MM
AF Wang, Xi
   Kruithof-de Julio, Marianna
   Economides, Kyriakos D.
   Walker, David
   Yu, Hailong
   Halili, M. Vivienne
   Hu, Ya-Ping
   Price, Sandy M.
   Abate-Shen, Cory
   Shen, Michael M.
TI A luminal epithelial stem cell that is a cell of origin for prostate cancer
SO NATURE
LA English
DT Article
ID androgen-induced regeneration; basal-cells; recombinase activity; tumor initiation; mouse prostate; homeobox gene; mutant mice; in-vivo; nkx3.1; expression
AB In epithelial tissues, the lineage relationship between normal progenitor cells and cell type(s) of origin for cancer has been poorly understood. Here we show that a known regulator of prostate epithelial differentiation, the homeobox gene Nkx3-1, marks a stem cell population that functions during prostate regeneration. Genetic lineage-marking demonstrates that rare luminal cells that express Nkx3-1 in the absence of testicular androgens (castration-resistant Nkx3-1-expressing cells, CARNs) are bipotential and can self-renew in vivo, and single-cell transplantation assays show that CARNs can reconstitute prostate ducts in renal grafts. Functional assays of Nkx3-1 mutant mice in serial prostate regeneration suggest that Nkx3-1 is required for stem cell maintenance. Furthermore, targeted deletion of the Pten tumour suppressor gene in CARNs results in rapid carcinoma formation after androgen-mediated regeneration. These observations indicate that CARNs represent a new luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer.
C1 [Wang, Xi; Kruithof-de Julio, Marianna; Shen, Michael M.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
   [Wang, Xi; Kruithof-de Julio, Marianna; Shen, Michael M.] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA.
   [Abate-Shen, Cory] Columbia Univ Coll Phys & Surg, Dept Urol, New York, NY 10032 USA.
   [Abate-Shen, Cory] Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
   [Wang, Xi; Economides, Kyriakos D.; Walker, David; Yu, Hailong; Halili, M. Vivienne; Hu, Ya-Ping; Price, Sandy M.; Abate-Shen, Cory; Shen, Michael M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
   [Wang, Xi; Walker, David; Yu, Hailong; Halili, M. Vivienne; Hu, Ya-Ping; Price, Sandy M.; Shen, Michael M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, Piscataway, NJ 08854 USA.
   [Economides, Kyriakos D.; Abate-Shen, Cory] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Piscataway, NJ 08854 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences
RP Shen, MM (corresponding author), Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
EM mshen@columbia.edu
FU NIH; DOD Prostate Cancer Research Program; NCI Mouse Models of Human Cancer Consortium
NR 50
TC 579
Z9 728
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 24
PY 2009
VL 461
IS 7263
BP 495
EP U61
DI 10.1038/nature08361
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900033
PM 19741607
DA 2026-03-09
ER

PT J
AU Thomas, AM
   Nadeau, RM
   Bürgmann, R
AF Thomas, Amanda M.
   Nadeau, Robert M.
   Buergmann, Roland
TI Tremor-tide correlations and near-lithostatic pore pressure on the deep San Andreas fault
SO NATURE
LA English
DT Article
ID non-volcanic tremor; earth tides; nonvolcanic tremor; episodic tremor; slip; parkfield; subduction
AB Since its initial discovery nearly a decade ago(1), non-volcanic tremor has provided information about a region of the Earth that was previously thought incapable of generating seismic radiation. A thorough explanation of the geologic process responsible for tremor generation has, however, yet to be determined. Owing to their location at the plate interface, temporal correlation with geodetically measured slow-slip events and dominant shear wave energy, tremor observations in southwest Japan have been interpreted as a superposition of many low-frequency earthquakes that represent slip on a fault surface(2,3). Fluids may also be fundamental to the failure process in subduction zone environments, as teleseismic and tidal modulation of tremor in Cascadia and Japan and high Poisson ratios in both source regions are indicative of pressurized pore fluids(3-7). Here we identify a robust correlation between extremely small, tidally induced shear stress parallel to the San Andreas fault and non-volcanic tremor activity near Parkfield, California. We suggest that this tremor represents shear failure on a critically stressed fault in the presence of near-lithostatic pore pressure. There are a number of similarities between tremor in subduction zone environments, such as Cascadia and Japan, and tremor on the deep San Andreas transform(3-12), suggesting that the results presented here may also be applicable in other tectonic settings.
C1 [Thomas, Amanda M.; Nadeau, Robert M.; Buergmann, Roland] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley Seismol Lab, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Thomas, AM (corresponding author), Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley Seismol Lab, 307 McCone Hall, Berkeley, CA 94720 USA.
EM amthomas@berkeley.edu
FU National Science Foundation [EAR-0537641, EAR-0544730]; US Geological Survey [06HQGR0167, 07HQAG0014, 08HQGR0100]
NR 28
TC 202
Z9 225
U1 1
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1048
EP U105
DI 10.1038/nature08654
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000045
PM 20033046
DA 2026-03-09
ER

PT J
AU Wei, CL
   Wang, XH
   Chen, M
   Ouyang, K
   Song, LS
   Cheng, HP
AF Wei, Chaoliang
   Wang, Xianhua
   Chen, Min
   Ouyang, Kunfu
   Song, Long-Sheng
   Cheng, Heping
TI Calcium flickers steer cell migration
SO NATURE
LA English
DT Article
ID cation channels; chemotaxis; activation; dictyostelium; transient; movement; signals; back; loop; rac
AB Directional movement is a property common to all cell types during development and is critical to tissue remodelling and regeneration after damage(1-3). In migrating cells, calcium has a multifunctional role in directional sensing, cytoskeleton redistribution, traction force generation, and relocation of focal adhesions(1,4) (-7). Here we visualize high- calcium microdomains ('calcium flickers') and their patterned activation in migrating human embryonic lung fibroblasts. Calcium flicker activity is dually coupled to membrane tension ( by means of TRPM7, a stretch-activated Ca2(+)permeant channel of the transient receptor potential superfamily(8)) and chemoattractant signal transduction ( by means of type 2 inositol-1,4,5-trisphosphate-receptors). Interestingly, calcium flickers are most active at the leading lamella of migrating cells, displaying a 4: 1 front- to- rear polarization opposite to the global calcium gradient(6). When exposed to a platelet- derived growth factor gradient perpendicular to cell movement, asymmetric calcium flicker activity develops across the lamella and promotes the turning of migrating fibroblasts. These findings show how the exquisite spatiotemporal organization of calcium microdomains can orchestrate complex cellular processes such as cell migration.
C1 [Wei, Chaoliang; Wang, Xianhua; Chen, Min; Ouyang, Kunfu; Cheng, Heping] Peking Univ, Inst Mol Med, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China.
   [Song, Long-Sheng] Univ Iowa, Carver Coll Med, Div Cardiovasc Med, Dept Internal Med, Iowa City, IA 52242 USA.
C3 Peking University; University of Iowa
RP Cheng, HP (corresponding author), Peking Univ, Inst Mol Med, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China.
EM chaoliang.wei@gmail.com; chengp@pku.edu.cn
FU Major State Basic Research Development Program of China [2007CB512100]; National Natural Science Foundation of China [30630021, 30800371]; NIH [HL090905]
NR 30
TC 499
Z9 610
U1 2
U2 136
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 12
PY 2009
VL 457
IS 7231
BP 901
EP 905
DI 10.1038/nature07577
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700049
PM 19118385
DA 2026-03-09
ER

PT J
AU Aimanianda, V
   Bayry, J
   Bozza, S
   Kniemeyer, O
   Perruccio, K
   Elluru, SR
   Clavaud, C
   Paris, S
   Brakhage, AA
   Kaveri, SV
   Romani, L
   Latgé, JP
AF Aimanianda, Vishukumar
   Bayry, Jagadeesh
   Bozza, Silvia
   Kniemeyer, Olaf
   Perruccio, Katia
   Elluru, Sri Ramulu
   Clavaud, Cecile
   Paris, Sophie
   Brakhage, Axel A.
   Kaveri, Srini V.
   Romani, Luigina
   Latge, Jean-Paul
TI Surface hydrophobin prevents immune recognition of airborne fungal spores
SO NATURE
LA English
DT Article
ID aspergillus-fumigatus; cell-wall; alveolar macrophages; cladosporium; responses; proteins; antigens
AB The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10 9 per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus(1-4). Although these conidia contain many antigens and allergens(5-7), it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (Delta rodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.
C1 [Aimanianda, Vishukumar; Clavaud, Cecile; Paris, Sophie; Latge, Jean-Paul] Inst Pasteur, Unite Aspergillus, F-75015 Paris, France.
   [Bayry, Jagadeesh; Elluru, Sri Ramulu; Kaveri, Srini V.] Univ Paris 06, INSERM, UMR S 872, U872, F-75006 Paris, France.
   [Bayry, Jagadeesh; Elluru, Sri Ramulu; Kaveri, Srini V.] Univ Paris 06, Ctr Rech Cordeliers, UMR S 872, F-75006 Paris, France.
   [Bayry, Jagadeesh; Elluru, Sri Ramulu; Kaveri, Srini V.] Univ Paris 05, UMR S 872, F-75006 Paris, France.
   [Bozza, Silvia; Romani, Luigina] Univ Perugia, Dept Expt Med & Biochem Sci, I-06122 Perugia, Italy.
   [Perruccio, Katia] Univ Perugia, Dept Clin & Expt Med, I-06122 Perugia, Italy.
   [Kniemeyer, Olaf; Brakhage, Axel A.] Leibniz Inst Nat Prod Res & Infect Biol HKI, Dept Mol & Appl Microbiol, D-07745 Jena, Germany.
   [Kniemeyer, Olaf; Brakhage, Axel A.] Univ Jena, D-07745 Jena, Germany.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Universite Paris Cite; Universite Paris Cite; University of Perugia; University of Perugia; Leibniz Association; Hans Knoll Institute (HKI); Friedrich Schiller University of Jena
RP Latgé, JP (corresponding author), Inst Pasteur, Unite Aspergillus, F-75015 Paris, France.
EM jplatge@pasteur.fr
FU Deutsche Forschungsgemeinschaft (DFG); EU-STREP [LSHB-CT-2004-511952, MANASP LSGBH37899]; INSERM; CNRS; Universities Paris 5 and 6
NR 30
TC 620
Z9 736
U1 5
U2 154
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1117
EP 1121
DI 10.1038/nature08264
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000036
PM 19713928
DA 2026-03-09
ER

PT J
AU Fernandes-Alnemri, T
   Yu, JW
   Datta, P
   Wu, JH
   Alnemri, ES
AF Fernandes-Alnemri, Teresa
   Yu, Je-Wook
   Datta, Pinaki
   Wu, Jianghong
   Alnemri, Emad S.
TI AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
SO NATURE
LA English
DT Article
ID innate immune-response; nalp3 inflammasome; asc pyroptosome; caspase-1; silica; family; genes; beta
AB Host-and pathogen-associated cytoplasmic double-stranded DNA triggers the activation of a NALP3 (also known as cryopyrin and NLRP3)-independent inflammasome(1), which activates caspase-1 leading to maturation of pro-interleukin-1 beta and inflammation. The nature of the cytoplasmic-DNA-sensing inflammasome is currently unknown. Here we show that AIM2 (absent in melanoma 2), an interferon-inducible HIN-200 family member that contains an amino-terminal pyrin domain and a carboxy-terminal oligonucleotide/oligosaccharide-binding domain(2,3), senses cytoplasmic DNA by means of its oligonucleotide/oligosaccharide-binding domain and interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1. The interaction of AIM2 with ASC also leads to the formation of the ASC pyroptosome(4), which induces pyroptotic cell death in cells containing caspase-1. Knockdown of AIM2 by short interfering RNA reduced inflammasome/pyroptosome activation by cytoplasmic DNA in human and mouse macrophages, whereas stable expression of AIM2 in the non-responsive human embryonic kidney 293T cell line conferred responsiveness to cytoplasmic DNA. Our results show that cytoplasmic DNA triggers formation of the AIM2 inflammasome by inducing AIM2 oligomerization. This study identifies AIM2 as an important inflammasome component that senses potentially dangerous cytoplasmic DNA, leading to activation of the ASC pyroptosome and caspase-1.
C1 [Fernandes-Alnemri, Teresa; Yu, Je-Wook; Datta, Pinaki; Wu, Jianghong; Alnemri, Emad S.] Thomas Jefferson Univ, Kimmel Canc Inst, Ctr Apoptosis Res, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA.
C3 Thomas Jefferson University
RP Alnemri, ES (corresponding author), Thomas Jefferson Univ, Kimmel Canc Inst, Ctr Apoptosis Res, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA.
EM E_Alnemri@lac.jci.tju.edu
FU NIH [AG14357, AR055398]
NR 18
TC 1525
Z9 1816
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 MAR 26
PY 2009
VL 458
IS 7237
BP 509
EP U5
DI 10.1038/nature07710
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400045
PM 19158676
DA 2026-03-09
ER

PT J
AU Ishizaki, K
   Noda, S
AF Ishizaki, Kenji
   Noda, Susumu
TI Manipulation of photons at the surface of three-dimensional photonic crystals
SO NATURE
LA English
DT Article
ID spontaneous-emission control; light-emission; waves; equations; layer
AB In three-dimensional (3D) photonic crystals(1-12), refractive-index variations with a periodicity comparable to the wavelength of the light passing through the crystal give rise to so-called photonic bandgaps, which are analogous to electronic bandgaps for electrons moving in the periodic electrostatic potential of a material's crystal structure. Such 3D photonic bandgap crystals are envisioned to become fundamental building blocks for the control and manipulation of photons in optical circuits. So far, such schemes have been pursued by embedding artificial defects(3-5,8-12) and light emitters(4-9) inside the crystals, making use of 3D bandgap directional effects. Here we show experimentally that photons can be controlled and manipulated even at the 'surface' of 3D photonic crystals, where 3D periodicity is terminated, establishing a new and versatile route for photon manipulation. By making use of an evanescent-mode coupling technique, we demonstrate that 3D photonic crystals possess two-dimensional surface states, and we map their band structure. We show that photons can be confined and propagate through these two-dimensional surface states, and we realize their localization at arbitrary surface points by designing artificial surface-defect structures through the formation of a surface-mode gap. Surprisingly, the quality factors of the surface-defect mode are the largest reported for 3D photonic crystal nanocavities (Q up to similar to 9,000). In addition to providing a new approach for photon manipulation by photonic crystals, our findings are relevant for the generation and control of plasmon-polaritons in metals and the related surface photon physics. The absorption-free nature of the 3D photonic crystal surface may enable new sensing applications and provide routes for the realization of efficient light-matter interactions.
C1 [Ishizaki, Kenji; Noda, Susumu] Kyoto Univ, Dept Elect Sci & Engn, Kyoto 6158510, Japan.
   [Ishizaki, Kenji; Noda, Susumu] Japan Sci & Technol Agcy, Kyoto 6158510, Japan.
C3 Kyoto University; Japan Science & Technology Agency (JST)
RP Noda, S (corresponding author), Kyoto Univ, Dept Elect Sci & Engn, Kyoto 6158510, Japan.
EM snoda@kuee.kyoto-u.ac.jp
FU Global Centre of Excellence for Education and Research on Photonics and Electronics Science and Engineering of Kyoto University, Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Society for the Promotion of Science (JSPS); JSPS
NR 27
TC 170
Z9 194
U1 4
U2 149
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 367
EP U78
DI 10.1038/nature08190
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000032
PM 19606144
DA 2026-03-09
ER

PT J
AU Dawson, MA
   Bannister, AJ
   Göttgens, B
   Foster, SD
   Bartke, T
   Green, AR
   Kouzarides, T
AF Dawson, Mark A.
   Bannister, Andrew J.
   Goettgens, Berthold
   Foster, Samuel D.
   Bartke, Till
   Green, Anthony R.
   Kouzarides, Tony
TI JAK2 phosphorylates histone H3Y41 and excludes HP1α from chromatin
SO NATURE
LA English
DT Article
ID dna-replication; lysine 9; h3; mutations; protein; cells; hp1; methylation; activation; therapy
AB Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies(1-6). JAK2 is a non-receptor tyrosine kinase that regulates several cellular processes by inducing cytoplasmic signalling cascades. Here we show that human JAK2 is present in the nucleus of haematopoietic cells and directly phosphorylates Tyr 41 (Y41) on histone H3. Heterochromatin protein 1 alpha (HP1 alpha), but not HP1 beta, specifically binds to this region of H3 through its chromo-shadow domain. Phosphorylation of H3Y41 by JAK2 prevents this binding. Inhibition of JAK2 activity in human leukaemic cells decreases both the expression of the haematopoietic oncogene lmo2 and the phosphorylation of H3Y41 at its promoter, while simultaneously increasing the binding of HP1a at the same site. These results identify a previously unrecognized nuclear role for JAK2 in the phosphorylation of H3Y41 and reveal a direct mechanistic link between two genes, jak2 and lmo2, involved in normal haematopoiesis and leukaemia(1-9).
C1 [Dawson, Mark A.; Goettgens, Berthold; Foster, Samuel D.; Green, Anthony R.] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
   [Dawson, Mark A.; Goettgens, Berthold; Foster, Samuel D.; Green, Anthony R.] Univ Cambridge, Dept Haematol, Cambridge CB2 0XY, England.
   [Dawson, Mark A.; Green, Anthony R.] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 0QQ, England.
   [Bannister, Andrew J.; Bartke, Till; Kouzarides, Tony] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England.
   [Bannister, Andrew J.; Bartke, Till; Kouzarides, Tony] Univ Cambridge, Dept Pathol, Cambridge CB2 1QN, England.
C3 University of Cambridge; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Cambridge; University of Cambridge
RP Green, AR (corresponding author), Univ Cambridge, Cambridge Inst Med Res, Hills Rd, Cambridge CB2 0XY, England.
EM arg1000@cam.ac.uk; t.kouzarides@gurdon.cam.ac.uk
FU General Sir John Monash Foundation; Cambridge Commonwealth Trust; Raymond and Beverly Sackler; UK Leukaemia Research Fund; Wellcome Trust; Leukemia & Lymphoma Society of America; National Institute for Health Research Cambridge Biomedical Research Centre; Leukaemia Research Fund; Cancer Research UK; Medical Research Council; 6th Research Framework Programme of the European Union ( Epitron, HEROIC and SMARTER).; MRC [G0800784] Funding Source: UKRI; Medical Research Council [G0800784, G0300723B, G0800784B] Funding Source: researchfish
NR 33
TC 104
Z9 145
U1 1
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 8
PY 2009
VL 461
IS 7265
BP 819
EP U79
DI 10.1038/nature08448
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500041
PM 19783980
DA 2026-03-09
ER

PT J
AU Hattori, Y
   Nagai, K
   Furukawa, S
   Song, XJ
   Kawano, R
   Sakakibara, H
   Wu, JZ
   Matsumoto, T
   Yoshimura, A
   Kitano, H
   Matsuoka, M
   Mori, H
   Ashikari, M
AF Hattori, Yoko
   Nagai, Keisuke
   Furukawa, Shizuka
   Song, Xian-Jun
   Kawano, Ritsuko
   Sakakibara, Hitoshi
   Wu, Jianzhong
   Matsumoto, Takashi
   Yoshimura, Atsushi
   Kitano, Hidemi
   Matsuoka, Makoto
   Mori, Hitoshi
   Ashikari, Motoyuki
TI The ethylene response factors SNORKEL1 and SNORKEL2 allow rice to adapt to deep water
SO NATURE
LA English
DT Article
ID submergence tolerance; internode elongation; growth-response; floating rice; abscisic-acid; grain width; major qtl; gibberellin; gene; agrobacterium
AB Living organisms must acquire new biological functions to adapt to changing and hostile environments. Deepwater rice has evolved and adapted to flooding by acquiring the ability to significantly elongate its internodes, which have hollow structures and function as snorkels to allow gas exchange with the atmosphere, and thus prevent drowning(1-3). Many physiological studies have shown that the phytohormones ethylene, gibberellin and abscisic acid are involved in this response(4-8), but the gene(s) responsible for this trait has not been identified. Here we show the molecular mechanism of deepwater response through the identification of the genes SNORKEL1 and SNORKEL2, which trigger deepwater response by encoding ethylene response factors involved in ethylene signalling. Under deepwater conditions, ethylene accumulates in the plant and induces expression of these two genes. The products of SNORKEL1 and SNORKEL2 then trigger remarkable internode elongation via gibberellin. We also demonstrate that the introduction of three quantitative trait loci from deepwater rice into non-deepwater rice enabled the latter to become deepwater rice. This discovery will contribute to rice breeding in lowland areas that are frequently flooded during the rainy season.
C1 [Hattori, Yoko; Nagai, Keisuke; Furukawa, Shizuka; Song, Xian-Jun; Kitano, Hidemi; Matsuoka, Makoto; Ashikari, Motoyuki] Nagoya Univ, Biosci & Biotechnol Ctr, Nagoya, Aichi 4648601, Japan.
   [Mori, Hitoshi] Nagoya Univ, Grad Sch Bioagr Sci, Nagoya, Aichi 4648601, Japan.
   [Kawano, Ritsuko; Yoshimura, Atsushi] Kyushu Univ, Sch Agr, Fukuoka 8128581, Japan.
   [Sakakibara, Hitoshi] RIKEN, Plant Sci Ctr, Yokohama, Kanagawa 2300045, Japan.
   [Wu, Jianzhong; Matsumoto, Takashi] Natl Inst Agrobiol Resources, Tsukuba, Ibaraki 3058602, Japan.
C3 Nagoya University; Nagoya University; Kyushu University; RIKEN; National Institute of Agrobiological Sciences - Japan
RP Ashikari, M (corresponding author), Nagoya Univ, Biosci & Biotechnol Ctr, Nagoya, Aichi 4648601, Japan.
EM ashi@agr.nagoya-u.ac.jp
FU Ministry of Agriculture, Forestry, and Fisheries of Japan [QT-2003, QT-4002]; Japan Society for the Promotion of Science (Y. H.); National Bioresource Project, MEXT, Japan; International Rice Research Institute, Philippines
NR 34
TC 797
Z9 924
U1 5
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 AUG 20
PY 2009
VL 460
IS 7258
BP 1026
EP U116
DI 10.1038/nature08258
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500037
PM 19693083
DA 2026-03-09
ER

PT J
AU Guarda, G
   Dostert, C
   Staehli, F
   Cabalzar, K
   Castillo, R
   Tardivel, A
   Schneider, P
   Tschopp, J
AF Guarda, Greta
   Dostert, Catherine
   Staehli, Francesco
   Cabalzar, Katrin
   Castillo, Rosa
   Tardivel, Aubry
   Schneider, Pascal
   Tschopp, Juerg
TI T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes
SO NATURE
LA English
DT Article
ID dendritic cells; lymph-nodes; mice; activation; deficient; crystals; members; family; mouse
AB Inflammation is a protective attempt by the host to remove injurious stimuli and initiate the tissue healing process(1). The inflammatory response must be actively terminated, however, because failure to do so can result in 'bystander' damage to tissues and diseases such as arthritis or type-2 diabetes. Yet the mechanisms controlling excessive inflammatory responses are still poorly understood. Here we show that mouse effector and memory CD4(+) T cells abolish macrophage inflammasome-mediated caspase-1 activation and subsequent interleukin 1 beta release in a cognate manner. Inflammasome inhibition is observed for all tested NLRP1 (commonly called NALP1) and NLRP3 (NALP3 or cryopyrin) activators, whereas NLRC4 (IPAF) inflammasome function and release of other inflammatory mediators such as CXCL2, interleukin 6 and tumour necrosis factor are not affected. Suppression of the NLRP3 inflammasome requires cell-to-cell contact and can be mimicked by macrophage stimulation with selected ligands of the tumour necrosis factor family, such as CD40L (also known as CD40LG). In a NLRP3-dependent peritonitis model, effector CD4(+) T cells are responsible for decreasing neutrophil recruitment in an antigen-dependent manner. Our findings reveal an unexpected mechanism of inflammasome inhibition, whereby effector and memory T cells suppress potentially damaging inflammation, yet leave the primary inflammatory response, crucial for the onset of immunity, intact.
C1 [Guarda, Greta; Dostert, Catherine; Staehli, Francesco; Cabalzar, Katrin; Castillo, Rosa; Tardivel, Aubry; Schneider, Pascal; Tschopp, Juerg] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
C3 University of Lausanne
RP Tschopp, J (corresponding author), Univ Lausanne, Dept Biochem, Chemim Boveresses 155, CH-1066 Epalinges, Switzerland.
EM jurg.tschopp@unil.ch
FU Swiss National Science foundation; NCCR Molecular Oncology; EMBO
NR 29
TC 215
Z9 246
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 269
EP U136
DI 10.1038/nature08100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000043
PM 19494813
DA 2026-03-09
ER

PT J
AU Chi, SW
   Zang, JB
   Mele, A
   Darnell, RB
AF Chi, Sung Wook
   Zang, Julie B.
   Mele, Aldo
   Darnell, Robert B.
TI Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps
SO NATURE
LA English
DT Article
ID systematic identification; neuronal differentiation; target predictions; binding proteins; cross-linking; brain; elegans; cells; immunoprecipitation; translation
AB MicroRNAs (miRNAs) have critical roles in the regulation of gene expression; however, as miRNA activity requires base pairing with only 628 nucleotides of messenger RNA, predicting target mRNAs is a major challenge. Recently, high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) has identified functional protein-RNA interaction sites. Here we use HITS-CLIP to covalently crosslink native argonaute (Ago, also called Eif2c) protein-RNA complexes in mouse brain. This produced two simultaneous data sets-Ago-miRNA and Ago-mRNA binding sites-that were combined with bioinformatic analysis to identify interaction sites between miRNA and target mRNA. We validated genome-wide interaction maps for miR-124, and generated additional maps for the 20 most abundant miRNAs present in P13 mouse brain. Ago HITS-CLIP provides a general platform for exploring the specificity and range of miRNA action in vivo, and identifies precise sequences for targeting clinically relevant miRNA-mRNA interactions.
C1 [Chi, Sung Wook; Zang, Julie B.; Mele, Aldo; Darnell, Robert B.] Rockefeller Univ, Mol Neurooncol Lab, New York, NY 10021 USA.
   [Chi, Sung Wook; Zang, Julie B.; Mele, Aldo; Darnell, Robert B.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA.
C3 Rockefeller University; Rockefeller University; Howard Hughes Medical Institute
RP Darnell, RB (corresponding author), Rockefeller Univ, Mol Neurooncol Lab, 1230 York Ave, New York, NY 10021 USA.
EM darnelr@rockefeller.edu
FU NIH; Cornell/Rockefeller/Sloan-Kettering Tri-Institutional Program in Computational Biology and Medicine; MD-PhD Program
NR 50
TC 1442
Z9 1748
U1 1
U2 173
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 479
EP 486
DI 10.1038/nature08170
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000031
PM 19536157
DA 2026-03-09
ER

PT J
AU Maslowski, KM
   Vieira, AT
   Ng, A
   Kranich, J
   Sierro, F
   Yu, D
   Schilter, HC
   Rolph, MS
   Mackay, F
   Artis, D
   Xavier, RJ
   Teixeira, MM
   Mackay, CR
AF Maslowski, Kendle M.
   Vieira, Angelica T.
   Ng, Aylwin
   Kranich, Jan
   Sierro, Frederic
   Yu, Di
   Schilter, Heidi C.
   Rolph, Michael S.
   Mackay, Fabienne
   Artis, David
   Xavier, Ramnik J.
   Teixeira, Mauro M.
   Mackay, Charles R.
TI Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
SO NATURE
LA English
DT Article
ID chain fatty-acids; distal ulcerative-colitis; nf-kappa-b; functional-characterization; intestinal microbiota; bowel-disease; mice; eosinophils; irrigation; inhibition
AB The immune system responds to pathogens by a variety of pattern recognition molecules such as the Toll-like receptors (TLRs), which promote recognition of dangerous foreign pathogens. However, recent evidence indicates that normal intestinal microbiota might also positively influence immune responses, and protect against the development of inflammatory diseases(1,2). One of these elements may be short-chain fatty acids (SCFAs), which are produced by fermentation of dietary fibre by intestinal microbiota. A feature of human ulcerative colitis and other colitic diseases is a change in 'healthy' microbiota such as Bifidobacterium and Bacteriodes(3), and a concurrent reduction in SCFAs4. Moreover, increased intake of fermentable dietary fibre, or SCFAs, seems to be clinically beneficial in the treatment of colitis(5-9). SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as FFAR2)(10,11), and here we show that SCFA-GPR43 interactions profoundly affect inflammatory responses. Stimulation of GPR43 by SCFAs was necessary for the normal resolution of certain inflammatory responses, because GPR43-deficient (Gpr43(-/-)) mice showed exacerbated or unresolving inflammation in models of colitis, arthritis and asthma. This seemed to relate to increased production of inflammatory mediators by Gpr43(-/-) immune cells, and increased immune cell recruitment. Germ-free mice, which are devoid of bacteria and express little or no SCFAs, showed a similar dysregulation of certain inflammatory responses. GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.
C1 [Maslowski, Kendle M.; Vieira, Angelica T.; Kranich, Jan; Sierro, Frederic; Yu, Di; Schilter, Heidi C.; Rolph, Michael S.; Mackay, Fabienne; Mackay, Charles R.] St Vincents Hosp, Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia.
   [Maslowski, Kendle M.; Kranich, Jan; Schilter, Heidi C.; Rolph, Michael S.; Mackay, Charles R.] Cooperat Res Ctr Asthma & Airways, Camperdown, NSW 2050, Australia.
   [Maslowski, Kendle M.; Schilter, Heidi C.; Mackay, Charles R.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW 2010, Australia.
   [Vieira, Angelica T.; Teixeira, Mauro M.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, Brazil.
   [Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
   [Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Mackay, Fabienne; Mackay, Charles R.] Monash Univ, Fac Med, Clayton, Vic 3800, Australia.
   [Artis, David] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
   [Xavier, Ramnik J.] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Xavier, Ramnik J.] Harvard Univ, Cambridge, MA 02142 USA.
C3 Garvan Institute of Medical Research; NSW Health; St Vincents Hospital Sydney; University of New South Wales Sydney; Universidade Federal de Minas Gerais; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Monash University; University of Pennsylvania; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University
RP Mackay, CR (corresponding author), St Vincents Hosp, Garvan Inst Med Res, 384 Victoria St, Darlinghurst, NSW 2010, Australia.
EM charles.mackay@med.monash.edu.au
FU Australian NHMRC; CRC for Asthma and Airways; Crohn's and Colitis Foundation of America; Cancer Institute NSW; National Institute of Allergy and Infectious Diseases [R01AI095466] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK040561] Funding Source: NIH RePORTER
NR 44
TC 2593
Z9 3023
U1 18
U2 656
PU NATURE PUBLISHING 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 29
PY 2009
VL 461
IS 7268
BP 1282
EP U119
DI 10.1038/nature08530
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800049
PM 19865172
DA 2026-03-09
ER

PT J
AU Hu, WQ
   Sweet, TJ
   Chamnongpol, S
   Baker, KE
   Coller, J
AF Hu, Wenqian
   Sweet, Thomas J.
   Chamnongpol, Sangpen
   Baker, Kristian E.
   Coller, Jeff
TI Co-translational mRNA decay in Saccharomyces cerevisiae
SO NATURE
LA English
DT Article
ID p-body formation; cells; degradation; pathways; turnover; body
AB The rates of RNA decay and transcription determine the steady-state levels of allmessenger RNA and both can be subject to regulation. Although the details of transcriptional regulation are becoming increasingly understood, the mechanism(s) controlling mRNA decay remain unclear. In yeast, a major pathway of mRNA decay begins with deadenylation followed by decapping and 5'-3' exonuclease digestion. Importantly, it is hypothesized that ribosomes must be removed from mRNA before transcripts are destroyed. Contrary to this prediction, here we show that decay takes place while mRNAs are associated with actively translating ribosomes. The data indicate that dissociation of ribosomes from mRNA is not a prerequisite for decay and we suggest that the 5'-3' polarity of mRNA degradation has evolved to ensure that the last translocating ribosome can complete translation.
C1 [Hu, Wenqian; Sweet, Thomas J.; Baker, Kristian E.; Coller, Jeff] Case Western Reserve Univ, Ctr RNA Mol Biol, Cleveland, OH 44106 USA.
   [Chamnongpol, Sangpen] Affymetrix Inc, Cleveland, OH 44128 USA.
C3 University System of Ohio; Case Western Reserve University; Affymetrix
RP Coller, J (corresponding author), Case Western Reserve Univ, Ctr RNA Mol Biol, Cleveland, OH 44106 USA.
EM jmc71@case.edu
FU American Heart Association; National Institutes of Health
NR 23
TC 257
Z9 320
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 SEP 10
PY 2009
VL 461
IS 7261
BP 225
EP U96
DI 10.1038/nature08265
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600036
PM 19701183
DA 2026-03-09
ER

PT J
AU Day, JMD
   Ash, RD
   Liu, Y
   Bellucci, JJ
   Rumble, D
   McDonough, WF
   Walker, RJ
   Taylor, LA
AF Day, James M. D.
   Ash, Richard D.
   Liu, Yang
   Bellucci, Jeremy J.
   Rumble, Douglas, III
   McDonough, William F.
   Walker, Richard J.
   Taylor, Lawrence A.
TI Early formation of evolved asteroidal crust
SO NATURE
LA English
DT Article
ID oxygen-isotope; fractionation; constraints; differentiation; oceans; age
AB Mechanisms for the formation of crust on planetary bodies remain poorly understood(1). It is generally accepted that Earth's andesitic continental crust is the product of plate tectonics(1,2), whereas the Moon acquired its feldspar- rich crust by way of plagioclase flotation in a magma ocean(3,4). Basaltic meteorites provide evidence that, like the terrestrial planets, some asteroids generated crust and underwent large- scale differentiation processes(5). Until now, however, no evolved felsic asteroidal crust has been sampled or observed. Here we report age and compositional data for the newly discovered, paired and differentiated meteorites Graves Nunatak ( GRA) 06128 and GRA 06129. These meteorites are feldspar- rich, with andesite bulk compositions. Their age of 4.5+/-0.06 Gyr demonstrates formation early in Solar System history. The isotopic and elemental compositions, degree of metamorphic re-equilibration and sulphide- rich nature of the meteorites are most consistent with an origin as partial melts from a volatile- rich, oxidized asteroid. GRA 06128 and 06129 are the result of a newly recognized style of evolved crust formation, bearing witness to incomplete differentiation of their parent asteroid and to previously unrecognized diversity of early- formed materials in the Solar System.
C1 [Day, James M. D.; Ash, Richard D.; Bellucci, Jeremy J.; McDonough, William F.; Walker, Richard J.] Univ Maryland, Dept Geol, College Pk, MD 20742 USA.
   [Liu, Yang; Taylor, Lawrence A.] Univ Tennessee, Dept Earth & Planetary Sci, Planetary Geosci Inst, Knoxville, TN 37996 USA.
   [Rumble, Douglas, III] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
C3 University System of Maryland; University of Maryland College Park; University of Tennessee System; University of Tennessee Knoxville; Carnegie Institution for Science
RP Day, JMD (corresponding author), Univ Maryland, Dept Geol, College Pk, MD 20742 USA.
EM jamesday@umd.edu
FU NASA Cosmochemistry Program [NNX07AM29G, NNX08AH76G, NNG05GG03G]; Division Of Earth Sciences; Directorate For Geosciences [0739006] Funding Source: National Science Foundation; NASA [101330, NNX08AH76G] Funding Source: Federal RePORTER
NR 40
TC 97
Z9 111
U1 1
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 8
PY 2009
VL 457
IS 7226
BP 179
EP U68
DI 10.1038/nature07651
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200029
PM 19129845
DA 2026-03-09
ER

PT J
AU Chassagneux, Y
   Colombelli, R
   Maineult, W
   Barbieri, S
   Beere, HE
   Ritchie, DA
   Khanna, SP
   Linfield, EH
   Davies, AG
AF Chassagneux, Y.
   Colombelli, R.
   Maineult, W.
   Barbieri, S.
   Beere, H. E.
   Ritchie, D. A.
   Khanna, S. P.
   Linfield, E. H.
   Davies, A. G.
TI Electrically pumped photonic-crystal terahertz lasers controlled by boundary conditions
SO NATURE
LA English
DT Article
ID quantum-cascade lasers; semiconductor-lasers; wave-guides; design; resonators; cavity
AB Semiconductor lasers based on two-dimensional photonic crystals(1,2) generally rely on an optically pumped central area, surrounded by un- pumped, and therefore absorbing, regions(3). This ideal configuration is lost when photonic- crystal lasers are electrically pumped, which is practically more attractive as an external laser source is not required. In this case, in order to avoid lateral spreading of the electrical current, the device active area must be physically defined by appropriate semiconductor processing. This creates an abrupt change in the complex dielectric constant at the device boundaries, especially in the case of lasers operating in the far- infrared, where the large emission wavelengths impose device thicknesses of several micrometres. Here we show that such abrupt boundary conditions can dramatically influence the operation of electrically pumped photonic- crystal lasers. By demonstrating a general technique to implement reflecting or absorbing boundaries, we produce evidence that whispering- gallery- like modes or true photonic- crystal states can be alternatively excited. We illustrate the power of this technique by fabricating photonic- crystal terahertz ( THz) semiconductor lasers, where the photonic crystal is implemented via the sole patterning of the device top metallization. Single- mode laser action is obtained in the 2.55-2.88 THz range, and the emission far field exhibits a small angular divergence, thus providing a solution for the quasi- total lack of directionality typical of THz semiconductor lasers based on metal - metal waveguides(4).
C1 [Chassagneux, Y.; Colombelli, R.] Univ Paris 11, Inst Elect Fondamentale, F-91405 Orsay, France.
   [Chassagneux, Y.; Colombelli, R.] CNRS, UMR 8622, F-91405 Orsay, France.
   [Maineult, W.; Barbieri, S.] Univ Paris 07, Lab MPQ, F-75013 Paris, France.
   [Maineult, W.; Barbieri, S.] CNRS, UMR 7162, F-75013 Paris, France.
   [Beere, H. E.; Ritchie, D. A.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Khanna, S. P.; Linfield, E. H.; Davies, A. G.] Univ Leeds, Sch Elect & Elect Engn, Leeds LS2 9JT, W Yorkshire, England.
C3 Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Universite Paris Cite; University of Cambridge; University of Leeds
RP Colombelli, R (corresponding author), Univ Paris 11, Inst Elect Fondamentale, F-91405 Orsay, France.
EM raffaele.colombelli@u-psud.fr
FU Conseil General de l'Essonne; EPSRC [EP/E048811/1, EP/D025532/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/C002881/1, EP/E048811/1, EP/D025532/1] Funding Source: researchfish
NR 30
TC 271
Z9 304
U1 1
U2 183
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 8
PY 2009
VL 457
IS 7226
BP 174
EP 178
DI 10.1038/nature07636
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200028
PM 19129844
DA 2026-03-09
ER

PT J
AU Egholm, DL
   Nielsen, SB
   Pedersen, VK
   Lesemann, JE
AF Egholm, D. L.
   Nielsen, S. B.
   Pedersen, V. K.
   Lesemann, J. -E.
TI Glacial effects limiting mountain height
SO NATURE
LA English
DT Article
ID relief production; erosion; climate; landscapes; morphology; evolution; belts; range; model; usa
AB The height of mountain ranges reflects the balance between tectonic rock uplift, crustal strength and surface denudation. Tectonic deformation and surface denudation are interdependent, however, and feedback mechanisms-in particular, the potential link to climate-are subjects of intense debate(1,2). Spatial variations in fluvial denudation rate caused by precipitation gradients are known to provide first-order controls on mountain range width, crustal deformation rates and rock uplift(3,4). Moreover, limits to crustal strength(5) are thought to constrain the maximum elevation of large continental plateaus, such as those in Tibet and the central Andes. There are indications that the general height of mountain ranges is also directly influenced by the extent of glaciation through an efficient denudation mechanism known as the glacial buzzsaw(6-9). Here we use a global analysis of topography and show that variations in maximum mountain height correlate closely with climate-controlled gradients in snowline altitude for many high mountain ranges across orogenic ages and tectonic styles. With the aid of a numerical model, we further demonstrate how a combination of erosional destruction of topography above the snowline by glacier-sliding and commensurate isostatic landscape uplift caused by erosional unloading can explain observations of maximum mountain height by driving elevations towards an altitude window just below the snowline. The model thereby self-consistently produces the hypsometric signature of the glacial buzzsaw, and suggests that differences in the height of mountain ranges mainly reflect variations in local climate rather than tectonic forces.
C1 [Egholm, D. L.; Nielsen, S. B.; Pedersen, V. K.; Lesemann, J. -E.] Aarhus Univ, Dept Earth Sci, DK-8000 Aarhus, Denmark.
C3 Aarhus University
RP Egholm, DL (corresponding author), Aarhus Univ, Dept Earth Sci, DK-8000 Aarhus, Denmark.
EM david@geo.au.dk
NR 40
TC 282
Z9 319
U1 5
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 13
PY 2009
VL 460
IS 7257
BP 884
EP U120
DI 10.1038/nature08263
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300036
PM 19675651
DA 2026-03-09
ER

PT J
AU Singh, I
   Rose, N
AF Singh, Ilina
   Rose, Nikolas
TI Biomarkers in psychiatry
SO NATURE
LA English
DT Article
ID mental-illness; prevention; genotype; disorder; medicine; genetics; genome; genes; risk; race
C1 [Singh, Ilina; Rose, Nikolas] London Sch Econ, BIOS Ctr, London WC2A 2AE, England.
C3 University of London; London School Economics & Political Science
RP Singh, I (corresponding author), London Sch Econ, BIOS Ctr, Houghton St, London WC2A 2AE, England.
EM i.a.singh@lse.ac.uk
FU ESRC [ES/E020585/1] Funding Source: UKRI; Economic and Social Research Council [ES/E020585/1] Funding Source: researchfish
NR 41
TC 265
Z9 309
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 202
EP 207
DI 10.1038/460202a
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000030
PM 19587761
DA 2026-03-09
ER

PT J
AU Brunner, DO
   De Zanche, N
   Fröhlich, J
   Paska, J
   Pruessmann, KP
AF Brunner, David O.
   De Zanche, Nicola
   Froehlich, Juerg
   Paska, Jan
   Pruessmann, Klaas P.
TI Travelling-wave nuclear magnetic resonance
SO NATURE
LA English
DT Article
ID human mri; nmr; coils; 9.4t
AB Nuclear magnetic resonance(1,2) (NMR) is one of the most versatile experimental methods in chemistry, physics and biology(3), providing insight into the structure and dynamics of matter at the molecular scale. Its imaging variant - magnetic resonance imaging(4,5) (MRI) - is widely used to examine the anatomy, physiology and metabolism of the human body. NMRsignal detection is traditionally based on Faraday induction(6) in one or multiple radio- frequency resonators(7-10) that are brought into close proximity with the sample. Alternative principles involving structured-material flux guides(11), superconducting quantum interference devices(12), atomic magnetometers(13), Hall probes(14) or magnetoresistive elements(15) have been explored. However, a common feature of all NMR implementations until now is that they rely on close coupling between the detector and the object under investigation. Here we show that NMR can also be excited and detected by long-range interaction, relying on travelling radio- frequency waves sent and received by an antenna. One benefit of this approach is more uniform coverage of samples that are larger than the wavelength of the NMR signal - an important current issue in MRI of humans at very high magnetic fields. By allowing a significant distance between the probe and the sample, travelling- wave interaction also introduces new possibilities in the design of NMR experiments and systems.
C1 [Brunner, David O.; De Zanche, Nicola; Pruessmann, Klaas P.] Univ Zurich, Inst Biomed Engn, CH-8092 Zurich, Switzerland.
   [Brunner, David O.; De Zanche, Nicola; Froehlich, Juerg; Paska, Jan; Pruessmann, Klaas P.] ETH, Lab Electromagnet Fields & Microwave Elect, CH-8092 Zurich, Switzerland.
C3 University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Pruessmann, KP (corresponding author), Univ Zurich, Inst Biomed Engn, Gloriastr 35, CH-8092 Zurich, Switzerland.
EM pruessmann@biomed.ee.ethz.ch
FU Swiss National Science Foundation [116400]; Velux Foundation
NR 28
TC 154
Z9 181
U1 2
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 19
PY 2009
VL 457
IS 7232
BP 994
EP U2
DI 10.1038/nature07752
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400038
PM 19225521
DA 2026-03-09
ER

PT J
AU Shukla, VK
   Doyon, Y
   Miller, JC
   DeKelver, RC
   Moehle, EA
   Worden, SE
   Mitchell, JC
   Arnold, NL
   Gopalan, S
   Meng, XD
   Choi, VM
   Rock, JM
   Wu, YY
   Katibah, GE
   Zhifang, G
   McCaskill, D
   Simpson, MA
   Blakeslee, B
   Greenwalt, SA
   Butler, HJ
   Hinkley, SJ
   Zhang, L
   Rebar, EJ
   Gregory, PD
   Urnov, FD
AF Shukla, Vipula K.
   Doyon, Yannick
   Miller, Jeffrey C.
   DeKelver, Russell C.
   Moehle, Erica A.
   Worden, Sarah E.
   Mitchell, Jon C.
   Arnold, Nicole L.
   Gopalan, Sunita
   Meng, Xiangdong
   Choi, Vivian M.
   Rock, Jeremy M.
   Wu, Ying-Ying
   Katibah, George E.
   Zhifang, Gao
   McCaskill, David
   Simpson, Matthew A.
   Blakeslee, Beth
   Greenwalt, Scott A.
   Butler, Holly J.
   Hinkley, Sarah J.
   Zhang, Lei
   Rebar, Edward J.
   Gregory, Philip D.
   Urnov, Fyodor D.
TI Precise genome modification in the crop species Zea mays using zinc-finger nucleases
SO NATURE
LA English
DT Article
ID homologous recombination; mediated transformation; gene; expression; maize; cleavage; sequence; cells; mutagenesis; disruption
AB Agricultural biotechnology is limited by the inefficiencies of conventional random mutagenesis and transgenesis. Because targeted genome modification in plants has been intractable(1), plant trait engineering remains a laborious, time-consuming and unpredictable undertaking. Here we report a broadly applicable, versatile solution to this problem: the use of designed zinc-finger nucleases (ZFNs) that induce a double-stranded break at their target locus(2). We describe the use of ZFNs to modify endogenous loci in plants of the crop species Zea mays. We show that simultaneous expression of ZFNs and delivery of a simple heterologous donor molecule leads to precise targeted addition of an herbicide-tolerance gene at the intended locus in a significant number of isolated events. ZFN-modified maize plants faithfully transmit these genetic changes to the next generation. Insertional disruption of one target locus, IPK1, results in both herbicide tolerance and the expected alteration of the inositol phosphate profile in developing seeds. ZFNs can be used in any plant species amenable to DNA delivery; our results therefore establish a new strategy for plant genetic manipulation in basic science and agricultural applications.
C1 [Shukla, Vipula K.; Worden, Sarah E.; Mitchell, Jon C.; Arnold, Nicole L.; Zhifang, Gao; McCaskill, David; Simpson, Matthew A.; Blakeslee, Beth; Greenwalt, Scott A.; Butler, Holly J.] Dow AgroSci, Indianapolis, IN 46268 USA.
   [Doyon, Yannick; Miller, Jeffrey C.; DeKelver, Russell C.; Moehle, Erica A.; Gopalan, Sunita; Meng, Xiangdong; Choi, Vivian M.; Rock, Jeremy M.; Wu, Ying-Ying; Katibah, George E.; Hinkley, Sarah J.; Zhang, Lei; Rebar, Edward J.; Gregory, Philip D.; Urnov, Fyodor D.] Point Richmond Tech Ctr, Richmond, CA 94804 USA.
C3 Dow Chemical Company
RP Shukla, VK (corresponding author), Dow AgroSci, 9330 Zionsville Rd, Indianapolis, IN 46268 USA.
EM vkshukla@dow.com
NR 44
TC 647
Z9 862
U1 4
U2 241
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2009
VL 459
IS 7245
BP 437
EP U156
DI 10.1038/nature07992
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700048
PM 19404259
DA 2026-03-09
ER

PT J
AU Katija, K
   Dabiri, JO
AF Katija, Kakani
   Dabiri, John O.
TI A viscosity-enhanced mechanism for biogenic ocean mixing
SO NATURE
LA English
DT Article
ID drift; turbulence; flow
AB Recent observations of biologically generated turbulence in the ocean have led to conflicting conclusions regarding the significance of the contribution of animal swimming to ocean mixing. Measurements indicate elevated turbulent dissipation-comparable with levels caused by winds and tides-in the vicinity of large populations of planktonic animals swimming together(1). However, it has also been noted that elevated turbulent dissipation is by itself insufficient proof of substantial biogenic mixing, because much of the turbulent kinetic energy of small animals is injected below the Ozmidov buoyancy length scale, where it is primarily dissipated as heat by the fluid viscosity before it can affect ocean mixing(2). Ongoing debate regarding biogenic mixing has focused on comparisons between animal wake turbulence and ocean turbulence(3,4). Here, we show that a second, previously neglected mechanism of fluid mixing-first described over 50 years ago by Charles Darwin(5)-is the dominant mechanism of mixing by swimming animals. The efficiency of mixing by Darwin's mechanism is dependent on animal shape rather than fluid length scale and, unlike turbulent wake mixing, is enhanced by fluid viscosity. Therefore, it provides a means of biogenic mixing that can be equally effective in small zooplankton and large mammals. A theoretical model for the relative contributions of Darwinian mixing and turbulent wake mixing is created and validated by in situ field measurements of swimming jellyfish using a newly developed scuba-based laser velocimetry device(6). Extrapolation of these results to other animals is straightforward given knowledge of the animal shape and orientation during vertical migration. On the basis of calculations of a broad range of aquatic animal species, we conclude that biogenic mixing via Darwin's mechanism can be a significant contributor to ocean mixing and nutrient transport.
C1 [Dabiri, John O.] CALTECH, Grad Aeronaut Labs, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Dabiri, JO (corresponding author), CALTECH, Grad Aeronaut Labs, Pasadena, CA 91125 USA.
EM kakani@caltech.edu; jodabiri@caltech.edu
FU National Science Foundation Biological Oceanography Program; NSF; Office of Naval Research; NDSEG; Charles Lee Powell Foundation
NR 20
TC 148
Z9 179
U1 2
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 624
EP U87
DI 10.1038/nature08207
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300049
PM 19641595
DA 2026-03-09
ER

PT J
AU Artal-Sanz, M
   Tavernarakis, N
AF Artal-Sanz, Marta
   Tavernarakis, Nektarios
TI Prohibitin couples diapause signalling to mitochondrial metabolism during ageing in C-elegans
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; life-span; transcription factor; regulates longevity; oxidative stress; proteins; kinase; gene; senescence; nutrition
AB Marked alterations in cellular energy metabolism are a universal hallmark of the ageing process(1). The biogenesis and function of mitochondria, the energy-generating organelles in eukaryotic cells, are primary longevity determinants. Genetic or pharmacological manipulations of mitochondrial activity profoundly affect the life-span of diverse organisms(2). However, the molecular mechanisms regulating mitochondrial biogenesis and energy metabolism during ageing are poorly understood. Prohibitins are ubiquitous, evolutionarily conserved proteins, which form a ring-like, high-molecular-mass complex at the inner membrane of mitochondria(3). Here, we show that the mitochondrial prohibitin complex promotes longevity by modulating mitochondrial function and fat metabolism in the nematode Caenorhabditis elegans. We found that prohibitin deficiency shortens the lifespan of otherwise wild-type animals. Notably, knockdown of prohibitin promotes longevity in diapause mutants or under conditions of dietary restriction. In addition, prohibitin deficiency extends the lifespan of animals with compromised mitochondrial function or fat metabolism. Depletion of prohibitin influences ATP levels, animal fat content and mitochondrial proliferation in a genetic-background- and age-specific manner. Together, these findings reveal a novel mechanism regulating mitochondrial biogenesis and function, with opposing effects on energy metabolism, fat utilization and ageing in C. elegans. Prohibitin may have a similar key role in modulating energy metabolism during ageing in mammals.
C1 [Artal-Sanz, Marta; Tavernarakis, Nektarios] Fdn Res & Technol, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece.
RP Tavernarakis, N (corresponding author), Fdn Res & Technol, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece.
EM martal@ibv.csic.es; tavernarakis@imbb.forth.gr
FU EMBO; European Research Council ( ERC); Marie Curie Fellowships; European Commission [LSHM-CT-2005-19063]
NR 34
TC 163
Z9 196
U1 3
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 8
PY 2009
VL 461
IS 7265
BP 793
EP U47
DI 10.1038/nature08466
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500036
PM 19812672
DA 2026-03-09
ER

PT J
AU Purcell, SM
   Wray, NR
   Stone, JL
   Visscher, PM
   O'Donovan, MC
   Sullivan, PF
   Sklar, P
   Ruderfer, DM
   McQuillin, A
   Morris, DW
   O'Dushlaine, CT
   Corvin, A
   Holmans, PA
   Macgregor, S
   Gurling, H
   Blackwood, DHR
   Craddock, NJ
   Gill, M
   Hultman, CM
   Kirov, GK
   Lichtenstein, P
   Muir, WJ
   Owen, MJ
   Pato, CN
   Scolnick, EM
   St Clair, D
   Williams, NM
   Georgieva, L
   Nikolov, I
   Norton, N
   Williams, H
   Toncheva, D
   Milanova, V
   Thelander, EF
   Sullivan, P
   Kenny, E
   Quinn, EM
   Choudhury, K
   Datta, S
   Pimm, J
   Thirumalai, S
   Puri, V
   Krasucki, R
   Lawrence, J
   Quested, D
   Bass, N
   Crombie, C
   Fraser, G
   Kuan, SL
   Walker, N
   McGhee, KA
   Pickard, B
   Malloy, P
   Maclean, AW
   Van Beck, M
   Pato, MT
   Medeiros, H
   Middleton, F
   Carvalho, C
   Morley, C
   Fanous, A
   Conti, D
   Knowles, JA
   Ferreira, CP
   Macedo, A
   Azevedo, MH
   Kirby, AN
   Ferreira, MAR
   Daly, MJ
   Chambert, K
   Kuruvilla, F
   Gabriel, SB
   Ardlie, K
   Moran, JL
AF Purcell, Shaun M.
   Wray, Naomi R.
   Stone, Jennifer L.
   Visscher, Peter M.
   O'Donovan, Michael C.
   Sullivan, Patrick F.
   Sklar, Pamela
   Ruderfer, Douglas M.
   McQuillin, Andrew
   Morris, Derek W.
   O'Dushlaine, Colm T.
   Corvin, Aiden
   Holmans, Peter A.
   Macgregor, Stuart
   Gurling, Hugh
   Blackwood, Douglas H. R.
   Craddock, Nick J.
   Gill, Michael
   Hultman, Christina M.
   Kirov, George K.
   Lichtenstein, Paul
   Muir, Walter J.
   Owen, Michael J.
   Pato, Carlos N.
   Scolnick, Edward M.
   St Clair, David
   Williams, Nigel M.
   Georgieva, Lyudmila
   Nikolov, Ivan
   Norton, N.
   Williams, H.
   Toncheva, Draga
   Milanova, Vihra
   Thelander, Emma F.
   Sullivan, Patrick
   Kenny, Elaine
   Quinn, Emma M.
   Choudhury, Khalid
   Datta, Susmita
   Pimm, Jonathan
   Thirumalai, Srinivasa
   Puri, Vinay
   Krasucki, Robert
   Lawrence, Jacob
   Quested, Digby
   Bass, Nicholas
   Crombie, Caroline
   Fraser, Gillian
   Kuan, Soh Leh
   Walker, Nicholas
   McGhee, Kevin A.
   Pickard, Ben
   Malloy, Pat
   Maclean, Alan W.
   Van Beck, Margaret
   Pato, Michele T.
   Medeiros, Helena
   Middleton, Frank
   Carvalho, Celia
   Morley, Christopher
   Fanous, Ayman
   Conti, David
   Knowles, James A.
   Ferreira, Carlos Paz
   Macedo, Antonio
   Azevedo, M. Helena
   Kirby, Andrew N.
   Ferreira, Manuel A. R.
   Daly, Mark J.
   Chambert, Kimberly
   Kuruvilla, Finny
   Gabriel, Stacey B.
   Ardlie, Kristin
   Moran, Jennifer L.
TI Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
SO NATURE
LA English
DT Article
ID genome-wide association; multiple rare alleles; psychiatric-disorders; disease; genes; loci; twin
AB Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
C1 [Purcell, Shaun M.; Stone, Jennifer L.; Sklar, Pamela; Ruderfer, Douglas M.; Ferreira, Manuel A. R.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
   [Purcell, Shaun M.; Stone, Jennifer L.; Sklar, Pamela; Ruderfer, Douglas M.; Scolnick, Edward M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Purcell, Shaun M.; Stone, Jennifer L.; Sklar, Pamela; Ruderfer, Douglas M.; Scolnick, Edward M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.; Chambert, Kimberly] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Purcell, Shaun M.; Stone, Jennifer L.; Sklar, Pamela; Ruderfer, Douglas M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.; Chambert, Kimberly; Kuruvilla, Finny; Gabriel, Stacey B.; Ardlie, Kristin; Moran, Jennifer L.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Wray, Naomi R.; Visscher, Peter M.; Macgregor, Stuart] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
   [O'Donovan, Michael C.; Holmans, Peter A.; Craddock, Nick J.; Kirov, George K.; Owen, Michael J.; Williams, Nigel M.; Georgieva, Lyudmila; Nikolov, Ivan; Norton, N.; Williams, H.] Cardiff Univ, Sch Med, Dept Psychol Med, MRC Ctr Neuropsychiat Genet & Gen, Cardiff C14 4XN, Wales.
   [Sullivan, Patrick F.; Sullivan, Patrick] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Sullivan, Patrick F.; Sullivan, Patrick] Univ N Carolina, Dept Psychiat & Epidemiol, Chapel Hill, NC 27599 USA.
   [McQuillin, Andrew; Gurling, Hugh; Choudhury, Khalid; Datta, Susmita; Pimm, Jonathan; Puri, Vinay; Krasucki, Robert; Lawrence, Jacob; Bass, Nicholas] UCL, Sch Med, Mol Psychiat Lab, Res Dept Mental Hlth Sci,Windeyer Inst Med Sci, London W1T 4JF, England.
   [Morris, Derek W.; O'Dushlaine, Colm T.; Corvin, Aiden; Gill, Michael; Kenny, Elaine; Quinn, Emma M.] Univ Dublin Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland.
   [Morris, Derek W.; O'Dushlaine, Colm T.; Corvin, Aiden; Gill, Michael; Kenny, Elaine; Quinn, Emma M.] Univ Dublin Trinity Coll, Inst Mol Med, Dublin 2, Ireland.
   [Blackwood, Douglas H. R.; Muir, Walter J.; McGhee, Kevin A.; Pickard, Ben; Malloy, Pat; Maclean, Alan W.; Van Beck, Margaret] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland.
   [Hultman, Christina M.; Lichtenstein, Paul; Thelander, Emma F.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
   [Hultman, Christina M.] Uppsala Univ, Dept Neurosci, SE-75017 Uppsala, Sweden.
   [Pato, Carlos N.; Pato, Michele T.; Medeiros, Helena; Carvalho, Celia; Fanous, Ayman; Conti, David; Knowles, James A.] Univ So Calif, Ctr Genom Psychiat, Los Angeles, CA 90033 USA.
   [St Clair, David; Walker, Nicholas] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
   [Crombie, Caroline; Fraser, Gillian] Univ Aberdeen, Dept Mental Hlth, Aberdeen AB25 2ZD, Scotland.
   [Toncheva, Draga] Univ Hosp Maichin Dom, Dept Med Genet, Sofia 1431, Bulgaria.
   [Milanova, Vihra] Alexander Univ Hosp, Psychiat Clin 1, Dept Psychiat, Sofia 1431, Bulgaria.
   [Thirumalai, Srinivasa] W Berkshire NHS Trust, Reading RG3 5LR, Berks, England.
   [Quested, Digby] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England.
   [Kuan, Soh Leh] Ravenscraig Hosp, Greenock PA16 9HA, Scotland.
   [Middleton, Frank; Morley, Christopher] SUNY Syracuse, Upstate Med Univ Syracuse, Syracuse, NY 13210 USA.
   [Fanous, Ayman] Washington VA Med Ctr, Washington, DC 20422 USA.
   [Fanous, Ayman] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC 20057 USA.
   [Fanous, Ayman] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA.
   [Ferreira, Carlos Paz] Dept Psychiat, P-9500310 Sao Miguel, Azores, Portugal.
   [Macedo, Antonio; Azevedo, M. Helena] Univ Coimbra, Dept Psychiat, P-3004504 Coimbra, Portugal.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; QIMR Berghofer Medical Research Institute; Cardiff University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of London; University College London; UCL Medical School; Trinity College Dublin; Trinity College Dublin; University of Edinburgh; Royal Infirmary of Edinburgh; Karolinska Institutet; Uppsala University; University of Southern California; University of Aberdeen; University of Aberdeen; Medical University Sofia; Medical University Sofia; University of Oxford; State University of New York (SUNY) System; SUNY Upstate Medical University; Georgetown University; Virginia Commonwealth University; Universidade de Coimbra
RP Sklar, P (corresponding author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 185 Cambridge St, Boston, MA 02114 USA.
EM shaun@pngu.mgh.harvard.edu; sklar@chgr.mgh.harvard.edu
FU Stanley Medical Research Institute; Sylvan C. Herman Foundation [MH071681]; Medical Research Council (UK) Programme; National Institutes of Mental Health (USA) [CONTE: 2 P50 MH066392-05A1]; Swedish Council for Working Life and Social Research [FO 184/2000, 2001-2368]; Stanley Medical Research Institute [MH071681, MH077139]; Narsad Young Investigator Award; Australian National Health and Medical Research Council [389892, 442915, 496688, 496674]; Science Foundation Ireland; Health Research Board (Ireland); Wellcome Trust; National Institutes of Mental Health and the Department of Veterans Affairs; National Health and Medical Research Council (NHMRC) [496674] Funding Source: National Health and Medical Research Council (NHMRC); Medical Research Council [G0500791, G0801418, G0800509] Funding Source: researchfish; MRC [G0800509, G0500791, G0801418] Funding Source: UKRI
NR 26
TC 3677
Z9 4181
U1 3
U2 554
PU NATURE PUBLISHING 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 6
PY 2009
VL 460
IS 7256
BP 748
EP 752
DI 10.1038/nature08185
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300041
PM 19571811
DA 2026-03-09
ER

PT J
AU Shi, YM
   Tyson, GW
   DeLong, EF
AF Shi, Yanmei
   Tyson, Gene W.
   DeLong, Edward F.
TI Metatranscriptomics reveals unique microbial small RNAs in the ocean's water column
SO NATURE
LA English
DT Article
ID noncoding rnas; genes; expression; identification; riboswitches; prediction; sequences; alignment; database
AB Microbial gene expression in the environment has recently been assessed via pyrosequencing of total RNA extracted directly from natural microbial assemblages. Several such 'metatranscriptomic' studies(1,2) have reported that many complementary DNA sequences shared no significant homology with known peptide sequences, and so might represent transcripts from uncharacterized proteins. Here we report that a large fraction of cDNA sequences detected in microbial metatranscriptomic data sets are comprised of well-known small RNAs ( sRNAs) 3, as well as new groups of previously unrecognized putative sRNAs ( psRNAs). These psRNAs mapped specifically to intergenic regions of microbial genomes recovered from similar habitats, displayed characteristic conserved secondary structures and were frequently flanked by genes that indicated potential regulatory functions. Depth-dependent variation of psRNAs generally reflected known depth distributions of broad taxonomic groups(4), but fine-scale differences in the psRNAs within closely related populations indicated potential roles in niche adaptation. Genome-specific mapping of a subset of psRNAs derived from predominant planktonic species such as Pelagibacter revealed recently discovered as well as potentially new regulatory elements. Our analyses show that metatranscriptomic data sets can reveal new information about the diversity, taxonomic distribution and abundance of sRNAs in naturally occurring microbial communities, and indicate their involvement in environmentally relevant processes including carbon metabolism and nutrient acquisition.
C1 [Shi, Yanmei; Tyson, Gene W.; DeLong, Edward F.] MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA.
   [DeLong, Edward F.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP DeLong, EF (corresponding author), MIT, Dept Civil & Environm Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM delong@mit.edu
FU Craig Venter Institute; Gordon and Betty Moore Foundation for the genome sequence of Pelagibacter [HTCC7211]; Gordon and Betty Moore Foundation; National Science Foundation Microbial Observatory [MCB-0348001]; Department of Energy Genomics GTL Program; Department of Energy Microbial Genomics Program; NSF Science and Technology award; C-MORE
NR 46
TC 202
Z9 236
U1 5
U2 96
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 266
EP U154
DI 10.1038/nature08055
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100044
PM 19444216
DA 2026-03-09
ER

PT J
AU Heintzman, ND
   Hon, GC
   Hawkins, RD
   Kheradpour, P
   Stark, A
   Harp, LF
   Ye, Z
   Lee, LK
   Stuart, RK
   Ching, CW
   Ching, KA
   Antosiewicz-Bourget, JE
   Liu, H
   Zhang, XM
   Green, RD
   Lobanenkov, VV
   Stewart, R
   Thomson, JA
   Crawford, GE
   Kellis, M
   Ren, B
AF Heintzman, Nathaniel D.
   Hon, Gary C.
   Hawkins, R. David
   Kheradpour, Pouya
   Stark, Alexander
   Harp, Lindsey F.
   Ye, Zhen
   Lee, Leonard K.
   Stuart, Rhona K.
   Ching, Christina W.
   Ching, Keith A.
   Antosiewicz-Bourget, Jessica E.
   Liu, Hui
   Zhang, Xinmin
   Green, Roland D.
   Lobanenkov, Victor V.
   Stewart, Ron
   Thomson, James A.
   Crawford, Gregory E.
   Kellis, Manolis
   Ren, Bing
TI Histone modifications at human enhancers reflect global cell-type-specific gene expression
SO NATURE
LA English
DT Article
ID human genome; binding-sites; transcription; promoters; elements; sequence; receptor; map
AB The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene(1-3), the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome(4-6). Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.
C1 [Heintzman, Nathaniel D.; Hon, Gary C.; Hawkins, R. David; Harp, Lindsey F.; Ye, Zhen; Lee, Leonard K.; Stuart, Rhona K.; Ching, Christina W.; Ching, Keith A.; Ren, Bing] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Heintzman, Nathaniel D.] Univ Calif San Diego, Sch Med, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
   [Hon, Gary C.] Univ Calif San Diego, Sch Med, Bioinformat Program, La Jolla, CA 92093 USA.
   [Ren, Bing] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Kheradpour, Pouya; Stark, Alexander; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Stark, Alexander; Kellis, Manolis] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Antosiewicz-Bourget, Jessica E.; Stewart, Ron; Thomson, James A.] Morgridge Inst Res, Madison, WI 53707 USA.
   [Liu, Hui; Zhang, Xinmin; Green, Roland D.] Roche NimbleGen Inc, Madison, WI 53719 USA.
   [Lobanenkov, Victor V.] NIAID, Rockville, MD 20852 USA.
   [Thomson, James A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA.
   [Crawford, Gregory E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA.
   [Crawford, Gregory E.] Duke Univ, Dept Pediat, Durham, NC 27708 USA.
C3 Ludwig Institute for Cancer Research; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Wisconsin System; University of Wisconsin Madison; The Morgridge Institute for Research, Inc.; Roche Holding; Roche Holding USA; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Wisconsin System; University of Wisconsin Madison; Duke University; Duke University
RP Ren, B (corresponding author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM biren@ucsd.edu
FU American Cancer Society; NIAID; LICR; NHGRI; NCI; CIRM; Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF); National Institute of Allergy and Infectious Diseases [ZIAAI000860] Funding Source: NIH RePORTER
NR 25
TC 1969
Z9 2520
U1 1
U2 198
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 7
PY 2009
VL 459
IS 7243
BP 108
EP 112
DI 10.1038/nature07829
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300039
PM 19295514
DA 2026-03-09
ER

PT J
AU Xu, X
   Clark, JM
   Mo, JY
   Choiniere, J
   Forster, CA
   Erickson, GM
   Hone, DWE
   Sullivan, C
   Eberth, DA
   Nesbitt, S
   Zhao, Q
   Hernandez, R
   Jia, CK
   Han, FL
   Guo, Y
AF Xu, Xing
   Clark, James M.
   Mo, Jinyou
   Choiniere, Jonah
   Forster, Catherine A.
   Erickson, Gregory M.
   Hone, David W. E.
   Sullivan, Corwin
   Eberth, David A.
   Nesbitt, Sterling
   Zhao, Qi
   Hernandez, Rene
   Jia, Cheng-kai
   Han, Feng-lu
   Guo, Yu
TI A Jurassic ceratosaur from China helps clarify avian digital homologies
SO NATURE
LA English
DT Article
ID abelisauroid dinosauria; theropoda; evolution; expression; reduction; patterns; birds
AB Theropods have traditionally been assumed to have lost manual digits from the lateral side inward, which differs from the bilateral reduction pattern seen in other tetrapod groups. This unusual reduction pattern is clearly present in basal theropods, and has also been inferred in non-avian tetanurans based on identification of their three digits as the medial ones of the hand (I-II-III). This contradicts the many developmental studies indicating II-III-IV identities for the three manual digits of the only extant tetanurans, the birds. Here we report a new basal ceratosaur from the Oxfordian stage of the Jurassic period of China (156-161 million years ago), representing the first known Asian ceratosaur and the only known beaked, herbivorous Jurassic theropod. Most significantly, this taxon possesses a strongly reduced manual digit I, documenting a complex pattern of digital reduction within the Theropoda. Comparisons among theropod hands show that the three manual digits of basal tetanurans are similar in many metacarpal features to digits II-III-IV, but in phalangeal features to digits I-II-III, of more basal theropods. Given II-III-IV identities in avians, the simplest interpretation is that these identities were shared by all tetanurans. The transition to tetanurans involved complex changes in the hand including a shift in digit identities, with ceratosaurs displaying an intermediate condition.
C1 [Xu, Xing; Hone, David W. E.; Sullivan, Corwin; Zhao, Qi; Han, Feng-lu; Guo, Yu] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
   [Clark, James M.; Choiniere, Jonah; Forster, Catherine A.] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA.
   [Mo, Jinyou] Nat Hist Museum Guangxi, Nanning 530012, Guangxi, Peoples R China.
   [Mo, Jinyou] China Univ Geosci, Fac Earth Sci, Wuhan 430074, Hubei, Peoples R China.
   [Erickson, Gregory M.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
   [Eberth, David A.] Royal Tyrrell Museum, Drumheller, AB T0J 0Y0, Canada.
   [Nesbitt, Sterling] Amer Museum Nat Hist, New York, NY 10024 USA.
   [Hernandez, Rene] Univ Nacl Autonoma Mexico, Inst Geol, Mexico City 04510, DF, Mexico.
   [Jia, Cheng-kai] Xinjiang Oilfield Co, Res Inst Explorat & Dev, Karamay 834000, Xinjiang, Peoples R China.
   [Han, Feng-lu; Guo, Yu] Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; George Washington University; China University of Geosciences; State University System of Florida; Florida State University; American Museum of Natural History (AMNH); Universidad Nacional Autonoma de Mexico; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
RP Xu, X (corresponding author), Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
EM xingxu@vip.sina.com
FU Chinese Academy of Sciences; National Science Foundation Division of Earth Sciences of the USA; National Natural Science Foundation of China
NR 44
TC 184
Z9 211
U1 7
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 18
PY 2009
VL 459
IS 7249
BP 940
EP 944
DI 10.1038/nature08124
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500033
PM 19536256
DA 2026-03-09
ER

PT J
AU Albarède, F
AF Albarede, Francis
TI Volatile accretion history of the terrestrial planets and dynamic implications
SO NATURE
LA English
DT Article
ID isotopic variations; plate-tectonics; trace-elements; solar-system; ridge basalt; noble-gases; water; mantle; origin; evolution
AB Accretion left the terrestrial planets depleted in volatile components. Here I examine evidence for the hypothesis that the Moon and the Earth were essentially dry immediately after the formation of the Moon-by a giant impact on the proto-Earth-and only much later gained volatiles through accretion of wet material delivered from beyond the asteroid belt. This view is supported by U-Pb and I-Xe chronologies, which show that water delivery peaked similar to 100 million years after the isolation of the Solar System. Introduction of water into the terrestrial mantle triggered plate tectonics, which may have been crucial for the emergence of life. This mechanism may also have worked for the young Venus, but seems to have failed for Mars.
C1 [Albarede, Francis] Univ Lyon 1, Ecole Normale Super, F-69007 Lyon, France.
   [Albarede, Francis] CNRS, F-69007 Lyon, France.
C3 Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS)
RP Albarède, F (corresponding author), Univ Lyon 1, Ecole Normale Super, 46 Allee Italie, F-69007 Lyon, France.
EM albarede@ens-lyon.fr
FU Agence Nationale de la Recherche; Programme National de Planetologie (INSU-CEA)
NR 89
TC 384
Z9 428
U1 4
U2 161
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 29
PY 2009
VL 461
IS 7268
BP 1227
EP 1233
DI 10.1038/nature08477
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800038
PM 19865163
DA 2026-03-09
ER

PT J
AU Wender, PA
   Miller, BL
AF Wender, Paul A.
   Miller, Benjamin L.
TI Synthesis at the molecular frontier
SO NATURE
LA English
DT Article
ID organic-synthesis; oriented synthesis; natural-products; in-vitro; discovery; chemistry; analogs; identification; prostratin; conversion
C1 [Wender, Paul A.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Wender, Paul A.] Stanford Univ, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Miller, Benjamin L.] Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA.
C3 Stanford University; Stanford University; University of Rochester
RP Wender, PA (corresponding author), Stanford Univ, Dept Chem, 333 Campus Dr, Stanford, CA 94305 USA.
EM wenderp@stanford.edu; Benjamin_miller@urmc.rochester.edu
FU NCI NIH HHS [R37 CA031845] Funding Source: Medline; Division Of Chemistry; Direct For Mathematical & Physical Scien [0848280] Funding Source: National Science Foundation
NR 50
TC 488
Z9 543
U1 1
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 JUL 9
PY 2009
VL 460
IS 7252
BP 197
EP 201
DI 10.1038/460197a
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000029
PM 19587760
DA 2026-03-09
ER

PT J
AU Zhao, XY
   Li, W
   Lv, Z
   Liu, L
   Tong, M
   Hai, T
   Hao, J
   Guo, CL
   Ma, QW
   Wang, L
   Zeng, FY
   Zhou, Q
AF Zhao, Xiao-yang
   Li, Wei
   Lv, Zhuo
   Liu, Lei
   Tong, Man
   Hai, Tang
   Hao, Jie
   Guo, Chang-long
   Ma, Qing-wen
   Wang, Liu
   Zeng, Fanyi
   Zhou, Qi
TI iPS cells produce viable mice through tetraploid complementation
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; fibroblasts; generation; induction; absence
AB Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat(1-6). It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells(7,8). However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, fertile live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.
C1 [Zhao, Xiao-yang; Li, Wei; Lv, Zhuo; Liu, Lei; Tong, Man; Hai, Tang; Hao, Jie; Guo, Chang-long; Ma, Qing-wen; Wang, Liu; Zhou, Qi] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China.
   [Zhao, Xiao-yang; Li, Wei; Lv, Zhuo; Tong, Man; Hao, Jie; Guo, Chang-long] Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China.
   [Ma, Qing-wen; Zeng, Fanyi] Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Shanghai Inst Med Genet, Shanghai 200040, Peoples R China.
   [Zeng, Fanyi] Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Shanghai 200025, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Zoology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Shanghai Jiao Tong University; Shanghai Jiao Tong University
RP Zhou, Q (corresponding author), Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China.
EM fzeng@sjtu.edu.cn; qzhou@ioz.ac.cn
FU China National Basic Research Program [2006CB701500, 2007CB947800, 2007CB947700]; National Science Foundation of China [30525040];  [30871379/C0607]
NR 35
TC 602
Z9 821
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 SEP 3
PY 2009
VL 461
IS 7260
BP 86
EP U88
DI 10.1038/nature08267
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800035
PM 19672241
DA 2026-03-09
ER

PT J
AU Hood, E
   Fellman, J
   Spencer, RGM
   Hernes, PJ
   Edwards, R
   D'Amore, D
   Scott, D
AF Hood, Eran
   Fellman, Jason
   Spencer, Robert G. M.
   Hernes, Peter J.
   Edwards, Rick
   D'Amore, David
   Scott, Durelle
TI Glaciers as a source of ancient and labile organic matter to the marine environment
SO NATURE
LA English
DT Article
ID carbon; alaska; export; fate
AB Riverine organic matter supports of the order of one-fifth of estuarine metabolism(1). Coastal ecosystems are therefore sensitive to alteration of both the quantity and lability of terrigenous dissolved organic matter (DOM) delivered by rivers. The lability of DOM is thought to vary with age, with younger, relatively unaltered organic matter being more easily metabolized by aquatic heterotrophs than older, heavily modified material(2-4). This view is developed exclusively from work in watersheds where terrestrial plant and soil sources dominate streamwater DOM. Here we characterize streamwater DOM from 11 coastal watersheds on the Gulf of Alaska that vary widely in glacier coverage (0-64 per cent). In contrast to non-glacial rivers, we find that the bioavailability of DOM to marine microorganisms is significantly correlated with increasing C-14 age. Moreover, the most heavily glaciated watersheds are the source of the oldest (similar to 4 kyr C-14 age) and most labile (66 per cent bioavailable) DOM. These glacial watersheds have extreme runoff rates, in part because they are subject to some of the highest rates of glacier volume loss on Earth(5). We estimate the cumulative flux of dissolved organic carbon derived from glaciers contributing runoff to the Gulf of Alaska at 0.13 +/- 0.01 Tg yr(-1) (1 Tg = 10(12) g), of which similar to 0.10 Tg is highly labile. This indicates that glacial runoff is a quantitatively important source of labile reduced carbon to marine ecosystems. Moreover, because glaciers and ice sheets represent the second largest reservoir of water in the global hydrologic system, our findings indicate that climatically driven changes in glacier volume could alter the age, quantity and reactivity of DOM entering coastal oceans.
C1 [Hood, Eran] Univ Alaska SE, Environm Sci & Geog Program, Juneau, AK 99801 USA.
   [Fellman, Jason] Univ Alaska Fairbanks, Inst Arctic Biol, Fairbanks, AK 99775 USA.
   [Spencer, Robert G. M.; Hernes, Peter J.] Univ Calif Davis, Dept Land Air & Water Resources, Davis, CA 95616 USA.
   [Edwards, Rick; D'Amore, David] US Forest Serv, Pacific NW Res Stn, USDA, Juneau, AK 99801 USA.
   [Scott, Durelle] Virginia Tech, Blacksburg, VA 24061 USA.
C3 University of Alaska System; University of Alaska Southeastern; University of Alaska System; University of Alaska Fairbanks; University of California System; University of California Davis; United States Department of Agriculture (USDA); United States Forest Service; Virginia Polytechnic Institute & State University
RP Hood, E (corresponding author), Univ Alaska SE, Environm Sci & Geog Program, Juneau, AK 99801 USA.
EM eran.hood@uas.alaska.edu
FU US National Science Foundation [EAR-0838587]; University of Alaska Seed Grant; USDA Forest Service, Pacific Northwest Research Station; Directorate For Geosciences; Division Of Earth Sciences [0838497, 0838587] Funding Source: National Science Foundation
NR 34
TC 470
Z9 548
U1 9
U2 312
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1044
EP U100
DI 10.1038/nature08580
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000044
PM 20033045
DA 2026-03-09
ER

PT J
AU Revnivtsev, M
   Sazonov, S
   Churazov, E
   Forman, W
   Vikhlinin, A
   Sunyaev, R
AF Revnivtsev, M.
   Sazonov, S.
   Churazov, E.
   Forman, W.
   Vikhlinin, A.
   Sunyaev, R.
TI Discrete sources as the origin of the Galactic X-ray ridge emission
SO NATURE
LA English
DT Article
ID iron line; chandra; galaxy; asca; extinction; plane; view
AB An unresolved X-ray glow (at energies above a few kiloelectron-volts) was discovered about 25 years ago and found to be coincident with the Galactic disk-the Galactic ridge X-ray emission(1,2). This emission(3-10) has a spectrum characteristic of a similar to 10(8) K optically thin thermal plasma, with a prominent iron emission line at 6.7 keV. The gravitational well of the Galactic disk, however, is far too shallow to confine such a hot interstellar medium; instead, it would flow away at a velocity of a few thousand kilometres per second, exceeding the speed of sound in the gas. To replenish the energy losses requires a source of 10(43) erg s(-1), exceeding by orders of magnitude all plausible energy sources in the Milky Way(11). An alternative is that the hot plasma is bound to a multitude of faint sources(12), which is supported by the recently observed similarities in the X-ray and near-infrared surface brightness distributions(13,14) (the latter traces the Galactic stellar distribution). Here we report that at energies of similar to 6-7 keV, more than 80 per cent of the seemingly diffuse X-ray emission is resolved into discrete sources, probably accreting white dwarfs and coronally active stars.
C1 [Revnivtsev, M.] Tech Univ Munich, Excellence Cluster Univ, D-85748 Garching, Germany.
   [Revnivtsev, M.; Sazonov, S.; Churazov, E.; Vikhlinin, A.; Sunyaev, R.] Space Res Inst, Moscow 117997, Russia.
   [Sazonov, S.; Churazov, E.; Sunyaev, R.] Max Planck Inst Astrophys, D-85748 Garching, Germany.
   [Forman, W.; Vikhlinin, A.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
C3 Technical University of Munich; Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences; Max Planck Society; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory
RP Revnivtsev, M (corresponding author), Tech Univ Munich, Excellence Cluster Univ, D-85748 Garching, Germany.
EM mikej@mpa-garching.mpg.de
FU DFG Cluster of Excellence; NASA Chandra [GO8-9132A]; Russian Academy of Sciences [OFH-17]; RFFI [07-02-01004, 07-02-00961]
NR 28
TC 200
Z9 211
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 APR 30
PY 2009
VL 458
IS 7242
BP 1142
EP 1144
DI 10.1038/nature07946
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600041
PM 19407795
DA 2026-03-09
ER

PT J
AU Bard, E
   Rickaby, REM
AF Bard, Edouard
   Rickaby, Rosalind E. M.
TI Migration of the subtropical front as a modulator of glacial climate
SO NATURE
LA English
DT Article
ID atlantic overturning circulation; indian-ocean; organic-matter; south atlantic; record; sediments; model; fluctuations; temperature; variability
AB Ice cores extracted from the Antarctic ice sheet suggest that glacial conditions, and the relationship between isotopically derived temperatures and atmospheric p(CO2) have been constant over the last 800,000 years of the Late Pleistocene epoch(1). But independent lines of evidence, such as the extent of Northern Hemisphere ice sheets(2), sea level(3) and other temperature records(4), point towards a fluctuating severity of glacial periods, particularly during the more extreme glacial stadials centred around 340,000 and 420,000 years ago (marine isotope stages 10 and 12). Previously unidentified mechanisms therefore appear to have mediated the relationship between insolation, CO2 and climate. Here we test whether northward migration of the subtropical front (STF) off the southeastern coast of South Africa acts as a gatekeeper for the Agulhas current(5,6), which controls the transport of heat and salt from the Indo-Pacific Ocean to the Atlantic Ocean. Using a new 800,000-year record of sea surface temperature and ocean productivity from ocean sediment core MD962077, we demonstrate that during cold stadials (particularly marine isotope stages 10 and 12), productivity peaked and sea surface temperature was up to 6 degrees C cooler than modern temperatures. This suggests that during these cooler stadials, the STF moved northward by up to 76 latitude, nearly shutting off the Agulhas current. Our results, combined with faunal assemblages from the south Atlantic(7,8) show that variable northwards migration of the Southern Hemisphere STF can modulate the severity of each glacial period by altering the strength of the Agulhas current carrying heat and salt to the Atlantic meridional overturning circulation. We show hence that the degree of northwards migration of the STF can partially decouple global climate from atmospheric partial pressure of carbon dioxide, p(CO2), and help to resolve the long-standing puzzle of differing glacial amplitudes within a consistent range of atmospheric p(CO2).
C1 [Bard, Edouard] Univ Paul Cezanne Aix Marseille, CNRS, IRD, Coll France,CEREGE,UMR 6635, F-13545 Aix En Provence 4, France.
   [Rickaby, Rosalind E. M.] Univ Oxford, Dept Earth Sci, Oxford OX1 3PR, England.
C3 Aix-Marseille Universite; Universite PSL; College de France; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); University of Oxford
RP Bard, E (corresponding author), Univ Paul Cezanne Aix Marseille, CNRS, IRD, Coll France,CEREGE,UMR 6635, Europole Arbois BP 80, F-13545 Aix En Provence 4, France.
EM bard@cerege.fr; rosr@earth.ox.ac.uk
FU Gary Comer Foundation; CNRS; College de France
NR 47
TC 204
Z9 231
U1 1
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 380
EP U93
DI 10.1038/nature08189
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000035
PM 19606147
DA 2026-03-09
ER

PT J
AU Lin, G
   Li, DY
   de Carvalho, LPS
   Deng, HT
   Tao, H
   Vogt, G
   Wu, KY
   Schneider, J
   Chidawanyika, T
   Warren, JD
   Li, HL
   Nathan, C
AF Lin, Gang
   Li, Dongyang
   de Carvalho, Luiz Pedro Sorio
   Deng, Haiteng
   Tao, Hui
   Vogt, Guillaume
   Wu, Kangyun
   Schneider, Jean
   Chidawanyika, Tamutenda
   Warren, J. David
   Li, Huilin
   Nathan, Carl
TI Inhibitors selective for mycobacterial versus human proteasomes
SO NATURE
LA English
DT Article
ID ubiquitin-like protein; tuberculosis proteasome; nitric-oxide; software; identification; tools
AB Many anti-infectives inhibit the synthesis of bacterial proteins, but none selectively inhibits their degradation. Most anti-infectives kill replicating pathogens, but few preferentially kill pathogens that have been forced into a non-replicating state by conditions in the host. To explore these alternative approaches we sought selective inhibitors of the proteasome of Mycobacterium tuberculosis. Given that the proteasome structure is extensively conserved, it is not surprising that inhibitors of all chemical classes tested have blocked both eukaryotic and prokaryotic proteasomes, and no inhibitor has proved substantially more potent on proteasomes of pathogens than of their hosts. Here we show that certain oxathiazol-2-one compounds kill non-replicating M. tuberculosis and act as selective suicide-substrate inhibitors of the M. tuberculosis proteasome by cyclocarbonylating its active site threonine. Major conformational changes protect the inhibitor-enzyme intermediate from hydrolysis, allowing formation of an oxazolidin-2-one and preventing regeneration of active protease. Residues outside the active site whose hydrogen bonds stabilize the critical loop before and after it moves are extensively non-conserved. This may account for the ability of oxathiazol-2-one compounds to inhibit the mycobacterial proteasome potently and irreversibly while largely sparing the human homologue.
C1 [Lin, Gang; de Carvalho, Luiz Pedro Sorio; Vogt, Guillaume; Wu, Kangyun; Schneider, Jean; Chidawanyika, Tamutenda; Nathan, Carl] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA.
   [Tao, Hui; Warren, J. David] Weill Cornell Med Coll, Milstein Chem Core Facil, New York, NY 10065 USA.
   [Tao, Hui; Warren, J. David] Weill Cornell Med Coll, Dept Biochem & Struct Biol, New York, NY 10065 USA.
   [Li, Dongyang; Li, Huilin] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
   [Deng, Haiteng] Rockefeller Univ, Prote Resource Ctr, New York, NY 10065 USA.
   [Li, Huilin] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA.
C3 Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; United States Department of Energy (DOE); Brookhaven National Laboratory; Rockefeller University; State University of New York (SUNY) System; Stony Brook University
RP Nathan, C (corresponding author), Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA.
EM gal2005@med.cornell.edu; hli@bnl.gov; cnathan@med.cornell.edu
FU NIH [PO1-AI056293, R01AI070285]; Milstein Program in Chemical Biology of Infectious Diseases; US DOE; William Randolph Hearst Foundation; National Institute of Allergy and Infectious Diseases [R01AI070285] Funding Source: NIH RePORTER
NR 30
TC 180
Z9 218
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 OCT 1
PY 2009
VL 461
IS 7264
BP 621
EP U63
DI 10.1038/nature08357
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600033
PM 19759536
DA 2026-03-09
ER

PT J
AU Ni, ZF
   Kim, ED
   Ha, MS
   Lackey, E
   Liu, JX
   Zhang, YR
   Sun, QX
   Chen, ZJ
AF Ni, Zhongfu
   Kim, Eun-Deok
   Ha, Misook
   Lackey, Erika
   Liu, Jianxin
   Zhang, Yirong
   Sun, Qixin
   Chen, Z. Jeffrey
TI Altered circadian rhythms regulate growth vigour in hybrids and allopolyploids
SO NATURE
LA English
DT Article
ID gene-expression; arabidopsis allotetraploids; starch degradation; flowering-time; clock; thaliana; mutant; plants; cca1; transcription
AB Segregating hybrids and stable allopolyploids display morphological vigour(1-3), and Arabidopsis allotetraploids are larger than the parents Arabidopsis thaliana and Arabidopsis arenosa(1,4)- the mechanisms for this are unknown. Circadian clocks mediate metabolic pathways and increase fitness in animals and plants(5-8). Here we report that epigenetic modifications of the circadian clock genes CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY)(9-11) and their reciprocal regulators TIMING OF CAB EXPRESSION 1 ( TOC1) and GIGANTEA (GI)(10,12,13) mediate expression changes in downstream genes and pathways. During the day, epigenetic repression of CCA1 and LHY induced the expression of TOC1, GI and downstream genes containing evening elements(14) in chlorophyll and starch metabolic pathways in allotetraploids and F-1 hybrids, which produced more chlorophyll and starch than the parents in the same environment. Mutations in cca1 and cca1 lhy and the daily repression of cca1 by RNA interference (RNAi) in TOC1:: cca1(RNAi) transgenic plants increased the expression of downstream genes and increased chlorophyll and starch content, whereas constitutively expressing CCA1 or ectopically expressing TOC1:: CCA1 had the opposite effect. The causal effects of CCA1 on output traits suggest that hybrids and allopolyploids gain advantages from the control of circadian- mediated physiological and metabolic pathways, leading to growth vigour and increased biomass.
C1 [Ni, Zhongfu; Kim, Eun-Deok; Ha, Misook; Lackey, Erika; Liu, Jianxin; Zhang, Yirong; Chen, Z. Jeffrey] Univ Texas Austin, Sect Mol Cell & Dev Biol, Austin, TX 78712 USA.
   [Ha, Misook; Chen, Z. Jeffrey] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
   [Ha, Misook; Chen, Z. Jeffrey] Univ Texas Austin, Ctr Computat Biol & Bioinformat, Austin, TX 78712 USA.
   [Chen, Z. Jeffrey] Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA.
   [Sun, Qixin] China Agr Univ, Dept Genet & Plant Breeding, Beijing 100094, Peoples R China.
C3 University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; China Agricultural University
RP Chen, ZJ (corresponding author), Univ Texas Austin, Sect Mol Cell & Dev Biol, 1 University Stn,A-4800, Austin, TX 78712 USA.
EM zjchen@mail.utexas.edu
FU National Science Foundation Plant Genome Research Program [DBI0733857, DBI0624077]; National Institutes of Health [GM067015]; National Basic Research Program of China [2007CB109000]
NR 42
TC 542
Z9 656
U1 5
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 JAN 15
PY 2009
VL 457
IS 7227
BP 327
EP U7
DI 10.1038/nature07523
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900042
PM 19029881
DA 2026-03-09
ER

PT J
AU Zapka, M
   Heyers, D
   Hein, CM
   Engels, S
   Schneider, NL
   Hans, J
   Weiler, S
   Dreyer, D
   Kishkinev, D
   Wild, JM
   Mouritsen, H
AF Zapka, Manuela
   Heyers, Dominik
   Hein, Christine M.
   Engels, Svenja
   Schneider, Nils-Lasse
   Hans, Joerg
   Weiler, Simon
   Dreyer, David
   Kishkinev, Dmitry
   Wild, J. Martin
   Mouritsen, Henrik
TI Visual but not trigeminal mediation of magnetic compass information in a migratory bird
SO NATURE
LA English
DT Article
ID homing pigeons; magnetoreception; orientation; songbirds; beak; sensitivity; intensity; animals; nerve; brain
AB Magnetic compass information has a key role in bird orientation(1-3), but the physiological mechanisms enabling birds to sense the Earth's magnetic field remain one of the unresolved mysteries in biology(2,4). Two biophysical mechanisms have become established as the most promising magnetodetection candidates. The iron-mineral-based hypothesis suggests that magnetic information is detected by magnetoreceptors in the upper beak and transmitted through the ophthalmic branch of the trigeminal nerve to the brain(5-10). The light-dependent hypothesis suggests that magnetic field direction is sensed by radical pair-forming photopigments in the eyes(11-15) and that this visual signal is processed in cluster N, a specialized, night-time active, light-processing forebrain region(16-19). Here we report that European robins with bilateral lesions of cluster N are unable to show oriented magnetic-compass-guided behaviour but are able to perform sun compass and star compass orientation behaviour. In contrast, bilateral section of the ophthalmic branch of the trigeminal nerve in European robins did not influence the birds' ability to use their magnetic compass for orientation. These data show that cluster N is required for magnetic compass orientation in this species and indicate that it may be specifically involved in processing of magnetic compass information. Furthermore, the data strongly suggest that a vision-mediated mechanism underlies the magnetic compass in this migratory songbird, and that the putative iron-mineral-based receptors in the upper beak connected to the brain by the trigeminal nerve(6-8) are neither necessary nor sufficient for magnetic compass orientation in European robins.
C1 [Zapka, Manuela; Heyers, Dominik; Hein, Christine M.; Engels, Svenja; Schneider, Nils-Lasse; Hans, Joerg; Weiler, Simon; Dreyer, David; Kishkinev, Dmitry; Mouritsen, Henrik] Carl von Ossietzky Univ Oldenburg, IBU, AG Neurosensorik Anim Nav, D-26111 Oldenburg, Germany.
   [Wild, J. Martin] Univ Auckland, Fac Med & Hlth Sci, Dept Anat, Auckland 1142, New Zealand.
C3 Carl von Ossietzky Universitat Oldenburg; University of Auckland
RP Mouritsen, H (corresponding author), Carl von Ossietzky Univ Oldenburg, IBU, AG Neurosensorik Anim Nav, D-26111 Oldenburg, Germany.
EM henrik.mouritsen@uni-oldenburg.de
FU Volkswagenstiftung; Deutsche Forschungsgemeinschaft
NR 30
TC 221
Z9 243
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 OCT 29
PY 2009
VL 461
IS 7268
BP 1274
EP U108
DI 10.1038/nature08528
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800047
PM 19865170
DA 2026-03-09
ER

PT J
AU Honjoh, S
   Yamamoto, T
   Uno, M
   Nishida, E
AF Honjoh, Sakiko
   Yamamoto, Takuya
   Uno, Masaharu
   Nishida, Eisuke
TI Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C-elegans
SO NATURE
LA English
DT Article
ID life-span extension; restriction-induced longevity; messenger-rna translation; caenorhabditis-elegans; dietary restriction; tor; daf-16; deprivation; inhibition; resistance
AB Dietary restriction is the most effective and reproducible intervention to extend lifespan in divergent species(1). In mammals, two regimens of dietary restriction, intermittent fasting ( IF) and chronic caloric restriction, have proven to extend lifespan and reduce the incidence of age- related disorders(2). An important characteristic of IF is that it can increase lifespan even when there is little or no overall decrease in calorie intake(2). The molecular mechanisms underlying IF- induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans, and show that the low molecular weight GTPase RHEB- 1 has a dual role in lifespan regulation; RHEB- 1 is required for the IF- induced longevity, whereas inhibition of RHEB- 1 mimics the caloric- restriction effects. RHEB- 1 exerts its effects in part by the insulin/ insulin growth factor ( IGF)- like signalling effector DAF- 16 in IF. Our analyses demonstrate that most fasting- induced upregulated genes require RHEB- 1 function for their induction, and that RHEB- 1 and TOR signalling are required for the fasting- induced downregulation of an insulin- like peptide, INS- 7. These findings identify the essential role of signalling by RHEB- 1 in IF- induced longevity and gene expression changes, and suggest a molecular link between the IF- induced longevity and the insulin/ IGF- like signalling pathway.
C1 [Honjoh, Sakiko; Yamamoto, Takuya; Uno, Masaharu; Nishida, Eisuke] Kyoto Univ, Dept Cell & Dev Biol, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068502, Japan.
C3 Kyoto University
RP Nishida, E (corresponding author), Kyoto Univ, Dept Cell & Dev Biol, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068502, Japan.
EM L50174@sakura.kudpc.kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan; NIH National Center for Research Resources
NR 33
TC 213
Z9 269
U1 1
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 726
EP U6
DI 10.1038/nature07583
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700042
PM 19079239
DA 2026-03-09
ER

PT J
AU Mo, YF
   Turner, KT
   Szlufarska, I
AF Mo, Yifei
   Turner, Kevin T.
   Szlufarska, Izabela
TI Friction laws at the nanoscale
SO NATURE
LA English
DT Article
ID self-assembled monolayers; force microscopy; boundary friction; contact mechanics; surface forces; adhesion; model; nanotribology; deformation; asperity
AB Macroscopic laws of friction do not generally apply to nanoscale contacts. Although continuum mechanics models have been predicted to break down at the nanoscale(1), they continue to be applied for lack of a better theory. An understanding of how friction force depends on applied load and contact area at these scales is essential for the design of miniaturized devices with optimal mechanical performance(2,3). Here we use large-scale molecular dynamics simulations with realistic force fields to establish friction laws in dry nanoscale contacts. We show that friction force depends linearly on the number of atoms that chemically interact across the contact. By defining the contact area as being proportional to this number of interacting atoms, we show that the macroscopically observed linear relationship between friction force and contact area can be extended to the nanoscale. Our model predicts that as the adhesion between the contacting surfaces is reduced, a transition takes place from nonlinear to linear dependence of friction force on load. This transition is consistent with the results of several nanoscale friction experiments(4-7). We demonstrate that the breakdown of continuum mechanics can be understood as a result of the rough (multi-asperity) nature of the contact, and show that roughness theories(8-10) of friction can be applied at the nanoscale.
C1 [Mo, Yifei; Turner, Kevin T.; Szlufarska, Izabela] Univ Wisconsin, Mat Sci Program, Madison, WI 53706 USA.
   [Turner, Kevin T.] Univ Wisconsin, Dept Mech Engn, Madison, WI 53706 USA.
   [Turner, Kevin T.; Szlufarska, Izabela] Univ Wisconsin, Dept Mat Sci & Engn, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
RP Szlufarska, I (corresponding author), Univ Wisconsin, Mat Sci Program, Madison, WI 53706 USA.
EM izabela@engr.wisc.edu
FU National Science Foundation [DMR-0512228]; American Chemical Society [PRF-47978-G5]
NR 35
TC 804
Z9 908
U1 12
U2 702
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 26
PY 2009
VL 457
IS 7233
BP 1116
EP 1119
DI 10.1038/nature07748
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100037
PM 19242472
DA 2026-03-09
ER

PT J
AU Kaji, K
   Norrby, K
   Paca, A
   Mileikovsky, M
   Mohseni, P
   Woltjen, K
AF Kaji, Keisuke
   Norrby, Katherine
   Paca, Agnieszka
   Mileikovsky, Maria
   Mohseni, Paria
   Woltjen, Knut
TI Virus-free induction of pluripotency and subsequent excision of reprogramming factors
SO NATURE
LA English
DT Article
ID embryonic stem-cells; human somatic-cells; c-myc; mouse; generation; fibroblasts; expression; differentiation; blocks
AB Reprogramming of somatic cells to pluripotency, thereby creating induced pluripotent stem (iPS) cells, promises to transform regenerative medicine. Most instances of direct reprogramming have been achieved by forced expression of defined factors using multiple viral vectors(1-7). However, such iPS cells contain a large number of viral vector integrations(1,8), any one of which could cause unpredictable genetic dysfunction. Whereas c-Myc is dispensable for reprogramming(9,10), complete elimination of the other exogenous factors is also desired because ectopic expression of either Oct4 (also known as Pou5f1) or Klf4 can induce dysplasia(11,12). Two transient transfection-reprogramming methods have been published to address this issue(13,14). However, the efficiency of both approaches is extremely low, and neither has been applied successfully to human cells so far. Here we show that non-viral transfection of a single multiprotein expression vector, which comprises the coding sequences of c-Myc, Klf4, Oct4 and Sox2 linked with 2A peptides, can reprogram both mouse and human fibroblasts. Moreover, the transgene can be removed once reprogramming has been achieved. iPS cells produced with this nonviral vector show robust expression of pluripotency markers, indicating a reprogrammed state confirmed functionally by in vitro differentiation assays and formation of adult chimaeric mice. When the single-vector reprogramming system was combined with a piggyBac transposon(15,16), we succeeded in establishing reprogrammed human cell lines from embryonic fibroblasts with robust expression of pluripotency markers. This system minimizes genome modification in iPS cells and enables complete elimination of exogenous reprogramming factors, efficiently providing iPS cells that are applicable to regenerative medicine, drug screening and the establishment of disease models.
C1 [Kaji, Keisuke; Norrby, Katherine; Paca, Agnieszka] Univ Edinburgh, Inst Stem Cell Res, Ctr Regenerat Med, MRC, Edinburgh EH9 3JQ, Midlothian, Scotland.
   [Mileikovsky, Maria; Mohseni, Paria; Woltjen, Knut] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   [Mohseni, Paria] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
C3 University of Edinburgh; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto
RP Kaji, K (corresponding author), Univ Edinburgh, Inst Stem Cell Res, Ctr Regenerat Med, MRC, Edinburgh EH9 3JQ, Midlothian, Scotland.
EM keisuke.kaji@ed.ac.uk
FU MRC; BBSRC; Canadian Stem Cell Network; Juvenile Diabetes Research Foundation; MRC [G0700672] Funding Source: UKRI; Medical Research Council [G0700672, G0700711B] Funding Source: researchfish
NR 27
TC 948
Z9 1286
U1 2
U2 179
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 9
PY 2009
VL 458
IS 7239
BP 771
EP U112
DI 10.1038/nature07864
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600043
PM 19252477
DA 2026-03-09
ER

PT J
AU Dias, A
   Bouvier, D
   Crépin, T
   McCarthy, AA
   Hart, DJ
   Baudin, F
   Cusack, S
   Ruigrok, RWH
AF Dias, Alexandre
   Bouvier, Denis
   Crepin, Thibaut
   McCarthy, Andrew A.
   Hart, Darren J.
   Baudin, Florence
   Cusack, Stephen
   Ruigrok, Rob W. H.
TI The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit
SO NATURE
LA English
DT Article
ID rna-polymerase; structural basis; crystal-structure; messenger-rna; cleavage; binding; sites; pb2; transcription; recognition
AB The influenza virus polymerase, a heterotrimer composed of three subunits, PA, PB1 and PB2, is responsible for replication and transcription of the eight separate segments of the viral RNA genome in the nuclei of infected cells. The polymerase synthesizes viral messenger RNAs using short capped primers derived from cellular transcripts by a unique 'cap-snatching' mechanism(1). The PB2 subunit binds the 59 cap of host pre-mRNAs(2-4), which are subsequently cleaved after 10-13 nucleotides by the viral endonuclease, hitherto thought to reside in the PB2 (ref. 5) or PB1 (ref. 2) subunits. Here we describe biochemical and structural studies showing that the amino-terminal 209 residues of the PA subunit contain the endonuclease active site. We show that this domain has intrinsic RNA and DNA endonuclease activity that is strongly activated by manganese ions, matching observations reported for the endonuclease activity of the intact trimeric polymerase(6,7). Furthermore, this activity is inhibited by 2,4-dioxo-4-phenylbutanoic acid, a known inhibitor of the influenza endonuclease(8). The crystal structure of the domain reveals a structural core closely resembling resolvases and type II restriction endonucleases. The active site comprises a histidine and a cluster of three acidic residues, conserved in all influenza viruses, which bind two manganese ions in a configuration similar to other two-metal-dependent endonucleases. Two active site residues have previously been shown to specifically eliminate the polymerase endonuclease activity when mutated(9). These results will facilitate the optimisation of endonuclease inhibitors(10-12) as potential new anti-influenza drugs.
C1 [Dias, Alexandre; Bouvier, Denis; Crepin, Thibaut; McCarthy, Andrew A.; Hart, Darren J.; Baudin, Florence; Cusack, Stephen; Ruigrok, Rob W. H.] UJF, EMBL, CNRS, Unit Virus Host Cell Interact,UMR 5233, F-38042 Grenoble 9, France.
   [McCarthy, Andrew A.; Hart, Darren J.; Cusack, Stephen] European Mol Biol Lab, Grenoble Outstn, F-38042 Grenoble 9, France.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); European Molecular Biology Laboratory (EMBL); Centre National de la Recherche Scientifique (CNRS); European Molecular Biology Laboratory (EMBL)
RP Cusack, S (corresponding author), UJF, EMBL, CNRS, Unit Virus Host Cell Interact,UMR 5233, 6 Rue Jules Horowitz,BP181, F-38042 Grenoble 9, France.
EM cusack@embl.fr
FU EU FLUPOL [SP5B-CT-2007-044263]; ANR FLU INTERPOL [ANR-06-MIME-014-02]; MENRT
NR 30
TC 638
Z9 843
U1 2
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 APR 16
PY 2009
VL 458
IS 7240
BP 914
EP 918
DI 10.1038/nature07745
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500048
PM 19194459
DA 2026-03-09
ER

PT J
AU Brown, SP
   Hestrin, S
AF Brown, Solange P.
   Hestrin, Shaul
TI Intracortical circuits of pyramidal neurons reflect their long-range axonal targets
SO NATURE
LA English
DT Article
ID visual-cortex; layer-v; corticostriatal neurons; synaptic connections; projection neurons; morphology; cells; corticopontine; organization; patterns
AB Cortical columns generate separate streams of information that are distributed to numerous cortical and subcortical brain regions(1). We asked whether local intracortical circuits reflect these different processing streams by testing whether the intracortical connectivity among pyramidal neurons reflects their long-range axonal targets. We recorded simultaneously from up to four retrogradely labelled pyramidal neurons that projected to the superior colliculus, the contralateral striatum or the contralateral cortex to assess their synaptic connectivity. Here we show that the probability of synaptic connection depends on the functional identities of both the presynaptic and postsynaptic neurons. We first found that the frequency of monosynaptic connections among corticostriatal pyramidal neurons is significantly higher than among corticocortical or corticotectal pyramidal neurons. We then show that the probability of feed-forward connections from corticocortical neurons to corticotectal neurons is approximately three- to four-fold higher than the probability of monosynaptic connections among corticocortical or corticotectal cells. Moreover, we found that the average axodendritic overlap of the presynaptic and postsynaptic pyramidal neurons could not fully explain the differences in connection probability that we observed. The selective synaptic interactions we describe demonstrate that the organization of local networks of pyramidal cells reflects the long-range targets of both the presynaptic and postsynaptic neurons.
C1 [Brown, Solange P.; Hestrin, Shaul] Stanford Univ, Sch Med, Dept Comparat Med, Stanford, CA 94305 USA.
C3 Stanford University
RP Hestrin, S (corresponding author), Stanford Univ, Sch Med, Dept Comparat Med, 300 Pasteur Dr,Edwards Bldg,R314, Stanford, CA 94305 USA.
EM shaul.hestrin@stanford.edu
FU National Institutes of Health
NR 36
TC 281
Z9 347
U1 0
U2 16
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 26
PY 2009
VL 457
IS 7233
BP 1133
EP U89
DI 10.1038/nature07658
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100041
PM 19151698
DA 2026-03-09
ER

PT J
AU Kosaka, H
   Inagaki, T
   Rikitake, Y
   Imamura, H
   Mitsumori, Y
   Edamatsu, K
AF Kosaka, Hideo
   Inagaki, Takahiro
   Rikitake, Yoshiaki
   Imamura, Hiroshi
   Mitsumori, Yasuyoshi
   Edamatsu, Keiichi
TI Spin state tomography of optically injected electrons in a semiconductor
SO NATURE
LA English
DT Article
ID quantum-dot; single-electron; coherence; memory; beats
AB Spin is a fundamental property of electrons, with an important role in information storage(1-4). For spin- based quantum information technology, preparation and read- out of the electron spin state are essential functions(5-13). Coherence of the spin state is a manifestation of its quantum nature, so both the preparation and read- out should be spin- coherent. However, the traditional spin measurement technique based on Kerr rotation, which measures spin population using the rotation of the reflected light polarization that is due to the magneto- optical Kerr effect, requires an extra step of spin manipulation or precession to infer the spin coherence(14-20). Here we describe a technique that generalizes the traditional Kerr rotation approach to enable us to measure the electron spin coherence directly without needing to manipulate the spin dynamics, which allows for a spin projection measurement on an arbitrary set of basis states. Because this technique enables spin state tomography, we call it tomographic Kerr rotation. We demonstrate that the polarization coherence of light is transferred to the spin coherence of electrons, and confirm this by applying the tomographic Kerr rotation method to semiconductor quantum wells with precessing and non- precessing electrons. Spin state transfer and tomography offers a tool for performing basis- independent preparation and read- out of a spin quantum state in a solid.
C1 [Kosaka, Hideo; Inagaki, Takahiro; Mitsumori, Yasuyoshi; Edamatsu, Keiichi] Tohoku Univ, Lab Nanoelect & Spintron, Res Inst Elect Commun, Sendai, Miyagi 9808577, Japan.
   [Kosaka, Hideo; Rikitake, Yoshiaki; Imamura, Hiroshi; Mitsumori, Yasuyoshi] CREST JST, Kawaguchi, Saitama 3320012, Japan.
   [Rikitake, Yoshiaki] Sendai Natl Coll Technol, Dept Informat Engn, Sendai, Miyagi 9893128, Japan.
   [Imamura, Hiroshi] AIST, Nanotechnol Res Inst, Tsukuba, Ibaraki 3058568, Japan.
C3 Tohoku University; Japan Science & Technology Agency (JST); National Institute of Advanced Industrial Science & Technology (AIST)
RP Kosaka, H (corresponding author), Tohoku Univ, Lab Nanoelect & Spintron, Res Inst Elect Commun, Sendai, Miyagi 9808577, Japan.
EM kosaka@riec.tohoku.ac.jp
FU Strategic Information and Communications R & D Promotion Program; Ministry of Internal Affairs and Communications in Japan;  [SCOPE 41402001]
NR 25
TC 89
Z9 91
U1 1
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 702
EP 705
DI 10.1038/nature07729
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700036
PM 19194446
DA 2026-03-09
ER

PT J
AU Chaudhury, S
   Smith, A
   Anderson, BE
   Ghose, S
   Jessen, PS
AF Chaudhury, S.
   Smith, A.
   Anderson, B. E.
   Ghose, S.
   Jessen, P. S.
TI Quantum signatures of chaos in a kicked top
SO NATURE
LA English
DT Article
ID decoherence
AB Chaotic behaviour is ubiquitous and plays an important part in most fields of science. In classical physics, chaos is characterized by hypersensitivity of the time evolution of a system to initial conditions. Quantum mechanics does not permit a similar definition owing in part to the uncertainty principle, and in part to the Schrodinger equation, which preserves the overlap between quantum states. This fundamental disconnect poses a challenge to quantum-classical correspondence(1), and has motivated a long-standing search for quantum signatures of classical chaos(2,3). Here we present the experimental realization of a common paradigm for quantum chaos-the quantum kicked top(2,4)- and the observation directly in quantum phase space of dynamics that have a chaotic classical counterpart. Our system is based on the combined electronic and nuclear spin of a single atom and is therefore deep in the quantum regime; nevertheless, we find good correspondence between the quantum dynamics and classical phase space structures. Because chaos is inherently a dynamical phenomenon, special significance attaches to dynamical signatures such as sensitivity to perturbation(1,5) or the generation of entropy(6) and entanglement(7,8), for which only indirect evidence has been available(9- 11). We observe clear differences in the sensitivity to perturbation in chaotic versus regular, non-chaotic regimes, and present experimental evidence for dynamical entanglement as a signature of chaos.
C1 [Chaudhury, S.; Smith, A.; Anderson, B. E.; Jessen, P. S.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA.
   [Ghose, S.] Wilfrid Laurier Univ, Dept Phys & Comp Sci, Waterloo, ON N2L 3C5, Canada.
C3 University of Arizona; Wilfrid Laurier University
RP Jessen, PS (corresponding author), Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA.
EM poul.jessen@optics.arizona.edu
FU National Science Foundation [0653631]; Office of Naval Research [N00014-05-1-420]; NSERC Discovery; Direct For Mathematical & Physical Scien; Division Of Physics [0653631] Funding Source: National Science Foundation
NR 30
TC 250
Z9 278
U1 2
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 8
PY 2009
VL 461
IS 7265
BP 768
EP 771
DI 10.1038/nature08396
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500030
PM 19812668
DA 2026-03-09
ER

PT J
AU Chandran, V
   Fronzes, R
   Duquerroy, S
   Cronin, N
   Navaza, J
   Waksman, G
AF Chandran, Vidya
   Fronzes, Remi
   Duquerroy, Stephane
   Cronin, Nora
   Navaza, Jorge
   Waksman, Gabriel
TI Structure of the outer membrane complex of a type IV secretion system
SO NATURE
LA English
DT Article
ID agrobacterium virb10; proteins; biogenesis; machinery; software
AB Type IV secretion systems are secretion nanomachines spanning the two membranes of Gram-negative bacteria. Three proteins, VirB7, VirB9 and VirB10, assemble into a 1.05 megadalton (MDa) core spanning the inner and outer membranes. This core consists of 14 copies of each of the proteins and forms two layers, the I and O layers, inserting in the inner and outer membrane, respectively. Here we present the crystal structure of a similar to 0.6 MDa outer-membrane complex containing the entire O layer. This structure is the largest determined for an outer-membrane channel and is unprecedented in being composed of three proteins. Unexpectedly, this structure identifies VirB10 as the outer-membrane channel with a unique hydrophobic double-helical transmembrane region. This structure establishes VirB10 as the only known protein crossing both membranes of Gram-negative bacteria. Comparison of the cryo-electron microscopy (cryo-EM) and crystallographic structures points to conformational changes regulating channel opening and closing.
C1 [Chandran, Vidya; Fronzes, Remi; Cronin, Nora; Waksman, Gabriel] UCL, Inst Struct & Mol Biol, London WC1E 7HX, England.
   [Chandran, Vidya; Fronzes, Remi; Cronin, Nora; Waksman, Gabriel] Univ London Birkbeck Coll, London WC1E 7HX, England.
   [Duquerroy, Stephane] Inst Pasteur, Unite Virol Struct, Dept Virol, F-75724 Paris, France.
   [Duquerroy, Stephane] CNRS, URA 3015, F-75724 Paris, France.
   [Duquerroy, Stephane] Univ Paris 11, F-91405 Orsay, France.
   [Navaza, Jorge] Inst Biol Struct JP Ebel, Lab Microscopie Elect, F-38027 Grenoble 1, France.
C3 University of London; Birkbeck University London; University College London; University of London; Birkbeck University London; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS)
RP Waksman, G (corresponding author), UCL, Inst Struct & Mol Biol, Malet St, London WC1E 7HX, England.
EM g.waksman@ucl.ac.uk
FU Wellcome Trust [082227]
NR 33
TC 257
Z9 301
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 DEC 24
PY 2009
VL 462
IS 7276
BP 1011
EP U66
DI 10.1038/nature08588
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000037
PM 19946264
DA 2026-03-09
ER

PT J
AU Schneider, MC
   Prosser, BE
   Caesar, JJE
   Kugelberg, E
   Li, S
   Zhang, Q
   Quoraishi, S
   Lovett, JE
   Deane, JE
   Sim, RB
   Roversi, P
   Johnson, S
   Tang, CM
   Lea, SM
AF Schneider, Muriel C.
   Prosser, Beverly E.
   Caesar, Joseph J. E.
   Kugelberg, Elisabeth
   Li, Su
   Zhang, Qian
   Quoraishi, Sadik
   Lovett, Janet E.
   Deane, Janet E.
   Sim, Robert B.
   Roversi, Pietro
   Johnson, Steven
   Tang, Christoph M.
   Lea, Susan M.
TI Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates
SO NATURE
LA English
DT Article
ID macular degeneration; meningococcal disease; alternative pathway; maximum-likelihood; complement; binding; lipoprotein; antibody; gna1870; refinement
AB The complement system is an essential component of the innate and acquired immune system(1), and consists of a series of proteolytic cascades that are initiated by the presence of microorganisms. In health, activation of complement is precisely controlled through membrane-bound and soluble plasma-regulatory proteins including complement factor H (fH; ref.2), a 155 kDa protein composed of 20 domains (termed complement control protein repeats). Many pathogens have evolved the ability to avoid immune-killing by recruiting host complement regulators(3) and several pathogens have adapted to avoid complement-mediated killing by sequestering fH to their surface(4). Here we present the structure of a complement regulator in complex with its pathogen surface-protein ligand. This reveals how the important human pathogen Neisseria meningitidis subverts immune responses by mimicking the host, using protein instead of charged-carbohydrate chemistry to recruit the host complement regulator, fH. The structure also indicates the molecular basis of the host-specificity of the interaction between fH and the meningococcus, and informs attempts to develop novel therapeutics and vaccines.
C1 [Prosser, Beverly E.; Caesar, Joseph J. E.; Quoraishi, Sadik; Lovett, Janet E.; Deane, Janet E.; Roversi, Pietro; Johnson, Steven; Lea, Susan M.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
   [Schneider, Muriel C.; Kugelberg, Elisabeth; Li, Su; Zhang, Qian; Tang, Christoph M.] Univ London Imperial Coll Sci Technol & Med, Ctr Mol Microbiol & Infect, London SW7 2AZ, England.
   [Sim, Robert B.] Univ Oxford, Dept Biochem, MRC, Immunochem Unit, Oxford OX1 3QU, England.
C3 University of Oxford; Imperial College London; University of Oxford
RP Lea, SM (corresponding author), Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England.
EM c.tang@imperial.ac.uk; susan.lea@path.ox.ac.uk
FU Wellcome Trust; Medical Research Council; Engineering and Physical Sciences Research; EMBO; Medical Research Council [G0500367, G0400775, G0601195] Funding Source: researchfish; MRC [G0601195, G0500367, G0400775] Funding Source: UKRI
NR 40
TC 271
Z9 333
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 16
PY 2009
VL 458
IS 7240
BP 890
EP U9
DI 10.1038/nature07769
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500043
PM 19225461
DA 2026-03-09
ER

PT J
AU Ristenpart, WD
   Bird, JC
   Belmonte, A
   Dollar, F
   Stone, HA
AF Ristenpart, W. D.
   Bird, J. C.
   Belmonte, A.
   Dollar, F.
   Stone, H. A.
TI Non-coalescence of oppositely charged drops
SO NATURE
LA English
DT Article
ID in-oil emulsions; water drops; electric field; liquid-drops; droplets; particles; stability; motions; devices; fluid
AB Electric fields induce motion in many fluid systems, including polymer melts(1), surfactant micelles(2) and colloidal suspensions(3). Likewise, electric fields can be used to move liquid drops(4). Electrically induced droplet motion manifests itself in processes as diverse as storm cloud formation(5), commercial ink-jet printing(6), petroleum and vegetable oil dehydration(7), electrospray ionization for use in mass spectrometry(8), electrowetting(9) and lab-on-a-chip manipulations(10). An important issue in practical applications is the tendency for adjacent drops to coalesce, and oppositely charged drops have long been assumed to experience an attractive force that favours their coalescence(11-13). Here we report the existence of a critical field strength above which oppositely charged drops do not coalesce. We observe that appropriately positioned and oppositely charged drops migrate towards one another in an applied electric field; but whereas the drops coalesce as expected at low field strengths, they are repelled from one another after contact at higher field strengths. Qualitatively, the drops appear to 'bounce' off one another. We directly image the transient formation of a meniscus bridge between the bouncing drops, and propose that this temporary bridge is unstable with respect to capillary pressure when it forms in an electric field exceeding a critical strength. The observation of oppositely charged drops bouncing rather than coalescing in strong electric fields should affect our understanding of any process involving charged liquid drops, including de-emulsification, electrospray ionization and atmospheric conduction.
C1 [Ristenpart, W. D.] Univ Calif Davis, Dept Chem Engn & Mat Sci, Davis, CA 95616 USA.
   [Ristenpart, W. D.] Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA.
   [Bird, J. C.; Dollar, F.; Stone, H. A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Belmonte, A.] Penn State Univ, Dept Math, WG Pritchard Labs, University Pk, PA 16802 USA.
C3 University of California System; University of California Davis; University of California System; University of California Davis; Harvard University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Ristenpart, WD (corresponding author), Univ Calif Davis, Dept Chem Engn & Mat Sci, 1 Shields Dr, Davis, CA 95616 USA.
EM wdristenpart@ucdavis.edu
FU Harvard University's MRSEC
NR 30
TC 270
Z9 312
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 SEP 17
PY 2009
VL 461
IS 7262
BP 377
EP 380
DI 10.1038/nature08294
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100035
PM 19759616
DA 2026-03-09
ER

PT J
AU Kalaany, NY
   Sabatini, DM
AF Kalaany, Nada Y.
   Sabatini, David M.
TI Tumours with PI3K activation are resistant to dietary restriction
SO NATURE
LA English
DT Article
ID growth-factor-i; caloric restriction; life-span; phosphatidylinositol 3-kinases; energy restriction; human cancer; cell-growth; mutations; insulin; gene
AB Dietary restriction delays the incidence and decreases the growth of various types of tumours, but the mechanisms underlying the sensitivity of tumours to food restriction remain unknown. Here we show that certain human cancer cell lines, when grown as tumour xenografts in mice, are highly sensitive to the anti-growth effects of dietary restriction, whereas others are resistant. Cancer cells that form dietary-restriction-resistant tumours carry mutations that cause constitutive activation of the phosphatidylinositol-3-kinase (PI3K) pathway and in culture proliferate in the absence of insulin or insulin-like growth factor 1. Substitution of an activated mutant allele of PI3K with wild-type PI3K in otherwise isogenic cancer cells, or the restoration of PTEN expression in a PTEN-null cancer cell line, is sufficient to convert a dietary-restriction-resistant tumour into one that is dietary-restriction-sensitive. Dietary restriction does not affect a PTEN-null mouse model of prostate cancer, but it significantly decreases tumour burden in a mouse model of lung cancer lacking constitutive PI3K signalling. Thus, the PI3K pathway is an important determinant of the sensitivity of tumours to dietary restriction, and activating mutations in the pathway may influence the response of cancers to dietary restriction-mimetic therapies.
C1 [Kalaany, Nada Y.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Kalaany, Nada Y.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA.
   [Kalaany, Nada Y.; Sabatini, David M.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Sabatini, David M.] Broad Inst, Cambridge, MA 02142 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Sabatini, DM (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM sabatini@wi.mit.edu
FU Alexander and Margaret Stewart Trust Award; David H. Koch Cancer Research Award; National Institutes of Health [R01 AI04389, R01 CA129105]; Howard Hughes Medical Institute; National Cancer Institute [R01CA129105] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI047389] Funding Source: NIH RePORTER
NR 38
TC 372
Z9 422
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 9
PY 2009
VL 458
IS 7239
BP 725
EP U61
DI 10.1038/nature07782
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600032
PM 19279572
DA 2026-03-09
ER

PT J
AU Kang, B
   Ceder, G
AF Kang, Byoungwoo
   Ceder, Gerbrand
TI Battery materials for ultrafast charging and discharging
SO NATURE
LA English
DT Article
ID rechargeable lithium battery; phosphate-glasses; photoelectron-spectroscopy; electrochemical property; nanostructured materials; active materials; energy-storage; ion battery; lifepo4; transport
AB The storage of electrical energy at high charge and discharge rate is an important technology in today's society, and can enable hybrid and plug-in hybrid electric vehicles and provide back-up for wind and solar energy. It is typically believed that in electrochemical systems very high power rates can only be achieved with supercapacitors, which trade high power for low energy density as they only store energy by surface adsorption reactions of charged species on an electrode material(1-3). Here we show that batteries(4,5) which obtain high energy density by storing charge in the bulk of a material can also achieve ultrahigh discharge rates, comparable to those of supercapacitors. We realize this in LiFePO4 (ref. 6), a material with high lithium bulk mobility(7,8), by creating a fast ion-conducting surface phase through controlled off-stoichiometry. A rate capability equivalent to full battery discharge in 10-20 s can be achieved.
C1 [Kang, Byoungwoo; Ceder, Gerbrand] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Ceder, G (corresponding author), MIT, Dept Mat Sci & Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM gceder@mit.edu
FU US National Science Foundation through the Materials Research Science and Engineering Centers programme; Batteries for Advanced Transportation Program of the US Department of Energy; Direct For Mathematical & Physical Scien; Division Of Materials Research [0819762] Funding Source: National Science Foundation
NR 30
TC 3258
Z9 3643
U1 38
U2 3627
PU NATURE PUBLISHING 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 12
PY 2009
VL 458
IS 7235
BP 190
EP 193
DI 10.1038/nature07853
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700040
PM 19279634
DA 2026-03-09
ER

PT J
AU Morinière, J
   Rousseaux, S
   Steuerwald, U
   Soler-López, M
   Curtet, S
   Vitte, AL
   Govin, J
   Gaucher, J
   Sadoul, K
   Hart, DJ
   Krijgsveld, J
   Khochbin, S
   Müller, CW
   Petosa, C
AF Moriniere, Jeanne
   Rousseaux, Sophie
   Steuerwald, Ulrich
   Soler-Lopez, Montserrat
   Curtet, Sandrine
   Vitte, Anne-Laure
   Govin, Jerome
   Gaucher, Jonathan
   Sadoul, Karin
   Hart, Darren J.
   Krijgsveld, Jeroen
   Khochbin, Saadi
   Mueller, Christoph W.
   Petosa, Carlo
TI Cooperative binding of two acetylation marks on a histone tail by a single bromodomain
SO NATURE
LA English
DT Article
ID chromatin modifications; mitotic chromosm; recognition; proteins; brdt; cbp; h4
AB A key step in many chromatin-related processes is the recognition of histone post-translational modifications by effector modules such as bromodomains and chromo-like domains of the Royal family(1,2). Whereas effector-mediated recognition of single post-translational modifications is well characterized(3), how the cell achieves combinatorial readout of histones bearing multiple modifications is poorly understood. One mechanism involves multivalent binding by linked effector modules(4). For example, the tandem bromodomains of human TATA-binding protein-associated factor-1 (TAF1) bind better to a diacetylated histone H4 tail than to monoacetylated tails, a cooperative effect attributed to each bromodomain engaging one acetyl-lysine mark(5). Here we report a distinct mechanism of combinatorial readout for the mouse TAF1 homologue Brdt, a testis-specific member of the BET protein family(6). Brdt associates with hyperacetylated histone H4 (ref. 7) and is implicated in the marked chromatin remodelling that follows histone hyperacetylation during spermiogenesis, the stage of spermatogenesis in which post-meiotic germ cells mature into fully differentiated sperm(7-10). Notably, we find that a single bromodomain (BD1) of Brdt is responsible for selectively recognizing histone H4 tails bearing two or more acetylation marks. The crystal structure of BD1 bound to a diacetylated H4 tail shows how two acetyl-lysine residues cooperate to interact with one binding pocket. Structure-based mutagenesis that reduces the selectivity of BD1 towards diacetylated tails destabilizes the association of Brdt with acetylated chromatin in vivo. Structural analysis suggests that other chromatin-associated proteins may be capable of a similar mode of ligand recognition, including yeast Bdf1, human TAF1 and human CBP/p300 (also known as CREBBP and EP300, respectively). Our findings describe a new mechanism for the combinatorial readout of histone modifications in which a single effector module engages two marks on a histone tail as a composite binding epitope.
C1 [Steuerwald, Ulrich; Krijgsveld, Jeroen; Mueller, Christoph W.] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Moriniere, Jeanne; Soler-Lopez, Montserrat; Hart, Darren J.] European Mol Biol Lab, Grenoble Outstn, F-38042 Grenoble 9, France.
   [Moriniere, Jeanne; Soler-Lopez, Montserrat; Hart, Darren J.] Univ Grenoble 1, CNRS, EMBL, Unit Virus Host Cell Interact,UMI 3265, F-38042 Grenoble 9, France.
   [Rousseaux, Sophie; Curtet, Sandrine; Vitte, Anne-Laure; Govin, Jerome; Gaucher, Jonathan; Sadoul, Karin; Khochbin, Saadi] Univ Grenoble 1, INSERM, U823, Inst Albert Bonniot, F-38700 Grenoble, France.
   [Petosa, Carlo] Univ Grenoble 1, CNRS, CEA, Inst Biol Struct Jean Pierre Ebel,UMR 5075, F-38027 Grenoble 1, France.
C3 European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Institut National de la Sante et de la Recherche Medicale (Inserm); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
RP Müller, CW (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM christoph.mueller@embl.de
FU Rhone-Alpes region; EU; ANRS/Fondation de France AIJC; CNRS ATIP programmes
NR 28
TC 372
Z9 463
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 1
PY 2009
VL 461
IS 7264
BP 664
EP U112
DI 10.1038/nature08397
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600043
PM 19794495
DA 2026-03-09
ER

PT J
AU Read, PL
   Dowling, TE
   Schubert, G
AF Read, P. L.
   Dowling, T. E.
   Schubert, G.
TI Saturn's rotation period from its atmospheric planetary-wave configuration
SO NATURE
LA English
DT Article
ID potential-vorticity; 2nd stability; zonal-wind; jupiter; dynamics; jets; disturbances; cassini; theorem
AB The rotation period of a gas giant's magnetic field (called the System III reference frame) is commonly used to infer its bulk rotation(1). Saturn's dipole magnetic field is not tilted relative to its rotation axis (unlike Jupiter, Uranus and Neptune), so the surrogate measure of its long-wavelength (kilometric) radiation is currently used to fix the System III rotation period(2). The period as measured now by the Cassini spacecraft is up to similar to 7 min longer(3) than the value of 10 h 39 min 24 s measured 28 years ago by Voyager(2). Here we report a determination of Saturn's rotation period based on an analysis of potential vorticity. The resulting reference frame (which we call System IIIw) rotates with a period of 10 h 34 min 13 +/- 20 s. This shifted reference frame is consistent with a pattern of alternating jets on Saturn that is more symmetrical between eastward and westward flow. This suggests that Saturn's winds are much more like those of Jupiter than hitherto believed(4).
C1 [Read, P. L.] Univ Oxford, Dept Phys, Oxford OX1 3PU, England.
   [Dowling, T. E.] Univ Louisville, Dept Phys & Astron, Louisville, KY 40292 USA.
   [Schubert, G.] Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
C3 University of Oxford; University of Louisville; University of California System; University of California Los Angeles
RP Read, PL (corresponding author), Univ Oxford, Dept Phys, Oxford OX1 3PU, England.
EM p.read1@physics.ox.ac.uk
FU UK Science and Technology Facilities Council; NASA's Planetary Atmospheres and Outer Planet Research Programs
NR 23
TC 108
Z9 115
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 608
EP 610
DI 10.1038/nature08194
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300045
DA 2026-03-09
ER

PT J
AU Nishida, Y
   Arakawa, S
   Fujitani, K
   Yamaguchi, H
   Mizuta, T
   Kanaseki, T
   Komatsu, M
   Otsu, K
   Tsujimoto, Y
   Shimizu, S
AF Nishida, Yuya
   Arakawa, Satoko
   Fujitani, Kenji
   Yamaguchi, Hirofumi
   Mizuta, Takeshi
   Kanaseki, Toku
   Komatsu, Masaaki
   Otsu, Kinya
   Tsujimoto, Yoshihide
   Shimizu, Shigeomi
TI Discovery of Atg5/Atg7-independent alternative macroautophagy
SO NATURE
LA English
DT Article
ID autophagosome formation; starvation; protein; degradation; endosm; beclin-1; disease; lc3
AB Macroautophagy is a process that leads to the bulk degradation of subcellular constituents by producing autophagosomes/autolysosomes(1-3). It is believed that Atg5 (ref. 4) and Atg7 (ref. 5) are essential genes for mammalian macroautophagy. Here we show, however, that mouse cells lacking Atg5 or Atg7 can still form autophagosomes/autolysosomes and perform autophagy-mediated protein degradation when subjected to certain stressors. Although lipidation of the microtubule-associated protein light chain 3 (LC3, also known as Map1lc3a) to form LC3-II is generally considered to be a good indicator of macroautophagy(6), it did not occur during the Atg5/Atg7-independent alternative process of macroautophagy. We also found that this alternative process of macroautophagy was regulated by several autophagic proteins, including Unc-51-like kinase 1 (Ulk1) and beclin 1. Unlike conventional macroautophagy, autophagosomes seemed to be generated in aRab9-dependent manner by the fusion of isolation membranes with vesicles derived from the trans-Golgi and late endosomes. In vivo, Atg5-independent alternative macroautophagy was detected in several embryonic tissues. It also had a function in clearing mitochondria during erythroid maturation. These results indicate that mammalian macroautophagy can occur through at least two different pathways: an Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway.
C1 [Nishida, Yuya; Arakawa, Satoko; Fujitani, Kenji; Yamaguchi, Hirofumi; Mizuta, Takeshi; Kanaseki, Toku; Shimizu, Shigeomi] Tokyo Med & Dent Univ, Med Res Inst, Dept Pathol Cell Biol, Bunkyo Ku, Tokyo 1138510, Japan.
   [Otsu, Kinya] Osaka Univ, Sch Med, Dept Cardiovasc Med, Suita, Osaka 5650871, Japan.
   [Nishida, Yuya; Tsujimoto, Yoshihide] Osaka Univ, Sch Med, Dept Med Genet, Suita, Osaka 5650871, Japan.
   [Komatsu, Masaaki] Tokyo Metropolitan Inst Med Sci, Lab Frontier Sci, Bunkyo Ku, Tokyo 1138613, Japan.
C3 Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); University of Osaka; University of Osaka; Tokyo Metropolitan Institute of Medical Science
RP Shimizu, S (corresponding author), Tokyo Med & Dent Univ, Med Res Inst, Dept Pathol Cell Biol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan.
EM shimizu.pcb@mri.tmd.ac.jp
FU Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO); Creative Scientific Research; Japanese Ministry of Education, Science, Sports and Culture; Japanese Ministry of Health, Labor and Welfare; Japan Science and Technology Corporation; Uehara Memorial Foundation; Sagawa Foundation for Promotion of Cancer Research; YASUDA Medical Foundation; Astellas foundation for research on metabolic disorders; Foundation for Promotion of Cancer Research
NR 28
TC 942
Z9 1077
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 1
PY 2009
VL 461
IS 7264
BP 654
EP U99
DI 10.1038/nature08455
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600041
PM 19794493
DA 2026-03-09
ER

PT J
AU Weston, EM
   Lister, AM
AF Weston, Eleanor M.
   Lister, Adrian M.
TI Insular dwarfism in hippos and a model for brain size reduction in Homo floresiensis
SO NATURE
LA English
DT Article
ID evolution; allometry; morphology; pleistocene; primates; hominin; sapiens; dmanisi; georgia; rules
AB Body size reduction in mammals is usually associated with only moderate brain size reduction, because the brain and sensory organs complete their growth before the rest of the body during ontogeny(1,2). On this basis, 'phyletic dwarfs' are predicted to have a greater relative brain size than 'phyletic giants'(1,3). However, this trend has been questioned in the special case of dwarfism of mammals on islands(4). Here we show that the endocranial capacities of extinct dwarf species of hippopotamus from Madagascar are up to 30% smaller than those of a mainland African ancestor scaled to equivalent body mass. These results show that brain size reduction is much greater than predicted from an intraspecific 'late ontogenetic' model of dwarfism in which brain size scales to body size with an exponent of 0.35. The nature of the proportional change or grade shift(2,5) observed here indicates that selective pressures on brain size are potentially independent of those on body size. This study demonstrates empirically that it is mechanistically possible for dwarf mammals on islands to evolve significantly smaller brains than would be predicted from a model of dwarfing based on the intraspecific scaling of the mainland ancestor. Our findings challenge current understanding of brain-body allometric relationships in mammals and suggest that the process of dwarfism could in principle explain small brain size, a factor relevant to the interpretation of the small-brained hominin found on the Island of Flores, Indonesia(6).
C1 [Weston, Eleanor M.; Lister, Adrian M.] Nat Hist Museum, Dept Palaeontol, London SW7 5BD, England.
C3 Natural History Museum London
RP Weston, EM (corresponding author), Nat Hist Museum, Dept Palaeontol, Cromwell Rd, London SW7 5BD, England.
EM e.weston@nhm.ac.uk
FU Biotechnology and Biological Sciences Research Council [BB/D522689/1, BB/D522689/2] Funding Source: Medline; BBSRC [BB/D522689/2] Funding Source: UKRI; NERC [NE/F017936/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/D522689/2, BB/D522689/1] Funding Source: researchfish; Natural Environment Research Council [NE/F017936/1] Funding Source: researchfish
NR 30
TC 105
Z9 118
U1 0
U2 77
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 7
PY 2009
VL 459
IS 7243
BP 85
EP U88
DI 10.1038/nature07922
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300034
PM 19424156
DA 2026-03-09
ER

PT J
AU Amo, A
   Sanvitto, D
   Laussy, FP
   Ballarini, D
   del Valle, E
   Martin, MD
   Lemaître, A
   Bloch, J
   Krizhanovskii, DN
   Skolnick, MS
   Tejedor, C
   Viña, L
AF Amo, A.
   Sanvitto, D.
   Laussy, F. P.
   Ballarini, D.
   del Valle, E.
   Martin, M. D.
   Lemaitre, A.
   Bloch, J.
   Krizhanovskii, D. N.
   Skolnick, M. S.
   Tejedor, C.
   Vina, L.
TI Collective fluid dynamics of a polariton condensate in a semiconductor microcavity
SO NATURE
LA English
DT Article
ID bose-einstein condensation; cavity; flow
AB Semiconductor microcavities offer unique systems in which to investigate the physics of weakly interacting bosons. Their elementary excitations, polaritons - mixtures of excitons and photons - can accumulate in macroscopically degenerate states to form various types of condensate in a wide range of experimental configurations, under either incoherent(1,2) or coherent(3,4) excitation. Condensates of polaritons have been put forward as candidates for superfluidity(5,6), and the formation of vortices(7) as well as elementary excitations with linear dispersion(8) are actively sought as evidence to support this. Here, using a coherent excitation triggered by a short optical pulse, we have created and set in motion a macroscopically degenerate state of polaritons that can be made to collide with a variety of defects present in the microcavity. Our experiments show striking manifestations of a coherent light - matter packet, travelling at high speed ( of the order of one per cent of the speed of light) and displaying collective dynamics consistent with superfluidity, although one of a highly unusual character as it involves an out- of- equilibrium dissipative system. Our main results are the observation of a linear polariton dispersion accompanied by diffusionless motion; flow without resistance when crossing an obstacle; suppression of Rayleigh scattering; and splitting into two fluids when the size of the obstacle is comparable to the size of the wave packet. This work opens the way to the investigation of new phenomenology of out- of- equilibrium condensates.
C1 [Amo, A.; Sanvitto, D.; Ballarini, D.; Martin, M. D.; Vina, L.] Univ Autonoma Madrid, Dept Fis Mat, E-28049 Madrid, Spain.
   [Laussy, F. P.; del Valle, E.; Tejedor, C.] Univ Autonoma Madrid, Dept Fis Teor Mat Condensada, E-28049 Madrid, Spain.
   [Lemaitre, A.; Bloch, J.] LPN CNRS, F-91460 Marcoussis, France.
   [Krizhanovskii, D. N.; Skolnick, M. S.] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
C3 Autonomous University of Madrid; Autonomous University of Madrid; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); University of Sheffield
RP Sanvitto, D (corresponding author), Univ Autonoma Madrid, Dept Fis Mat, E-28049 Madrid, Spain.
EM daniele.sanvitto@uam.es
FU Spanish Ministerio de Educacion y Ciencia [MAT2005-01388, NAN2004-09109-C04-04, QOIT-CSD2006-00019]; Comunidad Autonoma de Madrid [S-0505/ESP-0200]; IMDEA-Nanociencia; Formacion de Profesorado Universitario; EPSRC [EP/D505712/1, EP/E051448/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/D505712/1, EP/E051448/1] Funding Source: researchfish
NR 27
TC 488
Z9 517
U1 3
U2 158
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 291
EP U3
DI 10.1038/nature07640
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900034
PM 19148095
DA 2026-03-09
ER

PT J
AU Turner, SL
   Ray, A
AF Turner, Stephanie Lynn
   Ray, Anandasankar
TI Modification of CO2 avoidance behaviour in Drosophila by inhibitory odorants
SO NATURE
LA English
DT Article
ID carbon-dioxide; receptors; banana; ethylene; antenna; flight; aroma; life
AB The fruitfly Drosophila melanogaster exhibits a robust and innate olfactory-based avoidance behaviour to CO2, a component of odour emitted from stressed flies(1). Specialized neurons in the antenna and a dedicated neuronal circuit in the higher olfactory system mediate CO2 detection and avoidance(1,2). However, fruitflies need to overcome this avoidance response in some environments that contain CO2 such as ripening fruits and fermenting yeast, which are essential food sources. Very little is known about the molecular and neuronal basis of this unique, context-dependent modification of innate olfactory avoidance behaviour. Here we identify a new class of odorants present in food that directly inhibit CO2-sensitive neurons in the antenna. Using an in vivo expression system we establish that the odorants act on the Gr21a/Gr63a CO2 receptor(3). The presence of these odorants significantly and specifically reduces CO2-mediated avoidance behaviour, as well as avoidance mediated by 'Drosophila stress odour'. We propose a model in which behavioural avoidance to CO2 is directly influenced by inhibitory interactions of the novel odours with CO2 receptors. Furthermore, we observe differences in the temporal dynamics of inhibition: the effect of one of these odorants lasts several minutes beyond the initial exposure. Notably, animals that have been briefly pre-exposed to this odorant do not respond to the CO2 avoidance cue even after the odorant is no longer present. We also show that related odorants are effective inhibitors of the CO2 response in Culex mosquitoes that transmit West Nile fever and filariasis. Our findings have broader implications in highlighting the important role of inhibitory odorants in olfactory coding, and in their potential to disrupt CO2-mediated host-seeking behaviour in disease-carrying insects like mosquitoes.
C1 [Ray, Anandasankar] Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA.
   [Turner, Stephanie Lynn] Univ Calif Riverside, Cellular Mol & Dev Biol Program, Riverside, CA 92521 USA.
C3 University of California System; University of California Riverside; University of California System; University of California Riverside
RP Ray, A (corresponding author), Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA.
EM anand.ray@ucr.edu
NR 29
TC 147
Z9 194
U1 1
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 10
PY 2009
VL 461
IS 7261
BP 277
EP U159
DI 10.1038/nature08295
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600047
PM 19710651
DA 2026-03-09
ER

PT J
AU Miyazono, K
   Miyakawa, T
   Sawano, Y
   Kubota, K
   Kang, HJ
   Asano, A
   Miyauchi, Y
   Takahashi, M
   Zhi, YH
   Fujita, Y
   Yoshida, T
   Kodaira, KS
   Yamaguchi-Shinozaki, K
   Tanokura, M
AF Miyazono, Ken-ichi
   Miyakawa, Takuya
   Sawano, Yoriko
   Kubota, Keiko
   Kang, Hee-Jin
   Asano, Atsuko
   Miyauchi, Yumiko
   Takahashi, Mihoko
   Zhi, Yuehua
   Fujita, Yasunari
   Yoshida, Takuya
   Kodaira, Ken-Suke
   Yamaguchi-Shinozaki, Kazuko
   Tanokura, Masaru
TI Structural basis of abscisic acid signalling
SO NATURE
LA English
DT Article
ID protein-kinases; stress; identification; transduction; calmodulin; family; growth
AB The phytohormone abscisic acid (ABA) mediates the adaptation of plants to environmental stresses such as drought and regulates developmental signals such as seed maturation. Within plants, the PYR/PYL/RCAR family of START proteins receives ABA to inhibit the phosphatase activity of the group-A protein phosphatases 2C (PP2Cs), which are major negative regulators in ABA signalling. Here we present the crystal structures of the ABA receptor PYL1 bound with (+)-ABA, and the complex formed by the further binding of (+)-ABA-bound PYL1 with the PP2C protein ABI1. PYL1 binds (+)-ABA using the START-protein-specific ligand-binding site, thereby forming a hydrophobic pocket on the surface of the closed lid. (+)-ABA-bound PYL1 tightly interacts with a PP2C domain of ABI1 by using the hydrophobic pocket to cover the active site of ABI1 like a plug. Our results reveal the structural basis of the mechanism of (+)-ABA-dependent inhibition of ABI1 by PYL1 in ABA signalling.
C1 [Miyazono, Ken-ichi; Miyakawa, Takuya; Sawano, Yoriko; Kubota, Keiko; Kang, Hee-Jin; Asano, Atsuko; Miyauchi, Yumiko; Takahashi, Mihoko; Zhi, Yuehua; Tanokura, Masaru] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Tokyo 1138657, Japan.
   [Fujita, Yasunari; Yoshida, Takuya; Kodaira, Ken-Suke; Yamaguchi-Shinozaki, Kazuko] Japan Int Res Ctr Agr Sci, Biol Resources Div, Tsukuba 3058686, Japan.
   [Yoshida, Takuya; Kodaira, Ken-Suke; Yamaguchi-Shinozaki, Kazuko] Univ Tokyo, Grad Sch Agr & Life Sci, Lab Plant Mol Physiol, Tokyo 1138657, Japan.
C3 University of Tokyo; Japan International Research Center for Agricultural Sciences; University of Tokyo
RP Tanokura, M (corresponding author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Tokyo 1138657, Japan.
EM amtanok@mail.ecc.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology, Japan;  [2008S2-001]
NR 29
TC 477
Z9 565
U1 5
U2 172
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 609
EP U79
DI 10.1038/nature08583
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900032
PM 19855379
DA 2026-03-09
ER

PT J
AU Hartung, T
AF Hartung, Thomas
TI Toxicology for the twenty-first century
SO NATURE
LA English
DT Article
ID skin irritation; food; toxicity; thought; future; safety; risk; prevalence; revolution; evolution
C1 [Hartung, Thomas] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
   [Hartung, Thomas] Johns Hopkins Ctr Alternat Anim Testing, Baltimore, MD USA.
   [Hartung, Thomas] Univ Konstanz, D-7750 Constance, Germany.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Johns Hopkins University; University of Konstanz
RP Hartung, T (corresponding author), Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
EM thartung@jhsph.edu
NR 38
TC 484
Z9 540
U1 6
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 JUL 9
PY 2009
VL 460
IS 7252
BP 208
EP 212
DI 10.1038/460208a
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000031
PM 19587762
DA 2026-03-09
ER

PT J
AU Vance, D
   Teagle, DAH
   Foster, GL
AF Vance, Derek
   Teagle, Damon A. H.
   Foster, Gavin L.
TI Variable Quaternary chemical weathering fluxes and imbalances in marine geochemical budgets
SO NATURE
LA English
DT Article
ID isotope systematics; early holocene; sea-level; soil age; strontium; rates; erosion; ocean; pleistocene; evolution
AB Rivers are the dominant source of many elements and isotopes to the ocean. But this input from the continents is not balanced by the loss of the elements and isotopes through hydrothermal and sedimentary exchange with the oceanic crust, or by temporal changes in the marine inventory for elements that are demonstrably not in steady state(1-4). To resolve the problem of the observed imbalance in marine geochemical budgets, attention has been focused on uncertainties in the hydrothermal and sedimentary fluxes(1-4). In recent Earth history, temporally dynamic chemical weathering fluxes from the continents are an inevitable consequence of periodic glaciations(5-9). Chemical weathering rates on modern Earth are likely to remain far from equilibrium owing to the physical production of finely ground material at glacial terminations(10-13) that acts as a fertile substrate for chemical weathering. Here we explore the implications of temporal changes in the riverine chemical weathering flux for oceanic geochemical budgets. We contend that the riverine flux obtained from observations of modern rivers is broadly accurate, but not representative of time-scales appropriate for elements with oceanic residence longer than Quaternary glacial-interglacial cycles. We suggest that the pulse of rapid chemical weathering initiated at the last deglaciation has not yet decayed away and that weathering rates remain about two to three times the average for an entire late Quaternary glacial cycle. Taking into account the effect of the suggested non-steady-state process on the silicate weathering flux helps to reconcile the modelled marine strontium isotope budget with available data. Overall, we conclude that consideration of the temporal variability in riverine fluxes largely ameliorates long-standing problems with chemical and isotopic mass balances in the ocean.
C1 [Vance, Derek; Foster, Gavin L.] Univ Bristol, Dept Earth Sci, Bristol Isotope Grp, Bristol BS8 1RJ, Avon, England.
   [Teagle, Damon A. H.] Univ Southampton, Natl Oceanog Ctr, Sch Ocean & Earth Sci, Southampton SO14 3ZH, Hants, England.
C3 University of Bristol; NERC National Oceanography Centre; University of Southampton
RP Vance, D (corresponding author), Univ Bristol, Dept Earth Sci, Bristol Isotope Grp, Wills Mem Bldg, Bristol BS8 1RJ, Avon, England.
EM d.vance@bristol.ac.uk
FU Blaustein Visiting Research Professorship at Stanford; NERC [NE/E001971/1] Funding Source: UKRI; Natural Environment Research Council [NE/E001971/1, NER/T/S/2003/00048] Funding Source: researchfish
NR 30
TC 210
Z9 225
U1 0
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 493
EP 496
DI 10.1038/nature07828
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400041
PM 19325631
DA 2026-03-09
ER

PT J
AU Trompette, A
   Divanovic, S
   Visintin, A
   Blanchard, C
   Hegde, RS
   Madan, R
   Thorne, PS
   Wills-Karp, M
   Gioannini, TL
   Weiss, JP
   Karp, CL
AF Trompette, Aurelien
   Divanovic, Senad
   Visintin, Alberto
   Blanchard, Carine
   Hegde, Rashmi S.
   Madan, Rajat
   Thorne, Peter S.
   Wills-Karp, Marsha
   Gioannini, Theresa L.
   Weiss, Jerry P.
   Karp, Christopher L.
TI Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein
SO NATURE
LA English
DT Article
ID tlr4-md-2 complex; crystal-structure; allergic disease; cell activation; endotoxin; md-2; asthma; lipopolysaccharide; responses; exposure
AB Aeroallergy results from maladaptive immune responses to ubiquitous, otherwise innocuous environmental proteins(1). Although the proteins targeted by aeroallergic responses represent a tiny fraction of the airborne proteins humans are exposed to, allergenicity is a quite public phenomenon - the same proteins typically behave as aeroallergens across the human population. Why particular proteins tend to act as allergens in susceptible hosts is a fundamental mechanistic question that remains largely unanswered. The main house- dust- mite allergen, Der p 2, has structural homology with MD- 2 ( also known as LY96), the lipopolysaccharide ( LPS)- binding component of the Toll- like receptor ( TLR) 4 signalling complex(2-4). Here we show that Der p 2 also has functional homology, facilitating signalling through direct interactions with the TLR4 complex, and reconstituting LPS- driven TLR4 signalling in the absence of MD- 2. Mirroring this, airway sensitization and challenge with Der p 2 led to experimental allergic asthma in wild type and MD- 2- deficient, but not TLR4- deficient, mice. Our results indicate that Der p 2 tends to be targeted by adaptive immune responses because of its auto-adjuvant properties. The fact that other members of the MD- 2- like lipid- binding family are allergens, and that most defined major allergens are thought to be lipid- binding proteins(5), suggests that intrinsic adjuvant activity by such proteins and their accompanying lipid cargo may have some generality as a mechanism underlying the phenomenon of allergenicity.
C1 [Trompette, Aurelien; Divanovic, Senad; Madan, Rajat; Karp, Christopher L.] Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH 45229 USA.
   [Blanchard, Carine] Childrens Hosp, Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA.
   [Hegde, Rashmi S.] Childrens Hosp, Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
   [Wills-Karp, Marsha] Childrens Hosp, Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA.
   Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA.
   [Visintin, Alberto] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Dept Med, Worcester, MA 01606 USA.
   [Thorne, Peter S.] Univ Iowa, Dept Occupat & Environm Med, Iowa City, IA 52241 USA.
   [Gioannini, Theresa L.; Weiss, Jerry P.] Univ Iowa, Inflammat Program, Dept Internal Med, Iowa City, IA 52241 USA.
   [Gioannini, Theresa L.; Weiss, Jerry P.] Vet Affairs Med Ctr, Iowa City, IA 52247 USA.
C3 University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; University System of Ohio; University of Cincinnati; University of Massachusetts System; University of Massachusetts Worcester; University of Iowa; University of Iowa; US Department of Veterans Affairs; Veterans Health Administration (VHA); Iowa City VA Health Care System
RP Karp, CL (corresponding author), Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH 45229 USA.
EM chris.karp@chmcc.org
FU Sandler Foundation for Asthma Research; National Institute of Allergy and Infectious Diseases; Veteran's Administration
NR 30
TC 613
Z9 677
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 JAN 29
PY 2009
VL 457
IS 7229
BP 585
EP U91
DI 10.1038/nature07548
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200042
PM 19060881
DA 2026-03-09
ER

PT J
AU Marión, RM
   Strati, K
   Li, H
   Murga, M
   Blanco, R
   Ortega, S
   Fernandez-Capetillo, O
   Serrano, M
   Blasco, MA
AF Marion, Rosa M.
   Strati, Katerina
   Li, Han
   Murga, Matilde
   Blanco, Raquel
   Ortega, Sagrario
   Fernandez-Capetillo, Oscar
   Serrano, Manuel
   Blasco, Maria A.
TI A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; mouse; fibroblasts; atm; p53; senescence; generation; telomeres; absence; mice
AB The reprogramming of differentiated cells to pluripotent cells (induced pluripotent stem (iPS) cells) is known to be an inefficient process. We recently reported that cells with short telomeres cannot be reprogrammed to iPS cells despite their normal proliferation rates(1,2), probably reflecting the existence of 'reprogramming barriers' that abort the reprogramming of cells with uncapped telomeres. Here we show that p53 (also known as Trp53 in mice and TP53 in humans) is critically involved in preventing the reprogramming of cells carrying various types of DNA damage, including short telomeres, DNA repair deficiencies, or exogenously inflicted DNA damage. Reprogramming in the presence of pre-existing, but tolerated, DNA damage is aborted by the activation of a DNA damage response and p53-dependent apoptosis. Abrogation of p53 allows efficient reprogramming in the face of DNA damage and the generation of iPS cells carrying persistent DNA damage and chromosomal aberrations. These observations indicate that during reprogramming cells increase their intolerance to different types of DNA damage and that p53 is critical in preventing the generation of human and mouse pluripotent cells from suboptimal parental cells.
C1 [Marion, Rosa M.; Strati, Katerina; Blanco, Raquel; Blasco, Maria A.] Spanish Natl Canc Res Ctr CNIO, Telomeres & Telomerase Grp, Melchor Fernandez Almagro 3, E-28029 Madrid, Spain.
   [Li, Han; Serrano, Manuel] Spanish Natl Canc Res Ctr CNIO, Tumor Suppress Grp, E-28029 Madrid, Spain.
   [Murga, Matilde; Fernandez-Capetillo, Oscar] Spanish Natl Canc Res Ctr CNIO, Genet Instabil Grp, Mol Oncol Program, E-28029 Madrid, Spain.
   [Ortega, Sagrario] Spanish Natl Canc Res Ctr CNIO, Biotechnol Program, Transgen Mice Unit, E-28029 Madrid, Spain.
C3 Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO)
RP Blasco, MA (corresponding author), Spanish Natl Canc Res Ctr CNIO, Telomeres & Telomerase Grp, Melchor Fernandez Almagro 3, E-28029 Madrid, Spain.
EM mblasco@cnio.es
FU Spanish Association Against Cancer (AECC); MICINN (CONSOLIDER); Regional Government of Madrid; European Union; European Research Council (ERC); AECC; Korber European Research Award
NR 29
TC 829
Z9 969
U1 0
U2 114
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1149
EP 1153
DI 10.1038/nature08287
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000043
PM 19668189
DA 2026-03-09
ER

PT J
AU Nojiri, M
   Koteishi, H
   Nakagami, T
   Kobayashi, K
   Inoue, T
   Yamaguchi, K
   Suzuki, S
AF Nojiri, Masaki
   Koteishi, Hiroyasu
   Nakagami, Takuya
   Kobayashi, Kazuo
   Inoue, Tsuyoshi
   Yamaguchi, Kazuya
   Suzuki, Shinnichiro
TI Structural basis of inter-protein electron transfer for nitrite reduction in denitrification
SO NATURE
LA English
DT Article
ID x-ray-structure; cytochrome-c; alcaligenes-xylosoxidans; pseudomonas-aeruginosa; transfer complex; crystal-structure; redox property; molecular-basis; copper; achromobacter
AB Recent earth science studies have pointed out that massive acceleration of the global nitrogen cycle by anthropogenic addition of bio-available nitrogen has led to a host of environmental problems(1). Nitrous oxide (N2O) is a greenhouse gas that is an intermediate during the biological process known as denitrification(2). Copper-containing nitrite reductase (CuNIR) is a key enzyme in the process; it produces a precursor for N2O by catalysing the one-electron reduction of nitrite (NO2-) to nitric oxide (NO)(3). The reduction step is performed by an efficient electron-transfer reaction with a redox-partner protein(4-6). However, details of the mechanism during the electron-transfer reaction are still unknown. Here we show the high-resolution crystal structure of the electron-transfer complex for CuNIR with its cognate cytochrome c as the electron donor. The hydrophobic electron-transfer path is formed at the docking interface by desolvation owing to close contact between the two proteins. Structural analysis of the interface highlights an essential role for the loop region with a hydrophobic patch for protein-protein recognition; it also shows how interface construction allows the variation in atomic components to achieve diverse biological electron transfers.
C1 [Nojiri, Masaki; Koteishi, Hiroyasu; Nakagami, Takuya; Yamaguchi, Kazuya; Suzuki, Shinnichiro] Osaka Univ, Grad Sch Sci, Dept Chem, Osaka 5600043, Japan.
   [Kobayashi, Kazuo] Osaka Univ, Inst Sci & Ind Res, Osaka 5670047, Japan.
   [Inoue, Tsuyoshi] Osaka Univ, Grad Sch Engn, Dept Chem Mat, Suita, Osaka 5650871, Japan.
C3 University of Osaka; University of Osaka; University of Osaka
RP Nojiri, M (corresponding author), Osaka Univ, Grad Sch Sci, Dept Chem, Osaka 5600043, Japan.
EM nojiri@ch.wani.osaka-u.ac.jp; bic@ch.wani.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan [20750137]; Sumitomo Foundation;  [20350078]; Grants-in-Aid for Scientific Research [20750137] Funding Source: KAKEN
NR 43
TC 99
Z9 108
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 5
PY 2009
VL 462
IS 7269
BP 117
EP U132
DI 10.1038/nature08507
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200044
PM 19890332
DA 2026-03-09
ER

PT J
AU Dash, SP
   Sharma, S
   Patel, RS
   de Jong, MP
   Jansen, R
AF Dash, Saroj P.
   Sharma, Sandeep
   Patel, Ram S.
   de Jong, Michel P.
   Jansen, Ron
TI Electrical creation of spin polarization in silicon at room temperature
SO NATURE
LA English
DT Article
ID injection; resonance; barrier; absorption; transport
AB The control and manipulation of the electron spin in semiconductors is central to spintronics(1,2), which aims to represent digital information using spin orientation rather than electron charge. Such spin-based technologies may have a profound impact on nanoelectronics, data storage, and logic and computer architectures. Recently it has become possible to induce and detect spin polarization in otherwise non-magnetic semiconductors ( gallium arsenide and silicon) using all-electrical structures(3-9), but so far only at temperatures below 150 K and in n- type materials, which limits further development. Here we demonstrate room-temperature electrical injection of spin polarization into n-type and p-type silicon from a ferromagnetic tunnel contact, spin manipulation using the Hanle effect and the electrical detection of the induced spin accumulation. A spin splitting as large as 2.9 meV is created in n-type silicon, corresponding to an electron spin polarization of 4.6%. The extracted spin lifetime is greater than 140 ps for conduction electrons in heavily doped n- type silicon at 300 K and greater than 270 ps for holes in heavily doped p-type silicon at the same temperature. The spin diffusion length is greater than 230 nm for electrons and 310 nm for holes in the corresponding materials. These results open the way to the implementation of spin functionality in complementary silicon devices and electronic circuits operating at ambient temperature, and to the exploration of their prospects and the fundamental rules that govern their behaviour.
C1 [Dash, Saroj P.; Sharma, Sandeep; Patel, Ram S.; de Jong, Michel P.; Jansen, Ron] Univ Twente, MESA Inst Nanotechnol, NL-7500 AE Enschede, Netherlands.
C3 University of Twente
RP Jansen, R (corresponding author), Univ Twente, MESA Inst Nanotechnol, POB 217, NL-7500 AE Enschede, Netherlands.
EM ron.jansen@el.utwente.nl
FU NWO-VIDI; Netherlands Foundation
NR 26
TC 557
Z9 617
U1 1
U2 210
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 491
EP 494
DI 10.1038/nature08570
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200040
PM 19940922
DA 2026-03-09
ER

PT J
AU Ansmann, M
   Wang, H
   Bialczak, RC
   Hofheinz, M
   Lucero, E
   Neeley, M
   O'Connell, AD
   Sank, D
   Weides, M
   Wenner, J
   Cleland, AN
   Martinis, JM
AF Ansmann, Markus
   Wang, H.
   Bialczak, Radoslaw C.
   Hofheinz, Max
   Lucero, Erik
   Neeley, M.
   O'Connell, A. D.
   Sank, D.
   Weides, M.
   Wenner, J.
   Cleland, A. N.
   Martinis, John M.
TI Violation of Bell's inequality in Josephson phase qubits
SO NATURE
LA English
DT Article
ID superconducting qubits; entanglement
AB The measurement process plays an awkward role in quantum mechanics, because measurement forces a system to 'choose' between possible outcomes in a fundamentally unpredictable manner. Therefore, hidden classical processes have been considered as possibly predetermining measurement outcomes while preserving their statistical distributions(1). However, a quantitative measure that can distinguish classically determined correlations from stronger quantum correlations exists in the form of the Bell inequalities, measurements of which provide strong experimental evidence that quantum mechanics provides a complete description(2-4). Here we demonstrate the violation of a Bell inequality in a solid-state system. We use a pair of Josephson phase qubits(5-7) acting as spin-1/2 particles, and show that the qubits can be entangled(8,9) and measured so as to violate the Clauser-Horne-Shimony-Holt (CHSH) version of the Bell inequality(10). We measure a Bell signal of 2.0732 +/- 0.0003, exceeding the maximum amplitude of 2 for a classical system by 244 standard deviations. In the experiment, we deterministically generate the entangled state, and measure both qubits in a single-shot manner, closing the detection loophole(11). Because the Bell inequality was designed to test for non-classical behaviour without assuming the applicability of quantum mechanics to the system in question, this experiment provides further strong evidence that a macroscopic electrical circuit is really a quantum system(7).
C1 [Ansmann, Markus; Wang, H.; Bialczak, Radoslaw C.; Hofheinz, Max; Lucero, Erik; Neeley, M.; O'Connell, A. D.; Sank, D.; Weides, M.; Wenner, J.; Cleland, A. N.; Martinis, John M.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara
RP Martinis, JM (corresponding author), Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
EM martinis@physics.ucsb.edu
FU IARPA [W911NF-04-1-0204]; NSF [CCF-0507227]
NR 27
TC 320
Z9 369
U1 2
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 SEP 24
PY 2009
VL 461
IS 7263
BP 504
EP 506
DI 10.1038/nature08363
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900035
PM 19779447
DA 2026-03-09
ER

PT J
AU Kim, N
   Jinks-Robertson, S
AF Kim, Nayun
   Jinks-Robertson, Sue
TI dUTP incorporation into genomic DNA is linked to transcription in yeast
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; translesion synthesis; repair; damage; recombination; specificity; proteins
AB Highly activated transcription is associated with eukaryotic genome instability, resulting in increased rates of mitotic recombination and mutagenesis. The association between high transcription and genome stability is probably due to a variety of factors including an enhanced accumulation of DNA damage, transcription-associated supercoiling, collision between replication forks and the transcription machinery, and the persistence of RNA-DNA hybrids(1). In the case of transcription-associated mutagenesis, we previously showed that there is a direct proportionality between the level of transcription and themutation rate in the yeast Saccharomyces cerevisiae(2), and that the molecular nature of the mutations is affected by highly activated transcription(2,3). Here we show that the accumulation of apurinic/apyrimidinic sites is greatly enhanced in highly transcribed yeast DNA. We further demonstrate that most apurinic/apyrimidinic sites in highly transcribed DNA are derived from the removal of uracil, the presence of which is linked to direct incorporation of dUTP in place of dTTP. These results show an unexpected relationship between transcription and the fidelity of DNA synthesis, and raise intriguing cell biological issues with regard to nucleotide pool compartmentalization.
C1 [Kim, Nayun; Jinks-Robertson, Sue] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
C3 Duke University
RP Jinks-Robertson, S (corresponding author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM sue.robertson@duke.edu
FU National Institutes of Health [R01 GM038464]
NR 15
TC 56
Z9 71
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 25
PY 2009
VL 459
IS 7250
BP 1150
EP 1153
DI 10.1038/nature08033
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700048
PM 19448611
DA 2026-03-09
ER

PT J
AU Levison, HF
   Bottke, WF
   Gounelle, M
   Morbidelli, A
   Nesvorny, D
   Tsiganis, K
AF Levison, Harold F.
   Bottke, William F.
   Gounelle, Matthieu
   Morbidelli, Alessandro
   Nesvorny, David
   Tsiganis, Kleomenis
TI Contamination of the asteroid belt by primordial trans-Neptunian objects
SO NATURE
LA English
DT Article
ID size distribution; main-belt; numerical simulations; trojan asteroids; chaotic capture; origin; oxygen; meteorites
AB The main asteroid belt, which inhabits a relatively narrow annulus similar to 2.1-3.3 AU from the Sun, contains a surprising diversity of objects ranging from primitive ice-rock mixtures to igneous rocks. The standard model used to explain this assumes that most asteroids formed in situ from a primordial disk that experienced radical chemical changes within this zone(1). Here we show that the violent dynamical evolution of the giant-planet orbits required by the so-called Nice model(2-4) leads to the insertion of primitive trans-Neptunian objects into the outer belt. This result implies that the observed diversity of the asteroid belt is not a direct reflection of the intrinsic compositional variation of the proto-planetary disk. The dark captured bodies, composed of organic-rich materials, would have been more susceptible to collisional evolution than typical main-belt asteroids. Their weak nature makes them a prodigious source of micrometeorites-sufficient to explain why most are primitive in composition and are isotopically different from most macroscopic meteorites(5,6).
C1 [Levison, Harold F.; Bottke, William F.; Nesvorny, David] SW Res Inst, Boulder, CO 80302 USA.
   [Levison, Harold F.; Bottke, William F.; Nesvorny, David] NASA, Lunar Sci Inst, Ctr Lunar Origin & Evolut, Boulder, CO 80302 USA.
   [Gounelle, Matthieu] CNRS, Lab Mineral & Cosmochim Museum, F-75005 Paris, France.
   [Gounelle, Matthieu] Museum Natl Hist Nat, F-75005 Paris, France.
   [Morbidelli, Alessandro] Observ Cote Azur, F-06304 Nice, France.
   [Tsiganis, Kleomenis] Aristotle Univ Thessaloniki, Dept Phys, Thessaloniki 54006, Greece.
C3 National Aeronautics & Space Administration (NASA); Centre National de la Recherche Scientifique (CNRS); Museum National d'Histoire Naturelle (MNHN); Universite Cote d'Azur; Observatoire de la Cote d'Azur; Aristotle University of Thessaloniki
RP Levison, HF (corresponding author), SW Res Inst, 1050 Walnut St,Suite 300, Boulder, CO 80302 USA.
EM hal@boulder.swri.edu
FU NASA's; S National Science Foundation's Astronomy Astrophysics; European Community
NR 29
TC 244
Z9 263
U1 0
U2 16
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 364
EP 366
DI 10.1038/nature08094
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000031
PM 19606143
DA 2026-03-09
ER

PT J
AU Kelly, JX
   Smilkstein, MJ
   Brun, R
   Wittlin, S
   Cooper, RA
   Lane, KD
   Janowsky, A
   Johnson, RA
   Dodean, RA
   Winter, R
   Hinrichs, DJ
   Riscoe, MK
AF Kelly, Jane X.
   Smilkstein, Martin J.
   Brun, Reto
   Wittlin, Sergio
   Cooper, Roland A.
   Lane, Kristin D.
   Janowsky, Aaron
   Johnson, Robert A.
   Dodean, Rozalia A.
   Winter, Rolf
   Hinrichs, David J.
   Riscoe, Michael K.
TI Discovery of dual function acridones as a new antimalarial chemotype
SO NATURE
LA English
DT Article
ID chloroquine resistance transporter; transmembrane protein pfcrt; plasmodium-falciparum; digestive vacuole; beta-hematin; in-vitro; drug; malaria; mutations; mechanism
AB Preventing and delaying the emergence of drug resistance is an essential goal of antimalarial drug development. Monotherapy and highly mutable drug targets have each facilitated resistance, and both are undesirable in effective long-term strategies against multi-drug-resistant malaria. Haem remains an immutable and vulnerable target, because it is not parasite-encoded and its detoxification during haemoglobin degradation, critical to parasite survival, can be subverted by drug-haem interaction as in the case of quinolines and many other drugs(1-5). Here we describe a new antimalarial chemotype that combines the haem-targeting character of acridones, together with a chemosensitizing component that counteracts resistance to quinoline antimalarial drugs. Beyond the essential intrinsic characteristics common to deserving candidate antimalarials ( high potency in vitro against pan-sensitive and multi-drug-resistant Plasmodium falciparum, efficacy and safety in vivo after oral administration, inexpensive synthesis and favourable physicochemical properties), our initial lead, T3.5 (3-chloro-6-(2-diethylamino-ethoxy)-10-(2-diethylamino-ethyl)acridone), demonstrates unique synergistic properties. In addition to 'verapamil-like' chemosensitization to chloroquine and amodiaquine against quinoline-resistant parasites, T3.5 also results in an apparently mechanistically distinct synergism with quinine and with piperaquine. This synergy, evident in both quinoline-sensitive and quinoline-resistant parasites, has been demonstrated both in vitro and in vivo. In summary, this innovative acridone design merges intrinsic potency and resistance-counteracting functions in one molecule, and represents a new strategy to expand, enhance and sustain effective antimalarial drug combinations.
C1 [Kelly, Jane X.; Smilkstein, Martin J.; Janowsky, Aaron; Johnson, Robert A.; Dodean, Rozalia A.; Winter, Rolf; Hinrichs, David J.; Riscoe, Michael K.] Portland VA Med Ctr, Portland, OR 97239 USA.
   [Kelly, Jane X.; Smilkstein, Martin J.; Dodean, Rozalia A.; Winter, Rolf; Riscoe, Michael K.] Portland State Univ, Dept Chem, Portland, OR 97201 USA.
   [Smilkstein, Martin J.; Janowsky, Aaron; Johnson, Robert A.; Hinrichs, David J.; Riscoe, Michael K.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
   [Brun, Reto; Wittlin, Sergio] Swiss Trop Inst, CH-4002 Basel, Switzerland.
   [Cooper, Roland A.; Lane, Kristin D.] Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA); Portland VA Medical Center; Portland State University; Oregon Health & Science University; University of Basel; Swiss Tropical & Public Health Institute; Swiss School of Public Health (SSPH+); Old Dominion University
RP Kelly, JX (corresponding author), Portland VA Med Ctr, Portland, OR 97239 USA.
EM kellyja@ohsu.edu; riscoem@ohsu.edu
FU Merit Review Program of the Department of Veterans Affairs
NR 28
TC 163
Z9 190
U1 0
U2 44
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 270
EP 273
DI 10.1038/nature07937
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100045
PM 19357645
DA 2026-03-09
ER

PT J
AU Yeh, SW
   Kug, JS
   Dewitte, B
   Kwon, MH
   Kirtman, BP
   Jin, FF
AF Yeh, Sang-Wook
   Kug, Jong-Seong
   Dewitte, Boris
   Kwon, Min-Ho
   Kirtman, Ben P.
   Jin, Fei-Fei
TI El Nino in a changing climate
SO NATURE
LA English
DT Article
ID pacific rim; sensitivity; anomaly; modoki
AB El Nino events, characterized by anomalous warming in the eastern equatorial Pacific Ocean, have global climatic teleconnections and are the most dominant feature of cyclic climate variability on subdecadal timescales. Understanding changes in the frequency or characteristics of El Nino events in a changing climate is therefore of broad scientific and socioeconomic interest. Recent studies(1-5) show that the canonical El Nino has become less frequent and that a different kind of El Nino has become more common during the late twentieth century, in which warm sea surface temperatures (SSTs) in the central Pacific are flanked on the east and west by cooler SSTs. This type of El Nino, termed the central Pacific El Nino (CP-El Nino; also termed the dateline El Nino(2), El Nino Modoki(3) or warm pool El Nino(5)), differs from the canonical eastern Pacific El Nino (EP-El Nino) in both the location of maximum SST anomalies and tropical-midlatitude teleconnections. Here we show changes in the ratio of CP-El Nino to EP-El Nino under projected global warming scenarios from the Coupled Model Intercomparison Project phase 3 multi-model data set(6). Using calculations based on historical El Nino indices, we find that projections of anthropogenic climate change are associated with an increased frequency of the CP-El Nino compared to the EP-El Nino. When restricted to the six climate models with the best representation of the twentieth-century ratio of CP-El Nino to EP-El Nino, the occurrence ratio of CP-El Nino/EP-El Nino is projected to increase as much as five times under global warming. The change is related to a flattening of the thermocline in the equatorial Pacific.
C1 [Yeh, Sang-Wook; Kug, Jong-Seong] Korea Ocean Res & Dev Inst, Climate Change & Coastal Disaster Res Dept, Ansan 426744, South Korea.
   [Dewitte, Boris] Lab Etud Geophys & Oceanog Spatiale, F-31400 Toulouse, France.
   [Kwon, Min-Ho; Jin, Fei-Fei] Univ Hawaii, Sch Ocean & Earth Sci & Technol, Dept Meteorol, Honolulu, HI 96822 USA.
   [Kirtman, Ben P.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33149 USA.
C3 Korea Institute of Ocean Science & Technology (KIOST); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National d'Etudes Spatiales (CNES); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Laboratoire d'Etudes en Geophysique et oceanographie spatiales; University of Hawaii System; University of Miami
RP Yeh, SW (corresponding author), Korea Ocean Res & Dev Inst, Climate Change & Coastal Disaster Res Dept, Ansan 426744, South Korea.
EM swyeh@kordi.re.kr
FU KORDI [PE98401, PP00720]; PCCC project; ANR (Agence Nationale de la Recherche); NSF [ATM 060552, AMT 065145]; NOAA [GC01-229]
NR 28
TC 1366
Z9 1574
U1 27
U2 688
PU NATURE PUBLISHING 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 24
PY 2009
VL 461
IS 7263
BP 511
EP U70
DI 10.1038/nature08316
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900037
PM 19779449
DA 2026-03-09
ER

PT J
AU Lubenov, EV
   Siapas, AG
AF Lubenov, Evgueniy V.
   Siapas, Athanassios G.
TI Hippocampal theta oscillations are travelling waves
SO NATURE
LA English
DT Article
ID medial entorhinal cortex; freely-moving rat; synaptic plasticity; field potentials; pyramidal cells; stellate cells; behaving rat; ca1 neurons; layer-ii; rhythm
AB Theta oscillations clock hippocampal activity during awake behaviour and rapid eye movement (REM) sleep. These oscillations are prominent in the local field potential, and they also reflect the subthreshold membrane potential and strongly modulate the spiking of hippocampal neurons. The prevailing view is that theta oscillations are synchronized throughout the hippocampus, despite the lack of conclusive experimental evidence. In contrast, here we show that in freely behaving rats, theta oscillations in area CA1 are travelling waves that propagate roughly along the septotemporal axis of the hippocampus. Furthermore, we find that spiking in the CA1 pyramidal cell layer is modulated in a consistent travelling wave pattern. Our results demonstrate that theta oscillations pattern hippocampal activity not only in time, but also across anatomical space. The presence of travelling waves indicates that the instantaneous output of the hippocampus is topographically organized and represents a segment, rather than a point, of physical space.
C1 [Lubenov, Evgueniy V.; Siapas, Athanassios G.] CALTECH, Div Engn & Appl Sci, Div Biol, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Siapas, AG (corresponding author), CALTECH, Div Engn & Appl Sci, Div Biol, Pasadena, CA 91125 USA.
EM lubenov@caltech.edu; thanos@caltech.edu
FU Caltech Information Science and Technology Center for Biological Circuit Design; 21st Century McDonnell Foundation Award; Bren Foundation; McKnight Foundation
NR 50
TC 333
Z9 417
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 MAY 28
PY 2009
VL 459
IS 7246
BP 534
EP 539
DI 10.1038/nature08010
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500031
PM 19489117
DA 2026-03-09
ER

PT J
AU Hadjur, S
   Williams, LM
   Ryan, NK
   Cobb, BS
   Sexton, T
   Fraser, P
   Fisher, AG
   Merkenschlager, M
AF Hadjur, Suzana
   Williams, Luke M.
   Ryan, Natalie K.
   Cobb, Bradley S.
   Sexton, Tom
   Fraser, Peter
   Fisher, Amanda G.
   Merkenschlager, Matthias
TI Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus
SO NATURE
LA English
DT Article
ID ccctc-binding factor; gene-expression; cell differentiation; interferon-gamma; control region; ctcf; transcription; chromatin; conformation; genome
AB Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair(1,2). In addition, evidence from model organisms(3-6) and from human genetics(7) suggests that cohesin is involved in the control of gene expression(8,9). This non-canonical role has recently been rationalized by the findings that mammalian cohesin complexes are recruited to a subset of DNase I hypersensitive sites and to conserved noncoding sequences by the DNA-binding protein CTCF10-13. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure)(14), and cohesin contributes to its enhancer-blocking activity(10,11). The underlying mechanisms remain unknown, and the full spectrum of cohesin functions remains to be determined. Here we show that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG. Hence, the ability of cohesin to constrain chromosome topology is used not only for the purpose of sister chromatid cohesion(1,2), but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development(3-6) and disease(7).
C1 [Hadjur, Suzana; Williams, Luke M.; Ryan, Natalie K.; Cobb, Bradley S.; Fisher, Amanda G.; Merkenschlager, Matthias] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Lymphocyte Dev Grp, London W12 0NN, England.
   [Sexton, Tom; Fraser, Peter] Babraham Inst, Lab Chromatin & Gene Express, Cambridge CB2 4AT, England.
C3 Imperial College London; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute
RP Merkenschlager, M (corresponding author), Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Lymphocyte Dev Grp, Cane Rd, London W12 0NN, England.
EM matthias.merkenschlager@csc.mrc.ac.uk
FU Medical Research Council, UK; Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C151] Funding Source: researchfish; Medical Research Council [MC_U120027516, G117/530] Funding Source: researchfish; BBSRC [BBS/E/B/0000C151] Funding Source: UKRI; MRC [MC_U120027516, G117/530] Funding Source: UKRI
NR 30
TC 425
Z9 518
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 16
PY 2009
VL 460
IS 7253
BP 410
EP U130
DI 10.1038/nature08079
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000042
PM 19458616
DA 2026-03-09
ER

PT J
AU Lefèvre, F
   Forget, F
AF Lefevre, Franck
   Forget, Francois
TI Observed variations of methane on Mars unexplained by known atmospheric chemistry and physics
SO NATURE
LA English
DT Article
ID martian dust devils; interannual variability; oxidant enhancement; storms; origin; life
AB The detection of methane on Mars(1-3) has revived the possibility of past or extant life on this planet, despite the fact that an abiogenic origin is thought to be equally plausible(4). An intriguing aspect of the recent observations of methane on Mars is that methane concentrations appear to be locally enhanced and change with the seasons(3). However, methane has a photochemical lifetime of several centuries, and is therefore expected to have a spatially uniform distribution on the planet(5). Here we use a global climate model of Mars with coupled chemistry(6-8) to examine the implications of the recently observed variations of Martian methane for our understanding of the chemistry of methane. We find that photochemistry as currently understood does not produce measurable variations in methane concentrations, even in the case of a current, local and episodic methane release. In contrast, we find that the condensation-sublimation cycle of Mars' carbon dioxide atmosphere can generate large-scale methane variations differing from those observed. In order to reproduce local methane enhancements similar to those recently reported(3), we show that an atmospheric lifetime of less than 200 days is necessary, even if a local source of methane is only active around the time of the observation itself. This implies an unidentified methane loss process that is 600 times faster than predicted by standard photochemistry. The existence of such a fast loss in the Martian atmosphere is difficult to reconcile with the observed distribution of other trace gas species. In the case of a destruction mechanism only active at the surface of Mars, destruction of methane must occur with an even shorter timescale of the order of similar to 1 hour to explain the observations. If recent observations of spatial and temporal variations of methane are confirmed, this would suggest an extraordinarily harsh environment for the survival of organics on the planet.
C1 [Lefevre, Franck] Univ Paris 06, CNRS, LATMOS, F-75005 Paris, France.
   [Forget, Francois] Univ Paris 06, CNRS, Meteorol Dynam Lab, F-75005 Paris, France.
C3 Universite Paris Saclay; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Institut Polytechnique de Paris; Ecole Polytechnique; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite
RP Lefèvre, F (corresponding author), Univ Paris 06, CNRS, LATMOS, F-75005 Paris, France.
EM franck.lefevre@upmc.fr
FU CNRS; ESA; CNES
NR 30
TC 197
Z9 211
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 AUG 6
PY 2009
VL 460
IS 7256
BP 720
EP 723
DI 10.1038/nature08228
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300034
PM 19661912
DA 2026-03-09
ER

PT J
AU Yang, G
   Pan, F
   Gan, WB
AF Yang, Guang
   Pan, Feng
   Gan, Wen-Biao
TI Stably maintained dendritic spines are associated with lifelong memories
SO NATURE
LA English
DT Article
ID cerebral-cortex; somatosensory cortex; synaptic plasticity; ocular dominance; diverse regions; striate cortex; motor cortex; adult cortex; in-vivo; synapses
AB Changes in synaptic connections are considered essential for learning and memory formation(1-6). However, it is unknown how neural circuits undergo continuous synaptic changes during learning while maintaining lifelong memories. Here we show, by following postsynaptic dendritic spines over time in the mouse cortex(7,8), that learning and novel sensory experience lead to spine formation and elimination by a protracted process. The extent of spine remodelling correlates with behavioural improvement after learning, suggesting a crucial role of synaptic structural plasticity in memory formation. Importantly, a small fraction of new spines induced by novel experience, together with most spines formed early during development and surviving experience-dependent elimination, are preserved and provide a structural basis for memory retention throughout the entire life of an animal. These studies indicate that learning and daily sensory experience leave minute but permanent marks on cortical connections and suggest that lifelong memories are stored in largely stably connected synaptic networks.
C1 [Yang, Guang; Pan, Feng; Gan, Wen-Biao] NYU, Sch Med,Helen & Martin Kimmel Ctr Biol & Med, Skirball Inst Biomol Med,Dept Physiol & Neurosci, Mol Neurobiol Program, New York, NY 10016 USA.
C3 New York University
RP Gan, WB (corresponding author), NYU, Sch Med,Helen & Martin Kimmel Ctr Biol & Med, Skirball Inst Biomol Med,Dept Physiol & Neurosci, Mol Neurobiol Program, New York, NY 10016 USA.
EM gan@saturn.med.nyu.edu
FU National Institutes of Health [R01 NS047325]; Dart Foundation Fellowship; Ellison/AFAR Postdoctoral Fellowship
NR 35
TC 907
Z9 1115
U1 2
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 17
PY 2009
VL 462
IS 7275
BP 920
EP U114
DI 10.1038/nature08577
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400043
PM 19946265
DA 2026-03-09
ER

PT J
AU Laprise, P
   Lau, KM
   Harris, KP
   Silva-Gagliardi, NF
   Paul, SM
   Beronja, S
   Beitel, GJ
   McGlade, CJ
   Tepass, U
AF Laprise, Patrick
   Lau, Kimberly M.
   Harris, Kathryn P.
   Silva-Gagliardi, Nancy F.
   Paul, Sarah M.
   Beronja, Slobodan
   Beitel, Greg J.
   McGlade, C. Jane
   Tepass, Ulrich
TI Yurt, Coracle, Neurexin IV and the Na+,K+-ATPase form a novel group of epithelial polarity proteins
SO NATURE
LA English
DT Article
ID drosophila tracheal system; tube-size control; septate junction function; blood-nerve barrier; cell polarity; plasma-membrane; na+/k+ atpase; mesenchymal transition; apical membrane; crumbs complex
AB The integrity of polarized epithelia is critical for development and human health. Many questions remain concerning the full complement and the function of the proteins that regulate cell polarity(1). Here we report that the Drosophila FERM proteins Yurt (Yrt)(2) and Coracle (Cora)(3) and the membrane proteins Neurexin IV(Nrx-IV)(4) and Na+,K+-ATPase(5) are a new group of functionally cooperating epithelial polarity proteins. This 'Yrt/Cora group' promotes basolateral membrane stability and shows negative regulatory interactions with the apical determinant Crumbs (Crb). Genetic analyses indicate that Nrx-IV and Na+,K+-ATPase act together with Cora in one pathway, whereas Yrt acts in a second redundant pathway. Moreover, we show that the Yrt/Cora group is essential for epithelial polarity during organogenesis but not when epithelial polarity is first established or during terminal differentiation. This property of Yrt/Cora group proteins explains the recovery of polarity in embryos lacking the function of the Lethal giant larvae (Lgl) group of basolateral polarity proteins(6,7). We also find that the mammalian Yrt orthologue EPB41L5 ( also known as YMO1 and Limulus)(8-10) is required for lateral membrane formation, indicating a conserved function of Yrt proteins in epithelial polarity.
C1 [Laprise, Patrick; Harris, Kathryn P.; Beronja, Slobodan; Tepass, Ulrich] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 3G5, Canada.
   [Lau, Kimberly M.; Silva-Gagliardi, Nancy F.; McGlade, C. Jane] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1X8, Canada.
   [Lau, Kimberly M.; Silva-Gagliardi, Nancy F.; McGlade, C. Jane] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada.
   [Paul, Sarah M.; Beitel, Greg J.] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA.
C3 University of Toronto; University of Toronto; University of Toronto; Hospital for Sick Children (SickKids); Northwestern University
RP Tepass, U (corresponding author), Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 3G5, Canada.
EM u.tepass@utoronto.ca
FU CIHR; Vision Science Research Program, University of Toronto; NIH Lung Biology Training; Foundation Fighting Blindness Canada; NIH
NR 46
TC 127
Z9 174
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1141
EP U134
DI 10.1038/nature08067
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700046
PM 19553998
DA 2026-03-09
ER

PT J
AU Myrskylä, M
   Kohler, HP
   Billari, FC
AF Myrskylae, Mikko
   Kohler, Hans-Peter
   Billari, Francesco C.
TI Advances in development reverse fertility declines
SO NATURE
LA English
DT Article
ID lowest-low fertility; population-growth; europe; consequences; childbearing; transition
AB During the twentieth century, the global population has gone through unprecedented increases in economic and social development that coincided with substantial declines in human fertility and population growth rates(1,2). The negative association of fertility with economic and social development has therefore become one of the most solidly established and generally accepted empirical regularities in the social sciences(1-3). As a result of this close connection between development and fertility decline, more than half of the global population now lives in regions with below-replacement fertility (less than 2.1 children per woman)(4). In many highly developed countries, the trend towards low fertility has also been deemed irreversible(5-9). Rapid population ageing, and in some cases the prospect of significant population decline, have therefore become a central socioeconomic concern and policy challenge(10). Here we show, using new cross-sectional and longitudinal analyses of the total fertility rate and the human development index (HDI), a fundamental change in the well-established negative relationship between fertility and development as the global population entered the twenty-first century. Although development continues to promote fertility decline at low and medium HDI levels, our analyses show that at advanced HDI levels, further development can reverse the declining trend in fertility. The previously negative development-fertility relationship has become J-shaped, with the HDI being positively associated with fertility among highly developed countries. This reversal of fertility decline as a result of continued economic and social development has the potential to slow the rates of population ageing, thereby ameliorating the social and economic problems that have been associated with the emergence and persistence of very low fertility.
C1 [Myrskylae, Mikko; Kohler, Hans-Peter] Univ Penn, Ctr Populat Studies, Philadelphia, PA 19104 USA.
   [Billari, Francesco C.] Univ Bocconi, DONDENA Carlo F Dondena Ctr Res Social Dynam, Dept Decis Sci, I-20136 Milan, Italy.
   [Billari, Francesco C.] Univ Bocconi, IGIER, I-20136 Milan, Italy.
C3 University of Pennsylvania; Bocconi University; Bocconi University
RP Kohler, HP (corresponding author), Univ Penn, Ctr Populat Studies, 3718 Locust Walk, Philadelphia, PA 19104 USA.
EM hpkohler@pop.upenn.edu
FU University of Pennsylvania; Finnish Cultural Foundation; Ella and Georg Ehrnrooth foundation; Center for Advanced Studies at the Norwegian Academy of Science; Universita Bocconi; Italian Ministry for University and Research
NR 21
TC 372
Z9 466
U1 5
U2 160
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 6
PY 2009
VL 460
IS 7256
BP 741
EP 743
DI 10.1038/nature08230
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300039
PM 19661915
DA 2026-03-09
ER

PT J
AU Zhao, C
   Chen, A
   Jamieson, CH
   Fereshteh, M
   Abrahamsson, A
   Blum, J
   Kwon, HY
   Kim, J
   Chute, JP
   Rizzieri, D
   Munchhof, M
   VanArsdale, T
   Beachy, PA
   Reya, T
AF Zhao, Chen
   Chen, Alan
   Jamieson, Catriona H.
   Fereshteh, Mark
   Abrahamsson, Annelie
   Blum, Jordan
   Kwon, Hyog Young
   Kim, Jynho
   Chute, John P.
   Rizzieri, David
   Munchhof, Michael
   VanArsdale, Todd
   Beachy, Philip A.
   Reya, Tannishtha
TI Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia
SO NATURE
LA English
DT Article
ID chronic myelogenous leukemia; bcr-abl; sonic hedgehog; resistance; gene; proliferation; progenitors; mechanisms; pathways; therapy
AB Although the role of Hedgehog (Hh) signalling in embryonic pattern formation is well established(1), its functions in adult tissue renewal and maintenance remain unclear, and the relationship of these functions to cancer development has not been determined. Here we show that the loss of Smoothened (Smo), an essential component of the Hh pathway(2), impairs haematopoietic stem cell renewal and decreases induction of chronic myelogenous leukaemia (CML) by the BCR-ABL1 oncoprotein(3). Loss of Smo causes depletion of CML stem cells-the cells that propagate the leukaemia-whereas constitutively active Smo augments CML stem cell number and accelerates disease. As a possible mechanism for Smo action, we show that the cell fate determinant Numb, which depletes CML stem cells, is increased in the absence of Smo activity. Furthermore, pharmacological inhibition of Hh signalling impairs not only the propagation of CML driven by wild-type BCR-ABL1, but also the growth of imatinib-resistant mouse and human CML. These data indicate that Hh pathway activity is required for maintenance of normal and neoplastic stem cells of the haematopoietic system and raise the possibility that the drug resistance and disease recurrence associated with imatinib treatment of CML4,5 might be avoided by targeting this essential stem cell maintenance pathway.
C1 [Zhao, Chen; Chen, Alan; Fereshteh, Mark; Blum, Jordan; Kwon, Hyog Young; Reya, Tannishtha] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Chute, John P.; Rizzieri, David] Duke Univ, Med Ctr, Dept Med, Div Cellular Therapy, Durham, NC 27710 USA.
   [Jamieson, Catriona H.; Abrahamsson, Annelie] Moores UCSD Canc Ctr Jolla, Stem Cell Res Program, Dept Med, La Jolla, CA 92093 USA.
   [Kim, Jynho; Beachy, Philip A.] Stanford Univ, Med Ctr, Howard Hughes Med Inst, Dept Dev Biol,Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Munchhof, Michael] Pfizer Labs, Div Med Chem, Groton, CT 06340 USA.
   [VanArsdale, Todd] Pfizer Labs, Div Oncol, La Jolla, CA 92121 USA.
C3 Duke University; Duke University; Stanford University; Howard Hughes Medical Institute; Pfizer; Pfizer USA; Pfizer; Pfizer USA
RP Reya, T (corresponding author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
EM t.reya@duke.edu
FU CRI; EMF; Leukemia and Lymphoma Society; Duke Molecular Cancer Biology Training; California Institute of Regenerative Medicine; National Institutes of Health [DK63031, DK072234, AI067798]; Lisa Stafford Memorial Prize; NIH Office of the Director [U19AI067798] Funding Source: NIH RePORTER
NR 30
TC 722
Z9 843
U1 0
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 9
PY 2009
VL 458
IS 7239
BP 776
EP U117
DI 10.1038/nature07737
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600044
PM 19169242
DA 2026-03-09
ER

PT J
AU Rebouissou, S
   Amessou, M
   Couchy, G
   Poussin, K
   Imbeaud, S
   Pilati, C
   Izard, T
   Balabaud, C
   Bioulac-Sage, P
   Zucman-Rossi, J
AF Rebouissou, Sandra
   Amessou, Mohamed
   Couchy, Gabrielle
   Poussin, Karine
   Imbeaud, Sandrine
   Pilati, Camilla
   Izard, Tina
   Balabaud, Charles
   Bioulac-Sage, Paulette
   Zucman-Rossi, Jessica
TI Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours
SO NATURE
LA English
DT Article
ID signal transducer; molecular-cloning; cytokine receptor; il-6; interleukin-6; binding; adenoma; gene; classification; transcription
AB Inflammatory hepatocellular adenomas are benign liver tumours defined by the presence of inflammatory infiltrates and by the increased expression of inflammatory proteins in tumour hepatocytes(1,2). Here we show a marked activation of the interleukin ( IL)- 6 signalling pathway in this tumour type; sequencing candidate genes pinpointed this response to somatic gain- of- function mutations in the IL6ST gene, which encodes the signalling co- receptor gp130. Indeed, 60% of inflammatory hepatocellular adenomas harbour small in- frame deletions that target the binding site of gp130 for IL- 6, and expression of four different gp130 mutants in hepatocellular cells activates signal transducer and activator of transcription 3 ( STAT3) in the absence of ligand. Furthermore, analysis of hepatocellular carcinomas revealed that rare gp130 alterations are always accompanied by beta-catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant conversion of hepatocytes. The recurrent gain- of function gp130 mutations in these human hepatocellular adenomas fully explains activation of the acute inflammatory phase observed in tumourous hepatocytes, and suggests that similar alterations may occur in other inflammatory epithelial tumours with STAT3 activation.
C1 [Rebouissou, Sandra; Amessou, Mohamed; Couchy, Gabrielle; Poussin, Karine; Pilati, Camilla; Zucman-Rossi, Jessica] INSERM, Genom Fonct Tumeurs Solides U674, F-75010 Paris, France.
   [Rebouissou, Sandra; Amessou, Mohamed; Couchy, Gabrielle; Poussin, Karine; Pilati, Camilla; Zucman-Rossi, Jessica] Univ Paris 07, Inst Univ Hematol, F-75010 Paris, France.
   [Imbeaud, Sandrine] CNRS, Arrays IMAGE Genexpress Funct Genom & Syst Biol H, UMR 7091, F-94801 Villejuif, France.
   [Imbeaud, Sandrine] Univ Paris 06, F-94801 Villejuif, France.
   [Imbeaud, Sandrine] CNRS, Ctr Genet Mol, Gif Orsay DNA Microarray Platform GODMAP, UPR 2167, F-91198 Gif Sur Yvette, France.
   [Imbeaud, Sandrine] Univ Paris 11, F-91198 Gif Sur Yvette, France.
   [Izard, Tina] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA.
   [Balabaud, Charles; Bioulac-Sage, Paulette] INSERM, U889, F-33076 Bordeaux, France.
   [Balabaud, Charles; Bioulac-Sage, Paulette] Univ Bordeaux 2, IFR66, F-33076 Bordeaux, France.
   [Balabaud, Charles] Hop St Andre, Serv Hepatol, CHU Bordeaux, F-33076 Bordeaux, France.
   [Bioulac-Sage, Paulette] Hop Pellegrin, Serv Anat Pathol, CHU Bordeaux, F-33076 Bordeaux, France.
C3 Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Bordeaux; Universite de Bordeaux; CHU Bordeaux; Universite de Bordeaux; CHU Bordeaux
RP Zucman-Rossi, J (corresponding author), INSERM, Genom Fonct Tumeurs Solides U674, F-75010 Paris, France.
EM zucman@cephb.fr
FU Inserm (Reseaux de Recherche Clinique et Reseaux de Recherche en Sante des Populations); Ligue Nationale Contre le Cancer ("Cartes d'Identite des Tumeurs'' program); ARC [5158]; Fondation de France; la Ligue Nationale Contre le Cancer; Inca; Inserm; Bordeaux Hospital; National Institutes of Health [GM071596, AI055894, AI067949]
NR 34
TC 370
Z9 412
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 JAN 8
PY 2009
VL 457
IS 7226
BP 200
EP U96
DI 10.1038/nature07475
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200034
PM 19020503
DA 2026-03-09
ER

PT J
AU Hamdan, SM
   Loparo, JJ
   Takahashi, M
   Richardson, CC
   van Oijen, AM
AF Hamdan, Samir M.
   Loparo, Joseph J.
   Takahashi, Masateru
   Richardson, Charles C.
   van Oijen, Antoine M.
TI Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis
SO NATURE
LA English
DT Article
ID okazaki fragment synthesis; bacteriophage t7; single-molecule; polymerase; fork; primase; processivity; proteins; dissociation; extension
AB In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading- strand polymerase to advance in a continuous fashion, but forces the lagging- strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging- strand polymerase restarts at short intervals and produces Okazaki fragments(1,2).At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging- strand DNA polymerase so that it advances in parallel with the leading- strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis(3). Here we use single- molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.
C1 [Hamdan, Samir M.; Loparo, Joseph J.; Takahashi, Masateru; Richardson, Charles C.; van Oijen, Antoine M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP van Oijen, AM (corresponding author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA.
EM antoine_van_oijen@hms.harvard.edu
FU National Institutes of Health [GM-077248, GM-54397]; National Science Foundation [CAREER 0543784]; Jane Coffin Childs Memorial Fund
NR 27
TC 122
Z9 141
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 336
EP U9
DI 10.1038/nature07512
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900044
PM 19029884
DA 2026-03-09
ER

PT J
AU Kim, MS
   Kondo, T
   Takada, I
   Youn, MY
   Yamamoto, Y
   Takahashi, S
   Matsumoto, T
   Fujiyama, S
   Shirode, Y
   Yamaoka, I
   Kitagawa, H
   Takeyama, KI
   Shibuya, H
   Ohtake, F
   Kato, S
AF Kim, Mi-Sun
   Kondo, Takeshi
   Takada, Ichiro
   Youn, Min-Young
   Yamamoto, Yoko
   Takahashi, Sayuri
   Matsumoto, Takahiro
   Fujiyama, Sally
   Shirode, Yuko
   Yamaoka, Ikuko
   Kitagawa, Hirochika
   Takeyama, Ken-Ichi
   Shibuya, Hiroshi
   Ohtake, Fumiaki
   Kato, Shigeaki
TI RETRACTED: DNA demethylation in hormone-induced transcriptional derepression (Retracted article. See vol. 486, pg. 280, 2012)
SO NATURE
LA English
DT Article; Retracted Publication
ID vitamin-d-receptor; nuclear receptor; glycosylase; epigenetics; promoter; activation; methylation; repair; sites; dnmt1
AB Epigenetic modifications at the histone level affect gene regulation in response to extracellular signals(1,2). However, regulated epigenetic modifications at the DNA level, especially active DNA demethylation, in gene activation are not well understood(3-5). Here we report that DNA methylation/demethylation is hormonally switched to control transcription of the cytochrome p450 27B1 (CYP27B1) gene. Reflecting vitamin-D-mediated transrepression of the CYP27B1 gene by the negative vitamin D response element (nVDRE)(6,7), methylation of CpG sites ((5m)CpG) is induced by vitamin D in this gene promoter. Conversely, treatment with parathyroid hormone, a hormone known to activate the CYP27B1 gene(8), induces active demethylation of the (5m)CpG sites in this promoter. Biochemical purification of a complex associated with the nVDRE-binding protein (VDIR, also known as TCF3)(6,7) identified two DNA methyl-transferases, DNMT1 and DNMT3B, for methylation of CpG sites(9), as well as a DNA glycosylase, MBD4 (ref. 10). Protein-kinase-C-phosphorylated MBD4 by parathyroid hormone stimulation promotes incision of methylated DNA through glycosylase activity(11), and a base-excision repair process seems to complete DNA demethylation in the MBD4-bound promoter. Such parathyroid-hormone- induced DNA demethylation and subsequent transcriptional derepression are impaired in Mbd4(-/-) mice(12). Thus, the present findings suggest that methylation switching at the DNA level contributes to the hormonal control of transcription.
C1 [Kim, Mi-Sun; Matsumoto, Takahiro; Fujiyama, Sally; Shirode, Yuko; Yamaoka, Ikuko; Ohtake, Fumiaki; Kato, Shigeaki] Japan Sci & Technol Agcy, ERATO, Kawaguchisi, Saitama 3320012, Japan.
   [Kim, Mi-Sun; Kondo, Takeshi; Takada, Ichiro; Youn, Min-Young; Yamamoto, Yoko; Takahashi, Sayuri; Matsumoto, Takahiro; Fujiyama, Sally; Shirode, Yuko; Yamaoka, Ikuko; Kitagawa, Hirochika; Takeyama, Ken-Ichi; Ohtake, Fumiaki; Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Kim, Mi-Sun; Shibuya, Hiroshi] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Cell Biol, Bunkyo Ku, Tokyo 1138510, Japan.
   [Kim, Mi-Sun; Shibuya, Hiroshi] Tokyo Med & Dent Univ, Sch Biomed Sci, Bunkyo Ku, Tokyo 1138510, Japan.
C3 Japan Science & Technology Agency (JST); University of Tokyo; Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU)
RP Kato, S (corresponding author), Japan Sci & Technol Agcy, ERATO, 4-1-8 Honcho, Kawaguchisi, Saitama 3320012, Japan.
EM uskato@mail.ecc.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology
NR 30
TC 179
Z9 204
U1 0
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 1007
EP 1012
DI 10.1038/nature08456
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700053
PM 19829383
DA 2026-03-09
ER

PT J
AU Nakanishi, Y
   Lu, B
   Gerard, C
   Iwasaki, A
AF Nakanishi, Yusuke
   Lu, Bao
   Gerard, Craig
   Iwasaki, Akiko
TI CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help
SO NATURE
LA English
DT Article
ID herpes-simplex-virus; dendritic cells; type-2 infection; memory; localization; responses; effector; immunity; ctl
AB CD4(+) T helper cells are well known for their role in providing critical signals during priming of cytotoxic CD8(+) T lymphocyte (CTL) responses in vivo. T-cell help is required for the generation of primary CTL responses as well as in promoting protective CD8(+) memory T-cell development(1). However, the role of CD4 help in the control of CTL responses at the effector stage is unknown. Here we show that fully helped effector CTLs are themselves not self-sufficient for entry into the infected tissue, but rely on the CD4(+) T cells to provide the necessary cue. CD4(+) T helper cells control the migration of CTL indirectly through the secretion of IFN-gamma and induction of local chemokine secretion in the infected tissue. Our results reveal a previously unappreciated role of CD4 help in mobilizing effector CTL to the peripheral sites of infection where they help to eliminate infected cells.
C1 [Nakanishi, Yusuke; Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Lu, Bao; Gerard, Craig] Harvard Univ, Childrens Hosp, Div Pulm, Sch Med, Boston, MA 02115 USA.
C3 Yale University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School
RP Iwasaki, A (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.
EM akiko.iwasaki@yale.edu
FU NIH [AI054359, AI062428, AI39759, HL51366]; Japan Society for the Promotion of Science; Burroughs Wellcome Investigators
NR 25
TC 451
Z9 568
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 NOV 26
PY 2009
VL 462
IS 7272
BP 510
EP U205
DI 10.1038/nature08511
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200045
PM 19898495
DA 2026-03-09
ER

PT J
AU Guo, P
   Hirano, M
   Herrin, BR
   Li, JX
   Yu, CL
   Sadlonova, A
   Cooper, MD
AF Guo, Peng
   Hirano, Masayuki
   Herrin, Brantley R.
   Li, Jianxu
   Yu, Cuiling
   Sadlonova, Andrea
   Cooper, Max D.
TI Dual nature of the adaptive immune system in lampreys
SO NATURE
LA English
DT Article
ID variable lymphocyte receptors; migration-inhibitory factor; t-cell repertoire; differentiation; evolution; responses; diversity; thymus; genes; diversification
AB Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine-rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomplete germline VLRA and VLRB genes. Here we show that in sea lampreys (Petromyzon marinus) VLRA and VLRB anticipatory receptors are expressed by separate lymphocyte populations by monoallelic VLRA or VLRB assembly, together with expression of cytosine deaminase 1 (CDA1) or 2 (CDA2), respectively. Distinctive gene expression profiles for VLRA(+) and VLRB+ lymphocytes resemble those of mammalian T and B cells. Although both the VLRA and the VLRB cells proliferate in response to antigenic stimulation, only the VLRB lymphocytes bind native antigens and differentiate into VLR antibody-secreting cells. Conversely, VLRA lymphocytes respond preferentially to a classical T-cell mitogen and upregulate the expression of the pro-inflammatory cytokine genes interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF). The finding of T-like and B-like lymphocytes in lampreys offers new insight into the evolution of adaptive immunity.
C1 [Guo, Peng; Hirano, Masayuki; Herrin, Brantley R.; Li, Jianxu; Yu, Cuiling; Sadlonova, Andrea; Cooper, Max D.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Guo, Peng; Hirano, Masayuki; Herrin, Brantley R.; Li, Jianxu; Yu, Cuiling; Sadlonova, Andrea; Cooper, Max D.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
C3 Emory University; Emory University
RP Cooper, MD (corresponding author), Emory Univ, Emory Vaccine Ctr, 1462 Clifton Rd NE, Atlanta, GA 30322 USA.
EM max.cooper@emory.edu
FU National Institutes of Health; Georgia Research Alliance; National Institute of Allergy and Infectious Diseases [R01AI072435, T32AI007051] Funding Source: NIH RePORTER
NR 50
TC 276
Z9 342
U1 1
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 796
EP U1
DI 10.1038/nature08068
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500029
PM 19474790
DA 2026-03-09
ER

PT J
AU Lu, R
   Markowetz, F
   Unwin, RD
   Leek, JT
   Airoldi, EM
   MacArthur, BD
   Lachmann, A
   Rozov, R
   Ma'ayan, A
   Boyer, LA
   Troyanskaya, OG
   Whetton, AD
   Lemischka, IR
AF Lu, Rong
   Markowetz, Florian
   Unwin, Richard D.
   Leek, Jeffrey T.
   Airoldi, Edoardo M.
   MacArthur, Ben D.
   Lachmann, Alexander
   Rozov, Roye
   Ma'ayan, Avi
   Boyer, Laurie A.
   Troyanskaya, Olga G.
   Whetton, Anthony D.
   Lemischka, Ihor R.
TI Systems-level dynamic analyses of fate change in murine embryonic stem cells
SO NATURE
LA English
DT Article
ID transcriptional regulatory circuitry; self-renewal; gene-expression; nanog; pluripotency; network; mouse; chromatin; oct4; differentiation
AB Molecular regulation of embryonic stem cell (ESC) fate involves a coordinated interaction between epigenetic(1-4), transcriptional(5-10) and translational(11,12) mechanisms. It is unclear how these different molecular regulatory mechanisms interact to regulate changes in stem cell fate. Here we present a dynamic systems-level study of cell fate change in murine ESCs following a well-defined perturbation. Global changes in histone acetylation, chromatin-bound RNA polymerase II, messenger RNA (mRNA), and nuclear protein levels were measured over 5 days after downregulation of Nanog, a key pluripotency regulator(13-15). Our data demonstrate how a single genetic perturbation leads to progressive widespread changes in several molecular regulatory layers, and provide a dynamic view of information flow in the epigenome, transcriptome and proteome. We observe that a large proportion of changes in nuclear protein levels are not accompanied by concordant changes in the expression of corresponding mRNAs, indicating important roles for translational and post-translational regulation of ESC fate. Gene-ontology analysis across different molecular layers indicates that although chromatin reconfiguration is important for altering cell fate, it is preceded by transcription-factor- mediated regulatory events. The temporal order of gene expression alterations shows the order of the regulatory network reconfiguration and offers further insight into the gene regulatory network. Our studies extend the conventional systems biology approach to include many molecular species, regulatory layers and temporal series, and underscore the complexity of the multi-layer regulatory mechanisms responsible for changes in protein expression that determine stem cell fate.
C1 [Lu, Rong; Lemischka, Ihor R.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Markowetz, Florian; Airoldi, Edoardo M.; Troyanskaya, Olga G.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Markowetz, Florian; Airoldi, Edoardo M.; Troyanskaya, Olga G.] Princeton Univ, Dept Comp Sci, Princeton, NJ 08544 USA.
   [Unwin, Richard D.; Whetton, Anthony D.] Univ Manchester, Wolfson Mol Imaging Ctr,Sch Canc & Imaging Sci, Manchester Acad Hlth Sci Ctr, Stem Cell & Leukaemia Prote Lab, Manchester M20 4QL, Lancs, England.
   [Leek, Jeffrey T.; MacArthur, Ben D.; Rozov, Roye; Lemischka, Ihor R.] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA.
   [Leek, Jeffrey T.; MacArthur, Ben D.; Rozov, Roye; Lemischka, Ihor R.] Mt Sinai Sch Med, Black Family Stem Cell Inst, New York, NY 10029 USA.
   [MacArthur, Ben D.; Lachmann, Alexander; Ma'ayan, Avi] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
   [MacArthur, Ben D.; Lachmann, Alexander; Ma'ayan, Avi] Mt Sinai Sch Med, Syst Biol Ctr New York, New York, NY 10029 USA.
   [Boyer, Laurie A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Princeton University; Princeton University; Princeton University; University of Manchester; 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; Massachusetts Institute of Technology (MIT)
RP Lemischka, IR (corresponding author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
EM rlu@stanford.edu; ihor.lemischka@mssm.edu
FU NIH; BBSRC; Leukaemia Research UK; US National Science Foundation; Division Of Mathematical Sciences; Direct For Mathematical & Physical Scien [0907439] Funding Source: National Science Foundation
NR 37
TC 235
Z9 290
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 NOV 19
PY 2009
VL 462
IS 7271
BP 358
EP U126
DI 10.1038/nature08575
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300046
PM 19924215
DA 2026-03-09
ER

PT J
AU Luan, B
   Zhao, J
   Wu, HY
   Duan, BY
   Shu, GW
   Wang, XY
   Li, DS
   Jia, WP
   Kang, JH
   Pei, G
AF Luan, Bing
   Zhao, Jian
   Wu, Haiya
   Duan, Baoyu
   Shu, Guangwen
   Wang, Xiaoying
   Li, Dangsheng
   Jia, Weiping
   Kang, Jiuhong
   Pei, Gang
TI Deficiency of a β-arrestin-2 signal complex contributes to insulin resistance
SO NATURE
LA English
DT Article
ID phosphatidylinositol 3-kinase; activation; protein; kinase; akt; src; obesity; phosphorylation; transduction; pathways
AB Insulin resistance, a hallmark of type 2 diabetes, is a defect of insulin in stimulating insulin receptor signalling(1,2), which has become one of the most serious public health threats. Upon stimulation by insulin, insulin receptor recruits and phosphorylates insulin receptor substrate proteins(3), leading to activation of the phosphatidylinositol-3-OH kinase (PI(3) K)-Akt pathway. Activated Akt phosphorylates downstream kinases and transcription factors, thus mediating most of the metabolic actions of insulin(4-6). beta-arrestins mediate biological functions of G-protein-coupled receptors by linking activated receptors with distinct sets of accessory and effecter proteins, thereby determining the specificity, efficiency and capacity of signals(7-11). Here we show that in diabetic mouse models, beta-arrestin-2 is severely downregulated. Knockdown of beta-arrestin-2 exacerbates insulin resistance, whereas administration of beta-arrestin-2 restores insulin sensitivity in mice. Further investigation reveals that insulin stimulates the formation of a new beta-arrestin-2 signal complex, in which beta-arrestin-2 scaffolds Akt and Src to insulin receptor. Loss or dysfunction of beta-arrestin-2 results in deficiency of this signal complex and disturbance of insulin signalling in vivo, thereby contributing to the development of insulin resistance and progression of type 2 diabetes. Our findings provide new insight into the molecular pathogenesis of insulin resistance, and implicate new preventive and therapeutic strategies against insulin resistance and type 2 diabetes.
C1 [Luan, Bing; Zhao, Jian; Duan, Baoyu; Shu, Guangwen; Kang, Jiuhong; Pei, Gang] Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.
   [Luan, Bing; Zhao, Jian; Duan, Baoyu; Shu, Guangwen; Kang, Jiuhong; Pei, Gang] Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China.
   [Li, Dangsheng] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Informat Ctr Life Sci, Shanghai 200031, Peoples R China.
   [Wu, Haiya; Jia, Weiping] Shanghai Jiao Tong Univ, Dept Endocrinol & Metab, Affiliated Peoples Hosp 6, Shanghai, Peoples R China.
   [Wu, Haiya; Jia, Weiping] Shanghai Diabet Inst, Shanghai, Peoples R China.
   [Wu, Haiya; Jia, Weiping] Shanghai Clin Ctr Diabet, Shanghai 200233, Peoples R China.
   [Wang, Xiaoying] Fudan Univ, Affiliated Zhongshan Hosp, Shanghai 200032, Peoples R China.
   [Pei, Gang] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
C3 Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences; Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS; Shanghai Jiao Tong University; Fudan University; Tongji University
RP Pei, G (corresponding author), Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.
EM gpei@sibs.ac.cn
FU Ministry of Science and Technology [2005CB522406, 2006CB943900, 2007CB947904, 2007CB947100, 2007CB948000, 2009CB941100]; National Natural Science Foundation of China [30621091, 30625014, 30623003, 30871285, 90713047]; Shanghai Municipal Commission for Science and Technology [07PJ14099, 06DZ22032]; Chinese Academy of Sciences [KSCX2-YW-R-56, 2007KIP204]
NR 26
TC 196
Z9 236
U1 0
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 26
PY 2009
VL 457
IS 7233
BP 1146
EP U105
DI 10.1038/nature07617
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100044
PM 19122674
DA 2026-03-09
ER

PT J
AU Zhang, YB
   Tang, TT
   Girit, C
   Hao, Z
   Martin, MC
   Zettl, A
   Crommie, MF
   Shen, YR
   Wang, F
AF Zhang, Yuanbo
   Tang, Tsung-Ta
   Girit, Caglar
   Hao, Zhao
   Martin, Michael C.
   Zettl, Alex
   Crommie, Michael F.
   Shen, Y. Ron
   Wang, Feng
TI Direct observation of a widely tunable bandgap in bilayer graphene
SO NATURE
LA English
DT Article
ID berrys phase
AB The electronic bandgap is an intrinsic property of semiconductors and insulators that largely determines their transport and optical properties. As such, it has a central role in modern device physics and technology and governs the operation of semiconductor devices such as p-n junctions, transistors, photodiodes and lasers(1). A tunable bandgap would be highly desirable because it would allow great flexibility in design and optimization of such devices, in particular if it could be tuned by applying a variable external electric field. However, in conventional materials, the bandgap is fixed by their crystalline structure, preventing such bandgap control. Here we demonstrate the realization of a widely tunable electronic bandgap in electrically gated bilayer graphene. Using a dual-gate bilayer graphene field-effect transistor (FET)(2) and infrared microspectroscopy(3-5), we demonstrate a gate-controlled, continuously tunable bandgap of up to 250 meV. Our technique avoids uncontrolled chemical doping(6-8) and provides direct evidence of a widely tunable bandgap-spanning a spectral range from zero to mid-infrared-that has eluded previous attempts(2,9). Combined with the remarkable electrical transport properties of such systems, this electrostatic bandgap control suggests novel nanoelectronic and nanophotonic device applications based on graphene.
C1 [Zhang, Yuanbo; Tang, Tsung-Ta; Girit, Caglar; Zettl, Alex; Crommie, Michael F.; Shen, Y. Ron; Wang, Feng] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Hao, Zhao; Martin, Michael C.] Univ Calif Berkeley, Lawrence Berkeley Lab, Adv Light Source Div, Berkeley, CA 94720 USA.
   [Zettl, Alex; Crommie, Michael F.; Shen, Y. Ron; Wang, Feng] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Hao, Zhao] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Earth Sci, 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; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Wang, F (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
EM fengwang76@berkeley.edu
FU Office of Basic Energy Sciences, US Department of Energy [DE-AC03-76SF0098, DE-AC02-05CH11231]; Sloan fellowship; Miller fellowship; National Science Council of Taiwan
NR 26
TC 3201
Z9 3732
U1 23
U2 2121
PU NATURE PUBLISHING 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 11
PY 2009
VL 459
IS 7248
BP 820
EP 823
DI 10.1038/nature08105
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500034
PM 19516337
DA 2026-03-09
ER

PT J
AU Kondo, T
   Khasanov, R
   Takeuchi, T
   Schmalian, J
   Kaminski, A
AF Kondo, Takeshi
   Khasanov, Rustem
   Takeuchi, Tsunehiro
   Schmalian, Joerg
   Kaminski, Adam
TI Competition between the pseudogap and superconductivity in the high-Tc copper oxides
SO NATURE
LA English
DT Article
ID high-temperature superconductors; cuprate superconductors; superfluid density; underdoped bi2212; normal-state; bi2sr2cacu2o8+delta; gaps
AB In a classical Bardeen - Cooper - Schrieffer superconductor, pairing and coherence of electrons are established simultaneously below the critical transition temperature ( T-c), giving rise to a gap in the electronic energy spectrum. In the high- T-c copper oxide superconductors, however, a pseudogap(1-8) extends above T-c. The relationship between the pseudogap and superconductivity is one of the central issues in this field(9-17). Spectral gaps arising from pairing precursors are qualitatively similar to those caused by competing electronic states, rendering a standard approach to their analysis inconclusive(10-16). The issue can be settled, however, by studying the correlation between the weights associated with the pseudogap and superconductivity spectral features. Here we report a study of two spectral weights using angle- resolved photo-emission spectroscopy. The weight of the superconducting coherent peak increases away from the node following the trend of the superconducting gap, but starts to decrease in the antinodal region. This striking non- monotonicity reveals the presence of a competing state. We emonstrate a direct correlation, for different values of momenta and doping, between the loss in the low- energy spectral weight arising from the opening of the pseudogap and a decrease in the spectral weight associated with superconductivity. We therefore conclude that the pseudogap competes with the superconductivity by depleting the spectral weight available for pairing.
C1 [Kondo, Takeshi; Schmalian, Joerg; Kaminski, Adam] Iowa State Univ, Ames Lab, Ames, IA 50011 USA.
   [Kondo, Takeshi; Schmalian, Joerg; Kaminski, Adam] Iowa State Univ, Dept Phys & Astron, Ames, IA 50011 USA.
   [Khasanov, Rustem] Paul Scherrer Inst, Lab Muon Spin Spect, CH-5232 Villigen, Switzerland.
   [Takeuchi, Tsunehiro] Nagoya Univ, Dept Crystalline Mat Sci, Nagoya, Aichi 4648603, Japan.
   [Takeuchi, Tsunehiro] Nagoya Univ, EcoTopia Sci Inst, Nagoya, Aichi 4648603, Japan.
C3 United States Department of Energy (DOE); Ames National Laboratory; Iowa State University; Iowa State University; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Nagoya University; Nagoya University
RP Kaminski, A (corresponding author), Iowa State Univ, Ames Lab, Ames, IA 50011 USA.
EM kondo@ameslab.gov; kaminski@ameslab.gov
FU Basic Energy Sciences; US Department of Energy
NR 30
TC 237
Z9 273
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 JAN 15
PY 2009
VL 457
IS 7227
BP 296
EP 300
DI 10.1038/nature07644
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900035
PM 19148096
DA 2026-03-09
ER

PT J
AU Kaplan, N
   Moore, IK
   Fondufe-Mittendorf, Y
   Gossett, AJ
   Tillo, D
   Field, Y
   LeProust, EM
   Hughes, TR
   Lieb, JD
   Widom, J
   Segal, E
AF Kaplan, Noam
   Moore, Irene K.
   Fondufe-Mittendorf, Yvonne
   Gossett, Andrea J.
   Tillo, Desiree
   Field, Yair
   LeProust, Emily M.
   Hughes, Timothy R.
   Lieb, Jason D.
   Widom, Jonathan
   Segal, Eran
TI The DNA-encoded nucleosome organization of a eukaryotic genome
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; high-resolution; multiple alignment; promoter element; yeast genome; sequence; histone; transcription; sites; core
AB Nucleosome organization is critical for gene regulation(1). In living cells this organization is determined by multiple factors, including the action of chromatin remodellers(2), competition with site-specific DNA-binding proteins(3), and the DNA sequence preferences of the nucleosomes themselves(4-8). However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo(7,9-11), because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for similar to 40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.
C1 [Moore, Irene K.; Fondufe-Mittendorf, Yvonne; Widom, Jonathan] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA.
   [Kaplan, Noam; Field, Yair; Segal, Eran] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Segal, Eran] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
   [Gossett, Andrea J.; Lieb, Jason D.] Univ N Carolina, Dept Biol, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Gossett, Andrea J.; Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Tillo, Desiree; Hughes, Timothy R.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [LeProust, Emily M.] Genom LSSU, Agilent Technol Inc, Santa Clara, CA 95051 USA.
   [Hughes, Timothy R.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
   [Hughes, Timothy R.] Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
C3 Northwestern University; Weizmann Institute of Science; Weizmann Institute of Science; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of Toronto; Agilent Technologies; University of Toronto; University of Toronto
RP Widom, J (corresponding author), Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, 2153 Sheridan Rd, Evanston, IL 60208 USA.
EM j-widom@northwestern.edu; eran.segal@weizmann.ac.il
FU CIHR; NIH; European Research Council (ERC); NSERC; Lineberger Comprehensive Cancer Center; University Cancer Research Funds
NR 37
TC 955
Z9 1212
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 19
PY 2009
VL 458
IS 7236
BP 362
EP U129
DI 10.1038/nature07667
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600046
PM 19092803
DA 2026-03-09
ER

PT J
AU Ganem, NJ
   Godinho, SA
   Pellman, D
AF Ganem, Neil J.
   Godinho, Susana A.
   Pellman, David
TI A mechanism linking extra centrosomes to chromosomal instability
SO NATURE
LA English
DT Article
ID merotelic kinetochore orientation; clonal evolution; cancer-cells; aneuploidy; amplification; mitosis; numbers
AB Chromosomal instability (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes(1-4). However, a direct mechanistic link between extra centrosomes and CIN has not been established. It has been proposed that extra centrosomes generate CIN by promoting multipolar anaphase, a highly abnormal division that produces three or more aneuploid daughter cells. Here we use long-term live-cell imaging to demonstrate that cells with multiple centrosomes rarely undergo multipolar cell divisions, and the progeny of these divisions are typically inviable. Thus, multipolar divisions cannot explain observed rates of CIN. In contrast, we observe that CIN cells with extra centrosomes routinely undergo bipolar cell divisions, but display a significantly increased frequency of lagging chromosomes during anaphase. To define the mechanism underlying this mitotic defect, we generated cells that differ only in their centrosome number. We demonstrate that extra centrosomes alone are sufficient to promote chromosome missegregation during bipolar cell division. These segregation errors are a consequence of cells passing through a transient 'multipolar spindle intermediate' in which merotelic kinetochore-microtubule attachment errors accumulate before centrosome clustering and anaphase. These findings provide a direct mechanistic link between extra centrosomes and CIN, two common characteristics of solid tumours. We propose that this mechanism may be a common underlying cause of CIN in human cancer.
C1 [Ganem, Neil J.; Godinho, Susana A.; Pellman, David] Harvard Univ, Sch Med,Dept Pediat Oncol, Dana Farber Canc Inst,Dept Cell Biol, Howard Hughes Med Inst,Childrens Hosp, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Boston Children's Hospital
RP Pellman, D (corresponding author), Harvard Univ, Sch Med,Dept Pediat Oncol, Dana Farber Canc Inst,Dept Cell Biol, Howard Hughes Med Inst,Childrens Hosp, 44 Binney St, Boston, MA 02115 USA.
EM david_pellman@dfci.harvard.edu
FU Leukemia and Lymphoma Society; NIH [GM083299]
NR 30
TC 1120
Z9 1365
U1 0
U2 150
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 278
EP U146
DI 10.1038/nature08136
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000045
PM 19506557
DA 2026-03-09
ER

PT J
AU Beaumont, HJE
   Gallie, J
   Kost, C
   Ferguson, GC
   Rainey, PB
AF Beaumont, Hubertus J. E.
   Gallie, Jenna
   Kost, Christian
   Ferguson, Gayle C.
   Rainey, Paul B.
TI Experimental evolution of bet hedging
SO NATURE
LA English
DT Article
ID pseudomonas-fluorescens; experimental populations; adaptive divergence; diversity
AB Bet hedging-stochastic switching between phenotypic states(1-3)-is a canonical example of an evolutionary adaptation that facilitates persistence in the face of fluctuating environmental conditions. Although bet hedging is found in organisms ranging from bacteria to humans(4-10), direct evidence for an adaptive origin of this behaviour is lacking(11). Here we report the de novo evolution of bet hedging in experimental bacterial populations. Bacteria were subjected to an environment that continually favoured new phenotypic states. Initially, our regime drove the successive evolution of novel phenotypes by mutation and selection; however, in two (of 12) replicates this trend was broken by the evolution of bet-hedging genotypes that persisted because of rapid stochastic phenotype switching. Genome re-sequencing of one of these switching types revealed nine mutations that distinguished it from the ancestor. The final mutation was both necessary and sufficient for rapid phenotype switching; nonetheless, the evolution of bet hedging was contingent upon earlier mutations that altered the relative fitness effect of the final mutation. These findings capture the adaptive evolution of bet hedging in the simplest of organisms, and suggest that risk-spreading strategies may have been among the earliest evolutionary solutions to life in fluctuating environments.
C1 [Beaumont, Hubertus J. E.; Gallie, Jenna; Kost, Christian; Ferguson, Gayle C.; Rainey, Paul B.] Massey Univ, Allan Wilson Ctr Mol Ecol & Evolut, N Shore Mail Ctr, North Shore 0745, Auckland, New Zealand.
   [Beaumont, Hubertus J. E.; Gallie, Jenna; Kost, Christian; Ferguson, Gayle C.; Rainey, Paul B.] Massey Univ, New Zealand Inst Adv Study, N Shore Mail Ctr, N Shore City 0745, Auckland, New Zealand.
   [Beaumont, Hubertus J. E.] Leiden Univ, Inst Biol Leiden, NL-2300 RA Leiden, Netherlands.
C3 Massey University; Massey University; Leiden University - Excl LUMC; Leiden University
RP Beaumont, HJE (corresponding author), Leiden Univ, Inst Biol Leiden, POB 9505, NL-2300 RA Leiden, Netherlands.
EM h.j.e.beaumont@biology.leidenuniv.nl
FU Royal Society of New Zealand; Netherlands Organisation for Scientific Research(NWO); New Zealand Foundation for Research, Science and Technology; Alexander von Humboldt Foundation, Germany
NR 30
TC 465
Z9 559
U1 4
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 NOV 5
PY 2009
VL 462
IS 7269
BP 90
EP U97
DI 10.1038/nature08504
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200038
PM 19890329
DA 2026-03-09
ER

PT J
AU Takeuchi, JK
   Bruneau, BG
AF Takeuchi, Jun K.
   Bruneau, Benoit G.
TI Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors
SO NATURE
LA English
DT Article
ID chromatin-remodeling complex; anteroposterior axis; stem-cells; mesp1; differentiation; transcription; gene; expression; induction; myocardin
AB Heart disease is the leading cause of mortality and morbidity in the western world. The heart has little regenerative capacity after damage, leading to much interest in understanding the factors required to produce new cardiac myocytes. Despite a robust understanding of the molecular networks regulating cardiac differentiation(1,2), no single transcription factor or combination of factors has been shown to activate the cardiac gene program de novo in mammalian cells or tissues. Here we define the minimal requirements for transdifferentiation of mouse mesoderm to cardiac myocytes. We show that two cardiac transcription factors, Gata4 and Tbx5, and a cardiac-specific subunit of BAF chromatin-remodelling complexes, Baf60c (also called Smarcd3), can direct ectopic differentiation of mouse mesoderm into beating cardiomyocytes, including the normally non-cardiogenic posterior mesoderm and the extraembryonic mesoderm of the amnion. Gata4 with Baf60c initiated ectopic cardiac gene expression. Addition of Tbx5 allowed differentiation into contracting cardiomyocytes and repression of non-cardiac mesodermal genes. Baf60c was essential for the ectopic cardiogenic activity of Gata4 and Tbx5, partly by permitting binding of Gata4 to cardiac genes, indicating a novel instructive role for BAF complexes in tissues-specific regulation. The combined function of these factors establishes a robust mechanism for controlling cellular differentiation, and may allow reprogramming of new cardiomyocytes for regenerative purposes.
C1 [Takeuchi, Jun K.; Bruneau, Benoit G.] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Takeuchi, Jun K.] Tokyo Inst Technol, Global Edge Inst, Div Cardiovasc Res, Midori Ku, Kanagawa 2268503, Japan.
   [Bruneau, Benoit G.] Univ Calif San Francisco, Dept Pediat, Cardiovasc Res Inst, San Francisco, CA 94158 USA.
   [Bruneau, Benoit G.] Univ Calif San Francisco, Inst Regenerat Med, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; The J David Gladstone Institutes; Institute of Science Tokyo; Tokyo Institute of Technology; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Bruneau, BG (corresponding author), Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
EM takeuchi.j.ab@m.titech.ac.jp; bbruneau@gladstone.ucsf.edu
FU Human Frontiers Science Program CDA; MEXT's program for young independent researchers; Mitsubishi Foundation; Takeda Science Foundation; NHLBI [R01HL085860]; NIH/NCRR [C06 RR018928]; William H. Younger, Jr
NR 30
TC 421
Z9 533
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 JUN 4
PY 2009
VL 459
IS 7247
BP 708
EP U112
DI 10.1038/nature08039
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600045
PM 19396158
DA 2026-03-09
ER

PT J
AU Du, JF
   Rong, X
   Zhao, N
   Wang, Y
   Yang, JH
   Liu, RB
AF Du, Jiangfeng
   Rong, Xing
   Zhao, Nan
   Wang, Ya
   Yang, Jiahui
   Liu, R. B.
TI Preserving electron spin coherence in solids by optimal dynamical decoupling
SO NATURE
LA English
DT Article
ID coupled electron; quantum; manipulation; qubits
AB To exploit the quantum coherence of electron spins in solids in future technologies such as quantum computing(1,2), it is first vital to overcome the problem of spin decoherence due to their coupling to the noisy environment. Dynamical decoupling(3-9), which uses stroboscopic spin flips to give an average coupling to the environment that is effectively zero, is a particularly promising strategy for combating decoherence because it can be naturally integrated with other desired functionalities, such as quantum gates. Errors are inevitably introduced in each spin flip, so it is desirable to minimize the number of control pulses used to realize dynamical decoupling having a given level of precision. Such optimal dynamical decoupling sequences have recently been explored(9-12). The experimental realization of optimal dynamical decoupling in solid-state systems, however, remains elusive. Here we use pulsed electron paramagnetic resonance to demonstrate experimentally optimal dynamical decoupling for preserving electron spin coherence in irradiated malonic acid crystals at temperatures from 50 K to room temperature. Using a seven-pulse optimal dynamical decoupling sequence, we prolonged the spin coherence time to about 30 mu s; it would otherwise be about 0.04 mu s without control or 6.2 mu s under one-pulse control. By comparing experiments with microscopic theories, we have identified the relevant electron spin decoherence mechanisms in the solid. Optimal dynamical decoupling may be applied to other solid-state systems, such as diamonds with nitrogen-vacancy centres(13-15), and so lay the foundation for quantum coherence control of spins in solids at room temperature.
C1 [Du, Jiangfeng; Rong, Xing; Wang, Ya; Yang, Jiahui] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
   [Du, Jiangfeng; Rong, Xing; Wang, Ya; Yang, Jiahui] Univ Sci & Technol China, Dept Modern Phys, Hefei 230026, Anhui, Peoples R China.
   [Zhao, Nan; Liu, R. B.] Chinese Univ Hong Kong, Dept Phys, Shatin, Hong Kong, Peoples R China.
C3 Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese University of Hong Kong
RP Du, JF (corresponding author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
EM djf@ustc.edu.cn; rbliu@phy.cuhk.edu.hk
FU National Natural Science Foundation of China; Chinese Academy of Sciences; Ministry of Education of PRC; National Fundamental Research Program [2007CB925200]; Hong Kong GRF Projects [CUHK401906, CUHK402209]
NR 30
TC 346
Z9 390
U1 2
U2 222
PU NATURE PUBLISHING 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 29
PY 2009
VL 461
IS 7268
BP 1265
EP 1268
DI 10.1038/nature08470
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800045
PM 19865168
DA 2026-03-09
ER

PT J
AU Jiao, LY
   Zhang, L
   Wang, XR
   Diankov, G
   Dai, HJ
AF Jiao, Liying
   Zhang, Li
   Wang, Xinran
   Diankov, Georgi
   Dai, Hongjie
TI Narrow graphene nanoribbons from carbon nanotubes
SO NATURE
LA English
DT Article
ID few-layer graphene
AB Graphene nanoribbons (GNRs) are materials with properties distinct from those of other carbon allotropes(1-5). The all-semiconducting nature of sub-10-nm GNRs could bypass the problem of the extreme chirality dependence of the metal or semiconductor nature of carbon nanotubes (CNTs) in future electronics(1,2). Currently, making GNRs using lithographic(3,4,6), chemical(7-9) or sonochemical(1) methods is challenging. It is difficult to obtain GNRs with smooth edges and controllable widths at high yields. Here we show an approach to making GNRs by unzipping multi-walled carbon nanotubes by plasma etching of nanotubes partly embedded in a polymer film. The GNRs have smooth edges and a narrow width distribution (10-20 nm). Raman spectroscopy and electrical transport measurements reveal the high quality of the GNRs. Unzipping CNTs with well-defined structures in an array will allow the production of GNRs with controlled widths, edge structures, placement and alignment in a scalable fashion for device integration.
C1 [Jiao, Liying; Zhang, Li; Wang, Xinran; Diankov, Georgi; Dai, Hongjie] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Jiao, Liying; Zhang, Li; Wang, Xinran; Diankov, Georgi; Dai, Hongjie] Stanford Univ, Adv Mat Lab, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Dai, HJ (corresponding author), Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
EM hdai@stanford.edu
FU Microelectronics Advanced Research Corporation - Materials, Structures, and Devices Center; Intel; US Office of Naval Research
NR 29
TC 2128
Z9 2514
U1 9
U2 1550
PU 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 16
PY 2009
VL 458
IS 7240
BP 877
EP 880
DI 10.1038/nature07919
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500040
PM 19370031
DA 2026-03-09
ER

PT J
AU Eichmann, U
   Nubbemeyer, T
   Rottke, H
   Sandner, W
AF Eichmann, U.
   Nubbemeyer, T.
   Rottke, H.
   Sandner, W.
TI Acceleration of neutral atoms in strong short-pulse laser fields
SO NATURE
LA English
DT Article
ID multiphoton ionization; electron-beams; plasma; light; particles; optics; waves
AB A charged particle exposed to an oscillating electric field experiences a force proportional to the cycle-averaged intensity gradient. This so-called ponderomotive force(1) plays a major part in a variety of physical situations such as Paul traps(2,3) for charged particles, electron diffraction in strong (standing) laser fields(4-6) (the Kapitza-Dirac effect) and laser-based particle acceleration(7-9). Comparably weak forces on neutral atoms in inhomogeneous light fields may arise from the dynamical polarization of an atom(10-12); these are physically similar to the cycle-averaged forces. Here we observe previously unconsidered extremely strong kinematic forces on neutral atoms in short-pulse laser fields. We identify the ponderomotive force on electrons as the driving mechanism, leading to ultrastrong acceleration of neutral atoms with a magnitude as high as similar to 10(14) times the Earth's gravitational acceleration, g. To our knowledge, this is by far the highest observed acceleration on neutral atoms in external fields and may lead to new applications in both fundamental and applied physics.
C1 [Eichmann, U.; Nubbemeyer, T.; Rottke, H.; Sandner, W.] Max Born Inst, D-12489 Berlin, Germany.
   [Eichmann, U.; Sandner, W.] Tech Univ Berlin, Inst Opt & Atomare Phys, D-10632 Berlin, Germany.
C3 Leibniz Association; Max Born Institute for Nonlinear Optics & Short Term Spectroscopy; Technical University of Berlin
RP Eichmann, U (corresponding author), Max Born Inst, Max Born Str 2A, D-12489 Berlin, Germany.
EM ulli.eichmann@mbi-berlin.de
NR 25
TC 221
Z9 243
U1 3
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 29
PY 2009
VL 461
IS 7268
BP 1261
EP U93
DI 10.1038/nature08481
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800044
PM 19865167
DA 2026-03-09
ER

PT J
AU Lee, HC
   Chang, SS
   Choudhary, S
   Aalto, AP
   Maiti, M
   Bamford, DH
   Liu, Y
AF Lee, Heng-Chi
   Chang, Shwu-Shin
   Choudhary, Swati
   Aalto, Antti P.
   Maiti, Mekhala
   Bamford, Dennis H.
   Liu, Yi
TI qiRNA is a new type of small interfering RNA induced by DNA damage
SO NATURE
LA English
DT Article
ID neurospora-crassa; protein; transcription; sirna; methylation; sensitivity; histidine; interacts; mutants; pathway
AB RNA interference pathways use small RNAs to mediate gene silencing in eukaryotes. In addition to small interfering RNAs (siRNAs) and microRNAs, several types of endogenously produced small RNAs have important roles in gene regulation, germ cell maintenance and transposon silencing(1-4). The production of some of these RNAs requires the synthesis of aberrant RNAs (aRNAs) or pre-siRNAs, which are specifically recognized by RNA-dependent RNA polymerases to make double-stranded RNA. The mechanism for aRNA synthesis and recognition is largely unknown. Here we show that DNA damage induces the expression of the Argonaute protein QDE-2 and a new class of small RNAs in the filamentous fungus Neurospora crassa. This class of small RNAs, known as qiRNAs because of their interaction with QDE-2, are about 20-21 nucleotides long (several nucleotides shorter than Neurospora siRNAs), with a strong preference for uridine at the 59 end, and originate mostly from the ribosomal DNA locus. The production of qiRNAs requires the RNA-dependent RNA polymerase QDE-1, the Werner and Bloom RecQ DNA helicase homologue QDE-3 and dicers. qiRNA biogenesis also requires DNA-damage-induced aRNAs as precursors, a process that is dependent on both QDE-1 and QDE-3. Notably, our results suggest that QDE-1 is the DNA-dependent RNA polymerase that produces aRNAs. Furthermore, the Neurospora RNA interference mutants show increased sensitivity to DNA damage, suggesting a role for qiRNAs in the DNA-damage response by inhibiting protein translation.
C1 [Lee, Heng-Chi; Chang, Shwu-Shin; Choudhary, Swati; Maiti, Mekhala; Liu, Yi] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
   [Aalto, Antti P.; Bamford, Dennis H.] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland.
   [Aalto, Antti P.; Bamford, Dennis H.] Univ Helsinki, Dept Biol & Environm Sci, FIN-00014 Helsinki, Finland.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Helsinki; University of Helsinki
RP Liu, Y (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Physiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM yi.liu@UTSouthwestern.edu
FU Welch Foundation; National Institutes of Health (NIH); Academy of Finland Finnish Centre of Excellence [1213467, 1213992]; Helsinki Graduate School in Biotechnology and Molecular Biology
NR 31
TC 222
Z9 270
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 MAY 14
PY 2009
VL 459
IS 7244
BP 274
EP U163
DI 10.1038/nature08041
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100046
PM 19444217
DA 2026-03-09
ER

PT J
AU Haas, BJ
   Kamoun, S
   Zody, MC
   Jiang, RHY
   Handsaker, RE
   Cano, LM
   Grabherr, M
   Kodira, CD
   Raffaele, S
   Torto-Alalibo, T
   Bozkurt, TO
   Ah-Fong, AMV
   Alvarado, L
   Anderson, VL
   Armstrong, MR
   Avrova, A
   Baxter, L
   Beynon, J
   Boevink, PC
   Bollmann, SR
   Bos, JIB
   Bulone, V
   Cai, GH
   Cakir, C
   Carrington, JC
   Chawner, M
   Conti, L
   Costanzo, S
   Ewan, R
   Fahlgren, N
   Fischbach, MA
   Fugelstad, J
   Gilroy, EM
   Gnerre, S
   Green, PJ
   Grenville-Briggs, LJ
   Griffith, J
   Grünwald, NJ
   Horn, K
   Horner, NR
   Hu, CH
   Huitema, E
   Jeong, DH
   Jones, AME
   Jones, JDG
   Jones, RW
   Karlsson, EK
   Kunjeti, SG
   Lamour, K
   Liu, ZY
   Ma, LJ
   MacLean, D
   Chibucos, MC
   McDonald, H
   McWalters, J
   Meijer, HJG
   Morgan, W
   Morris, PF
   Munro, CA
   O'Neill, K
   Ospina-Giraldo, M
   Pinzón, A
   Pritchard, L
   Ramsahoye, B
   Ren, QH
   Restrepo, S
   Roy, S
   Sadanandom, A
   Savidor, A
   Schornack, S
   Schwartz, DC
   Schumann, UD
   Schwessinger, B
   Seyer, L
   Sharpe, T
   Silvar, C
   Song, J
   Studholme, DJ
   Sykes, S
   Thines, M
   van de Vondervoort, PJI
   Phuntumart, V
   Wawra, S
   Weide, R
   Win, J
   Young, C
   Zhou, SG
   Fry, W
   Meyers, BC
   van West, P
   Ristaino, J
   Govers, F
   Birch, PRJ
   Whisson, SC
   Judelson, HS
   Nusbaum, C
AF Haas, Brian J.
   Kamoun, Sophien
   Zody, Michael C.
   Jiang, Rays H. Y.
   Handsaker, Robert E.
   Cano, Liliana M.
   Grabherr, Manfred
   Kodira, Chinnappa D.
   Raffaele, Sylvain
   Torto-Alalibo, Trudy
   Bozkurt, Tolga O.
   Ah-Fong, Audrey M. V.
   Alvarado, Lucia
   Anderson, Vicky L.
   Armstrong, Miles R.
   Avrova, Anna
   Baxter, Laura
   Beynon, Jim
   Boevink, Petra C.
   Bollmann, Stephanie R.
   Bos, Jorunn I. B.
   Bulone, Vincent
   Cai, Guohong
   Cakir, Cahid
   Carrington, James C.
   Chawner, Megan
   Conti, Lucio
   Costanzo, Stefano
   Ewan, Richard
   Fahlgren, Noah
   Fischbach, Michael A.
   Fugelstad, Johanna
   Gilroy, Eleanor M.
   Gnerre, Sante
   Green, Pamela J.
   Grenville-Briggs, Laura J.
   Griffith, John
   Gruenwald, Niklaus J.
   Horn, Karolyn
   Horner, Neil R.
   Hu, Chia-Hui
   Huitema, Edgar
   Jeong, Dong-Hoon
   Jones, Alexandra M. E.
   Jones, Jonathan D. G.
   Jones, Richard W.
   Karlsson, Elinor K.
   Kunjeti, Sridhara G.
   Lamour, Kurt
   Liu, Zhenyu
   Ma, LiJun
   MacLean, Daniel
   Chibucos, Marcus C.
   McDonald, Hayes
   McWalters, Jessica
   Meijer, Harold J. G.
   Morgan, William
   Morris, Paul F.
   Munro, Carol A.
   O'Neill, Keith
   Ospina-Giraldo, Manuel
   Pinzon, Andres
   Pritchard, Leighton
   Ramsahoye, Bernard
   Ren, Qinghu
   Restrepo, Silvia
   Roy, Sourav
   Sadanandom, Ari
   Savidor, Alon
   Schornack, Sebastian
   Schwartz, David C.
   Schumann, Ulrike D.
   Schwessinger, Ben
   Seyer, Lauren
   Sharpe, Ted
   Silvar, Cristina
   Song, Jing
   Studholme, David J.
   Sykes, Sean
   Thines, Marco
   van de Vondervoort, Peter J. I.
   Phuntumart, Vipaporn
   Wawra, Stephan
   Weide, Rob
   Win, Joe
   Young, Carolyn
   Zhou, Shiguo
   Fry, William
   Meyers, Blake C.
   van West, Pieter
   Ristaino, Jean
   Govers, Francine
   Birch, Paul R. J.
   Whisson, Stephen C.
   Judelson, Howard S.
   Nusbaum, Chad
TI Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
SO NATURE
LA English
DT Article
ID effector proteins; rxlr effectors; cell-death; plant; avirulence; avr3a; resistance; infection; genes
AB Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
C1 [Kamoun, Sophien; Cano, Liliana M.; Raffaele, Sylvain; Bozkurt, Tolga O.; Jones, Alexandra M. E.; Jones, Jonathan D. G.; MacLean, Daniel; Schornack, Sebastian; Schwessinger, Ben; Silvar, Cristina; Studholme, David J.; Thines, Marco; Win, Joe] Sainsbury Lab, Norwich NR4 7UH, Norfolk, England.
   [Haas, Brian J.; Zody, Michael C.; Handsaker, Robert E.; Grabherr, Manfred; Kodira, Chinnappa D.; Alvarado, Lucia; Gnerre, Sante; Karlsson, Elinor K.; Ma, LiJun; O'Neill, Keith; Sharpe, Ted; Sykes, Sean; Nusbaum, Chad] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA.
   [Kamoun, Sophien; Torto-Alalibo, Trudy; Bos, Jorunn I. B.; Cakir, Cahid; Huitema, Edgar; Liu, Zhenyu; Song, Jing; Young, Carolyn] Ohio State Univ, Ohio Agr Res & Dev Ctr, Dept Plant Pathol, Wooster, OH 44691 USA.
   [Zody, Michael C.] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75124 Uppsala, Sweden.
   [Jiang, Rays H. Y.; Meijer, Harold J. G.; van de Vondervoort, Peter J. I.; Weide, Rob; Govers, Francine] Univ Wageningen & Res Ctr, Phytopathol Lab, NL-6708 PB Wageningen, Netherlands.
   [Ah-Fong, Audrey M. V.; Roy, Sourav; Judelson, Howard S.] Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA.
   [Anderson, Vicky L.; Grenville-Briggs, Laura J.; Horner, Neil R.; Schumann, Ulrike D.; Wawra, Stephan; van West, Pieter] Univ Aberdeen, Aberdeen Oomycete Lab, Coll Life Sci & Med, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
   [Armstrong, Miles R.; Avrova, Anna; Boevink, Petra C.; Gilroy, Eleanor M.; Pritchard, Leighton; Whisson, Stephen C.] Scottish Crop Res Inst, Plant Pathol Programme, Dundee DD2 5DA, Scotland.
   [Baxter, Laura; Beynon, Jim] Univ Warwick, Warwick CV35 9EF, England.
   [Bollmann, Stephanie R.; Gruenwald, Niklaus J.] ARS, USDA, Hort Crops Res Lab, Corvallis, OR 97330 USA.
   [Bulone, Vincent; Fugelstad, Johanna] AlbaNova Univ Ctr, Sch Biotechnol, Royal Inst Technol KTH, SE-10691 Stockholm, Sweden.
   [Cai, Guohong; Fry, William] Cornell Univ, Dept Plant Pathol & Plant Microbe Biol, Ithaca, NY 14853 USA.
   [Carrington, James C.; Fahlgren, Noah] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
   [Carrington, James C.; Fahlgren, Noah] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA.
   [Chawner, Megan; Griffith, John; Horn, Karolyn; McWalters, Jessica; Ospina-Giraldo, Manuel; Seyer, Lauren] Lafayette Coll, Dept Biol, Easton, PA 18042 USA.
   [Conti, Lucio; Ewan, Richard; Sadanandom, Ari] Univ Glasgow, Plant Mol Sci Fac Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
   [Costanzo, Stefano] ARS, USDA, Dale Bumpers Natl Rice Res Ctr, Stuttgart, AR 72160 USA.
   [Fischbach, Michael A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Green, Pamela J.; Jeong, Dong-Hoon; Meyers, Blake C.] Univ Delaware, Delaware Biotechnol Inst, Newark, DE 19711 USA.
   [Hu, Chia-Hui; Ristaino, Jean] N Carolina State Univ, Dept Plant Pathol, Raleigh, NC 27695 USA.
   [Jones, Richard W.] ARS, USDA, Beltsville, MD 20705 USA.
   [Kunjeti, Sridhara G.] Univ Delaware, Dept Plant & Soil Sci, Newark, DE 19716 USA.
   [Lamour, Kurt] Univ Tennessee, Dept Entomol & Plant Pathol, Knoxville, TN 37996 USA.
   [Chibucos, Marcus C.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
   [McDonald, Hayes] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA.
   [Morgan, William] Coll Wooster, Dept Biol, Wooster, OH 44691 USA.
   [Morris, Paul F.; Phuntumart, Vipaporn] Bowling Green State Univ, Dept Biol Sci, Bowling Green, OH 43403 USA.
   [Munro, Carol A.] Univ Aberdeen, Sch Med Sci, Coll Life Sci & Med, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
   [Pinzon, Andres; Restrepo, Silvia] Univ Los Andes, Mycol & Phytopathol Lab, Bogota, Colombia.
   [Ramsahoye, Bernard] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Canc Res Ctr, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Schwartz, David C.; Zhou, Shiguo] Univ Wisconsin, Dept Chem, Genet Lab, Ctr Biotechnol,Lab Mol & Computat Genom, Madison, WI 53706 USA.
   [Thines, Marco] Univ Hohenheim, Inst Bot 210, D-70593 Stuttgart, Germany.
   [Birch, Paul R. J.] Univ Dundee, SCRI, Coll Life Sci, Div Plant Sci, Dundee DD2 5DA, Scotland.
   [Ren, Qinghu] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Savidor, Alon] Tel Aviv Univ, Dept Plant Sci, IL-69978 Tel Aviv, Israel.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University System of Ohio; Ohio State University; Uppsala University; Wageningen University & Research; University of California System; University of California Riverside; University of Aberdeen; James Hutton Institute; University of Warwick; United States Department of Agriculture (USDA); Royal Institute of Technology; Cornell University; Oregon State University; Oregon State University; Lafayette College; University of Glasgow; United States Department of Agriculture (USDA); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Delaware; North Carolina State University; United States Department of Agriculture (USDA); University of Delaware; University of Tennessee System; University of Tennessee Knoxville; UT Institute of Agriculture; University System of Maryland; University of Maryland Baltimore; Vanderbilt University; University System of Ohio; College of Wooster; University System of Ohio; Bowling Green State University; University of Aberdeen; Universidad de los Andes (Colombia); University of Edinburgh; University of Wisconsin System; University of Wisconsin Madison; University Hohenheim; University of Dundee; James Hutton Institute; J. Craig Venter Institute; Tel Aviv University
RP Kamoun, S (corresponding author), Sainsbury Lab, Norwich NR4 7UH, Norfolk, England.
EM sophien.kamoun@tsl.ac.uk; chad@broad.mit.edu
FU National Research Initiative of the USDA Cooperative State Research, Education and Extension Service [2004-35600-15024, 2006-35600-16623]; National Science Foundation [EF-0333274, EF-0523670]; Gatsby Charitable Foundation; BBSRC [BB/E007120/1, BB/E006795/1, BB/G015244/1] Funding Source: UKRI; MRC [G0400284] Funding Source: UKRI; NERC [NE/F012578/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/E007120/1, BB/G015244/1, BB/C509123/1, BB/E006795/1, BBS/B/07152] Funding Source: researchfish; Medical Research Council [G0400284] Funding Source: researchfish; Natural Environment Research Council [NE/F012578/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Materials Research [0832760] Funding Source: National Science Foundation
NR 24
TC 1161
Z9 1508
U1 14
U2 512
PU NATURE PUBLISHING 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 17
PY 2009
VL 461
IS 7262
BP 393
EP 398
DI 10.1038/nature08358
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100039
PM 19741609
DA 2026-03-09
ER

PT J
AU Mandel, MJ
   Wollenberg, MS
   Stabb, EV
   Visick, KL
   Ruby, EG
AF Mandel, Mark J.
   Wollenberg, Michael S.
   Stabb, Eric V.
   Visick, Karen L.
   Ruby, Edward G.
TI A single regulatory gene is sufficient to alter bacterial host range
SO NATURE
LA English
DT Article
ID vibrio-fischeri; symbiotic colonization; biofilm formation; comparative genomics; euprymna-scolopes; sequence; interface; evolution; alignment; islands
AB Microbial symbioses are essential for the normal development and growth of animals(1-3). Often, symbionts must be acquired from the environment during each generation, and identification of the relevant symbiotic partner against a myriad of unwanted relationships is a formidable task(4). Although examples of this specificity are well-documented, the genetic mechanisms governing it are poorly characterized(5). Here we show that the two-component sensor kinase RscS is necessary and sufficient for conferring efficient colonization of Euprymna scolopes squid by bioluminescent Vibrio fischeri from the North Pacific Ocean. In the squid symbiont V. fischeri ES114, RscS controls light-organ colonization by inducing the Syp exopolysaccharide, a mediator of biofilm formation during initial infection. A genome-level comparison revealed that rscS, although present in squid symbionts, is absent from the fish symbiont V. fischeri MJ11. We found that heterologous expression of RscS in strain MJ11 conferred the ability to colonize E. scolopes in a manner comparable to that of natural squid isolates. Furthermore, phylogenetic analyses support an important role for rscS in the evolution of the squid symbiosis. Our results demonstrate that a regulatory gene can alter the host range of animal-associated bacteria. We show that, by encoding a regulator and not an effector that interacts directly with the host, a single gene can contribute to the evolution of host specificity by switching 'on' pre-existing capabilities for interaction with animal tissue.
C1 [Mandel, Mark J.; Wollenberg, Michael S.; Ruby, Edward G.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
   [Stabb, Eric V.] Univ Georgia, Dept Microbiol, Athens, GA 30602 USA.
   [Visick, Karen L.] Loyola Univ Chicago, Dept Microbiol & Immunol, Maywood, IL 60153 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; University System of Georgia; University of Georgia; Loyola University Chicago
RP Mandel, MJ (corresponding author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Microbiol & Immunol, 1550 Linden Dr, Madison, WI 53706 USA.
EM mmandel@wisc.edu
FU Gordon and Betty Moore Foundation Marine Microbial Genome Sequencing Project; National Institutes of Health - National Center for Research Resources; National Science Foundation Division of Integrative Organismal Systems; National Science Foundation CAREER Award; National Institute of General Medical Sciences; National Institute of General Medical Sciences National Research Service Award Postdoctoral Fellowship; National Science Foundation Predoctoral Fellowship and a National Institutes of Health Molecular Biosciences Training
NR 45
TC 166
Z9 223
U1 0
U2 63
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 215
EP U7
DI 10.1038/nature07660
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700046
PM 19182778
DA 2026-03-09
ER

PT J
AU Naito, K
   Zhang, F
   Tsukiyama, T
   Saito, H
   Hancock, CN
   Richardson, AO
   Okumoto, Y
   Tanisaka, T
   Wessler, SR
AF Naito, Ken
   Zhang, Feng
   Tsukiyama, Takuji
   Saito, Hiroki
   Hancock, C. Nathan
   Richardson, Aaron O.
   Okumoto, Yutaka
   Tanisaka, Takatoshi
   Wessler, Susan R.
TI Unexpected consequences of a sudden and massive transposon amplification on rice gene expression
SO NATURE
LA English
DT Article
ID nucleosome organization; elements; insertion; genome; regions; system
AB High-copy-number transposable elements comprise the majority of eukaryotic genomes where they are major contributors to gene and genome evolution(1). However, it remains unclear how a host genome can survive a rapid burst of hundreds or thousands of insertions because such bursts are exceedingly rare in nature and therefore difficult to observe in real time(2). In a previous study we reported that in a few rice strains the DNA transposon mPing was increasing its copy number by similar to 40 per plant per generation(3). Here we exploit the completely sequenced rice genome to determine 1,664 insertion sites using high-throughput sequencing of 24 individual rice plants and assess the impact of insertion on the expression of 710 genes by comparative microarray analysis. We find that the vast majority of transposable element insertions either upregulate or have no detectable effect on gene transcription. This modest impact reflects a surprising avoidance of exon insertions by mPing and a preference for insertion into 5' flanking sequences of genes. Furthermore, we document the generation of new regulatory networks by a subset of mPing insertions that render adjacent genes stress inducible. As such, this study provides evidence for models first proposed previously(4-6) for the involvement of transposable elements and other repetitive sequences in genome restructuring and gene regulation.
C1 [Naito, Ken; Zhang, Feng; Hancock, C. Nathan; Richardson, Aaron O.; Wessler, Susan R.] Univ Georgia, Dept Plant Biol, Athens, GA 30602 USA.
   [Naito, Ken; Tsukiyama, Takuji; Saito, Hiroki; Okumoto, Yutaka; Tanisaka, Takatoshi] Kyoto Univ, Grad Sch Agr, Div Agron & Hort Sci, Sakyo Ku, Kyoto 6068502, Japan.
C3 University System of Georgia; University of Georgia; Kyoto University
RP Wessler, SR (corresponding author), Univ Georgia, Dept Plant Biol, Athens, GA 30602 USA.
EM tanisaka@kais.kyoto-u.ac.jp; sue@plantbio.uga.edu
FU National Institute of Agrobiological Science in Japan [A123, A157]; NSF Plant Genome; University of Georgia Research Foundation; Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Scientific Research [21380004] Funding Source: KAKEN
NR 30
TC 375
Z9 430
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 OCT 22
PY 2009
VL 461
IS 7267
BP 1130
EP U232
DI 10.1038/nature08479
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600046
PM 19847266
DA 2026-03-09
ER

PT J
AU Blanchon, P
   Eisenhauer, A
   Fietzke, J
   Liebetrau, V
AF Blanchon, Paul
   Eisenhauer, Anton
   Fietzke, Jan
   Liebetrau, Volker
TI Rapid sea-level rise and reef back-stepping at the close of the last interglacial highstand
SO NATURE
LA English
DT Article
ID u-series; coral-reefs; precise; event; duration; system; record; rates
AB Widespread evidence of a +4-6-m sea-level highstand during the last interglacial period (Marine Isotope Stage 5e) has led to warnings that modern ice sheets will deteriorate owing to global warming and initiate a rise of similar magnitude by AD 2100 (ref. 1). The rate of this projected rise is based on ice-sheet melting simulations and downplays discoveries of more rapid ice loss(2,3). Knowing the rate at which sea level reached its highstand during the last interglacial period is fundamental in assessing if such rapid ice-loss processes could lead to future catastrophic sea-level rise. The best direct record of sea level during this highstand comes from well-dated fossil reefs in stable areas(4-6). However, this record lacks both reef-crest development up to the full highstand elevation, as inferred(7) from widespread intertidal indicators at +6m, and a detailed chronology, owing to the difficulty of replicating U-series ages on submillennial timescales(8). Here we present a complete reef-crest sequence for the last interglacial highstand and its U-series chronology from the stable northeast Yucatan peninsula, Mexico. We find that reef development during the highstand was punctuated by reef-crest demise at +3m and back-stepping to +6m. The abrupt demise of the lower-reef crest, but continuous accretion between the lower-lagoonal unit and the upper-reef crest, allows us to infer that this back-stepping occurred on an ecological timescale and was triggered by a 2-3-m jump in sea level. Using strictly reliable Th-230 ages of corals from the upper-reef crest, and improved stratigraphic screening of coral ages from other stable sites, we constrain this jump to have occurred similar to 121 kyr ago and conclude that it supports an episode of ice-sheet instability during the terminal phase of the last interglacial period.
C1 [Blanchon, Paul] Univ Nacl Autonoma Mexico, Inst Marine & Limnol Sci, Cancun, Quintana Roo, Mexico.
   [Eisenhauer, Anton; Fietzke, Jan; Liebetrau, Volker] IFM GEOMAR, Leibniz Inst Marine Sci, D-24148 Kiel, Germany.
C3 Universidad Nacional Autonoma de Mexico; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel
RP Blanchon, P (corresponding author), Univ Nacl Autonoma Mexico, Inst Marine & Limnol Sci, AP1152, Cancun, Quintana Roo, Mexico.
EM blanchon@icmyl.unam.mx
FU DGAPA [IN218799]
NR 32
TC 183
Z9 211
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 16
PY 2009
VL 458
IS 7240
BP 881
EP U6
DI 10.1038/nature07933
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500041
PM 19370032
DA 2026-03-09
ER

PT J
AU Rubenstein, DR
   Lovette, IJ
AF Rubenstein, Dustin R.
   Lovette, Irby J.
TI Reproductive skew and selection on female ornamentation in social species
SO NATURE
LA English
DT Article
ID sexual selection; genetic variance; variability; competition; evolution; dichromatism; phylogeny; behavior; drives
AB Male animals are typically more elaborately ornamented than females(1). Classic sexual selection theory notes that because sperm are cheaper to produce than eggs(2), and because males generally compete more intensely for reproductive opportunities and invest less in parental care than females(3), males can obtain greater fitness benefits from mating multiply(2,4). Therefore, sexual selection typically results in male-biased sex differences in secondary sexual characters(1,4). This generality has recently been questioned, because in cooperatively breeding vertebrates, the strength of selection on traits used in intra-sexual competition for access to mates (sexual selection(1,4)) or other resources linked to reproduction (social selection(5,6)) is similar in males and females(7,8). Because selection is acting with comparable intensity in both sexes in cooperatively breeding species, the degree of sexual dimorphism in traits used in intrasexual competition should be reduced in cooperative breeders(6). Here we use the socially diverse African starlings (Sturnidae) to demonstrate that the degree of sexual dimorphism in plumage and body size is reduced in cooperatively breeding species as a result of increased selection on females for traits that increase access to reproductive opportunities, other resources, or higher social status. In cooperative breeders such as these, where there is unequal sharing of reproduction (reproductive skew) among females, and where female dominance rank influences access to mates and other resources, intrasexual competition among females may be intense(7) and ultimately select for female trait elaboration(9). Selection is thereby acting with different intensities on males and females in cooperatively versus non-cooperatively breeding species, and female-female interactions in group-living vertebrates will have important consequences for the evolution of female morphological, physiological and behavioural traits.
C1 [Rubenstein, Dustin R.] Columbia Univ, Dept Ecol Evolut & Environm Biol, New York, NY 10027 USA.
   [Rubenstein, Dustin R.] Univ Calif Berkeley, Dept Integrat Biol, Museum Vertebrate Zool, Berkeley, CA 94720 USA.
   [Rubenstein, Dustin R.; Lovette, Irby J.] Cornell Lab Ornithol, Fuller Evolutionary Biol Program, Ithaca, NY 14850 USA.
C3 Columbia University; University of California System; University of California Berkeley; Cornell University
RP Rubenstein, DR (corresponding author), Columbia Univ, Dept Ecol Evolut & Environm Biol, 10th Floor Schermerhorn Extens,1200 Amsterdam Ave, New York, NY 10027 USA.
EM dr2497@columbia.edu
FU NSF [DEB-0515981]; Miller Institute for Basic Research in Science at the University of California, Berkeley
NR 30
TC 127
Z9 146
U1 0
U2 104
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 786
EP U106
DI 10.1038/nature08614
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900038
PM 20010686
DA 2026-03-09
ER

PT J
AU Moellering, RE
   Cornejo, M
   Davis, TN
   Del Bianco, C
   Aster, JC
   Blacklow, SC
   Kung, AL
   Gilliland, DG
   Verdine, GL
   Bradner, JE
AF Moellering, Raymond E.
   Cornejo, Melanie
   Davis, Tina N.
   Del Bianco, Cristina
   Aster, Jon C.
   Blacklow, Stephen C.
   Kung, Andrew L.
   Gilliland, D. Gary
   Verdine, Gregory L.
   Bradner, James E.
TI Direct inhibition of the NOTCH transcription factor complex
SO NATURE
LA English
DT Article
ID acute lymphoblastic-leukemia; gamma-secretase inhibitors; t-cell leukemia; progenitor cells; human homolog; c-myc; mutations; gene; mastermind; activation
AB Direct inhibition of transcription factor complexes remains a central challenge in the discipline of ligand discovery. In general, these proteins lack surface involutions suitable for high-affinity binding by small molecules. Here we report the design of synthetic, cell-permeable, stabilized alpha-helical peptides that target a critical protein-protein interface in the NOTCH transactivation complex. We demonstrate that direct, high-affinity binding of the hydrocarbon-stapled peptide SAHM1 prevents assembly of the active transcriptional complex. Inappropriate NOTCH activation is directly implicated in the pathogenesis of several disease states, including T-cell acute lymphoblastic leukaemia (T-ALL). The treatment of leukaemic cells with SAHM1 results in genome-wide suppression of NOTCH-activated genes. Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL.
C1 [Moellering, Raymond E.; Bradner, James E.] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA 02142 USA.
   [Moellering, Raymond E.; Verdine, Gregory L.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA.
   [Moellering, Raymond E.; Verdine, Gregory L.; Bradner, James E.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA.
   [Cornejo, Melanie; Gilliland, D. Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Del Bianco, Cristina; Aster, Jon C.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Davis, Tina N.; Kung, Andrew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Davis, Tina N.; Kung, Andrew L.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
   [Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Bradner, JE (corresponding author), Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA 02142 USA.
EM gregory_verdine@harvard.edu; james_bradner@dfci.harvard.edu
FU Leukaemia & Lymphoma Society; AACR Centennial Pre-doctoral Research Fellowship in Cancer Research; American Society of Hematology; MCCB-NIH [5T32GM007598]; Human Frontier Science Program; Harvard & Dana Farber Program in Cancer Chemical Biology; National Cancer Institute's Initiative for Chemical Genetics, National Institutes of Health [N01-CO-12400]
NR 50
TC 650
Z9 836
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 12
PY 2009
VL 462
IS 7270
BP 182
EP U57
DI 10.1038/nature08543
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100035
PM 19907488
DA 2026-03-09
ER

PT J
AU Gonnermann, HM
   Mukhopadhyay, S
AF Gonnermann, Helge M.
   Mukhopadhyay, Sujoy
TI Preserving noble gases in a convecting mantle
SO NATURE
LA English
DT Article
ID earths mantle; isotopic evidence; helium; evolution; reservoirs; constraints; systematics; circulation; basalts; fluxes
AB High (3)He/(4)He ratios sampled at many ocean islands are usually attributed to an essentially undegassed lower-mantle reservoir with high (3)He concentrations(1-4). A large and mostly undegassed mantle reservoir is also required to balance the Earth's (40)Ar budget, because only half of the (40)Ar produced from the radioactive decay of 40 K is accounted for by the atmosphere and upper mantle(5). However, geophysical(6,7) and geochemical observations(8) suggest slab subduction into the lower mantle, implying that most or all of Earth's mantle should have been processed by partial melting beneath mid-ocean ridges and hotspot volcanoes. This should have left noble gases in both the upper and the lower mantle extensively outgassed, contrary to expectations from (3)He/(4)He ratios and the Earth's (40)Ar budget. Here we suggest a simple solution: recycling and mixing of noble-gas-depleted slabs dilutes the concentrations of noble gases in the mantle, thereby decreasing the rate of mantle degassing and leaving significant amounts of noble gases in the processed mantle. As a result, even when the mass flux across the 660-km seismic discontinuity is equivalent to approximately one lower-mantlemass over the Earth's history, high (3)He contents, high (3)He/(4)He ratios and (40)Ar concentrations high enough to satisfy the (40)Ar mass balance of the Earth can be preserved in the lower mantle. The differences in (3)He/(4)He ratios between mid-ocean-ridge basalts and ocean island basalts, as well as high concentrations of (3)He and (40)Ar in the mantle source of ocean island basalts(4), can be explained within the framework of different processing rates for the upper and the lower mantle. Hence, to preserve primitive noble gas signatures, we find no need for hidden reservoirs or convective isolation of the lower mantle for any length of time.
C1 [Gonnermann, Helge M.] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Mukhopadhyay, Sujoy] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Rice University; Harvard University
RP Gonnermann, HM (corresponding author), Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
EM helge@rice.edu; sujoy@eps.harvard.edu
FU University of Hawaii; SOEST Young Investigator programme; US National Science Foundation [EAR 0509721]
NR 31
TC 96
Z9 107
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 MAY 28
PY 2009
VL 459
IS 7246
BP 560
EP U88
DI 10.1038/nature08018
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500037
PM 19478782
DA 2026-03-09
ER

PT J
AU Vogl, U
   Weitz, M
AF Vogl, Ulrich
   Weitz, Martin
TI Laser cooling by collisional redistribution of radiation
SO NATURE
LA English
DT Article
ID photothermal deflection spectroscopy; fluorescence; polaritons; scattering; gases; atoms; water
AB The general idea that optical radiation may cool matter was put forward 80 years ago(1). Doppler cooling of dilute atomic gases is an extremely successful application of this concept(2,3). More recently, anti-Stokes cooling in multilevel systems has been explored(4,5), culminating in the optical refrigeration of solids(6-9). Collisional redistribution of radiation has been proposed(10) as a different cooling mechanism for atomic two-level systems, although experimental investigations using moderate-density gases have not reached the cooling regime(11). Here we experimentally demonstrate laser cooling of an atomic gas based on collisional redistribution of radiation, using rubidium atoms in argon buffer gas at a pressure of 230 bar. The frequent collisions in the ultradense gas transiently shift a highly red-detuned laser beam(that is, one detuned to a much lower frequency) into resonance, whereas spontaneous decay occurs close to the unperturbed atomic resonance frequency. During each excitation cycle, kinetic energy of order k(B)T-that is, the thermal energy (k(B), Boltzmann's constant; T, temperature)-is extracted from the dense atomic sample. In a proof-of-principle experiment with a thermally non-isolated sample, we demonstrate relative cooling by 66 K. The cooled gas has a density more than ten orders of magnitude greater than the typical values used in Doppler-cooling experiments, and the cooling power reaches 87 mW. Future applications of the technique may include supercooling beyond the homogeneous nucleation temperature(12,13) and optical chillers(9).
C1 [Vogl, Ulrich; 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 [FOR557]
NR 30
TC 50
Z9 53
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 3
PY 2009
VL 461
IS 7260
BP 70
EP 73
DI 10.1038/nature08203
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800031
PM 19727195
DA 2026-03-09
ER

PT J
AU Essers, MAG
   Offner, S
   Blanco-Bose, WE
   Waibler, Z
   Kalinke, U
   Duchosal, MA
   Trumpp, A
AF Essers, Marieke A. G.
   Offner, Sandra
   Blanco-Bose, William E.
   Waibler, Zoe
   Kalinke, Ulrich
   Duchosal, Michel A.
   Trumpp, Andreas
TI IFNα activates dormant haematopoietic stem cells in vivo
SO NATURE
LA English
DT Article
ID chronic myeloid-leukemia; self-renewal; interferons; niches; expression; therapy; disease; mice
AB Maintenance of the blood system is dependent on dormant haematopoietic stem cells (HSCs) with long-term self-renewal capacity. After injury these cells are induced to proliferate to quickly reestablish homeostasis(1). The signalling molecules promoting the exit of HSCs out of the dormant stage remain largely unknown. Here we show that in response to treatment of mice with interferon-alpha (IFN alpha), HSCs efficiently exit G(0) and enter an active cell cycle. HSCs respond to IFN alpha treatment by the increased phosphorylation of STAT1 and PKB/Akt (also known as AKT1), the expression of IFN alpha target genes, and the upregulation of stem cell antigen-1 (Sca-1, also known as LY6A). HSCs lacking the IFN alpha/beta receptor (IFNAR)(2), STAT1 (ref. 3) or Sca-1 (ref. 4) are insensitive to IFN alpha stimulation, demonstrating that STAT1 and Sca-1 mediate IFN alpha-induced HSC proliferation. Although dormant HSCs are resistant to the anti-proliferative chemotherapeutic agent 5-fluoro-uracil(1,5), HSCs pre-treated (primed) with IFN alpha and thus induced to proliferate are efficiently eliminated by 5-fluoro-uracil exposure in vivo. Conversely, HSCs chronically activated by IFN alpha are functionally compromised and are rapidly out-competed by non-activatable Ifnar(-/-) cells in competitive repopulation assays. Whereas chronic activation of the IFN alpha pathway in HSCs impairs their function, acute IFN alpha treatment promotes the proliferation of dormant HSCs in vivo. These data may help to clarify the so far unexplained clinical effects of IFN alpha on leukaemic cells(6,7), and raise the possibility for new applications of type I interferons to target cancer stem cells(8).
C1 [Essers, Marieke A. G.; Trumpp, Andreas] DKFZ ZMBH Alliance, Deutsch Krebsforschungszentrum, Div Stem Cells & Canc, D-69120 Heidelberg, Germany.
   [Essers, Marieke A. G.; Trumpp, Andreas] Heidelberg Inst Stem Cell Technol & Expt Med HI S, D-69120 Heidelberg, Germany.
   [Offner, Sandra; Blanco-Bose, William E.; Trumpp, Andreas] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res, Sch Life Sci, CH-1015 Lausanne, Switzerland.
   [Waibler, Zoe; Kalinke, Ulrich] Paul Ehrlich Inst, Div Immunol, D-63225 Langen, Germany.
   [Kalinke, Ulrich] TWINCORE Ctr Expt & Clin Infect Res, D-30625 Hannover, Germany.
   [Duchosal, Michel A.] Univ Lausanne Hosp, CHUV, Serv & Cent Lab Hematol, CH-1011 Lausanne, Switzerland.
C3 Helmholtz Association; German Cancer Research Center (DKFZ); Swiss Institute Experimental Cancer Research; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Paul Ehrlich Institute; Helmholtz Association; Helmholtz-Center for Infection Research; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV)
RP Trumpp, A (corresponding author), DKFZ ZMBH Alliance, Deutsch Krebsforschungszentrum, Div Stem Cells & Canc, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM a.trumpp@dkfz-heidelberg.de
FU Swiss National Science Foundation; Swiss Cancer League; EU; Deutsche Forschungsgemeinschaft [SFB432.B15]
NR 30
TC 1137
Z9 1288
U1 1
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 16
PY 2009
VL 458
IS 7240
BP 904
EP U11
DI 10.1038/nature07815
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500046
PM 19212321
DA 2026-03-09
ER

PT J
AU Hofheinz, M
   Wang, H
   Ansmann, M
   Bialczak, RC
   Lucero, E
   Neeley, M
   O'Connell, AD
   Sank, D
   Wenner, J
   Martinis, JM
   Cleland, AN
AF Hofheinz, Max
   Wang, H.
   Ansmann, M.
   Bialczak, Radoslaw C.
   Lucero, Erik
   Neeley, M.
   O'Connell, A. D.
   Sank, D.
   Wenner, J.
   Martinis, John M.
   Cleland, A. N.
TI Synthesizing arbitrary quantum states in a superconducting resonator
SO NATURE
LA English
DT Article
ID wigner function; generation
AB The superposition principle is a fundamental tenet of quantum mechanics. It allows a quantum system to be 'in two places at the same time', because the quantum state of a physical system can simultaneously include measurably different physical states. The preparation and use of such superposed states forms the basis of quantum computation and simulation(1). The creation of complex superpositions in harmonic systems (such as the motional state of trapped ions(2), microwave resonators(3-5) or optical cavities(6)) has presented a significant challenge because it cannot be achieved with classical control signals. Here we demonstrate the preparation and measurement of arbitrary quantum states in an electromagnetic resonator, superposing states with different numbers of photons in a completely controlled and deterministic manner. We synthesize the states using a superconducting phase qubit to phase-coherently pump photons into the resonator, making use of an algorithm(7) that generalizes a previously demonstrated method of generating photon number (Fock) states in a resonator(8). We completely characterize the resonator quantum state using Wigner tomography, which is equivalent to measuring the resonator's full density matrix.
C1 [Hofheinz, Max; Wang, H.; Ansmann, M.; Bialczak, Radoslaw C.; Lucero, Erik; Neeley, M.; O'Connell, A. D.; Sank, D.; 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 Cleland@physics.ucsb.edu
FU NSF [CCF-0507227]; IARPA [W911NF-04-1-0204]
NR 29
TC 737
Z9 847
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 28
PY 2009
VL 459
IS 7246
BP 546
EP 549
DI 10.1038/nature08005
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500034
PM 19478780
DA 2026-03-09
ER

PT J
AU Buonamici, S
   Trimarchi, T
   Ruocco, MG
   Reavie, L
   Cathelin, S
   Mar, BG
   Klinakis, A
   Lukyanov, Y
   Tseng, JC
   Sen, F
   Gehrie, E
   Li, ML
   Newcomb, E
   Zavadil, J
   Meruelo, D
   Lipp, M
   Ibrahim, S
   Efstratiadis, A
   Zagzag, D
   Bromberg, JS
   Dustin, ML
   Aifantis, I
AF Buonamici, Silvia
   Trimarchi, Thomas
   Ruocco, Maria Grazia
   Reavie, Linsey
   Cathelin, Severine
   Mar, Brenton G.
   Klinakis, Apostolos
   Lukyanov, Yevgeniy
   Tseng, Jen-Chieh
   Sen, Filiz
   Gehrie, Eric
   Li, Mengling
   Newcomb, Elizabeth
   Zavadil, Jiri
   Meruelo, Daniel
   Lipp, Martin
   Ibrahim, Sherif
   Efstratiadis, Argiris
   Zagzag, David
   Bromberg, Jonathan S.
   Dustin, Michael L.
   Aifantis, Iannis
TI CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia
SO NATURE
LA English
DT Article
ID acute lymphoblastic-leukemia; secondary lymphoid organs; in-vivo; molecular pathogenesis; chemokine receptors; multiple-sclerosis; breast-cancer; activation; immunity; inflammation
AB T-cell acute lymphoblastic leukaemia (T-ALL) is a blood malignancy afflicting mainly children and adolescents(1). T-ALL patients present at diagnosis with increased white cell counts and hepatosplenomegaly, and are at an increased risk of central nervous system (CNS) relapse(2,3). For that reason, T-ALL patients usually receive cranial irradiation in addition to intensified intrathecal chemotherapy. The marked increase in survival is thought to be worth the considerable side-effects associated with this therapy. Such complications include secondary tumours, neurocognitive deficits, endocrine disorders and growth impairment(3). Little is known about the mechanism of leukaemic cell infiltration of the CNS, despite its clinical importance(4). Here we show, using T-ALL animal modelling and gene-expression profiling, that the chemokine receptor CCR7 (ref. 5) is the essential adhesion signal required for the targeting of leukaemic T-cells into the CNS. Ccr7 gene expression is controlled by the activity of the T-ALL oncogene Notch1 and is expressed in human tumours carrying Notch1-activating mutations. Silencing of either CCR7 or its chemokine ligand CCL19 (ref. 6) in an animal model of T-ALL specifically inhibits CNS infiltration. Furthermore, murine CNS-targeting by human T-ALL cells depends on their ability to express CCR7. These studies identify a single chemokine-receptor interaction as a CNS 'entry' signal, and open the way for future pharmacological targeting. Targeted inhibition of CNS involvement in T-ALL could potentially decrease the intensity of CNS-targeted therapy, thus reducing its associated short- and long-term complications.
C1 [Buonamici, Silvia; Trimarchi, Thomas; Ruocco, Maria Grazia; Reavie, Linsey; Cathelin, Severine; Lukyanov, Yevgeniy; Tseng, Jen-Chieh; Sen, Filiz; Newcomb, Elizabeth; Zavadil, Jiri; Meruelo, Daniel; Ibrahim, Sherif; Zagzag, David; Dustin, Michael L.; Aifantis, Iannis] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Buonamici, Silvia; Trimarchi, Thomas; Ruocco, Maria Grazia; Reavie, Linsey; Cathelin, Severine; Lukyanov, Yevgeniy; Tseng, Jen-Chieh; Sen, Filiz; Newcomb, Elizabeth; Zavadil, Jiri; Meruelo, Daniel; Ibrahim, Sherif; Zagzag, David; Dustin, Michael L.; Aifantis, Iannis] NYU, Sch Med, Inst Canc, New York, NY 10016 USA.
   [Buonamici, Silvia; Trimarchi, Thomas; Reavie, Linsey; Cathelin, Severine; Sen, Filiz; Aifantis, Iannis] NYU, Sch Med, Helen L & Martin S Kimmel Stem Cell Ctr, New York, NY 10016 USA.
   [Ruocco, Maria Grazia; Dustin, Michael L.] NYU, Sch Med, Program Mol Pathogenesis,Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Mar, Brenton G.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
   [Klinakis, Apostolos; Efstratiadis, Argiris] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA.
   [Gehrie, Eric; Bromberg, Jonathan S.] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA.
   [Gehrie, Eric; Bromberg, Jonathan S.] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA.
   [Li, Mengling] NYU, Inst Canc, Div Biostat, New York, NY 10016 USA.
   [Lipp, Martin] Max Delbruck Ctr Mol Med, Dept Tumor Genet & Immunogenet, D-13092 Berlin, Germany.
C3 New York University; New York University; New York University; New York University; Columbia University; Columbia University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; New York University; Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Aifantis, I (corresponding author), NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
EM iannis.aifantis@nyumc.org
FU National Institutes of Health [RO1CA105129, RO1CA133379, R56AI070310, P30CA016087, RO1AI41428, RO1AI072039]; American Cancer Society [RSG0806801]; Dana Foundation; Chemotherapy Foundation; Alex's Lemonade Stand Foundation; Lauri Strauss Leukemia Foundation; GP Foundation; NYU Molecular Oncology and Immunology; American Society of Hematology; Juvenile Diabetes Research Foundation [JDRFI1-2008-90, 5-2008-236]; National Cancer Institute [1 P01 CA97403]; Berrie Foundation; Jane Coffin Childs Memorial Fund for Medical Research; National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER
NR 29
TC 219
Z9 256
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 JUN 18
PY 2009
VL 459
IS 7249
BP 1000
EP U129
DI 10.1038/nature08020
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500046
PM 19536265
DA 2026-03-09
ER

PT J
AU Butt, Y
AF Butt, Yousaf
TI Beyond the myth of the supernova-remnant origin of cosmic rays
SO NATURE
LA English
DT Article
ID molecular clouds; ob associations; acceleration; emission; discovery; shock; reacceleration; constraints; propagation; superbubble
AB The origin of Galactic cosmic-ray ions has remained an enigma for almost a century. Although it has generally been thought that they are accelerated in the shock waves associated with powerful supernova explosions-for which there have been recent claims of evidence-the mystery is far from resolved. In fact, we may be on the wrong track altogether in looking for isolated regions of cosmic-ray acceleration.
C1 Harvard Smithsonian Ctr Astrophys, Div High Energy Astrophys, Cambridge, MA 02138 USA.
C3 Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory
RP Butt, Y (corresponding author), Harvard Smithsonian Ctr Astrophys, Div High Energy Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
EM ybutt@cfa.harvard.edu
FU NASA Long Term Space Astrophysics
NR 46
TC 76
Z9 86
U1 1
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 AUG 6
PY 2009
VL 460
IS 7256
BP 701
EP 704
DI 10.1038/nature08127
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300030
PM 19661909
DA 2026-03-09
ER

PT J
AU Lange, A
   Wickström, SA
   Jakobson, M
   Zent, R
   Sainio, K
   Fässler, R
AF Lange, Anika
   Wickstroem, Sara A.
   Jakobson, Madis
   Zent, Roy
   Sainio, Kirsi
   Faessler, Reinhard
TI Integrin-linked kinase is an adaptor with essential functions during mouse development
SO NATURE
LA English
DT Article
ID hair follicle morphogenesis; neurotrophic factor; protein-kinase; cell-adhesion; ilk; actin; inactivation; cytoskeleton; expression; parvin
AB The development of multicellular organisms requires integrin-mediated interactions between cells and their extracellular environment. Integrin binding to extracellular matrix catalyses assembly of multiprotein complexes, which transduce mechanical and chemical signals that regulate many aspects of cell physiology(1,2). Integrin-linked kinase (Ilk) is a multifunctional protein that binds beta-integrin cytoplasmic domains and regulates actin dynamics by recruiting actin binding regulatory proteins such as alpha-and beta-parvin(3). Ilk has also been shown to possess serine/threonine kinase activity(4) and to phosphorylate signalling proteins such as Akt1 and glycogen synthase kinase 3 beta (Gsk3 beta) in mammalian cells(5); however, these functions have been shown by genetic studies(6,7) not to occur in flies and worms. Here we show that mice carrying point mutations in the proposed autophosphorylation site of the putative kinase domain and in the pleckstrin homology domain are normal. In contrast, mice with point mutations in the conserved lysine residue of the potential ATP-binding site of the kinase domain, which mediates Ilk binding to alpha-parvin, die owing to renal agenesis. Similar renal defects occur in alpha-parvin-null mice. Thus, we provide genetic evidence that the kinase activity of Ilk is dispensable for mammalian development; however, an interaction between Ilk and alpha-parvin is critical for kidney development.
C1 [Lange, Anika; Wickstroem, Sara A.; Faessler, Reinhard] Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany.
   [Jakobson, Madis; Sainio, Kirsi] Univ Helsinki, Inst Biomed Med Biochem & Dev Biol, FIN-00014 Helsinki, Finland.
   [Zent, Roy] Vanderbilt Univ Sch Med, Dept Med, Div Nephrol, Nashville, TN 37232 USA.
   [Zent, Roy] Vet Affairs Hosp, Nashville, TN 37232 USA.
C3 Max Planck Society; University of Helsinki; Vanderbilt University
RP Fässler, R (corresponding author), Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany.
EM Faessler@biochem.mpg.de
FU Sigrid Juselius Foundation; Academy of Finland; Finnish Cultural Foundation; NIDDK [DK065123, DK075594, DK65123]; AHA; Department of Veterans Affairs; Austrian Science Funds [SFB021]; Max Planck Society
NR 33
TC 114
Z9 133
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 OCT 15
PY 2009
VL 461
IS 7266
BP 1002
EP U269
DI 10.1038/nature08468
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700052
PM 19829382
DA 2026-03-09
ER

PT J
AU Van Raamsdonk, CD
   Bezrookove, V
   Green, G
   Bauer, J
   Gaugler, L
   O'Brien, JM
   Simpson, EM
   Barsh, GS
   Bastian, BC
AF Van Raamsdonk, Catherine D.
   Bezrookove, Vladimir
   Green, Gary
   Bauer, Juergen
   Gaugler, Lona
   O'Brien, Joan M.
   Simpson, Elizabeth M.
   Barsh, Gregory S.
   Bastian, Boris C.
TI Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi
SO NATURE
LA English
DT Article
ID kinase-c; braf; melanocytes; pathway; cells
AB BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures, and lead to constitutive activation of the mitogen- activated protein ( MAP) kinase pathway(1,2). However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown(3). Here we report frequent somatic mutations in the heterotrimeric G protein alpha-subunit, GNAQ, in blue naevi (83%) and ocular melanoma of the uvea ( 46%). The mutations occur exclusively in codon 209 in the Ras- like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention.
C1 [Bezrookove, Vladimir; Green, Gary; Bauer, Juergen; Gaugler, Lona; Bastian, Boris C.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
   [Bezrookove, Vladimir; Green, Gary; Bauer, Juergen; Gaugler, Lona; O'Brien, Joan M.; Bastian, Boris C.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
   [O'Brien, Joan M.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
   [Bauer, Juergen] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany.
   [Simpson, Elizabeth M.] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V6T 1Z3, Canada.
   [Simpson, Elizabeth M.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada.
   [Barsh, Gregory S.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of California System; University of California San Francisco; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; University of British Columbia; University of British Columbia; Stanford University
RP Bastian, BC (corresponding author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
EM bastian@cc.ucsf.edu
FU National Cancer Institute [P01 CA025874 Project 2]; Melanoma Research Alliance, the Canadian Institutes of Health Research [MOP-79511]; National Institutes of Health
NR 23
TC 1237
Z9 1383
U1 1
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 29
PY 2009
VL 457
IS 7229
BP 599
EP U108
DI 10.1038/nature07586
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200045
PM 19078957
DA 2026-03-09
ER

PT J
AU Yamanaka, S
AF Yamanaka, Shinya
TI Elite and stochastic models for induced pluripotent stem cell generation
SO NATURE
LA English
DT Article
ID human fibroblasts; self-renewal; mouse; differentiation; induction; expression; system; genes; myc
AB Induced pluripotent stem cells offer unprecedented potential for disease research, drug screening, toxicology and regenerative medicine. However, the process of reprogramming is inefficient and often incomplete. Here I consider reasons for bottlenecks in induced pluripotent stem cell generation, and propose a model in which most or all cells have the potential to become pluripotent.
C1 [Yamanaka, Shinya] Kyoto Univ, CiRA, Kyoto 6068507, Japan.
   [Yamanaka, Shinya] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
C3 Kyoto University; University of California System; University of California San Francisco; The J David Gladstone Institutes
RP Yamanaka, S (corresponding author), Kyoto Univ, CiRA, Kyoto 6068507, Japan.
EM yamanaka@cira.kyoto-u.ac.jp
NR 40
TC 389
Z9 480
U1 2
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 49
EP 52
DI 10.1038/nature08180
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200027
PM 19571877
DA 2026-03-09
ER

PT J
AU Vernazza, P
   Binzel, RP
   Rossi, A
   Fulchignoni, M
   Birlan, M
AF Vernazza, P.
   Binzel, R. P.
   Rossi, A.
   Fulchignoni, M.
   Birlan, M.
TI Solar wind as the origin of rapid reddening of asteroid surfaces
SO NATURE
LA English
DT Article
ID near-earth asteroids; spectral property; ion irradiation; space; simulation; regions; albedo
AB A comparison of the laboratory reflectance spectra of meteorites with observations of asteroids revealed that the latter are much 'redder', with the spectral difference explained by 'space weathering'(1,2), though the actual processes and timescales involved have remained controversial(3,4). A recent study(5) of young asteroid families concluded that they suffered only minimal space weathering. Here we report additional observations of those families, revealing that space weathering must be a very rapid process-the final colour of a silicate-rich asteroid is acquired shortly after its 'birth' (within 10(6) years of undergoing a catastrophic collision). This rapid timescale favours solar wind implantation as the main mechanism of space weathering, as laboratory experiments have shown that it is the most rapid of several competing processes. We further demonstrate the necessity to take account of composition when evaluating weathering effectiveness, as both laboratory and asteroid data show an apparent dependence of weathering on olivine abundance. The rapid colour change that we find implies that colour trends seen among asteroids are most probably due to compositional or surface-particle-size properties, rather than to different relative ages. Apparently fresh surfaces most frequently seen among small near-Earth asteroids may be the result of tidal shaking that rejuvenates their surfaces during planetary encounters(6,7).
C1 [Vernazza, P.] European Space Agcy, Res & Sci Support Dept, NL-2201 AZ Noordwijk, Netherlands.
   [Binzel, R. P.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Rossi, A.] ISTI CNR, Spaceflight Dynam Sect, I-56124 Pisa, Italy.
   [Fulchignoni, M.] Observ Paris, Lab Etud Spatiales & Instrumentat Astrophys, F-92195 Meudon, France.
   [Birlan, M.] Observ Paris, IMCCE, F-75014 Paris, France.
C3 European Space Agency; Massachusetts Institute of Technology (MIT); Consiglio Nazionale delle Ricerche (CNR); Istituto di Scienza e Tecnologie dell'Informazione Alessandro Faedo (ISTI-CNR); Sorbonne Universite; Universite PSL; Observatoire de Paris; Sorbonne Universite; Universite PSL; Observatoire de Paris
RP Vernazza, P (corresponding author), European Space Agcy, Res & Sci Support Dept, Keplerlaan 1, NL-2201 AZ Noordwijk, Netherlands.
EM pierre.vernazza@esa.int
FU National Science Foundation [0506716]; NASA [NAG5-12355]
NR 30
TC 188
Z9 205
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 APR 23
PY 2009
VL 458
IS 7241
BP 993
EP 995
DI 10.1038/nature07956
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900034
PM 19396138
DA 2026-03-09
ER

PT J
AU Zheng, XT
   You, HL
   Xu, X
   Dong, ZM
AF Zheng, Xiao-Ting
   You, Hai-Lu
   Xu, Xing
   Dong, Zhi-Ming
TI An Early Cretaceous heterodontosaurid dinosaur with filamentous integumentary structures
SO NATURE
LA English
DT Article
ID ornithischian dinosaurs; feathers; china; origin; bird; sinosauropteryx
AB Ornithischia is one of the two major groups of dinosaurs, with heterodontosauridae as one of its major clades. Heterodontosauridae is characterized by small, gracile bodies and a problematic phylogenetic position(1,2). Recent phylogenetic work indicates that it represents the most basal group of all well-known ornithischians(3). Previous heterodontosaurid records are mainly from the Early Jurassic period (205-190 million years ago) of Africa(1,3). Here we report a new heterodontosaurid, Tianyulong confuciusi gen. et sp. nov., from the Early Cretaceous period (144-99 million years ago) of western Liaoning Province, China. Tianyulong extends the geographical distribution of heterodontosaurids to Asia and confirms the clade's previously questionable temporal range extension into the Early Cretaceous period. More surprisingly, Tianyulong bears long, singular and unbranched filamentous integumentary (outer skin) structures. This represents the first confirmed report, to our knowledge, of filamentous integumentary structures in an ornithischian dinosaur.
C1 [You, Hai-Lu] Chinese Acad Geol Sci, Inst Geol, Beijing 100037, Peoples R China.
   [Zheng, Xiao-Ting] Shandong Tianyu Museum Nat, Pingyi 273300, Shandong, Peoples R China.
   [Xu, Xing; Dong, Zhi-Ming] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
C3 China Geological Survey; Institute of Geology, Chinese Academy of Geological Sciences; Chinese Academy of Geological Sciences; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS
RP You, HL (corresponding author), Chinese Acad Geol Sci, Inst Geol, 26 Baiwanzhuang Rd, Beijing 100037, Peoples R China.
EM youhailu@gmail.com
FU National Natural Science Foundation of China [40672007]; Ministry of Science and Technology; Hundred Talents Project of the Ministry of Land and Resources of China
NR 30
TC 137
Z9 154
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 MAR 19
PY 2009
VL 458
IS 7236
BP 333
EP 336
DI 10.1038/nature07856
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600040
PM 19295609
DA 2026-03-09
ER

PT J
AU Xu, XD
   Yao, W
   Sun, B
   Steel, DG
   Bracker, AS
   Gammon, D
   Sham, LJ
AF Xu, Xiaodong
   Yao, Wang
   Sun, Bo
   Steel, Duncan G.
   Bracker, Allan S.
   Gammon, Daniel
   Sham, L. J.
TI Optically controlled locking of the nuclear field via coherent dark-state spectroscopy
SO NATURE
LA English
DT Article
ID single quantum dots; electron-spin; magnetic-resonance; manipulation
AB A single electron or hole spin trapped inside a semiconductor quantum dot forms the foundation for many proposed quantum logic devices(1-6). In group III-V materials, the resonance and coherence between two ground states of the single spin are inevitably affected by the lattice nuclear spins through the hyperfine interaction(7-9), while the dynamics of the single spin also influence the nuclear environment(10-15). Recent efforts(12,16) have been made to protect the coherence of spins in quantum dots by suppressing the nuclear spin fluctuations. However, coherent control of a single spin in a single dot with simultaneous suppression of the nuclear fluctuations has yet to be achieved. Here we report the suppression of nuclear field fluctuations in a singly charged quantum dot to well below the thermal value, as shown by an enhancement of the single electron spin dephasing time T-2*, which we measure using coherent dark-state spectroscopy. The suppression of nuclear fluctuations is found to result from a hole-spin assisted dynamic nuclear spin polarization feedback process, where the stable value of the nuclear field is determined only by the laser frequencies at fixed laser powers. This nuclear field locking is further demonstrated in a three-laser measurement, indicating a possible enhancement of the electron spin T-2* by a factor of several hundred. This is a simple and powerful method of enhancing the electron spin coherence time without use of 'spin echo'-type techniques(8,12). We expect that our results will enable the reproducible preparation of the nuclear spin environment for repetitive control and measurement of a single spin with minimal statistical broadening.
C1 [Xu, Xiaodong; Sun, Bo; Steel, Duncan G.] Univ Michigan, Harrison M Randall Lab Phys, Ann Arbor, MI 48109 USA.
   [Bracker, Allan S.; Gammon, Daniel] USN, Res Lab, Washington, DC 20375 USA.
   [Sham, L. J.] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [Yao, Wang] Univ Hong Kong, Dept Phys, Hong Kong, Hong Kong, Peoples R China.
C3 University of Michigan System; University of Michigan; United States Department of Defense; United States Navy; United States Naval Research Laboratory; NRL Chesapeake; University of California System; University of California San Diego; University of Hong Kong
RP Steel, DG (corresponding author), Univ Michigan, Harrison M Randall Lab Phys, Ann Arbor, MI 48109 USA.
EM dst@umich.edu
FU US ARO; AFOSR; ONR; NSA/LPS; FOCUS-NSF
NR 30
TC 196
Z9 213
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 JUN 25
PY 2009
VL 459
IS 7250
BP 1105
EP 1109
DI 10.1038/nature08120
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700038
PM 19553994
DA 2026-03-09
ER

PT J
AU Kubanek, A
   Koch, M
   Sames, C
   Ourjoumtsev, A
   Pinkse, PWH
   Murr, K
   Rempe, G
AF Kubanek, A.
   Koch, M.
   Sames, C.
   Ourjoumtsev, A.
   Pinkse, P. W. H.
   Murr, K.
   Rempe, G.
TI Photon-by-photon feedback control of a single-atom trajectory
SO NATURE
LA English
DT Article
AB Feedback is one of the most powerful techniques for the control of classical systems. An extension into the quantum domain is desirable as it could allow the production of non-trivial quantum states(1-4) and protection against decoherence(5,6). The difficulties associated with quantum, as opposed to classical, feedback arise from the quantum measurement process-in particular the quantum projection noise and the limited measurement rate-as well as from quantum fluctuations perturbing the evolution in a driven open system. Here we demonstrate real-time feedback control(7-12) of the motion of a single atom trapped in an optical cavity. Individual probe photons carrying information about the atomic position(13,14) activate a dipole laser that steers the atom on timescales 70 times shorter than the atom's oscillation period in the trap. Depending on the specific implementation, the trapping time is increased by a factor of more than four owing to feedback cooling, which can remove almost all the kinetic energy of the atom in a quarter of an oscillation period(12). Our results show that the detected photon flux reflects the atomic motion, and thus mark a step towards the exploration of the quantum trajectory(15,16) of a single atom at the standard quantum limit.
C1 [Kubanek, A.; Koch, M.; Sames, C.; Ourjoumtsev, A.; Pinkse, P. W. H.; Murr, K.; Rempe, G.] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
C3 Max Planck Society
RP Kubanek, A (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM alexander.kubanek@mpq.mpg.de; gerhard.rempe@mpq.mpg.de
FU Bavarian PhD programme of excellence QCCC; Deutsche Forschungsgemeinschaft [635]; European Union project SCALA
NR 21
TC 70
Z9 76
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 DEC 17
PY 2009
VL 462
IS 7275
BP 898
EP 901
DI 10.1038/nature08563
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400038
PM 20016597
DA 2026-03-09
ER

PT J
AU Klin, A
   Lin, DJ
   Gorrindo, P
   Ramsay, G
   Jones, W
AF Klin, Ami
   Lin, David J.
   Gorrindo, Phillip
   Ramsay, Gordon
   Jones, Warren
TI Two-year-olds with autism orient to non-social contingencies rather than biological motion
SO NATURE
LA English
DT Article
ID perception; face; area; recognition; fixation; deficits; infants
AB Typically developing human infants preferentially attend to biological motion within the first days of life(1). This ability is highly conserved across species(2,3) and is believed to be critical for filial attachment and for detection of predators(4). The neural underpinnings of biological motion perception are overlapping with brain regions involved in perception of basic social signals such as facial expression and gaze direction(5), and preferential attention to biological motion is seen as a precursor to the capacity for attributing intentions to others(6). However, in a serendipitous observation(7), we recently found that an infant with autism failed to recognize point-light displays of biological motion, but was instead highly sensitive to the presence of a non-social, physical contingency that occurred within the stimuli by chance. This observation raised the possibility that perception of biological motion may be altered in children with autism from a very early age, with cascading consequences for both social development and the lifelong impairments in social interaction that are a hallmark of autism spectrum disorders(8). Here we show that two-year-olds with autism fail to orient towards point-light displays of biological motion, and their viewing behaviour when watching these point-light displays can be explained instead as a response to non-social, physical contingencies-physical contingencies that are disregarded by control children. This observation has far-reaching implications for understanding the altered neurodevelopmental trajectory of brain specialization in autism(9).
C1 [Klin, Ami; Lin, David J.; Gorrindo, Phillip; Ramsay, Gordon; Jones, Warren] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06519 USA.
   [Ramsay, Gordon] Haskins Labs Inc, New Haven, CT 06511 USA.
   [Jones, Warren] Yale Univ, Sch Med, Interdepartmental Neurosci Program, New Haven, CT 06520 USA.
C3 Yale University; Yale University; Haskins Laboratories; Yale University
RP Klin, A (corresponding author), Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06519 USA.
EM ami.klin@yale.edu; warren.jones@yale.edu
FU National Institutes of Mental Health [U54-MH66494]; Autism Speaks; Simons Foundation
NR 36
TC 607
Z9 756
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 MAY 14
PY 2009
VL 459
IS 7244
BP 257
EP U142
DI 10.1038/nature07868
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100042
PM 19329996
DA 2026-03-09
ER

PT J
AU Tamgüney, G
   Miller, MW
   Wolfe, LL
   Sirochman, TM
   Glidden, DV
   Palmer, C
   Lemus, A
   DeArmond, SJ
   Prusiner, SB
AF Tamgueney, Gueltekin
   Miller, Michael W.
   Wolfe, Lisa L.
   Sirochman, Tracey M.
   Glidden, David V.
   Palmer, Christina
   Lemus, Azucena
   DeArmond, Stephen J.
   Prusiner, Stanley B.
TI Asymptomatic deer excrete infectious prions in faeces
SO NATURE
LA English
DT Article
ID chronic wasting disease; bovine spongiform encephalopathy; mule deer; transgenic mice; odocoileus-hemionus; incubation-time; transmission; scrapie; protein; sheep
AB Infectious prion diseases(1)-scrapie of sheep(2) and chronic wasting disease (CWD) of several species in the deer family(3,4)-are transmitted naturally within affected host populations. Although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals(5-8), the biological importance of these sources in sustaining epidemics remains unclear. Here we show that asymptomatic CWD-infected mule deer (Odocoileus hemionus) excrete CWD prions in their faeces long before they develop clinical signs of prion disease. Intracerebral inoculation of irradiated deer faeces into transgenic mice overexpressing cervid prion protein (PrP) revealed infectivity in 14 of 15 faecal samples collected from five deer at 7-11 months before the onset of neurological disease. Although prion concentrations in deer faeces were considerably lower than in brain tissue from the same deer collected at the end of the disease, the estimated total infectious dose excreted in faeces by an infected deer over the disease course may approximate the total contained in a brain. Prolonged faecal prion excretion by infected deer provides a plausible natural mechanism that might explain the high incidence and efficient horizontal transmission of CWD within deer herds(3,4,9), as well as prion transmission among other susceptible cervids.
C1 [Tamgueney, Gueltekin; Palmer, Christina; DeArmond, Stephen J.; Prusiner, Stanley B.] Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA.
   [Tamgueney, Gueltekin; Prusiner, Stanley B.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Miller, Michael W.; Wolfe, Lisa L.; Sirochman, Tracey M.] Colorado Div Wildlife, Wildlife Res Lab, Ft Collins, CO 80526 USA.
   [Glidden, David V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Lemus, Azucena; DeArmond, Stephen J.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Prusiner, SB (corresponding author), Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA.
EM stanley@ind.ucsf.edu
FU Colorado Division of Wildlife; US Department of Defense National Prion Research Program [NP020152]; National Institutes of Health [AG02132]; Hillblom Foundation; National Institute on Aging [P01AG002132] Funding Source: NIH RePORTER
NR 41
TC 226
Z9 275
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 24
PY 2009
VL 461
IS 7263
BP 529
EP U90
DI 10.1038/nature08289
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900041
PM 19741608
DA 2026-03-09
ER

PT J
AU Erb, RM
   Son, HS
   Samanta, B
   Rotello, VM
   Yellen, BB
AF Erb, Randall M.
   Son, Hui S.
   Samanta, Bappaditya
   Rotello, Vincent M.
   Yellen, Benjamin B.
TI Magnetic assembly of colloidal superstructures with multipole symmetry
SO NATURE
LA English
DT Article
ID particles; crystals; crystallization; clusters
AB The assembly of complex structures out of simple colloidal building blocks is of practical interest for building materials with unique optical properties ( for example photonic crystals(1) and DNA biosensors(2)) and is of fundamental importance in improving our understanding of self- assembly processes occurring on molecular to macroscopic length scales(3-5). Here we demonstrate a self-assembly principle that is capable of organizing a diverse set of colloidal particles into highly reproducible, rotationally symmetric arrangements. The structures are assembled using the magneto-static interaction between effectively diamagnetic and paramagnetic particles within a magnetized ferrofluid. The resulting multipolar geometries resemble electrostatic charge configurations such as axial quadrupoles ('Saturn rings'), axial octupoles ('flowers'), linear quadrupoles (poles) and mixed multipole arrangements ('two tone'), which represent just a few examples of the type of structure that can be built using this technique.
C1 [Erb, Randall M.; Son, Hui S.; Yellen, Benjamin B.] Duke Univ, Dept Mech Engn & Mat Sci, Ctr Biol Inspired Mat & Mat Syst, Durham, NC 27708 USA.
   [Samanta, Bappaditya; Rotello, Vincent M.] Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA.
C3 Duke University; University of Massachusetts System; University of Massachusetts Amherst
RP Yellen, BB (corresponding author), Duke Univ, Dept Mech Engn & Mat Sci, Ctr Biol Inspired Mat & Mat Syst, Box 90300,Hudson Hall, Durham, NC 27708 USA.
EM yellen@duke.edu
FU US National Science Foundation [NSEC DMI-0531171, MRSEC DMR-0213695, CMMI-0608819, CMMI-0625480]
NR 23
TC 409
Z9 500
U1 4
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 FEB 19
PY 2009
VL 457
IS 7232
BP 999
EP 1002
DI 10.1038/nature07766
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400039
PM 19225522
DA 2026-03-09
ER

PT J
AU Yorozu, S
   Wong, A
   Fischer, BJ
   Dankert, H
   Kernan, MJ
   Kamikouchi, A
   Ito, K
   Anderson, DJ
AF Yorozu, Suzuko
   Wong, Allan
   Fischer, Brian J.
   Dankert, Heiko
   Kernan, Maurice J.
   Kamikouchi, Azusa
   Ito, Kei
   Anderson, David J.
TI Distinct sensory representations of wind and near-field sound in the Drosophila brain
SO NATURE
LA English
DT Article
ID green fluorescent protein; melanogaster; hearing; transduction; dispersal; song; map
AB Behavioural responses to wind are thought to have a critical role in controlling the dispersal and population genetics of wild Drosophila species(1,2), as well as their navigation in flight(3), but their underlying neurobiological basis is unknown. We show that Drosophila melanogaster, like wild-caught Drosophila strains(4), exhibits robust wind-induced suppression of locomotion in response to air currents delivered at speeds normally encountered in nature(1,2). Here we identify wind-sensitive neurons in Johnston's organ, an antennal mechanosensory structure previously implicated in near-field sound detection (reviewed in refs 5 and 6). Using enhancer trap lines targeted to different subsets of Johnston's organ neurons(7), and a genetically encoded calcium indicator(8), we show that wind and near-field sound (courtship song) activate distinct populations of Johnston's organ neurons, which project to different regions of the antennal and mechanosensory motor centre in the central brain. Selective genetic ablation of wind-sensitive Johnston's organ neurons in the antenna abolishes wind-induced suppression of locomotion behaviour, without impairing hearing. Moreover, different neuronal subsets within the wind-sensitive population respond to different directions of arista deflection caused by air flow and project to different regions of the antennal and mechanosensory motor centre, providing a rudimentary map of wind direction in the brain. Importantly, sound- and wind-sensitive Johnston's organ neurons exhibit different intrinsic response properties: the former are phasically activated by small, bi-directional, displacements of the aristae, whereas the latter are tonically activated by unidirectional, static deflections of larger magnitude. These different intrinsic properties are well suited to the detection of oscillatory pulses of near-field sound and laminar air flow, respectively. These data identify wind-sensitive neurons in Johnston's organ, a structure that has been primarily associated with hearing, and reveal how the brain can distinguish different types of air particle movements using a common sensory organ.
C1 [Yorozu, Suzuko; Wong, Allan; Fischer, Brian J.; Dankert, Heiko; Anderson, David J.] CALTECH, Div Biol 216 76, Pasadena, CA 91125 USA.
   [Yorozu, Suzuko; Wong, Allan; Anderson, David J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [Dankert, Heiko] CALTECH, Div Engn & Appl Sci 136 93, Pasadena, CA 91125 USA.
   [Kernan, Maurice J.] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA.
   [Kamikouchi, Azusa; Ito, Kei] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Kamikouchi, Azusa] Univ Cologne, Inst Zool, Sensory Syst Lab, D-50923 Cologne, Germany.
C3 California Institute of Technology; California Institute of Technology; Howard Hughes Medical Institute; California Institute of Technology; State University of New York (SUNY) System; Stony Brook University; University of Tokyo; University of Cologne
RP Anderson, DJ (corresponding author), CALTECH, Div Biol 216 76, Pasadena, CA 91125 USA.
EM yorozu@caltech.edu; mancusog@caltech.edu
FU NSF [EF-0623527]
NR 25
TC 193
Z9 235
U1 1
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 201
EP U4
DI 10.1038/nature07843
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700043
PM 19279637
DA 2026-03-09
ER

PT J
AU Rivière, S
   Challet, L
   Fluegge, D
   Spehr, M
   Rodriguez, I
AF Riviere, Stephane
   Challet, Ludivine
   Fluegge, Daniela
   Spehr, Marc
   Rodriguez, Ivan
TI Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors
SO NATURE
LA English
DT Article
ID putative pheromone receptors; multigene family; mammals; individuals; recognition; neurons; genes
AB Mammals rely heavily on olfaction to interact adequately with each other and with their environment(1). They make use of seven-transmembrane G-protein-coupled receptors to identify odorants and pheromones. These receptors are present on dendrites of olfactory sensory neurons located in the main olfactory or vomeronasal sensory epithelia, and pertain to the odorant(2), trace amine-associated receptor(3) and vomeronasal type 1 (ref. 4) or 2 (refs 5-7) receptor superfamilies. Whether these four sensor classes represent the complete olfactory molecular repertoire used by mammals to make sense of the outside world is unknown. Here we report the expression of formyl peptide receptor-related genes by vomeronasal sensory neurons, in multiple mammalian species. Similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium. In vitro expression of mouse formyl peptide receptor-like 1, 3, 4, 6 and 7 provides sensitivity to disease/inflammation-related ligands. Establishing an in situ approach that combines whole-mount vomeronasal preparations with dendritic calcium imaging in the intact neuroepithelium, we show neuronal responses to the same molecules, which therefore represent a new class of vomeronasal agonists. Taken together, these results suggest that formyl peptide receptor-like proteins have an olfactory function associated with the identification of pathogens, or of pathogenic states.
C1 [Riviere, Stephane; Challet, Ludivine; Rodriguez, Ivan] Univ Geneva, Dept Zool & Anim Biol, CH-1205 Geneva, Switzerland.
   [Riviere, Stephane; Challet, Ludivine; Rodriguez, Ivan] Univ Geneva, Natl Ctr Competence Frontiers Genet, CH-1205 Geneva, Switzerland.
   [Fluegge, Daniela; Spehr, Marc] Ruhr Univ Bochum, Dept Cellular Physiol, D-44780 Bochum, Germany.
C3 University of Geneva; University of Geneva; Ruhr University Bochum
RP Rodriguez, I (corresponding author), Univ Geneva, Dept Zool & Anim Biol, CH-1205 Geneva, Switzerland.
EM ivan.rodriguez@unige.ch
FU Swiss National Science Foundation; Claraz, Schmidheiny; Volkswagen; Schlumberger Foundations; Deutsche Forschungsgemeinschaft
NR 20
TC 277
Z9 335
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 MAY 28
PY 2009
VL 459
IS 7246
BP 574
EP 577
DI 10.1038/nature08029
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500040
PM 19387439
DA 2026-03-09
ER

PT J
AU Valenti, S
   Pastorello, A
   Cappellaro, E
   Benetti, S
   Mazzali, PA
   Manteca, J
   Taubenberger, S
   Elias-Rosa, N
   Ferrando, R
   Harutyunyan, A
   Hentunen, VP
   Nissinen, M
   Pian, E
   Turatto, M
   Zampieri, L
   Smartt, SJ
AF Valenti, S.
   Pastorello, A.
   Cappellaro, E.
   Benetti, S.
   Mazzali, P. A.
   Manteca, J.
   Taubenberger, S.
   Elias-Rosa, N.
   Ferrando, R.
   Harutyunyan, A.
   Hentunen, V. P.
   Nissinen, M.
   Pian, E.
   Turatto, M.
   Zampieri, L.
   Smartt, S. J.
TI A low-energy core-collapse supernova without a hydrogen envelope
SO NATURE
LA English
DT Article
ID gamma-ray burst; sn 2005hk; evolution; spectroscopy; models; 2002cx; stars
AB The final fate of massive stars depends on many factors. Theory suggests that some with initial masses greater than 25 to 30 solar masses end up as Wolf-Rayet stars, which are deficient in hydrogen in their outer layers because of mass loss through strong stellar winds. The most massive of these stars have cores which may form a black hole and theory predicts that the resulting explosion of some of them produces ejecta of low kinetic energy, a faint optical luminosity and a small mass fraction of radioactive nickel(1-3). An alternative origin for low-energy supernovae is the collapse of the oxygen-neon core of a star of 7-9 solar masses(4,5). No weak, hydrogen-deficient, core-collapse supernovae have hitherto been seen. Here we report that SN 2008ha is a faint hydrogen-poor supernova. We propose that other similar events have been observed but have been misclassified as peculiar thermonuclear supernovae (sometimes labelled SN 2002cx-like events(6)). This discovery could link these faint supernovae to some long-duration gamma-ray bursts, because extremely faint, hydrogen-stripped core-collapse supernovae have been proposed to produce such long gamma-ray bursts, the afterglows of which do not show evidence of associated supernovae(7-9).
C1 [Valenti, S.; Pastorello, A.; Smartt, S. J.] Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
   [Cappellaro, E.; Benetti, S.; Mazzali, P. A.; Harutyunyan, A.; Zampieri, L.] INAF Osservatorio Astron Padova, I-35122 Padua, Italy.
   [Mazzali, P. A.; Taubenberger, S.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Manteca, J.] Begues Observ, Barcelona 08859, Spain.
   [Elias-Rosa, N.] CALTECH, Spitzer Sci Ctr, Pasadena, CA 91125 USA.
   [Harutyunyan, A.] Fdn Galileo Galilei INAF, E-38700 Tenerife, Spain.
   [Hentunen, V. P.; Nissinen, M.] Taurus Hill Observ, Kangaslampi 79480, Finland.
   [Hentunen, V. P.] Univ Turku, Dept Phys & Astron, Tuorla Observ, FI-21500 Piikkio, Finland.
   [Pian, E.] INAF Osservatorio Astron Trieste, I-34131 Trieste, Italy.
   [Turatto, M.] INAF Osservatorio Astrofis Catania, I-95123 Catania, Italy.
C3 Queens University Belfast; Istituto Nazionale Astrofisica (INAF); Max Planck Society; California Institute of Technology; Istituto Nazionale Astrofisica (INAF); University of Turku; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF)
RP Valenti, S (corresponding author), Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
EM s.valenti@qub.ac.uk
FU European Science Foundation EURYI Awards; PRIN of Italian Ministry of University and Science Research; STFC [ST/G009465/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/G009465/1] Funding Source: researchfish
NR 30
TC 166
Z9 184
U1 1
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 JUN 4
PY 2009
VL 459
IS 7247
BP 674
EP 677
DI 10.1038/nature08023
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600037
PM 19494909
DA 2026-03-09
ER

PT J
AU Lim, DA
   Huang, YC
   Swigut, T
   Mirick, AL
   Garcia-Verdugo, JM
   Wysocka, J
   Ernst, P
   Alvarez-Buylla, A
AF Lim, Daniel A.
   Huang, Yin-Cheng
   Swigut, Tomek
   Mirick, Anika L.
   Manuel Garcia-Verdugo, Jose
   Wysocka, Joanna
   Ernst, Patricia
   Alvarez-Buylla, Arturo
TI Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells
SO NATURE
LA English
DT Article
ID adult mammalian brain; subventricular zone; neuronal migration; self-renewal; progenitors; mice; oligodendrocytes; proliferation; expression; polycomb
AB Epigenetic mechanisms that maintain neurogenesis throughout adult life remain poorly understood(1). Trithorax group (trxG) and Polycomb group (PcG) gene products are part of an evolutionarily conserved chromatin remodelling system that activate or silence gene expression, respectively(2). Although PcG member Bmi1 has been shown to be required for postnatal neural stem cell self-renewal(3,4), the role of trxG genes remains unknown. Here we show that the trxG member Mll1 (mixed-lineage leukaemia 1) is required for neurogenesis in the mouse postnatal brain. Mll1-deficient subventricular zone neural stem cells survive, proliferate and efficiently differentiate into glial lineages; however, neuronal differentiation is severely impaired. In Mll1-deficient cells, early proneural Mash1 (also known as Ascl1) and gliogenic Olig2 expression are preserved, but Dlx2, a key downstream regulator of subventricular zone neurogenesis, is not expressed. Overexpression of Dlx2 can rescue neurogenesis in Mll1-deficient cells. Chromatin immunoprecipitation demonstrates that Dlx2 is a direct target of MLL in subventricular zone cells. In differentiating wild-type subventricular zone cells, Mash1, Olig2 and Dlx2 loci have high levels of histone 3 trimethylated at lysine 4 (H3K4me3), consistent with their transcription. In contrast, in Mll1-deficient subventricular zone cells, chromatin at Dlx2 is bivalently marked by both H3K4me3 and histone 3 trimethylated at lysine 27 (H3K27me3), and the Dlx2 gene fails to properly activate. These data support a model in which Mll1 is required to resolve key silenced bivalent loci in postnatal neural precursors to the actively transcribed state for the induction of neurogenesis, but not for gliogenesis.
C1 [Lim, Daniel A.; Huang, Yin-Cheng; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
   [Lim, Daniel A.; Huang, Yin-Cheng; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Inst Regenerat Med, San Francisco, CA 94143 USA.
   [Lim, Daniel A.] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
   [Swigut, Tomek; Wysocka, Joanna] Stanford Univ, Sch Med, Dept Dev Biol, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Mirick, Anika L.; Ernst, Patricia] Dartmouth Med Sch, Dept Genet, Hanover, NH 03755 USA.
   [Manuel Garcia-Verdugo, Jose] Univ Valencia, Inst Cavanilles, Lab Neurobiol Comparada, Valencia 46012, Spain.
   [Manuel Garcia-Verdugo, Jose] CIBERNED, Ctr Invest Principe Felipe, Lab Morfol Celular, Valencia 46012, Spain.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; US Department of Veterans Affairs; Veterans Health Administration (VHA); University of California System; University of California San Francisco; Stanford University; Dartmouth College; University of Valencia; Prince Felipe Research Center; CIBERNED
RP Lim, DA (corresponding author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus St M779, San Francisco, CA 94143 USA.
EM limd@neurosurg.ucsf.edu; abuylla@stemcell.ucsf.edu
FU Neurosurgery Research and Education Foundation/American Association of Neurological Surgeons; Sandler Family Foundation; Northern California Institute for Research and Education; Clinical and Translational Research Institute at the University of California, San Francisco; California Institute for Regenerative Medicine New Faculty Award; Chicago Community Trust Searle Scholar Award; Goldhirsch Foundation; J. G. Bowes Research Fund; National Institutes of Health (NIH) [5R37-NS028478]
NR 31
TC 312
Z9 375
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 529
EP U9
DI 10.1038/nature07726
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400049
PM 19212323
DA 2026-03-09
ER

PT J
AU Singh, R
   Kaushik, S
   Wang, YJ
   Xiang, YQ
   Novak, I
   Komatsu, M
   Tanaka, K
   Cuervo, AM
   Czaja, MJ
AF Singh, Rajat
   Kaushik, Susmita
   Wang, Yongjun
   Xiang, Youqing
   Novak, Inna
   Komatsu, Masaaki
   Tanaka, Keiji
   Cuervo, Ana Maria
   Czaja, Mark J.
TI Autophagy regulates lipid metabolism
SO NATURE
LA English
DT Article
ID low-density-lipoprotein; phosphatidylinositol 3-kinase; triacylglycerol; lipolysis; disease; stress; cyp2e1; roles; liver
AB The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.
C1 [Singh, Rajat; Kaushik, Susmita; Wang, Yongjun; Xiang, Youqing; Cuervo, Ana Maria; Czaja, Mark J.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA.
   [Singh, Rajat; Kaushik, Susmita; Wang, Yongjun; Xiang, Youqing; Novak, Inna; Cuervo, Ana Maria; Czaja, Mark J.] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Bronx, NY 10461 USA.
   [Kaushik, Susmita; Cuervo, Ana Maria] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
   [Kaushik, Susmita; Cuervo, Ana Maria] Albert Einstein Coll Med, Inst Aging Studies, Bronx, NY 10461 USA.
   [Novak, Inna] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA.
   [Komatsu, Masaaki; Tanaka, Keiji] Tokyo Metropolitan Inst Med Sci, Lab Frontier Sci, Bunkyo Ku, Tokyo 1138613, Japan.
C3 Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Tokyo Metropolitan Institute of Medical Science
RP Czaja, MJ (corresponding author), Albert Einstein Coll Med, Dept Med, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM amcuervo@aecom.yu.edu; czaja@aecom.yu.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; American Liver Foundation Postdoctoral Research Fellowship Award; National Institute on Aging [P01AG031782] Funding Source: NIH RePORTER
NR 35
TC 3307
Z9 3788
U1 17
U2 711
PU NATURE PUBLISHING 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 30
PY 2009
VL 458
IS 7242
BP 1131
EP U64
DI 10.1038/nature07976
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600039
PM 19339967
DA 2026-03-09
ER

PT J
AU Vasseur, DA
   Fox, JW
AF Vasseur, David A.
   Fox, Jeremy W.
TI Phase-locking and environmental fluctuations generate synchrony in a predator-prey community
SO NATURE
LA English
DT Article
ID population-dynamics; spatial synchrony; dispersal; patterns; systems; noise
AB Spatially synchronized fluctuations in system state are common in physical and biological systems ranging from individual atoms(1) to species as diverse as viruses, insects and mammals(2-10). Although the causal factors are well known for many synchronized phenomena, several processes concurrently have an impact on spatial synchrony of species, making their separate effects and interactions difficult to quantify. Here we develop a general stochastic model of predator-prey spatial dynamics to predict the outcome of a laboratory microcosm experiment testing for interactions among all known synchronizing factors: ( 1) dispersal of individuals between populations; ( 2) spatially synchronous fluctuations in exogenous environmental factors ( the Moran effect); and ( 3) interactions with other species ( for example, predators) that are themselves spatially synchronized. The Moran effect synchronized populations of the ciliate protist Tetrahymena pyriformis; however, dispersal only synchronized prey populations in the presence of the predator Euplotes patella. Both model and data indicate that synchrony depends on cyclic dynamics generated by the predator. Dispersal, but not the Moran effect, 'phase-locks' cycles, which otherwise become 'decoherent' and drift out of phase. In the absence of cycles, phase-locking is not possible and the synchronizing effect of dispersal is negligible. Interspecific interactions determine population synchrony, not by providing an additional source of synchronized fluctuations, but by altering population dynamics and thereby enhancing the action of dispersal. Our results are robust to wide variation in model parameters representative of many natural predator-prey or host-pathogen systems. This explains why cyclic systems provide many of the most dramatic examples of spatial synchrony in nature.
C1 [Vasseur, David A.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
   [Fox, Jeremy W.] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada.
C3 Yale University; University of Calgary
RP Vasseur, DA (corresponding author), Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
EM david.vasseur@yale.edu
FU Alberta Ingenuity; NSERC
NR 31
TC 125
Z9 141
U1 1
U2 95
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 1007
EP U90
DI 10.1038/nature08208
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500033
PM 19626006
DA 2026-03-09
ER

PT J
AU Fujii, H
   Chinnusamy, V
   Rodrigues, A
   Rubio, S
   Antoni, R
   Park, SY
   Cutler, SR
   Sheen, J
   Rodriguez, PL
   Zhu, JK
AF Fujii, Hiroaki
   Chinnusamy, Viswanathan
   Rodrigues, Americo
   Rubio, Silvia
   Antoni, Regina
   Park, Sang-Youl
   Cutler, Sean R.
   Sheen, Jen
   Rodriguez, Pedro L.
   Zhu, Jian-Kang
TI In vitro reconstitution of an abscisic acid signalling pathway
SO NATURE
LA English
DT Article
ID protein phosphatases; gene-expression; identification; transduction; receptors; interacts; growth; aba
AB The phytohormone abscisic acid (ABA) regulates the expression of many genes in plants; it has critical functions in stress resistance and in growth and development(1-7). Several proteins have been reported to function as ABA receptors(8-13), and many more are known to be involved in ABA signalling(3,4,14). However, the identities of ABA receptors remain controversial and the mechanism of signalling from perception to downstream gene expression is unclear(15,16). Here we show that by combining the recently identified ABA receptor PYR1 with the type 2C protein phosphatase (PP2C) ABI1, the serine/threonine protein kinase SnRK2.6/OST1 and the transcription factor ABF2/AREB1, we can reconstitute ABA-triggered phosphorylation of the transcription factor in vitro. Introduction of these four components into plant protoplasts results in ABA-responsive gene expression. Protoplast and test-tube reconstitution assays were used to test the function of various members of the receptor, protein phosphatase and kinase families. Our results suggest that the default state of the SnRK2 kinases is an autophosphorylated, active state and that the SnRK2 kinases are kept inactive by the PP2Cs through physical interaction and dephosphorylation. We found that in the presence of ABA, the PYR/PYL (pyrabactin resistance 1/PYR1-like) receptor proteins can disrupt the interaction between the SnRK2s and PP2Cs, thus preventing the PP2C-mediated dephosphorylation of the SnRK2s and resulting in the activation of the SnRK2 kinases. Our results reveal new insights into ABA signalling mechanisms and define a minimal set of core components of a complete major ABA signalling pathway.
C1 [Fujii, Hiroaki; Chinnusamy, Viswanathan; Park, Sang-Youl; Cutler, Sean R.; Zhu, Jian-Kang] Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
   [Fujii, Hiroaki; Chinnusamy, Viswanathan; Zhu, Jian-Kang] 4700 King Abdullah Univ Sci & Technol, Ctr Plant Stress Genom & Technol, Thuwal 239556900, Saudi Arabia.
   [Rodrigues, Americo; Rubio, Silvia; Antoni, Regina; Rodriguez, Pedro L.] Univ Politecn Valencia, CSIC, Inst Biol Mol & Celular Plantas, ES-46022 Valencia, Spain.
   [Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
C3 University of California System; University of California Riverside; King Abdullah University of Science & Technology; Consejo Superior de Investigaciones Cientificas (CSIC); Universitat Politecnica de Valencia; CSIC-UPV - Instituto de Biologia Molecular y Celular de Plantas (IBMCP); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Zhu, JK (corresponding author), Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
EM jian-kang.zhu@ucr.edu
FU National Institutes of Health; MICIIN; CSIC; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0843244] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0820508] Funding Source: National Science Foundation
NR 30
TC 1055
Z9 1213
U1 19
U2 441
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 660
EP U138
DI 10.1038/nature08599
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900043
PM 19924127
DA 2026-03-09
ER

PT J
AU Eilken, HM
   Nishikawa, SI
   Schroeder, T
AF Eilken, Hanna M.
   Nishikawa, Shin-Ichi
   Schroeder, Timm
TI Continuous single-cell imaging of blood generation from haemogenic endothelium
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; definitive hematopoiesis; mouse embryo; expression; origin; cd41; differentiation; vasculogenesis; progenitors; commitment
AB Despite decades of research, the identity of the cells generating the first haematopoietic cells in mammalian embryos is unknown(1). Indeed, whether blood cells arise from mesodermal cells, mesenchymal progenitors, bipotent endothelial - haematopoietic precursors or haemogenic endothelial cells remains controversial(2-9). Proximity of endothelial and blood cells at sites of embryonic haematopoiesis, as well as their similar gene expression, led to the hypothesis of the endothelium generating blood. However, owing to lacking technology(10) it has been impossible to observe blood cell emergence continuously at the single- cell level, and the postulated existence of haemogenic endothelial cells remains disputed(1). Here, using new imaging and cell- tracking methods, we show that embryonic endothelial cells can be haemogenic. By continuous long- term single- cell observation of mouse mesodermal cells generating endothelial cell and blood colonies, it was possible to detect haemogenic endothelial cells giving rise to blood cells. Living endothelial and haematopoietic cells were identified by simultaneous detection of morphology and multiple molecular and functional markers. Detachment of nascent blood cells from endothelium is not directly linked to asymmetric cell division, and haemogenic endothelial cells are specified from cells already expressing endothelial markers. These results improve our understanding of the developmental origin of mammalian blood and the potential generation of haematopoietic stem cells from embryonic stem cells.
C1 [Eilken, Hanna M.; Schroeder, Timm] Helmholtz Ctr Munich, German Res Ctr Environm Hlth GmbH, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
   [Nishikawa, Shin-Ichi] RIKEN, Ctr Dev Biol, Lab Stem Cell Biol, Kobe, Hyogo 6500047, Japan.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; RIKEN
RP Schroeder, T (corresponding author), Helmholtz Ctr Munich, German Res Ctr Environm Hlth GmbH, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
EM timm.schroeder@helmholtz-muenchen.de
FU Deutsche Forschungsgemeinschaft; Leading Project for the Realization of Regenerative Medicine
NR 30
TC 468
Z9 560
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 12
PY 2009
VL 457
IS 7231
BP 896
EP 900
DI 10.1038/nature07760
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700048
PM 19212410
DA 2026-03-09
ER

PT J
AU Adriani, O
   Barbarino, GC
   Bazilevskaya, GA
   Bellotti, R
   Boezio, M
   Bogomolov, EA
   Bonechi, L
   Bongi, M
   Bonvicini, V
   Bottai, S
   Bruno, A
   Cafagna, F
   Campana, D
   Carlson, P
   Casolino, M
   Castellini, G
   De Pascale, MP
   De Rosa, G
   De Simone, N
   Di Felice, V
   Galper, AM
   Grishantseva, L
   Hofverberg, P
   Koldashov, SV
   Krutkov, SY
   Kvashnin, AN
   Leonov, A
   Malvezzi, V
   Marcelli, L
   Menn, W
   Mikhailov, VV
   Mocchiutti, E
   Orsi, S
   Osteria, G
   Papini, P
   Pearce, M
   Picozza, P
   Ricci, M
   Ricciarini, SB
   Simon, M
   Sparvoli, R
   Spillantini, P
   Stozhkov, YI
   Vacchi, A
   Vannuccini, E
   Vasilyev, G
   Voronov, SA
   Yurkin, YT
   Zampa, G
   Zampa, N
   Zverev, VG
AF Adriani, O.
   Barbarino, G. C.
   Bazilevskaya, G. A.
   Bellotti, R.
   Boezio, M.
   Bogomolov, E. A.
   Bonechi, L.
   Bongi, M.
   Bonvicini, V.
   Bottai, S.
   Bruno, A.
   Cafagna, F.
   Campana, D.
   Carlson, P.
   Casolino, M.
   Castellini, G.
   De Pascale, M. P.
   De Rosa, G.
   De Simone, N.
   Di Felice, V.
   Galper, A. M.
   Grishantseva, L.
   Hofverberg, P.
   Koldashov, S. V.
   Krutkov, S. Y.
   Kvashnin, A. N.
   Leonov, A.
   Malvezzi, V.
   Marcelli, L.
   Menn, W.
   Mikhailov, V. V.
   Mocchiutti, E.
   Orsi, S.
   Osteria, G.
   Papini, P.
   Pearce, M.
   Picozza, P.
   Ricci, M.
   Ricciarini, S. B.
   Simon, M.
   Sparvoli, R.
   Spillantini, P.
   Stozhkov, Y. I.
   Vacchi, A.
   Vannuccini, E.
   Vasilyev, G.
   Voronov, S. A.
   Yurkin, Y. T.
   Zampa, G.
   Zampa, N.
   Zverev, V. G.
TI An anomalous positron abundance in cosmic rays with energies 1.5-100 GeV
SO NATURE
LA English
DT Article
ID dark-matter; electron; fraction; particle
AB Antiparticles account for a small fraction of cosmic rays and are known to be produced in interactions between cosmic-ray nuclei and atoms in the interstellar medium(1), which is referred to as a 'secondary source'. Positrons might also originate in objects such as pulsars(2) and microquasars(3) or through dark matter annihilation(4), which would be 'primary sources'. Previous statistically limited measurements(5-7) of the ratio of positron and electron fluxes have been interpreted as evidence for a primary source for the positrons, as has an increase in the total electron+positron flux at energies between 300 and 600 GeV (ref. 8). Here we report a measurement of the positron fraction in the energy range 1.5-100 GeV. We find that the positron fraction increases sharply overmuch of that range, in a way that appears to be completely inconsistent with secondary sources. We therefore conclude that a primary source, be it an astrophysical object or dark matter annihilation, is necessary.
C1 [Casolino, M.; De Pascale, M. P.; De Simone, N.; Di Felice, V.; Malvezzi, V.; Marcelli, L.; Orsi, S.; Picozza, P.; Sparvoli, R.] Ist Nazl Fis Nucl, Sez Roma Tor Vergata, I-00133 Rome, Italy.
   [Adriani, O.; Bonechi, L.; Spillantini, P.] Univ Florence, Dept Phys, I-50019 Florence, Italy.
   [Adriani, O.; Bonechi, L.; Bongi, M.; Bottai, S.; Papini, P.; Ricciarini, S. B.; Spillantini, P.; Vannuccini, E.] Ist Nazl Fis Nucl, Sez Florene, I-50019 Florence, Italy.
   [Barbarino, G. C.] Univ Naples Federico II, Dept Phys, I-80126 Naples, Italy.
   [Barbarino, G. C.; Campana, D.; De Rosa, G.; Osteria, G.] Univ Naples Federico II, Sez Naples, I-80126 Naples, Italy.
   [Bazilevskaya, G. A.; Kvashnin, A. N.; Stozhkov, Y. I.] PN Lebedev Phys Inst, RU-119991 Moscow, Russia.
   [Bellotti, R.; Bruno, A.] Univ Bari, Dept Phys, I-70126 Bari, Italy.
   [Bellotti, R.; Bruno, A.; Cafagna, F.] Ist Nazl Fis Nucl, Sez Bari, I-70126 Bari, Italy.
   [Boezio, M.; Bonvicini, V.; Mocchiutti, E.; Vacchi, A.; Zampa, G.; Zampa, N.] Ist Nazl Fis Nucl, Sez Trieste, I-34012 Trieste, Italy.
   [Bogomolov, E. A.; Krutkov, S. Y.; Vasilyev, G.] AF Ioffe Phys Tech Inst, RU-194021 St Petersburg, Russia.
   [Carlson, P.; Hofverberg, P.; Orsi, S.; Pearce, M.] AlbaNova Univ Ctr, Dept Phys, KTH, SE-10691 Stockholm, Sweden.
   [Castellini, G.] IFAC, I-50019 Florence, Italy.
   [De Pascale, M. P.; De Simone, N.; Di Felice, V.; Picozza, P.; Sparvoli, R.] Univ Roma Tor Vergata, Dept Phys, I-00133 Rome, Italy.
   [Galper, A. M.; Grishantseva, L.; Koldashov, S. V.; Leonov, A.; Mikhailov, V. V.; Voronov, S. A.; Yurkin, Y. T.; Zverev, V. G.] Moscow Engn & Phys Inst, RU-11540 Moscow, Russia.
   [Menn, W.; Simon, M.] Univ Siegen, D-57068 Siegen, Germany.
   [Pearce, M.] AlbaNova Univ Ctr, Oskar Klein Ctr Cosmoparticle Phys, SE-10691 Stockholm, Sweden.
   [Ricci, M.] Ist Nazl Fis Nucl, Lab Nazl Frascati, I-00044 Frascati, Italy.
C3 Istituto Nazionale di Fisica Nucleare (INFN); University of Florence; Istituto Nazionale di Fisica Nucleare (INFN); University of Naples Federico II; University of Naples Federico II; Russian Academy of Sciences; Russian Academy of Science Lebedev Physical Institute; Universita degli Studi di Bari Aldo Moro; Istituto Nazionale di Fisica Nucleare (INFN); Istituto Nazionale di Fisica Nucleare (INFN); Russian Academy of Sciences; St. Petersburg Scientific Centre of the Russian Academy of Sciences; Ioffe Physical Technical Institute; Royal Institute of Technology; Consiglio Nazionale delle Ricerche (CNR); Istituto di Fisica Applicata Nello Carrara (IFAC-CNR); University of Rome Tor Vergata; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); Universitat Siegen; Oskar Klein Centre; Istituto Nazionale di Fisica Nucleare (INFN)
RP Picozza, P (corresponding author), Ist Nazl Fis Nucl, Sez Roma Tor Vergata, Via Ricerca Sci 1, I-00133 Rome, Italy.
EM Piergiorgio.Picozza@roma2.infn.it
FU The Italian Space Agency (ASI); Deutsches Zentrumfur Luftund Raumfahrt (DLR); The Swedish National Space Board; The Swedish Research Council; The Russian Space Agency (Roscosmos); The Russian Foundation for Basic Research
NR 30
TC 1788
Z9 1989
U1 0
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 2
PY 2009
VL 458
IS 7238
BP 607
EP 609
DI 10.1038/nature07942
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200035
PM 19340076
DA 2026-03-09
ER

PT J
AU Meylan, E
   Dooley, AL
   Feldser, DM
   Shen, L
   Turk, E
   Ouyang, C
   Jacks, T
AF Meylan, Etienne
   Dooley, Alison L.
   Feldser, David M.
   Shen, Lynn
   Turk, Erin
   Ouyang, Chensi
   Jacks, Tyler
TI Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma
SO NATURE
LA English
DT Article
ID ikk-beta; cellular-transformation; kinase complex; k-ras; cancer; p53; activation; inflammation; integrator; inhibition
AB NF-kappa B transcription factors function as crucial regulators of inflammatory and immune responses as well as of cell survival(1). They have also been implicated in cellular transformation and tumorigenesis(2-6). However, despite extensive biochemical characterization of NF-kappa B signalling during the past twenty years, the requirement for NF-kappa B in tumour development in vivo, particularly in solid tumours, is not completely understood. Here we show that the NF-kappa B pathway is required for the development of tumours in a mouse model of lung adenocarcinoma. Concomitant loss of p53 (also known as Trp53) and expression of oncogenic Kras(G12D) resulted in NF-kappa B activation in primary mouse embryonic fibroblasts. Conversely, in lung tumour cell lines expressing Kras(G12D) and lacking p53, p53 restoration led to NF-kappa B inhibition. Furthermore, the inhibition of NF-kappa B signalling induced apoptosis in p53-null lung cancer cell lines. Inhibition of the pathway in lung tumours in vivo, from the time of tumour initiation or after tumour progression, resulted in significantly reduced tumour development. Together, these results indicate a critical function for NF-kappa B signalling in lung tumour development and, further, that this requirement depends on p53 status. These findings also provide support for the development of NF-kappa B inhibitory drugs as targeted therapies for the treatment of patients with defined mutations in Kras and p53.
C1 [Meylan, Etienne; Dooley, Alison L.; Feldser, David M.; Shen, Lynn; Turk, Erin; Ouyang, Chensi; Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Meylan, Etienne; Dooley, Alison L.; Feldser, David M.; Shen, Lynn; Turk, Erin; Ouyang, Chensi; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Meylan, Etienne; Dooley, Alison L.; Feldser, David M.; Shen, Lynn; Turk, Erin; Ouyang, Chensi; Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
RP Jacks, T (corresponding author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM tjacks@mit.edu
FU Howard Hughes Medical Institute; NCI [P30-CA14051]; International Human Frontier Science Program Organization; Swiss National Science Foundation; Leukemia & Lymphoma Society Fellow Award; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER
NR 30
TC 459
Z9 526
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 NOV 5
PY 2009
VL 462
IS 7269
BP 104
EP U115
DI 10.1038/nature08462
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200041
PM 19847165
DA 2026-03-09
ER

PT J
AU Pollard, RT
   Salter, I
   Sanders, RJ
   Lucas, MI
   Moore, CM
   Mills, RA
   Statham, PJ
   Allen, JT
   Baker, AR
   Bakker, DCE
   Charette, MA
   Fielding, S
   Fones, GR
   French, M
   Hickman, AE
   Holland, RJ
   Hughes, JA
   Jickells, TD
   Lampitt, RS
   Morris, PJ
   Nédélec, FH
   Nielsdóttir, M
   Planquette, H
   Popova, EE
   Poulton, AJ
   Read, JF
   Seeyave, S
   Smith, T
   Stinchcombe, M
   Taylor, S
   Thomalla, S
   Venables, HJ
   Williamson, R
   Zubkov, MV
AF Pollard, Raymond T.
   Salter, Ian
   Sanders, Richard J.
   Lucas, Mike I.
   Moore, C. Mark
   Mills, Rachel A.
   Statham, Peter J.
   Allen, John T.
   Baker, Alex R.
   Bakker, Dorothee C. E.
   Charette, Matthew A.
   Fielding, Sophie
   Fones, Gary R.
   French, Megan
   Hickman, Anna E.
   Holland, Ross J.
   Hughes, J. Alan
   Jickells, Timothy D.
   Lampitt, Richard S.
   Morris, Paul J.
   Nedelec, Florence H.
   Nielsdottir, Maria
   Planquette, Helene
   Popova, Ekaterina E.
   Poulton, Alex J.
   Read, Jane F.
   Seeyave, Sophie
   Smith, Tania
   Stinchcombe, Mark
   Taylor, Sarah
   Thomalla, Sandy
   Venables, Hugh J.
   Williamson, Robert
   Zubkov, Mike V.
TI Southern Ocean deep-water carbon export enhanced by natural iron fertilization
SO NATURE
LA English
DT Article
ID phytoplankton bloom; crozet plateau; radium isotopes; co2; sequestration; responses; north; scale; si
AB The addition of iron to high- nutrient, low- chlorophyll regions induces phytoplankton blooms that take up carbon(1-3). Carbon export from the surface layer and, in particular, the ability of the ocean and sediments to sequester carbon for many years remains, however, poorly quantified(3). Here we report data from the CROZEX experiment(4) in the Southern Ocean, which was conducted to test the hypothesis that the observed north - south gradient in phytoplankton concentrations in the vicinity of the Crozet Islands is induced by natural iron fertilization that results in enhanced organic carbon flux to the deep ocean. We report annual particulate carbon fluxes out of the surface layer, at three kilometres below the ocean surface and to the ocean floor. We find that carbon fluxes from a highly productive, naturally iron-fertilized region of the sub- Antarctic Southern Ocean are two to three times larger than the carbon fluxes from an adjacent high-nutrient, low- chlorophyll area not fertilized by iron. Our findings support the hypothesis that increased iron supply to the glacial sub- Antarctic may have directly enhanced carbon export to the deep ocean(5). The CROZEX sequestration efficiency(6) ( the amount of carbon sequestered below the depth of winter mixing for a given iron supply) of 8,600 mol mol(-1) was 18 times greater than that of a phytoplankton bloom induced artificially by adding iron(7), but 77 times smaller than that of another bloom(8) initiated, like CROZEX, by a natural supply of iron. Large losses of purposefully added iron can explain the lower efficiency of the induced bloom(6). The discrepancy between the blooms naturally supplied with iron may result in part from an underestimate of horizontal iron supply.
C1 [Pollard, Raymond T.; Salter, Ian; Sanders, Richard J.; Moore, C. Mark; Mills, Rachel A.; Statham, Peter J.; Allen, John T.; Holland, Ross J.; Hughes, J. Alan; Lampitt, Richard S.; Morris, Paul J.; Nielsdottir, Maria; Popova, Ekaterina E.; Poulton, Alex J.; Read, Jane F.; Seeyave, Sophie; Smith, Tania; Stinchcombe, Mark; Taylor, Sarah; Zubkov, Mike V.] Natl Environm Res Council, Natl Oceanog Ctr Southampton, Southampton SO14 3ZH, Hants, England.
   [Pollard, Raymond T.; Salter, Ian; Sanders, Richard J.; Moore, C. Mark; Mills, Rachel A.; Statham, Peter J.; Allen, John T.; Holland, Ross J.; Hughes, J. Alan; Lampitt, Richard S.; Morris, Paul J.; Nielsdottir, Maria; Popova, Ekaterina E.; Poulton, Alex J.; Read, Jane F.; Seeyave, Sophie; Smith, Tania; Stinchcombe, Mark; Taylor, Sarah; Zubkov, Mike V.] Univ Southampton, Southampton SO14 3ZH, Hants, England.
   [Salter, Ian] Observ Oceanol, BP44, F-66651 Banyuls Sur Mer, France.
   [Lucas, Mike I.] Univ Cape Town, Dept Zool, ZA-7701 Rondebosch, South Africa.
   [Baker, Alex R.; Bakker, Dorothee C. E.; French, Megan; Jickells, Timothy D.] Univ E Anglia, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
   [Charette, Matthew A.] Woods Hole Oceanog Inst, Dept Marine Chem & Geochem MS25, Woods Hole, MA 02543 USA.
   [Fielding, Sophie; Venables, Hugh J.] British Antarctic Survey, Cambridge CB3 0ET, England.
   [Fones, Gary R.] Univ Portsmouth, Sch Earth & Environm Sci, Portsmouth PO1 3QL, Hants, England.
   [Hickman, Anna E.] Univ Liverpool, Dept Earth & Ocean Sci, Liverpool L69 3GP, Merseyside, England.
   [Nedelec, Florence H.] IFREMER, Lab Environm & Resources Normandie, F-14520 Port En Bessen, France.
   [Planquette, Helene] Rutgers State Univ, Inst Marine & Coastal Sci, New Brunswick, NJ 08901 USA.
   [Thomalla, Sandy; Williamson, Robert] Univ Cape Town, Dept Oceanog, ZA-7701 Rondebosch, South Africa.
C3 NERC National Oceanography Centre; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); University of Southampton; University of Southampton; Sorbonne Universite; University of Cape Town; University of East Anglia; Woods Hole Oceanographic Institution; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; University of Portsmouth; University of Liverpool; Ifremer; Rutgers University System; Rutgers University New Brunswick; University of Cape Town
RP Sanders, RJ (corresponding author), Natl Environm Res Council, Natl Oceanog Ctr Southampton, European Way, Southampton SO14 3ZH, Hants, England.
EM rics@noc.soton.ac.uk
FU Natural Environment Research Council; Natural Environment Research Council [NE/B502844/1, NE/F017359/1, bas010017, NE/C507353/1, soc010008] Funding Source: researchfish; NERC [soc010008, bas010017, NE/F017359/1] Funding Source: UKRI
NR 32
TC 284
Z9 313
U1 3
U2 237
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 29
PY 2009
VL 457
IS 7229
BP 577
EP U81
DI 10.1038/nature07716
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200040
PM 19177128
DA 2026-03-09
ER

PT J
AU Jost, PJ
   Grabow, S
   Gray, D
   McKenzie, MD
   Nachbur, U
   Huang, DCS
   Bouillet, P
   Thomas, HE
   Borner, C
   Silke, J
   Strasser, A
   Kaufmann, T
AF Jost, Philipp J.
   Grabow, Stephanie
   Gray, Daniel
   McKenzie, Mark D.
   Nachbur, Ueli
   Huang, David C. S.
   Bouillet, Philippe
   Thomas, Helen E.
   Borner, Christoph
   Silke, John
   Strasser, Andreas
   Kaufmann, Thomas
TI XIAP discriminates between type I and type II FAS-induced apoptosis
SO NATURE
LA English
DT Article
ID alpha-dependent apoptosis; deficient mice; immune-system; t-lymphocytes; cytochrome-c; cell-death; protein; smac; activation; receptor
AB FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development(1-4). Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis(1-4). In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the proapoptotic BCL-2 family member BID (BH3 interacting domain death agonist) 5 is essential(6-8). Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) 9,10 function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC(11,) also called DIABLO(12); direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.
C1 [Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; Huang, David C. S.; Bouillet, Philippe; Strasser, Andreas; Kaufmann, Thomas] Univ Melbourne, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
   [Grabow, Stephanie; McKenzie, Mark D.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3050, Australia.
   [McKenzie, Mark D.; Thomas, Helen E.] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia.
   [Nachbur, Ueli; Silke, John] La Trobe Univ, Inst Biochem, Bundoora, Vic 3086, Australia.
   [Borner, Christoph] Ctr Biochem & Mol Cell Res, Inst Mol Med & Cell Res, D-79104 Freiburg, Germany.
C3 Walter & Eliza Hall Institute; University of Melbourne; University of Melbourne; St. Vincent's Institute of Medical Research; La Trobe University
RP Strasser, A (corresponding author), Univ Melbourne, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
EM strasser@wehi.edu.au; thomas.kaufmann@pki.unibe.ch
FU NHMRC ( Canberra); NCI [CA 80188, CA 43540]; Leukemia and Lymphoma Society of America [7015]; JDRF/ NHMRC; Cancer Council Victoria; Leukemia Foundation of Australia; Swiss National Science Foundation; Novartis Jubilaeumsstiftung; HepatoSys programme; German Jose Carreras Leukemia Foundation [06/09]; Spemann Graduate School of Biology and Medicine [GSC-4]; Dr. Mildred-Scheel Stiftung/Deutsche Krebshilfe;  [257502];  [251608];  [384404]
NR 35
TC 373
Z9 455
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 AUG 20
PY 2009
VL 460
IS 7258
BP 1035
EP U128
DI 10.1038/nature08229
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500039
PM 19626005
DA 2026-03-09
ER

PT J
AU Huang, Y
   Ji, LJ
   Huang, QC
   Vassylyev, DG
   Chen, XM
   Ma, JB
AF Huang, Ying
   Ji, Lijuan
   Huang, Qichen
   Vassylyev, Dmitry G.
   Chen, Xuemei
   Ma, Jin-Biao
TI Structural insights into mechanisms of the small RNA methyltransferase HEN1
SO NATURE
LA English
DT Article
ID small interfering rna; piwi-interacting rnas; 3'-end recognition; microrna; methylation; protein; homolog; family; la; 2'-o-methylation
AB RNA silencing is a conserved regulatory mechanism in fungi, plants and animals that regulates gene expression and defence against viruses and transgenes(1). Small silencing RNAs of similar to 20-30 nucleotides and their associated effector proteins, the Argonaute family proteins, are the central components in RNA silencing(2). A subset of small RNAs, such as microRNAs and small interfering RNAs (siRNAs) in plants, Piwi-interacting RNAs in animals and siRNAs in Drosophila, requires an additional crucial step for their maturation; that is, 2'-O-methylation on the 39 terminal nucleotide(3-6). A conserved S-adenosyl-L-methionine-dependent RNA methyltransferase, HUA ENHANCER 1 (HEN1), and its homologues are responsible for this specific modification(3-5,7,8). Here we report the 3.1 angstrom crystal structure of full-length HEN1 from Arabidopsis in complex with a 22-nucleotide small RNA duplex and cofactor product S-adenosyl-L-homocysteine. Highly cooperative recognition of the small RNA substrate by multiple RNA binding domains and the methyltransferase domain in HEN1 measures the length of the RNA duplex and determines the substrate specificity. Metal ion coordination by both 2' and 3' hydroxyls on the 3'-terminal nucleotide and four invariant residues in the active site of the methyltransferase domain suggests a novel Mg2+-dependent 2'-O-methylation mechanism.
C1 [Huang, Ying; Huang, Qichen; Vassylyev, Dmitry G.; Ma, Jin-Biao] Univ Alabama Birmingham, Dept Biochem, Birmingham, AL 35294 USA.
   [Huang, Ying; Huang, Qichen; Vassylyev, Dmitry G.; Ma, Jin-Biao] Univ Alabama Birmingham, Sch Med, Dept Mol Genet, Birmingham, AL 35294 USA.
   [Huang, Ying; Huang, Qichen; Vassylyev, Dmitry G.; Ma, Jin-Biao] Univ Alabama Birmingham, Sch Dent, Birmingham, AL 35294 USA.
   [Ji, Lijuan; Chen, Xuemei] Univ Calif Riverside, Dept Bot & Plant Sci, Inst Integrat Genome Biol, Riverside, CA 92521 USA.
   [Ma, Jin-Biao] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
C3 University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham; University of California System; University of California Riverside; University of Alabama System; University of Alabama Birmingham
RP Ma, JB (corresponding author), Univ Alabama Birmingham, Dept Biochem, Birmingham, AL 35294 USA.
EM jma@biochemistry.uab.edu
FU V Foundation for Cancer Research; National Science Foundation [MCB-0718029]; National Institutes of Health [R01 GM074252, R01 GM074840]; National Institute of General Medical Sciences [R01GM061146] Funding Source: NIH RePORTER
NR 38
TC 116
Z9 134
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 OCT 8
PY 2009
VL 461
IS 7265
BP 823
EP U86
DI 10.1038/nature08433
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500042
PM 19812675
DA 2026-03-09
ER

PT J
AU Davies, A
   Kemp, AES
   Pike, J
AF Davies, Andrew
   Kemp, Alan E. S.
   Pike, Jennifer
TI Late Cretaceous seasonal ocean variability from the Arctic
SO NATURE
LA English
DT Article
ID sea; temperatures; entrainment; perspective; sediment; diatoms; cycle; gyre
AB The modern Arctic Ocean is regarded as a barometer of global change and amplifier of global warming(1) and therefore records of past Arctic change are critical for palaeoclimate reconstruction. Little is known of the state of the Arctic Ocean in the greenhouse period of the Late Cretaceous epoch (65-99 million years ago), yet records from such times may yield important clues to Arctic Ocean behaviour in near-future warmer climates. Here we present a seasonally resolved Cretaceous sedimentary record from the Alpha ridge of the Arctic Ocean. This palaeo-sediment trap provides new insight into the workings of the Cretaceous marine biological carbon pump. Seasonal primary production was dominated by diatom algae but was not related to upwelling as was previously hypothesized(2). Rather, production occurred within a stratified water column, involving specially adapted species in blooms resembling those of the modern North Pacific subtropical gyre(3), or those indicated for the Mediterranean sapropels(4). With increased CO2 levels and warming currently driving increased stratification in the global ocean(5), this style of production that is adapted to stratification may become more widespread. Our evidence for seasonal diatom production and flux testify to an ice-free summer, but thin accumulations of terrigenous sediment within the diatom ooze are consistent with the presence of intermittent sea ice in the winter, supporting a wide body of evidence for low temperatures in the Late Cretaceous Arctic Ocean(6-8), rather than recent suggestions of a 15 degrees C mean annual temperature at this time(9).
C1 [Davies, Andrew; Kemp, Alan E. S.] Univ Southampton, Sch Ocean & Earth Sci, Natl Oceanog Ctr Southampton, Southampton SO14 3ZH, Hants, England.
   [Pike, Jennifer] Cardiff Univ, Sch Ocean & Earth Sci, Cardiff CF10 3YE, S Glam, Wales.
C3 NERC National Oceanography Centre; University of Southampton; Cardiff University
RP Kemp, AES (corresponding author), Univ Southampton, Sch Ocean & Earth Sci, Natl Oceanog Ctr Southampton, Southampton SO14 3ZH, Hants, England.
EM aesk@noc.soton.ac.uk
FU NERC
NR 33
TC 84
Z9 101
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 9
PY 2009
VL 460
IS 7252
BP 254
EP U118
DI 10.1038/nature08141
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000040
PM 19587768
DA 2026-03-09
ER

PT J
AU Yuan, HQ
   Singleton, J
   Balakirev, FF
   Baily, SA
   Chen, GF
   Luo, JL
   Wang, NL
AF Yuan, H. Q.
   Singleton, J.
   Balakirev, F. F.
   Baily, S. A.
   Chen, G. F.
   Luo, J. L.
   Wang, N. L.
TI Nearly isotropic superconductivity in (Ba,K)Fe2As2
SO NATURE
LA English
DT Article
ID upper critical-field; fermi-surface
AB Superconductivity was recently observed(1-7) in iron- arsenic- based compounds with a superconducting transition temperature (T-c) as high as 56 K, naturally raising comparisons with the high-T-c copper oxides. The copper oxides have layered crystal structures with quasi- two- dimensional electronic properties, which led to speculation that reduced dimensionality ( that is, extreme anisotropy) is a necessary prerequisite for superconductivity at temperatures above 40 K ( refs 8, 9). Early work on the iron- arsenic compounds seemed to support this view(7,10). Here we report measurements of the electrical resistivity in single crystals of (Ba,K)Fe2As2 in a magnetic field up to 60 T. We find that the superconducting properties are in fact quite isotropic, being rather independent of the direction of the applied magnetic fields at low temperature. Such behaviour is strikingly different from all previously known layered superconductors(9,11), and indicates that reduced dimensionality in these compounds is not a prerequisite for 'high- temperature' superconductivity. We suggest that this situation arises because of the underlying electronic structure of the iron- arsenic compounds, which appears to be much more three dimensional than that of the copper oxides. Extrapolations of low- field single- crystal data incorrectly suggest a high anisotropy and a greatly exaggerated zero- temperature upper critical field.
C1 [Yuan, H. Q.] Zhejiang Univ, Dept Phys, Hangzhou 310027, Peoples R China.
   [Yuan, H. Q.; Singleton, J.; Balakirev, F. F.; Baily, S. A.] Los Alamos Natl Lab, NHMFL, MS E536, Los Alamos, NM 87545 USA.
   [Chen, G. F.; Luo, J. L.; Wang, N. L.] Chinese Acad Sci, Beijing Natl Lab Condensed Matter Phys, Beijing 10080, Peoples R China.
C3 Zhejiang University; United States Department of Energy (DOE); Los Alamos National Laboratory; Chinese Academy of Sciences
RP Yuan, HQ (corresponding author), Zhejiang Univ, Dept Phys, Hangzhou 310027, Peoples R China.
EM hqyuan@zju.edu.cn
FU DOE BES program 'Science in 100T'; NHMFL-UCGP; National Science Foundation of China; National Basic Research Program of China [973]; Chinese Academy of Sciences; PCSIRT; Ministry of Education of China
NR 27
TC 499
Z9 533
U1 3
U2 254
PU 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 29
PY 2009
VL 457
IS 7229
BP 565
EP 568
DI 10.1038/nature07676
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200037
PM 19177125
DA 2026-03-09
ER

PT J
AU Marino, AM
   Pooser, RC
   Boyer, V
   Lett, PD
AF Marino, A. M.
   Pooser, R. C.
   Boyer, V.
   Lett, P. D.
TI Tunable delay of Einstein-Podolsky-Rosen entanglement
SO NATURE
LA English
DT Article
ID electromagnetically induced transparency; quantum; information; paradox
AB Entangled systems display correlations that are stronger than can be obtained classically. This makes entanglement an essential resource for a number of applications, such as quantum information processing, quantum computing and quantum communications(1,2). The ability to control the transfer of entanglement between different locations will play a key role in these quantum protocols and enable quantum networks(3). Such a transfer requires a system that can delay quantum correlations without significant degradation, effectively acting as a short- term quantum memory. An important benchmark for such systems is the ability to delay Einstein - Podolsky - Rosen ( EPR) levels of entanglement and to be able to tune the delay. EPR entanglement is the basis for a number of quantum protocols, allowing the remote inference of the properties of one system ( to better than its standard quantum limit) through measurements on the other correlated system. Here we show that a four- wave mixing process based on a double- lambda scheme in hot Rb-85 vapour allows us to obtain an optically tunable delay for EPR entangled beams of light. A significant maximum delay, of the order of the width of the cross- correlation function, is achieved. The four- wave mixing also preserves the quantum spatial correlations of the entangled beams. We take advantage of this property to delay entangled images, making this the first step towards a quantum memory for images(4).
C1 [Marino, A. M.; Pooser, R. C.; Boyer, V.; Lett, P. D.] Natl Inst Stand & Technol, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
   [Marino, A. M.; Pooser, R. C.; Boyer, V.; Lett, P. D.] Univ Maryland, Gaithersburg, MD 20899 USA.
   [Boyer, V.] Univ Birmingham, MUARC, Sch Phys & Astron, Birmingham B15 2TT, W Midlands, England.
C3 National Institute of Standards & Technology (NIST) - USA; University System of Maryland; University of Maryland College Park; University of Birmingham
RP Marino, AM (corresponding author), Natl Inst Stand & Technol, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
EM alberto.marino@nist.gov
FU Intelligence Community Postdoctoral Program; Engineering and Physical Sciences Research Council [EP/E036473/1] Funding Source: researchfish; EPSRC [EP/E036473/1] Funding Source: UKRI
NR 29
TC 228
Z9 249
U1 1
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 12
PY 2009
VL 457
IS 7231
BP 859
EP 862
DI 10.1038/nature07751
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700040
PM 19212406
DA 2026-03-09
ER

PT J
AU Husale, S
   Persson, HHJ
   Sahin, O
AF Husale, Sudhir
   Persson, Henrik H. J.
   Sahin, Ozgur
TI DNA nanomechanics allows direct digital detection of complementary DNA and microRNA targets
SO NATURE
LA English
DT Article
ID label-free detection; gene-expression; electrical detection; hybridization; nanoparticles; pcr
AB Techniques to detect and quantify DNA and RNA molecules in biological samples have had a central role in genomics research(1-3). Over the past decade, several techniques have been developed to improve detection performance and reduce the cost of genetic analysis(4-10). In particular, significant advances in label-free methods have been reported(11-17). Yet detection of DNA molecules at concentrations below the femtomolar level requires amplified detection schemes(1,8). Here we report a unique nanomechanical response of hybridized DNA and RNA molecules that serves as an intrinsic molecular label. Nanomechanical measurements on a microarray surface have sufficient background signal rejection to allow direct detection and counting of hybridized molecules. The digital response of the sensor provides a large dynamic range that is critical for gene expression profiling. We have measured differential expressions of microRNAs in tumour samples; such measurements have been shown to help discriminate between the tissue origins of metastatic tumours(18). Two hundred picograms of total RNA is found to be sufficient for this analysis. In addition, the limit of detection in pure samples is found to be one attomolar. These results suggest that nanomechanical read-out of microarrays promises attomolar-level sensitivity and large dynamic range for the analysis of gene expression, while eliminating biochemical manipulations, amplification and labelling.
C1 [Husale, Sudhir; Sahin, Ozgur] Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02142 USA.
   [Persson, Henrik H. J.] Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA.
C3 Harvard University; Stanford University
RP Sahin, O (corresponding author), Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02142 USA.
EM sahin@rowland.harvard.edu
FU Rowland Junior Fellows Program; US National Institutes of Health [HG000205]
NR 31
TC 127
Z9 151
U1 0
U2 116
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 24
PY 2009
VL 462
IS 7276
BP 1075
EP U138
DI 10.1038/nature08626
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 535UB
UT WOS:000272996000051
PM 20010806
DA 2026-03-09
ER

PT J
AU Knigge, C
   Leigh, N
   Sills, A
AF Knigge, Christian
   Leigh, Nathan
   Sills, Alison
TI A binary origin for 'blue stragglers' in globular clusters
SO NATURE
LA English
DT Article
ID stellar collision products; radial-distribution; main-sequence; 47 tucanae; milky-way; evolution; stars; core; progenitors; parameters
AB Blue stragglers in globular clusters are abnormally massive stars that should have evolved off the stellar main sequence long ago. There are two known processes that can create these objects: direct stellar collisions(1) and binary evolution(2). However, the relative importance of these processes has remained unclear. In particular, the total number of blue stragglers found in a given cluster does not seem to correlate with the predicted collision rate(3,4), providing indirect support for the binary- evolution model. Yet the radial distributions of blue stragglers in many clusters are bimodal, with a dominant central peak(5-7): this has been interpreted as an indication that collisions do dominate blue straggler production, at least in the high- density cluster cores(7,8). Here we report that there is a clear, but sublinear, correlation between the number of blue stragglers found in a cluster core and the total stellar mass contained within it. From this we conclude that most blue stragglers, even those found in cluster cores, come from binary systems. The parent binaries, however, may themselves have been affected by dynamical encounters. This may be the key to reconciling all of the seemingly conflicting results found to date.
C1 [Knigge, Christian] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Leigh, Nathan; Sills, Alison] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada.
C3 University of Southampton; McMaster University
RP Knigge, C (corresponding author), Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
EM christian@astro.soton.ac.uk
FU Natural Sciences and Engineering Research Council of Canada; STFC [PP/D001013/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/D001013/1] Funding Source: researchfish
NR 31
TC 134
Z9 141
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 JAN 15
PY 2009
VL 457
IS 7227
BP 288
EP 290
DI 10.1038/nature07635
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900033
PM 19148094
DA 2026-03-09
ER

PT J
AU Biastoch, A
   Böning, CW
   Schwarzkopf, FU
   Lutjeharms, JRE
AF Biastoch, A.
   Boening, C. W.
   Schwarzkopf, F. U.
   Lutjeharms, J. R. E.
TI Increase in Agulhas leakage due to poleward shift of Southern Hemisphere westerlies
SO NATURE
LA English
DT Article
ID thermohaline circulation; ocean; atlantic; variability; model; ice
AB The transport of warm and salty Indian Ocean waters into the Atlantic Ocean-the Agulhas leakage-has a crucial role in the global oceanic circulation(1) and thus the evolution of future climate. At present these waters provide the main source of heat and salt for the surface branch of the Atlantic meridional overturning circulation (MOC)(2). There is evidence from past glacial-to-interglacial variations in foraminiferal assemblages(3) and model studies(4) that the amount of Agulhas leakage and its corresponding effect on the MOC has been subject to substantial change, potentially linked to latitudinal shifts in the Southern Hemisphere westerlies(5). A progressive poleward migration of the westerlies has been observed during the past two to three decades and linked to anthropogenic forcing(6), but because of the sparse observational records it has not been possible to determine whether there has been a concomitant response of Agulhas leakage. Here we present the results of a high-resolution ocean general circulation model(7,8) to show that the transport of Indian Ocean waters into the South Atlantic via the Agulhas leakage has increased during the past decades in response to the change in wind forcing. The increased leakage has contributed to the observed salinification(9) of South Atlantic thermocline waters. Both model and historic measurements off South America suggest that the additional Indian Ocean waters have begun to invade the North Atlantic, with potential implications for the future evolution of the MOC.
C1 [Biastoch, A.; Boening, C. W.; Schwarzkopf, F. U.] Leibniz Inst Meereswissensch, D-24105 Kiel, Germany.
   [Lutjeharms, J. R. E.] Univ Cape Town, Dept Oceanog, ZA-7700 Rondebosch, South Africa.
C3 Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; University of Cape Town
RP Biastoch, A (corresponding author), Leibniz Inst Meereswissensch, Dusternbrooker Weg 20, D-24105 Kiel, Germany.
EM abiastoch@ifm-geomar.de
FU DFG [BO 907/2-2, SFB 754]; BMBF [SUA 07/004]; South African National Research Foundation
NR 40
TC 276
Z9 294
U1 1
U2 63
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 495
EP U188
DI 10.1038/nature08519
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200041
PM 19940923
DA 2026-03-09
ER

PT J
AU Utikal, J
   Polo, JM
   Stadtfeld, M
   Maherali, N
   Kulalert, W
   Walsh, RM
   Khalil, A
   Rheinwald, JG
   Hochedlinger, K
AF Utikal, Jochen
   Polo, Jose M.
   Stadtfeld, Matthias
   Maherali, Nimet
   Kulalert, Warakorn
   Walsh, Ryan M.
   Khalil, Adam
   Rheinwald, James G.
   Hochedlinger, Konrad
TI Immortalization eliminates a roadblock during cellular reprogramming into iPS cells
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; tumor suppression; ink4a locus; life-span; fibroblasts; efficiency; system; generation; promoter; limits
AB The overexpression of defined transcription factors in somatic cells results in their reprogramming into induced pluripotent stem (iPS) cells(1-3). The extremely low efficiency and slow kinetics of in vitro reprogramming suggest that further rare events are required to generate iPS cells. The nature and identity of these events, however, remain elusive. We noticed that the reprogramming potential of primary murine fibroblasts into iPS cells decreases after serial passaging and the concomitant onset of senescence. Consistent with the notion that loss of replicative potential provides a barrier for reprogramming, here we show that cells with low endogenous p19(Arf) (encoded by the Ink4a/Arf locus, also known as Cdkn2a locus) protein levels and immortal fibroblasts deficient in components of the Arf-Trp53 pathway yield iPS cell colonies with up to threefold faster kinetics and at a significantly higher efficiency than wild-type cells, endowing almost every somatic cell with the potential to form iPS cells. Notably, the acute genetic ablation of Trp53 (also known as p53) in cellular sub-populations that normally fail to reprogram rescues their ability to produce iPS cells. Our results show that the acquisition of immortality is a crucial and rate-limiting step towards the establishment of a pluripotent state in somatic cells and underscore the similarities between induced pluripotency and tumorigenesis.
C1 [Utikal, Jochen; Polo, Jose M.; Stadtfeld, Matthias; Maherali, Nimet; Kulalert, Warakorn; Walsh, Ryan M.; Khalil, Adam; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA.
   [Utikal, Jochen; Polo, Jose M.; Stadtfeld, Matthias; Maherali, Nimet; Kulalert, Warakorn; Walsh, Ryan M.; Khalil, Adam; Hochedlinger, Konrad] Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Utikal, Jochen; Polo, Jose M.; Stadtfeld, Matthias; Maherali, Nimet; Kulalert, Warakorn; Walsh, Ryan M.; Khalil, Adam; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Utikal, Jochen] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Dermatol Venereol & Allergol, D-68135 Mannheim, Germany.
   [Maherali, Nimet] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Rheinwald, James G.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
   [Rheinwald, James G.] Harvard Skin Dis Res Ctr, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Ruprecht Karls University Heidelberg; Harvard University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School
RP Hochedlinger, K (corresponding author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA.
EM khochedlinger@helix.mgh.harvard.edu
FU Mildred Scheel Foundation; ECOR fellowship; Schering Foundation; NIH Skin Disease Research Center Grant; Natural Sciences and Engineering Council of Canada; NIH Director's Innovator Award; Harvard Stem Cell Institute; Kimmel Foundation and the V Foundation
NR 29
TC 679
Z9 822
U1 0
U2 59
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1145
EP 1148
DI 10.1038/nature08285
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000042
PM 19668190
DA 2026-03-09
ER

PT J
AU Schlichting, HE
   Ofek, EO
   Wenz, M
   Sari, R
   Gal-Yam, A
   Livio, M
   Nelan, E
   Zucker, S
AF Schlichting, H. E.
   Ofek, E. O.
   Wenz, M.
   Sari, R.
   Gal-Yam, A.
   Livio, M.
   Nelan, E.
   Zucker, S.
TI A single sub-kilometre Kuiper belt object from a stellar occultation in archival data
SO NATURE
LA English
DT Article
ID trans-neptunian objects; size distribution; millisecond dips; scorpius x-1; sco x-1; search; body; stars
AB The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects(1-4). Small, sub-kilometre-sized, Kuiper belt objects elude direct detection, but the signature of their occultations of background stars should be detectable(5-9). Observations at both optical(10) and X-ray(11) wavelengths claim to have detected such occultations, but their implied abundances are inconsistent with each other and far exceed theoretical expectations. Here we report an analysis of archival data that reveals an occultation by a body with an approximately 500-metre radius at a distance of 45 astronomical units. The probability of this event arising from random statistical fluctuations within our data set is about two per cent. Our survey yields a surface density of Kuiper belt objects with radii exceeding 250 metres of 2.1(-1.7)(+4.8) x 10(7) deg(-2), ruling out inferred surface densities from previous claimed detections by more than 5 sigma. The detection of only one event reveals a deficit of sub-kilometre-sized Kuiper belt objects compared to a population extrapolated from objects with radii exceeding 50 kilometres. This implies that sub-kilometre-sized objects are undergoing collisional erosion, just like debris disks observed around other stars.
C1 [Schlichting, H. E.; Ofek, E. O.; Sari, R.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Schlichting, H. E.] Univ Toronto, CITA, Toronto, ON M5S 3H8, Canada.
   [Wenz, M.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Sari, R.] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Gal-Yam, A.] Weizmann Inst Sci, Fac Phys, IL-76100 Rehovot, Israel.
   [Livio, M.; Nelan, E.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Zucker, S.] Tel Aviv Univ, Dept Geophys & Planetary Sci, IL-69978 Tel Aviv, Israel.
C3 California Institute of Technology; University of Toronto; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Hebrew University of Jerusalem; Weizmann Institute of Science; Space Telescope Science Institute; Tel Aviv University
RP Schlichting, HE (corresponding author), CALTECH, Dept Astron, Pasadena, CA 91125 USA.
EM hes@astro.caltech.edu; eran@astro.caltech.edu
FU NASA through a grant from the Space Telescope Science Institute; ERC; Packard Foundation; Israeli Science Foundation; EU Seventh Framework Programme Marie Curie IRG fellowship; Benoziyo Center for Astrophysics; Peter and Patricia Gruber Awards; William Z. and Eda Bess Novick New Scientists Fund; Israel Science Foundation-Adler Foundation
NR 28
TC 80
Z9 92
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 DEC 17
PY 2009
VL 462
IS 7275
BP 895
EP 897
DI 10.1038/nature08608
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400037
PM 20016596
DA 2026-03-09
ER

PT J
AU Hubbard, J
   Shaw, JH
AF Hubbard, Judith
   Shaw, John H.
TI Uplift of the Longmen Shan and Tibetan plateau, and the 2008 Wenchuan (M=7.9) earthquake
SO NATURE
LA English
DT Article
ID lower crustal flow; eastern margin; deformation; topography; kinematics; evolution
AB The Longmen Shan mountain range, site of the devastating 12 May 2008 Wenchuan (M = 7.9) earthquake, defines the eastern margin of the Himalayan orogen and exhibits greater topographic relief than anywhere else in the Tibetan plateau. However, before the earthquake, geodetic and geologic surveys measured little shortening across the range front(1-3), inspiring a vigorous debate about the process by which the topography of the mountain belt is produced and maintained. Two endmember models have been proposed: (1) brittle crustal thickening, in which thrust faults with large amounts of slip that are rooted in the lithosphere cause uplift(4), and (2) crustal flow, in which low-viscosity material in the lower crust extrudes outward from the Tibetan plateau and inflates the crust north and east of the Himalayas(5-7). Here we use balanced geologic cross-sections to show that crustal shortening, structural relief, and topography are strongly correlated in the range front. This suggests that crustal shortening is a primary driver for uplift and topography of the Longmen Shan on the flanks of the plateau. The 2008 Wenchuan (M = 7.9) earthquake, which ruptured a large thrust fault along the range front causing tens of thousands of fatalities and widespread damage, is an active manifestation of this shortening process.
C1 [Hubbard, Judith; Shaw, John H.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Harvard University
RP Hubbard, J (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM jhubbard@fas.harvard.edu
NR 20
TC 599
Z9 742
U1 9
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 MAR 12
PY 2009
VL 458
IS 7235
BP 194
EP 197
DI 10.1038/nature07837
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700041
PM 19279635
DA 2026-03-09
ER

PT J
AU Wang, YL
   Juranek, S
   Li, HT
   Sheng, G
   Wardle, GS
   Tuschl, T
   Patel, DJ
AF Wang, Yanli
   Juranek, Stefan
   Li, Haitao
   Sheng, Gang
   Wardle, Greg S.
   Tuschl, Thomas
   Patel, Dinshaw J.
TI Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes
SO NATURE
LA English
DT Article
ID crystal-structure; structural basis; recognition; argonaute; dna; messenger; risc; mechanisms; slicer; interference
AB The slicer activity of the RNA-induced silencing complex resides within its Argonaute (Ago) component, in which the PIWI domain provides the catalytic residues governing guide-strand mediated site-specific cleavage of target RNA. Here we report on structures of ternary complexes of Thermus thermophilus Ago catalytic mutants with 5'-phosphorylated 21-nucleotide guide DNA and complementary target RNAs of 12, 15 and 19 nucleotides in length, which define the molecular basis for Mg2+-facilitated site-specific cleavage of the target. We observe pivot-like domain movements within the Ago scaffold on proceeding from nucleation to propagation steps of guide-target duplex formation, with duplex zippering beyond one turn of the helix requiring the release of the 3'-end of the guide from the PAZ pocket. Cleavage assays on targets of various lengths supported this model, and sugar-phosphate-backbone-modified target strands showed the importance of structural and catalytic divalent metal ions observed in the crystal structures.
C1 [Wang, Yanli; Li, Haitao; Sheng, Gang; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Juranek, Stefan; Wardle, Greg S.; Tuschl, Thomas] Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Rockefeller University; Howard Hughes Medical Institute
RP Patel, DJ (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
EM ttuschl@mail.rockefeller.edu; pateld@mskcc.org
FU National Institutes of Health (NIH); Starr Foundation; Howard Hughes Medical Institute (HHMI)
NR 48
TC 440
Z9 574
U1 4
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 OCT 8
PY 2009
VL 461
IS 7265
BP 754
EP U3
DI 10.1038/nature08434
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500028
PM 19812667
DA 2026-03-09
ER

PT J
AU Putnam, CD
   Hayes, TK
   Kolodner, RD
AF Putnam, Christopher D.
   Hayes, Tikvah K.
   Kolodner, Richard D.
TI Specific pathways prevent duplication-mediated genome rearrangements
SO NATURE
LA English
DT Article
ID gross chromosomal rearrangements; saccharomyces-cerevisiae homolog; break-induced replication; s-phase checkpoint; dna helicase; alu repeats; mitotic recombination; genetic instability; repair proteins; crossing-over
AB We have investigated the ability of different regions of the left arm of Saccharomyces cerevisiae chromosome V to participate in the formation of gross chromosomal rearrangements (GCRs). We found that the 4.2-kilobase HXT13-DSF1 region sharing divergent homology with chromosomes IV, X and XIV, similar to mammalian segmental duplications, was 'at risk' for participating in duplication-mediated GCRs generated by homologous recombination. Numerous genes and pathways, including SGS1, TOP3, RMI1, SRS2, RAD6, SLX1, SLX4, SLX5, MSH2, MSH6, RAD10 and the DNA replication stress checkpoint requiring MRC1 and TOF1, were highly specific for suppressing these GCRs compared to GCRs mediated by single-copy sequences. These results indicate that the mechanisms for formation and suppression of rearrangements occurring in regions containing at-risk sequences differ from those occurring in regions of single-copy sequence. This explains how extensive genome instability is prevented in eukaryotic cells whose genomes contain numerous divergent repeated sequences.
C1 [Putnam, Christopher D.; Hayes, Tikvah K.; Kolodner, Richard D.] Univ Calif San Diego, Sch Med, Dept Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Putnam, Christopher D.; Hayes, Tikvah K.; Kolodner, Richard D.] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Putnam, Christopher D.; Hayes, Tikvah K.; Kolodner, Richard D.] Univ Calif San Diego, Sch Med, Ctr Canc, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Ludwig Institute for Cancer Research; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Kolodner, RD (corresponding author), Univ Calif San Diego, Sch Med, Dept Med, Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM rkolodner@ucsd.edu
FU NIH [GM26017]; National Institute of General Medical Sciences [R01GM026017] Funding Source: NIH RePORTER
NR 52
TC 112
Z9 135
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 AUG 20
PY 2009
VL 460
IS 7258
BP 984
EP U65
DI 10.1038/nature08217
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500028
PM 19641493
DA 2026-03-09
ER

PT J
AU Delmo, MP
   Yamamoto, S
   Kasai, S
   Ono, T
   Kobayashi, K
AF Delmo, Michael P.
   Yamamoto, Shinpei
   Kasai, Shinya
   Ono, Teruo
   Kobayashi, Kensuke
TI Large positive magnetoresistive effect in silicon induced by the space-charge effect
SO NATURE
LA English
DT Article
ID room-temperature; giant magnetoresistance; limited currents; magnetic-field; semiconductors; solids; inhomogeneity; sensors; films; insb
AB Recent discoveries of large magnetoresistance in non-magnetic semiconductors(1-8) have gained much attention because the size of the effect is comparable to, or even larger than, that of magnetoresistance in magnetic systems(9-14). Conventional magnetoresistance in doped semiconductors is straightforwardly explained as the effect of the Lorentz force on the carrier motion(15), but the reported unusually large effects imply that the underlying mechanisms have not yet been fully explored. Here we report that a simple device, based on a lightly doped silicon substrate between two metallic contacts, shows a large positive magnetoresistance of more than 1,000 per cent at room temperature (300 K) and 10,000 per cent at 25 K, for magnetic fields between 0 and 3 T. A high electric field is applied to the device, so that conduction is space-charge limited(16-18). For substrates with a charge carrier density below similar to 10(13) cm(-3), the magnetoresistance exhibits a linear dependence on the magnetic field between 3 and 9 T. We propose that the observed large magnetoresistance can be explained by quasi-neutrality breaking of the space-charge effect, where insufficient charge is present to compensate the electrons injected into the device. This introduces an electric field inhomogeneity, analogous to the situation in other semiconductors in which a large, non-saturating magnetoresistance was observed(1-5,19). In this regime, the motions of electrons become correlated, and thus become dependent on magnetic field. Although large positive magnetoresistance at room temperature has been achieved in metal-semiconductor hybrid devices(6-8), we have now realized it in a simpler structure and in a way different from other known magnetoresistive effects(9-14,20). It could be used to develop new magnetic devices from silicon, which may further advance silicon technology.
C1 [Delmo, Michael P.; Kasai, Shinya; Ono, Teruo; Kobayashi, Kensuke] Kyoto Univ, Inst Chem Res, Kyoto 6110011, Japan.
   [Yamamoto, Shinpei] Kyoto Univ, Inst Integrated Cell Mat Sci, Kyoto 6110011, Japan.
C3 Kyoto University; Kyoto University
RP Kobayashi, K (corresponding author), Kyoto Univ, Inst Chem Res, Kyoto 6110011, Japan.
EM kensuke@scl.kyoto-u.ac.jp
FU KAKENHI; ICR; Asahi Glass Foundation; Sumitomo Foundation; JSPS; Grants-in-Aid for Scientific Research [19GS0207] Funding Source: KAKEN
NR 30
TC 153
Z9 168
U1 0
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 26
PY 2009
VL 457
IS 7233
BP 1112
EP U65
DI 10.1038/nature07711
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100036
PM 19242471
DA 2026-03-09
ER

PT J
AU Wiersig, J
   Gies, C
   Jahnke, F
   Assmann, M
   Berstermann, T
   Bayer, M
   Kistner, C
   Reitzenstein, S
   Schneider, C
   Höfling, S
   Forchel, A
   Kruse, C
   Kalden, J
   Hommel, D
AF Wiersig, J.
   Gies, C.
   Jahnke, F.
   Assmann, M.
   Berstermann, T.
   Bayer, M.
   Kistner, C.
   Reitzenstein, S.
   Schneider, C.
   Hoefling, S.
   Forchel, A.
   Kruse, C.
   Kalden, J.
   Hommel, D.
TI Direct observation of correlations between individual photon emission events of a microcavity laser
SO NATURE
LA English
DT Article
AB Lasers are recognized for coherent light emission, the onset of which is reflected in a change in the photon statistics(1). For many years, attempts have been made to directly measure correlations in the individual photon emission events of semiconductor lasers(2,3). Previously, the temporal decay of these correlations below or at the lasing threshold was considerably faster than could be measured with the time resolution provided by the Hanbury Brown/Twiss measurement set-up(4) used. Here we demonstrate a measurement technique using a streak camera that overcomes this limitation and provides a record of the arrival times of individual photons. This allows us to investigate the dynamical evolution of correlations between the individual photon emission events. We apply our studies to micropillar lasers(5) with semiconductor quantum dots(2,3,6-8) as the active material, operating in the regime of cavity quantum electrodynamics(9). For laser resonators with a low cavity quality factor, Q, a smooth transition from photon bunching to uncorrelated emission with increasing pumping is observed; for high-Q resonators, we see a non-monotonic dependence around the threshold where quantum light emission can occur. We identify regimes of dynamical anti-bunching of photons in agreement with the predictions of a microscopic theory that includes semiconductor-specific effects.
C1 [Wiersig, J.; Gies, C.; Jahnke, F.; Kruse, C.; Kalden, J.; Hommel, D.] Univ Bremen, Dept Phys, D-28334 Bremen, Germany.
   [Assmann, M.; Berstermann, T.; Bayer, M.] Tech Univ Dortmund, D-44221 Dortmund, Germany.
   [Kistner, C.; Reitzenstein, S.; Schneider, C.; Hoefling, S.; Forchel, A.] Univ Wurzburg, D-97074 Wurzburg, Germany.
C3 University of Bremen; Dortmund University of Technology; University of Wurzburg
RP Jahnke, F (corresponding author), Univ Bremen, Dept Phys, D-28334 Bremen, Germany.
EM jahnke@itp.uni-bremen.de; manfred.bayer@tu-dortmund.de
FU Deutsche Forschungsgemeinschaft
NR 25
TC 199
Z9 218
U1 2
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 JUL 9
PY 2009
VL 460
IS 7252
BP 245
EP U108
DI 10.1038/nature08126
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000038
PM 19587766
DA 2026-03-09
ER

PT J
AU Cicchillo, RM
   Zhang, HJ
   Blodgett, JAV
   Whitteck, JT
   Li, GY
   Nair, SK
   van der Donk, WA
   Metcalf, WW
AF Cicchillo, Robert M.
   Zhang, Houjin
   Blodgett, Joshua A. V.
   Whitteck, John T.
   Li, Gongyong
   Nair, Satish K.
   van der Donk, Wilfred A.
   Metcalf, William W.
TI An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis
SO NATURE
LA English
DT Article
ID isopenicillin n-synthase; myoinositol oxygenase; mechanism; activation; fosfomycin; enzyme; products; insight; water
AB Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture(1). One such compound, phosphinothricin tripeptide, contains the unusual amino acid phosphinothricin attached to two alanine residues. Synthetic phosphinothricin (glufosinate) is a component of two top-selling herbicides (Basta and Liberty), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during phosphinothricin tripeptide biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP)(2). Here we report the in vitro reconstitution of this unprecedented C(sp(3))-C(sp(3)) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-haem iron(II)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons. The current study expands the scope of reactions catalysed by the 2-His-1-carboxylate mononuclear non-haem iron family of enzymes.
C1 [Cicchillo, Robert M.; Zhang, Houjin; Whitteck, John T.; Nair, Satish K.; van der Donk, Wilfred A.; Metcalf, William W.] Univ Illinois, Inst Genom Biol, Urbana, IL 61802 USA.
   [Cicchillo, Robert M.; van der Donk, Wilfred A.] Univ Illinois, Howard Hughes Med Inst, Urbana, IL 61802 USA.
   [Zhang, Houjin; Nair, Satish K.; van der Donk, Wilfred A.] Univ Illinois, Dept Biochem, Urbana, IL 61802 USA.
   [Blodgett, Joshua A. V.; Metcalf, William W.] Univ Illinois, Dept Microbiol, Urbana, IL 61802 USA.
   [Cicchillo, Robert M.; Whitteck, John T.; Li, Gongyong; van der Donk, Wilfred A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; Howard Hughes Medical Institute; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Nair, SK (corresponding author), Univ Illinois, Inst Genom Biol, Urbana, IL 61802 USA.
EM s-nair@life.uiuc.edu; vddonk@illinois.edu; metcalf@illinois.edu
FU National Institutes of Health [PO1 GM077596, RO1 GM59334]; University of Illinois
NR 22
TC 110
Z9 137
U1 2
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 871
EP U10
DI 10.1038/nature07972
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500045
PM 19516340
DA 2026-03-09
ER

PT J
AU Hwang, J
   Pototschnig, M
   Lettow, R
   Zumofen, G
   Renn, A
   Götzinger, S
   Sandoghdar, V
AF Hwang, J.
   Pototschnig, M.
   Lettow, R.
   Zumofen, G.
   Renn, A.
   Goetzinger, S.
   Sandoghdar, V.
TI A single-molecule optical transistor
SO NATURE
LA English
DT Article
ID photon; fluorescence; atom; spectroscopy; excitation; resonance; emission; blockade; cavity; fields
AB The transistor is one of the most influential inventions of modern times and is ubiquitous in present-day technologies. In the continuing development of increasingly powerful computers as well as alternative technologies based on the prospects of quantum information processing, switching and amplification functionalities are being sought in ultrasmall objects, such as nanotubes, molecules or atoms(1-9). Among the possible choices of signal carriers, photons are particularly attractive because of their robustness against decoherence, but their control at the nano-metre scale poses a significant challenge as conventional nonlinear materials become ineffective. To remedy this shortcoming, resonances in optical emitters can be exploited, and atomic ensembles have been successfully used to mediate weak light beams(7). However, single-emitter manipulation of photonic signals has remained elusive and has only been studied in high-finesse microcavities(10-13) or waveguides(8,14). Here we demonstrate that a single dye molecule can operate as an optical transistor and coherently attenuate or amplify a tightly focused laser beam, depending on the power of a second 'gating' beam that controls the degree of population inversion. Such a quantum optical transistor has also the potential for manipulating non-classical light fields down to the single-photon level. We discuss some of the hurdles along the road towards practical implementations, and their possible solutions.
C1 [Hwang, J.; Pototschnig, M.; Lettow, R.; Zumofen, G.; Renn, A.; Goetzinger, S.; Sandoghdar, V.] ETH, Phys Chem Lab, CH-8093 Zurich, Switzerland.
   [Hwang, J.; Pototschnig, M.; Lettow, R.; Zumofen, G.; Renn, A.; Goetzinger, S.; Sandoghdar, V.] ETH, OptETH, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Sandoghdar, V (corresponding author), ETH, Phys Chem Lab, CH-8093 Zurich, Switzerland.
EM vahid.sandoghdar@ethz.ch
FU Swiss National Foundation (SNF); ETH Zurich [PP-01 07-02]
NR 30
TC 306
Z9 333
U1 0
U2 163
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 76
EP 80
DI 10.1038/nature08134
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200032
PM 19571881
DA 2026-03-09
ER

PT J
AU Mummery-Widmer, JL
   Yamazaki, M
   Stoeger, T
   Novatchkova, M
   Bhalerao, S
   Chen, D
   Dietzl, G
   Dickson, BJ
   Knoblich, JA
AF Mummery-Widmer, Jennifer L.
   Yamazaki, Masakazu
   Stoeger, Thomas
   Novatchkova, Maria
   Bhalerao, Sheetal
   Chen, Doris
   Dietzl, Georg
   Dickson, Barry J.
   Knoblich, Juergen A.
TI Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi
SO NATURE
LA English
DT Article
ID cell-fate; protein trafficking; boundary formation; gene; hairless; localization; numb; integration; suppressor; endocytosis
AB Genome-wide RNA interference (RNAi) screens have identified near-complete sets of genes involved in cellular processes. However, this methodology has not yet been used to study complex developmental processes in a tissue-specific manner. Here we report the use of a library of Drosophila strains expressing inducible hairpin RNAi constructs to study the Notch signalling pathway during external sensory organ development. We assigned putative loss-of-function phenotypes to 21.2% of the protein-coding Drosophila genes. Using secondary assays, we identified 6 new genes involved in asymmetric cell division and 23 novel genes regulating the Notch signalling pathway. By integrating our phenotypic results with protein interaction data, we constructed a genome-wide, functionally validated interaction network governing Notch signalling and asymmetric cell division. We used clustering algorithms to identify nuclear import pathways and the COP9 signallosome as Notch regulators. Our results show that complex developmental processes can be analysed on a genome-wide level and provide a unique resource for functional annotation of the Drosophila genome.
C1 [Mummery-Widmer, Jennifer L.; Yamazaki, Masakazu; Stoeger, Thomas; Novatchkova, Maria; Bhalerao, Sheetal; Knoblich, Juergen A.] Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria.
   [Novatchkova, Maria; Bhalerao, Sheetal; Dietzl, Georg; Dickson, Barry J.] Res Inst Mol Pathol, A-1030 Vienna, Austria.
   [Chen, Doris] MFPL, Dept Biochem, A-1030 Vienna, Austria.
C3 Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL)
RP Knoblich, JA (corresponding author), Austrian Acad Sci, Inst Mol Biotechnol, Dr Bohr Gasse 3, A-1030 Vienna, Austria.
EM juergen.knoblich@imba.oeaw.ac.at
FU Austrian Science Fund FWF [P 16629] Funding Source: Medline
NR 54
TC 255
Z9 318
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 23
PY 2009
VL 458
IS 7241
BP 987
EP U59
DI 10.1038/nature07936
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900033
PM 19363474
DA 2026-03-09
ER

PT J
AU Zijlstra, P
   Chon, JWM
   Gu, M
AF Zijlstra, Peter
   Chon, James W. M.
   Gu, Min
TI Five-dimensional optical recording mediated by surface plasmons in gold nanorods
SO NATURE
LA English
DT Article
ID data-storage; nanocomposite
AB Multiplexed optical recording provides an unparalleled approach to increasing the information density beyond 10(12) bits per cm(3) (1 Tbit cm(-3)) by storing multiple, individually addressable patterns within the same recording volume. Although wavelength(1-3), polarization(4-8) and spatial dimensions(9-13) have all been exploited for multiplexing, these approaches have never been integrated into a single technique that could ultimately increase the information capacity by orders of magnitude. The major hurdle is the lack of a suitable recording medium that is extremely selective in the domains of wavelength and polarization and in the three spatial domains, so as to provide orthogonality in all five dimensions. Here we show true five-dimensional optical recording by exploiting the unique properties of the longitudinal surface plasmon resonance (SPR) of gold nanorods. The longitudinal SPR exhibits an excellent wavelength and polarization sensitivity, whereas the distinct energy threshold required for the photothermal recording mechanism provides the axial selectivity. The recordings were detected using longitudinal SPR-mediated two-photon luminescence, which we demonstrate to possess an enhanced wavelength and angular selectivity compared to conventional linear detection mechanisms. Combined with the high cross-section of two-photon luminescence, this enabled non-destructive, crosstalk-free readout. This technique can be immediately applied to optical patterning, encryption and data storage, where higher data densities are pursued.
C1 [Zijlstra, Peter; Chon, James W. M.; Gu, Min] Swinburne Univ Technol, Fac Engn & Ind Sci, Ctr Micro Photon, Hawthorn, Vic 3122, Australia.
C3 Swinburne University of Technology
RP Chon, JWM (corresponding author), Swinburne Univ Technol, Fac Engn & Ind Sci, Ctr Micro Photon, POB 218, Hawthorn, Vic 3122, Australia.
EM JChon@groupwise.swin.edu.au
FU Australian Research Council
NR 30
TC 1116
Z9 1292
U1 6
U2 697
PU NATURE PUBLISHING 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 21
PY 2009
VL 459
IS 7245
BP 410
EP 413
DI 10.1038/nature08053
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700042
PM 19458719
DA 2026-03-09
ER

PT J
AU White, SH
AF White, Stephen H.
TI Biophysical dissection of membrane proteins
SO NATURE
LA English
DT Article
ID light-harvesting complex; crystal-structure; mechanism; bacteriorhodopsin; evolution; transport; dynamics; insights; reveals; model
AB The first atomic-resolution structure of a membrane protein was solved in 1985. Twenty-four years and more than 180 unique structures later, what have we have learned? An examination of the atomic details of several diverse membrane proteins reveals some remarkable biophysical features and suggests that we can expect to achieve much more in the decades to come.
C1 [White, Stephen H.] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA.
   [White, Stephen H.] Univ Calif Irvine, Ctr Biomembrane Syst, Irvine, CA 92697 USA.
C3 University of California System; University of California Irvine; University of California System; University of California Irvine
RP White, SH (corresponding author), Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA.
EM stephen.white@uci.edu
FU National Institute of General Medical Science; National Institute of Neurological Disorders and Stroke; Grants-in-Aid for Scientific Research [13J00727] Funding Source: KAKEN
NR 50
TC 228
Z9 286
U1 0
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2009
VL 459
IS 7245
BP 344
EP 346
DI 10.1038/nature08142
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700031
PM 19458709
DA 2026-03-09
ER

PT J
AU Park, BS
   Song, DH
   Kim, HM
   Choi, BS
   Lee, H
   Lee, JO
AF Park, Beom Seok
   Song, Dong Hyun
   Kim, Ho Min
   Choi, Byong-Seok
   Lee, Hayyoung
   Lee, Jie-Oh
TI The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex
SO NATURE
LA English
DT Article
ID toll-like receptors; crystal-structure; human md-2; lipid-a; endotoxin; responsiveness; binding; roles; tlr4; bacterial
AB The lipopolysaccharide (LPS) of Gram negative bacteria is a well-known inducer of the innate immune response(1). Toll-like receptor (TLR) 4 and myeloid differentiation factor 2 (MD-2) form a heterodimer that recognizes a common 'pattern' in structurally diverse LPS molecules. To understand the ligand specificity and receptor activation mechanism of the TLR4-MD-2-LPS complex we determined its crystal structure. LPS binding induced the formation of an m-shaped receptor multimer composed of two copies of the TLR4-MD-2-LPS complex arranged symmetrically. LPS interacts with a large hydrophobic pocket in MD-2 and directly bridges the two components of the multimer. Five of the six lipid chains of LPS are buried deep inside the pocket and the remaining chain is exposed to the surface of MD-2, forming a hydrophobic interaction with the conserved phenylalanines of TLR4. The F126 loop of MD-2 undergoes localized structural change and supports this core hydrophobic interface by making hydrophilic interactions with TLR4. Comparison with the structures of tetra-acylated antagonists bound to MD-2 indicates that two other lipid chains in LPS displace the phosphorylated glucosamine backbone by similar to 5 angstrom towards the solvent area(2,3). This structural shift allows phosphate groups of LPS to contribute to receptor multimerization by forming ionic interactions with a cluster of positively charged residues in TLR4 and MD-2. The TLR4-MD-2-LPS structure illustrates the remarkable versatility of the ligand recognition mechanisms employed by the TLR family(4,5), which is essential for defence against diverse microbial infection.
C1 [Park, Beom Seok; Song, Dong Hyun; Kim, Ho Min; Choi, Byong-Seok; Lee, Jie-Oh] Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea.
   [Lee, Jie-Oh] Korea Adv Inst Sci & Technol, Inst BioCentury, Taejon 305701, South Korea.
   [Lee, Hayyoung] Chungnam Natl Univ, Sch Biosci & Biotechnol, Dept Biol, Taejon 305764, South Korea.
C3 Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Chungnam National University
RP Lee, JO (corresponding author), Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea.
EM jieoh.lee@kaist.ac.kr
FU Ministry of Education, Science and Technology of Korea
NR 34
TC 1950
Z9 2332
U1 11
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 APR 30
PY 2009
VL 458
IS 7242
BP 1191
EP U130
DI 10.1038/nature07830
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600051
PM 19252480
DA 2026-03-09
ER

PT J
AU Hai, PN
   Ohya, S
   Tanaka, M
   Barnes, SE
   Maekawa, S
AF Hai, Pham Nam
   Ohya, Shinobu
   Tanaka, Masaaki
   Barnes, Stewart E.
   Maekawa, Sadamichi
TI Electromotive force and huge magnetoresistance in magnetic tunnel junctions
SO NATURE
LA English
DT Article
ID room-temperature; films; gaas; mnas
AB The electromotive force (e.m.f.) predicted by Faraday's law reflects the forces acting on the charge, -e, of an electron moving through a device or circuit, and is proportional to the time derivative of the magnetic field. This conventional e.m.f. is usually absent for stationary circuits and static magnetic fields. There are also forces that act on the spin of an electron; it has been recently predicted(1,2) that, for circuits that are in part composed of ferromagnetic materials, there arises an e.m.f. of spin origin even for a static magnetic field. This e.m.f. can be attributed to a time-varying magnetization of the host material, such as the motion of magnetic domains in a static magnetic field, and reflects the conversion of magnetic to electrical energy. Here we show that such an e.m.f. can indeed be induced by a static magnetic field in magnetic tunnel junctions containing zinc-blende-structured MnAs quantum nanomagnets. The observed e.m.f. operates on a timescale of approximately 10(2)-10(3) seconds and results from the conversion of the magnetic energy of the superparamagnetic MnAs nanomagnets into electrical energy when these magnets undergo magnetic quantum tunnelling. As a consequence, a huge magnetoresistance of up to 100,000 per cent is observed for certain bias voltages. Our results strongly support the contention that, in magnetic nanostructures, Faraday's law of induction must be generalized to account for forces of purely spin origin. The huge magnetoresistance and e.m.f. may find potential applications in high sensitivity magnetic sensors, as well as in new active devices such as 'spin batteries'.
C1 [Hai, Pham Nam; Ohya, Shinobu; Tanaka, Masaaki] Univ Tokyo, Dept Elect Engn & Informat Syst, Bunkyo Ku, Tokyo 1138656, Japan.
   [Ohya, Shinobu; Tanaka, Masaaki] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan.
   [Barnes, Stewart E.] Univ Miami, Dept Phys, Coral Gables, FL 33124 USA.
   [Barnes, Stewart E.] Univ Cambridge, Cavendish Lab, TCM, Cambridge CB3 0HE, England.
   [Maekawa, Sadamichi] Tohoku Univ, Inst Mat Res, Sendai, Miyagi 9808577, Japan.
   [Maekawa, Sadamichi] Japan Sci & Technol Agcy, CREST, Tokyo 1000075, Japan.
C3 University of Tokyo; Japan Science & Technology Agency (JST); University of Miami; University of Cambridge; Tohoku University; Japan Science & Technology Agency (JST)
RP Tanaka, M (corresponding author), Univ Tokyo, Dept Elect Engn & Informat Syst, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan.
EM masaaki@ee.t.u-tokyo.ac.jp
FU MEXT, PRESTO of JST, and EPSRC (UK) [18106007, 19048018, 20686002]; JSPS Research Fellowship; Grants-in-Aid for Scientific Research [20686002, 19048018, 19048009, 18106007] Funding Source: KAKEN
NR 21
TC 149
Z9 167
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 MAR 26
PY 2009
VL 458
IS 7237
BP 489
EP U2
DI 10.1038/nature07879
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400040
PM 19270681
DA 2026-03-09
ER

PT J
AU Chen, K
   Baran, PS
AF Chen, Ke
   Baran, Phil S.
TI Total synthesis of eudesmane terpenes by site-selective C-H oxidations
SO NATURE
LA English
DT Article
ID enzymes; oxyfunctionalization; functionalization; sesquiterpenoids; biosynthesis; hydrocarbons; activation; efficient; taxol
AB From menthol to cholesterol to Taxol, terpenes are a ubiquitous group of molecules (over 55,000 members isolated so far) that have long provided humans with flavours, fragrances, hormones, medicines and even commercial products such as rubber(1). Although they possess a seemingly endless variety of architectural complexities, the biosynthesis of terpenes often occurs in a unified fashion as a 'two-phase' process(2,3). In the first phase (the cyclase phase), simple linear hydrocarbon phosphate building blocks are stitched together by means of 'prenyl coupling', followed by enzymatically controlled molecular cyclizations and rearrangements. In the second phase (the oxidase phase), oxidation of alkenes and carbon-hydrogen bonds results in a large array of structural diversity. Although organic chemists have made great progress in developing the logic(3-5) needed for the cyclase phase of terpene synthesis, particularly in the area of polyene cyclizations(6), much remains to be learned if the oxidase phase is to be mimicked in the laboratory. Here we show how the logic of terpene biosynthesis has inspired the highly efficient and stereocontrolled syntheses of five oxidized members of the eudesmane family of terpenes in a modicum of steps by a series of simple carbocycle-forming reactions followed by multiple site-selective inter-and intramolecular carbon-hydrogen oxidations. This work establishes an intellectual framework in which to conceive the laboratory synthesis of other complex terpenes using a 'two-phase' approach.
C1 [Chen, Ke; Baran, Phil S.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Baran, PS (corresponding author), Scripps Res Inst, Dept Chem, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM pbaran@scripps.edu
FU Bristol-Myers Squibb
NR 30
TC 355
Z9 420
U1 2
U2 273
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 824
EP 828
DI 10.1038/nature08043
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500035
PM 19440196
DA 2026-03-09
ER

PT J
AU Roy, R
   Kozlov, AG
   Lohman, TM
   Ha, T
AF Roy, Rahul
   Kozlov, Alexander G.
   Lohman, Timothy M.
   Ha, Taekjip
TI SSB protein diffusion on single-stranded DNA stimulates RecA filament formation
SO NATURE
LA English
DT Article
ID escherichia-coli; binding-protein; homologous recombination; genetic-recombination; molecule fret; complexes; repair; mechanism; ssdna; modes
AB Single-stranded DNA generated in the cell during DNA metabolism is stabilized and protected by binding of ssDNA-binding (SSB) proteins. Escherichia coli SSB, a representative homotetrameric SSB, binds to ssDNA by wrapping the DNA using its four subunits. However, such a tightly wrapped, high-affinity protein-DNA complex still needs to be removed or repositioned quickly for unhindered action of other proteins. Here we show, using single-molecule two- and three-colour fluorescence resonance energy transfer, that tetrameric SSB can spontaneously migrate along ssDNA. Diffusional migration of SSB helps in the local displacement of SSB by an elongating RecA filament. SSB diffusion also melts short DNA hairpins transiently and stimulates RecA filament elongation on DNA with secondary structure. This observation of diffusional movement of a protein on ssDNA introduces a new model for how an SSB protein can be redistributed, while remaining tightly bound to ssDNA during recombination and repair processes.
C1 [Roy, Rahul; Ha, Taekjip] Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA.
   [Roy, Rahul; Ha, Taekjip] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Roy, Rahul; Ha, Taekjip] Univ Illinois, Ctr Phys Living Cells, Urbana, IL 61801 USA.
   [Kozlov, Alexander G.; Lohman, Timothy M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
   [Ha, Taekjip] Howard Hughes Med Inst, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Washington University (WUSTL); Howard Hughes Medical Institute
RP Ha, T (corresponding author), Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA.
EM tjha@illinois.edu
FU National Institutes of Health; National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [0822613] Funding Source: National Science Foundation
NR 41
TC 228
Z9 276
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1092
EP 1097
DI 10.1038/nature08442
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600037
PM 19820696
DA 2026-03-09
ER

PT J
AU Cordes, KR
   Sheehy, NT
   White, MP
   Berry, EC
   Morton, SU
   Muth, AN
   Lee, TH
   Miano, JM
   Ivey, KN
   Srivastava, D
AF Cordes, Kimberly R.
   Sheehy, Neil T.
   White, Mark P.
   Berry, Emily C.
   Morton, Sarah U.
   Muth, Alecia N.
   Lee, Ting-Hein
   Miano, Joseph M.
   Ivey, Kathryn N.
   Srivastava, Deepak
TI miR-145 and miR-143 regulate smooth muscle cell fate and plasticity
SO NATURE
LA English
DT Article
ID serum response factor; embryonic stem-cells; gene-expression; progenitor cells; vascular injury; microrna; differentiation; myocardin; activation; proliferation
AB MicroRNAs (miRNAs) are regulators of myriad cellular events, but evidence for a single miRNA that can efficiently differentiate multipotent stem cells into a specific lineage or regulate direct reprogramming of cells into an alternative cell fate has been elusive. Here we show that miR-145 and miR-143 are co-transcribed in multipotent murine cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem-cell-derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5) and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4 (Kruppel-like factor 4), myocardin and Elk-1 (ELK1, member of ETS oncogene family), to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells.
C1 [Cordes, Kimberly R.; Sheehy, Neil T.; White, Mark P.; Berry, Emily C.; Morton, Sarah U.; Muth, Alecia N.; Ivey, Kathryn N.; Srivastava, Deepak] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Cordes, Kimberly R.; Sheehy, Neil T.; White, Mark P.; Berry, Emily C.; Morton, Sarah U.; Muth, Alecia N.; Ivey, Kathryn N.; Srivastava, Deepak] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94543 USA.
   [Cordes, Kimberly R.; Sheehy, Neil T.; White, Mark P.; Berry, Emily C.; Morton, Sarah U.; Muth, Alecia N.; Ivey, Kathryn N.; Srivastava, Deepak] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
   [Lee, Ting-Hein; Miano, Joseph M.] Univ Rochester, Sch Med & Dent, Aab Cardiovasc Res Inst, Rochester, NY 14642 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 Rochester
RP Srivastava, D (corresponding author), Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
EM dsrivastava@gladstone.ucsf.edu
FU NHLBI/NIH [HL62572, HL091168]; California Institute for Regenerative Medicine (CIRM); NIH/NCRR [C06 RR018928]
NR 42
TC 1379
Z9 1615
U1 0
U2 153
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 6
PY 2009
VL 460
IS 7256
BP 705
EP U80
DI 10.1038/nature08195
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300031
PM 19578358
DA 2026-03-09
ER

PT J
AU Kopp, RE
   Simons, FJ
   Mitrovica, JX
   Maloof, AC
   Oppenheimer, M
AF Kopp, Robert E.
   Simons, Frederik J.
   Mitrovica, Jerry X.
   Maloof, Adam C.
   Oppenheimer, Michael
TI Probabilistic assessment of sea level during the last interglacial stage
SO NATURE
LA English
DT Article
ID abrolhos islands; climate; rise; age; warmth; period; model; earth
AB With polar temperatures, similar to 3-5 degrees C warmer than today, the last interglacial stage (similar to 125 kyr ago) serves as a partial analogue for 1-2 degrees C global warming scenarios. Geological records from several sites indicate that local sea levels during the last interglacial were higher than today, but because local sea levels differ from global sea level, accurately reconstructing past global sea level requires an integrated analysis of globally distributed data sets. Here we present an extensive compilation of local sea level indicators and a statistical approach for estimating global sea level, local sea levels, ice sheet volumes and their associated uncertainties. We find a 95% probability that global sea level peaked at least 6.6 m higher than today during the last interglacial; it is likely (67% probability) to have exceeded 8.0 m but is unlikely (33% probability) to have exceeded 9.4 m. When global sea level was close to its current level (>=-10 m), the millennial average rate of global sea level rise is very likely to have exceeded 5.6 m kyr(-1) but is unlikely to have exceeded 9.2 m kyr(-1). Our analysis extends previous last interglacial sea level studies by integrating literature observations within a probabilistic framework that accounts for the physics of sea level change. The results highlight the long-term vulnerability of ice sheets to even relatively low levels of sustained global warming.
C1 [Kopp, Robert E.; Simons, Frederik J.; Maloof, Adam C.; Oppenheimer, Michael] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
   [Kopp, Robert E.; Oppenheimer, Michael] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.
   [Mitrovica, Jerry X.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Princeton University; Princeton University; Harvard University
RP Kopp, RE (corresponding author), Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
EM rkopp@alumni.caltech.edu
FU Princeton Institute for Computational Science and Engineering; Princeton University Office of Information Technology; Science, Technology, and Environmental Policy
NR 43
TC 556
Z9 624
U1 1
U2 130
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 17
PY 2009
VL 462
IS 7275
BP 863
EP U51
DI 10.1038/nature08686
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400031
PM 20016591
DA 2026-03-09
ER

PT J
AU Bohorquez, JC
   Gourley, S
   Dixon, AR
   Spagat, M
   Johnson, NF
AF Camilo Bohorquez, Juan
   Gourley, Sean
   Dixon, Alexander R.
   Spagat, Michael
   Johnson, Neil F.
TI Common ecology quantifies human insurgency
SO NATURE
LA English
DT Article
ID power-law distributions; decision-making; behavior
AB Many collective human activities, including violence, have been shown to exhibit universal patterns(1-19). The size distributions of casualties both in whole wars from 1816 to 1980 and terrorist attacks have separately been shown to follow approximate power-law distributions(6,7,9,10). However, the possibility of universal patterns ranging across wars in the size distribution or timing of within-conflict events has barely been explored. Here we show that the sizes and timing of violent events within different insurgent conflicts exhibit remarkable similarities. We propose a unified model of human insurgency that reproduces these commonalities, and explains conflict-specific variations quantitatively in terms of underlying rules of engagement. Our model treats each insurgent population as an ecology of dynamically evolving, self-organized groups following common decision-making processes. Our model is consistent with several recent hypotheses about modern insurgency(18-20), is robust to many generalizations(21), and establishes a quantitative connection between human insurgency, global terrorism(10) and ecology(13-17,22,23). Its similarity to financial market models(24-26) provides a surprising link between violent and non-violent forms of human behaviour.
C1 [Gourley, Sean; Johnson, Neil F.] Univ Miami, Dept Phys, Complex Syst Grp, Miami, FL 33126 USA.
   [Camilo Bohorquez, Juan] Univ Los Andes, Dept Ind Engn, Bogota, Colombia.
   [Camilo Bohorquez, Juan] Univ Los Andes, CEIBA Complex Syst Res Ctr, Bogota, Colombia.
   [Dixon, Alexander R.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Spagat, Michael] Univ London, Royal Holloway Coll, Dept Econ, Egham TW20 0EX, Surrey, England.
C3 University of Miami; Universidad de los Andes (Colombia); CEIBA; Universidad de los Andes (Colombia); University of Cambridge; University of London; Royal Holloway University London
RP Johnson, NF (corresponding author), Univ Miami, Dept Phys, Complex Syst Grp, Miami, FL 33126 USA.
EM njohnson@physics.miami.edu
NR 30
TC 158
Z9 184
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 17
PY 2009
VL 462
IS 7275
BP 911
EP 914
DI 10.1038/nature08631
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400041
PM 20016600
DA 2026-03-09
ER

PT J
AU Jaramillo, R
   Feng, YJ
   Lang, JC
   Islam, Z
   Srajer, G
   Littlewood, PB
   McWhan, DB
   Rosenbaum, TF
AF Jaramillo, R.
   Feng, Yejun
   Lang, J. C.
   Islam, Z.
   Srajer, G.
   Littlewood, P. B.
   McWhan, D. B.
   Rosenbaum, T. F.
TI Breakdown of the Bardeen-Cooper-Schrieffer ground state at a quantum phase transition
SO NATURE
LA English
DT Article
ID spin-density waves; x-ray-scattering; itinerant antiferromagnetism; chromium; superconductivity; charge; temperature; criticality; dependence; gas
AB Advances in solid-state and atomic physics are exposing the hidden relationships between conventional and exotic states of quantum matter. Prominent examples include the discovery of exotic superconductivity proximate to conventional spin and charge order(1,2), and the crossover from long-range phase order to preformed pairs achieved in gases of cold fermions(3-5) and inferred for copper oxide superconductors(5). The unifying theme is that incompatible ground states can be connected by quantum phase transitions. Quantum fluctuations about the transition are manifestations of the competition between qualitatively distinct organizing principles(6,7), such as a long-wavelength density wave and a short-coherence-length condensate. They may even give rise to 'protected' phases, like fluctuation-mediated superconductivity that survives only in the vicinity of an antiferromagnetic quantum critical point(8,9). However, few model systems that demonstrate continuous quantum phase transitions have been identified, and the complex nature of many systems of interest hinders efforts to more fully understand correlations and fluctuations near a zero-temperature instability. Here we report the suppression of magnetism by hydrostatic pressure in elemental chromium, a simple cubic metal that demonstrates a subtle form of itinerant antiferromagnetism(10-16) formally equivalent to the Bardeen-Cooper-Schrieffer (BCS) state in conventional superconductors. By directly measuring the associated charge order in a diamond anvil cell at low temperatures, we find a phase transition at pressures of similar to 10 GPa driven by fluctuations that destroy the BCS-like state but preserve the strong magnetic interaction between itinerant electrons and holes. Chromium is unique among stoichiometric magnetic metals studied so far in that the quantum phase transition is continuous, allowing experimental access to the quantum singularity and a direct probe of the competition between conventional and exotic order in a theoretically tractable material.
C1 [Jaramillo, R.; Feng, Yejun; Rosenbaum, T. F.] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA.
   [Jaramillo, R.; Feng, Yejun; Rosenbaum, T. F.] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
   [Feng, Yejun; Lang, J. C.; Islam, Z.; Srajer, G.] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
   [Littlewood, P. B.] Univ Cambridge, Cavendish Lab, Cambridge CB3 OHE, England.
   [McWhan, D. B.] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 University of Chicago; University of Chicago; United States Department of Energy (DOE); Argonne National Laboratory; University of Cambridge; Massachusetts Institute of Technology (MIT)
RP Rosenbaum, TF (corresponding author), Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM tfr@uchicago.edu
FU US National Science Foundation (NSF) Division of Materials Research; US NSF Earth Sciences; Department of Energy (DOE) Geosciences; US DOE Office of Basic Energy Sciences
NR 30
TC 44
Z9 54
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 MAY 21
PY 2009
VL 459
IS 7245
BP 405
EP 409
DI 10.1038/nature08008
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700041
PM 19458718
DA 2026-03-09
ER

PT J
AU Kim, KJ
   Lee, JC
   Ahn, SM
   Lee, KS
   Lee, CW
   Cho, YJ
   Seo, S
   Shin, KH
   Choe, SB
   Lee, HW
AF Kim, Kab-Jin
   Lee, Jae-Chul
   Ahn, Sung-Min
   Lee, Kang-Soo
   Lee, Chang-Won
   Cho, Young Jin
   Seo, Sunae
   Shin, Kyung-Ho
   Choe, Sug-Bong
   Lee, Hyun-Woo
TI Interdimensional universality of dynamic interfaces
SO NATURE
LA English
DT Article
ID magnetization reversal; domain-wall; criticality; creep; avalanches; behavior; films
AB Despite the complexity and diversity of nature, there exists universality in the form of critical scaling laws among various dissimilar systems and processes such as stock markets(1), earthquakes(2), crackling noise(3), lung inflation(4) and vortices in superconductors(5). This universality is mainly independent of the microscopic details, depending only on the symmetry and dimension of the system. Exploring how universality is affected by the system dimensions is an important unresolved problem. Here we demonstrate experimentally that universality persists even at a dimensionality crossover in ferromagnetic nanowires. As the wire width decreases, the magnetic domain wall dynamics changes from elastic creep(6-9) in two dimensions to a particle-like stochastic behaviour(10) in one dimension. Applying finite-size scaling, we find that all our experimental data in one and two dimensions (including the crossover regime) collapse onto a single curve, signalling universality at the criticality transition. The crossover to the one-dimensional regime occurs at a few hundred nanometres, corresponding to the integration scale for modern nanodevices.
C1 [Kim, Kab-Jin; Lee, Jae-Chul; Ahn, Sung-Min; Lee, Kang-Soo; Choe, Sug-Bong] Seoul Natl Univ, Ctr Subwavelength Opt, Seoul 151742, South Korea.
   [Kim, Kab-Jin; Lee, Jae-Chul; Ahn, Sung-Min; Lee, Kang-Soo; Choe, Sug-Bong] Seoul Natl Univ, Sch Phys & Astron, Seoul 151742, South Korea.
   [Lee, Jae-Chul; Shin, Kyung-Ho] Korea Adv Inst Sci & Technol, Ctr Spintron Res, Seoul 136791, South Korea.
   [Lee, Chang-Won; Cho, Young Jin; Seo, Sunae] Samsung Adv Inst Technol, Yongin 449712, South Korea.
   [Lee, Hyun-Woo] Pohang Univ Sci & Technol, PCTP, Pohang 790784, Kyungbuk, South Korea.
   [Lee, Hyun-Woo] Pohang Univ Sci & Technol, Dept Phys, Pohang 790784, Kyungbuk, South Korea.
C3 Seoul National University (SNU); Seoul National University (SNU); Korea Advanced Institute of Science & Technology (KAIST); Samsung; Pohang University of Science & Technology (POSTECH); Pohang University of Science & Technology (POSTECH)
RP Choe, SB (corresponding author), Seoul Natl Univ, Ctr Subwavelength Opt, Seoul 151742, South Korea.
EM sugbong@snu.ac.kr; hwl@postech.ac.kr
FU KOSEF [R0A-2007-000-20032-0, R01-2007-000-20281-0, R11-2000-071, R11-2008-095-01000-0]; Seoul Science Fellowship; KIST; MEST
NR 21
TC 136
Z9 143
U1 2
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 9
PY 2009
VL 458
IS 7239
BP 740
EP 742
DI 10.1038/nature07874
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600035
PM 19360082
DA 2026-03-09
ER

PT J
AU Airan, RD
   Thompson, KR
   Fenno, LE
   Bernstein, H
   Deisseroth, K
AF Airan, Raag D.
   Thompson, Kimberly R.
   Fenno, Lief E.
   Bernstein, Hannah
   Deisseroth, Karl
TI Temporally precise in vivo control of intracellular signalling
SO NATURE
LA English
DT Article
ID activation; nucleus; photostimulation; addiction; receptors; reveals
AB In the study of complex mammalian behaviours, technological limitations have prevented spatiotemporally precise control over intracellular signalling processes. Here we report the development of a versatile family of genetically encoded optical tools ('optoXRs') that leverage common structure -function relationships(1) among G-protein-coupled receptors (GPCRs) to recruit and control, with high spatiotemporal precision, receptor-initiated biochemical signalling pathways. In particular, we have developed and characterized two optoXRs that selectively recruit distinct, targeted signalling pathways in response to light. The two optoXRs exerted opposing effects on spike firing in nucleus accumbens in vivo, and precisely timed optoXR photostimulation in nucleus accumbens by itself sufficed to drive conditioned place preference in freely moving mice. The optoXR approach allows testing of hypotheses regarding the causal impact of biochemical signalling in behaving mammals, in a targetable and temporally precise manner.
C1 [Airan, Raag D.; Thompson, Kimberly R.; Fenno, Lief E.; Bernstein, Hannah; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Deisseroth, K (corresponding author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
EM deissero@stanford.edu
FU NIH/NIMH National Research Service Award; Stanford Medical Scientist Training Program; NARSAD Young Investigator Award; CIRM; McKnight; Coulter; Klingenstein; Keck; NSF; NIDA; NIH Pioneer Award; Albert Yu and Mary Bechmann Foundation; Kinetics Foundation
NR 30
TC 553
Z9 739
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 23
PY 2009
VL 458
IS 7241
BP 1025
EP 1029
DI 10.1038/nature07926
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900042
PM 19295515
DA 2026-03-09
ER

PT J
AU Steele, IA
   Mundell, CG
   Smith, RJ
   Kobayashi, S
   Guidorzi, C
AF Steele, I. A.
   Mundell, C. G.
   Smith, R. J.
   Kobayashi, S.
   Guidorzi, C.
TI Ten per cent polarized optical emission from GRB 090102
SO NATURE
LA English
DT Article
ID gamma-ray bursts; space-telescope; afterglows; grb-021206; fireball; model; shock
AB The nature of the jets and the role of magnetic fields in gamma-ray bursts (GRBs) remains unclear(1,2). In a baryon-dominated jet only weak, tangled fields generated in situ through shocks would be present(3). In an alternative model, jets are threaded with large-scale magnetic fields that originate at the central engine and that accelerate and collimate the material(4). To distinguish between the models the degree of polarization in early-time emission must be measured; however, previous claims of gamma-ray polarization have been controversial(5-8). Here we report that the early optical emission from GRB 090102 was polarized at 10 +/- 1 per cent, indicating the presence of large-scale fields originating in the expanding fireball. If the degree of polarization and its position angle were variable on timescales shorter than our 60-second exposure, then the peak polarization may have been larger than ten per cent.
C1 [Steele, I. A.; Mundell, C. G.; Smith, R. J.; Kobayashi, S.] Liverpool John Moores Univ, Astrophys Res Inst, Liverpool CH41 1LD, Merseyside, England.
   [Guidorzi, C.] Univ Ferrara, Dept Phys, I-44122 Ferrara, Italy.
C3 Liverpool John Moores University; University of Ferrara
RP Steele, IA (corresponding author), Liverpool John Moores Univ, Astrophys Res Inst, Liverpool CH41 1LD, Merseyside, England.
EM ias@astro.livjm.ac.uk
FU UK Science and Technology Facilities Council; Royal Society and Research Councils UK; STFC [PP/E001149/1, ST/G009465/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [GR/T27969/01] Funding Source: researchfish; Science and Technology Facilities Council [PP/E001149/1, ST/G009465/1] Funding Source: researchfish
NR 30
TC 131
Z9 135
U1 0
U2 4
PU NATURE PUBLISHING 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 10
PY 2009
VL 462
IS 7274
BP 767
EP 769
DI 10.1038/nature08590
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900033
PM 20010682
DA 2026-03-09
ER

PT J
AU Krummel, DAP
   Oubridge, C
   Leung, AKW
   Li, J
   Nagai, K
AF Krummel, Daniel A. Pomeranz
   Oubridge, Chris
   Leung, Adelaine K. W.
   Li, Jade
   Nagai, Kiyoshi
TI Crystal structure of human spliceosomal U1 snRNP at 5.5Å resolution
SO NATURE
LA English
DT Article
ID small nuclear ribonucleoprotein; pre-messenger-rna; binding domain; angstrom-resolution; protein-c; complex; identification; recognition; site; u2
AB Human spliceosomal U1 small nuclear ribonucleoprotein particles (snRNPs), which consist of U1 small nuclear RNA and ten proteins, recognize the 5' splice site within precursor messenger RNAs and initiate the assembly of the spliceosome for intron excision. An electron density map of the functional core of U1 snRNP at 5.5 angstrom resolution has enabled us to build the RNA and, in conjunction with site-specific labelling of individual proteins, to place the seven Sm proteins, U1-C and U1-70K into the map. Here we present the detailed structure of a spliceosomal snRNP, revealing a hierarchical network of intricate interactions between subunits. A striking feature is the amino (N)-terminal polypeptide of U1-70K, which extends over a distance of 180 angstrom from its RNA binding domain, wraps around the core domain consisting of the seven Sm proteins and finally contacts U1-C, which is crucial for 5'-splice-site recognition. The structure of U1 snRNP provides insights into U1 snRNP assembly and suggests a possible mechanism of 5'-splice-site recognition.
C1 [Krummel, Daniel A. Pomeranz; Oubridge, Chris; Leung, Adelaine K. W.; Li, Jade; Nagai, Kiyoshi] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Nagai, K (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM kn@mrc-lmb.cam.ac.uk
FU Medical Research Council; Human Frontier Science Program (HFSP); National Science and Engineering Research Council of Canada; ORS Fund; Cambridge Commonwealth Trust; Sidney Sussex College Junior Research Fellowship; MRC [MC_U105184330] Funding Source: UKRI; Medical Research Council [MC_U105184330] Funding Source: researchfish
NR 57
TC 192
Z9 195
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 475
EP U1
DI 10.1038/nature07851
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400037
DA 2026-03-09
ER

PT J
AU López-Avilés, S
   Kapuy, O
   Novák, B
   Uhlmann, F
AF Lopez-Aviles, Sandra
   Kapuy, Orsolya
   Novak, Bela
   Uhlmann, Frank
TI Irreversibility of mitotic exit is the consequence of systems-level feedback
SO NATURE
LA English
DT Article
ID anaphase promoting complex; cell-cycle; saccharomyces-cerevisiae; budding yeast; phosphatase cdc14; protein-kinase; phosphorylation; apc; proteolysis; inhibitor
AB The eukaryotic cell cycle comprises an ordered series of events, orchestrated by the activity of cyclin-dependent kinases (Cdks), leading from chromosome replication during S phase to their segregation in mitosis. The unidirectionality of cell-cycle transitions is fundamental for the successful completion of this cycle. It is thought that irrevocable proteolytic degradation of key cell-cycle regulators makes cell-cycle transitions irreversible, thereby enforcing directionality(1-3). Here we have experimentally examined the contribution of cyclin proteolysis to the irreversibility of mitotic exit, the transition from high mitotic Cdk activity back to low activity in G1. We show that forced cyclin destruction in mitotic budding yeast cells efficiently drives mitotic exit events. However, these remain reversible after termination of cyclin proteolysis, with recovery of the mitotic state and cyclin levels. Mitotic exit becomes irreversible only after longer periods of cyclin degradation, owing to activation of a double-negative feedback loop involving the Cdk inhibitor Sic1 (refs 4, 5). Quantitative modelling suggests that feedback is required to maintain low Cdk activity and to prevent cyclin resynthesis. Our findings demonstrate that the unidirectionality of mitotic exit is not the consequence of proteolysis but of systems-level feedback required to maintain the cell cycle in a new stable state.
C1 [Lopez-Aviles, Sandra; Uhlmann, Frank] Canc Res UK London Res Inst, Chromosome Segregat Lab, London WC2A 3PX, England.
   [Kapuy, Orsolya; Novak, Bela] Univ Oxford, Dept Biochem, Oxford Ctr Integrat Syst Biol, Oxford OX1 3QU, England.
   [Kapuy, Orsolya] Budapest Univ Technol & Econ, H-1521 Budapest, Hungary.
C3 Cancer Research UK; University of Oxford; Budapest University of Technology & Economics
RP Uhlmann, F (corresponding author), Canc Res UK London Res Inst, Chromosome Segregat Lab, 44 Lincolns Inn Fields, London WC2A 3PX, England.
EM frank.uhlmann@cancer.org.uk
FU European Commission Marie Curie Individual Fellowship; BBSRC; EC FP7
NR 30
TC 83
Z9 96
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 28
PY 2009
VL 459
IS 7246
BP 592
EP 595
DI 10.1038/nature07984
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500044
PM 19387440
DA 2026-03-09
ER

PT J
AU Kamikouchi, A
   Inagaki, HK
   Effertz, T
   Hendrich, O
   Fiala, A
   Göpfert, MC
   Ito, K
AF Kamikouchi, Azusa
   Inagaki, Hidehiko K.
   Effertz, Thomas
   Hendrich, Oliver
   Fiala, Andre
   Goepfert, Martin C.
   Ito, Kei
TI The neural basis of Drosophila gravity-sensing and hearing
SO NATURE
LA English
DT Article
ID transduction channel; trp channels; melanogaster; expression; mutations; pathways; cerebellum; audition; neurons; nuclei
AB The neural substrates that the fruitfly Drosophila uses to sense smell, taste and light share marked structural and functional similarities with ours, providing attractive models to dissect sensory stimulus processing. Here we focus on two of the remaining and less understood prime sensory modalities: graviception and hearing. We show that the fly has implemented both sensory modalities into a single system, Johnston's organ, which houses specialized clusters of mechanosensory neurons, each of which monitors specific movements of the antenna. Gravity- and sound-sensitive neurons differ in their response characteristics, and only the latter express the candidate mechanotransducer channel NompC. The two neural subsets also differ in their central projections, feeding into neural pathways that are reminiscent of the vestibular and auditory pathways in our brain. By establishing the Drosophila counterparts of these sensory systems, our findings provide the basis for a systematic functional and molecular dissection of how different mechanosensory stimuli are detected and processed.
C1 [Kamikouchi, Azusa; Inagaki, Hidehiko K.; Ito, Kei] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Kamikouchi, Azusa; Effertz, Thomas; Hendrich, Oliver; Goepfert, Martin C.] Univ Cologne, Inst Zool, Sensory Syst Lab, D-50923 Cologne, Germany.
   [Kamikouchi, Azusa] Tokyo Univ Pharm & Life Sci, Sch Life Sci, Tokyo 1920392, Japan.
   [Effertz, Thomas; Hendrich, Oliver; Fiala, Andre; Goepfert, Martin C.] Univ Gottingen, Johann Friedrich Blumenbach Inst, D-37073 Gottingen, Germany.
   [Fiala, Andre] Univ Wurzburg, Dept Genet & Neurobiol, Theodor Boveri Inst, D-97074 Wurzburg, Germany.
C3 University of Tokyo; University of Cologne; Tokyo University of Pharmacy & Life Sciences; University of Gottingen; University of Wurzburg
RP Ito, K (corresponding author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
EM mgoepfe@gwdg.de; itokei@iam.u-tokyo.ac.jp
FU Japanese Cell Science Research Foundation; Alexander von Humboldt Foundation; Japan Society for the Promotion of Science; DFG Collaborative Research Centre 554; Volkswagen Foundation; BMBF Bernstein Network for Computational Neuroscience; DFG Research Centre Molecular Physiology of the Brain; Human Frontier Science Program Organisation; BIRD/Japan Science and Technology Agency
NR 43
TC 297
Z9 357
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 MAR 12
PY 2009
VL 458
IS 7235
BP 165
EP U1
DI 10.1038/nature07810
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700035
PM 19279630
DA 2026-03-09
ER

PT J
AU LaHaye, MD
   Suh, J
   Echternach, PM
   Schwab, KC
   Roukes, ML
AF LaHaye, M. D.
   Suh, J.
   Echternach, P. M.
   Schwab, K. C.
   Roukes, M. L.
TI Nanomechanical measurements of a superconducting qubit
SO NATURE
LA English
DT Article
ID resonator; states; phase
AB The observation of the quantum states of motion of a macroscopic mechanical structure remains an open challenge in quantum-state preparation and measurement. One approach that has received extensive theoretical attention(1-13) is the integration of superconducting qubits as control and detection elements in nanoelectromechanical systems (NEMS). Here we report measurements of a NEMS resonator coupled to a superconducting qubit, a Cooper-pair box. We demonstrate that the coupling results in a dispersive shift of the nanomechanical frequency that is the mechanical analogue of the 'single-atom index effect'(14) experienced by electromagnetic resonators in cavity quantum electrodynamics. The large magnitude of the dispersive interaction allows us to perform NEMS-based spectroscopy of the superconducting qubit, and enables observation of Landau-Zener interference effects-a demonstration of nanomechanical read-out of quantum interference.
C1 [LaHaye, M. D.; Suh, J.; Roukes, M. L.] CALTECH, Kavli Nanosci Inst, Pasadena, CA 91125 USA.
   [Echternach, P. M.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 California Institute of Technology; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL)
RP Roukes, ML (corresponding author), CALTECH, Kavli Nanosci Inst, MS 114-36, Pasadena, CA 91125 USA.
EM roukes@caltech.edu
FU US National Science Foundation [DMR-0804567]; Foundational Questions Institute [RFP2-08-27]; Center for the Physics of Information, California Institute of Technology; US National Aeronautics and Space Administration
NR 30
TC 354
Z9 401
U1 1
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 18
PY 2009
VL 459
IS 7249
BP 960
EP 964
DI 10.1038/nature08093
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500037
PM 19536259
DA 2026-03-09
ER

PT J
AU Khare, A
   Santorelli, LA
   Strassmann, JE
   Queller, DC
   Kuspa, A
   Shaulsky, G
AF Khare, Anupama
   Santorelli, Lorenzo A.
   Strassmann, Joan E.
   Queller, David C.
   Kuspa, Adam
   Shaulsky, Gad
TI Cheater-resistance is not futile
SO NATURE
LA English
DT Article
ID dictyostelium-discoideum; social ameba; cooperation; dna; evolution; society; responses; mutants
AB Cooperative social systems are susceptible to cheating by individuals that reap the benefits of cooperation without incurring the costs(1). There are various theoretical mechanisms for the repression of cheating(2) and many have been tested experimentally. One possibility that has not been tested rigorously is the evolution of mutations that confer resistance to cheating. Here we show that the presence of a cheater in a population of randomly mutated social amoebae can select for cheater-resistance. Furthermore, we show that this cheater-resistance can be a noble strategy because the resister strain does not necessarily exploit other strains. Thus, the evolution of resisters may be instrumental in preserving cooperative behaviour in the face of cheating.
C1 [Khare, Anupama; Santorelli, Lorenzo A.; Kuspa, Adam; Shaulsky, Gad] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Santorelli, Lorenzo A.; Strassmann, Joan E.; Queller, David C.; Kuspa, Adam; Shaulsky, Gad] Rice Univ, Dept Ecol & Evolutionary Biol, Houston, TX 77005 USA.
   [Kuspa, Adam] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Rice University; Baylor College of Medicine
RP Shaulsky, G (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA.
EM gadi@bcm.edu
FU National Science Foundation; Cullen Foundation
NR 26
TC 56
Z9 63
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 OCT 15
PY 2009
VL 461
IS 7266
BP 980
EP U240
DI 10.1038/nature08472
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700047
PM 19794414
DA 2026-03-09
ER

PT J
AU Abrahám, P
   Juhász, A
   Dullemond, CP
   Kóspál, A
   Van Boekel, R
   Bouwman, J
   Henning, T
   Moór, A
   Mosoni, L
   Sicilia-Aguilar, A
   Sipos, N
AF Abraham, P.
   Juhasz, A.
   Dullemond, C. P.
   Kospal, A.
   Van Boekel, R.
   Bouwman, J.
   Henning, Th.
   Moor, A.
   Mosoni, L.
   Sicilia-Aguilar, A.
   Sipos, N.
TI Episodic formation of cometary material in the outburst of a young Sun-like star
SO NATURE
LA English
DT Article
ID crystalline silicates; dust; evolution; spectra; grains; disks
AB The Solar System originated in a cloud of interstellar gas and dust. The dust is in the form of amorphous silicate particles(1,2) and carbonaceous dust. The composition of cometary material, however, shows that a significant fraction of the amorphous silicate dust was transformed into crystalline form during the early evolution of the protosolar nebula(3). How and when this transformation happened has been a question of debate, with the main options being heating by the young Sun(4,5) and shock heating(6). Here we report mid-infrared features in the outburst spectrum of the young Sun-like star EX Lupi that were not present in quiescence. We attribute them to crystalline forsterite. We conclude that the crystals were produced through thermal annealing in the surface layer of the inner disk by heat from the outburst, a process that has hitherto not been considered. The observed lack of cold crystals excludes shock heating at larger radii.
C1 [Abraham, P.; Moor, A.; Mosoni, L.; Sipos, N.] Hungarian Acad Sci, Konkoly Observ Budapest, H-1525 Budapest, Hungary.
   [Juhasz, A.; Dullemond, C. P.; Van Boekel, R.; Bouwman, J.; Henning, Th.; Mosoni, L.; Sicilia-Aguilar, A.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Kospal, A.] Leiden Univ, Leiden Observ, NL-2333 CA Leiden, Netherlands.
C3 HUN-REN; HUN-REN Research Centre for Astronomy & Earth Sciences; Konkoly Thege Miklos Astronomical Institute; Hungarian Academy of Sciences; Max Planck Society; Leiden University; Leiden University - Excl LUMC
RP Abrahám, P (corresponding author), Hungarian Acad Sci, Konkoly Observ Budapest, POB 67, H-1525 Budapest, Hungary.
EM abraham@konkoly.hu
FU Hungarian Research Fund; Netherlands Organization for Scientific Research
NR 26
TC 130
Z9 138
U1 1
U2 5
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 224
EP 226
DI 10.1038/nature08004
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100034
PM 19444209
DA 2026-03-09
ER

PT J
AU Saito, K
   Inagaki, S
   Mituyama, T
   Kawamura, Y
   Ono, Y
   Sakota, E
   Kotani, H
   Asai, K
   Siomi, H
   Siomi, MC
AF Saito, Kuniaki
   Inagaki, Sachi
   Mituyama, Toutai
   Kawamura, Yoshinori
   Ono, Yukiteru
   Sakota, Eri
   Kotani, Hazuki
   Asai, Kiyoshi
   Siomi, Haruhiko
   Siomi, Mikiko C.
TI A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila
SO NATURE
LA English
DT Article
ID germline stem-cells; rna pathway; pirna; mechanisms; mutations; division; encodes; gonad; risc
AB PIWI-interacting RNAs (piRNAs) silence retrotransposons in Drosophila germ lines by associating with the PIWI proteins Argonaute 3 (AGO3), Aubergine (Aub) and Piwi(1,2). piRNAs in Drosophila are produced from intergenic repetitive genes and piRNA clusters by two systems: the primary processing pathway and the amplification loop(1-7). The amplification loop occurs in a Dicer-independent, PIWI-Slicer-dependent manner(3,4,8). However, primary piRNA processing remains elusive. Here we analysed piRNA processing in a Drosophila ovarian somatic cell line where Piwi, but not Aub or AGO3, is expressed; thus, only the primary piRNAs exist. In addition to flamenco, a Piwi-specific piRNA cluster(3), traffic jam (tj)(9), a large Maf gene, was determined as a new piRNA cluster. piRNAs arising from tj correspond to the untranslated regions of tj messenger RNA and are sense-oriented. piRNA loading on to Piwi may occur in the cytoplasm. zucchini(10), a gene encoding a putative cytoplasmic nuclease, is required for tj-derived piRNA production. In tj and piwi mutant ovaries, somatic cells fail to intermingle with germ cells and Fasciclin III is overexpressed. Loss of tj abolishes Piwi expression in gonadal somatic cells. Thus, in gonadal somatic cells, tj gives rise simultaneously to two different molecules: the TJ protein, which activates Piwi expression, and piRNAs, which define the Piwi targets for silencing.
C1 [Saito, Kuniaki; Inagaki, Sachi; Kawamura, Yoshinori; Kotani, Hazuki; Siomi, Haruhiko; Siomi, Mikiko C.] Keio Univ, Sch Med, Tokyo 1608582, Japan.
   [Mituyama, Toutai; Asai, Kiyoshi] Natl Inst Adv Ind Sci & Technol, CBRC, Tokyo 1350064, Japan.
   [Kawamura, Yoshinori] Univ Tokushima, Inst Hlth Biosci, Tokushima 7708503, Japan.
   [Ono, Yukiteru] Informat & Math Sci Lab Inc, Dept Life Sci, Tokushima 1120012, Japan.
   [Sakota, Eri] JBIC, Tokyo 1358073, Japan.
   [Asai, Kiyoshi] Univ Tokyo, Grad Sch Frontier Sci, Chiba 2778583, Japan.
   [Siomi, Mikiko C.] CREST, JST, Kawaguchi, Saitama 3320012, Japan.
C3 Keio University; National Institute of Advanced Industrial Science & Technology (AIST); Tokushima University; University of Tokyo; Japan Science & Technology Agency (JST)
RP Siomi, H (corresponding author), Keio Univ, Sch Med, Tokyo 1608582, Japan.
EM awa403@sc.itc.keio.ac.jp; siomim@sc.itc.keio.ac.jp
FU MEXT; NEDO ( New Energy and Industrial Technology Development Organization); CREST; Grants-in-Aid for Scientific Research [19061001] Funding Source: KAKEN
NR 30
TC 350
Z9 402
U1 1
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 29
PY 2009
VL 461
IS 7268
BP 1296
EP U135
DI 10.1038/nature08501
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800052
PM 19812547
DA 2026-03-09
ER

PT J
AU Yanai, H
   Ban, T
   Wang, ZC
   Choi, MK
   Kawamura, T
   Negishi, H
   Nakasato, M
   Lu, Y
   Hangai, S
   Koshiba, R
   Savitsky, D
   Ronfani, L
   Akira, S
   Bianchi, ME
   Honda, K
   Tamura, T
   Kodama, T
   Taniguchi, T
AF Yanai, Hideyuki
   Ban, Tatsuma
   Wang, ZhiChao
   Choi, Myoung Kwon
   Kawamura, Takeshi
   Negishi, Hideo
   Nakasato, Makoto
   Lu, Yan
   Hangai, Sho
   Koshiba, Ryuji
   Savitsky, David
   Ronfani, Lorenza
   Akira, Shizuo
   Bianchi, Marco E.
   Honda, Kenya
   Tamura, Tomohiko
   Kodama, Tatsuhiko
   Taniguchi, Tadatsugu
TI HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses
SO NATURE
LA English
DT Article
ID rig-i; cytosolic dna; rna; recognition; cells; induction; activation; family; member
AB The activation of innate immune responses by nucleic acids is crucial to protective and pathological immunities and is mediated by the transmembrane Toll-like receptors (TLRs) and cytosolic receptors(1,2). However, it remains unknown whether a mechanism exists that integrates these nucleic-acid-sensing systems. Here we show that high-mobility group box (HMGB) proteins 1, 2 and 3 function as universal sentinels for nucleic acids. HMGBs bind to all immunogenic nucleic acids examined with a correlation between affinity and immunogenic potential. Hmgb1(-/-) and Hmgb2(-/-) mouse cells are defective in type-I interferon and inflammatory cytokine induction by DNA or RNA targeted to activate the cytosolic nucleic-acid-sensing receptors; cells in which the expression of all three HMGBs is suppressed show a more profound defect, accompanied by impaired activation of the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-kappa B. The absence of HMGBs also severely impairs the activation of TLR3, TLR7 and TLR9 by their cognate nucleic acids. Our results therefore indicate a hierarchy in the nucleic-acid-mediated activation of immune responses, wherein the selective activation of nucleic-acid-sensing receptors is contingent on the more promiscuous sensing of nucleic acids by HMGBs. These findings may have implications for understanding the evolution of the innate immune system and for the treatment of immunological disorders.
C1 [Yanai, Hideyuki; Ban, Tatsuma; Wang, ZhiChao; Choi, Myoung Kwon; Negishi, Hideo; Nakasato, Makoto; Lu, Yan; Hangai, Sho; Koshiba, Ryuji; Savitsky, David; Honda, Kenya; Tamura, Tomohiko; Taniguchi, Tadatsugu] Univ Tokyo, Grad Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 1130033, Japan.
   [Yanai, Hideyuki; Ban, Tatsuma; Wang, ZhiChao; Choi, Myoung Kwon; Negishi, Hideo; Nakasato, Makoto; Lu, Yan; Hangai, Sho; Koshiba, Ryuji; Savitsky, David; Honda, Kenya; Tamura, Tomohiko; Taniguchi, Tadatsugu] Univ Tokyo, Fac Med, Bunkyo Ku, Tokyo 1130033, Japan.
   [Kawamura, Takeshi; Kodama, Tatsuhiko] Univ Tokyo, RCAST, Lab Syst Biol & Med, Meguro Ku, Tokyo 1538904, Japan.
   [Ronfani, Lorenza; Bianchi, Marco E.] San Raffaele Univ, Fac Med, I-20132 Milan, Italy.
   [Akira, Shizuo] Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan.
C3 University of Tokyo; University of Tokyo; University of Tokyo; Vita-Salute San Raffaele University; University of Osaka
RP Taniguchi, T (corresponding author), Univ Tokyo, Grad Sch Med, Dept Immunol, Bunkyo Ku, Hongo 7-3-1, Tokyo 1130033, Japan.
EM tada@m.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan; Korea Science and Engineering Foundation; Japan Society for the Promotion of Science
NR 33
TC 565
Z9 667
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 NOV 5
PY 2009
VL 462
IS 7269
BP 99
EP U110
DI 10.1038/nature08512
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200040
PM 19890330
DA 2026-03-09
ER

PT J
AU Garcia, V
   Fusil, S
   Bouzehouane, K
   Enouz-Vedrenne, S
   Mathur, ND
   Barthélémy, A
   Bibes, M
AF Garcia, V.
   Fusil, S.
   Bouzehouane, K.
   Enouz-Vedrenne, S.
   Mathur, N. D.
   Barthelemy, A.
   Bibes, M.
TI Giant tunnel electroresistance for non-destructive readout of ferroelectric states
SO NATURE
LA English
DT Article
ID atomic-force microscopy; junctions; physics
AB Ferroelectrics possess a polarization that is spontaneous, stable and electrically switchable(1), and submicrometre-thick ferroelectric films are currently used as non-volatile memory elements with destructive capacitive readout(2). Memories based on tunnel junctions with ultrathin ferroelectric barriers would enable non-destructive resistive readout(3). However, the achievement of room-temperature polarization stability and switching at very low thickness is challenging(4,5). Here we use piezoresponse force microscopy at room temperature to show robust ferroelectricity down to 1 nm in highly strained BaTiO3 films; we also use room-temperature conductive-tip atomic force microscopy to demonstrate resistive readout of the polarization state through its influence on the tunnel current(6,7). The resulting electroresistance effect scales exponentially with ferroelectric film thickness, reaching similar to 75,000% at 3 nm. Our approach exploits the otherwise undesirable leakage current-dominated by tunnelling at these very low thicknesses-to read the polarization state without destroying it. We demonstrate scalability down to 70 nm, corresponding to potential densities of >16 Gbit inch(-2). These results pave the way towards ferroelectric memories with simplified architectures, higher densities and faster operation, and should inspire further exploration of the interplay between quantum tunnelling and ferroelectricity at the nanoscale.
C1 [Garcia, V.; Fusil, S.; Bouzehouane, K.; Barthelemy, A.; Bibes, M.] Unite Mixte Phys CNRS Thales, F-91767 Palaiseau, France.
   [Garcia, V.; Fusil, S.; Bouzehouane, K.; Barthelemy, A.; Bibes, M.] Univ Paris Sud, F-91405 Orsay, France.
   [Garcia, V.; Mathur, N. D.] Univ Cambridge, Dept Mat Sci, Cambridge CB2 3QZ, England.
   [Fusil, S.] Univ dEvry Val dEssonne, F-91025 Evry, France.
   [Enouz-Vedrenne, S.] Thales Res & Technol, F-91767 Palaiseau, France.
C3 Centre National de la Recherche Scientifique (CNRS); Thales Group; Universite Paris Saclay; University of Cambridge; Universite Paris Saclay; Thales Group
RP Bibes, M (corresponding author), Unite Mixte Phys CNRS Thales, 1 Av A Fresnel,Campus Ecole Polytech, F-91767 Palaiseau, France.
EM manuel.bibes@thalesgroup.com
FU France-UKPMCAlliance programme; French RTRA Triangle de la Physique; EU STRP Macomufi; EU STRP CoMePhS; UK EPSRC [EP/E026206/I]; French ANR Femmes; French ANR Alicante
NR 26
TC 841
Z9 921
U1 11
U2 653
PU NATURE PUBLISHING 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 2
PY 2009
VL 460
IS 7251
BP 81
EP 84
DI 10.1038/nature08128
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200033
PM 19483675
DA 2026-03-09
ER

PT J
AU Biercuk, MJ
   Uys, H
   VanDevender, AP
   Shiga, N
   Itano, WM
   Bollinger, JJ
AF Biercuk, Michael J.
   Uys, Hermann
   VanDevender, Aaron P.
   Shiga, Nobuyasu
   Itano, Wayne M.
   Bollinger, John J.
TI Optimized dynamical decoupling in a model quantum memory
SO NATURE
LA English
DT Article
ID crystallized ion plasmas; decoherence; systems
AB Any quantum system, such as those used in quantum information or magnetic resonance, is subject to random phase errors that can dramatically affect the fidelity of a desired quantum operation or measurement(1). In the context of quantum information, quantum error correction techniques have been developed to correct these errors, but resource requirements are extraordinary. The realization of a physically tractable quantum information system will therefore be facilitated if qubit (quantum bit) error rates are far below the so-called fault-tolerance error threshold(1), predicted to be of the order of 10(-3)-10(-6). The need to realize such low error rates motivates a search for alternative strategies to suppress dephasing in quantum systems(2). Here we experimentally demonstrate massive suppression of qubit error rates by the application of optimized dynamical decoupling(3-8) pulse sequences, using a model quantum system capable of simulating a variety of qubit technologies. We demonstrate an analytically derived pulse sequence(9), UDD, and find novel sequences through active, real-time experimental feedback. The latter sequences are tailored to maximize error suppression without the need for a priori knowledge of the ambient noise environment, and are capable of suppressing errors by orders of magnitude compared to other existing sequences (including the benchmark multi-pulse spin echo(10,11)). Our work includes the extension of a treatment to predict qubit decoherence(12,13) under realistic conditions, yielding strong agreement between experimental data and theory for arbitrary pulse sequences incorporating nonidealized control pulses. These results demonstrate the robustness of qubit memory error suppression through dynamical decoupling techniques across a variety of qubit technologies(11,14-16).
C1 [Biercuk, Michael J.; Uys, Hermann; VanDevender, Aaron P.; Shiga, Nobuyasu; Itano, Wayne M.; Bollinger, John J.] NIST, Div Time & Frequency, Boulder, CO 80305 USA.
   [Biercuk, Michael J.] Georgia Inst Technol, Atlanta, GA USA.
   [Uys, Hermann] CSIR, ZA-0001 Pretoria, South Africa.
C3 National Institute of Standards & Technology (NIST) - USA; University System of Georgia; Georgia Institute of Technology; Council for Scientific & Industrial Research (CSIR) - South Africa
RP Biercuk, MJ (corresponding author), NIST, Div Time & Frequency, Boulder, CO 80305 USA.
EM biercuk@boulder.nist.gov
FU IARPA; NIST; Georgia Tech.; CSIR
NR 30
TC 518
Z9 576
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 APR 23
PY 2009
VL 458
IS 7241
BP 996
EP 1000
DI 10.1038/nature07951
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900035
PM 19396139
DA 2026-03-09
ER

PT J
AU Pearson, PN
   Foster, GL
   Wade, BS
AF Pearson, Paul N.
   Foster, Gavin L.
   Wade, Bridget S.
TI Atmospheric carbon dioxide through the Eocene-Oligocene climate transition
SO NATURE
LA English
DT Article
ID boron isotope; antarctic glaciation; seawater; evolution; cycle; sea; calibration; greenhouse; boundary; record
AB Geological and geochemical evidence(1-3) indicates that the Antarctic ice sheet formed during the Eocene-Oligocene transition(4), 33.5-34.0 million years ago. Modelling studies(5,6) suggest that such ice-sheet formation might have been triggered when atmospheric carbon dioxide levels (p(CO2)(atm)) fell below a critical threshold of similar to 750 p. p. m. v., but the timing and magnitude of p(CO2)(atm) relative to the evolution of the ice sheet has remained unclear. Here we use the boron isotope pH proxy(7,8) on exceptionally well-preserved carbonate microfossils from a recently discovered geological section in Tanzania(9,10) to estimate p(CO2)(atm) before, during and after the climate transition. Our data suggest that a reduction in p(CO2)(atm) occurred before the main phase of ice growth, followed by a sharp recovery to pre-transition values and then a more gradual decline. During maximum ice-sheet growth, p(CO2)(atm) was between similar to 450 and similar to 1,500 p. p. m. v., with a central estimate of similar to 760 p. p. m. v. The ice cap survived the period of p(CO2)(atm) recovery, although possibly with some reduction in its volume, implying (as models predict(11)) a nonlinear response to climate forcing during melting. Overall, our results confirm the central role of declining p(CO2)(atm) in the development of the Antarctic ice sheet (in broad agreement with carbon cycle modelling(12)) and help to constrain mechanisms and feedbacks associated with the Earth's biggest climate switch of the past 65 Myr.
C1 [Pearson, Paul N.] Cardiff Univ, Sch Earth & Ocean Sci, Cardiff CF10 3YE, Wales.
   [Foster, Gavin L.] Univ Bristol, Dept Earth Sci, Bristol Isotope Grp, Bristol BS8 1RJ, Avon, England.
   [Wade, Bridget S.] Texas A&M Univ, Dept Geol & Geophys, College Stn, TX 77843 USA.
C3 Cardiff University; University of Bristol; Texas A&M University System; Texas A&M University College Station
RP Pearson, PN (corresponding author), Cardiff Univ, Sch Earth & Ocean Sci, Cardiff CF10 3YE, Wales.
EM pearsonp@cardiff.ac.uk
FU NERC
NR 38
TC 327
Z9 387
U1 0
U2 142
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1110
EP U204
DI 10.1038/nature08447
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600041
PM 19749741
DA 2026-03-09
ER

PT J
AU Wannamaker, PE
   Caldwell, TG
   Jiracek, GR
   Maris, V
   Hill, GJ
   Ogawa, Y
   Bibby, HM
   Bennie, SL
   Heise, W
AF Wannamaker, Philip E.
   Caldwell, T. Grant
   Jiracek, George R.
   Maris, Virginie
   Hill, Graham J.
   Ogawa, Yasuo
   Bibby, Hugh M.
   Bennie, Stewart L.
   Heise, Wiebke
TI Fluid and deformation regime of an advancing subduction system at Marlborough, New Zealand
SO NATURE
LA English
DT Article
ID south island; fault system; seismicity; beneath; alps
AB Newly forming subduction zones on Earth can provide insights into the evolution of major fault zone geometries from shallow levels to deep in the lithosphere and into the role of fluids in element transport and in promoting rock failure by several modes(1,2). The transpressional subduction regime of New Zealand, which is advancing laterally to the southwest below the Marlborough strike-slip fault system of the northern South Island(3,4), is an ideal setting in which to investigate these processes. Here we acquired a dense, high-quality transect of magnetotelluric soundings across the system, yielding an electrical resistivity cross-section to depths beyond 100 km. Our data imply three distinct processes connecting fluid generation along the upper mantle plate interface to rock deformation in the crust as the subduction zone develops. Massive fluid release just inland of the trench induces fault-fracture meshes through the crust above that undoubtedly weaken it as regional shear initiates. Narrow strike-slip faults in the shallow brittle regime of interior Marlborough diffuse in width upon entering the deeper ductile domain aided by fluids and do not project as narrow deformation zones. Deep subduction-generated fluids rise from 100 km or more and invade upper crustal seismogenic zones that have exhibited historic great earthquakes on high-angle thrusts that are poorly oriented for failure under dry conditions. The fluid-deformation connections described in our work emphasize the need to include metamorphic and fluid transport processes in geodynamic models.
C1 [Wannamaker, Philip E.] Univ Utah, Energy & Geosci Inst, Salt Lake City, UT 84108 USA.
   [Caldwell, T. Grant; Hill, Graham J.; Bibby, Hugh M.; Bennie, Stewart L.; Heise, Wiebke] GNS Sci, Wellington 6315, New Zealand.
   [Jiracek, George R.] San Diego State Univ, Dept Geol Sci, San Diego, CA 92182 USA.
   [Maris, Virginie] Univ Utah, Dept Geol & Geophys, Salt Lake City, UT 84112 USA.
   [Ogawa, Yasuo] Tokyo Inst Technol, Volcan Fluid Res Ctr, Meguro Ku, Tokyo 1528551, Japan.
C3 Utah System of Higher Education; University of Utah; Earth Sciences New Zealand; GNS Science - New Zealand; California State University System; San Diego State University; Utah System of Higher Education; University of Utah; Institute of Science Tokyo; Tokyo Institute of Technology
RP Wannamaker, PE (corresponding author), Univ Utah, Energy & Geosci Inst, 423 Wakara Way,Suite 300, Salt Lake City, UT 84108 USA.
EM pewanna@egi.utah.edu
FU US National Science Foundation [EAR0440050]; New Zealand Foundation for Research, Science and Technology; Grants-in-Aid for Scientific Research [21109003] Funding Source: KAKEN
NR 38
TC 212
Z9 220
U1 1
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 6
PY 2009
VL 460
IS 7256
BP 733
EP U90
DI 10.1038/nature08204
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300037
PM 19661914
DA 2026-03-09
ER

PT J
AU Jost, JD
   Home, JP
   Amini, JM
   Hanneke, D
   Ozeri, R
   Langer, C
   Bollinger, JJ
   Leibfried, D
   Wineland, DJ
AF Jost, J. D.
   Home, J. P.
   Amini, J. M.
   Hanneke, D.
   Ozeri, R.
   Langer, C.
   Bollinger, J. J.
   Leibfried, D.
   Wineland, D. J.
TI Entangled mechanical oscillators
SO NATURE
LA English
DT Article
ID current situation; quantum; ions; states
AB Hallmarks of quantum mechanics include superposition and entanglement. In the context of large complex systems, these features should lead to situations as envisaged in the 'Schrodinger's cat'(1) thought experiment (where the cat exists in a superposition of alive and dead states entangled with a radioactive nucleus). Such situations are not observed in nature. This may be simply due to our inability to sufficiently isolate the system of interest from the surrounding environment(2,3)- a technical limitation. Another possibility is some as-yet-undiscovered mechanism that prevents the formation of macroscopic entangled states(4). Such a limitation might depend on the number of elementary constituents in the system(5) or on the types of degrees of freedom that are entangled. Tests of the latter possibility have been made with photons, atoms and condensed matter devices(6,7). One system ubiquitous to nature where entanglement has not been previously demonstrated consists of distinct mechanical oscillators. Here we demonstrate deterministic entanglement of separated mechanical oscillators, consisting of the vibrational states of two pairs of atomic ions held in different locations. We also demonstrate entanglement of the internal states of an atomic ion with a distant mechanical oscillator. These results show quantum entanglement in a degree of freedom that pervades the classical world. Such experiments may lead to the generation of entangled states of larger-scale mechanical oscillators(8-10), and offer possibilities for testing non-locality with mesoscopic systems(11). In addition, the control developed here is an important ingredient for scaling-up quantum information processing with trapped atomic ions(12-14).
C1 [Jost, J. D.; Home, J. P.; Amini, J. M.; Hanneke, D.; Bollinger, J. J.; Leibfried, D.; Wineland, D. J.] Natl Inst Stand & Technol, Div Time & Frequency, Boulder, CO 80305 USA.
   [Ozeri, R.] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
   [Langer, C.] Lockheed Martin, Denver, CO 80127 USA.
C3 National Institute of Standards & Technology (NIST) - USA; Weizmann Institute of Science; Lockheed Martin
RP Jost, JD (corresponding author), Natl Inst Stand & Technol, Div Time & Frequency, Boulder, CO 80305 USA.
EM john.d.jost@gmail.com
FU IARPA; NIST Quantum Information Program; Lindemann Trust fellowship
NR 31
TC 152
Z9 179
U1 0
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 683
EP U84
DI 10.1038/nature08006
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600039
PM 19494911
DA 2026-03-09
ER

PT J
AU Wang, Z
   Chong, YD
   Joannopoulos, JD
   Soljacic, M
AF Wang, Zheng
   Chong, Yidong
   Joannopoulos, J. D.
   Soljacic, Marin
TI Observation of unidirectional backscattering-immune topological electromagnetic states
SO NATURE
LA English
DT Article
ID magnetic response; quantum; phase; light; slow
AB One of the most striking phenomena in condensed-matter physics is the quantum Hall effect, which arises in two-dimensional electron systems(1-4) subject to a large magnetic field applied perpendicular to the plane in which the electrons reside. In such circumstances, current is carried by electrons along the edges of the system, in so-called chiral edge states (CESs). These are states that, as a consequence of nontrivial topological properties of the bulk electronic band structure, have a unique directionality and are robust against scattering from disorder. Recently, it was theoretically predicted(5-7) that electromagnetic analogues of such electronic edge states could be observed in photonic crystals, which are materials having refractive-index variations with a periodicity comparable to the wavelength of the light passing through them. Here we report the experimental realization and observation of such electromagnetic CESs in a magneto-optical photonic crystal(7) fabricated in the microwave regime. We demonstrate that, like their electronic counterparts(8-13), electromagnetic CESs can travel in only one direction and are very robust against scattering from disorder; we find that even large metallic scatterers placed in the path of the propagating edge modes do not induce reflections. These modes may enable the production of new classes of electromagnetic device and experiments that would be impossible using conventional reciprocal photonic states alone. Furthermore, our experimental demonstration and study of photonic CESs provides strong support for the generalization and application of topological band theories to classical and bosonic systems, and may lead to the realization and observation of topological phenomena in a generally much more controlled and customizable fashion than is typically possible with electronic systems.
C1 [Wang, Zheng; Chong, Yidong; Joannopoulos, J. D.; Soljacic, Marin] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Wang, Z (corresponding author), MIT, Dept Phys, Cambridge, MA 02139 USA.
EM zhwang@mit.edu
FU Materials Research Science and Engineering Program; US National Science Foundation [DMR-0819762]; US Army Research Office through the Institute for Soldier Nanotechnologies [W911NF-07-D-0004]; Division Of Materials Research; Direct For Mathematical & Physical Scien [0819762] Funding Source: National Science Foundation
NR 30
TC 2676
Z9 2923
U1 41
U2 817
PU NATURE PUBLISHING 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 8
PY 2009
VL 461
IS 7265
BP 772
EP U20
DI 10.1038/nature08293
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500031
PM 19812669
DA 2026-03-09
ER

PT J
AU Dang, L
   White, DW
   Gross, S
   Bennett, BD
   Bittinger, MA
   Driggers, EM
   Fantin, VR
   Jang, HG
   Jin, S
   Keenan, MC
   Marks, KM
   Prins, RM
   Ward, PS
   Yen, KE
   Liau, LM
   Rabinowitz, JD
   Cantley, LC
   Thompson, CB
   Heiden, MGV
   Su, SM
AF Dang, Lenny
   White, David W.
   Gross, Stefan
   Bennett, Bryson D.
   Bittinger, Mark A.
   Driggers, Edward M.
   Fantin, Valeria R.
   Jang, Hyun Gyung
   Jin, Shengfang
   Keenan, Marie C.
   Marks, Kevin M.
   Prins, Robert M.
   Ward, Patrick S.
   Yen, Katharine E.
   Liau, Linda M.
   Rabinowitz, Joshua D.
   Cantley, Lewis C.
   Thompson, Craig B.
   Heiden, Matthew G. Vander
   Su, Shinsan M.
TI Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
SO NATURE
LA English
DT Article
ID tandem mass-spectrometry; acid; d-2-hydroxyglutarate
AB Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers. These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse conversion of isocitrate to alpha-ketoglutarate. However, only a single copy of the gene is mutated in tumours, raising the possibility that the mutations do not result in a simple loss of function. Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of alpha-ketoglutarate to R(2)-2-hydroxyglutarate (2HG). Structural studies demonstrate that when arginine 132 is mutated to histidine, residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG. Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumours in patients with inborn errors of 2HG metabolism. Similarly, in human malignant gliomas harbouring IDH1 mutations, we find markedly elevated levels of 2HG. These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.
C1 [Dang, Lenny; White, David W.; Gross, Stefan; Bittinger, Mark A.; Driggers, Edward M.; Fantin, Valeria R.; Jang, Hyun Gyung; Jin, Shengfang; Keenan, Marie C.; Marks, Kevin M.; Yen, Katharine E.; Heiden, Matthew G. Vander; Su, Shinsan M.] Agios Pharmaceut, Cambridge, MA 02139 USA.
   [Bennett, Bryson D.; Rabinowitz, Joshua D.] Princeton Univ, Dept Chem & Integrat Genom, Princeton, NJ 08544 USA.
   [Prins, Robert M.; Liau, Linda M.] Univ Calif Los Angeles, Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA.
   [Ward, Patrick S.; Thompson, Craig B.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
   [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Cantley, Lewis C.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
C3 Agios Pharmaceuticals; Princeton University; 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 Pennsylvania; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School
RP Su, SM (corresponding author), Agios Pharmaceut, Cambridge, MA 02139 USA.
EM michael.su@agios.com
FU NIH [R21 CA128620]
NR 26
TC 3098
Z9 3730
U1 12
U2 365
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 739
EP U52
DI 10.1038/nature08617
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900029
PM 19935646
DA 2026-03-09
ER

PT J
AU Laundal, KM
   Ostgaard, N
AF Laundal, K. M.
   Ostgaard, N.
TI Asymmetric auroral intensities in the Earth's Northern and Southern hemispheres
SO NATURE
LA English
DT Article
ID polar spacecraft; conjugacy
AB It is commonly assumed that the aurora borealis (Northern Hemisphere) and aurora australis (Southern Hemisphere) are mirror images of each other because the charged particles causing the aurora follow the magnetic field lines connecting the two hemispheres. The particles are believed to be evenly distributed between the two hemispheres, from the source region in the equatorial plane of the magnetosphere. Although it has been shown that similar auroral features in the opposite hemispheres can be displaced tens of degree in longitude(1,2) and that seasonal effects can cause differences in global intensity(3,4), the overall auroral patterns were still similar. Here we report observations that clearly contradict the common assumption about symmetric aurora: intense spots are seen at dawn in the Northern summer Hemisphere, and at dusk in the Southern winter Hemisphere. The asymmetry is interpreted in terms of inter-hemispheric currents related to seasons, which have been predicted(5,6) but hitherto had not been seen.
C1 [Laundal, K. M.; Ostgaard, N.] Univ Bergen, Dept Phys & Technol, N-5007 Bergen, Norway.
C3 University of Bergen
RP Ostgaard, N (corresponding author), Univ Bergen, Dept Phys & Technol, Allegt 55, N-5007 Bergen, Norway.
EM nikolai.ostgaard@uib.no
FU Norwegian Research Council [176045/S30]
NR 17
TC 87
Z9 92
U1 0
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 491
EP 493
DI 10.1038/nature08154
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000033
DA 2026-03-09
ER

PT J
AU Konhauser, KO
   Pecoits, E
   Lalonde, SV
   Papineau, D
   Nisbet, EG
   Barley, ME
   Arndt, NT
   Zahnle, K
   Kamber, BS
AF Konhauser, Kurt O.
   Pecoits, Ernesto
   Lalonde, Stefan V.
   Papineau, Dominic
   Nisbet, Euan G.
   Barley, Mark E.
   Arndt, Nicholas T.
   Zahnle, Kevin
   Kamber, Balz S.
TI Oceanic nickel depletion and a methanogen famine before the Great Oxidation Event
SO NATURE
LA English
DT Article
ID rise; ni; geochemistry; tectonics; chemistry; sulfur; growth; crust; iron; pb
AB It has been suggested that a decrease in atmospheric methane levels triggered the progressive rise of atmospheric oxygen, the so-called Great Oxidation Event, about 2.4 Gyr ago(1). Oxidative weathering of terrestrial sulphides, increased oceanic sulphate, and the ecological success of sulphate-reducing microorganisms over methanogens has been proposed as a possible cause for the methane collapse(1), but this explanation is difficult to reconcile with the rock record(2,3). Banded iron formations preserve a history of Precambrian oceanic elemental abundance and can provide insights into our understanding of early microbial life and its influence on the evolution of the Earth system(4,5). Here we report a decline in the molar nickel to iron ratio recorded in banded iron formations about 2.7 Gyr ago, which we attribute to a reduced flux of nickel to the oceans, a consequence of cooling upper-mantle temperatures and decreased eruption of nickel-rich ultramafic rocks at the time. We measured nickel partition coefficients between simulated Precambrian sea water and diverse iron hydroxides, and subsequently determined that dissolved nickel concentrations may have reached similar to 400nM throughout much of the Archaean eon, but dropped below similar to 200nM by 2.5 Gyr ago and to modern day values(6) (similar to 9 nM) by similar to 550 Myr ago. Nickel is a key metal cofactor in several enzymes of methanogens(7) and we propose that its decline would have stifled their activity in the ancient oceans and disrupted the supply of biogenic methane. A decline in biogenic methane production therefore could have occurred before increasing environmental oxygenation and not necessarily be related to it. The enzymatic reliance of methanogens on a diminishing supply of volcanic nickel links mantle evolution to the redox state of the atmosphere.
C1 [Konhauser, Kurt O.; Pecoits, Ernesto; Lalonde, Stefan V.] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Papineau, Dominic] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Nisbet, Euan G.] Royal Holloway Univ London, Dept Earth Sci, Egham TW20 0EX, Surrey, England.
   [Barley, Mark E.] Univ Western Australia, Sch Earth & Environm, Crawley, WA 6009, Australia.
   [Arndt, Nicholas T.] Univ Grenoble 1, Lab Geodynam Chaine Alpines Maison Geosci, F-38041 Grenoble, France.
   [Zahnle, Kevin] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Kamber, Balz S.] Laurentian Univ, Dept Earth Sci, Sudbury, ON P3E 2C6, Canada.
C3 University of Alberta; Carnegie Institution for Science; University of London; Royal Holloway University London; University of Western Australia; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Laurentian University
RP Konhauser, KO (corresponding author), Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
EM kurtk@ualberta.ca
FU Natural Science and Engineering Research Council of Canada (NSERC); Australian Research Council (ARC)
NR 40
TC 384
Z9 453
U1 7
U2 241
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 9
PY 2009
VL 458
IS 7239
BP 750
EP U85
DI 10.1038/nature07858
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600038
PM 19360085
DA 2026-03-09
ER

PT J
AU Gore, J
   Youk, H
   van Oudenaarden, A
AF Gore, Jeff
   Youk, Hyun
   van Oudenaarden, Alexander
TI Snowdrift game dynamics and facultative cheating in yeast
SO NATURE
LA English
DT Article
ID cooperation; evolution; conflict; populations; competition; gene
AB The origin of cooperation is a central challenge to our understanding of evolution(1-3). The fact that microbial interactions can be manipulated in ways that animal interactions cannot has led to a growing interest in microbial models of cooperation(4-10) and competition(11,12). For the budding yeast Saccharomyces cerevisiae to grow on sucrose, the disaccharide must first be hydrolysed by the enzyme invertase(13,14). This hydrolysis reaction is performed outside the cytoplasm in the periplasmic space between the plasma membrane and the cell wall. Here we demonstrate that the vast majority ( 99 per cent) of the monosaccharides created by sucrose hydrolysis diffuse away before they can be imported into the cell, serving to make invertase production and secretion a cooperative behaviour(15,16). A mutant cheater strain that does not produce invertase is able to take advantage of and invade a population of wild-type cooperator cells. However, over a wide range of conditions, the wild-type cooperator can also invade a population of cheater cells. Therefore, we observe steady-state coexistence between the two strains in well-mixed culture resulting from the fact that rare strategies outperform common strategies-the defining features of what game theorists call the snowdrift game(17). A model of the cooperative interaction incorporating nonlinear benefits explains the origin of this coexistence. We are able to alter the outcome of the competition by varying either the cost of cooperation or the glucose concentration in the media. Finally, we note that glucose repression of invertase expression in wild-type cells produces a strategy that is optimal for the snowdrift game-wild-type cells cooperate only when competing against cheater cells.
C1 [Gore, Jeff; Youk, Hyun; van Oudenaarden, Alexander] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP van Oudenaarden, A (corresponding author), MIT, Dept Phys, Cambridge, MA 02139 USA.
EM avano@mit.edu
FU Pappalardo Postdoctoral Fellowship; NIH K99 Pathways to Independence; Lester Wolfe Fellowship
NR 29
TC 520
Z9 607
U1 1
U2 131
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 253
EP 256
DI 10.1038/nature07921
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100041
PM 19349960
DA 2026-03-09
ER

PT J
AU Diehn, M
   Cho, RW
   Lobo, NA
   Kalisky, T
   Dorie, MJ
   Kulp, AN
   Qian, DL
   Lam, JS
   Ailles, LE
   Wong, MZ
   Joshua, B
   Kaplan, MJ
   Wapnir, I
   Dirbas, FM
   Somlo, G
   Garberoglio, C
   Paz, B
   Shen, J
   Lau, SK
   Quake, SR
   Brown, JM
   Weissman, IL
   Clarke, MF
AF Diehn, Maximilian
   Cho, Robert W.
   Lobo, Neethan A.
   Kalisky, Tomer
   Dorie, Mary Jo
   Kulp, Angela N.
   Qian, Dalong
   Lam, Jessica S.
   Ailles, Laurie E.
   Wong, Manzhi
   Joshua, Benzion
   Kaplan, Michael J.
   Wapnir, Irene
   Dirbas, Frederick M.
   Somlo, George
   Garberoglio, Carlos
   Paz, Benjamin
   Shen, Jeannie
   Lau, Sean K.
   Quake, Stephen R.
   Brown, J. Martin
   Weissman, Irving L.
   Clarke, Michael F.
TI Association of reactive oxygen species levels and radioresistance in cancer stem cells
SO NATURE
LA English
DT Article
ID oxidative stress; ionizing-radiation; mammary-gland; self-renewal; progenitors; differentiation; identification; glutathione; enrichment; biology
AB The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells(1,2) and haematopoietic stem cells and early progenitors(3-6) contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing(7,8), CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.
C1 [Diehn, Maximilian; Cho, Robert W.; Lobo, Neethan A.; Kulp, Angela N.; Qian, Dalong; Lam, Jessica S.; Ailles, Laurie E.; Wong, Manzhi; Weissman, Irving L.; Clarke, Michael F.] Stanford Univ, Sch Med, Stanford Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Diehn, Maximilian; Dorie, Mary Jo; Brown, J. Martin] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA.
   [Cho, Robert W.] Stanford Univ, Sch Med, Dept Pediat, Div Stem Cell Transplantat, Stanford, CA 94305 USA.
   [Joshua, Benzion; Kaplan, Michael J.] Stanford Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA.
   [Wapnir, Irene; Dirbas, Frederick M.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA.
   [Weissman, Irving L.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [Weissman, Irving L.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
   [Clarke, Michael F.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
   [Kalisky, Tomer; Quake, Stephen R.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Kalisky, Tomer; Quake, Stephen R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Somlo, George] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
   [Garberoglio, Carlos; Paz, Benjamin; Shen, Jeannie] City Hope Natl Med Ctr, Dept Surg, Duarte, CA 91010 USA.
   [Lau, Sean K.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University; City of Hope; City of Hope; City of Hope
RP Clarke, MF (corresponding author), Stanford Univ, Sch Med, Stanford Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
EM mfclarke@stanford.edu
FU National Institutes of Health; Virginia and D. K. Ludwig Foundation; Breast Cancer Research Foundation; Machiah foundation; American Society for Therapeutic Radiology and Oncology; Radiological Society of North America; Leonard B. Holman Research Pathway fellowship
NR 31
TC 2078
Z9 2413
U1 6
U2 525
PU NATURE PUBLISHING 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 9
PY 2009
VL 458
IS 7239
BP 780
EP U123
DI 10.1038/nature07733
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600045
PM 19194462
DA 2026-03-09
ER

PT J
AU Ohya, T
   Miaczynska, M
   Coskun, U
   Lommer, B
   Runge, A
   Drechsel, D
   Kalaidzidis, Y
   Zerial, M
AF Ohya, Takeshi
   Miaczynska, Marta
   Coskun, Unal
   Lommer, Barbara
   Runge, Anja
   Drechsel, David
   Kalaidzidis, Yannis
   Zerial, Marino
TI Reconstitution of Rab- and SNARE-dependent membrane fusion by synthetic endosomes
SO NATURE
LA English
DT Article
ID transport-vesicle; gdp/gtp exchange; effector eea1; alpha-snap; complex; proteins; docking; specificity; domain; dissociation
AB Rab GTPases and SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are evolutionarily conserved essential components of the eukaryotic intracellular transport system. Although pairing of cognate SNAREs is sufficient to fuse membranes in vitro, a complete reconstitution of the Rab-SNARE machinery has never been achieved. Here we report the reconstitution of the early endosomal canine Rab5 GTPase, its key regulators and effectors together with SNAREs into proteoliposomes using a set of 17 recombinant human proteins. These vesicles behave like minimal 'synthetic' endosomes, fusing with purified early endosomes or with each other in vitro. Membrane fusion measured by content-mixing and morphological assays requires the cooperativity between Rab5 effectors and cognate SNAREs which, together, form a more efficient 'core machinery' than SNAREs alone. In reconstituting a fusion mechanism dependent on both a Rab GTPase and SNAREs, our work shows that the two machineries act coordinately to increase the specificity and efficiency of the membrane tethering and fusion process.
C1 [Ohya, Takeshi; Miaczynska, Marta; Coskun, Unal; Lommer, Barbara; Runge, Anja; Drechsel, David; Kalaidzidis, Yannis; Zerial, Marino] Max Planck Inst Mol Cell Biol & Genet, D-01309 Dresden, Germany.
   [Kalaidzidis, Yannis] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119899, Russia.
C3 Max Planck Society; Lomonosov Moscow State University
RP Zerial, M (corresponding author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01309 Dresden, Germany.
EM zerial@mpi-cbg.de
FU German Ministry for Education and Research [0313082J]; EU Integrated Project EndoTrack; DFG; Max Planck Society; The Nakatomi Foundation
NR 50
TC 174
Z9 218
U1 3
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1091
EP U77
DI 10.1038/nature08107
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700035
PM 19458617
DA 2026-03-09
ER

PT J
AU Gertz, J
   Siggia, ED
   Cohen, BA
AF Gertz, Jason
   Siggia, Eric D.
   Cohen, Barak A.
TI Analysis of combinatorial cis-regulation in synthetic and genomic promoters
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; gene-expression; patterns; associations; sequence; network; models
AB Transcription factor binding sites are being discovered at a rapid pace(1,2). It is now necessary to turn attention towards understanding how these sites work in combination to influence gene expression. Quantitative models that accurately predict gene expression from promoter sequence(3-5) will be a crucial part of solving this problem. Here we present such a model, based on the analysis of synthetic promoter libraries in yeast ( Saccharomyces cerevisiae). Thermodynamic models based only on the equilibrium binding of transcription factors to DNA and to each other captured a large fraction of the variation in expression in every library. Thermodynamic analysis of these libraries uncovered several phenomena in our system, including cooperativity and the effects of weak binding sites. When applied to the S. cerevisiae genome, a model of repression by Mig1 ( which was trained on synthetic promoters) predicts a number of Mig1- regulated genes that lack significant Mig1- binding sites in their promoters. The success of the thermodynamic approach suggests that the information encoded by combinations of cis- regulatory sites is interpreted primarily through simple protein - DNA and protein - protein interactions, with complicated biochemical reactions - such as nucleosome modifications - being downstream events. Quantitative analyses of synthetic promoter libraries will be an important tool in unravelling the rules underlying combinatorial cis- regulation.
C1 [Gertz, Jason; Cohen, Barak A.] Washington Univ, Sch Med, Ctr Genome Sci, Dept Genet, St Louis, MO 63108 USA.
   [Siggia, Eric D.] Rockefeller Univ, Ctr Studies Phys & Biol, New York, NY 10021 USA.
C3 Washington University (WUSTL); Rockefeller University
RP Cohen, BA (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci, Dept Genet, 4444 Forest Park Ave, St Louis, MO 63108 USA.
EM cohen@genetics.wustl.edu
FU NIH [R01 GM078222]; NSF [DMR0129848, DGE-0202737]
NR 26
TC 233
Z9 310
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 JAN 8
PY 2009
VL 457
IS 7226
BP 215
EP U113
DI 10.1038/nature07521
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200037
PM 19029883
DA 2026-03-09
ER

PT J
AU Ohtsuki, H
   Iwasa, Y
   Nowak, MA
AF Ohtsuki, Hisashi
   Iwasa, Yoh
   Nowak, Martin A.
TI Indirect reciprocity provides only a narrow margin of efficiency for costly punishment
SO NATURE
LA English
DT Article
ID social norms; altruistic punishment; cooperation; evolution; reputation; humans; rules
AB Indirect reciprocity(1-5) is a key mechanism for the evolution of human cooperation. Our behaviour towards other people depends not only on what they have done to us but also on what they have done to others. Indirect reciprocity works through reputation(5-17). The standard model of indirect reciprocity offers a binary choice: people can either cooperate or defect. Cooperation implies a cost for the donor and a benefit for the recipient. Defection has no cost and yields no benefit. Currently there is considerable interest in studying the effect of costly (or altruistic) punishment on human behaviour(18-25). Punishment implies a cost for the punished person. Costly punishment means that the punisher also pays a cost. It has been suggested that costly punishment between individuals can promote cooperation. Here we study the role of costly punishment in an explicit model of indirect reciprocity. We analyse all social norms, which depend on the action of the donor and the reputation of the recipient. We allow errors in assigning reputation and study gossip as a mechanism for establishing coherence. We characterize all strategies that allow the evolutionary stability of cooperation. Some of those strategies use costly punishment; others do not. We find that punishment strategies typically reduce the average payoff of the population. Consequently, there is only a small parameter region where costly punishment leads to an efficient equilibrium. In most cases the population does better by not using costly punishment. The efficient strategy for indirect reciprocity is to withhold help for defectors rather than punishing them.
C1 [Ohtsuki, Hisashi] Tokyo Inst Technol, Dept Value & Decis Sci, Tokyo 1528552, Japan.
   [Ohtsuki, Hisashi] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Iwasa, Yoh] Kyushu Univ, Dept Biol, Fac Sci, Fukuoka 8128581, Japan.
   [Nowak, Martin A.] Harvard Univ, Program Evolutionary Dynam, Dept Organism & Evolut Biol, Dept Math, Cambridge, MA 02138 USA.
C3 Institute of Science Tokyo; Tokyo Institute of Technology; Japan Science & Technology Agency (JST); Kyushu University; Harvard University
RP Ohtsuki, H (corresponding author), Tokyo Inst Technol, Dept Value & Decis Sci, Tokyo 1528552, Japan.
EM ohtsuki.h.aa@m.titech.ac.jp
FU John Templeton Foundation; Japan Society for the Promotion of Science; NSF/NIH joint program in mathematical biology; NIH [R01GM078986]
NR 30
TC 282
Z9 316
U1 3
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 1
PY 2009
VL 457
IS 7225
BP 79
EP 82
DI 10.1038/nature07601
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900034
PM 19122640
DA 2026-03-09
ER

PT J
AU Scott, KL
   Kabbarah, O
   Liang, MC
   Ivanova, E
   Anagnostou, V
   Wu, J
   Dhakal, S
   Wu, M
   Chen, SJ
   Feinberg, T
   Huang, J
   Saci, A
   Widlund, HR
   Fisher, DE
   Xiao, YH
   Rimm, DL
   Protopopov, A
   Wong, KK
   Chin, L
AF Scott, Kenneth L.
   Kabbarah, Omar
   Liang, Mei-Chih
   Ivanova, Elena
   Anagnostou, Valsamo
   Wu, Joyce
   Dhakal, Sabin
   Wu, Min
   Chen, Shujuan
   Feinberg, Tamar
   Huang, Joseph
   Saci, Abdel
   Widlund, Hans R.
   Fisher, David E.
   Xiao, Yonghong
   Rimm, David L.
   Protopopov, Alexei
   Wong, Kwok-Kin
   Chin, Lynda
TI GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer
SO NATURE
LA English
DT Article
ID p70 s6 kinase; cell-size; golgi; target; growth; tor; glycosyltransferases; phosphorylation; localization; progression
AB Genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma ( 32%). Here, using integrative analysis of a genomic profile of the region, we identify a Golgi protein, GOLPH3, as a candidate targeted for amplification. Gain- and loss-of-function studies in vitro and in vivo validated GOLPH3 as a potent oncogene. Physically, GOLPH3 localizes to the trans- Golgi network and interacts with components of the retromer complex, which in yeast has been linked to target of rapamycin ( TOR) signalling. Mechanistically, GOLPH3 regulates cell size, enhances growth-factor-induced mTOR (also known as FRAP1) signalling in human cancer cells, and alters the response to an mTOR inhibitor in vivo. Thus, genomic and genetic, biological, functional and biochemical data in yeast and humans establishes GOLPH3 as a new oncogene that is commonly targeted for amplification in human cancer, and is capable of modulating the response to rapamycin, a cancer drug in clinical use.
C1 [Scott, Kenneth L.; Kabbarah, Omar; Liang, Mei-Chih; Wu, Joyce; Dhakal, Sabin; Wu, Min; Chen, Shujuan; Feinberg, Tamar; Huang, Joseph; Wong, Kwok-Kin; Chin, Lynda] Harvard Univ, Ctr Canc, Dept Med Oncol, Boston, MA 02115 USA.
   [Ivanova, Elena; Xiao, Yonghong; Protopopov, Alexei; Chin, Lynda] Harvard Univ, Ctr Canc, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Widlund, Hans R.; Fisher, David E.] Harvard Univ, Ctr Canc, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Wong, Kwok-Kin] Harvard Univ, Ctr Canc, Ludwig Ctr Dana Farber, Boston, MA 02115 USA.
   [Anagnostou, Valsamo; Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
   [Saci, Abdel] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Widlund, Hans R.; Chin, Lynda] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
   [Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
C3 Harvard University; Harvard University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Yale University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Chin, L (corresponding author), Harvard Univ, Ctr Canc, Dept Med Oncol, Boston, MA 02115 USA.
EM lynda_chin@dfci.harvard.edu
FU American Cancer Society [PF-07-039-01-CSM]; National Institutes of Health (NIH) [5-T32-AR07098-31, R01 AG2400401, R01 CA122794, RO-1 CA 114277, RO1 CA93947, P50 CA93683]; Program of Research Excellence (SPORE) grant [P50 CA090578]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32AR007098] Funding Source: NIH RePORTER
NR 33
TC 303
Z9 352
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1085
EP U68
DI 10.1038/nature08109
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700034
PM 19553991
DA 2026-03-09
ER

PT J
AU Aouadi, M
   Tesz, GJ
   Nicoloro, SM
   Wang, MX
   Chouinard, M
   Soto, E
   Ostroff, GR
   Czech, MP
AF Aouadi, Myriam
   Tesz, Gregory J.
   Nicoloro, Sarah M.
   Wang, Mengxi
   Chouinard, My
   Soto, Ernesto
   Ostroff, Gary R.
   Czech, Michael P.
TI Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation
SO NATURE
LA English
DT Article
ID tumor-necrosis-factor; in-vivo delivery; nonhuman-primates; rna interference; gene-expression; adult mice; galactosamine; inhibition; resistance; lethality
AB Gene silencing by double-stranded RNA, denoted RNA interference, represents a new paradigm for rational drug design(1). However, the transformative therapeutic potential of short interfering RNA ( siRNA) has been stymied by a key obstacle-safe delivery to specified target cells in vivo(2). Macrophages are particularly attractive targets for RNA interference therapy because they promote pathogenic inflammatory responses in diseases such as rheumatoid arthritis, atherosclerosis, inflammatory bowel disease and diabetes(3). Here we report the engineering of beta 1,3-D-glucan-encapsulated siRNA particles (GeRPs) as efficient oral delivery vehicles that potently silence genes in mouse macrophages in vitro and in vivo. Oral gavage of mice with GeRPs containing as little as 20 mu g kg(-1) siRNA directed against tumour necrosis factor alpha (Tnf-alpha) depleted its messenger RNA in macrophages recovered from the peritoneum, spleen, liver and lung, and lowered serum Tnf-a levels. Screening with GeRPs for inflammation genes revealed that the mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) is a previously unknown mediator of cytokine expression. Importantly, silencing Map4k4 in macrophages in vivo protected mice from lipopolysaccharide-induced lethality by inhibiting Tnf-alpha and interleukin-1 beta production. This technology defines a new strategy for oral delivery of siRNA to attenuate inflammatory responses in human disease.
C1 [Aouadi, Myriam; Tesz, Gregory J.; Nicoloro, Sarah M.; Wang, Mengxi; Chouinard, My; Soto, Ernesto; Ostroff, Gary R.; Czech, Michael P.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester
RP Czech, MP (corresponding author), Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
EM gary.ostroff@umassmed.edu; michael.czech@umassmed.edu
FU The University of Massachusetts Diabetes and Endocrinology Center [DK 32520]; Diabetes Genome Anatomy Project [DK 60837]; Commonwealth Medicine; NIH [DK 30898]; National Institute of Diabetes and Digestive and Kidney Diseases [R37DK030898] Funding Source: NIH RePORTER
NR 30
TC 496
Z9 572
U1 5
U2 224
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 30
PY 2009
VL 458
IS 7242
BP 1180
EP U116
DI 10.1038/nature07774
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600049
PM 19407801
DA 2026-03-09
ER

PT J
AU Inomata, K
   Ohno, A
   Tochio, H
   Isogai, S
   Tenno, T
   Nakase, I
   Takeuchi, T
   Futaki, S
   Ito, Y
   Hiroaki, H
   Shirakawa, M
AF Inomata, Kohsuke
   Ohno, Ayako
   Tochio, Hidehito
   Isogai, Shin
   Tenno, Takeshi
   Nakase, Ikuhiko
   Takeuchi, Toshihide
   Futaki, Shiroh
   Ito, Yutaka
   Hiroaki, Hidekazu
   Shirakawa, Masahiro
TI High-resolution multi-dimensional NMR spectroscopy of proteins in human cells
SO NATURE
LA English
DT Article
ID internalization mechanisms; penetrating peptides; living cells; ubiquitin; delivery; transduction; domains; oocytes; design; fk506
AB In-cell NMR is an isotope-aided multi-dimensional NMR technique that enables observations of conformations and functions of proteins in living cells at the atomic level(1). This method has been successfully applied to proteins overexpressed in bacteria, providing information on protein-ligand interactions(2) and conformations(3,4). However, the application of in-cell NMR to eukaryotic cells has been limited to Xenopus laevis oocytes(5-7). Wider application of the technique is hampered by inefficient delivery of isotope-labelled proteins into eukaryote somatic cells. Here we describe a method to obtain high-resolution two-dimensional (2D) heteronuclear NMR spectra of proteins inside living human cells. Proteins were delivered to the cytosol by the pyrenebutyrate-mediated action of cell-penetrating peptides(8) linked covalently to the proteins. The proteins were subsequently released from cell-penetrating peptides by endogenous enzymatic activity or by autonomous reductive cleavage. The heteronuclear 2D spectra of three different proteins inside human cells demonstrate the broad application of this technique to studying interactions and protein processing. The in-cell NMR spectra of FKBP12 (also known as FKBP1A) show the formation of specific complexes between the protein and extracellularly administered immunosuppressants, demonstrating the utility of this technique in drug screening programs. Moreover, in-cell NMRspectroscopy demonstrates that ubiquitin has much higher hydrogen exchange rates in the intracellular environment, possibly due to multiple interactions with endogenous proteins.
C1 [Inomata, Kohsuke; Ohno, Ayako; Tochio, Hidehito; Isogai, Shin; Shirakawa, Masahiro] Kyoto Univ, Grad Sch Engn, Dept Mol Engn, Nishikyo Ku, Kyoto 6158510, Japan.
   [Inomata, Kohsuke; Tochio, Hidehito; Tenno, Takeshi; Ito, Yutaka; Hiroaki, Hidekazu; Shirakawa, Masahiro] JST, CREST, Kawaguchi, Saitama 3320012, Japan.
   [Futaki, Shiroh] JST, SORST, Kawaguchi, Saitama 3320012, Japan.
   [Tenno, Takeshi; Hiroaki, Hidekazu] Kobe Univ, Grad Sch Med, Div Struct Biol, Chuo Ku, Kobe, Hyogo 6500017, Japan.
   [Nakase, Ikuhiko; Takeuchi, Toshihide; Futaki, Shiroh] Kyoto Univ, Inst Chem Res, Kyoto 6110011, Japan.
   [Ito, Yutaka] Tokyo Metropolitan Univ, Dept Chem, Tokyo 1920397, Japan.
   [Shirakawa, Masahiro] RIKEN, Yokohama Inst, Yokohama, Kanagawa 2300045, Japan.
C3 Kyoto University; Japan Science & Technology Agency (JST); Japan Science & Technology Agency (JST); Kobe University; Kyoto University; Tokyo Metropolitan University; RIKEN
RP Shirakawa, M (corresponding author), Kyoto Univ, Grad Sch Engn, Dept Mol Engn, Nishikyo Ku, Kyoto 6158510, Japan.
EM tochio@moleng.kyoto-u.ac.jp; shirakawa@moleng.kyoto-u.ac.jp
FU Japan Science and Technology Agency and the Ministry of Education, Culture, Sports, Science and Technology-Japan (MEXT); Global COE Program 'International Center for Integrated Research and Advanced Education in Materials Science' [B-09]; Japan Society for the Promotion of Science; Innovative Techno-Hub for Integrated Medical Bio-imaging Project of the Special Coordination Funds for Promoting Science and Technology, from MEXT; MEXT;  [FKBP12]
NR 28
TC 384
Z9 424
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 MAR 5
PY 2009
VL 458
IS 7234
BP 106
EP U11
DI 10.1038/nature07839
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000042
PM 19262675
DA 2026-03-09
ER

PT J
AU Boroson, TA
   Lauer, TR
AF Boroson, Todd A.
   Lauer, Tod R.
TI A candidate sub-parsec supermassive binary black hole system
SO NATURE
LA English
DT Article
ID digital-sky-survey; quasars; spectra; oj-287
AB The role of mergers in producing galaxies, together with the finding that most large galaxies harbour black holes in their nuclei(1), implies that binary supermassive black hole systems should be common. Here we report that the quasar SDSS J153636.22+ 044127.0 is a plausible example of such a system. This quasar shows two broad-line emission systems, separated in velocity by 3,500km s(-1). A third system of unresolved absorption lines has an intermediate velocity. These characteristics are unique among known quasars. We interpret this object as a binary system of two black holes, having masses of 10(7.3) and 10(8.9) solar masses separated by similar to 0.1 parsec with an orbital period of similar to 100 years.
C1 [Boroson, Todd A.; Lauer, Tod R.] Natl Opt Astron Observ, Tucson, AZ 85726 USA.
C3 National Optical Astronomy Observatory
RP Boroson, TA (corresponding author), Natl Opt Astron Observ, Tucson, AZ 85726 USA.
EM tyb@noao.edu
FU Alfred P. Sloan Foundation; NSF; US Department of Energy; National Aeronautics and Space Administration (NASA); Japanese Monbukagakusho; Max Planck Society; Higher Education Funding Council for England
NR 21
TC 193
Z9 214
U1 0
U2 4
PU NATURE PUBLISHING 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 5
PY 2009
VL 458
IS 7234
BP 53
EP 55
DI 10.1038/nature07779
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000030
PM 19262667
DA 2026-03-09
ER

PT J
AU Fabian, AC
   Zoghbi, A
   Ross, RR
   Uttley, P
   Gallo, LC
   Brandt, WN
   Blustin, AJ
   Boller, T
   Caballero-Garcia, MD
   Larsson, J
   Miller, JM
   Miniutti, G
   Ponti, G
   Reis, RC
   Reynolds, CS
   Tanaka, Y
   Young, AJ
AF Fabian, A. C.
   Zoghbi, A.
   Ross, R. R.
   Uttley, P.
   Gallo, L. C.
   Brandt, W. N.
   Blustin, A. J.
   Boller, T.
   Caballero-Garcia, M. D.
   Larsson, J.
   Miller, J. M.
   Miniutti, G.
   Ponti, G.
   Reis, R. C.
   Reynolds, C. S.
   Tanaka, Y.
   Young, A. J.
TI Broad line emission from iron K- and L-shell transitions in the active galaxy 1H 0707-495
SO NATURE
LA English
DT Article
ID x-ray variability; narrow-line; black-hole; seyfert-1 galaxy-1h-0707-495; galactic nuclei; reflection; disk; 1h-0707-495; binary; spectra
AB Since the 1995 discovery of the broad iron K-line emission from the Seyfert galaxy MCG-6-30-15 (ref. 1), broad iron K lines have been found in emission from several other Seyfert galaxies(2), from accreting stellar-mass black holes(3) and even from accreting neutron stars(4). The iron K line is prominent in the reflection spectrum(5,6) created by the hard-X-ray continuum irradiating dense accreting matter. Relativistic distortion(7) of the line makes it sensitive to the strong gravity and spin of the black hole(8). The accompanying iron L-line emission should be detectable when the iron abundance is high. Here we report the presence of both iron K and iron L emission in the spectrum of the narrow-line Seyfert 1 galaxy(9) 1H 0707-495. The bright iron L emission has enabled us to detect a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the black hole. The observed reverberation timescale is comparable to the light-crossing time of the innermost radii around a supermassive black hole. The combination of spectral and timing data on 1H 0707-495 provides strong evidence that we are witnessing emission from matter within a gravitational radius, or a fraction of a light minute, from the event horizon of a rapidly spinning, massive black hole.
C1 [Fabian, A. C.; Zoghbi, A.; Blustin, A. J.; Caballero-Garcia, M. D.; Larsson, J.; Reis, R. C.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Ross, R. R.] Coll Holy Cross, Dept Phys, Worcester, MA 01610 USA.
   [Uttley, P.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Gallo, L. C.] St Marys Univ, Dept Phys & Astron, Halifax, NS B3H 3C3, Canada.
   [Brandt, W. N.] Penn State Univ, Dept Astron & Astrophys, University Pk, PA 16802 USA.
   [Boller, T.; Tanaka, Y.] Max Planck Inst Extraterr Phys, D-85741 Garching, Germany.
   [Miller, J. M.] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Miniutti, G.] LAEFF, Ctr Astrobiol CSIC INTA, LAEX, E-28691 Madrid, Spain.
   [Ponti, G.] Lab APC, UMR 7164, F-75205 Paris, France.
   [Reynolds, C. S.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Reynolds, C. S.] Univ Maryland, Ctr Theory & Computat, College Pk, MD 20742 USA.
   [Young, A. J.] Univ Bristol, HH Wills Phys Lab, Bristol BS8 1TL, Avon, England.
C3 University of Cambridge; College of the Holy Cross; University of Southampton; Saint Marys University - Canada; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Max Planck Society; University of Michigan System; University of Michigan; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite PSL; Observatoire de Paris; CEA; Universite Paris Cite; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; University of Bristol
RP Fabian, AC (corresponding author), Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
EM acf@ast.cam.ac.uk
FU ESA; USA (NASA); Algerian Higher Education Ministry; UK Science and Technology Facilities Council (STFC); Spanish Ministerio de Ciencia e Innovacion; French National Research Agency; Science and Technology Facilities Council [PP/D003636/2, ST/G002339/1, PP/D00571X/1] Funding Source: researchfish; STFC [PP/D00571X/1, PP/D003636/2, ST/G002339/1] Funding Source: UKRI
NR 20
TC 497
Z9 532
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 28
PY 2009
VL 459
IS 7246
BP 540
EP 542
DI 10.1038/nature08007
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500032
PM 19478778
DA 2026-03-09
ER

PT J
AU Chew, SK
   Chen, P
   Link, N
   Galindo, KA
   Pogue, K
   Abrams, JM
AF Chew, Su Kit
   Chen, Po
   Link, Nichole
   Galindo, Kathleen A.
   Pogue, Kristi
   Abrams, John M.
TI Genome-wide silencing in Drosophila captures conserved apoptotic effectors
SO NATURE
LA English
DT Article
ID apical caspase dronc; cell-death; cytochrome-c; rna interference; activation; protein; pathways; growth; assays; diap1
AB Apoptosis is a conserved form of programmed cell death firmly established in the aetiology, pathogenesis and treatment of many human diseases. Central to the core machinery of apoptosis are the caspases and their proximal regulators. Current models for caspase control involve a balance of opposing elements, with variable contributions from positive and negative regulators among different cell types and species(1). To advance a comprehensive view of components that support caspase-dependent cell death, we conducted a genome-wide silencing screen in the Drosophila model. Our strategy used a library of double-stranded RNAs together with a chemical antagonist of Inhibitor of apoptosis proteins (IAPs) that simulates the action of native regulators in the Reaper and Smac (also known as Diablo) families(2). Here we present a highly validated set of targets that is necessary for death provoked by several stimuli. Among these, Tango7 is identified as a new effector. Cells depleted for this gene resisted apoptosis at a step before the induction of effector caspase activity, and the directed silencing of Tango7 in Drosophila prevented caspase-dependent programmed cell death. Unlike known apoptosis regulators in this model system(3), Tango7 activity did not influence stimulus-dependent loss of Drosophila DIAP1 (also known as th and IAP1), but instead regulated levels of the apical caspase Dronc (Nc). Similarly, the human Tango7 counterpart, PCID1 (also known as EIF3M), impinged on caspase 9, revealing a new regulatory axis affecting the apoptosome.
C1 [Chew, Su Kit; Chen, Po; Link, Nichole; Galindo, Kathleen A.; Pogue, Kristi; Abrams, John M.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center
RP Abrams, JM (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
EM john.abrams@utsouthwestern.edu
FU National Institute of General Medical Sciences; National Institute on Alcohol Abuse and Alcoholism; UTSW High Impact/High Risk Grant Program; National Research Service Award
NR 29
TC 31
Z9 37
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 123
EP U141
DI 10.1038/nature08087
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200042
PM 19483676
DA 2026-03-09
ER

PT J
AU Ebert, AD
   Yu, JY
   Rose, FF
   Mattis, VB
   Lorson, CL
   Thomson, JA
   Svendsen, CN
AF Ebert, Allison D.
   Yu, Junying
   Rose, Ferrill F., Jr.
   Mattis, Virginia B.
   Lorson, Christian L.
   Thomson, James A.
   Svendsen, Clive N.
TI Induced pluripotent stem cells from a spinal muscular atrophy patient
SO NATURE
LA English
DT Article
ID motor-neuron gene; valproic acid increases; protein-level; smn; survival; complex; mouse; normalization; specification; product
AB Spinal muscular atrophy is one of the most common inherited forms of neurological disease leading to infant mortality. Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death. Although patient fibroblasts have been used extensively to study spinal muscular atrophy, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy. These cells expanded robustly in culture, maintained the disease genotype and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.
C1 [Ebert, Allison D.; Svendsen, Clive N.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
   [Ebert, Allison D.; Thomson, James A.; Svendsen, Clive N.] Univ Wisconsin, Stem Cell & Regenerat Med Ctr, Madison, WI 53705 USA.
   [Yu, Junying; Thomson, James A.] Univ Wisconsin, Genome Ctr, Madison, WI 53706 USA.
   [Yu, Junying; Thomson, James A.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA.
   [Rose, Ferrill F., Jr.; Mattis, Virginia B.; Lorson, Christian L.] Univ Missouri, Dept Vet Pathobiol, Bond Life Sci Ctr, Columbia, MO 65211 USA.
   [Thomson, James A.; Svendsen, Clive N.] Univ Wisconsin, Dept Anat, Madison, WI 53706 USA.
   [Svendsen, Clive N.] Univ Wisconsin, Dept Neurol, Madison, WI 53792 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; University of Missouri System; University of Missouri Columbia; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
RP Ebert, AD (corresponding author), Univ Wisconsin, Waisman Ctr, 1500 Highland Ave, Madison, WI 53705 USA.
EM ebert@waisman.wisc.edu; cnsvendsen@wisc.edu
FU Amyotrophic Lateral Sclerosis Association; National Institutes of Neurological Disorders and Stroke [P01NS057778, R01NS41584]; National Institutes of Child Health and Human Development [R01HD054413]; National Institutes of General Medical Sciences [T32GM008396]; National Institute of General Medical Sciences [T32GM008396] Funding Source: NIH RePORTER
NR 41
TC 1126
Z9 1458
U1 3
U2 197
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 277
EP U1
DI 10.1038/nature07677
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900031
PM 19098894
DA 2026-03-09
ER

PT J
AU Scheid, JF
   Mouquet, H
   Feldhahn, N
   Seaman, MS
   Velinzon, K
   Pietzsch, J
   Ott, RG
   Anthony, RM
   Zebroski, H
   Hurley, A
   Phogat, A
   Chakrabarti, B
   Li, YX
   Connors, M
   Pereyra, F
   Walker, BD
   Wardemann, H
   Ho, D
   Wyatt, RT
   Mascola, JR
   Ravetch, JV
   Nussenzweig, MC
AF Scheid, Johannes F.
   Mouquet, Hugo
   Feldhahn, Niklas
   Seaman, Michael S.
   Velinzon, Klara
   Pietzsch, John
   Ott, Rene G.
   Anthony, Robert M.
   Zebroski, Henry
   Hurley, Arlene
   Phogat, Adhuna
   Chakrabarti, Bimal
   Li, Yuxing
   Connors, Mark
   Pereyra, Florencia
   Walker, Bruce D.
   Wardemann, Hedda
   Ho, David
   Wyatt, Richard T.
   Mascola, John R.
   Ravetch, Jeffrey V.
   Nussenzweig, Michel C.
TI Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
SO NATURE
LA English
DT Article
ID human-immunodeficiency-virus; human monoclonal-antibody; passive transfer; binding-site; type-1; epitope; glycoprotein; generation; gp41
AB Antibodies to conserved epitopes on the human immunodeficiency virus (HIV) surface protein gp140 can protect against infection in non-human primates, and some infected individuals show high titres of broadly neutralizing immunoglobulin (Ig)G antibodies in their serum. However, little is known about the specificity and activity of these antibodies(1-3). To characterize the memory antibody responses to HIV, we cloned 502 antibodies from HIV envelope-binding memory B cells from six HIV-infected patients with broadly neutralizing antibodies and low to intermediate viral loads. We show that in these patients, the B-cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity neutralizing antibodies to the gp120 variable loops, the CD4-binding site, the co-receptor-binding site, and to a new neutralizing epitope that is in the same region of gp120 as the CD4-binding site. Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.
C1 [Scheid, Johannes F.; Mouquet, Hugo; Feldhahn, Niklas; Velinzon, Klara; Pietzsch, John; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
   [Ott, Rene G.; Anthony, Robert M.; Ravetch, Jeffrey V.] Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10065 USA.
   [Zebroski, Henry] Rockefeller Univ, Prote Resource Ctr, New York, NY 10065 USA.
   [Hurley, Arlene] Rockefeller Univ, Rockefeller Univ Hosp, New York, NY 10065 USA.
   [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Scheid, Johannes F.] Charite, D-10117 Berlin, Germany.
   [Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Pietzsch, John] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany.
   [Phogat, Adhuna; Chakrabarti, Bimal; Li, Yuxing; Wyatt, Richard T.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Pereyra, Florencia; Walker, Bruce D.] Mass Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA.
   [Wardemann, Hedda] Max Planck Inst Infect Biol, D-10117 Berlin, Germany.
   [Pereyra, Florencia; Walker, Bruce D.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   [Ho, David] Aaron Diamond AIDS Res Ctr, New York, NY 10065 USA.
C3 Rockefeller University; Rockefeller University; Rockefeller University; Rockefeller University; Howard Hughes Medical Institute; Rockefeller University; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; 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); Max Planck Society; Harvard University
RP Nussenzweig, MC (corresponding author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussen@mail.rockefeller.edu
FU Rockefeller University; International Aids Vaccine Initiative; Bill and Melinda Gates Foundation; Intramural Research Program of the Vaccine Research Center; Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Deutscher Akademischer Austauschdienst; Fondation Recherche Medicale; National Institute of Allergy and Infectious Diseases [ZIAAI001090] Funding Source: NIH RePORTER; NIH Office of the Director; National Institute of Allergy and Infectious Diseases [ZIAAI005095] Funding Source: NIH RePORTER
NR 29
TC 737
Z9 970
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 APR 2
PY 2009
VL 458
IS 7238
BP 636
EP 640
DI 10.1038/nature07930
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200042
PM 19287373
DA 2026-03-09
ER

PT J
AU Head, JJ
   Bloch, JI
   Hastings, AK
   Bourque, JR
   Cadena, EA
   Herrera, FA
   Polly, PD
   Jaramillo, CA
AF Head, Jason J.
   Bloch, Jonathan I.
   Hastings, Alexander K.
   Bourque, Jason R.
   Cadena, Edwin A.
   Herrera, Fabiany A.
   Polly, P. David
   Jaramillo, Carlos A.
TI Giant boid snake from the Palaeocene neotropics reveals hotter past equatorial temperatures
SO NATURE
LA English
DT Article
ID body-size; gigantism; climate; nuclear; co2
AB The largest extant snakes live in the tropics of South America and southeast Asia(1-3) where high temperatures facilitate the evolution of large body sizes among air- breathing animals whose body temperatures are dependant on ambient environmental temperatures ( poikilothermy)(4,5). Very little is known about ancient tropical terrestrial ecosystems, limiting our understanding of the evolution of giant snakes and their relationship to climate in the past. Here we describe a boid snake from the oldest known neotropical rainforest fauna from the Cerrejon Formation ( 58 - 60 Myr ago) in northeastern Colombia. We estimate a body length of 13 and a mass of 1,135 kg, making it the largest known snake(6-9). The maximum size of poikilothermic animals at a given temperature is limited by metabolic rate(4), and a snake of this size would require a minimum mean annual temperature of 30 - 34 degrees C to survive. This estimate is consistent with hypotheses of hot Palaeocene neotropics with high concentrations of atmospheric CO2 based on climate models(10). Comparison of palaeotemperature estimates from the equator to those from South American mid- latitudes indicates a relatively steep temperature gradient during the early Palaeogene greenhouse, similar to that of today. Depositional environments and faunal composition of the Cerrejon Formation indicate an anaconda- like ecology for the giant snake, and an earliest Cenozoic origin of neotropical vertebrate faunas.
C1 [Head, Jason J.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
   [Bloch, Jonathan I.; Hastings, Alexander K.; Bourque, Jason R.; Cadena, Edwin A.; Herrera, Fabiany A.] Univ Florida, Florida Museum Nat Hist, Gainesville, FL 32611 USA.
   [Cadena, Edwin A.; Herrera, Fabiany A.; Jaramillo, Carlos A.] Smithsonian Trop Res Inst, Balboa, Panama.
   [Polly, P. David] Indiana Univ, Dept Geol Sci, Bloomington, IN 47405 USA.
C3 University of Toronto; University Toronto Mississauga; State University System of Florida; University of Florida; Smithsonian Institution; Smithsonian Tropical Research Institute; Indiana University System; Indiana University Bloomington
RP Head, JJ (corresponding author), Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
EM jason.head@utoronto.ca
FU National Science Foundation; Fondo para Investigaciones del Banco de la Republica de Colombia; Smithsonian Tropical Research Institute Paleobiology Fund; Florida Museum of Natural History; Geological Society of America Graduate Student Research Grant; National Sciences and Engineering Research Council of Canada Discovery Grant
NR 30
TC 192
Z9 226
U1 3
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 715
EP U4
DI 10.1038/nature07671
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700039
PM 19194448
DA 2026-03-09
ER

PT J
AU Kawamura, T
   Suzuki, J
   Wang, YV
   Menendez, S
   Morera, LB
   Raya, A
   Wahl, GM
   Belmonte, JCI
AF Kawamura, Teruhisa
   Suzuki, Jotaro
   Wang, Yunyuan V.
   Menendez, Sergio
   Batlle Morera, Laura
   Raya, Angel
   Wahl, Geoffrey M.
   Izpisua Belmonte, Juan Carlos
TI Linking the p53 tumour suppressor pathway to somatic cell reprogramming
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; expression cloning; human fibroblasts; c-myc; generation; mouse; induction; differentiation; efficiency; oct4
AB Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes(1-8), but the low frequency and tendency to induce malignant transformation(9) compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. Here we show that reprogramming factors can activate the p53 (also known as Trp53 in mice, TP53 in humans) pathway. Reducing signalling to p53 by expressing a mutated version of one of its negative regulators, by deleting or knocking down p53 or its target gene, p21 (also known as Cdkn1a), or by antagonizing reprogramming-induced apoptosis in mouse fibroblasts increases reprogramming efficiency. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline-transmitting chimaeric mice using only Oct4 ( also known as Pou5f1) and Sox2. Furthermore, silencing of p53 significantly increased the reprogramming efficiency of human somatic cells. These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes.
C1 [Kawamura, Teruhisa; Suzuki, Jotaro; Wang, Yunyuan V.; Wahl, Geoffrey M.; Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Kawamura, Teruhisa] Kyoto Univ, Career Path Promot Unit Young Life Scientists, Kyoto 6068501, Japan.
   [Wang, Yunyuan V.] Astellas Pharma Inc, Drug Discovery Res, Tsukuba, Ibaraki 3058585, Japan.
   [Menendez, Sergio; Batlle Morera, Laura; Raya, Angel; Izpisua Belmonte, Juan Carlos] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain.
   [Raya, Angel] ICREA, Barcelona 08010, Spain.
   [Raya, Angel] Networking Ctr Biomed Res Bioengn Biomat & Nanome, Barcelona 08003, Spain.
C3 Salk Institute; Kyoto University; Astellas Pharmaceuticals; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro de Medicina Regenerativa de Barcelona; University of Barcelona; ICREA
RP Belmonte, JCI (corresponding author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM wahl@salk.edu; belmonte@salk.edu
FU Astellas Pharma Inc; Japan Society for the Promotion of Science; NIH [5 R01 CA061449, CA100845]; Leila Y. Mathers Charitable Foundation and Fundacion Cellex; ICREA Funding Source: Custom
NR 38
TC 887
Z9 1091
U1 0
U2 127
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1140
EP 1144
DI 10.1038/nature08311
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000041
PM 19668186
DA 2026-03-09
ER

PT J
AU Crisp, MD
   Arroyo, MTK
   Cook, LG
   Gandolfo, MA
   Jordan, GJ
   McGlone, MS
   Weston, PH
   Westoby, M
   Wilf, P
   Linder, HP
AF Crisp, Michael D.
   Arroyo, Mary T. K.
   Cook, Lyn G.
   Gandolfo, Maria A.
   Jordan, Gregory J.
   McGlone, Matt S.
   Weston, Peter H.
   Westoby, Mark
   Wilf, Peter
   Linder, H. Peter
TI Phylogenetic biome conservatism on a global scale
SO NATURE
LA English
DT Article
ID genus oreomyrrhis apiaceae; long-distance dispersal; molecular phylogeny; new-zealand; niche conservatism; sequence data; sensu-lato; evolution; biogeography; chloroplast
AB How and why organisms are distributed as they are has long intrigued evolutionary biologists(1-4). The tendency for species to retain their ancestral ecology has been demonstrated in distributions on local and regional scales(5-7), but the extent of ecological conservatism over tens of millions of years and across continents has not been assessed(8-13). Here we show that biome stasis at speciation has outweighed biome shifts by a ratio of more than 25:1, by inferring ancestral biomes for an ecologically diverse sample of more than 11,000 plant species from around the Southern Hemisphere. Stasis was also prevalent in transocean colonizations. Availability of a suitable biome could have substantially influenced which lineages establish on more than one landmass, in addition to the influence of the rarity of the dispersal events themselves. Conversely, the taxonomic composition of biomes has probably been strongly influenced by the rarity of species' transitions between biomes. This study has implications for the future because if clades have inherently limited capacity to shift biomes(13), then their evolutionary potential could be strongly compromised by biome contraction as climate changes.
C1 [Crisp, Michael D.] Australian Natl Univ, Sch Bot & Zool, Canberra, ACT 0200, Australia.
   [Arroyo, Mary T. K.] Univ Chile, Inst Ecol & Biodivers, Santiago, Chile.
   [Cook, Lyn G.] Univ Queensland, Sch Integrat Biol, Brisbane, Qld 4072, Australia.
   [Gandolfo, Maria A.] Cornell Univ, Dept Plant Biol, LH Bailey Hortorium, Ithaca, NY 14853 USA.
   [Jordan, Gregory J.] Univ Tasmania, Sch Plant Sci, Hobart, Tas 7001, Australia.
   [McGlone, Matt S.] Landcare Res, Lincoln 7640, New Zealand.
   [Weston, Peter H.] Natl Herbarium New S Wales, Sydney, NSW 2000, Australia.
   [Westoby, Mark] Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia.
   [Wilf, Peter] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Linder, H. Peter] Univ Zurich, Inst Systemat Biol, CH-8008 Zurich, Switzerland.
C3 Australian National University; Universidad de Chile; University of Queensland; Cornell University; University of Tasmania; Landcare Research - New Zealand; Macquarie University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Zurich
RP Crisp, MD (corresponding author), Australian Natl Univ, Sch Bot & Zool, GPO Box 4, Canberra, ACT 0200, Australia.
EM mike.crisp@anu.edu.au
FU Australian Research Council-New Zealand Research Network for Vegetation Function; US National Science Foundation
NR 127
TC 594
Z9 653
U1 4
U2 259
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 9
PY 2009
VL 458
IS 7239
BP 754
EP U90
DI 10.1038/nature07764
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433GZ
UT WOS:000265193600039
PM 19219025
DA 2026-03-09
ER

PT J
AU Bocquet, N
   Nury, H
   Baaden, M
   Le Poupon, C
   Changeux, JP
   Delarue, M
   Corringer, PJ
AF Bocquet, Nicolas
   Nury, Hugues
   Baaden, Marc
   Le Poupon, Chantal
   Changeux, Jean-Pierre
   Delarue, Marc
   Corringer, Pierre-Jean
TI X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation
SO NATURE
LA English
DT Article
ID nicotinic acetylcholine-receptor; cys-loop; crystal-structure; gating mechanism; binding-site; amino-acids; domain; identification; selectivity; permeation
AB Pentameric ligand-gated ion channels from the Cys- loop family mediate fast chemo-electrical transduction(1-3), but the mechanisms of ion permeation and gating of these membrane proteins remain elusive. Here we present the X- ray structure at 2.9 angstrom resolution of the bacterial Gloeobacter violaceus pentameric ligand- gated ion channel homologue(4) ( GLIC) at pH 4.6 in an apparently open conformation. This cationic channel is known to be permanently activated by protons(5). The structure is arranged as a funnel- shaped transmembrane pore widely open on the outer side and lined by hydrophobic residues. On the inner side, a 5 angstrom constriction matches with rings of hydrophilic residues that are likely to contribute to the ionic selectivity(6-9). Structural comparison with ELIC, a bacterial homologue from Erwinia chrysanthemi solved in a presumed closed conformation(10), shows a wider pore where the narrow hydrophobic constriction found in ELIC is removed. Comparative analysis of GLIC and ELIC reveals, in concert, a rotation of each extracellular beta-sandwich domain as a rigid body, interface rearrangements, and a reorganization of the transmembrane domain, involving a tilt of the M2 and M3 alpha-helices away from the pore axis. These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation.
C1 [Nury, Hugues; Delarue, Marc] Inst Pasteur, Unit Struct Dynam & Macromol, CNRS, URA 2185, F-75015 Paris, France.
   [Bocquet, Nicolas; Nury, Hugues; Le Poupon, Chantal; Changeux, Jean-Pierre; Corringer, Pierre-Jean] Inst Pasteur, Grp Channel Receptor G5, CNRS, URA 2182, F-75015 Paris, France.
   [Baaden, Marc] CNRS, Inst Biol Physicochim, UPR 9080, F-75005 Paris, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC)
RP Delarue, M (corresponding author), Inst Pasteur, Unit Struct Dynam & Macromol, CNRS, URA 2185, F-75015 Paris, France.
EM marc.delarue@pasteur.fr; pjcorrin@pasteur.fr
FU Region Ile-de-France; Association Francaise contre les Myopathies; College de France; Commission of the European Communities; Network of European Neuroscience Institutes
NR 30
TC 605
Z9 676
U1 0
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 1
PY 2009
VL 457
IS 7225
BP 111
EP 114
DI 10.1038/nature07462
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900041
PM 18987633
DA 2026-03-09
ER

PT J
AU Levskaya, A
   Weiner, OD
   Lim, WA
   Voigt, CA
AF Levskaya, Anselm
   Weiner, Orion D.
   Lim, Wendell A.
   Voigt, Christopher A.
TI Spatiotemporal control of cell signalling using a light-switchable protein interaction
SO NATURE
LA English
DT Article
ID actin polymerization; neuronal-activity; phytochrome-b; remote; activation; bacteria; receptor; pif3
AB Genetically encodable optical reporters, such as green fluorescent protein, have revolutionized the observation and measurement of cellular states. However, the inverse challenge of using light to control precisely cellular behaviour has only recently begun to be addressed; semi-synthetic chromophore-tethered receptors(1) and naturally occurring channel rhodopsins have been used to perturb directly neuronal networks(2,3). The difficulty of engineering light-sensitive proteins remains a significant impediment to the optical control of most cell-biological processes. Here we demonstrate the use of a new genetically encoded light-control system based on an optimized, reversible protein-protein interaction from the phytochrome signalling network of Arabidopsis thaliana. Because protein-protein interactions are one of the most general currencies of cellular information, this system can, in principle, be generically used to control diverse functions. Here we show that this system can be used to translocate target proteins precisely and reversibly to the membrane with micrometre spatial resolution and at the second timescale. We show that light-gated translocation of the upstream activators of Rho-family GTPases, which control the actin cytoskeleton, can be used to precisely reshape and direct the cell morphology of mammalian cells. The light-gated protein-protein interaction that has been optimized here should be useful for the design of diverse light-programmable reagents, potentially enabling a new generation of perturbative, quantitative experiments in cell biology.
C1 [Levskaya, Anselm; Weiner, Orion D.; Lim, Wendell A.; Voigt, Christopher A.] Univ Calif San Francisco, UCB NIH Nanomed Dev Ctr, Cell Prop Lab, San Francisco, CA 94158 USA.
   [Levskaya, Anselm] Univ Calif San Francisco, Grad Program Biophys, San Francisco, CA 94158 USA.
   [Levskaya, Anselm; Voigt, Christopher A.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Weiner, Orion D.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA.
   [Lim, Wendell A.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Lim, Wendell A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco
RP Lim, WA (corresponding author), Univ Calif San Francisco, UCB NIH Nanomed Dev Ctr, Cell Prop Lab, San Francisco, CA 94158 USA.
EM lim@cmp.ucsf.edu
FU NSFGR; NIH [R01 GM084040, GM55040, GM62583, EY016546, NIH AI067699, NSF BES-0547637]; Searles Scholar Award; Packard Fellowship; Howard Hughes Medical Institute; Pew Fellowship; Office of Naval Research; UC-Discovery; SynBERC NSF ERC
NR 26
TC 828
Z9 1060
U1 1
U2 243
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 997
EP 1001
DI 10.1038/nature08446
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700051
PM 19749742
DA 2026-03-09
ER

PT J
AU Bu, L
   Jiang, X
   Martin-Puig, S
   Caron, L
   Zhu, SJ
   Shao, Y
   Roberts, DJ
   Huang, PL
   Domian, IJ
   Chien, KR
AF Bu, Lei
   Jiang, Xin
   Martin-Puig, Silvia
   Caron, Leslie
   Zhu, Shenjun
   Shao, Ying
   Roberts, Drucilla J.
   Huang, Paul L.
   Domian, Ibrahim J.
   Chien, Kenneth R.
TI Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
SO NATURE
LA English
DT Article
ID embryonic stem-cells; cardiac progenitors; smooth-muscle; cardiomyocyte; differentiation; cardiogenesis; population; precursors; contribute; origins
AB The generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential(1-4). Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart(5-8). In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1(+) cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that purified ISL1(+) primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine.
C1 [Bu, Lei; Jiang, Xin; Martin-Puig, Silvia; Caron, Leslie; Zhu, Shenjun; Shao, Ying; Huang, Paul L.; Domian, Ibrahim J.; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   [Bu, Lei; Jiang, Xin; Martin-Puig, Silvia; Caron, Leslie; Domian, Ibrahim J.; Chien, Kenneth R.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA.
   [Roberts, Drucilla J.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs,Med Sch, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School
RP Chien, KR (corresponding author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Plaza,CPZN 3208,185 Cambridge St, Boston, MA 02114 USA.
EM krchien@partners.org
FU Foundation Alfonso Martin Escudero, Spain; Harvard Stem Cell Institute; Leducq Foundation
NR 25
TC 430
Z9 537
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 JUL 2
PY 2009
VL 460
IS 7251
BP 113
EP U130
DI 10.1038/nature08191
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200040
PM 19571884
DA 2026-03-09
ER

PT J
AU Min, BK
   Ostby, E
   Sorger, V
   Ulin-Avila, E
   Yang, L
   Zhang, X
   Vahala, K
AF Min, Bumki
   Ostby, Eric
   Sorger, Volker
   Ulin-Avila, Erick
   Yang, Lan
   Zhang, Xiang
   Vahala, Kerry
TI High-Q surface-plasmon-polariton whispering-gallery microcavity
SO NATURE
LA English
DT Article
ID nanocavity; resonators; optics; modes; limit; chip
AB Surface plasmon polaritons (SPPs) are electron density waves excited at the interfaces between metals and dielectric materials(1). Owing to their highly localized electromagnetic fields, they may be used for the transport and manipulation of photons on subwavelength scales(2-9). In particular, plasmonic resonant cavities represent an application that could exploit this field compression to create ultra-smal-lmode- volume devices. Akey figure of merit in this regard is the ratio of cavity quality factor, Q ( related to the dissipation rate of photons confined to the cavity), to cavity mode volume, V ( refs 10, 11). However, plasmonic cavity Q factors have so far been limited to values less than 100 both for visible and near- infrared wave-lengths(12) (-16). Significantly, such values are far below the theoretically achievable Q factors for plasmonic resonant structures. Here we demonstrate a high- Q SPP whispering- gallery microcavity that is made by coating the surface of a high- Q silica microresonator with a thin layer of a noble metal. Using this structure, Q factors of 1,376+/-65 can be achieved in the near infrared for surface- plasmonic whispering- gallery modes at room temperature. This nearly ideal value, which is close to the theoretical metal- loss- limited Q factor, is attributed to the suppression and minimization of radiation and scattering losses that are made possible by the geometrical structure and the fabrication method. The SPP eigenmodes, as well as the dielectric eigenmodes, are confined within the whispering- gallery microcavity and accessed evanescently using a single strand of low-loss, tapered optical waveguide(17,18). This coupling scheme provides a convenient way of selectively exciting and probing confined SPP eigenmodes. Up to 49.7 per cent of input power is coupled by phase- matching control between the microcavity SPP and the tapered fibre eigenmodes.
C1 [Min, Bumki; Sorger, Volker; Ulin-Avila, Erick; Zhang, Xiang] Univ Calif Berkeley, Nanoscale Sci & Engn Ctr, Berkeley, CA 94720 USA.
   [Min, Bumki; Ostby, Eric; Yang, Lan; Vahala, Kerry] CALTECH, Thomas J Watson Lab Appl Phys, Pasadena, CA 91125 USA.
   [Zhang, Xiang] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; California Institute of Technology; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Zhang, X (corresponding author), Univ Calif Berkeley, Nanoscale Sci & Engn Ctr, 5130 Etcheverry Hall, Berkeley, CA 94720 USA.
EM xiang@berkeley.edu; vahala@caltech.edu
FU US Air Force Office of Scientific Research MURI [FA9550-04-1-0434]; NSF Nanoscale Science and Engineering Center [DMI-0327077]; Directorate For Engineering; Div Of Civil, Mechanical, & Manufact Inn [0751621] Funding Source: National Science Foundation; National Research Foundation of Korea [과C6A1808] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
NR 30
TC 441
Z9 511
U1 5
U2 555
PU NATURE PUBLISHING 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 22
PY 2009
VL 457
IS 7228
BP 455
EP U3
DI 10.1038/nature07627
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200041
PM 19158793
DA 2026-03-09
ER

PT J
AU Frolov, SM
   Lüscher, S
   Yu, W
   Ren, Y
   Folk, JA
   Wegscheider, W
AF Frolov, S. M.
   Luescher, S.
   Yu, W.
   Ren, Y.
   Folk, J. A.
   Wegscheider, W.
TI Ballistic spin resonance
SO NATURE
LA English
DT Article
ID magnetic-fields; semiconductors; injection
AB The phenomenon of spin resonance has had far-reaching influence since its discovery 70 years ago(1). Electron spin resonance driven by high-frequency magnetic fields has enhanced our understanding of quantum mechanics, and finds application in fields as diverse as medicine and quantum information(2). Spin resonance can also be induced by high-frequency electric fields in materials with a spin orbit interaction; the oscillation of the electrons creates a momentum-dependent effective magnetic field acting on the electron spin(3-9). Here we report electron spin resonance due to a spin orbit interaction that does not require external driving fields. The effect, which we term ballistic spin resonance, is driven by the free motion of electrons that bounce at frequencies of tens of gigahertz in micrometre-scale channels of a two-dimensional electron gas. This is a frequency range that is experimentally challenging to access in spin resonance, and especially difficult on a chip. The resonance is manifest in electrical measurements of pure spin currents(10)-we see a strong suppression of spin relaxation length when the oscillating spin-orbit field is in resonance with spin precession in a static magnetic field. These findings illustrate how the spin-orbit interaction can be harnessed for spin manipulation in a spintronic circuit(11), and point the way to gate-tunable coherent spin rotations in ballistic nanostructures without external alternating current fields.
C1 [Frolov, S. M.; Luescher, S.; Yu, W.; Ren, Y.; Folk, J. A.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z4, Canada.
   [Wegscheider, W.] Univ Regensburg, Inst Angew & Expt Phys, D-93040 Regensburg, Germany.
C3 University of British Columbia; University of Regensburg
RP Folk, JA (corresponding author), Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z4, Canada.
EM jfolk@physics.ubc.ca
FU NSERC; CFI; CIFAR; Deutsche Forschungsgemeinschaft (DFG) [SPP 1285]
NR 18
TC 82
Z9 85
U1 2
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 16
PY 2009
VL 458
IS 7240
BP 868
EP 871
DI 10.1038/nature07873
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500038
PM 19370029
DA 2026-03-09
ER

PT J
AU Yu, SR
   Burkhardt, M
   Nowak, M
   Ries, J
   Petrásek, Z
   Scholpp, S
   Schwille, P
   Brand, M
AF Yu, Shuizi Rachel
   Burkhardt, Markus
   Nowak, Matthias
   Ries, Jonas
   Petrasek, Zdenek
   Scholpp, Steffen
   Schwille, Petra
   Brand, Michael
TI Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules
SO NATURE
LA English
DT Article
ID fluorescence correlation spectroscopy; early xenopus embryo; cross-correlation; zebrafish; differentiation; endocytosis; transport; dynamics; pattern; range
AB It is widely accepted that tissue differentiation and morphogenesis in multicellular organisms are regulated by tightly controlled concentration gradients of morphogens(1,2). How exactly these gradients are formed, however, remains unclear(3-12). Here we show that Fgf8 morphogen gradients in living zebrafish embryos are established andmaintained by two essential factors: fast, free diffusion of single molecules away from the source through extracellular space, and a sink function of the receiving cells, regulated by receptor-mediated endocytosis. Evidence is provided by directly examining single molecules of Fgf8 in living tissue by fluorescence correlation spectroscopy, quantifying their local mobility and concentration with high precision. By changing the degree of uptake of Fgf8 into its target cells, we are able to alter the shape of the Fgf8 gradient. Our results demonstrate that a freely diffusing morphogen can set up concentration gradients in a complex multicellular tissue by a simple source-sink mechanism.
C1 [Yu, Shuizi Rachel; Burkhardt, Markus; Nowak, Matthias; Ries, Jonas; Petrasek, Zdenek; Scholpp, Steffen; Schwille, Petra; Brand, Michael] TUD, Ctr Biotechnol, D-01307 Dresden, Germany.
   [Yu, Shuizi Rachel; Burkhardt, Markus; Nowak, Matthias; Ries, Jonas; Petrasek, Zdenek; Schwille, Petra; Brand, Michael] TUD, Ctr Regenerat Therapies, D-01307 Dresden, Germany.
C3 Technische Universitat Dresden; Technische Universitat Dresden
RP Schwille, P (corresponding author), TUD, Ctr Biotechnol, Tatzberg 47-49, D-01307 Dresden, Germany.
EM petra.schwille@biotec.tu-dresden.de; michael.brand@biotec.tu-dresden.de
FU HFSP network grant [050503-50]; EU [050503-52]
NR 32
TC 314
Z9 373
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 SEP 24
PY 2009
VL 461
IS 7263
BP 533
EP U100
DI 10.1038/nature08391
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900042
PM 19741606
DA 2026-03-09
ER

PT J
AU Zhang, ZX
   Xu, N
   Chen, DTN
   Yunker, P
   Alsayed, AM
   Aptowicz, KB
   Habdas, P
   Liu, AJ
   Nagel, SR
   Yodh, AG
AF Zhang, Zexin
   Xu, Ning
   Chen, Daniel T. N.
   Yunker, Peter
   Alsayed, Ahmed M.
   Aptowicz, Kevin B.
   Habdas, Piotr
   Liu, Andrea J.
   Nagel, Sidney R.
   Yodh, Arjun G.
TI Thermal vestige of the zero-temperature jamming transition
SO NATURE
LA English
DT Article
ID colloidal crystals; video microscopy; glass-transition; suspensions; relaxation; particles; dynamics; mixture
AB When the packing fraction is increased sufficiently, loose particulates jam to form a rigid solid in which the constituents are no longer free to move. In typical granular materials and foams, the thermal energy is too small to produce structural rearrangements. In this zero-temperature (T = 0) limit, multiple diverging(1-8) and vanishing(2,9,10) length scales characterize the approach to a sharp jamming transition. However, because thermal motion becomes relevant when the particles are small enough, it is imperative to understand how these length scales evolve as the temperature is increased. Here we used both colloidal experiments and computer simulations to progress beyond the zero-temperature limit to track one of the key parameters-the overlap distance between neighbouring particles-which vanishes at the T = 0 jamming transition. We find that this structural feature retains a vestige of its T = 0 behaviour and evolves in an unusual manner, which has masked its appearance until now. It is evident as a function of packing fraction at fixed temperature, but not as a function of temperature at fixed packing fraction or pressure. Our results conclusively demonstrate that length scales associated with the T = 0 jamming transition persist in thermal systems, not only in simulations but also in laboratory experiments.
C1 [Zhang, Zexin; Xu, Ning; Chen, Daniel T. N.; Yunker, Peter; Alsayed, Ahmed M.; Liu, Andrea J.; Yodh, Arjun G.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
   [Xu, Ning; Nagel, Sidney R.] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA.
   [Aptowicz, Kevin B.] W Chester Univ, Dept Phys, W Chester, PA 19383 USA.
   [Habdas, Piotr] St Josephs Univ, Dept Phys, Philadelphia, PA 19131 USA.
C3 University of Pennsylvania; University of Chicago; Pennsylvania State System of Higher Education (PASSHE); West Chester University of Pennsylvania; Saint Joseph's University
RP Zhang, ZX (corresponding author), Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
EM zexin@sas.upenn.edu; ningxu@sas.upenn.edu
FU Department of Energy; National Science Foundation [DE-FG02-05ER46199, DE-FG02-03ER46088]; University of Chicago MRSEC [DMR-0820054, DMR-080488]; PENN MRSEC [DMR-0520020]; Rhodia; Teraport computer cluster at the University of Chicago; Division Of Materials Research; Direct For Mathematical & Physical Scien [0804881] Funding Source: National Science Foundation
NR 30
TC 243
Z9 291
U1 3
U2 112
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 230
EP 233
DI 10.1038/nature07998
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100036
PM 19444211
DA 2026-03-09
ER

PT J
AU Mirouze, M
   Reinders, J
   Bucher, E
   Nishimura, T
   Schneeberger, K
   Ossowski, S
   Cao, J
   Weigel, D
   Paszkowski, J
   Mathieu, O
AF Mirouze, Marie
   Reinders, Jon
   Bucher, Etienne
   Nishimura, Taisuke
   Schneeberger, Korbinian
   Ossowski, Stephan
   Cao, Jun
   Weigel, Detlef
   Paszkowski, Jerzy
   Mathieu, Olivier
TI Selective epigenetic control of retrotransposition in Arabidopsis
SO NATURE
LA English
DT Article
ID dna methylation; transposable elements; cpg methylation; genome-wide; rna; methyltransferases; maintenance; stability; epigenome; lysine-9
AB Retrotransposons are mobile genetic elements that populate chromosomes, where the host largely controls their activities(1-3). In plants and mammals, retrotransposons are transcriptionally silenced by DNA methylation(1,4), which in Arabidopsis is propagated at CG dinucleotides by METHYLTRANSFERASE 1 (MET1)(5). In met1 mutants, however, mobilization of retrotransposons is not observed, despite their transcriptional activation(4-6). A post-transcriptional mechanism therefore seems to be preventing retrotransposition. Here we show that a copia-type retrotransposon (Evade, French for 'fugitive') evaded suppression of its movement during inbreeding of hybrid epigenomes consisting of met1-and wild-type-derived chromosomes. Evade (EVD) reinsertions caused a series of developmental mutations that allowed its identification. Genetic testing of host control of the EVD life cycle showed that transcriptional suppression occurred by CG methylation supported by RNA-directed DNA methylation. On transcriptional reactivation, subsequent steps of the EVD cycle were inhibited by plant-specific RNA polymerase IV/V-7,V-8 and the histone methyltransferase KRYPTONITE (KYP). Moreover, genome resequencing demonstrated retrotransposition of EVD but no other potentially active retroelements when this combination of epigenetic mechanisms was compromised. Our results demonstrate that epigenetic control of retrotransposons extends beyond transcriptional suppression and can be individualized for particular elements.
C1 [Mirouze, Marie; Reinders, Jon; Bucher, Etienne; Nishimura, Taisuke; Paszkowski, Jerzy; Mathieu, Olivier] Univ Geneva, Dept Plant Biol, CH-1211 Geneva 4, Switzerland.
   [Schneeberger, Korbinian; Ossowski, Stephan; Cao, Jun; Weigel, Detlef] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany.
   [Mathieu, Olivier] Univ Clermont Ferrand 2, CNRS, INSERM, GReD,UMR 6247,U931, F-63177 Clermont Ferrand, France.
C3 University of Geneva; Max Planck Society; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Clermont Auvergne (UCA)
RP Paszkowski, J (corresponding author), Univ Geneva, Dept Plant Biol, Sci III,30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
EM jerzy.paszkowski@unige.ch; olivier.mathieu@univ-bpclermont.fr
FU Swiss National Science Foundation [3100A0-102107]; European Commission [LSHG-CT-2004- 503433]; Targeted Gene Integration in Plants (TAGIP) [018785]; Max Planck Society
NR 31
TC 268
Z9 297
U1 0
U2 62
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 427
EP U130
DI 10.1038/nature08328
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100047
PM 19734882
DA 2026-03-09
ER

PT J
AU He, LM
   Xue, L
   Xu, JH
   McNeil, BD
   Bai, L
   Melicoff, E
   Adachi, R
   Wu, LG
AF He, Liming
   Xue, Lei
   Xu, Jianhua
   McNeil, Benjamin D.
   Bai, Li
   Melicoff, Ernestina
   Adachi, Roberto
   Wu, Ling-Gang
TI Compound vesicle fusion increases quantal size and potentiates synaptic transmission
SO NATURE
LA English
DT Article
ID multivesicular release; posttetanic potentiation; transmitter release; rat calyx; 2 modes; exocytosis; endocytosis; capacitance; membrane; currents
AB Exocytosis at synapses involves fusion between vesicles and the plasma membrane(1). Although compound fusion between vesicles(2,3) was proposed to occur at ribbon-type synapses(4,5), whether it exists, how it is mediated, and what role it plays at conventional synapses remain unclear. Here we report the existence of compound fusion, its underlying mechanism, and its role at a nerve terminal containing conventional active zones in rats and mice. We found that high potassium application and high frequency firing induced giant capacitance up-steps, reflecting exocytosis of vesicles larger than regular ones, followed by giant down-steps, reflecting bulk endocytosis. These intense stimuli also induced giant vesicle-like structures, as observed with electron microscopy, and giant miniature excitatory postsynaptic currents (mEPSCs), reflecting more transmitter release. Calcium and its sensor for vesicle fusion, synaptotagmin, were required for these giant events. After high frequency firing, calcium/synaptotagmin-dependent mEPSC size increase was paralleled by calcium/synaptotagmin-dependent post-tetanic potentiation. These results suggest a new route of exocytosis and endocytosis composed of three steps. First, calcium/synaptotagmin mediates compound fusion between vesicles. Second, exocytosis of compound vesicles increases quantal size, which increases synaptic strength and contributes to the generation of post-tetanic potentiation. Third, exocytosed compound vesicles are retrieved via bulk endocytosis. We suggest that this vesicle cycling route be included in models of synapses in which only vesicle fusion with the plasma membrane is considered(1).
C1 [He, Liming; Xue, Lei; Xu, Jianhua; McNeil, Benjamin D.; Bai, Li; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA.
   [Melicoff, Ernestina; Adachi, Roberto] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); University of Texas System; UTMD Anderson Cancer Center
RP Wu, LG (corresponding author), NINDS, 35 Convent Dr,Bldg 35,Room 2B 1012, Bethesda, MD 20892 USA.
EM wul@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke Intramural Research Program; American Heart Association; National Institute of Neurological Disorders and Stroke [ZIANS003009] Funding Source: NIH RePORTER
NR 33
TC 107
Z9 117
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 MAY 7
PY 2009
VL 459
IS 7243
BP 93
EP U99
DI 10.1038/nature07860
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300036
PM 19279571
DA 2026-03-09
ER

PT J
AU Zhu, M
   Zhao, WJ
   Jia, LT
   Lu, J
   Qiao, T
   Qu, QM
AF Zhu, Min
   Zhao, Wenjin
   Jia, Liantao
   Lu, Jing
   Qiao, Tuo
   Qu, Qingming
TI The oldest articulated osteichthyan reveals mosaic gnathostome characters
SO NATURE
LA English
DT Article
ID bony fishes; interrelationships
AB The evolutionary history of osteichthyans (bony fishes plus tetrapods) extends back to the Ludlow epoch of the Silurian period. However, these Silurian forms have been documented exclusively by fragmentary fossils. Here we report the discovery of an exceptionally preserved primitive fish from the Ludlow of Yunnan, China, that represents the oldest near-complete gnathostome (jawed vertebrate). The postcranial skeleton of this fish includes a primitive pectoral girdle and median fin spine as in non-osteichthyan gnathostomes, but a derived macromeric squamation as in crown osteichthyans, and substantiates the unexpected mix of postcranial features in basal sarcopterygians, previously restored from the disarticulated remains of Psarolepis. As the oldest articulated sarcopterygian, the new taxon offers insights into the origin and early divergence of osteichthyans, and indicates that the minimum date for the actinopterygian-sarcopterygian split was no later than 419 million years ago.
C1 [Zhu, Min; Zhao, Wenjin; Jia, Liantao; Lu, Jing; Qiao, Tuo; Qu, Qingming] Chinese Acad Sci, IVPP, Key Lab Evolutionary Systemat Vertebrates, Beijing 100044, Peoples R China.
   [Lu, Jing; Qiao, Tuo; Qu, Qingming] Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China.
C3 Chinese Academy of Sciences; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
RP Zhu, M (corresponding author), Chinese Acad Sci, IVPP, Key Lab Evolutionary Systemat Vertebrates, POB 643, Beijing 100044, Peoples R China.
EM zhumin@ivpp.ac.cn
FU MST of China [2006CB806400]; Chinese Academy of Sciences; National Natural Science Foundation of China; CAS/SAFEA International Partnership Program for Creative Research Teams; Australian Research Council Discovery [DP0772138]; Australian Research Council [DP0772138] Funding Source: Australian Research Council
NR 50
TC 188
Z9 226
U1 2
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 26
PY 2009
VL 458
IS 7237
BP 469
EP 474
DI 10.1038/nature07855
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400036
PM 19325627
DA 2026-03-09
ER

PT J
AU Huang, SMA
   Mishina, YM
   Liu, SM
   Cheung, A
   Stegmeier, F
   Michaud, GA
   Charlat, O
   Wiellette, E
   Zhang, Y
   Wiessner, S
   Hild, M
   Shi, XY
   Wilson, CJ
   Mickanin, C
   Myer, V
   Fazal, A
   Tomlinson, R
   Serluca, F
   Shao, WL
   Cheng, H
   Shultz, M
   Rau, C
   Schirle, M
   Schlegl, J
   Ghidelli, S
   Fawell, S
   Lu, C
   Curtis, D
   Kirschner, MW
   Lengauer, C
   Finan, PM
   Tallarico, JA
   Bouwmeester, T
   Porter, JA
   Bauer, A
   Cong, F
AF Huang, Shih-Min A.
   Mishina, Yuji M.
   Liu, Shanming
   Cheung, Atwood
   Stegmeier, Frank
   Michaud, Gregory A.
   Charlat, Olga
   Wiellette, Elizabeth
   Zhang, Yue
   Wiessner, Stephanie
   Hild, Marc
   Shi, Xiaoying
   Wilson, Christopher J.
   Mickanin, Craig
   Myer, Vic
   Fazal, Aleem
   Tomlinson, Ronald
   Serluca, Fabrizio
   Shao, Wenlin
   Cheng, Hong
   Shultz, Michael
   Rau, Christina
   Schirle, Markus
   Schlegl, Judith
   Ghidelli, Sonja
   Fawell, Stephen
   Lu, Chris
   Curtis, Daniel
   Kirschner, Marc W.
   Lengauer, Christoph
   Finan, Peter M.
   Tallarico, John A.
   Bouwmeester, Tewis
   Porter, Jeffery A.
   Bauer, Andreas
   Cong, Feng
TI Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling
SO NATURE
LA English
DT Article
ID beta-catenin; colorectal tumors; ubiquitin ligase; regeneration; pathway; cancer; apc; mutations; telomeres; complex
AB The stability of the Wnt pathway transcription factor beta-catenin is tightly regulated by the multi-subunit destruction complex. Deregulated Wnt pathway activity has been implicated in many cancers, making this pathway an attractive target for anticancer therapies. However, the development of targeted Wnt pathway inhibitors has been hampered by the limited number of pathway components that are amenable to small molecule inhibition. Here, we used a chemical genetic screen to identify a small molecule, XAV939, which selectively inhibits beta-catenin-mediated transcription. XAV939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. Thus, our study provides new mechanistic insights into the regulation of axin protein homeostasis and presents new avenues for targeted Wnt pathway therapies.
C1 [Huang, Shih-Min A.; Mishina, Yuji M.; Liu, Shanming; Cheung, Atwood; Stegmeier, Frank; Michaud, Gregory A.; Charlat, Olga; Wiellette, Elizabeth; Zhang, Yue; Wiessner, Stephanie; Hild, Marc; Shi, Xiaoying; Wilson, Christopher J.; Mickanin, Craig; Myer, Vic; Fazal, Aleem; Tomlinson, Ronald; Serluca, Fabrizio; Shao, Wenlin; Cheng, Hong; Shultz, Michael; Fawell, Stephen; Lu, Chris; Curtis, Daniel; Lengauer, Christoph; Finan, Peter M.; Tallarico, John A.; Porter, Jeffery A.; Cong, Feng] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Rau, Christina; Schirle, Markus; Schlegl, Judith; Ghidelli, Sonja; Bouwmeester, Tewis; Bauer, Andreas] Cellzome AG, D-69117 Heidelberg, Germany.
   [Kirschner, Marc W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
C3 Novartis; Novartis USA; GlaxoSmithKline; Cellzome GmbH; Harvard University; Harvard Medical School
RP Cong, F (corresponding author), Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA.
EM feng.cong@novartis.com
NR 29
TC 1779
Z9 2123
U1 8
U2 206
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 1
PY 2009
VL 461
IS 7264
BP 614
EP 620
DI 10.1038/nature08356
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600032
PM 19759537
DA 2026-03-09
ER

PT J
AU Dong, XH
   Biswas, A
   Süel, KE
   Jackson, LK
   Martinez, R
   Gu, HM
   Chook, YM
AF Dong, Xiuhua
   Biswas, Anindita
   Sueel, Katherine E.
   Jackson, Laurie K.
   Martinez, Rita
   Gu, Hongmei
   Chook, Yuh Min
TI Structural basis for leucine-rich nuclear export signal recognition by CRM1
SO NATURE
LA English
DT Article
ID protein export; nucleocytoplasmic transport; sequence requirements; importin-beta; t-antigen; localization; prediction; pathway; complex; system
AB CRM1 (also known as XPO1 and exportin 1) mediates nuclear export of hundreds of proteins through the recognition of the leucine-rich nuclear export signal (LR-NES). Here we present the 2.9 angstrom structure of CRM1 bound to snurportin 1 (SNUPN). Snurportin 1 binds CRM1 in a bipartite manner by means of an amino-terminal LR-NES and its nucleotide-binding domain. The LR-NES is a combined alpha-helical-extended structure that occupies a hydrophobic groove between two CRM1 outer helices. The LR-NES interface explains the consensus hydrophobic pattern, preference for intervening electronegative residues and inhibition by leptomycin B. The second nuclear export signal epitope is a basic surface on the snurportin 1 nucleotide-binding domain, which binds an acidic patch on CRM1 adjacent to the LR-NES site. Multipartite recognition of individually weak nuclear export signal epitopes may be common to CRM1 substrates, enhancing CRM1 binding beyond the generally low affinity LR-NES. Similar energetic construction is also used in multipartite nuclear localization signals to provide broad substrate specificity and rapid evolution in nuclear transport.
C1 [Dong, Xiuhua; Biswas, Anindita; Sueel, Katherine E.; Jackson, Laurie K.; Martinez, Rita; Gu, Hongmei; Chook, Yuh Min] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center
RP Chook, YM (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Pharmacol, 6001 Forest Pk, Dallas, TX 75390 USA.
EM yuhmin.chook@utsouthwestern.edu
FU National Institute of Health (NIH) [R01GM069909, R01GM069909-03S1, 5-T32-GM008297]; Welch Foundation [I-1532]; UT Southwestern Endowed Scholars Program; US Department of Energy; Office of Energy Research [W-31-109-ENG-38]
NR 50
TC 277
Z9 316
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 APR 30
PY 2009
VL 458
IS 7242
BP 1136
EP U71
DI 10.1038/nature07975
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600040
PM 19339969
DA 2026-03-09
ER

PT J
AU Turnbaugh, PJ
   Hamady, M
   Yatsunenko, T
   Cantarel, BL
   Duncan, A
   Ley, RE
   Sogin, ML
   Jones, WJ
   Roe, BA
   Affourtit, JP
   Egholm, M
   Henrissat, B
   Heath, AC
   Knight, R
   Gordon, JI
AF Turnbaugh, Peter J.
   Hamady, Micah
   Yatsunenko, Tanya
   Cantarel, Brandi L.
   Duncan, Alexis
   Ley, Ruth E.
   Sogin, Mitchell L.
   Jones, William J.
   Roe, Bruce A.
   Affourtit, Jason P.
   Egholm, Michael
   Henrissat, Bernard
   Heath, Andrew C.
   Knight, Rob
   Gordon, Jeffrey I.
TI A core gut microbiome in obese and lean twins
SO NATURE
LA English
DT Article
ID comparative metagenomics; dna-sequences; diversity; protein; ecology; sets
AB The human distal gut harbours a vast ensemble of microbes ( the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides(1-6). Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes(6-8), yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota ( the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored(3-5). Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full- length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co- variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum- level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from his core are associated with different physiological states (obese compared with lean).
C1 [Turnbaugh, Peter J.; Yatsunenko, Tanya; Ley, Ruth E.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci, St Louis, MO 63108 USA.
   [Duncan, Alexis; Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63108 USA.
   [Hamady, Micah] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA.
   [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Cantarel, Brandi L.; Henrissat, Bernard] CNRS, UMR6098, Marseille, France.
   [Sogin, Mitchell L.] Marine Biol Lab, Josephine Bay Paul Ctr, Woods Hole, MA 02543 USA.
   [Jones, William J.] Univ S Carolina, Environm Genome Core Facil, Columbia, SC 29208 USA.
   [Roe, Bruce A.] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA.
   [Roe, Bruce A.] Univ Oklahoma, Adv Ctr Genome Technol, Norman, OK 73019 USA.
   [Affourtit, Jason P.; Egholm, Michael] 454 Life Sci, Branford, CT 06405 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; Centre National de la Recherche Scientifique (CNRS); Marine Biological Laboratory - Woods Hole; University of South Carolina System; University of South Carolina Columbia; University of Oklahoma System; University of Oklahoma - Norman; University of Oklahoma System; University of Oklahoma - Norman
RP Gordon, JI (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci, St Louis, MO 63108 USA.
EM jgordon@wustl.edu
FU National Institutes of Health [DK78669, ES012742, AA09022, HD049024]; National Science Foundation [OCE0430724]; W.M. Keck Foundation; Crohn's and Colitis Foundation of America; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056341] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM065103] Funding Source: NIH RePORTER; Action Medical Research; Crohn&apos;s & Colitis Foundation [2158] Funding Source: researchfish
NR 34
TC 6147
Z9 7515
U1 21
U2 2203
PU NATURE PUBLISHING 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 22
PY 2009
VL 457
IS 7228
BP 480
EP U7
DI 10.1038/nature07540
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200047
PM 19043404
DA 2026-03-09
ER

PT J
AU Morran, LT
   Parmenter, MD
   Phillips, PC
AF Morran, Levi T.
   Parmenter, Michelle D.
   Phillips, Patrick C.
TI Mutation load and rapid adaptation favour outcrossing over self-fertilization
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; inbreeding depression; sex determination; selection; advantage; gene; extinction; evolution; males
AB The tendency of organisms to reproduce by cross-fertilization despite numerous disadvantages relative to self-fertilization is one of the oldest puzzles in evolutionary biology. For many species, the primary obstacle to the evolution of outcrossing is the cost of production of males(1), individuals that do not directly contribute offspring and thus diminish the long-term reproductive output of a lineage. Self-fertilizing ('selfing') organisms do not incur the cost of males and therefore should possess at least a twofold numerical advantage over most outcrossing organisms(2). Two competing explanations for the widespread prevalence of outcrossing in nature despite this inherent disadvantage are the avoidance of inbreeding depression generated by selfing(3-5) and the ability of outcrossing populations to adapt more rapidly to environmental change(1,6,7). Here we show that outcrossing is favoured in populations of Caenorhabditis elegans subject to experimental evolution both under conditions of increased mutation rate and during adaptation to a novel environment. In general, fitness increased with increasing rates of outcrossing. Thus, each of the standard explanations for the maintenance of outcrossing are correct, and it is likely that outcrossing is the predominant mode of reproduction inmost species because it is favoured under ecological conditions that are ubiquitous in natural environments.
C1 [Morran, Levi T.; Parmenter, Michelle D.; Phillips, Patrick C.] 5289 Univ Oregon, Ctr Ecol & Evolutionary Biol, Eugene, OR 97403 USA.
C3 University of Oregon
RP Phillips, PC (corresponding author), 5289 Univ Oregon, Ctr Ecol & Evolutionary Biol, Eugene, OR 97403 USA.
EM pphil@uoregon.edu
FU NSF [DEB-0236180, DEB-0710386, DEB-0641066]; NIH; National Institute of General Medical Sciences [T32GM007413] Funding Source: NIH RePORTER
NR 30
TC 170
Z9 211
U1 0
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 19
PY 2009
VL 462
IS 7271
BP 350
EP 352
DI 10.1038/nature08496
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300044
PM 19847164
DA 2026-03-09
ER

PT J
AU Kim, S
   Takahashi, H
   Lin, WW
   Descargues, P
   Grivennikov, S
   Kim, Y
   Luo, JL
   Karin, M
AF Kim, Sunhwa
   Takahashi, Hiroyuki
   Lin, Wan-Wan
   Descargues, Pascal
   Grivennikov, Sergei
   Kim, Youngjun
   Luo, Jun-Li
   Karin, Michael
TI Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis
SO NATURE
LA English
DT Article
ID lewis-lung-carcinoma; cancer metastasis; prostate-cancer; innate immunity; tumor-growth; proteoglycan; inflammation; macrophages; angiogenesis; hyaluronan
AB Metastatic progression depends on genetic alterations intrinsic to cancer cells as well as the inflammatory microenvironment of advanced tumours(1,2). To understand how cancer cells affect the inflammatory microenvironment, we conducted a biochemical screen for macrophage- activating factors secreted by metastatic carcinomas. Here we show that, among the cell lines screened, Lewis lung carcinoma (LLC)(3) were the most potent macrophage activators leading to production of interleukin-6 (IL-6) and tumour-necrosis factor-alpha (TNF-alpha) through activation of the Toll-like receptor (TLR) family members(4) TLR2 and TLR6. Both TNF-alpha and TLR2 were found to be required for LLC metastasis. Biochemical purification of LLC- conditioned medium ( LCM) led to identification of the extracellular matrix proteoglycan versican, which is upregulated in many human tumours including lung cancer(5,6), as a macrophage activator that acts through TLR2 and its coreceptors TLR6 and CD14. By activating TLR2: TLR6 complexes and inducing TNF-alpha secretion by myeloid cells, versican strongly enhances LLC metastatic growth. These results explain how advanced cancer cells usurp components of the host innate immune system, including bone- marrow- derived myeloid progenitors(7), to generate an inflammatory microenvironment hospitable for metastatic growth.
C1 [Kim, Sunhwa; Takahashi, Hiroyuki; Lin, Wan-Wan; Descargues, Pascal; Grivennikov, Sergei; Kim, Youngjun; Luo, Jun-Li; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Kim, Sunhwa; Takahashi, Hiroyuki; Lin, Wan-Wan; Descargues, Pascal; Grivennikov, Sergei; Kim, Youngjun; Luo, Jun-Li; Karin, Michael] Univ Calif San Diego, Sch Med, Ctr Canc, La Jolla, CA 92093 USA.
   [Lin, Wan-Wan] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10764, Taiwan.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; National Taiwan University
RP Karin, M (corresponding author), Univ Calif San Diego, Sch Med, Dept Pharmacol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM karinoffice@ucsd.edu
FU International Human Frontier Science Program Organization; National Cancer Institute-sponsored Cancer Therapeutic Training Program; Ruth L. Kirschstein National Research Service Award; California Institute of Regenerative Medicine; Japanese Respiratory Society; Life Science Research Foundation; IHFSPO; Crohn's and Colitis Foundation of America; National Institutes of Health; Littlefield-AACR; National Cancer Institute [T32CA121938] Funding Source: NIH RePORTER
NR 27
TC 921
Z9 1064
U1 4
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 1
PY 2009
VL 457
IS 7225
BP 102
EP U108
DI 10.1038/nature07623
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900039
PM 19122641
DA 2026-03-09
ER

PT J
AU Wang, XY
   Ren, XF
   Kahen, K
   Hahn, MA
   Rajeswaran, M
   Maccagnano-Zacher, S
   Silcox, J
   Cragg, GE
   Efros, AL
   Krauss, TD
AF Wang, Xiaoyong
   Ren, Xiaofan
   Kahen, Keith
   Hahn, Megan A.
   Rajeswaran, Manju
   Maccagnano-Zacher, Sara
   Silcox, John
   Cragg, George E.
   Efros, Alexander L.
   Krauss, Todd D.
TI RETRACTED: Non-blinking semiconductor nanocrystals (Retracted article. See vol. 527, 2015)
SO NATURE
LA English
DT Article; Retracted Publication
ID single-quantum-dot; cadmium selenide nanocrystals; fluorescence intermittency; spectroscopy; suppression; emission; dynamics
AB The photoluminescence from a variety of individual molecules(1) and nanometre-sized crystallites(2) is defined by large intensity fluctuations, known as 'blinking', whereby their photoluminescence turns 'on' and 'off' intermittently, even under continuous photoexcitation(2). For semiconductor nanocrystals, it was originally proposed(3) that these 'off' periods corresponded to a nanocrystal with an extra charge. A charged nanocrystal could have its photoluminescence temporarily quenched owing to the high efficiency of non-radiative ( for example, Auger) recombination processes between the extra charge and a subsequently excited electron-hole pair; photoluminescence would resume only after the nanocrystal becomes neutralized again. Despite over a decade of research, completely non-blinking nanocrystals(4,5) have not been synthesized and an understanding of the blinking phenomenon(6) remains elusive. Here we report ternary core/shell CdZnSe/ZnSe semiconductor nanocrystals that individually exhibit continuous, non-blinking photoluminescence. Unexpectedly, these nanocrystals strongly photoluminesce despite being charged, as indicated by a multi-peaked photoluminescence spectral shape and short lifetime. To model the unusual photoluminescence properties of the CdZnSe/ZnSe nanocrystals, we softened the abrupt confinement potential of a typical core/shell nanocrystal, suggesting that the structure is a radially graded alloy of CdZnSe into ZnSe. As photoluminescence blinking severely limits the usefulness of nanocrystals in applications requiring a continuous output of single photons, these non-blinking nanocrystals may enable substantial advances in fields ranging from single-molecule biological labelling(7) to low-threshold lasers(8).
C1 [Wang, Xiaoyong; Hahn, Megan A.; Krauss, Todd D.] Univ Rochester, Dept Chem, Rochester, NY 14627 USA.
   [Krauss, Todd D.] Univ Rochester, Inst Opt, Rochester, NY 14627 USA.
   [Ren, Xiaofan; Kahen, Keith; Rajeswaran, Manju] Eastman Kodak Co, Rochester, NY 14650 USA.
   [Maccagnano-Zacher, Sara; Silcox, John] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14583 USA.
   [Cragg, George E.; Efros, Alexander L.] USN, Res Lab, Washington, DC 20375 USA.
C3 University of Rochester; University of Rochester; Eastman Kodak; Cornell University; United States Department of Defense; United States Navy; United States Naval Research Laboratory; NRL Chesapeake
RP Krauss, TD (corresponding author), Univ Rochester, Dept Chem, Rochester, NY 14627 USA.
EM keith.kahen@kodak.com; efros@dave.nrl.navy.mil; krauss@chem.rochester.edu
FU DOE [DE-FC26-06NT42864]; NSF [CHE 0616378, CHE 0619418, EEC-0117770, DMR-9632275]; NYSTAR; University of Rochester Center for Electronic Imaging Systems; Cornell Center for Nanoscale Systems; Office of Naval Research; Alexander von Humboldt Foundation
NR 30
TC 537
Z9 654
U1 3
U2 377
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 686
EP 689
DI 10.1038/nature08072
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600040
PM 19430463
DA 2026-03-09
ER

PT J
AU van Mameren, J
   Modesti, M
   Kanaar, R
   Wyman, C
   Peterman, EJG
   Wuite, GJL
AF van Mameren, Joost
   Modesti, Mauro
   Kanaar, Roland
   Wyman, Claire
   Peterman, Erwin J. G.
   Wuite, Gijs J. L.
TI Counting RAD51 proteins disassembling from nucleoprotein filaments under tension
SO NATURE
LA English
DT Article
ID dna strand-exchange; atp hydrolysis; biochemical-characterization; homologous recombination; rad51-dsdna filament; reca filaments; molecules; dynamics; binding; resolution
AB The central catalyst in eukaryotic ATP- dependent homologous recombination consists of RAD51 proteins, polymerized around single- stranded DNA. This nucleoprotein filament recognizes and invades a homologous duplex DNA segment(1,2). After strand exchange, the nucleoprotein filament should disassemble so that the recombination process can be completed(3). The molecular mechanism of RAD51 filament disassembly is poorly understood. Here we show, by combining optical tweezers with single- molecule fluorescence microscopy and microfluidics(4,5), that disassembly of human RAD51 nucleoprotein filaments results from the interplay between ATP hydrolysis and the release of the tension stored in the filament. By applying external tension to the DNA, we found that disassembly slows down and can even be stalled. We quantified the fluorescence of RAD51 patches and found that disassembly occurs in bursts interspersed by long pauses. After relaxation of a stalled complex, pauses were suppressed resulting in a large burst. These results indicate that tension- dependent disassembly takes place only from filament ends, after tension- independent ATP hydrolysis. This integrative single-molecule approach allowed us to dissect the mechanism of this principal homologous recombination reaction step, which in turn clarifies how disassembly can be influenced by accessory proteins.
C1 [van Mameren, Joost; Peterman, Erwin J. G.; Wuite, Gijs J. L.] Vrije Univ Amsterdam, Ctr Laser, NL-1081 HV Amsterdam, Netherlands.
   [van Mameren, Joost; Peterman, Erwin J. G.; Wuite, Gijs J. L.] Vrije Univ Amsterdam, Dept Phys & Astron, NL-1081 HV Amsterdam, Netherlands.
   [Modesti, Mauro; Kanaar, Roland; Wyman, Claire] Erasmus MC, Dept Cell Biol & Genet, NL-3000 CA Rotterdam, Netherlands.
   [Modesti, Mauro] Univ Aix Marseille 2, CNRS, Unite Propre Rech 3081, F-13402 Marseille 20, France.
   [Kanaar, Roland; Wyman, Claire] Erasmus MC, Dept Radiat Oncol, NL-3000 CA Rotterdam, Netherlands.
C3 Vrije Universiteit Amsterdam; Vrije Universiteit Amsterdam; Erasmus University Rotterdam; Erasmus MC; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Erasmus University Rotterdam; Erasmus MC
RP Peterman, EJG (corresponding author), Vrije Univ Amsterdam, Ctr Laser, Boelelaan 1081, NL-1081 HV Amsterdam, Netherlands.
EM erwinp@few.vu.nl; gwuite@few.vu.nl
FU Biomolecular Physics; Dutch organization for Fundamental Research of Matter (FOM); Dutch Cancer Society; Netherlands Organization for Scientific Research; Netherlands Genomics Initiative/NWO; Association for International Cancer Research; European Commission Integrated Projects Molecular Imaging; DNA Repair; National Cancer Institute-National Institutes of Health USA; NWO Vidi; NWO Vici; National Cancer Institute [P01CA092584] Funding Source: NIH RePORTER
NR 30
TC 148
Z9 172
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 745
EP 748
DI 10.1038/nature07581
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700046
PM 19060884
DA 2026-03-09
ER

PT J
AU Bidère, N
   Ngo, VN
   Lee, J
   Collins, C
   Zheng, LX
   Wan, FY
   Davis, RE
   Lenz, G
   Anderson, DE
   Arnoult, D
   Vazquez, A
   Sakai, K
   Zhang, J
   Meng, ZJ
   Veenstra, TD
   Staudt, LM
   Lenardo, MJ
AF Bidere, Nicolas
   Ngo, Vu N.
   Lee, Jeansun
   Collins, Cailin
   Zheng, Lixin
   Wan, Fengyi
   Davis, R. Eric
   Lenz, Georg
   Anderson, D. Eric
   Arnoult, Damien
   Vazquez, Aime
   Sakai, Keiko
   Zhang, Jun
   Meng, Zhaojing
   Veenstra, Timothy D.
   Staudt, Louis M.
   Lenardo, Michael J.
TI Casein kinase 1α governs antigen-receptor-induced NF-κB activation and human lymphoma cell survival
SO NATURE
LA English
DT Article
ID t-cell; carma1; requirement; phosphorylation; beta; wnt; ubiquitination; proliferation; addiction; regulator
AB The transcription factor NF-kappa B is required for lymphocyte activation and proliferation as well as the survival of certain lymphoma types(1,2). Antigen receptor stimulation assembles an NF-kappa B activating platform containing the scaffold protein CARMA1 (also called CARD11), the adaptor BCL10 and the paracaspase MALT1 (the CBM complex), linked to the inhibitor of NF-kappa B kinase complex(3-12), but signal transduction is not fully understood(1). We conducted parallel screens involving a mass spectrometry analysis of CARMA1 binding partners and an RNA interference screen for growth inhibition of the CBM-dependent 'activated B-cell-like' (ABC) subtype of diffuse large B-cell lymphoma (DLBCL)(12). Here we report that both screens identified casein kinase 1 alpha (CK1 alpha) as a bifunctional regulator of NF-kappa B. CK1 alpha dynamically associates with the CBM complex on T-cell-receptor (TCR) engagement to participate in cytokine production and lymphocyte proliferation. However, CK1 alpha kinase activity has a contrasting role by subsequently promoting the phosphorylation and inactivation of CARMA1. CK1 alpha has thus a dual 'gating' function which first promotes and then terminates receptor-induced NF-kappa B. ABCDLBCL cells required CK1 alpha for constitutive NF-kappa B activity, indicating that CK1 alpha functions as a conditionally essential malignancy gene-a member of a new class of potential cancer therapeutic targets.
C1 [Bidere, Nicolas; Lee, Jeansun; Zheng, Lixin; Wan, Fengyi; Sakai, Keiko; Zhang, Jun; Lenardo, Michael J.] NIAID, Mol Dev Sect, Immunol Lab, Bethesda, MD 20892 USA.
   [Ngo, Vu N.; Collins, Cailin; Davis, R. Eric; Lenz, Georg; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Anderson, D. Eric] NIDDK, Proteom & Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA.
   [Arnoult, Damien; Vazquez, Aime] Univ Paris Sud, Hop Paul Brousse, INSERM, U542, F-94800 Villejuif, France.
   [Meng, Zhaojing; Veenstra, Timothy D.] NCI, LPAT, Frederick, MD 21702 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Paul-Brousse - APHP; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Lenardo, MJ (corresponding author), NIAID, Mol Dev Sect, Immunol Lab, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov; lenardo@nih.gov
FU Intramural Research Program of the NIH; NIAID; NCI; NIDDK; Agence Nationale de la Recherche (ANR); National Cancer Institute [ZIABC011008, ZIABC011007] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI000565] Funding Source: NIH RePORTER
NR 31
TC 132
Z9 157
U1 0
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 5
PY 2009
VL 458
IS 7234
BP 92
EP U7
DI 10.1038/nature07613
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000039
PM 19118383
DA 2026-03-09
ER

PT J
AU Abramov, O
   Mojzsis, SJ
AF Abramov, Oleg
   Mojzsis, Stephen J.
TI Microbial habitability of the Hadean Earth during the late heavy bombardment
SO NATURE
LA English
DT Article
ID supracrustal rocks; lunar cataclysm; west greenland; origin; life; meteorite; zircons; age; evolution; history
AB Lunar rocks(1,2) and impact melts(3), lunar(4) and asteroidal meteorites(5), and an ancient martian meteorite(6) record thermal metamorphic events with ages that group around and/or do not exceed 3.9 Gyr. That such a diverse suite of solar system materials share this feature is interpreted to be the result of a post-primary-accretion cataclysmic spike in the number of impacts commonly referred to as the late heavy bombardment (LHB)(1-7). Despite its obvious significance to the preservation of crust and the survivability of an emergent biosphere, the thermal effects of this bombardment on the young Earth remain poorly constrained. Here we report numerical models constructed to probe the degree of thermal metamorphism in the crust in the effort to recreate the effect of the LHB on the Earth as a whole; outputs were used to assess habitable volumes of crust for a possible near-surface and subsurface primordial microbial biosphere. Our analysis shows that there is no plausible situation in which the habitable zone was fully sterilized on Earth, at least since the termination of primary accretion of the planets and the postulated impact origin of the Moon. Our results explain the root location of hyperthermophilic bacteria in the phylogenetic tree for 16S small-subunit ribosomal RNA(8), and bode well for the persistence of microbial biospheres even on planetary bodies strongly reworked by impacts.
C1 [Abramov, Oleg; Mojzsis, Stephen J.] Univ Colorado, Dept Geol Sci, Boulder, CO 80309 USA.
C3 University of Colorado System; University of Colorado Boulder
RP Abramov, O (corresponding author), Univ Colorado, Dept Geol Sci, 2200 Colorado Ave,UCB 399, Boulder, CO 80309 USA.
EM oleg.abramov@colorado.edu
FU NASA Astrobiology Institute; NASA Exobiology program
NR 30
TC 175
Z9 214
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 MAY 21
PY 2009
VL 459
IS 7245
BP 419
EP 422
DI 10.1038/nature08015
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700044
PM 19458721
DA 2026-03-09
ER

PT J
AU Zaher, HS
   Green, R
AF Zaher, Hani S.
   Green, Rachel
TI Quality control by the ribosome following peptide bond formation
SO NATURE
LA English
DT Article
ID aminoacyl-transfer-rna; escherichia-coli; codon recognition; release factors; e-site; translation; accuracy; discrimination; termination; errors
AB The overall fidelity of protein synthesis has been thought to rely on the combined accuracy of two basic processes: the aminoacylation of transfer RNAs with their cognate amino acid by the aminoacyl- tRNA synthetases, and the selection of cognate aminoacyl- tRNAs by the ribosome in cooperation with the GTPase elongation factor EF- Tu. These two processes, which together ensure the specific acceptance of a correctly charged cognate tRNA into the aminoacyl ( A) site, operate before peptide bond formation. Here we report the identification of an additional mechanism that contributes to high fidelity protein synthesis after peptidyl transfer, using a well- defined in vitro bacterial translation system. In this retrospective quality control step, the incorporation of an amino acid from a non- cognate tRNA into the growing polypeptide chain leads to a general loss of specificity in the A site of the ribosome, and thus to a propagation of errors that results in abortive termination of protein synthesis.
C1 [Zaher, Hani S.; Green, Rachel] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
C3 Howard Hughes Medical Institute; Johns Hopkins University
RP Green, R (corresponding author), Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
EM ragreen@jhmi.edu
FU National Institutes of Health; Howard Hughes Medical Institute.
NR 39
TC 168
Z9 252
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 8
PY 2009
VL 457
IS 7226
BP 161
EP U51
DI 10.1038/nature07582
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200025
PM 19092806
DA 2026-03-09
ER

PT J
AU Collins, CA
   Stott, JP
   Hilton, M
   Kay, ST
   Stanford, SA
   Davidson, M
   Hosmer, M
   Hoyle, B
   Liddle, A
   Lloyd-Davies, E
   Mann, RG
   Mehrtens, N
   Miller, CJ
   Nichol, RC
   Romer, AK
   Sahlén, M
   Viana, PTP
   West, MJ
AF Collins, Chris A.
   Stott, John P.
   Hilton, Matt
   Kay, Scott T.
   Stanford, S. Adam
   Davidson, Michael
   Hosmer, Mark
   Hoyle, Ben
   Liddle, Andrew
   Lloyd-Davies, Ed
   Mann, Robert G.
   Mehrtens, Nicola
   Miller, Christopher J.
   Nichol, Robert C.
   Romer, A. Kathy
   Sahlen, Martin
   Viana, Pedro T. P.
   West, Michael J.
TI Early assembly of the most massive galaxies
SO NATURE
LA English
DT Article
ID brightest cluster galaxy; luminous red galaxy; evolution; xmm; discovery; stellar; z=1.26
AB The current consensus is that galaxies begin as small density fluctuations in the early Universe and grow by in situ star formation and hierarchical merging(1). Stars begin to form relatively quickly in sub-galactic-sized building blocks called haloes which are subsequently assembled into galaxies. However, exactly when this assembly takes place is a matter of some debate(2,3). Here we report that the stellar masses of brightest cluster galaxies, which are the most luminous objects emitting stellar light, some 9 billion years ago are not significantly different from their stellar masses today. Brightest cluster galaxies are almost fully assembled 425 billion years after the Big Bang, having grown to more than 90 per cent of their final stellar mass by this time. Our data conflict with the most recent galaxy formation models(4,5) based on the largest simulations of dark-matter halo development(1). These models predict protracted formation of brightest cluster galaxies over a Hubble time, with only 22 per cent of the stellar mass assembled at the epoch probed by our sample. Our findings suggest a new picture in which brightest cluster galaxies experience an early period of rapid growth rather than prolonged hierarchical assembly.
C1 [Collins, Chris A.; Stott, John P.; Hilton, Matt] Liverpool John Moores Univ, Astrophys Res Inst, Birkenhead CH41 1LD, Merseyside, England.
   [Hilton, Matt] Univ KwaZulu Natal, Sch Math Sci, Astrophys & Cosmol Res Unit, ZA-4000 Durban, South Africa.
   [Hilton, Matt] S African Astron Observ, ZA-7935 Cape Town, South Africa.
   [Kay, Scott T.] Univ Manchester, Sch Phys & Astron, Jodrell Bank, Ctr Astrophys, Manchester M13 9PL, Lancs, England.
   [Stanford, S. Adam] Univ Calif Davis, Dept Phys, Davis, CA 95616 USA.
   [Stanford, S. Adam] Lawrence Livermore Natl Lab, Inst Geophys & Planetary Phys, Livermore, CA 94551 USA.
   [Davidson, Michael; Mann, Robert G.] Univ Edinburgh, Royal Observ, Inst Astron, SUPA, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Hosmer, Mark; Liddle, Andrew; Lloyd-Davies, Ed; Mehrtens, Nicola; Romer, A. Kathy; Sahlen, Martin] Univ Sussex, Ctr Astron, Brighton BN1 9QH, E Sussex, England.
   [Hoyle, Ben; Nichol, Robert C.] Univ Portsmouth, ICG, Portsmouth PO1 2EG, Hants, England.
   [Miller, Christopher J.] Natl Opt Astron Observ, Cerro Tololo Inter Amer Observ, Tucson, AZ 85719 USA.
   [Viana, Pedro T. P.] Univ Porto, Fac Ciencias, Dept Matemat Aplicada, P-4169007 Oporto, Portugal.
   [Viana, Pedro T. P.] Univ Porto, Ctr Astrofis, P-4150762 Oporto, Portugal.
   [West, Michael J.] European So Observ, Santiago 19001, Chile.
C3 Liverpool John Moores University; University of Kwazulu Natal; National Research Foundation - South Africa; South African Astronomical Observatory; University of Manchester; Jodrell Bank Centre for Astrophysics; University of California System; University of California Davis; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Edinburgh; University of Sussex; University of Portsmouth; National Optical Astronomy Observatory; Universidade do Porto; Universidade do Porto; European Southern Observatory
RP Collins, CA (corresponding author), Liverpool John Moores Univ, Astrophys Res Inst, 12 Quays House, Birkenhead CH41 1LD, Merseyside, England.
EM cac@astro.livjm.ac.uk
FU NASA; Liverpool John Moores University; STFC; South African National Research Foundation; Research in Astronomy, Inc.; STFC [ST/H001581/1, PP/E001149/1, ST/F002858/1, ST/F006977/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/H001581/1, PP/E001149/1, ST/F002858/1, ST/F006977/1] Funding Source: researchfish
NR 30
TC 141
Z9 153
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 APR 2
PY 2009
VL 458
IS 7238
BP 603
EP 606
DI 10.1038/nature07865
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200034
PM 19340075
DA 2026-03-09
ER

PT J
AU Cook, PJ
   Ju, BG
   Telese, F
   Wang, XT
   Glass, CK
   Rosenfeld, MG
AF Cook, Peter J.
   Ju, Bong Gun
   Telese, Francesca
   Wang, Xiangting
   Glass, Christopher K.
   Rosenfeld, Michael G.
TI Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions
SO NATURE
LA English
DT Article
ID double-strand breaks; dna-damage response; histone h2ax; eyes absent; genomic instability; signaling pathways; cellular-response; drosophila eye; in-vivo; protein
AB Life and death fate decisions allow cells to avoid massive apoptotic death in response to genotoxic stress. Although the regulatory mechanisms and signalling pathways controlling DNA repair and apoptosis are well characterized, the precise molecular strategies that determine the ultimate choice of DNA repair and survival or apoptotic cell death remain incompletely understood. Here we report that a protein tyrosine phosphatase, EYA, is involved in promoting efficient DNA repair rather than apoptosis in response to genotoxic stress in mammalian embryonic kidney cells by executing a damage-signal-dependent dephosphorylation of an H2AX carboxy-terminal tyrosine phosphate (Y142). This post-translational modification determines the relative recruitment of either DNA repair or pro-apoptotic factors to the tail of serine phosphorylated histone H2AX (gamma-H2AX) and allows it to function as an active determinant of repair/survival versus apoptotic responses to DNA damage, revealing an additional phosphorylation-dependent mechanism that modulates survival/apoptotic decisions during mammalian organogenesis.
C1 [Cook, Peter J.; Ju, Bong Gun; Telese, Francesca; Wang, Xiangting; Rosenfeld, Michael G.] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Cook, Peter J.] Univ Calif San Diego, Sch Med, Dept Biol Grad Program, La Jolla, CA 92093 USA.
   [Ju, Bong Gun] Sogang Univ, Dept Life Sci, Seoul 121742, South Korea.
   [Glass, Christopher K.] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Sogang University; University of California System; University of California San Diego
RP Rosenfeld, MG (corresponding author), Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
EM mrosenfeld@ucsd.edu
FU NIH; NCI; Sogang University Research Grant of 2008; USAMRAA; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK039949] Funding Source: NIH RePORTER
NR 35
TC 452
Z9 555
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 2
PY 2009
VL 458
IS 7238
BP 591
EP U53
DI 10.1038/nature07849
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200032
PM 19234442
DA 2026-03-09
ER

PT J
AU Calcraft, PJ
   Ruas, M
   Pan, Z
   Cheng, XT
   Arredouani, A
   Hao, XM
   Tang, JS
   Rietdorf, K
   Teboul, L
   Chuang, KT
   Lin, PH
   Xiao, R
   Wang, CB
   Zhu, YM
   Lin, YK
   Wyatt, CN
   Parrington, J
   Ma, JJ
   Evans, AM
   Galione, A
   Zhu, MX
AF Calcraft, Peter J.
   Ruas, Margarida
   Pan, Zui
   Cheng, Xiaotong
   Arredouani, Abdelilah
   Hao, Xuemei
   Tang, Jisen
   Rietdorf, Katja
   Teboul, Lydia
   Chuang, Kai-Ting
   Lin, Peihui
   Xiao, Rui
   Wang, Chunbo
   Zhu, Yingmin
   Lin, Yakang
   Wyatt, Christopher N.
   Parrington, John
   Ma, Jianjie
   Evans, A. Mark
   Galione, Antony
   Zhu, Michael X.
TI NAADP mobilizes calcium from acidic organelles through two-pore channels
SO NATURE
LA English
DT Article
ID adenine-dinucleotide phosphate; cyclic adp-ribose; pancreatic beta-cells; ca2+ release; inositol trisphosphate; ryanodine receptors; stores; heart; mechanism; messenger
AB Ca2+ mobilization from intracellular stores represents an important cell signalling process(1) that is regulated, in mammalian cells, by inositol-1,4,5-trisphosphate (InsP(3)), cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). InsP(3) and cyclic ADP ribose cause the release of Ca2+ from sarcoplasmic/endoplasmic reticulum stores by the activation of InsP(3) and ryanodine receptors (InsP(3)Rs and RyRs). In contrast, the nature of the intracellular stores targeted by NAADP and the molecular identity of the NAADP receptors remain controversial(1,2), although evidence indicates that NAADP mobilizes Ca2+ from lysosome-related acidic compartments(3,4). Here we show that two-pore channels (TPCs) comprise a family of NAADP receptors, with human TPC1 (also known as TPCN1) and chicken TPC3 (TPCN3) being expressed on endosomal membranes, and human TPC2 (TPCN2) on lysosomal membranes when expressed in HEK293 cells. Membranes enriched with TPC2 show high affinity NAADP binding, and TPC2 underpins NAADP-induced Ca2+ release from lysosome-related stores that is subsequently amplified by Ca2+-induced Ca2+ release by InsP3Rs. Responses to NAADP were abolished by disrupting the lysosomal proton gradient and by ablating TPC2 expression, but were only attenuated by depleting endoplasmic reticulum Ca2+ stores or by blocking InsP3Rs. Thus, TPCs form NAADP receptors that release Ca2+ from acidic organelles, which can trigger further Ca2+ signals via sarcoplasmic/endoplasmic reticulum. TPCs therefore provide new insights into the regulation and organization of Ca2+ signals in animal cells, and will advance our understanding of the physiological role of NAADP.
C1 [Hao, Xuemei; Tang, Jisen; Xiao, Rui; Wang, Chunbo; Zhu, Yingmin; Lin, Yakang; Zhu, Michael X.] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA.
   [Hao, Xuemei; Tang, Jisen; Xiao, Rui; Wang, Chunbo; Zhu, Yingmin; Lin, Yakang; Zhu, Michael X.] Ohio State Univ, Ctr Mol Neurobiol, Columbus, OH 43210 USA.
   [Calcraft, Peter J.; Wyatt, Christopher N.; Evans, A. Mark] Univ Edinburgh, Coll Med & Vet Med, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland.
   [Ruas, Margarida; Cheng, Xiaotong; Arredouani, Abdelilah; Rietdorf, Katja; Chuang, Kai-Ting; Parrington, John; Galione, Antony] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England.
   [Pan, Zui; Lin, Peihui; Ma, Jianjie] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA.
   [Hao, Xuemei] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China.
   [Teboul, Lydia] MRC Harwell, Mary Lyon Ctr, Didcot OX11 0RD, Oxon, England.
C3 University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University of Edinburgh; University of Oxford; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Peking University; MRC Harwell
RP Zhu, MX (corresponding author), Ohio State Univ, Dept Neurosci, 1060 Carmack Rd, Columbus, OH 43210 USA.
EM zhu.55@osu.ed
FU UK Wellcome Trust [070772]; British Heart Foundation; US National Institutes of Health; American Heart Association; British Heart Foundation [FS/05/050]; US National Institutes of Health [P30-NS045758]; MRC [MC_UP_1502/1] Funding Source: UKRI; Medical Research Council [MC_UP_1502/1] Funding Source: researchfish
NR 30
TC 631
Z9 709
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 MAY 28
PY 2009
VL 459
IS 7246
BP 596
EP U130
DI 10.1038/nature08030
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500045
PM 19387438
DA 2026-03-09
ER

PT J
AU Clusel, M
   Corwin, EI
   Siemens, AON
   Brujic, J
AF Clusel, Maxime
   Corwin, Eric I.
   Siemens, Alexander O. N.
   Brujic, Jasna
TI A 'granocentric' model for random packing of jammed emulsions
SO NATURE
LA English
DT Article
ID geometrical approach; dynamics; liquids; density; solids
AB Packing problems are ubiquitous(1,2), ranging from oil extraction through porous rocks to grain storage in silos and the compaction of pharmaceutical powders into tablets. At a given density, particulate systems pack into a mechanically stable and amorphous jammed state(3,4). Previous theoretical studies have explored a connection between this jammed state and the glass transition(4-8), the thermodynamics of jamming(9-12) and geometric modelling of random packings(13-15). Nevertheless, a simple underlying mechanism for the random assembly of athermal particles, analogous to crystalline ordering, remains unknown. Here we use three-dimensional measurements of packings of polydisperse emulsion droplets to build a simple statistical model in which the complexity of the global packing is distilled into a local stochastic process. From the perspective of a single particle, the packing problem is reduced to the random formation of nearest neighbours, followed by a choice of contacts among them. The two key parameters in the model-the available space around a particle and the ratio of contacts to neighbours-are directly obtained from experiments. We demonstrate that this 'granocentric' view captures the properties of the polydisperse emulsion packing-ranging from the microscopic distributions of nearest neighbours and contacts, to local density fluctuations, to the global packing density. Application of our results to monodisperse and bidisperse systems produces quantitative agreement with previously measured trends in global density(16). Our model therefore reveals a general principle of organization for random packing and may provide the foundations for a theory of jammed matter.
C1 [Clusel, Maxime; Corwin, Eric I.; Siemens, Alexander O. N.; Brujic, Jasna] New York Univ, Dept Phys, Ctr Soft Matter Res, New York, NY 10003 USA.
C3 New York University
RP Brujic, J (corresponding author), New York Univ, Dept Phys, Ctr Soft Matter Res, 4 Washington Pl, New York, NY 10003 USA.
EM jb2929@nyu.edu
FU NYU MRSEC [DMR: 0820341]
NR 30
TC 156
Z9 177
U1 2
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 611
EP 615
DI 10.1038/nature08158
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300046
DA 2026-03-09
ER

PT J
AU Pawlowski, M
   Paterek, T
   Kaszlikowski, D
   Scarani, V
   Winter, A
   Zukowski, M
AF Pawlowski, Marcin
   Paterek, Tomasz
   Kaszlikowski, Dagomir
   Scarani, Valerio
   Winter, Andreas
   Zukowski, Marek
TI Information causality as a physical principle
SO NATURE
LA English
DT Article
ID quantum; communication
AB Quantum physics has remarkable distinguishing characteristics. For example, it gives only probabilistic predictions (non-determinism) and does not allow copying of unknown states (no-cloning(1)). Quantum correlations may be stronger than any classical ones(2), but information cannot be transmitted faster than light (no-signalling). However, these features do not uniquely define quantum physics. A broad class of theories exist that share such traits and allow even stronger (than quantum) correlations(3). Here we introduce the principle of 'information causality' and show that it is respected by classical and quantum physics but violated by all no-signalling theories with stronger than (the strongest) quantum correlations. The principle relates to the amount of information that an observer ( Bob) can gain about a data set belonging to another observer (Alice), the contents of which are completely unknown to him. Using all his local resources (which may be correlated with her resources) and allowing classical communication from her, the amount of information that Bob can recover is bounded by the information volume (m) of the communication. Namely, if Alice communicates m bits to Bob, the total information obtainable by Bob cannot be greater than m. For m = 0, information causality reduces to the standard no-signalling principle. However, no-signalling theories with maximally strong correlations would allow Bob access to all the data in any m-bit subset of the whole data set held by Alice. If only one bit is sent by Alice (m = 1), this is tantamount to Bob's being able to access the value of any single bit of Alice's data (but not all of them). Information causality may therefore help to distinguish physical theories from non-physical ones. We suggest that information causality-a generalization of the no-signalling condition-might be one of the foundational properties of nature.
C1 [Pawlowski, Marcin; Zukowski, Marek] Univ Gdansk, Inst Theoret Phys & Astrophys, PL-80952 Gdansk, Poland.
   [Paterek, Tomasz; Kaszlikowski, Dagomir; Scarani, Valerio; Winter, Andreas] Natl Univ Singapore, Ctr Quantum Technol, Singapore 117543, Singapore.
   [Paterek, Tomasz; Kaszlikowski, Dagomir; Scarani, Valerio; Winter, Andreas] Natl Univ Singapore, Dept Phys, Singapore 117543, Singapore.
   [Winter, Andreas] Univ Bristol, Dept Math, Bristol BS8 1TW, Avon, England.
C3 Fahrenheit Universities; University of Gdansk; National University of Singapore; National University of Singapore; University of Bristol
RP Pawlowski, M (corresponding author), Univ Gdansk, Inst Theoret Phys & Astrophys, PL-80952 Gdansk, Poland.
EM dokmpa@univ.gda.pl
FU National Research Foundation; Ministry of Education in Singapore; European Commission through the Integrated Project Qubit Applications; UK Engineering and Physical Sciences Research Council through the Quantum Information Processing Interdisciplinary Research Collaboration; Royal Society Wolfson Merit Award; Philip Leverhulme Prize; EPSRC [EP/D071461/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/D071461/1] Funding Source: researchfish
NR 30
TC 501
Z9 528
U1 3
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 22
PY 2009
VL 461
IS 7267
BP 1101
EP 1104
DI 10.1038/nature08400
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 509BU
UT WOS:000270987600039
PM 19847260
DA 2026-03-09
ER

PT J
AU Wu, YI
   Frey, D
   Lungu, OI
   Jaehrig, A
   Schlichting, I
   Kuhlman, B
   Hahn, KM
AF Wu, Yi I.
   Frey, Daniel
   Lungu, Oana I.
   Jaehrig, Angelika
   Schlichting, Ilme
   Kuhlman, Brian
   Hahn, Klaus M.
TI A genetically encoded photoactivatable Rac controls the motility of living cells
SO NATURE
LA English
DT Article
ID light; binding; rho; dynamics; activation; migration; domains; sites
AB The precise spatio-temporal dynamics of protein activity are often critical in determining cell behaviour, yet for most proteins they remain poorly understood; it remains difficult to manipulate protein activity at precise times and places within living cells. Protein activity has been controlled by light, through protein derivatization with photocleavable moieties(1) or using photoreactive small-molecule ligands(2). However, this requires use of toxic ultraviolet wavelengths, activation is irreversible, and/or cell loading is accomplished via disruption of the cell membrane (for example, through microinjection). Here we have developed a new approach to produce genetically encoded photoactivatable derivatives of Rac1, a key GTPase regulating actin cytoskeletal dynamics in metazoan cells(3,4.) Rac1 mutants were fused to the photoreactive LOV (light oxygen voltage) domain from phototropin(5,6), sterically blocking Rac1 interactions until irradiation unwound a helix linking LOV to Rac1. Photoactivatable Rac1 (PA-Rac1) could be reversibly and repeatedly activated using 458-or 473-nm light to generate precisely localized cell protrusions and ruffling. Localized Rac activation or inactivation was sufficient to produce cell motility and control the direction of cell movement. Myosin was involved in Rac control of directionality but not in Rac-induced protrusion, whereas PAK was required for Rac-induced protrusion. PA-Rac1 was used to elucidate Rac regulation of RhoA in cell motility. Rac and Rho coordinate cytoskeletal behaviours with seconds and submicrometre precision(7,8). Their mutual regulation remains controversial(9), with data indicating that Rac inhibits and/or activates Rho(10,11). Rac was shown to inhibit RhoA in mouse embryonic fibroblasts, with inhibition modulated at protrusions and ruffles. A PA-Rac crystal structure and modelling revealed LOV-Rac interactions that will facilitate extension of this photoactivation approach to other proteins.
C1 [Wu, Yi I.; Lungu, Oana I.; Jaehrig, Angelika; Hahn, Klaus M.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Lungu, Oana I.; Kuhlman, Brian] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
   [Wu, Yi I.; Lungu, Oana I.; Jaehrig, Angelika; Kuhlman, Brian; Hahn, Klaus M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Frey, Daniel; Schlichting, Ilme] Max Planck Inst Med Res, Dept Biomol Mech, D-69120 Heidelberg, Germany.
C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Max Planck Society
RP Hahn, KM (corresponding author), Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
EM yiwu@med.unc.edu; khahn@med.unc.edu
FU American Heart Association; National Institutes of Health [GM057464, GM64346]
NR 29
TC 883
Z9 1114
U1 0
U2 194
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 104
EP U111
DI 10.1038/nature08241
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800039
PM 19693014
DA 2026-03-09
ER

PT J
AU Bokov, K
   Steinberg, SV
AF Bokov, Konstantin
   Steinberg, Sergey V.
TI A hierarchical model for evolution of 23S ribosomal RNA
SO NATURE
LA English
DT Article
ID peptidyl transferase center; angstrom resolution; bond formation; subunit; base; site; origin
AB The emergence of the ribosome constituted a pivotal step in the evolution of life. This event happened nearly four billion years ago, and any traces of early stages of ribosome evolution are generally thought to have completely eroded away. Surprisingly, a detailed analysis of the structure of the modern ribosome reveals a concerted and modular scheme of its early evolution.
C1 [Bokov, Konstantin; Steinberg, Sergey V.] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada.
C3 Universite de Montreal
RP Steinberg, SV (corresponding author), Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada.
EM serguei.chteinberg@umontreal.ca
FU NSERC
NR 25
TC 172
Z9 212
U1 1
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 19
PY 2009
VL 457
IS 7232
BP 977
EP 980
DI 10.1038/nature07749
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400035
PM 19225518
DA 2026-03-09
ER

PT J
AU Liu, RH
   Wu, T
   Wu, G
   Chen, H
   Wang, XF
   Xie, YL
   Ying, JJ
   Yan, YJ
   Li, QJ
   Shi, BC
   Chu, WS
   Wu, ZY
   Chen, XH
AF Liu, R. H.
   Wu, T.
   Wu, G.
   Chen, H.
   Wang, X. F.
   Xie, Y. L.
   Ying, J. J.
   Yan, Y. J.
   Li, Q. J.
   Shi, B. C.
   Chu, W. S.
   Wu, Z. Y.
   Chen, X. H.
TI A large iron isotope effect in SmFeAsO1-xFx and Ba1-xKxFe2As2
SO NATURE
LA English
DT Article
ID superconductivity; coexistence
AB The recent discovery of superconductivity in oxypnictides with a critical transition temperature (T-C) higher than the McMillan limit of 39K (the theoretical maximum predicted by Bardeen-Cooper-Schrieffer theory) has generated great excitement(1-5). Theoretical calculations indicate that the electron-phonon interaction is not strong enough to give rise to such high transition temperatures(6), but strong ferromagnetic/antiferromagnetic fluctuations have been proposed to be responsible(7-9). Superconductivity and magnetism in pnictide superconductors, however, show a strong sensitivity to the crystal lattice, suggesting the possibility of unconventional electron-phonon coupling. Here we report the effect of oxygen and iron isotope substitution on T-C and the spin-density wave (SDW) transition temperature (T-SDW) in the SmFeAsO1-xFx and Ba1-xKxFe2As2 systems. The oxygen isotope effect on T-C and T-SDW is very small, while the iron isotope exponent alpha(C) =-dlnT(C)/dlnM is about 0.35 (0.5 corresponds to the full isotope effect). Surprisingly, the iron isotope exchange shows the same effect on T-SDW as T-C. This indicates that electron-phonon interaction plays some role in the superconducting mechanism, but a simple electron-phonon coupling mechanism seems unlikely because a strong magnon-phonon coupling is included.
C1 [Liu, R. H.; Wu, T.; Wu, G.; Chen, H.; Wang, X. F.; Xie, Y. L.; Ying, J. J.; Yan, Y. J.; Li, Q. J.; Shi, B. C.; Chen, X. H.] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
   [Liu, R. H.; Wu, T.; Wu, G.; Chen, H.; Wang, X. F.; Xie, Y. L.; Ying, J. J.; Yan, Y. J.; Li, Q. J.; Shi, B. C.; Chen, X. H.] Univ Sci & Technol China, Dept Phys, Hefei 230026, Anhui, Peoples R China.
   [Chu, W. S.; Wu, Z. Y.] Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Facil, Beijing 100049, Peoples R China.
   [Chu, W. S.; Wu, Z. Y.] Univ Sci & Technol China, Natl Synchrotron Radiat Lab, Hefei 230026, Anhui, Peoples R China.
C3 Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; Institute of High Energy Physics, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS
RP Chen, XH (corresponding author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
EM chenxh@ustc.edu.cn
FU Nature Science Foundation of China; Ministry of Science and Technology of China and Chinese Academy of Sciences
NR 24
TC 155
Z9 174
U1 1
U2 154
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 7
PY 2009
VL 459
IS 7243
BP 64
EP 67
DI 10.1038/nature07981
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300029
PM 19424151
DA 2026-03-09
ER

PT J
AU Kim, JV
   Kang, SS
   Dustin, ML
   McGavern, DB
AF Kim, Jiyun V.
   Kang, Silvia S.
   Dustin, Michael L.
   McGavern, Dorian B.
TI Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis
SO NATURE
LA English
DT Article
ID blood-brain-barrier; murine lymphocytic choriomeningitis; central-nervous-system; virus-infection; t-cells; anticonvulsant prolongation; chemokine receptor; host-defense; mice; permeability
AB Lymphocytic choriomeningitis virus(1) infection of the mouse central nervous system (CNS) elicits fatal immunopathology through blood - brain barrier breakdown(2) and convulsive seizures(3). Although lymphocytic- choriomeningitis- virus- specific cytotoxic T lymphocytes ( CTLs) are essential for disease(4), their mechanism of action is not known. To gain insights into disease pathogenesis, we observed the dynamics of immune cells in the meninges by two-photon microscopy. Here we report visualization of motile CTLs and massive secondary recruitment of pathogenic monocytes and neutrophils that were required for vascular leakage and acute lethality. CTLs expressed multiple chemoattractants capable of recruiting myelomonocytic cells. We conclude that a CD8(+) T- cell- dependent disorder can proceed in the absence of direct T- cell effector mechanisms and rely instead on CTL- recruited myelomonocytic cells.
C1 [Kim, Jiyun V.; Dustin, Michael L.] NYU, Sch Med, Helen L & Martin S Kimmel Ctr Biol & Med, Skirball Inst Biomol Med,Program Mol Pathogenesis, New York, NY 10016 USA.
   [Kang, Silvia S.; McGavern, Dorian B.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
C3 New York University; Scripps Research Institute
RP Dustin, ML (corresponding author), NYU, Sch Med, Helen L & Martin S Kimmel Ctr Biol & Med, Skirball Inst Biomol Med,Program Mol Pathogenesis, New York, NY 10016 USA.
EM dustin@saturn.med.nyu.edu; mcgad@scripps.edu
FU National Institutes of Health [AI070967-01, AI055037, NS041219-06]; The Burroughs Wellcome Fund; Dana Foundation; National Research Service [NS061447-01]; Multiple Sclerosis Society Center Grant; National Institute of Neurological Disorders and Stroke [ZIANS003112] Funding Source: NIH RePORTER
NR 36
TC 280
Z9 325
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 JAN 8
PY 2009
VL 457
IS 7226
BP 191
EP U85
DI 10.1038/nature07591
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200032
PM 19011611
DA 2026-03-09
ER

PT J
AU Kirchmair, G
   Zähringer, F
   Gerritsma, R
   Kleinmann, M
   Gühne, O
   Cabello, A
   Blatt, R
   Roos, CF
AF Kirchmair, G.
   Zaehringer, F.
   Gerritsma, R.
   Kleinmann, M.
   Guehne, O.
   Cabello, Adan
   Blatt, R.
   Roos, C. F.
TI State-independent experimental test of quantum contextuality
SO NATURE
LA English
DT Article
ID kochen-specker theorem; hidden-variables; trapped ions; bell inequality; violation; mechanics
AB The question of whether quantum phenomena can be explained by classical models with hidden variables is the subject of a long-lasting debate(1,2). In 1964, Bell showed that certain types of classical models cannot explain the quantum mechanical predictions for specific states of distant particles, and some types of hidden variable models(3-9) have been experimentally ruled out. An intuitive feature of classical models is non-contextuality: the property that any measurement has a value independent of other compatible measurements being carried out at the same time. However, a theorem derived by Kochen, Specker and Bell(10-12) shows that non-contextuality is in conflict with quantum mechanics. The conflict resides in the structure of the theory and is independent of the properties of special states. It has been debated whether the Kochen-Specker theorem could be experimentally tested at all(13,14). First tests of quantum contextuality have been proposed only recently, and undertaken with photons(15,16) and neutrons(17,18). But these tests required the generation of special quantum states and left various loopholes open. Here we perform an experiment with trapped ions that demonstrates a state-independent conflict with non-contextuality. The experiment is not subject to the detection loophole and we show that, despite imperfections and possible measurement disturbances, our results cannot be explained in non-contextual terms.
C1 [Kirchmair, G.; Zaehringer, F.; Gerritsma, R.; Kleinmann, M.; Guehne, O.; Blatt, R.; Roos, C. F.] Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
   [Kirchmair, G.; Zaehringer, F.; Gerritsma, R.; Blatt, R.; Roos, C. F.] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Guehne, O.] Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
   [Cabello, Adan] Univ Seville, Dept Fis Aplicada 2, E-41012 Seville, Spain.
C3 Austrian Academy of Sciences; University of Innsbruck; University of Innsbruck; University of Sevilla
RP Roos, CF (corresponding author), Austrian Acad Sci, Inst Quantenopt & Quanteninformat, Otto Hittmair Pl 1, A-6020 Innsbruck, Austria.
EM Christian.Roos@uibk.ac.at
FU Austrian Science Fund (FWF); European Commission; Institut fur Quanteninformation GmbH; Spanish MCI [FIS2008-05596]; Junta de Andalucia Excellence [P06-FQM-02243]; IARPA
NR 30
TC 290
Z9 304
U1 0
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 494
EP +
DI 10.1038/nature08172
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000034
DA 2026-03-09
ER

PT J
AU Khatiwala, S
   Primeau, F
   Hall, T
AF Khatiwala, S.
   Primeau, F.
   Hall, T.
TI Reconstruction of the history of anthropogenic CO2 concentrations in the ocean
SO NATURE
LA English
DT Article
ID deep-water; carbon; transport
AB The release of fossil fuel CO2 to the atmosphere by human activity has been implicated as the predominant cause of recent global climate change(1). The ocean plays a crucial role in mitigating the effects of this perturbation to the climate system, sequestering 20 to 35 per cent of anthropogenic CO2 emissions(2-4). Although much progress has been made in recent years in understanding and quantifying this sink, considerable uncertainties remain as to the distribution of anthropogenic CO2 in the ocean, its rate of uptake over the industrial era, and the relative roles of the ocean and terrestrial biosphere in anthropogenic CO2 sequestration. Here we address these questions by presenting an observationally based reconstruction of the spatially resolved, time-dependent history of anthropogenic carbon in the ocean over the industrial era. Our approach is based on the recognition that the transport of tracers in the ocean can be described by a Green's function, which we estimate from tracer data using a maximum entropy deconvolution technique. Our results indicate that ocean uptake of anthropogenic CO2 has increased sharply since the 1950s, with a small decline in the rate of increase in the last few decades. We estimate the inventory and uptake rate of anthropogenic CO2 in 2008 at 140 +/- 25 Pg C and 2.3 +/- 0.6 Pg C yr(-1), respectively. We find that the Southern Ocean is the primary conduit by which this CO2 enters the ocean (contributing over 40 per cent of the anthropogenic CO2 inventory in the ocean in 2008). Our results also suggest that the terrestrial biosphere was a source of CO2 until the 1940s, subsequently turning into a sink. Taken over the entire industrial period, and accounting for uncertainties, we estimate that the terrestrial biosphere has been anywhere from neutral to a net source of CO2, contributing up to half as muchCO(2) as has been taken up by the ocean over the same period.
C1 [Khatiwala, S.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Primeau, F.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
   [Hall, T.] NASA, Goddard Inst Space Studies, New York, NY 10025 USA.
C3 Columbia University; University of California System; University of California Irvine; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Goddard Institute for Space Studies
RP Khatiwala, S (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
EM spk@ldeo.columbia.edu
FU US NSF [OCE 06-23366, OCE 07-26871]
NR 41
TC 500
Z9 586
U1 1
U2 231
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 19
PY 2009
VL 462
IS 7271
BP 346
EP U110
DI 10.1038/nature08526
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300043
PM 19924213
DA 2026-03-09
ER

PT J
AU Reubi, O
   Blundy, J
AF Reubi, Olivier
   Blundy, Jon
TI A dearth of intermediate melts at subduction zone volcanoes and the petrogenesis of arc andesites
SO NATURE
LA English
DT Article
ID medicine lake volcano; olivine phenocrysts; granitic magmas; plutonic roots; inclusions; crystallization; genesis; crustal; evolution; differentiation
AB Andesites represent a large proportion of the magmas erupted at continental arc volcanoes and are regarded as a major component in the formation of continental crust(1). Andesite petrogenesis is therefore fundamental in terms of both volcanic hazard and differentiation of the Earth. Andesites typically contain a significant proportion of crystals showing disequilibrium petrographic characteristics indicative of mixing or mingling between silicic and mafic magmas, which fuels a long-standing debate regarding the significance of these processes in andesite petrogenesis(2) and ultimately questions the abundance of true liquids with andesitic composition. Central to this debate is the distinction between liquids (or melts) and magmas, mixtures of liquids with crystals, which may or may not be co-genetic. With this distinction comes the realization that bulk-rock chemical analyses of petrologically complex andesites can lead to a blurred picture of the fundamental processes behind arc magmatism. Here we present an alternative view of andesite petrogenesis, based on a review of quenched glassy melt inclusions trapped in phenocrysts, whole-rock chemistry, and high-pressure and high-temperature experiments. We argue that true liquids of intermediate composition (59 to 66 wt% SiO2) are far less common in the sub-volcanic reservoirs of arc volcanoes than is suggested by the abundance of erupted magma within this compositional range. Effective mingling within upper crustal magmatic reservoirs obscures a compositional bimodality of melts ascending from the lower crust, and masks the fundamental role of silicic melts (>= 66 wt% SiO2) beneath intermediate arc volcanoes. This alternative view resolves several puzzling aspects of arc volcanism and provides important clues to the integration of plutonic and volcanic records.
C1 [Reubi, Olivier; Blundy, Jon] Univ Bristol, Dept Earth Sci, Bristol BS8 1RJ, Avon, England.
C3 University of Bristol
RP Reubi, O (corresponding author), ETH, Inst Isotope Geochem & Mineral Resources, CH-8092 Zurich, Switzerland.
EM olivier.reubi@erdw.ethz.ch
FU Marie Curie Fellowship; NERC; NERC [IMF010001] Funding Source: UKRI; Natural Environment Research Council [IMF010001] Funding Source: researchfish
NR 37
TC 354
Z9 401
U1 5
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 OCT 29
PY 2009
VL 461
IS 7268
BP 1269
EP U103
DI 10.1038/nature08510
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800046
PM 19865169
DA 2026-03-09
ER

PT J
AU Ge, DL
   Fellay, J
   Thompson, AJ
   Simon, JS
   Shianna, KV
   Urban, TJ
   Heinzen, EL
   Qiu, P
   Bertelsen, AH
   Muir, AJ
   Sulkowski, M
   McHutchison, JG
   Goldstein, DB
AF Ge, Dongliang
   Fellay, Jacques
   Thompson, Alexander J.
   Simon, Jason S.
   Shianna, Kevin V.
   Urban, Thomas J.
   Heinzen, Erin L.
   Qiu, Ping
   Bertelsen, Arthur H.
   Muir, Andrew J.
   Sulkowski, Mark
   McHutchison, John G.
   Goldstein, David B.
TI Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance
SO NATURE
LA English
DT Article
ID peginterferon alpha-2b; ribavirin
AB Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide and is the leading cause of cirrhosis in North America(1). Although the recommended treatment for chronic infection involves a 48-week course of peginterferon-alpha-2b (PegIFN-alpha-2b) or-alpha-2a (PegIFN-alpha-2a) combined with ribavirin (RBV), it is well known that many patients will not be cured by treatment, and that patients of European ancestry have a significantly higher probability of being cured than patients of African ancestry. In addition to limited efficacy, treatment is often poorly tolerated because of side effects that prevent some patients from completing therapy. For these reasons, identification of the determinants of response to treatment is a high priority. Here we report that a genetic polymorphism near the IL28B gene, encoding interferon-lambda-3 (IFN-lambda-3), is associated with an approximately twofold change in response to treatment, both among patients of European ancestry (P = 1.06 x 10(-25)) and African-Americans (P = 2.06 x 10(-3)). Because the genotype leading to better response is in substantially greater frequency in European than African populations, this genetic polymorphism also explains approximately half of the difference in response rates between African-Americans and patients of European ancestry.
C1 [Ge, Dongliang; Fellay, Jacques; Shianna, Kevin V.; Urban, Thomas J.; Heinzen, Erin L.; 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, Duke Clin Res Inst, Durham, NC 27705 USA.
   [Thompson, Alexander J.; Muir, Andrew J.; McHutchison, John G.] Duke Univ, Div Gastroenterol, Sch Med, Durham, NC 27705 USA.
   [Simon, Jason S.; Qiu, Ping; Bertelsen, Arthur H.] 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 d.goldstein@duke.edu
FU National Health and Medical Research Council of Australia; Gastroenterological Society of Australia
NR 19
TC 2894
Z9 3177
U1 2
U2 154
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 399
EP 401
DI 10.1038/nature08309
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100040
PM 19684573
DA 2026-03-09
ER

PT J
AU Kozuka, Y
   Kim, M
   Bell, C
   Kim, BG
   Hikita, Y
   Hwang, HY
AF Kozuka, Y.
   Kim, M.
   Bell, C.
   Kim, B. G.
   Hikita, Y.
   Hwang, H. Y.
TI Two-dimensional normal-state quantum oscillations in a superconducting heterostructure
SO NATURE
LA English
DT Article
ID dielectric-property; srtio3; enhancement; transition; titanate; surface
AB Semiconductor heterostructures provide an ideal platform for studying high-mobility, low-density electrons in reduced dimensions(1-4). The realization of superconductivity in heavily doped diamond(5), silicon(6), silicon carbide(7) and germanium(8) suggests that Cooper pairs eventually may be directly incorporated in semiconductor heterostructures(9), but these newly discovered superconductors are currently limited by their extremely large electronic disorder. Similarly, the electron mean free path in low-dimensional superconducting thin films is usually limited by interface scattering, in single-crystal or polycrystalline samples, or atomic-scale disorder, in amorphous materials, confining these examples to the extreme 'dirty limit'(10). Here we report the fabrication of a high-quality superconducting layer within a thin-film heterostructure based on SrTiO3 ( the first known superconducting semiconductor(11)). By selectively doping a narrow region of SrTiO3 with the electron-donor niobium, we form a superconductor that is two-dimensional, as probed by the anisotropy of the upper critical magnetic field. Unlike in previous examples, however, the electron mobility is high enough that the normal state resistance exhibits Shubnikov-de Haas oscillations that scale with the perpendicular field, indicating two-dimensional states. These results suggest that delta-doped SrTiO3 provides a model system in which to explore the quantum transport and interplay(12) of both superconducting and normal electrons. They also demonstrate that high-quality complex oxide heterostructures can maintain electron coherence on the macroscopic scales probed by transport, as well as on the microscopic scales demonstrated previously(13).
C1 [Kozuka, Y.; Kim, M.; Bell, C.; Kim, B. G.; Hikita, Y.; Hwang, H. Y.] Univ Tokyo, Dept Adv Mat Sci, Chiba 2778561, Japan.
   [Bell, C.; Hwang, H. Y.] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan.
   [Kim, B. G.] Pusan Natl Univ, Dept Phys, Pusan 609735, South Korea.
C3 University of Tokyo; Japan Science & Technology Agency (JST); Pusan National University
RP Hwang, HY (corresponding author), Univ Tokyo, Dept Adv Mat Sci, Chiba 2778561, Japan.
EM hyhwang@k.u-tokyo.ac.jp
NR 30
TC 228
Z9 256
U1 5
U2 246
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 487
EP 490
DI 10.1038/nature08566
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200039
PM 19940921
DA 2026-03-09
ER

PT J
AU Bos, PD
   Zhang, XHF
   Nadal, C
   Shu, WP
   Gomis, RR
   Nguyen, DX
   Minn, AJ
   van de Vijver, MJ
   Gerald, WL
   Foekens, JA
   Massagué, J
AF Bos, Paula D.
   Zhang, Xiang H. -F.
   Nadal, Cristina
   Shu, Weiping
   Gomis, Roger R.
   Nguyen, Don X.
   Minn, Andy J.
   van de Vijver, Marc J.
   Gerald, William L.
   Foekens, John A.
   Massague, Joan
TI Genes that mediate breast cancer metastasis to the brain
SO NATURE
LA English
DT Article
ID lung metastasis; growth-factor; in-vitro; expression; cells; bone; beta; progression; barrier; tissue
AB The molecular basis for breast cancer metastasis to the brain is largely unknown(1,2). Brain relapse typically occurs years after the removal of a breast tumour(2-4), suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood-brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the alpha 2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood-brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver(5,6), suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain(7), the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood-brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.
C1 [Bos, Paula D.; Zhang, Xiang H. -F.; Nadal, Cristina; Shu, Weiping; Gomis, Roger R.; Nguyen, Don X.; Massague, Joan] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA.
   [Minn, Andy J.] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA.
   [Minn, Andy J.] Univ Chicago, Ludwig Ctr Metastasis Res, Chicago, IL 60637 USA.
   [van de Vijver, Marc J.] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands.
   [Gerald, William L.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
   [Foekens, John A.] Erasmus MC, Josephine Nefkens Inst, Dept Med Oncol, Rotterdam, Netherlands.
   [Foekens, John A.] Canc Genom Ctr, Rotterdam, Netherlands.
   [Massague, Joan] Howard Hughes Med Inst, Chevy Chase, MD 20185 USA.
C3 Memorial Sloan Kettering Cancer Center; University of Chicago; University of Chicago; Vrije Universiteit Amsterdam; University of Amsterdam; Academic Medical Center Amsterdam; Memorial Sloan Kettering Cancer Center; Erasmus University Rotterdam; Erasmus MC; Howard Hughes Medical Institute
RP Massagué, J (corresponding author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA.
EM j-massague@ski.mskcc.org
FU National Institutes of Health [U54 CA126518]; Kleberg Foundation and the Hearst Foundation; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO); Howard Hughes Medical Institute; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 35
TC 1461
Z9 1732
U1 4
U2 225
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 18
PY 2009
VL 459
IS 7249
BP 1005
EP U137
DI 10.1038/nature08021
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500047
PM 19421193
DA 2026-03-09
ER

PT J
AU Stefansson, H
   Ophoff, RA
   Steinberg, S
   Andreassen, OA
   Cichon, S
   Rujescu, D
   Werge, T
   Pietiläinen, OPH
   Mors, O
   Mortensen, PB
   Sigurdsson, E
   Gustafsson, O
   Nyegaard, M
   Tuulio-Henriksson, A
   Ingason, A
   Hansen, T
   Suvisaari, J
   Lonnqvist, J
   Paunio, T
   Borglum, AD
   Hartmann, A
   Fink-Jensen, A
   Nordentoft, M
   Hougaard, D
   Norgaard-Pedersen, B
   Böttcher, Y
   Olesen, J
   Breuer, R
   Möller, HJ
   Giegling, I
   Rasmussen, HB
   Timm, S
   Mattheisen, M
   Bitter, I
   Réthelyi, JM
   Magnusdottir, BB
   Sigmundsson, T
   Olason, P
   Mason, G
   Gulcher, JR
   Haraldsson, M
   Fossdal, R
   Thorgeirsson, TE
   Thorsteinsdottir, U
   Ruggeri, M
   Tosato, S
   Franke, B
   Strengman, E
   Kiemeney, LA
   Melle, I
   Djurovic, S
   Abramova, L
   Kaleda, V
   Sanjuan, J
   de Frutos, R
   Bramon, E
   Vassos, E
   Fraser, G
   Ettinger, U
   Picchioni, M
   Walker, N
   Toulopoulou, T
   Need, AC
   Ge, D
   Yoon, JL
   Shianna, KV
   Freimer, NB
   Cantor, RM
   Murray, R
   Kong, A
   Golimbet, V
   Carracedo, A
   Arango, C
   Costas, J
   Jönsson, EG
   Terenius, L
   Agartz, I
   Petursson, H
   Nöthen, MM
   Rietschel, M
   Matthews, PM
   Muglia, P
   Peltonen, L
   St Clair, D
   Goldstein, DB
   Stefansson, K
   Collier, DA
AF Stefansson, Hreinn
   Ophoff, Roel A.
   Steinberg, Stacy
   Andreassen, Ole A.
   Cichon, Sven
   Rujescu, Dan
   Werge, Thomas
   Pietilainen, Olli P. H.
   Mors, Ole
   Mortensen, Preben B.
   Sigurdsson, Engilbert
   Gustafsson, Omar
   Nyegaard, Mette
   Tuulio-Henriksson, Annamari
   Ingason, Andres
   Hansen, Thomas
   Suvisaari, Jaana
   Lonnqvist, Jouko
   Paunio, Tiina
   Borglum, Anders D.
   Hartmann, Annette
   Fink-Jensen, Anders
   Nordentoft, Merete
   Hougaard, David
   Norgaard-Pedersen, Bent
   Bottcher, Yvonne
   Olesen, Jes
   Breuer, Rene
   Moeller, Hans-Jurgen
   Giegling, Ina
   Rasmussen, Henrik B.
   Timm, Sally
   Mattheisen, Manuel
   Bitter, Istvan
   Rethelyi, Janos M.
   Magnusdottir, Brynja B.
   Sigmundsson, Thordur
   Olason, Pall
   Mason, Gisli
   Gulcher, Jeffrey R.
   Haraldsson, Magnus
   Fossdal, Ragnheidur
   Thorgeirsson, Thorgeir E.
   Thorsteinsdottir, Unnur
   Ruggeri, Mirella
   Tosato, Sarah
   Franke, Barbara
   Strengman, Eric
   Kiemeney, Lambertus A.
   Melle, Ingrid
   Djurovic, Srdjan
   Abramova, Lilia
   Kaleda, Vasily
   Sanjuan, Julio
   de Frutos, Rosa
   Bramon, Elvira
   Vassos, Evangelos
   Fraser, Gillian
   Ettinger, Ulrich
   Picchioni, Marco
   Walker, Nicholas
   Toulopoulou, Timi
   Need, Anna C.
   Ge, Dongliang
   Yoon, Joeng Lim
   Shianna, Kevin V.
   Freimer, Nelson B.
   Cantor, Rita M.
   Murray, Robin
   Kong, Augustine
   Golimbet, Vera
   Carracedo, Angel
   Arango, Celso
   Costas, Javier
   Joensson, Erik G.
   Terenius, Lars
   Agartz, Ingrid
   Petursson, Hannes
   Nothen, Markus M.
   Rietschel, Marcella
   Matthews, Paul M.
   Muglia, Pierandrea
   Peltonen, Leena
   St Clair, David
   Goldstein, David B.
   Stefansson, Kari
   Collier, David A.
TI Common variants conferring risk of schizophrenia
SO NATURE
LA English
DT Article
ID genome-wide association; mental-retardation; gene; neurogranin; population; deletions; diseases; 1q21.1; memory; scan
AB Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders(1-3). The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized(4). Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
C1 [Stefansson, Hreinn; Steinberg, Stacy; Gustafsson, Omar; Ingason, Andres; Bottcher, Yvonne; Olason, Pall; Mason, Gisli; Gulcher, Jeffrey R.; Fossdal, Ragnheidur; Thorgeirsson, Thorgeir E.; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari] DeCODE Genet, IS-101 Reykjavik, Iceland.
   [Ophoff, Roel A.; Strengman, Eric] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CG Utrecht, Netherlands.
   [Ophoff, Roel A.; Strengman, Eric] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands.
   [Ophoff, Roel A.; Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA.
   [Andreassen, Ole A.; Melle, Ingrid] Ullevaal Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway.
   [Andreassen, Ole A.; Melle, Ingrid] Univ Oslo, Inst Psychiat, N-0407 Oslo, Norway.
   [Cichon, Sven; Mattheisen, Manuel] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany.
   [Rujescu, Dan; Hartmann, Annette; Giegling, Ina] Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-80336 Munich, Germany.
   [Werge, Thomas; Hansen, Thomas; Rasmussen, Henrik B.] Univ Copenhagen, Mental Hlth Ctr Sct Hans, Res Inst Biol Psychiat, DK-4000 Roskilde, Denmark.
   [Pietilainen, Olli P. H.; Peltonen, Leena] Biomedicum Helsinki, Inst Mol Med, Helsinki 00290, Finland.
   [Pietilainen, Olli P. H.; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Mors, Ole; Borglum, Anders D.] Aarhus Univ Hosp, Ctr Psychiat Res, DK-8240 Risskov, Denmark.
   [Mortensen, Preben B.] Aarhus Univ, Natl Ctr Register Based Res, DK-8000 Aarhus, Denmark.
   [Sigurdsson, Engilbert; Magnusdottir, Brynja B.; Sigmundsson, Thordur; Haraldsson, Magnus; Petursson, Hannes] Natl Univ Hosp Reykjavik, Dept Psychiat, IS-101 Reykjavik, Iceland.
   [Sigurdsson, Engilbert; Magnusdottir, Brynja B.; Sigmundsson, Thordur; Haraldsson, Magnus; Petursson, Hannes; Stefansson, Kari] Univ Iceland, Sch Med, IS-101 Reykjavik, Iceland.
   [Nyegaard, Mette; Borglum, Anders D.] Aarhus Univ, Dept Human Genet, DK-8000 Aarhus C, Denmark.
   [Suvisaari, Jaana; Lonnqvist, Jouko] Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, FIN-00300 Helsinki, Finland.
   [Paunio, Tiina] Biomedicum, Natl Publ Hlth Inst, Dept Mol Med, Helsinki 00290, Finland.
   [Fink-Jensen, Anders] Copenhagen Univ Hosp, Mental Hlth Ctr, Rigshosp, DK-2100 Copenhagen O, Denmark.
   [Nordentoft, Merete] Bispebjerg Hosp, Psychiat Ctr Bisbebjerg, DK-2400 Copenhagen NV, Denmark.
   [Hougaard, David; Norgaard-Pedersen, Bent] State Serum Inst, Sect Neonatal Screening & Hormones, Dept Clin Chem & Immunol, DK-2300 Copenhagen S, Denmark.
   [Olesen, Jes] Glostrup Cty Hosp, Dept Neurol, DK-2600 Glostrup, Denmark.
   [Breuer, Rene; Rietschel, Marcella] Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Germany.
   [Moeller, Hans-Jurgen] Univ Munich, Dept Psychiat, D-80336 Munich, Germany.
   [Timm, Sally] Copenhagen Univ Hosp, Mental Hlth Ctr Frederiksberg, DK-2000 Copenhagen, Denmark.
   [Bitter, Istvan; Rethelyi, Janos M.] Semmelweis Univ, Dept Psychiat & Psychotherapy, H-1083 Budapest, Hungary.
   [Ruggeri, Mirella; Tosato, Sarah] Univ Verona, Sect Psychiat & Clin Psychol, I-37134 Verona, Italy.
   [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
   [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands.
   [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands.
   [Djurovic, Srdjan] Ullevaal Univ Hosp, Dept Med Genet, N-0407 Oslo, Norway.
   [Djurovic, Srdjan] Univ Oslo, Inst Psychiat, N-0407 Oslo, Norway.
   [Abramova, Lilia; Kaleda, Vasily; Golimbet, Vera] Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 117152, Russia.
   [Sanjuan, Julio] Univ Valencia, Unidad Psiquiatria, Fac Biol, CIBERSAM, Valencia 46010, Spain.
   [de Frutos, Rosa] Univ Valencia, Dept Genet, Fac Biol, CIBERSAM, Valencia 46010, Spain.
   [Bramon, Elvira; Vassos, Evangelos; Ettinger, Ulrich; Picchioni, Marco; Murray, Robin] Kings Coll London, Inst Psychiat, Div Psychol Med, London SE5 8AF, England.
   [Vassos, Evangelos; Ettinger, Ulrich; Toulopoulou, Timi; Murray, Robin] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.
   [Fraser, Gillian; St Clair, David] Univ Aberdeen, Royal Cornhill Hosp, Dept Mental Hlth, Aberdeen AB25 2ZD, Scotland.
   [Walker, Nicholas] Ravenscraig Hosp, Greenock PA16 9HA, Scotland.
   [Need, Anna C.; Ge, Dongliang; Shianna, Kevin V.; Goldstein, David B.] Duke Univ, Inst Genome Sci & Policy, Ctr Populat Genom & Pharmacogenet, Durham, NC 27708 USA.
   [Yoon, Joeng Lim; Cantor, Rita M.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Carracedo, Angel] Univ Santiago de Compostela, Fdn Publ Galega Med, Xenom Complexo Univ Hosp Santiago, IML, Santiago De Compostela 15782, Spain.
   [Carracedo, Angel] Univ Santiago de Compostela, CIBERER, IML, Santiago De Compostela 15782, Spain.
   [Arango, Celso] Hosp Gen Univ Gregorio Maran, CIBERSAM, Madrid, Spain.
   [Costas, Javier] Fdn Publ Galega Med Xen, Valencia 46010, Spain.
   [Costas, Javier] CIBERER, Valencia 46010, Spain.
   [Joensson, Erik G.; Terenius, Lars; Agartz, Ingrid] Karolinska Hosp & Inst, Dept Clin Neurosci, HUBIN Project, SE-17176 Stockholm, Sweden.
   [Nothen, Markus M.] Univ Bonn, Inst Human Genet, D-53111 Bonn, Germany.
   [Matthews, Paul M.] GlaxoSmithKline, Hammersmith Hosp, Clin Imaging Ctr, Clin Pharmacol & Discovery Med, London W12 ONN, England.
   [Muglia, Pierandrea] GlaxoSmithKline R&D, Med Genet, I-37135 Verona, Italy.
   [Collier, David A.] Sichuan Univ, W China Hosp, Dept Psychiat, Sichuan 610065, Peoples R China.
C3 Decode Genetics; Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; University of California System; University of California Los Angeles; University of Oslo; University of Oslo; University of Bonn; University of Munich; University of Copenhagen; University of Helsinki; Wellcome Trust Sanger Institute; Aarhus University; Aarhus University; Danish National Environmental Research Institute; Landspitali National University Hospital; University of Iceland; Aarhus University; Finland National Institute for Health & Welfare; Finland National Institute for Health & Welfare; University of Helsinki; Rigshospitalet; University of Copenhagen; Copenhagen University Hospital; University of Copenhagen; Copenhagen University Hospital; Bispebjerg Hospital; Statens Serum Institut; University of Copenhagen; Central Institute of Mental Health; Ruprecht Karls University Heidelberg; University of Munich; University of Copenhagen; Copenhagen University Hospital; Semmelweis University; University of Verona; Radboud University Nijmegen; Radboud University Nijmegen; Radboud University Nijmegen; University of Oslo; University of Oslo; Russian Academy of Medical Sciences; CIBER - Centro de Investigacion Biomedica en Red; CIBERSAM; University of Valencia; University of Valencia; CIBER - Centro de Investigacion Biomedica en Red; CIBERSAM; University of London; King's College London; University of London; King's College London; University of Aberdeen; Duke University; University of California System; University of California Los Angeles; Universidade de Santiago de Compostela; CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Universidade de Santiago de Compostela; CIBER - Centro de Investigacion Biomedica en Red; CIBERSAM; General University Gregorio Maranon Hospital; CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Karolinska Institutet; Karolinska University Hospital; University of Bonn; GlaxoSmithKline; Glaxosmithkline United Kingdom; Imperial College London; GlaxoSmithKline; GlaxoSmithKline Italy; Sichuan University
RP Stefansson, K (corresponding author), DeCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.
EM kari.stefansson@decode.is
FU EU [LSHM-CT-2006-037761, PIAP-GA-2008-218251, HEALTH-F2-2009-223423]; NIMH [R01 MH078075]; German Federal Ministry of Education and Research [NGFN-2]; Marie Curie [PIAP-GA-2008-218251]; GlaxoSmithKline; National Institutes of Health [1R01HL087679-01]; STAMPEED; National Institute for Health Research [PDA/02/06/016] Funding Source: researchfish
NR 27
TC 1334
Z9 1512
U1 0
U2 248
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 6
PY 2009
VL 460
IS 7256
BP 744
EP U99
DI 10.1038/nature08186
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300040
PM 19571808
DA 2026-03-09
ER

PT J
AU Swiezewski, S
   Liu, FQ
   Magusin, A
   Dean, C
AF Swiezewski, Szymon
   Liu, Fuquan
   Magusin, Andreas
   Dean, Caroline
TI Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target
SO NATURE
LA English
DT Article
ID protein; vernalization; fca; normalization; expression; thaliana; requires; homolog; genome; genes
AB Transcription in eukaryotic genomes generates an extensive array of non-protein-coding RNA, the functional significance of which is mostly unknown(1). We are investigating the link between non-coding RNA and chromatin regulation through analysis of FLC - a regulator of flowering time in Arabidopsis and a target of several chromatin pathways. Here we use an unbiased strategy to characterize non-coding transcripts of FLC and show that sense/antisense transcript levels correlate in a range of mutants and treatments, but change independently in cold-treated plants. Prolonged cold epigenetically silences FLC in a Polycomb-mediated process called vernalization(2). Our data indicate that upregulation of long non-coding antisense transcripts covering the entire FLC locus may be part of the cold-sensing mechanism. Induction of these antisense transcripts occurs earlier than, and is independent of, other vernalization markers(3) and coincides with a reduction in sense transcription. We show that addition of the FLC antisense promoter sequences to a reporter gene is sufficient to confer cold-induced silencing of the reporter. Our data indicate that cold-induced FLC antisense transcripts have an early role in the epigenetic silencing of FLC, acting to silence FLC transcription transiently. Recruitment of the Polycomb machinery then confers the epigenetic memory. Antisense transcription events originating from 3' ends of genes might be a general mechanism to regulate the corresponding sense transcription in a condition/stage-dependent manner.
C1 [Swiezewski, Szymon; Liu, Fuquan; Magusin, Andreas; Dean, Caroline] John Innes Ctr Plant Sci Res, Norwich NR4 7UH, Norfolk, England.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre
RP Dean, C (corresponding author), John Innes Ctr Plant Sci Res, Norwich NR4 7UH, Norfolk, England.
EM caroline.dean@bbsrc.ac.uk
FU BBSRC [BB/D010799/1]; NERC [NE/C507629]; EU SIROCCO [LSHG-CT-2006-037900]; Biotechnology and Biological Sciences Research Council [BB/D010799/1, BBS/E/J/000CA305] Funding Source: researchfish; Natural Environment Research Council [NE/C507629/1] Funding Source: researchfish; BBSRC [BB/D010799/1, BBS/E/J/000CA305] Funding Source: UKRI
NR 32
TC 711
Z9 826
U1 1
U2 246
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 799
EP U122
DI 10.1038/nature08618
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900041
PM 20010688
DA 2026-03-09
ER

PT J
AU Conard, NJ
AF Conard, Nicholas J.
TI A female figurine from the basal Aurignacian of Hohle Fels Cave in southwestern Germany
SO NATURE
LA English
DT Article
ID western eurasia; late middle; europe
AB Despite well over 100 years of research and debate, the origins of art remain contentious(1-3). In recent years, abstract depictions have been documented at southern African sites dating to similar to 75 kyr before present ( BP) 4,5, and the earliest figurative art, which is often seen as an important proxy for advanced symbolic communication, has been documented in Europe as dating to between 30 and 40 kyr BP2. Here I report the discovery of a female mammoth-ivory figurine in the basal Aurignacian deposit at Hohle Fels Cave in the Swabian Jura of southwestern Germany during excavations in 2008. This figurine was produced at least 35,000 calendar years ago, making it one of the oldest known examples of figurative art. This discovery predates the well-known Venuses from the Gravettian culture by at least 5,000 years and radically changes our views of the context and meaning of the earliest Palaeolithic art.
C1 Univ Tubingen, Abt Altere Urgeschichte & Quartarokol, Inst Ur & Fruhgeschichte & Archaol Mittelalters, D-72070 Tubingen, Germany.
C3 Eberhard Karls University of Tubingen
RP Conard, NJ (corresponding author), Univ Tubingen, Abt Altere Urgeschichte & Quartarokol, Inst Ur & Fruhgeschichte & Archaol Mittelalters, D-72070 Tubingen, Germany.
EM nicholas.conard@uni-tuebingen.de
FU Deutsche Forschungsgemeinschaft; University of Tubingen; Heidelberger Akademie der Wissenschaften; Landesamt fur Denkmalpflege Baden-Wurttemberg; Alb-Donau-Kreis; Heidelberg Cement; Museumsgesellschaft Schelklingen; Gesellschaft fur Urgeschichte
NR 28
TC 236
Z9 284
U1 0
U2 27
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 248
EP 252
DI 10.1038/nature07995
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100040
PM 19444215
DA 2026-03-09
ER

PT J
AU Pagani, M
   Caldeira, K
   Berner, R
   Beerling, DJ
AF Pagani, Mark
   Caldeira, Ken
   Berner, Robert
   Beerling, David J.
TI The role of terrestrial plants in limiting atmospheric CO2 decline over the past 24 million years
SO NATURE
LA English
DT Article
ID carbon-cycle; evolution; climate; model; vegetation; feedbacks; dynamics; leaves; ma
AB Environmental conditions during the past 24 million years are thought to have been favourable for enhanced rates of atmospheric carbon dioxide drawdown by silicate chemical weathering(1-7). Proxy records indicate, however, that the Earth's atmospheric carbon dioxide concentrations did not fall below about 200-250 parts per million during this period(8). The stabilization of atmospheric carbon dioxide concentrations near this minimum value suggests that strong negative feedback mechanisms inhibited further drawdown of atmospheric carbon dioxide by high rates of global silicate rock weathering. Here we investigate one possible negative feedback mechanism, occurring under relatively low carbon dioxide concentrations and in warm climates, that is related to terrestrial plant productivity and its role in the decomposition of silicate minerals(9-11). We use simulations of terrestrial and geochemical carbon cycles and available experimental evidence to show that vegetation activity in upland regions of active orogens was severely limited by near-starvation of carbon dioxide in combination with global warmth over this period. These conditions diminished biotic-driven silicate rock weathering and thereby attenuated an important long-term carbon dioxide sink. Although our modelling results are semi-quantitative and do not capture the full range of biogeochemical feedbacks that could influence the climate, our analysis indicates that the dynamic equilibrium between plants, climate and the geosphere probably buffered the minimum atmospheric carbon dioxide concentrations over the past 24 million years.
C1 [Pagani, Mark; Berner, Robert] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Caldeira, Ken] Carnegie Inst Sci, Dept Global Ecol, Stanford, CA 94305 USA.
   [Beerling, David J.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
C3 Yale University; Carnegie Institution for Science; University of Sheffield
RP Pagani, M (corresponding author), Yale Univ, Dept Geol & Geophys, POB 6666, New Haven, CT 06520 USA.
EM mark.pagani@yale.edu
FU NSF [OCE-0095734]; DOE [DE-FG02-01ER15173]; Leverhulme Trust; Natural Environment Research Council [NE/E015190/1]; Royal Society-Wolfson Research Merit Award; Yale Climate and Energy Institute; NERC [NE/E015190/1] Funding Source: UKRI; Natural Environment Research Council [NE/E015190/1] Funding Source: researchfish
NR 44
TC 114
Z9 128
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 JUL 2
PY 2009
VL 460
IS 7251
BP 85
EP U94
DI 10.1038/nature08133
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200034
PM 19571882
DA 2026-03-09
ER

PT J
AU Grande, C
   Patel, NH
AF Grande, Cristina
   Patel, Nipam H.
TI Nodal signalling is involved in left-right asymmetry in snails
SO NATURE
LA English
DT Article
ID sea-urchin embryo; conserved role; expression; deuterostm; establishment; inheritance; evolution; inversus; limnaea; axes
AB Many animals display specific internal or external features with left right asymmetry. In vertebrates, the molecular pathway that leads to this asymmetry uses the signalling molecule Nodal, a member of the transforming growth factor-beta superfamily(1), which is expressed in the left lateral plate mesoderm(2), and loss of nodal function produces a randomization of the left - right asymmetry of visceral organs(3,4). Orthologues of nodal have also been described in other deuterostomes, including ascidians and sea urchins(5,6), but no nodal orthologue has been reported in the other two main clades of Bilateria: Ecdysozoa ( including flies and nematodes) and Lophotrochozoa ( including snails and annelids). Here we report the first evidence for a nodal orthologue in a non- deuterostome group. We isolated nodal and Pitx ( one of the targets of Nodal signalling) in two species of snails and found that the side of the embryo that expresses nodal and Pitx is related to body chirality: both genes are expressed on the right side of the embryo in the dextral ( right- handed) species Lottia gigantea and on the left side in the sinistral ( left- handed) species Biomphalaria glabrata. We pharmacologically inhibited the Nodal pathway and found that nodal acts upstream of Pitx, and that some treated animals developed with a loss of shell chirality. These results indicate that the involvement of the Nodal pathway in left - right asymmetry might have been an ancestral feature of the Bilateria.
C1 [Grande, Cristina; Patel, Nipam H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Grande, Cristina; Patel, Nipam H.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Grande, Cristina; Patel, Nipam H.] Univ Calif Berkeley, Ctr Integrat Genom, 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
RP Patel, NH (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM nipam@uclink.berkeley.edu
FU Ministerio de Educacion y Ciencia (Spain); Center for Integrative Genomics
NR 28
TC 218
Z9 248
U1 1
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 19
PY 2009
VL 457
IS 7232
BP 1007
EP 1011
DI 10.1038/nature07603
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400041
PM 19098895
DA 2026-03-09
ER

PT J
AU Lee, G
   Papapetrou, EP
   Kim, H
   Chambers, SM
   Tomishima, MJ
   Fasano, CA
   Ganat, YM
   Menon, J
   Shimizu, F
   Viale, A
   Tabar, V
   Sadelain, M
   Studer, L
AF Lee, Gabsang
   Papapetrou, Eirini P.
   Kim, Hyesoo
   Chambers, Stuart M.
   Tomishima, Mark J.
   Fasano, Christopher A.
   Ganat, Yosif M.
   Menon, Jayanthi
   Shimizu, Fumiko
   Viale, Agnes
   Tabar, Viviane
   Sadelain, Michel
   Studer, Lorenz
TI Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; human es; messenger-rna; differentiation; expression; disease; inhibition; induction; defects
AB The isolation of human induced pluripotent stem cells (iPSCs)(1-3) offers a new strategy for modelling human disease. Recent studies have reported the derivation and differentiation of disease-specific human iPSCs(4-7). However, a key challenge in the field is the demonstration of disease-related phenotypes and the ability to model pathogenesis and treatment of disease in iPSCs. Familial dysautonomia (FD) is a rare but fatal peripheral neuropathy, caused by a point mutation in the IKBKAP(8) gene involved in transcriptional elongation(9). The disease is characterized by the depletion of autonomic and sensory neurons. The specificity to the peripheral nervous system and the mechanism of neuron loss in FD are poorly understood owing to the lack of an appropriate model system. Here we report the derivation of patient-specific FD-iPSCs and the directed differentiation into cells of all three germ layers including peripheral neurons. Gene expression analysis in purified FD-iPSC-derived lineages demonstrates tissue-specific mis-splicing of IKBKAP in vitro. Patient-specific neural crest precursors express particularly low levels of normal IKBKAP transcript, suggesting a mechanism for disease specificity. FD pathogenesis is further characterized by transcriptome analysis and cell-based assays revealing marked defects in neurogenic differentiation and migration behaviour. Furthermore, we use FD-iPSCs for validating the potency of candidate drugs in reversing aberrant splicing and ameliorating neuronal differentiation and migration. Our study illustrates the promise of iPSC technology for gaining new insights into human disease pathogenesis and treatment.
C1 [Papapetrou, Eirini P.; Tomishima, Mark J.; Tabar, Viviane; Sadelain, Michel; Studer, Lorenz] Sloan Kettering Inst, Ctr Cell Engn, New York, NY 10065 USA.
   [Lee, Gabsang; Kim, Hyesoo; Chambers, Stuart M.; Tomishima, Mark J.; Fasano, Christopher A.; Ganat, Yosif M.; Studer, Lorenz] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA.
   [Tomishima, Mark J.] Sloan Kettering Inst, SKI Stem Cell Res Facil, New York, NY 10065 USA.
   [Menon, Jayanthi; Shimizu, Fumiko; Tabar, Viviane; Studer, Lorenz] Sloan Kettering Inst, Dept Neurosurg, New York, NY 10065 USA.
   [Viale, Agnes] Sloan Kettering Inst, Genom Core Facil, New York, NY 10065 USA.
   [Ganat, Yosif M.] Weill Cornell Grad Sch, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine
RP Studer, L (corresponding author), Sloan Kettering Inst, Dev Biol Program, 1275 York Ave, New York, NY 10065 USA.
EM studerl@mskcc.org
FU Starr Foundation; NYSTEM; New York Stem Cell Foundation (NYCSF); Druckenmiller fellowships; Starr Scholar fellowship
NR 30
TC 679
Z9 830
U1 2
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 SEP 17
PY 2009
VL 461
IS 7262
BP 402
EP U100
DI 10.1038/nature08320
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100041
PM 19693009
DA 2026-03-09
ER

PT J
AU Roelofs, J
   Park, S
   Haas, W
   Tian, G
   McAllister, FE
   Huo, Y
   Lee, BH
   Zhang, F
   Shi, YG
   Gygi, SP
   Finley, D
AF Roelofs, Jeroen
   Park, Soyeon
   Haas, Wilhelm
   Tian, Geng
   McAllister, Fiona E.
   Huo, Ying
   Lee, Byung-Hoon
   Zhang, Fan
   Shi, Yigong
   Gygi, Steven P.
   Finley, Daniel
TI Chaperone-mediated pathway of proteasome regulatory particle assembly
SO NATURE
LA English
DT Article
ID yeast 26s proteasome; 20s proteasm; s proteasome; complex; proteins; subunits; atpase; transcription; oncoprotein; substrate
AB The proteasome is a protease that controls diverse processes in eukaryotic cells. Its regulatory particle (RP) initiates the degradation of ubiquitin-protein conjugates by unfolding the substrate and translocating it into the proteasome core particle (CP) to be degraded(1). The RP has 19 subunits, and their pathway of assembly is not understood. Here we show that in the yeast Saccharomyces cerevisiae three proteins are found associated with RP but not with the RP-CP holoenzyme: Nas6, Rpn14 and Hsm3. Mutations in the corresponding genes confer proteasome loss-of-function phenotypes, despite their virtual absence from the holoenzyme. These effects result from deficient RP assembly. Thus, Nas6, Rpn14 and Hsm3 are RP chaperones. The RP contains six ATPases-the Rpt proteins-and each RP chaperone binds to the carboxy-terminal domain of a specific Rpt. We show in an accompanying study(2) that RP assembly is templated through the Rpt C termini, apparently by their insertion into binding pockets in the CP. Thus, RP chaperones may regulate proteasome assembly by directly restricting the accessibility of Rpt C termini to the CP. In addition, competition between the RP chaperones and the CP for Rpt engagement may explain the release of RP chaperones as proteasomes mature.
C1 [Roelofs, Jeroen; Park, Soyeon; Haas, Wilhelm; Tian, Geng; McAllister, Fiona E.; Huo, Ying; Lee, Byung-Hoon; Gygi, Steven P.; Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Zhang, Fan; Shi, Yigong] Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA.
C3 Harvard University; Harvard Medical School; Princeton University
RP Finley, D (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM daniel_finley@hms.harvard.edu
FU NIH [GM043601, GM67945]; NIH NRSA [5F32GM75737-2]; EMBO; National Institute of General Medical Sciences [R01GM067945] Funding Source: NIH RePORTER
NR 29
TC 148
Z9 185
U1 2
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 JUN 11
PY 2009
VL 459
IS 7248
BP 861
EP 865
DI 10.1038/nature08063
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500043
PM 19412159
DA 2026-03-09
ER

PT J
AU Kato, M
   Sanada, M
   Kato, I
   Sato, Y
   Takita, J
   Takeuchi, K
   Niwa, A
   Chen, YY
   Nakazaki, K
   Nomoto, J
   Asakura, Y
   Muto, S
   Tamura, A
   Iio, M
   Akatsuka, Y
   Hayashi, Y
   Mori, H
   Igarashi, T
   Kurokawa, M
   Chiba, S
   Mori, S
   Ishikawa, Y
   Okamoto, K
   Tobinai, K
   Nakagama, H
   Nakahata, T
   Yoshino, T
   Kobayashi, Y
   Ogawa, S
AF Kato, Motohiro
   Sanada, Masashi
   Kato, Itaru
   Sato, Yasuharu
   Takita, Junko
   Takeuchi, Kengo
   Niwa, Akira
   Chen, Yuyan
   Nakazaki, Kumi
   Nomoto, Junko
   Asakura, Yoshitaka
   Muto, Satsuki
   Tamura, Azusa
   Iio, Mitsuru
   Akatsuka, Yoshiki
   Hayashi, Yasuhide
   Mori, Hiraku
   Igarashi, Takashi
   Kurokawa, Mineo
   Chiba, Shigeru
   Mori, Shigeo
   Ishikawa, Yuichi
   Okamoto, Koji
   Tobinai, Kensei
   Nakagama, Hitoshi
   Nakahata, Tatsutoshi
   Yoshino, Tadashi
   Kobayashi, Yukio
   Ogawa, Seishi
TI Frequent inactivation of A20 in B-cell lymphomas
SO NATURE
LA English
DT Article
ID nf-kappa-b; classical hodgkin lymphoma; systemic-lupus-erythematosus; necrosis factor-alpha; zinc-finger protein; epstein-barr-virus; activation; tnfaip3; gene; inhibitor
AB A20 is a negative regulator of the NF-kappa B pathway and was initially identified as being rapidly induced after tumour-necrosis factor-alpha stimulation(1). It has a pivotal role in regulation of the immune response and prevents excessive activation of NF-kappa B in response to a variety of external stimuli(2-7); recent genetic studies have disclosed putative associations of polymorphic A20 (also called TNFAIP3) alleles with autoimmune disease risk(8,9). However, the involvement of A20 in the development of human cancers is unknown. Here we show, using a genome-wide analysis of genetic lesions in 238 B-cell lymphomas, that A20 is a common genetic target in B-lineage lymphomas. A20 is frequently inactivated by somatic mutations and/or deletions in mucosa-associated tissue lymphoma (18 out of 87; 21.8%) and Hodgkin's lymphoma of ;nodular sclerosis histology (5 out of 15; 33.3%), and, to a lesser extent, in other B-lineage lymphomas. When re-expressed in a lymphoma-derived cell line with no functional A20 alleles, wildtype A20, but not mutant A20, resulted in suppression of cell growth and induction of apoptosis, accompanied by down-regulation of NF-kappa B activation. The A20-deficient cells stably generated tumours in immunodeficient mice, whereas the tumorigenicity was effectively suppressed by re-expression of A20. In A20-deficient cells, suppression of both cell growth and NF-kappa B activity due to re-expression of A20 depended, at least partly, on cell-surface-receptor signalling, including the tumour-necrosis factor receptor. Considering the physiological function of A20 in the negative modulation of NF-kappa B activation induced by multiple upstream stimuli, our findings indicate that uncontrolled signalling of NF-kappa B caused by loss of A20 function is involved in the pathogenesis of subsets of B-lineage lymphomas.
C1 [Kato, Motohiro; Sanada, Masashi; Takita, Junko; Chen, Yuyan; Nakazaki, Kumi; Muto, Satsuki; Tamura, Azusa; Iio, Mitsuru; Ogawa, Seishi] Univ Tokyo, Canc Genom Project, Bunkyo Ku, Tokyo 1138655, Japan.
   [Kato, Motohiro; Takita, Junko; Chen, Yuyan; Igarashi, Takashi] Univ Tokyo, Dept Pediat, Bunkyo Ku, Tokyo 1138655, Japan.
   [Takita, Junko; Chiba, Shigeru] Univ Tokyo, Dept Cell Therapy & Transplantat Med, Bunkyo Ku, Tokyo 1138655, Japan.
   [Nakazaki, Kumi; Kurokawa, Mineo] Univ Tokyo, Dept Hematol & Oncol, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan.
   [Sanada, Masashi; Nakazaki, Kumi; Ogawa, Seishi] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Kawaguchi, Saitama 3320012, Japan.
   [Kato, Itaru; Niwa, Akira; Nakahata, Tatsutoshi] Kyoto Univ, Grad Sch Med, Dept Pediat, Sakyo Ku, Kyoto 6068507, Japan.
   [Sato, Yasuharu; Yoshino, Tadashi] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol, Kita Ku, Okayama 7008558, Japan.
   [Takeuchi, Kengo; Ishikawa, Yuichi] Japanese Fdn Canc Res, Inst Canc, Div Pathol, Koto Ku, Tokyo 1358550, Japan.
   [Nomoto, Junko; Asakura, Yoshitaka; Tobinai, Kensei; Kobayashi, Yukio] Natl Canc Ctr, Div Hematol, Chuo Ku, Tokyo 1040045, Japan.
   [Okamoto, Koji; Nakagama, Hitoshi] Natl Canc Ctr, Early Oncogenesis Res Project, Res Inst, Chuo Ku, Tokyo 1040045, Japan.
   [Asakura, Yoshitaka] Aichi Canc Ctr, Res Inst, Div Immunol, Chikusa Ku, Nagoya, Aichi 4648681, Japan.
   [Hayashi, Yasuhide] Gunma Childrens Med Ctr, Shibukawa 3778577, Japan.
   [Mori, Hiraku] Showa Univ, Fujigaoka Hosp, Div Hematol, Aoba Ku, Yokohama, Kanagawa 2278501, Japan.
   [Mori, Shigeo] Teikyo Univ, Sch Med, Dept Pathol, Itabashi Ku, Tokyo 1738605, Japan.
C3 University of Tokyo; University of Tokyo; University of Tokyo; University of Tokyo; Japan Science & Technology Agency (JST); Kyoto University; Okayama University; Japanese Foundation for Cancer Research; National Cancer Center - Japan; National Cancer Center - Japan; Aichi Cancer Center; Gunma Children's Medical Centre; Showa Medical University; Teikyo University
RP Ogawa, S (corresponding author), Univ Tokyo, Canc Genom Project, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM ykkobaya@ncc.go.jp; sogawa-tky@umin.ac.jp
FU Core Research for Evolutional Science and Technology; Japan Science and Technology Agency; Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Health, Labor and Welfare of Japan; Grants-in-Aid for Scientific Research [21390316] Funding Source: KAKEN
NR 29
TC 457
Z9 510
U1 1
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 712
EP U118
DI 10.1038/nature07969
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600046
PM 19412163
DA 2026-03-09
ER

PT J
AU Gross, O
   Poeck, H
   Bscheider, M
   Dostert, C
   Hannesschläger, N
   Endres, S
   Hartmann, G
   Tardivel, A
   Schweighoffer, E
   Tybulewicz, V
   Mocsai, A
   Tschopp, J
   Ruland, J
AF Gross, Olaf
   Poeck, Hendrik
   Bscheider, Michael
   Dostert, Catherine
   Hannesschlaeger, Nicole
   Endres, Stefan
   Hartmann, Gunther
   Tardivel, Aubry
   Schweighoffer, Edina
   Tybulewicz, Victor
   Mocsai, Attila
   Tschopp, Juerg
   Ruland, Juergen
TI Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence
SO NATURE
LA English
DT Article
ID nalp3 inflammasome; rheumatoid-arthritis; tyrosine kinase; activation; receptor; il-1-beta; inhibitor; deficient; crystals; immunity
AB Fungal infections represent a serious threat, particularly in immunocompromised patients(1). Interleukin-1 beta (IL-1 beta) is a key pro-inflammatory factor in innate antifungal immunity(2). The mechanism by which the mammalian immune system regulates IL-1 beta production after fungal recognition is unclear. Two signals are generally required for IL-1 beta production: an NF-kappa B-dependent signal that induces the synthesis of pro-IL-1 beta (p35), and a second signal that triggers proteolytic pro-IL-1 beta processing to produce bioactive IL-1 beta (p17) via Caspase-1-containing multiprotein complexes called inflammasomes(3). Here we demonstrate that the tyrosine kinase Syk, operating downstream of several immunoreceptor tyrosine-based activation motif (ITAM)-coupled fungal pattern recognition receptors, controls both pro-IL-1 beta synthesis and inflammasome activation after cell stimulation with Candida albicans. Whereas Syk signalling for pro-IL-1 beta synthesis selectively uses the Card9 pathway, inflammasome activation by the fungus involves reactive oxygen species production and potassium efflux. Genetic deletion or pharmalogical inhibition of Syk selectively abrogated inflammasome activation by C. albicans but not by inflammasome activators such as Salmonella typhimurium or the bacterial toxin nigericin. Nlrp3 (also known as NALP3) was identified as the critical NOD-like receptor family member that transduces the fungal recognition signal to the inflammasome adaptor Asc (Pycard) for Caspase-1 (Casp1) activation and pro-IL-1 beta processing. Consistent with an essential role for Nlrp3 inflammasomes in antifungal immunity, we show that Nlrp3-deficient mice are hypersusceptible to Candida albicans infection. Thus, our results demonstrate the molecular basis for IL-1 beta production after fungal infection and identify a crucial function for the Nlrp3 inflammasome in mammalian host defence in vivo.
C1 [Gross, Olaf; Poeck, Hendrik; Hannesschlaeger, Nicole; Ruland, Juergen] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 3, D-81675 Munich, Germany.
   [Gross, Olaf; Dostert, Catherine; Tardivel, Aubry; Tschopp, Juerg] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
   [Bscheider, Michael; Endres, Stefan] Univ Munich, Dept Internal Med, Div Clin Pharmacol, D-80539 Munich, Germany.
   [Hartmann, Gunther] Univ Klinikum Bonn, Inst Clin Chem & Pharmacol, D-53127 Bonn, Germany.
   [Schweighoffer, Edina; Tybulewicz, Victor] Natl Inst Med Res, London NW7 1AA, England.
   [Mocsai, Attila] Semmelweis Univ, Sch Med, Budapest, Hungary.
C3 Technical University of Munich; University of Lausanne; University of Munich; University of Bonn; MRC National Institute for Medical Research; Semmelweis University
RP Ruland, J (corresponding author), Tech Univ Munich, Klinikum Rechts Isar, Med Klin 3, Ismaninger Str 22, D-81675 Munich, Germany.
EM jruland@lrz.tum.de
FU Marie Curie RTN ApopTrain Fellowship; Swiss National Science Foundation; Deutsche Krebshilfe; Sonderforschungsbereich; Deutsche Forschungsgemeinschaft; MRC [MC_U117527252] Funding Source: UKRI
NR 29
TC 768
Z9 893
U1 2
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2009
VL 459
IS 7245
BP 433
EP U149
DI 10.1038/nature07965
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700047
PM 19339971
DA 2026-03-09
ER

PT J
AU Tsukahara, S
   Kobayashi, A
   Kawabe, A
   Mathieu, O
   Miura, A
   Kakutani, T
AF Tsukahara, Sayuri
   Kobayashi, Akie
   Kawabe, Akira
   Mathieu, Olivier
   Miura, Asuka
   Kakutani, Tetsuji
TI Bursts of retrotransposition reproduced in Arabidopsis
SO NATURE
LA English
DT Article
ID non-cg methylation; dna methylation; diversity; thaliana; genome; transposons; mutation; elements
AB Retrotransposons, which proliferate by reverse transcription of RNA intermediates, comprise a major portion of plant genomes(1,2). Plants often change the genome size and organization during evolution by rapid proliferation and deletion of long terminal repeat (LTR) retrotransposons(3,4). Precise transposon sequences throughout the Arabidopsis thaliana genome and the trans-acting mutations affecting epigenetic states make it an ideal model organism with which to study transposon dynamics(5-9). Here we report the mobilization of various families of endogenous A. thaliana LTR retrotransposons identified through genetic and genomic approaches with high-resolution genomic tiling arrays and mutants in the chromatin-remodelling gene DDM1 (DECREASE IN DNA METHYLATION1)(10,11). Using multiple lines of self-pollinated ddm1 mutant, we detected an increase in copy number, and verified this for various retrotransposons in a gypsy family (ATGP3) and copia families (ATCOPIA13, ATCOPIA21, ATCOPIA93), and also for a DNA transposon of a Mutator family, VANDAL21. A burst of retrotransposition occurred stochastically and independently for each element, suggesting an additional autocatalytic process. Furthermore, comparison of the identified LTR retrotransposons in related Arabidopsis species revealed that a lineage-specific burst of retrotransposition of these elements did indeed occur in natural Arabidopsis populations. The recent burst of retrotransposition in natural population is targeted to centromeric repeats, which is presumably less harmful than insertion into genes. The ddm1-induced retrotransposon proliferations and genome rearrangements mimic the transposon-mediated genome dynamics during evolution and provide experimental systems with which to investigate the controlling molecular factors directly.
C1 [Tsukahara, Sayuri; Kobayashi, Akie; Kawabe, Akira; Miura, Asuka; Kakutani, Tetsuji] Natl Inst Genet, Dept Integrated Genet, Mishima, Shizuoka 4118540, Japan.
   [Tsukahara, Sayuri; Kakutani, Tetsuji] Grad Univ Adv Studies, Sch Life Sci, Dept Genet, Mishima, Shizuoka 4118540, Japan.
   [Mathieu, Olivier] Univ Geneva, Dept Plant Biol, CH-1211 Geneva 4, Switzerland.
   [Mathieu, Olivier] Univ Clermont Ferrand 2, CNRS, INSERMU, GReD,UMR 6247,U931, F-63177 Clermont Ferrand, France.
C3 Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Graduate University for Advanced Studies - Japan; University of Geneva; Centre National de la Recherche Scientifique (CNRS); Universite Clermont Auvergne (UCA); Institut National de la Sante et de la Recherche Medicale (Inserm)
RP Kakutani, T (corresponding author), Natl Inst Genet, Dept Integrated Genet, Yata 1111, Mishima, Shizuoka 4118540, Japan.
EM tkakutan@lab.nig.ac.jp
FU Takeda Science Foundation
NR 29
TC 291
Z9 320
U1 0
U2 43
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 423
EP U125
DI 10.1038/nature08351
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100046
PM 19734880
DA 2026-03-09
ER

PT J
AU Organ, CL
   Janes, DE
   Meade, A
   Pagel, M
AF Organ, Chris L.
   Janes, Daniel E.
   Meade, Andrew
   Pagel, Mark
TI Genotypic sex determination enabled adaptive radiations of extinct marine reptiles
SO NATURE
LA English
DT Article
ID correlated evolution; discrete characters; viviparous reptile; live birth; lizards; ichthyosaurs; constraints; history
AB Adaptive radiations often follow the evolution of key traits, such as the origin of the amniotic egg and the subsequent radiation of terrestrial vertebrates. The mechanism by which a species determines the sex of its offspring has been linked to critical ecological and life-history traits(1-3) but not to major adaptive radiations, in part because sex-determining mechanisms do not fossilize. Here we establish a previously unknown coevolutionary relationship in 94 amniote species between sex-determining mechanism and whether a species bears live young or lays eggs. We use that relationship to predict the sex-determining mechanism in three independent lineages of extinct Mesozoic marine reptiles (mosasaurs, sauropterygians and ichthyosaurs), each of which is known from fossils to have evolved live birth(4-7). Our results indicate that each lineage evolved genotypic sex determination before acquiring live birth. This enabled their pelagic radiations, where the relatively stable temperatures of the open ocean constrain temperature-dependent sex determination in amniote species. Freed from the need to move and nest on land(4,5,8), extreme physical adaptations to a pelagic lifestyle evolved in each group, such as the fluked tails, dorsal fins and wing-shaped limbs of ichthyosaurs. With the inclusion of ichthyosaurs, mosasaurs and sauropterygians, genotypic sex determination is present in all known fully pelagic amniote groups (sea snakes, sirenians and cetaceans), suggesting that this mode of sex determination and the subsequent evolution of live birth are key traits required for marine adaptive radiations in amniote lineages.
C1 [Organ, Chris L.; Janes, Daniel E.] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA.
   [Meade, Andrew; Pagel, Mark] Univ Reading, Sch Biol Sci, Reading RG6 6AJ, Berks, England.
C3 Harvard University; University of Reading
RP Organ, CL (corresponding author), Harvard Univ, Museum Comparat Zool, 26 Oxford St, Cambridge, MA 02138 USA.
EM corgan@oeb.harvard.edu; m.pagel@reading.ac.uk
FU Museum of Comparative Zoology; National Institutes of Health [1 F32 GM075490-01, 5 F32 GM072494]; Natural Environment Research Council [NE/C51992X/1]; Natural Environment Research Council [NE/C51992X/1] Funding Source: researchfish
NR 28
TC 53
Z9 56
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 17
PY 2009
VL 461
IS 7262
BP 389
EP 392
DI 10.1038/nature08350
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100038
PM 19759619
DA 2026-03-09
ER

PT J
AU Kuroda, R
   Endo, B
   Abe, M
   Shimizu, M
AF Kuroda, Reiko
   Endo, Bunshiro
   Abe, Masanori
   Shimizu, Miho
TI Chiral blastomere arrangement dictates zygotic left-right asymmetry pathway in snails
SO NATURE
LA English
DT Article
ID left-right axis; nodal flow; unconventional myosin; handedness; drosophila; mechanism; elegans; embryo; origin; shell
AB Most animals display internal and/or external left-right asymmetry. Several mechanisms for left-right asymmetry determination have been proposed for vertebrates(1-10) and invertebrates(1,2,4,9,11-14) but they are still not well characterized, particularly at the early developmental stage. The gastropods Lymnaea stagnalis and the closely related Lymnaea peregra have both the sinistral (recessive) and the dextral (dominant) snails within a species and the chirality is hereditary, determined by a single locus that functions maternally(15-18). Intriguingly, the handedness-determining gene(s) and the mechanisms are not yet identified. Here we show that in L. stagnalis, the chiral blastomere arrangement at the eight-cell stage (but not the two-or four-cell stage) determines the left-right asymmetry throughout the developmental programme, and acts upstream of the Nodal signalling pathway. Thus, we could demonstrate that mechanical micromanipulation of the third cleavage chirality (from the four-to the eight-cell stage) leads to reversal of embryonic handedness. These manipulated embryos grew to 'dextralized' sinistral and 'sinistralized' dextral snails-that is, normal healthy fertile organisms with all the usual left-right asymmetries reversed to that encoded by the mothers' genetic information. Moreover, manipulation reversed the embryonic nodal expression patterns. Using backcrossed F-7 congenic animals, we could demonstrate a strong genetic linkage between the handedness-determining gene( s) and the chiral cytoskeletal dynamics at the third cleavage that promotes the dominant-type blastomere arrangement. These results establish the crucial importance of the maternally determined blastomere arrangement at the eight-cell stage in dictating zygotic signalling pathways in the organismal chiromorphogenesis. Similar chiral blastomere configuration mechanisms may also operate upstream of the Nodal pathway in left-right patterning of deuterostomes/vertebrates.
C1 [Kuroda, Reiko] Univ Tokyo, Grad Sch Arts & Sci, Dept Life Sci, Meguro Ku, Tokyo 1538902, Japan.
   [Kuroda, Reiko; Endo, Bunshiro; Abe, Masanori; Shimizu, Miho] JST, ERATO SORST, Kuroda Chiromorphol Team, Meguro Ku, Tokyo 1530041, Japan.
   [Kuroda, Reiko] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130033, Japan.
C3 University of Tokyo; Japan Science & Technology Agency (JST); University of Tokyo
RP Kuroda, R (corresponding author), Univ Tokyo, Grad Sch Arts & Sci, Dept Life Sci, Meguro Ku, Tokyo 1538902, Japan.
EM ckuroda@mail.ecc.u-tokyo.ac.jp
NR 27
TC 150
Z9 164
U1 1
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 790
EP U112
DI 10.1038/nature08597
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900039
PM 19940849
DA 2026-03-09
ER

PT J
AU Koder, RL
   Anderson, JLR
   Solomon, LA
   Reddy, KS
   Moser, CC
   Dutton, PL
AF Koder, Ronald L.
   Anderson, J. L. Ross
   Solomon, Lee A.
   Reddy, Konda S.
   Moser, Christopher C.
   Dutton, P. Leslie
TI Design and engineering of an O2 transport protein
SO NATURE
LA English
DT Article
ID cytochrome-c-oxidase; heme-proteins; ligand-binding; computational design; electron-transfer; enzyme catalysis; 4-helix bundle; hemoglobin; maquette; mechanism
AB The principles of natural protein engineering are obscured by overlapping functions and complexity accumulated through natural selection and evolution. Completely artificial proteins offer a clean slate on which to define and test these protein engineering principles, while recreating and extending natural functions. Here we introduce this method with the design of an oxygen transport protein, akin to human neuroglobin. Beginning with a simple and unnatural helix-forming sequence with just three different amino acids, we assembled a four-helix bundle, positioned histidines to bis-histidine ligate haems, and exploited helical rotation and glutamate burial on haem binding to introduce distal histidine strain and facilitate O-2 binding. For stable oxygen binding without haem oxidation, water is excluded by simple packing of the protein interior and loops that reduce helical-interface mobility. O-2 affinities and exchange timescales match natural globins with distal histidines, with the remarkable exception that O-2 binds tighter than CO.
C1 [Koder, Ronald L.; Anderson, J. L. Ross; Solomon, Lee A.; Reddy, Konda S.; Moser, Christopher C.; Dutton, P. Leslie] Univ Penn, Dept Biochem & Biophys, Johnson Res Fdn, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania
RP Dutton, PL (corresponding author), Univ Penn, Dept Biochem & Biophys, Johnson Res Fdn, Philadelphia, PA 19104 USA.
EM dutton@mail.med.upenn.edu
FU US Department of Energy; US National Institute of Health; US National Science Foundation
NR 54
TC 194
Z9 247
U1 2
U2 100
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 305
EP U64
DI 10.1038/nature07841
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600034
PM 19295603
DA 2026-03-09
ER

PT J
AU Terret, ME
   Sherwood, R
   Rahman, S
   Qin, J
   Jallepalli, PV
AF Terret, Marie-Emilie
   Sherwood, Rebecca
   Rahman, Sadia
   Qin, Jun
   Jallepalli, Prasad V.
TI Cohesin acetylation speeds the replication fork
SO NATURE
LA English
DT Article
ID sister-chromatid cohesion; xenopus egg extracts; human-cells; s-phase; saccharomyces-cerevisiae; establishment; yeast; ctcf; dna; senescence
AB Cohesin not only links sister chromatids but also inhibits the transcriptional machinery's interaction with and movement along chromatin(1-6). In contrast, replication forks must traverse such cohesin-associated obstructions to duplicate the entire genome in S phase. How this occurs is unknown. Through single-molecule analysis, we demonstrate that the replication factor C (RFC)-CTF18 clamp loader (RFCCTF18)(1,7) controls the velocity, spacing and restart activity of replication forks in human cells and is required for robust acetylation of cohesin's SMC3 subunit and sister chromatid cohesion. Unexpectedly, we discovered that cohesin acetylation itself is a central determinant of fork processivity, as slow-moving replication forks were found in cells lacking the Eco1-related acetyltransferases ESCO1 or ESCO2 (refs 8 -10) (including those derived from Roberts' syndrome patients, in whom ESCO2 is biallelically mutated(11)) and in cells expressing a form of SMC3 that cannot be acetylated. This defect was a consequence of cohesin's hyperstable interaction with two regulatory cofactors, WAPL and PDS5A (refs 12, 13); removal of either cofactor allowed forks to progress rapidly without ESCO1, ESCO2, or RFCCTF18. Our results show a novel mechanism for clamp-loader-dependent fork progression, mediated by the post-translational modification and structural remodelling of the cohesin ring. Loss of this regulatory mechanism leads to the spontaneous accrual of DNA damage and may contribute to the abnormalities of the Roberts' syndrome cohesinopathy.
C1 [Terret, Marie-Emilie; Sherwood, Rebecca; Rahman, Sadia; Jallepalli, Prasad V.] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA.
   [Qin, Jun] Baylor Coll Med, Dept Biochem & Mol Biol, Ctr Mol Discovery, Houston, TX 77030 USA.
C3 Memorial Sloan Kettering Cancer Center; Baylor College of Medicine
RP Jallepalli, PV (corresponding author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, 1275 York Ave, New York, NY 10065 USA.
EM jallepap@mskcc.org
FU National Institutes of Health; Pew Scholar in the Biochemical Sciences award; National Institute of General Medical Sciences [R01GM094972] Funding Source: NIH RePORTER
NR 35
TC 198
Z9 244
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 NOV 12
PY 2009
VL 462
IS 7270
BP 231
EP U106
DI 10.1038/nature08550
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100045
PM 19907496
DA 2026-03-09
ER

PT J
AU Du, LQ
   Ali, GS
   Simons, KA
   Hou, JG
   Yang, TB
   Reddy, ASN
   Poovaiah, BW
AF Du, Liqun
   Ali, Gul S.
   Simons, Kayla A.
   Hou, Jingguo
   Yang, Tianbao
   Reddy, A. S. N.
   Poovaiah, B. W.
TI Ca2+/calmodulin regulates salicylic-acid-mediated plant immunity
SO NATURE
LA English
DT Article
ID systemic acquired-resistance; calmodulin-binding protein; disease-resistance; transcriptional regulation; hypersensitive response; arabidopsis-thaliana; signaling pathways; cell-death; defense; family
AB Intracellular calcium transients during plant-pathogen interactions are necessary early events leading to local and systemic acquired resistance(1). Salicylic acid, a critical messenger, is also required for both of these responses(2,3), but whether and how salicylic acid level is regulated by Ca2+ signalling during plant-pathogen interaction is unclear. Here we report a mechanism connecting Ca2+ signal to salicylic-acid-mediated immune response through calmodulin, AtSR1 (also known as CAMTA3), a Ca2+/calmodulin-binding transcription factor, and EDS1, an established regulator of salicylic acid level. Constitutive disease resistance and elevated levels of salicylic acid in loss-of-function alleles of Arabidopsis AtSR1 suggest that AtSR1 is a negative regulator of plant immunity. This was confirmed by epistasis analysis with mutants of compromised salicylic acid accumulation and disease resistance. We show that AtSR1 interacts with the promoter of EDS1 and represses its expression. Furthermore, Ca2+/calmodulin-binding to AtSR1 is required for suppression of plant defence, indicating a direct role for Ca2+/calmodulin in regulating the function of AtSR1. These results reveal a previously unknown regulatory mechanism linking Ca2+ signalling to salicylic acid level.
C1 [Du, Liqun; Simons, Kayla A.; Yang, Tianbao; Poovaiah, B. W.] Washington State Univ, Ctr Integrated Biotechnol, Pullman, WA 99164 USA.
   [Du, Liqun; Simons, Kayla A.; Yang, Tianbao; Poovaiah, B. W.] Washington State Univ, Dept Hort, Pullman, WA 99164 USA.
   [Hou, Jingguo] Washington State Univ, Dept Chem, Pullman, WA 99164 USA.
   [Ali, Gul S.; Reddy, A. S. N.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
   [Ali, Gul S.; Reddy, A. S. N.] Colorado State Univ, Program Mol Plant Biol, Ft Collins, CO 80523 USA.
C3 Washington State University; Washington State University; Washington State University; Colorado State University System; Colorado State University Fort Collins; Colorado State University System; Colorado State University Fort Collins
RP Poovaiah, BW (corresponding author), Washington State Univ, Ctr Integrated Biotechnol, Pullman, WA 99164 USA.
EM poovaiah@wsu.edu
FU United States Department of Agriculture [2002-00741, 2005-01107, 2008-01034]; National Science Foundation [MCB-0424898, MCB-0424895, DBI 0743097, IOS-0642146]; Colorado Sate University Academic Enrichment Program [180470]; Office of Naval Research [N0014-08-1-0470]; Washington State University Agricultural Research Center
NR 40
TC 459
Z9 564
U1 11
U2 242
PU 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 26
PY 2009
VL 457
IS 7233
BP 1154
EP U116
DI 10.1038/nature07612
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100046
PM 19122675
DA 2026-03-09
ER

PT J
AU Chen, DN
   Pacal, M
   Wenzel, P
   Knoepfler, PS
   Leone, G
   Bremner, R
AF Chen, Danian
   Pacal, Marek
   Wenzel, Pamela
   Knoepfler, Paul S.
   Leone, Gustavo
   Bremner, Rod
TI Division and apoptosis of E2f-deficient retinal progenitors
SO NATURE
LA English
DT Article
ID e2f family-members; cell-cycle; c-myc; chromatin immunoprecipitation; neuronal differentiation; transcription factors; tumor-suppressor; target gene; proliferation; p53
AB The activating E2f transcription factors (E2f1, E2f2 and E2f3) induce transcription and are widely viewed as essential positive cell cycle regulators. Indeed, they drive cells out of quiescence, and the 'cancer cell cycle' in Rb1 null cells is E2f-dependent(1,2). Absence of activating E2fs in flies or mammalian fibroblasts causes cell cycle arrest(3,4), but this block is alleviated by removing repressive E2f or the tumour suppressor p53, respectively(5-7). Thus, whether activating E2fs are indispensable for normal division is an area of debate(1). Activating E2fs are also well known pro-apoptotic factors, providing a defence against oncogenesis(8), yet E2f1 can limit irradiation-induced apoptosis(9,10). In flies this occurs through repression of hid (also called Wrinkled; Smac/Diablo in mammals). However, in mammals the mechanism is unclear because Smac/Diablo is induced, not repressed, by E2f1(11), and in keratinocytes survival is promoted indirectly through induction of DNA repair targets(12). Thus, a direct pro-survival function for E2f1-3 and/or its relevance beyond irradiation has not been established. To address E2f1-3 function in normal cells in vivo we focused on the mouse retina, which is a relatively simple central nervous system component that can be manipulated genetically without compromising viability and has provided considerable insight into development and cancer(2,13). Here we show that unlike fibroblasts, E2f1-3 null retinal progenitor cells or activated Muller glia can divide. We attribute this effect to functional interchangeability with Mycn. However, loss of activating E2fs caused down-regulation of the p53 deacetylase Sirt1, p53 hyperacetylation and elevated apoptosis, establishing a novel E2f-Sirt1-p53 survival axis in vivo. Thus, activating E2fs are not universally required for normal mammalian cell division, but have an unexpected pro-survival role in development.
C1 [Chen, Danian; Pacal, Marek; Bremner, Rod] Univ Toronto, Univ Hlth Network, Toronto Western Res Inst, Dept Ophthalmol & Visual Sci, Toronto, ON M5T 2S8, Canada.
   [Chen, Danian; Pacal, Marek; Bremner, Rod] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5T 2S8, Canada.
   [Wenzel, Pamela; Leone, Gustavo] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH 43210 USA.
   [Wenzel, Pamela; Leone, Gustavo] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Genet, Columbus, OH 43210 USA.
   [Knoepfler, Paul S.] Univ Calif Davis, Sch Med, Dept Cell Biol, Davis, CA 95616 USA.
   [Knoepfler, Paul S.] Univ Calif Davis, Sch Med, Dept Human Anat, Davis, CA 95616 USA.
C3 University of Toronto; University Health Network Toronto; University of Toronto; James Cancer Hospital & Solove Research Institute; University System of Ohio; Ohio State University; James Cancer Hospital & Solove Research Institute; University System of Ohio; Ohio State University; University of California System; University of California Davis; University of California System; University of California Davis
RP Bremner, R (corresponding author), Univ Toronto, Univ Hlth Network, Toronto Western Res Inst, Dept Ophthalmol & Visual Sci, Toronto, ON M5T 2S8, Canada.
EM rbremner@uhnres.utoronto.ca
FU Canadian Institutes for Health Research [MOP-74570]
NR 46
TC 122
Z9 154
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 17
PY 2009
VL 462
IS 7275
BP 925
EP U120
DI 10.1038/nature08544
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400044
PM 20016601
DA 2026-03-09
ER

PT J
AU Naveiras, O
   Nardi, V
   Wenzel, PL
   Hauschka, PV
   Fahey, F
   Daley, GQ
AF Naveiras, Olaia
   Nardi, Valentina
   Wenzel, Pamela L.
   Hauschka, Peter V.
   Fahey, Frederic
   Daley, George Q.
TI Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment
SO NATURE
LA English
DT Article
ID stem-cell niche; insulin-resistance; progenitor cells; self-renewal; in-vivo; differentiation; growth; identification; rosiglitazone; adiponectin
AB Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow(1-3). Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia(4). To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes(5), and in mice treated with the peroxisome proliferator-activated receptor-c inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis(6), marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.
C1 [Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA.
   [Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Manton Ctr Orphan Dis, Boston, MA 02115 USA.
   [Hauschka, Peter V.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA.
   [Hauschka, Peter V.] Harvard Univ, Sch Med, Dept Oral & Dev Biol, Boston, MA 02115 USA.
   [Hauschka, Peter V.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
   [Fahey, Frederic] Harvard Univ, Childrens Hosp, Sch Med, Dept Radiol,Div Nucl Med PET, 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; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School
RP Daley, GQ (corresponding author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
FU Barrie de la Maza Foundation; National Institutes of Health (NIH) [T32-HL-7623]; Burroughs Wellcome Fund; Leukemia and Lymphoma Society
NR 33
TC 896
Z9 1066
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 JUL 9
PY 2009
VL 460
IS 7252
BP 259
EP U124
DI 10.1038/nature08099
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000041
PM 19516257
DA 2026-03-09
ER

PT J
AU Torchinsky, MB
   Garaude, J
   Martin, AP
   Blander, JM
AF Torchinsky, Miriam Beer
   Garaude, Johan
   Martin, Andrea P.
   Blander, J. Magarian
TI Innate immune recognition of infected apoptotic cells directs TH17 cell differentiation
SO NATURE
LA English
DT Article
ID escherichia-coli espf; t-helper-cells; tgf-beta; interleukin-22; il-17; mitochondria; inflammation; cytokine
AB Adaptive immune responses rely on differentiation of CD4 Thelper cells into subsets with distinct effector functions best suited for host defence against the invading pathogen. Interleukin (IL)-17 producing T helper cells (T(H)17) are a recently identified subset, separate from the T helper type 1 (T(H)1) and T helper type 2 (T(H)2) subsets(1). Synergy between the cytokines transforming growth factor-beta and IL-6 in vitro induces development of TH17 cells in mouse(1-5) and human(6) systems, whereas IL-23 supports expansion of these cells(2,4,5). However, it is not known which conditions in vivo would induce this combination of cytokines. Furthermore, it is enigmatic that a combination of pro-inflammatory and anti-inflammatory cytokines would be required to generate an effector TH17 response. Here we show that the relevant physiological stimulus triggering this combination of cytokines is the recognition and phagocytosis of infected apoptotic cells by dendritic cells. Phagocytosis of infected apoptotic cells uniquely triggers the combination of IL-6 and transforming growth factor-beta through recognition of pathogen-associated molecular patterns(7) and phosphatidylserine exposed on apoptotic cells(8), respectively. Conversely, phagocytosis of apoptotic cells in the absence of microbial signals induces differentiation of the closely related regulatory T cells, which are important for controlling autoimmunity(9). Blocking apoptosis during infection of the mouse intestinal epithelium with the rodent pathogen Citrobacter rodentium(10), which models human infections with the attaching and effacing enteropathogenic and enterohaemorrhagic Escherichia coli, impairs the characteristic TH17 response in the lamina propria. Our results demonstrate that infected apoptotic cells are a critical component of the innate immune signals instructing TH17 differentiation, and point to pathogens particularly adept at triggering apoptosis that might preferentially induce T(H)17-mediated immunity. Because TH17 cells have been correlated with autoimmune diseases(1), investigation of the pathways of innate recognition of infected apoptotic cells might lead to improved understanding of the causative defects in autoimmunity.
C1 [Torchinsky, Miriam Beer; Garaude, Johan; Martin, Andrea P.; Blander, J. Magarian] Mt Sinai Sch Med, Dept Med, Inst Immunol, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai
RP Blander, JM (corresponding author), Mt Sinai Sch Med, Dept Med, Inst Immunol, 1425 Madison Ave, New York, NY 10029 USA.
EM julie.blander@mssm.edu
FU NIH [AI073899]; Kinship Foundation Searle Scholar Award
NR 30
TC 300
Z9 348
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 MAR 5
PY 2009
VL 458
IS 7234
BP 78
EP 82
DI 10.1038/nature07781
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000036
PM 19262671
DA 2026-03-09
ER

PT J
AU Harrison, DE
   Strong, R
   Sharp, ZD
   Nelson, JF
   Astle, CM
   Flurkey, K
   Nadon, NL
   Wilkinson, JE
   Frenkel, K
   Carter, CS
   Pahor, M
   Javors, MA
   Fernandez, E
   Miller, RA
AF Harrison, David E.
   Strong, Randy
   Sharp, Zelton Dave
   Nelson, James F.
   Astle, Clinton M.
   Flurkey, Kevin
   Nadon, Nancy L.
   Wilkinson, J. Erby
   Frenkel, Krystyna
   Carter, Christy S.
   Pahor, Marco
   Javors, Martin A.
   Fernandez, Elizabeth
   Miller, Richard A.
TI Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
SO NATURE
LA English
DT Article
ID tor; pathway; design; target; yeast
AB Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies(1-5); however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
C1 [Harrison, David E.; Astle, Clinton M.; Flurkey, Kevin] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA.
   [Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Res Serv, Dept Pharmacol, San Antonio, TX 78229 USA.
   [Strong, Randy; Sharp, Zelton Dave; Nelson, James F.; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
   [Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78245 USA.
   [Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
   [Nadon, Nancy L.] NIA, Div Aging Biol, Bethesda, MD 20892 USA.
   [Wilkinson, J. Erby] Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI 48109 USA.
   [Frenkel, Krystyna] NYU, Sch Med, New York, NY 10016 USA.
   [Carter, Christy S.; Pahor, Marco] Wake Forest Univ, Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Winston Salem, Winston Salem, NC 27157 USA.
   [Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
   [Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
C3 Jackson Laboratory; Geriatric Research Education & Clinical Center; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Michigan System; University of Michigan; New York University; Wake Forest University; University of Texas System; University of Texas at San Antonio; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Harrison, DE (corresponding author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM david.harrison@jax.org
FU NIA [AG022303, AG025707, AG022308, AG022307, AG13319]; Department of Veterans Affairs; DoD [W81XWH-07-1-0605]; National Institute on Aging [P30AG013319, P30AG028740, U01AG022303, U01AG022308, U01AG022307] Funding Source: NIH RePORTER
NR 30
TC 2982
Z9 3578
U1 8
U2 406
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 392
EP U108
DI 10.1038/nature08221
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000038
PM 19587680
DA 2026-03-09
ER

PT J
AU Kawashima, Y
   Pfafferott, K
   Frater, J
   Matthews, P
   Payne, R
   Addo, M
   Gatanaga, H
   Fujiwara, M
   Hachiya, A
   Koizumi, H
   Kuse, N
   Oka, S
   Duda, A
   Prendergast, A
   Crawford, H
   Leslie, A
   Brumme, Z
   Brumme, C
   Allen, T
   Brander, C
   Kaslow, R
   Tang, J
   Hunter, E
   Allen, S
   Mulenga, J
   Branch, S
   Roach, T
   John, M
   Mallal, S
   Ogwu, A
   Shapiro, R
   Prado, JG
   Fidler, S
   Weber, J
   Pybus, OG
   Klenerman, P
   Ndung'u, T
   Phillips, R
   Heckerman, D
   Harrigan, PR
   Walker, BD
   Takiguchi, M
   Goulder, P
AF Kawashima, Yuka
   Pfafferott, Katja
   Frater, John
   Matthews, Philippa
   Payne, Rebecca
   Addo, Marylyn
   Gatanaga, Hiroyuki
   Fujiwara, Mamoru
   Hachiya, Atsuko
   Koizumi, Hirokazu
   Kuse, Nozomi
   Oka, Shinichi
   Duda, Anna
   Prendergast, Andrew
   Crawford, Hayley
   Leslie, Alasdair
   Brumme, Zabrina
   Brumme, Chanson
   Allen, Todd
   Brander, Christian
   Kaslow, Richard
   Tang, James
   Hunter, Eric
   Allen, Susan
   Mulenga, Joseph
   Branch, Songee
   Roach, Tim
   John, Mina
   Mallal, Simon
   Ogwu, Anthony
   Shapiro, Roger
   Prado, Julia G.
   Fidler, Sarah
   Weber, Jonathan
   Pybus, Oliver G.
   Klenerman, Paul
   Ndung'u, Thumbi
   Phillips, Rodney
   Heckerman, David
   Harrigan, P. Richard
   Walker, Bruce D.
   Takiguchi, Masafumi
   Goulder, Philip
TI Adaptation of HIV-1 to human leukocyte antigen class I
SO NATURE
LA English
DT Article
ID t-lymphocyte response; mhc-class-i; escape mutations; cell responses; viral load; hla-b; gag; transmission; polymorphisms; associations
AB The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection(1). Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from. 2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P=0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n=14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.
C1 [Pfafferott, Katja; Matthews, Philippa; Payne, Rebecca; Prendergast, Andrew; Crawford, Hayley; Leslie, Alasdair; Prado, Julia G.; Goulder, Philip] Dept Paediat, Oxford OX1 3SY, England.
   [Frater, John; Duda, Anna; Klenerman, Paul; Phillips, Rodney] Nuffield Dept Clin Med, Oxford OX1 3SY, England.
   [Frater, John; Duda, Anna; Klenerman, Paul; Phillips, Rodney] James Martin 21st Century Sch, Oxford OX1 3SY, England.
   [Kawashima, Yuka; Fujiwara, Mamoru; Hachiya, Atsuko; Koizumi, Hirokazu; Kuse, Nozomi; Takiguchi, Masafumi] Kumamoto Univ, Div Viral Immunol, Kumamoto 8600811, Japan.
   [Gatanaga, Hiroyuki; Oka, Shinichi] Kumamoto Univ, Div Infect Dis, Ctr AIDS Res, Kumamoto 8600811, Japan.
   [Pfafferott, Katja; John, Mina; Mallal, Simon; Goulder, Philip] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia.
   [Pfafferott, Katja; John, Mina; Mallal, Simon; Goulder, Philip] Murdoch Univ, Murdoch, WA 6000, Australia.
   [Addo, Marylyn; Brumme, Zabrina; Brumme, Chanson; Allen, Todd; Brander, Christian; Walker, Bruce D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA.
   [Gatanaga, Hiroyuki; Hachiya, Atsuko; Oka, Shinichi] Int Med Ctr Japan, AIDS Clin Ctr, Shinjuku Ku, Tokyo 1628655, Japan.
   [Brander, Christian] Hosp Badalona Germans Trias & Pujol, Fundacio IrsiCaixa HIVACAT, Badalona, Spain.
   [Brander, Christian] ICREA, Barcelona 08916, Spain.
   [Kaslow, Richard; Tang, James] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
   [Hunter, Eric] Emory Univ, Vaccine Ctr, Atlanta, GA 30329 USA.
   [Hunter, Eric] Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Allen, Susan; Mulenga, Joseph] Zambia Emory HIV Res Project, Lusaka, Zambia.
   [Allen, Susan; Mulenga, Joseph] Zambia Blood Transfus Serv, Lusaka, Zambia.
   [Branch, Songee; Roach, Tim] Univ W Indies, Ladymeade Reference Unit, BB-11156 Bridgetown, Barbados.
   [Ogwu, Anthony; Shapiro, Roger] Botswana Harvard Sch Publ Hlth, AIDS Initiat Partnership, Gaborone, Botswana.
   [Fidler, Sarah; Weber, Jonathan] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Wright Fleming Inst, Div Med, London W2 1PG, England.
   [Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3SY, England.
   [Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa.
   [Harrigan, P. Richard] Miscrosoft Res, Redmond, WA USA.
   [Heckerman, David] BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada.
   [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20185 USA.
C3 University of Oxford; University of Oxford; Kumamoto University; Kumamoto University; University of Western Australia; East Metropolitan Health Service; Royal Perth Hospital; Murdoch University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Japan Institute for Health Security (JIHS); National Center for Global Health & Medicine - Japan; Institut de Recerca de la Sida - IrsiCaixa; Hospital Germans Trias i Pujol; ICREA; University of Alabama System; University of Alabama Birmingham; Emory University; University West Indies Mona Jamaica; University of the West Indies Open Campus; Imperial College London; University of Oxford; University of Kwazulu Natal; B.C. Centre for Excellence in HIV/AIDS; Howard Hughes Medical Institute
RP Goulder, P (corresponding author), Dept Paediat, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England.
EM philip.goulder@paediatrics.ox.ac.uk
FU National Institutes of Health [RO1AI46995, 1 R01 AI067073, R01AI64060]; Wellcome Trust; UK Medical Research Council; Mark and Lisa Schwartz Foundation; Ministry of Health, Labour and Welfare [012]; Ministry of Education, Science, Sports and Culture [18390141]; NIHR Biomedical Research Centre Programme; Elizabeth Glaser Pediatric AIDS Foundation Scientist; Marie Curie Fellow [IEF-041811]; ICREA Funding Source: Custom; Grants-in-Aid for Scientific Research [18390141] Funding Source: KAKEN; Medical Research Council [G0501777, G0500384, G108/626] Funding Source: researchfish; National Institute for Health Research [NF-SI-0507-10313] Funding Source: researchfish; MRC [G108/626, G0501777, G0500384] Funding Source: UKRI
NR 30
TC 367
Z9 419
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 APR 2
PY 2009
VL 458
IS 7238
BP 641
EP U108
DI 10.1038/nature07746
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200043
PM 19242411
DA 2026-03-09
ER

PT J
AU Ghosh, D
   Griswold, J
   Erman, M
   Pangborn, W
AF Ghosh, Debashis
   Griswold, Jennifer
   Erman, Mary
   Pangborn, Walter
TI Structural basis for androgen specificity and oestrogen synthesis in human aromatase
SO NATURE
LA English
DT Article
ID human placental aromatase; cytochrome-p450 aromatase; kinetic-property; crystal-structures; dioxygen complex; wild-type; purification; inhibitors; model; mechanism
AB Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens(1-3). Aromatase inhibitors therefore constitute a front-line therapy for oestrogen- dependent breast cancer(3,4). In a three-step process, each step requiring 1 mol of O-2, 1 mol of NADPH, and coupling with its redox partner cytochrome P450 reductase, aromatase converts androstenedione, testosterone and 16 alpha-hydroxytestosterone to oestrone, 17 beta-oestradiol and 17 beta, 16 alpha-oestriol, respectively(1-3). The first two steps are C19- methyl hydroxylation steps, and the third involves the aromatization of the steroid A- ring, unique to aromatase. Whereas most P450s are not highly substrate selective, it is the hallmark androgenic specificity that sets aromatase apart. The structure of this enzyme of the endoplasmic reticulum membrane has remained unknown for decades, hindering elucidation of the biochemical mechanism. Here we present the crystal structure of human placental aromatase, the only natural mammalian, full- length P450 and P450 in hormone biosynthetic pathways to be crystallized so far. Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen- specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino- terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site. The molecular basis for the enzyme's androgenic specificity and unique catalytic mechanism can be used for developing next- generation aromatase inhibitors.
C1 [Ghosh, Debashis; Griswold, Jennifer; Erman, Mary; Pangborn, Walter] Hauptman Woodward Res Inst, Buffalo, NY 14203 USA.
   [Ghosh, Debashis] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
C3 Hauptman Woodward Medical Research Institute; Roswell Park Comprehensive Cancer Center
RP Ghosh, D (corresponding author), Hauptman Woodward Res Inst, 700 Ellicott St, Buffalo, NY 14203 USA.
EM ghosh@hwi.buffalo.edu
FU National Institutes of Health [GM62794, GM59450]
NR 36
TC 481
Z9 557
U1 1
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 8
PY 2009
VL 457
IS 7226
BP 219
EP U119
DI 10.1038/nature07614
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200038
PM 19129847
DA 2026-03-09
ER

PT J
AU Murayama, M
   Pérez-Garci, E
   Nevian, T
   Bock, T
   Senn, W
   Larkum, ME
AF Murayama, Masanori
   Perez-Garci, Enrique
   Nevian, Thomas
   Bock, Tobias
   Senn, Walter
   Larkum, Matthew E.
TI Dendritic encoding of sensory stimuli controlled by deep cortical interneurons
SO NATURE
LA English
DT Article
ID neocortical pyramidal neurons; primary somatosensory cortex; distal apical dendrites; mouse smi cortex; action-potentials; in-vivo; layer-i; projection neurons; cells; rat
AB The computational power of single neurons is greatly enhanced by active dendritic conductances(1) that have a large influence on their spike activity(2-4). In cortical output neurons such as the large pyramidal cells of layer 5 (L5), activation of apical dendritic calcium channels leads to plateau potentials that increase the gain of the input/output function(5) and switch the cell to burst-firing mode(6-9). The apical dendrites are innervated by local excitatory and inhibitory inputs as well as thalamic(10-13) and corticocortical projections(14-16), which makes it a formidable task to predict how these inputs influence active dendritic properties in vivo. Here we investigate activity in populations of L5 pyramidal dendrites of the somatosensory cortex in awake and anaesthetized rats following sensory stimulation using a new fibre-optic method(17) for recording dendritic calcium changes. We show that the strength of sensory stimulation is encoded in the combined dendritic calcium response of a local population of L5 pyramidal cells in a graded manner. The slope of the stimulus-response function was under the control of a particular subset of inhibitory neurons activated by synaptic inputs predominantly in L5. Recordings from single apical tuft dendrites in vitro showed that activity in L5 pyramidal neurons disynaptically coupled via interneurons directly blocks the initiation of dendritic calcium spikes in neighbouring pyramidal neurons. The results constitute a functional description of a cortical microcircuit in awake animals that relies on the active properties of L5 pyramidal dendrites and their very high sensitivity to inhibition. The microcircuit is organized so that local populations of apical dendrites can adaptively encode bottom-up sensory stimuli linearly across their full dynamic range.
C1 [Murayama, Masanori; Perez-Garci, Enrique; Nevian, Thomas; Bock, Tobias; Senn, Walter; Larkum, Matthew E.] Univ Bern, Inst Physiol, CH-3012 Bern, Switzerland.
C3 University of Bern
RP Larkum, ME (corresponding author), Univ Bern, Inst Physiol, Buhlpl 5, CH-3012 Bern, Switzerland.
EM larkum@pyl.unibe.ch
FU Swiss National Science Foundation [PP00A-102721/1]
NR 26
TC 293
Z9 357
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 26
PY 2009
VL 457
IS 7233
BP 1137
EP U95
DI 10.1038/nature07663
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100042
PM 19151696
DA 2026-03-09
ER

PT J
AU Tubbs, JL
   Latypov, V
   Kanugula, S
   Butt, A
   Melikishvili, M
   Kraehenbuehl, R
   Fleck, O
   Marriott, A
   Watson, AJ
   Verbeek, B
   McGown, G
   Thorncroft, M
   Santibanez-Koref, MF
   Millington, C
   Arvai, AS
   Kroeger, MD
   Peterson, LA
   Williams, DM
   Fried, MG
   Margison, GP
   Pegg, AE
   Tainer, JA
AF Tubbs, Julie L.
   Latypov, Vitaly
   Kanugula, Sreenivas
   Butt, Amna
   Melikishvili, Manana
   Kraehenbuehl, Rolf
   Fleck, Oliver
   Marriott, Andrew
   Watson, Amanda J.
   Verbeek, Barbara
   McGown, Gail
   Thorncroft, Mary
   Santibanez-Koref, Mauro F.
   Millington, Christopher
   Arvai, Andrew S.
   Kroeger, Matthew D.
   Peterson, Lisa A.
   Williams, David M.
   Fried, Michael G.
   Margison, Geoffrey P.
   Pegg, Anthony E.
   Tainer, John A.
TI Flipping of alkylated DNA damage bridges base and nucleotide excision repair
SO NATURE
LA English
DT Article
ID o-6-alkylguanine-dna alkyltransferase; escherichia-coli; o-6-methylguanine-dna methyltransferase; structural basis; endonuclease-v; protein; recognition; binding; genome; substrate
AB Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer chemotherapy target O-6-alkylguanine-DNA alkyltransferase (AGT) and paradoxically protect cells from the biological effects of DNA alkylation damage, despite lacking the reactive cysteine and alkyltransferase activity of AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with damaged DNA containing the endogenous lesion O-6-methylguanine or cigarette-smoke-derived O-6-4-(3-pyridyl)-4-oxobutylguanine. These results reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and binding pocket size compared to AGT. Our analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life. Genetic connections to mammalian XPG (also known as ERCC5) and ERCC1 in S. pombe homologues Rad13 and Swi10 and biochemical interactions with Escherichia coli UvrA and UvrC combined with structural results reveal that ATLs sculpt alkylated DNA to create a genetic and structural intersection of base damage processing with nucleotide excision repair.
C1 [Tubbs, Julie L.; Arvai, Andrew S.; Kroeger, Matthew D.; Tainer, John A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Tubbs, Julie L.; Arvai, Andrew S.; Kroeger, Matthew D.; Tainer, John A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Latypov, Vitaly; Butt, Amna; Marriott, Andrew; Watson, Amanda J.; Verbeek, Barbara; McGown, Gail; Thorncroft, Mary; Margison, Geoffrey P.] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Carcinogenesis Grp, Manchester M20 4BX, Lancs, England.
   [Kanugula, Sreenivas; Pegg, Anthony E.] Penn State Univ, Coll Med, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA.
   [Melikishvili, Manana; Fried, Michael G.] Univ Kentucky, Dept Mol & Cellular Biochem, Struct Biol Ctr, Lexington, KY 40536 USA.
   [Kraehenbuehl, Rolf; Fleck, Oliver] Bangor Univ, NWCRF Inst, Bangor LL57 2UW, Gwynedd, Wales.
   [Santibanez-Koref, Mauro F.] Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
   [Millington, Christopher; Williams, David M.] Univ Sheffield, Dept Chem, Ctr Chem Biol, Sheffield S3 7HF, S Yorkshire, England.
   [Peterson, Lisa A.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Peterson, Lisa A.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN 55455 USA.
   [Tainer, John A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
C3 Scripps Research Institute; Scripps Research Institute; Paterson Institute for Cancer Research; University of Manchester; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Penn State Health; University of Kentucky; Bangor University; Newcastle University - UK; University of Sheffield; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Tainer, JA (corresponding author), Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
EM aep1@psu.edu; jat@scripps.edu
FU US Department of Energy; NIH [CA097209, CA018137, GM070662, CA59887]; Skaggs Institute for Chemical Biology; North West Cancer Research Fund [CR675]; Cancer Research-UK; CHEMORES
NR 50
TC 111
Z9 129
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 JUN 11
PY 2009
VL 459
IS 7248
BP 808
EP 813
DI 10.1038/nature08076
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500031
PM 19516334
DA 2026-03-09
ER

PT J
AU Catalli, K
   Shim, SH
   Prakapenka, V
AF Catalli, Krystle
   Shim, Sang-Heon
   Prakapenka, Vitali
TI Thickness and Clapeyron slope of the post-perovskite boundary
SO NATURE
LA English
DT Article
ID earths lower mantle; phase-transition; lowermost-mantle; d''-layer; mgsio3; postperovskite; discontinuity
AB The thicknesses and Clapeyron slopes of mantle phase boundaries strongly influence the seismic detectability of the boundaries and convection in the mantle. The unusually large positive Clapeyron slope found for the boundary between perovskite (Pv) and post-perovskite (pPv)(1-3) ( the 'pPv boundary') would destabilize high-temperature anomalies in the lowermost mantle(4), in disagreement with the seismic observations(5). Here we report the thickness of the pPv boundary in (Mg0.91Fe0.092+)SiO3 and (Mg0.9Fe0.13+)(Al0.1Si0.9)O-3 as determined in a laser-heated diamond-anvil cell under in situ high-pressure (up to 145 GPa), high-temperature ( up to 3,000 K) conditions. The measured Clapeyron slope is consistent with the D '' discontinuity(6). In both systems, however, the pPv boundary thickness increases to 400-600 +/- 100 km, which is substantially greater than the thickness of the D '' discontinuity (< 30 km)(7). Although the Fe2+ buffering effect of ferropericlase(8-10) could decrease the pPv boundary thickness, the boundary may remain thick in a pyrolitic composition because of the effects of Al and the rapid temperature increase in the D '' layer. The pPv boundary would be particularly thick in regions with an elevated Al content and/or a low Mg/Si ratio, reducing the effects of the large positive Clapeyron slope on the buoyancy of thermal anomalies and stabilizing compositional heterogeneities in the lowermost mantle. If the pPv transition is the source of the D '' discontinuity, regions with sharp discontinuities may require distinct compositions, such as a higher Mg/Si ratio or a lower Al content.
C1 [Catalli, Krystle; Shim, Sang-Heon] MIT, Cambridge, MA 02139 USA.
   [Prakapenka, Vitali] Univ Chicago, GeoSoilEnviroCARS, Chicago, IL 60637 USA.
C3 Massachusetts Institute of Technology (MIT); University of Chicago
RP Shim, SH (corresponding author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM sangshim@mit.edu
FU US National Science Foundation (NSF) [EAR0738655]; US Department of Energy ( DOE) National Nuclear Security Administration Stewardship Science Graduate Fellowship
NR 34
TC 101
Z9 114
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 DEC 10
PY 2009
VL 462
IS 7274
BP 782
EP U101
DI 10.1038/nature08598
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900037
PM 20010685
DA 2026-03-09
ER

PT J
AU Laurén, J
   Gimbel, DA
   Nygaard, HB
   Gilbert, JW
   Strittmatter, SM
AF Lauren, Juha
   Gimbel, David A.
   Nygaard, Haakon B.
   Gilbert, John W.
   Strittmatter, Stephen M.
TI Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
SO NATURE
LA English
DT Article
ID alzheimers-disease; natural oligomers; transgenic mice; binding-sites; prp; receptors; memory; identification; transmission; a-beta(1-42)
AB A pathological hallmark of Alzheimer's disease is an accumulation of insoluble plaque containing the amyloid-beta peptide of 40-42 amino acid residues(1). Prefibrillar, soluble oligomers of amyloid-beta have been recognized to be early and key intermediates in Alzheimer's-disease-related synaptic dysfunction(2-9). At nanomolar concentrations, soluble amyloid-beta oligomers block hippocampal long-term potentiation(7), cause dendritic spine retraction from pyramidal cells(5,8) and impair rodent spatial memory(2). Soluble amyloid-beta oligomers have been prepared from chemical syntheses, transfected cell culture supernatants, transgenic mouse brain and human Alzheimer's disease brain(2,4,7,9). Together, these data imply a high-affinity cell-surface receptor for soluble amyloid-beta oligomers on neurons-one that is central to the pathophysiological process in Alzheimer's disease. Here we identify the cellular prion protein (PrPC) as an amyloid-beta-oligomer receptor by expression cloning. Amyloid-beta oligomers bind with nanomolar affinity to PrPC, but the interaction does not require the infectious PrPSc conformation. Synaptic responsiveness in hippocampal slices from young adult PrP null mice is normal, but the amyloid-beta oligomer blockade of long-term potentiation is absent. Anti-PrP antibodies prevent amyloid-beta-oligomer binding to PrPC and rescue synaptic plasticity in hippocampal slices from oligomeric amyloid-beta. Thus, PrPC is a mediator of amyloid-beta-oligomer-induced synaptic dysfunction, and PrPC-specific pharmaceuticals may have therapeutic potential for Alzheimer's disease.
C1 [Lauren, Juha; Gimbel, David A.; Nygaard, Haakon B.; Gilbert, John W.; Strittmatter, Stephen M.] Yale Univ, Sch Med, Cellular Neurosci Neurodegenerat & Repair Program, New Haven, CT 06536 USA.
C3 Yale University
RP Strittmatter, SM (corresponding author), Yale Univ, Sch Med, Cellular Neurosci Neurodegenerat & Repair Program, 333 Cedar St, New Haven, CT 06536 USA.
EM stephen.strittmatter@yale.edu
FU Brown-Coxe Postdoctoral Fellow; NIH [5T32GN07205]; Kavli Institute for Neuroscience at Yale University; Falk Medical Research Trust; NIDA; National Institute on Drug Abuse [P30DA018343] Funding Source: NIH RePORTER
NR 37
TC 1348
Z9 1558
U1 1
U2 275
PU NATURE PUBLISHING 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 26
PY 2009
VL 457
IS 7233
BP 1128
EP U84
DI 10.1038/nature07761
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 411VI
UT WOS:000263680100040
PM 19242475
DA 2026-03-09
ER

PT J
AU Spite, M
   Norling, LV
   Summers, L
   Yang, R
   Cooper, D
   Petasis, NA
   Flower, RJ
   Perretti, M
   Serhan, CN
AF Spite, Matthew
   Norling, Lucy V.
   Summers, Lisa
   Yang, Rong
   Cooper, Dianne
   Petasis, Nicos A.
   Flower, Roderick J.
   Perretti, Mauro
   Serhan, Charles N.
TI Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis
SO NATURE
LA English
DT Article
ID nitric-oxide; lipid mediators; acute-inflammation; endotoxic-shock; in-vivo; macrophages; activation; resolution; receptors; mortality
AB A growing body of evidence indicates that resolution of acute inflammation is an active process(1,2). Resolvins are a new family of lipid mediators enzymatically generated within resolution networks that possess unique and specific functions to orchestrate catabasis, the phase in which disease declines(2,3). Resolvin D2 (RvD2) was originally identified in resolving exudates, yet its individual contribution in resolution remained to be elucidated. Here, we establish RvD2's potent stereoselective actions in reducing excessive neutrophil trafficking to inflammatory loci. RvD2 decreased leukocyte-endothelial interactions in vivo by endothelial-dependent nitric oxide production, and by direct modulation of leukocyte adhesion receptor expression. In mice with microbial sepsis initiated by caecal ligation and puncture, RvD2 sharply decreased both local and systemic bacterial burden, excessive cytokine production and neutrophil recruitment, while increasing peritoneal mononuclear cells and macrophage phagocytosis. These multi-level pro-resolving actions of RvD2 translate to increased survival from sepsis induced by caecal ligation and puncture and surgery. Together, these results identify RvD2 as a potent endogenous regulator of excessive inflammatory responses that acts via multiple cellular targets to stimulate resolution and preserve immune vigilance.
C1 [Spite, Matthew; Norling, Lucy V.; Summers, Lisa; Yang, Rong; Serhan, Charles N.] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
   [Spite, Matthew; Norling, Lucy V.; Summers, Lisa; Yang, Rong; Serhan, Charles N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Norling, Lucy V.; Cooper, Dianne; Flower, Roderick J.; Perretti, Mauro] Queen Mary Univ London, Barts & London Med Sch, William Harvey Res Inst, London EC1M 6BQ, England.
   [Petasis, Nicos A.] Univ So Calif, Loker Hydrocarbon Res Inst, Los Angeles, CA 90089 USA.
   [Petasis, Nicos A.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of London; Queen Mary University London; University of Southern California; University of Southern California
RP Serhan, CN (corresponding author), Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA.
EM cnserhan@zeus.bwh.harvard.edu
FU National Institutes of Health [GM-38765, P50-DE016191]; Welcome Trust [086867/Z/08/Z, 085903/Z/08]; Arthritis Research Campaign UK [18445, 18103]; NHLBI [HL087526]; Versus Arthritis [18103] Funding Source: researchfish; Wellcome Trust [086867/Z/08/Z] Funding Source: Wellcome Trust
NR 32
TC 577
Z9 635
U1 1
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 29
PY 2009
VL 461
IS 7268
BP 1287
EP U125
DI 10.1038/nature08541
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800050
PM 19865173
DA 2026-03-09
ER

PT J
AU Pagel, M
AF Pagel, Mark
TI Natural selection 150 years on
SO NATURE
LA English
DT Article
ID evolution; speciation; drosophila; language; dynamics; animals; rise
C1 [Pagel, Mark] Univ Reading, Sch Biol Sci, Reading RG6 6AJ, 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 6AJ, Berks, England.
EM m.pagel@reading.ac.uk
FU Natural Environment Research Council [NE/C51992X/1] Funding Source: researchfish
NR 28
TC 14
Z9 18
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 FEB 12
PY 2009
VL 457
IS 7231
BP 808
EP 811
DI 10.1038/nature07889
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700029
PM 19212397
DA 2026-03-09
ER

PT J
AU Rodell, M
   Velicogna, I
   Famiglietti, JS
AF Rodell, Matthew
   Velicogna, Isabella
   Famiglietti, James S.
TI Satellite-based estimates of groundwater depletion in India
SO NATURE
LA English
DT Article
ID water-resources; grace; precipitation; system
AB Groundwater is a primary source of fresh water in many parts of the world. Some regions are becoming overly dependent on it, consuming groundwater faster than it is naturally replenished and causing water tables to decline unremittingly(1). Indirect evidence suggests that this is the case in northwest India(2), but there has been no regional assessment of the rate of groundwater depletion. Here we use terrestrial water storage-change observations from the NASA Gravity Recovery and Climate Experiment satellites(3) and simulated soil-water variations from a data-integrating hydrological modelling system(4) to show that groundwater is being depleted at a mean rate of 4.0 +/- 1.0 cm yr(-1) equivalent height of water (17.7 +/- 4.5 km(3) yr(-1)) over the Indian states of Rajasthan, Punjab and Haryana (including Delhi). During our study period of August 2002 to October 2008, groundwater depletion was equivalent to a net loss of 109 km(3) of water, which is double the capacity of India's largest surface-water reservoir. Annual rainfall was close to normal throughout the period and we demonstrate that the other terrestrial water storage components (soil moisture, surface waters, snow, glaciers and biomass) did not contribute significantly to the observed decline in total water levels. Although our observational record is brief, the available evidence suggests that unsustainable consumption of groundwater for irrigation and other anthropogenic uses is likely to be the cause. If measures are not taken soon to ensure sustainable groundwater usage, the consequences for the 114,000,000 residents of the region may include a reduction of agricultural output and shortages of potable water, leading to extensive socioeconomic stresses.
C1 [Rodell, Matthew] NASA, Goddard Space Flight Ctr, Hydrol Sci Branch, Greenbelt, MD 20771 USA.
   [Velicogna, Isabella; Famiglietti, James S.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
   [Velicogna, Isabella] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Velicogna, Isabella] Univ Udine, Dept Phys, I-33100 Udine, Italy.
C3 National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of California System; University of California Irvine; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of Udine
RP Rodell, M (corresponding author), NASA, Goddard Space Flight Ctr, Hydrol Sci Branch, Code 614-3, Greenbelt, MD 20771 USA.
EM matthew.rodell@nasa.gov
FU NASA's Solid Earth; Natural Hazards Program; Terrestrial Hydrology Program; Cryospheric Science Program
NR 30
TC 2115
Z9 2432
U1 22
U2 893
PU 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 20
PY 2009
VL 460
IS 7258
BP 999
EP U80
DI 10.1038/nature08238
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500031
PM 19675570
DA 2026-03-09
ER

PT J
AU Haji-Akbari, A
   Engel, M
   Keys, AS
   Zheng, XY
   Petschek, RG
   Palffy-Muhoray, P
   Glotzer, SC
AF Haji-Akbari, Amir
   Engel, Michael
   Keys, Aaron S.
   Zheng, Xiaoyu
   Petschek, Rolfe G.
   Palffy-Muhoray, Peter
   Glotzer, Sharon C.
TI Disordered, quasicrystalline and crystalline phases of densely packed tetrahedra
SO NATURE
LA English
DT Article
ID packings
AB All hard, convex shapes are conjectured by Ulam to pack more densely than spheres(1), which have a maximum packing fraction of phi = pi/root 18 approximate to 0.7405. Simple lattice packings of many shapes easily surpass this packing fraction(2,3). For regular tetrahedra, this conjecture was shown to be true only very recently; an ordered arrangement was obtained via geometric construction with phi = 0.7786 (ref. 4), which was subsequently compressed numerically to phi = 0.7820 (ref. 5), while compressing with different initial conditions led to phi = 0.8230 ( ref. 6). Here we show that tetrahedra pack even more densely, and in a completely unexpected way. Following a conceptually different approach, using thermodynamic computer simulations that allow the system to evolve naturally towards high-density states, we observe that a fluid of hard tetrahedra undergoes a first-order phase transition to a dodecagonal quasicrystal(7-10), which can be compressed to a packing fraction of phi = 0.8324. By compressing a crystalline approximant of the quasicrystal, the highest packing fraction we obtain is phi = 0.8503. If quasicrystal formation is suppressed, the system remains disordered, jams and compresses to phi = 0.7858. Jamming and crystallization are both preceded by an entropy-driven transition from a simple fluid of independent tetrahedra to a complex fluid characterized by tetrahedra arranged in densely packed local motifs of pentagonal dipyramids that form a percolating network at the transition. The quasicrystal that we report represents the first example of a quasicrystal formed from hard or non-spherical particles. Our results demonstrate that particle shape and entropy can produce highly complex, ordered structures.
C1 [Haji-Akbari, Amir; Engel, Michael; Keys, Aaron S.; Glotzer, Sharon C.] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA.
   [Glotzer, Sharon C.] Univ Michigan, Dept Mat Sci & Engn, Ann Arbor, MI 48109 USA.
   [Palffy-Muhoray, Peter] Kent State Univ, Inst Liquid Crystal, Kent, OH 44242 USA.
   [Zheng, Xiaoyu] Kent State Univ, Dept Math Sci, Kent, OH 44242 USA.
   [Petschek, Rolfe G.] Case Western Reserve Univ, Dept Phys, Cleveland, OH 44106 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University System of Ohio; Kent State University; Kent State University Kent; Kent State University Salem; University System of Ohio; Kent State University; Kent State University Kent; Kent State University Salem; University System of Ohio; Case Western Reserve University
RP Glotzer, SC (corresponding author), Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA.
EM sglotzer@umich.edu
FU The Air Force Office of Scientific Research; The National Science Foundation; Deutsche Forschungsgemeinschaft; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [0807954] Funding Source: National Science Foundation
NR 32
TC 375
Z9 442
U1 2
U2 235
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 773
EP U91
DI 10.1038/nature08641
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900035
PM 20010683
DA 2026-03-09
ER

PT J
AU McConnachie, AW
   Irwin, MJ
   Ibata, RA
   Dubinski, J
   Widrow, LM
   Martin, NF
   Côté, P
   Dotter, AL
   Navarro, JF
   Ferguson, AMN
   Puzia, TH
   Lewis, GF
   Babul, A
   Barmby, P
   Bienaymé, O
   Chapman, SC
   Cockcroft, R
   Collins, MLM
   Fardal, MA
   Harris, WE
   Huxor, A
   Mackey, AD
   Peñarrubia, J
   Rich, RM
   Richer, HB
   Siebert, A
   Tanvir, N
   Valls-Gabaud, D
   Venn, KA
AF McConnachie, Alan W.
   Irwin, Michael J.
   Ibata, Rodrigo A.
   Dubinski, John
   Widrow, Lawrence M.
   Martin, Nicolas F.
   Cote, Patrick
   Dotter, Aaron L.
   Navarro, Julio F.
   Ferguson, Annette M. N.
   Puzia, Thomas H.
   Lewis, Geraint F.
   Babul, Arif
   Barmby, Pauline
   Bienayme, Olivier
   Chapman, Scott C.
   Cockcroft, Robert
   Collins, Michelle L. M.
   Fardal, Mark A.
   Harris, William E.
   Huxor, Avon
   Mackey, A. Dougal
   Penarrubia, Jorge
   Rich, R. Michael
   Richer, Harvey B.
   Siebert, Arnaud
   Tanvir, Nial
   Valls-Gabaud, David
   Venn, Kimberly A.
TI The remnants of galaxy formation from a panoramic survey of the region around M31
SO NATURE
LA English
DT Article
ID local group galaxy; andromeda galaxy; galactic satellites; proper motion; halo; substructure; origin; stars; disk; sagittarius
AB In hierarchical cosmological models(1), galaxies grow in mass through the continual accretion of smaller ones. The tidal disruption of these systems is expected to result in loosely bound stars surrounding the galaxy, at distances that reach 10-100 times the radius of the central disk(2,3). The number, luminosity and morphology of the relics of this process provide significant clues to galaxy formation history(4), but obtaining a comprehensive survey of these components is difficult because of their intrinsic faintness and vast extent. Here we report a panoramic survey of the Andromeda galaxy (M31). We detect stars and coherent structures that are almost certainly remnants of dwarf galaxies destroyed by the tidal field of M31. An improved census of their surviving counterparts implies that three-quarters of M31's satellites brighter than M(v) =-6 await discovery. The brightest companion, Triangulum (M33), is surrounded by a stellar structure that provides persuasive evidence for a recent encounter with M31. This panorama of galaxy structure directly confirms the basic tenets of the hierarchical galaxy formation model and reveals the shared history of M31 and M33 in the unceasing build-up of galaxies.
C1 [McConnachie, Alan W.; Cote, Patrick; Puzia, Thomas H.] NRC Herzberg Inst Astrophys, Victoria, BC V9E 2E7, Canada.
   [Irwin, Michael J.; Chapman, Scott C.; Collins, Michelle L. M.; Penarrubia, Jorge] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Ibata, Rodrigo A.; Bienayme, Olivier; Siebert, Arnaud] Observ Strasbourg, F-67000 Strasbourg, France.
   [Dubinski, John] Univ Toronto, Dept Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Widrow, Lawrence M.] Queens Univ, Dept Phys Engn Phys & Astron, Kingston, ON K7L 3N6, Canada.
   [Martin, Nicolas F.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Dotter, Aaron L.; Navarro, Julio F.; Babul, Arif; Venn, Kimberly A.] Univ Victoria, Dept Phys & Astron, Victoria, BC V8P 5C2, Canada.
   [Ferguson, Annette M. N.; Mackey, A. Dougal] Univ Edinburgh, Inst Astron, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Lewis, Geraint F.] Univ Sydney, Sch Phys, Sydney Inst Astron, Sydney, NSW 2006, Australia.
   [Barmby, Pauline] Univ Western Ontario, Dept Phys & Astron, London, ON N6A 3K7, Canada.
   [Cockcroft, Robert; Harris, William E.] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada.
   [Fardal, Mark A.] Univ Massachusetts, Dept Astron, Amherst, MA 01003 USA.
   [Huxor, Avon] Univ Bristol, HH Wills Phys Lab, Dept Phys, Astrophys Grp, Bristol BS8 1TL, Avon, England.
   [Rich, R. Michael] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Richer, Harvey B.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Tanvir, Nial] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Valls-Gabaud, David] Observ Paris, CNRS, UMR 8111, Lab Galaxies & Etoiles Phys & Instrumentat, F-92195 Meudon, France.
C3 National Research Council Canada; University of Cambridge; University of Toronto; Queens University - Canada; Max Planck Society; University of Victoria; University of Edinburgh; University of Sydney; Western University (University of Western Ontario); McMaster University; University of Massachusetts System; University of Massachusetts Amherst; University of Bristol; University of California System; University of California Los Angeles; University of British Columbia; University of Leicester; Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite
RP McConnachie, AW (corresponding author), NRC Herzberg Inst Astrophys, 5071 W Saanich Rd, Victoria, BC V9E 2E7, Canada.
EM alan.mcconnachie@nrc-cnrc.gc.ca
FU European Commission [MCEXT-CT-2005-025869]; Australian Nuclear Science and Technology Organisation (ANSTO); National Science Foundation [AST-0709479]; Space Telescope Science Institute [GO-9453, GO-10265, GO-10816]; Science and Technology Facilities Council [PP/C002229/1, ST/F001967/1, PP/E00105X/1, ST/H004165/1, ST/H004157/1] Funding Source: researchfish; STFC [ST/F001967/1, ST/H004157/1, PP/E00105X/1, ST/H004165/1, PP/C002229/1] Funding Source: UKRI
NR 30
TC 535
Z9 601
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 SEP 3
PY 2009
VL 461
IS 7260
BP 66
EP 69
DI 10.1038/nature08327
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800030
PM 19727194
DA 2026-03-09
ER

PT J
AU Agarwal, N
   Lamichhane, G
   Gupta, R
   Nolan, S
   Bishai, WR
AF Agarwal, Nisheeth
   Lamichhane, Gyanu
   Gupta, Radhika
   Nolan, Scott
   Bishai, William R.
TI Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase
SO NATURE
LA English
DT Article
ID necrosis-factor-alpha; phagosome maturation; infection; transcription; murine; genes; lungs; granulomas; expansion; arrest
AB With 8.9 million new cases and 1.7 million deaths per year, tuberculosis is a leading global killer that has not been effectively controlled(1,2). The causative agent, Mycobacterium tuberculosis, proliferates within host macrophages where it modifies both its intracellular and local tissue environment, resulting in caseous granulomas with incomplete bacterial sterilization(3,4). Although infection by various mycobacterial species produces a cyclic AMP burst within macrophages that influences cell signalling, the underlying mechanism for the cAMP burst remains unclear(5-7). Here we show that among the 17 adenylate cyclase genes present in M. tuberculosis, at least one (Rv0386) is required for virulence. Furthermore, we demonstrate that the Rv0386 adenylate cyclase facilitates delivery of bacterial-derived cAMP into the macrophage cytoplasm. Loss of Rv0386 and the intramacrophage cAMP it delivers results in reductions in TNF-alpha production via the protein kinase A and cAMP response-element-binding protein pathway, decreased immunopathology in animal tissues, and diminished bacterial survival. Direct intoxication of host cells by bacterial-derived cAMP may enable M. tuberculosis to modify both its intracellular and tissue environments to facilitate its long-term survival.
C1 [Agarwal, Nisheeth; Lamichhane, Gyanu; Gupta, Radhika; Nolan, Scott; Bishai, William R.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD 21231 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Bishai, WR (corresponding author), Johns Hopkins Sch Med, Dept Med, CRB2,Room 1-08,1550 Orleans St, Baltimore, MD 21231 USA.
EM wbishai@jhmi.edu
FU National Institutes of Health (NIH) [AI30036, AI36973, AI37856]
NR 34
TC 183
Z9 211
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 2
PY 2009
VL 460
IS 7251
BP 98
EP U112
DI 10.1038/nature08123
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200037
PM 19516256
DA 2026-03-09
ER

PT J
AU Jungers, WL
   Harcourt-Smith, WEH
   Wunderlich, RE
   Tocheri, MW
   Larson, SG
   Sutikna, T
   Due, RA
   Morwood, MJ
AF Jungers, W. L.
   Harcourt-Smith, W. E. H.
   Wunderlich, R. E.
   Tocheri, M. W.
   Larson, S. G.
   Sutikna, T.
   Due, Rhokus Awe
   Morwood, M. J.
TI The foot of Homo floresiensis
SO NATURE
LA English
DT Article
ID pressure distribution; late pleistocene; hadar hominids; evolution; locomotion; bipedalism; indonesia; dmanisi; fossils; gait
AB Homo floresiensis is an endemic hominin species that occupied Liang Bua, a limestone cave on Flores in eastern Indonesia, during the Late Pleistocene epoch(1,2). The skeleton of the type specimen (LB1) of H. floresiensis includes a relatively complete left foot and parts of the right foot(3). These feet provide insights into the evolution of bipedalism and, together with the rest of the skeleton, have implications for hominin dispersal events into Asia. Here we show that LB1's foot is exceptionally long relative to the femur and tibia, proportions never before documented in hominins but seen in some African apes. Although the metatarsal robusticity sequence is human-like and the hallux is fully adducted, other intrinsic proportions and pedal features are more ape-like. The postcranial anatomy of H. floresiensis is that of a biped(1-3), but the unique lower-limb proportions and surprising combination of derived and primitive pedal morphologies suggest kinematic and biomechanical differences from modern human gait. Therefore, LB1 offers the most complete glimpse of a bipedal hominin foot that lacks the full suite of derived features characteristic of modern humans and whose mosaic design may be primitive for the genus Homo. These new findings raise the possibility that the ancestor of H. floresiensis was not Homo erectus but instead some other, more primitive, hominin whose dispersal into southeast Asia is still undocumented.
C1 [Jungers, W. L.; Larson, S. G.] SUNY Stony Brook, Med Ctr, Dept Anat Sci, Stony Brook, NY 11794 USA.
   [Harcourt-Smith, W. E. H.] Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA.
   [Wunderlich, R. E.] James Madison Univ, Dept Biol Sci, Harrisonburg, VA 22807 USA.
   [Tocheri, M. W.] Smithsonian Inst, Natl Museum Nat Hist, Dept Anthropol, Humans Origins Program, Washington, DC 20013 USA.
   [Sutikna, T.; Due, Rhokus Awe] Natl Res & Dev Ctr Archaeol, Jakarta 12001, Indonesia.
   [Morwood, M. J.] Univ Wollongong, Sch Earth & Environm Sci, Wollongong, NSW 2522, Australia.
C3 State University of New York (SUNY) System; Stony Brook University; American Museum of Natural History (AMNH); James Madison University; Smithsonian Institution; Smithsonian National Museum of Natural History; National Research & Development Centre for Archaeology - Indonesia; University of Wollongong
RP Jungers, WL (corresponding author), SUNY Stony Brook, Med Ctr, Dept Anat Sci, Stony Brook, NY 11794 USA.
EM william.jungers@stonybrook.edu
FU Australian Research Council; National Geographic Society; Wenner-Gren Foundation for Anthropological Research; Wellcome Trust and the Leakey Foundation
NR 30
TC 134
Z9 173
U1 0
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 7
PY 2009
VL 459
IS 7243
BP 81
EP 84
DI 10.1038/nature07989
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300033
PM 19424155
DA 2026-03-09
ER

PT J
AU Boland, MJ
   Hazen, JL
   Nazor, KL
   Rodriguez, AR
   Gifford, W
   Martin, G
   Kupriyanov, S
   Baldwin, KK
AF Boland, Michael J.
   Hazen, Jennifer L.
   Nazor, Kristopher L.
   Rodriguez, Alberto R.
   Gifford, Wesley
   Martin, Greg
   Kupriyanov, Sergey
   Baldwin, Kristin K.
TI Adult mice generated from induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID tetraploid cells; fibroblasts; expression; induction; neurons
AB Recent landmark experiments have shown that transient overexpression of a small number of transcription factors can reprogram differentiated cells into induced pluripotent stem (iPS) cells that resemble embryonic stem (ES) cells(1-7). These iPS cells hold great promise for medicine because they have the potential to generate patient-specific cell types for cell replacement therapy and produce in vitro models of disease, without requiring embryonic tissues or oocytes(8-10). Although current iPS cell lines resemble ES cells, they have not passed the most stringent test of pluripotency by generating full-term or adult mice in tetraploid complementation assays(3,11), raising questions as to whether they are sufficiently potent to generate all of the cell types in an organism. Whether this difference between iPS and ES cells reflects intrinsic limitations of direct reprogramming is not known. Here we report fertile adult mice derived entirely from iPS cells that we generated by inducible genetic reprogramming of mouse embryonic fibroblasts. Producing adult mice derived entirely from a reprogrammed fibroblast shows that all features of a differentiated cell can be restored to an embryonic level of pluripotency without exposure to unknown ooplasmic factors. Comparing these fully pluripotent iPS cell lines to less developmentally potent lines may reveal molecular markers of different pluripotent states. Furthermore, mice derived entirely from iPS cells will provide a new resource to assess the functional and genomic stability of cells and tissues derived from iPS cells, which is important to validate their utility in cell replacement therapy and research applications.
C1 [Boland, Michael J.; Hazen, Jennifer L.; Nazor, Kristopher L.; Baldwin, Kristin K.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
   [Rodriguez, Alberto R.; Martin, Greg; Kupriyanov, Sergey] Scripps Res Inst, Mouse Genet Core Facil, La Jolla, CA 92037 USA.
   [Gifford, Wesley] Univ Calif San Diego, Med Scientist Training Program, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; Scripps Research Institute; University of California System; University of California San Diego
RP Baldwin, KK (corresponding author), Scripps Res Inst, Dept Cell Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM kitnazor@scripps.edu; kbaldwin@scripps.edu
FU Pew Scholars Award; California Institute of Regenerative Medicine; Whitehall Foundation; O'Keefe Foundation; Shapiro Family Foundation
NR 32
TC 350
Z9 437
U1 0
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 91
EP U94
DI 10.1038/nature08310
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800036
PM 19672243
DA 2026-03-09
ER

PT J
AU Hattori, D
   Chen, Y
   Matthews, BJ
   Salwinski, L
   Sabatti, C
   Grueber, WB
   Zipursky, SL
AF Hattori, Daisuke
   Chen, Yi
   Matthews, Benjamin J.
   Salwinski, Lukasz
   Sabatti, Chiara
   Grueber, Wesley B.
   Zipursky, S. Lawrence
TI Robust discrimination between self and non-self neurites requires thousands of Dscam1 isoforms
SO NATURE
LA English
DT Article
ID drosophila mushroom body; sensory neurons; axon guidance; molecular diversity; structural basis; specificity; binding; morphogenesis; organization; recognition
AB Down Syndrome cell adhesion molecule (Dscam) genes encode neuronal cell recognition proteins of the immunoglobulin superfamily(1,2). In Drosophila, Dscam1 generates 19,008 different ectodomains by alternative splicing of three exon clusters, each encoding half or a complete variable immunoglobulin domain(3). Identical isoforms bind to each other, but rarely to isoforms differing at any one of the variable immunoglobulin domains(4,5). Binding between isoforms on opposing membranes promotes repulsion(6). Isoform diversity provides the molecular basis for neurite self-avoidance(6-11). Self-avoidance refers to the tendency of branches from the same neuron (self-branches) to selectively avoid one another(12). To ensure that repulsion is restricted to self-branches, different neurons express different sets of isoforms in a biased stochastic fashion(7,13). Genetic studies demonstrated that Dscam1 diversity has a profound role in wiring the fly brain(11). Here we show how many isoforms are required to provide an identification system that prevents non-self branches from inappropriately recognizing each other. Using homologous recombination, we generated mutant animals encoding 12, 24, 576 and 1,152 potential isoforms. Mutant animals with deletions encoding 4,752 and 14,256 isoforms(14) were also analysed. Branching phenotypes were assessed in three classes of neurons. Branching patterns improved as the potential number of isoforms increased, and this was independent of the identity of the isoforms. Although branching defects in animals with 1,152 potential isoforms remained substantial, animals with 4,752 isoforms were indistinguishable from wild-type controls. Mathematical modelling studies were consistent with the experimental results that thousands of isoforms are necessary to ensure acquisition of unique Dscam1 identities in many neurons. We conclude that thousands of isoforms are essential to provide neurons with a robust discrimination mechanism to distinguish between self and non-self during self-avoidance.
C1 [Hattori, Daisuke; Chen, Yi; Zipursky, S. Lawrence] Univ Calif Los Angeles, David Geffen Sch Med, Howard Hughes Med Inst, Dept Biol Chem, Los Angeles, CA 90095 USA.
   [Matthews, Benjamin J.] Columbia Univ, Med Ctr, Ctr Neurobiol & Behav, New York, NY 10032 USA.
   [Salwinski, Lukasz] Univ Calif Los Angeles, Inst Mol Biol, Howard Hughes Med Inst, DOE Inst Genom & Prote, Los Angeles, CA 90095 USA.
   [Sabatti, Chiara] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Grueber, Wesley B.] Columbia Univ, Med Ctr, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Grueber, Wesley B.] Columbia Univ, Med Ctr, Dept Neurosci, New York, NY 10032 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; Howard Hughes Medical Institute; Columbia University; Howard Hughes Medical Institute; United States Department of Energy (DOE); 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; Columbia University; Columbia University
RP Zipursky, SL (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Howard Hughes Med Inst, Dept Biol Chem, Los Angeles, CA 90095 USA.
EM lzipursky@mednet.ucla.edu
FU NIH; NRSA; NIH/NINDS; Howard Hughes Medical Institute
NR 26
TC 128
Z9 170
U1 1
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 OCT 1
PY 2009
VL 461
IS 7264
BP 644
EP U87
DI 10.1038/nature08431
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600039
PM 19794492
DA 2026-03-09
ER

PT J
AU Gielen, M
   Retchless, BS
   Mony, L
   Johnson, JW
   Paoletti, P
AF Gielen, Marc
   Retchless, Beth Siegler
   Mony, Laetitia
   Johnson, Jon W.
   Paoletti, Pierre
TI Mechanism of differential control of NMDA receptor activity by NR2 subunits
SO NATURE
LA English
DT Article
ID d-aspartate receptor; glutamate-receptor; zinc inhibition; ligand-binding; molecular determinants; channel; domain; affinity; activation; proton
AB N-methyl-D-aspartate ( NMDA) receptors (NMDARs) are a major class of excitatory neurotransmitter receptors in the central nervous system. They form glutamate-gated ion channels that are highly permeable to calcium and mediate activity-dependent synaptic plasticity(1). NMDAR dysfunction is implicated in multiple brain disorders, including stroke, chronic pain and schizophrenia(2). NMDARs exist as multiple subtypes with distinct pharmacological and biophysical properties that are largely determined by the type of NR2 subunit (NR2A to NR2D) incorporated in the heteromeric NR1/NR2 complex(1,3,4). A fundamental difference between NMDAR subtypes is their channel maximal open probability (Po), which spans a 50-fold range from about 0.5 for NR2A-containing receptors to about 0.01 for receptors containing NR2C and NR2D; NR2B-containing receptors have an intermediate value (about 0.1)(5-9). These differences in Po confer unique charge transfer capacities and signalling properties on each receptor subtype(4,6,10,11). The molecular basis for this profound difference in activity between NMDAR subtypes is unknown. Here we show that the subunit-specific gating of NMDARs is controlled by the region formed by the NR2 amino-terminal domain (NTD), an extracellular clamshell-like domain previously shown to bind allosteric inhibitors(12-15), and the short linker connecting the NTD to the agonist-binding domain (ABD). The subtype specificity of NMDAR Po largely reflects differences in the spontaneous (ligand-independent) equilibrium between open-cleft and closed-cleft conformations of the NR2-NTD. This NTD-driven gating control also affects pharmacological properties by setting the sensitivity to the endogenous inhibitors zinc and protons. Our results provide a proof of concept for a drug-based bidirectional control of NMDAR activity by using molecules acting either as NR2-NTD 'closers' or 'openers' promoting receptor inhibition or potentiation, respectively.
C1 [Gielen, Marc; Mony, Laetitia; Paoletti, Pierre] CNRS, Ecole Normale Super, Neurobiol Lab, F-75005 Paris, France.
   [Retchless, Beth Siegler; Johnson, Jon W.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA.
C3 Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Paoletti, P (corresponding author), CNRS, Ecole Normale Super, Neurobiol Lab, 46 Rue Ulm, F-75005 Paris, France.
EM paoletti@biologie.ens.fr
FU Ministere de la Recherche; Universite Pierre et Marie Curie (UPMC); Fondation pour la Recherche Medicale (FRM); NIH [R01 MH045817]; Institut National de la Sante et de la Recherche Medicale (INSERM); Agence Nationale pour la Recherche (ANR); GlaxoSmith Kline; Equipe FRM
NR 38
TC 269
Z9 335
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 JUN 4
PY 2009
VL 459
IS 7247
BP 703
EP U107
DI 10.1038/nature07993
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600044
PM 19404260
DA 2026-03-09
ER

PT J
AU Nienborg, H
   Cumming, BG
AF Nienborg, Hendrikje
   Cumming, Bruce G.
TI Decision-related activity in sensory neurons reflects more than a neuron's causal effect
SO NATURE
LA English
DT Article
ID early visual-cortex; perceptual decision; task strategy; v2 neurons; area mt; choice; responses; discrimination; representation; variability
AB During perceptual decisions, the activity of sensory neurons correlates with a subject's percept, even when the physical stimulus is identical(1-9). The origin of this correlation is unknown. Current theory proposes a causal effect of noise in sensory neurons on perceptual decisions(10-12), but the correlation could result from different brain states associated with the perceptual choice(13) (a top-down explanation). These two schemes have very different implications for the role of sensory neurons in forming decisions(14). Here we use white-noise analysis(15) to measure tuning functions of V2 neurons associated with choice and simultaneously measure how the variation in the stimulus affects the subjects' (two macaques) perceptual decisions(16-18). In causal models, stronger effects of the stimulus upon decisions, mediated by sensory neurons, are associated with stronger choice-related activity. However, we find that over the time course of the trial these measures change in different directions-at odds with causal models. An analysis of the effect of reward size also supports this conclusion. Finally, we find that choice is associated with changes in neuronal gain that are incompatible with causal models. All three results are readily explained if choice is associated with changes in neuronal gain caused by top-down phenomena that closely resemble attention(19). We conclude that top-down processes contribute to choice-related activity. Thus, even forming simple sensory decisions involves complex interactions between cognitive processes and sensory neurons.
C1 [Nienborg, Hendrikje; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
RP Nienborg, H (corresponding author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM hnienb@gmail.com
FU US National Institutes of Health; National Eye Institute; National Eye Institute [ZIAEY000404] Funding Source: NIH RePORTER
NR 31
TC 252
Z9 295
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 MAY 7
PY 2009
VL 459
IS 7243
BP 89
EP U93
DI 10.1038/nature07821
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300035
PM 19270683
DA 2026-03-09
ER

PT J
AU Gu, LC
   Wang, B
   Kulkarni, A
   Geders, TW
   Grindberg, RV
   Gerwick, L
   Hakansson, K
   Wipf, P
   Smith, JL
   Gerwick, WH
   Sherman, DH
AF Gu, Liangcai
   Wang, Bo
   Kulkarni, Amol
   Geders, Todd W.
   Grindberg, Rashel V.
   Gerwick, Lena
   Hakansson, Kristina
   Wipf, Peter
   Smith, Janet L.
   Gerwick, William H.
   Sherman, David H.
TI Metamorphic enzyme assembly in polyketide diversification
SO NATURE
LA English
DT Article
ID cyanobacterium lyngbya-majuscula; biosynthetic gene-cluster; peptide synthetase; barbamide biosynthesis; bacterial symbiont; mass-spectrometry; bacillus-subtilis; crystal-structure; natural-product; curacin-a
AB Natural product chemical diversity is fuelled by the emergence and ongoing evolution of biosynthetic pathways in secondary metabolism(1). However, co-evolution of enzymes for metabolic diversification is not well understood, especially at the biochemical level. Here, two parallel assemblies with an extraordinarily high sequence identity from Lyngbya majuscula forma beta-branched cyclopropane in the curacin A pathway (Cur), and a vinyl chloride group in the jamaicamide pathway (Jam). The components include a halogenase, a 3-hydroxy-3-methylglutaryl enzyme cassette for polyketide beta-branching, and an enoyl reductase domain. The halogenase from CurA, and the dehydratases (ECH(1)s), decarboxylases (ECH(2)s) and enoyl reductase domains from both Cur and Jam, were assessed biochemically to determine the mechanisms of cyclopropane and vinyl chloride formation. Unexpectedly, the polyketide beta-branching pathway was modified by introduction of a gamma-chlorination step on (S)-3-hydroxy-3-methylglutaryl mediated by Cur halogenase, a non-haem Fe(II), alpha-ketoglutarate-dependent enzyme(2). In a divergent scheme, Cur ECH2 was found to catalyse formation of the alpha,beta enoyl thioester, whereas Jam ECH2 formed a vinyl chloride moiety by selectively generating the corresponding beta, gamma enoyl thioester of the 3-methyl-4-chloroglutaconyl decarboxylation product. Finally, the enoyl reductase domain of CurF specifically catalysed an unprecedented cyclopropanation on the chlorinated product of Cur ECH2 instead of the canonical alpha,beta C=C saturation reaction. Thus, the combination of chlorination and polyketide beta-branching, coupled with mechanistic diversification of ECH2 and enoyl reductase, leads to the formation of cyclopropane and vinyl chloride moieties. These results reveal a parallel interplay of evolutionary events in multienzyme systems leading to functional group diversity in secondary metabolites.
C1 [Gu, Liangcai; Geders, Todd W.; Smith, Janet L.; Sherman, David H.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
   [Gu, Liangcai; Sherman, David H.] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA.
   [Wang, Bo; Hakansson, Kristina; Sherman, David H.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
   [Smith, Janet L.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
   [Sherman, David H.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
   [Kulkarni, Amol; Wipf, Peter] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA.
   [Kulkarni, Amol; Wipf, Peter] Univ Pittsburgh, Ctr Chem Methodol & Lib Dev, Pittsburgh, PA 15260 USA.
   [Grindberg, Rashel V.; Gerwick, Lena; Gerwick, William H.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Grindberg, Rashel V.; Gerwick, Lena; Gerwick, William H.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of California System; University of California San Diego
RP Sherman, DH (corresponding author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
EM davidhs@umich.edu
FU National Institutes of Health; Eli Lilly Co.; Rackham Predoctoral Fellowship; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK042303] Funding Source: NIH RePORTER
NR 29
TC 150
Z9 187
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 JUN 4
PY 2009
VL 459
IS 7247
BP 731
EP 735
DI 10.1038/nature07870
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600050
PM 19494914
DA 2026-03-09
ER

PT J
AU Melcher, K
   Ng, LM
   Zhou, XE
   Soon, FF
   Xu, Y
   Suino-Powell, KM
   Park, SY
   Weiner, JJ
   Fujii, H
   Chinnusamy, V
   Kovach, A
   Li, J
   Wang, YH
   Li, JY
   Peterson, FC
   Jensen, DR
   Yong, EL
   Volkman, BF
   Cutler, SR
   Zhu, JK
   Xu, HE
AF Melcher, Karsten
   Ng, Ley-Moy
   Zhou, X. Edward
   Soon, Fen-Fen
   Xu, Yong
   Suino-Powell, Kelly M.
   Park, Sang-Youl
   Weiner, Joshua J.
   Fujii, Hiroaki
   Chinnusamy, Viswanathan
   Kovach, Amanda
   Li, Jun
   Wang, Yonghong
   Li, Jiayang
   Peterson, Francis C.
   Jensen, Davin R.
   Yong, Eu-Leong
   Volkman, Brian F.
   Cutler, Sean R.
   Zhu, Jian-Kang
   Xu, H. Eric
TI A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors
SO NATURE
LA English
DT Article
ID phosphatase-activity; gene-expression; protein-kinase; arabidopsis; binding; system; transduction; dehydration; germination
AB Abscisic acid (ABA) is a ubiquitous hormone that regulates plant growth, development and responses to environmental stresses. Its action is mediated by the PYR/PYL/RCAR family of START proteins, but it remains unclear how these receptors bind ABA and, in turn, how hormone binding leads to inhibition of the downstream type 2C protein phosphatase (PP2C) effectors. Here we report crystal structures of apo and ABA-bound receptors as well as a ternary PYL2-ABA-PP2C complex. The apo receptors contain an open ligand-binding pocket flanked by a gate that closes in response to ABA by way of conformational changes in two highly conserved beta-loops that serve as a gate and latch. Moreover, ABA-induced closure of the gate creates a surface that enables the receptor to dock into and competitively inhibit the PP2C active site. A conserved tryptophan in the PP2C inserts directly between the gate and latch, which functions to further lock the receptor in a closed conformation. Together, our results identify a conserved gate-latch-lock mechanism underlying ABA signalling.
C1 [Melcher, Karsten; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Xu, Yong; Suino-Powell, Kelly M.; Kovach, Amanda; Li, Jun; Xu, H. Eric] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA.
   [Ng, Ley-Moy; Soon, Fen-Fen; Li, Jun; Yong, Eu-Leong] Natl Univ Singapore, Dept Obstet & Gynecol, Natl Univ Singapore Hosp, Yong Loo Lin Sch Med,Grad Sch Integrat Sci & Engn, Singapore 119074, Singapore.
   [Park, Sang-Youl; Fujii, Hiroaki; Chinnusamy, Viswanathan; Cutler, Sean R.; Zhu, Jian-Kang] Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
   [Weiner, Joshua J.; Peterson, Francis C.; Jensen, Davin R.; Volkman, Brian F.] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA.
   [Fujii, Hiroaki; Chinnusamy, Viswanathan; Zhu, Jian-Kang] King Abdullah Univ Sci & Technol, Ctr Plant Stress Genom & Technol, Thuwal 239556900, Saudi Arabia.
   [Wang, Yonghong; Li, Jiayang] Chinese Acad Sci, Natl Ctr Plant Gene Res, Inst Genet & Dev Biol, State Key Lab Plant Genom, Beijing 100101, Peoples R China.
C3 Van Andel Institute; Van Andel Research Institute; National University of Singapore; University of California System; University of California Riverside; Medical College of Wisconsin; King Abdullah University of Science & Technology; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS
RP Xu, HE (corresponding author), Van Andel Res Inst, Lab Struct Sci, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA.
EM eric.xu@vai.org
FU Michigan Economic Development Corporation; Michigan Technology Tri-Corridor; Office of Science of the US Department of Energy; Jay and Betty Van Andel Foundation; National Institutes of Health; National Science Foundation; NUS Graduate School for Integrative Sciences & Engineering (NGS)
NR 41
TC 592
Z9 712
U1 8
U2 239
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 602
EP U72
DI 10.1038/nature08613
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900031
PM 19898420
DA 2026-03-09
ER

PT J
AU Thomson, M
   Gunawardena, J
AF Thomson, Matthew
   Gunawardena, Jeremy
TI Unlimited multistability in multisite phosphorylation systems
SO NATURE
LA English
DT Article
ID protein-phosphorylation; mass-spectrometry; histone code; transcription; kinase; ultrasensitivity; memory; switch
AB Reversible phosphorylation on serine, threonine and tyrosine is the most widely studied posttranslational modification of proteins(1,2). The number of phosphorylated sites on a protein (n) shows a significant increase from prokaryotes, with n <= 7 sites, to eukaryotes, with examples having n >= 150 sites(3). Multisite phosphorylation has many roles(4,5) and site conservation indicates that increasing numbers of sites cannot be due merely to promiscuous phosphorylation. A substrate with n sites has an exponential number (2(n)) of phospho-forms and individual phospho-forms may have distinct biological effects(6,7). The distribution of these phospho-forms and how this distribution is regulated have remained unknown. Here we show that, when kinase and phosphatase act in opposition on a multisite substrate, the system can exhibit distinct stable phospho-form distributions at steady state and that the maximum number of such distributions increases with n. Whereas some stable distributions are focused on a single phospho-form, others are more diffuse, giving the phosphoproteome the potential to behave as a fluid regulatory network able to encode information and flexibly respond to varying demands. Such plasticity may underlie complex information processing in eukaryotic cells(8) and suggests a functional advantage in having many sites. Our results follow from the unusual geometry of the steady-state phospho-form concentrations, which we show to constitute a rational algebraic curve, irrespective of n. We thereby reduce the complexity of calculating steady states from simulating 3 x 2(n) differential equations to solving two algebraic equations, while treating parameters symbolically. We anticipate that these methods can be extended to systems with multiple substrates and multiple enzymes catalysing different modifications, as found in posttranslational modification 'codes'(9) such as the histone code(10,11). Whereas simulations struggle with exponentially increasing molecular complexity, mathematical methods of the kind developed here can provide a new language in which to articulate the principles of cellular information processing(12).
C1 [Gunawardena, Jeremy] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Thomson, Matthew] Harvard Univ, Biophys Program, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Harvard University
RP Gunawardena, J (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM jeremy@hms.harvard.edu
FU NIH [R01-GM081578]
NR 30
TC 195
Z9 212
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 9
PY 2009
VL 460
IS 7252
BP 274
EP 277
DI 10.1038/nature08102
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000044
PM 19536158
DA 2026-03-09
ER

PT J
AU Fujiki, R
   Chikanishi, T
   Hashiba, W
   Ito, H
   Takada, I
   Roeder, RG
   Kitagawa, H
   Kato, S
AF Fujiki, Ryoji
   Chikanishi, Toshihiro
   Hashiba, Waka
   Ito, Hiroaki
   Takada, Ichiro
   Roeder, Robert G.
   Kitagawa, Hirochika
   Kato, Shigeaki
TI RETRACTED: GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis (Retracted Article)
SO NATURE
LA English
DT Article; Retracted Publication
ID o-glcnac transferase; transcriptional regulation; n-acetylglucosamine; myeloid-leukemia; chromatin; complex; proteins; receptor; cells; glycosylation
AB The post-translational modifications of histone tails generate a 'histone code' that defines local and global chromatin states(1). The resultant regulation of gene function is thought to govern cell fate, proliferation and differentiation(2). Reversible histone modifications such as methylation are under mutual controls to organize chromosomal events(3,4). Among the histone modifications, methylation of specific lysine and arginine residues seems to be critical for chromatin configuration and control of gene expression(5). Methylation of histone H3 lysine 4 (H3K4) changes chromatin into a transcriptionally active state(6). Reversible modification of proteins by beta-N-acetylglucosamine (O-GlcNAc) in response to serum glucose levels regulates diverse cellular processes(7,8,9). However, the epigenetic impact of protein GlcNAcylation is unknown. Here we report that nuclear GlcNAcylation of a histone lysine methyltransferase (HKMT), MLL5, by O-GlcNAc transferase facilitates retinoic-acid-induced granulopoiesis in human HL60 promyelocytes through methylation of H3K4. MLL5 is biochemically identified in a GlcNAcylation-dependent multi-subunit complex associating with nuclear retinoic acid receptor RAR alpha (also known as RARA), serving as a mono-and di-methyl transferase to H3K4. GlcNAcylation at Thr 440 in the MLL5 SET domain evokes its H3K4 HKMT activity and co-activates RARa in target gene promoters. Increased nuclear GlcNAcylation by means of O-GlcNAc transferase potentiates retinoic-acid-induced HL60 granulopoiesis and restores the retinoic acid response in the retinoic-acid-resistant HL60-R2 cell line. Thus, nuclear MLL5 GlcNAcylation triggers cell lineage determination of HL60 through activation of its HKMT activity.
C1 [Fujiki, Ryoji; Chikanishi, Toshihiro; Hashiba, Waka; Ito, Hiroaki; Takada, Ichiro; Kitagawa, Hirochika; Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Fujiki, Ryoji; Chikanishi, Toshihiro; Kato, Shigeaki] Japan Sci & Technol Agcy, ERATO, Kawaguchi, Saitama 3320012, Japan.
   [Roeder, Robert G.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA.
C3 University of Tokyo; Japan Science & Technology Agency (JST); Rockefeller University
RP Kato, S (corresponding author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan.
EM uskato@mail.ecc.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology
NR 27
TC 140
Z9 173
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 21
PY 2009
VL 459
IS 7245
BP 455
EP U179
DI 10.1038/nature07954
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700052
PM 19377461
DA 2026-03-09
ER

PT J
AU Harvey, CD
   Collman, F
   Dombeck, DA
   Tank, DW
AF Harvey, Christopher D.
   Collman, Forrest
   Dombeck, Daniel A.
   Tank, David W.
TI Intracellular dynamics of hippocampal place cells during virtual navigation
SO NATURE
LA English
DT Article
ID theta phase precession; barrel cortex; unit-activity; in-vivo; oscillations; recordings; awake; code; mechanisms; experience
AB Hippocampal place cells encode spatial information in rate and temporal codes. To examine the mechanisms underlying hippocampal coding, here we measured the intracellular dynamics of place cells by combining in vivo whole-cell recordings with a virtual-reality system. Head-restrained mice, running on a spherical treadmill, interacted with a computer-generated visual environment to perform spatial behaviours. Robust place-cell activity was present during movement along a virtual linear track. From whole-cell recordings, we identified three subthreshold signatures of place fields: an asymmetric ramp-like depolarization of the baseline membrane potential, an increase in the amplitude of intracellular theta oscillations, and a phase precession of the intracellular theta oscillation relative to the extracellularly recorded theta rhythm. These intracellular dynamics underlie the primary features of place-cell rate and temporal codes. The virtual-reality system developed here will enable new experimental approaches to study the neural circuits underlying navigation.
C1 [Harvey, Christopher D.; Collman, Forrest; Dombeck, Daniel A.; Tank, David W.] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA.
   [Harvey, Christopher D.; Collman, Forrest; Dombeck, Daniel A.; Tank, David W.] Princeton Univ, Lewis Sigler Inst Integrat Gen, Princeton, NJ 08544 USA.
   [Harvey, Christopher D.; Collman, Forrest; Dombeck, Daniel A.; Tank, David W.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Princeton University
RP Tank, DW (corresponding author), Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA.
EM dwtank@princeton.edu
FU NIH [1R01MH083686-01, 5R01MH060651-09]; Helen Hay Whitney Fellowship; Patterson Trust Fellowship
NR 43
TC 664
Z9 824
U1 2
U2 143
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 941
EP U196
DI 10.1038/nature08499
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700039
PM 19829374
DA 2026-03-09
ER

PT J
AU Lake, JA
AF Lake, James A.
TI Evidence for an early prokaryotic endosymbiosis
SO NATURE
LA English
DT Article
ID horizontal gene-transfer; symbiobacterium-thermophilum; community structure; genome sequence; early evolution; life; tree; root; bacterium; depends
AB Endosymbioses have dramatically altered eukaryotic life, but are thought to have negligibly affected prokaryotic evolution. Here, by analysing the flows of protein families, I present evidence that the double-membrane, Gram-negative prokaryotes were formed as the result of a symbiosis between an ancient actinobacterium and an ancient clostridium. The resulting taxon has been extraordinarily successful, and has profoundly altered the evolution of life by providing endosymbionts necessary for the emergence of eukaryotes and by generating Earth's oxygen atmosphere. Their double-membrane architecture and the observed genome flows into them suggest a common evolutionary mechanism for their origin: an endosymbiosis between a clostridium and actinobacterium.
C1 [Lake, James A.] Univ Calif Los Angeles, Dept Mol Cellular & Dev Biol, Los Angeles, CA 90095 USA.
   [Lake, James A.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
   [Lake, James A.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Lake, James A.] Univ Calif Los Angeles, UCLA Astrobiol 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 Lake, JA (corresponding author), Univ Calif Los Angeles, Dept Mol Cellular & Dev Biol, Los Angeles, CA 90095 USA.
EM lake@mbi.ucla.edu
FU NSF; UCLA NASA Astrobiology Institute
NR 51
TC 46
Z9 57
U1 3
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 967
EP 971
DI 10.1038/nature08183
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500025
PM 19693078
DA 2026-03-09
ER

PT J
AU Sime, LC
   Wolff, EW
   Oliver, KIC
   Tindall, JC
AF Sime, L. C.
   Wolff, E. W.
   Oliver, K. I. C.
   Tindall, J. C.
TI Evidence for warmer interglacials in East Antarctic ice cores
SO NATURE
LA English
DT Article
ID center climate model; precipitation; variability; impact; ocean
AB Stable isotope ratios of oxygen and hydrogen in the Antarctic ice core record have revolutionized our understanding of Pleistocene climate variations and have allowed reconstructions of Antarctic temperature over the past 800,000 years (800 kyr; refs 1, 2). The relationship between the D/H ratio of mean annual precipitation and mean annual surface air temperature is said to be uniform +/- 10% over East Antarctica(3) and constant with time +/- 20% (refs 3-5). In the absence of strong independent temperature proxy evidence allowing us to calibrate individual ice cores, prior general circulation model (GCM) studies have supported the assumption of constant uniform conversion for climates cooler than that of the present day(3,5). Here we analyse the three available 340 kyr East Antarctic ice core records alongside input from GCM modelling. We show that for warmer interglacial periods the relationship between temperature and the isotopic signature varies among ice core sites, and that therefore the conversions must be nonlinear for at least some sites. Model results indicate that the isotopic composition of East Antarctic ice is less sensitive to temperature changes during warmer climates. We conclude that previous temperature estimates from interglacial climates are likely to be too low. The available evidence is consistent with a peak Antarctic interglacial temperature that was at least 6K higher than that of the present day -approximately double the widely quoted 3 +/- 1.5K (refs 5, 6).
C1 [Sime, L. C.; Wolff, E. W.] British Antarctic Survey, Cambridge CB3 0ET, England.
   [Oliver, K. I. C.] Open Univ, Dept Earth & Environm Sci, Milton Keynes MK7 6AA, Bucks, England.
   [Tindall, J. C.] Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
C3 UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; Open University - UK; University of Bristol
RP Sime, LC (corresponding author), British Antarctic Survey, Cambridge CB3 0ET, England.
EM lsim@bas.ac.uk
FU Natural Environment Research Council [NE/D001803/1, bas0100024, NER/T/S/2002/00460] Funding Source: researchfish; NERC [NE/D001803/1, bas0100024] Funding Source: UKRI
NR 30
TC 120
Z9 129
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 19
PY 2009
VL 462
IS 7271
BP 342
EP U105
DI 10.1038/nature08564
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300042
PM 19924212
DA 2026-03-09
ER

PT J
AU Fraser, JS
   Clarkson, MW
   Degnan, SC
   Erion, R
   Kern, D
   Alber, T
AF Fraser, James S.
   Clarkson, Michael W.
   Degnan, Sheena C.
   Erion, Renske
   Kern, Dorothee
   Alber, Tom
TI Hidden alternative structures of proline isomerase essential for catalysis
SO NATURE
LA English
DT Article
ID cyclophilin-a insights; x-ray-diffraction; chemical-exchange; ribonuclease-a; dynamics; temperature; proteins; transition; mechanism; crystals
AB A long-standing challenge is to understand at the atomic level how protein dynamics contribute to enzyme catalysis. X-ray crystallography can provide snapshots of conformational substates sampled during enzymatic reactions(1), while NMR relaxation methods reveal the rates of interconversion between substates and the corresponding relative populations(1,2). However, these current methods cannot simultaneously reveal the detailed atomic structures of the rare states and rationalize the finding that intrinsic motions in the free enzyme occur on a timescale similar to the catalytic turnover rate. Here we introduce dual strategies of ambient-temperature X-ray crystallographic data collection and automated electron-density sampling to structurally unravel interconverting substates of the human proline isomerase, cyclophilin A (CYPA, also known as PPIA). A conservative mutation outside the active site was designed to stabilize features of the previously hidden minor conformation. This mutation not only inverts the equilibrium between the substates, but also causes large, parallel reductions in the conformational interconversion rates and the catalytic rate. These studies introduce crystallographic approaches to define functional minor protein conformations and, in combination with NMR analysis of the enzyme dynamics in solution, show how collective motions directly contribute to the catalytic power of an enzyme.
C1 [Fraser, James S.; Degnan, Sheena C.; Erion, Renske; Alber, Tom] Univ Calif Berkeley, Dept Mol & Cell Biol QB3, Berkeley, CA 94720 USA.
   [Clarkson, Michael W.; Kern, Dorothee] Brandeis Univ, Howard Hughes Med Inst, Dept Biochem, Waltham, MA 02454 USA.
C3 University of California System; University of California Berkeley; Howard Hughes Medical Institute; Brandeis University
RP Alber, T (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol QB3, Berkeley, CA 94720 USA.
EM dkern@brandeis.edu; tom@ucxray.berkeley.edu
FU US NSF; Canadian NSERC; US National Institutes of Health; US Department of Energy Office of Basic Energy Sciences; Howard Hughes Medical Institute
NR 45
TC 419
Z9 510
U1 2
U2 129
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 669
EP U149
DI 10.1038/nature08615
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900045
PM 19956261
DA 2026-03-09
ER

PT J
AU Mitchell, A
   Romano, GH
   Groisman, B
   Yona, A
   Dekel, E
   Kupiec, M
   Dahan, O
   Pilpel, Y
AF Mitchell, Amir
   Romano, Gal H.
   Groisman, Bella
   Yona, Avihu
   Dekel, Erez
   Kupiec, Martin
   Dahan, Orna
   Pilpel, Yitzhak
TI Adaptive prediction of environmental changes by microorganisms
SO NATURE
LA English
DT Article
ID escherichia-coli; saccharomyces-cerevisiae; fluctuating environments; gene-expression; stress-response; yeast; genome; resistance; evolution; growth
AB Natural habitats of some microorganisms may fluctuate erratically, whereas others, which are more predictable, offer the opportunity to prepare in advance for the next environmental change. In analogy to classical Pavlovian conditioning, microorganisms may have evolved to anticipate environmental stimuli by adapting to their temporal order of appearance. Here we present evidence for environmental change anticipation in two model microorganisms, Escherichia coli and Saccharomyces cerevisiae. We show that anticipation is an adaptive trait, because pre-exposure to the stimulus that typically appears early in the ecology improves the organism's fitness when encountered with a second stimulus. Additionally, we observe loss of the conditioned response in E. coli strains that were repeatedly exposed in a laboratory evolution experiment only to the first stimulus. Focusing on the molecular level reveals that the natural temporal order of stimuli is embedded in the wiring of the regulatory network-early stimuli pre-induce genes that would be needed for later ones, yet later stimuli only induce genes needed to cope with them. Our work indicates that environmental anticipation is an adaptive trait that was repeatedly selected for during evolution and thus may be ubiquitous in biology.
C1 [Mitchell, Amir; Groisman, Bella; Yona, Avihu; Dahan, Orna; Pilpel, Yitzhak] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
   [Romano, Gal H.; Kupiec, Martin] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel.
   [Dekel, Erez] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
   [Pilpel, Yitzhak] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
C3 Weizmann Institute of Science; Tel Aviv University; Weizmann Institute of Science; Harvard University; Harvard Medical School
RP Pilpel, Y (corresponding author), Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
EM pilpel@weizmann.ac.il
FU Tauber Foundation; Minerva Foundation; Israel Science Foundation; European Research Council; Ben May Foundation; Israeli Ministry of Science and Technology
NR 29
TC 428
Z9 501
U1 10
U2 149
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 220
EP U80
DI 10.1038/nature08112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000033
PM 19536156
DA 2026-03-09
ER

PT J
AU Coufal, NG
   Garcia-Perez, JL
   Peng, GE
   Yeo, GW
   Mu, YL
   Lovci, MT
   Morell, M
   O'Shea, KS
   Moran, JV
   Gage, FH
AF Coufal, Nicole G.
   Garcia-Perez, Jose L.
   Peng, Grace E.
   Yeo, Gene W.
   Mu, Yangling
   Lovci, Michael T.
   Morell, Maria
   O'Shea, K. Sue
   Moran, John V.
   Gage, Fred H.
TI L1 retrotransposition in human neural progenitor cells
SO NATURE
LA English
DT Article
ID embryonic stem-cells; line-1 retrotransposition; elements
AB Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo(1). Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.
C1 [Coufal, Nicole G.; Peng, Grace E.; Yeo, Gene W.; Mu, Yangling; Lovci, Michael T.; Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [Garcia-Perez, Jose L.; Moran, John V.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Garcia-Perez, Jose L.; Moran, John V.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Garcia-Perez, Jose L.] Univ Granada, Ctr Biomed Res, Andalusian Stem Cell Bank, Granada 18100, Spain.
   [Morell, Maria; O'Shea, K. Sue] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
   [Moran, John V.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Salk Institute; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Granada; University of Michigan System; University of Michigan; Howard Hughes Medical Institute
RP Gage, FH (corresponding author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM gage@salk.edu
FU Picower Foundation; G. Harold and Leila Y. Mathers Charitable Foundation; Lookout Fund [MH082070]; California Institute for Regenerative Medicine (CIRM).; Plan Estabilizacion Grupos SNS ENCYT 2015 [EMER07/56]; Marie Curie program [IRG-FP7-PEOPLE-2007]; National Institutes of Health (NIH) [GM069985, NS048187, GM082970]; Howard Hughes Medical Institute; National Institute of General Medical Sciences [R01GM060518] Funding Source: NIH RePORTER
NR 28
TC 648
Z9 813
U1 0
U2 51
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 27
PY 2009
VL 460
IS 7259
BP 1127
EP 1131
DI 10.1038/nature08248
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000038
PM 19657334
DA 2026-03-09
ER

PT J
AU Barends, TRM
   Hartmann, E
   Griese, JJ
   Beitlich, T
   Kirienko, NV
   Ryjenkov, DA
   Reinstein, J
   Shoeman, RL
   Gomelsky, M
   Schlichting, I
AF Barends, Thomas R. M.
   Hartmann, Elisabeth
   Griese, Julia J.
   Beitlich, Thorsten
   Kirienko, Natalia V.
   Ryjenkov, Dmitri A.
   Reinstein, Jochen
   Shoeman, Robert L.
   Gomelsky, Mark
   Schlichting, Ilme
TI Structure and mechanism of a bacterial light-regulated cyclic nucleotide phosphodiesterase
SO NATURE
LA English
DT Article
ID automated structure solution; mediated signal-transduction; fad-binding domain; bluf domain; density modification; rhodobacter-sphaeroides; crystal-structures; nmr system; photoreceptor; protein
AB The ability to respond to light is crucial for most organisms. BLUF is a recently identified photoreceptor protein domain that senses blue light using a FAD chromophore(1). BLUF domains are present in various proteins from the Bacteria, Euglenozoa and Fungi. Although structures of single-domain BLUF proteins have been determined(2-4), none are available for a BLUF protein containing a functional output domain; the mechanism of light activation in this new class of photoreceptors has thus remained poorly understood. Here we report the biochemical, structural and mechanistic characterization of a full-length, active photoreceptor, BlrP1 (also known as KPN_01598), from Klebsiella pneumoniae(5). BlrP1 consists of a BLUF sensor domain and a phosphodiesterase EAL output domain which hydrolyses cyclic dimeric GMP (c-di-GMP). This ubiquitous second messenger controls motility, biofilm formation, virulence and antibiotic resistance in the Bacteria(6-9). Crystal structures of BlrP1 complexed with its substrate and metal ions involved in catalysis or in enzyme inhibition provide a detailed understanding of the mechanism of the EAL-domain c-di-GMP phosphodiesterases. These structures also sketch out a path of light activation of the phosphodiesterase output activity. Photon absorption by the BLUF domain of one subunit of the antiparallel BlrP1 homodimer activates the EAL domain of the second subunit through allosteric communication transmitted through conserved domain-domain interfaces.
C1 [Kirienko, Natalia V.; Ryjenkov, Dmitri A.; Gomelsky, Mark] Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA.
   [Barends, Thomas R. M.; Hartmann, Elisabeth; Griese, Julia J.; Beitlich, Thorsten; Reinstein, Jochen; Shoeman, Robert L.; Schlichting, Ilme] Max Planck Inst Med Res, Dept Biomol Mech, D-69120 Heidelberg, Germany.
C3 University of Wyoming; Max Planck Society
RP Gomelsky, M (corresponding author), Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA.
EM gomelsky@uwyo.edu; ilme.schlichting@mpimf-heidelberg.mpg.de
FU Deutsche Forschungsgemeinschaft [FOR 526]; US National Science Foundation [MCB 0645876]; Boehringer Ingelheim Fonds
NR 40
TC 242
Z9 311
U1 1
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 18
PY 2009
VL 459
IS 7249
BP 1015
EP U150
DI 10.1038/nature07966
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500049
PM 19536266
DA 2026-03-09
ER

PT J
AU Ferraro, FR
   Dalessandro, E
   Mucciarelli, A
   Beccari, G
   Rich, RM
   Origlia, L
   Lanzoni, B
   Rood, RT
   Valenti, E
   Bellazzini, M
   Ransom, SM
   Cocozza, G
AF Ferraro, F. R.
   Dalessandro, E.
   Mucciarelli, A.
   Beccari, G.
   Rich, R. M.
   Origlia, L.
   Lanzoni, B.
   Rood, R. T.
   Valenti, E.
   Bellazzini, M.
   Ransom, S. M.
   Cocozza, G.
TI The cluster Terzan 5 as a remnant of a primordial building block of the Galactic bulge
SO NATURE
LA English
DT Article
ID hst nicmos photometry; globular-clusters; omega-centauri; relative ages; giant branch; milky-way; population; sagittarius; telescope; gradients
AB Globular star clusters are compact and massive stellar systems old enough to have witnessed the entire history of our Galaxy, the Milky Way. Although recent results(1-3) suggest that their formation may have been more complex than previously thought, they still are the best approximation to a stellar population formed over a relatively short timescale (less than 1 Gyr) and with virtually no dispersion in the iron content. Indeed, only one cluster-like system (omega Centauri) in the Galactic halo is known to have multiple stellar populations with a significant spread in iron abundance and age(4,5). Similar findings in the Galactic bulge have been hampered by the obscuration arising from thick and varying layers of interstellar dust. Here we report that Terzan 5, a globular-cluster-like system in the Galactic bulge, has two stellar populations with different iron contents and ages. Terzan 5 could be the surviving remnant of one of the primordial building blocks that are thought to merge and form galaxy bulges.
C1 [Ferraro, F. R.; Dalessandro, E.; Mucciarelli, A.; Lanzoni, B.] Univ Bologna, Dept Astron, I-40127 Bologna, Italy.
   [Beccari, G.] ESA, Dept Space Sci, NL-2200 AG Noordwijk, Netherlands.
   [Rich, R. M.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Origlia, L.; Bellazzini, M.; Cocozza, G.] INAF Osservatorio Astron Bologna, I-40127 Bologna, Italy.
   [Rood, R. T.] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Valenti, E.] European So Observ, Santiago 19, Chile.
   [Valenti, E.] Pontificia Univ Catolica Chile, Dept Astron, Santiago 7820436, Chile.
   [Ransom, S. M.] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
C3 University of Bologna; University of California System; University of California Los Angeles; Istituto Nazionale Astrofisica (INAF); University of Virginia; European Southern Observatory; Pontificia Universidad Catolica de Chile; National Radio Astronomy Observatory (NRAO)
RP Ferraro, FR (corresponding author), Univ Bologna, Dept Astron, Via Ranzani 1, I-40127 Bologna, Italy.
EM francesco.ferraro3@unibo.it
FU "Progetti Strategici di Ateneo 2006'' (University of Bologna); "Progetti di Ricerca di Interesse Nazionale; Agenzia Spaziale Italiana; Ministero dell'Istruzione; dell'Universita e della Ricerca; ESTEC; NSF; STScI; W. M. Keck Foundation
NR 25
TC 226
Z9 233
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 26
PY 2009
VL 462
IS 7272
BP 483
EP 486
DI 10.1038/nature08581
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200038
PM 19940920
DA 2026-03-09
ER

PT J
AU Levin, EJ
   Quick, M
   Zhou, M
AF Levin, Elena J.
   Quick, Matthias
   Zhou, Ming
TI Crystal structure of a bacterial homologue of the kidney urea transporter
SO NATURE
LA English
DT Article
ID ammonia transport; collecting duct; molecular-basis; channel; water; mechanism; phosphorylation; cloning; family; ut-a1
AB Urea is highly concentrated in the mammalian kidney to produce the osmotic gradient necessary for water re-absorption. Free diffusion of urea across cell membranes is slow owing to its high polarity, and specialized urea transporters have evolved to achieve rapid and selective urea permeation. Here we present the 2.3 angstrom structure of a functional urea transporter from the bacterium Desulfovibrio vulgaris. The transporter is a homotrimer, and each subunit contains a continuous membrane-spanning pore formed by the two homologous halves of the protein. The pore contains a constricted selectivity filter that can accommodate several dehydrated urea molecules in single file. Backbone and side-chain oxygen atoms provide continuous coordination of urea as it progresses through the filter, and well-placed alpha-helix dipoles provide further compensation for dehydration energy. These results establish that the urea transporter operates by a channel-like mechanism and reveal the physical and chemical basis of urea selectivity.
C1 [Levin, Elena J.; Zhou, Ming] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Quick, Matthias] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
   [Quick, Matthias] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
C3 Columbia University; Columbia University; New York State Psychiatry Institute
RP Zhou, M (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, 630 W 168th St, New York, NY 10032 USA.
EM mz2140@columbia.edu
FU US National Institutes of Health [HL086392, T32HL087745]; NIH [GM075026]; American Heart Association [0630148N]; American Heart Association (AHA) [0630148N] Funding Source: American Heart Association (AHA)
NR 47
TC 94
Z9 112
U1 1
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 10
PY 2009
VL 462
IS 7274
BP 757
EP U72
DI 10.1038/nature08558
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900031
PM 19865084
DA 2026-03-09
ER

PT J
AU Lui, CH
   Liu, L
   Mak, KF
   Flynn, GW
   Heinz, TF
AF Lui, Chun Hung
   Liu, Li
   Mak, Kin Fai
   Flynn, George W.
   Heinz, Tony F.
TI Ultraflat graphene
SO NATURE
LA English
DT Article
ID hydrogenation; sheets
AB Graphene, a single atomic layer of carbon connected by sp(2) hybridized bonds, has attracted intense scientific interest since its recent discovery(1). Much of the research on graphene has been directed towards exploration of its novel electronic properties, but the structural aspects of this model two-dimensional system are also of great interest and importance. In particular, microscopic corrugations have been observed on all suspended(2) and supported(3-8) graphene sheets studied so far. This rippling has been invoked to explain the thermodynamic stability of free-standing graphene sheets(9). Many distinctive electronic(10-12) and chemical(13-15) properties of graphene have been attributed to the presence of ripples, which are also predicted to give rise to new physical phenomena(16-26) that would be absent in a planar two-dimensional material. Direct experimental study of such novel ripple physics has, however, been hindered by the lack of flat graphene layers. Here we demonstrate the fabrication of graphene monolayers that are flat down to the atomic level. These samples are produced by deposition on the atomically flat terraces of cleaved mica surfaces. The apparent height variation in the graphene layers observed by high-resolution atomic force microscopy (AFM) is less than 25 picometres, indicating the suppression of any existing intrinsic ripples in graphene. The availability of such ultraflat samples will permit rigorous testing of the impact of ripples on various physical and chemical properties of graphene.
C1 [Lui, Chun Hung; Mak, Kin Fai; Heinz, Tony F.] Columbia Univ, Dept Phys, New York, NY 10027 USA.
   [Lui, Chun Hung; Mak, Kin Fai; Heinz, Tony F.] Columbia Univ, Dept Elect Engn, New York, NY 10027 USA.
   [Liu, Li; Flynn, George W.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
C3 Columbia University; Columbia University; Columbia University
RP Heinz, TF (corresponding author), Columbia Univ, Dept Phys, 538 W 120th St, New York, NY 10027 USA.
EM tony.heinz@columbia.edu
FU DARPA; Nano Electronics Research Corporation (NERC) through the INDEX Center; National Science Foundation [CHE-07-01483]; US Department of Energy [DE-FG02-88-ER13937]
NR 28
TC 638
Z9 731
U1 2
U2 576
PU 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 19
PY 2009
VL 462
IS 7271
BP 339
EP 341
DI 10.1038/nature08569
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300041
PM 19924211
DA 2026-03-09
ER

PT J
AU Guo, M
   Chong, YE
   Shapiro, R
   Beebe, K
   Yang, XL
   Schimmel, P
AF Guo, Min
   Chong, Yeeting E.
   Shapiro, Ryan
   Beebe, Kirk
   Yang, Xiang-Lei
   Schimmel, Paul
TI Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma
SO NATURE
LA English
DT Article
ID transfer-rna-synthetase; amino-acid; structural basis; discrimination; isoleucine; mechanism; sieve; motif
AB Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences(1-3). Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly(1,2). One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.
C1 [Guo, Min; Chong, Yeeting E.; Shapiro, Ryan; Beebe, Kirk; Yang, Xiang-Lei; Schimmel, Paul] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Guo, Min; Chong, Yeeting E.; Shapiro, Ryan; Beebe, Kirk; Yang, Xiang-Lei; Schimmel, Paul] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; Scripps Research Institute
RP Schimmel, P (corresponding author), Scripps Res Inst, Skaggs Inst Chem Biol, BCC 379,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM schimmel@scripps.edu
FU National Institutes of Health [GM 15539]; National Foundation for Cancer Research
NR 34
TC 87
Z9 120
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 DEC 10
PY 2009
VL 462
IS 7274
BP 808
EP U134
DI 10.1038/nature08612
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900043
PM 20010690
DA 2026-03-09
ER

PT J
AU Mancuso, K
   Hauswirth, WW
   Li, QH
   Connor, TB
   Kuchenbecker, JA
   Mauck, MC
   Neitz, J
   Neitz, M
AF Mancuso, Katherine
   Hauswirth, William W.
   Li, Qiuhong
   Connor, Thomas B.
   Kuchenbecker, James A.
   Mauck, Matthew C.
   Neitz, Jay
   Neitz, Maureen
TI Gene therapy for red-green colour blindness in adult primates
SO NATURE
LA English
DT Article
ID molecular-genetics; vision; expression; retina; deficiency; pigments
AB Red-green colour blindness, which results from the absence of either the long-(L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments(1) have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red-green colour deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders.
C1 [Mancuso, Katherine; Kuchenbecker, James A.; Neitz, Jay; Neitz, Maureen] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
   [Hauswirth, William W.; Li, Qiuhong] Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA.
   [Hauswirth, William W.; Li, Qiuhong] Univ Florida, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA.
   [Connor, Thomas B.; Mauck, Matthew C.] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.
C3 University of Washington; University of Washington Seattle; State University System of Florida; University of Florida; State University System of Florida; University of Florida; Medical College of Wisconsin
RP Neitz, J (corresponding author), Univ Washington, Dept Ophthalmol, Box 356485,1959 NE Pacific St, Seattle, WA 98195 USA.
EM jneitz@uw.edu
FU National Institutes of Health [R01EY016861, R01EY11123]; Research Training Program in Vision Science [T32EY014537]; NEI Core Grants [P30EY01931, P30EY01730, P30EY08571]; Harry J. Heeb Foundation; Posner Foundation; Macular Vision Research Foundation; Foundation Fighting Blindness; Hope for Vision; Research to Prevent Blindness; National Eye Institute [T32EY014537, P30EY001730] Funding Source: NIH RePORTER
NR 21
TC 246
Z9 331
U1 2
U2 213
PU NATURE PUBLISHING 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 8
PY 2009
VL 461
IS 7265
BP 784
EP U34
DI 10.1038/nature08401
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500034
PM 19759534
DA 2026-03-09
ER

PT J
AU Zuend, SJ
   Coughlin, MP
   Lalonde, MP
   Jacobsen, EN
AF Zuend, Stephan J.
   Coughlin, Matthew P.
   Lalonde, Mathieu P.
   Jacobsen, Eric N.
TI Scaleable catalytic asymmetric Strecker syntheses of unnatural α-amino acids
SO NATURE
LA English
DT Article
ID additions; cyanide; imines; virus
AB alpha-Amino acids are the building blocks of proteins and are widely used as components of medicinally active molecules and chiral catalysts(1-5). Efficient chemo-enzymatic methods for the synthesis of enantioenriched alpha-amino acids have been developed, but it is still a challenge to obtain non-naturalamino acids(6,7). Alkene hydrogenation is broadly useful for the enantioselective catalytic synthesis of many classes of amino acids(8,9), but it is not possible to obtain zeta-amino acids bearing aryl or quaternary alkyl alpha-substituents using this method. The Strecker synthesis-the reaction of an imine or imine equivalent with hydrogen cyanide, followed by nitrile hydrolysis-is an especially versatile chemical method for the synthesis of racemic alpha-amino acids(10,11). Asymmetric Strecker syntheses using stoichiometric amounts of a chiral reagent have been applied successfully on gram-to-kilogram scales, yielding enantiomerically enriched alpha-amino acids(12-14). In principle, Strecker syntheses employing sub-stoichiometric quantities of a chiral reagent could provide a practical alternative to these approaches, but the reported catalytic asymmetric methods have seen limited use on preparative scales (more than a gram)(15,16). The limited utility of existing catalytic methods may be due to several important factors, including the relatively complex and precious nature of the catalysts and the requisite use of hazardous cyanide sources. Here we report a new catalytic asymmetric method for the syntheses of highly enantiomerically enriched non-natural amino acids using a simple chiral amido-thiourea catalyst to control the key hydrocyanation step. This catalyst is robust, without sensitive functional groups, so it is compatible with aqueous cyanide salts, which are safer and easier to handle than other cyanide sources; this makes the method adaptable to large-scale synthesis. We have used this new method to obtain enantiopure amino acids that are not readily prepared by enzymatic methods or by chemical hydrogenation.
C1 [Zuend, Stephan J.; Coughlin, Matthew P.; Lalonde, Mathieu P.; Jacobsen, Eric N.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
C3 Harvard University
RP Jacobsen, EN (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
EM jacobsen@chemistry.harvard.edu
FU NIH; American Chemical Society and Roche; Natural Sciences and Engineering Research Council of Canada
NR 30
TC 335
Z9 379
U1 3
U2 196
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 15
PY 2009
VL 461
IS 7266
BP 968
EP U223
DI 10.1038/nature08484
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZF
UT WOS:000270817700044
PM 19829379
DA 2026-03-09
ER

PT J
AU Pereira, JP
   Kelly, LM
   Xu, Y
   Cyster, JG
AF Pereira, Joao P.
   Kelly, Lisa M.
   Xu, Ying
   Cyster, Jason G.
TI EBI2 mediates B cell segregation between the outer and centre follicle
SO NATURE
LA English
DT Article
ID tumor-necrosis-factor; receptor; expression; chemokine; lymphoma; responsiveness; visualization; architecture; lymphotoxin; antigen
AB B cell follicles are specialized microenvironments that support events necessary for humoral immunity(1-3). After antigen encounter, activated B cells initially seek T-cell help at the follicle-T-zone boundary and then move to interfollicular and T-zone distal ( outer) regions of the follicle(4-10). Subsequently, some cells move to the follicle centre, become germinal centre B cells and undergo antibody affinity maturation(1,2,11). Although germinal centres within follicles were described in 1885 (ref. 12), the molecular cues mediating segregation of B cells between the outer and centre follicle have remained undefined. Here we present a role for the orphan G-protein-coupled receptor, Epstein-Barr virus induced molecule-2 (EBI2, also known as GPR183)(13), in this process. EBI2 is expressed in mature B cells and increases in expression early after activation, before being downregulated in germinal centre B cells. EBI2 deficiency in mice led to a reduction in the early antibody response to a T-dependent antigen. EBI2-deficient B cells failed to move to the outer follicle at day 2 of activation, and instead were found in the follicle centre, whereas EBI2 overexpression was sufficient to promote B cell localization to the outer follicle. In mixed bone marrow chimaeras, EBI2-deficient B cells phenocopied germinal centre B cells in preferentially localizing to the follicle centre. When downregulation of EBI2 in wild-type B cells was antagonized, participation in the germinal centre reaction was impaired. These studies identify an important role for EBI2 in promoting B cell localization in the outer follicle, and show that differential expression of this receptor helps position B cells appropriately for mounting T-dependent antibody responses.
C1 [Pereira, Joao P.; Kelly, Lisa M.; Xu, Ying; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Pereira, Joao P.; Kelly, Lisa M.; Xu, Ying; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Cyster, JG (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
EM Jason.Cyster@ucsf.edu
FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [R01AI045073] Funding Source: NIH RePORTER
NR 31
TC 306
Z9 386
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 AUG 27
PY 2009
VL 460
IS 7259
BP 1122
EP 1126
DI 10.1038/nature08226
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 487YE
UT WOS:000269314000037
PM 19597478
DA 2026-03-09
ER

PT J
AU Ohtake, M
   Matsunaga, T
   Haruyama, J
   Yokota, Y
   Morota, T
   Honda, C
   Ogawa, Y
   Torii, M
   Miyamoto, H
   Arai, T
   Hirata, N
   Iwasaki, A
   Nakamura, R
   Hiroi, T
   Sugihara, T
   Takeda, H
   Otake, H
   Pieters, CM
   Saiki, K
   Kitazato, K
   Abe, M
   Asada, N
   Demura, H
   Yamaguchi, Y
   Sasaki, S
   Kodama, S
   Terazono, J
   Shirao, M
   Yamaji, A
   Minami, S
   Akiyama, H
   Josset, JL
AF Ohtake, Makiko
   Matsunaga, Tsuneo
   Haruyama, Junichi
   Yokota, Yasuhiro
   Morota, Tomokatsu
   Honda, Chikatoshi
   Ogawa, Yoshiko
   Torii, Masaya
   Miyamoto, Hideaki
   Arai, Tomoko
   Hirata, Naru
   Iwasaki, Akira
   Nakamura, Ryosuke
   Hiroi, Takahiro
   Sugihara, Takamitsu
   Takeda, Hiroshi
   Otake, Hisashi
   Pieters, Carle M.
   Saiki, Kazuto
   Kitazato, Kohei
   Abe, Masanao
   Asada, Noriaki
   Demura, Hirohide
   Yamaguchi, Yasushi
   Sasaki, Sho
   Kodama, Shinsuke
   Terazono, Junya
   Shirao, Motomaro
   Yamaji, Atsushi
   Minami, Shigeyuki
   Akiyama, Hiroaki
   Josset, Jean-Luc
TI The global distribution of pure anorthosite on the Moon
SO NATURE
LA English
DT Article
ID lunar-surface; crust; plagioclase; olivine; selene
AB It has been thought that the lunar highland crust was formed by the crystallization and floatation of plagioclase from a global magma ocean(1,2), although the actual generation mechanisms are still debated(2,3). The composition of the lunar highland crust is therefore important for understanding the formation of such a magma ocean and the subsequent evolution of the Moon. The Multiband Imager(4) on the Selenological and Engineering Explorer (SELENE)(5) has a high spatial resolution of optimized spectral coverage, which should allow a clear view of the composition of the lunar crust. Here we report the global distribution of rocks of high plagioclase abundance ( approaching 100 vol.%), using an unambiguous plagioclase absorption band recorded by the SELENE Multiband Imager. If the upper crust indeed consists of nearly 100 vol.% plagioclase, this is significantly higher than previous estimates of 82-92 vol.% (refs 2, 6, 7), providing a valuable constraint on models of lunar magma ocean evolution.
C1 [Ohtake, Makiko; Haruyama, Junichi; Yokota, Yasuhiro; Morota, Tomokatsu; Abe, Masanao] Japan Aerosp Explorat Agcy, Inst Space & Astronaut Sci, Sagamihara, Kanagawa 2298510, Japan.
   [Matsunaga, Tsuneo] Natl Inst Environm Studies, Ctr Global Environm Res, Tsukuba, Ibaraki 3058506, Japan.
   [Torii, Masaya] Fujitsu Ltd, Mihama Ku, Chiba 2618588, Japan.
   [Honda, Chikatoshi; Ogawa, Yoshiko; Hirata, Naru; Kitazato, Kohei; Asada, Noriaki; Demura, Hirohide; Terazono, Junya] Univ Aizu, Fukushima 9658580, Japan.
   [Miyamoto, Hideaki] Univ Tokyo, Univ Museum, Bunkyo Ku, Tokyo 1130033, Japan.
   [Arai, Tomoko] Chiba Inst Technol, Planetary Explorat Res Ctr, Chiba 2750016, Japan.
   [Iwasaki, Akira] Univ Tokyo, Adv Sci & Technol Res Ctr, Meguro Ku, Tokyo 1538904, Japan.
   [Nakamura, Ryosuke; Kodama, Shinsuke] Natl Inst Adv Ind Sci & Technol, Informat Technol Res Inst, Tsukuba, Ibaraki 3058568, Japan.
   [Hiroi, Takahiro; Pieters, Carle M.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Sugihara, Takamitsu] Japan Agcy Marine Earth Sci & Technol, Ctr Deep Earth Explorat, Kanazawa Ku, Yokohama, Kanagawa 2360001, Japan.
   [Takeda, Hiroshi] Chiba Inst Technol, Frontier Plasma Res Ctr, Chiba 2750016, Japan.
   [Otake, Hisashi] Japan Aerosp Explorat Agcy, Lunar & Planetary Explorat Program Grp, Tsukuba, Ibaraki 3058505, Japan.
   [Saiki, Kazuto] Osaka Univ, Dept Earth & Space Sci, Osaka 5600043, Japan.
   [Yamaguchi, Yasushi] Nagoya Univ, Grad Sch Environm Studies, Dept Earth & Environm Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Sasaki, Sho] Natl Inst Nat Sci, Natl Astron Observ Japan, RISE Project Off, Mizusawa, Oshu 0230861, Japan.
   [Yamaji, Atsushi] Kyoto Univ, Grad Sch Sci, Div Earth & Planetary Sci, Sakyo Ku, Kyoto 6068502, Japan.
   [Minami, Shigeyuki] Osaka City Univ, Dept Elect Engn, Sumiyoshi Ku, Osaka 5588585, Japan.
   [Akiyama, Hiroaki] Wakayama Univ, Wakayama 6408510, Japan.
   [Josset, Jean-Luc] Space Explorat Inst CP 774, CH-2002 Neuchatel, Switzerland.
C3 Japan Aerospace Exploration Agency (JAXA); Institute of Space & Astronautical Science (ISAS); National Institute for Environmental Studies - Japan; Fujitsu Ltd; University of Aizu; University of Tokyo; Chiba Institute of Technology; University of Tokyo; National Institute of Advanced Industrial Science & Technology (AIST); Brown University; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Chiba Institute of Technology; Japan Aerospace Exploration Agency (JAXA); University of Osaka; Nagoya University; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); Kyoto University; Osaka Metropolitan University; Wakayama University
RP Ohtake, M (corresponding author), Japan Aerosp Explorat Agcy, Inst Space & Astronaut Sci, 3-1-1 Yoshino Dai, Sagamihara, Kanagawa 2298510, Japan.
EM ohtake.makiko@jaxa.jp
NR 32
TC 276
Z9 319
U1 1
U2 125
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 10
PY 2009
VL 461
IS 7261
BP 236
EP U110
DI 10.1038/nature08317
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600038
PM 19741704
DA 2026-03-09
ER

PT J
AU Resulaj, A
   Kiani, R
   Wolpert, DM
   Shadlen, MN
AF Resulaj, Arbora
   Kiani, Roozbeh
   Wolpert, Daniel M.
   Shadlen, Michael N.
TI Changes of mind in decision-making
SO NATURE
LA English
DT Article
ID perceptual decision; accumulator model; neural basis; time; performance; choice; discrimination; integration; valuation; neurons
AB A decision is a commitment to a proposition or plan of action based on evidence and the expected costs and benefits associated with the outcome. Progress in a variety of fields has led to a quantitative understanding of the mechanisms that evaluate evidence and reach a decision(1-3). Several formalisms propose that a representation of noisy evidence is evaluated against a criterion to produce a decision(4-8). Without additional evidence, however, these formalisms fail to explain why a decision-maker would change their mind. Here we extend a model, developed to account for both the timing and the accuracy of the initial decision(9), to explain subsequent changes of mind. Subjects made decisions about a noisy visual stimulus, which they indicated by moving a handle. Although they received no additional information after initiating their movement, their hand trajectories betrayed a change of mind in some trials. We propose that noisy evidence is accumulated over time until it reaches a criterion level, or bound, which determines the initial decision, and that the brain exploits information that is in the processing pipeline when the initial decision is made to subsequently either reverse or reaffirm the initial decision. The model explains both the frequency of changes of mind as well as their dependence on both task difficulty and whether the initial decision was accurate or erroneous. The theoretical and experimental findings advance the understanding of decision-making to the highly flexible and cognitive acts of vacillation and self-correction.
C1 [Kiani, Roozbeh; Shadlen, Michael N.] Univ Washington, Howard Hughes Med Inst, Natl Primate Res Ctr, Seattle, WA 98195 USA.
   [Kiani, Roozbeh; Shadlen, Michael N.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
   [Resulaj, Arbora; Wolpert, Daniel M.] Univ Cambridge, Dept Engn, Computat & Biol Learning Lab, Cambridge CB2 1PZ, England.
   [Resulaj, Arbora] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Cambridge; Howard Hughes Medical Institute
RP Shadlen, MN (corresponding author), Univ Washington, Howard Hughes Med Inst, Natl Primate Res Ctr, Seattle, WA 98195 USA.
EM shadlen@uw.edu
FU Wellcome Trust; European grant SENSOPAC [IST-2005-028056]; Howard Hughes Medical Institute; US National Eye Institute [EY11378]; Trinity College, Cambridge
NR 36
TC 481
Z9 555
U1 4
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 10
PY 2009
VL 461
IS 7261
BP 263
EP U141
DI 10.1038/nature08275
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600044
PM 19693010
DA 2026-03-09
ER

PT J
AU Dean, S
   Marchetti, R
   Kirk, K
   Matthews, KR
AF Dean, Samuel
   Marchetti, Rosa
   Kirk, Kiaran
   Matthews, Keith R.
TI A surface transporter family conveys the trypanosome differentiation signal
SO NATURE
LA English
DT Article
ID blood-stream; life-cycle; african trypanosm; procyclic forms; brucei; transformation; malaria; acid; temperature; progression
AB Microbial pathogens use environmental cues to trigger the developmental events needed to infect mammalian hosts or transmit to disease vectors. The parasites causing African sleeping sickness respond to citrate or cis-aconitate (CCA) to initiate life-cycle development when transmitted to their tsetse fly vector. This requires hypersensitization of the parasites to CCA by exposure to low temperature, conditions encountered after tsetse fly feeding at dusk or dawn. Here we identify a carboxylate-transporter family, PAD (proteins associated with differentiation), required for perception of this differentiation signal. Consistent with predictions for the response of trypanosomes to CCA, PAD proteins are expressed on the surface of the transmission-competent 'stumpy-form' parasites in the bloodstream, and at least one member is thermoregulated, showing elevated expression and surface access at low temperature. Moreover, RNA-interference-mediated ablation of PAD expression diminishes CCA-induced differentiation and eliminates CCA hypersensitivity under cold-shock conditions. As well as being molecular transducers of the differentiation signal in these parasites, PAD proteins provide the first example of a surface marker able to discriminate the transmission stage of trypanosomes in their mammalian host.
C1 [Dean, Samuel; Matthews, Keith R.] Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Marchetti, Rosa; Kirk, Kiaran] Australian Natl Univ, Sch Biochem & Mol Biol, Canberra, ACT 0200, Australia.
C3 University of Edinburgh; Australian National University
RP Matthews, KR (corresponding author), Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, Ctr Immun Infect & Evolut, W Mains Rd, Edinburgh EH9 3JT, Midlothian, Scotland.
EM keith.matthews@ed.ac.uk
FU Wellcome Trust; BBSRC studentship; Wellcome Trust Programme; Centre for Immunity, Infection and Evolution; BBSRC REI; Biotechnology and Biological Sciences Research Council [BB/E012442/1] Funding Source: researchfish; BBSRC [BB/E012442/1] Funding Source: UKRI
NR 32
TC 171
Z9 197
U1 0
U2 20
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 213
EP U93
DI 10.1038/nature07997
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100032
PM 19444208
DA 2026-03-09
ER

PT J
AU Knauth, LP
   Kennedy, MJ
AF Knauth, L. Paul
   Kennedy, Martin J.
TI The late Precambrian greening of the Earth
SO NATURE
LA English
DT Article
ID stable isotopic evidence; carbonate cementation; oxygen; land; limestones; complex; rocks; life
AB Many aspects of the carbon cycle can be assessed from temporal changes in the C-13/C-12 ratio of oceanic bicarbonate. C-13/C-12 can temporarily rise when large amounts of C-13-depleted photosynthetic organic matter are buried at enhanced rates(1), and can decrease if phytomass is rapidly oxidized(2) or if low C-13 is rapidly released from methane clathrates(3). Assuming that variations of the marine C-13/C-12 ratio are directly recorded in carbonate rocks, thousands of carbon isotope analyses of late Precambrian examples have been published to correlate these otherwise undatable strata and to document perturbations to the carbon cycle just before the great expansion of metazoan life. Low C-13/C-12 in some Neoproterozoic carbonates is considered evidence of carbon cycle perturbations unique to the Precambrian. These include complete oxidation of all organic matter in the ocean(2) and complete productivity collapse such that low-C-13/C-12 hydrothermal CO2 becomes the main input of carbon(4). Here we compile all published oxygen and carbon isotope data for Neoproterozoic marine carbonates, and consider them in terms of processes known to alter the isotopic composition during transformation of the initial precipitate into limestone/dolostone. We show that the combined oxygen and carbon isotope systematics are identical to those of well-understood Phanerozoic examples that lithified in coastal pore fluids, receiving a large groundwater influx of photosynthetic carbon from terrestrial phytomass. Rather than being perturbations to the carbon cycle, widely reported decreases in C-13/C-12 in Neoproterozoic carbonates are more easily interpreted in the same way as is done for Phanerozoic examples. This influx of terrestrial carbon is not apparent in carbonates older than similar to 850 Myr, so we infer an explosion of photosynthesizing communities on late Precambrian land surfaces. As a result, biotically enhanced weathering generated carbon-bearing soils on a large scale and their detrital sedimentation sequestered carbon(5). This facilitated a rise in O-2 necessary for the expansion of multicellular life.
C1 [Knauth, L. Paul] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Kennedy, Martin J.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92557 USA.
C3 Arizona State University; Arizona State University-Tempe; University of California System; University of California Riverside
RP Knauth, LP (corresponding author), Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
EM Knauth@asu.edu
FU NASA Exobiology [NG04GJ47G, NNX08AT72G, NNG04GJ42G]; NSF [EAR 0345207]; NASA [95349, NNX08AT72G] Funding Source: Federal RePORTER
NR 28
TC 538
Z9 614
U1 3
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 AUG 6
PY 2009
VL 460
IS 7256
BP 728
EP 732
DI 10.1038/nature08213
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 479OO
UT WOS:000268670300036
PM 19587681
DA 2026-03-09
ER

PT J
AU Bolotin, KI
   Ghahari, F
   Shulman, MD
   Stormer, HL
   Kim, P
AF Bolotin, Kirill I.
   Ghahari, Fereshte
   Shulman, Michael D.
   Stormer, Horst L.
   Kim, Philip
TI Observation of the fractional quantum Hall effect in graphene
SO NATURE
LA English
DT Article
AB When electrons are confined in two dimensions and subject to strong magnetic fields, the Coulomb interactions between them can become very strong, leading to the formation of correlated states of matter, such as the fractional quantum Hall liquid(1,2). In this strong quantum regime, electrons and magnetic flux quanta bind to form complex composite quasiparticles with fractional electronic charge; these are manifest in transport measurements of the Hall conductivity as rational fractions of the elementary conductance quantum. The experimental discovery of an anomalous integer quantum Hall effect in graphene has enabled the study of a correlated two-dimensional electronic system, in which the interacting electrons behave like massless chiral fermions(3,4). However, owing to the prevailing disorder, graphene has so far exhibited only weak signatures of correlated electron phenomena(5,6), despite intense experimental and theoretical efforts(7-14). Here we report the observation of the fractional quantum Hall effect in ultraclean, suspended graphene. In addition, we show that at low carrier density graphene becomes an insulator with a magnetic-field-tunable energy gap. These newly discovered quantum states offer the opportunity to study correlated Dirac fermions in graphene in the presence of large magnetic fields.
C1 [Bolotin, Kirill I.; Ghahari, Fereshte; Stormer, Horst L.; Kim, Philip] Columbia Univ, Dept Phys, New York, NY 10027 USA.
   [Shulman, Michael D.; Stormer, Horst L.; Kim, Philip] Columbia Univ, Dept Appl Phys & Appl Math, New York, NY 10027 USA.
C3 Columbia University; Columbia University
RP Kim, P (corresponding author), Columbia Univ, Dept Phys, 538 W 120th St, New York, NY 10027 USA.
EM pk2015@columbia.edu
FU Microsoft Project Q; DARPA; Department of Energy (DOE)
NR 28
TC 872
Z9 1065
U1 6
U2 440
PU NATURE PUBLISHING 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 12
PY 2009
VL 462
IS 7270
BP 196
EP 199
DI 10.1038/nature08582
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100038
PM 19881489
DA 2026-03-09
ER

PT J
AU Ma, YM
   Eremets, M
   Oganov, AR
   Xie, Y
   Trojan, I
   Medvedev, S
   Lyakhov, AO
   Valle, M
   Prakapenka, V
AF Ma, Yanming
   Eremets, Mikhail
   Oganov, Artem R.
   Xie, Yu
   Trojan, Ivan
   Medvedev, Sergey
   Lyakhov, Andriy O.
   Valle, Mario
   Prakapenka, Vitali
TI Transparent dense sodium
SO NATURE
LA English
DT Article
ID high-pressure phases; crystal-structure prediction; augmented-wave method; lithium; superconductivity; metals
AB Under pressure, metals exhibit increasingly shorter interatomic distances. Intuitively, this response is expected to be accompanied by an increase in the widths of the valence and conduction bands and hence a more pronounced free-electron-like behaviour. But at the densities that can now be achieved experimentally, compression can be so substantial that core electrons overlap. This effect dramatically alters electronic properties from those typically associated with simple free-electron metals such as lithium (Li; refs 1-3) and sodium (Na; refs 4, 5), leading in turn to structurally complex phases(6-8) and superconductivity with a high critical temperature(9-11). But the most intriguing prediction-that the seemingly simple metals Li (ref. 1) and Na (ref. 4) will transform under pressure into insulating states, owing to pairing of alkali atoms-has yet to be experimentally confirmed. Here we report experimental observations of a pressure-induced transformation of Na into an optically transparent phase at similar to 200 GPa (corresponding to 5.0-fold compression). Experimental and computational data identify the new phase as a wide bandgap dielectric with a six-coordinated, highly distorted double-hexagonal close-packed structure. We attribute the emergence of this dense insulating state not to atom pairing, but to p-d hybridizations of valence electrons and their repulsion by core electrons into the lattice interstices. We expect that such insulating states may also form in other elements and compounds when compression is sufficiently strong that atomic cores start to overlap strongly.
C1 [Ma, Yanming; Xie, Yu] Jilin Univ, Natl Lab Superhard Mat, Changchun 130012, Peoples R China.
   [Ma, Yanming; Oganov, Artem R.; Lyakhov, Andriy O.] ETH, Dept Mat, Crystallog Lab, CH-8093 Zurich, Switzerland.
   [Eremets, Mikhail; Trojan, Ivan; Medvedev, Sergey] Max Planck Inst Chem, D-55020 Mainz, Germany.
   [Oganov, Artem R.] Moscow MV Lomonosov State Univ, Dept Geol, Moscow 119992, Russia.
   [Valle, Mario] Swiss Natl Supercomp Ctr CSCS, Data Anal & Visualizat Serv, CH-6928 Manno, Switzerland.
   [Prakapenka, Vitali] Univ Chicago, Consortium Adv Radiat Sources, Chicago, IL 60637 USA.
C3 Jilin University; Swiss Federal Institutes of Technology Domain; ETH Zurich; Max Planck Society; Lomonosov Moscow State University; University of Chicago
RP Ma, YM (corresponding author), Jilin Univ, Natl Lab Superhard Mat, Changchun 130012, Peoples R China.
EM mym@jlu.edu.cn
NR 28
TC 780
Z9 872
U1 7
U2 487
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 12
PY 2009
VL 458
IS 7235
BP 182
EP U3
DI 10.1038/nature07786
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700038
PM 19279632
DA 2026-03-09
ER

PT J
AU Chakraborty, P
   Gioia, G
   Kieffer, SW
AF Chakraborty, Pinaki
   Gioia, Gustavo
   Kieffer, Susan W.
TI Volcanic mesocyclones
SO NATURE
LA English
DT Article
ID eruption
AB A strong volcanic plume consists of a vertical column of hot gases and dust topped with a horizontal 'umbrella'(1). The column rises, buoyed by entrained and heated ambient air, reaches the neutral-buoyancy level, then spreads radially to form the umbrella. In classical models of strong volcanic plumes, the plume is assumed to remain always axisymmetric and non-rotating. Here we show that the updraught of the rising column induces a hydrodynamic effect not addressed to date-a 'volcanic mesocyclone'. This volcanic mesocyclone sets the entire plume rotating about its axis, as confirmed by an unprecedented analysis of satellite images from the 1991 eruption of Mount Pinatubo(2-4). Destabilized by the rotation, the umbrella loses axial symmetry and becomes lobate in plan view, in accord with satellite records of recent eruptions on Mounts Pinatubo, Manam, Reventador, Okmok, Chaiten and Ruang. The volcanic mesocyclone spawns waterspouts(5,6) or dust devils(6-8), as seen in numerous eruptions, and groups the electric charges about the plume to form the 'lightning sheath' that was so prominent in the recent eruption of Mount Chaiten. The concept of a volcanic mesocyclone provides a unified explanation for a disparate set of poorly understood phenomena in strong volcanic plumes(5-10).
C1 [Chakraborty, Pinaki; Kieffer, Susan W.] Univ Illinois, Dept Geol, Urbana, IL 61801 USA.
   [Gioia, Gustavo] Univ Illinois, Dept Mech Sci & Engn, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Chakraborty, P (corresponding author), Univ Illinois, Dept Geol, Urbana, IL 61801 USA.
EM chakrabo@illinois.edu
FU Walgreen Chair funds; NSF\EAR [06-09712]; NSF\DMR [06-04435]
NR 30
TC 20
Z9 21
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 26
PY 2009
VL 458
IS 7237
BP 497
EP 500
DI 10.1038/nature07866
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 423YJ
UT WOS:000264532400042
PM 19325632
DA 2026-03-09
ER

PT J
AU Pearce, EL
   Walsh, MC
   Cejas, PJ
   Harms, GM
   Shen, H
   Wang, LS
   Jones, RG
   Choi, YW
AF Pearce, Erika L.
   Walsh, Matthew C.
   Cejas, Pedro J.
   Harms, Gretchen M.
   Shen, Hao
   Wang, Li-San
   Jones, Russell G.
   Choi, Yongwon
TI Enhancing CD8 T-cell memory by modulating fatty acid metabolism
SO NATURE
LA English
DT Article
ID regulates lipid-metabolism; mammalian target; cutting edge; expression; homeostasis; activation; generation; rapamycin; pathway; cd4(+)
AB CD8 T cells, which have a crucial role in immunity to infection and cancer, are maintained in constant numbers, but on antigen stimulation undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific effector (T-E) populations, followed by the persistence of long-lived memory (T-M) cells(1,2). Although this predictable pattern of CD8 T-cell responses is well established, the underlying cellular mechanisms regulating the transition to T-M cells remain undefined(1,2). Here we show that tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an adaptor protein in the TNF-receptor and interleukin-1R/Toll-like receptor superfamily, regulates CD8 T-M-cell development after infection by modulating fatty acid metabolism. We show that mice with a T-cell-specific deletion of TRAF6 mount robust CD8 T-E-cell responses, but have a profound defect in their ability to generate T-M cells that is characterized by the disappearance of antigen-specific cells in the weeks after primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 display defective AMP-activated kinase activation and mitochondrial fatty acid oxidation (FAO) in response to growth factor withdrawal. Administration of the anti-diabetic drug metformin restored FAO and CD8 T-M-cell generation in the absence of TRAF6. This treatment also increased CD8 T-M cells in wild-type mice, and consequently was able to considerably improve the efficacy of an experimental anti-cancer vaccine.
C1 [Pearce, Erika L.; Walsh, Matthew C.; Cejas, Pedro J.; Harms, Gretchen M.; Wang, Li-San; Choi, Yongwon] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Shen, Hao] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Wang, Li-San] Univ Penn, Sch Med, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA.
   [Jones, Russell G.] McGill Univ, Dept Physiol, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; McGill University
RP Choi, YW (corresponding author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM ychoi3@mail.med.upenn.edu
FU NIH; CIHR; NCI Institutional Training Grant
NR 40
TC 1304
Z9 1575
U1 2
U2 167
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 103
EP U118
DI 10.1038/nature08097
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200038
PM 19494812
DA 2026-03-09
ER

PT J
AU Rodriguez, S
   Le Mouelic, S
   Rannou, P
   Tobie, G
   Baines, KH
   Barnes, JW
   Griffith, CA
   Hirtzig, M
   Pitman, KM
   Sotin, C
   Brown, RH
   Buratti, BJ
   Clark, RN
   Nicholson, PD
AF Rodriguez, Sebastien
   Le Mouelic, Stephane
   Rannou, Pascal
   Tobie, Gabriel
   Baines, Kevin H.
   Barnes, Jason W.
   Griffith, Caitlin A.
   Hirtzig, Mathieu
   Pitman, Karly M.
   Sotin, Christophe
   Brown, Robert H.
   Buratti, Bonnie J.
   Clark, Roger N.
   Nicholson, Phil D.
TI Global circulation as the main source of cloud activity on Titan
SO NATURE
LA English
DT Article
AB Clouds on Titan result from the condensation of methane and ethane and, as on other planets, are primarily structured by circulation of the atmosphere(1-4). At present, cloud activity mainly occurs in the southern (summer) hemisphere, arising near the pole(5-12) and at mid-latitudes(7,8,13-15) from cumulus updrafts triggered by surface heating and/or local methane sources, and at the north (winter) pole(16,17), resulting from the subsidence and condensation of ethane-rich air into the colder troposphere. General circulation models(1-3) predict that this distribution should change with the seasons on a 15-year timescale, and that clouds should develop under certain circumstances at temperate latitudes (similar to 40 degrees) in the winter hemisphere(2). The models, however, have hitherto been poorly constrained and their long-term predictions have not yet been observationally verified. Here we report that the global spatial cloud coverage on Titan is in general agreement with the models, confirming that cloud activity is mainly controlled by the global circulation. The non-detection of clouds at latitude similar to 40 degrees N and the persistence of the southern clouds while the southern summer is ending are, however, both contrary to predictions. This suggests that Titan's equator-to-pole thermal contrast is overestimated in the models and that its atmosphere responds to the seasonal forcing with a greater inertia than expected.
C1 [Rodriguez, Sebastien; Le Mouelic, Stephane; Tobie, Gabriel; Sotin, Christophe] Univ Nantes, CNRS, UMR 6112, Lab Planetol & Geodynam, F-44000 Nantes, France.
   [Rodriguez, Sebastien] Univ Paris 07, CNRS, CEA Saclay,DSM,IRFU,SAp, Lab AIM,UMR 7158, F-91191 Gif Sur Yvette, France.
   [Rannou, Pascal] Univ Reims, CNRS, Grp Spectrometrie Mol & Atmospher, UMR 6089, F-51687 Reims, France.
   [Rannou, Pascal] Univ Versailles St Quentin, CNRS, LATMOS, UMR 7620, F-91371 Verrieres Le Buisson, France.
   [Baines, Kevin H.; Pitman, Karly M.; Sotin, Christophe; Buratti, Bonnie J.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Barnes, Jason W.] NASA, Ames Res Ctr MS 244 30, Moffett Field, CA 94035 USA.
   [Griffith, Caitlin A.; Brown, Robert H.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Hirtzig, Mathieu] Univ Michigan, PSL, AOSS, Ann Arbor, MI 48109 USA.
   [Clark, Roger N.] US Geol Survey, Denver Fed Ctr, Denver, CO 80225 USA.
   [Nicholson, Phil D.] Cornell Univ, Dept Astron, Ithaca, NY 14853 USA.
C3 Nantes Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Saclay; CEA; Universite Paris Cite; Universite de Reims Champagne-Ardenne; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Saclay; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; National Aeronautics & Space Administration (NASA); University of Arizona; University of Michigan System; University of Michigan; United States Department of the Interior; United States Geological Survey; Cornell University
RP Rodriguez, S (corresponding author), Univ Nantes, CNRS, UMR 6112, Lab Planetol & Geodynam, 2 Rue Houssiniere, F-44000 Nantes, France.
EM sebastien.rodriguez@cea.fr
FU CNRS; CEA; CNES French; Universities of Paris Diderot and Nantes
NR 28
TC 81
Z9 90
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 4
PY 2009
VL 459
IS 7247
BP 678
EP 682
DI 10.1038/nature08014
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600038
PM 19494910
DA 2026-03-09
ER

PT J
AU Stein, S
   Liu, M
AF Stein, Seth
   Liu, Mian
TI Long aftershock sequences within continents and implications for earthquake hazard assessment
SO NATURE
LA English
DT Article
ID seismic-hazard; fault; deformation
AB One of the most powerful features of plate tectonics is that the known plate motions give insight into both the locations and average recurrence interval of future large earthquakes on plate boundaries. Plate tectonics gives no insight, however, into where and when earthquakes will occur within plates, because the interiors of ideal plates should not deform. As a result, within plate interiors, assessments of earthquake hazards rely heavily on the assumption that the locations of small earthquakes shown by the short historical record reflect continuing deformation that will cause future large earthquakes(1). Here, however, we show that many of these recent earthquakes are probably aftershocks of large earthquakes that occurred hundreds of years ago. We present a simple model predicting that the length of aftershock sequences varies inversely with the rate at which faults are loaded. Aftershock sequences within the slowly deforming continents are predicted to be significantly longer than the decade typically observed at rapidly loaded plate boundaries. These predictions are in accord with observations. So the common practice of treating continental earthquakes as steady-state seismicity overestimates the hazard in presently active areas and underestimates it elsewhere.
C1 [Stein, Seth] Northwestern Univ, Dept Earth & Planetary Sci, Evanston, IL 60208 USA.
   [Liu, Mian] Univ Missouri, Dept Geol Sci, Columbia, MO 65211 USA.
C3 Northwestern University; University of Missouri System; University of Missouri Columbia
RP Stein, S (corresponding author), Northwestern Univ, Dept Earth & Planetary Sci, Evanston, IL 60208 USA.
EM seth@earth.northwestern.edu
FU NSF/OISE [0730154]; Chinese Academy of Sciences; Office Of Internatl Science &Engineering; Office Of The Director [0730154] Funding Source: National Science Foundation
NR 30
TC 199
Z9 233
U1 2
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 5
PY 2009
VL 462
IS 7269
BP 87
EP 89
DI 10.1038/nature08502
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200037
PM 19890328
DA 2026-03-09
ER

PT J
AU Serganov, A
   Huang, LL
   Patel, DJ
AF Serganov, Alexander
   Huang, Lili
   Patel, Dinshaw J.
TI Coenzyme recognition and gene regulation by a flavin mononucleotide riboswitch
SO NATURE
LA English
DT Article
ID messenger-rna; structural basis; binding; expression; transcription; ribosome
AB The biosynthesis of several protein cofactors is subject to feedback regulation by riboswitches(1-3). Flavin mononucleotide (FMN)specific riboswitches(4,5), also known as RFN elements(6), direct expression of bacterial genes involved in the biosynthesis and transport of riboflavin (vitamin B-2) and related compounds. Here we present the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN, riboflavin and antibiotic roseoflavin(7). The FMN riboswitch structure, centred on an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like scaffold, stapled together by opposingly directed but nearly identically folded peripheral domains. FMN is positioned asymmetrically within the junctional site and is specifically bound to RNA through interactions with the isoalloxazine ring chromophore and direct and Mg2+-mediated contacts with the phosphate moiety. Our structural data, complemented by binding and footprinting experiments, imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket. The inherent plasticity of the FMN-binding pocket and the availability of large openings make the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds. Our studies also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provided molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains.
C1 [Serganov, Alexander; Huang, Lili; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center
RP Serganov, A (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
EM serganoa@mskcc.org; pateld@mskcc.org
FU the US Department of Energy; National Institutes of Health
NR 35
TC 232
Z9 322
U1 3
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 12
PY 2009
VL 458
IS 7235
BP 233
EP U10
DI 10.1038/nature07642
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700050
PM 19169240
DA 2026-03-09
ER

PT J
AU Choi, M
   Na, K
   Kim, J
   Sakamoto, Y
   Terasaki, O
   Ryoo, R
AF Choi, Minkee
   Na, Kyungsu
   Kim, Jeongnam
   Sakamoto, Yasuhiro
   Terasaki, Osamu
   Ryoo, Ryong
TI Stable single-unit-cell nanosheets of zeolite MFI as active and long-lived catalysts
SO NATURE
LA English
DT Article
ID coke formation
AB Zeolites-microporous crystalline aluminosilicates-are widely used in petrochemistry and fine-chemical synthesis(1-3) because strong acid sites within their uniform micropores enable size- and shape-selective catalysis. But the very presence of the micropores, with aperture diameters below 1 nm, often goes hand-in-hand with diffusion limitations(3-5) that adversely affect catalytic activity. The problem can be overcome by reducing the thickness of the zeolite crystals, which reduces diffusion path lengths and thus improves molecular diffusion(4,5). This has been realized by synthesizing zeolite nanocrystals(6), by exfoliating layered zeolites(7-9), and by introducing mesopores in the microporous material through templating strategies(10-17) or demetallation processes(18-22). But except for the exfoliation, none of these strategies has produced 'ultrathin' zeolites with thicknesses below 5 nm. Here we show that appropriately designed bifunctional surfactants can direct the formation of zeolite structures on themesoporous and microporous length scales simultaneously and thus yield MFI (ZSM-5, one of the most important catalysts in the petrochemical industry) zeolite nanosheets that are only 2 nm thick, which corresponds to the b-axis dimension of a single MFI unit cell. The large number of acid sites on the external surface of these zeolites renders them highly active for the catalytic conversion of large organic molecules, and the reduced crystal thickness facilitates diffusion and thereby dramatically suppresses catalyst deactivation through coke deposition during methanol-to-gasoline conversion. We expect that our synthesis approach could be applied to other zeolites to improve their performance in a range of important catalytic applications.
C1 [Choi, Minkee; Na, Kyungsu; Kim, Jeongnam; Ryoo, Ryong] Korea Adv Inst Sci & Technol, Dept Chem, Ctr Funct Nanomat, Taejon 305701, South Korea.
   [Kim, Jeongnam; Ryoo, Ryong] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, Taejon 305701, South Korea.
   [Ryoo, Ryong] Korea Adv Inst Sci & Technol, Inst NanoCentury, Taejon 305701, South Korea.
   [Terasaki, Osamu] Korea Adv Inst Sci & Technol, Grad Sch EEWS WCU, Taejon 305701, South Korea.
   [Sakamoto, Yasuhiro] Stockholm Univ, Arrhenius Lab, S-10691 Stockholm, Sweden.
   [Sakamoto, Yasuhiro; Terasaki, Osamu] Osaka Prefecture Univ, Nanosci & Nanotechnol Res Ctr, Sakai, Osaka 5998570, Japan.
C3 Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Stockholm University; Osaka Metropolitan University
RP Ryoo, R (corresponding author), Korea Adv Inst Sci & Technol, Dept Chem, Ctr Funct Nanomat, Taejon 305701, South Korea.
EM rryoo@kaist.ac.kr
FU National Honor Scientist Program of the Ministry of Education, Science and Technology in Korea; Knut and Alice Wallenberg Foundation; Swedish Research Council (VR); Japan Science and Technology Agency (JST)
NR 28
TC 2023
Z9 2250
U1 52
U2 2356
PU NATURE PUBLISHING 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 10
PY 2009
VL 461
IS 7261
BP 246
EP U120
DI 10.1038/nature08288
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600040
PM 19741706
DA 2026-03-09
ER

PT J
AU Brazeau, MD
AF Brazeau, Martin D.
TI The braincase and jaws of a Devonian 'acanthodian' and modern gnathostome origins
SO NATURE
LA English
DT Article
ID southeastern australia; placodermi; fish; fin
AB Modern gnathostomes ( jawed vertebrates) emerged in the early Palaeozoic era(1), but this event remains unclear owing to a scant early fossil record. The exclusively Palaeozoic 'acanthodians' are possibly the earliest(2,3) gnathostome group and exhibit amosaic of shark- and bony fish- like characters that has long given them prominence in discussions of early gnathostome evolution(1). Their relationships with modern gnathostomes have remained mysterious, partly because their un- mineralized endoskeletons rarely fossilized. Here I present the first- known braincase of an Early Devonian (approximately 418-412 Myr BP) acanthodian, Ptomacanthus anglicus(4), and re- evaluate the interrelationships of basal gnathostomes. Acanthodian braincases have previously been represented by a single genus, Acanthodes(5), which occurs more than 100 million years later in the fossil record. The braincase of Ptomacanthus differs radically from the osteichthyan- like braincase of Acanthodes(5) in exhibiting several plesiomorphic features shared with placoderms(6,7) and some early chondrichthyans(8,9). Most striking is its extremely short sphenoid region and its jaw suspension, which displays features intermediate between some Palaeozoic chondrichthyans and osteichthyans. Phylogenetic analysis resolves Ptomacanthus as either the most basal chondrichthyan or as the sister group of all living gnathostomes. These new data alter earlier conceptions of basal gnathostome phylogeny and thus help to provide a more detailed picture of the acquisition of early gnathostome characters.
C1 [Brazeau, Martin D.] Uppsala Univ, Evolut Biol Ctr, Dept Physiol & Dev Biol, Subdept Evolutionary Organismal Biol, SE-75236 Uppsala, Sweden.
C3 Uppsala University
RP Brazeau, MD (corresponding author), Uppsala Univ, Evolut Biol Ctr, Dept Physiol & Dev Biol, Subdept Evolutionary Organismal Biol, Norbyvagen 18A, SE-75236 Uppsala, Sweden.
EM martin.brazeau@gmail.com
FU Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship
NR 29
TC 202
Z9 235
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 305
EP 308
DI 10.1038/nature07436
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900037
PM 19148098
DA 2026-03-09
ER

PT J
AU Peelen, MV
   Fei-Fei, L
   Kastner, S
AF Peelen, Marius V.
   Fei-Fei, Li
   Kastner, Sabine
TI Neural mechanisms of rapid natural scene categorization in human visual cortex
SO NATURE
LA English
DT Article
ID feature-based attention; change-blindness; temporal cortex; search; fmri
AB The visual system has an extraordinary capability to extract categorical information from complex natural scenes. For example, subjects are able to rapidly detect the presence of object categories such as animals or vehicles in new scenes that are presented very briefly(1,2). This is even true when subjects do not pay attention to the scenes and simultaneously perform an unrelated attentionally demanding task(3), a stark contrast to the capacity limitations predicted by most theories of visual attention(4,5). Here we show a neural basis for rapid natural scene categorization in the visual cortex, using functional magnetic resonance imaging and an object categorization task in which subjects detected the presence of people or cars in briefly presented natural scenes. The multi-voxel pattern of neural activity in the object-selective cortex evoked by the natural scenes contained information about the presence of the target category, even when the scenes were task-irrelevant and presented outside the focus of spatial attention. These findings indicate that the rapid detection of categorical information in natural scenes is mediated by a category-specific biasing mechanism in object-selective cortex that operates in parallel across the visual field, and biases information processing in favour of objects belonging to the target object category.
C1 [Peelen, Marius V.; Fei-Fei, Li; Kastner, Sabine] Princeton Univ, Dept Psychol, Princeton, NJ 08540 USA.
   [Peelen, Marius V.; Kastner, Sabine] Princeton Univ, Ctr Study Brain Mind & Behav, Princeton, NJ 08540 USA.
   [Peelen, Marius V.; Kastner, Sabine] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08540 USA.
   [Fei-Fei, Li] Princeton Univ, Dept Comp Sci, Princeton, NJ 08540 USA.
C3 Princeton University; Princeton University; Princeton University; Princeton University
RP Peelen, MV (corresponding author), Princeton Univ, Dept Psychol, Princeton, NJ 08540 USA.
EM mpeelen@princeton.edu
FU National Institutes of Health [2RO1 MH64043, 1RO1 EY017699, 2P50 MH-62196]; Microsoft Research New Faculty Fellowship; National Eye Institute [R01EY017699] Funding Source: NIH RePORTER
NR 25
TC 226
Z9 270
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 94
EP U105
DI 10.1038/nature08103
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200036
PM 19506558
DA 2026-03-09
ER

PT J
AU Youk, H
   van Oudenaarden, A
AF Youk, Hyun
   van Oudenaarden, Alexander
TI Growth landscape formed by perception and import of glucose in yeast
SO NATURE
LA English
DT Article
ID individual hexose transporters; saccharomyces-cerevisiae; systems biology; metabolic pathways; network; phenotypes; protein; genes; expression; models
AB An important challenge in systems biology is to quantitatively describe microbial growth using a few measurable parameters that capture the essence of this complex phenomenon. Two key events at the cell membrane-extracellular glucose sensing and uptake-initiate the budding yeast's growth on glucose. However, conventional growth models focus almost exclusively on glucose uptake. Here we present results from growth-rate experiments that cannot be explained by focusing on glucose uptake alone. By imposing a glucose uptake rate independent of the sensed extracellular glucose level, we show that despite increasing both the sensed glucose concentration and uptake rate, the cell's growth rate can decrease or even approach zero. We resolve this puzzle by showing that the interaction between glucose perception and import, not their individual actions, determines the central features of growth, and characterize this interaction using a quantitative model. Disrupting this interaction by knocking out two key glucose sensors significantly changes the cell's growth rate, yet uptake rates are unchanged. This is due to a decrease in burden that glucose perception places on the cells. Our work shows that glucose perception and import are separate and pivotal modules of yeast growth, the interaction of which can be precisely tuned and measured.
C1 [Youk, Hyun; van Oudenaarden, Alexander] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [van Oudenaarden, Alexander] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
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 (NSF); Natural Sciences and Engineering Research Council of Canada's (NSERC)
NR 50
TC 71
Z9 84
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 DEC 17
PY 2009
VL 462
IS 7275
BP 875
EP U65
DI 10.1038/nature08653
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 533AX
UT WOS:000272795400033
PM 20016593
DA 2026-03-09
ER

PT J
AU Karklin, Y
   Lewicki, MS
AF Karklin, Yan
   Lewicki, Michael S.
TI Emergence of complex cell properties by learning to generalize in natural scenes
SO NATURE
LA English
DT Article
ID primary visual-cortex; cat striate cortex; receptive-fields; area v4; v1; responses; models; images; normalization; organization
AB A fundamental function of the visual system is to encode the building blocks of natural scenes - edges, textures and shapes - that subserve visual tasks such as object recognition and scene understanding. Essential to this process is the formation of abstract representations that generalize from specific instances of visual input. A common view holds that neurons in the early visual system signal conjunctions of image features(1,2), but how these produce invariant representations is poorly understood. Here we propose that to generalize over similar images, higher- level visual neurons encode statistical variations that characterize local image regions. We present a model in which neural activity encodes the probability distribution most consistent with a given image. Trained on natural images, the model generalizes by learning a compact set of dictionary elements for image distributions typically encountered in natural scenes. Model neurons show a diverse range of properties observed in cortical cells. These results provide a new functional explanation for nonlinear effects in complex cells(3-6) and offer insight into coding strategies in primary visual cortex (V1) and higher visual areas.
C1 [Karklin, Yan; Lewicki, Michael S.] Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA.
   [Karklin, Yan; Lewicki, Michael S.] Carnegie Mellon Univ, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA.
C3 Carnegie Mellon University; Carnegie Mellon University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Karklin, Y (corresponding author), NYU, Ctr Neural Sci, New York, NY 10003 USA.
EM yan.karklin@nyu.edu; michael.lewicki@case.edu
FU Department of Energy; Computational Science Graduate Fellowship; National Science Foundation [0413152, 0705677]; Office of Naval Research under the Multidisciplinary University Research Initiative [N000140710747]; Direct For Computer & Info Scie & Enginr; Div Of Information & Intelligent Systems [0905017, 0413152] Funding Source: National Science Foundation; Direct For Computer & Info Scie & Enginr; Div Of Information & Intelligent Systems [0705677] Funding Source: National Science Foundation
NR 31
TC 152
Z9 185
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 JAN 1
PY 2009
VL 457
IS 7225
BP 83
EP U85
DI 10.1038/nature07481
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900035
PM 19020501
DA 2026-03-09
ER

PT J
AU Gao, B
   Hu, JX
   Stricker, S
   Cheung, M
   Ma, G
   Law, KF
   Witte, F
   Briscoe, J
   Mundlos, S
   He, L
   Cheah, KSE
   Chan, D
AF Gao, Bo
   Hu, Jianxin
   Stricker, Sigmar
   Cheung, Martin
   Ma, Gang
   Law, Kit Fong
   Witte, Florian
   Briscoe, James
   Mundlos, Stefan
   He, Lin
   Cheah, Kathryn S. E.
   Chan, Danny
TI A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range
SO NATURE
LA English
DT Article
ID sonic hedgehog; indian hedgehog; endochondral bone; growth-plate; expression; gene; differentiation; cartilage; protein; embryo
AB Brachydactyly type A1 (BDA1) was the first recorded disorder of the autosomal dominant Mendelian trait in humans, characterized by shortened or absent middle phalanges in digits. It is associated with heterozygous missense mutations in indian hedgehog (IHH)(1,2). Hedgehog proteins are important morphogens for a wide range of developmental processes(3,4). The capacity and range of signalling is thought to be regulated by its interaction with the receptor PTCH1 and antagonist HIP1. Here we show that a BDA1 mutation (E95K) in Ihh impairs the interaction of IHH with PTCH1 and HIP1. This is consistent with a recent paper showing that BDA1 mutations cluster in a calcium-binding site essential for the interaction with its receptor and cell-surface partners(5). Furthermore, we show that in a mouse model that recapitulates the E95K mutation, there is a change in the potency and range of signalling. The mice have digit abnormalities consistent with the human disorder.
C1 [Gao, Bo; Hu, Jianxin; Cheung, Martin; Law, Kit Fong; Cheah, Kathryn S. E.; Chan, Danny] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
   [Gao, Bo; Hu, Jianxin; Ma, Gang; He, Lin] Shanghai Jiao Tong Univ, BioX Ctr, Shanghai 200030, Peoples R China.
   [Stricker, Sigmar; Witte, Florian; Mundlos, Stefan] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Stricker, Sigmar; Witte, Florian; Mundlos, Stefan] Charite Univ Med Berlin, Inst Med Genet, D-13353 Berlin, Germany.
   [Cheah, Kathryn S. E.; Chan, Danny] Univ Hong Kong, LKS Fac Med, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China.
   [Witte, Florian] Free Univ Berlin, Inst Chem Biochem, D-14195 Berlin, Germany.
   [Briscoe, James] Natl Inst Med Res, London NW7 1AA, England.
   [He, Lin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China.
   [He, Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China.
C3 University of Hong Kong; Shanghai Jiao Tong University; Max Planck Society; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; University of Hong Kong; Free University of Berlin; MRC National Institute for Medical Research; Chinese Academy of Sciences; Fudan University
RP Chan, D (corresponding author), Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
EM helinhelin@gmail.com; chand@hkusua.hku.hk
FU Research Grants Council [N_HKU705/02, HKU2/02C]; University Grants Council of Hong Kong [AoE/M-04/04]; National Key Scientific Program [2007CB947300]; MRC [MC_U117560541] Funding Source: UKRI; Medical Research Council [MC_U117560541] Funding Source: researchfish
NR 44
TC 82
Z9 100
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 APR 30
PY 2009
VL 458
IS 7242
BP 1196
EP U136
DI 10.1038/nature07862
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600052
PM 19252479
DA 2026-03-09
ER

PT J
AU Korennykh, AV
   Egea, PF
   Korostelev, AA
   Finer-Moore, J
   Zhang, C
   Shokat, KM
   Stroud, RM
   Walter, P
AF Korennykh, Alexei V.
   Egea, Pascal F.
   Korostelev, Andrei A.
   Finer-Moore, Janet
   Zhang, Chao
   Shokat, Kevan M.
   Stroud, Robert M.
   Walter, Peter
TI The unfolded protein response signals through high-order assembly of Ire1
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum; messenger-rna; er-stress; kinase; mechanism; autophosphorylation; activation; software
AB Aberrant folding of proteins in the endoplasmic reticulum activates the bifunctional transmembrane kinase/ endoribonuclease Ire1. Ire1 excises an intron from HAC1 messenger RNA in yeasts and Xbp1 messenger RNA in metozoans encoding homologous transcription factors. This non- conventional mRNA splicing event initiates the unfolded protein response, a transcriptional program that relieves the endoplasmic reticulum stress. Here we show that oligomerization is central to Ire1 function and is an intrinsic attribute of its cytosolic domains. We obtained the 3.2- A crystal structure of the oligomer of the Ire1 cytosolic domains in complex with a kinase inhibitor that acts as a potent activator of the Ire1 RNase. The structure reveals a rod- shaped assembly that has no known precedence among kinases. This assembly positions the kinase domain for trans- autophosphorylation, orders the RNase domain, and creates an interaction surface for binding of the mRNA substrate. Activation of Ire1 through oligomerization expands the mechanistic repertoire of kinase- based signalling receptors.
C1 [Korennykh, Alexei V.; Egea, Pascal F.; Finer-Moore, Janet; Stroud, Robert M.; Walter, Peter] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Zhang, Chao; Shokat, Kevan M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Korennykh, Alexei V.; Zhang, Chao; Shokat, Kevan M.; Walter, Peter] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Korostelev, Andrei A.] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California Santa Cruz
RP Korennykh, AV (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM alexei.korennykh@ucsf.edu
FU Jane Coffin Childs; National Parkinson Foundation; NIH [RO1 GM60641]
NR 35
TC 513
Z9 660
U1 2
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 687
EP U2
DI 10.1038/nature07661
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700033
PM 19079236
DA 2026-03-09
ER

PT J
AU Okuda, S
   Tsutsui, H
   Shiina, K
   Sprunck, S
   Takeuchi, H
   Yui, R
   Kasahara, RD
   Hamamura, Y
   Mizukami, A
   Susaki, D
   Kawano, N
   Sakakibara, T
   Namiki, S
   Itoh, K
   Otsuka, K
   Matsuzaki, M
   Nozaki, H
   Kuroiwa, T
   Nakano, A
   Kanaoka, MM
   Dresselhaus, T
   Sasaki, N
   Higashiyama, T
AF Okuda, Satohiro
   Tsutsui, Hiroki
   Shiina, Keiko
   Sprunck, Stefanie
   Takeuchi, Hidenori
   Yui, Ryoko
   Kasahara, Ryushiro D.
   Hamamura, Yuki
   Mizukami, Akane
   Susaki, Daichi
   Kawano, Nao
   Sakakibara, Takashi
   Namiki, Shoko
   Itoh, Kie
   Otsuka, Kurataka
   Matsuzaki, Motomichi
   Nozaki, Hisayoshi
   Kuroiwa, Tsuneyoshi
   Nakano, Akihiko
   Kanaoka, Masahiro M.
   Dresselhaus, Thomas
   Sasaki, Narie
   Higashiyama, Tetsuya
TI Defensin-like polypeptide LUREs are pollen tube attractants secreted from synergid cells
SO NATURE
LA English
DT Article
ID torenia-fournieri; female gametophyte; antimicrobial peptides; double fertilization; embryo sac; in-vitro; guidance; arabidopsis; genes; protein
AB For more than 140 years, pollen tube guidance in flowering plants has been thought to be mediated by chemoattractants derived from target ovules(1). However, there has been no convincing evidence of any particular molecule being the true attractant that actually controls the navigation of pollen tubes towards ovules. Emerging data indicate that two synergid cells on the side of the egg cell emit a diffusible, species-specific signal to attract the pollen tube at the last step of pollen tube guidance(1-3). Here we report that secreted, cysteine-rich polypeptides (CRPs) in a subgroup of defensin-like proteins are attractants derived from the synergid cells. We isolated synergid cells of Torenia fournieri, a unique plant with a protruding embryo sac, to identify transcripts encoding secreted proteins as candidate molecules for the chemoattractant(s). We found two CRPs, abundantly and predominantly expressed in the synergid cell, which are secreted to the surface of the egg apparatus. Moreover, they showed activity in vitro to attract competent pollen tubes of their own species and were named as LUREs. Injection of morpholino antisense oligomers against the LUREs impaired pollen tube attraction, supporting the finding that LUREs are the attractants derived from the synergid cells of T. fournieri.
C1 [Okuda, Satohiro; Tsutsui, Hiroki; Shiina, Keiko; Takeuchi, Hidenori; Yui, Ryoko; Kasahara, Ryushiro D.; Hamamura, Yuki; Mizukami, Akane; Susaki, Daichi; Kawano, Nao; Sakakibara, Takashi; Namiki, Shoko; Kanaoka, Masahiro M.; Sasaki, Narie; Higashiyama, Tetsuya] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Aichi 4648602, Japan.
   [Sprunck, Stefanie; Dresselhaus, Thomas] Univ Regensburg, D-93053 Regensburg, Germany.
   [Itoh, Kie] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Chiba 2778562, Japan.
   [Otsuka, Kurataka; Matsuzaki, Motomichi; Nozaki, Hisayoshi; Nakano, Akihiko] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Kuroiwa, Tsuneyoshi] Rikkyo St Pauls Univ, Grad Sch Sci, Res Informat Ctr Extremophile, Tokyo 1718501, Japan.
   [Nakano, Akihiko] RIKEN, Adv Sci Inst, Mol Membrane Biol Lab, Wako, Saitama 3510198, Japan.
C3 Nagoya University; University of Regensburg; University of Tokyo; University of Tokyo; Rikkyo University; RIKEN
RP Higashiyama, T (corresponding author), Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Furo Cho, Aichi 4648602, Japan.
EM higashi@bio.nagoya-u.ac.jp
FU Grant-in-Aid for Young Scientists (Start-up); Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan [20870020]; Creative Scientific Research, MEXT, Japan [18GS0314-01]; Yamada Science Foundation, Japan; Grant-in-Aid for Scientific Research (B), MEXT, Japan [19370017]; Grant-in-Aid for Scientific Research on Priority Areas [18075004]; PRESTO project; Japan Science and Technology Agency, Japan; Grants-in-Aid for Scientific Research [20870020, 20247032] Funding Source: KAKEN
NR 32
TC 495
Z9 569
U1 5
U2 185
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 357
EP U122
DI 10.1038/nature07882
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600045
PM 19295610
DA 2026-03-09
ER

PT J
AU Orso, G
   Pendin, D
   Liu, S
   Tosetto, J
   Moss, TJ
   Faust, JE
   Micaroni, M
   Egorova, A
   Martinuzzi, A
   McNew, JA
   Daga, A
AF Orso, Genny
   Pendin, Diana
   Liu, Song
   Tosetto, Jessica
   Moss, Tyler J.
   Faust, Joseph E.
   Micaroni, Massimo
   Egorova, Anastasia
   Martinuzzi, Andrea
   McNew, James A.
   Daga, Andrea
TI Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin
SO NATURE
LA English
DT Article
ID hereditary spastic paraplegia; endoplasmic-reticulum; drosophila; proteins; reconstitution; morphogenesis; liposm; neurons
AB Establishment and maintenance of proper architecture is essential for endoplasmic reticulum (ER) function. Homotypic membrane fusion is required for ER biogenesis and maintenance, and has been shown to depend on GTP hydrolysis. Here we demonstrate that Drosophila Atlastin-the fly homologue of the mammalian GTPase atlastin 1 involved in hereditary spastic paraplegia-localizes on ER membranes and that its loss causes ER fragmentation. Drosophila Atlastin embedded in distinct membranes has the ability to form trans-oligomeric complexes and its overexpression induces enlargement of ER profiles, consistent with excessive fusion of ER membranes. In vitro experiments confirm that Atlastin autonomously drives membrane fusion in a GTP-dependent fashion. In contrast, GTPase-deficient Atlastin is inactive, unable to form trans-oligomeric complexes owing to failure to self-associate, and incapable of promoting fusion in vitro. These results demonstrate that Atlastin mediates membrane tethering and fusion and strongly suggest that it is the GTPase activity that is required for ER homotypic fusion.
C1 [Orso, Genny; Pendin, Diana; Tosetto, Jessica; Martinuzzi, Andrea; Daga, Andrea] Eugenio Medea Sci Inst, I-31015 Conegliano, Italy.
   [Liu, Song; Moss, Tyler J.; Faust, Joseph E.; McNew, James A.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA.
   [Tosetto, Jessica] Univ Padua, Dept Pharmacol, I-35131 Padua, Italy.
   [Micaroni, Massimo] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
   [Egorova, Anastasia] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Italy.
   [Daga, Andrea] Eugenio Medea Sci Inst, Dulbecco Telethon Inst, I-35131 Padua, Italy.
   [Daga, Andrea] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
C3 IRCCS Eugenio Medea; Rice University; University of Padua; University of Queensland; Istituto di Ricerche Farmacologiche Mario Negri IRCCS; Consorzio Mario Negri Sud; Fondazione Telethon; Dulbecco Telethon Institute (DTI); University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
RP Daga, A (corresponding author), Eugenio Medea Sci Inst, I-31015 Conegliano, Italy.
EM mcnew@rice.edu; daga@unipd.it
FU National Institutes of Health [GM71832]; G. Harold and Leila Mathers Charitable Foundation; Telethon-Italy; Italian Ministry of Health and the Foundation Compagnia di San Paolo
NR 30
TC 386
Z9 465
U1 1
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 978
EP U58
DI 10.1038/nature08280
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500027
PM 19633650
DA 2026-03-09
ER

PT J
AU Harrison, SA
   Tong, F
AF Harrison, Stephenie A.
   Tong, Frank
TI Decoding reveals the contents of visual working memory in early visual areas
SO NATURE
LA English
DT Article
ID short-term-memory; prefrontal cortex; persistent activity; neural mechanisms; temporal cortex; motion task; capacity; performance; correlate; neurons
AB Visual working memory provides an essential link between perception and higher cognitive functions, allowing for the active maintenance of information about stimuli no longer in view(1,2). Research suggests that sustained activity in higher-order prefrontal, parietal, inferotemporal and lateral occipital areas supports visual maintenance(3-11), and may account for the limited capacity of working memory to hold up to 3-4 items(9-11). Because higher-order areas lack the visual selectivity of early sensory areas, it has remained unclear how observers can remember specific visual features, such as the precise orientation of a grating, with minimal decay in performance over delays of many seconds(12). One proposal is that sensory areas serve to maintain fine-tuned feature information(13), but early visual areas show little to no sustained activity over prolonged delays(14-16). Here we show that orientations held in working memory can be decoded from activity patterns in the human visual cortex, even when overall levels of activity are low. Using functional magnetic resonance imaging and pattern classification methods, we found that activity patterns in visual areas V1-V4 could predict which of two oriented gratings was held in memory with mean accuracy levels upwards of 80%, even in participants whose activity fell to baseline levels after a prolonged delay. These orientation-selective activity patterns were sustained throughout the delay period, evident in individual visual areas, and similar to the responses evoked by unattended, task-irrelevant gratings. Our results demonstrate that early visual areas can retain specific information about visual features held in working memory, over periods of many seconds when no physical stimulus is present.
C1 [Tong, Frank] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA.
   Vanderbilt Univ, Vanderbilt Vis Res Ctr, Nashville, TN 37240 USA.
C3 Vanderbilt University; Vanderbilt University
RP Tong, F (corresponding author), Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA.
EM frank.tong@vanderbilt.edu
FU National Eye Institute; National Institutes of Health; Natural Sciences and Engineering Research Council of Canada
NR 30
TC 983
Z9 1154
U1 0
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 2
PY 2009
VL 458
IS 7238
BP 632
EP 635
DI 10.1038/nature07832
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200041
PM 19225460
DA 2026-03-09
ER

PT J
AU Ginsberg, J
   Mohebbi, MH
   Patel, RS
   Brammer, L
   Smolinski, MS
   Brilliant, L
AF Ginsberg, Jeremy
   Mohebbi, Matthew H.
   Patel, Rajan S.
   Brammer, Lynnette
   Smolinski, Mark S.
   Brilliant, Larry
TI Detecting influenza epidemics using search engine query data
SO NATURE
LA English
DT Article
AB Seasonal influenza epidemics are a major public health concern, causing tens of millions of respiratory illnesses and 250,000 to 500,000 deaths worldwide each year(1). In addition to seasonal influenza, a new strain of influenza virus against which no previous immunity exists and that demonstrates human- to- human transmission could result in a pandemic with millions of fatalities(2). Early detection of disease activity, when followed by a rapid response, can reduce the impact of both seasonal and pandemic influenza(3,4). One way to improve early detection is to monitor health- seeking behaviour in the form of queries to online search engines, which are submitted by millions of users around the world each day. Here we present a method of analysing large numbers of Google search queries to track influenza- like illness in a population. Because the relative frequency of certain queries is highly correlated with the percentage of physician visits in which a patient presents with influenza- like symptoms, we can accurately estimate the current level of weekly influenza activity in each region of the United States, with a reporting lag of about one day. This approach may make it possible to use search queries to detect influenza epidemics in areas with a large population of web search users.
C1 [Ginsberg, Jeremy; Mohebbi, Matthew H.; Patel, Rajan S.; Smolinski, Mark S.; Brilliant, Larry] Google Inc, Mountain View, CA 94043 USA.
   [Brammer, Lynnette] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
C3 Alphabet Inc.; Google Incorporated; Centers for Disease Control & Prevention - USA
RP Ginsberg, J (corresponding author), Google Inc, 1600 Amphitheatre Pkwy, Mountain View, CA 94043 USA.
EM flutrends-support@google.com
NR 12
TC 2297
Z9 2938
U1 4
U2 154
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 19
PY 2009
VL 457
IS 7232
BP 1012
EP U4
DI 10.1038/nature07634
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408HF
UT WOS:000263425400042
PM 19020500
DA 2026-03-09
ER

PT J
AU Adamo, L
   Naveiras, O
   Wenzel, PL
   McKinney-Freeman, S
   Mack, PJ
   Gracia-Sancho, J
   Suchy-Dicey, A
   Yoshimoto, M
   Lensch, MW
   Yoder, MC
   García-Cardeña, G
   Daley, GQ
AF Adamo, Luigi
   Naveiras, Olaia
   Wenzel, Pamela L.
   McKinney-Freeman, Shannon
   Mack, Peter J.
   Gracia-Sancho, Jorge
   Suchy-Dicey, Astrid
   Yoshimoto, Momoko
   Lensch, M. William
   Yoder, Mervin C.
   Garcia-Cardena, Guillermo
   Daley, George Q.
TI Biomechanical forces promote embryonic haematopoiesis
SO NATURE
LA English
DT Article
ID nitric-oxide synthase; stem-cells; mouse embryo; definitive hematopoiesis; in-vitro; yolk-sac; expression defines; endothelial-cells; progenitor cells; flow
AB Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system(1,2). After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells(4). It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential(6). Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41(+)c-Kit(+) haematopoietic progenitor cells(7), concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling(8), compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.
C1 [Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
   [Adamo, Luigi; Mack, Peter J.; Gracia-Sancho, Jorge; Suchy-Dicey, Astrid; Garcia-Cardena, Guillermo] Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA.
   [Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA.
   [Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
   [Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Yoshimoto, Momoko; Yoder, Mervin C.] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Howard Hughes Medical Institute; Indiana University System; Indiana University Indianapolis
RP Daley, GQ (corresponding author), Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
EM guillermo_garcia-cardena@hms.harvard.edu; george.daley@childrens.harvard.edu
FU Giovanni Armenise- Harvard Foundation; Barrie de la Maza Foundation; National Institutes of Health; NIH Director's Pioneer Award of the NIH Roadmap for Medical Research; Burroughs Wellcome Fund Clinical Scientist Award; Howard Hughes Medical Institute
NR 33
TC 432
Z9 522
U1 2
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1131
EP U120
DI 10.1038/nature08073
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700044
PM 19440194
DA 2026-03-09
ER

PT J
AU Santra, MK
   Wajapeyee, N
   Green, MR
AF Santra, Manas K.
   Wajapeyee, Narendra
   Green, Michael R.
TI F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage
SO NATURE
LA English
DT Article
ID cancer; phosphorylation; heterozygosity; senescence; atm; checkpoints; pathway; kinase; gene
AB In response to DNA damage, eukaryotic cells initiate a complex signalling pathway, termed the DNA damage response (DDR), which coordinates cell cycle arrest with DNA repair. Studies have shown that oncogene-induced senescence, which provides a barrier to tumour development, involves activation of the DDR1-3. Using a genome-wide RNA interference (RNAi) screen, we have identified 17 factors required for oncogenic BRAF to induce senescence in primary fibroblasts and melanocytes(4). One of these factors is an F-box protein, FBXO31, a candidate tumour suppressor encoded in 16q24.3, a region in which there is loss of heterozygosity in breast, ovarian, hepatocellular and prostate cancers(5-9). Here we study the cellular role of FBXO31, identify its target substrate and determine the basis for its growth inhibitory activity. We show that ectopic expression of FBXO31 acts through a proteasome-directed pathway to mediate the degradation of cyclin D1, an important regulator of progression from G1 to S phase, resulting in arrest in G1. Cyclin D1 degradation results from a direct interaction with FBXO31 and is dependent on the F-box motif of FBXO31 and phosphorylation of cyclin D1 at Thr 286, which is known to be required for cyclin D1 proteolysis. The involvement of the DDR in oncogene-induced senescence prompted us to investigate the role of FBXO31 in DNA repair. We find that DNA damage induced by gamma-irradiation results in increased FBXO31 levels, which requires phosphorylation of FBXO31 by the DDR-initiating kinase ATM. RNAi-mediated knockdown of FBXO31 prevents cells from undergoing efficient arrest in G1 after gamma-irradiation and markedly increases sensitivity to DNA damage. Finally, we show that a variety of DNA damaging agents all result in a large increase in FBXO31 levels, indicating that induction of FBXO31 is a general response to genotoxic stress. Our results reveal FBXO31 as a regulator of the G1/S transition that is specifically required for DNA damage-induced growth arrest.
C1 [Santra, Manas K.; Wajapeyee, Narendra; Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Program Gene Funct & Express, Worcester, MA 01605 USA.
   [Santra, Manas K.; Wajapeyee, Narendra; Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Program Mol Med, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester; Howard Hughes Medical Institute; Howard Hughes Medical Institute; University of Massachusetts System; University of Massachusetts Worcester
RP Green, MR (corresponding author), Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Program Gene Funct & Express, Worcester, MA 01605 USA.
EM michael.green@umassmed.edu
FU Our Danny Cancer Fund; Howard Hughes Medical Institute
NR 23
TC 236
Z9 267
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 4
PY 2009
VL 459
IS 7247
BP 722
EP U129
DI 10.1038/nature08011
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600048
PM 19412162
DA 2026-03-09
ER

PT J
AU Sun, JL
   Bonneau, C
   Cantín, A
   Corma, A
   Diaz-Cabañas, MJ
   Moliner, M
   Zhang, DL
   Li, MR
   Zou, XD
AF Sun, Junliang
   Bonneau, Charlotte
   Cantin, Angel
   Corma, Avelino
   Diaz-Cabanas, Maria J.
   Moliner, Manuel
   Zhang, Daliang
   Li, Mingrun
   Zou, Xiaodong
TI The ITQ-37 mesoporous chiral zeolite
SO NATURE
LA English
DT Article
ID powder diffraction data; crystal-structures; rational design; catalyst; computer; program; pores; nets
AB The synthesis of crystalline molecular sieves with pore dimensions that fill the gap between microporous and mesoporous materials is a matter of fundamental and industrial interest(1-3). The preparation of zeolitic materials with extralarge pores and chiral frameworks would permit many new applications. Two important steps in this direction include the synthesis(4) of ITQ-33, a stable zeolite with 18 x 10 x 10 ring windows, and the synthesis(5) of SU-32, which has an intrinsically chiral zeolite structure and where each crystal exhibits only one handedness. Here we present a germanosilicate zeolite (ITQ-37) with extralarge 30-ring windows. Its structure was determined by combining selected area electron diffraction ( SAED) and powder X-ray diffraction (PXRD) in a charge-flipping algorithm(6). The framework follows the SrSi2 (srs) minimal net(7) and forms two unique cavities, each of which is connected to three other cavities to form a gyroidal channel system. These cavities comprise the enantiomorphous srs net of the framework. ITQ-37 is the first chiral zeolite with one single gyroidal channel. It has the lowest framework density (10.3 T atoms per 1,000 angstrom(3)) of all existing 4-coordinated crystalline oxide frameworks, and the pore volume of the corresponding silica polymorph would be 0.38 cm(3) g(-1).
C1 [Cantin, Angel; Corma, Avelino; Diaz-Cabanas, Maria J.; Moliner, Manuel] Univ Politecn Valencia, CSIC, Inst Tecnol Quim, E-46022 Valencia, Spain.
   [Sun, Junliang; Bonneau, Charlotte; Zhang, Daliang; Li, Mingrun; Zou, Xiaodong] Stockholm Univ, EXSELENT Porous Mat, Struct Chem & Berzelii Ctr, SE-10691 Stockholm, Sweden.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); Universitat Politecnica de Valencia; CSIC-UPV - Instituto de Tecnologia Quimica (ITQ); Stockholm University
RP Cantín, A (corresponding author), Univ Politecn Valencia, CSIC, Inst Tecnol Quim, Naranjos S-N, E-46022 Valencia, Spain.
EM acorma@itq.upv.es; zou@struc.su.se
FU CICYT [MAT 2006-14274-C02-01]; Swedish Research Council; Swedish Governmental Agency for Innovation Systems (VINNOVA); Carl-Trygger and Wenner-Gren foundations
NR 27
TC 496
Z9 541
U1 10
U2 493
PU NATURE PUBLISHING 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 30
PY 2009
VL 458
IS 7242
BP 1154
EP U90
DI 10.1038/nature07957
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600044
PM 19407798
DA 2026-03-09
ER

PT J
AU Moffitt, JR
   Chemla, YR
   Aathavan, K
   Grimes, S
   Jardine, PJ
   Anderson, DL
   Bustamante, C
AF Moffitt, Jeffrey R.
   Chemla, Yann R.
   Aathavan, K.
   Grimes, Shelley
   Jardine, Paul J.
   Anderson, Dwight L.
   Bustamante, Carlos
TI Intersubunit coordination in a homomeric ring ATPase
SO NATURE
LA English
DT Article
ID dna packaging motor; replicative hexameric helicase; optical tweezers; portal motor; bacteriophage phi-29; termination factor; internal force; mechanism; translocation; mechanochemistry
AB Homomeric ring ATPases perform many vital and varied tasks in the cell, ranging from chromosome segregation to protein degradation. Here we report the direct observation of the intersubunit coordination and step size of such a ring ATPase, the double- stranded- DNA packaging motor in the bacteriophage phi 29. Using high- resolution optical tweezers, we find that packaging occurs in increments of 10 base pairs ( bp). Statistical analysis of the preceding dwell times reveals that multiple ATPs bind during each dwell, and application of high force reveals that these 10- bp increments are composed of four 2.5- bp steps. These results indicate that the hydrolysis cycles of the individual subunits are highly coordinated by means of a mechanism novel for ring ATPases. Furthermore, a step size that is a non- integer number of base pairs demands new models for motor - DNA interactions.
C1 [Moffitt, Jeffrey R.; Chemla, Yann R.; Bustamante, Carlos] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Moffitt, Jeffrey R.; Chemla, Yann R.; Bustamante, Carlos] Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA.
   [Aathavan, K.; Bustamante, Carlos] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
   [Grimes, Shelley; Jardine, Paul J.; Anderson, Dwight L.] Univ Minnesota, Dept Diagnost & Biol Sci, Minneapolis, MN 55455 USA.
   [Anderson, Dwight L.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; 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
RP Bustamante, C (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
EM carlos@alice.berkeley.edu
FU National Science Foundation's Graduate Research Fellowship; Burroughs Welcome Fund's Career Awards at the Scientific Interface; NIH [GM-071552, DE-003606, GM-059604]
NR 50
TC 232
Z9 290
U1 2
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 22
PY 2009
VL 457
IS 7228
BP 446
EP U2
DI 10.1038/nature07637
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200039
PM 19129763
DA 2026-03-09
ER

PT J
AU Lyras, D
   O'Connor, JR
   Howarth, PM
   Sambol, SP
   Carter, GP
   Phumoonna, T
   Poon, R
   Adams, V
   Vedantam, G
   Johnson, S
   Gerding, DN
   Rood, JI
AF Lyras, Dena
   O'Connor, Jennifer R.
   Howarth, Pauline M.
   Sambol, Susan P.
   Carter, Glen P.
   Phumoonna, Tongted
   Poon, Rachael
   Adams, Vicki
   Vedantam, Gayatri
   Johnson, Stuart
   Gerding, Dale N.
   Rood, Julian I.
TI Toxin B is essential for virulence of Clostridium difficile
SO NATURE
LA English
DT Article
ID escherichia-coli; expression; hamsters; disease; system; strain; infection; epidemic
AB Clostridium difficile is the leading cause of infectious diarrhoea in hospitals worldwide, because of its virulence, spore-forming ability and persistence(1,2). C. difficile-associated diseases are induced by antibiotic treatment or disruption of the normal gastrointestinal flora(3,4). Recently, morbidity and mortality resulting from C. difficile-associated diseases have increased significantly due to changes in the virulence of the causative strains and antibiotic usage patterns(1,2,5,6). Since 2002, epidemic toxinotype III NAP1/027 strains(1,2), which produce high levels of the major virulence factors, toxin A and toxin B, have emerged. These toxins have 63 % amino acid sequence similarity(7) and are members of the large clostridial glucosylating toxin family, which are monoglucosyltransferases that are pro-inflammatory, cytotoxic and enterotoxic in the human colon(8-10). Inside host cells, both toxins catalyse the transfer of glucose onto the Rho family of GTPases, leading to cell death(8,11). However, the role of these toxins in the context of a C. difficile infection is unknown. Here we describe the construction of isogenic tcdA and tcdB (encoding toxin A and B, respectively) mutants of a virulent C. difficile strain and their use in the hamster disease model to show that toxin B is a key virulence determinant. Previous studies showed that purified toxin A alone can induce most of the pathology observed after infection of hamsters with C. difficile(8,9,12) and that toxin B is not toxic in animals unless it is co-administered with toxin A, suggesting that the toxins act synergistically(12). Our work provides evidence that toxin B, not toxin A, is essential for virulence. Furthermore, it is clear that the importance of these toxins in the context of infection cannot be predicted exclusively from studies using purified toxins, reinforcing the importance of using the natural infection process to dissect the role of toxins in disease.
C1 [Lyras, Dena; O'Connor, Jennifer R.; Howarth, Pauline M.; Carter, Glen P.; Phumoonna, Tongted; Poon, Rachael; Adams, Vicki; Rood, Julian I.] Monash Univ, Dept Microbiol, Australian Bacterial Pathogenesis Program, Clayton, Vic 3800, Australia.
   [Poon, Rachael; Rood, Julian I.] Monash Univ, Dept Microbiol, Australian Res Council, Ctr Excellence Struct & Funct Microbial Genom, Clayton, Vic 3800, Australia.
   [O'Connor, Jennifer R.; Sambol, Susan P.; Vedantam, Gayatri; Johnson, Stuart; Gerding, Dale N.] Hines VA Hosp, Med Serv, Hines, IL 60141 USA.
   [O'Connor, Jennifer R.; Sambol, Susan P.; Vedantam, Gayatri; Johnson, Stuart; Gerding, Dale N.] Hines VA Hosp, Res Serv, Hines, IL 60141 USA.
   Loyola Univ, Stritch Sch Med, Infect Dis Sect, Maywood, IL 60153 USA.
C3 Monash University; Monash University; US Department of Veterans Affairs; Veterans Health Administration (VHA); Edward Hines Jr. VA Hospital; US Department of Veterans Affairs; Veterans Health Administration (VHA); Edward Hines Jr. VA Hospital; Loyola University Chicago
RP Rood, JI (corresponding author), Monash Univ, Dept Microbiol, Australian Bacterial Pathogenesis Program, Clayton, Vic 3800, Australia.
EM julian.rood@med.monash.edu.au
FU Australian National Health and Medical Research Council [284214]; ARC Centre of Excellence in Structural and Functional Microbial Genomics; United States National Institute of Allergy and Infectious Diseases [AIO57637]; United States Department of Veterans Affairs Research Service; National Health and Medical Research Council (NHMRC) [284214] Funding Source: National Health and Medical Research Council (NHMRC)
NR 38
TC 601
Z9 735
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 APR 30
PY 2009
VL 458
IS 7242
BP 1176
EP 1181
DI 10.1038/nature07822
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600055
PM 19252482
DA 2026-03-09
ER

PT J
AU Alvarado, D
   Klein, DE
   Lemmon, MA
AF Alvarado, Diego
   Klein, Daryl E.
   Lemmon, Mark A.
TI ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor
SO NATURE
LA English
DT Article
ID extracellular domain; crystal-structure; region; reveals; system; her2; conformation; activation; herceptin; complex
AB The orphan receptor tyrosine kinase ErbB2 ( also known as HER2 or Neu) transforms cells when overexpressed(1), and it is an important therapeutic target in human cancer(2,3). Structural studies(4,5) have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor(6). Although ErbB2 is unique among the four human ErbB receptors(6,7), here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands(8), yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.
C1 [Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania
RP Lemmon, MA (corresponding author), Univ Penn, Sch Med, Dept Biochem & Biophys, 809C Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM mlemmon@mail.med.upenn.edu
FU National Cancer Institute; National Institute of General Medical Science; NIH; US Army Breast Cancer Research Program; Damon Runyon Cancer Research Foundation
NR 43
TC 66
Z9 90
U1 0
U2 26
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 10
PY 2009
VL 461
IS 7261
BP 287
EP U172
DI 10.1038/nature08297
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600049
PM 19718021
DA 2026-03-09
ER

PT J
AU Bastolla, U
   Fortuna, MA
   Pascual-García, A
   Ferrera, A
   Luque, B
   Bascompte, J
AF Bastolla, Ugo
   Fortuna, Miguel A.
   Pascual-Garcia, Alberto
   Ferrera, Antonio
   Luque, Bartolo
   Bascompte, Jordi
TI The architecture of mutualistic networks minimizes competition and increases biodiversity
SO NATURE
LA English
DT Article
ID coevolutionary networks; pollination networks; model-ecosystems; maintenance; diversity; stability; complex
AB The main theories of biodiversity either neglect species interactions(1,2) or assume that species interact randomly with each other(3,4). However, recent empirical work has revealed that ecological networks are highly structured(5-7), and the lack of a theory that takes into account the structure of interactions precludes further assessment of the implications of such network patterns for biodiversity. Here we use a combination of analytical and empirical approaches to quantify the influence of network architecture on the number of coexisting species. As a case study we consider mutualistic networks between plants and their animal pollinators or seed dispersers(5,8-11). These networks have been found to be highly nested(5), with the more specialist species interacting only with proper subsets of the species that interact with the more generalist. We show that nestedness reduces effective interspecific competition and enhances the number of coexisting species. Furthermore, we show that a nested network will naturally emerge if new species are more likely to enter the community where they have minimal competitive load. Nested networks seem to occur in many biological and social contexts(12-14), suggesting that our results are relevant in a wide range of fields.
C1 [Fortuna, Miguel A.; Bascompte, Jordi] CSIC, Estac Biol Donana, Integrat Ecol Grp, Seville 41092, Spain.
   [Bastolla, Ugo; Pascual-Garcia, Alberto] Univ Autonoma Madrid, CSIC, Ctr Mol Biol, E-28049 Madrid, Spain.
   [Ferrera, Antonio; Luque, Bartolo] Univ Politecn Madrid, Dept Matemat Aplicada & Estadist, ETSI Aeronaut, E-28040 Madrid, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Biologica de Donana (EBD); Autonomous University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC); Universidad Politecnica de Madrid
RP Bascompte, J (corresponding author), CSIC, Estac Biol Donana, Integrat Ecol Grp, C Amer Vespucio S-N, Seville 41092, Spain.
EM bascompte@ebd.csic.es
FU Spanish Ministry of Science and Technology; European Heads of Research Councils; European Science Foundation; EC; Ramon Areces Foundation
NR 30
TC 854
Z9 958
U1 10
U2 460
PU NATURE PUBLISHING 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 23
PY 2009
VL 458
IS 7241
BP 1018
EP U91
DI 10.1038/nature07950
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900040
PM 19396144
DA 2026-03-09
ER

PT J
AU West, JA
   Viswanathan, SR
   Yabuuchi, A
   Cunniff, K
   Takeuchi, A
   Park, IH
   Sero, JE
   Zhu, H
   Perez-Atayde, A
   Frazier, AL
   Surani, MA
   Daley, GQ
AF West, Jason A.
   Viswanathan, Srinivas R.
   Yabuuchi, Akiko
   Cunniff, Kerianne
   Takeuchi, Ayumu
   Park, In-Hyun
   Sero, Julia E.
   Zhu, Hao
   Perez-Atayde, Antonio
   Frazier, A. Lindsay
   Surani, M. Azim
   Daley, George Q.
TI A role for Lin28 in primordial germ-cell development and germ-cell malignancy
SO NATURE
LA English
DT Article
ID embryonic stem-cells; in-vitro; transgenic mice; down-regulation; mouse; microrna; lineage; let-7; specification; methylation
AB The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwart efforts to investigate molecular mechanisms of germ-cell specification. stella (also called Dppa3) marks the rare founder population of the germ lineage(1,2). Here we differentiate mouse embryonic stem cells carrying a stella transgenic reporter into putative PGCs in vitro. The Stella(+) cells possess a transcriptional profile similar to embryo-derived PGCs, and like their counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory RNAs to screen candidate genes for effects on the development of Stella(+) cells in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA processing(3-6), is essential for proper PGC development. Furthermore, we show that Blimp1 (also called Prdm1), a let-7 target and a master regulator of PGCspecification(7-9), can rescue the effect of Lin28 deficiency during PGC development, thereby establishing a mechanism of action for Lin28 during PGC specification. Overexpression of Lin28 promotes formation of Stella(+) cells in vitro and PGCs in chimaeric embryos, and is associated with human germ-cell tumours. The differentiation of putative PGCs from embryonic stem cells in vitro recapitulates the early stages of gamete development in vivo, and provides an accessible system for discovering novel genes involved in germ-cell development and malignancy.
C1 [West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Zhu, Hao; Frazier, A. Lindsay; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Zhu, Hao; Frazier, A. Lindsay; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Zhu, Hao; Daley, George Q.] Harvard Univ, Stem Cell Inst, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Sero, Julia E.; Perez-Atayde, Antonio] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA.
   [Frazier, A. Lindsay] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
   [Surani, M. Azim] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst Canc & Dev, Cambridge CB2 1QN, England.
   [Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
   [Daley, George Q.] 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; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Cambridge; Howard Hughes Medical Institute
RP Daley, GQ (corresponding author), Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
FU NIH; Harvard Stem Cell Institute; Burroughs Wellcome Fund Clinical Scientist Award in Translational Research; Medical Research Council [G0300723, G0800784, G0800784B, G0300723B] Funding Source: researchfish; National Cancer Institute [T32CA009172] Funding Source: NIH RePORTER; MRC [G0800784, G0300723] Funding Source: UKRI
NR 40
TC 309
Z9 363
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 13
PY 2009
VL 460
IS 7257
BP 909
EP U151
DI 10.1038/nature08210
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 483CB
UT WOS:000268938300042
PM 19578360
DA 2026-03-09
ER

PT J
AU Kim, KS
   Zhao, Y
   Jang, H
   Lee, SY
   Kim, JM
   Kim, KS
   Ahn, JH
   Kim, P
   Choi, JY
   Hong, BH
AF Kim, Keun Soo
   Zhao, Yue
   Jang, Houk
   Lee, Sang Yoon
   Kim, Jong Min
   Kim, Kwang S.
   Ahn, Jong-Hyun
   Kim, Philip
   Choi, Jae-Young
   Hong, Byung Hee
TI Large-scale pattern growth of graphene films for stretchable transparent electrodes
SO NATURE
LA English
DT Article
ID epitaxial graphene; silicon; oxide
AB Problems associated with large- scale pattern growth of graphene constitute one of the main obstacles to using this material in device applications(1). Recently, macroscopic- scale graphene films were prepared by two- dimensional assembly of graphene sheets chemically derived from graphite crystals and graphene oxides(2,3). However, the sheet resistance of these films was found to be much larger than theoretically expected values. Here we report the direct synthesis of large- scale graphene films using chemical vapour deposition on thin nickel layers, and present two different methods of patterning the films and transferring them to arbitrary substrates. The transferred graphene films show very low sheet resistance of similar to 280 Omega per square, with 80 per cent optical transparency. At low temperatures, the monolayers transferred to silicon dioxide substrates show electron mobility greater than 3,700 cm(2) V-1 s(-1) and exhibit the half- integer quantum Hall effect(4,5), implying that the quality of graphene grown by chemical vapour deposition is as high as mechanically cleaved graphene(6). Employing the outstanding mechanical properties of graphene(7), we also demonstrate the macroscopic use of these highly conducting and transparent electrodes in flexible, stretchable, foldable electronics(8,9).
C1 [Kim, Keun Soo; Hong, Byung Hee] Sungkyunkwan Univ, Dept Chem, Suwon 440746, South Korea.
   [Jang, Houk; Ahn, Jong-Hyun] Sungkyunkwan Univ, Sch Adv Mat Sci & Engn, Suwon 440746, South Korea.
   [Kim, Keun Soo; Ahn, Jong-Hyun; Kim, Philip; Hong, Byung Hee] Sungkyunkwan Univ, SKKU Adv Inst Nanotechnol, Suwon 440746, South Korea.
   [Kim, Keun Soo; Hong, Byung Hee] Sungkyunkwan Univ, Ctr Nanotubes & Nanostruct Composites, Suwon 440746, South Korea.
   [Lee, Sang Yoon; Kim, Jong Min; Choi, Jae-Young] Samsung Adv Inst Technol, Suwon 440600, South Korea.
   [Kim, Kwang S.] Pohang Univ Sci & Technol, Dept Chem, Pohang 790784, South Korea.
   [Zhao, Yue; Kim, Philip] Columbia Univ, Dept Phys, New York, NY 10027 USA.
C3 Sungkyunkwan University (SKKU); Sungkyunkwan University (SKKU); Sungkyunkwan University (SKKU); Sungkyunkwan University (SKKU); Samsung; Pohang University of Science & Technology (POSTECH); Columbia University
RP Hong, BH (corresponding author), Sungkyunkwan Univ, Dept Chem, POB 111, Suwon 440746, South Korea.
EM jaeyoung88.choi@samsung.com; byunghee@skku.edu
FU Korea Science and Engineering Foundation; Korea Ministry for Education, Science and Technology [R11-2001-091-00000-0]; Global Research Lab programme ( Korea Foundation for International Cooperation of Science and Technology); Brain Korea 21 project; Korea Ministry of Knowledge Economy [2008-F024-01]
NR 30
TC 8530
Z9 8945
U1 44
U2 7598
PU NATURE PUBLISHING 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 5
PY 2009
VL 457
IS 7230
BP 706
EP 710
DI 10.1038/nature07719
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700037
DA 2026-03-09
ER

PT J
AU Pollard, D
   DeConto, RM
AF Pollard, David
   DeConto, Robert M.
TI Modelling West Antarctic ice sheet growth and collapse through the past five million years
SO NATURE
LA English
DT Article
ID climate; shelf; evolution; parameterization; retreat; flow
AB The West Antarctic ice sheet (WAIS), with ice volume equivalent to similar to 5 m of sea level(1), has long been considered capable of past and future catastrophic collapse(2-4). Today, the ice sheet is fringed by vulnerable floating ice shelves that buttress the fast flow of inland ice streams. Grounding lines are several hundred metres below sea level and the bed deepens upstream, raising the prospect of runaway retreat(3,5). Projections of future WAIS behaviour have been hampered by limited understanding of past variations and their underlying forcing mechanisms(6,7). Its variation since the Last Glacial Maximum is best known, with grounding lines advancing to the continental-shelf edges around similar to 15 kyr ago before retreating to near-modern locations by similar to 3 kyr ago(8). Prior collapses during the warmth of the early Pliocene epoch(9) and some Pleistocene interglacials have been suggested indirectly from records of sea level and deep-sea-core isotopes, and by the discovery of open-ocean diatoms in subglacial sediments(10). Until now(11), however, little direct evidence of such behaviour has been available. Here we use a combined ice sheet/ice shelf model(12) capable of high-resolution nesting with a new treatment of grounding-line dynamics and ice-shelf buttressing 5 to simulate Antarctic ice sheet variations over the past five million years. Modelled WAIS variations range from full glacial extents with grounding lines near the continental shelf break, intermediate states similar to modern, and brief but dramatic retreats, leaving only small, isolated ice caps on West Antarctic islands. Transitions between glacial, intermediate and collapsed states are relatively rapid, taking one to several thousand years. Our simulation is in good agreement with a new sediment record (ANDRILL AND-1B) recovered from the western Ross Sea(11), indicating a long-term trend from more frequently collapsed to more glaciated states, dominant 40-kyr cyclicity in the Pliocene, and major retreats at marine isotope stage 31 (similar to 1.07 Myr ago) and other super-interglacials.
C1 [Pollard, David] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [DeConto, Robert M.] Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Massachusetts System; University of Massachusetts Amherst
RP Pollard, D (corresponding author), Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
EM pollard@essc.psu.edu
FU US National Science Foundation [ATM-0513402/0513421, ANT-034248, ANT-0424589]
NR 36
TC 754
Z9 875
U1 2
U2 224
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 329
EP U89
DI 10.1038/nature07809
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600039
PM 19295608
DA 2026-03-09
ER

PT J
AU Li, QS
   Estes, JD
   Schlievert, PM
   Duan, LJ
   Brosnahan, AJ
   Southern, PJ
   Reilly, CS
   Peterson, ML
   Schultz-Darken, N
   Brunner, KG
   Nephew, KR
   Pambuccian, S
   Lifson, JD
   Carlis, JV
   Haase, AT
AF Li, Qingsheng
   Estes, Jacob D.
   Schlievert, Patrick M.
   Duan, Lijie
   Brosnahan, Amanda J.
   Southern, Peter J.
   Reilly, Cavan S.
   Peterson, Marnie L.
   Schultz-Darken, Nancy
   Brunner, Kevin G.
   Nephew, Karla R.
   Pambuccian, Stefan
   Lifson, Jeffrey D.
   Carlis, John V.
   Haase, Ashley T.
TI Glycerol monolaurate prevents mucosal SIV transmission
SO NATURE
LA English
DT Article
ID simian immunodeficiency virus; cd4(+) t-cells; vaginal transmission; epithelial-cells; infection; hiv; responses; innate
AB Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection(1), preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission(2-4). Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)-rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry(5,6). Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3 alpha (also known as CCL20), plasmacytoid dendritic cells and CCR5(+) cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4(+) T cells to fuel this obligate expansion. We then show that glycerol monolaurate-a widely used antimicrobial compound(7) with inhibitory activity against the production of MIP-3 alpha and other proinflammatory cytokines(8)-can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to blockHIV-1 mucosal transmission.
C1 [Li, Qingsheng; Schlievert, Patrick M.; Duan, Lijie; Brosnahan, Amanda J.; Southern, Peter J.; Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
   [Estes, Jacob D.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
   [Reilly, Cavan S.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
   [Peterson, Marnie L.] Univ Minnesota, Coll Pharm, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA.
   [Schultz-Darken, Nancy; Brunner, Kevin G.; Nephew, Karla R.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
   [Pambuccian, Stefan] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
   [Carlis, John V.] Univ Minnesota, Inst Technol, Dept Comp Sci & Engn, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Science Applications International Corporation (SAIC); University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Wisconsin System; University of Wisconsin Madison; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities
RP Haase, AT (corresponding author), Univ Minnesota, Dept Microbiol, MMC 196,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM haase001@umn.edu
FU National Institute of Health (NIH) [R21 AI071976, P01 AI066314]; National Cancer Institute, NIH [N01-CO-12400, HHSN266200400088C]; National Center for Research Resources [P51 RR000167]; Research Facilities Improvement Program [RR15459-01, RR020141-01]
NR 26
TC 528
Z9 653
U1 3
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 23
PY 2009
VL 458
IS 7241
BP 1034
EP U113
DI 10.1038/nature07831
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900044
PM 19262509
DA 2026-03-09
ER

PT J
AU Lee, JW
   Kang, YW
   Lee, J
   Lee, YW
AF Lee, Jae-Woo
   Kang, Young-Woon
   Lee, Jina
   Lee, Young-Wook
TI Enrichment by supernovae in globular clusters with multiple populations
SO NATURE
LA English
DT Article
ID omega-centauri; chemical inhomogeneity; stellar populations; star-clusters; m22; photometry; system; galaxy; evolution; giants
AB The most massive globular cluster in the Milky Way, omega Centauri, is thought to be the remaining core of a disrupted dwarf galaxy(1,2), as expected within the model of hierarchical merging(3,4). It contains several stellar populations having different heavy elemental abundances supplied by supernovae(5)-a process known as metal enrichment. Although M 22 appears to be similar to omega Cen(6), other peculiar globular clusters do not(7,8). Therefore omega Cen and M 22 are viewed as exceptional, and the presence of chemical inhomogeneities in other clusters is seen as 'pollution' from the intermediate-mass asymptotic-giant-branch stars expected in normal globular clusters(9). Here we report Ca abundances for seven globular clusters and compare them to omega Cen. Calcium and other heavy elements can only be supplied through numerous supernovae explosions of massive stars in these stellar systems(10), but the gravitational potentials of the present-day clusters cannot preserve most of the ejecta from such explosions(11). We conclude that these globular clusters, like omega Cen, are most probably the relics of more massive primeval dwarf galaxies that merged and disrupted to form the proto-Galaxy.
C1 [Lee, Jae-Woo; Kang, Young-Woon; Lee, Jina] Sejong Univ, ARCSEC, Dept Astron & Space Sci, Seoul 143747, South Korea.
   [Lee, Young-Wook] Yonsei Univ, Ctr Space Astrophys, Seoul 120749, South Korea.
C3 Sejong University; Yonsei University
RP Lee, JW (corresponding author), Sejong Univ, ARCSEC, Dept Astron & Space Sci, Seoul 143747, South Korea.
EM jaewoolee@sejong.ac.kr; ywlee2@yonsei.ac.kr
FU National Research Foundation of Korea
NR 27
TC 131
Z9 134
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 26
PY 2009
VL 462
IS 7272
BP 480
EP 482
DI 10.1038/nature08565
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200037
PM 19940919
DA 2026-03-09
ER

PT J
AU Zhu, LQ
   Gibson, P
   Currle, DS
   Tong, Y
   Richardson, RJ
   Bayazitov, IT
   Poppleton, H
   Zakharenko, S
   Ellison, DW
   Gilbertson, RJ
AF Zhu, Liqin
   Gibson, Paul
   Currle, D. Spencer
   Tong, Yiai
   Richardson, Robert J.
   Bayazitov, Ildar T.
   Poppleton, Helen
   Zakharenko, Stanislav
   Ellison, David W.
   Gilbertson, Richard J.
TI Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation
SO NATURE
LA English
DT Article
ID hematopoietic stem; perivascular niche; colorectal-cancer; tumor-growth; mouse; identification; mutation; gene; tumorigenesis; polyposis
AB Cancer stem cells are remarkably similar to normal stem cells: both self- renew, are multipotent and express common surface markers, for example, prominin 1 ( PROM1, also called CD133)(1). What remains unclear is whether cancer stem cells are the direct progeny of mutated stem cells or more mature cells that reacquire stem cell properties during tumour formation. Answering this question will require knowledge of whether normal stem cells are susceptible to cancer- causing mutations; however, this has proved difficult to test because the identity of most adult tissue stem cells is not known. Here, using an inducible Cre, nuclear LacZ reporter allele knocked into the Prom1 locus (Prom1(C-L)), we show that Prom1 is expressed in a variety of developing and adult tissues. Lineage- tracing studies of adult Prom1(+/C-L) mice containing the Rosa26-YFP reporter allele showed that Prom1(+) cells are located at the base of crypts in the small intestine, co- express Lgr5 ( ref. 2), generate the entire intestinal epithelium, and are therefore the small intestinal stem cell. Prom1 was reported recently to mark cancer stem cells of human intestinal tumours that arise frequently as a consequence of aberrant wingless ( Wnt) signalling(3-5). Activation of endogenous Wnt signalling in Prom1(+/C-L) mice containing a Cre- dependent mutant allele of beta-catenin (Ctnnb1(lox(ex3))) resulted in a gross disruption of crypt architecture and a disproportionate expansion of Prom1(+) cells at the crypt base. Lineage tracing demonstrated that the progeny of these cells replaced the mucosa of the entire small intestine with neoplastic tissue that was characterized by focal high- grade intraepithelial neoplasia and crypt adenoma formation. Although all neoplastic cells arose from Prom1(+) cells in these mice, only 7% of tumour cells retained Prom1 expression. Our data indicate that Prom1 marks stem cells in the adult small intestine that are susceptible to transformation into tumours retaining a fraction of mutant Prom1(+) tumour cells.
C1 [Zhu, Liqin; Gibson, Paul; Currle, D. Spencer; Tong, Yiai; Richardson, Robert J.; Bayazitov, Ildar T.; Poppleton, Helen; Zakharenko, Stanislav; Gilbertson, Richard J.] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
   [Ellison, David W.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Gilbertson, Richard J.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA.
C3 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 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; National Cancer Institute [P30CA021765, P01CA096832] Funding Source: NIH RePORTER
NR 30
TC 542
Z9 624
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 29
PY 2009
VL 457
IS 7229
BP 603
EP U114
DI 10.1038/nature07589
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200046
PM 19092805
DA 2026-03-09
ER

PT J
AU Xia, ZP
   Sun, LJ
   Chen, X
   Pineda, G
   Jiang, XM
   Adhikari, A
   Zeng, WW
   Chen, ZJ
AF Xia, Zong-Ping
   Sun, Lijun
   Chen, Xiang
   Pineda, Gabriel
   Jiang, Xiaomo
   Adhikari, Anirban
   Zeng, Wenwen
   Chen, Zhijian J.
TI Direct activation of protein kinases by unanchored polyubiquitin chains
SO NATURE
LA English
DT Article
ID nf-kappa-b; ubiquitin-conjugating enzyme; lys63-linked polyubiquitination; binding; nemo; traf6; tak1; il-1; ikk; autoubiquitination
AB TRAF6 is a ubiquitin ligase that is essential for the activation of NF-kappa B and MAP kinases in several signalling pathways, including those emanating from the interleukin 1 and Toll-like receptors(1-3). TRAF6 functions together with a ubiquitin-conjugating enzyme complex consisting of UBC13 (also known as UBE2N) and UEV1A (UBE2V1) to catalyse Lys 63-linked polyubiquitination, which activates the TAK1 (also known as MAP3K7) kinase complex(4,5). TAK1 in turn phosphorylates and activates I kappa B kinase (IKK), leading to the activation of NF-kappa B. Although several proteins are known to be polyubiquitinated in the IL1R and Toll-like receptor pathways, it is not clear whether ubiquitination of any of these proteins is important for TAK1 or IKK activation. By reconstituting TAK1 activation in vitro using purified proteins, here we show that free Lys 63 polyubiquitin chains, which are not conjugated to any target protein, directly activate TAK1 by binding to the ubiquitin receptor TAB2 (also known as MAP3K7IP2). This binding leads to autophosphorylation and activation of TAK1. Furthermore, we found that unanchored polyubiquitin chains synthesized by TRAF6 and UBCH5C (also known as UBE2D3) activate the IKK complex. Disassembly of the polyubiquitin chains by deubiquitination enzymes prevented TAK1 and IKK activation. These results indicate that unanchored polyubiquitin chains directly activate TAK1 and IKK, suggesting a new mechanism of protein kinase regulation.
C1 [Xia, Zong-Ping; Sun, Lijun; Chen, Xiang; Pineda, Gabriel; Jiang, Xiaomo; Adhikari, Anirban; Zeng, Wenwen; Chen, Zhijian J.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Sun, Lijun; Chen, Xiang; Chen, Zhijian J.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center
RP Chen, ZJ (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
EM Zhijian.Chen@UTSouthwestern.edu
FU National Institute of Health [RO1-AI09919, RO1-GM63692]; Robert Welch Foundation [I-1389]; Howard Hughes Medical Institute
NR 30
TC 463
Z9 561
U1 1
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 114
EP U125
DI 10.1038/nature08247
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800041
PM 19675569
DA 2026-03-09
ER

PT J
AU Allen, MR
   Frame, DJ
   Huntingford, C
   Jones, CD
   Lowe, JA
   Meinshausen, M
   Meinshausen, N
AF Allen, Myles R.
   Frame, David J.
   Huntingford, Chris
   Jones, Chris D.
   Lowe, Jason A.
   Meinshausen, Malte
   Meinshausen, Nicolai
TI Warming caused by cumulative carbon emissions towards the trillionth tonne
SO NATURE
LA English
DT Article
ID climate-change; stabilization; temperature; uncertainty; feedback
AB Global efforts to mitigate climate change are guided by projections of future temperatures(1). But the eventual equilibrium global mean temperature associated with a given stabilization level of atmospheric greenhouse gas concentrations remains uncertain(1-3), complicating the setting of stabilization targets to avoid potentially dangerous levels of global warming(4-8). Similar problems apply to the carbon cycle: observations currently provide only a weak constraint on the response to future emissions(9-11). Here we use ensemble simulations of simple climate-carbon-cycle models constrained by observations and projections from more comprehensive models to simulate the temperature response to a broad range of carbon dioxide emission pathways. We find that the peak warming caused by a given cumulative carbon dioxide emission is better constrained than the warming response to a stabilization scenario. Furthermore, the relationship between cumulative emissions and peak warming is remarkably insensitive to the emission pathway (timing of emissions or peak emission rate). Hence policy targets based on limiting cumulative emissions of carbon dioxide are likely to be more robust to scientific uncertainty than emission-rate or concentration targets. Total anthropogenic emissions of one trillion tonnes of carbon (3.67 trillion tonnes of CO2), about half of which has already been emitted since industrialization began, results in a most likely peak carbon-dioxide-induced warming of 2 degrees C above pre-industrial temperatures, with a 5-95% confidence interval of 1.3-3.9 degrees C.
C1 [Allen, Myles R.; Frame, David J.] Univ Oxford, Dept Phys, Oxford OX1 3PU, England.
   [Frame, David J.] Univ Oxford, Smith Sch Enterprise & Environm, Oxford OX1 2BQ, England.
   [Huntingford, Chris] Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England.
   [Jones, Chris D.] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [Lowe, Jason A.] Univ Reading, Dept Meteorol, Met Off Hadley Ctr, Reading Unit, Reading RG6 6BB, Berks, England.
   [Meinshausen, Malte] Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany.
   [Meinshausen, Nicolai] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
C3 University of Oxford; University of Oxford; UK Centre for Ecology & Hydrology (UKCEH); Met Office - UK; Hadley Centre; University of Reading; Met Office - UK; Hadley Centre; Potsdam Institut fur Klimafolgenforschung; University of Oxford
RP Allen, MR (corresponding author), Univ Oxford, Dept Phys, Oxford OX1 3PU, England.
EM myles.allen@physics.ox.ac.uk
FU DOE Office of Science; Office of Biological and Environmental Research; NOAA Climate Program Office; British Council; CEH Science Budget Fund; Joint DECC; Defra and MoD Integrated Climate Programme [GA01101]; MoD [CBC/2B/0417_Annex C5]; Natural Environment Research Council [NE/C515747/1] Funding Source: researchfish
NR 30
TC 1168
Z9 1350
U1 17
U2 589
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 30
PY 2009
VL 458
IS 7242
BP 1163
EP 1166
DI 10.1038/nature08019
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441FL
UT WOS:000265754600046
PM 19407800
DA 2026-03-09
ER

PT J
AU Keele, BF
   Jones, JH
   Terio, KA
   Estes, JD
   Rudicell, RS
   Wilson, ML
   Li, YY
   Learn, GH
   Beasley, TM
   Schumacher-Stankey, J
   Wroblewski, E
   Mosser, A
   Raphael, J
   Kamenya, S
   Lonsdorf, EV
   Travis, DA
   Mlengeya, T
   Kinsel, MJ
   Else, JG
   Silvestri, G
   Goodall, J
   Sharp, PM
   Shaw, GM
   Pusey, AE
   Hahn, BH
AF Keele, Brandon F.
   Jones, James Holland
   Terio, Karen A.
   Estes, Jacob D.
   Rudicell, Rebecca S.
   Wilson, Michael L.
   Li, Yingying
   Learn, Gerald H.
   Beasley, T. Mark
   Schumacher-Stankey, Joann
   Wroblewski, Emily
   Mosser, Anna
   Raphael, Jane
   Kamenya, Shadrack
   Lonsdorf, Elizabeth V.
   Travis, Dominic A.
   Mlengeya, Titus
   Kinsel, Michael J.
   Else, James G.
   Silvestri, Guido
   Goodall, Jane
   Sharp, Paul M.
   Shaw, George M.
   Pusey, Anne E.
   Hahn, Beatrice H.
TI Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz
SO NATURE
LA English
DT Article
ID gombe national-park; immunodeficiency virus-infection; immune activation; hiv-infection; t-cells; transmission; resistance; community; absence; tissue
AB African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2)(1,2). Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts(3). Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4(+) T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4(+) T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.
C1 [Keele, Brandon F.; Li, Yingying; Learn, Gerald H.; Shaw, George M.; Hahn, Beatrice H.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
   [Rudicell, Rebecca S.; Hahn, Beatrice H.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
   [Beasley, T. Mark] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
   [Jones, James Holland] Stanford Univ, Dept Anthropol, Stanford, CA 94305 USA.
   [Terio, Karen A.; Kinsel, Michael J.] Univ Illinois, Zool Pathol Program, Maywood, IL 60153 USA.
   [Estes, Jacob D.] NCI, Sci Applicat Int Corp Frederick Inc, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
   [Wilson, Michael L.] Univ Minnesota, Dept Anthropol, Minneapolis, MN 55455 USA.
   [Wilson, Michael L.; Schumacher-Stankey, Joann; Wroblewski, Emily; Pusey, Anne E.] Univ Minnesota, Dept Ecol Evolut & Behav, Jane Goodall Inst Ctr Primate Studies, St Paul, MN 55108 USA.
   [Mosser, Anna; Raphael, Jane; Kamenya, Shadrack] Jane Goodall Inst, Gombe Stream Res Ctr, Kigoma, Tanzania.
   [Lonsdorf, Elizabeth V.] Lester E Fisher Ctr Study & Conservat Apes, Chicago, IL 60614 USA.
   [Travis, Dominic A.] Lincoln Pk Zoo, Dept Conservat & Sci, Chicago, IL 60614 USA.
   [Mlengeya, Titus] Tanzania Natl Pk, Arusha, Tanzania.
   [Else, James G.] Emory Univ, Yerkes Natl Primate Res Ctr, Div Anim Resources, Atlanta, GA 30322 USA.
   [Silvestri, Guido] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19107 USA.
   [Goodall, Jane] Jane Goodall Inst, Arlington, VA 22203 USA.
   [Sharp, Paul M.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
C3 University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham; Stanford University; University of Illinois System; University of Illinois Urbana-Champaign; Science Applications International Corporation (SAIC); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Emory University; University of Pennsylvania; University of Edinburgh
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 AI067854, T32 GM008111]; National Cancer Institute [HHSN266200400088C]; UAB Center for AIDS Research [P30 AI 27767]; Yerkes National Primate Research Center [RR-00165]; National Science Foundation [DBS-9021946, SBR-9319909, BSC-0452315, IIS-0431141, BSC-0648481]; Jane Goodall Institute; Harris Steel Group; University of Minnesota; University of Illinois; US Fish and Wildlife Service Great Ape Conservation Fund; Windibrow, Arcus, Guthman and Davee Foundations; Lincoln Park Zoo; Howard Hughes Medical Institute; National Institute of Allergy and Infectious Diseases [R01AI050529] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Minority Health and Health Disparities; National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research; National Institute of Nursing Research; National Heart Lung and Blood Institute; National Institute on Drug Abuse; National Institute on Aging; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30AI027767] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008111] Funding Source: NIH RePORTER
NR 29
TC 269
Z9 345
U1 3
U2 84
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 515
EP 519
DI 10.1038/nature08200
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000039
PM 19626114
DA 2026-03-09
ER

PT J
AU Grove, TL
   Till, CB
   Lev, E
   Chatterjee, N
   Médard, E
AF Grove, T. L.
   Till, C. B.
   Lev, E.
   Chatterjee, N.
   Medard, E.
TI Kinematic variables and water transport control the formation and location of arc volcanoes
SO NATURE
LA English
DT Article
ID mantle wedge; subduction; consequences; region; slabs; h2o
AB The processes that give rise to arc magmas at convergent plate margins have long been a subject of scientific research and debate(1-6). A consensus has developed that the mantle wedge overlying the subducting slab(3,4) and fluids and/or melts from the subducting slab itself(6-11) are involved in the melting process. However, the role of kinematic variables such as slab dip and convergence rate in the formation of arc magmas is still unclear. The depth to the top of the subducting slab beneath volcanic arcs, usually similar to 110 +/- 20 km, was previously thought to be constant among arcs(3,6,12). Recent studies(13,14) revealed that the depth of intermediate-depth earthquakes underneath volcanic arcs, presumably marking the slab wedge interface, varies systematically between similar to 60 and 173 km and correlates with slab dip and convergence rate. Water-rich magmas (over 4-6wt% H2O) are found in subduction zones with very different subduction parameters, including those with a shallow-dipping slab (north Japan), or steeply dipping slab (Marianas). Here we propose a simple model to address how kinematic parameters of plate subduction relate to the location of mantle melting at subduction zones. We demonstrate that the location of arc volcanoes is controlled by a combination of conditions: [GRAPHICS] melting in the wedge is induced at the overlap of regions in the wedge that are hotter than the melting curve (solidus) of vapour-saturated peridotite and regions where hydrous minerals both in the wedge and in the subducting slab break down. These two limits for melt generation, when combined with the kinematic parameters of slab dip and convergence rate, provide independent constraints on the thermal structure of the wedge and accurately predict the location of mantle wedge melting and the position of arc volcanoes.
C1 [Grove, T. L.; Till, C. B.; Lev, E.; Chatterjee, N.; Medard, E.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Grove, TL (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
EM tlgrove@mit.edu
FU NSF
NR 30
TC 174
Z9 202
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 JUN 4
PY 2009
VL 459
IS 7247
BP 694
EP 697
DI 10.1038/nature08044
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453KF
UT WOS:000266608600042
PM 19494913
DA 2026-03-09
ER

PT J
AU Aragón, T
   van Anken, E
   Pincus, D
   Serafimova, IM
   Korennykh, AV
   Rubio, CA
   Walter, P
AF Aragon, Tomas
   van Anken, Eelco
   Pincus, David
   Serafimova, Iana M.
   Korennykh, Alexei V.
   Rubio, Claudia A.
   Walter, Peter
TI Messenger RNA targeting to endoplasmic reticulum stress signalling sites
SO NATURE
LA English
DT Article
ID unfolded protein response; saccharomyces-cerevisiae; translation; yeast; kinase; localization; degradation; expression; mechanism; transport
AB Deficiencies in the protein- folding capacity of the endoplasmic reticulum (ER) in all eukaryotic cells lead to ER stress and trigger the unfolded protein response (UPR)(1-3). ER stress is sensed by Ire1, a transmembrane kinase/ endoribonuclease, which initiates the non- conventional splicing of the messenger RNA encoding a key transcription activator, Hac1 in yeast or XBP1 in metazoans. In the absence of ER stress, ribosomes are stalled on unspliced HAC1 mRNA. The translational control is imposed by a base- pairing interaction between the HAC1 intron and the HAC1 5' untranslated region(4). After excision of the intron, transfer RNA ligase joins the severed exons(5,6), lifting the translational block and allowing synthesis of Hac1 from the spliced HAC1 mRNA to ensue(4). Hac1 in turn drives the UPR gene expression program comprising 7-8% of the yeast genome(7) to counteract ER stress. Here we show that, on activation, Ire1 molecules cluster in the ER membrane into discrete foci of higher- order oligomers, to which unspliced HAC1 mRNA is recruited by means of a conserved bipartite targeting element contained in the 3' untranslated region. Disruption of either Ire1 clustering or HAC1 mRNA recruitment impairs UPR signalling. The HAC1 3' untranslated region element is sufficient to target other mRNAs to Ire1 foci, as long as their translation is repressed. Translational repression afforded by the intron fulfils this requirement for HAC1 mRNA. Recruitment of mRNA to signalling centres provides a new paradigm for the control of eukaryotic gene expression.
C1 [Aragon, Tomas; van Anken, Eelco; Pincus, David; Serafimova, Iana M.; Korennykh, Alexei V.; Rubio, Claudia A.; Walter, Peter] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Aragon, Tomas; van Anken, Eelco; Pincus, David; Serafimova, Iana M.; Korennykh, Alexei V.; Rubio, Claudia A.; Walter, Peter] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco
RP Aragón, T (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM Tomas.Aragon@ucsf.edu
FU Basque Foundation for Science; Howard Hughes Medical Institute; Netherlands Organization for Scientific Research (NWO); National Science Foundation; President's Dissertation Year Fellowship; Jane Childs Memorial Fund for Medical Research
NR 33
TC 256
Z9 344
U1 1
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 5
PY 2009
VL 457
IS 7230
BP 736
EP U9
DI 10.1038/nature07641
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 403EA
UT WOS:000263064700044
PM 19079237
DA 2026-03-09
ER

PT J
AU Pichevin, LE
   Reynolds, BC
   Ganeshram, RS
   Cacho, I
   Pena, L
   Keefe, K
   Ellam, RM
AF Pichevin, L. E.
   Reynolds, B. C.
   Ganeshram, R. S.
   Cacho, I.
   Pena, L.
   Keefe, K.
   Ellam, R. M.
TI Enhanced carbon pump inferred from relaxation of nutrient limitation in the glacial ocean
SO NATURE
LA English
DT Article
ID eastern equatorial pacific; icp-ms; flux; fractionation; temperature; nitrogen; ratios; opal
AB The modern Eastern Equatorial Pacific (EEP) Ocean is a large oceanic source of carbon to the atmosphere(1). Primary productivity over large areas of the EEP is limited by silicic acid and iron availability, and because of this constraint the organic carbon export to the deep ocean is unable to compensate for the outgassing of carbon dioxide that occurs through upwelling of deep waters. It has been suggested that the delivery of dust-borne iron to the glacial ocean(2,3) could have increased primary productivity and enhanced deep-sea carbon export in this region, lowering atmospheric carbon dioxide concentrations during glacial periods. Such a role for the EEP is supported by higher organic carbon burial rates documented in underlying glacial sediments(4,5), but lower opal accumulation rates cast doubts on the importance of the EEP as an oceanic region for significant glacial carbon dioxide drawdown(6,7). Here we present a new silicon isotope record that suggests the paradoxical decline in opal accumulation rate in the glacial EEP results from a decrease in the silicon to carbon uptake ratio of diatoms under conditions of increased iron availability from enhanced dust input. Consequently, our study supports the idea of an invigorated biological pump in this region during the last glacial period that could have contributed to glacial carbon dioxide drawdown. Additionally, using evidence from silicon and nitrogen isotope changes, we infer that, in contrast to the modern situation, the biological productivity in this region is not constrained by the availability of iron, silicon and nitrogen during the glacial period. We hypothesize that an invigorated biological carbon dioxide pump constrained perhaps only by phosphorus limitation was a more common occurrence in low-latitude areas of the glacial ocean.
C1 [Pichevin, L. E.; Ganeshram, R. S.] Univ Edinburgh, Grant Inst, Sch Geosci, Edinburgh EH10 3JW, Midlothian, Scotland.
   [Reynolds, B. C.] ETH, IGMR, CH-8092 Zurich, Switzerland.
   [Cacho, I.; Pena, L.] Univ Barcelona, Fac Geol, GRC Geociencies Marines, E-08028 Barcelona, Spain.
   [Keefe, K.; Ellam, R. M.] Scottish Univ Environm Res Ctr, E Kilbride G75 0QF, Lanark, Scotland.
C3 University of Edinburgh; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Barcelona; Scottish Universities Research & Reactor Center
RP Pichevin, LE (corresponding author), Univ Edinburgh, Grant Inst, Sch Geosci, W Main Rd, Edinburgh EH10 3JW, Midlothian, Scotland.
EM laetitia.pichevin@ed.ac.uk
FU Scottish Alliance for Geoscience Environment Society (SAGES); Natural Environment Research Council ( NERC) through a Standard NERC; Marie Curie Intra-European fellowship; ROMIAT; GRACCIE-CONSOLIDER; NERC [NE/E017738/1] Funding Source: UKRI; Natural Environment Research Council [NE/E017738/1] Funding Source: researchfish
NR 36
TC 89
Z9 101
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 25
PY 2009
VL 459
IS 7250
BP 1114
EP U98
DI 10.1038/nature08101
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700040
PM 19553996
DA 2026-03-09
ER

PT J
AU Seal, RP
   Wang, XD
   Guan, Y
   Raja, SN
   Woodbury, CJ
   Basbaum, AI
   Edwards, RH
AF Seal, Rebecca P.
   Wang, Xidao
   Guan, Yun
   Raja, Srinivasa N.
   Woodbury, C. Jeffery
   Basbaum, Allan I.
   Edwards, Robert H.
TI Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors
SO NATURE
LA English
DT Article
ID vesicular glutamate transporters; spinal dorsal-horn; substantia-gelatinosa; sensory neurons; mice lacking; inflammatory pain; neuropathic pain; afferent-fibers; marginal zone; pkc-gamma
AB Mechanical pain contributes to the morbidity associated with inflammation and trauma, but primary sensory neurons that convey the sensation of acute and persistentmechanical pain have not been identified. Dorsal root ganglion (DRG) neurons transmit sensory information to the spinal cord using the excitatory transmitter glutamate(1), a process that depends on glutamate transport into synaptic vesicles for regulated exocytotic release. Here we report that a small subset of cells in the DRG expresses the low abundance vesicular glutamate transporter VGLUT3 (also known as SLC17A8). In the dorsal horn of the spinal cord, these afferents project to lamina I and the innermost layer of lamina II, which has previously been implicated in persistent pain caused by injury(2). Because the different VGLUT isoforms generally have a non-redundant pattern of expression(3), we used Vglut3 knockout mice to assess the role of VGLUT3(+) primary afferents in the behavioural response to somatosensory input. The loss of VGLUT3 specifically impairs mechanical pain sensation, and in particular the mechanical hypersensitivity to normally innocuous stimuli that accompanies inflammation, nerve injury and trauma. Direct recording from VGLUT3(+) neurons in the DRG further identifies them as a poorly understood population of unmyelinated, low threshold mechanoreceptors (C-LTMRs)(4,5). The analysis of Vglut3(-/-) mice now indicates a critical role for C-LTMRs in the mechanical hypersensitivity caused by injury.
C1 [Seal, Rebecca P.; Edwards, Robert H.] Univ Calif San Francisco, San Francisco Sch Med, Dept Physiol, San Francisco, CA 94143 USA.
   [Seal, Rebecca P.; Edwards, Robert H.] Univ Calif San Francisco, San Francisco Sch Med, Dept Neurol, San Francisco, CA 94143 USA.
   [Wang, Xidao; Basbaum, Allan I.] Univ Calif San Francisco, San Francisco Sch Med, Dept Anat, San Francisco, CA 94158 USA.
   [Wang, Xidao; Basbaum, Allan I.] Univ Calif San Francisco, San Francisco Sch Med, Dept Physiol, San Francisco, CA 94158 USA.
   [Guan, Yun; Raja, Srinivasa N.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
   [Woodbury, C. Jeffery] Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82071 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; Johns Hopkins University; University of Wyoming
RP Edwards, RH (corresponding author), Univ Calif San Francisco, San Francisco Sch Med, Dept Physiol, San Francisco, CA 94143 USA.
EM robert.edwards@ucsf.edu
FU Johns Hopkins Blaustein Pain Research Fund; NARSAD; NIH
NR 30
TC 348
Z9 433
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 DEC 3
PY 2009
VL 462
IS 7273
BP 651
EP 655
DI 10.1038/nature08505
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900041
PM 19915548
DA 2026-03-09
ER

PT J
AU Farrell, SA
   Webb, NA
   Barret, D
   Godet, O
   Rodrigues, JM
AF Farrell, Sean A.
   Webb, Natalie A.
   Barret, Didier
   Godet, Olivier
   Rodrigues, Joana M.
TI An intermediate-mass black hole of over 500 solar masses in the galaxy ESO 243-49
SO NATURE
LA English
DT Article
ID x-ray observations; accretion
AB Ultraluminous X-ray sources are extragalactic objects located outside the nucleus of the host galaxy with bolometric luminosities(1) exceeding 10(39) erg s(-1). These extreme luminosities-if the emission is isotropic and below the theoretical (Eddington) limit, where the radiation pressure is balanced by the gravitational pressure-imply the presence of an accreting black hole with a mass of similar to 10(2)-10(5) solar masses (M-circle dot). The existence of such intermediate-mass black holes is in dispute, and though many candidates have been proposed, none are widely accepted as definitive. Here we report the detection of a variable X-ray source with a maximum 0.2-10 keV luminosity of up to 1.1 x 10(42) erg s(-1) in the edge-on spiral galaxy ESO 243-49, with an implied conservative lower limit for the mass of the black hole of similar to 500M(circle dot).
C1 [Farrell, Sean A.; Webb, Natalie A.; Barret, Didier; Rodrigues, Joana M.] Univ Toulouse, UPS, CESR, F-31028 Toulouse 9, France.
   [Farrell, Sean A.; Webb, Natalie A.; Barret, Didier; Rodrigues, Joana M.] CNRS, UMR5187, F-31028 Toulouse, France.
   [Godet, Olivier] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
C3 Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); University of Leicester
RP Farrell, SA (corresponding author), Univ Leicester, Dept Phys & Astron, Univ Rd, Leicester LE1 7RH, Leics, England.
EM saf28@star.le.ac.uk; natalie.webb@cesr.fr
FU ESA Member States; NASA; UK Space Agency [ST/G008655/1] Funding Source: researchfish
NR 25
TC 446
Z9 474
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 JUL 2
PY 2009
VL 460
IS 7251
BP 73
EP 75
DI 10.1038/nature08083
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200031
PM 19571880
DA 2026-03-09
ER

PT J
AU Reich, D
   Thangaraj, K
   Patterson, N
   Price, AL
   Singh, L
AF Reich, David
   Thangaraj, Kumarasamy
   Patterson, Nick
   Price, Alkes L.
   Singh, Lalji
TI Reconstructing Indian population history
SO NATURE
LA English
DT Article
ID y-chromosome; genetic affinity; mitochondrial; inference; genotype; caste; haplotype; patterns; origins
AB India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' ( ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.
C1 [Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Reich, David; Patterson, Nick; Price, Alkes L.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Thangaraj, Kumarasamy; Singh, Lalji] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India.
   [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Council of Scientific & Industrial Research (CSIR) - India; CSIR - Centre for Cellular & Molecular Biology (CCMB); Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health
RP Reich, D (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM reich@genetics.med.harvard.edu; lalji@ccmb.res.in
FU NIH [HG004168]; Burroughs Wellcome Career Development Award; Council of Scientific and Industrial Research of the Government of India; UKIERI Major Award [RG-4772]; National Human Genome Research Institute [R01HG006399] Funding Source: NIH RePORTER
NR 52
TC 1219
Z9 1385
U1 2
U2 220
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 24
PY 2009
VL 461
IS 7263
BP 489
EP U50
DI 10.1038/nature08365
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497SP
UT WOS:000270082900032
PM 19779445
DA 2026-03-09
ER

PT J
AU Yun, MH
   Hiom, K
AF Yun, Maximina H.
   Hiom, Kevin
TI CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle
SO NATURE
LA English
DT Article
ID homologous recombination; end resection; mammalian-cells; damage; brca1; ctip; domains; protein; gene; line
AB The repair of DNA double-strand breaks (DSBs) is tightly regulated during the cell cycle. In G1 phase, the absence of a sister chromatid means that repair of DSBs occurs through non-homologous end-joining or microhomology-mediated end-joining (MMEJ)(1). These pathways often involve loss of DNA sequences at the break site and are therefore error-prone. In late S and G2 phases, even though DNA end-joining pathways remain functional(2), there is an increase in repair of DSBs by homologous recombination, which is mostly error-free(3,4). Consequently, the relative contribution of these different pathways to DSB repair in the cell cycle has a large influence on the maintenance of genetic integrity. It has remained unknown how DSBs are directed for repair by different, potentially competing, repair pathways. Here we identify a role for CtIP (also known as RBBP8) in this process in the avian B-cell line DT40. We establish that CtIP is required not only for repair of DSBs by homologous recombination in S/G2 phase but also for MMEJ in G1. The function of CtIP in homologous recombination, but not MMEJ, is dependent on the phosphorylation of serine residue 327 and recruitment of BRCA1. Cells expressing CtIP protein that cannot be phosphorylated at serine 327 are specifically defective in homologous recombination and have a decreased level of single-stranded DNA after DNA damage, whereas MMEJ remains unaffected. Our data support a model in which phosphorylation of serine 327 of CtIP as cells enter S phase and the recruitment of BRCA1 functions as a molecular switch to shift the balance of DSB repair from error-prone DNA end-joining to error-free homologous recombination.
C1 [Yun, Maximina H.; Hiom, Kevin] MRC, Mol Biol Lab, Div Prot & Nucle Acid Chem, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Hiom, K (corresponding author), MRC, Mol Biol Lab, Div Prot & Nucle Acid Chem, Hills Rd, Cambridge CB2 0QH, England.
EM hiom@mrc-lmb.cam.ac.uk
FU Medical Research Council [U.1051.03.005(78826), MC_U105184300] Funding Source: Medline; Medical Research Council [MC_U105184300] Funding Source: researchfish; MRC [MC_U105184300] Funding Source: UKRI
NR 21
TC 429
Z9 569
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 MAY 21
PY 2009
VL 459
IS 7245
BP 460
EP U184
DI 10.1038/nature07955
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 448DQ
UT WOS:000266243700053
PM 19357644
DA 2026-03-09
ER

PT J
AU King, EM
   Stellmach, S
   Noir, J
   Hansen, U
   Aurnou, JM
AF King, Eric M.
   Stellmach, Stephan
   Noir, Jerome
   Hansen, Ulrich
   Aurnou, Jonathan M.
TI Boundary layer control of rotating convection systems
SO NATURE
LA English
DT Article
ID rayleigh-benard convection; spherical-shells; prandtl number; thermal turbulence; heat-transfer; zonal flow; driven; dynamos; model; temperature
AB Turbulent rotating convection controls many observed features of stars and planets, such as magnetic fields, atmospheric jets and emitted heat flux patterns(1-6). It has long been argued that the influence of rotation on turbulent convection dynamics is governed by the ratio of the relevant global- scale forces: the Coriolis force and the buoyancy force(7-12). Here, however, we present results from laboratory and numerical experiments which exhibit transitions between rotationally dominated and non- rotating behaviour that are not determined by this global force balance. Instead, the transition is controlled by the relative thicknesses of the thermal ( nonrotating) and Ekman ( rotating) boundary layers. We formulate a predictive description of the transition between the two regimes on the basis of the competition between these two boundary layers. This transition scaling theory unifies the disparate results of an extensive array of previous experiments(8-15), and is broadly applicable to natural convection systems.
C1 [King, Eric M.; Noir, Jerome; Aurnou, Jonathan M.] Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
   [Stellmach, Stephan; Hansen, Ulrich] Univ Munster, Inst Geophys, D-48149 Munster, Germany.
C3 University of California System; University of California Los Angeles; University of Munster
RP King, EM (corresponding author), Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
EM eric.king@ucla.edu
FU US National Science Foundation Earth Sciences Division Geophysics Program; NASA Planetary Atmospheres Program; German Research Foundation; NASA Solar and Heliospheric Physics Program
NR 30
TC 190
Z9 216
U1 0
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 15
PY 2009
VL 457
IS 7227
BP 301
EP 304
DI 10.1038/nature07647
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 394IR
UT WOS:000262440900036
PM 19148097
DA 2026-03-09
ER

PT J
AU Hosseini, M
   Sparkes, BM
   Hétet, G
   Longdell, JJ
   Lam, PK
   Buchler, BC
AF Hosseini, Mahdi
   Sparkes, Ben M.
   Hetet, Gabriel
   Longdell, Jevon J.
   Lam, Ping Koy
   Buchler, Ben C.
TI Coherent optical pulse sequencer for quantum applications
SO NATURE
LA English
DT Article
ID electromagnetically induced transparency; communication; propagation; photons; storage
AB The bandwidth and versatility of optical devices have revolutionized information technology systems and communication networks. Precise and arbitrary control of anoptical field that preserves optical coherence is an important requisite for many proposed photonic technologies. For quantum information applications(1,2), a device that allows storage and on-demand retrieval of arbitrary quantum states of light would form an ideal quantum optical memory. Recently, significant progress has been made in implementing atomic quantum memories using electromagnetically induced transparency, photon echo spectroscopy, off-resonance Raman spectroscopy and other atom-light interaction processes. Single-photon(3,4) and bright-optical-field(5,6) storage with quantum states have both been successfully demonstrated. Here we present a coherent optical memory based on photon echoes induced through controlled reversible inhomogeneous broadening. Our scheme allows storage of multiple pulses of light within a chosen frequency bandwidth, and stored pulses can be recalled in arbitrary order with any chosen delay between each recalled pulse. Furthermore, pulses can be time-compressed, time-stretched or split into multiple smaller pulses and recalled in several pieces at chosen times. Although our experimental results are so far limited to classical light pulses, our technique should enable the construction of an optical random-access memory for time-bin quantum information, and have potential applications in quantum information processing.
C1 [Hosseini, Mahdi; Sparkes, Ben M.; Hetet, Gabriel; Longdell, Jevon J.; Lam, Ping Koy; Buchler, Ben C.] Australian Natl Univ, Dept Quantum Sci, ARC Ctr Excellence Quantum Atom Opt, Canberra, ACT 0200, Australia.
   [Longdell, Jevon J.] Univ Otago, Dept Phys, Dunedin 9016, New Zealand.
C3 Australian National University; University of Western Australia; University of Otago
RP Buchler, BC (corresponding author), Australian Natl Univ, Dept Quantum Sci, ARC Ctr Excellence Quantum Atom Opt, GPO Box 4, Canberra, ACT 0200, Australia.
EM ben.buchler@anu.edu.au
FU Australian Research Council
NR 25
TC 151
Z9 172
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 10
PY 2009
VL 461
IS 7261
BP 241
EP 245
DI 10.1038/nature08325
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 492KN
UT WOS:000269654600039
PM 19741705
DA 2026-03-09
ER

PT J
AU Nilewski, C
   Geisser, RW
   Carreira, EM
AF Nilewski, Christian
   Geisser, Roger W.
   Carreira, Erick M.
TI Total synthesis of a chlorosulpholipid cytotoxin associated with seafood poisoning
SO NATURE
LA English
DT Article
ID coupling-constants; adriatic mussels; chlorosulfolipids; toxins; stereochemistry; ochromonas; oxidation; shellfish; lipids
AB Each year, there are many cases of seafood poisoning in humans worldwide(1). Among the various toxins isolated that contribute to these poisonings(2,3), the chlorosulpholipids are particularly intriguing because of their structural and stereochemical complexity(4-12). The mechanism of biological activity remains unknown and, although chlorosulpholipids are associated with membranes in the organisms from which they are isolated, little is understood about their role within biological membranes. The lack of availability of the natural products has impaired more in-depth biochemical studies. So far, none of the chlorosulpholipids have been obtained from total synthesis, and efficient routes to their synthesis would be desirable for the preparation ofmaterial for pharmacological characterization and proper evaluation of the risk to human health. Despite the notable advances in the science of organic synthesis, reliable methods for stereoselective construction of polychlorinated acyclic substrates are lacking, although some preliminary investigations have appeared(13-15). Here we report the synthesis of a chlorosulpholipid cytotoxin, leading to confirmation of the proposed structure and the discovery of unanticipated reactivity of polychlorinated hydrocarbons. The concise synthetic approach should enable the preparation of material in sufficient quantities to facilitate biological studies.
C1 [Nilewski, Christian; Geisser, Roger W.; Carreira, Erick M.] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Carreira, EM (corresponding author), ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland.
EM carreira@org.chem.ethz.ch
FU Swiss National Science Foundation; ETH Zurich; F. Hoffmann-La Roche; Eli Lilly; Boehringer Ingelheim
NR 27
TC 134
Z9 155
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 JAN 29
PY 2009
VL 457
IS 7229
BP 573
EP U76
DI 10.1038/nature07734
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200039
PM 19177127
DA 2026-03-09
ER

PT J
AU Zhang, C
   Wu, B
   Beglopoulos, V
   Wines-Samuelson, M
   Zhang, DW
   Dragatsis, I
   Südhof, TC
   Shen, J
AF Zhang, Chen
   Wu, Bei
   Beglopoulos, Vassilios
   Wines-Samuelson, Mary
   Zhang, Dawei
   Dragatsis, Ioannis
   Suedhof, Thomas C.
   Shen, Jie
TI Presenilins are essential for regulating neurotransmitter release
SO NATURE
LA English
DT Article
ID alzheimers-disease; synaptic plasticity; amyloid-beta; transmitter release; cortical-neurons; transgenic mice; receptor; memory; inactivation; probability
AB Mutations in the presenilin genes are the main cause of familial Alzheimer's disease. Loss of presenilin activity and/or accumulation of amyloid-beta peptides have been proposed to mediate the pathogenesis of Alzheimer's disease by impairing synaptic function(1-5). However, the precise site and nature of the synaptic dysfunction remain unknown. Here we use a genetic approach to inactivate presenilins conditionally in either presynaptic (CA3) or postsynaptic (CA1) neurons of the hippocampal Schaeffer-collateral pathway. We show that long-term potentiation induced by theta-burst stimulation is decreased after presynaptic but not postsynaptic deletion of presenilins. Moreover, we found that presynaptic but not postsynaptic inactivation of presenilins alters short-term plasticity and synaptic facilitation. The probability of evoked glutamate release, measured with the open-channel NMDA (N-methyl-D-aspartate) receptor antagonist MK-801, is reduced by presynaptic inactivation of presenilins. Notably, depletion of endoplasmic reticulum Ca2+ stores by thapsigargin, or blockade of Ca2+ release from these stores by ryanodine receptor inhibitors, mimics and occludes the effects of presynaptic presenilin inactivation. Collectively, these results indicate a selective role for presenilins in the activity-dependent regulation of neurotransmitter release and long-term potentiation induction by modulation of intracellular Ca2+ release in presynaptic terminals, and further suggest that presynaptic dysfunction might be an early pathogenic event leading to dementia and neurodegeneration in Alzheimer's disease.
C1 [Zhang, Chen; Wu, Bei; Beglopoulos, Vassilios; Wines-Samuelson, Mary; Zhang, Dawei; Shen, Jie] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Program Neurosci, Boston, MA 02115 USA.
   [Zhang, Chen; Suedhof, Thomas C.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Mol & Cellular Physiol, Palo Alto, CA 94304 USA.
   [Dragatsis, Ioannis] Univ Tennessee, Hlth Sci Ctr, Dept Physiol, Memphis, TN 38163 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Stanford University; Howard Hughes Medical Institute; University of Tennessee System; University of Tennessee Health Science Center
RP Shen, J (corresponding author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Program Neurosci, Boston, MA 02115 USA.
EM jshen@rics.bwh.harvard.edu
FU National Institutes of Health [R01NS041783]
NR 34
TC 238
Z9 272
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 JUL 30
PY 2009
VL 460
IS 7255
BP 632
EP U100
DI 10.1038/nature08177
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300051
PM 19641596
DA 2026-03-09
ER

PT J
AU Tzeng, SR
   Kalodimos, CG
AF Tzeng, Shiou-Ru
   Kalodimos, Charalampos G.
TI Dynamic activation of an allosteric regulatory protein
SO NATURE
LA English
DT Article
ID camp receptor protein; cap-dna complex; escherichia-coli; rotational diffusion; chemical-exchange; nmr-spectroscopy; order parameters; binding protein; conformational entropy; angstrom resolution
AB Allosteric regulation is used as a very efficient mechanism to control protein activity in most biological processes, including signal transduction, metabolism, catalysis and gene regulation(1-6). Allosteric proteins can exist in several conformational states with distinct binding or enzymatic activity. Effectors are considered to function in a purely structural manner by selectively stabilizing a specific conformational state, thereby regulating protein activity. Here we show that allosteric proteins can be regulated predominantly by changes in their structural dynamics. We have used NMR spectroscopy and isothermal titration calorimetry to characterize cyclic AMP (cAMP) binding to the catabolite activator protein (CAP), a transcriptional activator that has been a prototype for understanding effector-mediated allosteric control of protein activity(7). cAMP switches CAP from the 'off' state (inactive), which binds DNA weakly and non-specifically, to the 'on' state (active), which binds DNA strongly and specifically. In contrast, cAMP binding to a single CAP mutant, CAP-S62F, fails to elicit the active conformation; yet, cAMP binding to CAP-S62F strongly activates the protein for DNA binding. NMR and thermodynamic analyses show that despite the fact that CAP-S62F-cAMP(2) adopts the inactive conformation, its strong binding to DNA is driven by a large conformational entropy originating in enhanced protein motions induced by DNA binding. The results provide strong evidence that changes in protein motions may activate allosteric proteins that are otherwise structurally inactive.
C1 [Tzeng, Shiou-Ru; Kalodimos, Charalampos G.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
   [Tzeng, Shiou-Ru; Kalodimos, Charalampos G.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
C3 Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick
RP Kalodimos, CG (corresponding author), Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
EM babis@rutgers.edu
FU National Science Foundation (NSF) [MCB618259]
NR 53
TC 326
Z9 384
U1 1
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 19
PY 2009
VL 462
IS 7271
BP 368
EP U139
DI 10.1038/nature08560
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300048
PM 19924217
DA 2026-03-09
ER

PT J
AU Abdo, AA
   Ackermann, M
   Ajello, M
   Asano, K
   Atwood, WB
   Axelsson, M
   Baldini, L
   Ballet, J
   Barbiellini, G
   Baring, MG
   Bastieri, D
   Bechtol, K
   Bellazzini, R
   Berenji, B
   Bhat, PN
   Bissaldi, E
   Bloom, ED
   Bonamente, E
   Bonnell, J
   Borgland, AW
   Bouvier, A
   Bregeon, J
   Brez, A
   Briggs, MS
   Brigida, M
   Bruel, P
   Burgess, JM
   Burnett, TH
   Caliandro, GA
   Cameron, RA
   Caraveo, PA
   Casandjian, JM
   Cecchi, C
   Çelik, Ö
   Chaplin, V
   Charles, E
   Cheung, CC
   Chiang, J
   Ciprini, S
   Claus, R
   Cohen-Tanugi, J
   Cominsky, LR
   Connaughton, V
   Conrad, J
   Cutini, S
   Dermer, CD
   de Angelis, A
   de Palma, F
   Digel, SW
   Dingus, BL
   Silva, EDE
   Drell, PS
   Dubois, R
   Dumora, D
   Farnier, C
   Favuzzi, C
   Fegan, SJ
   Finke, J
   Fishman, G
   Focke, WB
   Foschini, L
   Fukazawa, Y
   Funk, S
   Fusco, P
   Gargano, F
   Gasparrini, D
   Gehrels, N
   Germani, S
   Gibby, L
   Giebels, B
   Giglietto, N
   Giordano, F
   Glanzman, T
   Godfrey, G
   Granot, J
   Greiner, J
   Grenier, IA
   Grondin, MH
   Grove, JE
   Grupe, D
   Guillemot, L
   Guiriec, S
   Hanabata, Y
   Harding, AK
   Hayashida, M
   Hays, E
   Hoversten, EA
   Hughes, RE
   Jóhannesson, G
   Johnson, AS
   Johnson, RP
   Johnson, WN
   Kamae, T
   Katagiri, H
   Kataoka, J
   Kawai, N
   Kerr, M
   Kippen, RM
   Knödlseder, J
   Kocevski, D
   Kouveliotou, C
   Kuehn, F
   Kuss, M
   Lande, J
   Latronico, L
   Lemoine-Goumard, M
   Longo, F
   Loparco, F
   Lott, B
   Lovellette, MN
   Lubrano, P
   Madejski, GM
   Makeev, A
   Mazziotta, MN
   McBreen, S
   McEnery, JE
   McGlynn, S
   Mészáros, P
   Meurer, C
   Michelson, PF
   Mitthumsiri, W
   Mizuno, T
   Moiseev, AA
   Monte, C
   Monzani, ME
   Moretti, E
   Morselli, A
   Moskalenko, IV
   Murgia, S
   Nakamori, T
   Nolan, PL
   Norris, JP
   Nuss, E
   Ohno, M
   Ohsugi, T
   Omodei, N
   Orlando, E
   Ormes, JF
   Ozaki, M
   Paciesas, WS
   Paneque, D
   Panetta, JH
   Parent, D
   Pelassa, V
   Pepe, M
   Pesce-Rollins, M
   Petrosian, V
   Piron, F
   Porter, TA
   Preece, R
   Rainò, S
   Ramirez-Ruiz, E
   Rando, R
   Razzano, M
   Razzaque, S
   Reimer, A
   Reimer, O
   Reposeur, T
   Ritz, S
   Rochester, LS
   Rodriguez, AY
   Roth, M
   Ryde, F
   Sadrozinski, HFW
   Sanchez, D
   Sander, A
   Parkinson, PMS
   Scargle, JD
   Schalk, TL
   Sgrò, C
   Siskind, EJ
   Smith, DA
   Smith, PD
   Spandre, G
   Spinelli, P
   Stamatikos, M
   Stecker, FW
   Strickman, MS
   Suson, DJ
   Tajima, H
   Takahashi, H
   Takahashi, T
   Tanaka, T
   Thayer, JB
   Thayer, JG
   Thompson, DJ
   Tibaldo, L
   Toma, K
   Torres, DF
   Tosti, G
   Troja, E
   Uchiyama, Y
   Uehara, T
   Usher, TL
   van der Horst, AJ
   Vasileiou, V
   Vilchez, N
   Vitale, V
   von Kienlin, A
   Waite, AP
   Wang, P
   Wilson-Hodge, C
   Winer, BL
   Wood, KS
   Wu, XF
   Yamazaki, R
   Ylinen, T
   Ziegler, M
AF Abdo, A. A.
   Ackermann, M.
   Ajello, M.
   Asano, K.
   Atwood, W. B.
   Axelsson, M.
   Baldini, L.
   Ballet, J.
   Barbiellini, G.
   Baring, M. G.
   Bastieri, D.
   Bechtol, K.
   Bellazzini, R.
   Berenji, B.
   Bhat, P. N.
   Bissaldi, E.
   Bloom, E. D.
   Bonamente, E.
   Bonnell, J.
   Borgland, A. W.
   Bouvier, A.
   Bregeon, J.
   Brez, A.
   Briggs, M. S.
   Brigida, M.
   Bruel, P.
   Burgess, J. M.
   Burnett, T. H.
   Caliandro, G. A.
   Cameron, R. A.
   Caraveo, P. A.
   Casandjian, J. M.
   Cecchi, C.
   Celik, Oe
   Chaplin, V.
   Charles, E.
   Cheung, C. C.
   Chiang, J.
   Ciprini, S.
   Claus, R.
   Cohen-Tanugi, J.
   Cominsky, L. R.
   Connaughton, V.
   Conrad, J.
   Cutini, S.
   Dermer, C. D.
   de Angelis, A.
   de Palma, F.
   Digel, S. W.
   Dingus, B. L.
   do Couto e Silva, E.
   Drell, P. S.
   Dubois, R.
   Dumora, D.
   Farnier, C.
   Favuzzi, C.
   Fegan, S. J.
   Finke, J.
   Fishman, G.
   Focke, W. B.
   Foschini, L.
   Fukazawa, Y.
   Funk, S.
   Fusco, P.
   Gargano, F.
   Gasparrini, D.
   Gehrels, N.
   Germani, S.
   Gibby, L.
   Giebels, B.
   Giglietto, N.
   Giordano, F.
   Glanzman, T.
   Godfrey, G.
   Granot, J.
   Greiner, J.
   Grenier, I. A.
   Grondin, M. -H.
   Grove, J. E.
   Grupe, D.
   Guillemot, L.
   Guiriec, S.
   Hanabata, Y.
   Harding, A. K.
   Hayashida, M.
   Hays, E.
   Hoversten, E. A.
   Hughes, R. E.
   Johannesson, G.
   Johnson, A. S.
   Johnson, R. P.
   Johnson, W. N.
   Kamae, T.
   Katagiri, H.
   Kataoka, J.
   Kawai, N.
   Kerr, M.
   Kippen, R. M.
   Knoedlseder, J.
   Kocevski, D.
   Kouveliotou, C.
   Kuehn, F.
   Kuss, M.
   Lande, J.
   Latronico, L.
   Lemoine-Goumard, M.
   Longo, F.
   Loparco, F.
   Lott, B.
   Lovellette, M. N.
   Lubrano, P.
   Madejski, G. M.
   Makeev, A.
   Mazziotta, M. N.
   McBreen, S.
   McEnery, J. E.
   McGlynn, S.
   Meszaros, P.
   Meurer, C.
   Michelson, P. F.
   Mitthumsiri, W.
   Mizuno, T.
   Moiseev, A. A.
   Monte, C.
   Monzani, M. E.
   Moretti, E.
   Morselli, A.
   Moskalenko, I. V.
   Murgia, S.
   Nakamori, T.
   Nolan, P. L.
   Norris, J. P.
   Nuss, E.
   Ohno, M.
   Ohsugi, T.
   Omodei, N.
   Orlando, E.
   Ormes, J. F.
   Ozaki, M.
   Paciesas, W. S.
   Paneque, D.
   Panetta, J. H.
   Parent, D.
   Pelassa, V.
   Pepe, M.
   Pesce-Rollins, M.
   Petrosian, V.
   Piron, F.
   Porter, T. A.
   Preece, R.
   Raino, S.
   Ramirez-Ruiz, E.
   Rando, R.
   Razzano, M.
   Razzaque, S.
   Reimer, A.
   Reimer, O.
   Reposeur, T.
   Ritz, S.
   Rochester, L. S.
   Rodriguez, A. Y.
   Roth, M.
   Ryde, F.
   Sadrozinski, H. F. -W.
   Sanchez, D.
   Sander, A.
   Parkinson, P. M. Saz
   Scargle, J. D.
   Schalk, T. L.
   Sgro, C.
   Siskind, E. J.
   Smith, D. A.
   Smith, P. D.
   Spandre, G.
   Spinelli, P.
   Stamatikos, M.
   Stecker, F. W.
   Strickman, M. S.
   Suson, D. J.
   Tajima, H.
   Takahashi, H.
   Takahashi, T.
   Tanaka, T.
   Thayer, J. B.
   Thayer, J. G.
   Thompson, D. J.
   Tibaldo, L.
   Toma, K.
   Torres, D. F.
   Tosti, G.
   Troja, E.
   Uchiyama, Y.
   Uehara, T.
   Usher, T. L.
   van der Horst, A. J.
   Vasileiou, V.
   Vilchez, N.
   Vitale, V.
   von Kienlin, A.
   Waite, A. P.
   Wang, P.
   Wilson-Hodge, C.
   Winer, B. L.
   Wood, K. S.
   Wu, X. F.
   Yamazaki, R.
   Ylinen, T.
   Ziegler, M.
TI A limit on the variation of the speed of light arising from quantum gravity effects
SO NATURE
LA English
DT Article
ID gamma-ray bursts; high-energy; violation; lorentz; tests; foam
AB A cornerstone of Einstein's special relativity is Lorentz invariance-the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, l(Planck) approximate to 1.62 x 10(-33) cm or E-Planck = M(Planck)c(2) approximate to 1.22 x 10(19) GeV), at which quantum effects are expected to strongly affect the nature of space-time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy(1-7). Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in gamma-ray burst (GRB) light-curves(2). Here we report the detection of emission up to similar to 31GeV from the distant and short GRB090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of l(Planck)/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories(3,6,7) in which the quantum nature of space-time on a very small scale linearly alters the speed of light.
C1 [Granot, J.] Univ Hertfordshire, Ctr Astrophys Res, Coll Lane, Hatfield AL10 9AB, Herts, England.
   [Abdo, A. A.; Cheung, C. C.; Dermer, C. D.; Finke, J.; Grove, J. E.; Johnson, W. N.; Lovellette, M. N.; Makeev, A.; Razzaque, S.; Strickman, M. S.; Wood, K. S.] USN, Res Lab, Div Space Sci, Washington, DC 20375 USA.
   [Abdo, A. A.; Cheung, C. C.; Finke, J.; Razzaque, S.] Natl Acad Sci, Natl Res Council Res Associate, Washington, DC 20001 USA.
   [Ackermann, M.; Ajello, M.; Bechtol, K.; Berenji, B.; Bloom, E. D.; Borgland, A. W.; Bouvier, A.; Cameron, R. A.; Charles, E.; Chiang, J.; Claus, R.; Digel, S. W.; do Couto e Silva, E.; Drell, P. S.; Dubois, R.; Focke, W. B.; Funk, S.; Glanzman, T.; Godfrey, G.; Hayashida, M.; Johannesson, G.; Johnson, A. S.; Kamae, T.; Kocevski, D.; Lande, J.; Madejski, G. M.; Michelson, P. F.; Mitthumsiri, W.; Monzani, M. E.; Moskalenko, I. V.; Murgia, S.; Nolan, P. L.; Paneque, D.; Panetta, J. H.; Petrosian, V.; Reimer, A.; Reimer, O.; Rochester, L. S.; Tajima, H.; Tanaka, T.; Thayer, J. B.; Thayer, J. G.; Uchiyama, Y.; Usher, T. L.; Waite, A. P.; Wang, P.] Stanford Univ, Dept Phys, WW Hansen Expt Phys Lab, Kavli Inst Particle Astrophys & Cosmol, Stanford, CA 94305 USA.
   [Ackermann, M.; Ajello, M.; Bechtol, K.; Berenji, B.; Bloom, E. D.; Borgland, A. W.; Bouvier, A.; Cameron, R. A.; Charles, E.; Chiang, J.; Claus, R.; Digel, S. W.; do Couto e Silva, E.; Drell, P. S.; Dubois, R.; Focke, W. B.; Funk, S.; Glanzman, T.; Godfrey, G.; Hayashida, M.; Johannesson, G.; Johnson, A. S.; Kamae, T.; Kocevski, D.; Lande, J.; Madejski, G. M.; Michelson, P. F.; Mitthumsiri, W.; Monzani, M. E.; Moskalenko, I. V.; Murgia, S.; Nolan, P. L.; Paneque, D.; Panetta, J. H.; Petrosian, V.; Reimer, A.; Reimer, O.; Rochester, L. S.; Tajima, H.; Tanaka, T.; Thayer, J. B.; Thayer, J. G.; Uchiyama, Y.; Usher, T. L.; Waite, A. P.; Wang, P.] Stanford Univ, SLAC Natl Accelerator Lab, Stanford, CA 94305 USA.
   [Asano, K.; Kataoka, J.; Kawai, N.; Nakamori, T.; Troja, E.] Tokyo Inst Technol, Dept Phys, Meguro, Tokyo 1528551, Japan.
   [Asano, K.] Tokyo Inst Technol, Interact Res Ctr Sci, Meguro, Tokyo 1528551, Japan.
   [Atwood, W. B.; Johnson, R. P.; Porter, T. A.; Ritz, S.; Sadrozinski, H. F. -W.; Parkinson, P. M. Saz; Schalk, T. L.; Ziegler, M.] Univ Calif Santa Cruz, Santa Cruz Inst Particle Phys, Dept Phys, Santa Cruz, CA 95064 USA.
   [Atwood, W. B.; Johnson, R. P.; Porter, T. A.; Ritz, S.; Sadrozinski, H. F. -W.; Parkinson, P. M. Saz; Schalk, T. L.; Ziegler, M.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Ramirez-Ruiz, E.] Univ Calif Santa Cruz, Univ Calif Observ, Lick Observ, Santa Cruz, CA 95064 USA.
   [Axelsson, M.] Stockholm Univ, Dept Astron, SE-10691 Stockholm, Sweden.
   [Axelsson, M.; Conrad, J.; McGlynn, S.; Meurer, C.; Ryde, F.; Ylinen, T.] Royal Inst Technol KTH, Oskar Klein Ctr Cosmoparticle Phys, SE-10691 Stockholm, Sweden.
   [Conrad, J.; McGlynn, S.; Meurer, C.; Ryde, F.; Ylinen, T.] Royal Inst Technol KTH, Dept Phys, SE-10691 Stockholm, Sweden.
   [Baldini, L.; Bellazzini, R.; Bregeon, J.; Brez, A.; Kuss, M.; Latronico, L.; Omodei, N.; Pesce-Rollins, M.; Razzano, M.; Sgro, C.; Spandre, G.] Ist Nazl Fis Nucl, Sez Pisa, I-56127 Pisa, Italy.
   [Ballet, J.; Casandjian, J. M.; Grenier, I. A.; Tibaldo, L.] Univ Paris Diderot, CEA Saclay, Lab AIM,CEA IRFU,CNRS, Serv Astrophys, F-91191 Gif Sur Yvette, France.
   [Barbiellini, G.; Longo, F.; Moretti, E.] Ist Nazl Fis Nucl, Sez Trieste, I-34127 Trieste, Italy.
   [Barbiellini, G.; Longo, F.; Moretti, E.] Univ Trieste, Dipartmento Fis, I-34127 Trieste, Italy.
   [Baring, M. G.] Rice Univ, Dept Phys & Astron, Houston, TX 77251 USA.
   [Bastieri, D.; Rando, R.; Tibaldo, L.] Ist Nazl Fis Nucl, Sez Padova, I-35131 Padua, Italy.
   [Bastieri, D.; Rando, R.; Tibaldo, L.] Univ Padua, Dipartimento Fis G Galilei, I-35131 Padua, Italy.
   [Bhat, P. N.; Briggs, M. S.; Burgess, J. M.; Chaplin, V.; Connaughton, V.; Guiriec, S.; Paciesas, W. S.; Preece, R.] Univ Alabama, CSPAR, Huntsville, AL 35899 USA.
   [Bissaldi, E.; Greiner, J.; McBreen, S.; Orlando, E.; von Kienlin, A.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Bonamente, E.; Cecchi, C.; Ciprini, S.; Germani, S.; Lubrano, P.; Pepe, M.; Tosti, G.] Ist Nazl Fis Nucl, Sez Perugia, I-06123 Perugia, Italy.
   [Bonamente, E.; Cecchi, C.; Ciprini, S.; Germani, S.; Lubrano, P.; Pepe, M.; Tosti, G.] Univ Perugia, Dipartimento Fis, I-06123 Perugia, Italy.
   [Bonnell, J.; Celik, Oe; Cheung, C. C.; Gehrels, N.; Harding, A. K.; Hays, E.; McEnery, J. E.; Stamatikos, M.; Stecker, F. W.; Thompson, D. J.; Troja, E.; Vasileiou, V.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Bonnell, J.; Gehrels, N.; Moiseev, A. A.; Spinelli, P.] Univ Maryland, College Pk, MD 20742 USA.
   [Brigida, M.; Caliandro, G. A.; de Palma, F.; Favuzzi, C.; Fusco, P.; Giglietto, N.; Giordano, F.; Loparco, F.; Monte, C.; Raino, S.] Univ & Politecn Bari, Dipartimento Fis M Merlin, I-70126 Bari, Italy.
   [Brigida, M.; Caliandro, G. A.; de Palma, F.; Favuzzi, C.; Fusco, P.; Gargano, F.; Giglietto, N.; Giordano, F.; Loparco, F.; Mazziotta, M. N.; Monte, C.; Raino, S.; Spinelli, P.] Ist Nazl Fis Nucl, Sez Bari, I-70126 Bari, Italy.
   [Bruel, P.; Fegan, S. J.; Giebels, B.; Sanchez, D.] Ecole Polytech, CNRS, IN2P3, Lab Leprince Ringuet, F-91128 Palaiseau, France.
   [Burnett, T. H.; Kerr, M.; Roth, M.] Univ Washington, Dept Phys, Seattle, WA 98195 USA.
   [Caraveo, P. A.] INAF Ist Astrofis Spaziale & Fis Cosm, I-20133 Milan, Italy.
   [Celik, Oe; Vasileiou, V.] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA.
   [Cohen-Tanugi, J.; Farnier, C.; Nuss, E.; Pelassa, V.; Piron, F.] Univ Montpellier 2, CNRS, IN2P3, Lab Phys Theor & Astroparticules, F-34095 Montpellier 5, France.
   [Cominsky, L. R.] Sonoma State Univ, Dept Phys & Astron, Rohnert Pk, CA 94928 USA.
   [Cutini, S.; Gasparrini, D.] ASI, Sci Data Ctr, I-00044 Frascati, Roma, Italy.
   [de Angelis, A.] Univ Udine, Dipartimento Fis, I-33100 Udine, Italy.
   [de Angelis, A.] Ist Nazl Fis Nucl, Sez Trieste, Grp Coll Udine, I-33100 Udine, Italy.
   [Dingus, B. L.; Kippen, R. M.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Dumora, D.; Grondin, M. -H.; Lemoine-Goumard, M.; Lott, B.; Parent, D.; Reposeur, T.; Smith, D. A.] Univ Bordeaux, F-33175 Gradignan, France.
   [Dumora, D.; Grondin, M. -H.; Lemoine-Goumard, M.; Lott, B.; Parent, D.; Reposeur, T.; Smith, D. A.] CEN Bordeaux Gradignan, CNRS, UMR 5797, IN2P3, F-33175 Gradignan, France.
   [Fishman, G.; Kouveliotou, C.; van der Horst, A. J.; Wilson-Hodge, C.] NASA, George C Marshall Space Flight Ctr, Space Sci Off, VP62, Huntsville, AL 35812 USA.
   [Foschini, L.] INAF Osservatorio Astron Brera, I-23807 Merate, Italy.
   [Fukazawa, Y.; Hanabata, Y.; Katagiri, H.; Mizuno, T.; Ohsugi, T.; Takahashi, H.; Uehara, T.; Yamazaki, R.] Hiroshima Univ, Dept Phys Sci, Hiroshima 7398526, Japan.
   [Gibby, L.] Jacobs Technol, Huntsville, AL 35806 USA.
   [Grupe, D.; Hoversten, E. A.; Meszaros, P.; Toma, K.; Wu, X. F.] Penn State Univ, Dept Astron & Astrophys, University Pk, PA 16802 USA.
   [Guillemot, L.] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Hughes, R. E.; Kuehn, F.; Sander, A.; Smith, P. D.; Stamatikos, M.; Winer, B. L.] Ohio State Univ, Dept Phys, Ctr Cosmol & Astroparticle Phys, Columbus, OH 43210 USA.
   [Kataoka, J.] Waseda Univ, Shinjuku Ku, Tokyo 1698050, Japan.
   [Kawai, N.] RIKEN, Inst Phys & Chem Res, Cosm Radiat Lab, Wako, Saitama 3510198, Japan.
   [Knoedlseder, J.; Vilchez, N.] UPS, CNRS, Ctr Etud Spatiale Rayonnements, F-31028 Toulouse 4, France.
   [Makeev, A.] George Mason Univ, Fairfax, VA 22030 USA.
   [McBreen, S.] Natl Univ Ireland Univ Coll Dublin, Dublin 4, Ireland.
   [Morselli, A.; Vitale, V.] Ist Nazl Fis Nucl, Sez Roma Tor Vergata, I-00133 Rome, Italy.
   [Vitale, V.] Univ Roma Tor Vergata, Dipartimento Fis, I-00133 Rome, Italy.
   [Norris, J. P.; Ormes, J. F.] Univ Denver, Dept Phys & Astron, Denver, CO 80208 USA.
   [Ohno, M.; Ozaki, M.; Takahashi, T.; Uchiyama, Y.] JAXA, Inst Space & Astronaut Sci, Sagamihara, Kanagawa 2298510, Japan.
   [Reimer, A.; Reimer, O.] Leopold Franzens Univ Innsbruck, Inst Astro & Teilchenphys, A-6020 Innsbruck, Austria.
   [Reimer, A.; Reimer, O.] Leopold Franzens Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
   [Rodriguez, A. Y.; Torres, D. F.] CSIC, IEEC, Inst Ciencies Espai, Barcelona 08193, Spain.
   [Scargle, J. D.] NASA, Ames Res Ctr, Div Space Sci, Moffett Field, CA 94035 USA.
   [Siskind, E. J.] NYCB Real Time Comp Inc, Lattingtown, NY 11560 USA.
   [Suson, D. J.] Purdue Univ Calumet, Dept Chem & Phys, Hammond, IN 46323 USA.
   [Torres, D. F.] ICREA, Barcelona 08193, Spain.
   [Wu, X. F.] Chinese Acad Sci, Joint Ctr Particle Nucl Phys & Cosmol, Nanjing 210008, Peoples R China.
   [Wu, X. F.] Chinese Acad Sci, Purple Mt Observ, Nanjing 210008, Peoples R China.
   [Ylinen, T.] Univ Kalmar, Sch Pure & Appl Nat Sci, SE-39182 Kalmar, Sweden.
C3 University of Hertfordshire; United States Department of Defense; United States Navy; United States Naval Research Laboratory; NRL Chesapeake; National Academies of Sciences, Engineering & Medicine; Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Institute of Science Tokyo; Tokyo Institute of Technology; Institute of Science Tokyo; Tokyo Institute of Technology; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Stockholm University; Royal Institute of Technology; Oskar Klein Centre; Royal Institute of Technology; Istituto Nazionale di Fisica Nucleare (INFN); CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite Paris Saclay; Istituto Nazionale di Fisica Nucleare (INFN); University of Trieste; Rice University; Istituto Nazionale di Fisica Nucleare (INFN); University of Padua; University of Alabama System; University of Alabama Huntsville; Max Planck Society; Istituto Nazionale di Fisica Nucleare (INFN); University of Perugia; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland College Park; Politecnico di Bari; Istituto Nazionale di Fisica Nucleare (INFN); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Institut Polytechnique de Paris; Ecole Polytechnique; University of Washington; University of Washington Seattle; Istituto Nazionale Astrofisica (INAF); University System of Maryland; University of Maryland Baltimore County; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); California State University System; Sonoma State University; Agenzia Spaziale Italiana (ASI); University of Udine; Istituto Nazionale di Fisica Nucleare (INFN); United States Department of Energy (DOE); Los Alamos National Laboratory; Universite de Bordeaux; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); National Aeronautics & Space Administration (NASA); NASA Marshall Space Flight Center; Istituto Nazionale Astrofisica (INAF); Hiroshima University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Max Planck Society; University System of Ohio; Ohio State University; Waseda University; RIKEN; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); George Mason University; University College Dublin; Istituto Nazionale di Fisica Nucleare (INFN); University of Rome Tor Vergata; University of Denver; Japan Aerospace Exploration Agency (JAXA); Institute of Space & Astronautical Science (ISAS); University of Innsbruck; University of Innsbruck; Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); University of Barcelona; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Nycb Real-Time Computing Inc.; Purdue University System; Purdue University Northwest; ICREA; Chinese Academy of Sciences; Purple Mountain Observatory, CAS; Chinese Academy of Sciences; Nanjing Institute of Astronomical Optics & Technology, NAOC, CAS; Linnaeus University; University of Kalmar
RP Granot, J (corresponding author), Univ Hertfordshire, Ctr Astrophys Res, Coll Lane, Hatfield AL10 9AB, Herts, England.
EM j.granot@herts.ac.uk; sylvain.guiriec@nasa.gov; ohno@astro.isas.jaxa.jp; pelassa@lpta.in2p3.fr
FU Royal Society Wolfson Research Merit Award; NASA United States; DRL Germany; Royal Swedish Academy of Sciences; K. A. Wallenberg Foundation; Canon Foundation in Europe; STFC [ST/G002630/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/G002630/1] Funding Source: researchfish; ICREA Funding Source: Custom
NR 25
TC 482
Z9 509
U1 1
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 NOV 19
PY 2009
VL 462
IS 7271
BP 331
EP 334
DI 10.1038/nature08574
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300039
PM 19865083
DA 2026-03-09
ER

PT J
AU Oganov, AR
   Chen, JH
   Gatti, C
   Ma, YZ
   Ma, YM
   Glass, CW
   Liu, ZX
   Yu, T
   Kurakevych, OO
   Solozhenko, VL
AF Oganov, Artem R.
   Chen, Jiuhua
   Gatti, Carlo
   Ma, Yanzhang
   Ma, Yanming
   Glass, Colin W.
   Liu, Zhenxian
   Yu, Tony
   Kurakevych, Oleksandr O.
   Solozhenko, Vladimir L.
TI Ionic high-pressure form of elemental boron
SO NATURE
LA English
DT Article
ID crystal-structure; stability; density
AB Boron is an element of fascinating chemical complexity. Controversies have shrouded this element since its discovery was announced in 1808: the new 'element' turned out to be a compound containing less than 60 - 70% of boron, and it was not until 1909 that 99% pure boron was obtained(1). And although we now know of at least 16 polymorphs(2), the stable phase of boron is not yet experimentally established even at ambient conditions(3). Boron's complexities arise from frustration: situated between metals and insulators in the periodic table, boron has only three valence electrons, which would favour metallicity, but they are sufficiently localized that insulating states emerge. However, this subtle balance between metallic and insulating states is easily shifted by pressure, temperature and impurities. Here we report the results of high- pressure experiments and ab initio evolutionary crystal structure predictions(4,5) that explore the structural stability of boron under pressure and, strikingly, reveal a partially ionic high-pressure boron phase. This new phase is stable between 19 and 89 GPa, can be quenched to ambient conditions, and has a hitherto unknown structure ( space group Pnnm, 28 atoms in the unit cell) consisting of icosahedral B(12) clusters and B(2) pairs in a NaCl- type arrangement. We find that the ionicity of the phase affects its electronic bandgap, infrared adsorption and dielectric constants, and that it arises from the different electronic properties of the B(2) pairs and B(12) clusters and the resultant charge transfer between them.
C1 [Oganov, Artem R.; Chen, Jiuhua] SUNY Stony Brook, Dept Geosci, Stony Brook, NY 11794 USA.
   [Oganov, Artem R.; Ma, Yanming; Glass, Colin W.] ETH, Crystallog Lab, Dept Mat, CH-8093 Zurich, Switzerland.
   [Oganov, Artem R.] Moscow MV Lomonosov State Univ, Dept Geol, Moscow 119992, Russia.
   [Chen, Jiuhua; Yu, Tony] Florida Int Univ, Ctr Study Matter & Extreme Condit, Miami, FL 33199 USA.
   [Chen, Jiuhua; Yu, Tony] Florida Int Univ, Dept Mech & Mat Engn, Miami, FL 33199 USA.
   [Chen, Jiuhua] SUNY Stony Brook, Inst Mineral Phys, Stony Brook, NY 11794 USA.
   [Chen, Jiuhua] SUNY Stony Brook, Dept Geosci, Stony Brook, NY 11794 USA.
   [Gatti, Carlo] CNR, ISTM, I-20133 Milan, Italy.
   [Ma, Yanzhang] Texas Univ Technol, Dept Mech Engn, Lubbock, TX 79409 USA.
   [Ma, Yanming] Jilin Univ, Natl Lab Superhard Mat, Changchun 130012, Peoples R China.
   [Liu, Zhenxian] Carnegie Inst Washington, Geophys Lab, Washington, DC 20015 USA.
   [Kurakevych, Oleksandr O.; Solozhenko, Vladimir L.] Univ Paris 13, LPMTM, CNRS, F-93430 Villetaneuse, France.
C3 State University of New York (SUNY) System; Stony Brook University; Swiss Federal Institutes of Technology Domain; ETH Zurich; Lomonosov Moscow State University; State University System of Florida; Florida International University; State University System of Florida; Florida International University; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; Consiglio Nazionale delle Ricerche (CNR); Istituto di Scienze e Tecnologie Molecolari (ISTM-CNR); Jilin University; Carnegie Institution for Science; Universite Paris 13; Centre National de la Recherche Scientifique (CNRS)
RP Oganov, AR (corresponding author), SUNY Stony Brook, Dept Geosci, Stony Brook, NY 11794 USA.
EM artem.oganov@sunysb.edu
FU Swiss National Science Foundation [200021-111847/1]; ETH Research Equipment Programme; NSF [EAR0711321, DMR-0619215]; DOE [DE-FG02-07ER46461, DE-FC03-03NA00144]; Agence Nationale de la Recherche [ANR-05-BLAN-0141)]; US Department of Energy [DE-AC02-98CH10886]; COMPRES [EAR 06-49658]; Agence Nationale de la Recherche (ANR) [ANR-05-BLAN-0141] Funding Source: Agence Nationale de la Recherche (ANR); U.S. Department of Energy (DOE) [DE-FG02-07ER46461] Funding Source: U.S. Department of Energy (DOE)
NR 27
TC 796
Z9 875
U1 6
U2 353
PU 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 12
PY 2009
VL 457
IS 7231
BP 863
EP 867
DI 10.1038/nature07736
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700041
PM 19182772
DA 2026-03-09
ER

PT J
AU Marshall, NM
   Garner, DK
   Wilson, TD
   Gao, YG
   Robinson, H
   Nilges, MJ
   Lu, Y
AF Marshall, Nicholas M.
   Garner, Dewain K.
   Wilson, Tiffany D.
   Gao, Yi-Gui
   Robinson, Howard
   Nilges, Mark J.
   Lu, Yi
TI Rationally tuning the reduction potential of a single cupredoxin beyond the natural range
SO NATURE
LA English
DT Article
ID blue copper center; pi-pi-interaction; active-site; crystal-structure; axial methionine; azurin; rusticyanin; proteins; mutagenesis; graphite
AB Redox processes are at the heart of numerous functions in chemistry and biology, from long-range electron transfer in photosynthesis and respiration to catalysis in industrial and fuel cell research. These functions are accomplished in nature by only a limited number of redox-active agents. A long-standing issue in these fields is how redox potentials are fine-tuned over a broad range with little change to the redox-active site or electron-transfer properties. Resolving this issue will not only advance our fundamental understanding of the roles of long-range, non-covalent interactions in redox processes, but also allow for design of redox-active proteins having tailor-made redox potentials for applications such as artificial photosynthetic centres(1,2) or fuel cell catalysts(3) for energy conversion. Here we show that two important secondary coordination sphere interactions, hydrophobicity and hydrogen-bonding, are capable of tuning the reduction potential of the cupredoxin azurin over a 700 mV range, surpassing the highest and lowest reduction potentials reported for any mononuclear cupredoxin, without perturbing the metal binding site beyond what is typical for the cupredoxin family of proteins. We also demonstrate that the effects of individual structural features are additive and that redox potential tuning of azurin is now predictable across the full range of cupredoxin potentials.
C1 [Marshall, Nicholas M.; Garner, Dewain K.; Wilson, Tiffany D.; Gao, Yi-Gui; Nilges, Mark J.; Lu, Yi] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Robinson, Howard] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; United States Department of Energy (DOE); Brookhaven National Laboratory
RP Lu, Y (corresponding author), Univ Illinois, Dept Chem, 1209 W Calif St, Urbana, IL 61801 USA.
EM yi-lu@illinois.edu
FU US National Science Foundation [CHE 05-52008]; National Institutes of Health [5 T32 GM070421]; National Institute of General Medical Sciences
NR 32
TC 260
Z9 309
U1 5
U2 144
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 5
PY 2009
VL 462
IS 7269
BP 113
EP U127
DI 10.1038/nature08551
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 514TT
UT WOS:000271419200043
PM 19890331
DA 2026-03-09
ER

PT J
AU Lancrin, C
   Sroczynska, P
   Stephenson, C
   Allen, T
   Kouskoff, V
   Lacaud, G
AF Lancrin, Christophe
   Sroczynska, Patrycja
   Stephenson, Catherine
   Allen, Terry
   Kouskoff, Valerie
   Lacaud, Georges
TI The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage
SO NATURE
LA English
DT Article
ID embryonic stem-cell; definitive hematopoiesis; mouse embryo; yolk-sac; common precursor; tyrosine kinase; in-vitro; expression; hemangioblast; commitment
AB It has been proposed that during embryonic development haematopoietic cells arise from a mesodermal progenitor with both endothelial and haematopoietic potential called the haemangioblast(1,2). A conflicting theory instead associates the first haematopoietic cells with a phenotypically differentiated endothelial cell that has haematopoietic potential ( that is, a haemogenic endothelium) (3-5). Support for the haemangioblast concept was initially provided by the identification during mouse embryonic stem cell differentiation of a clonal precursor, the blast colony- forming cell (BL-CFC), which gives rise to blast colonies with both endothelial and haematopoietic components(6,7). Although recent studies have now provided evidence for the presence of this bipotential precursor in vivo(8,9), the precise mechanism for generation of haematopoietic cells from the haemangioblast still remains completely unknown. Here we demonstrate that the haemangioblast generates haematopoietic cells through the formation of a haemogenic endothelium intermediate, providing the first direct link between these two precursor populations. The cell population containing the haemogenic endothelium is transiently generated during BL-CFC development. This cell population is also present in gastrulating mouse embryos and generates haematopoietic cells on further culture. At the molecular level, we demonstrate that the transcription factor Tal1 ( also known as Scl; ref. 10) is indispensable for the establishment of this haemogenic endothelium population whereas the core binding factor Runx1 ( also known as AML1; ref. 11) is critical for generation of definitive haematopoietic cells from haemogenic endothelium. Together our results merge the two a priori conflicting theories on the origin of haematopoietic development into a single linear developmental process.
C1 [Lancrin, Christophe; Sroczynska, Patrycja; Stephenson, Catherine; Lacaud, Georges] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Stem Cell Biol Grp, Manchester M20 4BX, Lancs, England.
   [Allen, Terry] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Struct Cell Biol Grp, Manchester M20 4BX, Lancs, England.
   [Kouskoff, Valerie] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Stem Cell Haematopoiesis Grp, Manchester M20 4BX, Lancs, England.
C3 Paterson Institute for Cancer Research; University of Manchester; University of Manchester; Paterson Institute for Cancer Research; Cancer Research UK; Paterson Institute for Cancer Research; University of Manchester
RP Lacaud, G (corresponding author), Univ Manchester, Paterson Inst Canc Res, Canc Res UK Stem Cell Biol Grp, Wilmslow Rd, Manchester M20 4BX, Lancs, England.
EM glacaud@picr.man.ac.uk
FU Cancer Research UK
NR 30
TC 507
Z9 627
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 12
PY 2009
VL 457
IS 7231
BP 892
EP 895
DI 10.1038/nature07679
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700047
PM 19182774
DA 2026-03-09
ER

PT J
AU Brinster, S
   Lamberet, G
   Staels, B
   Trieu-Cuot, P
   Gruss, A
   Poyart, C
AF Brinster, Sophie
   Lamberet, Gilles
   Staels, Bart
   Trieu-Cuot, Patrick
   Gruss, Alexandra
   Poyart, Claire
TI Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens
SO NATURE
LA English
DT Article
ID group-b streptococcus; biosynthesis; virulence; bacteria; disease; mutans; growth; contributes; inhibitor; discovery
AB Antimicrobial drugs targeting the reportedly essential type II fatty acid synthesis (FASII) pathway(1-5) have been recently acclaimed for their efficacy against infections caused by multiresistant Gram-positive bacteria(6-8). Our findings show that the strategy for antibiotic development based on FASII pathway targets is fundamentally flawed by the fact that exogenous fatty acids fully bypass inhibition of this pathway in both in vitro and in vivo conditions. We demonstrate that major Gram-positive pathogens-such as streptococci, pneumococci, enterococci and staphylococci-overcome drug-induced FASII pathway inhibition when supplied with exogenous fatty acids, and human serum proves to be a highly effective source of fatty acids. For opportunist pathogen Streptococcus agalactiae, growth in serum leads to an overall decrease of FASII gene expression. No antibiotic inhibitor could have a stronger effect than the inactivation of the target gene, so we challenged the role of FASII using deletion mutants. Our results unequivocally show that the FASII target enzymes are dispensable in vivo during S. agalactiae infection. The results of this study largely compromise the use of FASII-based antimicrobials for treating sepsis caused by Gram-positive pathogens.
C1 [Brinster, Sophie; Poyart, Claire] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France.
   [Brinster, Sophie; Poyart, Claire] INSERM, U567, Paris, France.
   [Lamberet, Gilles; Gruss, Alexandra] INRA, Unite Bacteries Lact & Pathogenes Opportunistes, UR888, F-78350 Jouy En Josas, France.
   [Staels, Bart] Univ Lille 2, Inst Pasteur Lille, UMR545, Lille, France.
   [Trieu-Cuot, Patrick; Poyart, Claire] Inst Pasteur, CNRS, URA 2172, Unite Biol Bacteries Pathogenes Gram Posi, Paris, France.
   [Poyart, Claire] Hop Cochin, Ctr Natl Reference Streptocoques, AP HP, F-75674 Paris, France.
C3 Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; INRAE; Universite de Lille; Pasteur Network; Institut Pasteur Lille; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Cochin - APHP
RP Poyart, C (corresponding author), Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France.
EM Alexandra.gruss@jouy.inra.fr; claire.poyart@cch.aphp.fr
FU French Agence Nationale de la Recherche; INSERM; INRA; Universite Paris Descartes; Institut Pasteur; ANR StrepRespire Project
NR 31
TC 270
Z9 324
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 MAR 5
PY 2009
VL 458
IS 7234
BP 83
EP U5
DI 10.1038/nature07772
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 414AJ
UT WOS:000263836000037
PM 19262672
DA 2026-03-09
ER

PT J
AU Leaver, M
   Domínguez-Cuevas, P
   Coxhead, JM
   Daniel, RA
   Errington, J
AF Leaver, M.
   Dominguez-Cuevas, P.
   Coxhead, J. M.
   Daniel, R. A.
   Errington, J.
TI Life without a wall or division machine in Bacillus subtilis
SO NATURE
LA English
DT Article
ID stable l-form; cell-wall; sequence; growth; mreb; induction; magnesium; variants; proteins
AB The cell wall is an essential structure for virtually all bacteria, forming a tough outer shell that protects the cell from damage and osmotic lysis. It is the target of our best antibiotics. L- form strains are wall- deficient derivatives of common bacteria that have been studied for decades. However, they are difficult to generate and typically require growth for many generations on osmotically protective media with antibiotics or enzymes that kill walled forms. Despite their potential importance for understanding antibiotic resistance and pathogenesis, little is known about their basic cell biology or their means of propagation. We have developed a controllable system for generating L- forms in the highly tractable model bacterium Bacillus subtilis. Here, using genome sequencing, we identify a single point mutation that predisposes cells to grow without a wall. We show that propagation of L- forms does not require the normal FtsZ- dependent division machine but occurs by a remarkable extrusion- resolution mechanism. This novel form of propagation provides insights into how early forms of cellular life may have proliferated.
C1 [Leaver, M.; Dominguez-Cuevas, P.; Daniel, R. A.; Errington, J.] Univ Newcastle, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Coxhead, J. M.] Univ Newcastle, Int Ctr Life, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
C3 Newcastle University - UK; Newcastle University - UK
RP Errington, J (corresponding author), Univ Newcastle, Inst Cell & Mol Biosci, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM jeff.errington@newcastle.ac.uk
FU UK Biotechnology and Biological Sciences Research Council; EMBO Long-Term Fellowship
NR 35
TC 231
Z9 263
U1 1
U2 81
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 12
PY 2009
VL 457
IS 7231
BP 849
EP 853
DI 10.1038/nature07742
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700038
PM 19212404
DA 2026-03-09
ER

PT J
AU Liu, ZF
   Gandhi, CS
   Rees, DC
AF Liu, Zhenfeng
   Gandhi, Chris S.
   Rees, Douglas C.
TI Structure of a tetrameric MscL in an expanded intermediate state
SO NATURE
LA English
DT Article
ID mechanosensitive ion-channel; escherichia-coli; mycobacterium-tuberculosis; gating mechanism; program; models; maps
AB The ability of cells to sense and respond to mechanical force underlies diverse processes such as touch and hearing in animals, gravitropism in plants, and bacterial osmoregulation(1,2). In bacteria, mechanosensation is mediated by the mechanosensitive channels of large (MscL), small (MscS), potassium-dependent (MscK) and mini (MscM) conductances. These channels act as 'emergency relief valves' protecting bacteria from lysis upon acute osmotic down-shock(3). Among them, MscL has been intensively studied since the original identification and characterization 15 years ago(4). MscL is reversibly and directly gated by changes in membrane tension. In the open state, MscL forms a non-selective 3 nS conductance channel which gates at tensions close to the lytic limit of the bacterial membrane. An earlier crystal structure at 3.5 angstrom resolution of a pentameric MscL from Mycobacterium tuberculosis represents a closed-state or non-conducting conformation(5,6). MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative non-conductive expanded state and at least three sub-conducting states(7). Although our understanding of the closed(5,6) and open(8-10) states of MscL has been increasing, little is known about the structures of the intermediate states despite their importance in elucidating the complete gating process of MscL. Here we present the crystal structure of a carboxy-terminal truncation mutant (Delta 95-120) of MscL from Staphylococcus aureus (SaMscL(C Delta 26)) at 3.8 angstrom resolution. Notably, SaMscL(C Delta 26) forms a tetrameric channel with both transmembrane helices tilted away from the membrane normal at angles close to that inferred for the open state(9), probably corresponding to a non-conductive but partially expanded intermediate state.
C1 [Liu, Zhenfeng; Gandhi, Chris S.; Rees, Douglas C.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Liu, Zhenfeng; Rees, Douglas C.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
C3 California Institute of Technology; California Institute of Technology; Howard Hughes Medical Institute
RP Rees, DC (corresponding author), CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
EM dcrees@caltech.edu
FU Howard Hughes Medical Institute; National Institutes of Health [GM084211]; Beckman Foundation
NR 46
TC 104
Z9 129
U1 1
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 120
EP U132
DI 10.1038/nature08277
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800042
PM 19701184
DA 2026-03-09
ER

PT J
AU Kumar, G
   Tang, HX
   Schroers, J
AF Kumar, Golden
   Tang, Hong X.
   Schroers, Jan
TI Nanomoulding with amorphous metals
SO NATURE
LA English
DT Article
ID imprint lithography; mechanical-behavior; nanoimprint lithography; glass; transition; alloys; ni
AB Nanoimprinting promises low- cost fabrication of micro- and nano-devices by embossing features from a hard mould onto thermoplastic materials, typically polymers with low glass transition temperature(1). The success and proliferation of such methods critically rely on the manufacturing of robust and durable master moulds(2). Silicon- based moulds are brittle(3) and have limited longevity(4). Metal moulds are stronger than semiconductors, but patterning of metals on the nano-metre scale is limited by their finite grain size. Amorphous metals ( metallic glasses) exhibit superior mechanical properties and are intrinsically free from grain size limitations. Here we demonstrate direct nanopatterning of metallic glasses by hot embossing, generating feature sizes as small as 13 nm. After subsequently crystallizing the as-formed metallic glass mould, we show that another amorphous sample of the same alloy can be formed on the crystallized mould. In addition, metallic glass replicas can also be used as moulds for polymers or other metallic glasses with lower softening temperatures. Using this 'spawning' process, we can massively replicate patterned surfaces through direct moulding without using conventional lithography. We anticipate that our findings will catalyse the development of micro- and nanoscale metallic glass applications that capitalize on the outstanding mechanical properties, microstructural homogeneity and isotropy, and ease of thermoplastic forming exhibited by these materials(5-7).
C1 [Kumar, Golden; Tang, Hong X.; Schroers, Jan] Yale Univ, New Haven, CT 06511 USA.
C3 Yale University
RP Schroers, J (corresponding author), Yale Univ, New Haven, CT 06511 USA.
EM jan.schroers@yale.edu
FU US National Science Foundation; Directorate For Engineering; Div Of Civil, Mechanical, & Manufact Inn [0826445] Funding Source: National Science Foundation
NR 31
TC 652
Z9 747
U1 4
U2 620
PU NATURE PUBLISHING 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 12
PY 2009
VL 457
IS 7231
BP 868
EP 872
DI 10.1038/nature07718
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 406AF
UT WOS:000263266700042
PM 19212407
DA 2026-03-09
ER

PT J
AU Donohoe, ME
   Silva, SS
   Pinter, SF
   Xu, N
   Lee, JT
AF Donohoe, Mary E.
   Silva, Susana S.
   Pinter, Stefan F.
   Xu, Na
   Lee, Jeannie T.
TI The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting
SO NATURE
LA English
DT Article
ID embryonic stem-cells; dosage compensation; inactivation; transcription; choice; tsix; identification; initiation; activator; protein
AB Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors(1,2). During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) in which one female X chromosome is silenced to achieve gene dosage parity between the sexes(3-5). Somatic XCI is regulated by homologous X-chromosome pairing(6,7) and counting(8-10), and by the random choice of future active and inactive X chromosomes. XCI and cell differentiation are tightly coupled(11), as blocking one process compromises the other(8,12) and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X chromosome reactivation(2). Recent evidence suggests coupling of Xist expression to pluripotency factors occurs(13), but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1)(14) lies at the top of the XCI hierarchy, and regulates XCI by triggering X-chromosome pairing and counting. Oct4 directly binds Tsix and Xite, two regulatory noncoding RNA genes of the X-inactivation centre(15,16), and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein-protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in the inactivation of both X chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-chromosome reprogramming.
C1 [Donohoe, Mary E.; Silva, Susana S.; Pinter, Stefan F.; Xu, Na; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
   [Donohoe, Mary E.; Silva, Susana S.; Pinter, Stefan F.; Xu, Na; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Donohoe, Mary E.; Silva, Susana S.; Pinter, Stefan F.; Xu, Na; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
   [Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Lee, JT (corresponding author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM lee@molbio.mgh.harvard.edu
FU National Institutes of Health [GM58839]; National Institute of General Medical Sciences [R01GM058839, R37GM058839] Funding Source: NIH RePORTER
NR 30
TC 230
Z9 274
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 2
PY 2009
VL 460
IS 7251
BP 128
EP U147
DI 10.1038/nature08098
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200043
PM 19536159
DA 2026-03-09
ER

PT J
AU Tamura, Y
   Kohno, K
   Nakanishi, K
   Hatsukade, B
   Iono, D
   Wilson, GW
   Yun, MS
   Takata, T
   Matsuda, Y
   Tosaki, T
   Ezawa, H
   Perera, TA
   Scott, KS
   Austermann, JE
   Hughes, DH
   Aretxaga, I
   Chung, A
   Oshima, T
   Yamaguchi, N
   Tanaka, K
   Kawabe, R
AF Tamura, Yoichi
   Kohno, Kotaro
   Nakanishi, Kouichiro
   Hatsukade, Bunyo
   Iono, Daisuke
   Wilson, Grant W.
   Yun, Min S.
   Takata, Tadafumi
   Matsuda, Yuichi
   Tosaki, Tomoka
   Ezawa, Hajime
   Perera, Thushara A.
   Scott, Kimberly S.
   Austermann, Jason E.
   Hughes, David H.
   Aretxaga, Itziar
   Chung, Aeree
   Oshima, Tai
   Yamaguchi, Nobuyuki
   Tanaka, Kunihiko
   Kawabe, Ryohei
TI Spatial correlation between submillimetre and Lyman-α galaxies in the SSA 22 protocluster
SO NATURE
LA English
DT Article
ID star-formation; high-redshift; deep field; emitting galaxy; number counts; population; z=3.1
AB Lyman-alpha emitters are thought to be young, low-mass galaxies with ages of similar to 10(8) yr (refs 1, 2). An overdensity of them in one region of the sky (the SSA 22 field) traces out a filamentary structure in the early Universe at a redshift of z approximate to 3.1 (equivalent to 15 per cent of the age of the Universe) and is believed to mark a forming protocluster(3,4). Galaxies that are bright at (sub) millimetre wavelengths are undergoing violent episodes of star formation(5-8), and there is evidence that they are preferentially associated with high-redshift radio galaxies(9), so the question of whether they are also associated with the most significant large-scale structure growing at high redshift (as outlined by Lyman-alpha emitters) naturally arises. Here we report an imaging survey of 1,100-mu m emission in the SSA 22 region. We find an enhancement of submillimetre galaxies near the core of the protocluster, and a large-scale correlation between the submillimetre galaxies and the low-mass Lyman-alpha emitters, suggesting synchronous formation of the two very different types of star-forming galaxy within the same structure at high redshift. These results are in general agreement with our understanding of the formation of cosmic structure.
C1 [Tamura, Yoichi] Univ Tokyo, Dept Astron, Bunkyo Ku, Tokyo 1130033, Japan.
   [Tamura, Yoichi; Nakanishi, Kouichiro; Takata, Tadafumi; Matsuda, Yuichi] Natl Astron Observ Japan, Tokyo 1818588, Japan.
   [Kohno, Kotaro; Hatsukade, Bunyo; Iono, Daisuke] Univ Tokyo, Inst Astron, Tokyo 1810015, Japan.
   [Nakanishi, Kouichiro; Iono, Daisuke; Tosaki, Tomoka; Ezawa, Hajime; Oshima, Tai; Yamaguchi, Nobuyuki; Tanaka, Kunihiko; Kawabe, Ryohei] Natl Astron Observ Japan, Nobeyama Radio Observ, Minamisa Ku, Minamimaki, Nagano 3841305, Japan.
   [Wilson, Grant W.; Yun, Min S.; Perera, Thushara A.; Scott, Kimberly S.; Austermann, Jason E.; Chung, Aeree] Univ Massachusetts, Dept Astron, Amherst, MA 01003 USA.
   [Hughes, David H.; Aretxaga, Itziar] Inst Nacl Astrofis Opt & Electr, Puebla 72000, Mexico.
C3 University of Tokyo; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); University of Tokyo; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); University of Massachusetts System; University of Massachusetts Amherst; Instituto Nacional de Astrofisica, Optica y Electronica
RP Tamura, Y (corresponding author), Univ Tokyo, Dept Astron, Bunkyo Ku, Tokyo 1130033, Japan.
EM yoichi.tamura@nao.ac.jp
FU Grants-in-Aid for Scientific Research [20001003] Funding Source: KAKEN
NR 29
TC 100
Z9 105
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 MAY 7
PY 2009
VL 459
IS 7243
BP 61
EP 63
DI 10.1038/nature07947
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 441WN
UT WOS:000265801300028
PM 19424150
DA 2026-03-09
ER

PT J
AU Weinberg, Z
   Perreault, J
   Meyer, MM
   Breaker, RR
AF Weinberg, Zasha
   Perreault, Jonathan
   Meyer, Michelle M.
   Breaker, Ronald R.
TI Exceptional structured noncoding RNAs revealed by bacterial metagenome analysis
SO NATURE
LA English
DT Article
ID comparative genomics; secondary structure; sequence-analysis; 6s rna; identification; regulator; database; riboswitches; expression; diversity
AB Estimates of the total number of bacterial species(1-3) indicate that existing DNA sequence databases carry only a tiny fraction of the total amount of DNA sequence space represented by this division of life. Indeed, environmental DNA samples have been shown to encode many previously unknown classes of proteins(4) and RNAs5. Bioinformatics searches(6-10) of genomic DNA from bacteria commonly identify new noncoding RNAs (ncRNAs)(10-12) such as riboswitches(13,14). In rare instances, RNAs that exhibit more extensive sequence and structural conservation across a wide range of bacteria are encountered(15,16). Given that large structured RNAs are known to carry out complex biochemical functions such as protein synthesis and RNA processing reactions, identifying more RNAs of great size and intricate structure is likely to reveal additional biochemical functions that can be achieved by RNA. We applied an updated computational pipeline(17) to discover ncRNAs that rival the known large ribozymes in size and structural complexity or that are among the most abundant RNAs in bacteria that encode them. These RNAs would have been difficult or impossible to detect without examining environmental DNA sequences, indicating that numerous RNAs with extraordinary size, structural complexity, or other exceptional characteristics remain to be discovered in unexplored sequence space.
C1 [Weinberg, Zasha; Breaker, Ronald R.] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Weinberg, Zasha; Perreault, Jonathan; Meyer, Michelle M.; Breaker, Ronald R.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Breaker, Ronald R.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
C3 Howard Hughes Medical Institute; Yale University; Yale University; Yale University
RP Breaker, RR (corresponding author), Yale Univ, Howard Hughes Med Inst, Box 208103, New Haven, CT 06520 USA.
EM ronald.breaker@yale.edu
FU NIH [RR19895-02]; Canadian Institutes of Health Research and National Institutes of Health; Howard Hughes Medical Institute Investigator
NR 62
TC 92
Z9 120
U1 0
U2 31
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 3
PY 2009
VL 462
IS 7273
BP 656
EP U131
DI 10.1038/nature08586
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 526HH
UT WOS:000272277900042
PM 19956260
DA 2026-03-09
ER

PT J
AU Laughlin, G
   Deming, D
   Langton, J
   Kasen, D
   Vogt, S
   Butler, RP
   Rivera, E
   Meschiari, S
AF Laughlin, Gregory
   Deming, Drake
   Langton, Jonathan
   Kasen, Daniel
   Vogt, Steve
   Butler, Robert Paul
   Rivera, Eugenio
   Meschiari, Stefano
TI Rapid heating of the atmosphere of an extrasolar planet
SO NATURE
LA English
DT Article
ID spitzer-space-telescope; hd 189733b; evolution; emission
AB Near- infrared observations of more than a dozen 'hot-Jupiter' extrasolar planets have now been reported(1-5). These planets display a wide diversity of properties, yet all are believed to have had their spin periods tidally spin- synchronized with their orbital periods, resulting in permanent star- facing hemispheres and surface flow patterns that are most likely in equilibrium. Planets in significantly eccentric orbits can enable direct measurements of global heating that are largely independent of the details of the hydrodynamic flow(6). Here we report 8-mu m photometric observations of the planet HD 80606b during a 30- hour interval bracketing the periastron passage of its extremely eccentric 111.4- day orbit. As the planet received its strongest irradiation ( 828 times larger than the flux received at apastron) its maximum 8- mm brightness temperature increased from 800 K to 1,500K over a six- hour period. We also detected a secondary eclipse for the planet, which implies an orbital inclination of i approximate to 90 degrees, fixes the planetary mass at four times the mass of Jupiter, and constrains the planet's tidal luminosity. Our measurement of the global heating rate indicates that the radiative time constant at the planet's 8- mu m photosphere is similar to 4.5 h, in comparison with 3 - 5 days in Earth's stratosphere(7).
C1 [Laughlin, Gregory; Langton, Jonathan; Kasen, Daniel; Vogt, Steve; Rivera, Eugenio; Meschiari, Stefano] Univ Calif Santa Cruz, Univ Calif Observ, Lick Observ, Santa Cruz, CA 95064 USA.
   [Deming, Drake] NASA, Goddard Space Flight Ctr, Planetary Syst Branch, Greenbelt, MD 20771 USA.
   [Butler, Robert Paul] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
C3 University of California System; University of California Santa Cruz; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Carnegie Institution for Science
RP Laughlin, G (corresponding author), Univ Calif Santa Cruz, Univ Calif Observ, Lick Observ, Santa Cruz, CA 95064 USA.
EM laughlin@ucolick.org
FU NASA
NR 25
TC 100
Z9 115
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 JAN 29
PY 2009
VL 457
IS 7229
BP 562
EP 564
DI 10.1038/nature07649
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400FA
UT WOS:000262852200036
PM 19177124
DA 2026-03-09
ER

PT J
AU Wang, Y
   Forsyth, DW
   Savage, B
AF Wang, Yun
   Forsyth, Donald W.
   Savage, Brian
TI Convective upwelling in the mantle beneath the Gulf of California
SO NATURE
LA English
DT Article
ID east pacific rise; midocean ridge basalts; sensitivity kernels; spreading centers; melt generation; ocean ridges; low-velocity; attenuation; segmentation; anisotropy
AB In the past six million years, Baja California has rifted obliquely apart from North America, opening up the Gulf of California(1). Between transform faults, seafloor spreading and rifting is well established in several basins. Other than hotspot-dominated Iceland, the Gulf of California is the only part of the world's seafloor-spreading system that has been surrounded by enough seismometers to provide horizontal resolution of upper-mantle structure at a scale of 100 kilometres over a distance great enough to include several spreading segments. Such resolution is needed to address the long-standing debate about the relative importance of dynamic and passive upwelling in the shallow mantle beneath spreading centres. Here we use Rayleigh-wave tomography to image the shear velocity in the upper 200 kilometres or so of the mantle. Low shear velocities similar to those beneath the East Pacific Rise oceanic spreading centre underlie the entire length of the Gulf, but there are three concentrated locations of anomalously low velocities spaced about 250 kilometres apart. These anomalies are 40 to 90 kilometres beneath the surface, at which depths petrological studies indicate that extensive melting of passively upwelling mantle should begin(2,3). We interpret these seismic velocity anomalies as indicating that partial melting triggers dynamic upwelling driven by either the buoyancy of retained melt or by the reduced density of depleted mantle.
C1 [Wang, Yun; Forsyth, Donald W.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Savage, Brian] Univ Rhode Isl, Dept Geosci, Kingston, RI 02881 USA.
C3 Brown University; University of Rhode Island
RP Wang, Y (corresponding author), Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
EM yun_wang@brown.edu
FU National Science Foundation
NR 28
TC 93
Z9 105
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 26
PY 2009
VL 462
IS 7272
BP 499
EP U192
DI 10.1038/nature08552
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 524LG
UT WOS:000272144200042
PM 19940924
DA 2026-03-09
ER

PT J
AU Aathavan, K
   Politzer, AT
   Kaplan, A
   Moffitt, JR
   Chemla, YR
   Grimes, S
   Jardine, PJ
   Anderson, DL
   Bustamante, C
AF Aathavan, K.
   Politzer, Adam T.
   Kaplan, Ariel
   Moffitt, Jeffrey R.
   Chemla, Yann R.
   Grimes, Shelley
   Jardine, Paul J.
   Anderson, Dwight L.
   Bustamante, Carlos
TI Substrate interactions and promiscuity in a viral DNA packaging motor
SO NATURE
LA English
DT Article
ID atp hydrolysis; portal motor; translocation; helicase; mechanism; backbone; tracking
AB The ASCE (additional strand, conserved E) superfamily of proteins consists of structurally similar ATPases associated with diverse cellular activities involving metabolism and transport of proteins and nucleic acids in all forms of life(1). A subset of these enzymes consists of multimeric ringed pumps responsible for DNA transport in processes including genome packaging in adenoviruses, herpesviruses, poxviruses and tailed bacteriophages(2). Although their mechanism of mechanochemical conversion is beginning to be understood(3), little is known about how these motors engage their nucleic acid substrates. Questions remain as to whether the motors contact a single DNA element, such as a phosphate or a base, or whether contacts are distributed over several parts of the DNA. Furthermore, the role of these contacts in the mechanochemical cycle is unknown. Here we use the genome packaging motor of the Bacillus subtilis bacteriophage phi 29 (ref. 4) to address these questions. The full mechanochemical cycle of the motor, in which the ATPase is a pentameric-ring(5) of gene product 16 (gp16), involves two phases-an ATP-loading dwell followed by a translocation burst of four 2.5-base-pair (bp) steps(6) triggered by hydrolysis product release(7). By challenging the motor with a variety of modified DNA substrates, we show that during the dwell phase important contacts are made with adjacent phosphates every 10-bp on the 5'-3' strand in the direction of packaging. As well as providing stable, long-lived contacts, these phosphate interactions also regulate the chemical cycle. In contrast, during the burst phase, we find that DNA translocation is driven against large forces by extensive contacts, some of which are not specific to the chemical moieties of DNA. Such promiscuous, nonspecific contacts may reflect common translocase-substrate interactions for both the nucleic acid and protein translocases of the ASCE superfamily(1).
C1 [Aathavan, K.; Politzer, Adam T.; Bustamante, Carlos] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
   [Aathavan, K.; Politzer, Adam T.; Kaplan, Ariel; Moffitt, Jeffrey R.; Chemla, Yann R.; Bustamante, Carlos] Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA.
   [Kaplan, Ariel; Bustamante, Carlos] Univ Calif Berkeley, Inst QB3, Berkeley, CA 94720 USA.
   [Kaplan, Ariel; Moffitt, Jeffrey R.; Chemla, Yann R.; Bustamante, Carlos] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Grimes, Shelley; Jardine, Paul J.; Anderson, Dwight L.] Univ Minnesota, Dept Diagnost & Biol Sci, Minneapolis, MN 55455 USA.
   [Grimes, Shelley; Jardine, Paul J.; Anderson, Dwight L.] Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA.
   [Anderson, Dwight L.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Dept Mol & Cell Biol, 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; University of California System; University of California Berkeley; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; 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 Bustamante, C (corresponding author), Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
EM carlos@alice.berkeley.edu
FU Burroughs Wellcome Fund; NIH Molecular Biophysics Training Grant; Human Frontier Science Program Cross-Disciplinary Fellowship; NSF Graduate Research Fellowship; Burroughs Wellcome Fund Career Award; National Institutes of Health ( NIH) [GM-071552, DE-003606, GM-059604]
NR 30
TC 96
Z9 112
U1 1
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 1
PY 2009
VL 461
IS 7264
BP 669
EP U118
DI 10.1038/nature08443
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500LH
UT WOS:000270302600044
PM 19794496
DA 2026-03-09
ER

PT J
AU Gertsman, I
   Gan, L
   Guttman, M
   Lee, K
   Speir, JA
   Duda, RL
   Hendrix, RW
   Komives, EA
   Johnson, JE
AF Gertsman, Ilya
   Gan, Lu
   Guttman, Miklos
   Lee, Kelly
   Speir, Jeffrey A.
   Duda, Robert L.
   Hendrix, Roger W.
   Komives, Elizabeth A.
   Johnson, John E.
TI An unexpected twist in viral capsid maturation
SO NATURE
LA English
DT Article
ID x-ray crystallography; virus maturation; common ancestry; coat protein; bacteriophages; transition; dynamics; domain; model; dna
AB Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging(1). The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 angstrom resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 angstrom (ref. 2). A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and beta-sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol(-1) of energy(3). We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process probably present in many dsDNA bacteriophage and possibly viruses such as herpesvirus, which share the HK97 subunit fold(4).
C1 [Gertsman, Ilya; Gan, Lu; Lee, Kelly; Speir, Jeffrey A.; Johnson, John E.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Gertsman, Ilya; Guttman, Miklos; Komives, Elizabeth A.; Johnson, John E.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92037 USA.
   [Duda, Robert L.; Hendrix, Roger W.] Univ Pittsburgh, Pittsburgh Bacteriophage Inst, Pittsburgh, PA 15260 USA.
   [Duda, Robert L.; Hendrix, Roger W.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
C3 Scripps Research Institute; University of California System; University of California San Diego; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Johnson, JE (corresponding author), Scripps Res Inst, Dept Mol Biol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM jackj@scripps.edu
FU NIH [RO1 AI40101, RO1 GM47795]; NIH Training Grant [GM08326]
NR 31
TC 110
Z9 141
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 2
PY 2009
VL 458
IS 7238
BP 646
EP U114
DI 10.1038/nature07686
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200044
PM 19204733
DA 2026-03-09
ER

PT J
AU Audet, P
   Bostock, MG
   Christensen, NI
   Peacock, SM
AF Audet, Pascal
   Bostock, Michael G.
   Christensen, Nikolas I.
   Peacock, Simon M.
TI Seismic evidence for overpressured subducted oceanic crust and megathrust fault sealing
SO NATURE
LA English
DT Article
ID zone; serpentinization; permeability; pressure; tremors; moho
AB Water and hydrous minerals play a key part in geodynamic processes at subduction zones(1-3) by weakening the plate boundary, aiding slip and permitting subduction - and indeed plate tectonics - to occur(4). The seismological signature of water within the forearc mantle wedge is evident in anomalies with low seismic shear velocity marking serpentinization(5-7). However, seismological observations bearing on the presence of water within the subducting plate itself are less well documented. Here we use converted teleseismic waves to obtain observations of anomalously high Poisson's ratios within the subducted oceanic crust from the Cascadia continental margin to its intersection with forearc mantle. On the basis of pressure, temperature and compositional considerations, the elevated Poisson's ratios indicate that water is pervasively present in fluid format pore pressures near lithostatic values. Combined with observations of a strong negative velocity contrast at the top of the oceanic crust, our results imply that the megathrust is a low- permeability boundary. The transition from a low- to high- permeability plate interface down dip into the mantle wedge is explained by hydrofracturing of the seal by volume changes across the interface caused by the onset of crustal eclogitization and mantle serpentinization. These results may have important implications for our understanding of seismogenesis, subduction zone structure and the mechanism of episodic tremor and slip.
C1 [Audet, Pascal; Bostock, Michael G.; Christensen, Nikolas I.; Peacock, Simon M.] Univ British Columbia, Dept Earth & Ocean Sci, Vancouver, BC V6T 1Z4, Canada.
   [Christensen, Nikolas I.] Univ Wisconsin, Dept Geol & Geophys, Madison, WI 53706 USA.
C3 University of British Columbia; University of Wisconsin System; University of Wisconsin Madison
RP Audet, P (corresponding author), Univ Calif Berkeley, Seismol Lab, 215 McCone Hall, Berkeley, CA 94720 USA.
EM paudet@berkeley.edu
NR 30
TC 495
Z9 573
U1 1
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 1
PY 2009
VL 457
IS 7225
BP 76
EP 78
DI 10.1038/nature07650
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900033
PM 19122639
DA 2026-03-09
ER

PT J
AU Acciari, VA
   Aliu, E
   Arlen, T
   Aune, T
   Bautista, M
   Beilicke, M
   Benbow, W
   Boltuch, D
   Bradbury, SM
   Buckley, JH
   Bugaev, V
   Byrum, K
   Cannon, A
   Celik, O
   Cesarini, A
   Chow, YC
   Ciupik, L
   Cogan, P
   Colin, P
   Cui, W
   Dickherber, R
   Duke, C
   Fegan, SJ
   Finley, JP
   Finnegan, G
   Fortin, P
   Fortson, L
   Furniss, A
   Galante, N
   Gall, D
   Gibbs, K
   Gillanders, GH
   Godambe, S
   Grube, J
   Guenette, R
   Gyuk, G
   Hanna, D
   Holder, J
   Horan, D
   Hui, CM
   Humensky, TB
   Imran, A
   Kaaret, P
   Karlsson, N
   Kertzman, M
   Kieda, D
   Kildea, J
   Konopelko, A
   Krawczynski, H
   Krennrich, F
   Lang, MJ
   LeBohec, S
   Maier, G
   McArthur, S
   McCann, A
   McCutcheon, M
   Millis, J
   Moriarty, P
   Mukherjee, R
   Nagai, T
   Ong, RA
   Otte, AN
   Pandel, D
   Perkins, JS
   Pizlo, F
   Pohl, M
   Quinn, J
   Ragan, K
   Reyes, LC
   Reynolds, PT
   Roache, E
   Rose, HJ
   Schroedter, M
   Sembroski, GH
   Smith, AW
   Steele, D
   Swordy, SP
   Theiling, M
   Thibadeau, S
   Varlotta, A
   Vassiliev, VV
   Vincent, S
   Wagner, RG
   Wakely, SP
   Ward, JE
   Weekes, TC
   Weinstein, A
   Weisgarber, T
   Williams, DA
   Wissel, S
   Wood, M
   Zitzer, B
AF Acciari, V. A.
   Aliu, E.
   Arlen, T.
   Aune, T.
   Bautista, M.
   Beilicke, M.
   Benbow, W.
   Boltuch, D.
   Bradbury, S. M.
   Buckley, J. H.
   Bugaev, V.
   Byrum, K.
   Cannon, A.
   Celik, O.
   Cesarini, A.
   Chow, Y. C.
   Ciupik, L.
   Cogan, P.
   Colin, P.
   Cui, W.
   Dickherber, R.
   Duke, C.
   Fegan, S. J.
   Finley, J. P.
   Finnegan, G.
   Fortin, P.
   Fortson, L.
   Furniss, A.
   Galante, N.
   Gall, D.
   Gibbs, K.
   Gillanders, G. H.
   Godambe, S.
   Grube, J.
   Guenette, R.
   Gyuk, G.
   Hanna, D.
   Holder, J.
   Horan, D.
   Hui, C. M.
   Humensky, T. B.
   Imran, A.
   Kaaret, P.
   Karlsson, N.
   Kertzman, M.
   Kieda, D.
   Kildea, J.
   Konopelko, A.
   Krawczynski, H.
   Krennrich, F.
   Lang, M. J.
   LeBohec, S.
   Maier, G.
   McArthur, S.
   McCann, A.
   McCutcheon, M.
   Millis, J.
   Moriarty, P.
   Mukherjee, R.
   Nagai, T.
   Ong, R. A.
   Otte, A. N.
   Pandel, D.
   Perkins, J. S.
   Pizlo, F.
   Pohl, M.
   Quinn, J.
   Ragan, K.
   Reyes, L. C.
   Reynolds, P. T.
   Roache, E.
   Rose, H. J.
   Schroedter, M.
   Sembroski, G. H.
   Smith, A. W.
   Steele, D.
   Swordy, S. P.
   Theiling, M.
   Thibadeau, S.
   Varlotta, A.
   Vassiliev, V. V.
   Vincent, S.
   Wagner, R. G.
   Wakely, S. P.
   Ward, J. E.
   Weekes, T. C.
   Weinstein, A.
   Weisgarber, T.
   Williams, D. A.
   Wissel, S.
   Wood, M.
   Zitzer, B.
TI A connection between star formation activity and cosmic rays in the starburst galaxy M82
SO NATURE
LA English
DT Article
ID radio; emission; clusters; model
AB Although Galactic cosmic rays (protons and nuclei) are widely believed to be mainly accelerated by the winds and supernovae of massive stars, definitive evidence of this origin remains elusive nearly a century after their discovery(1). The active regions of star-burst galaxies have exceptionally high rates of star formation, and their large size-more than 50 times the diameter of similar Galactic regions-uniquely enables reliable calorimetric measurements of their potentially high cosmic-ray density(2). The cosmic rays produced in the formation, life and death of massive stars in these regions are expected to produce diffuse gamma-ray emission through interactions with interstellar gas and radiation. M82, the prototype small starburst galaxy, is predicted(3,4) to be the brightest starburst galaxy in terms of gamma-ray emission. Here we report the detection of >700-GeV gamma-rays from M82. From these data we determine a cosmic-ray density of 250 eV cm(-3) in the starburst core, which is about 500 times the average Galactic density. This links cosmic-ray acceleration to star formation activity, and suggests that supernovae and massive-star winds are the dominant accelerators.
C1 [Acciari, V. A.; Benbow, W.; Galante, N.; Gibbs, K.; Kildea, J.; Perkins, J. S.; Roache, E.; Theiling, M.; Weekes, T. C.] Harvard Smithsonian Ctr Astrophys, Fred Lawrence Whipple Observ, Amado, AZ 85645 USA.
   [Acciari, V. A.; Aliu, E.; Boltuch, D.; Holder, J.] Univ Delaware, Bartol Res Inst, Newark, DE 19716 USA.
   [Acciari, V. A.; Aliu, E.; Boltuch, D.; Holder, J.] Univ Delaware, Dept Phys & Astron, Newark, DE 19716 USA.
   [Acciari, V. A.; Arlen, T.; Celik, O.; Chow, Y. C.; Fegan, S. J.; Ong, R. A.; Vassiliev, V. V.; Weinstein, A.; Wood, M.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Aune, T.; Furniss, A.; Otte, A. N.; Williams, D. A.] Univ Calif Santa Cruz, Santa Cruz Inst Particle Phys, Santa Cruz, CA 95064 USA.
   [Aune, T.; Furniss, A.; Otte, A. N.; Williams, D. A.] Univ Calif Santa Cruz, Dept Phys, Santa Cruz, CA 95064 USA.
   [Bautista, M.; Cogan, P.; Guenette, R.; Hanna, D.; Maier, G.; McCann, A.; McCutcheon, M.; Ragan, K.] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
   [Beilicke, M.; Buckley, J. H.; Bugaev, V.; Dickherber, R.; Krawczynski, H.; McArthur, S.; Thibadeau, S.] Washington Univ, Dept Phys, St Louis, MO 63130 USA.
   [Bradbury, S. M.; Rose, H. J.] Univ Leeds, Sch Phys & Astron, Leeds LS2 9JT, W Yorkshire, England.
   [Byrum, K.; Smith, A. W.; Wagner, R. G.] Argonne Natl Lab, Argonne, IL 60439 USA.
   [Cannon, A.; Grube, J.; Quinn, J.; Ward, J. E.] Univ Coll Dublin, Sch Phys, Dublin 4, Ireland.
   [Cesarini, A.; Gillanders, G. H.; Lang, M. J.] Natl Univ Ireland Univ Coll Galway, Sch Phys, Galway, Ireland.
   [Ciupik, L.; Fortson, L.; Gyuk, G.; Karlsson, N.; Steele, D.] Adler Planetarium & Astron Museum, Dept Astron, Chicago, IL 60605 USA.
   [Colin, P.; Finnegan, G.; Godambe, S.; Hui, C. M.; Kieda, D.; LeBohec, S.; Vincent, S.] Univ Utah, Dept Phys & Astron, Salt Lake City, UT 84112 USA.
   [Cui, W.; Finley, J. P.; Gall, D.; Pizlo, F.; Sembroski, G. H.; Varlotta, A.; Zitzer, B.] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA.
   [Duke, C.] Grinnell Coll, Dept Phys, Grinnell, IA 50112 USA.
   [Fortin, P.; Mukherjee, R.] Columbia Univ Barnard Coll, Dept Phys & Astron, New York, NY 10027 USA.
   [Horan, D.] Ecole Polytech, CNRS, IN2P3, Lab Leprince Ringuet, F-91128 Palaiseau, France.
   [Humensky, T. B.; Swordy, S. P.; Weisgarber, T.; Wissel, S.] Univ Chicago, Enrico Fermi Inst, Chicago, IL 60637 USA.
   [Imran, A.; Krennrich, F.; Nagai, T.; Pohl, M.; Schroedter, M.] Iowa State Univ, Dept Phys & Astron, Ames, IA 50011 USA.
   [Kaaret, P.; Pandel, D.] Univ Iowa, Dept Phys & Astron, Iowa City, IA 52242 USA.
   [Kertzman, M.] Depauw Univ, Dept Phys & Astron, Greencastle, IN 46135 USA.
   [Konopelko, A.] Pittsburg State Univ, Dept Phys, Pittsburg, KS 66762 USA.
   [Millis, J.] Anderson Univ, Dept Phys, Anderson, IN 46012 USA.
   [Moriarty, P.] Galway Mayo Inst Technol, Dept Life & Phys Sci, Galway, Ireland.
   [Reyes, L. C.] Univ Chicago, Kavli Inst Cosmol Phys, Chicago, IL 60637 USA.
   [Reynolds, P. T.] Cork Inst Technol, Dept Appl Phys & Instrumentat, Cork, Ireland.
C3 Harvard University; Smithsonian Institution; University of Delaware; University of Delaware; University of California System; University of California Los Angeles; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; McGill University; Washington University (WUSTL); University of Leeds; United States Department of Energy (DOE); Argonne National Laboratory; University College Dublin; Ollscoil na Gaillimhe-University of Galway; Utah System of Higher Education; University of Utah; Purdue University System; Purdue University; Grinnell College; Columbia University; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Institut Polytechnique de Paris; Ecole Polytechnique; University of Chicago; Iowa State University; University of Iowa; DePauw University; Pittsburg State University; Atlantic Technological University (ATU); University of Chicago; Munster Technological University (MTU)
RP Benbow, W (corresponding author), Harvard Smithsonian Ctr Astrophys, Fred Lawrence Whipple Observ, Amado, AZ 85645 USA.
EM wbenbow@cfa.harvard.edu
FU US Department of Energy; US National Science Foundation; Smithsonian Institution; National Science and Engineering Research Council of Canada; Science Foundation Ireland; UK Science and Technology Facilities Council; Direct For Mathematical & Physical Scien; Division Of Physics [0900928, 0855627] Funding Source: National Science Foundation
NR 29
TC 212
Z9 242
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 DEC 10
PY 2009
VL 462
IS 7274
BP 770
EP 772
DI 10.1038/nature08557
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 529ZZ
UT WOS:000272559900034
PM 19881491
DA 2026-03-09
ER

PT J
AU Vezys, V
   Yates, A
   Casey, KA
   Lanier, G
   Ahmed, R
   Antia, R
   Masopust, D
AF Vezys, Vaiva
   Yates, Andrew
   Casey, Kerry A.
   Lanier, Gibson
   Ahmed, Rafi
   Antia, Rustom
   Masopust, David
TI Memory CD8 T-cell compartment grows in size with immunological experience
SO NATURE
LA English
DT Article
ID immunity; protection; attrition; vaccine; virus
AB Memory CD8 T cells, generated by natural pathogen exposure or intentional vaccination, protect the host against specific viral infections(1). It has long been proposed that the number of memory CD8 T cells in the host is inflexible, and that individual cells are constantly competing for limited space(2,3). Consequently, vaccines that introduce over- abundant quantities of memory CD8 T cells specific for an agent of interest could have catastrophic consequences for the host by displacing memory CD8 T cells specific for all previous infections(4-6). To test this paradigm, we developed a vaccination regimen in mice that introduced as many new long- lived memory CD8 T cells specific for a single vaccine antigen as there were memory CD8 T cells in the host before vaccination. Here we show that, in contrast to expectations, the size of the memory CD8 T- cell compartment doubled to accommodate these new cells, a change due solely to the addition of effector memory CD8 T cells. This increase did not affect the number of CD4 T cells, B cells or naive CD8 T cells, and pre- existing memory CD8 T cells specific for a previously encountered infection were largely preserved. Thus, the number of effector memory CD8 T cells in the mammalian host adapts according to immunological experience. Developing vaccines that abundantly introduce new memory CD8 T cells should not necessarily ablate pre- existing immunity to other infections.
C1 [Vezys, Vaiva; Casey, Kerry A.; Masopust, David] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
   [Vezys, Vaiva; Casey, Kerry A.; Masopust, David] Univ Minnesota, Ctr Immunol, Minneapolis, MN 55455 USA.
   [Vezys, Vaiva; Lanier, Gibson; Ahmed, Rafi; Masopust, David] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Yates, Andrew; Antia, Rustom] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Emory University; Emory University
RP Masopust, D (corresponding author), Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
EM masopust@umn.edu
FU University of Minnesota Medical School; NIH [AI30048]; National Institute of Allergy and Infectious Diseases [R01AI030048] Funding Source: NIH RePORTER
NR 26
TC 182
Z9 218
U1 1
U2 10
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 8
PY 2009
VL 457
IS 7226
BP 196
EP U90
DI 10.1038/nature07486
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200033
PM 19005468
DA 2026-03-09
ER

PT J
AU Piao, SL
   Fang, JY
   Ciais, P
   Peylin, P
   Huang, Y
   Sitch, S
   Wang, T
AF Piao, Shilong
   Fang, Jingyun
   Ciais, Philippe
   Peylin, Philippe
   Huang, Yao
   Sitch, Stephen
   Wang, Tao
TI The carbon balance of terrestrial ecosystems in China
SO NATURE
LA English
DT Article
ID forest biomass; vegetation activity; northern; storage; inventory; croplands; dynamics; climate; europe; index
AB Global terrestrial ecosystems absorbed carbon at a rate of 1-4 Pg yr(-1) during the 1980s and 1990s, offsetting 10-60 per cent of the fossil-fuel emissions(1,2). The regional patterns and causes of terrestrial carbon sources and sinks, however, remain uncertain(1-3). With increasing scientific and political interest in regional aspects of the global carbon cycle, there is a strong impetus to better understand the carbon balance of China(1-3). This is not only because China is the world's most populous country and the largest emitter of fossil-fuel CO2 into the atmosphere(4), but also because it has experienced regionally distinct land-use histories and climate trends(1), which together control the carbon budget of its ecosystems. Here we analyse the current terrestrial carbon balance of China and its driving mechanisms during the 1980s and 1990s using three different methods: biomass and soil carbon inventories extrapolated by satellite greenness measurements, ecosystem models and atmospheric inversions. The three methods produce similar estimates of a net carbon sink in the range of 0.19-0.26 Pg carbon (PgC) per year, which is smaller than that in the conterminous United States(5) but comparable to that in geographic Europe(6). We find that northeast China is a net source of CO2 to the atmosphere owing to overharvesting and degradation of forests. By contrast, southern China accounts for more than 65 per cent of the carbon sink, which can be attributed to regional climate change, large-scale plantation programmes active since the 1980s and shrub recovery. Shrub recovery is identified as the most uncertain factor contributing to the carbon sink. Our data and model results together indicate that China's terrestrial ecosystems absorbed 28-37 per cent of its cumulated fossil carbon emissions during the 1980s and 1990s.
C1 [Piao, Shilong; Fang, Jingyun; Wang, Tao] Peking Univ, Dept Ecol, Coll Urban & Environm Sci, Beijing 100871, Peoples R China.
   [Piao, Shilong; Fang, Jingyun; Wang, Tao] Peking Univ, Key Lab Earth Surface Proc, Minist Educ, Beijing 100871, Peoples R China.
   [Ciais, Philippe] UMR CEA CNRS UVSQ, LSCE, F-91191 Gif Sur Yvette, France.
   [Peylin, Philippe] Lab Biogeochim Isotop, F-78026 Thiverval Grignon, France.
   [Huang, Yao] Chinese Acad Sci, Inst Atmospher Phys, State Key Lab Atmospher Boundary Layer Phys & Atm, Beijing 100029, Peoples R China.
   [Sitch, Stephen] Met Off Hadley Ctr JCHMR, Wallingford OX10 8BB, Oxon, England.
C3 Peking University; Peking University; CEA; Universite Paris Saclay; Chinese Academy of Sciences; Institute of Atmospheric Physics, CAS; Met Office - UK; Hadley Centre
RP Piao, SL (corresponding author), Peking Univ, Dept Ecol, Coll Urban & Environm Sci, Beijing 100871, Peoples R China.
EM slpiao@pku.edu.cn; jyfang@urban.pku.edu.cn
FU Foundation for the Author of National Excellent Doctoral Dissertation of China [FANEDD-200737]; National Natural Science Foundation of China [90711002, 30721140306]; Knowledge Innovation Program of the Chinese Academy of Sciences [KZCX1-SW-01-13]; DECC [GA0110]; MoD [CBC/2B/0417_Annex C5]
NR 51
TC 1472
Z9 1978
U1 87
U2 2549
PU NATURE PUBLISHING 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 23
PY 2009
VL 458
IS 7241
BP 1009
EP U82
DI 10.1038/nature07944
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900038
PM 19396142
DA 2026-03-09
ER

PT J
AU Snellen, IAG
   de Mooij, EJW
   Albrecht, S
AF Snellen, Ignas A. G.
   de Mooij, Ernst J. W.
   Albrecht, Simon
TI The changing phases of extrasolar planet CoRoT-1b
SO NATURE
LA English
DT Article
ID emission-spectrum; hd 209458b; temperature inversion; thermal emission; giant planets; light curves; hot jupiters; starlight; 189733b; search
AB Hot Jupiters are a class of extrasolar planet that orbit their parent stars at very short distances. They are expected to be tidally locked, which can lead to a large temperature difference between their daysides and nightsides. Infrared observations of eclipsing systems have yielded dayside temperatures for a number of transiting planets(1-5). The day-night contrast of the transiting extrasolar planet HD189733b was 'mapped' using infrared observations(6,7). It is expected that the contrast between the daysides and nightsides of hot Jupiters is much higher at visual wavelengths, shorter than that of the peak emission, and could be further enhanced by reflected stellar light. Here we report the analysis of optical photometric data(8) obtained over 36 planetary orbits of the transiting hot Jupiter CoRoT-1b. The data are consistent with the nightside hemisphere of the planet being entirely black, with the dayside flux dominating the optical phase curve. This means that at optical wavelengths the planet's phase variation is just as we see it for the interior planets in the Solar System. The data allow for only a small fraction of reflected light, corresponding to a geometric albedo of <0.20.
C1 [Snellen, Ignas A. G.; de Mooij, Ernst J. W.; Albrecht, Simon] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
C3 Leiden University; Leiden University - Excl LUMC
RP Snellen, IAG (corresponding author), Leiden Univ, Leiden Observ, Postbus 9513, NL-2300 RA Leiden, Netherlands.
EM snellen@strw.leidenuniv.nl
NR 29
TC 116
Z9 124
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 MAY 28
PY 2009
VL 459
IS 7246
BP 543
EP 545
DI 10.1038/nature08045
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 449ZS
UT WOS:000266370500033
PM 19478779
DA 2026-03-09
ER

PT J
AU Itoh, Y
   Shinya, K
   Kiso, M
   Watanabe, T
   Sakoda, Y
   Hatta, M
   Muramoto, Y
   Tamura, D
   Sakai-Tagawa, Y
   Noda, T
   Sakabe, S
   Imai, M
   Hatta, Y
   Watanabe, S
   Li, CJ
   Yamada, S
   Fujii, K
   Murakami, S
   Imai, H
   Kakugawa, S
   Ito, M
   Takano, R
   Iwatsuki-Horimoto, K
   Shimojima, M
   Horimoto, T
   Goto, H
   Takahashi, K
   Makino, A
   Ishigaki, H
   Nakayama, M
   Okamatsu, M
   Takahashi, K
   Warshauer, D
   Shult, PA
   Saito, R
   Suzuki, H
   Furuta, Y
   Yamashita, M
   Mitamura, K
   Nakano, K
   Nakamura, M
   Brockman-Schneider, R
   Mitamura, H
   Yamazaki, M
   Sugaya, N
   Suresh, M
   Ozawa, M
   Neumann, G
   Gern, J
   Kida, H
   Ogasawara, K
   Kawaoka, Y
AF Itoh, Yasushi
   Shinya, Kyoko
   Kiso, Maki
   Watanabe, Tokiko
   Sakoda, Yoshihiro
   Hatta, Masato
   Muramoto, Yukiko
   Tamura, Daisuke
   Sakai-Tagawa, Yuko
   Noda, Takeshi
   Sakabe, Saori
   Imai, Masaki
   Hatta, Yasuko
   Watanabe, Shinji
   Li, Chengjun
   Yamada, Shinya
   Fujii, Ken
   Murakami, Shin
   Imai, Hirotaka
   Kakugawa, Satoshi
   Ito, Mutsumi
   Takano, Ryo
   Iwatsuki-Horimoto, Kiyoko
   Shimojima, Masayuki
   Horimoto, Taisuke
   Goto, Hideo
   Takahashi, Kei
   Makino, Akiko
   Ishigaki, Hirohito
   Nakayama, Misako
   Okamatsu, Masatoshi
   Takahashi, Kazuo
   Warshauer, David
   Shult, Peter A.
   Saito, Reiko
   Suzuki, Hiroshi
   Furuta, Yousuke
   Yamashita, Makoto
   Mitamura, Keiko
   Nakano, Kunio
   Nakamura, Morio
   Brockman-Schneider, Rebecca
   Mitamura, Hiroshi
   Yamazaki, Masahiko
   Sugaya, Norio
   Suresh, M.
   Ozawa, Makoto
   Neumann, Gabriele
   Gern, James
   Kida, Hiroshi
   Ogasawara, Kazumasa
   Kawaoka, Yoshihiro
TI In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses
SO NATURE
LA English
DT Article
ID resistant influenza; a virus; cells; infection; transmission; model
AB Influenza A viruses cause recurrent outbreaks at local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On 11 June 2009 the World Health Organization declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses(1). Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) seem to be mild; however, a substantial number of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 ( H1N1; hereafter referred to as CA04), as well as several other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04 and other S- OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in non-human primates, causes more severe pathological lesions in the lungs of infected mice, ferrets and non-human primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen-free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting that these compounds could function as a first line of defence against the recently declared S- OIV pandemic.
C1 [Itoh, Yasushi; Makino, Akiko; Kawaoka, Yoshihiro] Kobe Univ, Dept Microbiol & Infect Dis, Kobe, Hyogo 6500017, Japan.
   [Itoh, Yasushi; Ishigaki, Hirohito; Nakayama, Misako; Ogasawara, Kazumasa] Shiga Univ Med Sci, Dept Pathol, Shiga 5202192, Japan.
   [Kiso, Maki; Tamura, Daisuke; Sakai-Tagawa, Yuko; Sakabe, Saori; Yamada, Shinya; Murakami, Shin; Imai, Hirotaka; Kakugawa, Satoshi; Ito, Mutsumi; Takano, Ryo; Iwatsuki-Horimoto, Kiyoko; Shimojima, Masayuki; Horimoto, Taisuke; Goto, Hideo; Takahashi, Kei; Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo 1088639, Japan.
   [Watanabe, Tokiko; Hatta, Masato; Imai, Masaki; Hatta, Yasuko; Watanabe, Shinji; Li, Chengjun; Suresh, M.; Ozawa, Makoto; Neumann, Gabriele; Kawaoka, Yoshihiro] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53711 USA.
   [Sakoda, Yoshihiro; Okamatsu, Masatoshi; Kida, Hiroshi] Hokkaido Univ, Grad Sch Vet Med, Dept Dis Control, Sapporo, Hokkaido 0600818, Japan.
   [Muramoto, Yukiko; Fujii, Ken; Kawaoka, Yoshihiro] ERATO Infect Induced Host Responses Project, Kawaguchi, Saitama 3320012, Japan.
   [Noda, Takeshi; Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Dept Special Pathogens, Tokyo 1088639, Japan.
   [Takahashi, Kazuo] Osaka Prefectural Inst Publ Hlth, Dept Infect Dis, Osaka 5370025, Japan.
   [Warshauer, David; Shult, Peter A.] Wisconsin State Lab Hyg, Madison, WI 53706 USA.
   [Saito, Reiko; Suzuki, Hiroshi] Niigata Univ, Grad Sch Med & Dent Sci, Dept Publ Hlth, Niigata 9518510, Japan.
   [Furuta, Yousuke] Toyama Chem Co Ltd, Toyama 9308508, Japan.
   [Yamashita, Makoto] Daiichi Sankyo Co Ltd, Tokyo 1408710, Japan.
   [Mitamura, Keiko; Nakano, Kunio; Nakamura, Morio] Eiju Gen Hosp, Tokyo 1108654, Japan.
   [Brockman-Schneider, Rebecca; Gern, James] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53792 USA.
   [Mitamura, Hiroshi] Mitamura Clin, Dept Internal Med, Shizuoka 4130103, Japan.
   [Yamazaki, Masahiko] Childrens Clin, Dept Pediat, Kanagawa 2280023, Japan.
   [Sugaya, Norio] Keiyu Hosp, Kanagawa 2200012, Japan.
   [Kawaoka, Yoshihiro] Hokkaido Univ, Creat Res Initiat, Sapporo, Hokkaido 0600818, Japan.
C3 Kobe University; Shiga University of Medical Science; University of Tokyo; University of Wisconsin System; University of Wisconsin Madison; Hokkaido University; Japan Science & Technology Agency (JST); University of Tokyo; University of Osaka; Osaka Prefectural Institute of Public Health; Niigata University; Toyama Chemical Co., Ltd.; Daiichi Sankyo Company Limited; University of Wisconsin System; University of Wisconsin Madison; Hokkaido University
RP Kawaoka, Y (corresponding author), Kobe Univ, Dept Microbiol & Infect Dis, Kobe, Hyogo 6500017, Japan.
EM kawaokay@svm.vetmed.wisc.edu
FU Centers for Disease Control (CDC) [A/California/04/09, A/Netherlands/603/09]; National Institute of Allergy and Infectious Diseases Public Health Service; NIAID [HHSN266200700010C]; Ministry of Education, Culture, Sports, Science and Technology; Ministry of Health and by ERATO ( Japan Science and Technology Agency)
NR 21
TC 886
Z9 989
U1 0
U2 121
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 20
PY 2009
VL 460
IS 7258
BP 1021
EP U110
DI 10.1038/nature08260
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 484YC
UT WOS:000269085500036
PM 19672242
DA 2026-03-09
ER

PT J
AU Connolly, JAD
   Schmidt, MW
   Solferino, G
   Bagdassarov, N
AF Connolly, James A. D.
   Schmidt, Max W.
   Solferino, Giulio
   Bagdassarov, Nikolai
TI Permeability of asthenospheric mantle and melt extraction rates at mid-ocean ridges
SO NATURE
LA English
DT Article
ID oceanic upper-mantle; upwelling mantle; beneath; disequilibria; generation; transport; flow; consequences; constraints; compaction
AB Magmatic production on Earth is dominated by asthenospheric melts of basaltic composition that have mostly erupted at mid-ocean ridges. The timescale for segregation and transport of these melts, which are ultimately responsible for formation of the Earth's crust, is critically dependent on the permeability of the partly molten asthenospheric mantle, yet this permeability is known mainly from semi-empirical and analogue models(1-6). Here we use a high-pressure, high-temperature centrifuge, at accelerations of 400g-700g, to measure the rate of basalt melt flow in olivine aggregates with porosities of 5-12 per cent. The resulting permeabilities are consistent with a microscopic model in which melt is completely connected, and are one to two orders of magnitude larger than predicted by current parameterizations(4,7). Extrapolation of the measurements to conditions characteristic(8) of asthenosphere below mid-ocean ridges yields proportionally higher transport speeds. Application of these results in a model(9) of porous-media channelling instabilities(10) yields melt transport times of similar to 1-2.5 kyr across the entire asthenosphere, which is sufficient to preserve the observed Th-230 excess of mid-ocean-ridge basalts and the mantle signatures of even shorter-lived isotopes such as Ra-226 (refs 5,11-14).
C1 [Connolly, James A. D.; Schmidt, Max W.; Solferino, Giulio] ETH, Inst Mineral & Petr, CH-8092 Zurich, Switzerland.
   [Bagdassarov, Nikolai] Goethe Univ Frankfurt, Inst Geowissensch, D-60438 Frankfurt, Germany.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Goethe University Frankfurt
RP Schmidt, MW (corresponding author), ETH, Inst Mineral & Petr, CH-8092 Zurich, Switzerland.
EM max.schmidt@erdw.ethz.ch
FU ETH [TH 20/03-2]; SNF [200020-111725-1]
NR 35
TC 94
Z9 105
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 NOV 12
PY 2009
VL 462
IS 7270
BP 209
EP U83
DI 10.1038/nature08517
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 517YM
UT WOS:000271655100041
PM 19907492
DA 2026-03-09
ER

PT J
AU Lister, R
   Pelizzola, M
   Dowen, RH
   Hawkins, RD
   Hon, G
   Tonti-Filippini, J
   Nery, JR
   Lee, L
   Ye, Z
   Ngo, QM
   Edsall, L
   Antosiewicz-Bourget, J
   Stewart, R
   Ruotti, V
   Millar, AH
   Thomson, JA
   Ren, B
   Ecker, JR
AF Lister, Ryan
   Pelizzola, Mattia
   Dowen, Robert H.
   Hawkins, R. David
   Hon, Gary
   Tonti-Filippini, Julian
   Nery, Joseph R.
   Lee, Leonard
   Ye, Zhen
   Ngo, Que-Minh
   Edsall, Lee
   Antosiewicz-Bourget, Jessica
   Stewart, Ron
   Ruotti, Victor
   Millar, A. Harvey
   Thomson, James A.
   Ren, Bing
   Ecker, Joseph R.
TI Human DNA methylomes at base resolution show widespread epigenomic differences
SO NATURE
LA English
DT Article
ID embryonic stem-cells; mammalian development; enzymatic-property; histone methylation; cpg methylation; human genome; gene; methyltransferases; binding; dnmt3a
AB DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.
C1 [Lister, Ryan; Pelizzola, Mattia; Dowen, Robert H.; Nery, Joseph R.; Ecker, Joseph R.] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA.
   [Hawkins, R. David; Hon, Gary; Lee, Leonard; Ye, Zhen; Ngo, Que-Minh; Edsall, Lee; Ren, Bing] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Ren, Bing] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Tonti-Filippini, Julian; Millar, A. Harvey] Univ Western Australia, ARC Ctr Excellence Plant Energy Biol, Crawley, WA 6009, Australia.
   [Antosiewicz-Bourget, Jessica; Stewart, Ron; Ruotti, Victor; Thomson, James A.] Morgridge Inst Res, Madison, WI 53707 USA.
   [Antosiewicz-Bourget, Jessica; Stewart, Ron; Ruotti, Victor; Thomson, James A.] Genome Ctr Wisconsin, Madison, WI 53706 USA.
   [Thomson, James A.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
   [Thomson, James A.] Univ Wisconsin, Dept Anat, Madison, WI 53706 USA.
C3 Salk Institute; Ludwig Institute for Cancer Research; University of California System; University of California San Diego; University of California System; University of California San Diego; ARC Centre of Excellence in Plant Energy Biology; University of Western Australia; University of Wisconsin System; University of Wisconsin Madison; The Morgridge Institute for Research, Inc.; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
RP Ecker, JR (corresponding author), Salk Inst Biol Studies, Genom Anal Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM ecker@salk.edu
FU Mary K. Chapman Foundation; National Institutes of Health [U01 ES017166, U01 1U01ES017166-01]; Australian Research Council [CE0561495, DP0771156]; Morgridge Institute for Research, Madison, Wisconsin; Australian Research Council [DP0771156] Funding Source: Australian Research Council
NR 46
TC 3538
Z9 4348
U1 5
U2 596
PU NATURE PUBLISHING 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 19
PY 2009
VL 462
IS 7271
BP 315
EP 322
DI 10.1038/nature08514
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300037
PM 19829295
DA 2026-03-09
ER

PT J
AU Takeda, A
   Baffi, JZ
   Kleinman, ME
   Cho, WG
   Nozaki, M
   Yamada, K
   Kaneko, H
   Albuquerque, RJC
   Dridi, S
   Saito, K
   Raisler, BJ
   Budd, SJ
   Geisen, P
   Munitz, A
   Ambati, BK
   Green, MG
   Ishibashi, T
   Wright, JD
   Humbles, AA
   Gerard, CJ
   Ogura, Y
   Pan, YZ
   Smith, JR
   Grisanti, S
   Hartnett, ME
   Rothenberg, ME
   Ambati, J
AF Takeda, Atsunobu
   Baffi, Judit Z.
   Kleinman, Mark E.
   Cho, Won Gil
   Nozaki, Miho
   Yamada, Kiyoshi
   Kaneko, Hiroki
   Albuquerque, Romulo J. C.
   Dridi, Sami
   Saito, Kuniharu
   Raisler, Brian J.
   Budd, Steven J.
   Geisen, Pete
   Munitz, Ariel
   Ambati, Balamurali K.
   Green, Martha G.
   Ishibashi, Tatsuro
   Wright, John D.
   Humbles, Alison A.
   Gerard, Craig J.
   Ogura, Yuichiro
   Pan, Yuzhen
   Smith, Justine R.
   Grisanti, Salvatore
   Hartnett, M. Elizabeth
   Rothenberg, Marc E.
   Ambati, Jayakrishna
TI CCR3 is a target for age-related macular degeneration diagnosis and therapy
SO NATURE
LA English
DT Article
ID endothelial growth-factor; retinal-pigment epithelium; experimental choroidal neovascularization; gene-expression profiles; mast-cells; eosinophil recruitment; visual function; eotaxin; vegf; model
AB Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.
C1 [Takeda, Atsunobu; Baffi, Judit Z.; Kleinman, Mark E.; Cho, Won Gil; Nozaki, Miho; Yamada, Kiyoshi; Kaneko, Hiroki; Albuquerque, Romulo J. C.; Dridi, Sami; Saito, Kuniharu; Raisler, Brian J.; Green, Martha G.; Ambati, Jayakrishna] Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
   [Albuquerque, Romulo J. C.; Raisler, Brian J.; Ambati, Jayakrishna] Univ Kentucky, Dept Physiol, Lexington, KY 40506 USA.
   [Nozaki, Miho; Ogura, Yuichiro] Nagoya City Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Nagoya, Aichi 4678601, Japan.
   [Budd, Steven J.; Geisen, Pete; Wright, John D.; Hartnett, M. Elizabeth] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC 27599 USA.
   [Munitz, Ariel; Rothenberg, Marc E.] Univ Cincinnati, Cincinnati Childrens Hosp, Med Ctr, Div Allergy & Immunol,Dept Pediat, Cincinnati, OH 45229 USA.
   [Ambati, Balamurali K.] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   [Ambati, Balamurali K.] Vet Affairs Salt Lake City Healthcare Syst, Dept Ophthalmol, Salt Lake City, UT 84148 USA.
   [Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 8128582, Japan.
   [Humbles, Alison A.; Gerard, Craig J.] Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA 02215 USA.
   [Pan, Yuzhen; Smith, Justine R.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA.
   [Grisanti, Salvatore] Med Univ Lubeck, Dept Ophthalmol, D-23538 Lubeck, Germany.
C3 University of Kentucky; University of Kentucky; Nagoya City University; University of North Carolina; University of North Carolina Chapel Hill; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Utah System of Higher Education; University of Utah; US Department of Veterans Affairs; Kyushu University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Oregon Health & Science University; University of Lubeck
RP Ambati, J (corresponding author), Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
EM jamba2@email.uky.edu
FU National Eye Institute/National Institutes of Health (NIH) [EY015422, EY018350, EY018836]; Doris Duke Distinguished Clinical Scientist Award; Burroughs Wellcome Fund Clinical Scientist Awar; Macula Vision Research Foundation; E. Matilda Ziegler Foundation for the Blind; American Health Assistance Foundation; NIH [EY017182, EY017950, AI45898, DK076893, AI039759, EY017011, EY015130, EY010572]; VA Merit Award and the Department of Defense; RPB Career Development Award; National Eye Institute [P30EY010572, R01EY017011, R01EY015130, R01EY017950] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI045898] Funding Source: NIH RePORTER
NR 47
TC 210
Z9 252
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 9
PY 2009
VL 460
IS 7252
BP 225
EP U87
DI 10.1038/nature08151
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000034
PM 19525930
DA 2026-03-09
ER

PT J
AU Barrick, JE
   Yu, DS
   Yoon, SH
   Jeong, H
   Oh, TK
   Schneider, D
   Lenski, RE
   Kim, JF
AF Barrick, Jeffrey E.
   Yu, Dong Su
   Yoon, Sung Ho
   Jeong, Haeyoung
   Oh, Tae Kwang
   Schneider, Dominique
   Lenski, Richard E.
   Kim, Jihyun F.
TI Genome evolution and adaptation in a long-term experiment with Escherichia coli
SO NATURE
LA English
DT Article
ID population-genetics; parallel changes; mutations; divergence; dynamics; sequence
AB The relationship between rates of genomic evolution and organismal adaptation remains uncertain, despite considerable interest. The feasibility of obtaining genome sequences from experimentally evolving populations offers the opportunity to investigate this relationship with new precision. Here we sequence genomes sampled through 40,000 generations from a laboratory population of Escherichia coli. Although adaptation decelerated sharply, genomic evolution was nearly constant for 20,000 generations. Such clock-like regularity is usually viewed as the signature of neutral evolution, but several lines of evidence indicate that almost all of these mutations were beneficial. This same population later evolved an elevated mutation rate and accumulated hundreds of additional mutations dominated by a neutral signature. Thus, the coupling between genomic and adaptive evolution is complex and can be counterintuitive even in a constant environment. In particular, beneficial substitutions were surprisingly uniform over time, whereas neutral substitutions were highly variable.
C1 [Barrick, Jeffrey E.; Lenski, Richard E.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
   [Yu, Dong Su; Yoon, Sung Ho; Jeong, Haeyoung; Oh, Tae Kwang; Kim, Jihyun F.] Korea Res Inst Biosci & Biotechnol, Ind Biotechnol & Bioenergy Res Ctr, Taejon 305806, South Korea.
   [Yu, Dong Su] Chungnam Natl Univ, Dept Comp Sci & Engn, Taejon 305764, South Korea.
   [Oh, Tae Kwang] 21C Frontier Microbial Genom & Applicat Ctr, Taejon 305806, South Korea.
   [Schneider, Dominique] Univ Grenoble 1, CNRS, UMR 5163, Inst Jean Roget,Lab Adaptat & Pathogenie Microorg, F-38042 Grenoble 9, France.
   [Kim, Jihyun F.] Univ Sci & Technol, Sch Sci, Funct Genom Program, Taejon 305333, South Korea.
C3 Michigan State University; Korea Research Institute of Bioscience & Biotechnology (KRIBB); Chungnam National University; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS)
RP Lenski, RE (corresponding author), Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
EM lenski@msu.edu; jfk@kribb.re.kr
FU DARPA 'Fun Bio' Program; US National Science Foundation; Agence Nationale de la Recherche Programme 'Genomique Microbienne a Grande Echelle, Centre National de la Recherche Scientifique, and Universite Joseph Fourier; Ministry of Education, Science and Technology, Republic of Korea
NR 50
TC 883
Z9 1096
U1 2
U2 364
PU NATURE PUBLISHING 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 29
PY 2009
VL 461
IS 7268
BP 1243
EP U74
DI 10.1038/nature08480
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800040
PM 19838166
DA 2026-03-09
ER

PT J
AU Zheng, Y
   Chaudhry, A
   Kas, A
   deRoos, P
   Kim, JM
   Chu, TT
   Corcoran, L
   Treuting, P
   Klein, U
   Rudensky, AY
AF Zheng, Ye
   Chaudhry, Ashutosh
   Kas, Arnold
   deRoos, Paul
   Kim, Jeong M.
   Chu, Tin-Tin
   Corcoran, Lynn
   Treuting, Piper
   Klein, Ulf
   Rudensky, Alexander Y.
TI Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses
SO NATURE
LA English
DT Article
ID self-tolerance; target genes; differentiation; foxp3; lineage; th2; interleukin-10; adenosine; disease; absence
AB In the course of infection or autoimmunity, particular transcription factors orchestrate the differentiation of T(H)1, T(H)2 or T(H)17 effector cells, the responses of which are limited by a distinct lineage of suppressive regulatory T cells (T-reg). T-reg cell differentiation and function are guided by the transcription factor Foxp3, and their deficiency due to mutations in Foxp3 results in aggressive fatal autoimmune disease associated with sharply augmented T(H)1 and T(H)2 cytokine production(1-3). Recent studies suggested that Foxp3 regulates the bulk of the Foxp3-dependent transcriptional program indirectly through a set of transcriptional regulators serving as direct Foxp3 targets(4,5). Here we show that in mouse T-reg cells, high amounts of interferon regulatory factor-4 (IRF4), a transcription factor essential for T(H)2 effector cell differentiation, is dependent on Foxp3 expression. We proposed that IRF4 expression endows T-reg cells with the ability to suppress T(H)2 responses. Indeed, ablation of a conditional Irf4 allele in T-reg cells resulted in selective dysregulation of T(H)2 responses, IL4-dependent immunoglobulin isotype production, and tissue lesions with pronounced plasma cell infiltration, in contrast to the mononuclear-cell-dominated pathology typical of mice lacking T-reg cells. Our results indicate that T-reg cells use components of the transcriptional machinery, promoting a particular type of effector CD4(+) T cell differentiation, to efficiently restrain the corresponding type of the immune response.
C1 [Zheng, Ye; Chaudhry, Ashutosh; Kas, Arnold; deRoos, Paul; Kim, Jeong M.; Chu, Tin-Tin; Rudensky, Alexander Y.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Zheng, Ye; Chaudhry, Ashutosh; Kas, Arnold; deRoos, Paul; Kim, Jeong M.; Chu, Tin-Tin; Rudensky, Alexander Y.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
   [Treuting, Piper] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA.
   [Corcoran, Lynn] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Parkville, Vic 3050, Australia.
   [Klein, Ulf] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA.
   [Klein, Ulf] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Melbourne Health; Royal Melbourne Hospital; Walter & Eliza Hall Institute; Columbia University; Columbia University
RP Rudensky, AY (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Immunol, New York, NY 10021 USA.
EM rudenska@mskcc.org
FU CRI-Irvington Institute; Howard Hughes Medical Institute; National Institutes of Health
NR 30
TC 782
Z9 946
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 19
PY 2009
VL 458
IS 7236
BP 351
EP U116
DI 10.1038/nature07674
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 420JH
UT WOS:000264285600044
PM 19182775
DA 2026-03-09
ER

PT J
AU Matthews, HD
   Gillett, NP
   Stott, PA
   Zickfeld, K
AF Matthews, H. Damon
   Gillett, Nathan P.
   Stott, Peter A.
   Zickfeld, Kirsten
TI The proportionality of global warming to cumulative carbon emissions
SO NATURE
LA English
DT Article
ID dynamics; model
AB The global temperature response to increasing atmospheric CO2 is often quantified by metrics such as equilibrium climate sensitivity and transient climate response(1). These approaches, however, do not account for carbon cycle feedbacks and therefore do not fully represent the net response of the Earth system to anthropogenic CO2 emissions. Climate-carbon modelling experiments have shown that: (1) the warming per unit CO2 emitted does not depend on the background CO2 concentration(2); (2) the total allowable emissions for climate stabilization do not depend on the timing of those emissions(3-5); and (3) the temperature response to a pulse of CO2 is approximately constant on timescales of decades to centuries(3,6-8). Here we generalize these results and show that the carbon-climate response (CCR), defined as the ratio of temperature change to cumulative carbon emissions, is approximately independent of both the atmospheric CO2 concentration and its rate of change on these timescales. From observational constraints, we estimate CCR to be in the range 1.0-2.1 degrees C per trillion tonnes of carbon (Tt C) emitted (5th to 95th percentiles), consistent with twenty-first-century CCR values simulated by climate-carbon models. Uncertainty in land-use CO2 emissions and aerosol forcing, however, means that higher observationally constrained values cannot be excluded. The CCR, when evaluated from climate-carbon models under idealized conditions, represents a simple yet robust metric for comparing models, which aggregates both climate feedbacks and carbon cycle feedbacks. CCR is also likely to be a useful concept for climate change mitigation and policy; by combining the uncertainties associated with climate sensitivity, carbon sinks and climate-carbon feedbacks into a single quantity, the CCR allows CO2-induced global mean temperature change to be inferred directly from cumulative carbon emissions.
C1 [Matthews, H. Damon] Concordia Univ, Dept Geog Planning & Environm, Montreal, PQ H3G 1M8, Canada.
   [Gillett, Nathan P.; Zickfeld, Kirsten] Environm Canada, Canadian Ctr Climate Modelling & Anal, Victoria, BC V8P 5C2, Canada.
   [Stott, Peter A.] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
C3 Concordia University - Canada; Environment & Climate Change Canada; Canadian Centre for Climate Modelling & Analysis (CCCma); Met Office - UK; Hadley Centre
RP Matthews, HD (corresponding author), Concordia Univ, Dept Geog Planning & Environm, 1455 Maisonneuve Blvd W, Montreal, PQ H3G 1M8, Canada.
EM dmatthew@alcor.concordia.ca
FU National Science and Engineering Research Council of Canada; Canadian Foundation for Climate and Atmospheric Sciences Project; DECC; Defra and MoD Integrated Climate Programme; Leverhulme Trust; Climate Change Detection and Attribution Project; NOAA's Office of Global Programs; US Department of Energy
NR 24
TC 773
Z9 927
U1 4
U2 270
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 829
EP U3
DI 10.1038/nature08047
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500036
PM 19516338
DA 2026-03-09
ER

PT J
AU Zehn, D
   Lee, SY
   Bevan, MJ
AF Zehn, Dietmar
   Lee, Sarah Y.
   Bevan, Michael J.
TI Complete but curtailed T-cell response to very low-affinity antigen
SO NATURE
LA English
DT Article
ID listeria-monocytogenes; precursor frequency; memory; effector; infection; selection; differentiation; recognition; activation; expression
AB After an infection, T cells that carry the CD8 marker are activated and undergo a characteristic kinetic sequence of rapid expansion, subsequent contraction and formation of memory cells(1-3). The pool of naive T-cell clones is diverse and contains cells bearing T-cell antigen receptors (TCRs) that differ in their affinity for the same antigen(4,5). How these differences in affinity affect the function and the response kinetics of individual T-cell clones was previously unknown. Here we show that during the in vivo response to microbial infection, even very weak TCR-ligand interactions are sufficient to activate naive T cells, induce rapid initial proliferation and generate effector and memory cells. The strength of the TCR ligand interaction critically affects when expansion stops, when the cells exit lymphoid organs and when contraction begins; that is, strongly stimulated T cells contract and exit lymphoid organs later than weakly stimulated cells. Our data challenge the prevailing view that strong TCR ligation is a prerequisite for CD8(+) T-cell activation. Instead, very weak interactions are sufficient for activation, but strong TCR ligation is required to sustain T-cell expansion. We propose that in response to microbial challenge, T-cell clones with a broad range of avidities for foreign ligands are initially recruited, and that the pool of T cells subsequently matures in affinity owing to the more prolonged expansion of high-affinity T-cell clones.
C1 [Zehn, Dietmar; Lee, Sarah Y.; Bevan, Michael J.] Univ Washington, Howard Hughes Med Inst, Dept Immunol, Seattle, WA 98195 USA.
C3 Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
RP Bevan, MJ (corresponding author), Univ Washington, Howard Hughes Med Inst, Dept Immunol, Box 357370, Seattle, WA 98195 USA.
EM mbevan@u.washington.edu
FU National Institutes of Health; Howard Hughes Medical Institute; Juvenile Diabetes Research Foundation; German Research Foundation
NR 26
TC 559
Z9 688
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 12
PY 2009
VL 458
IS 7235
BP 211
EP 214
DI 10.1038/nature07657
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 417EQ
UT WOS:000264059700045
PM 19182777
DA 2026-03-09
ER

PT J
AU Machacek, M
   Hodgson, L
   Welch, C
   Elliott, H
   Pertz, O
   Nalbant, P
   Abell, A
   Johnson, GL
   Hahn, KM
   Danuser, G
AF Machacek, Matthias
   Hodgson, Louis
   Welch, Christopher
   Elliott, Hunter
   Pertz, Olivier
   Nalbant, Perihan
   Abell, Amy
   Johnson, Gary L.
   Hahn, Klaus M.
   Danuser, Gaudenz
TI Coordination of Rho GTPase activities during cell protrusion
SO NATURE
LA English
DT Article
ID migrating cells; living cells; rac; activation; dynamics; actin; membrane; adhesion; polarity
AB The GTPases Rac1, RhoA and Cdc42 act together to control cytoskeleton dynamics(1-3). Recent biosensor studies have shown that all three GTPases are activated at the front of migrating cells(4-7), and biochemical evidence suggests that they may regulate one another: Cdc42 can activate Rac1 (ref. 8), and Rac1 and RhoA are mutually inhibitory(9-12). However, their spatiotemporal coordination, at the seconds and single-micrometre dimensions typical of individual protrusion events, remains unknown. Here we examine GTPase coordination in mouse embryonic fibroblasts both through simultaneous visualization of two GTPase biosensors and using a 'computational multiplexing' approach capable of defining the relationships between multiple protein activities visualized in separate experiments. We found that RhoA is activated at the cell edge synchronous with edge advancement, whereas Cdc42 and Rac1 are activated 2 mm behind the edge with a delay of 40s. This indicates that Rac1 and RhoA operate antagonistically through spatial separation and precise timing, and that RhoA has a role in the initial events of protrusion, whereas Rac1 and Cdc42 activate pathways implicated in reinforcement and stabilization of newly expanded protrusions.
C1 [Hodgson, Louis; Welch, Christopher; Abell, Amy; Johnson, Gary L.; Hahn, Klaus M.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Hodgson, Louis; Welch, Christopher; Abell, Amy; Johnson, Gary L.; Hahn, Klaus M.] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA.
   [Hodgson, Louis; Welch, Christopher; Abell, Amy; Johnson, Gary L.; Hahn, Klaus M.] Univ N Carolina, Dept Med Chem, Chapel Hill, NC 27599 USA.
   [Machacek, Matthias; Elliott, Hunter; Pertz, Olivier; Danuser, Gaudenz] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
   [Nalbant, Perihan] Univ Duisburg Essen, Ctr Med Biotechnol, Dept Mol Cell Biol, D-45117 Essen, Germany.
C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Scripps Research Institute; University of Duisburg Essen
RP Hahn, KM (corresponding author), Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
EM khahn@med.unc.edu; gdanuser@scripps.edu
FU Swiss National Science Foundation; Novartis Foundation; Ciba-Geigy Jubilee Foundation; NIGMS [U54 GM064346];  [NIH T32 GM008719];  [NIH F30 HL094020];  [NIH R01 GM57464];  [NIH R01 GM71868]; National Institute of General Medical Sciences [T32GM008719] Funding Source: NIH RePORTER
NR 28
TC 750
Z9 966
U1 2
U2 135
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 3
PY 2009
VL 461
IS 7260
BP 99
EP 103
DI 10.1038/nature08242
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 490DT
UT WOS:000269478800038
PM 19693013
DA 2026-03-09
ER

PT J
AU Eldar, A
   Chary, VK
   Xenopoulos, P
   Fontes, ME
   Losón, OC
   Dworkin, J
   Piggot, PJ
   Elowitz, MB
AF Eldar, Avigdor
   Chary, Vasant K.
   Xenopoulos, Panagiotis
   Fontes, Michelle E.
   Loson, Oliver C.
   Dworkin, Jonathan
   Piggot, Patrick J.
   Elowitz, Michael B.
TI Partial penetrance facilitates developmental evolution in bacteria
SO NATURE
LA English
DT Article
ID bacillus-subtilis sporulation; replication initiation; gene-expression; spore formation; hsp90; dna; differentiation; robustness; septation; capacitor
AB Development normally occurs similarly in all individuals within an isogenic population, but mutations often affect the fates of individual organisms differently(1-4). This phenomenon, known as partial penetrance, has been observed in diverse developmental systems. However, it remains unclear how the underlying genetic network specifies the set of possible alternative fates and how the relative frequencies of these fates evolve(5-8). Here we identify a stochastic cell fate determination process that operates in Bacillus subtilis sporulation mutants and show how it allows genetic control of the penetrance of multiple fates. Mutations in an intercompartmental signalling process generate a set of discrete alternative fates not observed in wild-type cells, including rare formation of two viable 'twin' spores, rather than one within a single cell. By genetically modulating chromosome replication and septation, we can systematically tune the penetrance of each mutant fate. Furthermore, signalling and replication perturbations synergize to significantly increase the penetrance of twin sporulation. These results suggest a potential pathway for developmental evolution between monosporulation and twin sporulation through states of intermediate twin penetrance. Furthermore, time-lapse microscopy of twin sporulation in wild-type Clostridium oceanicum shows a strong resemblance to twin sporulation in these B. subtilis mutants(9,10). Together the results suggest that noise can facilitate developmental evolution by enabling the initial expression of discrete morphological traits at low penetrance, and allowing their stabilization by gradual adjustment of genetic parameters.
C1 [Eldar, Avigdor; Fontes, Michelle E.; Loson, Oliver C.; Elowitz, Michael B.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [Eldar, Avigdor; Fontes, Michelle E.; Loson, Oliver C.; Elowitz, Michael B.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Eldar, Avigdor; Fontes, Michelle E.; Loson, Oliver C.; Elowitz, Michael B.] CALTECH, Dept Appl Phys, Pasadena, CA 91125 USA.
   [Chary, Vasant K.; Xenopoulos, Panagiotis; Piggot, Patrick J.] Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA.
   [Dworkin, Jonathan] Columbia Univ, Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA.
C3 California Institute of Technology; Howard Hughes Medical Institute; California Institute of Technology; California Institute of Technology; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University; Columbia University
RP Elowitz, MB (corresponding author), CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
EM melowitz@caltech.edu
FU US National Institutes of Health (NIH) [GM43577]; NIH [R01GM079771, P50 GM068763]; US National Science Foundation CAREER Award [0644463]; Packard Foundation; International Human Frontier Science Organization; European Molecular Biology Organization; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0644463] Funding Source: National Science Foundation
NR 34
TC 108
Z9 122
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 510
EP U86
DI 10.1038/nature08150
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000038
PM 19578359
DA 2026-03-09
ER

PT J
AU Zanoni, I
   Ostuni, R
   Capuano, G
   Collini, M
   Caccia, M
   Ronchi, AE
   Rocchetti, M
   Mingozzi, F
   Foti, M
   Chirico, G
   Costa, B
   Zaza, A
   Ricciardi-Castagnoli, P
   Granucci, F
AF Zanoni, Ivan
   Ostuni, Renato
   Capuano, Giusy
   Collini, Maddalena
   Caccia, Michele
   Ronchi, Antonella Ellena
   Rocchetti, Marcella
   Mingozzi, Francesca
   Foti, Maria
   Chirico, Giuseppe
   Costa, Barbara
   Zaza, Antonio
   Ricciardi-Castagnoli, Paola
   Granucci, Francesca
TI CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation
SO NATURE
LA English
DT Article
ID necrosis-factor-alpha; t-cells; il-2 production; receptors; induction; macrophages; resistance; proteins; bacteria; immunity
AB Toll-like receptors (TLRs) are the best characterized pattern recognition receptors(1). Individual TLRs recruit diverse combinations of adaptor proteins, triggering signal transduction pathways and leading to the activation of various transcription factors, including nuclear factor kappa B, activation protein 1 and interferon regulatory factors(2). Interleukin-2 is one of the molecules produced by mouse dendritic cells after stimulation by different pattern recognition receptor agonists(3-6). By analogy with the events after T-cell receptor engagement leading to interleukin-2 production, it is therefore plausible that the stimulation of TLRs on dendritic cells may lead to activation of the Ca2+/calcineurin and NFAT (nuclear factor of activated T cells) pathway. Here we show that mouse dendritic cell stimulation with lipopolysaccharide (LPS) induces Src-family kinase and phospholipase C gamma 2 activation, influx of extracellular Ca2+ and calcineurin-dependent nuclear NFAT translocation. The initiation of this pathway is independent of TLR4 engagement, and dependent exclusively on CD14. We also show that LPS-induced NFAT activation via CD14 is necessary to cause the apoptotic death of terminally differentiated dendritic cells, an event that is essential for maintaining self-tolerance and preventing autoimmunity(7,8). Consequently, blocking this pathway in vivo causes prolonged dendritic cell survival and an increase in T-cell priming capability. Our findings reveal novel aspects of molecular signalling triggered by LPS in dendritic cells, and identify a new role for CD14: the regulation of the dendritic cell life cycle through NFAT activation. Given the involvement of CD14 in disease, including sepsis and chronic heart failure(9,10), the discovery of signal transduction pathways activated exclusively via CD14 is an important step towards the development of potential treatments involving interference with CD14 functions.
C1 [Zanoni, Ivan; Ostuni, Renato; Capuano, Giusy; Ronchi, Antonella Ellena; Rocchetti, Marcella; Mingozzi, Francesca; Foti, Maria; Costa, Barbara; Zaza, Antonio; Ricciardi-Castagnoli, Paola; Granucci, Francesca] Univ Milano Bicocca, Dept Biosci & Biotechnol, I-20126 Milan, Italy.
   [Collini, Maddalena; Caccia, Michele; Chirico, Giuseppe] Univ Milano Bicocca, Dept Phys, I-20126 Milan, Italy.
C3 University of Milano-Bicocca; University of Milano-Bicocca
RP Granucci, F (corresponding author), Univ Milano Bicocca, Dept Biosci & Biotechnol, Piazza Sci 2, I-20126 Milan, Italy.
EM francesca.granucci@unimib.it
FU CARIPLO Foundation; European Commission; Associazione Italiana per la Ricerca sul Cancro (AIRC); Italian Ministry of Education and Research (COFIN)
NR 33
TC 259
Z9 308
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 264
EP U130
DI 10.1038/nature08118
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000042
PM 19525933
DA 2026-03-09
ER

PT J
AU Wittebolle, L
   Marzorati, M
   Clement, L
   Balloi, A
   Daffonchio, D
   Heylen, K
   De Vos, P
   Verstraete, W
   Boon, N
AF Wittebolle, Lieven
   Marzorati, Massimo
   Clement, Lieven
   Balloi, Annalisa
   Daffonchio, Daniele
   Heylen, Kim
   De Vos, Paul
   Verstraete, Willy
   Boon, Nico
TI Initial community evenness favours functionality under selective stress
SO NATURE
LA English
DT Article
ID current knowledge; species richness; biodiversity; diversity; stability; ecology; productivity; redundancy; systems
AB Owing to the present global biodiversity crisis, the biodiversity-stability relationship and the effect of biodiversity on ecosystem functioning have become major topics in ecology(1-3). Biodiversity is a complex term that includes taxonomic, functional, spatial and temporal aspects of organismic diversity, with species richness (the number of species) and evenness (the relative abundance of species) considered among the most important measures(4,5). With few exceptions (see, for example, ref. 6), the majority of studies of biodiversity-functioning and biodiversity-stability theory have predominantly examined richness(7-11). Here we show, using microbial microcosms, that initial community evenness is a key factor in preserving the functional stability of an ecosystem. Using experimental manipulations of both richness and initial evenness in microcosms with denitrifying bacterial communities, we found that the stability of the net ecosystem denitrification in the face of salinity stress was strongly influenced by the initial evenness of the community. Therefore, when communities are highly uneven, or there is extreme dominance by one or a few species, their functioning is less resistant to environmental stress. Further unravelling how evenness influences ecosystem processes in natural and humanized environments constitutes a major future conceptual challenge.
C1 [Wittebolle, Lieven; Marzorati, Massimo; Verstraete, Willy; Boon, Nico] Univ Ghent, Lab Microbial Ecol & Technol, LabMET, B-9000 Ghent, Belgium.
   [Clement, Lieven] Univ Ghent, BIOSTAT, Dept Appl Math Biometr & Proc Control, B-9000 Ghent, Belgium.
   [Heylen, Kim; De Vos, Paul] Univ Ghent, Microbiol Lab, Dept Biochem Physiol & Microbiol, LM UGent, B-9000 Ghent, Belgium.
   [Balloi, Annalisa; Daffonchio, Daniele] Univ Milan, Dipartimento Sci & Tecnol Alimentari & Microbiol, DISTAM, I-20133 Milan, Italy.
C3 Ghent University; Ghent University; Ghent University; University of Milan
RP Boon, N (corresponding author), Univ Ghent, Lab Microbial Ecol & Technol, LabMET, B-9000 Ghent, Belgium.
EM nico.boon@ugent.be
FU Institute for the Promotion of Innovation through Science and Technology in Flanders; Interuniversity Attraction Pole research network grant of the Belgian government, Belgian Science Policy; 'Program Master and Back' from Regione Sardegna; 'Programma dell'Universita' per la Ricerca,; Geconcerteerde Onderzoeksactie of Ghent University; Ministerie van de Vlaamse Gemeenschap; Bestuur Wetenschappelijk Onderzoek
NR 30
TC 792
Z9 914
U1 13
U2 478
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 2
PY 2009
VL 458
IS 7238
BP 623
EP 626
DI 10.1038/nature07840
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200039
PM 19270679
DA 2026-03-09
ER

PT J
AU Lee, JY
   Hong, BH
   Kim, WY
   Min, SK
   Kim, Y
   Jouravlev, MV
   Bose, R
   Kim, KS
   Hwang, IC
   Kaufman, LJ
   Wong, CW
   Kim, P
   Kim, KS
AF Lee, Ju Young
   Hong, Byung Hee
   Kim, Woo Youn
   Min, Seung Kyu
   Kim, Yukyung
   Jouravlev, Mikhail V.
   Bose, Ranojoy
   Kim, Keun Soo
   Hwang, In-Chul
   Kaufman, Laura J.
   Wong, Chee Wei
   Kim, Philip
   Kim, Kwang S.
TI Near-field focusing and magnification through self-assembled nanoscale spherical lenses
SO NATURE
LA English
DT Article
ID microlenses; resolution; arrays
AB It is well known that a lens-based far-field optical microscope cannot resolve two objects beyond Abbe's diffraction limit. Recently, it has been demonstrated that this limit can be overcome by lensing effects driven by surface-plasmon excitation(1-3), and by fluorescence microscopy driven by molecular excitation(4). However, the resolution obtained using geometrical lens-based optics without such excitation schemes remains limited by Abbe's law even when using the immersion technique(5), which enhances the resolution by increasing the refractive indices of immersion liquids. As for submicrometre-scale or nanoscale objects, standard geometrical optics fails for visible light because the interactions of such objects with light waves are described inevitably by near-field optics(6). Here we report near-field high resolution by nanoscale spherical lenses that are self-assembled by bottom-up integration(7) of organic molecules. These nano-lenses, in contrast to geometrical optics lenses, exhibit curvilinear trajectories of light, resulting in remarkably short near-field focal lengths. This in turn results in near-field magnification that is able to resolve features beyond the diffraction limit. Such spherical nanolenses provide new pathways for lens-based near-field focusing and high-resolution optical imaging at very low intensities, which are useful for bio-imaging, near-field lithography, optical memory storage, light harvesting, spectral signal enhancing, and optical nano-sensing.
C1 [Lee, Ju Young; Hong, Byung Hee; Kim, Woo Youn; Min, Seung Kyu; Kim, Yukyung; Jouravlev, Mikhail V.; Hwang, In-Chul; Kim, Kwang S.] Pohang Univ Sci & Technol, Dept Chem, Ctr Superfunct Mat, Pohang 790784, South Korea.
   [Hong, Byung Hee; Kim, Keun Soo] Sungkyunkwan Univ, Dept Chem, Suwon 440746, South Korea.
   [Hong, Byung Hee; Kim, Keun Soo] Sungkyunkwan Univ, SKKU Adv Inst Nanotechnol, Suwon 440746, South Korea.
   [Bose, Ranojoy; Wong, Chee Wei] Columbia Univ, Dept Mech Engn, New York, NY 10027 USA.
   [Kaufman, Laura J.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
   [Kim, Philip] Columbia Univ, Dept Phys, New York, NY 10027 USA.
C3 Pohang University of Science & Technology (POSTECH); Sungkyunkwan University (SKKU); Sungkyunkwan University (SKKU); Columbia University; Columbia University; Columbia University
RP Kim, KS (corresponding author), Pohang Univ Sci & Technol, Dept Chem, Ctr Superfunct Mat, Pohang 790784, South Korea.; Kim, P (corresponding author), Columbia Univ, Dept Phys, New York, NY 10027 USA.
EM pkim@phys.columbia.edu; kim@postech.ac.kr
FU Korea Foundation for International Cooperation of Science and Technology; Korea Government [R32-2008-000-10180-0, R33-2008-000-10138-0, 2009-0063312, 2009-0062808, 2009-0060271]; Brain Korea 21 (Korea Research Foundation); National Science Foundation [CHE-0641523, ECCS-0747787]; New York State Office of Science (NYSTAR)
NR 28
TC 351
Z9 387
U1 1
U2 267
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 498
EP 501
DI 10.1038/nature08173
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000035
DA 2026-03-09
ER

PT J
AU Raya, A
   Rodríguez-Pizà, I
   Guenechea, G
   Vassena, R
   Navarro, S
   Barrero, MJ
   Consiglio, A
   Castellà, M
   Rìo, P
   Sleep, E
   González, F
   Tiscornia, G
   Garreta, E
   Aasen, T
   Veiga, A
   Verma, IM
   Surrallés, J
   Bueren, J
   Belmonte, JCI
AF Raya, Angel
   Rodriguez-Piza, Ignasi
   Guenechea, Guillermo
   Vassena, Rita
   Navarro, Susana
   Jose Barrero, Maria
   Consiglio, Antonella
   Castella, Maria
   Rio, Paula
   Sleep, Eduard
   Gonzalez, Federico
   Tiscornia, Gustavo
   Garreta, Elena
   Aasen, Trond
   Veiga, Anna
   Verma, Inder M.
   Surralles, Jordi
   Bueren, Juan
   Izpisua Belmonte, Juan Carlos
TI Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID lentiviral vectors; gene-therapy; generation; mouse; efficient; fibroblasts; mosaicism; promoter; fancd2; damage
AB The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.
C1 [Raya, Angel; Rodriguez-Piza, Ignasi; Navarro, Susana; Jose Barrero, Maria; Sleep, Eduard; Gonzalez, Federico; Tiscornia, Gustavo; Garreta, Elena; Aasen, Trond; Veiga, Anna; Izpisua Belmonte, Juan Carlos] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain.
   [Raya, Angel] ICREA, Madrid 28040, Spain.
   [Raya, Angel; Sleep, Eduard; Garreta, Elena; Aasen, Trond] Networking Ctr Biomed Res Bioengn Biomat & Nanome, Madrid 28040, Spain.
   [Guenechea, Guillermo; Navarro, Susana; Rio, Paula; Bueren, Juan] CIEMAT, Hematopoiesis & Gene Therapy Div, E-28040 Madrid, Spain.
   [Guenechea, Guillermo; Navarro, Susana; Castella, Maria; Rio, Paula; Surralles, Jordi; Bueren, Juan] Networking Ctr Biomed Res Rare Dis CIBERER, I-25123 Brescia, Italy.
   [Consiglio, Antonella] Univ Brescia, Dept Biomed Sci & Biotechnol, I-25123 Brescia, Italy.
   [Castella, Maria; Surralles, Jordi] Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain.
   [Verma, Inder M.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
C3 Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro de Medicina Regenerativa de Barcelona; University of Barcelona; ICREA; Centro de Investigaciones Energeticas, Medioambientales Tecnologicas; University of Brescia; Autonomous University of Barcelona; Salk Institute; Salk Institute
RP Belmonte, JCI (corresponding author), Ctr Regenerat Med Barcelona, Dr Aiguader 88, Barcelona 08003, Spain.
EM belmonte@salk.edu
FU MEC; DIUE; Ramon y Cajal program; ICREA-Academia program; Ministerio de Educacion y Ciencia [BFU2006-12251, SAF2005-00058, SAF2006-3440]; Genoma Espana (FANCOGENE); European Commission 'Marie-Curie Reintegration Grant' [MIRG-CT-2007-046523]; European Program CONSERT [LSHB-CT-2004-5242]; Fondo de Investigaciones Sanitarias [RETIC-RD06/0010/0016, PI061897, PI061099]; Marato de TV3 [063430]; G. Harold and Leila Y. Mathers Charitable Foundation; Fundacion Marcelino Botin; Fundacion Cellex; ICREA Funding Source: Custom
NR 48
TC 550
Z9 642
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 JUL 2
PY 2009
VL 460
IS 7251
BP 53
EP U61
DI 10.1038/nature08129
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200028
PM 19483674
DA 2026-03-09
ER

PT J
AU Kosynkin, DV
   Higginbotham, AL
   Sinitskii, A
   Lomeda, JR
   Dimiev, A
   Price, BK
   Tour, JM
AF Kosynkin, Dmitry V.
   Higginbotham, Amanda L.
   Sinitskii, Alexander
   Lomeda, Jay R.
   Dimiev, Ayrat
   Price, B. Katherine
   Tour, James M.
TI Longitudinal unzipping of carbon nanotubes to form graphene nanoribbons
SO NATURE
LA English
DT Article
ID exfoliated graphite oxide; aqueous dispersions; chemical-reduction; films; permanganate; nanosheets; oxidation; phase
AB Graphene, or single-layered graphite, with its high crystallinity and interesting semimetal electronic properties, has emerged as an exciting two-dimensional material showing great promise for the fabrication of nanoscale devices(1-3). Thin, elongated strips of graphene that possess straight edges, termed graphene ribbons, gradually transform from semiconductors to semimetals as their width increases(4-7), and represent a particularly versatile variety of graphene. Several lithographic(7,8), chemical(9-11) and synthetic(12) procedures are known to produce microscopic samples of graphene nanoribbons, and one chemical vapour deposition process(13) has successfully produced macroscopic quantities of nanoribbons at 950 degrees C. Here we describe a simple solution-based oxidative process for producing a nearly 100% yield of nanoribbon structures by lengthwise cutting and unravelling of multiwalled carbon nanotube (MWCNT) side walls. Although oxidative shortening of MWCNTs has previously been achieved(14), lengthwise cutting is hitherto unreported. Ribbon structures with high water solubility are obtained. Subsequent chemical reduction of the nanoribbons from MWCNTs results in restoration of electrical conductivity. These early results affording nanoribbons could eventually lead to applications in fields of electronics and composite materials where bulk quantities of nanoribbons are required(15-17).
C1 [Kosynkin, Dmitry V.; Higginbotham, Amanda L.; Sinitskii, Alexander; Lomeda, Jay R.; Dimiev, Ayrat; Price, B. Katherine; Tour, James M.] Rice Univ, Dept Chem, Houston, TX 77005 USA.
   [Tour, James M.] Rice Univ, Dept Mech Engn & Mat Sci, Houston, TX 77005 USA.
   [Tour, James M.] Rice Univ, 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, MS 222,6100 Main St, Houston, TX 77005 USA.
EM tour@rice.edu
FU US Defense Advanced Research Projects Agency; US Federal Aviation Administration, Department of Energy [DE-FC-36-05GO15073]; Wright Patterson Air Force Laboratory through the US Air Force Office of Scientific Research
NR 30
TC 3054
Z9 3514
U1 15
U2 2126
PU 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 16
PY 2009
VL 458
IS 7240
BP 872
EP U5
DI 10.1038/nature07872
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433CS
UT WOS:000265182500039
PM 19370030
DA 2026-03-09
ER

PT J
AU Powner, MW
   Gerland, B
   Sutherland, JD
AF Powner, Matthew W.
   Gerland, Beatrice
   Sutherland, John D.
TI Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions
SO NATURE
LA English
DT Article
ID nucleosides; rna; phosphorylation; phosphorus; chemistry; phosphate; evolution; minerals; cytidine; origin
AB At some stage in the origin of life, an informational polymer must have arisen by purely chemical means. According to one version of the 'RNA world' hypothesis(1-3) this polymer was RNA, but attempts to provide experimental support for this have failed(4,5). In particular, although there has been some success demonstrating that 'activated' ribonucleotides can polymerize to form RNA(6,7), it is far from obvious how such ribonucleotides could have formed from their constituent parts ( ribose and nucleobases). Ribose is difficult to form selectively(8,9), and the addition of nucleobases to ribose is inefficient in the case of purines(10) and does not occur at all in the case of the canonical pyrimidines(11). Here we show that activated pyrimidine ribonucleotides can be formed in a short sequence that bypasses free ribose and the nucleobases, and instead proceeds through arabinose amino-oxazoline and anhydronucleoside intermediates. The starting materials for the synthesis-cyanamide, cyanoacetylene, glycolaldehyde, glyceraldehyde and inorganic phosphate-are plausible prebiotic feedstock molecules(12-15), and the conditions of the synthesis are consistent with potential early-Earth geochemical models. Although inorganic phosphate is only incorporated into the nucleotides at a late stage of the sequence, its presence from the start is essential as it controls three reactions in the earlier stages by acting as a general acid/base catalyst, a nucleophilic catalyst, a pH buffer and a chemical buffer. For prebiotic reaction sequences, our results highlight the importance of working with mixed chemical systems in which reactants for a particular reaction step can also control other steps.
C1 [Powner, Matthew W.; Gerland, Beatrice; Sutherland, John D.] Univ Manchester, Sch Chem, Manchester M13 9PL, Lancs, England.
C3 University of Manchester
RP Sutherland, JD (corresponding author), Univ Manchester, Sch Chem, Oxford Rd, Manchester M13 9PL, Lancs, England.
EM john.sutherland@manchester.ac.uk
FU UK Engineering and Physical Sciences Research Council; Engineering and Physical Sciences Research Council [EP/D05592X/1, EP/E032753/1] Funding Source: researchfish; EPSRC [EP/D05592X/1, EP/E032753/1] Funding Source: UKRI
NR 30
TC 993
Z9 1129
U1 7
U2 456
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 14
PY 2009
VL 459
IS 7244
BP 239
EP 242
DI 10.1038/nature08013
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 445FR
UT WOS:000266036100038
PM 19444213
DA 2026-03-09
ER

PT J
AU Martin, AC
   Kaschube, M
   Wieschaus, EF
AF Martin, Adam C.
   Kaschube, Matthias
   Wieschaus, Eric F.
TI Pulsed contractions of an actin-myosin network drive apical constriction
SO NATURE
LA English
DT Article
ID cell-shape changes; drosophila gastrulation; folded-gastrulation; adherens junctions; morphogenesis; microfilaments; localization; microtubules; neurulation; mechanism
AB Apical constriction facilitates epithelial sheet bending and invagination during morphogenesis(1,2). Apical constriction is conventionally thought to be driven by the continuous purse- string- like contraction of a circumferential actin and non- muscle myosin- II ( myosin) belt underlying adherens junctions(3-7). However, it is unclear whether other force- generating mechanisms can drive this process. Here we show, with the use of real- time imaging and quantitative image analysis of Drosophila gastrulation, that the apical constriction of ventral furrow cells is pulsed. Repeated constrictions, which are asynchronous between neighbouring cells, are interrupted by pauses in which the constricted state of the cell apex is maintained. In contrast to the purse- string model, constriction pulses are powered by actin - myosin network contractions that occur at the medial apical cortex and pull discrete adherens junction sites inwards. The transcription factors Twist and Snail differentially regulate pulsed constriction. Expression of snail initiates actin - myosin network contractions, whereas expression of twist stabilizes the constricted state of the cell apex. Our results suggest a new model for apical constriction in which a cortical actin - myosin cytoskeleton functions as a developmentally controlled subcellular ratchet to reduce apical area incrementally.
C1 [Martin, Adam C.; Wieschaus, Eric F.] Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
   [Martin, Adam C.; Wieschaus, Eric F.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Kaschube, Matthias] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Kaschube, Matthias] Princeton Univ, Joseph Henry Labs Phys, Princeton, NJ 08544 USA.
C3 Howard Hughes Medical Institute; Princeton University; Princeton University; Princeton University; Princeton University
RP Wieschaus, EF (corresponding author), Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
EM efw@princeton.edu
FU American Cancer Society [PF-06-143-01-DDC]; National Institutes of Health/National Institute of General Medical Sciences [P50 GM071508]; National Institute of Child Health and Human Development [5R37HD15587]
NR 29
TC 947
Z9 1144
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 JAN 22
PY 2009
VL 457
IS 7228
BP 495
EP U11
DI 10.1038/nature07522
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200050
PM 19029882
DA 2026-03-09
ER

PT J
AU Viale, A
   De Franco, F
   Orleth, A
   Cambiaghi, V
   Giuliani, V
   Bossi, D
   Ronchini, C
   Ronzoni, S
   Muradore, I
   Monestiroli, S
   Gobbi, A
   Alcalay, M
   Minucci, S
   Pelicci, PG
AF Viale, Andrea
   De Franco, Francesca
   Orleth, Annette
   Cambiaghi, Valeria
   Giuliani, Virginia
   Bossi, Daniela
   Ronchini, Chiara
   Ronzoni, Simona
   Muradore, Ivan
   Monestiroli, Silvia
   Gobbi, Alberto
   Alcalay, Myriam
   Minucci, Saverio
   Pelicci, Pier Giuseppe
TI Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; oncogene-induced senescence; hematopoietic stem; repopulating ability; progenitor cells; gene-transfer; repair; replication; expression; breaks
AB Rare cells with the properties of stem cells are integral to the development and perpetuation of leukaemias. A defining characteristic of stem cells is their capacity to self- renew, which is markedly extended in leukaemia stem cells. The underlying molecular mechanisms, however, are largely unknown. Here we demonstrate that expression of the cell- cycle inhibitor p21 is indispensable for maintaining self- renewal of leukaemia stem cells. Expression of leukaemia- associated oncogenes in mouse haematopoietic stem cells ( HSCs) induces DNA damage and activates a p21- dependent cellular response, which leads to reversible cell- cycle arrest and DNA repair. Activated p21 is critical in preventing excess DNA- damage accumulation and functional exhaustion of leukaemic stem cells. These data unravel the oncogenic potential of p21 and suggest that inhibition of DNA repair mechanisms might function as potent strategy for the eradication of the slowly proliferating leukaemia stem cells.
C1 [Viale, Andrea; De Franco, Francesca; Orleth, Annette; Cambiaghi, Valeria; Giuliani, Virginia; Bossi, Daniela; Ronchini, Chiara; Ronzoni, Simona; Muradore, Ivan; Monestiroli, Silvia; Gobbi, Alberto; Alcalay, Myriam; Minucci, Saverio; Pelicci, Pier Giuseppe] European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy.
   [De Franco, Francesca; Orleth, Annette] Univ Perugia, Dipartimento Med Clin & Sperimentale, Monteluce Policlin, I-06100 Perugia, Italy.
   [Minucci, Saverio] Univ Milan, Dipartimento Sci Biomol & Biotecnol, I-20100 Milan, Italy.
   [Alcalay, Myriam; Pelicci, Pier Giuseppe] Univ Milan, Dipartimento Med Chirurg & Odontoiatria, I-20100 Milan, Italy.
C3 IRCCS European Institute of Oncology (IEO); University of Perugia; University of Milan; University of Milan
RP Viale, A (corresponding author), European Inst Oncol, Dept Expt Oncol, IFOM IEO Campus, I-20141 Milan, Italy.
EM andrea.viale@ifom-ieo-campus.it; piergiuseppe.pelicci@ifom-ieo-campus.it
FU Italian Association on Cancer Research; Ministero Italiano della Salute, Cariplo; European Community (FP6: EPITRON and GENICA); Vollaro Foundation
NR 46
TC 250
Z9 291
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 1
PY 2009
VL 457
IS 7225
BP 51
EP U52
DI 10.1038/nature07618
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 389OR
UT WOS:000262104900028
PM 19122635
DA 2026-03-09
ER

PT J
AU Keller, GB
   Hahnloser, RHR
AF Keller, Georg B.
   Hahnloser, Richard H. R.
TI Neural processing of auditory feedback during vocal practice in a songbird
SO NATURE
LA English
DT Article
ID male zebra finches; adult birdsong; system; telencephalon; perturbation; connections; behavior; neurons; cortex; model
AB Songbirds are capable of vocal learning and communication(1,2) and are ideally suited to the study of neural mechanisms of complex sensory and motor processing. Vocal communication in a noisy bird colony and vocal learning of a specific song template both require the ability to monitor auditory feedback(3,4) to distinguish self-generated vocalizations from external sounds and to identify mismatches between the developing song and a memorized template acquired from a tutor(5). However, neurons that respond to auditory feedback from vocal output have not been found in song-control areas despite intensive searching(6-8). Here we investigate feedback processing outside the traditional song system, in single auditory forebrain neurons of juvenile zebra finches that were in a late developmental stage of song learning. Overall, we found similarity of spike responses during singing and during playback of the bird's own song, with song responses commonly leading by a few milliseconds. However, brief time- locked acoustic perturbations of auditory feedback revealed complex sensitivity that could not be predicted from passive playback responses. Some neurons that responded to playback perturbations did not respond to song perturbations, which is reminiscent of sensory- motor mirror neurons(8,9). By contrast, some neurons were highly feedback sensitive in that they responded vigorously to song perturbations, but not to unperturbed songs or perturbed playback. These findings suggest that a computational function of forebrain auditory areas may be to detect errors between actual feedback and mirrored feedback deriving from an internal model of the bird's own song or that of its tutor. Such feedback- sensitive spikes could constitute the key signals that trigger adaptive motor responses to song disruptions(10,11) or reinforce exploratory motor gestures for vocal learning(12).
C1 [Keller, Georg B.; Hahnloser, Richard H. R.] Univ Zurich, ETH, Inst Neuroinformat, CH-8057 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich
RP Hahnloser, RHR (corresponding author), Univ Zurich, ETH, Inst Neuroinformat, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM rich@ini.phys.ethz.ch
FU Swiss National Science Foundation
NR 30
TC 164
Z9 196
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 8
PY 2009
VL 457
IS 7226
BP 187
EP U78
DI 10.1038/nature07467
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200031
PM 19005471
DA 2026-03-09
ER

PT J
AU Meng, JQ
   Liu, GD
   Zhang, WT
   Zhao, L
   Liu, HY
   Jia, XW
   Mu, DX
   Liu, SY
   Dong, XL
   Zhang, J
   Lu, W
   Wang, GL
   Zhou, Y
   Zhu, Y
   Wang, XY
   Xu, ZY
   Chen, CT
   Zhou, XJ
AF Meng, Jianqiao
   Liu, Guodong
   Zhang, Wentao
   Zhao, Lin
   Liu, Haiyun
   Jia, Xiaowen
   Mu, Daixiang
   Liu, Shanyu
   Dong, Xiaoli
   Zhang, Jun
   Lu, Wei
   Wang, Guiling
   Zhou, Yong
   Zhu, Yong
   Wang, Xiaoyang
   Xu, Zuyan
   Chen, Chuangtian
   Zhou, X. J.
TI Coexistence of Fermi arcs and Fermi pockets in a high-Tc copper oxide superconductor
SO NATURE
LA English
DT Article
ID high-temperature superconductors; quantum oscillations; surface; bi2sr2cacu2o8+delta; evolution; pseudogap; state; gap
AB In the pseudogap state of the high-transition-temperature (high-T-c) copper oxide superconductors(1), angle-resolved photoemission (ARPES) measurements have seen Fermi arcs-that is, open-ended gapless sections in the large Fermi surface(2-8)-rather than a closed loop expected of an ordinary metal. This is all the more puzzling because Fermi pockets (small closed Fermi surface features) have been suggested by recent quantum oscillation measurements(9-14). The Fermi arcs cannot be understood in terms of existing theories, although there is a solution in the form of conventional Fermi surface pockets associated with competing order, but with a back side that is for detailed reasons invisible to photoemission probes(15). Here we report ARPES measurements of Bi2Sr2-xLaxCuO6+delta (La-Bi2201) that reveal Fermi pockets. The charge carriers in the pockets are holes, and the pockets show an unusual dependence on doping: they exist in underdoped but not overdoped samples. A surprise is that these Fermi pockets appear to coexist with the Fermi arcs. This coexistence has not been expected theoretically.
C1 [Meng, Jianqiao; Liu, Guodong; Zhang, Wentao; Zhao, Lin; Liu, Haiyun; Jia, Xiaowen; Mu, Daixiang; Liu, Shanyu; Dong, Xiaoli; Zhang, Jun; Lu, Wei; Zhou, X. J.] Chinese Acad Sci, Inst Phys, Beijing Natl Lab Condensed Matter Phys, Natl Lab Superconduct, Beijing 100190, Peoples R China.
   [Wang, Guiling; Zhou, Yong; Zhu, Yong; Wang, Xiaoyang; Xu, Zuyan; Chen, Chuangtian] Chinese Acad Sci, Tech Inst Phys & Chem, Beijing 100190, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Physics, CAS; Chinese Academy of Sciences; Technical Institute of Physics & Chemistry, CAS
RP Zhou, XJ (corresponding author), Chinese Acad Sci, Inst Phys, Beijing Natl Lab Condensed Matter Phys, Natl Lab Superconduct, Beijing 100190, Peoples R China.
EM XJZhou@aphy.iphy.ac.cn
FU NSFC; MOST of China; Chinese Academy of Sciences
NR 32
TC 203
Z9 226
U1 2
U2 143
PU 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 19
PY 2009
VL 462
IS 7271
BP 335
EP 338
DI 10.1038/nature08521
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 521DF
UT WOS:000271899300040
PM 19924210
DA 2026-03-09
ER

