PT J
AU Setiawan, J
   Henning, T
   Launhardt, R
   Müller, A
   Weise, P
   Kürster, M
AF Setiawan, J.
   Henning, Th.
   Launhardt, R.
   Mueller, A.
   Weise, P.
   Kuerster, M.
TI A young massive planet in a star-disk system
SO NATURE
LA English
DT Article
ID t-tauri stars; inner disk; giant; accretion; hydrae; gas; variability; companion; evolution; models
AB There is a general consensus that planets form within disks of dust and gas around newly born stars(1,2). Details of their formation process, however, are still a matter of ongoing debate. The timescale of planet formation remains unclear, so the detection of planets around young stars with protoplanetary disks is potentially of great interest. Hitherto, no such planet has been found. Here we report the detection of a planet of mass (9.8 +/- 3.3) M-Jupiter around TW Hydrae (TW Hya), a nearby young star with an age of only 8-10 Myr that is surrounded by a well- studied circumstellar disk. It orbits the star with a period of 3.56 days at 0.04 AU, inside the inner rim of the disk. This demonstrates that planets can form within 10 Myr, before the disk has been dissipated by stellar winds and radiation.
C1 [Setiawan, J.; Henning, Th.; Launhardt, R.; Mueller, A.; Weise, P.; Kuerster, M.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
C3 Max Planck Society
RP Setiawan, J (corresponding author), Max Planck Inst Astron, D-69117 Heidelberg, Germany.
EM setiawan@mpia.de; rlau@mpia.de
NR 29
TC 128
Z9 134
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 JAN 3
PY 2008
VL 451
IS 7174
BP 38
EP 41
DI 10.1038/nature06426
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300027
PM 18172492
DA 2026-03-09
ER

PT J
AU Cai, CL
   Martin, JC
   Sun, YF
   Cui, L
   Wang, LC
   Ouyang, K
   Yang, L
   Bu, L
   Liang, XQ
   Zhang, XX
   Stallcup, WB
   Denton, CP
   McCulloch, A
   Chen, J
   Evans, SM
AF Cai, Chen-Leng
   Martin, Jody C.
   Sun, Yunfu
   Cui, Li
   Wang, Lianchun
   Ouyang, Kunfu
   Yang, Lei
   Bu, Lei
   Liang, Xingqun
   Zhang, Xiaoxue
   Stallcup, William B.
   Denton, Christopher P.
   McCulloch, Andrew
   Chen, Ju
   Evans, Sylvia M.
TI A myocardial lineage derives from Tbx18 epicardial cells
SO NATURE
LA English
DT Article
ID smooth-muscle-cells; pericardial mesoderm; heart; population; expression; mouse; differentiation; morphogenesis; mesothelium; septum
AB Understanding the origins and roles of cardiac progenitor cells is important for elucidating the pathogenesis of congenital and acquired heart diseases(1,2). Moreover, manipulation of cardiac myocyte progenitors has potential for cell- based repair strategies for various myocardial disorders(3). Here we report the identification in mouse of a previously unknown cardiac myocyte lineage that derives from the proepicardial organ. These progenitor cells, which express the T- box transcription factor Tbx18, migrate onto the outer cardiac surface to form the epicardium, and then make a substantial contribution to myocytes in the ventricular septum and the atrial and ventricular walls. Tbx18- expressing cardiac progenitors also give rise to cardiac fibroblasts and coronary smooth muscle cells. The pluripotency of Tbx18 proepicardial cells provides a theoretical framework for applying these progenitors to effect cardiac repair and regeneration.
C1 [Cai, Chen-Leng; Sun, Yunfu; Cui, Li; Yang, Lei; Bu, Lei; Zhang, Xiaoxue; Evans, Sylvia M.] Univ Calif San Diego, Skaggs Sch Pharm, La Jolla, CA 92093 USA.
   [Martin, Jody C.; McCulloch, Andrew] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Ouyang, Kunfu; Liang, Xingqun; Chen, Ju; Evans, Sylvia M.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Cai, Chen-Leng] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA.
   [Cai, Chen-Leng] Mt Sinai Sch Med, Ctr Mol Cardiol, New York, NY 10029 USA.
   [Cai, Chen-Leng] Mt Sinai Sch Med, Black Family Stem Cell Inst, New York, NY 10029 USA.
   [Wang, Lianchun] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA.
   [Stallcup, William B.] Burnham Inst, Dev Neurobiol Programme, La Jolla, CA 92037 USA.
   [Denton, Christopher P.] UCL Royal Free & Univ Coll Med Sch, Ctr Rheumatol, London NW3 2PF, England.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University System of Georgia; University of Georgia; Sanford Burnham Prebys Medical Discovery Institute; University of London; University College London; UCL Medical School
RP Evans, SM (corresponding author), Univ Calif San Diego, Skaggs Sch Pharm, La Jolla, CA 92093 USA.
EM syevans@ucsd.edu
FU National Heart Lung and Blood Institute [T32HL007444] Funding Source: NIH RePORTER; NCRR NIH HHS [P41 RR005351] Funding Source: Medline; NHLBI NIH HHS [T32 HL007444, R01 HL070867, DP1 HL117649] Funding Source: Medline; NIH HHS [DP1 OD006428] Funding Source: Medline
NR 29
TC 627
Z9 779
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 104
EP U4
DI 10.1038/nature06969
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300046
PM 18480752
DA 2026-03-09
ER

PT J
AU Prather, JF
   Peters, S
   Nowicki, S
   Mooney, R
AF Prather, J. F.
   Peters, S.
   Nowicki, S.
   Mooney, R.
TI Precise auditory-vocal mirroring in neurons for learned vocal communication
SO NATURE
LA English
DT Article
ID identified hvc neurons; zebra finch; action recognition; premotor cortex; efference copy; adult song; mechanisms; language; nucleus; lesions
AB Brain mechanisms for communication must establish a correspondence between sensory and motor codes used to represent the signal. One idea is that this correspondence is established at the level of single neurons that are active when the individual performs a particular gesture or observes a similar gesture performed by another individual. Although neurons that display a precise auditory- vocal correspondence could facilitate vocal communication, they have yet to be identified. Here we report that a certain class of neurons in the swamp sparrow forebrain displays a precise auditory- vocal correspondence. We show that these neurons respond in a temporally precise fashion to auditory presentation of certain note sequences in this songbird's repertoire and to similar note sequences in other birds' songs. These neurons display nearly identical patterns of activity when the bird sings the same sequence, and disrupting auditory feedback does not alter this singing- related activity, indicating it is motor in nature. Furthermore, these neurons innervate striatal structures important for song learning, raising the possibility that singing- related activity in these cells is compared to auditory feedback to guide vocal learning.
C1 [Prather, J. F.; Nowicki, S.; Mooney, R.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
   [Peters, S.; Nowicki, S.] Duke Univ, Dept Biol, Durham, NC 27710 USA.
C3 Duke University; Duke University
RP Mooney, R (corresponding author), Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
EM mooney@neuro.duke.edu
FU NIDCD NIH HHS [R01 DC002524] Funding Source: Medline
NR 43
TC 305
Z9 364
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 JAN 17
PY 2008
VL 451
IS 7176
BP 305
EP U2
DI 10.1038/nature06492
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100043
PM 18202651
DA 2026-03-09
ER

PT J
AU Lu, JH
   Marnell, LL
   Marjon, KD
   Mold, C
   Du Clos, TW
   Sun, PD
AF Lu, Jinghua
   Marnell, Lorraine L.
   Marjon, Kristopher D.
   Mold, Carolyn
   Du Clos, Terry W.
   Sun, Peter D.
TI Structural recognition and functional activation of FcγR by innate pentraxins
SO NATURE
LA English
DT Article
ID c-reactive protein; amyloid-p-component; crystal-structure; human monocytes; receptor; expression; complex; binding; riia; phagocytosis
AB Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component ( SAP) and C- reactive protein, which are two of the acute- phase proteins synthesized in response to infection(1,2). Both recognize microbial pathogens and activate the classical complement pathway through C1q ( refs 3 and 4). More recently, members of the pentraxin family were found to interact with cell- surface Fc gamma receptors (Fc gamma R) and activate leukocyte-mediated phagocytosis(5-8). Here we describe the structural mechanism for pentraxin's binding to Fc gamma R and its functional activation of Fc gamma R- mediated phagocytosis and cytokine secretion. The complex structure between human SAP and Fc gamma RIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. The 1: 1 stoichiometry between SAP and Fc gamma RIIa infers the requirement for multivalent pathogen binding for receptor aggregation. Mutational and binding studies show that pentraxins are diverse in their binding specificity for Fc gamma R isoforms but conserved in their recognition structure. The shared binding site for SAP and IgG results in competition for Fc gamma R binding and the inhibition of immune- complex- mediated phagocytosis by soluble pentraxins. These results establish antibody- like functions for pentraxins in the Fc gamma R pathway, suggest an evolutionary overlap between the innate and adaptive immune systems, and have new therapeutic implications for autoimmune diseases.
C1 [Lu, Jinghua; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
   [Marnell, Lorraine L.; Marjon, Kristopher D.; Mold, Carolyn; Du Clos, Terry W.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
   [Marnell, Lorraine L.; Marjon, Kristopher D.; Mold, Carolyn; Du Clos, Terry W.] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA.
   [Du Clos, Terry W.] Vet Adm Med Ctr, Albuquerque, NM 87108 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of New Mexico; University of New Mexico; US Department of Veterans Affairs; Veterans Health Administration (VHA)
RP Sun, PD (corresponding author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM psun@nih.gov
FU US Department of Energy; Basic Energy Sciences; Office of Science [W-31-109-Eng-83]; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Department of Veterans Affairs; [RO1 AI28358]; National Institute of Allergy and Infectious Diseases [ZIAAI000853, T32AI007538] Funding Source: NIH RePORTER
NR 41
TC 260
Z9 301
U1 0
U2 20
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 989
EP U86
DI 10.1038/nature07468
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300054
PM 19011614
DA 2026-03-09
ER

PT J
AU Shafir, S
   Reich, T
   Tsur, E
   Erev, I
   Lotem, A
AF Shafir, Sharoni
   Reich, Taly
   Tsur, Erez
   Erev, Ido
   Lotem, Arnon
TI Perceptual accuracy and conflicting effects of certainty on risk-taking behaviour
SO NATURE
LA English
DT Article
ID apis-mellifera; decision; choice
AB The 'certainty effect'(1,2) is a notable violation of expected utility theory by decision makers(3-6). It shows that people's tendency to select the safer of two prospects increases when this prospect provides a good outcome with certainty ( for example, people prefer a monetary gain of 3 with certainty over 4 with a probability of 0.8, but do not prefer 3 with a probability of 0.25 over 4 with a probability of 0.2). Subsequent work on experience- based decision making in rats(7) extended the certainty effect to other animals, suggesting its generality across different species and different decision- making mechanisms. However, an attempt to replicate this study with human subjects showed a surprising 'reversed certainty effect'(8,9), namely, the tendency to prefer the safer option decreases when this prospect is associated with certainty ( and people now prefer 4 with a probability of 0.8 over 3 with certainty). Here we show that these conflicting results can be explained by perceptual noise and that the certainty effect can be restored experimentally by reducing perceptual accuracy. Using complementary experiments in humans and honeybees ( Apis mellifera), we show that by manipulating perceptual accuracy in experience-based tasks, both the certainty and the reversed certainty effects can be exhibited by humans and other animals: the certainty effect emerges when it is difficult to discriminate between the different rewards, whereas the reversed certainty effect emerges when discrimination is easy. Our results fit a simple process- based model of matching behaviour(10,11), capable of explaining the certainty effect in humans and other animals that make repeated decisions based on experience. This mechanism should probably be distinguished from those involved in the original certainty effect that was exhibited by human subjects in single description- based problems(1,2).
C1 [Lotem, Arnon] Tel Aviv Univ, Dept Zool, Fac Life Sci, IL-69978 Tel Aviv, Israel.
   [Shafir, Sharoni; Tsur, Erez] Hebrew Univ Jerusalem, B Triwaks Bee Res Ctr, Dept Entomol, Fac Agr Food & Environm Qual Sci, IL-76100 Rehovot, Israel.
   [Reich, Taly; Erev, Ido] Technion Israel Inst Technol, Max Wertheimer Minerva Ctr Cognit Studies, Fac Ind Engn & Management, IL-32000 Haifa, Israel.
C3 Tel Aviv University; Hebrew University of Jerusalem; Technion Israel Institute of Technology
RP Lotem, A (corresponding author), Tel Aviv Univ, Dept Zool, Fac Life Sci, IL-69978 Tel Aviv, Israel.
EM erev@techunix.technion.ac.il; lotem@post.tau.ac.il
NR 22
TC 66
Z9 72
U1 1
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 JUN 12
PY 2008
VL 453
IS 7197
BP 917
EP U51
DI 10.1038/nature06841
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000043
PM 18548069
DA 2026-03-09
ER

PT J
AU Liu, M
   Duke, JL
   Richter, DJ
   Vinuesa, CG
   Goodnow, CC
   Kleinstein, SH
   Schatz, DG
AF Liu, Man
   Duke, Jamie L.
   Richter, Daniel J.
   Vinuesa, Carola G.
   Goodnow, Christopher C.
   Kleinstein, Steven H.
   Schatz, David G.
TI Two levels of protection for the B cell genome during somatic hypermutation
SO NATURE
LA English
DT Article
ID induced cytidine deaminase; class switch recombination; gene-expression; c-myc; aid; ig; translocations; immunoglobulin; mutation; protooncogenes
AB Somatic hypermutation introduces point mutations into immunoglobulin genes in germinal centre B cells during an immune response. The reaction is initiated by cytosine deamination by the activation- induced deaminase ( AID) and completed by error- prone processing of the resulting uracils by mismatch and base excision repair factors(1). Somatic hypermutation represents a threat to genome integrity(2) and it is not known how the B cell genome is protected from the mutagenic effects of somatic hypermutation nor how often these protective mechanisms fail. Here we show, by extensive sequencing of murine B cell genes, that the genome is protected by two distinct mechanisms: selective targeting of AID and gene- specific, high- fidelity repair of AID- generated uracils. Numerous genes linked to B cell tumorigenesis, including Myc, Pim1, Pax5, Ocab ( also called Pou2af1), H2afx, Rhoh and Ebf1, are deaminated by AID but escape acquisition of most mutations through the combined action of mismatch and base excision repair. However, approximately 25% of expressed genes analysed were not fully protected by either mechanism and accumulated mutations in germinal centre B cells. Our results demonstrate that AID acts broadly on the genome, with the ultimate distribution of mutations determined by a balance between high- fidelity and error- prone DNA repair.
C1 [Liu, Man; Schatz, David G.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA.
   [Kleinstein, Steven H.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
   [Duke, Jamie L.; Kleinstein, Steven H.] Yale Univ, Interdept Program Computat Biol & Bioinformat, New Haven, CT 06511 USA.
   [Richter, Daniel J.] MIT, Broad Inst, Cambridge, MA 02141 USA.
   [Richter, Daniel J.] Harvard Univ, Cambridge, MA 02141 USA.
   [Vinuesa, Carola G.; Goodnow, Christopher C.] Australian Natl Univ, Div Immunol & Genet, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
   [Goodnow, Christopher C.] Australian Phenom Facil, Canberra, ACT 2601, Australia.
   [Schatz, David G.] Howard Hughes Med Inst, New Haven, CT 06510 USA.
C3 Yale University; Yale University; Yale University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Australian National University; John Curtin School of Medical Research; Howard Hughes Medical Institute
RP Schatz, DG (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06510 USA.
EM david.schatz@yale.edu
NR 48
TC 474
Z9 599
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 841
EP U11
DI 10.1038/nature06547
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400045
PM 18273020
DA 2026-03-09
ER

PT J
AU Jones, DM
   Head, IM
   Gray, ND
   Adams, JJ
   Rowan, AK
   Aitken, CM
   Bennett, B
   Huang, H
   Brown, A
   Bowler, BFJ
   Oldenburg, T
   Erdmann, M
   Larter, SR
AF Jones, D. M.
   Head, I. M.
   Gray, N. D.
   Adams, J. J.
   Rowan, A. K.
   Aitken, C. M.
   Bennett, B.
   Huang, H.
   Brown, A.
   Bowler, B. F. J.
   Oldenburg, T.
   Erdmann, M.
   Larter, S. R.
TI Crude-oil biodegradation via methanogenesis in subsurface petroleum reservoirs
SO NATURE
LA English
DT Article
ID deep subsurface; aromatic-hydrocarbons; field; degradation; oxidation; origin
AB Biodegradation of crude oil in subsurface petroleum reservoirs has adversely affected the majority of the world's oil, making recovery and refining of that oil more costly(1). The prevalent occurrence of biodegradation in shallow subsurface petroleum reservoirs(2,3) has been attributed to aerobic bacterial hydrocarbon degradation stimulated by surface recharge of oxygen- bearing meteoric waters(2). This hypothesis is empirically supported by the likelihood of encountering biodegraded oils at higher levels of degradation in reservoirs near the surface(4,5). More recent findings, however, suggest that anaerobic degradation processes dominate subsurface sedimentary environments(6), despite slow reaction kinetics and uncertainty as to the actual degradation pathways occurring in oil reservoirs. Here we use laboratory experiments in microcosms monitoring the hydrocarbon composition of degraded oils and generated gases, together with the carbon isotopic compositions of gas and oil samples taken at wellheads and a Rayleigh isotope fractionation box model, to elucidate the probable mechanisms of hydrocarbon degradation in reservoirs. We find that crude- oil hydrocarbon degradation under methanogenic conditions in the laboratory mimics the characteristic sequential removal of compound classes seen in reservoir- degraded petroleum. The initial preferential removal of n-alkanes generates close to stoichiometric amounts of methane, principally by hydrogenotrophic methanogenesis. Our data imply a common methanogenic biodegradation mechanism in subsurface degraded oil reservoirs, resulting in consistent patterns of hydrocarbon alteration, and the common association of dry gas with severely degraded oils observed worldwide. Energy recovery from oilfields in the form of methane, based on accelerating natural methanogenic biodegradation, may offer a route to economic production of difficult- to- recover energy from oilfields.
C1 [Jones, D. M.; Head, I. M.; Gray, N. D.; Rowan, A. K.; Aitken, C. M.; Brown, A.; Bowler, B. F. J.; Larter, S. R.] Newcastle Univ, Sch Civil Engn & Geosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Adams, J. J.; Bennett, B.; Huang, H.; Oldenburg, T.; Larter, S. R.] Univ Calgary, Dept Geol & Geophys, Petr Reservoir Grp, Calgary, AB T2A 1N4, Canada.
   [Erdmann, M.] Norsk Hydro Oil & Energy, R&D Ctr, N-5020 Bergen, Norway.
C3 Newcastle University - UK; University of Calgary
RP Larter, SR (corresponding author), Newcastle Univ, Sch Civil Engn & Geosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
EM slarter@ucalgary.ca
FU NERC [NE/E01657X/1] Funding Source: UKRI; Natural Environment Research Council [NE/E01657X/1] Funding Source: researchfish
NR 37
TC 556
Z9 649
U1 4
U2 393
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 176
EP U6
DI 10.1038/nature06484
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400039
PM 18075503
DA 2026-03-09
ER

PT J
AU Simmons, NB
   Seymour, KL
   Habersetzer, J
   Gunnell, GF
AF Simmons, Nancy B.
   Seymour, Kevin L.
   Habersetzer, Joerg
   Gunnell, Gregg F.
TI Primitive Early Eocene bat from Wyoming and the evolution of flight and echolocation
SO NATURE
LA English
DT Article
ID biogeography; chiroptera; fossil
AB Bats ( Chiroptera) represent one of the largest and most diverse radiations of mammals, accounting for one- fifth of extant species(1). Although recent studies unambiguously support bat monophyly(2-4) and consensus is rapidly emerging about evolutionary relationships among extant lineages(5-8), the fossil record of bats extends over 50 million years, and early evolution of the group remains poorly understood(5,7-9). Here we describe a new bat from the Early Eocene Green River Formation of Wyoming, USA, with features that are more primitive than seen in any previously known bat. The evolutionary pathways that led to flapping flight and echolocation in bats have been in dispute(7-18), and until now fossils have been of limited use in documenting transitions involved in this marked change in lifestyle. Phylogenetically informed comparisons of the new taxon with other bats and non- flying mammals reveal that critical morphological and functional changes evolved incrementally. Forelimb anatomy indicates that the new bat was capable of powered flight like other Eocene bats, but ear morphology suggests that it lacked their echolocation abilities, supporting a 'flight first' hypothesis for chiropteran evolution. The shape of the wings suggests that an undulating gliding - fluttering flight style may be primitive for bats, and the presence of a long calcar indicates that a broad tail membrane evolved early in Chiroptera, probably functioning as an additional airfoil rather than as a prey-capture device. Limb proportions and retention of claws on all digits indicate that the new bat may have been an agile climber that employed quadrupedal locomotion and under- branch hanging behaviour.
C1 [Simmons, Nancy B.] Amer Museum Nat Hist, New York, NY 10024 USA.
   [Seymour, Kevin L.] Royal Ontario Museum, Toronto, ON M5S 2C6, Canada.
   [Habersetzer, Joerg] Forschungsinst Senckenberg, D-60325 Frankfurt, Germany.
   [Gunnell, Gregg F.] Univ Michigan, Museum Paleontol, Ann Arbor, MI 48109 USA.
C3 American Museum of Natural History (AMNH); Royal Ontario Museum; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); University of Michigan System; University of Michigan
RP Simmons, NB (corresponding author), Amer Museum Nat Hist, Cent Park W & 79th St, New York, NY 10024 USA.
EM simmons@amnh.org
NR 38
TC 314
Z9 381
U1 2
U2 280
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 818
EP U6
DI 10.1038/nature06549
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400040
PM 18270539
DA 2026-03-09
ER

PT J
AU Lisiecki, LE
   Raymo, ME
   Curry, WB
AF Lisiecki, Lorraine E.
   Raymo, Maureen E.
   Curry, William B.
TI Atlantic overturning responses to Late Pleistocene climate forcings
SO NATURE
LA English
DT Article
ID thermohaline circulation; deep-water; ocean; cycles; termination; glaciation; evolution
AB The factors driving glacial changes in ocean overturning circulation are not well understood. On the basis of a comparison of 20 climate variables over the past four glacial cycles, the SPECMAP project(1) proposed that summer insolation at high northern latitudes ( that is, Milankovitch forcing) drives the same sequence of ocean circulation and other climate responses over 100- kyr eccentricity cycles, 41- kyr obliquity cycles and 23- kyr precession cycles. SPECMAP analysed the circulation response at only a few sites in the Atlantic Ocean, however, and the phase of circulation response has been shown to vary by site and orbital band(2). Here we test the SPECMAP hypothesis by measuring the phase of orbital responses in benthic delta C-13 ( a proxy indicator of ocean nutrient content) at 24 sites throughout the Atlantic over the past 425 kyr. On the basis of delta C-13 responses at 3,000 - 4,010 mwater depth, we find that maxima in Milankovitch forcing are associated with greater mid- depth overturning in the obliquity band but less overturning in the precession band. This suggests that Atlantic overturning is strongly sensitive to factors beyond ice volume and summer insolation at high northern latitudes. A better understanding of these processes could lead to improvements in model estimates of overturning rates, which range from a 40 per cent increase to a 40 per cent decrease at the Last Glacial Maximum(3) and a 10 - 50 per cent decrease over the next 140 yr in response to projected increases in atmospheric CO2 ( ref. 4).
C1 [Lisiecki, Lorraine E.; Raymo, Maureen E.] Boston Univ, Dept Earth Sci, Boston, MA 02215 USA.
   [Curry, William B.] Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
C3 Boston University; Woods Hole Oceanographic Institution
RP Lisiecki, LE (corresponding author), Univ Calif Santa Barbara, Dept Earth Sci, Santa Barbara, CA 93106 USA.
EM lisiecki@alumni.brown.edu
FU NOAA Postdoctoral Program in Climate and Global Change; NSF
NR 30
TC 69
Z9 82
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 85
EP 88
DI 10.1038/nature07425
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000045
PM 18987740
DA 2026-03-09
ER

PT J
AU Impellizzeri, CMV
   McKean, JP
   Castangia, P
   Roy, AL
   Henkel, C
   Brunthaler, A
   Wucknitz, O
AF Impellizzeri, C. M. Violette
   McKean, John P.
   Castangia, Paola
   Roy, Alan L.
   Henkel, Christian
   Brunthaler, Andreas
   Wucknitz, Olaf
TI A gravitationally lensed water maser in the early Universe
SO NATURE
LA English
DT Article
ID mg 0414+0534; accretion disk; emission; galaxy; h2o; absorption; j0414+0534; redshift; parsec; megamaser
AB Water masers(1-4) are found in dense molecular clouds closely associated with supermassive black holes at the centres of active galaxies. On the basis of the understanding of the local water- maser luminosity function(5), it was expected that masers at intermediate and high redshifts would be extremely rare. However, galaxies at redshifts z > 2 might be quite different from those found locally, not least because of more frequent mergers and interaction events. Here we use gravitational lensing to search for masers at higher redshifts than would otherwise be possible, and find a water maser at redshift 2.64 in the dust- and gas- rich, gravitationally lensed type- 1 quasar MGJ0414+0534 ( refs 6 - 13). The isotropic luminosity is 10,000L.(L., solar luminosity), which is twice that of the most powerful local water maser(14) and half that of the most distant maser previously known(15). Using the locally determined luminosity function5, the probability of finding a maser this luminous associated with any single active galaxy is 10(-6). The fact that we see such a maser in the first galaxy we observe must mean that the volume densities and luminosities of masers are higher at redshift 2.64.
C1 [Impellizzeri, C. M. Violette; McKean, John P.; Castangia, Paola; Roy, Alan L.; Henkel, Christian; Brunthaler, Andreas] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Castangia, Paola] Osservatorio Astron Cagliari, INAF, I-09012 Capoterra, CA, Italy.
   [Wucknitz, Olaf] Argelander Inst Astron, D-53121 Bonn, Germany.
C3 Max Planck Society; Istituto Nazionale Astrofisica (INAF); University of Bonn
RP Impellizzeri, CMV (corresponding author), Max Planck Inst Radioastron, Hugel 69, D-53121 Bonn, Germany.
EM violette@mpifr-bonn.mpg.de
FU European Community's Sixth Framework Marie Curie Research Training Network 'ANGLES'; Priority and Emmy-Noether- Programmes of the Deutsche Forschungsgemeinschaft
NR 30
TC 47
Z9 51
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 DEC 18
PY 2008
VL 456
IS 7224
BP 927
EP 929
DI 10.1038/nature07544
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300039
PM 19092930
DA 2026-03-09
ER

PT J
AU Li, C
   Wu, XC
   Rieppel, O
   Wang, LT
   Zhao, LJ
AF Li, Chun
   Wu, Xiao-Chun
   Rieppel, Olivier
   Wang, Li-Ting
   Zhao, Li-Jun
TI An ancestral turtle from the Late Triassic of southwestern China
SO NATURE
LA English
DT Article
ID chelydra-serpentina reptilia; origin; shell; histology; evolution; guizhou; osteoderms; area
AB The origin of the turtle body plan remains one of the great mysteries of reptile evolution. The anatomy of turtles is highly derived, which renders it difficult to establish the relationships of turtles with other groups of reptiles. The oldest known turtle, Proganochelys from the Late Triassic period of Germany(1), has a fully formed shell and offers no clue as to its origin. Here we describe a new 220- million- year- old turtle from China, somewhat older than Proganochelys, that documents an intermediate step in the evolution of the shell and associated structures. A ventral plastron is fully developed, but the dorsal carapace consists of neural plates only. The dorsal ribs are expanded, and osteoderms are absent. The new species shows that the plastron evolved before the carapace and that the first step of carapace formation is the ossification of the neural plates coupled with a broadening of the ribs. This corresponds to early embryonic stages of carapace formation in extant turtles, and shows that the turtle shell is not derived from a fusion of osteoderms. Phylogenetic analysis places the new species basal to all known turtles, fossil and extant. The marine deposits that yielded the fossils indicate that this primitive turtle inhabited marginal areas of the sea or river deltas.
C1 [Li, Chun] Chinese Acad Sci, Lab Evolut Systemat Vertebrates, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
   [Wu, Xiao-Chun] Canadian Museum Nat, Ottawa, ON K1P 6P4, Canada.
   [Rieppel, Olivier] Field Museum Nat Hist, Dept Geol, Chicago, IL 60605 USA.
   [Wang, Li-Ting] Geol Survey Guizhou Prov, Guiyang 550005, Peoples R China.
   [Zhao, Li-Jun] Zhejiang Museum Nat Hist, Hangzhou 310012, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Field Museum of Natural History (Chicago)
RP Li, C (corresponding author), Chinese Acad Sci, Lab Evolut Systemat Vertebrates, Inst Vertebrate Paleontol & Paleoanthropol, POB 643, Beijing 100044, Peoples R China.
EM lichun@ivpp.ac.cn; xcwu@mus-nature.ca
FU Major Basic Research Projects [2006CB806400]; Ministry of Science and Technology of China; National Natural Science Foundation [40772015, 40121202]; Chinese Academy of Sciences; Canadian Museum of Nature [RS 34]; CAS/SAFEA International Partnership Program for Creative Research Teams
NR 30
TC 278
Z9 322
U1 3
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 497
EP 501
DI 10.1038/nature07533
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500037
PM 19037315
DA 2026-03-09
ER

PT J
AU Wagner, GP
   Kenney-Hunt, JP
   Pavlicev, M
   Peck, JR
   Waxman, D
   Cheverud, JM
AF Wagner, Gunter P.
   Kenney-Hunt, Jane P.
   Pavlicev, Mihaela
   Peck, Joel R.
   Waxman, David
   Cheverud, James M.
TI Pleiotropic scaling of gene effects and the 'cost of complexity'
SO NATURE
LA English
DT Article
ID quantitative trait loci; mutation-selection balance; murine growth; modularity; mice; evolvability; architecture; evolution
AB As perceived by Darwin, evolutionary adaptation by the processes of mutation and selection is difficult to understand for complex features that are the product of numerous traits acting in concert, for example the eye or the apparatus of flight. Typically, mutations simultaneously affect multiple phenotypic characters. This phenomenon is known as pleiotropy. The impact of pleiotropy on evolution has for decades been the subject of formal analysis(1-6). Some authors have suggested that pleiotropy can impede evolutionary progress ( a so- called 'cost of complexity'(5)). The plausibility of various phenomena attributed to pleiotropy depends on how many traits are affected by each mutation and on our understanding of the correlation between the number of traits affected by each gene substitution and the size of mutational effects on individual traits. Here we show, by studying pleiotropy in mice with the use of quantitative trait loci ( QTLs) affecting skeletal characters, that most QTLs affect a relatively small subset of traits and that a substitution at a QTL has an effect on each trait that increases with the total number of traits affected. This suggests that evolution of higher organisms does not suffer a 'cost of complexity' because most mutations affect few traits and the size of the effects does not decrease with pleiotropy.
C1 [Wagner, Gunter P.] Yale Univ, Dept Ecol & Evolut Biol, New Haven, CT 06520 USA.
   [Kenney-Hunt, Jane P.; Pavlicev, Mihaela; Cheverud, James M.] Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
   [Peck, Joel R.; Waxman, David] Univ Sussex, Sch Life Sci, Ctr Study Evolut, Brighton BN1 9QG, E Sussex, England.
C3 Yale University; Washington University (WUSTL); University of Sussex
RP Wagner, GP (corresponding author), Yale Univ, Dept Ecol & Evolut Biol, New Haven, CT 06520 USA.
EM gunter.wagner@yale.edu; cheverud@pcg.wustl.edu
NR 26
TC 184
Z9 217
U1 0
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 470
EP U9
DI 10.1038/nature06756
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300031
PM 18368117
DA 2026-03-09
ER

PT J
AU Campbell, P
AF Campbell, Philip
TI Horizons
SO NATURE
LA English
DT Article
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 643
EP 643
DI 10.1038/451643a
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500026
DA 2026-03-09
ER

PT J
AU Tseng, YH
   Kokkotou, E
   Schulz, TJ
   Huang, TL
   Winnay, JN
   Taniguchi, CM
   Tran, TT
   Suzuki, R
   Espinoza, DO
   Yamamoto, Y
   Ahrens, MJ
   Dudley, AT
   Norris, AW
   Kulkarni, RN
   Kahn, CR
AF Tseng, Yu-Hua
   Kokkotou, Efi
   Schulz, Tim J.
   Huang, Tian Lian
   Winnay, Jonathon N.
   Taniguchi, Cullen M.
   Tran, Thien T.
   Suzuki, Ryo
   Espinoza, Daniel O.
   Yamamoto, Yuji
   Ahrens, Molly J.
   Dudley, Andrew T.
   Norris, Andrew W.
   Kulkarni, Rohit N.
   Kahn, C. Ronald
TI New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure
SO NATURE
LA English
DT Article
ID adipocyte differentiation; transcriptional control; glucose-uptake; insulin; fat; stimulation; cells; commitment; expression; c3h10t1/2
AB Adipose tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue, which is specialized in energy expenditure and can counteract obesity61. Factors that specify the developmental fate and function of white and brown adipose tissue remain poorly understood(2,3). Here we demonstrate that whereas some members of the family of bone morphogenetic proteins ( BMPs) support white adipocyte differentiation, BMP7 singularly promotes differentiation of brown preadipocytes even in the absence of the normally required hormonal induction cocktail. BMP7 activates a full program of brown adipogenesis including induction of early regulators of brown fat fate PRDM16 ( PR- domain- containing 16; ref. 4) and PGC-1 alpha ( peroxisome proliferator- activated receptor-gamma ( PPAR gamma) coactivator-1 alpha; ref. 5), increased expression of the brown- fat- defining marker uncoupling protein 1 ( UCP1) and adipogenic transcription factors PPAR gamma and CCAAT/ enhancer- binding proteins ( C/ EBPs), and induction of mitochondrial biogenesis via p38 mitogen- activated protein ( MAP) kinase-( also known as Mapk14) and PGC- 1- dependent pathways. Moreover, BMP7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage, and implantation of these cells into nude mice results in development of adipose tissue containing mostly brown adipocytes. Bmp7 knockout embryos show a marked paucity of brown fat and an almost complete absence of UCP1. Adenoviral-ediated expression of BMP7 in mice results in a significant increase in brown, but not white, fat mass and leads to an increase in energy expenditure and a reduction in weight gain. These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity.
C1 [Tseng, Yu-Hua; Schulz, Tim J.; Huang, Tian Lian; Winnay, Jonathon N.; Taniguchi, Cullen M.; Tran, Thien T.; Suzuki, Ryo; Espinoza, Daniel O.; Yamamoto, Yuji; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Obes & Hormone Act, Boston, MA 02215 USA.
   [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Cell & Mol Physiol, Boston, MA 02215 USA.
   [Kokkotou, Efi] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA.
   [Ahrens, Molly J.; Dudley, Andrew T.] Northwestern Univ, Dept Biochem, Evanston, IL 60208 USA.
   [Norris, Andrew W.] Univ Iowa, Childrens Hosp, Div Pediat Endocrinol, Iowa City, IA 52242 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Joslin Diabetes Center, Inc.; Harvard University; Harvard University Medical Affiliates; Joslin Diabetes Center, Inc.; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Northwestern University; University of Iowa
RP Tseng, YH (corresponding author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Obes & Hormone Act, Boston, MA 02215 USA.
EM yu-hua.tseng@joslin.harvard.edu
FU National Institutes of Health [R01 DK077097, R21 DK070722, P30 DK46200, P30 DK040561, R01 DK67536, K08 DK64906, R01 DK 060837]; Tanita Healthy Weight Community; Eleanor and Miles Shore 50th Anniversary Scholar Program; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK067536, P30DK040561, P30DK046200] Funding Source: NIH RePORTER
NR 36
TC 890
Z9 1081
U1 1
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 21
PY 2008
VL 454
IS 7207
BP 1000
EP U44
DI 10.1038/nature07221
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000040
PM 18719589
DA 2026-03-09
ER

PT J
AU Yang, HB
   Rameau, JD
   Johnson, PD
   Valla, T
   Tsvelik, A
   Gu, GD
AF Yang, H. -B.
   Rameau, J. D.
   Johnson, P. D.
   Valla, T.
   Tsvelik, A.
   Gu, G. D.
TI Emergence of preformed Cooper pairs from the doped Mott insulating state in Bi2Sr2CaCu2O8+δ
SO NATURE
LA English
DT Article
ID cuprate superconductors; underdoped bi2212; energy-gap; pseudogap; transition; spin; photoemission; surface; onset
AB Superconductors are characterized by an energy gap that represents the energy needed to break the pairs of electrons (Cooper pairs) apart. At temperatures considerably above those associated with superconductivity, the high- transition- temperature copper oxides have an additional 'pseudogap'. It has been unclear whether this represents preformed pairs of electrons that have not achieved the coherence necessary for superconductivity, or whether it reflects some alternative ground state that competes with superconductivity(1). Paired electrons should display particle - hole symmetry with respect to the Fermi level (the energy of the highest occupied level in the electronic system), but competing states(2-4) need not show such symmetry. Here we report a photoemission study of the underdoped copper oxide Bi2Sr2CaCu2O8+delta that shows the opening of a symmetric gap only in the anti-nodal region, contrary to the expectation that pairing would take place in the nodal region. It is therefore evident that the pseudogap does reflect the formation of preformed pairs of electrons and that the pairing occurs only in well- defined directions of the underlying lattice.
C1 [Yang, H. -B.; Rameau, J. D.; Johnson, P. D.; Valla, T.; Tsvelik, A.; Gu, G. D.] Brookhaven Natl Lab, Condensed Matter Phys & Mat Sci Dept, Upton, NY 11973 USA.
C3 United States Department of Energy (DOE); Brookhaven National Laboratory
RP Johnson, PD (corresponding author), Brookhaven Natl Lab, Condensed Matter Phys & Mat Sci Dept, Upton, NY 11973 USA.
EM pdj@bnl.gov
FU US Department of Energy
NR 25
TC 207
Z9 235
U1 1
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 77
EP 80
DI 10.1038/nature07400
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000043
PM 18987738
DA 2026-03-09
ER

PT J
AU Brown, RH
   Soderblom, LA
   Soderblom, JM
   Clark, RN
   Jaumann, R
   Barnes, JW
   Sotin, C
   Buratti, B
   Baines, KH
   Nicholson, PD
AF Brown, R. H.
   Soderblom, L. A.
   Soderblom, J. M.
   Clark, R. N.
   Jaumann, R.
   Barnes, J. W.
   Sotin, C.
   Buratti, B.
   Baines, K. H.
   Nicholson, P. D.
TI The identification of liquid ethane in Titan's Ontario Lacus
SO NATURE
LA English
DT Article
ID surface; ice; saturn; ocean; lakes; seas
AB Titan was once thought to have global oceans of light hydrocarbons on its surface(1-5), but after 40 close flybys of Titan by the Cassini spacecraft, it has become clear that no such oceans exist(6). There are, however, features similar to terrestrial lakes and seas(7), and widespread evidence for fluvial erosion(8,9), presumably driven by precipitation of liquid methane from Titan's dense, nitrogen-dominated atmosphere(10). Here we report infrared spectroscopic data, obtained by the Visual and Infrared Mapping Spectrometer(11) ( VIMS) on board the Cassini spacecraft, that strongly indicate that ethane, probably in liquid solution with methane, nitrogen and other low- molecular- mass hydrocarbons, is contained within Titan's Ontario Lacus.
C1 [Brown, R. H.; Soderblom, J. M.] Univ Arizona, Dept Planetary Sci, Tucson, AZ 85721 USA.
   [Soderblom, L. A.] US Geol Survey, Flagstaff, AZ 86001 USA.
   [Clark, R. N.] US Geol Survey, Lakewood, CO 80225 USA.
   [Jaumann, R.] Deutsch Zentrum Luft & Raumfahrt, D-12489 Berlin, Germany.
   [Barnes, J. W.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Sotin, C.; Buratti, B.; Baines, K. H.] CALTECH, Jet Prop Lab, Pasadena, CA 91107 USA.
   [Nicholson, P. D.] Cornell Univ, Dept Astron, Ithaca, NY 14853 USA.
C3 University of Arizona; United States Department of the Interior; United States Geological Survey; United States Department of the Interior; United States Geological Survey; Helmholtz Association; German Aerospace Centre (DLR); National Aeronautics & Space Administration (NASA); NASA Ames Research Center; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); Cornell University
RP Brown, RH (corresponding author), Univ Arizona, Dept Planetary Sci, Tucson, AZ 85721 USA.
EM rhb@lpl.arizona.edu
NR 29
TC 213
Z9 239
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 31
PY 2008
VL 454
IS 7204
BP 607
EP 610
DI 10.1038/nature07100
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500039
PM 18668101
DA 2026-03-09
ER

PT J
AU Schunck, CH
   Shin, YI
   Schirotzek, A
   Ketterle, W
AF Schunck, Christian H.
   Shin, Yong-il
   Schirotzek, Andre
   Ketterle, Wolfgang
TI Determination of the fermion pair size in a resonantly interacting superfluid
SO NATURE
LA English
DT Article
ID bose-condensation; gas; superconductivity; state; bcs
AB Fermionic superfluidity requires the formation of particle pairs, the size of which varies from the femtometre scale in neutron stars and nuclei to the micrometre scale in conventional superconductors. Many properties of the superfluid depend on the pair size relative to the interparticle spacing. This is expressed in 'BCS-BEC crossover' theories(,)(1-3) describing the crossover from a Bardeen Cooper-Schrieffer (BCS)-type superfluid of loosely bound, large Cooper pairs to Bose-Einstein condensates (BECs) of tightly bound molecules. Such a crossover superfluid has been realized in ultracold atomic gases where high-temperature superfluidity has been observed(4,5). The microscopic properties of the fermion pairs can be probed using radio- frequency spectroscopy. However, previous work(6-8) was difficult to interpret owing to strong final-state interactions that were not well understood. Here we realize a superfluid spin mixture in which such interactions have negligible influence and present fermion pair dissociation spectra that reveal the underlying pairing correlations. This allows us to determine that the spectroscopic pair size in the resonantly interacting gas is 20 per cent smaller than the interparticle spacing. These are the smallest pairs so far observed in fermionic superfluids, highlighting the importance of small fermion pairs for superfluidity at high critical temperatures(9). We have also identified transitions from fermion pairs to bound molecular states and to many-body bound states in the case of strong final- state interactions.
C1 [Schunck, Christian H.; Shin, Yong-il; Schirotzek, Andre; Ketterle, Wolfgang] MIT, Dept Phys, MIT Harvard Ctr Ultracold Atoms, Cambridge, MA 02139 USA.
   [Schunck, Christian H.; Shin, Yong-il; Schirotzek, Andre; Ketterle, Wolfgang] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Schunck, CH (corresponding author), MIT, Dept Phys, MIT Harvard Ctr Ultracold Atoms, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM chs@mit.edu
NR 30
TC 108
Z9 121
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 7
PY 2008
VL 454
IS 7205
BP 739
EP U70
DI 10.1038/nature07176
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000039
PM 18685702
DA 2026-03-09
ER

PT J
AU Licatalosi, DD
   Mele, A
   Fak, JJ
   Ule, J
   Kayikci, M
   Chi, SW
   Clark, TA
   Schweitzer, AC
   Blume, JE
   Wang, XN
   Darnell, JC
   Darnell, RB
AF Licatalosi, Donny D.
   Mele, Aldo
   Fak, John J.
   Ule, Jernej
   Kayikci, Melis
   Chi, Sung Wook
   Clark, Tyson A.
   Schweitzer, Anthony C.
   Blume, John E.
   Wang, Xuning
   Darnell, Jennifer C.
   Darnell, Robert B.
TI HITS-CLIP yields genome-wide insights into brain alternative RNA processing
SO NATURE
LA English
DT Article
ID pre-messenger-rna; binding protein; nova; polyadenylation; gene; identification; network; disease; antigen; target
AB Protein - RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome- wide means of mapping protein - RNA binding sites in vivo, by high- throughput sequencing of RNA isolated by crosslinking immunoprecipitation ( HITS- CLIP). HITS- CLIP analysis of the neuron- specific splicing factor Nova revealed extremely reproducible RNA- binding maps in multiple mouse brains. These maps provide genome- wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS- CLIP revealed a large number of Nova - RNA interactions in 39 untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS- CLIP, therefore, provides a robust, unbiased means to identify functional protein - RNA interactions in vivo.
C1 [Licatalosi, Donny D.; Mele, Aldo; Fak, John J.; Chi, Sung Wook; Wang, Xuning; Darnell, Jennifer C.; Darnell, Robert B.] Rockefeller Univ, Mol Neurooncol Lab, New York, NY 10021 USA.
   [Licatalosi, Donny D.; Mele, Aldo; Fak, John J.; Chi, Sung Wook; Darnell, Jennifer C.; Darnell, Robert B.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA.
   [Ule, Jernej; Kayikci, Melis] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
   [Clark, Tyson A.; Schweitzer, Anthony C.; Blume, John E.] Affymetrix Inc, Express Res, Santa Clara, CA 95051 USA.
C3 Rockefeller University; Rockefeller University; Howard Hughes Medical Institute; MRC Laboratory Molecular Biology; Affymetrix
RP Darnell, RB (corresponding author), Rockefeller Univ, Mol Neurooncol Lab, 1230 York Ave, New York, NY 10021 USA.
EM darnelr@rockefeller.edu
FU NIH [R01 NS34389]; Howard Hughes Medical Institute; MRC [MC_U105185858] Funding Source: UKRI; Medical Research Council [MC_U105185858] Funding Source: researchfish
NR 48
TC 1087
Z9 1371
U1 3
U2 139
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 464
EP U22
DI 10.1038/nature07488
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500030
PM 18978773
DA 2026-03-09
ER

PT J
AU Shiraishi, R
   Ohtani, E
   Kanagawa, K
   Shimojuku, A
   Zhao, DP
AF Shiraishi, Rei
   Ohtani, Eiji
   Kanagawa, Kyuichi
   Shimojuku, Akira
   Zhao, Dapeng
TI Crystallographic preferred orientation of akimotoite and seismic anisotropy of Tonga slab
SO NATURE
LA English
DT Article
ID fabric transitions; high-pressures; beneath fiji; mantle; temperature; ilmenite; water; deformation; minerals; olivine
AB The mineral akimotoite, ilmenite- structured MgSiO3, exists at the bottom of the Earth's mantle transition zone and within the uppermost lower mantle, especially under low- temperature conditions(1). Akimotoite is thought to be a major constituent of the harzburgite layer of subducting slabs, and the most anisotropic mineral in the mantle transition zone(2-4). It has been predicted that if akimotoite crystals are preferentially oriented by plastic deformation, a cold subducted slab would be extremely anisotropic(5). However, there have been no studies of crystallographic preferred orientations and very few reports of plastic deformation experiments for MgSiO3 ilmenite. Here we present plastic deformation experiments on polycrystalline akimotoite, which were conducted at confining pressures of 20-22 GPa and temperatures of 1,000-1,300 degrees C. We found a change in crystallographic preferred orientation pattern of akimotoite with temperature, where the c-axis maximum parallel to the compression direction develops at high temperature, whereas the c axes are preferentially oriented parallel to the shear direction or perpendicular to the compression direction at lower temperature. The previously reported difference in compressional- wave seismic anisotropy between the northern and southern segments of the Tonga slab at depths of the mantle transition zone(6) can conceivably be attributed to the difference in the crystallographic preferred orientation pattern of akimotoite at varying temperature within the slab.
C1 [Shiraishi, Rei; Ohtani, Eiji; Shimojuku, Akira] Tohoku Univ, Inst Mineral Petrol & Econ Geol, Sendai, Miyagi 9808578, Japan.
   [Zhao, Dapeng] Tohoku Univ, Dept Geophys, Sendai, Miyagi 9808578, Japan.
   [Kanagawa, Kyuichi] Chiba Univ, Dept Earth Sci, Chiba 2638522, Japan.
   [Shimojuku, Akira] Kyushu Univ, Dept Earth & Planetary Sci, Fac Sci, Fukuoka 8128581, Japan.
C3 Tohoku University; Tohoku University; Chiba University; Kyushu University
RP Shiraishi, R (corresponding author), Tohoku Univ, Inst Mineral Petrol & Econ Geol, Sendai, Miyagi 9808578, Japan.
EM siraisir@ganko.tohoku.ac.jp
FU Grant-in-Aid for Scientific Research; Ministry of Education, Culture, Science, Sport, and Technology of the Japanese Government.
NR 26
TC 24
Z9 27
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 OCT 2
PY 2008
VL 455
IS 7213
BP 657
EP 660
DI 10.1038/nature07301
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700045
PM 18833278
DA 2026-03-09
ER

PT J
AU François, M
   Caprini, A
   Hosking, B
   Orsenigo, F
   Wilhelm, D
   Browne, C
   Paavonen, K
   Karnezis, T
   Shayan, R
   Downes, M
   Davidson, T
   Tutt, D
   Cheah, KSE
   Stacker, SA
   Muscat, GEO
   Achen, MG
   Dejana, E
   Koopman, P
AF Francois, Mathias
   Caprini, Andrea
   Hosking, Brett
   Orsenigo, Fabrizio
   Wilhelm, Dagmar
   Browne, Catherine
   Paavonen, Karri
   Karnezis, Tara
   Shayan, Ramin
   Downes, Meredith
   Davidson, Tara
   Tutt, Desmond
   Cheah, Kathryn S. E.
   Stacker, Steven A.
   Muscat, George E. O.
   Achen, Marc G.
   Dejana, Elisabetta
   Koopman, Peter
TI Sox18 induces development of the lymphatic vasculature in mice
SO NATURE
LA English
DT Article
ID endothelial-cells; box gene; system; mouse; expression; mutations; prox1; lymphangiogenesis; differentiation; angiogenesis
AB The lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and lymphatic defects underlie many pathological states including lymphoedema, lymphangiectasia, lymphangioma and lymphatic dysplasia(1-3). However, the origins of the lymphatic system in the embryo, and the mechanisms that direct growth of the network of lymphatic vessels, remain unclear. Lymphatic vessels are thought to arise from endothelial precursor cells budding from the cardinal vein under the influence of the lymphatic hallmark gene Prox1 ( prospero homeobox 1; ref. 4). Defects in the transcription factor gene SOX18 ( SRY ( sex determining region Y) box 18) cause lymphatic dysfunction in the human syndrome hypotrichosis- lymphoedema- telangiectasia(5), suggesting that Sox18 may also play a role in lymphatic development or function. Here we use molecular, cellular and genetic assays in mice to show that Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells. Sox18 is expressed in a subset of cardinal vein cells that later co- express Prox1 and migrate to form lymphatic vessels. Sox18 directly activates Prox1 transcription by binding to its proximal promoter. Overexpression of Sox18 in blood vascular endothelial cells induces them to express Prox1 and other lymphatic endothelial markers, while Sox18- null embryos show a complete blockade of lymphatic endothelial cell differentiation from the cardinal vein. Our findings demonstrate a critical role for Sox18 in developmental lymphangiogenesis, and suggest new avenues to investigate for therapeutic management of human lymphangiopathies.
C1 [Francois, Mathias; Hosking, Brett; Wilhelm, Dagmar; Browne, Catherine; Downes, Meredith; Davidson, Tara; Tutt, Desmond; Muscat, George E. O.; Koopman, Peter] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
   [Caprini, Andrea; Orsenigo, Fabrizio; Dejana, Elisabetta] FIRC Inst Mol Oncol, IFOM, I-20139 Milan, Italy.
   [Paavonen, Karri; Karnezis, Tara; Shayan, Ramin; Stacker, Steven A.; Achen, Marc G.] Royal Melbourne Hosp, Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia.
   [Shayan, Ramin] Univ Melbourne, Dept Surg, Parkville, Vic 3052, Australia.
   [Cheah, Kathryn S. E.] Univ Hong Kong, Dept Biochem, Hong Kong, Peoples R China.
   [Cheah, Kathryn S. E.] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Peoples R China.
   [Dejana, Elisabetta] Univ Milan, Dept Biomol Sci & Biotechnol, I-20129 Milan, Italy.
C3 University of Queensland; IFOM - FIRC Institute of Molecular Oncology; Melbourne Health; Royal Melbourne Hospital; Ludwig Institute for Cancer Research; University of Melbourne; University of Hong Kong; University of Hong Kong; University of Milan
RP Koopman, P (corresponding author), Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
EM elisabetta.dejana@ifom-ieo-campus.it; p.koopman@imb.uq.edu.au
FU National Health and Medical Research Council (Australia); INSERM ( France); Associazione Italiana per la Ricerca sul Cancro (Italy); European Community [LSHG-CT-2004-503573]; Pfizer Foundation (Australia); Australia), the Research Grants Council ( Hong Kong); Research Grants Council (Hong Kong); Raelene Boyle Sporting Chance Foundation (Australia); Royal Australasian College of Surgeons; Heart Foundation of Australia; Australian Research Council
NR 33
TC 450
Z9 516
U1 1
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 4
PY 2008
VL 456
IS 7222
BP 643
EP 669
DI 10.1038/nature07391
PG 27
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000042
PM 18931657
DA 2026-03-09
ER

PT J
AU Neumüller, RA
   Betschinger, J
   Fischer, A
   Bushati, N
   Poernbacher, I
   Mechtler, K
   Cohen, SM
   Knoblich, JA
AF Neumueller, Ralph A.
   Betschinger, Joerg
   Fischer, Anja
   Bushati, Natascha
   Poernbacher, Ingrid
   Mechtler, Karl
   Cohen, Stephen M.
   Knoblich, Juergen A.
TI Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage
SO NATURE
LA English
DT Article
ID neuroblast self-renewal; ribosomal-rna synthesis; asymmetric division; tumor-suppressor; proliferation; melanogaster; protein; cancer; polarity; brain
AB Drosophila neuroblasts(1) and ovarian stem cells(2,3) are well characterized models for stem cell biology. In both cell types, one daughter cell self- renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Whereas neuroblasts segregate the Trim - NHL( tripartite motif and Ncl- 1, HT2A and Lin- 41 domain)- containing protein Brain tumour ( Brat) into one of the two daughter cells(4-6), ovarian stem cells are regulated by an extracellular signal from the surrounding stem cell niche. After division, one daughter cell looses niche contact. It undergoes 4 transit- amplifying divisions to form a cyst of 16 interconnected cells that reduce their rate of growth and stop to proliferate mitotically. Here we show that the Trim - NHL protein Mei- P26 ( refs 7, 8) restricts growth and proliferation in the ovarian stem cell lineage. Mei- P26 expression is low in stem cells but is strongly induced in 16- cell cysts. In mei- P26 mutants, transit-amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. Like brat, mei- P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. We identify Argonaute- 1, a component of the RISC complex, as a common binding partner of Brat and Mei- P26, and show that Mei- P26 acts by inhibiting the microRNA pathway. Mei- P26 and Brat have a similar domain composition that is also found in other tumour suppressors and might be a defining property of a new family of microRNA regulators that act specifically in stem cell lineages.
C1 [Neumueller, Ralph A.; Betschinger, Joerg; Fischer, Anja; Poernbacher, Ingrid; Mechtler, Karl; Knoblich, Juergen A.] Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria.
   [Bushati, Natascha; Cohen, Stephen M.] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Mechtler, Karl] Res Inst Mol Pathol, A-1030 Vienna, Austria.
C3 Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Austrian Academy of Sciences; European Molecular Biology Laboratory (EMBL); Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP)
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 28
TC 188
Z9 225
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 241
EP U72
DI 10.1038/nature07014
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900049
PM 18528333
DA 2026-03-09
ER

PT J
AU Raymond, PA
   Oh, NH
   Turner, RE
   Broussard, W
AF Raymond, Peter A.
   Oh, Neung-Hwan
   Turner, R. Eugene
   Broussard, Whitney
TI Anthropogenically enhanced fluxes of water and carbon from the Mississippi River
SO NATURE
LA English
DT Article
ID united-states; streamflow trends; north-america; dioxide; co2; transport; chemistry; baseflow; increase; quality
AB The water and dissolved inorganic carbon exported by rivers are important net fluxes that connect terrestrial and oceanic water and carbon reservoirs(1). For most rivers, the majority of dissolved inorganic carbon is in the form of bicarbonate. The riverine bicarbonate flux originates mainly from the dissolution of rock minerals by soil water carbon dioxide, a process called chemical weathering, which controls the buffering capacity and mineral content of receiving streams and rivers(2). Here we introduce an unprecedented high- temporal- resolution, 100- year data set from the Mississippi River and couple it with sub- watershed and precipitation data to reveal that the large increase in bicarbonate flux that has occurred over the past 50 years ( ref. 3) is clearly anthropogenically driven. We show that the increase in bicarbonate and water fluxes is caused mainly by an increase in discharge from agricultural watersheds that has not been balanced by a rise in precipitation, which is also relevant to nutrient and pesticide fluxes to the Gulf of Mexico. These findings demonstrate that alterations in chemical weathering are relevant to improving contemporary biogeochemical budgets. Furthermore, land use change and management were arguably more important than changes in climate and plant CO2 fertilization to increases in riverine water and carbon export from this large region over the past 50 years.
C1 [Raymond, Peter A.; Oh, Neung-Hwan] Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA.
   [Turner, R. Eugene] Louisiana State Univ, Coastal Ecol Inst, Baton Rouge, LA 70803 USA.
   [Broussard, Whitney] Louisiana State Univ, Dept Oceanog & Coastal Sci, Baton Rouge, LA 70803 USA.
C3 Yale University; Louisiana State University System; Louisiana State University; Louisiana State University System; Louisiana State University
RP Raymond, PA (corresponding author), Yale Univ, Sch Forestry & Environm Studies, 21 Sachem St, New Haven, CT 06511 USA.
EM peter.raymond@yale.edu
NR 29
TC 494
Z9 592
U1 8
U2 339
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 24
PY 2008
VL 451
IS 7177
BP 449
EP 452
DI 10.1038/nature06505
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100041
PM 18216851
DA 2026-03-09
ER

PT J
AU Richardson, JD
   Kasper, JC
   Wang, C
   Belcher, JW
   Lazarus, AJ
AF Richardson, John D.
   Kasper, Justin C.
   Wang, Chi
   Belcher, John W.
   Lazarus, Alan J.
TI Cool heliosheath plasma and deceleration of the upstream solar wind at the termination shock
SO NATURE
LA English
DT Article
ID interstellar magnetic-field; voyager-1
AB The solar wind blows outward from the Sun and forms a bubble of solar material in the interstellar medium. The termination shock occurs where the solar wind changes from being supersonic ( with respect to the surrounding interstellar medium) to being subsonic. The shock was crossed by Voyager 1 at a heliocentric radius of 94 AU ( 1 AU is the Earth - Sun distance) in December 2004 ( refs 1 - 3). The Voyager 2 plasma experiment observed a decrease in solar wind speed commencing on about 9 June 2007, which culminated in several crossings of the termination shock between 30 August and 1 September 2007 ( refs 4 - 7). Since then, Voyager 2 has remained in the heliosheath, the region of shocked solar wind. Here we report observations of plasma at and near the termination shock and in the heliosheath. The heliosphere is asymmetric, pushed inward in the Voyager 2 direction relative to the Voyager 1 direction. The termination shock is a weak, quasi- perpendicular shock that heats the thermal plasma very little. An unexpected finding is that the flow is still supersonic with respect to the thermal ions downstream of the termination shock. Most of the solar wind energy is transferred to the pickup ions or other energetic particles both upstream of and at the termination shock.
C1 [Richardson, John D.; Belcher, John W.; Lazarus, Alan J.] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Richardson, John D.; Wang, Chi] Chinese Acad Sci, Ctr Space Sci & Appl Res, State Key Lab Space Weather, Beijing 100080, Peoples R China.
   [Kasper, Justin C.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
C3 Massachusetts Institute of Technology (MIT); Chinese Academy of Sciences; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory
RP Richardson, JD (corresponding author), MIT, Kavli Inst Astrophys & Space Res, 37-655, Cambridge, MA 02139 USA.
EM jdr@space.mit.edu
NR 19
TC 395
Z9 418
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 63
EP 66
DI 10.1038/nature07024
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300035
PM 18596800
DA 2026-03-09
ER

PT J
AU Ahel, I
   Ahel, D
   Matsusaka, T
   Clark, AJ
   Pines, J
   Boulton, SJ
   West, SC
AF Ahel, Ivan
   Ahel, Dragana
   Matsusaka, Takahiro
   Clark, Allison J.
   Pines, Jonathon
   Boulton, Simon J.
   West, Stephen C.
TI Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins
SO NATURE
LA English
DT Article
ID vertebrate somatic-cells; damage checkpoint; mammalian-cells; strand breaks; chfr; entry; poly(adp-ribosyl)ation; polymerase; responses; prophase
AB Post- translational modification ( PTM) of proteins plays an important part in mediating protein interactions and/ or the recruitment of specific protein targets(1,2). PTM can be mediated by the addition of functional groups ( for example, acetylation or phosphorylation), peptides ( for example, ubiquitylation or sumoylation), or nucleotides ( for example, poly( ADP- ribosyl) ation). Poly( ADP- ribosyl) ation often involves the addition of long chains of ADP- ribose units, linked by glycosidic ribose - ribose bonds(3), and is critical for a wide range of processes, including DNA repair, regulation of chromosome structure, transcriptional regulation, mitosis and apoptosis(4). Here we identify a novel poly( ADP- ribose)- binding zinc finger ( PBZ) motif in a number of eukaryotic proteins involved in the DNA damage response and checkpoint regulation. The PBZ motif is also required for posttranslational poly( ADP- ribosyl) ation. We demonstrate interaction of poly( ADP- ribose) with this motif in two representative human proteins, APLF ( aprataxin PNK- like factor) and CHFR ( checkpoint protein with FHA and RING domains), and show that the actions of CHFR in the antephase checkpoint are abrogated by mutations in PBZ or by inhibition of poly( ADP- ribose) synthesis.
C1 [Ahel, Dragana; Clark, Allison J.; Boulton, Simon J.] Canc Res UK London Res Inst, Clare Hall Labs, DNA Damage Response Lab, S Mimms EN6 3LD, Herts, England.
   [Ahel, Ivan; West, Stephen C.] Canc Res UK London Res Inst, Clare Hall Labs, Genet Recombinat Lab, S Mimms EN6 3LD, Herts, England.
   [Matsusaka, Takahiro; Pines, Jonathon] Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QR, England.
C3 Cancer Research UK; Cancer Research UK
RP Boulton, SJ (corresponding author), Canc Res UK London Res Inst, Clare Hall Labs, DNA Damage Response Lab, S Mimms EN6 3LD, Herts, England.
EM simon.boulton@cancer.org.uk; stephen.west@cancer.org.uk
NR 26
TC 367
Z9 433
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 81
EP U12
DI 10.1038/nature06420
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300038
PM 18172500
DA 2026-03-09
ER

PT J
AU Hilf, RJC
   Dutzler, R
AF Hilf, Ricarda J. C.
   Dutzler, Raimund
TI X-ray structure of a prokaryotic pentameric ligand-gated ion channel
SO NATURE
LA English
DT Article
ID nicotinic acetylcholine-receptor; selectivity filter; gating mechanism; amino-acids; k+ channel; binding; loop; mutations; reveals; program
AB Pentameric ligand- gated ion channels ( pLGICs) are key players in the early events of electrical signal transduction at chemical synapses. The family codes for a structurally conserved scaffold of channel proteins that open in response to the binding of neurotransmitter molecules. All proteins share a pentameric organization of identical or related subunits that consist of an extracellular ligand- binding domain followed by a transmembrane channel domain. The nicotinic acetylcholine receptor ( nAChR) is the most thoroughly studied member of the pLGIC family ( for recent reviews see refs 1 - 3). Two sources of structural information provided an architectural framework for the family. The structure of the soluble acetylcholine- binding protein ( AChBP) defined the organization of the extracellular domain and revealed the chemical basis of ligand interaction(4-6). Electron microscopy studies of the nAChR from Torpedo electric ray have yielded a picture of the full- length protein and have recently led to the interpretation of an electron density map at 4.0 angstrom resolution(7-9). Despite the wealth of experimental information, high- resolution structures of any family member have so far not been available. Until recently, the pLGICs were believed to be only expressed in multicellular eukaryotic organisms. The abundance of prokaryotic genome sequences, however, allowed the identification of several homologous proteins in bacterial sources(10,11). Here we present the X- ray structure of a prokaryotic pLGIC from the bacterium Erwinia chrysanthemi ( ELIC) at 3.3 angstrom resolution. Our study reveals the first structure of a pLGIC at high resolution and provides an important model system for the investigation of the general mechanisms of ion permeation and gating within the family.
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, Winterthurer Str 190, CH-8057 Zurich, Switzerland.
EM dutzler@bioc.uzh.ch
NR 43
TC 586
Z9 683
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 MAR 20
PY 2008
VL 452
IS 7185
BP 375
EP U12
DI 10.1038/nature06717
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400052
PM 18322461
DA 2026-03-09
ER

PT J
AU Deborde, S
   Perret, E
   Gravotta, D
   Deora, A
   Salvarezza, S
   Schreiner, R
   Rodriguez-Boulan, E
AF Deborde, Sylvie
   Perret, Emilie
   Gravotta, Diego
   Deora, Ami
   Salvarezza, Susana
   Schreiner, Ryan
   Rodriguez-Boulan, Enrique
TI Clathrin is a key regulator of basolateral polarity
SO NATURE
LA English
DT Article
ID darby canine kidney; epithelial-cells; mdck cells; plasma-membrane; proteins; endosm; receptor; trafficking; endocytosis; transport
AB Clathrin-coated vesicles are vehicles for intracellular trafficking in all nucleated cells, from yeasts to humans. Many studies have demonstrated their essential roles in endocytosis and cellular signalling processes at the plasma membrane. By contrast, very few of their non-endocytic trafficking roles are known, the best characterized being the transport of hydrolases from the Golgi complex to the lysosome. Here we show that clathrin is required for polarity of the basolateral plasma membrane proteins in the epithelial cell line MDCK. Clathrin knockdown depolarized most basolateral proteins, by interfering with their biosynthetic delivery and recycling, but did not affect the polarity of apical proteins. Quantitative live imaging showed that chronic and acute clathrin knockdown selectively slowed down the exit of basolateral proteins from the Golgi complex, and promoted their mis-sorting into apical carrier vesicles. Our results demonstrate a broad requirement for clathrin in basolateral protein trafficking in epithelial cells.
C1 [Deborde, Sylvie; Perret, Emilie; Gravotta, Diego; Deora, Ami; Salvarezza, Susana; Schreiner, Ryan; Rodriguez-Boulan, Enrique] Cornell Univ, Dept Ophthalmol, Dyson Vis Res Inst, New York, NY 10065 USA.
   [Rodriguez-Boulan, Enrique] Cornell Univ, Dept Cell & Dev Biol, Weill Med Coll, New York, NY 10065 USA.
C3 Dyson; Cornell University; Cornell University; Weill Cornell Medicine
RP Rodriguez-Boulan, E (corresponding author), Cornell Univ, Dept Ophthalmol, Dyson Vis Res Inst, LC-300,1300 York Ave, New York, NY 10065 USA.
EM boulan@med.cornell.edu
FU NEI NIH HHS [R01 EY008538] Funding Source: Medline; NIGMS NIH HHS [R01 GM034107] Funding Source: Medline
NR 39
TC 160
Z9 194
U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 10
PY 2008
VL 452
IS 7188
BP 719
EP U3
DI 10.1038/nature06828
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500038
PM 18401403
DA 2026-03-09
ER

PT J
AU Poon, VY
   Klassen, MP
   Shen, K
AF Poon, Vivian Y.
   Klassen, Matthew P.
   Shen, Kang
TI UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites
SO NATURE
LA English
DT Article
ID c-elegans; caenorhabditis-elegans; netrin receptor; axon guidance; colorectal-cancer; synapse formation; drosophila; encodes; wnt; expression
AB Polarity is an essential feature of many cell types, including neurons that receive information from local inputs within their dendrites and propagate nerve impulses to distant targets through a single axon. It is generally believed that intrinsic structural differences between axons and dendrites dictate the polarized localization of axonal and dendritic proteins(1). However, whether extracellular cues also instruct this process in vivo has not been explored. Here we show that the axon guidance cue UNC-6/netrin and its receptor UNC-5 act throughout development to exclude synaptic vesicle and active zone proteins from the dendrite of the Caenorhabditis elegans motor neuron DA9, which is proximal to a source of UNC- 6/ netrin. In unc- 6/ netrin and unc- 5 loss- of-function mutants, presynaptic components mislocalize to the DA9 dendrite. In addition, ectopically expressed UNC- 6/ netrin, acting through UNC- 5, is sufficient to exclude endogenous synapses from adjacent subcellular domains within the DA9 axon. Furthermore, this anti- synaptogenic activity is interchangeable with that of LIN- 44/ Wnt despite being transduced through different receptors, suggesting that extracellular cues such as netrin and Wnts not only guide axon navigation but also regulate the polarized accumulation of presynaptic components through local exclusion.
C1 [Poon, Vivian Y.; Klassen, Matthew P.; Shen, Kang] Stanford Univ, Sch Med, Neurosci Program, Stanford, CA 94305 USA.
   [Shen, Kang] Stanford Univ, Howard Hughes Med Inst, Dept Biol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Howard Hughes Medical Institute
RP Shen, K (corresponding author), Stanford Univ, Sch Med, Neurosci Program, 300 Pasteur Dr, Stanford, CA 94305 USA.
EM kangshen@stanford.edu
FU W. M. Keck Foundation; McKnight Endowment Fund; Searle Scholar Award; Howard Hughes Medical Institute
NR 29
TC 108
Z9 164
U1 1
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 2
PY 2008
VL 455
IS 7213
BP 669
EP U68
DI 10.1038/nature07291
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700048
PM 18776887
DA 2026-03-09
ER

PT J
AU Chen, YQ
   Zhu, J
   Lum, PY
   Yang, X
   Pinto, S
   MacNeil, DJ
   Zhang, CS
   Lamb, J
   Edwards, S
   Sieberts, SK
   Leonardson, A
   Castellini, LW
   Wang, S
   Champy, MF
   Zhang, B
   Emilsson, V
   Doss, S
   Ghazalpour, A
   Horvath, S
   Drake, TA
   Lusis, AJ
   Schadt, EE
AF Chen, Yanqing
   Zhu, Jun
   Lum, Pek Yee
   Yang, Xia
   Pinto, Shirly
   MacNeil, Douglas J.
   Zhang, Chunsheng
   Lamb, John
   Edwards, Stephen
   Sieberts, Solveig K.
   Leonardson, Amy
   Castellini, Lawrence W.
   Wang, Susanna
   Champy, Marie-France
   Zhang, Bin
   Emilsson, Valur
   Doss, Sudheer
   Ghazalpour, Anatole
   Horvath, Steve
   Drake, Thomas A.
   Lusis, Aldons J.
   Schadt, Eric E.
TI Variations in DNA elucidate molecular networks that cause disease
SO NATURE
LA English
DT Article
ID familial combined hyperlipidemia; upstream transcription factor-1; segregating mouse-population; tissue-specific expression; factor-h polymorphism; gene-expression; lipoprotein-lipase; trait analysis; atherosclerosis; identify
AB Identifying variations in DNA that increase susceptibility to disease is one of the primary aims of genetic studies using a forward genetics approach. However, identification of disease- susceptibility genes by means of such studies provides limited functional information on how genes lead to disease. In fact, in most cases there is an absence of functional information altogether, preventing a definitive identification of the susceptibility gene or genes. Here we develop an alternative to the classic forward genetics approach for dissecting complex disease traits where, instead of identifying susceptibility genes directly affected by variations in DNA, we identify gene networks that are perturbed by susceptibility loci and that in turn lead to disease. Application of this method to liver and adipose gene expression data generated from a segregating mouse population results in the identification of a macrophage- enriched network supported as having a causal relationship with disease traits associated with metabolic syndrome. Three genes in this network, lipoprotein lipase ( Lpl), lactamase beta ( Lactb) and protein phosphatase 1- like ( Ppm1l), are validated as previously unknown obesity genes, strengthening the association between this network and metabolic disease traits. Our analysis provides direct experimental support that complex traits such as obesity are emergent properties of molecular networks that are modulated by complex genetic loci and environmental factors.
C1 [Chen, Yanqing; Zhu, Jun; Lum, Pek Yee; Yang, Xia; Zhang, Chunsheng; Lamb, John; Edwards, Stephen; Sieberts, Solveig K.; Leonardson, Amy; Zhang, Bin; Emilsson, Valur; Schadt, Eric E.] Merck & Co Inc, Rosetta Inpharmat LLC, Seattle, WA 98109 USA.
   [Pinto, Shirly; MacNeil, Douglas J.] Merck & Co Inc, Dept Metab Disorders, Rahway, NJ 07065 USA.
   [Castellini, Lawrence W.; Wang, Susanna; Doss, Sudheer; Ghazalpour, Anatole; Lusis, Aldons J.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA.
   [Horvath, Steve; Lusis, Aldons J.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Drake, Thomas A.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
   [Champy, Marie-France] ULP, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France.
C3 Merck & Company; Merck & Company USA; Merck & Company; Merck & Company USA; 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; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS)
RP Schadt, EE (corresponding author), Merck & Co Inc, Rosetta Inpharmat LLC, 401 Terry Ave N, Seattle, WA 98109 USA.
EM eric_schadt@merck.com
FU NHLBI NIH HHS [P01 HL030568, P01 HL028481] Funding Source: Medline; NIDDK NIH HHS [R01 DK071673] Funding Source: Medline
NR 50
TC 710
Z9 843
U1 1
U2 76
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 429
EP 435
DI 10.1038/nature06757
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300023
PM 18344982
DA 2026-03-09
ER

PT J
AU Mathur, N
AF Mathur, Neil
TI Materials science - A desirable wind up
SO NATURE
LA English
DT Article
ID thin-film heterostructures; multiferroic bifeo3
C1 [Mathur, Neil] Dept Mat Sci, Cambridge CB2 3QZ, England.
RP Mathur, N (corresponding author), Dept Mat Sci, New Museums Site,Pembroke St, Cambridge CB2 3QZ, England.
EM ndm12@cam.ac.uk
NR 16
TC 59
Z9 63
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 JUL 31
PY 2008
VL 454
IS 7204
BP 591
EP 592
DI 10.1038/454591a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500032
PM 18668097
DA 2026-03-09
ER

PT J
AU Altschuler, SJ
   Angenent, SB
   Wang, YQ
   Wu, LF
AF Altschuler, Steven J.
   Angenent, Sigurd B.
   Wang, Yanqin
   Wu, Lani F.
TI On the spontaneous emergence of cell polarity
SO NATURE
LA English
DT Article
ID exchange factor cdc24p; positive feedback; symmetry-breaking; plasma-membrane; polarization; gtpase; cdc42p; proteins; system; model
AB Diverse cell polarity networks require positive feedback for locally amplifying distributions of signalling molecules at the plasma membrane(1). Additional mechanisms, such as directed transport(2) or coupled inhibitors(3,4), have been proposed to be required for reinforcing a unique axis of polarity. Here we analyse a simple model of positive feedback, with strong analogy to the 'stepping stone' model of population genetics(5), in which a single species of diffusible, membrane-bound signalling molecules can self-recruit from a cytoplasmic pool. We identify an intrinsic stochastic mechanism through which positive feedback alone is sufficient to account for the spontaneous establishment of a single site of polarity. We find that the polarization frequency has an inverse dependence on the number of signalling molecules: the frequency of polarization decreases as the number of molecules becomes large. Experimental observation of polarizing Cdc42 in budding yeast is consistent with this prediction. Our work suggests that positive feedback can work alone or with additional mechanisms to create robust cell polarity.
C1 [Altschuler, Steven J.; Wang, Yanqin; Wu, Lani F.] Univ Texas SW Med Ctr Dallas, Green Ctr Syst Biol, Dept Pharmacol, Dallas, TX 75390 USA.
   [Altschuler, Steven J.; Wang, Yanqin; Wu, Lani F.] Univ Texas SW Med Ctr Dallas, Simmons Canc Ctr, Dallas, TX 75390 USA.
   [Angenent, Sigurd B.] Univ Wisconsin, Dept Math, Madison, WI 53706 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Wisconsin System; University of Wisconsin Madison
RP Altschuler, SJ (corresponding author), Univ Texas SW Med Ctr Dallas, Green Ctr Syst Biol, Dept Pharmacol, Dallas, TX 75390 USA.
EM steven.altschuler@utsouthwestern.edu; lani.wu@utsouthwestern.edu
FU NIGMS NIH HHS [R01 GM071794] Funding Source: Medline
NR 30
TC 200
Z9 239
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 14
PY 2008
VL 454
IS 7206
BP 886
EP U41
DI 10.1038/nature07119
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600036
PM 18704086
DA 2026-03-09
ER

PT J
AU Strigari, LE
   Bullock, JS
   Kaplinghat, M
   Simon, JD
   Geha, M
   Willman, B
   Walker, MG
AF Strigari, Louis E.
   Bullock, James S.
   Kaplinghat, Manoj
   Simon, Joshua D.
   Geha, Marla
   Willman, Beth
   Walker, Matthew G.
TI A common mass scale for satellite galaxies of the Milky Way
SO NATURE
LA English
DT Article
ID dark-matter substructure; dwarf galaxy; evolution; profiles; origin; haloes
AB The Milky Way has at least twenty- three known satellite galaxies that shine with luminosities ranging from about a thousand to a billion times that of the Sun. Half of these galaxies were discovered(1,2) in the past few years in the Sloan Digital Sky Survey, and they are among the least luminous galaxies in the known Universe. A determination of the mass of these galaxies provides a test of galaxy formation at the smallest scales(3,4) and probes the nature of the dark matter that dominates the mass density of the Universe(5). Here we use new measurements of the velocities of the stars in these galaxies(6,7) to show that they are consistent with them having a common mass of about 10(7) M. within their central 300 parsecs. This result demonstrates that the faintest of the Milky Way satellites are the most dark- matter- dominated galaxies known, and could be a hint of a new scale in galaxy formation or a characteristic scale for the clustering of dark matter.
C1 [Strigari, Louis E.; Bullock, James S.; Kaplinghat, Manoj] Univ Calif Irvine, Ctr Cosmol, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Bullock, James S.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Geha, Marla] Yale Univ, Dept Astron, New Haven, CT 06520 USA.
   [Willman, Beth] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Walker, Matthew G.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
C3 University of California System; University of California Irvine; California Institute of Technology; Yale University; Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; University of Cambridge
RP Strigari, LE (corresponding author), Univ Calif Irvine, Ctr Cosmol, Dept Phys & Astron, Irvine, CA 92697 USA.
EM lstrigar@uci.edu
FU STFC [PP/E00105X/1, ST/F001967/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/E00105X/1, ST/F001967/1] Funding Source: researchfish
NR 31
TC 445
Z9 487
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 28
PY 2008
VL 454
IS 7208
BP 1096
EP 1097
DI 10.1038/nature07222
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600032
PM 18756252
DA 2026-03-09
ER

PT J
AU Burlaga, LF
   Ness, NF
   Acuña, MH
   Lepping, RP
   Connerney, JEP
   Richardson, JD
AF Burlaga, L. F.
   Ness, N. F.
   Acuna, M. H.
   Lepping, R. P.
   Connerney, J. E. P.
   Richardson, J. D.
TI Magnetic fields at the solar wind termination shock
SO NATURE
LA English
DT Article
ID collisionless-shock; perpendicular shocks; voyager-1; plasma; heliosheath; waves; ions
AB A transition between the supersonic solar wind and the subsonic heliosheath was observed by Voyager 1, but the expected termination shock was not seen owing to a gap in the telemetry(1-4). Here we report observations of the magnetic field structure and dynamics of the termination shock, made by Voyager 2 on 31 August - 1 September 2007 at a distance of 83.7 AU from the Sun ( 1 AU is the Earth - Sun distance). A single crossing of the shock was expected, with a boundary that was stable on a timescale of several days. But the data reveal a complex, rippled, quasi- perpendicular supercritical magnetohydrodynamic shock of moderate strength undergoing reformation on a scale of a few hours. The observed structure suggests the importance of ionized interstellar atoms shock.
C1 [Burlaga, L. F.; Acuna, M. H.; Lepping, R. P.; Connerney, J. E. P.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Ness, N. F.] Catholic Univ Amer, Washington, DC 20064 USA.
   [Richardson, J. D.] MIT, Cambridge, MA 02139 USA.
C3 National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Catholic University of America; Massachusetts Institute of Technology (MIT)
RP Burlaga, LF (corresponding author), NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
EM Leonard.F.Burlaga@nasa.gov
NR 23
TC 216
Z9 230
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 75
EP 77
DI 10.1038/nature07029
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300038
PM 18596803
DA 2026-03-09
ER

PT J
AU Whittaker, JM
   Müller, RD
   Roest, WR
   Wessel, P
   Smith, WHF
AF Whittaker, Joanne M.
   Muller, R. Dietmar
   Roest, Walter R.
   Wessel, Paul
   Smith, Walter H. F.
TI How supercontinents and superoceans affect seafloor roughness
SO NATURE
LA English
DT Article
ID australian-antarctic discordance; mantle; gravity; variability; seamounts; basalts; plume
AB Seafloor roughness varies considerably across the world's ocean basins and is fundamental to controlling the circulation and mixing of heat in the ocean(1) and dissipating eddy kinetic energy(2). Models derived from analyses of active mid- ocean ridges suggest that ocean floor roughness depends on seafloor spreading rates(3), with rougher basement forming below a half- spreading rate threshold of 30 - 35 mm yr(-1) ( refs 4, 5), as well as on the local interaction of mid- ocean ridges with mantle plumes or coldspots(6). Here we present a global analysis of marine gravity- derived roughness, sediment thickness, seafloor isochrons and palaeo-spreading rates(7) of Cretaceous to Cenozoic ridge flanks. Our analysis reveals that, after eliminating effects related to spreading rate and sediment thickness, residual roughness anomalies of 5 - 20 m Gal remain over large swaths of ocean floor. We found that the roughness as a function of palaeo- spreading directions and isochron orientations(7) indicates that most of the observed excess roughness is not related to spreading obliquity, as this effect is restricted to relatively rare occurrences of very high obliquity angles (>45 degrees). Cretaceous Atlantic ocean floor, formed over mantle previously overlain by the Pangaea supercontinent, displays anomalously low roughness away from mantle plumes and is independent of spreading rates. We attribute this observation to a sub-Pangaean supercontinental mantle temperature anomaly(8) leading to slightly thicker than normal Late Jurassic and Cretaceous Atlantic crust(9), reduced brittle fracturing and smoother basement relief. In contrast, ocean crust formed above Pacific superswells(10), probably reflecting metasomatized lithosphere underlain by mantle at only slightly elevated temperatures(11), is not associated with basement roughness anomalies. These results highlight a fundamental difference in the nature of large- scale mantle upwellings below supercontinents and superoceans, and their impact on oceanic crustal accretion.
C1 [Whittaker, Joanne M.; Muller, R. Dietmar] Univ Sydney, Earthbyte Grp, Sch Geosci, Sydney, NSW 2006, Australia.
   [Roest, Walter R.] IFREMER, Ctr Brest, Dept Marine Geosci, F-29280 Plouzane, France.
   [Wessel, Paul] Univ Hawaii Manoa, Dept Geol & Geophys, SOEST, Honolulu, HI 96822 USA.
   [Smith, Walter H. F.] NOAA, Silver Spring, MD 20910 USA.
C3 University of Sydney; Universite Paris Cite; Ifremer; University of Hawaii System; University of Hawaii Manoa; National Oceanic Atmospheric Admin (NOAA) - USA
RP Whittaker, JM (corresponding author), GETECH, Kitson House,Elmete Hall,Elmete Lane, Leeds LS8 2LJ, W Yorkshire, England.
EM jw@getech.com
NR 30
TC 32
Z9 34
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 DEC 18
PY 2008
VL 456
IS 7224
BP 938
EP U73
DI 10.1038/nature07573
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300042
PM 19092932
DA 2026-03-09
ER

PT J
AU Bell, JJ
   Bhandoola, A
AF Bell, J. Jeremiah
   Bhandoola, Avinash
TI The earliest thymic progenitors for T cells possess myeloid lineage potential
SO NATURE
LA English
DT Article
ID common lymphoid progenitors; hematopoietic stem-cells; bone-marrow; dendritic cells; identification; precursor; differentiation; transcription; macrophages; commitment
AB There exists controversy over the nature of haematopoietic progenitors of T cells. Most T cells develop in the thymus, but the lineage potential of thymus-colonizing progenitors is unknown. One approach to resolving this question is to determine the lineage potentials of the earliest thymic progenitors (ETPs). Previous work has shown that ETPs possess T and natural killer lymphoid potentials, and rare subsets of ETPs also possess B lymphoid potential(1), suggesting an origin from lymphoid-restricted progenitor cells. However, whether ETPs also possess myeloid potential is unknown. Here we show that nearly all ETPs in adult mice possess both T and myeloid potential in clonal assays. The existence of progenitors possessing T and myeloid potential within the thymus is incompatible with the current dominant model of haematopoiesis, in which T cells are proposed to arise from lymphoid-restricted progenitors(2). Our results indicate that alternative models for lineage commitment during haematopoiesis must be considered.
C1 [Bell, J. Jeremiah; Bhandoola, Avinash] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania
RP Bhandoola, A (corresponding author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM bhandooa@mail.med.upenn.edu
NR 29
TC 347
Z9 458
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 10
PY 2008
VL 452
IS 7188
BP 764
EP U9
DI 10.1038/nature06840
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500048
PM 18401411
DA 2026-03-09
ER

PT J
AU Schoelkopf, RJ
   Girvin, SM
AF Schoelkopf, R. J.
   Girvin, S. M.
TI Wiring up quantum systems
SO NATURE
LA English
DT Article
ID superconducting qubits; single-photon; state; atom; entanglement; field; dynamics; collapse; dot
C1 [Schoelkopf, R. J.; Girvin, S. M.] Yale Univ, Dept Appl Phys, New Haven, CT 06520 USA.
   [Schoelkopf, R. J.; Girvin, S. M.] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
C3 Yale University; Yale University
RP Schoelkopf, RJ (corresponding author), Yale Univ, Dept Appl Phys, New Haven, CT 06520 USA.
NR 64
TC 787
Z9 928
U1 1
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 FEB 7
PY 2008
VL 451
IS 7179
BP 664
EP 669
DI 10.1038/451664a
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500031
PM 18256662
DA 2026-03-09
ER

PT J
AU Nedjic, J
   Aichinger, M
   Emmerich, J
   Mizushima, N
   Klein, L
AF Nedjic, Jelena
   Aichinger, Martin
   Emmerich, Jan
   Mizushima, Noboru
   Klein, Ludger
TI Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance
SO NATURE
LA English
DT Article
ID genome-wide association; class-ii presentation; crohn-disease; in-vivo; antigen; selection; aire; medulla; protein; vitro
AB Recognition of self- antigen- derived epitopes presented by major histocompatibility complex class II ( MHC II) molecules on thymic epithelial cells ( TECs) is critical for the generation of a functional and self- tolerant CD4 T- cell repertoire. Whereas haematopoietic antigen- presenting cells generate MHC- II - peptide complexes predominantly through the processing of endocytosed polypeptides(1), it remains unknown if and how TECs use unconventional pathways of antigen presentation. Here we address the role of macroautophagy, a process that has recently been shown to allow for endogenous MHC II loading(2-6), in T- cell repertoire selection in the mouse thymus. In contrast to most other tissues, TECs had a high constitutive level of autophagy. Genetic interference with autophagy specifically in TECs led to altered selection of certain MHC-II-restricted T- cell specificities and resulted in severe colitis and multi- organ inflammation. Our findings indicate that autophagy focuses the MHC- II - peptide repertoire of TECs on their intracellular milieu, which notably comprises a wide array of otherwise strictly 'tissue-specific' self antigens(7,8). In doing so, it contributes to T- cell selection and is essential for the generation of a self- tolerant T- cell repertoire.
C1 [Nedjic, Jelena; Aichinger, Martin; Emmerich, Jan; Klein, Ludger] Res Inst Mol Pathol, A-1030 Vienna, Austria.
   [Mizushima, Noboru] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Bunkyo Ku, Tokyo 1138613, Japan.
   [Klein, Ludger] Univ Munich, Inst Immunol, D-80336 Munich, Germany.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); University of Munich
RP Klein, L (corresponding author), Res Inst Mol Pathol, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
EM ludger.klein@med.lmu.de
FU Austrian National Science Fund [F023, Z58-B01]; European Union; FP6 Integrated Project Eurothymaide [LSHB-CT-2003-503410]; Boehringer Ingelheim
NR 32
TC 409
Z9 490
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 396
EP U49
DI 10.1038/nature07208
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200046
PM 18701890
DA 2026-03-09
ER

PT J
AU Morton, JJL
   Tyryshkin, AM
   Brown, RM
   Shankar, S
   Lovett, BW
   Ardavan, A
   Schenkel, T
   Haller, EE
   Ager, JW
   Lyon, SA
AF Morton, John J. L.
   Tyryshkin, Alexei M.
   Brown, Richard M.
   Shankar, Shyam
   Lovett, Brendon W.
   Ardavan, Arzhang
   Schenkel, Thomas
   Haller, Eugene E.
   Ager, Joel W.
   Lyon, S. A.
TI Solid-state quantum memory using the 31P nuclear spin
SO NATURE
LA English
DT Article
ID electron-spin; qubits; decoherence; coherence; silicon
AB The transfer of information between different physical forms - for example processing entities and memory - is a central theme in communication and computation. This is crucial in quantum computation(1), where great effort(2) must be taken to protect the integrity of a fragile quantum bit ( qubit). However, transfer of quantum information is particularly challenging, as the process must remain coherent at all times to preserve the quantum nature of the information(3). Here we demonstrate the coherent transfer of a superposition state in an electron- spin 'processing' qubit to a nuclear- spin 'memory' qubit, using a combination of microwave and radio- frequency pulses applied to P-31 donors in an isotopically pure Si-28 crystal(4,5). The state is left in the nuclear spin on a time-scale that is long compared with the electron decoherence time, and is then coherently transferred back to the electron spin, thus demonstrating the P-31 nuclear spin as a solid-state quantum memory. The overall store - readout fidelity is about 90 per cent, with the loss attributed to imperfect rotations, and can be improved through the use of composite pulses(6). The coherence lifetime of the quantum memory element at 5.5 K exceeds 1 s.
C1 [Morton, John J. L.; Brown, Richard M.; Lovett, Brendon W.] Univ Oxford, Dept Mat, Oxford OX1 3PH, England.
   [Morton, John J. L.; Ardavan, Arzhang] Univ Oxford, Dept Phys, Clarendon Lab, CAESR, Oxford OX1 3PU, England.
   [Tyryshkin, Alexei M.; Shankar, Shyam; Lyon, S. A.] Princeton Univ, Dept Elect Engn, Princeton, NJ 08544 USA.
   [Schenkel, Thomas; Haller, Eugene E.; Ager, Joel W.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Haller, Eugene E.] Univ Calif Berkeley, Dept Mat Sci & Engn, Berkeley, CA 94720 USA.
C3 University of Oxford; University of Oxford; Princeton University; 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
RP Morton, JJL (corresponding author), Univ Oxford, Dept Mat, Parks Rd, Oxford OX1 3PH, England.
EM john.morton@materials.ox.ac.uk
FU National Security Agency [MOD 713106A]; EPSRC [GR/S82176/01]; CAESR [EP/D048559/1]; St John's College, Oxford; Royal Society; US National Science Foundation [DMR-0213706]; Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division of the US Department of Energy [DE-AC02-05CH11231]; Engineering and Physical Sciences Research Council [EP/D048559/1, GR/S82176/01] Funding Source: researchfish; Division Of Materials Research; Direct For Mathematical & Physical Scien [0819860] Funding Source: National Science Foundation; EPSRC [EP/D048559/1] Funding Source: UKRI
NR 31
TC 345
Z9 398
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 23
PY 2008
VL 455
IS 7216
BP 1085
EP 1088
DI 10.1038/nature07295
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600039
DA 2026-03-09
ER

PT J
AU Stipanovich, A
   Valjent, E
   Matamales, M
   Nishi, A
   Ahn, JH
   Maroteaux, M
   Bertran-Gonzalez, J
   Brami-Cherrier, K
   Enslen, H
   Corbillé, AG
   Filhol, O
   Nairn, AC
   Greengard, P
   Hervé, D
   Girault, JA
AF Stipanovich, Alexandre
   Valjent, Emmanuel
   Matamales, Miriam
   Nishi, Akinori
   Ahn, Jung-Hyuck
   Maroteaux, Matthieu
   Bertran-Gonzalez, Jesus
   Brami-Cherrier, Karen
   Enslen, Herve
   Corbille, Anne-Gaelle
   Filhol, Odile
   Nairn, Angus C.
   Greengard, Paul
   Herve, Denis
   Girault, Jean-Antoine
TI A phosphatase cascade by which rewarding stimuli control nucleosomal response
SO NATURE
LA English
DT Article
ID histone h3 phosphorylation; innervated brain-regions; nuclear export; dopaminergic neurotransmission; regulated phosphoprotein; protein phosphatase-1; gene-expression; drug-addiction; kinase; darpp-32
AB Dopamine orchestrates motor behaviour and reward- driven learning. Perturbations of dopamine signalling have been implicated in several neurological and psychiatric disorders, and in drug addiction. The actions of dopamine are mediated in part by the regulation of gene expression in the striatum, through mechanisms that are not fully understood. Here we show that drugs of abuse, as well as food reinforcement learning, promote the nuclear accumulation of 32- kDa dopamine- regulated and cyclic- AMP- regulated phosphoprotein ( DARPP- 32). This accumulation is mediated through a signalling cascade involving dopamine D1 receptors, cAMP- dependent activation of protein phosphatase- 2A, dephosphorylation of DARPP- 32 at Ser 97 and inhibition of its nuclear export. The nuclear accumulation of DARPP- 32, a potent inhibitor of protein phosphatase- 1, increases the phosphorylation of histone H3, an important component of nucleosomal response. Mutation of Ser 97 profoundly alters behavioural effects of drugs of abuse and decreases motivation for food, underlining the functional importance of this signalling cascade.
C1 [Stipanovich, Alexandre; Valjent, Emmanuel; Matamales, Miriam; Maroteaux, Matthieu; Bertran-Gonzalez, Jesus; Brami-Cherrier, Karen; Enslen, Herve; Corbille, Anne-Gaelle; Herve, Denis; Girault, Jean-Antoine] INSERM, UMR S 839, F-75005 Paris, France.
   [Stipanovich, Alexandre; Valjent, Emmanuel; Matamales, Miriam; Maroteaux, Matthieu; Bertran-Gonzalez, Jesus; Brami-Cherrier, Karen; Enslen, Herve; Corbille, Anne-Gaelle; Herve, Denis; Girault, Jean-Antoine] Univ Paris 06, F-75005 Paris, France.
   [Stipanovich, Alexandre; Valjent, Emmanuel; Matamales, Miriam; Maroteaux, Matthieu; Bertran-Gonzalez, Jesus; Brami-Cherrier, Karen; Enslen, Herve; Corbille, Anne-Gaelle; Herve, Denis; Girault, Jean-Antoine] Inst Fer Moulin, F-75005 Paris, France.
   [Nishi, Akinori] Kurume Univ, Sch Med, Dept Pharmacol, Fukuoka 8300011, Japan.
   [Nishi, Akinori; Ahn, Jung-Hyuck; Nairn, Angus C.; Greengard, Paul] Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA.
   [Filhol, Odile] CEA, INSERM, U873, F-38054 Grenoble, France.
   [Nairn, Angus C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06508 USA.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Sorbonne Universite; Sorbonne Universite; Kurume University; Rockefeller University; Institut National de la Sante et de la Recherche Medicale (Inserm); CEA; Yale University
RP Girault, JA (corresponding author), INSERM, UMR S 839, F-75005 Paris, France.
EM girault@fer-a-moulin.inserm.fr
FU NIDA NIH HHS [P01 DA010044, DA10044] Funding Source: Medline; NIMH NIH HHS [P50 MH074866, MH74866] Funding Source: Medline
NR 44
TC 188
Z9 224
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 879
EP U23
DI 10.1038/nature06994
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000034
PM 18496528
DA 2026-03-09
ER

PT J
AU Meissner, A
   Mikkelsen, TS
   Gu, HC
   Wernig, M
   Hanna, J
   Sivachenko, A
   Zhang, XL
   Bernstein, BE
   Nusbaum, C
   Jaffe, DB
   Gnirke, A
   Jaenisch, R
   Lander, ES
AF Meissner, Alexander
   Mikkelsen, Tarjei S.
   Gu, Hongcang
   Wernig, Marius
   Hanna, Jacob
   Sivachenko, Andrey
   Zhang, Xiaolan
   Bernstein, Bradley E.
   Nusbaum, Chad
   Jaffe, David B.
   Gnirke, Andreas
   Jaenisch, Rudolf
   Lander, Eric S.
TI Genome-scale DNA methylation maps of pluripotent and differentiated cells
SO NATURE
LA English
DT Article
ID embryonic stem-cells; distinct; cancer; genes; hypermethylation; signatures; promoters; patterns; display
AB DNA methylation is essential for normal development(1-3) and has been implicated in many pathologies including cancer(4,5). Our knowledge about the genome-wide distribution of DNA methylation, how it changes during cellular differentiation and how it relates to histone methylation and other chromatin modifications in mammals remains limited. Here we report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput reduced representation bisulphite sequencing(6) and single-molecule-based sequencing, we generated DNA methylation maps covering most CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for mouse embryonic stem cells, embryonic-stem-cell-derived and primary neural cells, and eight other primary tissues. Several key findings emerge from the data. First, DNA methylation patterns are better correlated with histone methylation patterns than with the underlying genome sequence context. Second, methylation of CpGs are dynamic epigenetic marks that undergo extensive changes during cellular differentiation, particularly in regulatory regions outside of core promoters. Third, analysis of embryonic-stem-cell-derived and primary cells reveals that 'weak' CpG islands associated with a specific set of developmentally regulated genes undergo aberrant hypermethylation during extended proliferation in vitro, in a pattern reminiscent of that reported in some primary tumours. More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.
C1 [Meissner, Alexander; Wernig, Marius; Hanna, Jacob; Jaenisch, Rudolf; Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Meissner, Alexander; Mikkelsen, Tarjei S.; Gu, Hongcang; Sivachenko, Andrey; Zhang, Xiaolan; Bernstein, Bradley E.; Nusbaum, Chad; Jaffe, David B.; Gnirke, Andreas; Lander, Eric S.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Mikkelsen, Tarjei S.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Bernstein, Bradley E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.
   [Bernstein, Bradley E.] Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA.
   [Bernstein, Bradley E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Jaenisch, Rudolf; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School
RP Jaenisch, R (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM jaenisch@wi.mit.edu; lander@broad.mit.edu
FU NHGRI NIH HHS [U54 HG003067, R01 HG004401] Funding Source: Medline
NR 30
TC 1973
Z9 2465
U1 1
U2 354
PU 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 7
PY 2008
VL 454
IS 7205
BP 766
EP U91
DI 10.1038/nature07107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000045
PM 18600261
DA 2026-03-09
ER

PT J
AU Kermode, JR
   Albaret, T
   Sherman, D
   Bernstein, N
   Gumbsch, P
   Payne, MC
   Csányi, G
   De Vita, A
AF Kermode, J. R.
   Albaret, T.
   Sherman, D.
   Bernstein, N.
   Gumbsch, P.
   Payne, M. C.
   Csanyi, G.
   De Vita, A.
TI Low-speed fracture instabilities in a brittle crystal
SO NATURE
LA English
DT Article
ID silicon single-crystals; cleavage fracture; dynamic fracture; crack front; simulation; anisotropy; velocity; surface; path
AB When a brittle material is loaded to the limit of its strength, it fails by the nucleation and propagation of a crack(1). The conditions for crack propagation are created by stress concentration in the region of the crack tip and depend on macroscopic parameters such as the geometry and dimensions of the specimen(2). The way the crack propagates, however, is entirely determined by atomic- scale phenomena, because brittle crack tips are atomically sharp and propagate by breaking the variously oriented interatomic bonds, one at a time, at each point of the moving crack front(1,3). The physical interplay of multiple length scales makes brittle fracture a complex 'multi-scale' phenomenon. Several intermediate scales may arise in more complex situations, for example in the presence of microdefects or grain boundaries. The occurrence of various instabilities in crack propagation at very high speeds is well known(1), and significant advances have been made recently in understanding their origin(4,5). Here we investigate low- speed propagation instabilities in silicon using quantum- mechanical hybrid, multi- scale modelling and single- crystal fracture experiments. Our simulations predict a crack- tip reconstruction that makes low- speed crack propagation unstable on the ( 111) cleavage plane, which is conventionally thought of as the most stable cleavage plane. We perform experiments in which this instability is observed at a range of low speeds, using an experimental technique designed for the investigation of fracture under low tensile loads. Further simulations explain why, conversely, at moderately high speeds crack propagation on the ( 110) cleavage plane becomes unstable and deflects onto ( 111) planes, as previously observed experimentally(6,7).
C1 [Csanyi, G.] Univ Cambridge, Engn Lab, Cambridge CB2 1PZ, England.
   [De Vita, A.] Kings Coll London, Dept Phys, London WC2R 2LS, England.
   [De Vita, A.] Univ Trieste, INFM, DEMOCRITOS Natl Simulat Ctr, I-34127 Trieste, Italy.
   [De Vita, A.] Univ Trieste, INFM, Ctr Excellence Nanostruct Mat, I-34127 Trieste, Italy.
   [Kermode, J. R.; Payne, M. C.] Univ Cambridge, Cavendish Lab, Condensed Matter Theory Grp, Cambridge CB3 0HE, England.
   [Albaret, T.] Univ Lyon 1, CNRS, LPMCN, UMR 5586, F-69622 Villeurbanne, France.
   [Sherman, D.] Technion Israel Inst Technol, Dept Mat Engn, IL-32000 Haifa, Israel.
   [Bernstein, N.] USN, Res Lab, Ctr Computat Mat Sci, Washington, DC 20375 USA.
   [Gumbsch, P.] Univ Karlsruhe, Inst Zuverlassigkeit von Bauteilen & Syst, D-76131 Karlsruhe, Germany.
   [Gumbsch, P.] Fraunhofer Inst Werkstoffmech, D-79108 Freiburg, Germany.
C3 University of Cambridge; University of London; King's College London; Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale per la Fisica della Materia (INFM-CNR); University of Trieste; University of Trieste; Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale per la Fisica della Materia (INFM-CNR); University of Cambridge; Centre National de la Recherche Scientifique (CNRS); Universite Lyon 1; Technion Israel Institute of Technology; United States Department of Defense; United States Navy; United States Naval Research Laboratory; NRL Chesapeake; Helmholtz Association; Karlsruhe Institute of Technology; Fraunhofer Gesellschaft
RP Csányi, G (corresponding author), Univ Cambridge, Engn Lab, Cambridge CB2 1PZ, England.
EM gc121@cam.ac.uk
FU Deutsche Forschungsgemeinschaft [Gu 367/30]; NRL; ONR; ISF [1110/04]; EPSRC [GR/S61263/01, EP/5C23938/1, EP/C52392X/1]; ANR-France [ANR-05-CIGC:LN3M]; IDRIS, Orsay, France [051841]; EPSRC [EP/C523938/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/C523938/1, EP/C52392X/1, GR/S61263/01] Funding Source: researchfish
NR 30
TC 195
Z9 208
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 OCT 30
PY 2008
VL 455
IS 7217
BP 1224
EP U41
DI 10.1038/nature07297
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100040
DA 2026-03-09
ER

PT J
AU Li, Y
   Van Hooser, SD
   Mazurek, M
   White, LE
   Fitzpatrick, D
AF Li, Ye
   Van Hooser, Stephen D.
   Mazurek, Mark
   White, Leonard E.
   Fitzpatrick, David
TI Experience with moving visual stimuli drives the early development of cortical direction selectivity
SO NATURE
LA English
DT Article
ID lateral geniculate-nucleus; ocular dominance columns; receptive-fields; orientation maps; in-vivo; cortex; cat; organization; kittens; sensitivity
AB The onset of vision occurs when neural circuits in the visual cortex are immature, lacking both the full complement of connections(1,2) and the response selectivity that defines functional maturity(3,4). Direction- selective responses are particularly vulnerable to the effects of early visual deprivation, but it remains unclear how stimulus- driven neural activity guides the emergence of cortical direction selectivity. Here we report observations from a motion training protocol that allowed us to monitor the impact of experience on the development of direction- selective responses in visually naive ferrets. Using intrinsic signal imaging techniques, we found that training with a single axis of motion induced the rapid emergence of direction columns that were confined to cortical regions preferentially activated by the training stimulus. Using two- photon calcium imaging techniques, we found that single neurons in visually naive animals exhibited weak directional biases and lacked the strong local coherence in the spatial organization of direction preference that was evident in mature animals. Training with a moving stimulus, but not with a flashed stimulus, strengthened the direction- selective responses of individual neurons and preferentially reversed the direction biases of neurons that deviated from their neighbours. Both effects contributed to an increase in local coherence. We conclude that early experience with moving visual stimuli drives the rapid emergence of direction-selective responses in the visual cortex.
C1 [Li, Ye; Van Hooser, Stephen D.; Mazurek, Mark; White, Leonard E.; Fitzpatrick, David] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA.
   [White, Leonard E.] Duke Univ, Sch Med, Dept Community & Family Med, Doctor Phys Therapy Div, Durham, NC 27710 USA.
   [Fitzpatrick, David] Duke Univ, Duke Inst Brain Sci, Durham, NC 27710 USA.
C3 Duke University; Duke University; Duke University
RP Fitzpatrick, D (corresponding author), Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA.
EM fitzpat@neuro.duke.edu
FU Whitehall Foundation; US National Institutes of Health; National Eye Institute [P30EY005722, R01EY011488] Funding Source: NIH RePORTER
NR 30
TC 145
Z9 182
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 952
EP 956
DI 10.1038/nature07417
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300046
PM 18946471
DA 2026-03-09
ER

PT J
AU Zhang, FC
   Zhou, ZH
   Xu, X
   Wang, XL
   Sullivan, C
AF Zhang, Fucheng
   Zhou, Zhonghe
   Xu, Xing
   Wang, Xiaolin
   Sullivan, Corwin
TI A bizarre Jurassic maniraptoran from China with elongate ribbon-like feathers
SO NATURE
LA English
DT Article
ID bird; dinosaur; theropod; origin
AB Recent coelurosaurian discoveries have greatly enriched our knowledge of the transition from dinosaurs to birds, but all reported taxa close to this transition are from relatively well known coelurosaurian groups(1-3). Here we report a new basal avialan, Epidexipteryx hui gen. et sp. nov., from the Middle to Late Jurassic of Inner Mongolia, China. This new species is characterized by an unexpected combination of characters seen in several different theropod groups, particularly the Oviraptorosauria. Phylogenetic analysis shows it to be the sister taxon to Epidendrosaurus(4,5), forming a new clade at the base of Avialae(6). Epidexipteryx also possesses two pairs of elongate ribbon- like tail feathers, and its limbs lack contour feathers for flight. This finding shows that a member of the avialan lineage experimented with integumentary ornamentation as early as the Middle to Late Jurassic, and provides further evidence relating to this aspect of the transition from non- avian theropods to birds.
C1 [Zhang, Fucheng; Zhou, Zhonghe; Xu, Xing; Wang, Xiaolin; Sullivan, Corwin] Chinese Acad Sci, Lab Evolutionary Systemat Vertebrates, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS
RP Zhang, FC (corresponding author), Chinese Acad Sci, Lab Evolutionary Systemat Vertebrates, Inst Vertebrate Paleontol & Paleoanthropol, POB 643, Beijing 100044, Peoples R China.
EM zhangfucheng@ivpp.ac.cn
FU National Natural Science Foundation of China; Chinese Academy of Sciences; Major Basic Research Projects of the Ministry of Science and Technology, China
NR 30
TC 174
Z9 215
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 OCT 23
PY 2008
VL 455
IS 7216
BP 1105
EP 1108
DI 10.1038/nature07447
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600044
PM 18948955
DA 2026-03-09
ER

PT J
AU Sato, K
   Pellegrino, M
   Nakagawa, T
   Nakagawa, T
   Vosshall, LB
   Touhara, K
AF Sato, Koji
   Pellegrino, Maurizio
   Nakagawa, Takao
   Nakagawa, Tatsuro
   Vosshall, Leslie B.
   Touhara, Kazushige
TI Insect olfactory receptors are heteromeric ligand-gated ion channels
SO NATURE
LA English
DT Article
ID drosophila-antenna; odorant receptor; membrane topology; transduction; neurons; system; model
AB In insects, each olfactory sensory neuron expresses between one and three ligand- binding members of the olfactory receptor ( OR) gene family, along with the highly conserved and broadly expressed Or83b co-receptor(1-9). The functional insect OR consists of a heteromeric complex of unknown stoichiometry but comprising at least one variable odorant- binding subunit and one constant Or83b family subunit(10-16). Insect ORs lack homology to G- protein-coupled chemosensory receptors in vertebrates(17) and possess a distinct seven- transmembrane topology with the amino terminus located intracellularly(10,18). Here we provide evidence that heteromeric insect ORs comprise a new class of ligand- activated nonselective cation channels. Heterologous cells expressing silkmoth, fruitfly or mosquito heteromeric OR complexes showed extracellular Ca2+ influx and cation- non- selective ion conductance on stimulation with odorant. Odour- evoked OR currents are independent of known G- protein- coupled second messenger pathways. The fast response kinetics and OR- subunit- dependent K+ ion selectivity of the insect OR complex support the hypothesis that the complex between OR and Or83b itself confers channel activity. Direct evidence for odorant- gated channels was obtained by outside- out patch- clamp recording of Xenopus oocyte and HEK293T cell membranes expressing insect OR complexes. The ligand- gated ion channel formed by an insect OR complex seems to be the basis for a unique strategy that insects have acquired to respond to the olfactory environment.
C1 [Sato, Koji; Nakagawa, Takao; Nakagawa, Tatsuro; Touhara, Kazushige] Univ Tokyo, Dept Integrated Biosci, Chiba 2778562, Japan.
   [Pellegrino, Maurizio; Vosshall, Leslie B.] Rockefeller Univ, Lab Neurogenet & Behav, New York, NY 10065 USA.
C3 University of Tokyo; Rockefeller University
RP Touhara, K (corresponding author), Univ Tokyo, Dept Integrated Biosci, Chiba 2778562, Japan.
EM touhara@k.u-tokyo.ac.jp
NR 31
TC 857
Z9 1058
U1 8
U2 271
PU 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 24
PY 2008
VL 452
IS 7190
BP 1002
EP U9
DI 10.1038/nature06850
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600041
PM 18408712
DA 2026-03-09
ER

PT J
AU Wang, LH
   Lin, RP
   Larson, DE
   Luhmann, JG
AF Wang, Linghua
   Lin, Robert P.
   Larson, Davin E.
   Luhmann, Janet G.
TI Domination of heliosheath pressure by shock-accelerated pickup ions from observations of neutral atoms
SO NATURE
LA English
DT Article
ID low-energy ions; termination shock; solar-wind; hydrogen; helium
AB The solar wind blows an immense magnetic bubble, the heliosphere, in the local interstellar medium ( mostly neutral gas) flowing by the Sun(1). Recent measurements by Voyager 2 across the termination shock, where the solar wind is slowed to subsonic speeds before entering the heliosheath, found that the shocked solar wind plasma(2) contains only similar to 20 per cent of the energy released by the termination shock, whereas energetic particles(3) above similar to 28 keV contain only similar to 10 per cent; similar to 70 per cent of the energy is unaccounted for, leading to speculation(2,3) that the unmeasured pickup ions or energetic particles below similar to 28 keV contain the missing energy. Here we report the detection and mapping of heliosheath energetic ( 4 - 20 keV) neutral atoms produced by charge exchange of suprathermal ions with interstellar neutral atoms. The energetic neutral atoms come from a source similar to 60 degrees wide in longitude straddling the direction of the local interstellar medium. Their energy spectra resemble those of solar wind pickup ions, but with a knee at similar to 11 keV instead of similar to 4 keV, indicating that their parent ions are pickup ions energized by the termination shock. These termination- shock- energized pickup ions contain the missing similar to 70 per cent of the energy dissipated in the termination shock, and they dominate the pressure in the heliosheath.
C1 [Wang, Linghua; Lin, Robert P.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Wang, Linghua; Lin, Robert P.; Larson, Davin E.; Luhmann, Janet G.] Univ Calif Berkeley, Space Sci Lab, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Wang, LH (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
EM windsound@ssl.berkeley.edu
NR 15
TC 16
Z9 19
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 3
PY 2008
VL 454
IS 7200
BP 81
EP 83
DI 10.1038/nature07068
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300040
PM 18596805
DA 2026-03-09
ER

PT J
AU McMurray, HR
   Sampson, ER
   Compitello, G
   Kinsey, C
   Newman, L
   Smith, B
   Chen, SR
   Klebanov, L
   Salzman, P
   Yakovlev, A
   Land, H
AF McMurray, Helene R.
   Sampson, Erik R.
   Compitello, George
   Kinsey, Conan
   Newman, Laurel
   Smith, Bradley
   Chen, Shaw-Ree
   Klebanov, Lev
   Salzman, Peter
   Yakovlev, Andrei
   Land, Hartmut
TI Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype
SO NATURE
LA English
DT Article
ID cell-cycle arrest; tumor-suppressor; epithelial-cells; c-myc; p53; transformation; metastasis; pathway; mice; reveals
AB Understanding the molecular underpinnings of cancer is of critical importance to the development of targeted intervention strategies. Identification of such targets, however, is notoriously difficult and unpredictable. Malignant cell transformation requires the cooperation of a few oncogenic mutations that cause substantial reorganization of many cell features(1) and induce complex changes in gene expression patterns(2-6). Genes critical to this multifaceted cellular phenotype have therefore only been identified after signalling pathway analysis(7-10) or on an ad hoc basis(4,11-14). Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signalling circuitry(15-17) suggest that malignant transformation is a highly cooperative process, involving synergy at multiple levels of regulation, including gene expression. Here we show that a large proportion of genes controlled synergistically by loss-of-function p53 and Ras activation are critical to the malignant state of murine and human colon cells. Notably, 14 out of 24 'cooperation response genes' were found to contribute to tumour formation in gene perturbation experiments. In contrast, only 1 in 14 perturbations of the genes responding in a non-synergistic manner had a similar effect. Synergistic control of gene expression by oncogenic mutations thus emerges as an underlying key to malignancy, and provides an attractive rationale for identifying intervention targets in gene networks downstream of oncogenic gain- and loss-of-function mutations.
C1 [McMurray, Helene R.; Sampson, Erik R.; Compitello, George; Kinsey, Conan; Newman, Laurel; Smith, Bradley; Chen, Shaw-Ree; Land, Hartmut] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA.
   [Klebanov, Lev; Salzman, Peter; Yakovlev, Andrei] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA.
   [Yakovlev, Andrei; Land, Hartmut] Univ Rochester, Med Ctr, James Wilmot Canc Ctr, Rochester, NY 14642 USA.
   [Klebanov, Lev] Charles Univ Prague, Dept Probabil & Stat, CZ-18675 Prague 8, Czech Republic.
C3 University of Rochester; University of Rochester; University of Rochester; Charles University Prague
RP Land, H (corresponding author), Univ Rochester, Med Ctr, Dept Biomed Genet, 601 Elmwood Ave, Rochester, NY 14642 USA.
EM land@urmc.rochester.edu
FU NCI NIH HHS [T32 CA009363, R01 CA120317, T32 CA09363, CA120317, CA90663, R01 CA090663] Funding Source: Medline; NIGMS NIH HHS [GM075299, R01 GM075299] Funding Source: Medline; NLM NIH HHS [K99 LM009477] Funding Source: Medline
NR 37
TC 125
Z9 165
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 JUN 19
PY 2008
VL 453
IS 7198
BP 1112
EP U10
DI 10.1038/nature06973
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900059
PM 18500333
DA 2026-03-09
ER

PT J
AU Han, YL
   Shokef, Y
   Alsayed, AM
   Yunker, P
   Lubensky, TC
   Yodh, AG
AF Han, Yilong
   Shokef, Yair
   Alsayed, Ahmed M.
   Yunker, Peter
   Lubensky, Tom C.
   Yodh, Arjun G.
TI Geometric frustration in buckled colloidal monolayers
SO NATURE
LA English
DT Article
ID triangular lattice; glassy dynamics; hard-spheres; crystals; transition; defects; entropy; system; arrays; antiferromagnet
AB Geometric frustration arises when lattice structure prevents simultaneous minimization of local interaction energies. It leads to highly degenerate ground states and, subsequently, to complex phases of matter, such as water ice, spin ice, and frustrated magnetic materials. Here we report a simple geometrically frustrated system composed of closely packed colloidal spheres confined between parallel walls. Diameter- tunable microgel spheres are self- assembled into a buckled triangular lattice with either up or down displacements, analogous to an antiferromagnetic Ising model on a triangular lattice. Experiment and theory reveal single- particle dynamics governed by in- plane lattice distortions that partially relieve frustration and produce ground states with zigzagging stripes and subextensive entropy, rather than the more random configurations and extensive entropy of the antiferromagnetic Ising model. This tunable soft- matter system provides a means to directly visualize the dynamics of frustration, thermal excitations and defects.
C1 [Han, Yilong; Shokef, Yair; Alsayed, Ahmed M.; Yunker, Peter; Lubensky, Tom C.; Yodh, Arjun G.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
   [Han, Yilong] Hong Kong Univ Sci & Technol, Dept Phys, Kowloon, Hong Kong, Peoples R China.
C3 University of Pennsylvania; Hong Kong University of Science & Technology
RP Shokef, Y (corresponding author), Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
EM yilong@ust.hk; yair.shokef@weizmann.ac.il
FU NSF [DMR-0804881]; MRSEC [DMR-0520020]; NASA [NAG-2939]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0804881] Funding Source: National Science Foundation
NR 46
TC 206
Z9 244
U1 2
U2 131
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 898
EP 903
DI 10.1038/nature07595
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300034
PM 19092926
DA 2026-03-09
ER

PT J
AU Keenlyside, NS
   Latif, M
   Jungclaus, J
   Kornblueh, L
   Roeckner, E
AF Keenlyside, N. S.
   Latif, M.
   Jungclaus, J.
   Kornblueh, L.
   Roeckner, E.
TI Advancing decadal-scale climate prediction in the North Atlantic sector
SO NATURE
LA English
DT Article
ID thermohaline circulation; interdecadal variations; surface-temperature; variability; predictability; oscillation; rainfall
AB The climate of the North Atlantic region exhibits fluctuations on decadal timescales that have large societal consequences. Prominent examples include hurricane activity in the Atlantic(1), and surface- temperature and rainfall variations over North America(2), Europe(3) and northern Africa(4). Although these multidecadal variations are potentially predictable if the current state of the ocean is known(5-7), the lack of subsurface ocean observations(8) that constrain this state has been a limiting factor for realizing the full skill potential of such predictions(9). Here we apply a simple approach - that uses only sea surface temperature ( SST) observations - to partly overcome this difficulty and perform retrospective decadal predictions with a climate model. Skill is improved significantly relative to predictions made with incomplete knowledge of the ocean state(10), particularly in the North Atlantic and tropical Pacific oceans. Thus these results point towards the possibility of routine decadal climate predictions. Using this method, and by considering both internal natural climate variations and projected future anthropogenic forcing, we make the following forecast: over the next decade, the current Atlantic meridional overturning circulation will weaken to its long- term mean; moreover, North Atlantic SST and European and North American surface temperatures will cool slightly, whereas tropical Pacific SST will remain almost unchanged. Our results suggest that global surface temperature may not increase over the next decade, as natural climate variations in the North Atlantic and tropical Pacific temporarily offset the projected anthropogenic warming.
C1 [Keenlyside, N. S.; Latif, M.] Leibniz Inst Marine Sci, D-24105 Kiel, Germany.
   [Jungclaus, J.; Kornblueh, L.; Roeckner, E.] Max Planck Inst Meteorol, D-20146 Hamburg, Germany.
C3 Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; Max Planck Society
RP Keenlyside, NS (corresponding author), Leibniz Inst Marine Sci, Dusternbrooker Weg 20, D-24105 Kiel, Germany.
EM nkeenlyside@ifm-geomar.de
NR 29
TC 577
Z9 631
U1 0
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 1
PY 2008
VL 453
IS 7191
BP 84
EP 88
DI 10.1038/nature06921
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800043
PM 18451859
DA 2026-03-09
ER

PT J
AU Valentine, J
   Zhang, S
   Zentgraf, T
   Ulin-Avila, E
   Genov, DA
   Bartal, G
   Zhang, X
AF Valentine, Jason
   Zhang, Shuang
   Zentgraf, Thomas
   Ulin-Avila, Erick
   Genov, Dentcho A.
   Bartal, Guy
   Zhang, Xiang
TI Three-dimensional optical metamaterial with a negative refractive index
SO NATURE
LA English
DT Article
ID transmission; frequency; terahertz; light
AB Metamaterials are artificially engineered structures that have properties, such as a negative refractive index(1-4), not attainable with naturally occurring materials. Negative- index metamaterials (NIMs) were first demonstrated for microwave frequencies(5,6), but it has been challenging to design NIMs for optical frequencies and they have so far been limited to optically thin samples because of significant fabrication challenges and strong energy dissipation in metals(7,8). Such thin structures are analogous to a monolayer of atoms, making it difficult to assign bulk properties such as the index of refraction. Negative refraction of surface plasmons was recently demonstrated but was confined to a two- dimensional waveguide(9). Three- dimensional ( 3D) optical metamaterials have come into focus recently, including the realization of negative refraction by using layered semiconductor metamaterials and a 3D magnetic metamaterial in the infrared frequencies; however, neither of these had a negative index of refraction(10,11). Here we report a 3D optical metamaterial having negative refractive index with a very high figure of merit of 3.5 ( that is, low loss). This metamaterial is made of cascaded 'fishnet' structures, with a negative index existing over a broad spectral range. Moreover, it can readily be probed from free space, making it functional for optical devices. We construct a prism made of this optical NIM to demonstrate negative refractive index at optical frequencies, resulting unambiguously from the negative phase evolution of the wave propagating inside the metamaterial. Bulk optical metamaterials open up prospects for studies of 3D optical effects and applications associated with NIMs and zero-index materials such as reversed Doppler effect, superlenses, optical tunnelling devices(12,13), compact resonators and highly directional sources(14).
C1 [Valentine, Jason; Zhang, Shuang; Zentgraf, Thomas; Ulin-Avila, Erick; Genov, Dentcho A.; Bartal, Guy; Zhang, Xiang] Univ Calif Berkeley, NSF Nanoscale Sci & Engn Ctr NSEC, Berkeley, CA 94720 USA.
   [Zhang, Xiang] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Sci Mat, Berkeley, CA 94720 USA.
C3 National Science Foundation (NSF); 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 Zhang, X (corresponding author), Univ Calif Berkeley, NSF Nanoscale Sci & Engn Ctr NSEC, 3112 Etcheverry Hall, Berkeley, CA 94720 USA.
EM xiang@berkeley.edu
FU US Army Research Office (ARO) MURI programme [50432-PH-MUR]; NSF Nano-scale Science and Engineering Center [DMI-0327077]; Alexander von Humboldt Foundation; Office of Science; Office of Basic Energy Sciences; US Department of Energy [DE-AC02-05CH11231]; Directorate For Engineering [0751621] Funding Source: National Science Foundation; Div Of Civil, Mechanical, & Manufact Inn [0751621] Funding Source: National Science Foundation
NR 30
TC 2019
Z9 2356
U1 32
U2 1641
PU NATURE PUBLISHING 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 18
PY 2008
VL 455
IS 7211
BP 376
EP U32
DI 10.1038/nature07247
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200041
PM 18690249
DA 2026-03-09
ER

PT J
AU Stockmann, C
   Doedens, A
   Weidemann, A
   Zhang, N
   Takeda, N
   Greenberg, JI
   Cheresh, DA
   Johnson, RS
AF Stockmann, Christian
   Doedens, Andrew
   Weidemann, Alexander
   Zhang, Na
   Takeda, Norihiko
   Greenberg, Joshua I.
   Cheresh, David A.
   Johnson, Randall S.
TI Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis
SO NATURE
LA English
DT Article
ID breast-cancer; mouse model; macrophages; expression; angiogenesis; vegf; mice
AB Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor ( VEGF-A), from both malignant and stromal cell types(1). Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A(2). Here we show that the deletion of inflammatory-cell-derived VEGF- A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice. Vasculature in tumours lacking myeloid- cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF- A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF- A levels in the tumours are unaffected. However, deletion of myeloid- cell VEGF- A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia. Furthermore, loss of myeloid- cell VEGF- A increased the susceptibility of tumours to chemotherapeutic cytotoxicity. This shows that myeloid- derived VEGF- A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression.
C1 [Stockmann, Christian; Doedens, Andrew; Weidemann, Alexander; Zhang, Na; Takeda, Norihiko; Johnson, Randall S.] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
   [Greenberg, Joshua I.] Univ Calif San Diego, Dept Surg, La Jolla, CA 92093 USA.
   [Cheresh, David A.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
   [Cheresh, David A.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Johnson, RS (corresponding author), Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
EM rsjohnson@ucsd.edu
FU Deutsche Forschungsgemeinschaft [STO 787/1-1, WE 4275/1-1]; Susan G. Komen Dissertation Research Award [DISS0402406]; National Institutes of Health [CA82515, CA118165, AI060840]
NR 12
TC 385
Z9 456
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 814
EP U107
DI 10.1038/nature07445
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900054
PM 18997773
DA 2026-03-09
ER

PT J
AU Zhang, WW
   Luck, SJ
AF Zhang, Weiwei
   Luck, Steven J.
TI Discrete fixed-resolution representations in visual working memory
SO NATURE
LA English
DT Article
ID short-term-memory; fourier descriptors; capacity; information; number; attention; limits; model; shape
AB Limits on the storage capacity of working memory significantly affect cognitive abilities in a wide range of domains(1), but the nature of these capacity limits has been elusive(2). Some researchers have proposed that working memory stores a limited set of discrete, fixed- resolution representations(3), whereas others have proposed that working memory consists of a pool of resources that can be allocated flexibly to provide either a small number of high-resolution representations or a large number of low- resolution representations(4). Here we resolve this controversy by providing independent measures of capacity and resolution. We show that, when presented with more than a few simple objects, human observers store a high- resolution representation of a subset of the objects and retain no information about the others. Memory resolution varied over a narrow range that cannot be explained in terms of a general resource pool but can be well explained by a small set of discrete, fixed- resolution representations.
C1 [Zhang, Weiwei] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA.
   [Zhang, Weiwei; Luck, Steven J.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95618 USA.
C3 University of Iowa; University of California System; University of California Davis
RP Zhang, WW (corresponding author), Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA.
EM wwzhang@ucdavis.edu
FU NIMH NIH HHS [R01 MH076226] Funding Source: Medline
NR 28
TC 1296
Z9 1490
U1 7
U2 219
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 233
EP U13
DI 10.1038/nature06860
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400042
PM 18385672
DA 2026-03-09
ER

PT J
AU Piao, SL
   Ciais, P
   Friedlingstein, P
   Peylin, P
   Reichstein, M
   Luyssaert, S
   Margolis, H
   Fang, JY
   Barr, A
   Chen, AP
   Grelle, A
   Hollinger, DY
   Laurila, T
   Lindroth, A
   Richardson, AD
   Vesala, T
AF Piao, Shilong
   Ciais, Philippe
   Friedlingstein, Pierre
   Peylin, Philippe
   Reichstein, Markus
   Luyssaert, Sebastiaan
   Margolis, Hank
   Fang, Jingyun
   Barr, Alan
   Chen, Anping
   Grelle, Achim
   Hollinger, David Y.
   Laurila, Tuomas
   Lindroth, Anders
   Richardson, Andrew D.
   Vesala, Timo
TI Net carbon dioxide losses of northern ecosystems in response to autumn warming
SO NATURE
LA English
DT Article
ID atmospheric co2; seasonal cycle; forest; uncertainty; sensitivity; exchange; balance; scheme
AB The carbon balance of terrestrial ecosystems is particularly sensitive to climatic changes in autumn and spring(1-4), with spring and autumn temperatures over northern latitudes having risen by about 1.1 degrees C and 0.8 degrees C, respectively, over the past two decades(5). A simultaneous greening trend has also been observed, characterized by a longer growing season and greater photosynthetic activity(6,7). These observations have led to speculation that spring and autumn warming could enhance carbon sequestration and extend the period of net carbon uptake in the future(8). Here we analyse interannual variations in atmospheric carbon dioxide concentration data and ecosystem carbon dioxide fluxes. We find that atmospheric records from the past 20 years show a trend towards an earlier autumn- to- winter carbon dioxide build- up, suggesting a shorter net carbon uptake period. This trend cannot be explained by changes in atmospheric transport alone and, together with the ecosystem flux data, suggest increasing carbon losses in autumn. We use a process- based terrestrial biosphere model and satellite vegetation greenness index observations to investigate further the observed seasonal response of northern ecosystems to autumnal warming. We find that both photosynthesis and respiration increase during autumn warming, but the increase in respiration is greater. In contrast, warming increases photosynthesis more than respiration in spring. Our simulations and observations indicate that northern terrestrial ecosystems may currently lose carbon dioxide in response to autumn warming, with a sensitivity of about 0.2 PgC degrees C-1, offsetting 90% of the increased carbon dioxide uptake during spring. If future autumn warming occurs at a faster rate than in spring, the ability of northern ecosystems to sequester carbon may be diminished earlier than previously suggested(9,10).
C1 [Piao, Shilong; Ciais, Philippe; Friedlingstein, Pierre] CNRS, CEA, UMR, LSCE, F-91191 Gif Sur Yvette, France.
   [Peylin, Philippe] LBI, F-78026 Thiverval Grignon, France.
   [Reichstein, Markus] Max Planck Inst Biogeochem, D-07701 Jena, Germany.
   [Luyssaert, Sebastiaan] Univ Antwerp, Dept Biol, B-2610 Antwerp, Belgium.
   [Margolis, Hank] Univ Laval, Fac Foresterie & Geomat, Ste Foy, PQ G1K 7P4, Canada.
   [Fang, Jingyun] Peking Univ, Dept Ecol, Beijing 100871, Peoples R China.
   [Barr, Alan] Environm Canada, Div Climate Res, Saskatoon, SK S7N 3H5, Canada.
   [Chen, Anping] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [Grelle, Achim] Swedish Univ Agr Sci, Dept Ecol, SE-75007 Uppsala, Sweden.
   [Hollinger, David Y.] US Forest Serv, USDA, No Res Stn, Durham, NH 03824 USA.
   [Laurila, Tuomas] Finnish Meteorol Inst, FIN-00101 Helsinki, Finland.
   [Lindroth, Anders] Lund Univ, Dept Phys Geog & Ecosyst Anal, SE-22362 Lund, Sweden.
   [Richardson, Andrew D.] Univ New Hampshire, Complex Syst Res Ctr, Durham, NH 03824 USA.
   [Vesala, Timo] Univ Helsinki, Dept Phys Sci, FIN-00014 Helsinki, Finland.
C3 Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Max Planck Society; University of Antwerp; Laval University; Peking University; Environment & Climate Change Canada; Princeton University; Swedish University of Agricultural Sciences; United States Department of Agriculture (USDA); United States Forest Service; Finnish Meteorological Institute; Lund University; University System Of New Hampshire; University of New Hampshire; University of Helsinki
RP Piao, SL (corresponding author), CNRS, CEA, UMR, LSCE, Batiment 709,CE, F-91191 Gif Sur Yvette, France.
EM slpiao@lsce.ipsl.fr; philippe.ciais@lsce.ipsl.fr
NR 35
TC 964
Z9 1159
U1 16
U2 981
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 49
EP U3
DI 10.1038/nature06444
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300030
PM 18172494
DA 2026-03-09
ER

PT J
AU Liu, X
   Wang, L
   Zhao, KH
   Thompson, PR
   Hwang, Y
   Marmorstein, R
   Cole, PA
AF Liu, Xin
   Wang, Ling
   Zhao, Kehao
   Thompson, Paul R.
   Hwang, Yousang
   Marmorstein, Ronen
   Cole, Philip A.
TI The structural basis of protein acetylation by the p300/CBP transcriptional coactivator
SO NATURE
LA English
DT Article
ID histone acetyltransferase activity; cbp; inhibitors; cancer; cells; hat; mutations; roles; pcaf; gene
AB The transcriptional coactivator p300/ CBP ( CREBBP) is a histone acetyltransferase ( HAT) that regulates gene expression by acetylating histones and other transcription factors. Dysregulation of p300/ CBP HAT activity contributes to various diseases including cancer(1-4). Sequence alignments, enzymology experiments and inhibitor studies on p300/ CBP have led to contradictory results about its catalytic mechanism and its structural relation to the Gcn5/ PCAF and MYST HATs(5-9). Here we describe a high- resolution X- ray crystal structure of a semi- synthetic heterodimeric p300 HAT domain in complex with a bi- substrate inhibitor, Lys- CoA. This structure shows that p300/ CBP is a distant cousin of other structurally characterized HATs, but reveals several novel features that explain the broad substrate specificity and preference for nearby basic residues. Based on this structure and accompanying biochemical data, we propose that p300/ CBP uses an unusual 'hitandrun' ( Theorell - Chance) catalytic mechanism that is distinct from other characterized HATs. Several disease- associated mutations can also be readily accounted for by the p300 HAT structure. These studies pave the way for new epigenetic therapies involving modulation of p300/ CBP HAT activity.
C1 [Liu, Xin; Zhao, Kehao; Marmorstein, Ronen] Wistar Inst Anat & Biol, Program Gene Express & Regulat, Philadelphia, PA 19104 USA.
   [Liu, Xin; Marmorstein, Ronen] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
   [Wang, Ling; Thompson, Paul R.; Hwang, Yousang; Cole, Philip A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
C3 The Wistar Institute; University of Pennsylvania; Johns Hopkins University
RP Marmorstein, R (corresponding author), Wistar Inst Anat & Biol, Program Gene Express & Regulat, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM marmor@wistar.org; pcole@jhmi.edu
NR 30
TC 356
Z9 446
U1 4
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 846
EP 850
DI 10.1038/nature06546
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400046
PM 18273021
DA 2026-03-09
ER

PT J
AU Tavazoie, SF
   Alarcón, C
   Oskarsson, T
   Padua, D
   Wang, QQ
   Bos, PD
   Gerald, WL
   Massagué, J
AF Tavazoie, Sohail F.
   Alarcon, Claudio
   Oskarsson, Thordur
   Padua, David
   Wang, Qiongqing
   Bos, Paula D.
   Gerald, William L.
   Massague, Joan
TI Endogenous human microRNAs that suppress breast cancer metastasis
SO NATURE
LA English
DT Article
ID expression profiles; cells; beta; differentiation; signatures; invasion; tumors; genes; sox-4; core
AB A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo. Of these microRNAs, miR- 126 restoration reduces overall tumour growth and proliferation, whereas miR- 335 inhibits metastatic cell invasion. miR- 335 regulates a set of genes whose collective expression in a large cohort of human tumours is associated with risk of distal metastasis. miR- 335 suppresses metastasis and migration through targeting of the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C. Expression of miR- 126 and miR- 335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis- free survival. miR- 335 and miR- 126 are thus identified as metastasis suppressor microRNAs in human breast cancer.
C1 [Tavazoie, Sohail F.; Alarcon, Claudio; Oskarsson, Thordur; Padua, David; Wang, Qiongqing; Bos, Paula D.; Massague, Joan] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA.
   [Tavazoie, Sohail F.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
   [Gerald, William L.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
RP Massagué, J (corresponding author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA.
EM massaguj@mskcc.org
FU National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; NCI NIH HHS [P01 CA094060, P30 CA008748] Funding Source: Medline
NR 33
TC 1588
Z9 1894
U1 1
U2 238
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 147
EP U3
DI 10.1038/nature06487
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400033
PM 18185580
DA 2026-03-09
ER

PT J
AU Caviglia, AD
   Gariglio, S
   Reyren, N
   Jaccard, D
   Schneider, T
   Gabay, M
   Thiel, S
   Hammerl, G
   Mannhart, J
   Triscone, JM
AF Caviglia, A. D.
   Gariglio, S.
   Reyren, N.
   Jaccard, D.
   Schneider, T.
   Gabay, M.
   Thiel, S.
   Hammerl, G.
   Mannhart, J.
   Triscone, J. -M.
TI Electric field control of the LaAlO3/SrTiO3 interface ground state
SO NATURE
LA English
DT Article
ID films
AB Interfaces between complex oxides are emerging as one of the most interesting systems in condensed matter physics(1). In this special setting, in which translational symmetry is artificially broken, a variety of new and unusual electronic phases can be promoted(2). Theoretical studies predict complex phase diagrams and suggest the key role of the charge carrier density in determining the systems' ground states. A particularly fascinating system is the conducting interface between the band insulators LaAlO3 and SrTiO3 ( ref. 3). Recently two possible ground states have been experimentally identified: a magnetic state(4) and a two- dimensional superconducting condensate(5). Here we use the electric field effect to explore the phase diagramof the system. The electrostatic tuning of the carrier density allows an on/off switching of superconductivity and drives a quantum phase transition(6-8) between a two- dimensional superconducting state and an insulating state. Analyses of the magnetotransport properties in the insulating state are consistent with weak localization and do not provide evidence for magnetism. The electric field control of superconductivity demonstrated here opens the way to the development of new mesoscopic superconducting circuits.
C1 [Caviglia, A. D.; Gariglio, S.; Reyren, N.; Jaccard, D.; Triscone, J. -M.] Univ Geneva, Dept Phys Mat Condensee, CH-1211 Geneva 4, Switzerland.
   [Schneider, T.] Univ Zurich, Inst Phys, CH-8057 Zurich, Switzerland.
   [Gabay, M.] Univ Paris 11, Phys Solides Lab, F-91405 Orsay, France.
   [Thiel, S.; Hammerl, G.; Mannhart, J.] Univ Augsburg, Inst Phys, Ctr Elect Correlat & Magnetism, D-86135 Augsburg, Germany.
C3 University of Geneva; University of Zurich; Universite Paris Saclay; University of Augsburg
RP Caviglia, AD (corresponding author), Univ Geneva, Dept Phys Mat Condensee, 24 Quai E Ansermet, CH-1211 Geneva 4, Switzerland.
EM andrea.caviglia@unige.ch
FU Swiss National Science Foundation; European Union; Deutsche Forschungsgemeinschaft [SFB484]; European Science Foundation
NR 29
TC 1106
Z9 1202
U1 8
U2 630
PU NATURE PUBLISHING 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 4
PY 2008
VL 456
IS 7222
BP 624
EP 627
DI 10.1038/nature07576
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000037
PM 19052624
DA 2026-03-09
ER

PT J
AU Handschin, C
   Spiegelman, BM
AF Handschin, Christoph
   Spiegelman, Bruce M.
TI The role of exercise and PGC1α in inflammation and chronic disease
SO NATURE
LA English
DT Article
ID necrosis-factor-alpha; transcriptional coactivator pgc-1-alpha; skeletal-muscle; physical-activity; oxidative-phosphorylation; antioxidant defense; metabolic syndrome; gene-expression; plasticity; obesity
AB Inadequate physical activity is linked to many chronic diseases. But the mechanisms that tie muscle activity to health are unclear. The transcriptional coactivator PGC1 alpha has recently been shown to regulate several exercise-associated aspects of muscle function. We propose that this protein controls muscle plasticity, suppresses a broad inflammatory response and mediates the beneficial effects of exercise.
C1 [Handschin, Christoph] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland.
   [Handschin, Christoph] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, CH-8057 Zurich, Switzerland.
   [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 University of Zurich; University of Zurich; Zurich Center Integrative Human Physiology (ZIHP); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School
RP Handschin, C (corresponding author), Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland.
EM christoph.handschin@access.uzh.ch; bruce_spiegelman@dfci.harvard.edu
FU NIDDK NIH HHS [R01 DK054477] Funding Source: Medline
NR 75
TC 863
Z9 991
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 JUL 24
PY 2008
VL 454
IS 7203
BP 463
EP 469
DI 10.1038/nature07206
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300041
PM 18650917
DA 2026-03-09
ER

PT J
AU Kawamura, Y
   Saito, K
   Kin, T
   Ono, Y
   Asai, K
   Sunohara, T
   Okada, TN
   Siomi, MC
   Siomi, H
AF Kawamura, Yoshinori
   Saito, Kuniaki
   Kin, Taishin
   Ono, Yukiteru
   Asai, Kiyoshi
   Sunohara, Takafumi
   Okada, Tomoko N.
   Siomi, Mikiko C.
   Siomi, Haruhiko
TI Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells
SO NATURE
LA English
DT Article
ID piwi-interacting rnas; distinct roles; interference; germline; pathways; proteins; heterochromatin; elements; sirnas; genome
AB RNA silencing is a conserved mechanism in which small RNAs trigger various forms of sequence- specific gene silencing by guiding Argonaute complexes to target RNAs by means of base pairing(1,2). RNA silencing is thought to have evolved as a form of nucleic- acid- based immunity to inactivate viruses and transposable elements. Although the activity of transposable elements in animals has been thought largely to be restricted to the germ line, recent studies have shown that they may also actively transpose in somatic cells, creating somatic mosaicism in animals(3). In the Drosophila germ line, Piwi- interacting RNAs arise from repetitive intergenic elements including retrotransposons by a Dicer-independent pathway and function through the Piwi subfamily of Argonautes to ensure silencing of retrotransposons(4-9). Here we show that, in cultured Drosophila S2 cells, Argonaute 2 ( AGO2), an AGO subfamily member of Argonautes, associates with endogenous small RNAs of 20 - 22 nucleotides in length, which we have collectively named endogenous short interfering RNAs ( esiRNAs). esiRNAs can be divided into two groups: one that mainly corresponds to a subset of retrotransposons, and the other that arises from stem - loop structures. esiRNAs are produced in a Dicer- 2-dependent manner from distinctive genomic loci, are modified at their 39 ends and can direct AGO2 to cleave target RNAs. Mutations in Dicer- 2 caused an increase in retrotransposon transcripts. Together, our findings indicate that different types of small RNAs and Argonautes are used to repress retrotransposons in germline and somatic cells in Drosophila.
C1 [Kawamura, Yoshinori; Saito, Kuniaki; Sunohara, Takafumi; Okada, Tomoko N.; Siomi, Mikiko C.; Siomi, Haruhiko] Univ Tokushima, Inst Genome Res, Tokushima 7708503, Japan.
   [Saito, Kuniaki; Okada, Tomoko N.; Siomi, Mikiko C.; Siomi, Haruhiko] Keio Univ, Sch Med, Dept Mol Biol, Shinjuku Ku, Tokyo 1608582, Japan.
   [Kin, Taishin; Asai, Kiyoshi] Natl Inst Adv Ind Sci & Technol, Computat Biol Res Ctr, Tokyo 1350664, Japan.
   [Ono, Yukiteru] Informat & Math Sci Lab Inc, Tokyo 1120012, Japan.
   [Asai, Kiyoshi] Univ Tokyo, Grad Sch Frontier Sci, Chiba 2778561, Japan.
   [Siomi, Mikiko C.] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
C3 Tokushima University; Keio University; National Institute of Advanced Industrial Science & Technology (AIST); University of Tokyo; Japan Science & Technology Agency (JST)
RP Siomi, MC (corresponding author), Univ Tokushima, Inst Genome Res, Tokushima 7708503, Japan.
EM siomim@sc.itc.keio.ac.jp; awa403@sc.itc.keio.ac.jp
NR 29
TC 360
Z9 448
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 JUN 5
PY 2008
VL 453
IS 7196
BP 793
EP U5
DI 10.1038/nature06938
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300046
PM 18463636
DA 2026-03-09
ER

PT J
AU Kanner, BI
AF Kanner, Baruch I.
TI Structural biology - It's not all in the family
SO NATURE
LA English
DT Article
ID neurotransmitter transporters; bacterial homolog; crystal-structure; binding-site
C1 [Kanner, Baruch I.] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel.
C3 Hebrew University of Jerusalem
RP Kanner, BI (corresponding author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel.
EM kannerb@cc.huji.ac.il
NR 8
TC 3
Z9 5
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 593
EP 594
DI 10.1038/454593a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500034
PM 18668099
DA 2026-03-09
ER

PT J
AU Amrani, N
   Ghosh, S
   Mangus, DA
   Jacobson, A
AF Amrani, Nadia
   Ghosh, Shubhendu
   Mangus, David A.
   Jacobson, Allan
TI Translation factors promote the formation of two states of the closed-loop mRNP
SO NATURE
LA English
DT Article
ID yeast poly(a)-binding protein; messenger-rna; poly(a) tail; initiation; binding; cap; recognition; termination; eif4g; domain
AB Efficient translation initiation and optimal stability of most eukaryotic messenger RNAs depends on the formation of a closed- loop structure and the resulting synergistic interplay between the 59 m (7)G cap and the 3 ' poly( A) tail(1,2). Evidence of eIF4G and Pab1 interaction supports the notion of a closed- loop mRNP(3), but the mechanistic events that lead to its formation and maintenance are still unknown. Here we use toeprinting and polysome profiling assays to delineate ribosome positioning at initiator AUG codons and ribosome - mRNA association, respectively, and find that two distinct stable ( resistant to cap analogue) closed- loop structures are formed during initiation in yeast cell- free extracts. The integrity of both forms requires the mRNA cap and poly( A) tail, as well as eIF4E, eIF4G, Pab1 and eIF3, and is dependent on the length of both the mRNA and the poly( A) tail. Formation of the first structure requires the 48S ribosomal complex, whereas the second requires an 80S ribosome and the termination factors eRF3/ Sup35 and eRF1/ Sup45. The involvement of the termination factors is independent of a termination event.
C1 [Amrani, Nadia; Ghosh, Shubhendu; Mangus, David A.; Jacobson, Allan] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester
RP Jacobson, A (corresponding author), Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA.
EM allan.jacobson@umassmed.edu
FU NIGMS NIH HHS [R01 GM027757, R37 GM027757] Funding Source: Medline
NR 30
TC 161
Z9 205
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1276
EP U85
DI 10.1038/nature06974
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800051
PM 18496529
DA 2026-03-09
ER

PT J
AU Hirota, K
   Miyoshi, T
   Kugou, K
   Hoffman, CS
   Shibata, T
   Ohta, K
AF Hirota, Kouji
   Miyoshi, Tomoichiro
   Kugou, Kazuto
   Hoffman, Charles S.
   Shibata, Takehiko
   Ohta, Kunihiro
TI Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs
SO NATURE
LA English
DT Article
ID beta-globin locus; protein-kinase-a; fission yeast; schizosaccharomyces-pombe; intergenic transcription; recombination hotspot; gene; activation; resolution; ade6-m26
AB Recent transcriptome analyses using high- density tiling arrays(1-3) and data from large- scale analyses of full- length complementary DNA libraries by the FANTOM3 consortium(4,5) demonstrate that many transcripts are non- coding RNAs ( ncRNAs). These transcriptome analyses indicate that many of the non- coding regions, previously thought to be functionally inert, are actually transcriptionally active regions with various features. Furthermore, most relatively large ( several kilobases) polyadenylated messenger RNA transcripts are transcribed from regions harbouring little coding potential. However, the function of such ncRNAs is mostly unknown and has been a matter of debate(2). Here we show that RNA polymerase II ( RNAPII) transcription of ncRNAs is required for chromatin remodelling at the fission yeast Schizosaccharomyces pombe fbp1(+) locus during transcriptional activation. The chromatin at fbp1(+) is progressively converted to an open configuration, as several species of ncRNAs are transcribed through fbp1(+). This is coupled with the translocation of RNAPII through the region upstream of the eventual fbp1(+) transcriptional start site. Insertion of a transcription terminator into this upstream region abolishes both the cascade of transcription of ncRNAs and the progressive chromatin alteration. Our results demonstrate that transcription through the promoter region is required to make DNA sequences accessible to transcriptional activators and to RNAPII.
C1 [Hirota, Kouji; Kugou, Kazuto; Shibata, Takehiko; Ohta, Kunihiro] RIKEN, Adv Sci Inst, Mol & Cellular Biol Lab, Wako, Saitama 3510198, Japan.
   [Hirota, Kouji; Miyoshi, Tomoichiro; Kugou, Kazuto; Ohta, Kunihiro] Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan.
   [Hoffman, Charles S.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA.
C3 RIKEN; University of Tokyo; Boston College
RP Hirota, K (corresponding author), Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Yoshida Konoe, Kyoto 6068501, Japan.
EM khirota@rg.med.kyoto-u.ac.jp; kohta@bio.c.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology, Japan
NR 24
TC 226
Z9 267
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 NOV 6
PY 2008
VL 456
IS 7218
BP 130
EP U15
DI 10.1038/nature07348
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000055
PM 18820678
DA 2026-03-09
ER

PT J
AU Sakamoto, T
   Webb, MR
   Forgacs, E
   White, HD
   Sellers, JR
AF Sakamoto, Takeshi
   Webb, Martin R.
   Forgacs, Eva
   White, Howard D.
   Sellers, James R.
TI Direct observation of the mechanochemical coupling in myosin Va during processive movement
SO NATURE
LA English
DT Article
ID single-molecule; kinetic mechanism; neck length; adp; atp; motor
AB Myosin Va transports intracellular cargoes along actin filaments in cells(1). This processive, two- headed motor takes multiple 36- nm steps in which the two heads swing forward alternately towards the barbed end of actin driven by ATP hydrolysis(2). The ability of myosin Va to move processively is a function of its long lever arm, the high duty ratio of its kinetic cycle and the gating of the kinetics between the two heads such that ADP release from the lead head is greatly retarded(3-10). Mechanical studies at the multiple- and the single- molecule level suggest that there is tight coupling ( that is, one ATP is hydrolysed per power stroke), but this has not been directly demonstrated(4,5,11). We therefore investigated the coordination between the ATPase mechanism of the two heads of myosin Va and directly visualized the binding and dissociation of single fluorescently labelled nucleotide molecules, while simultaneously observing the stepping motion of the fluorescently labelled myosin Va as it moved along an actin filament. Here we show that preferential ADP dissociation from the trail head of mouse myosin Va is followed by ATP binding and a synchronous 36- nm step. Even at low ATP concentrations, the myosin Va molecule retained at least one nucleotide ( ADP in the lead head position) when moving. Thus, we directly demonstrate tight coupling between myosin Va movement and the binding and dissociation of nucleotidebysimultaneouslyimagingwithnearnanometreprecision.
C1 [Sakamoto, Takeshi; Sellers, James R.] NHLBI, Lab Mol Physiol, Bethesda, MD 20892 USA.
   [Webb, Martin R.] Natl Inst Med Res, MRC, London NW7 1AA, England.
   [Forgacs, Eva; White, Howard D.] Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); MRC National Institute for Medical Research; Eastern Virginia Medical School
RP Sellers, JR (corresponding author), NHLBI, Lab Mol Physiol, Bldg 10, Bethesda, MD 20892 USA.
EM Sellersj@mail.nih.gov
FU Medical Research Council, UK; National Heart, Lung and Blood Intramural Program; NIH [EB00209]; American Heart Association; MRC [MC_U117512742] Funding Source: UKRI; Medical Research Council [MC_U117512742] Funding Source: researchfish; National Heart Lung and Blood Institute [ZIAHL004229] Funding Source: NIH RePORTER
NR 27
TC 103
Z9 127
U1 1
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 128
EP U99
DI 10.1038/nature07188
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200051
PM 18668042
DA 2026-03-09
ER

PT J
AU Elsner, JB
   Kossin, JP
   Jagger, TH
AF Elsner, James B.
   Kossin, James P.
   Jagger, Thomas H.
TI The increasing intensity of the strongest tropical cyclones
SO NATURE
LA English
DT Article
ID hurricane intensity; potential intensity; sensitivity; environment; satellite; climate; model
AB Atlantic tropical cyclones are getting stronger on average, with a 30- year trend that has been related to an increase in ocean temperatures over the Atlantic Ocean and elsewhere(1-4). Over the rest of the tropics, however, possible trends in tropical cyclone intensity are less obvious, owing to the unreliability and incompleteness of the observational record and to a restricted focus, in previous trend analyses, on changes in average intensity. Here we overcome these two limitations by examining trends in the upper quantiles of per- cyclone maximum wind speeds ( that is, the maximum intensities that cyclones achieve during their lifetimes), estimated from homogeneous data derived from an archive of satellite records. We find significant upward trends for wind speed quantiles above the 70th percentile, with trends as high as 0.3 +/- 0.09 m s(-1) yr(-1) (s.e.) for the strongest cyclones. We note separate upward trends in the estimated lifetime-maximum wind speeds of the very strongest tropical cyclones ( 99th percentile) over each ocean basin, with the largest increase at this quantile occurring over the North Atlantic, although not all basins show statistically significant increases. Our results are qualitatively consistent with the hypothesis that as the seas warm, the ocean has more energy to convert to tropical cyclone wind.
C1 [Elsner, James B.; Jagger, Thomas H.] Florida State Univ, Dept Geog, Tallahassee, FL 32306 USA.
   [Kossin, James P.] Univ Wisconsin, Cooperat Inst Meteorol Satellite Studies, Madison, WI 53706 USA.
C3 State University System of Florida; Florida State University; University of Wisconsin System; University of Wisconsin Madison
RP Elsner, JB (corresponding author), Florida State Univ, Dept Geog, Tallahassee, FL 32306 USA.
EM jelsner@fsu.edu
FU US National Science Foundation [ATM-0738172, ATM-0614812]; Risk Prediction Initiative of the Bermuda Institute for Ocean Studies [RPI06-3-001]; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [0738172] Funding Source: National Science Foundation
NR 25
TC 879
Z9 1030
U1 11
U2 258
PU NATURE PUBLISHING 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 4
PY 2008
VL 455
IS 7209
BP 92
EP 95
DI 10.1038/nature07234
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200043
PM 18769438
DA 2026-03-09
ER

PT J
AU Lee, DS
   Nioche, P
   Hamberg, M
   Raman, CS
AF Lee, Dong-Sun
   Nioche, Pierre
   Hamberg, Mats
   Raman, C. S.
TI Structural insights into the evolutionary paths of oxylipin biosynthetic enzymes
SO NATURE
LA English
DT Article
ID allene oxide synthase; lipoxygenase fusion protein; hydroperoxide lyase; fatty-acid; methylobacterium-nodulans; signal-transduction; cytochrome-p450; identification; arabidopsis; purification
AB The oxylipin pathway generates not only prostaglandin- like jasmonates but also green leaf volatiles ( GLVs), which confer characteristic aromas to fruits and vegetables. Although allene oxide synthase ( AOS) and hydroperoxide lyase are atypical cytochrome P450 family members involved in the synthesis of jasmonates and GLVs, respectively, it is unknown how these enzymes rearrange their hydroperoxide substrates into different products. Here we present the crystal structures of Arabidopsis thaliana AOS, free and in complex with substrate or intermediate analogues. The structures reveal an unusual active site poised to control the reactivity of an epoxyallylic radical and its cation by means of interactions with an aromatic pi- system. Replacing the amino acid involved in these steps by a non- polar residue markedly reduces AOS activity and, unexpectedly, is both necessary and sufficient for converting AOS into a GLV biosynthetic enzyme. Furthermore, by combining our structural data with bioinformatic and biochemical analyses, we have discovered previously unknown hydroperoxide lyase in plant growth- promoting rhizobacteria, AOS in coral, and epoxyalcohol synthase in amphioxus. These results indicate that oxylipin biosynthetic genes were present in the last common ancestor of plants and animals, but were subsequently lost in all metazoan lineages except Placozoa, Cnidaria and Cephalochordata.
C1 [Lee, Dong-Sun; Raman, C. S.] Univ Texas Houston, Sch Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Nioche, Pierre] Univ Paris 05, INSERM, UMR S 747, F-75270 Paris 06, France.
   [Hamberg, Mats] Karolinska Inst, Div Physiol Chem 2, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden.
C3 University of Texas System; University of Texas Health Science Center Houston; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Karolinska Institutet
RP Raman, CS (corresponding author), Univ Texas Houston, Sch Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
EM ramancs@gmail.com
FU Pew Charitable Trusts; Pew Scholar Award; The Robert A. Welch Foundation; The National Institutes of Health; American Heart Association; INSERM Avenir Grant; La Fondation pour la Recherche Medicale
NR 74
TC 243
Z9 280
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 363
EP U27
DI 10.1038/nature07307
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200038
PM 18716621
DA 2026-03-09
ER

PT J
AU Cassou, C
AF Cassou, Christophe
TI Intraseasonal interaction between the Madden-Julian Oscillation and the North Atlantic Oscillation
SO NATURE
LA English
DT Article
ID weather regimes; atmospheric blocking; variability; prediction; wave; dynamics; patterns; winter; flow; nao
AB Bridging the traditional gap between the spatio- temporal scales of weather and climate is a significant challenge facing the atmospheric community. In particular, progress in both medium- range and seasonal- to- interannual climate prediction relies on our understanding of recurrent weather patterns and the identification of specific causes responsible for their favoured occurrence, persistence or transition. Within this framework, I here present evidence that the main climate intra- seasonal oscillation in the tropics - the Madden - Julian Oscillation(1,2) ( MJO) - controls part of the distribution and sequences of the four daily weather regimes defined over the North Atlantic - European region in winter(3). North Atlantic Oscillation(4) ( NAO) regimes are the most affected, allowing for medium- range predictability of their phase far exceeding the limit of around one week that is usually quoted. The tropical - extratropical lagged relationship is asymmetrical. Positive NAO events mostly respond to a mid- latitude low- frequency wave train initiated by the MJO in the western - central tropical Pacific and propagating eastwards. Precursors for negative NAO events are found in the eastern tropical Pacific - western Atlantic, leading to changes along the North Atlantic storm track. Wave- breaking diagnostics tend to support the MJO preconditioning and the role of transient eddies in setting the phase of the NAO. I present a simple statistical model to quantitatively assess the potential predictability of the daily NAO index or the sign of the NAO regimes when they occur. Forecasts are successful in similar to 70 per cent of the cases based on the knowledge of the previous similar to 12- day MJO phase used as a predictor. This promising skill could be of importance considering the tight link(4) between weather regimes and both mean conditions and the chances of extreme events occurring over Europe. These findings are useful for further stressing the need to better simulate and forecast the tropical coupled ocean - atmosphere dynamics, which is a source of medium- to- long range predictability and is the Achilles' heel of the current seamless prediction suites(5-7).
C1 [Cassou, Christophe] CERFACS, CNRS, Global Change & Climate Modelling Project, F-31057 Toulouse, France.
C3 Centre National de la Recherche Scientifique (CNRS); CERFACS
RP Cassou, C (corresponding author), CERFACS, CNRS, Global Change & Climate Modelling Project, 42 Ave G Coriolis, F-31057 Toulouse, France.
EM cassou@cerfacs.fr
FU CNRS; European Union's Sixth Framework Programme ( DYNAMITE and ENSEMBLES)
NR 29
TC 661
Z9 725
U1 2
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 523
EP 527
DI 10.1038/nature07286
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600044
PM 18818656
DA 2026-03-09
ER

PT J
AU Plikus, MV
   Mayer, JA
   de la Cruz, D
   Baker, RE
   Maini, PK
   Maxson, R
   Chuong, CM
AF Plikus, Maksim V.
   Mayer, Julie Ann
   de la Cruz, Damon
   Baker, Ruth E.
   Maini, Philip K.
   Maxson, Robert
   Chuong, Cheng-Ming
TI Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration
SO NATURE
LA English
DT Article
ID self-renewal; skin; growth; induction; follicles; niche; differentiation; modulation; alopecia; hedgehog
AB In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life(1,) and are an important model for organ regeneration. Hair stem cells located in the follicle bulge(2) are regulated by the surrounding microenvironment, or niche(3). The activation of such stem cells is cyclic, involving periodic beta-catenin activity(4-7). In the adult mouse, regeneration occurs in waves in a follicle population, implying coordination among adjacent follicles and the extrafollicular environment. Here we show that unexpected periodic expression of bone morphogenetic protein 2 ( Bmp2) and Bmp4 in the dermis regulates this process. This BMP cycle is out of phase with the WNT/beta-catenin cycle, thus dividing the conventional telogen into new functional phases: one refractory and the other competent for hair regeneration, characterized by high and low BMP signalling, respectively. Overexpression of noggin, a BMP antagonist, in mouse skin resulted in a markedly shortened refractory phase and faster propagation of the regenerative wave. Transplantation of skin from this mutant onto a wild- type host showed that follicles in donor and host can affect their cycling behaviours mutually, with the outcome depending on the equilibrium of BMP activity in the dermis. Administration of BMP4 protein caused the competent region to become refractory. These results show that BMPs may be the long- sought 'chalone' inhibitors of hair growth postulated by classical experiments. Taken together, results presented in this study provide an example of hierarchical regulation of local organ stem cell homeostasis by the inter- organ macro-environment. The expression of Bmp2 in subcutaneous adipocytes indicates physiological integration between these two thermoregulatory organs. Our findings have practical importance for studies using mouse skin as a model for carcinogenesis, intracutaneous drug delivery and stem cell engineering studies, because they highlight the acute need to differentiate supportive versus inhibitory regions in the host skin.
C1 [Plikus, Maksim V.; Mayer, Julie Ann; de la Cruz, Damon; Chuong, Cheng-Ming] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
   [Baker, Ruth E.; Maini, Philip K.] Math Inst, Ctr Math Biol, Oxford OX1 3LB, England.
   [Maini, Philip K.] Univ Oxford, Dept Biochem, Oxford Ctr Integrat Syst Biol, Oxford OX1 3QU, England.
   [Maxson, Robert] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA.
C3 University of Southern California; University of Oxford; University of Oxford; University of Southern California
RP Chuong, CM (corresponding author), Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
EM cmchuong@usc.edu
FU NIAMS NIH HHS [R01 AR042177, R01 AR047364] Funding Source: Medline; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR047364] Funding Source: NIH RePORTER
NR 30
TC 608
Z9 744
U1 0
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 340
EP U8
DI 10.1038/nature06457
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100051
PM 18202659
DA 2026-03-09
ER

PT J
AU Johnson, JB
   Lees, JM
   Gerst, A
   Sahagian, D
   Varley, N
AF Johnson, Jeffrey B.
   Lees, Jonathan M.
   Gerst, Alexander
   Sahagian, Dork
   Varley, Nick
TI Long-period earthquakes and co-eruptive dome inflation seen with particle image velocimetry
SO NATURE
LA English
DT Article
ID mount st-helens; wave-fields; volcano; seismicity; extrusion
AB Dome growth and explosive degassing are fundamental processes in the cycle of continental arc volcanism(1,2). Because both processes generate seismic energy, geophysical field studies of volcanic processes are often grounded in the interpretation of volcanic earthquakes(3). Although previous seismic studies have provided important constraints on volcano dynamics(4-6), such inversion results do not uniquely constrain magma source dimension and material properties. Here we report combined optical geodetic and seismic observations that robustly constrain the sources of long-period volcanic earthquakes coincident with frequent explosive eruptions at the volcano Santiaguito, in Guatemala. The acceleration of dome deformation, extracted from high- resolution optical image processing, is shown to be associated with recorded long-period seismic sources and the frequency content of seismic signals measured across a broadband network. These earthquake sources are observed as abrupt subvertical surface displacements of the dome, in which 20 - 50- cm uplift originates at the central vent and propagates at similar to 50 m s(-1) towards the 200- m- diameter periphery. Episodic shifts of the 20 - 80- m thick dome induce peak forces greater than 10(9) N and reflect surface manifestations of the volcanic long- period earthquakes, a broad class of volcano seismic activity that is poorly understood and observed at many volcanic centres worldwide(7). On the basis of these observations, the abrupt mass shift of solidified domes, conduit magma or magma pads may play a part in generating long- period earthquakes at silicic volcanic systems.
C1 [Johnson, Jeffrey B.] New Mexico Inst Min & Technol, Dept Earth & Environm Sci, Socorro, NM 87801 USA.
   [Lees, Jonathan M.] Univ N Carolina, Chapel Hill, NC 27599 USA.
   [Gerst, Alexander] Univ Hamburg, Inst Geophys, D-20146 Hamburg, Germany.
   [Sahagian, Dork] Lehigh Univ, Bethlehem, PA 18015 USA.
   [Varley, Nick] Univ Colima, Fac Ciencias, Colima 28045, Mexico.
C3 New Mexico Institute of Mining Technology; University of North Carolina; University of North Carolina Chapel Hill; University of Hamburg; Lehigh University; Universidad de Colima
RP Johnson, JB (corresponding author), New Mexico Inst Min & Technol, Dept Earth & Environm Sci, Socorro, NM 87801 USA.
EM jeff.johnson@ees.nmt.edu
FU US National Science Foundation EAR [0440225, 0440054]; Directorate For Geosciences; Division Of Earth Sciences [0838395, 0738802] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0440054, 0440225] Funding Source: National Science Foundation
NR 27
TC 75
Z9 89
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 20
PY 2008
VL 456
IS 7220
BP 377
EP 381
DI 10.1038/nature07429
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600041
PM 19020619
DA 2026-03-09
ER

PT J
AU Vignolle, B
   Carrington, A
   Cooper, RA
   French, MMJ
   Mackenzie, AP
   Jaudet, C
   Vignolles, D
   Proust, C
   Hussey, NE
AF Vignolle, B.
   Carrington, A.
   Cooper, R. A.
   French, M. M. J.
   Mackenzie, A. P.
   Jaudet, C.
   Vignolles, D.
   Proust, Cyril
   Hussey, N. E.
TI Quantum oscillations in an overdoped high-Tc superconductor
SO NATURE
LA English
DT Article
ID fermi-surface; temperature superconductor; transport; liquid; parameters; pseudogap; sr2ruo4
AB The nature of the metallic phase in the high- transition- temperature ( high-T(c)) copper oxide superconductors, and its evolution with carrier concentration, has been a long-standing mystery(1). A central question is how coherent electronic states, or quasiparticles, emerge from the antiferromagnetic insulator with doping. Recent quantum oscillation experiments on lightly doped copper oxides have shown evidence for small pockets of Fermi surface(2-5), the formation of which has been associated with the opening of the pseudogap - ananisotropic gap in the normal state excitation spectrum of unknown origin(1). As the doping is increased, experiments suggest that the full Fermi surface is restored(6,7), although the doping level at which the pseudogap closes and the nature of the electronic ground state beyond this point have yet to be determined. Here we report the observation of quantum oscillations in the over-doped superconductor Tl(2)Ba(2)CuO(6+delta) that show the existence of a large Fermi surface of well- defined quasiparticles covering two-thirds of the Brillouin zone. These measurements confirm that, in overdoped superconducting copper oxides, coherence is established at all Fermi wavevectors, even near the zone boundary where the pseudogap is maximal and electronic interactions are strongest; they also firmly establish the applicability of a generalized Fermi-liquid picture on the overdoped side of the superconducting phase diagram.
C1 [Carrington, A.; Cooper, R. A.; French, M. M. J.; Hussey, N. E.] Univ Bristol, HH Wills Phys Lab, Bristol BS8 1TL, Avon, England.
   [Vignolle, B.; Jaudet, C.; Vignolles, D.; Proust, Cyril] CNRS UPS INSA, UMR 5147, LNCMP, F-31400 Toulouse, France.
   [Mackenzie, A. P.] Univ St Andrews, Sch Phys & Astron, Scottish Univ Phys Alliance, St Andrews KY16 9SS, Fife, Scotland.
C3 University of Bristol; Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite de Toulouse; Institut National des Sciences Appliquees de Toulouse; Universite Toulouse III - Paul Sabatier; University of St Andrews
RP Hussey, NE (corresponding author), Univ Bristol, HH Wills Phys Lab, Tyndall Ave, Bristol BS8 1TL, Avon, England.
EM n.e.hussey@bristol.ac.uk
FU EPSRC; LNCMP; French ANR IceNET; EuroMagNET; EPSRC [EP/F038836/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/F038836/1, EP/C523229/1, EP/C511778/1] Funding Source: researchfish
NR 30
TC 242
Z9 281
U1 0
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 952
EP 955
DI 10.1038/nature07323
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300046
DA 2026-03-09
ER

PT J
AU Cook, B
   Hardy, RW
   McConnaughey, WB
   Zuker, CS
AF Cook, Boaz
   Hardy, Robert W.
   McConnaughey, William B.
   Zuker, Charles S.
TI Preserving cell shape under environmental stress
SO NATURE
LA English
DT Article
ID mechanosensory transduction; mechanical-property; drosophila retina; cytochalasin-d; mechanoreceptors; eyes
AB Maintaining cell shape and tone is crucial for the function and survival of cells and tissues. Mechanotransduction relies on the transformation of minuscule mechanical forces into high- fidelity electrical responses(1-3). When mechanoreceptors are stimulated, mechanically sensitive cation channels open and produce an inward transduction current that depolarizes the cell. For this process to operate effectively, the transduction machinery has to retain integrity and remain unfailingly independent of environmental changes. This is particularly challenging for poikilothermic organisms, where changes in temperature in the environment may impact the function of mechanoreceptor neurons. Thus, we wondered how insects whose habitat might quickly vary over several tens of degrees of temperature manage to maintain highly effective mechanical senses. We screened for Drosophila mutants with defective mechanical responses at elevated ambient temperatures, and identified a gene, spam, whose role is to protect the mechanosensory organ from massive cellular deformation caused by heat-induced osmotic imbalance. Here we show that Spam protein forms an extracellular shield that guards mechanosensory neurons from environmental insult. Remarkably, heterologously expressed Spam protein also endowed other cells with superb defence against physically and chemically induced deformation. We studied the mechanical impact of Spam coating and show that spam- coated cells are up to ten times stiffer than uncoated controls. Together, these results help explain how poikilothermic organisms preserve the architecture of critical cells during environmental stress, and illustrate an elegant and simple solution to such challenge.
C1 [Cook, Boaz; Hardy, Robert W.; Zuker, Charles S.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Cook, Boaz; Hardy, Robert W.; Zuker, Charles S.] Univ Calif San Diego, Dept Neurobiol, La Jolla, CA 92093 USA.
   [Cook, Boaz; Hardy, Robert W.; Zuker, Charles S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [McConnaughey, William B.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
C3 University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Washington University (WUSTL)
RP Zuker, CS (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
EM charles@flyeye.ucsd.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NEI NIH HHS [R01 EY006979] Funding Source: Medline
NR 18
TC 41
Z9 46
U1 1
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 MAR 20
PY 2008
VL 452
IS 7185
BP 361
EP U9
DI 10.1038/nature06603
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400049
PM 18297055
DA 2026-03-09
ER

PT J
AU Salart, D
   Baas, A
   Branciard, C
   Gisin, N
   Zbinden, H
AF Salart, Daniel
   Baas, Augustin
   Branciard, Cyril
   Gisin, Nicolas
   Zbinden, Hugo
TI Testing the speed of 'spooky action at a distance'
SO NATURE
LA English
DT Article
ID bell inequality; violation
AB Correlations are generally described by one of two mechanisms: either a first event influences a second one by sending information encoded in bosons or other physical carriers, or the correlated events have some common causes in their shared history. Quantum physics predicts an entirely different kind of cause for some correlations, named entanglement. This reveals itself in correlations that violate Bell inequalities (implying that they cannot be described by common causes) between space-like separated events (implying that they cannot be described by classical communication). Many Bell tests have been performed(1), and loopholes related to locality(2-4) and detection(5,6) have been closed in several independent experiments. It is still possible that a first event could influence a second, but the speed of this hypothetical influence (Einstein's 'spooky action at a distance') would need to be defined in some universal privileged reference frame and be greater than the speed of light. Here we put stringent experimental bounds on the speed of all such hypothetical influences. We performed a Bell test over more than 24 hours between two villages separated by 18 km and approximately east-west oriented, with the source located precisely in the middle. We continuously observed two-photon interferences well above the Bell inequality threshold. Taking advantage of the Earth's rotation, the configuration of our experiment allowed us to determine, for any hypothetically privileged frame, a lower bound for the speed of the influence. For example, if such a privileged reference frame exists and is such that the Earth's speed in this frame is less than 10(-3) times that of the speed of light, then the speed of the influence would have to exceed that of light by at least four orders of magnitude.
C1 [Salart, Daniel; Baas, Augustin; Branciard, Cyril; Gisin, Nicolas; Zbinden, Hugo] Univ Geneva, Appl Phys Grp, CH-1211 Geneva 4, Switzerland.
C3 University of Geneva
RP Salart, D (corresponding author), Univ Geneva, Appl Phys Grp, 20 Rue Ecole Med, CH-1211 Geneva 4, Switzerland.
EM daniel.salart@physics.unige.ch
NR 22
TC 167
Z9 188
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 AUG 14
PY 2008
VL 454
IS 7206
BP 861
EP 864
DI 10.1038/nature07121
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600030
PM 18704081
DA 2026-03-09
ER

PT J
AU Richards, S
   Gibbs, RA
   Weinstock, GM
   Brown, SJ
   Denell, R
   Beeman, RW
   Gibbs, R
   Bucher, G
   Friedrich, M
   Grimmelikhuijzen, CJP
   Klingler, M
   Lorenzen, MD
   Roth, S
   Schröder, R
   Tautz, D
   Zdobnov, EM
   Muzny, D
   Attaway, T
   Bell, S
   Buhay, CJ
   Chandrabose, MN
   Chavez, D
   Clerk-Blankenburg, KP
   Cree, A
   Dao, M
   Davis, C
   Chacko, J
   Dinh, H
   Dugan-Rocha, S
   Fowler, G
   Garner, TT
   Garnes, J
   Gnirke, A
   Hawes, A
   Hernandez, J
   Hines, S
   Holder, M
   Hume, J
   Jhangiani, SN
   Joshi, V
   Khan, ZM
   Jackson, L
   Kovar, C
   Kowis, A
   Lee, S
   Lewis, LR
   Margolis, J
   Morgan, M
   Nazareth, LV
   Nguyen, N
   Okwuonu, G
   Parker, D
   Ruiz, SJ
   Santibanez, J
   Savard, J
   Scherer, SE
   Schneider, B
   Sodergren, E
   Vattahil, S
   Villasana, D
   White, CS
   Wright, R
   Park, Y
   Lord, J
   Oppert, B
   Brown, S
   Wang, LJ
   Savard, J
   Liu, Y
   Worley, K
   Elsik, CG
   Reese, JT
   Elhaik, E
   Landan, G
   Graur, D
   Arensburger, P
   Atkinson, P
   Beidler, J
   Demuth, JP
   Drury, DW
   Du, YZ
   Fujiwara, H
   Maselli, V
   Osanai, M
   Robertson, HM
   Tu, Z
   Wang, JJ
   Wang, SZ
   Song, H
   Zhang, L
   Sodergren, E
   Werner, D
   Stanke, M
   Morgenstern, B
   Solovyev, V
   Kosarev, P
   Brown, G
   Chen, HC
   Ermolaeva, O
   Hlavina, W
   Kapustin, Y
   Kiryutin, B
   Kitts, P
   Maglott, D
   Pruitt, K
   Sapojnikov, V
   Souvorov, A
   Mackey, AJ
   Waterhouse, RM
   Wyder, S
   Zdobnov, EM
   Kriventseva, EV
   Kadowaki, T
   Bork, P
   Aranda, M
   Bao, RY
   Beermann, A
   Berns, N
   Bolognesi, R
   Bonneton, F
   Bopp, D
   Butts, T
   Chaumot, A
   Denell, RE
   Ferrier, DEK
   Gordon, CM
   Jindra, M
   Klingler, M
   Lan, Q
   Lattorff, HMG
   Laudet, V
   von Levetsow, C
   Liu, ZY
   Lutz, R
   Lynch, JA
   da Fonseca, RN
   Posnien, N
   Reuter, R
   Roth, S
   Schinko, JB
   Schmitt, C
   Schoppmeier, M
   Shippy, TD
   Simonnet, F
   Marques-Souza, H
   Tomoyasu, Y
   Trauner, J
   Van der Zee, M
   Vervoort, M
   Wittkopp, N
   Wimmer, EA
   Yang, XY
   Jones, AK
   Sattelle, DB
   Ebert, PR
   Nelson, D
   Scott, JG
   Muthukrishnan, S
   Kramer, KJ
   Arakane, Y
   Zhu, QS
   Hogenkamp, D
   Dixit, R
   Jiang, HB
   Zou, Z
   Marshall, J
   Elpidina, E
   Vinokurov, K
   Oppert, C
   Evans, J
   Lu, ZQ
   Zhao, PC
   Sumathipala, N
   Altincicek, B
   Vilcinskas, A
   Williams, M
   Hultmark, D
   Hetru, C
   Hauser, F
   Cazzamali, G
   Williamson, M
   Li, B
   Tanaka, Y
   Predel, R
   Neupert, S
   Schachtner, J
   Verleyen, P
   Raible, F
   Walden, KKO
   Robertson, HM
   Angeli, S
   Forêt, S
   Schuetz, S
   Maleszka, R
   Miller, SC
   Grossmann, D
AF Richards, Stephen
   Gibbs, Richard A.
   Weinstock, George M.
   Brown, Susan J.
   Denell, Robin
   Beeman, Richard W.
   Gibbs, Richard
   Bucher, Gregor
   Friedrich, Markus
   Grimmelikhuijzen, Cornelis J. P.
   Klingler, Martin
   Lorenzen, Marce D.
   Roth, Siegfried
   Schroeder, Reinhard
   Tautz, Diethard
   Zdobnov, Evgeny M.
   Muzny, Donna
   Attaway, Tony
   Bell, Stephanie
   Buhay, Christian J.
   Chandrabose, Mimi N.
   Chavez, Dean
   Clerk-Blankenburg, Kerstin P.
   Cree, Andrew
   Dao, Marvin
   Davis, Clay
   Chacko, Joseph
   Dinh, Huyen
   Dugan-Rocha, Shannon
   Fowler, Gerald
   Garner, Toni T.
   Garnes, Jeffrey
   Gnirke, Andreas
   Hawes, Alica
   Hernandez, Judith
   Hines, Sandra
   Holder, Michael
   Hume, Jennifer
   Jhangiani, Shalini N.
   Joshi, Vandita
   Khan, Ziad Mohid
   Jackson, LaRonda
   Kovar, Christie
   Kowis, Andrea
   Lee, Sandra
   Lewis, Lora R.
   Margolis, Jon
   Morgan, Margaret
   Nazareth, Lynne V.
   Nguyen, Ngoc
   Okwuonu, Geoffrey
   Parker, David
   Ruiz, San-Juana
   Santibanez, Jireh
   Savard, Joel
   Scherer, Steven E.
   Schneider, Brian
   Sodergren, Erica
   Vattahil, Selina
   Villasana, Donna
   White, Courtney S.
   Wright, Rita
   Park, Yoonseong
   Lord, Jeff
   Oppert, Brenda
   Brown, Susan
   Wang, Liangjiang
   Savard, Joel
   Liu, Yue
   Worley, Kim
   Elsik, Christine G.
   Reese, Justin T.
   Elhaik, Eran
   Landan, Giddy
   Graur, Dan
   Arensburger, Peter
   Atkinson, Peter
   Beidler, Jim
   Demuth, Jeffery P.
   Drury, Douglas W.
   Du, Yu-Zhou
   Fujiwara, Haruhiko
   Maselli, Vincenza
   Osanai, Mizuko
   Robertson, Hugh M.
   Tu, Zhijian
   Wang, Jian-Jun
   Wang, Suzhi
   Song, Henry
   Zhang, Lan
   Sodergren, Erica
   Werner, Doreen
   Stanke, Mario
   Morgenstern, Burkhard
   Solovyev, Victor
   Kosarev, Peter
   Brown, Garth
   Chen, Hsiu-Chuan
   Ermolaeva, Olga
   Hlavina, Wratko
   Kapustin, Yuri
   Kiryutin, Boris
   Kitts, Paul
   Maglott, Donna
   Pruitt, Kim
   Sapojnikov, Victor
   Souvorov, Alexandre
   Mackey, Aaron J.
   Waterhouse, Robert M.
   Wyder, Stefan
   Zdobnov, Evgeny M.
   Kriventseva, Evgenia V.
   Kadowaki, Tatsuhiko
   Bork, Peer
   Aranda, Manuel
   Bao, Riyue
   Beermann, Anke
   Berns, Nicola
   Bolognesi, Renata
   Bonneton, Francois
   Bopp, Daniel
   Butts, Thomas
   Chaumot, Arnaud
   Denell, Robin E.
   Ferrier, David E. K.
   Gordon, Cassondra M.
   Jindra, Marek
   Klingler, Martin
   Lan, Que
   Lattorff, H. Michael G.
   Laudet, Vincent
   von Levetsow, Cornelia
   Liu, Zhenyi
   Lutz, Rebekka
   Lynch, Jeremy A.
   da Fonseca, Rodrigo Nunes
   Posnien, Nico
   Reuter, Rolf
   Roth, Siegfried
   Schinko, Johannes B.
   Schmitt, Christian
   Schoppmeier, Michael
   Shippy, Teresa D.
   Simonnet, Franck
   Marques-Souza, Henrique
   Tomoyasu, Yoshinori
   Trauner, Jochen
   Van der Zee, Maurijn
   Vervoort, Michel
   Wittkopp, Nadine
   Wimmer, Ernst A.
   Yang, Xiaoyun
   Jones, Andrew K.
   Sattelle, David B.
   Ebert, Paul R.
   Nelson, David
   Scott, Jeffrey G.
   Muthukrishnan, Subbaratnam
   Kramer, Karl J.
   Arakane, Yasuyuki
   Zhu, Qingsong
   Hogenkamp, David
   Dixit, Radhika
   Jiang, Haobo
   Zou, Zhen
   Marshall, Jeremy
   Elpidina, Elena
   Vinokurov, Konstantin
   Oppert, Cris
   Evans, Jay
   Lu, Zhiqiang
   Zhao, Picheng
   Sumathipala, Niranji
   Altincicek, Boran
   Vilcinskas, Andreas
   Williams, Michael
   Hultmark, Dan
   Hetru, Charles
   Hauser, Frank
   Cazzamali, Giuseppe
   Williamson, Michael
   Li, Bin
   Tanaka, Yoshiaki
   Predel, Reinhard
   Neupert, Susanne
   Schachtner, Joachim
   Verleyen, Peter
   Raible, Florian
   Walden, Kimberly K. O.
   Robertson, Hugh M.
   Angeli, Sergio
   Foret, Sylvain
   Schuetz, Stefan
   Maleszka, Ryszard
   Miller, Sherry C.
   Grossmann, Daniela
TI The genome of the model beetle and pest Tribolium castaneum
SO NATURE
LA English
DT Article
ID short-germ insect; red flour beetle; drosophila-melanogaster; gene superfamily; apis-mellifera; messenger-rna; bombyx-mori; honey-bee; protein; segmentation
AB Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell - cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short- germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
C1 [Richards, Stephen; Gibbs, Richard A.; Weinstock, George M.; Gibbs, Richard; Bucher, Gregor; Muzny, Donna; Attaway, Tony; Bell, Stephanie; Buhay, Christian J.; Chandrabose, Mimi N.; Chavez, Dean; Clerk-Blankenburg, Kerstin P.; Cree, Andrew; Dao, Marvin; Davis, Clay; Chacko, Joseph; Dinh, Huyen; Dugan-Rocha, Shannon; Fowler, Gerald; Garner, Toni T.; Hawes, Alica; Hernandez, Judith; Hines, Sandra; Holder, Michael; Hume, Jennifer; Jhangiani, Shalini N.; Joshi, Vandita; Khan, Ziad Mohid; Jackson, LaRonda; Kovar, Christie; Kowis, Andrea; Lee, Sandra; Lewis, Lora R.; Morgan, Margaret; Nazareth, Lynne V.; Nguyen, Ngoc; Okwuonu, Geoffrey; Parker, David; Ruiz, San-Juana; Santibanez, Jireh; Scherer, Steven E.; Schneider, Brian; Sodergren, Erica; Vattahil, Selina; Villasana, Donna; White, Courtney S.; Wright, Rita; Liu, Yue; Worley, Kim; Song, Henry; Zhang, Lan; Sodergren, Erica] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Richards, Stephen; Gibbs, Richard A.; Weinstock, George M.; Gibbs, Richard; Bucher, Gregor; Muzny, Donna; Attaway, Tony; Bell, Stephanie; Buhay, Christian J.; Chandrabose, Mimi N.; Chavez, Dean; Clerk-Blankenburg, Kerstin P.; Cree, Andrew; Dao, Marvin; Davis, Clay; Chacko, Joseph; Dinh, Huyen; Dugan-Rocha, Shannon; Fowler, Gerald; Garner, Toni T.; Hawes, Alica; Hernandez, Judith; Hines, Sandra; Holder, Michael; Hume, Jennifer; Jhangiani, Shalini N.; Joshi, Vandita; Khan, Ziad Mohid; Jackson, LaRonda; Kovar, Christie; Kowis, Andrea; Lee, Sandra; Lewis, Lora R.; Morgan, Margaret; Nazareth, Lynne V.; Nguyen, Ngoc; Okwuonu, Geoffrey; Parker, David; Ruiz, San-Juana; Santibanez, Jireh; Scherer, Steven E.; Schneider, Brian; Sodergren, Erica; Vattahil, Selina; Villasana, Donna; White, Courtney S.; Wright, Rita; Liu, Yue; Worley, Kim; Song, Henry; Zhang, Lan; Sodergren, Erica] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Brown, Susan J.; Denell, Robin; Lorenzen, Marce D.; Brown, Susan; Wang, Liangjiang; Wang, Suzhi; Bolognesi, Renata; Denell, Robin E.; Gordon, Cassondra M.; Shippy, Teresa D.; Tomoyasu, Yoshinori; Marshall, Jeremy; Miller, Sherry C.] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA.
   [Beeman, Richard W.; Lorenzen, Marce D.; Lord, Jeff; Oppert, Brenda; Kramer, Karl J.; Arakane, Yasuyuki; Oppert, Cris] ARS, Grain Mkt & Prod Res Ctr, USDA, Manhattan, KS 66502 USA.
   [Posnien, Nico; Schinko, Johannes B.; Simonnet, Franck; Wimmer, Ernst A.; Schuetz, Stefan; Grossmann, Daniela] Univ Gottingen, Johann Friedrich Blumenbach Inst, Dept Dev Biol, D-37077 Gottingen, Germany.
   [Friedrich, Markus; Bao, Riyue; Yang, Xiaoyun] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA.
   [Grimmelikhuijzen, Cornelis J. P.; Hauser, Frank; Cazzamali, Giuseppe; Williamson, Michael] Univ Copenhagen, Ctr Funct & Comparat Insect Genom, DK-2100 Copenhagen, Denmark.
   [Hauser, Frank; Cazzamali, Giuseppe; Williamson, Michael] Univ Copenhagen, Dept Cell Biol & Comparat Zool, Inst Biol, DK-2100 Copenhagen, Denmark.
   [Klingler, Martin; Klingler, Martin; Schmitt, Christian; Schoppmeier, Michael; Trauner, Jochen] Friedrich Alexander Univ Erlangen, Dept Dev Biol, Inst Biol, D-91058 Erlangen, Germany.
   [Roth, Siegfried; von Levetsow, Cornelia; Lynch, Jeremy A.; da Fonseca, Rodrigo Nunes; Roth, Siegfried] Univ Cologne, Inst Dev Biol, D-50674 Cologne, Germany.
   [Schroeder, Reinhard; Beermann, Anke; Berns, Nicola; Lutz, Rebekka; Reuter, Rolf; Wittkopp, Nadine] Univ Tubingen, Interfac Inst Cell Biol, D-72076 Tubingen, Germany.
   [Tautz, Diethard; Savard, Joel; Savard, Joel; Aranda, Manuel; Marques-Souza, Henrique; Van der Zee, Maurijn] Univ Cologne, Dept Genet, D-50674 Cologne, Germany.
   [Zdobnov, Evgeny M.; Wyder, Stefan; Zdobnov, Evgeny M.; Kriventseva, Evgenia V.] Univ Geneva, Med Sch, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
   [Zdobnov, Evgeny M.; Zdobnov, Evgeny M.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland.
   [Zdobnov, Evgeny M.; Waterhouse, Robert M.; Zdobnov, Evgeny M.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
   Childrens Hosp Oakland, Res Inst, BACPAC Resources, Oakland, CA 94609 USA.
   [Garnes, Jeffrey] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Garnes, Jeffrey] Harvard Univ, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Gnirke, Andreas; Margolis, Jon] AgraQuest Inc, Davis, CA 95616 USA.
   [Park, Yoonseong; Li, Bin] Kansas State Univ, Dept Entomol, Manhattan, KS 66506 USA.
   [Elsik, Christine G.; Reese, Justin T.] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA.
   [Elhaik, Eran; Landan, Giddy; Graur, Dan] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.
   [Arensburger, Peter; Atkinson, Peter] Univ Calif, Dept Entomol, Riverside, CA 92521 USA.
   [Beidler, Jim; Tu, Zhijian] Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA.
   [Demuth, Jeffery P.] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
   [Drury, Douglas W.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Du, Yu-Zhou; Wang, Jian-Jun] Yangzhou Univ, Dept Plant Protect, Yangzhou 225009, Peoples R China.
   [Fujiwara, Haruhiko; Osanai, Mizuko] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Chiba 2778562, Japan.
   [Maselli, Vincenza] European Sch Mol Med, I-80131 Naples, Italy.
   Telethon Inst Genet & Med, I-80131 Naples, Italy.
   [Robertson, Hugh M.; Walden, Kimberly K. O.; Robertson, Hugh M.] Univ Illinois, Dept Entomol, Urbana, IL 61801 USA.
   [Werner, Doreen; Stanke, Mario; Morgenstern, Burkhard] Univ Gottingen, Dept Bioinformat, Inst Microbiol & Genet, D-37077 Gottingen, Germany.
   [Solovyev, Victor] Univ London, Dept Comp Sci, Surrey TW20 0EX, England.
   [Kosarev, Peter] Softberry Inc, Mt Kisco, NY 10549 USA.
   [Brown, Garth; Chen, Hsiu-Chuan; Ermolaeva, Olga; Hlavina, Wratko; Kapustin, Yuri; Kiryutin, Boris; Kitts, Paul; Maglott, Donna; Pruitt, Kim; Sapojnikov, Victor; Souvorov, Alexandre] Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Mackey, Aaron J.] GlaxoSmithKline, Collegeville, PA 19426 USA.
   [Kriventseva, Evgenia V.] Univ Geneva, Dept Struct Biol & Bioinformat, Sch Med, CH-1211 Geneva, Switzerland.
   [Kadowaki, Tatsuhiko] Nagoya Univ, Grad Sch Bioagr Sci, Nagoya, Aichi 4648601, Japan.
   [Bork, Peer; Raible, Florian] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Bork, Peer] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
   [Bonneton, Francois; Laudet, Vincent] Univ Lyon 1, Inst Genom Fonctionnelle Lyon, Equipe Zool Mol, ENS Lyon,CNRS,UMR 5242,INRA,IFR128, F-69364 Lyon 07, France.
   [Bopp, Daniel] Univ Zurich, Zool Inst, CH-8057 Zurich, Switzerland.
   [Butts, Thomas; Ferrier, David E. K.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Chaumot, Arnaud] Irstea, Lab Ecotoxicol, F-69336 Lyon 09, France.
   [Jindra, Marek] Inst Entomol ASCR, Ceske Budejovice 37005, Czech Republic.
   [Lan, Que] Univ Wisconsin, Dept Entomol, Madison, WI 53706 USA.
   [Lattorff, H. Michael G.] Univ Halle Wittenberg, Inst Biol, D-06099 Halle, Saale, Germany.
   [Liu, Zhenyi] Washington Univ, Dept Mol Biol & Pharmacol, Sch Med, St Louis, MO 63110 USA.
   [Vervoort, Michel] Univ Paris 07, Ctr Genet Mol, CNRS UPR 2167, F-91198 Gif Sur Yvette, France.
   [Jones, Andrew K.; Sattelle, David B.] Univ Oxford, MRC Funct Genet Unit, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
   [Ebert, Paul R.] Univ Queensland, Sch Integrat Biol, St Lucia, Qld 4072, Australia.
   [Ebert, Paul R.] Univ Queensland, Sch Mol & Microbial Sci, St Lucia, Qld 4072, Australia.
   [Nelson, David] Univ Tennessee, Dept Mol Sci, Memphis, TN 38163 USA.
   [Nelson, David] Univ Tennessee, Ct Excellence Genom & Bioinformat, Memphis, TN 38163 USA.
   [Scott, Jeffrey G.] Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA.
   [Muthukrishnan, Subbaratnam; Kramer, Karl J.; Arakane, Yasuyuki; Zhu, Qingsong; Hogenkamp, David; Dixit, Radhika] Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA.
   [Jiang, Haobo; Zou, Zhen; Lu, Zhiqiang; Zhao, Picheng; Sumathipala, Niranji] Oklahoma State Univ, Dept Entomol & Plant Pathol, Stillwater, OK 74078 USA.
   [Elpidina, Elena; Vinokurov, Konstantin] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119992, Russia.
   [Evans, Jay] ARS, USDA, Bee Res Lab, Beltsville, MD 20705 USA.
   [Altincicek, Boran; Vilcinskas, Andreas] Univ Giessen, Inst Phytopathol & Appl Zool, Interdisciplinary Res Ctr, D-35392 Giessen, Germany.
   [Williams, Michael; Hultmark, Dan] Umea Univ, Umea Ctr Mol Pathogenesis, SE-90187 Umea, Sweden.
   [Hetru, Charles] CNRS, Inst Biol Molec Cell, F-67084 Strasbourg, France.
   [Tanaka, Yoshiaki] Natl Inst Agrobiol Sci, Div Insect Sci, Tsukuba, Ibaraki 3058634, Japan.
   [Predel, Reinhard; Neupert, Susanne] Univ Jena, Inst Gen Zool, D-07743 Jena, Germany.
   [Schachtner, Joachim] Univ Marburg, Dept Anim Physiol, D-35032 Marburg, Germany.
   [Verleyen, Peter] Univ Louvain, Dept Anim Physiol & Neurobiol, BE-3000 Louvain, Belgium.
   [Angeli, Sergio] Inst Forest Zool & Forest Conservat, D-37077 Gottingen, Germany.
   [Foret, Sylvain; Maleszka, Ryszard] Australian Natl Univ, Visual Sci & ARC Ctr Mol Genet Dev, Res Sch Biol Sci, Canberra, ACT 0200, Australia.
C3 Baylor College of Medicine; Baylor College of Medicine; Kansas State University; United States Department of Agriculture (USDA); University of Gottingen; Wayne State University; University of Copenhagen; University of Copenhagen; University of Erlangen Nuremberg; University of Cologne; Eberhard Karls University of Tubingen; University of Cologne; University of Geneva; Swiss Institute of Bioinformatics; Imperial College London; Children's Hospital Oakland Research Institute; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Kansas State University; Texas A&M University System; Texas A&M University College Station; University of Houston System; University of Houston; University of California System; University of California Riverside; Virginia Polytechnic Institute & State University; University of Texas System; University of Texas Arlington; Indiana University System; Indiana University Bloomington; Yangzhou University; University of Tokyo; Fondazione Telethon; Telethon Institute of Genetics & Medicine (TIGEM); University of Illinois System; University of Illinois Urbana-Champaign; University of Gottingen; University of London; Royal Holloway University London; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM); GlaxoSmithKline; Glaxosmithkline USA; University of Geneva; Nagoya University; European Molecular Biology Laboratory (EMBL); Helmholtz Association; Max Delbruck Center for Molecular Medicine; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Ecole Normale Superieure de Lyon (ENS de LYON); CHU Lyon; INRAE; Universite Lyon 1; University of Zurich; University of Oxford; INRAE; Czech Academy of Sciences; University of Wisconsin System; University of Wisconsin Madison; Martin Luther University Halle Wittenberg; Washington University (WUSTL); Universite Paris Cite; University of Oxford; University of Queensland; University of Queensland; University of Tennessee System; University of Tennessee Health Science Center; University of Tennessee System; University of Tennessee Health Science Center; Cornell University; Kansas State University; Oklahoma State University System; Oklahoma State University - Stillwater; Lomonosov Moscow State University; United States Department of Agriculture (USDA); Justus Liebig University Giessen; Umea University; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); National Institute of Agrobiological Sciences - Japan; Friedrich Schiller University of Jena; Philipps University Marburg; Australian National University
RP Richards, S (corresponding author), Baylor Coll Med, Human Genome Sequencing Ctr, 1 Baylor Plaza, Houston, TX 77030 USA.
FU Biotechnology and Biological Sciences Research Council [BBS/B/12067, BBS/B/12067/2] Funding Source: Medline; NICHD NIH HHS [R01 HD029594] Funding Source: Medline; Intramural NIH HHS Funding Source: Medline; National Institute of General Medical Sciences [R01GM058634] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BBS/B/12067, BBS/B/12067/2] Funding Source: researchfish; BBSRC [BBS/B/12067/2] Funding Source: UKRI
NR 51
TC 1139
Z9 1306
U1 6
U2 354
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 24
PY 2008
VL 452
IS 7190
BP 949
EP 955
DI 10.1038/nature06784
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600030
PM 18362917
DA 2026-03-09
ER

PT J
AU Cheng, HC
   Skehan, BM
   Campellone, KG
   Leong, JM
   Rosen, MK
AF Cheng, Hui-Chun
   Skehan, Brian M.
   Campellone, Kenneth G.
   Leong, John M.
   Rosen, Michael K.
TI Structural mechanism of WASP activation by the enterohaemorrhagic E-coli effector EspFU
SO NATURE
LA English
DT Article
ID n-wasp; arp2/3 complex; wasp/scar proteins; nmr; tir; binding; tccp; autoinhibition; spectroscopy; integration
AB During infection, enterohaemorrhagic Escherichia coli ( EHEC) takes over the actin cytoskeleton of eukaryotic cells by injecting the EspFU protein into the host cytoplasm(1,2). EspFU controls actin by activating members of the Wiskott - Aldrich syndrome protein ( WASP) family(1-5). Here we show that EspFU binds to the autoinhibitory GTPase binding domain ( GBD) in WASP proteins and displaces it from the activity- bearing VCA domain ( for verprolin homology, central hydrophobic and acidic regions). This interaction potently activates WASP and neural ( N)- WASP in vitro and induces localized actin assembly in cells. In the solution structure of the GBD - EspFU complex, EspFU forms an amphipathic helix that binds the GBD, mimicking interactions of the VCA domain in autoinhibited WASP. Thus, EspFU activates WASP by competing directly for the VCA binding site on the GBD. This mechanism is distinct from that used by the eukaryotic activators Cdc42 and SH2 domains, which globally destabilize the GBD fold to release the VCA(6-8). Such diversity of mechanism in WASP proteins is distinct from other multimodular systems, and may result from the intrinsically unstructured nature of the isolated GBD and VCA elements. The structural incompatibility of the GBD complexes with EspFU and Cdc42/SH2, plus high- affinity EspFU binding, enable EHEC to hijack the eukaryotic cytoskeletal machinery effectively.
C1 [Cheng, Hui-Chun; Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Cheng, Hui-Chun; Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Skehan, Brian M.; Campellone, Kenneth G.; Leong, John M.] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 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; University of Massachusetts System; University of Massachusetts Worcester
RP Rosen, MK (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
EM michael.rosen@utsouthwestern.edu
FU National Institute of Health [NIH-R01-GM56322, NIH-R01-AI46454]; Welch Foundation [I-1544]; Chilton Foundation Fellowship
NR 43
TC 89
Z9 105
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 AUG 21
PY 2008
VL 454
IS 7207
BP 1009
EP U54
DI 10.1038/nature07160
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000042
PM 18650809
DA 2026-03-09
ER

PT J
AU Novembre, J
   Johnson, T
   Bryc, K
   Kutalik, Z
   Boyko, AR
   Auton, A
   Indap, A
   King, KS
   Bergmann, S
   Nelson, MR
   Stephens, M
   Bustamante, CD
AF Novembre, John
   Johnson, Toby
   Bryc, Katarzyna
   Kutalik, Zoltan
   Boyko, Adam R.
   Auton, Adam
   Indap, Amit
   King, Karen S.
   Bergmann, Sven
   Nelson, Matthew R.
   Stephens, Matthew
   Bustamante, Carlos D.
TI Genes mirror geography within Europe
SO NATURE
LA English
DT Article
ID genome-wide association; stratification; ancestry; genotype; loci
AB Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high- throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations(1-5). Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing(6); an individual's DNA can be used to infer their geographic origin with surprising accuracy often to within a few hundred kilometres.
C1 [Novembre, John] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Interdept Program Bioinformat, Los Angeles, CA 90095 USA.
   [Novembre, John; Stephens, Matthew] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Stephens, Matthew] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
   [Johnson, Toby; Kutalik, Zoltan; Bergmann, Sven] Univ Lausanne, CHUV, Dept Med Genet, CH-1005 Lausanne, Switzerland.
   [Johnson, Toby] Univ Lausanne, CHUV, Univ Inst Social & Preventat Med, CH-1005 Lausanne, Switzerland.
   [Johnson, Toby; Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, Cent Adm, CH-1015 Lausanne, Switzerland.
   [Bryc, Katarzyna; Boyko, Adam R.; Auton, Adam; Indap, Amit; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
   [King, Karen S.; Nelson, Matthew R.] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA.
C3 University of California System; University of California Los Angeles; University of Chicago; University of Chicago; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Swiss Institute of Bioinformatics; Cornell University; GlaxoSmithKline; Glaxosmithkline USA
RP Novembre, J (corresponding author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Interdept Program Bioinformat, Los Angeles, CA 90095 USA.
EM jnovembre@ucla.edu
FU Giorgi-Cavaglieri Foundation; Swiss National Science Foundation; US National Science Foundation Postdoctoral Fellowship in Bioinformatics; US National Institutes of Health; GlaxoSmithKline
NR 28
TC 1016
Z9 1250
U1 2
U2 211
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 98
EP U5
DI 10.1038/nature07331
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000048
PM 18758442
DA 2026-03-09
ER

PT J
AU Soucek, L
   Whitfield, J
   Martins, CP
   Finch, AJ
   Murphy, DJ
   Sodir, NM
   Karnezis, AN
   Swigart, LB
   Nasi, S
   Evan, GI
AF Soucek, Laura
   Whitfield, Jonathan
   Martins, Carla P.
   Finch, Andrew J.
   Murphy, Daniel J.
   Sodir, Nicole M.
   Karnezis, Anthony N.
   Swigart, Lamorna Brown
   Nasi, Sergio
   Evan, Gerard I.
TI Modelling Myc inhibition as a cancer therapy
SO NATURE
LA English
DT Article
ID c-myc; neoplastic phenotype; expression; proliferation; progression; oncogene; gene; skin; dimerization; induction
AB Myc is a pleiotropic basic helix - loop - helix leucine zipper transcription factor that coordinates expression of the diverse intracellular and extracellular programs that together are necessary for growth and expansion of somatic cells(1). In principle, this makes inhibition of Myc an attractive pharmacological approach for treating diverse types of cancer. However, enthusiasm has been muted by lack of direct evidence that Myc inhibition would be therapeutically efficacious, concerns that it would induce serious side effects by inhibiting proliferation of normal tissues, and practical difficulties in designing Myc inhibitory drugs. We have modelled genetically both the therapeutic impact and the side effects of systemic Myc inhibition in a preclinical mouse model of Ras- induced lung adenocarcinoma by reversible, systemic expression of a dominant- interfering Myc mutant. We show that Myc inhibition triggers rapid regression of incipient and established lung tumours, defining an unexpected role for endogenous Myc function in the maintenance of Ras- dependent tumours in vivo. Systemic Myc inhibition also exerts profound effects on normal regenerating tissues. However, these effects are well tolerated over extended periods and rapidly and completely reversible. Our data demonstrate the feasibility of targeting Myc, a common downstream conduit for many oncogenic signals, as an effective, efficient and tumour- specific cancer therapy.
C1 [Soucek, Laura; Whitfield, Jonathan; Martins, Carla P.; Finch, Andrew J.; Murphy, Daniel J.; Sodir, Nicole M.; Karnezis, Anthony N.; Nasi, Sergio; Evan, Gerard I.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Soucek, Laura; Whitfield, Jonathan; Martins, Carla P.; Finch, Andrew J.; Murphy, Daniel J.; Sodir, Nicole M.; Karnezis, Anthony N.; Swigart, Lamorna Brown; Evan, Gerard I.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
   [Nasi, Sergio] Univ Roma La Sapienza, CNR, Ist Biol & Patol Mol, I-00185 Rome, Italy.
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; Sapienza University Rome; Consiglio Nazionale delle Ricerche (CNR); Istituto di Biologia e Patologia Molecolari (IBPM-CNR)
RP Evan, GI (corresponding author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
EM gevan@cc.ucsf.edu
FU National Cancer Institute [2R01 CA98018]; AIRC; ASI; CNR; MIUR FIRB; FIRS; Human Frontier Science Program; National Cancer Institute [T32CA108462] Funding Source: NIH RePORTER
NR 30
TC 695
Z9 865
U1 0
U2 52
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 679
EP 683
DI 10.1038/nature07260
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700050
PM 18716624
DA 2026-03-09
ER

PT J
AU Singh, SK
   Kagalwala, MN
   Parker-Thornburg, J
   Adams, H
   Majumder, S
AF Singh, Sanjay K.
   Kagalwala, Mohamedi N.
   Parker-Thornburg, Jan
   Adams, Henry
   Majumder, Sadhan
TI REST maintains self-renewal and pluripotency of embryonic stem cells
SO NATURE
LA English
DT Article
ID transcriptional regulation; neuronal differentiation; rest/nrsf; chromatin; network; genes; tumors; nanog
AB The neuronal repressor REST ( RE1- silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem ( ES) cells(1), but its role in these cells is unclear. Here we show that REST maintains self- renewal and pluripotency in mouse ES cells through suppression of the microRNA miR- 21. We found that, as with known self- renewal markers, the level of REST expression is much higher in self- renewing mouse ES cells than in differentiating mouse ES ( embryoid body, EB) cells. Heterozygous deletion of Rest ( Rest(+/-)) and its short- interfering-RNA- mediated knockdown in mouse ES cells cause a loss of self- renewal - even when these cells are grown under self- renewal conditions - and lead to the expression of markers specific for multiple lineages. Conversely, exogenously added REST maintains self- renewal in mouse EB cells. Furthermore, Rest(+/-) mouse ES cells cultured under self- renewal conditions express substantially reduced levels of several self- renewal regulators, including Oct4 ( also called Pou5f1), Nanog, Sox2 and c- Myc, and exogenously added REST in mouse EB cells maintains the self- renewal phenotypes and expression of these self- renewal regulators. We also show that in mouse ES cells, REST is bound to the gene chromatin of a set of miRNAs that potentially target self- renewal genes. Whereas mouse ES cells and mouse EB cells containing exogenously added REST express lower levels of these miRNAs, EB cells, Rest(+/-) ES cells and ES cells treated with short interfering RNA targeting Rest express higher levels of these miRNAs. At least one of these REST- regulated miRNAs, miR- 21, specifically suppresses the self- renewal of mouse ES cells, corresponding to the decreased expression of Oct4, Nanog, Sox2 and c- Myc. Thus, REST is a newly discovered element of the interconnected regulatory network that maintains the self- renewal and pluripotency of mouse ES cells.
C1 [Singh, Sanjay K.; Kagalwala, Mohamedi N.; Adams, Henry; Majumder, Sadhan] Univ Texas MD Anderson Canc Ctr, Dept Canc Genet, Houston, TX 77030 USA.
   [Parker-Thornburg, Jan] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Majumder, Sadhan] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
   [Majumder, Sadhan] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA.
   [Singh, Sanjay K.; Kagalwala, Mohamedi N.; Majumder, Sadhan] Univ Texas MD Anderson Canc Ctr, Ctr Stem Cell & Dev Biol, Houston, TX 77030 USA.
   [Majumder, Sadhan] Univ Texas Houston, Grad Sch Biomed Sci, Program Genes & Dev, Houston, TX 77030 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; University of Texas Health Science Center Houston
RP Majumder, S (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Canc Genet, Houston, TX 77030 USA.
EM smajumder@mdanderson.org
FU NCI NIH HHS [CA97124, CA81255, R01 CA081255, R01 CA097124] Funding Source: Medline
NR 24
TC 268
Z9 331
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 223
EP U11
DI 10.1038/nature06863
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400040
PM 18362916
DA 2026-03-09
ER

PT J
AU Andäng, M
   Hjerling-Leffler, J
   Moliner, A
   Lundgren, TK
   Castelo-Branco, G
   Nanou, E
   Pozas, E
   Bryja, V
   Halliez, S
   Nishimaru, H
   Wilbertz, J
   Arenas, E
   Koltzenburg, M
   Charnay, P
   El Manira, A
   Ibañez, CF
   Ernfors, P
AF Andang, Michael
   Hjerling-Leffler, Jens
   Moliner, Annalena
   Lundgren, T. Kalle
   Castelo-Branco, Goncalo
   Nanou, Evanthia
   Pozas, Ester
   Bryja, Vitezslav
   Halliez, Sophie
   Nishimaru, Hiroshi
   Wilbertz, Johannes
   Arenas, Ernest
   Koltzenburg, Martin
   Charnay, Patrick
   El Manira, Abdeljabbar
   Ibanez, Carlos F.
   Ernfors, Patrik
TI Histone H2AX-dependent GABAA receptor regulation of stem cell proliferation
SO NATURE
LA English
DT Article
ID dna-damage; boundary cap; h2ax; phosphorylation; differentiation; expression; hindbrain; phase; atm
AB Stem cell self- renewal implies proliferation under continued maintenance of multipotency. Small changes in numbers of stem cells may lead to large differences in differentiated cell numbers, resulting in significant physiological consequences. Proliferation is typically regulated in the G1 phase, which is associated with differentiation and cell cycle arrest(1). However, embryonic stem ( ES) cells may lack a G1 checkpoint(2,3). Regulation of proliferation in the 'DNA damage' S/G2 cell cycle checkpoint pathway is known for its role in the maintenance of chromatin structural integrity(4). Here we show that autocrine/paracrine gamma-aminobutyric acid ( GABA) signalling by means of GABA(A) receptors negatively controls ES cell and peripheral neural crest stem ( NCS) cell proliferation, preimplantation embryonic growth and proliferation in the boundary- cap stem cell niche, resulting in an attenuation of neuronal progenies from this stem cell niche. Activation of GABA(A) receptors leads to hyperpolarization, increased cell volume and accumulation of stem cells in S phase, thereby causing a rapid decrease in cell proliferation. GABA(A) receptors signal through S- phase checkpoint kinases of the phosphatidylinositol-3-OH kinase- related kinase family and the histone variant H2AX. This signalling pathway critically regulates proliferation independently of differentiation, apoptosis and overt damage to DNA. These results indicate the presence of a fundamentally different mechanism of proliferation control in these stem cells, in comparison with most somatic cells, involving proteins in the DNA damage checkpoint pathway.
C1 [Andang, Michael; Hjerling-Leffler, Jens; Lundgren, T. Kalle; Pozas, Ester; Bryja, Vitezslav; Arenas, Ernest; Ernfors, Patrik] Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, S-17177 Stockholm, Sweden.
   [Moliner, Annalena; Castelo-Branco, Goncalo; Nanou, Evanthia; Nishimaru, Hiroshi; El Manira, Abdeljabbar; Ibanez, Carlos F.] Karolinska Inst, Dept Neurosci, Lab Mol Neurodev, S-17177 Stockholm, Sweden.
   [Wilbertz, Johannes] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
   [Halliez, Sophie; Charnay, Patrick] Ecole Normale Super, INSERM, U784, F-75230 Paris 05, France.
   [Koltzenburg, Martin] UCL, Inst Child Hlth, Neural Plast Unit, London WC1E 6BT, England.
C3 Karolinska Institutet; Karolinska Institutet; Karolinska Institutet; Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); University of London; University College London
RP Ernfors, P (corresponding author), Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, S-17177 Stockholm, Sweden.
EM patrik.ernfors@ki.se
FU MRC [G0601943] Funding Source: UKRI; Medical Research Council [G0601943] Funding Source: researchfish; Medical Research Council [G0601943] Funding Source: Medline
NR 21
TC 235
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 
J9 NATURE
JI Nature
PD JAN 24
PY 2008
VL 451
IS 7177
BP 460
EP U4
DI 10.1038/nature06488
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100044
PM 18185516
DA 2026-03-09
ER

PT J
AU Reece, SE
   Drew, DR
   Gardner, A
AF Reece, Sarah E.
   Drew, Damien R.
   Gardner, Andy
TI Sex ratio adjustment and kin discrimination in malaria parasites
SO NATURE
LA English
DT Article
ID local mate competition; plasmodium-falciparum; population-structure; toxoplasma-gondii; blood parasites; premature rejection; fertility insurance; evolution; virulence; transmission
AB Malaria parasites and related Apicomplexans are the causative agents of the some of the most serious infectious diseases of humans, companion animals, livestock and wildlife. These parasites must undergo sexual reproduction to transmit from vertebrate hosts to vectors, and their sex ratios are consistently female- biased. Sex allocation theory, a cornerstone of evolutionary biology, is remarkably successful at explaining female- biased sex ratios in multicellular taxa, but has proved controversial when applied to malaria parasites. Here we show that, as predicted by theory, sex ratio is an important fitness- determining trait and Plasmodium chabaudi parasites adjust their sex allocation in response to the presence of unrelated conspecifics. This suggests that P. chabaudi parasites use kin discrimination to evaluate the genetic diversity of their infections, and they adjust their behaviour in response to environmental cues. Malaria parasites provide a novel way to test evolutionary theory, and support the generality and power of a darwinian approach.
C1 [Reece, Sarah E.; Gardner, Andy] Univ Edinburgh, Inst Evolut Biol, Ashworth Labs, Sch Biol Sci, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Reece, Sarah E.; Drew, Damien R.] Univ Edinburgh, Inst Immunol & Infect Res, Ashworth Labs, Sch Biol Sci, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Drew, Damien R.] Walter & Eliza Hall Inst Med Res, Ctr Biotechnol, Bundoora, Vic 3086, Australia.
C3 University of Edinburgh; University of Edinburgh; Walter & Eliza Hall Institute
RP Reece, SE (corresponding author), Univ Edinburgh, Inst Evolut Biol, Ashworth Labs, Sch Biol Sci, W Mains Rd, Edinburgh EH9 3JT, Midlothian, Scotland.
EM sarah.reece@ed.ac.uk
FU Biotechnology and Biological Sciences Research Council Funding Source: Medline; Wellcome Trust Funding Source: Medline
NR 50
TC 175
Z9 198
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 MAY 29
PY 2008
VL 453
IS 7195
BP 609
EP U1
DI 10.1038/nature06954
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200034
PM 18509435
DA 2026-03-09
ER

PT J
AU Wang, YL
   Sheng, G
   Juranek, S
   Tuschl, T
   Patel, DJ
AF Wang, Yanli
   Sheng, Gang
   Juranek, Stefan
   Tuschl, Thomas
   Patel, Dinshaw J.
TI Structure of the guide-strand-containing argonaute silencing complex
SO NATURE
LA English
DT Article
ID a-aeolicus argonaute; crystal-structure; rna recognition; risc; slicer; specificity; cleavage; insights; disease
AB The slicer activity of the RNA- induced silencing complex is associated with argonaute, the RNase H- like PIWI domain of which catalyses guide- strand- mediated sequence- specific cleavage of target messenger RNA. Here we report on the crystal structure of Thermus thermophilus argonaute bound to a 5 '- phosphorylated 21- base DNA guide strand, thereby identifying the nucleic- acid- binding channel positioned between the PAZ- and PIWI- containing lobes, as well as the pivot- like conformational changes associated with complex formation. The bound guide strand is anchored at both of its ends, with the solvent- exposed Watson - Crick edges of stacked bases 2 to 6 positioned for nucleation with the mRNA target, whereas two critically positioned arginines lock bases 10 and 11 at the cleavage site into an unanticipated orthogonal alignment. Biochemical studies indicate that key amino acid residues at the active site and those lining the 5 '- phosphate- binding pocket made up of the Mid domain are critical for cleavage activity, whereas alterations of residues lining the 2- nucleotide 39- end- binding pocket made up of the PAZ domain show little effect.
C1 [Wang, Yanli; Sheng, Gang; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Juranek, Stefan; Tuschl, Thomas] Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute; Rockefeller University
RP Patel, DJ (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
EM pateld@mskcc.org
FU NIH; US Department of Energy; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 39
TC 426
Z9 536
U1 3
U2 97
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 13
PY 2008
VL 456
IS 7219
BP 209
EP U34
DI 10.1038/nature07315
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300033
PM 18754009
DA 2026-03-09
ER

PT J
AU Yauch, RL
   Gould, SE
   Scales, SJ
   Tang, T
   Tian, H
   Ahn, CP
   Marshall, D
   Fu, L
   Januario, T
   Kallop, D
   Nannini-Pepe, M
   Kotkow, K
   Marsters, JC
   Rubin, LL
   de Sauvage, FJ
AF Yauch, Robert L.
   Gould, Stephen E.
   Scales, Suzie J.
   Tang, Tracy
   Tian, Hua
   Ahn, Christina P.
   Marshall, Derek
   Fu, Ling
   Januario, Thomas
   Kallop, Dara
   Nannini-Pepe, Michelle
   Kotkow, Karen
   Marsters, James C., Jr.
   Rubin, Lee L.
   de Sauvage, Frederic J.
TI A paracrine requirement for hedgehog signalling in cancer
SO NATURE
LA English
DT Article
ID sonic hedgehog; pancreatic-cancer; growth-factor; stromal fibroblasts; mesenchymal cells; pathway; medulloblastoma; renewal; tract
AB Ligand- dependent activation of the hedgehog (Hh) signalling pathway has been associated with tumorigenesis in a number of human tissues(1-7). Here we show that, although previous reports have described a cell- autonomous role for Hh signalling in these tumours(1-7), Hh ligands fail to activate signalling in tumour epithelial cells. In contrast, our data support ligand- dependent activation of the Hh pathway in the stromal microenvironment. Specific inhibition of Hh signalling using small molecule inhibitors, a neutralizing anti- Hh antibody or genetic deletion of smoothened ( Smo) in the mouse stroma results in growth inhibition in xenograft tumour models. Taken together, these studies demonstrate a paracrine requirement for Hh ligand signalling in the tumorigenesis of Hh- expressing cancers and have important implications for the development of Hh pathway antagonists in cancer.
C1 [Yauch, Robert L.; Gould, Stephen E.; Scales, Suzie J.; Tang, Tracy; Tian, Hua; Ahn, Christina P.; Marshall, Derek; Fu, Ling; Januario, Thomas; Kallop, Dara; Nannini-Pepe, Michelle; Marsters, James C., Jr.; de Sauvage, Frederic J.] Genentech Inc, San Francisco, CA 94080 USA.
   [Kotkow, Karen; Rubin, Lee L.] Curis Inc, Cambridge, MA 02138 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Curis, Inc.
RP de Sauvage, FJ (corresponding author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
EM sauvage@gene.com
FU National Cancer Institute; National Center for Research Resources; National Institutes of Health
NR 30
TC 813
Z9 981
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 406
EP U61
DI 10.1038/nature07275
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200048
PM 18754008
DA 2026-03-09
ER

PT J
AU Lam, FH
   Steger, DJ
   O'Shea, EK
AF Lam, Felix H.
   Steger, David J.
   O'Shea, Erin K.
TI Chromatin decouples promoter threshold from dynamic range
SO NATURE
LA English
DT Article
ID transcription factor pho4; cyclin-cdk complex; saccharomyces-cerevisiae; in-vivo; target site; nucleosome; yeast; binding; activation; elements
AB Chromatin influences gene expression by restricting access of DNA binding proteins to their cognate sites in the genome(1-3). Large- scale characterization of nucleosome positioning in Saccharomyces cerevisiae has revealed a stereotyped promoter organization in which a nucleosome- free region ( NFR) is present within several hundred base pairs upstream of the translation start site(4,5). Many transcription factors bind within NFRs and nucleate chromatin remodelling events which then expose other cis- regulatory elements(6-9). However, it is not clear how transcription- factor binding and chromatin influence quantitative attributes of gene expression. Here we show that nucleosomes function largely to decouple the threshold of induction from dynamic range. With a series of variants of one promoter, we establish that the affinity of exposed binding sites is a primary determinant of the level of physiological stimulus necessary for substantial gene activation, and sites located within nucleosomal regions serve to scale expression once chromatin is remodelled. Furthermore, we find that the S. cerevisiae phosphate response ( PHO) pathway exploits these promoter designs to tailor gene expression to different environmental phosphate levels. Our results suggest that the interplay of chromatin and binding- site affinity provides a mechanism for fine-tuning responses to the same cellular state. Moreover, these findings may be a starting point for more detailed models of eukaryotic transcriptional control.
C1 [Lam, Felix H.; Steger, David J.; O'Shea, Erin K.] Harvard Univ, Fac Arts & Sci, Ctr Syst Biol, Dept Mol & Cellular Biol,Howard Hughes Med Inst, Cambridge, MA 02138 USA.
   [Lam, Felix H.; Steger, David J.; O'Shea, Erin K.] Harvard Univ, Fac Arts & Sci, Ctr Syst Biol, Dept Chem & Chem Biol,Howard Hughes Med Inst, Cambridge, MA 02138 USA.
   [Lam, Felix H.] Univ Calif San Francisco, Grad Grp Biophys, San Francisco, CA 94158 USA.
C3 Howard Hughes Medical Institute; Harvard University; Howard Hughes Medical Institute; Harvard University; University of California System; University of California San Francisco
RP O'Shea, EK (corresponding author), Harvard Univ, Fac Arts & Sci, Ctr Syst Biol, Dept Mol & Cellular Biol,Howard Hughes Med Inst, 7 Divin Ave,Bauer 307, Cambridge, MA 02138 USA.
EM erin_oshea@harvard.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIGMS NIH HHS [R01 GM051377] Funding Source: Medline
NR 34
TC 207
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 8
PY 2008
VL 453
IS 7192
BP 246
EP U16
DI 10.1038/nature06867
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400045
PM 18418379
DA 2026-03-09
ER

PT J
AU Verpy, E
   Weil, D
   Leibovici, M
   Goodyear, RJ
   Hamard, G
   Houdon, C
   Lefèvre, GM
   Hardelin, JP
   Richardson, GP
   Avan, P
   Petit, C
AF Verpy, Elisabeth
   Weil, Dominique
   Leibovici, Michel
   Goodyear, Richard J.
   Hamard, Ghislaine
   Houdon, Carine
   Lefevre, Gaelle M.
   Hardelin, Jean-Pierre
   Richardson, Guy P.
   Avan, Paul
   Petit, Christine
TI Stereocilin-deficient mice reveal the origin of cochlear waveform distortions
SO NATURE
LA English
DT Article
ID outer hair-cells; tectorial membrane; chinchilla cochlea; basilar-membrane; tuning curves; mechanics; responses; links; mutations; emissions
AB Although the cochlea is an amplifier and a remarkably sensitive and finely tuned detector of sounds, it also produces conspicuous mechanical and electrical waveform distortions(1). These distortions reflect nonlinear mechanical interactions within the cochlea. By allowing one tone to suppress another ( masking effect), they contribute to speech intelligibility(2). Tones can also combine to produce sounds with frequencies not present in the acoustic stimulus(3). These sounds compose the otoacoustic emissions that are extensively used to screen hearing in newborns. Because both cochlear amplification and distortion originate from the outer hair cells - one of the two types of sensory receptor cells - it has been speculated that they stem from a common mechanism. Here we show that the nonlinearity underlying cochlear waveform distortions relies on the presence of stereocilin, a protein defective in a recessive form of human deafness(4). Stereocilin was detected in association with horizontal top connectors(5-7), lateral links that join adjacent stereocilia within the outer hair cell's hair bundle. These links were absent in stereocilin- null mutant mice, which became progressively deaf. At the onset of hearing, however, their cochlear sensitivity and frequency tuning were almost normal, although masking was much reduced and both acoustic and electrical waveform distortions were completely lacking. From this unique functional situation, we conclude that the main source of cochlear waveform distortions is a deflection- dependent hair bundle stiffness resulting from constraints imposed by the horizontal top connectors, and not from the intrinsic nonlinear behaviour of the mechanoelectrical transducer channel.
C1 [Verpy, Elisabeth; Weil, Dominique; Leibovici, Michel; Houdon, Carine; Lefevre, Gaelle M.; Hardelin, Jean-Pierre; Petit, Christine] Inst Pasteur, Unite Genet & Physiol Audit, F-75015 Paris, France.
   [Verpy, Elisabeth; Weil, Dominique; Leibovici, Michel; Houdon, Carine; Lefevre, Gaelle M.; Hardelin, Jean-Pierre; Petit, Christine] INSERM, UMRS 587, F-75015 Paris, France.
   [Verpy, Elisabeth; Weil, Dominique; Leibovici, Michel; Houdon, Carine; Lefevre, Gaelle M.; Hardelin, Jean-Pierre; Petit, Christine] Coll France, F-75015 Paris, France.
   [Verpy, Elisabeth; Weil, Dominique; Leibovici, Michel; Houdon, Carine; Lefevre, Gaelle M.; Hardelin, Jean-Pierre; Petit, Christine] Univ Paris 06, F-75015 Paris, France.
   [Goodyear, Richard J.; Richardson, Guy P.] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England.
   [Hamard, Ghislaine] Inst Cochin Genet Mol, F-75014 Paris, France.
   [Avan, Paul] Univ Auvergne, Lab Biophys Sensorielle, F-63001 Clermont Ferrand, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Bordeaux; Universite PSL; College de France; Sorbonne Universite; University of Sussex; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Clermont Auvergne (UCA)
RP Petit, C (corresponding author), Inst Pasteur, Unite Genet & Physiol Audit, F-75015 Paris, France.
EM everpy@pasteur.fr; cpetit@pasteur.fr
FU European Commission FP6 Integrated Project EuroHear,; Fondation Raymonde et Guy Strittmatter; Region Ile-de-France (Programme Sesame); Wellcome Trust
NR 34
TC 117
Z9 137
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 13
PY 2008
VL 456
IS 7219
BP 255
EP U56
DI 10.1038/nature07380
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300043
PM 18849963
DA 2026-03-09
ER

PT J
AU Castelnovo, C
   Moessner, R
   Sondhi, SL
AF Castelnovo, C.
   Moessner, R.
   Sondhi, S. L.
TI Magnetic monopoles in spin ice
SO NATURE
LA English
DT Article
ID pyrochlore; dy2ti2o7; systems; state
AB Electrically charged particles, such as the electron, are ubiquitous. In contrast, no elementary particles with a net magnetic charge have ever been observed, despite intensive and prolonged searches ( see ref. 1 for example). We pursue an alternative strategy, namely that of realizing them not as elementary but rather as emergent particles - that is, as manifestations of the correlations present in a strongly interacting many- body system. The most prominent examples of emergent quasiparticles are the ones with fractional electric charge e/3 in quantum Hall physics(2). Here we propose that magnetic monopoles emerge in a class of exotic magnets known collectively as spin ice(3-5): the dipole moment of the underlying electronic degrees of freedom fractionalises into monopoles. This would account for a mysterious phase transition observed experimentally in spin ice in a magnetic field(6,7), which is a liquid - gas transition of the magnetic monopoles. These monopoles can also be detected by other means, for example, in an experiment modelled after the Stanford magnetic monopole search(8).
C1 [Castelnovo, C.; Moessner, R.] Univ Oxford, Rudolf Peierls Ctr Theoret Phys, Oxford OX1 3NP, England.
   [Moessner, R.] Max Planck Inst Phys Komplexer Syst, D-01187 Dresden, Germany.
   [Sondhi, S. L.] Princeton Univ, PCTP, Princeton, NJ 08544 USA.
   [Sondhi, S. L.] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
C3 University of Oxford; Max Planck Society; Princeton University; Princeton University
RP Castelnovo, C (corresponding author), Univ Oxford, Rudolf Peierls Ctr Theoret Phys, S Parks Rd, Oxford OX1 3NP, England.
EM castel@physics.ox.ac.uk
NR 25
TC 1243
Z9 1339
U1 6
U2 345
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 42
EP 45
DI 10.1038/nature06433
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300028
PM 18172493
DA 2026-03-09
ER

PT J
AU Scott, C
   Lyons, TW
   Bekker, A
   Shen, Y
   Poulton, SW
   Chu, X
   Anbar, AD
AF Scott, C.
   Lyons, T. W.
   Bekker, A.
   Shen, Y.
   Poulton, S. W.
   Chu, X.
   Anbar, A. D.
TI Tracing the stepwise oxygenation of the Proterozoic ocean
SO NATURE
LA English
DT Article
ID sulfur; rise; iron; molybdenum; evolution; anoxia; constraints; transition; chemistry; oxidation
AB Biogeochemical signatures preserved in ancient sedimentary rocks provide clues to the nature and timing of the oxygenation of the Earth's atmosphere. Geochemical data(1-6) suggest that oxygenation proceeded in two broad steps near the beginning and end of the Proterozoic eon ( 2,500 to 542 million years ago). The oxidation state of the Proterozoic ocean between these two steps and the timing of deep- ocean oxygenation have important implications for the evolutionary course of life on Earth but remain poorly known. Here we present a new perspective on ocean oxygenation based on the authigenic accumulation of the redox- sensitive transition element molybdenum in sulphidic black shales. Accumulation of authigenic molybdenum from sea water is already seen in shales by 2,650 Myr ago; however, the small magnitudes of these enrichments reflect weak or transient(7) sources of dissolved molybdenum before about 2,200 Myr ago, consistent with minimal oxidative weathering of the continents. Enrichments indicative of persistent and vigorous oxidative weathering appear in shales deposited at roughly 2,150 Myr ago, more than 200 million years after the initial rise in atmospheric oxygen(1,2). Subsequent expansion of sulphidic conditions after about 1,800 Myr ago ( refs 8, 9) maintained a mid- Proterozoic molybdenum reservoir below 20 per cent of the modern inventory, which in turn may have acted as a nutrient feedback limiting the spatiotemporal distribution of euxinic ( sulphidic) bottom waters and perhaps the evolutionary and ecological expansion of eukaryotic organisms(10). By 551 Myr ago, molybdenum contents reflect a greatly expanded oceanic reservoir due to oxygenation of the deep ocean and corresponding decrease in sulphidic conditions in the sediments and water column.
C1 [Scott, C.; Lyons, T. W.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Bekker, A.] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Shen, Y.] Univ Quebec, Dept Sci Terre & Atmosphere, Montreal, PQ H3C 3P8, Canada.
   [Poulton, S. W.] Univ Newcastle, Sch Civil Engn & Geosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Chu, X.] Chinese Acad Sci, Key Lab Mineral Resources, Inst Geol & Geophys, Beijing 100029, Peoples R China.
   [Anbar, A. D.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Anbar, A. D.] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
C3 University of California System; University of California Riverside; Carnegie Institution for Science; University of Quebec; University of Quebec Montreal; Newcastle University - UK; Chinese Academy of Sciences; Institute of Geology & Geophysics, CAS; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe
RP Scott, C (corresponding author), Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
EM cscot002@ucr.edu
FU NERC [NE/C518465/2] Funding Source: UKRI; Natural Environment Research Council [NE/C518465/2] Funding Source: researchfish
NR 32
TC 881
Z9 1052
U1 6
U2 327
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 456
EP U5
DI 10.1038/nature06811
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300028
PM 18368114
DA 2026-03-09
ER

PT J
AU Nagamune, K
   Hicks, LM
   Fux, B
   Brossier, F
   Chini, EN
   Sibley, LD
AF Nagamune, Kisaburo
   Hicks, Leslie M.
   Fux, Blima
   Brossier, Fabien
   Chini, Eduardo N.
   Sibley, L. David
TI Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii
SO NATURE
LA English
DT Article
ID cyclic adp-ribose; microneme secretion; biosynthesis; pathway; accumulation; reveals; strains
AB Calcium controls a number of critical events, including motility, secretion, cell invasion and egress by apicomplexan parasites(1). Compared to animal(2) and plant cells(3), the molecular mechanisms that govern calcium signalling in parasites are poorly understood. Here we show that the production of the phytohormone abscisic acid ( ABA) controls calcium signalling within the apicomplexan parasite Toxoplasma gondii, an opportunistic human pathogen. In plants, ABA controls a number of important events, including environmental stress responses, embryo development and seed dormancy(4,5). ABA induces production of the second- messenger cyclic ADP ribose ( cADPR), which controls release of intracellular calcium stores in plants(6). cADPR also controls intracellular calcium release in the protozoan parasite T. gondii(7,8); however, previous studies have not revealed the molecular basis of this pathway(9). We found that addition of exogenous ABA induced formation of cADPR in T. gondii, stimulated calcium- dependent protein secretion, and induced parasite egress from the infected host cell in a density- dependent manner. Production of endogenous ABA within the parasite was confirmed by purification ( using high- performance liquid chromatography) and analysis ( by gas chromatography- mass spectrometry). Selective disruption of ABA synthesis by the inhibitor fluridone delayed egress and induced development of the slow- growing, dormant cyst stage of the parasite. Thus, ABA- mediated calcium signalling controls the decision between lytic and chronic stage growth, a developmental switch that is central in pathogenesis and transmission. The pathway for ABA production was probably acquired with an algal endosymbiont that was retained as a non- photosynthetic plastid known as the apicoplast. The plant- like nature of this pathway may be exploited therapeutically, as shown by the ability of a specific inhibitor of ABA synthesis to prevent toxoplasmosis in the mouse model.
C1 [Nagamune, Kisaburo; Fux, Blima; Brossier, Fabien; Sibley, L. David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Hicks, Leslie M.] Donald Danforth Plant Sci Ctr, St Louis, MO 63132 USA.
   [Chini, Eduardo N.] Mayo Clin & Mayo Fdn, Dept Anesthesiol, Rochester, MN 55905 USA.
C3 Washington University (WUSTL); Donald Danforth Plant Science Center; Mayo Clinic
RP Sibley, LD (corresponding author), Washington Univ, Sch Med, Dept Mol Microbiol, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM sibley@wustl.edu
FU NIAID NIH HHS [R21 AI067051, R01 AI034036] Funding Source: Medline
NR 30
TC 179
Z9 223
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 JAN 10
PY 2008
VL 451
IS 7175
BP 207
EP U11
DI 10.1038/nature06478
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400046
PM 18185591
DA 2026-03-09
ER

PT J
AU Hung, RJ
   Mckay, JD
   Gaborieau, V
   Boffetta, P
   Hashibe, M
   Zaridze, D
   Mukeria, A
   Szeszenia-Dabrowska, N
   Lissowska, J
   Rudnai, P
   Fabianova, E
   Mates, D
   Bencko, V
   Foretova, L
   Janout, V
   Chen, C
   Goodman, G
   Field, JK
   Liloglou, T
   Xinarianos, G
   Cassidy, A
   McLaughlin, J
   Liu, G
   Narod, S
   Krokan, HE
   Skorpen, F
   Elvestad, MB
   Hveem, K
   Vatten, L
   Linseisen, J
   Clavel-Chapelon, F
   Vineis, P
   Bueno-De-Mesquita, HB
   Lund, E
   Martinez, C
   Bingham, S
   Rasmuson, T
   Hainaut, P
   Riboli, E
   Ahrens, W
   Benhamou, S
   Lagiou, P
   Trichopoulos, D
   Holcátová, I
   Merletti, F
   Kjaerheim, K
   Agudo, A
   Macfarlane, G
   Talamini, R
   Simonato, L
   Lowry, R
   Conway, DI
   Znaor, A
   Healy, C
   Zelenika, D
   Boland, A
   Delepine, M
   Foglio, M
   Lechner, D
   Matsuda, F
   Blanche, H
   Gut, I
   Heath, S
   Lathrop, M
   Brennan, P
AF Hung, Rayjean J.
   Mckay, James D.
   Gaborieau, Valerie
   Boffetta, Paolo
   Hashibe, Mia
   Zaridze, David
   Mukeria, Anush
   Szeszenia-Dabrowska, Neonilia
   Lissowska, Jolanta
   Rudnai, Peter
   Fabianova, Eleonora
   Mates, Dana
   Bencko, Vladimir
   Foretova, Lenka
   Janout, Vladimir
   Chen, Chu
   Goodman, Gary
   Field, John K.
   Liloglou, Triantafillos
   Xinarianos, George
   Cassidy, Adrian
   McLaughlin, John
   Liu, Geoffrey
   Narod, Steven
   Krokan, Hans E.
   Skorpen, Frank
   Elvestad, Maiken Bratt
   Hveem, Kristian
   Vatten, Lars
   Linseisen, Jakob
   Clavel-Chapelon, Francoise
   Vineis, Paolo
   Bueno-de-Mesquita, H. Bas
   Lund, Eiliv
   Martinez, Carmen
   Bingham, Sheila
   Rasmuson, Torgny
   Hainaut, Pierre
   Riboli, Elio
   Ahrens, Wolfgang
   Benhamou, Simone
   Lagiou, Pagona
   Trichopoulos, Dimitrios
   Holcatova, Ivana
   Merletti, Franco
   Kjaerheim, Kristina
   Agudo, Antonio
   Macfarlane, Gary
   Talamini, Renato
   Simonato, Lorenzo
   Lowry, Ray
   Conway, David I.
   Znaor, Ariana
   Healy, Claire
   Zelenika, Diana
   Boland, Anne
   Delepine, Marc
   Foglio, Mario
   Lechner, Doris
   Matsuda, Fumihiko
   Blanche, Helene
   Gut, Ivo
   Heath, Simon
   Lathrop, Mark
   Brennan, Paul
TI A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
SO NATURE
LA English
DT Article
ID fagerstrom tolerance questionnaire; genome-wide association; haplotype map; dependence; expression; smokers; cells; snps
AB Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually(1). To identify genetic factors that modify disease risk, we conducted a genome- wide association study by analysing 317,139 single- nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer ( P= 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls ( P = 5 x 10(-20) overall), and it was found to account for 14%( attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits ( CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines(2,3), and they bind to N'- nitrosonornicotine and potential lung carcinogens(4). A non- synonymous variant of CHRNA5 that induces an amino acid substitution ( D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets(5).
C1 [Hung, Rayjean J.; Mckay, James D.; Gaborieau, Valerie; Boffetta, Paolo; Hashibe, Mia; Hainaut, Pierre; Brennan, Paul] IARC, F-69008 Lyon, France.
   [Hung, Rayjean J.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
   [Zaridze, David; Mukeria, Anush] Canc Res Ctr, Inst Carcinogenesis, Moscow 115478, Russia.
   [Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Dept Epidemiol, PL-90950 Lodz, Poland.
   [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, PL-02781 Warsaw, Poland.
   [Rudnai, Peter] Natl Inst Environm Hlth, H-1097 Budapest, Hungary.
   [Fabianova, Eleonora] Specialized Inst Hyg & Epidemiol, Banska Bystrica 97556, Slovakia.
   [Mates, Dana] Inst Publ Hlth, Bucharest 050463, Romania.
   [Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague 12800 2, Czech Republic.
   [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic.
   [Janout, Vladimir] Palacky Univ, Olomouc 77515, Czech Republic.
   [Chen, Chu; Goodman, Gary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Field, John K.; Liloglou, Triantafillos; Xinarianos, George; Cassidy, Adrian] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool L3 9TA, Merseyside, England.
   [McLaughlin, John] Canc Care Ontario, Toronto, ON M5G 2L7, Canada.
   [McLaughlin, John] Samuel Lunenfeld Res Inst, Toronto, ON M5G 2L7, Canada.
   [Liu, Geoffrey] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
   [Narod, Steven] Womens Coll Res Inst, Toronto, ON M5G 1N8, Canada.
   [Krokan, Hans E.; Skorpen, Frank; Elvestad, Maiken Bratt; Hveem, Kristian; Vatten, Lars] Norwegian Univ Sci & Technol, N-7489 Trondheim, Norway.
   [Linseisen, Jakob] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
   [Clavel-Chapelon, Francoise] Inst Gustave Roussy, INSERM, ER120, F-94805 Villejuif, France.
   [Vineis, Paolo; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England.
   [Vineis, Paolo] ISI, I-10133 Turin, Italy.
   [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, Ctr Nutr & Hlth, NL-3710 BA Bilthoven, Netherlands.
   [Lund, Eiliv] Univ Tromso, Inst Community Med, N-9037 Tromso, Norway.
   [Martinez, Carmen] Andalusian Sch Publ Hlth & Ciber Epidemiol & Salu, Granada 18011, Spain.
   [Bingham, Sheila] Univ Cambridge, MRC Ctr Nutr & Canc, Dept Publ Hlth & Primary Care, Cambridge CB2 0XY, England.
   [Bingham, Sheila] MRC Dunn Human Nutr Unit, Cambridge CB2 0XY, England.
   [Rasmuson, Torgny] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden.
   [Ahrens, Wolfgang] Bremen Inst Prevent Res & Social Med, D-28359 Bremen, Germany.
   [Benhamou, Simone] Fdn Jean Dausset CEPH, INSERM, U794, F-75010 Paris, France.
   [Benhamou, Simone] Inst Gustave Roussy, CNRS, FRE2939, F-94805 Villejuif, France.
   [Lagiou, Pagona; Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens 11527, Greece.
   [Lagiou, Pagona; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Holcatova, Ivana] Inst Hyg & Epidemiol, Prague 12800 2, Czech Republic.
   [Merletti, Franco] Univ Turin, I-10126 Turin, Italy.
   [Kjaerheim, Kristina] Canc Registry Norway, N-0310 Oslo, Norway.
   [Agudo, Antonio] Inst Catala Oncol, Barcelona 08907, Spain.
   [Macfarlane, Gary] Univ Aberdeen, Sch Med, Aberdeen AB25 2ZD, Scotland.
   [Talamini, Renato] Aviano Canc Ctr, I-33081 Aviano, Italy.
   [Simonato, Lorenzo] Univ Padua, Dept Environm Med & Publ Hlth, I-35131 Padua, Italy.
   [Lowry, Ray] Univ Newcastle, Sch Dent, Newcastle Upon Tyne NE2 4BW, Tyne & Wear, England.
   [Conway, David I.] Univ Glasgow, Sch Dent, Glasgow G2 3JZ, Lanark, Scotland.
   [Znaor, Ariana] Natl Inst Publ Hlth, Croatian Natl Canc Registry, Zagreb 10000, Croatia.
   [Healy, Claire] Univ Dublin Trinity Coll, Sch Dent Sci, Dublin 2, Ireland.
   [Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Matsuda, Fumihiko; Gut, Ivo; Lathrop, Mark] Commiss Energie Atom, Ctr Natl Genotype, Inst Genom, F-91000 Evry, France.
   [Blanche, Helene; Heath, Simon; Lathrop, Mark] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France.
C3 World Health Organization; International Agency for Research on Cancer (IARC); University of California System; University of California Berkeley; Nofer Institute of Occupational Medicine; Maria Sklodowska-Curie National Research Institute of Oncology; Charles University Prague; Masaryk Memorial Cancer Institute; Palacky University Olomouc; Fred Hutchinson Cancer Center; University of Liverpool; Cancer Care Ontario; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; Womens College Hospital; Norwegian University of Science & Technology (NTNU); Helmholtz Association; German Cancer Research Center (DKFZ); Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Gustave Roussy; Imperial College London; Netherlands National Institute for Public Health & the Environment; UiT The Arctic University of Tromso; Escuela Andaluza de Salud Publica; CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; University of Cambridge; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); MRC Human Nutrition Research; Umea University; Leibniz Association; Leibniz Institute for Prevention Research & Epidemiology (BIPS); Foundation Jean Dausset-CEPH; Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Gustave Roussy; Centre National de la Recherche Scientifique (CNRS); National & Kapodistrian University of Athens; Harvard University; Harvard T.H. Chan School of Public Health; University of Turin; University of Oslo; Institut Catala d'Oncologia; University of Aberdeen; University of Padua; Newcastle University - UK; University of Glasgow; Trinity College Dublin; Universite Paris Saclay; CEA; Foundation Jean Dausset-CEPH
RP Brennan, P (corresponding author), IARC, F-69008 Lyon, France.
EM brennan@iarc.fr
FU Medical Research Council [G9900432] Funding Source: Medline; NCI NIH HHS [R01 CA092039] Funding Source: Medline; MRC [G9900432] Funding Source: UKRI; Medical Research Council [G9900432] Funding Source: researchfish
NR 23
TC 1025
Z9 1158
U1 1
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 633
EP 637
DI 10.1038/nature06885
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200046
PM 18385738
DA 2026-03-09
ER

PT J
AU Beninca, E
   Huisman, J
   Heerkloss, R
   Johnk, KD
   Branco, P
   Van Nes, EH
   Scheffer, M
   Ellner, SP
AF Beninca, Elisa
   Huisman, Jef
   Heerkloss, Reinhard
   Johnk, Klaus D.
   Branco, Pedro
   Van Nes, Egbert H.
   Scheffer, Marten
   Ellner, Stephen P.
TI Chaos in a long-term experiment with a plankton community
SO NATURE
LA English
DT Article
ID cycles; series; oscillations; models
AB Mathematical models predict that species interactions such as competition and predation can generate chaos(1-8). However, experimental demonstrations of chaos in ecology are scarce, and have been limited to simple laboratory systems with a short duration and artificial species combinations(9-12). Here, we present the first experimental demonstration of chaos in a long- term experiment with a complex food web. Our food web was isolated from the Baltic Sea, and consisted of bacteria, several phytoplankton species, herbivorous and predatory zooplankton species, and detritivores. The food web was cultured in a laboratory mesocosm, and sampled twice a week for more than 2,300 days. Despite constant external conditions, the species abundances showed striking fluctuations over several orders of magnitude. These fluctuations displayed a variety of different periodicities, which could be attributed to different species interactions in the food web. The population dynamics were characterized by positive Lyapunov exponents of similar magnitude for each species. Predictability was limited to a time horizon of 15 - 30 days, only slightly longer than the local weather forecast. Hence, our results demonstrate that species interactions in food webs can generate chaos. This implies that stability is not required for the persistence of complex food webs, and that the long- term prediction of species abundances can be fundamentally impossible.
C1 [Beninca, Elisa; Huisman, Jef; Johnk, Klaus D.; Branco, Pedro] Univ Amsterdam, Inst Biodivers & Ecosyst Dynam, NL-1018 WS Amsterdam, Netherlands.
   [Beninca, Elisa; Van Nes, Egbert H.; Scheffer, Marten] Univ Wageningen & Res Ctr, Aquat Ecol & Water Qual Management, Wageningen, Netherlands.
   [Heerkloss, Reinhard] Univ Rostock, Inst Biosci, Rostock, Germany.
   [Ellner, Stephen P.] Cornell Univ, Ithaca, NY 14853 USA.
C3 University of Amsterdam; Wageningen University & Research; University of Rostock; Cornell University
RP Huisman, J (corresponding author), Univ Amsterdam, Inst Biodivers & Ecosyst Dynam, Nieuwe Achtergracht 127, NL-1018 WS Amsterdam, Netherlands.
EM jef.huisman@science.uva.nl
NR 30
TC 324
Z9 374
U1 9
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 FEB 14
PY 2008
VL 451
IS 7180
BP 822
EP U7
DI 10.1038/nature06512
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400041
PM 18273017
DA 2026-03-09
ER

PT J
AU Camara, CG
   Escobar, JV
   Hird, JR
   Putterman, SJ
AF Camara, Carlos G.
   Escobar, Juan V.
   Hird, Jonathan R.
   Putterman, Seth J.
TI Correlation between nanosecond X-ray flashes and stick-slip friction in peeling tape
SO NATURE
LA English
DT Article
ID electrification; crystal
AB Relative motion between two contacting surfaces can produce visible light, called triboluminescence(1). This concentration of diffuse mechanical energy into electromagnetic radiation has previously been observed to extend even to X-ray energies(2). Here we report that peeling common adhesive tape in a moderate vacuum produces radio and visible emission(3,4), along with nanosecond, 100-mW X- ray pulses that are correlated with stick - slip peeling events. For the observed 15- keV peak in X- ray energy, various models(5,6) give a competing picture of the discharge process, with the length of the gap between the separating faces of the tape being 30 or 300 mm at the moment of emission. The intensity of X- ray triboluminescence allowed us to use it as a source for X- ray imaging. The limits on energies and flash widths that can be achieved are beyond current theories of tribology.
C1 [Camara, Carlos G.; Escobar, Juan V.; Hird, Jonathan R.; Putterman, Seth J.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles
RP Camara, CG (corresponding author), Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
EM camara@physics.ucla.edu; escobar@physics.ucla.edu
FU Office of Naval Research and the Defense Advanced Research Projects Agency (Microsystems Technologies Office and Defense Sciences Office); Fulbright-Garcia Robles Scholarship Program; UC-MEXUS-CONACYT
NR 33
TC 203
Z9 233
U1 10
U2 214
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1089
EP U7
DI 10.1038/nature07378
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600040
DA 2026-03-09
ER

PT J
AU Hochbaum, AI
   Chen, RK
   Delgado, RD
   Liang, WJ
   Garnett, EC
   Najarian, M
   Majumdar, A
   Yang, PD
AF Hochbaum, Allon I.
   Chen, Renkun
   Delgado, Raul Diaz
   Liang, Wenjie
   Garnett, Erik C.
   Najarian, Mark
   Majumdar, Arun
   Yang, Peidong
TI Enhanced thermoelectric performance of rough silicon nanowires
SO NATURE
LA English
DT Article
ID thermal-conductivity; arrays; nanostructures; scattering; devices; growth; layers; merit; si
AB Approximately 90 per cent of the world's power is generated by heat engines that use fossil fuel combustion as a heat source and typically operate at 30 - 40 per cent efficiency, such that roughly 15 terawatts of heat is lost to the environment. Thermoelectric modules could potentially convert part of this low- grade waste heat to electricity. Their efficiency depends on the thermoelectric figure of merit ZT of their material components, which is a function of the Seebeck coefficient, electrical resistivity, thermal conductivity and absolute temperature. Over the past five decades it has been challenging to increase ZT > 1, since the parameters of ZT are generally interdependent(1). While nanostructured thermoelectric materials can increase ZT > 1 ( refs 2 - 4), the materials ( Bi, Te, Pb, Sb, and Ag) and processes used are not often easy to scale to practically useful dimensions. Here we report the electrochemical synthesis of large- area, wafer- scale arrays of rough Si nanowires that are 20-300 nm in diameter. These nanowires have Seebeck coefficient and electrical resistivity values that are the same as doped bulk Si, but those with diameters of about 50 nm exhibit 100- fold reduction in thermal conductivity, yielding ZT = 0.6 at room temperature. For such nanowires, the lattice contribution to thermal conductivity approaches the amorphous limit for Si, which cannot be explained by current theories. Although bulk Si is a poor thermoelectric material, by greatly reducing thermal conductivity without much affecting the Seebeck coefficient and electrical resistivity, Si nanowire arrays show promise as high- performance, scalable thermoelectric materials.
C1 [Chen, Renkun; Majumdar, Arun] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA.
   [Hochbaum, Allon I.; Delgado, Raul Diaz; Liang, Wenjie; Garnett, Erik C.; Yang, Peidong] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Najarian, Mark; Majumdar, Arun; Yang, Peidong] Univ Calif Berkeley, Dept Mat Sci & Engn, Berkeley, CA 94720 USA.
   [Majumdar, Arun; Yang, Peidong] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Majumdar, A (corresponding author), Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA.
EM majumdar@me.berkeley.edu; p_yang@berkeley.edu
NR 28
TC 3694
Z9 4210
U1 17
U2 2530
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 163
EP U5
DI 10.1038/nature06381
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400036
PM 18185582
DA 2026-03-09
ER

PT J
AU Bshary, R
   Grutter, AS
   Willener, AST
   Leimar, O
AF Bshary, Redouan
   Grutter, Alexandra S.
   Willener, Astrid S. T.
   Leimar, Olof
TI Pairs of cooperating cleaner fish provide better service quality than singletons
SO NATURE
LA English
DT Article
ID tit-for-tat; partner control; labroides dimidiatus; animal society; reef fish; mutualism; evolution; punishment; ecology; rates
AB Service providers may vary service quality depending on whether they work alone or provide the service simultaneously with a partner. The latter case resembles a prisoner's dilemma(1-4), in which one provider may try to reap the benefits of the interaction without providing the service. Here we present a game- theory model based on the marginal value theorem(5), which predicts that as long as the client determines the duration, and the providers cooperate towards mutual gain, service quality will increase in the pair situation. This prediction is consistent with field observations and with an experiment on cleaning mutualism, in which stable male - female pairs of the cleaner wrasse Labroides dimidiatus repeatedly inspect client fish jointly. Cleaners cooperate by eating ectoparasites(6) off clients but actually prefer to cheat and eat client mucus(7). Because clients often leave in response to such cheating, the benefits of cheating can be gained by only one cleaner during a pair inspection. In both data sets, the increased service quality during pair inspection was mainly due to the smaller females behaving significantly more cooperatively than their larger male partners. In contrast, during solitary inspections, cleaning behaviour was very similar between the sexes. Our study highlights the importance of incorporating interactions between service providers to make more quantitative predictions about cooperation between species.
C1 [Bshary, Redouan; Willener, Astrid S. T.] Univ Neuchatel, Dept Zool, CH-2009 Neuchatel, Switzerland.
   [Grutter, Alexandra S.] Univ Queensland, Sch Integrat Biol, St Lucia, Qld 4072, Australia.
   [Leimar, Olof] Stockholm Univ, Dept Zool, SE-10691 Stockholm, Sweden.
C3 University of Neuchatel; University of Queensland; Stockholm University
RP Bshary, R (corresponding author), Univ Neuchatel, Dept Zool, Rue Emile Argand 11 Case Postale 158, CH-2009 Neuchatel, Switzerland.
EM redouan.bshary@unine.ch
FU Natural Environment Research Council; Swiss Science Foundation; Australian Research Council
NR 28
TC 103
Z9 115
U1 1
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 964
EP U46
DI 10.1038/nature07184
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300049
PM 18923522
DA 2026-03-09
ER

PT J
AU Cox, PM
   Harris, PP
   Huntingford, C
   Betts, RA
   Collins, M
   Jones, CD
   Jupp, TE
   Marengo, JA
   Nobre, CA
AF Cox, Peter M.
   Harris, Phil P.
   Huntingford, Chris
   Betts, Richard A.
   Collins, Matthew
   Jones, Chris D.
   Jupp, Tim E.
   Marengo, Jose A.
   Nobre, Carlos A.
TI Increasing risk of Amazonian drought due to decreasing aerosol pollution
SO NATURE
LA English
DT Article
ID sea-surface temperature; climate-change; tropical atlantic; rainy-season; rainfall; model; variability; basin; trends; future
AB The Amazon rainforest plays a crucial role in the climate system, helping to drive atmospheric circulations in the tropics by absorbing energy and recycling about half of the rainfall that falls on it. This region ( Amazonia) is also estimated to contain about one-tenth of the total carbon stored in land ecosystems, and to account for one-tenth of global, net primary productivity(1). The resilience of the forest to the combined pressures of deforestation and global warming is therefore of great concern(2), especially as some general circulation models ( GCMs) predict a severe drying of Amazonia in the twenty- first century(3-5). Here we analyse these climate projections with reference to the 2005 drought in western Amazonia, which was associated(6) with unusually warm North Atlantic sea surface temperatures ( SSTs). We show that reduction of dry-season ( July - October) rainfall in western Amazonia correlates well with an index of the north - south SST gradient across the equatorial Atlantic ( the 'Atlantic N - S gradient'). Our climate model is unusual among current GCMs in that it is able to reproduce this relationship and also the observed twentieth- century multidecadal variability in the Atlantic N - S gradient(7), provided that the effects of aerosols are included in the model(8). Simulations for the twenty- first century using the same model(3,8) show a strong tendency for the SST conditions associated with the 2005 drought to become much more common, owing to continuing reductions in reflective aerosol pollution in the Northern Hemisphere(9).
C1 [Cox, Peter M.; Jupp, Tim E.] Univ Exeter, Sch Engn Comp & Math, Exeter EX4 4QF, Devon, England.
   [Cox, Peter M.; Betts, Richard A.; Collins, Matthew; Jones, Chris D.] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [Harris, Phil P.; Huntingford, Chris] Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England.
   [Marengo, Jose A.; Nobre, Carlos A.] INPE, CPTEC, Brazilian Ctr Weather Forecasting & Climate Studi, Sao Paulo, Brazil.
C3 University of Exeter; Met Office - UK; Hadley Centre; UK Centre for Ecology & Hydrology (UKCEH); Instituto Nacional de Pesquisas Espaciais (INPE)
RP Cox, PM (corresponding author), Univ Exeter, Sch Engn Comp & Math, Exeter EX4 4QF, Devon, England.
EM p.m.cox@exeter.ac.uk
FU NERC [earth010002, earth010004] Funding Source: UKRI; Natural Environment Research Council [earth010004, earth010002] Funding Source: researchfish
NR 29
TC 296
Z9 326
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 MAY 8
PY 2008
VL 453
IS 7192
BP 212
EP U7
DI 10.1038/nature06960
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400037
PM 18464740
DA 2026-03-09
ER

PT J
AU Sanz, J
   Fayad, ZA
AF Sanz, Javier
   Fayad, Zahi A.
TI Imaging of atherosclerotic cardiovascular disease
SO NATURE
LA English
DT Article
ID coronary-artery-disease; cardiac magnetic-resonance; computed-tomography; in-vivo; plaque inflammation; vulnerable plaque; risk-assessment; contrast agent; working group; angiography
AB Atherosclerosis is characterized by thickening of the walls of the arteries, a process that occurs slowly and 'silently' over decades. This prolonged course of disease provides a window of opportunity for diagnosis before symptoms occur. But, until recently, only advanced atherosclerotic disease could be observed. Now, developments in imaging technology offer many enticing prospects, including detecting atherosclerosis early, grouping individuals by the probability that they will develop symptoms of atherosclerosis, assessing the results of treatment and improving the current understanding of the biology of atherosclerosis.
C1 [Sanz, Javier; Fayad, Zahi A.] Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA.
   [Sanz, Javier; Fayad, Zahi A.] Mt Sinai Sch Med, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY 10029 USA.
   [Fayad, Zahi A.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, Imaging Sci Labs, Dept Radiol, New York, NY 10029 USA.
   [Fayad, Zahi A.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, Imaging Sci Labs, Dept Med, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Fayad, ZA (corresponding author), Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM zahi.fayad@mssm.edu
NR 40
TC 458
Z9 523
U1 0
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 953
EP 957
DI 10.1038/nature06803
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100037
PM 18288186
DA 2026-03-09
ER

PT J
AU Westbrook, TF
   Hu, G
   Ang, XLL
   Mulligan, P
   Pavlova, NN
   Liang, A
   Leng, YM
   Maehr, R
   Shi, Y
   Harper, JW
   Elledge, SJ
AF Westbrook, Thomas F.
   Hu, Guang
   Ang, Xiaolu L.
   Mulligan, Peter
   Pavlova, Natalya N.
   Liang, Anthony
   Leng, Yumei
   Maehr, Rene
   Shi, Yang
   Harper, J. Wade
   Elledge, Stephen J.
TI SCFβ-TRCP controls oncogenic transformation and neural differentiation through REST degradation
SO NATURE
LA English
DT Article
ID restrictive silencer factor; ubiquitin-ligase complex; box protein beta-trcp1; embryonic stem-cells; f-box; in-vitro; expression; genes; transcription; precursors
AB The RE1- silencing transcription factor ( REST, also known as NRSF) is a master repressor of neuronal gene expression and neuronal programmes in non- neuronal lineages(1-3). Recently, REST was identified as a human tumour suppressor in epithelial tissues(4), suggesting that its regulation may have important physiological and pathological consequences. However, the pathways controlling REST have yet to be elucidated. Here we show that REST is regulated by ubiquitin- mediated proteolysis, and use an RNA interference ( RNAi) screen to identify a Skp1- Cul1- F- box protein complex containing the F- box protein beta- TRCP ( SCF beta-TRCP) as an E3 ubiquitin ligase responsible for REST degradation. beta- TRCP binds and ubiquitinates REST and controls its stability through a conserved phospho- degron. During neural differentiation, REST is degraded in a beta-TRCP- dependent manner. beta- TRCP is required for proper neural differentiation only in the presence of REST, indicating that beta- TRCP facilitates this process through degradation of REST. Conversely, failure to degrade REST attenuates differentiation. Furthermore, we find that beta-TRCP overexpression, which is common in human epithelial cancers, causes oncogenic transformation of human mammary epithelial cells and that this pathogenic function requires REST degradation. Thus, REST is a key target in beta- TRCP- driven transformation and the beta- TRCP - REST axis is a new regulatory pathway controlling neurogenesis.
C1 [Westbrook, Thomas F.; Hu, Guang; Pavlova, Natalya N.; Liang, Anthony; Leng, Yumei; Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA.
   [Ang, Xiaolu L.; Mulligan, Peter; Shi, Yang; Harper, J. Wade] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Maehr, Rene] Harvard Univ, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Howard Hughes Medical Institute
RP Elledge, SJ (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Harvard Partners Ctr Genet & Genom, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM wade_harper@hms.harvard.edu; selledge@genetics.med.harvard.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIA NIH HHS [R01 AG011085] Funding Source: Medline; NIGMS NIH HHS [R01 GM071004, R01 GM054137] Funding Source: Medline; NINDS NIH HHS [F31 NS054507] Funding Source: Medline; National Institute on Aging [R01AG011085] Funding Source: NIH RePORTER
NR 27
TC 267
Z9 314
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 370
EP U11
DI 10.1038/nature06780
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400051
PM 18354483
DA 2026-03-09
ER

PT J
AU Takeuchi, A
   Reyes, N
   Artigas, P
   Gadsby, DC
AF Takeuchi, Ayako
   Reyes, Nicolas
   Artigas, Pablo
   Gadsby, David C.
TI The ion pathway through the opened Na+,K+-ATPase pump
SO NATURE
LA English
DT Article
ID na,k-atpase alpha-subunit; transmembrane segment m1; calcium-pump; crystal-structure; k+-atpase; binding; cysteine; occlusion; mechanism; transport
AB P-type ATPases pump ions across membranes, generating steep electrochemical gradients that are essential for the function of all cells. Access to the ion-binding sites within the pumps alternates between the two sides of the membrane(1) to avoid the dissipation of the gradients that would occur during simultaneous access. In Na+,K+-ATPase pumps treated with the marine agent palytoxin, this strict alternation is disrupted and binding sites are sometimes simultaneously accessible from both sides of the membrane, transforming the pumps into ion channels (see, for example, refs 2, 3). Current recordings in these channels can monitor accessibility of introduced cysteine residues to water-soluble sulphydryl-specific reagents(4). We found previously(5) that Na+,K+ pump-channels open to the extracellular surface through a deep and wide vestibule that emanates from a narrower pathway between transmembrane helices 4 and 6 (TM4 and TM6). Here we report that cysteine scans from TM1 to TM6 reveal a single unbroken cation pathway that traverses palytoxin-bound Na+,K+ pump-channels from one side of the membrane to the other. This pathway comprises residues from TM1, TM2, TM4 and TM6, passes through ion-binding site II,and is probably conserved in structurally and evolutionarily related P-type pumps, such as sarcoplasmic- and endoplasmic-reticulum Ca2+-ATPases and H+,K+-ATPases.
C1 [Takeuchi, Ayako; Reyes, Nicolas; Artigas, Pablo; Gadsby, David C.] Rockefeller Univ, Lab Cardiac Membrane Physiol, New York, NY 10065 USA.
C3 Rockefeller University
RP Gadsby, DC (corresponding author), Rockefeller Univ, Lab Cardiac Membrane Physiol, New York, NY 10065 USA.
EM gadsby@rockefeller.edu
FU NIH; Vicente Trust
NR 30
TC 68
Z9 76
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 20
PY 2008
VL 456
IS 7220
BP 413
EP 416
DI 10.1038/nature07350
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600049
PM 18849964
DA 2026-03-09
ER

PT J
AU Kirkwood, TBL
AF Kirkwood, Thomas B. L.
TI A systematic look at an old problem
SO NATURE
LA English
DT Article
ID mitochondrial-dna deletions; substantia-nigra neurons; life-span; caenorhabditis-elegans; c-elegans; stress; disease; genes; age; restriction
C1 Univ Newcastle, Integrated Syst Biol Ageing & Nutr, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England.
C3 Newcastle University - UK
RP Kirkwood, TBL (corresponding author), Univ Newcastle, Integrated Syst Biol Ageing & Nutr, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England.
EM tom.kirkwood@ncl.ac.uk
FU Biotechnology and Biological Sciences Research Council [BB/C008200/1] Funding Source: Medline; Biotechnology and Biological Sciences Research Council [BB/C008200/1] Funding Source: researchfish
NR 30
TC 252
Z9 318
U1 0
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 644
EP 647
DI 10.1038/451644a
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500027
PM 18256658
DA 2026-03-09
ER

PT J
AU Park, JH
   Scheerer, P
   Hofmann, KP
   Choe, HW
   Ernst, OP
AF Park, Jung Hee
   Scheerer, Patrick
   Hofmann, Klaus Peter
   Choe, Hui-Woog
   Ernst, Oliver Peter
TI Crystal structure of the ligand-free G-protein-coupled receptor opsin
SO NATURE
LA English
DT Article
ID beta(2)-adrenergic receptor; transmembrane helices; metarhodopsin-iii; bovine rhodopsin; dark-adaptation; activation; binding; crystallography; intermediate; transducin
AB In the G- protein- coupled receptor ( GPCR) rhodopsin, the inactivating ligand 11- cis- retinal is bound in the seven- transmembrane helix ( TM) bundle and is cis/ trans isomerized by light to form active metarhodopsin II. With metarhodopsin II decay, all- trans- retinal is released, and opsin is reloaded with new 11- cis- retinal. Here we present the crystal structure of ligand- free native opsin from bovine retinal rod cells at 2.9 angstrorm (angstrom) resolution. Compared to rhodopsin, opsin shows prominent structural changes in the conserved E(D)RY and NPxxY(x)(5,6)F regions and in TM5 - TM7. At the cytoplasmic side, TM6 is tilted outwards by 6 - 7 angstrom, whereas the helix structure of TM5 is more elongated and close to TM6. These structural changes, some of which were attributed to an active GPCR state, reorganize the empty retinal- binding pocket to disclose two openings that may serve the entry and exit of retinal. The opsin structure sheds new light on ligand binding to GPCRs and on GPCR activation.
C1 [Park, Jung Hee; Scheerer, Patrick; Hofmann, Klaus Peter; Choe, Hui-Woog; Ernst, Oliver Peter] Charite Univ Med Berlin, Inst Med Phys & Biophys CC2, D-10117 Berlin, Germany.
   [Hofmann, Klaus Peter] Humboldt Univ, Zentrum Biophys & Bioinformat, D-10115 Berlin, Germany.
   [Choe, Hui-Woog] Chonbuk Natl Univ, Coll Nat Sci, Dept Chem, Chonju 561756, South Korea.
C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Humboldt University of Berlin; Jeonbuk National University
RP Ernst, OP (corresponding author), Charite Univ Med Berlin, Inst Med Phys & Biophys CC2, Charitepl 1, D-10117 Berlin, Germany.
EM klaus_peter.hofmann@charite.de; hwchoe@chonbuk.ac.kr; oliver.ernst@charite.de
NR 52
TC 788
Z9 917
U1 2
U2 103
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 183
EP U33
DI 10.1038/nature07063
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900036
PM 18563085
DA 2026-03-09
ER

PT J
AU Erez, N
   Gordon, G
   Nest, M
   Kurizki, G
AF Erez, Noam
   Gordon, Goren
   Nest, Mathias
   Kurizki, Gershon
TI Thermodynamic control by frequent quantum measurements
SO NATURE
LA English
DT Article
ID decay; work; bath
AB Heat flow between a large thermal `bath' and a smaller system brings them progressively closer to thermal equilibrium while increasing their entropy(1). Fluctuations involving a small fraction of a statistical ensemble of systems interacting with the bath result in deviations from this trend. In this respect, quantum and classical thermodynamics are in agreement(1-5). Here we predict a different trend in a purely quantum mechanical setting: disturbances of thermal equilibrium between two-level systems (TLSs) and a bath(6), caused by frequent, brief quantum non-demolition(7-10) measurements of the TLS energy states. By making the measurements increasingly frequent, we encounter first the anti-Zeno regime and then the Zeno regime (namely where the TLSs' relaxation respectively speeds up and slows down(11-15)). The corresponding entropy and temperature of both the system and the bath are then found to either decrease or increase depending only on the rate of observation, contrary to the standard thermodynamical rules that hold for memory-less ( Markov) baths(2,5). From a practical viewpoint, these anomalies may offer the possibility of very fast control of heat and entropy in quantum systems, allowing cooling and state purification over an interval much shorter than the time needed for thermal equilibration or for a feedback control loop.
C1 [Erez, Noam; Gordon, Goren; Kurizki, Gershon] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel.
   [Nest, Mathias] Univ Potsdam, D-14476 Potsdam, Germany.
C3 Weizmann Institute of Science; University of Potsdam
RP Kurizki, G (corresponding author), Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel.
EM gershon.kurizki@weizmann.ac.il
NR 24
TC 170
Z9 179
U1 1
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 10
PY 2008
VL 452
IS 7188
BP 724
EP 727
DI 10.1038/nature06873
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500039
PM 18401404
DA 2026-03-09
ER

PT J
AU Murase, K
   Hirano, Y
   Sun, TP
   Hakoshima, T
AF Murase, Kohji
   Hirano, Yoshinori
   Sun, Tai-ping
   Hakoshima, Toshio
TI Gibberellin-induced DELLA recognition by the gibberellin receptor GID1
SO NATURE
LA English
DT Article
ID box protein tir1; f-box; arabidopsis-thaliana; floral development; signaling pathway; seed-germination; gene encodes; expression; repressor; targets
AB Gibberellins control a range of growth and developmental processes in higher plants and have been widely used in the agricultural industry. By binding to a nuclear receptor, GIBBERELLIN INSENSITIVE DWARF1 (GID1), gibberellins regulate gene expression by promoting degradation of the transcriptional regulator DELLA proteins, including GIBBERELLIN INSENSITIVE ( GAI). The precise manner in which GID1 discriminates and becomes activated by bioactive gibberellins for specific binding to DELLA proteins remains unclear. Here we present the crystal structure of a ternary complex of Arabidopsis thaliana GID1A, a bioactive gibberellin and the amino- terminal DELLA domain of GAI. In this complex, GID1A occludes gibberellin in a deep binding pocket covered by its N- terminal helical switch region, which in turn interacts with the DELLA domain containing DELLA, VHYNP and LExLE motifs. Our results establish a structural model of a plant hormone receptor that is distinct from the mechanism of the hormone perception and effector recognition of the known auxin receptors.
C1 [Murase, Kohji; Hirano, Yoshinori; Hakoshima, Toshio] Nara Inst Sci & Technol, Struct Biol Lab, Nara 6300192, Japan.
   [Sun, Tai-ping] Duke Univ, Dept Biol, Durham, NC 27708 USA.
C3 Nara Institute of Science & Technology; Duke University
RP Hakoshima, T (corresponding author), Nara Inst Sci & Technol, Struct Biol Lab, 8916-5 Takayama, Nara 6300192, Japan.
EM hakosima@bs.naist.jp
FU Mitsubishi Foundation, Japan; Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; National Science Foundation of the United States [IBN-0348814]; Young Scientists from the Japan Society for the Promotion of Science; Global COE Program in NAIST; MEXT of Japan.
NR 49
TC 615
Z9 766
U1 9
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 NOV 27
PY 2008
VL 456
IS 7221
BP 459
EP U15
DI 10.1038/nature07519
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500029
PM 19037309
DA 2026-03-09
ER

PT J
AU Niessen, F
   Schaffner, F
   Furlan-Freguia, C
   Pawlinski, R
   Bhattacharjee, G
   Chun, J
   Derian, CK
   Andrade-Gordon, P
   Rosen, H
   Ruf, W
AF Niessen, Frank
   Schaffner, Florence
   Furlan-Freguia, Christian
   Pawlinski, Rafal
   Bhattacharjee, Gourab
   Chun, Jerold
   Derian, Claudia K.
   Andrade-Gordon, Patricia
   Rosen, Hugh
   Ruf, Wolfram
TI Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation
SO NATURE
LA English
DT Article
ID protease-activated receptors; tissue factor; sphingosine 1-phosphate; polymicrobial sepsis; p2x(7) receptor; mice deficient; lymph-nodes; mouse model; responses; endotoxemia
AB Defining critical points of modulation across heterogeneous clinical syndromes may provide insight into new therapeutic approaches. Coagulation initiated by the cytokine- receptor family member known as tissue factor is a hallmark of systemic inflammatory response syndromes in bacterial sepsis and viral haemorrhagic fevers(1,2), and anticoagulants can be effective in severe sepsis with disseminated intravascular coagulation(3). The precise mechanism coupling coagulation and inflammation remains unresolved(4-7). Here we show that protease- activated receptor 1 ( PAR1) signalling sustains a lethal inflammatory response that can be interrupted by inhibition of either thrombin or PAR1 signalling. The sphingosine 1- phosphate ( S1P) axis is a downstream component of PAR1 signalling, and by combining chemical and genetic probes for S1P receptor 3 ( S1P3) we show a critical role for dendritic cell PAR1 - S1P3 cross- talk in regulating amplification of inflammation in sepsis syndrome. Conversely, dendritic cells sustain escalated systemic coagulation and are the primary hub at which coagulation and inflammation intersect within the lymphatic compartment. Loss of dendritic cell PAR1 - S1P3 signalling sequesters dendritic cells and inflammation into draining lymph nodes, and attenuates dissemination of interleukin-1 beta to the lungs. Thus, activation of dendritic cells by coagulation in the lymphatics emerges as a previously unknown mechanism that promotes systemic inflammation and lethality in decompensated innate immune responses.
C1 [Niessen, Frank; Schaffner, Florence; Furlan-Freguia, Christian; Pawlinski, Rafal; Bhattacharjee, Gourab; Rosen, Hugh; Ruf, Wolfram] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA.
   [Chun, Jerold] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Rosen, Hugh] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
   [Derian, Claudia K.; Andrade-Gordon, Patricia] Johnson & Johnson PRD, Spring House, PA 19477 USA.
C3 Scripps Research Institute; Scripps Research Institute; Scripps Research Institute; Johnson & Johnson; Johnson & Johnson USA
RP Ruf, W (corresponding author), Scripps Res Inst, Dept Immunol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM ruf@scripps.edu
NR 30
TC 246
Z9 289
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 654
EP 658
DI 10.1038/nature06663
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200051
PM 18305483
DA 2026-03-09
ER

PT J
AU Kennedy, M
   Mrofka, D
   von der Borch, C
AF Kennedy, Martin
   Mrofka, David
   von der Borch, Chris
TI Snowball Earth termination by destabilization of equatorial permafrost methane clathrate
SO NATURE
LA English
DT Article
ID isotopic evidence; hydrate; carbonates; glaciation; stability; basin; end
AB The start of the Ediacaran period is defined by one of the most severe climate change events recorded in Earth history - the recovery from the Marinoan 'snowball' ice age, similar to 635 Myr ago ( ref. 1). Marinoan glacial- marine deposits occur at equatorial palaeolatitudes(2), and are sharply overlain by a thin interval of carbonate that preserves marine carbon and sulphur isotopic excursions of about 25 and 115 parts per thousand, respectively(3-5); these deposits are thought to record widespread oceanic carbonate precipitation during postglacial sea level rise(1,3,4). This abrupt transition records a climate system in profound disequilibrium(3,6) and contrasts sharply with the cyclical stratigraphic signal imparted by the balanced feedbacks modulating Phanerozoic deglaciation. Hypotheses accounting for the abruptness of deglaciation include ice albedo feedback(3), deep- ocean out- gassing during post- glacial oceanic overturn(7) or methane hydrate destabilization(8-10). Here we report the broadest range of oxygen isotope values yet measured in marine sediments ( -25 parts per thousand to +12 parts per thousand) in methane seeps in Marinoan deglacial sediments underlying the cap carbonate. This range of values is likely to be the result of mixing between ice- sheet- derived meteoric waters and clathrate- derived fluids during the flushing and destabilization of a clathrate field by glacial meltwater. The equatorial palaeolatitude implies a highly volatile shelf permafrost pool that is an order of magnitude larger than that of the present day. A pool of this size could have provided a massive biogeochemical feedback capable of triggering deglaciation and accounting for the global postglacial marine carbon and sulphur isotopic excursions, abrupt unidirectional warming, cap carbonate deposition, and a marine oxygen crisis. Our findings suggest that methane released from low- latitude permafrost clathrates therefore acted as a trigger and/ or strong positive feedback for deglaciation and warming. Methane hydrate destabilization is increasingly suspected as an important positive feedback to climate change(11-13) that coincides with critical boundaries in the geological record(14,15) and may represent one particularly important mechanism active during conditions of strong climate forcing.
C1 [Kennedy, Martin; Mrofka, David] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [von der Borch, Chris] Flinders Univ S Australia, Sch Chem Phys & Earth Sci, Adelaide, SA 5001, Australia.
C3 University of California System; University of California Riverside; Flinders University
RP Kennedy, M (corresponding author), Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
EM martink@mail.ucr.edu
NR 30
TC 135
Z9 171
U1 1
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2008
VL 453
IS 7195
BP 642
EP 645
DI 10.1038/nature06961
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200041
PM 18509441
DA 2026-03-09
ER

PT J
AU Bowler, C
   Allen, AE
   Badger, JH
   Grimwood, J
   Jabbari, K
   Kuo, A
   Maheswari, U
   Martens, C
   Maumus, F
   Otillar, RP
   Rayko, E
   Salamov, A
   Vandepoele, K
   Beszteri, B
   Gruber, A
   Heijde, M
   Katinka, M
   Mock, T
   Valentin, K
   Verret, F
   Berges, JA
   Brownlee, C
   Cadoret, JP
   Chiovitti, A
   Choi, CJ
   Coesel, S
   De Martino, A
   Detter, JC
   Durkin, C
   Falciatore, A
   Fournet, J
   Haruta, M
   Huysman, MJJ
   Jenkins, BD
   Jiroutova, K
   Jorgensen, RE
   Joubert, Y
   Kaplan, A
   Kröger, N
   Kroth, PG
   La Roche, J
   Lindquist, E
   Lommer, M
   Martin-Jézéquel, V
   Lopez, PJ
   Lucas, S
   Mangogna, M
   McGinnis, K
   Medlin, LK
   Montsant, A
   Oudot-Le Secq, MP
   Napoli, C
   Obornik, M
   Parker, MS
   Petit, JL
   Porcel, BM
   Poulsen, N
   Robison, M
   Rychlewski, L
   Rynearson, TA
   Schmutz, J
   Shapiro, H
   Siaut, M
   Stanley, M
   Sussman, MR
   Taylor, AR
   Vardi, A
   von Dassow, P
   Vyverman, W
   Willis, A
   Wyrwicz, LS
   Rokhsar, DS
   Weissenbach, J
   Armbrust, EV
   Green, BR
   Van De Peer, Y
   Grigoriev, IV
AF Bowler, Chris
   Allen, Andrew E.
   Badger, Jonathan H.
   Grimwood, Jane
   Jabbari, Kamel
   Kuo, Alan
   Maheswari, Uma
   Martens, Cindy
   Maumus, Florian
   Otillar, Robert P.
   Rayko, Edda
   Salamov, Asaf
   Vandepoele, Klaas
   Beszteri, Bank
   Gruber, Ansgar
   Heijde, Marc
   Katinka, Michael
   Mock, Thomas
   Valentin, Klaus
   Verret, Frederic
   Berges, John A.
   Brownlee, Colin
   Cadoret, Jean-Paul
   Chiovitti, Anthony
   Choi, Chang Jae
   Coesel, Sacha
   De Martino, Alessandra
   Detter, J. Chris
   Durkin, Colleen
   Falciatore, Angela
   Fournet, Jerome
   Haruta, Miyoshi
   Huysman, Marie J. J.
   Jenkins, Bethany D.
   Jiroutova, Katerina
   Jorgensen, Richard E.
   Joubert, Yolaine
   Kaplan, Aaron
   Kroger, Nils
   Kroth, Peter G.
   La Roche, Julie
   Lindquist, Erica
   Lommer, Markus
   Martin-Jezequel, Veronique
   Lopez, Pascal J.
   Lucas, Susan
   Mangogna, Manuela
   McGinnis, Karen
   Medlin, Linda K.
   Montsant, Anton
   Oudot-Le Secq, Marie-Pierre
   Napoli, Carolyn
   Obornik, Miroslav
   Parker, Micaela Schnitzler
   Petit, Jean-Louis
   Porcel, Betina M.
   Poulsen, Nicole
   Robison, Matthew
   Rychlewski, Leszek
   Rynearson, Tatiana A.
   Schmutz, Jeremy
   Shapiro, Harris
   Siaut, Magali
   Stanley, Michele
   Sussman, Michael R.
   Taylor, Alison R.
   Vardi, Assaf
   von Dassow, Peter
   Vyverman, Wim
   Willis, Anusuya
   Wyrwicz, Lucjan S.
   Rokhsar, Daniel S.
   Weissenbach, Jean
   Armbrust, E. Virginia
   Green, Beverley R.
   Van de Peer, Yves
   Grigoriev, Igor V.
TI The Phaeodactylum genome reveals the evolutionary history of diatom genomes
SO NATURE
LA English
DT Article
ID reciprocal gene loss; thalassiosira-pseudonana; bacillariophyceae; metabolism; mechanisms; components; bacteria; yeasts
AB Diatoms are photosynthetic secondary endosymbionts found throughout marine and freshwater environments, and are believed to be responsible for around one- fifth of the primary productivity on Earth(1,2). The genome sequence of the marine centric diatom Thalassiosira pseudonana was recently reported, revealing a wealth of information about diatom biology(3-5). Here we report the complete genome sequence of the pennate diatom Phaeodactylum tricornutum and compare it with that of T. pseudonana to clarify evolutionary origins, functional significance and ubiquity of these features throughout diatoms. In spite of the fact that the pennate and centric lineages have only been diverging for 90 million years, their genome structures are dramatically different and a substantial fraction of genes (similar to 40%) are not shared by these representatives of the two lineages. Analysis of molecular divergence compared with yeasts and metazoans reveals rapid rates of gene diversification in diatoms. Contributing factors include selective gene family expansions, differential losses and gains of genes and introns, and differential mobilization of transposable elements. Most significantly, we document the presence of hundreds of genes from bacteria. More than 300 of these gene transfers are found in both diatoms, attesting to their ancient origins, and many are likely to provide novel possibilities for metabolite management and for perception of environmental signals. These findings go a long way towards explaining the incredible diversity and success of the diatoms in contemporary oceans.
C1 [Bowler, Chris; Allen, Andrew E.; Jabbari, Kamel; Maheswari, Uma; Maumus, Florian; Rayko, Edda; Heijde, Marc; De Martino, Alessandra; Lopez, Pascal J.; Montsant, Anton; Vardi, Assaf] Ecole Normale Super, CNRS, Dept Biol, UMR8186, F-75005 Paris, France.
   [Bowler, Chris; Coesel, Sacha; Falciatore, Angela; Mangogna, Manuela; Montsant, Anton; Siaut, Magali] Stn Zool A Dohrn, I-80121 Naples, Italy.
   [Allen, Andrew E.; Badger, Jonathan H.] J Craig Venter Inst, San Diego, CA 92121 USA.
   [Grimwood, Jane; Schmutz, Jeremy] Stanford Human Genome Ctr, Joint Genome Inst Stanford, Palo Alto, CA 94304 USA.
   [Kuo, Alan; Otillar, Robert P.; Salamov, Asaf; Detter, J. Chris; Lindquist, Erica; Lucas, Susan; Shapiro, Harris; Rokhsar, Daniel S.; Grigoriev, Igor V.] Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Martens, Cindy; Vandepoele, Klaas; Huysman, Marie J. J.; Van de Peer, Yves] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Beszteri, Bank; Valentin, Klaus; Medlin, Linda K.] Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany.
   [Gruber, Ansgar; Kroth, Peter G.] Univ Konstanz, Fachbereich Biol, D-78457 Constance, Germany.
   [Katinka, Michael; Petit, Jean-Louis; Porcel, Betina M.; Weissenbach, Jean] CNRS, CEA Inst Genom, UMR 8030, F-91057 Evry, France.
   [Mock, Thomas; Durkin, Colleen; Parker, Micaela Schnitzler; Armbrust, E. Virginia] Univ Washington, Sch Oceanog, Seattle, WA 98195 USA.
   [Verret, Frederic; Brownlee, Colin; Medlin, Linda K.; Taylor, Alison R.] Marine Biol Assoc United Kingdom Lab, Plymouth PL1 2PB, Devon, England.
   [Berges, John A.; Choi, Chang Jae] Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53201 USA.
   [Cadoret, Jean-Paul] IFREMER, PBA, F-44311 Nantes 03, France.
   [Chiovitti, Anthony; Willis, Anusuya] Univ Melbourne, Sch Bot, Melbourne, Vic 3010, Australia.
   [Fournet, Jerome; Joubert, Yolaine; Martin-Jezequel, Veronique] Univ Nantes, Lab Mer Mol Sante, Fac Tech Sci, EA 2160, F-44322 Nantes 3, France.
   [Haruta, Miyoshi; Robison, Matthew; Sussman, Michael R.] Univ Wisconsin, Ctr Biotechnol, Madison, WI 53706 USA.
   [Huysman, Marie J. J.; Vyverman, Wim] Univ Ghent, Lab Protistol & Aquat Ecol, B-9000 Ghent, Belgium.
   [Jenkins, Bethany D.] Univ Rhode Isl, Dept Cell & Mol Biol, Kingston, RI 02881 USA.
   [Jenkins, Bethany D.] Univ Rhode Isl, Grad Sch Oceanog, Kingston, RI 02881 USA.
   [Jiroutova, Katerina; Obornik, Miroslav] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic.
   [Jiroutova, Katerina; Obornik, Miroslav] Univ S Bohemia, Fac Sci, CR-37005 Ceske Budejovice, Czech Republic.
   [Jorgensen, Richard E.; McGinnis, Karen; Napoli, Carolyn] Univ Arizona, Bio5 Inst, Tucson, AZ 85719 USA.
   [Jorgensen, Richard E.; McGinnis, Karen; Napoli, Carolyn] Univ Arizona, Dept Plant Sci, Tucson, AZ 85719 USA.
   [Kaplan, Aaron] Hebrew Univ Jerusalem, Dept Plant & Environm Sci, IL-91904 Jerusalem, Israel.
   [Kroger, Nils] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA.
   [Kroger, Nils] Georgia Inst Technol, Sch Mat Sci & Engn, Atlanta, GA 30332 USA.
   [Kroger, Nils] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
   [La Roche, Julie; Lommer, Markus] Leibniz Inst Marine Sci, D-24105 Kiel, Germany.
   [Oudot-Le Secq, Marie-Pierre; Green, Beverley R.] Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada.
   [Poulsen, Nicole] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA.
   [Rychlewski, Leszek; Wyrwicz, Lucjan S.] BioInfoBank Inst, PL-60744 Poznan, Poland.
   [Rynearson, Tatiana A.] Univ Rhode Isl, Grad Sch Oceanog, Narragansett, RI 02882 USA.
   [Stanley, Michele] Dunstaffnage Marine Res Lab, Scottish Assoc Marine Sci, Oban PA37 1QA, Argyll, Scotland.
   [Taylor, Alison R.] Univ N Carolina, Dept Biol & Marine Biol, Wilmington, NC 28403 USA.
   [Vardi, Assaf] Rutgers State Univ, Inst Marine & Coastal Sci, Environm Biophys & Mol Ecol Grp, New Brunswick, NJ 08901 USA.
   [von Dassow, Peter] CNRS, Biol Stn, UMR7144, F-29682 Roscoff, France.
C3 Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Stazione Zoologica Anton Dohrn; J. Craig Venter Institute; Stanford University; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; Flanders Institute for Biotechnology (VIB); Ghent University; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; University of Konstanz; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); CEA; Universite Paris Saclay; University of Washington; University of Washington Seattle; Marine Biological Association United Kingdom; University of Wisconsin System; University of Wisconsin Milwaukee; Ifremer; University of Melbourne; Nantes Universite; University of Wisconsin System; University of Wisconsin Madison; Ghent University; University of Rhode Island; University of Rhode Island; Czech Academy of Sciences; Biology Centre of the Czech Academy of Sciences; University of South Bohemia Ceske Budejovice; University of Arizona; University of Arizona; Hebrew University of Jerusalem; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; University of British Columbia; University System of Georgia; Georgia Institute of Technology; University of Rhode Island; University of the Highlands & Islands; University of North Carolina; University of North Carolina Wilmington; Rutgers University System; Rutgers University New Brunswick; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE)
RP Bowler, C (corresponding author), Ecole Normale Super, CNRS, Dept Biol, UMR8186, 46 Rue Ulm, F-75005 Paris, France.
EM cbowler@biologie.ens.fr
FU EU-funded FP6 Diatomics [LSHG-CT-2004-512035]; EU-FP6 Marine Genomics Network of Excellence [GOCE-CT-2004-505403]; ATIP 'Blanche'; CNRS (France); Agence Nationale de la Recherche (France); Natural Environment Research Council [dml010007, mba010002] Funding Source: researchfish; NERC [mba010002, dml010007] Funding Source: UKRI
NR 30
TC 1348
Z9 1580
U1 12
U2 530
PU 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 13
PY 2008
VL 456
IS 7219
BP 239
EP 244
DI 10.1038/nature07410
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300040
PM 18923393
DA 2026-03-09
ER

PT J
AU Stewart, JT
   Gaebler, JP
   Jin, DS
AF Stewart, J. T.
   Gaebler, J. P.
   Jin, D. S.
TI Using photoemission spectroscopy to probe a strongly interacting Fermi gas
SO NATURE
LA English
DT Article
ID superfluidity
AB Ultracold atomic gases provide model systems in which to study many-body quantum physics. Recent experiments using Fermi gases have demonstrated a phase transition to a superfluid state with strong interparticle interactions(1-6). This system provides a realization of the 'BCS-BEC crossover'(7) connecting the physics of Bardeen-Cooper-Schrieffer (BCS) superconductivity with that of Bose-Einstein condensates (BECs). Although many aspects of this system have been investigated, it has not yet been possible to measure the single-particle excitation spectrum (a fundamental property directly predicted by many-body theories). Here we use photoemission spectroscopy to directly probe the elementary excitations and energy dispersion in a strongly interacting Fermi gas of K-40 atoms. In the experiments, a radio-frequency photon ejects an atom from the strongly interacting system by means of a spin-flip transition to a weakly interacting state. We measure the occupied density of single-particle states at the cusp of the BCS-BEC crossover and on the BEC side of the crossover, and compare these results to that for a nearly ideal Fermi gas. We show that, near the critical temperature, the single-particle spectral function is dramatically altered in a way that is consistent with a large pairing gap. Our results probe the many-body physics in a way that could be compared to data for the high-transition-temperature superconductors. As in photoemission spectroscopy for electronic materials, our measurement technique for ultracold atomic gases directly probes low-energy excitations and thus can reveal excitation gaps and/or pseudogaps. Furthermore, this technique can provide an analogue of angle-resolved photoemission spectroscopy for probing anisotropic systems, such as atoms in optical lattice potentials.
C1 [Stewart, J. T.; Gaebler, J. P.; Jin, D. S.] Univ Colorado, JILA, Quantum Phys Div, Natl Inst Stand & Technol, Boulder, CO 80309 USA.
   [Stewart, J. T.; Gaebler, J. P.; Jin, D. S.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder
RP Jin, DS (corresponding author), Univ Colorado, JILA, Quantum Phys Div, Natl Inst Stand & Technol, Boulder, CO 80309 USA.
EM jin@jilau1.colorado.edu
NR 30
TC 456
Z9 505
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 AUG 7
PY 2008
VL 454
IS 7205
BP 744
EP 747
DI 10.1038/nature07172
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000040
PM 18685703
DA 2026-03-09
ER

PT J
AU Guo, W
   Lasky, JL
   Chang, CJ
   Mosessian, S
   Lewis, X
   Xiao, Y
   Yeh, JE
   Chen, JY
   Iruela-Arispe, ML
   Varella-Garcia, M
   Wu, H
AF Guo, Wei
   Lasky, Joseph L.
   Chang, Chun-Ju
   Mosessian, Sherly
   Lewis, Xiaoman
   Xiao, Yun
   Yeh, Jennifer E.
   Chen, James Y.
   Iruela-Arispe, M. Luisa
   Varella-Garcia, Marileila
   Wu, Hong
TI Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation
SO NATURE
LA English
DT Article
ID acute lymphoblastic-leukemia; c-myc; notch1; expression; cancer; mouse; leukemia/lymphoma; translocations; inactivation; deletion
AB Cancer stem cells, which share many common properties and regulatory machineries with normal stem cells, have recently been proposed to be responsible for tumorigenesis and to contribute to cancer resistance(1). The main challenges in cancer biology are to identify cancer stem cells and to define the molecular events required for transforming normal cells to cancer stem cells. Here we show that Pten deletion in mouse haematopoietic stem cells leads to a myeloproliferative disorder, followed by acute T-lymphoblastic leukaemia (T-ALL). Self- renewable leukaemia stem cells (LSCs) are enriched in the c-Kit(mid)CD3(+)Lin(-) compartment, where unphosphorylated beta-catenin is significantly increased. Conditional ablation of one allele of the beta-catenin gene substantially decreases the incidence and delays the occurrence of T-ALL caused by Pten loss, indicating that activation of the beta-catenin pathway may contribute to the formation or expansion of the LSC population. Moreover, a recurring chromosomal translocation, T(14;15), results in aberrant overexpression of the c-myc oncogene in c-Kit mid CD3(+)Lin(-) LSCs and CD3(+) leukaemic blasts, recapitulating a subset of human T-ALL. No alterations in Notch1 signalling are detected in this model, suggesting that Pten inactivation and c-myc overexpression may substitute functionally for Notch1 abnormalities(2,3), leading to T-ALL development. Our study indicates that multiple genetic or molecular alterations contribute cooperatively to LSC transformation.
C1 [Guo, Wei; Chang, Chun-Ju; Mosessian, Sherly; Lewis, Xiaoman; Chen, James Y.; Wu, Hong] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
   [Lasky, Joseph L.] Univ Calif Los Angeles, Dept Pediat Hematol Oncol, Los Angeles, CA 90095 USA.
   [Iruela-Arispe, M. Luisa] Univ Calif Los Angeles, Dept Mol Cellular & Dev Biol, Los Angeles, CA 90095 USA.
   [Wu, Hong] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA.
   [Xiao, Yun; Varella-Garcia, Marileila] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Med Oncol,Univ Colorado Canc Ctr, Denver, CO 80262 USA.
   [Yeh, Jennifer E.] MIT, Dept Chem Engn, Cambridge, MA 02139 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 Colorado System; University of Colorado Anschutz Medical Campus; University of Colorado Denver; Massachusetts Institute of Technology (MIT)
RP Wu, H (corresponding author), Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
EM hwu@mednet.ucla.edu
FU NCI NIH HHS [CA16042, R01 CA121110, P30 CA016042] Funding Source: Medline; National Cancer Institute [P30CA016042] Funding Source: NIH RePORTER
NR 27
TC 192
Z9 232
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 MAY 22
PY 2008
VL 453
IS 7194
BP 529
EP U7
DI 10.1038/nature06933
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700044
PM 18463637
DA 2026-03-09
ER

PT J
AU Tyler, RH
AF Tyler, Robert H.
TI Strong ocean tidal flow and heating on moons of the outer planets
SO NATURE
LA English
DT Article
ID hot jupiters; galilean satellites; subsurface ocean; obliquity tides; dissipation; europa; titan
AB Data from recent space missions have added strong support for the idea that there are liquid oceans on several moons of the outer planets, with Jupiter's moon Europa having received the most attention(1-4). But given the extremely cold surface temperatures and meagre radiogenic heat sources of these moons, it is still unclear how these oceans remain liquid. The prevailing conjecture is that these oceans are heated by tidal forces that flex the solid moon ( rock plus ice) during its eccentric orbit, and that this heat entering the ocean does not rapidly escape because of the insulating layer of ice over the ocean surface. Here, however, I describe strong tidal dissipation ( and heating) in the liquid oceans; I show that a subdominant and previously unconsidered tidal force due to obliquity ( axial tilt of the moon with respect to its orbital plane) has the right form and frequency to resonantly excite large- amplitude Rossby waves in these oceans. In the specific case of Europa, the minimumkinetic energy of the flow associated with this resonance ( 7.3x10(18) J) is two thousand times larger than that of the flow excited by the dominant tidal forces, and dissipation of this energy seems large enough to be a primary ocean heat source.
C1 [Tyler, Robert H.] Univ Washington, Appl Phys Lab, Seattle, WA 98105 USA.
   [Tyler, Robert H.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98105 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Tyler, RH (corresponding author), Univ Washington, Appl Phys Lab, 1013 NE 40th St, Seattle, WA 98105 USA.
EM tyler@apl.washington.edu
FU NASA Outer Planets Research
NR 17
TC 106
Z9 116
U1 1
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 DEC 11
PY 2008
VL 456
IS 7223
BP 770
EP U55
DI 10.1038/nature07571
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900044
PM 19079055
DA 2026-03-09
ER

PT J
AU Hao, LH
   Sakurai, A
   Watanabe, T
   Sorensen, E
   Nidom, CA
   Newton, MA
   Ahlquist, P
   Kawaoka, Y
AF Hao, Linhui
   Sakurai, Akira
   Watanabe, Tokiko
   Sorensen, Ericka
   Nidom, Chairul A.
   Newton, Michael A.
   Ahlquist, Paul
   Kawaoka, Yoshihiro
TI Drosophila RNAi screen identifies host genes important for influenza virus replication
SO NATURE
LA English
DT Article
ID cytochrome-c-oxidase; messenger-rna; protein; export; apoptosis; targets
AB All viruses rely on host cell proteins and their associated mechanisms to complete the viral life cycle. Identifying the host molecules that participate in each step of virus replication could provide valuable new targets for antiviral therapy, but this goal may take several decades to achieve with conventional forward genetic screening methods and mammalian cell cultures. Here we describe a novel genome-wide RNA interference (RNAi) screen in Drosophila 1 that can be used to identify host genes important for influenza virus replication. After modifying influenza virus to allow infection of Drosophila cells and detection of influenza virus gene expression, we tested an RNAi library against 13,071 genes (90% of the Drosophila genome), identifying over 100 for which suppression in Drosophila cells significantly inhibited or stimulated reporter gene (Renilla luciferase) expression from an influenza-virus-derived vector. The relevance of these findings to influenza virus infection of mammalian cells is illustrated for a subset of the Drosophila genes identified; that is, for three implicated Drosophila genes, the corresponding human homologues ATP6V0D1, COX6A1 and NXF1 are shown to have key functions in the replication of H5N1 and H1N1 influenza A viruses, but not vesicular stomatitis virus or vaccinia virus, in human HEK 293 cells. Thus, we have demonstrated the feasibility of using genome-wide RNAi screens in Drosophila to identify previously unrecognized host proteins that are required for influenza virus replication. This could accelerate the development of new classes of antiviral drugs for chemoprophylaxis and treatment, which are urgently needed given the obstacles to rapid development of an effective vaccine against pandemic influenza and the probable emergence of strains resistant to available drugs.
C1 [Sakurai, Akira; Watanabe, Tokiko; Kawaoka, Yoshihiro] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA.
   [Hao, Linhui; Sorensen, Ericka; Ahlquist, Paul] Univ Wisconsin, Inst Mol Virol, Madison, WI 53706 USA.
   [Hao, Linhui; Ahlquist, Paul] Univ Wisconsin, Howard Hughes Med Inst, Madison, WI 53706 USA.
   [Newton, Michael A.] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA.
   [Newton, Michael A.] Univ Wisconsin, Dept Biostat, Madison, WI 53706 USA.
   [Newton, Michael A.] Univ Wisconsin, Dept Med Informat, Madison, WI 53706 USA.
   [Nidom, Chairul A.] Airlangga Univ, Fac Vet Med, Surabaya 60115, Indonesia.
   [Nidom, Chairul A.] Airlangga Univ, Collaborating Res Ctr Emerging & Reemerging Infec, Trop Dis Ctr, Surabaya 60115, Indonesia.
   [Kawaoka, Yoshihiro] Univ Tokyo, Div Virol, Dept Microbiol & Immunol, Tokyo 1088639, Japan.
   [Kawaoka, Yoshihiro] Univ Tokyo, Int Res Ctr Infect Dis, Inst Med Sci, Tokyo 1088639, Japan.
   [Kawaoka, Yoshihiro] Kobe Univ, Grad Sch Med, Div Zoonosis, Dept Microbiol & Infect Dis, Kobe, Hyogo 6500017, Japan.
C3 University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; Howard Hughes Medical Institute; 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; Airlangga University; Airlangga University; University of Tokyo; University of Tokyo; Kobe University
RP Kawaoka, Y (corresponding author), Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA.
EM ahlqust@wisc.edu; kawaokay@svm.vetmed.wisc.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIAID NIH HHS [R01 AI069274, R01 AI044386, R01 AI047446] Funding Source: Medline; NIGMS NIH HHS [R01 GM035072, R37 GM035072, GM35072] Funding Source: Medline
NR 28
TC 371
Z9 445
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 14
PY 2008
VL 454
IS 7206
BP 890
EP U46
DI 10.1038/nature07151
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600037
PM 18615016
DA 2026-03-09
ER

PT J
AU Choi, KS
   Deng, H
   Laurat, J
   Kimble, HJ
AF Choi, K. S.
   Deng, H.
   Laurat, J.
   Kimble, H. J.
TI Mapping photonic entanglement into and out of a quantum memory
SO NATURE
LA English
DT Article
ID electromagnetically induced transparency; single-photon; atomic ensembles; light; storage; communication; teleportation; retrieval; pulses; qubits
AB Developments in quantum information science(1) rely critically on entanglement - a fundamental aspect of quantum mechanics that causes parts of a composite system to show correlations stronger than can be explained classically(2). In particular, scalable quantum networks require the capability to create, store and distribute entanglement among distant matter nodes by means of photonic channels(3). Atomic ensembles can play the role of such nodes(4). Sofar, in the photon- counting regime, heralded entanglement between atomic ensembles has been successfully demonstrated through probabilistic protocols(5,6). But an inherent drawback of this approach is the compromise between the amount of entanglement and its preparation probability, leading to intrinsically low count rates for high entanglement. Here we report a protocol where entanglement between two atomic ensembles is created by coherent mapping of an entangled state of light. By splitting a single photon(7-9) and performing subsequent state transfer, we separate the generation of entanglement and its storage(10). After a programmable delay, the stored entanglement is mapped back into photonic modes with overall efficiency of 17%. Together with improvements in single- photon sources(11), our protocol will allow 'on- demand' entanglement of atomic ensembles, a powerful resource for quantum information science.
C1 [Choi, K. S.; Deng, H.; Laurat, J.; Kimble, H. J.] CALTECH, Norman Bridge Lab Phys 12 33, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Kimble, HJ (corresponding author), CALTECH, Norman Bridge Lab Phys 12 33, Pasadena, CA 91125 USA.
EM hjkimble@caltech.edu
NR 37
TC 468
Z9 526
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 6
PY 2008
VL 452
IS 7183
BP 67
EP U4
DI 10.1038/nature06670
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900047
PM 18322529
DA 2026-03-09
ER

PT J
AU Lape, R
   Colquhoun, D
   Sivilotti, LG
AF Lape, Remigijus
   Colquhoun, David
   Sivilotti, Lucia G.
TI On the nature of partial agonism in the nicotinic receptor superfamily
SO NATURE
LA English
DT Article
ID glycine receptors; ion channels; end-plate; acetylcholine; binding; activation; mechanism; currents
AB Partial agonists are ligands that bind to receptors but produce only a small maximum response even at concentrations where all receptors are occupied. In the case of ligand-activated ion channels, it has been supposed since 1957 that partial agonists evoke a small response because they are inefficient at eliciting the change of conformation between shut and open states of the channel. We have investigated partial agonists for two members of the nicotinic superfamily - the muscle nicotinic acetylcholine receptor and the glycine receptor - and find that the open-shut reaction is similar for both full and partial agonists, but the response to partial agonists is limited by an earlier conformation change ('flipping') that takes place while the channel is still shut. This has implications for the interpretation of structural studies, and in the future, for the design of partial agonists for therapeutic use.
C1 [Lape, Remigijus; Colquhoun, David; Sivilotti, Lucia G.] UCL, Dept Pharmacol, London WC1E 6BT, England.
C3 University of London; University College London
RP Colquhoun, D (corresponding author), UCL, Dept Pharmacol, Med Sci Bldg,Gower St, London WC1E 6BT, England.
EM d.colquhoun@ucl.ac.uk
FU Medical Research Council [G0400869(72542), G0400869] Funding Source: Medline; Wellcome Trust [074491] Funding Source: Medline; Medical Research Council [G0400869] Funding Source: researchfish; MRC [G0400869] Funding Source: UKRI
NR 26
TC 297
Z9 319
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 722
EP U56
DI 10.1038/nature07139
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000036
PM 18633353
DA 2026-03-09
ER

PT J
AU Saitoh, T
   Fujita, N
   Jang, MH
   Uematsu, S
   Yang, BG
   Satoh, T
   Omori, H
   Noda, T
   Yamamoto, N
   Komatsu, M
   Tanaka, K
   Kawai, T
   Tsujimura, T
   Takeuchi, O
   Yoshimori, T
   Akira, S
AF Saitoh, Tatsuya
   Fujita, Naonobu
   Jang, Myoung Ho
   Uematsu, Satoshi
   Yang, Bo-Gie
   Satoh, Takashi
   Omori, Hiroko
   Noda, Takeshi
   Yamamoto, Naoki
   Komatsu, Masaaki
   Tanaka, Keiji
   Kawai, Taro
   Tsujimura, Tohru
   Takeuchi, Osamu
   Yoshimori, Tamotsu
   Akira, Shizuo
TI Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production
SO NATURE
LA English
DT Article
ID genome-wide association; immune activation; crohn-disease; innate; macrophages; cells; inflammasome; recognition; receptors; membrane
AB Systems for protein degradation are essential for tight control of the inflammatory immune response(1,2). Autophagy, a bulk degradation system that delivers cytoplasmic constituents into autolysosomes, controls degradation of long- lived proteins, insoluble protein aggregates and invading microbes, and is suggested to be involved in the regulation of inflammation(3-5). However, the mechanism underlying the regulation of inflammatory response by autophagy is poorly understood. Here we show that Atg16L1 ( autophagy-related 16-like 1), which is implicated in Crohn's disease(6,7), regulates endotoxin- induced inflammasome activation in mice. Atg16L1- deficiency disrupts the recruitment of the Atg12-Atg5 conjugate to the isolation membrane, resulting in a loss of microtubule- associated protein 1 light chain 3 ( LC3) conjugation to phosphatidylethanolamine. Consequently, both autophagosome formation and degradation of long- lived proteins are severely impaired in Atg16L1- deficient cells. Following stimulation with lipopolysaccharide, a ligand for Toll- like receptor 4 ( refs 8, 9), Atg16L1- deficient macrophages produce high amounts of the inflammatory cytokines IL-1 beta and IL-18. In lipopolysaccharide-stimulated macrophages, Atg16L1- deficiency causes Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta ( TRIF)dependent activation of caspase- 1, leading to increased production of IL-1 beta. Mice lacking Atg16L1 in haematopoietic cells are highly susceptible to dextran sulphate sodium- induced acute colitis, which is alleviated by injection of anti-IL-1 beta and IL-18 antibodies, indicating the importance of Atg16L1 in the suppression of intestinal inflammation. These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin- induced inflammatory immune response.
C1 [Saitoh, Tatsuya; Uematsu, Satoshi; Yang, Bo-Gie; Satoh, Takashi; Kawai, Taro; Takeuchi, Osamu; Akira, Shizuo] Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan.
   [Jang, Myoung Ho] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Gastrointestinal Immunol, Suita, Osaka 5650871, Japan.
   [Saitoh, Tatsuya; Uematsu, Satoshi; Yang, Bo-Gie; Satoh, Takashi; Kawai, Taro; Takeuchi, Osamu; Akira, Shizuo] Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Suita, Osaka 5650871, Japan.
   [Fujita, Naonobu; Omori, Hiroko; Noda, Takeshi; Yoshimori, Tamotsu] Osaka Univ, Res Inst Microbial Dis, Dept Cellular Regulat, Suita, Osaka 5650871, Japan.
   [Yamamoto, Naoki] Natl Inst Infect Dis, AIDS Res Ctr, Shinjuku Ku, Tokyo 1628640, Japan.
   [Komatsu, Masaaki; Tanaka, Keiji] Tokyo Metropolitan Inst Med Sci, Lab Frontier Sci, Bunkyo Ku, Tokyo 1138613, Japan.
   [Komatsu, Masaaki] Juntendo Univ, Sch Med, Dept Biochem, Bunkyo Ku, Tokyo 1138421, Japan.
   [Komatsu, Masaaki] Japan Sci & Technol Corp, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Tsujimura, Tohru] Hyogo Coll Med, Dept Pathol, Nishinomiya, Hyogo 6638501, Japan.
   [Yoshimori, Tamotsu] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
C3 University of Osaka; University of Osaka; University of Osaka; University of Osaka; Japan Institute for Health Security (JIHS); National Institute of Infectious Diseases (NIID); Tokyo Metropolitan Institute of Medical Science; Juntendo University; Japan Science & Technology Agency (JST); Hyogo Medical University; Japan Science & Technology Agency (JST)
RP Akira, S (corresponding author), Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, 3-1 Yamadaoka, Suita, Osaka 5650871, Japan.
EM akira@biken.osaka-u.ac.jp
FU NIH [AI070167]; Ministry of Health, Labour and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan.; Grants-in-Aid for Scientific Research [20002008] Funding Source: KAKEN
NR 31
TC 1765
Z9 2002
U1 2
U2 176
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 13
PY 2008
VL 456
IS 7219
BP 264
EP U68
DI 10.1038/nature07383
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300045
PM 18849965
DA 2026-03-09
ER

PT J
AU Thum, T
   Gross, C
   Fiedler, J
   Fischer, T
   Kissler, S
   Bussen, M
   Galuppo, P
   Just, S
   Rottbauer, W
   Frantz, S
   Castoldi, M
   Soutschek, J
   Koteliansky, V
   Rosenwald, A
   Basson, MA
   Licht, JD
   Pena, JTR
   Rouhanifard, SH
   Muckenthaler, MU
   Tuschl, T
   Martin, GR
   Bauersachs, J
   Engelhardt, S
AF Thum, Thomas
   Gross, Carina
   Fiedler, Jan
   Fischer, Thomas
   Kissler, Stephan
   Bussen, Markus
   Galuppo, Paolo
   Just, Steffen
   Rottbauer, Wolfgang
   Frantz, Stefan
   Castoldi, Mirco
   Soutschek, Jurgen
   Koteliansky, Victor
   Rosenwald, Andreas
   Basson, M. Albert
   Licht, Jonathan D.
   Pena, John T. R.
   Rouhanifard, Sara H.
   Muckenthaler, Martina U.
   Tuschl, Thomas
   Martin, Gail R.
   Bauersachs, Johann
   Engelhardt, Stefan
TI MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
SO NATURE
LA English
DT Article
ID cardiac-hypertrophy; heart-failure; in-vivo; expression; regulator; mechanism; sprouty2; mice; play
AB MicroRNAs comprise a broad class of small non- coding RNAs that control expression of complementary target messenger RNAs(1,2). Dysregulation of microRNAs by several mechanisms has been described in various disease states(3-5) including cardiac disease(6-10). Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK - MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK - MAP kinase activity through inhibition of sprouty homologue 1 ( Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR- 21 by a specific antagomir in a mouse pressure- overload- induced disease model reduces cardiac ERK - MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR- 21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.
C1 [Thum, Thomas; Fiedler, Jan; Galuppo, Paolo; Frantz, Stefan; Bauersachs, Johann] Univ Wurzburg, Dept Med 1, D-97080 Wurzburg, Germany.
   [Thum, Thomas; Fiedler, Jan] Univ Wurzburg, Jr Res Grp, IZKF, D-97080 Wurzburg, Germany.
   [Gross, Carina; Fischer, Thomas; Kissler, Stephan; Engelhardt, Stefan] Univ Wurzburg, Rudolf Virchow Ctr, DFG, Res Ctr Expt Biomed, D-97080 Wurzburg, Germany.
   [Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-97080 Wurzburg, Germany.
   [Bussen, Markus] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94158 USA.
   [Just, Steffen; Rottbauer, Wolfgang] Univ Heidelberg, Dept Internal Med 3, D-69120 Heidelberg, Germany.
   [Castoldi, Mirco; Muckenthaler, Martina U.] Univ Heidelberg, Dept Pediat Hematol Oncol & Immunol, D-69120 Heidelberg, Germany.
   [Castoldi, Mirco; Muckenthaler, Martina U.] Univ Heidelberg, Mol Med Partnership Unit, D-69120 Heidelberg, Germany.
   [Soutschek, Jurgen] Regulus Therapeut, Carlsbad, CA 92008 USA.
   [Koteliansky, Victor] Alnylam Pharmaceut, Cambridge, MA 02142 USA.
   [Basson, M. Albert] Kings Coll London, Dept Craniofacial Dev, London SE1 9RT, England.
   [Licht, Jonathan D.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Pena, John T. R.; Rouhanifard, Sara H.; Tuschl, Thomas] Rockefeller Univ, Lab RNA Mol Biol, New York, NY 10065 USA.
   [Engelhardt, Stefan] Tech Univ Munich, Inst Pharmacol & Toxicol, D-80802 Munich, Germany.
C3 University of Wurzburg; University of Wurzburg; University of Wurzburg; German Research Foundation (DFG); University of Wurzburg; University of California System; University of California San Francisco; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Ionis Pharmaceuticals, Inc.; Alnylam Pharmaceuticals; University of London; King's College London; Northwestern University; Feinberg School of Medicine; Rockefeller University; Technical University of Munich
RP Bauersachs, J (corresponding author), Univ Wurzburg, Dept Med 1, D-97080 Wurzburg, Germany.
EM j.bauersachs@medizin.uni-wuerzburg.de; stefan.engelhardt@tum.de
FU IZKF [E-31]; Deutsche Forschungsgemeinschaft [DFG TH903/7-1]; Rudolf Virchow Center/DFG Research Center for Experimental Biomedicine; Bavarian Ministry of Technology; ProCorde; Sanofi-Aventis; US NIH [R01 CA78711]; The Medical Faculty of the University of Heidelberg; Cancer Research Net [BMBF (NGFN) 201GS0450]; Leopoldina Academy [BMBF-LPD 9901/8-141]
NR 30
TC 2047
Z9 2336
U1 4
U2 266
PU 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 18
PY 2008
VL 456
IS 7224
BP 980
EP U83
DI 10.1038/nature07511
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300052
PM 19043405
DA 2026-03-09
ER

PT J
AU Graves, AR
   Curran, PK
   Smith, CL
   Mindell, JA
AF Graves, Austin R.
   Curran, Patricia K.
   Smith, Carolyn L.
   Mindell, Joseph A.
TI The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes
SO NATURE
LA English
DT Article
ID osteopetrosis type-ii; functional reconstitution; torpedo-californica; proton pump; channel; proteins; mutation; disease; leads
AB Lysosomes are the stomachs of the cell - terminal organelles on the endocytic pathway where internalized macromolecules are degraded. Containing a wide range of hydrolytic enzymes, lysosomes depend on maintaining acidic luminal pH values for efficient function. Although acidification is mediated by a V- type proton ATPase, a parallel anion pathway is essential to allow bulk proton transport(1,2). The molecular identity of this anion transporter remains unknown. Recent results of knockout experiments raise the possibility that ClC- 7, a member of the CLC family of anion channels and transporters, is a contributor to this pathway in an osteoclast lysosome- like compartment, with loss of ClC- 7 function causing osteopetrosis(3). Several mammalian members of the CLC family have been characterized in detail; some ( including ClC- 0, ClC- 1 and ClC- 2) function as Cl(-) -conducting ion channels(4), whereas others act as Cl(-)/H(+) antiporters ( ClC- 4 and ClC-5) (5,6). However, previous attempts at heterologous expression of ClC- 7 have failed to yield evidence of functional protein, so it is unclear whether ClC- 7 has an important function in lysosomal biology, and also whether this protein functions as a Cl(-) channel, a Cl(-)/H(+) antiporter, or as something else entirely. Here we directly demonstrate an anion transport pathway in lysosomes that has the defining characteristics of a CLC Cl(-)/H(+) antiporter and show that this transporter is the predominant route for Cl(-) through the lysosomal membrane. Furthermore, knockdown of ClC- 7 expression by short interfering RNA can essentially ablate this lysosomal Cl(-)/H(+) antiport activity and can strongly diminish the ability of lysosomes to acidify in vivo, demonstrating that ClC- 7 is a Cl(-)/H(+) antiporter, that it constitutes the major Cl(-) permeability of lysosomes, and that it is important in lysosomal acidification.
C1 [Graves, Austin R.; Curran, Patricia K.; Mindell, Joseph A.] Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Smith, Carolyn L.] Natl Inst Neurol Disorders & Stroke, Light Microscopy Facil, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
RP Mindell, JA (corresponding author), Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Unit, Porter Neurosci Res Ctr, NIH, 35 Convent Dr,Bldg 35,MSC 3701, Bethesda, MD 20892 USA.
EM mindellj@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke [ZIANS003015] Funding Source: NIH RePORTER; Intramural NIH HHS Funding Source: Medline
NR 22
TC 320
Z9 379
U1 1
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 5
PY 2008
VL 453
IS 7196
BP 788
EP 792
DI 10.1038/nature06907
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300045
PM 18449189
DA 2026-03-09
ER

PT J
AU Takahashi, H
   Igawa, K
   Arii, K
   Kamihara, Y
   Hirano, M
   Hosono, H
AF Takahashi, Hiroki
   Igawa, Kazumi
   Arii, Kazunobu
   Kamihara, Yoichi
   Hirano, Masahiro
   Hosono, Hideo
TI Superconductivity at 43 K in an iron-based layered compound LaO1-xFxFeAs
SO NATURE
LA English
DT Article
AB The iron- and nickel-based layered compounds LaOFeP (refs 1, 2) and LaONiP (ref. 3) have recently been reported to exhibit low-temperature superconducting phases with transition temperatures T-c of 3 and 5 K, respectively. Furthermore, a large increase in the midpoint T-c of up to similar to 26 K has been realized(4) in the isocrystalline compound LaOFeAs on doping of fluoride ions at the O2- sites (LaO1-xFxFeAs). Experimental observations(5,6) and theoretical studies(7-9) suggest that these transitions are related to a magnetic instability, as is the case for most superconductors based on transition metals. In the copper-based high-temperature superconductors, as well as in LaOFeAs, an increase in T-c is often observed as a result of carrier doping in the two-dimensional electronic structure through ion substitution in the surrounding insulating layers, suggesting that the application of external pressure should further increase T-c by enhancing charge transfer between the insulating and conducting layers. The effects of pressure on these iron oxypnictide superconductors may be more prominent than those in the copper-based systems, because the As ion has a greater electronic polarizability, owing to the covalency of the Fe-As chemical bond, and, thus, is more compressible than the divalent O2- ion. Here we report that increasing the pressure causes a steep increase in the onset T-c of F-doped LaOFeAs, to a maximum of similar to 43 K at similar to 4 GPa. With the exception of the copper-based high-T-c superconductors, this is the highest T-c reported to date. The present result, together with the great freedom available in selecting the constituents of isocrystalline materials with the general formula LnOTMPn (Ln, Y or rare-earth metal; TM, transition metal; Pn, group-V, 'pnicogen', element), indicates that the layered iron oxypnictides are promising as a new material platform for further exploration of high-temperature superconductivity.
C1 [Takahashi, Hiroki; Igawa, Kazumi; Arii, Kazunobu] Nihon Univ, Dept Phys, Coll Humanities & Sci, Setagaya Ku, Tokyo 1568550, Japan.
   [Kamihara, Yoichi; Hirano, Masahiro; Hosono, Hideo] Tokyo Inst Technol, ERATO SORST, JST, Midori Ku, Yokohama, Kanagawa 2268503, Japan.
   [Hirano, Masahiro; Hosono, Hideo] Tokyo Inst Technol, Frontier Res Ctr, Midori Ku, Yokohama, Kanagawa 2268503, Japan.
C3 Nihon University; Japan Science & Technology Agency (JST); Institute of Science Tokyo; Tokyo Institute of Technology; Institute of Science Tokyo; Tokyo Institute of Technology
RP Takahashi, H (corresponding author), Nihon Univ, Dept Phys, Coll Humanities & Sci, Setagaya Ku, Tokyo 1568550, Japan.
EM hiroki@chs.nihon-u.ac.jp
NR 17
TC 1107
Z9 1230
U1 0
U2 527
PU 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 15
PY 2008
VL 453
IS 7193
BP 376
EP 378
DI 10.1038/nature06972
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400048
PM 18432191
DA 2026-03-09
ER

PT J
AU Marinova, MM
   Aharonson, O
   Asphaug, E
AF Marinova, Margarita M.
   Aharonson, Oded
   Asphaug, Erik
TI Mega-impact formation of the Mars hemispheric dichotomy
SO NATURE
LA English
DT Article
ID crustal dichotomy; giant impact; origin; topography; evolution; mantle; model; moon
AB The Mars hemispheric dichotomy is expressed as a dramatic difference in elevation, crustal thickness and crater density between the southern highlands and northern lowlands ( which cover similar to 42% of the surface)(1,2). Despite the prominence of the dichotomy, its origin has remained enigmatic and models for its formation largely untested(3-5). Endogenic degree-1 convection models with north - south asymmetry are incomplete in that they are restricted to simulating only mantle dynamics and they neglect crustal evolution, whereas exogenic multiple impact events are statistically unlikely to concentrate in one hemisphere(6). A single mega-impact of the requisite size has not previously been modelled. However, it has been hypothesized that such an event could obliterate the evidence of its occurrence by completely covering the surface with melt(7) or catastrophically disrupting the planet(3,8). Here we present a set of single- impact initial conditions by which a large impactor can produce features consistent with the observed dichotomy's crustal structure and persistence. Using three- dimensional hydrodynamic simulations, large variations are predicted in post- impact states depending on impact energy, velocity and, importantly, impact angle, with trends more pronounced or unseen in commonly studied smaller impacts(9). For impact energies of similar to(3-6) x 10(29) J, at low impact velocities (6-10 km s(-1)) and oblique impact angles ( 30 - 60 degrees), the resulting crustal removal boundary is similar in size and ellipticity to the observed characteristics of the lowlands basin. Under these conditions, the melt distribution is largely contained within the area of impact and thus does not erase the evidence of the impact's occurrence. The antiquity of the dichotomy(10) is consistent with the contemporaneous presence of impactors of diameter 1,600 - 2,700 km in Mars- crossing orbits(3), and the impact angle is consistent with the expected distribution(11).
C1 [Marinova, Margarita M.; Aharonson, Oded] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Asphaug, Erik] Univ Calif Santa Cruz, Dept Earth Sci, Santa Cruz, CA 95064 USA.
C3 California Institute of Technology; University of California System; University of California Santa Cruz
RP Marinova, MM (corresponding author), CALTECH, Div Geol & Planetary Sci, MC 150-21, Pasadena, CA 91125 USA.
EM mmm@caltech.edu
NR 29
TC 205
Z9 237
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 JUN 26
PY 2008
VL 453
IS 7199
BP 1216
EP 1219
DI 10.1038/nature07070
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800037
PM 18580945
DA 2026-03-09
ER

PT J
AU Agogué, H
   Brink, M
   Dinasquet, J
   Herndl, GJ
AF Agogue, Helene
   Brink, Maaike
   Dinasquet, Julie
   Herndl, Gerhard J.
TI Major gradients in putatively nitrifying and non-nitrifying Archaea in the deep North Atlantic
SO NATURE
LA English
DT Article
ID ammonia-oxidizing bacteria; water masses; planktonic archaea; amino-acids; ocean; sea; nitrification; crenarchaeota; oxidation; abundance
AB Aerobic nitrification of ammonia to nitrite and nitrate is a key process in the oceanic nitrogen cycling mediated by prokaryotes(1). Apart from Bacteria belonging to the beta- and gamma-Proteobacteria involved in the first nitrification step, Crenarchaeota have recently been recognized as main drivers of the oxidation of ammonia to nitrite in soil as well as in the ocean, as indicated by the dominance of archaeal ammonia monooxygenase (amoA) genes over bacterial amoA(2,3). Evidence is accumulating that archaeal amoA genes are common in a wide range of marine systems(3-6). Essentially, all these reports focused on surface and mesopelagic (200-1,000 m depth) waters, where ammonia concentrations are higher than in waters below 1,000 m depth. However, Crenarchaeota are also abundant in the water column below 1,000 m, where ammonia concentrations are extremely low. Here we show that, throughout the NorthAtlantic Ocean, the abundance of archaeal amoA genes decreases markedly from subsurface waters to 4,000 m depth, and from subpolar to equatorial deep waters, leading to pronounced vertical and latitudinal gradients in the ratio of archaeal amoA to crenarchaeal 16S ribosomal RNA ( rRNA) genes. The lack of significant copy numbers of amoA genes and the very low fixation rates of dark carbon dioxide in the bathypelagic North Atlantic suggest that most bathypelagic Crenarchaeota are not autotrophic ammonia oxidizers: most likely, they utilize organic matter and hence live heterotrophically.
C1 [Agogue, Helene; Brink, Maaike; Dinasquet, Julie; Herndl, Gerhard J.] Royal Netherlands Inst Sea Res, Dept Biol Oceanog, NL-1790 AB Den Burg, Texel, Netherlands.
C3 Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ)
RP Herndl, GJ (corresponding author), Univ Vienna, Vienna Ecol Ctr, Dept Marine Biol, Waehringer Guertel 18, A-1090 Vienna, Austria.
EM herndl@nioz.nl
FU Marie Curie Fellowship of the European Community; Earth and Life Science Division of the Dutch Science Foundation (ALW-NWO) (TRANSAT and ARCHIMEDES projects); 6th Framework Program of the European Union
NR 29
TC 218
Z9 250
U1 5
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 788
EP U72
DI 10.1038/nature07535
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900048
PM 19037244
DA 2026-03-09
ER

PT J
AU Hunte, F
   Jaroszynski, J
   Gurevich, A
   Larbalestier, DC
   Jin, R
   Sefat, AS
   McGuire, MA
   Sales, BC
   Christen, DK
   Mandrus, D
AF Hunte, F.
   Jaroszynski, J.
   Gurevich, A.
   Larbalestier, D. C.
   Jin, R.
   Sefat, A. S.
   McGuire, M. A.
   Sales, B. C.
   Christen, D. K.
   Mandrus, D.
TI Two-band superconductivity in LaFeAsO0.89F0.11 at very high magnetic fields
SO NATURE
LA English
DT Article
AB The recent synthesis of the superconductor LaFeAsO0.89F0.11 with transition temperature T-c approximate to 26 K ( refs 1 - 4) has been quickly followed by reports of even higher transition temperatures in related compounds: 41 K in CeFeAsO0.84F0.16 ( ref. 5), 43 K in SmFeAsO0.9F0.1 ( ref. 6), and 52 K in NdFeAsO0.89F0.11 and PrFeAsO0.89F0.11 ( refs 7, 8). These discoveries have generated much interest(9,10) in the mechanisms and manifestations of unconventional superconductivity in the family of doped quaternary layered oxypnictides LnOTMPn ( Ln: La, Pr, Ce, Sm; TM: Mn, Fe, Co, Ni; Pn: P, As), because many features of these materials set them apart from other known superconductors. Here we report resistance measurements of LaFeAsO0.89F0.11 at high magnetic fields, up to 45 T, that show a remarkable enhancement of the upper critical field B-c2 compared to values expected from the slopes dB(c2)/ dT approximate to 2 T K-1 near Tc, particularly at low temperatures where the deduced B-c2(0) approximate to 63 - 65 T exceeds the paramagnetic limit. We argue that oxypnictides represent a new class of high-field superconductors with B-c2 values surpassing those of Nb3Sn, MgB2 and the Chevrel phases, and perhaps exceeding the 100 T magnetic field benchmark of the high- T-c copper oxides.
C1 [Hunte, F.; Jaroszynski, J.; Gurevich, A.; Larbalestier, D. C.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
   [Jin, R.; Sefat, A. S.; McGuire, M. A.; Sales, B. C.; Christen, D. K.; Mandrus, D.] Oak Ridge Natl Lab, Mat Sci & Technol Div, Oak Ridge, TN 37831 USA.
C3 State University System of Florida; Florida State University; United States Department of Energy (DOE); Oak Ridge National Laboratory
RP Hunte, F (corresponding author), Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
EM hunte@asc.magnet.fsu.edu
NR 26
TC 503
Z9 535
U1 1
U2 176
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 903
EP 905
DI 10.1038/nature07058
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000039
PM 18509332
DA 2026-03-09
ER

PT J
AU Hejnol, A
   Martindale, MQ
AF Hejnol, Andreas
   Martindale, Mark Q.
TI Acoel development indicates the independent evolution of the bilaterian mouth and anus
SO NATURE
LA English
DT Article
ID gene-expression; nervous-system; gastrulation; brachyury; drosophila; flatworms; suggests; origins; pattern
AB Most bilaterian animals possess a through gut with a separate mouth and anus(1). It is commonly believed that during the transition from radial to bilateral symmetry, both openings evolved simultaneously by the lateral closure of a slit- like blastopore(1-4). Molecular phylogenies however, place the acoel flatworms, which have only one opening to their digestive system, as the sister group to all remaining Bilateria(5-7). To address how this single body opening is related to the mouth and anus of the protostomes and deuterostomes, we studied the expression of genes involved in bilaterian foregut and hindgut patterning during the development of the acoel Convolutriloba longifissura. Here we show that the genes brachyury and goosecoid are expressed in association with the acoel mouth, suggesting that this single opening is homologous to the mouth of other bilaterians(8). In addition, we find that the genes caudal, orthopedia and brachyury - which are expressed in various bilaterian hindguts(8-10) - are expressed in a small region at the posterior end of the animal, separated from the anterior oral brachyury- expressing region by a dorsal domain of ectodermal bmp2/4 expression. These results contradict the hypothesis that the bilaterian mouth and anus evolved simultaneously from a common blastoporal opening, and suggest that a through gut might have evolved independently in different animal lineages.
C1 [Hejnol, Andreas; Martindale, Mark Q.] Univ Hawaii, Kewalo Marine Lab, PBRC, Honolulu, HI 96813 USA.
C3 University of Hawaii System
RP Hejnol, A (corresponding author), Univ Hawaii, Kewalo Marine Lab, PBRC, 41 Ahui St, Honolulu, HI 96813 USA.
EM hejnol@hawaii.edu
FU National Science Foundation; AToL program [EF05-31558]; NASA; Deutsche Forschungsgemeinschaft [HE5183/2-1]
NR 30
TC 118
Z9 132
U1 3
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 20
PY 2008
VL 456
IS 7220
BP 382
EP U45
DI 10.1038/nature07309
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600042
PM 18806777
DA 2026-03-09
ER

PT J
AU Pesaran, B
   Nelson, MJ
   Andersen, RA
AF Pesaran, Bijan
   Nelson, Matthew J.
   Andersen, Richard A.
TI Free choice activates a decision circuit between frontal and parietal cortex
SO NATURE
LA English
DT Article
ID neuronal-activity; premotor; synchronization; representation; performance; potentials; coherence; attention; selection; direction
AB We often face alternatives that we are free to choose between. Planning movements to select an alternative involves several areas in frontal and parietal cortex(1-11) that are anatomically connected into long-range circuits(12). These areas must coordinate their activity to select a common movement goal, but how neural circuits make decisions remains poorly understood. Here we simultaneously record from the dorsal premotor area (PMd) in frontal cortex and the parietal reach region (PRR) in parietal cortex to investigate neural circuit mechanisms for decision making. We find that correlations in spike and local field potential (LFP) activity between these areas are greater when monkeys are freely making choices than when they are following instructions. We propose that a decision circuit featuring a sub-population of cells in frontal and parietal cortex may exchange information to coordinate activity between these areas. Cells participating in this decision circuit may influence movement choices by providing a common bias to the selection of movement goals.
C1 [Pesaran, Bijan] NYU, Ctr Neural Sci, New York, NY 10003 USA.
   [Nelson, Matthew J.; Andersen, Richard A.] CALTECH, Computat & Neural Syst Program, Pasadena, CA 91125 USA.
   [Pesaran, Bijan; Andersen, Richard A.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
C3 New York University; California Institute of Technology; California Institute of Technology
RP Pesaran, B (corresponding author), NYU, Ctr Neural Sci, 550 1St Ave, New York, NY 10003 USA.
EM bijan@nyu.edu
FU NEI NIH HHS [R01 EY007492] Funding Source: Medline
NR 30
TC 343
Z9 406
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 15
PY 2008
VL 453
IS 7193
BP 406
EP U61
DI 10.1038/nature06849
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400055
PM 18418380
DA 2026-03-09
ER

PT J
AU Mili, S
   Moissoglu, K
   Macara, IG
AF Mili, Stavroula
   Moissoglu, Konstadinos
   Macara, Ian G.
TI Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions
SO NATURE
LA English
DT Article
ID adenomatous polyposis-coli; actin messenger-rna; drosophila oocytes; f-actin; localization; migration; microtubules; oskar; transport; membrane
AB RNA localization is important for the establishment and maintenance of polarity in multiple cell types. Localized RNAs are usually transported along microtubules or actin filaments(1) and become anchored at their destination to some underlying subcellular structure. Retention commonly involves actin or actin- associated proteins(2-7), although cytokeratin filaments and dynein anchor certain RNAs8,9. RNA localization is important for diverse processes ranging from cell fate determination to synaptic plasticity; however, so far there have been few comprehensive studies of localized RNAs in mammalian cells. Here we have addressed this issue, focusing on migrating fibroblasts that polarize to form a leading edge and a tail in a process that involves asymmetric distribution of RNAs10-12. We used a fractionation scheme(13) combined with microarrays to identify, on a genome- wide scale, RNAs that localize in protruding pseudopodia of mouse fibroblasts in response to migratory stimuli. We find that a diverse group of RNAs accumulates in such pseudopodial protrusions. Through their 39 untranslated regions these transcripts are anchored in granules concentrated at the plus ends of detyrosinated microtubules. RNAs in the granules associate with the adenomatous polyposis coli ( APC) tumour suppressor and the fragile X mental retardation protein ( FMRP). APC is required for the accumulation of transcripts in protrusions. Our results suggest a new type of RNA anchoring mechanism as well as a new, unanticipated function for APC in localizing RNAs.
C1 [Mili, Stavroula; Macara, Ian G.] Univ Virginia, Hlth Sci Ctr, Dept Microbiol, Ctr Cell Signaling, Charlottesville, VA 22908 USA.
   [Moissoglu, Konstadinos] Univ Virginia, Hlth Sci Ctr, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia
RP Macara, IG (corresponding author), Univ Virginia, Hlth Sci Ctr, Dept Microbiol, Ctr Cell Signaling, Charlottesville, VA 22908 USA.
EM sm2ju@virginia.edu; igm9c@virginia.edu
FU National Institute of General Medical Sciences [R01GM070902] Funding Source: NIH RePORTER; NIGMS NIH HHS [R01 GM070902] Funding Source: Medline
NR 30
TC 238
Z9 294
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 1
PY 2008
VL 453
IS 7191
BP 115
EP +
DI 10.1038/nature06888
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800050
PM 18451862
DA 2026-03-09
ER

PT J
AU Li, M
   Pernice, WHP
   Xiong, C
   Baehr-Jones, T
   Hochberg, M
   Tang, HX
AF Li, Mo
   Pernice, W. H. P.
   Xiong, C.
   Baehr-Jones, T.
   Hochberg, M.
   Tang, H. X.
TI Harnessing optical forces in integrated photonic circuits
SO NATURE
LA English
DT Article
ID bistability; systems; motion
AB The force exerted by photons is of fundamental importance in light matter interactions. For example, in free space, optical tweezers have been widely used to manipulate atoms and microscale dielectric particles(1,2). This optical force is expected to be greatly enhanced in integrated photonic circuits in which light is highly concentrated at the nanoscale(3,4). Harnessing the optical force on a semiconductor chip will allow solid state devices, such as electromechanical systems, to operate under new physical principles. Indeed, recent experiments have elucidated the radiation forces of light in highfinesse optical microcavities(5-7), but the large footprint of these devices ultimately prevents scaling down to nanoscale dimensions. Recent theoreticalwork has predicted that a transverse optical force can be generated and used directly for electromechanical actuation without the need for a high- finesse cavity(3). However, on- chip exploitation of this force has been a significant challenge, primarily owing to the lack of efficient nanoscale mechanical transducers in the photonics domain. Here we report the direct detection and exploitation of transverse optical forces in an integrated silicon photonic circuit through an embedded nanomechanical resonator. The nanomechanical device, a free-standing waveguide, is driven by the optical force and read out through evanescent coupling of the guided light to the dielectric substrate. This new optical force enables all- optical operation of nanomechanical systems on a CMOS ( complementary metal- oxide- semiconductor)- compatible platform, with substantial bandwidth and design flexibility compared to conventional electrical- based schemes.
C1 [Li, Mo; Pernice, W. H. P.; Xiong, C.; Tang, H. X.] Yale Univ, Dept Elect Engn, New Haven, CT 06511 USA.
   [Li, Mo; Pernice, W. H. P.; Xiong, C.; Tang, H. X.] Yale Univ, Dept Mech Engn, New Haven, CT 06511 USA.
   [Baehr-Jones, T.; Hochberg, M.] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA.
C3 Yale University; Yale University; University of Washington; University of Washington Seattle
RP Tang, HX (corresponding author), Yale Univ, Dept Elect Engn, New Haven, CT 06511 USA.
EM hong.tang@yale.edu
FU Alexander von Humboldt postdoctoral fellowship programme; Air Force Office of Scientific Research Young Investigator Program; NSF STC MDITR Center
NR 28
TC 436
Z9 504
U1 4
U2 214
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 480
EP U28
DI 10.1038/nature07545
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500033
PM 19037311
DA 2026-03-09
ER

PT J
AU Smits, ECP
   Mathijssen, SGJ
   van Hal, PA
   Setayesh, S
   Geuns, TCT
   Mutsaers, KAHA
   Cantatore, E
   Wondergem, HJ
   Werzer, O
   Resel, R
   Kemerink, M
   Kirchmeyer, S
   Muzafarov, AM
   Ponomarenko, SA
   de Boer, B
   Blom, PWM
   de Leeuw, DM
AF Smits, Edsger C. P.
   Mathijssen, Simon G. J.
   van Hal, Paul A.
   Setayesh, Sepas
   Geuns, Thomas C. T.
   Mutsaers, Kees A. H. A.
   Cantatore, Eugenio
   Wondergem, Harry J.
   Werzer, Oliver
   Resel, Roland
   Kemerink, Martijn
   Kirchmeyer, Stephan
   Muzafarov, Aziz M.
   Ponomarenko, Sergei A.
   de Boer, Bert
   Blom, Paul W. M.
   de Leeuw, Dago M.
TI Bottom-up organic integrated circuits
SO NATURE
LA English
DT Article
ID thin-film transistors; self-assembled monolayers; field-effect transistors; semiconductors; mobility
AB Self- assembly - the autonomous organization of components into patterns and structures(1) - is a promising technology for the mass production of organic electronics. Making integrated circuits using a bottom- up approach involving self- assembling molecules was proposed(2) in the 1970s. The basic building block of such an integrated circuit is the self- assembled- monolayer field- effect transistor ( SAMFET), where the semiconductor is a monolayer spontaneously formed on the gate dielectric. In the SAMFETs fabricated so far, current modulation has only been observed in submicrometre channels(3-5), the lack of efficient charge transport in longer channels being due to defects and the limited intermolecular pi-pi coupling between the molecules in the self-assembled monolayers. Low field- effect carrier mobility, low yield and poor reproducibility have prohibited the realization of bottom- up integrated circuits. Here we demonstrate SAMFETs with long- range intermolecular pi - pi coupling in the monolayer. We achieve dense packing by using liquid- crystalline molecules consisting of a pi- conjugated mesogenic core separated by a long aliphatic chain from a monofunctionalized anchor group. The resulting SAMFETs exhibit a bulk- like carrier mobility, large current modulation and high reproducibility. As a first step towards functional circuits, we combine the SAMFETs into logic gates as inverters; the small parameter spread then allows us to combine the inverters into ring oscillators. We demonstrate real logic functionality by constructing a 15- bit code generator in which hundreds of SAMFETs are addressed simultaneously. Bridging the gap between discrete monolayer transistors and functional self-assembled integrated circuits puts bottom- up electronics in a new perspective.
C1 [Kirchmeyer, Stephan] HC Starck GmbH, D-51368 Leverkusen, Germany.
   [Smits, Edsger C. P.; de Boer, Bert; Blom, Paul W. M.; de Leeuw, Dago M.] Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
   [Smits, Edsger C. P.; Mathijssen, Simon G. J.; van Hal, Paul A.; Setayesh, Sepas; Geuns, Thomas C. T.; Mutsaers, Kees A. H. A.; Wondergem, Harry J.; de Leeuw, Dago M.] Philips Res Labs, NL-5656 AE Eindhoven, Netherlands.
   [Smits, Edsger C. P.] Dutch Polymer Inst, NL-5600 AX Eindhoven, Netherlands.
   [Mathijssen, Simon G. J.; Kemerink, Martijn] Eindhoven Univ Technol, Dept Appl Phys, NL-5600 MB Eindhoven, Netherlands.
   [Cantatore, Eugenio] Eindhoven Univ Technol, Mixed Signal Microelect Grp, Dept Elect Engn, NL-5600 MB Eindhoven, Netherlands.
   [Werzer, Oliver; Resel, Roland] Graz Univ Technol, Inst Solid State Phys, A-8010 Graz, Austria.
   [Muzafarov, Aziz M.; Ponomarenko, Sergei A.] Russian Acad Sci, Enikolopov Inst Synth Polymer Mat, Moscow 117393, Russia.
C3 University of Groningen; Philips; Philips Research; Dutch Polymer Institute; Eindhoven University of Technology; Eindhoven University of Technology; Graz University of Technology; Russian Academy of Sciences; Enikolopov Institute of Synthetic Polymeric Materials, Russian Academy of Sciences
RP Kirchmeyer, S (corresponding author), HC Starck GmbH, Chemiepk Leverkusen,Bldg B202, D-51368 Leverkusen, Germany.
EM stephan.kirchmeyer@hcstarck.com; dago.de.leeuw@philips.com
FU Dutch Polymer Institute [project 516]; EU project NAIMO [NMP4-CT-2004-500355]; Dutch Technology Foundation STW; Austrian Science Foundation
NR 20
TC 350
Z9 397
U1 0
U2 246
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 956
EP 959
DI 10.1038/nature07320
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300047
DA 2026-03-09
ER

PT J
AU Ladet, S
   David, L
   Domard, A
AF Ladet, Sebastien
   David, Laurent
   Domard, Alain
TI Multi-membrane hydrogels
SO NATURE
LA English
DT Article
ID physical hydrogels; hydroalcoholic medium; acetylated chitosans; aqueous-solution; transition; gels
AB Polysaccharide- based hydrogels are useful for numerous applications, from food(1) and cosmetic processing to drug delivery and tissue engineering(2,3). The formation of hydrogels from polyelectrolyte solutions is complex, involving a variety of molecular interactions. The physical gelation of polysaccharides can be achieved by balancing solvophobic and solvophilic interactions(4). Polymer chain reorganization can be obtained by solvent exchange, one of the processing routes forming a simple hydrogel assembly. Nevertheless, many studies on hydrogel formation are empirical with a limited understanding of the mechanisms involved, delaying the processing of more complex structures. Here we use a multi- step interrupted gelation process in controlled physico- chemical conditions to generate complex hydrogels with multi- membrane 'onion-like' architectures. Our approach greatly simplifies the processing of gels with complex shapes and a multi- membrane organization. In contrast with existing assemblies described in the literature, our method allows the formation of free 'inter-membrane' spaces well suited for cell or drug introduction. These architectures, potentially useful in biomedical applications, open interesting perspectives by taking advantage of tailor- made three- dimensional multimembrane tubular or spherical structures.
C1 [Ladet, Sebastien; David, Laurent; Domard, Alain] Univ Lyon 1, CNRS, Polymer Mat Polymeres & Biomat, UMR 5223, F-69622 Villeurbanne, France.
C3 Institut National des Sciences Appliquees de Lyon - INSA Lyon; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite Jean Monnet; Universite Lyon 1
RP David, L (corresponding author), Univ Lyon 1, CNRS, Polymer Mat Polymeres & Biomat, UMR 5223, 15 Blvd A Latarjet,Batiment ISTIL, F-69622 Villeurbanne, France.
EM laurent.david@univ-lyon1.fr; alain.domard@univ-lyon1.fr
NR 22
TC 482
Z9 537
U1 3
U2 627
PU 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 6
PY 2008
VL 452
IS 7183
BP 76
EP U6
DI 10.1038/nature06619
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900049
PM 18322531
DA 2026-03-09
ER

PT J
AU Strukov, DB
   Snider, GS
   Stewart, DR
   Williams, RS
AF Strukov, Dmitri B.
   Snider, Gregory S.
   Stewart, Duncan R.
   Williams, R. Stanley
TI The missing memristor found
SO NATURE
LA English
DT Article
ID memory; resistance; reduction
AB Anyone who ever took an electronics laboratory class will be familiar with the fundamental passive circuit elements: the resistor, the capacitor and the inductor. However, in 1971 Leon Chua reasoned from symmetry arguments that there should be a fourth fundamental element, which he called a memristor ( short for memory resistor)(1). Although he showed that such an element has many interesting and valuable circuit properties, until now no one has presented either a useful physical model or an example of a memristor. Here we show, using a simple analytical example, that memristance arises naturally in nanoscale systems in which solid- state electronic and ionic transport are coupled under an external bias voltage. These results serve as the foundation for understanding a wide range of hysteretic current - voltage behaviour observed in many nanoscale electronic devices(2-19) that involve the motion of charged atomic or molecular species, in particular certain titanium dioxide cross- point switches(20-22).
C1 [Strukov, Dmitri B.; Snider, Gregory S.; Stewart, Duncan R.; Williams, R. Stanley] HP Labs, Palo Alto, CA 94304 USA.
C3 Hewlett-Packard
RP Williams, RS (corresponding author), HP Labs, 1501 Page Mill Rd, Palo Alto, CA 94304 USA.
EM stan.williams@hp.com
NR 26
TC 9480
Z9 10639
U1 163
U2 3248
PU NATURE PUBLISHING 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 1
PY 2008
VL 453
IS 7191
BP 80
EP 83
DI 10.1038/nature06932
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800042
PM 18451858
DA 2026-03-09
ER

PT J
AU Barna, M
   Pusic, A
   Zollo, O
   Costa, M
   Kondrashov, N
   Rego, E
   Rao, PH
   Ruggero, D
AF Barna, Maria
   Pusic, Aya
   Zollo, Ornella
   Costa, Maria
   Kondrashov, Nadya
   Rego, Eduardo
   Rao, Pulivarthi H.
   Ruggero, Davide
TI Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency
SO NATURE
LA English
DT Article
ID kinase gene-complex; c-myc; cell-cycle; mediated translation; entry site; cancer; 1p36; tumorigenesis; cytokinesis; contributes
AB The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA(1,2). Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in E mu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc- overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a new mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective messenger RNAs. We show that an aberrant increase in cap- dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site ( IRES)- dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic- specific expression of the endogenous IRES- dependent form of Cdk11 ( also known as Cdc21 and PITSLRE)(3-5), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in E mu-Myc/+ mice. When accurate translational control is re- established in E mu-Myc/+ mice, genome instability is suppressed. Our findings demonstrate how perturbations in translational control provide a highly specific outcome for gene expression, genome stability and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post- genomic level.
C1 [Barna, Maria; Kondrashov, Nadya] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Pusic, Aya; Zollo, Ornella; Costa, Maria; Ruggero, Davide] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Sch Med, San Francisco, CA 94158 USA.
   [Pusic, Aya; Zollo, Ornella; Costa, Maria; Ruggero, Davide] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Urol, San Francisco, CA 94158 USA.
   [Rego, Eduardo] Univ Sao Paulo, Ctr Cell Based Therapy, Fdn Hemoctr Ribeirao Preto, BR-14048900 Sao Paulo, Brazil.
   [Rao, Pulivarthi H.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 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; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; Universidade de Sao Paulo; Baylor College of Medicine
RP Barna, M (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, Rock Hall Room 384C,1550 4th St, San Francisco, CA 94158 USA.
EM maria.barna@ucsf.edu; Davide.Ruggero@ucsf.edu
FU NIH; Sandler Foundation
NR 35
TC 357
Z9 420
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 971
EP U79
DI 10.1038/nature07449
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300050
PM 19011615
DA 2026-03-09
ER

PT J
AU Dial, KP
   Jackson, BE
   Segre, P
AF Dial, Kenneth P.
   Jackson, Brandon E.
   Segre, Paolo
TI A fundamental avian wing-stroke provides a new perspective on the evolution of flight
SO NATURE
LA English
DT Article
ID maneuvering flight; wide-range; origin; aerodynamics; kinematics; birds
AB The evolution of avian flight remains one of biology's major controversies, with a long history of functional interpretations of fossil forms given as evidence for either an arboreal or cursorial origin of flight. Despite repeated emphasis on the 'wing-stroke' as a necessary avenue of investigation for addressing the evolution of flight(1-4), no empirical data exist on wing-stroke dynamics in an experimental evolutionary context. Here we present the first comparison of wing-stroke kinematics of the primary locomotor modes (descending flight and incline flap- running) that lead to level- flapping flight in juvenile ground birds throughout development (Fig. 1). We offer results that are contrary both to popular perception and inferences from other studies(5-7). Starting shortly after hatching and continuing through adulthood, ground birds use a wing- stroke confined to a narrow range of less than 20 degrees, when referenced to gravity, that directs aerodynamic forces about 40 degrees above horizontal, permitting a 180 degrees range in the direction of travel. Based on our results, we put forth an ontogenetic- transitional wing hypothesis that posits that the incremental adaptive stages leading to the evolution of avian flight correspond behaviourally and morphologically to transitional stages observed in ontogenetic forms.
C1 [Dial, Kenneth P.; Jackson, Brandon E.; Segre, Paolo] Univ Montana, Div Biol Sci, Flight Lab, Missoula, MT 59812 USA.
C3 University of Montana System; University of Montana
RP Dial, KP (corresponding author), Univ Montana, Div Biol Sci, Flight Lab, 32 Campus Dr, Missoula, MT 59812 USA.
EM kdial@mso.umt.edu
NR 25
TC 76
Z9 96
U1 4
U2 131
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 985
EP U3
DI 10.1038/nature06517
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100047
PM 18216784
DA 2026-03-09
ER

PT J
AU Ip, SCY
   Rass, U
   Blanco, MG
   Flynn, HR
   Skehel, JM
   West, SC
AF Ip, Stephen C. Y.
   Rass, Ulrich
   Blanco, Miguel G.
   Flynn, Helen R.
   Skehel, J. Mark
   West, Stephen C.
TI Identification of Holliday junction resolvases from humans and yeast
SO NATURE
LA English
DT Article
ID escherichia-coli; saccharomyces-cerevisiae; mus81/mms4 endonuclease; flap endonuclease-1; mammalian-cells; gene conversion; nuclease family; crossing-over; in-vitro; recombination
AB Four-way DNA intermediates, also known as Holliday junctions, are formed during homologous recombination and DNA repair, and their resolution is necessary for proper chromosome segregation. Here we identify nucleases from Saccharomyces cerevisiae and human cells that promote Holliday junction resolution, in a manner analogous to that shown by the Escherichia coli Holliday junction resolvase RuvC. The human Holliday junction resolvase, GEN1, and its yeast orthologue, Yen1, were independently identified using two distinct experimental approaches: GEN1 was identified by mass spectrometry following extensive fractionation of HeLa cell- free extracts, whereas Yen1 was detected by screening a yeast gene fusion library for nucleases capable of Holliday junction resolution. The eukaryotic Holliday junction resolvases represent a new subclass of the Rad2/ XPG family of nucleases. Recombinant GEN1 and Yen1 resolve Holliday junctions by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated.
C1 [Ip, Stephen C. Y.; Rass, Ulrich; Blanco, Miguel G.; West, Stephen C.] Clare Hall Labs, London Res Inst, Canc Res UK, Genet Recombinat Lab, S Mimms EN6 3LD, Herts, England.
   [Flynn, Helen R.; Skehel, J. Mark] Clare Hall Labs, London Res Inst, Canc Res UK, Prot Anal & Proteom Lab, S Mimms EN6 3LD, Herts, England.
C3 Cancer Research UK; Cancer Research UK
RP West, SC (corresponding author), Clare Hall Labs, London Res Inst, Canc Res UK, Genet Recombinat Lab, S Mimms EN6 3LD, Herts, England.
EM stephen.west@cancer.org.uk
FU Cancer Research UK; Louis-Jeantet Foundation; EU DNA Repair Consortium; Croucher Foundation; Xunta de Galicia; Spanish Ministry of Education
NR 43
TC 323
Z9 442
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 20
PY 2008
VL 456
IS 7220
BP 357
EP U39
DI 10.1038/nature07470
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600036
PM 19020614
DA 2026-03-09
ER

PT J
AU Mou, XZ
   Sun, SL
   Edwards, RA
   Hodson, RE
   Moran, MA
AF Mou, Xiaozhen
   Sun, Shulei
   Edwards, Robert A.
   Hodson, Robert E.
   Moran, Mary Ann
TI Bacterial carbon processing by generalist species in the coastal ocean
SO NATURE
LA English
DT Article
ID marine; genes; bacterioplankton; assemblages; sequence; identification; biogeography; community; mortality; evolution
AB The assimilation and mineralization of dissolved organic carbon ( DOC) by marine bacterioplankton is a major process in the ocean carbon cycle(1). However, little information exists on the specific metabolic functions of participating bacteria and on whether individual taxa specialize on particular components of the marine DOC pool(2). Here we use experimental metagenomics to show that coastal communities are populated by taxa capable of metabolizing a wide variety of organic carbon compounds. Genomic DNA captured from bacterial community subsets metabolizing a single model component of the DOC pool ( either dimethylsulphoniopropionate or vanillate) showed substantial overlap in gene composition as well as a diversity of carbon- processing capabilities beyond the selected phenotypes. Our direct measure of niche breadth for bacterial functional assemblages indicates that, in accordance with ecological theory, heterogeneity in the composition and supply of organic carbon to coastal oceans may favour generalist bacteria. In the important interplay between microbial community structure and biogeochemical cycling, coastal heterotrophic communities may be controlled less by transient changes in the carbon reservoir that they process and more by factors such as trophic interactions and physical conditions.
C1 [Mou, Xiaozhen; Sun, Shulei; Hodson, Robert E.; Moran, Mary Ann] Univ Georgia, Dept Marine Sci, Athens, GA 30602 USA.
   [Edwards, Robert A.] San Diego State Univ, Dept Comp Sci, San Diego, CA 92182 USA.
C3 University System of Georgia; University of Georgia; California State University System; San Diego State University
RP Moran, MA (corresponding author), Univ Georgia, Dept Marine Sci, Athens, GA 30602 USA.
EM mmoran@uga.edu
NR 37
TC 238
Z9 284
U1 1
U2 144
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 708
EP U4
DI 10.1038/nature06513
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500039
PM 18223640
DA 2026-03-09
ER

PT J
AU Liu, HT
   Lalanne, P
AF Liu, Haitao
   Lalanne, Philippe
TI Microscopic theory of the extraordinary optical transmission
SO NATURE
LA English
DT Article
ID subwavelength hole arrays; evanescent-wave model; surface-plasmons; diffraction; resonance; field
AB The phenomenon of extraordinary light transmission through metallic films perforated by nanohole arrays at optical frequencies was first observed a decade ago(1) and initiated important further experimental and theoretical work. In view of potential applications of such structures-for example, subwavelength optics(2,3), optoelectronics devices(4,5), and chemical sensing(6) - it is important to understand the underlying physical processes in detail. Here we derive a microscopic theory of the transmission through subwavelength hole arrays, by considering the elementary processes associated with scattering of surface-plasmon-polariton (SPP) modes by individual one-dimensional chains of subwavelength holes. Using a SPP coupled-mode model that coherently gathers these elementary processes, we derive analytical expressions for all the transmission spectrum characteristics - such as the resonance wavelength, the peak transmission and the anti-resonance. Further comparisons of the model predictions with fully vectorial computational results allow us quantitatively to check the model accuracy and to discuss the respective impacts of SPP modes and of other electromagnetic fields on producing the extraordinary transmission of light. The model greatly expands our understanding of the phenomenon and may affect further engineering of nanoplasmonic devices.
C1 [Liu, Haitao; Lalanne, Philippe] Univ Paris Sud, Lab Charles Fabry, Inst Opt, CNRS, F-91127 Palaiseau, France.
   [Liu, Haitao] Nankai Univ, Key Lab Optoelect Informat Sci & Technol, Minist Educ, Inst Modern Opt, Tianjin 300071, Peoples R China.
C3 Universite Paris Saclay; Institut Polytechnique de Paris; Ecole Polytechnique; Centre National de la Recherche Scientifique (CNRS); Nankai University
RP Lalanne, P (corresponding author), Univ Paris Sud, Lab Charles Fabry, Inst Opt, CNRS, Campus Polytech,RD 128, F-91127 Palaiseau, France.
EM philippe.lalanne@institutoptique.fr
NR 25
TC 631
Z9 712
U1 10
U2 429
PU 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 10
PY 2008
VL 452
IS 7188
BP 728
EP 731
DI 10.1038/nature06762
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500040
PM 18401405
DA 2026-03-09
ER

PT J
AU Gruber, N
   Galloway, JN
AF Gruber, Nicolas
   Galloway, James N.
TI An Earth-system perspective of the global nitrogen cycle
SO NATURE
LA English
DT Article
ID carbon-cycle; denitrification; terrestrial
AB With humans having an increasing impact on the planet, the interactions between the nitrogen cycle, the carbon cycle and climate are expected to become an increasingly important determinant of the Earth system.
C1 [Gruber, Nicolas] ETH, Inst Biogeochem & Pollutant Dynam, Environm Phys Grp, CH-8092 Zurich, Switzerland.
   [Galloway, James N.] Univ Virginia, Dept Environm Sci, Charlottesville, VA 22904 USA.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Virginia
RP Gruber, N (corresponding author), ETH, Inst Biogeochem & Pollutant Dynam, Environm Phys Grp, Univ Str 16, CH-8092 Zurich, Switzerland.
EM nicolas.gruber@env.ethz.ch
NR 23
TC 2788
Z9 3435
U1 99
U2 2742
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 293
EP 296
DI 10.1038/nature06592
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100039
PM 18202647
DA 2026-03-09
ER

PT J
AU Veldhoen, M
   Hirota, K
   Westendorf, AM
   Buer, J
   Dumoutier, L
   Renauld, JC
   Stockinger, B
AF Veldhoen, Marc
   Hirota, Keiji
   Westendorf, Astrid M.
   Buer, Jan
   Dumoutier, Laure
   Renauld, Jean-Christophe
   Stockinger, Brigitta
TI The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
SO NATURE
LA English
DT Article
ID nf-kappa-b; ah receptor; th17 cells; mice lacking; differentiation; interleukin-22; il-22; encephalomyelitis; inflammation; hepatocytes
AB The aryl hydrocarbon receptor ( AHR) is a ligand- dependent transcription factor best known for mediating the toxicity of dioxin(1). Environmental factors are believed to contribute to the increased prevalence of autoimmune diseases, many of which are due to the activity of T(H)17 T cells, a new helper T- cell subset characterized by the production of the cytokine IL- 17. Here we show that in the CD4(+) T- cell lineage of mice AHR expression is restricted to the T(H)17 cell subset and its ligation results in the production of the T(H)17 cytokine interleukin ( IL)- 22. AHR is also expressed in human T(H)17 cells. Activation of AHR by a high-affinity ligand during T(H)17 cell development markedly increases the proportion of T(H)17 T cells and their production of cytokines. CD4(+) T cells from AHR- deficient mice can develop T(H)17 cell responses, but when confronted with AHR ligand fail to produce IL- 22 and do not show enhanced T(H)17 cell development. AHR activation during induction of experimental autoimmune encephalomyelitis causes accelerated onset and increased pathology in wild- type mice, but not AHR- deficient mice. AHR ligands may therefore represent co- factors in the development of autoimmune diseases.
C1 [Veldhoen, Marc; Hirota, Keiji; Stockinger, Brigitta] Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England.
   [Westendorf, Astrid M.; Buer, Jan] Univ Hosp Essen, Inst Med Microbiol, D-45122 Essen, Germany.
   [Westendorf, Astrid M.] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany.
   [Dumoutier, Laure; Renauld, Jean-Christophe] Ludwig Inst Canc Res, Brussels Branch, B-1200 Brussels, Belgium.
   [Dumoutier, Laure; Renauld, Jean-Christophe] Catholic Univ Louvain, Expt Med Unit, B-1200 Brussels, Belgium.
C3 MRC National Institute for Medical Research; University of Duisburg Essen; Helmholtz Association; Helmholtz-Center for Infection Research; Ludwig Institute for Cancer Research; Universite Catholique Louvain
RP Stockinger, B (corresponding author), Natl Inst Med Res, MRC, Div Mol Immunol, Ridgeway,Mill Hill, London NW7 1AA, England.
EM bstocki@nimr.mrc.ac.uk
FU Medical Research Council Funding Source: Medline
NR 30
TC 1341
Z9 1613
U1 3
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 1
PY 2008
VL 453
IS 7191
BP 106
EP +
DI 10.1038/nature06881
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800048
PM 18362914
DA 2026-03-09
ER

PT J
AU Fuller, BG
   Lampson, MA
   Foley, EA
   Rosasco-Nitcher, S
   Le, KV
   Tobelmann, P
   Brautigan, DL
   Stukenberg, PT
   Kapoor, TM
AF Fuller, Brian G.
   Lampson, Michael A.
   Foley, Emily A.
   Rosasco-Nitcher, Sara
   Le, Kim V.
   Tobelmann, Page
   Brautigan, David L.
   Stukenberg, P. Todd
   Kapoor, Tarun M.
TI Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient
SO NATURE
LA English
DT Article
ID in-situ; spindle; microtubules; cytokinesis; cleavage; reveals
AB Proper partitioning of the contents of a cell between two daughters requires integration of spatial and temporal cues. The anaphase array of microtubules that self-organize at the spindle midzone contributes to positioning the cell-division plane midway between the segregating chromosomes(1). How this signalling occurs over length scales of micrometres, from the midzone to the cell cortex, is not known. Here we examine the anaphase dynamics of protein phosphorylation by aurora B kinase, a key mitotic regulator, using fluorescence resonance energy transfer (FRET)-based sensors in living HeLa cells and immunofluorescence of native aurora B substrates. Quantitative analysis of phosphorylation dynamics, using chromosome- and centromere-targeted sensors, reveals that changes are due primarily to position along the division axis rather than time. These dynamics result in the formation of a spatial phosphorylation gradient early in anaphase that is centred at the spindle midzone. This gradient depends on aurora B targeting to a subpopulation of microtubules that activate it. Aurora kinase activity organizes the targeted microtubules to generate a structure-based feedback loop. We propose that feedback between aurora B kinase activation and midzone microtubules generates a gradient of post-translational marks that provides spatial information for events in anaphase and cytokinesis.
C1 [Fuller, Brian G.; Rosasco-Nitcher, Sara; Tobelmann, Page; Stukenberg, P. Todd] Univ Virginia, Sch Med, Dept Biochem, Charlottesville, VA 22908 USA.
   [Fuller, Brian G.; Rosasco-Nitcher, Sara; Tobelmann, Page; Stukenberg, P. Todd] Univ Virginia, Sch Med, Dept Mol Genet, Charlottesville, VA 22908 USA.
   [Lampson, Michael A.; Le, Kim V.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Foley, Emily A.; Kapoor, Tarun M.] Rockefeller Univ, Lab Chem & Cell Biol, New York, NY 10021 USA.
   [Brautigan, David L.] Univ Virginia, Sch Med, Ctr Cell Signaling, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Pennsylvania; Rockefeller University; University of Virginia
RP Stukenberg, PT (corresponding author), Univ Virginia, Sch Med, Dept Biochem, Charlottesville, VA 22908 USA.
EM lampson@sas.upenn.edu; pts7h@virginia.edu
FU NIGMS NIH HHS [R01 GM063045, R01 GM083988, R01 GM065933] Funding Source: Medline
NR 27
TC 298
Z9 375
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 JUN 19
PY 2008
VL 453
IS 7198
BP 1132
EP U14
DI 10.1038/nature06923
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900063
PM 18463638
DA 2026-03-09
ER

PT J
AU Kump, LR
AF Kump, Lee R.
TI The rise of atmospheric oxygen
SO NATURE
LA English
DT Article
ID mass-independent fractionation; sulfur; evolution; earth
AB Clues from ancient rocks are helping to produce a coherent picture of how Earth's atmosphere changed from one that was almost devoid of oxygen to one that is one- fifth oxygen.
C1 Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Kump, LR (corresponding author), Penn State Univ, Dept Geosci, 535 Deike Bldg, University Pk, PA 16802 USA.
EM lkump@psu.edu
NR 21
TC 366
Z9 458
U1 3
U2 232
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 277
EP 278
DI 10.1038/nature06587
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100034
PM 18202642
DA 2026-03-09
ER

PT J
AU Turner, M
   Golovko, VB
   Vaughan, OPH
   Abdulkin, P
   Berenguer-Murcia, A
   Tikhov, MS
   Johnson, BFG
   Lambert, RM
AF Turner, Mark
   Golovko, Vladimir B.
   Vaughan, Owain P. H.
   Abdulkin, Pavel
   Berenguer-Murcia, Angel
   Tikhov, Mintcho S.
   Johnson, Brian F. G.
   Lambert, Richard M.
TI Selective oxidation with dioxygen by gold nanoparticle catalysts derived from 55-atom clusters
SO NATURE
LA English
DT Article
ID supported metal-clusters; heterogeneous catalysts; molecular-oxygen; epoxidation; styrene; size; hydrogenation; mechanism
AB Supported gold nanoparticles have excited much interest owing to their unusual and somewhat unexpected catalytic properties(1-7), but the origin of the catalytic activity is still not fully understood. Experimental work(4) on gold particles supported on a titanium dioxide ( 110) single- crystal surface has established a striking size threshold effect associated with a metal- to- insulator transition, with gold particles catalytically active only if their diameters fall below similar to 3.5 nm. However, the remarkable catalytic behaviour might also in part arise from strong electronic interaction between the gold and the titanium dioxide support(2,3,5). In the case of industrially important selective oxidation reactions, explanation of the effectiveness of gold nanoparticle catalysts is complicated by the need for additives to drive the reaction(5,7,8), and/or the presence of strong support interactions and incomplete understanding of their possible catalytic role(1-3,5). Here we show that very small gold entities (similar to 1.4 nm) derived from 55- atom gold clusters and supported on inert materials are efficient and robust catalysts for the selective oxidation of styrene by dioxygen. We find a sharp size threshold in catalytic activity, in that particles with diameters of similar to 2 nm and above are completely inactive. Our observations suggest that catalytic activity arises from the altered electronic structure intrinsic to small gold nanoparticles, and that the use of 55- atom gold clusters may prove a viable route to the synthesis of robust gold catalysts suited to practical application.
C1 [Turner, Mark; Golovko, Vladimir B.; Vaughan, Owain P. H.; Abdulkin, Pavel; Berenguer-Murcia, Angel; Tikhov, Mintcho S.; Johnson, Brian F. G.; Lambert, Richard M.] Univ Cambridge, Chem Lab, Cambridge CB2 1EW, England.
C3 University of Cambridge
RP Lambert, RM (corresponding author), Univ Cambridge, Chem Lab, Cambridge CB2 1EW, England.
EM rml1@cam.ac.uk
FU UK Engineering and Physical Sciences Research Council; King's College, Cambridge
NR 29
TC 1231
Z9 1347
U1 3
U2 1000
PU NATURE PUBLISHING 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 21
PY 2008
VL 454
IS 7207
BP 981
EP U31
DI 10.1038/nature07194
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000035
PM 18719586
DA 2026-03-09
ER

PT J
AU Quintana, E
   Shackleton, M
   Sabel, MS
   Fullen, DR
   Johnson, TM
   Morrison, SJ
AF Quintana, Elsa
   Shackleton, Mark
   Sabel, Michael S.
   Fullen, Douglas R.
   Johnson, Timothy M.
   Morrison, Sean J.
TI Efficient tumour formation by single human melanoma cells
SO NATURE
LA English
DT Article
ID cancer stem-cells; acute myeloid-leukemia; nod/scid mice; lymphoblastic-leukemia; malignant-melanoma; basement-membrane; initiating cells; liver metastasis; progenitor cells; cd122(+) cells
AB A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells ( 0.1 - 0.0001%) form tumours when transplanted into non- obese diabetic/ severe combined immunodeficiency ( NOD/ SCID) mice. However, the extent to which NOD/ SCID mice underestimate the frequency of tumorigenic human cancer cells has been uncertain. Here we show that modified xenotransplantation assay conditions, including the use of more highly immunocompromised NOD/ SCID interleukin- 2 receptor gamma chain null (Il2rg(-/-)) mice, can increase the detection of tumorigenic melanoma cells by several orders of magnitude. In limiting dilution assays, approximately 25% of unselected melanoma cells from 12 different patients, including cells from primary and metastatic melanomas obtained directly from patients, formed tumours under these more permissive conditions. In single- cell transplants, an average of 27% of unselected melanoma cells from four different patients formed tumours. Modifications to xenotransplantation assays can therefore dramatically increase the detectable frequency of tumorigenic cells, demonstrating that they are common in some human cancers.
C1 [Quintana, Elsa; Shackleton, Mark; Morrison, Sean J.] Univ Michigan, Howard Hughes Med Inst, Inst Life Sci, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Quintana, Elsa; Shackleton, Mark; Morrison, Sean J.] Univ Michigan, Ctr Cell Biol, Ann Arbor, MI 48109 USA.
   [Sabel, Michael S.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
   [Fullen, Douglas R.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Johnson, Timothy M.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA.
C3 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; University of Michigan System; University of Michigan
RP Morrison, SJ (corresponding author), Univ Michigan, Howard Hughes Med Inst, Inst Life Sci, Dept Internal Med, Ann Arbor, MI 48109 USA.
EM seanjm@umich.edu
FU Howard Hughes Medical Institute; Allen H. Blondy Research Fellowship; Lewis and Lillian Becker; University of Michigan Comprehensive Cancer Center; National Institutes of Health [CA46592]; University of Michigan Flow Cytometry Core Facility; N. McAnsh and the University of Michigan Cancer Centre Histology Core; National Institute of Diabetes, Digestive, and Kidney Diseases [NIH5P60- DK20572]; Michigan Diabetes Research and Training Center; Spanish Ministry of Education; Marie Curie Outgoing International Fellowship from the European Commission; Australian National Health and Medical Research Council; Human Frontiers Science Program and Australia Post; National Cancer Institute [P30CA046592] Funding Source: NIH RePORTER
NR 43
TC 1436
Z9 1688
U1 1
U2 154
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 4
PY 2008
VL 456
IS 7222
BP 593
EP U33
DI 10.1038/nature07567
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000031
PM 19052619
DA 2026-03-09
ER

PT J
AU George, RE
   Sanda, T
   Hanna, M
   Fröhling, S
   Luther, W
   Zhang, JM
   Ahn, Y
   Zhou, WJ
   London, WB
   McGrady, P
   Xue, LQ
   Zozulya, S
   Gregor, VE
   Webb, TR
   Gray, NS
   Gilliland, DG
   Diller, L
   Greulich, H
   Morris, SW
   Meyerson, M
   Look, AT
AF George, Rani E.
   Sanda, Takaomi
   Hanna, Megan
   Frohling, Stefan
   Luther, William, II
   Zhang, Jianming
   Ahn, Yebin
   Zhou, Wenjun
   London, Wendy B.
   McGrady, Patrick
   Xue, Liquan
   Zozulya, Sergey
   Gregor, Vlad E.
   Webb, Thomas R.
   Gray, Nathanael S.
   Gilliland, D. Gary
   Diller, Lisa
   Greulich, Heidi
   Morris, Stephan W.
   Meyerson, Matthew
   Look, A. Thomas
TI Activating mutations in ALK provide a therapeutic target in neuroblastoma
SO NATURE
LA English
DT Article
ID anaplastic lymphoma kinase; high-risk neuroblastoma; eml4-alk fusion gene; cell lung-cancer; gefitinib; identification; inhibitor; transplantation; transformation; pleiotrophin
AB Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer(1). High- risk neuroblastomas are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal(2,3). Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non- synonymous sequence variations were identified in the kinase domain of ALK, of which three were somatic and two were germ line. The most frequent mutation, F1174L, was also identified in three different neuroblastoma cell lines. ALK complementary DNAs encoding the F1174L and R1275Q variants, but not the wild- type ALK cDNA, transformed interleukin-3-dependent murine haematopoietic Ba/F3 cells to cytokine-independent growth. Ba/F3 cells expressing these mutations were sensitive to the small- molecule inhibitor of ALK, TAE684 (ref. 4). Furthermore, two human neuroblastoma cell lines harbouring the F1174L mutation were also sensitive to the inhibitor. Cytotoxicity was associated with increased amounts of apoptosis as measured by TdT-mediated dUTP nick end labelling ( TUNEL). Short hairpin RNA (shRNA)- mediated knockdown of ALK expression in neuroblastoma cell lines with the F1174L mutation also resulted in apoptosis and impaired cell proliferation. Thus, activating alleles of the ALK receptor tyrosine kinase are present in primary neuroblastoma tumours and in established neuroblastoma cell lines, and confer sensitivity to ALK inhibition with small molecules, providing a molecular rationale for targeted therapy of this disease.
C1 [George, Rani E.; Sanda, Takaomi; Luther, William, II; Ahn, Yebin; Diller, Lisa; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Zhang, Jianming; Zhou, Wenjun; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Frohling, Stefan; Gilliland, D. Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [London, Wendy B.; McGrady, Patrick] Univ Florida, Childrens Oncol Grp Stat & Data Ctr, Gainesville, FL 32601 USA.
   [Xue, Liquan; Morris, Stephan W.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Xue, Liquan; Morris, Stephan W.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Webb, Thomas R.] St Jude Childrens Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA.
   [Zozulya, Sergey; Gregor, Vlad E.] ChemBridge Res Labs Inc, San Diego, CA 92127 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; State University System of Florida; University of Florida; Children's Oncology Group (COG); St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital
RP Look, AT (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM matthew_meyerson@dfci.harvard.edu; thomas_look@dfci.harvard.edu
FU National Institutes of Health; Friends for Life Neuroblastoma Fund; Children's Oncology Group; Alex's Lemonade Stand Foundation; NCI [CA69129]; Cancer Center Core [CA21765]; American Lebanese Syrian Associated Charities; St. Jude Children's Research Hospital; National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER
NR 27
TC 716
Z9 841
U1 0
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 975
EP 978
DI 10.1038/nature07397
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300052
PM 18923525
DA 2026-03-09
ER

PT J
AU Thingstad, TF
   Bellerby, RGJ
   Bratbak, G
   Borsheim, KY
   Egge, JK
   Heldal, M
   Larsen, A
   Neill, C
   Nejstgaard, J
   Norland, S
   Sandaa, RA
   Skjoldal, EF
   Tanaka, T
   Thyrhaug, R
   Töpper, B
AF Thingstad, T. F.
   Bellerby, R. G. J.
   Bratbak, G.
   Borsheim, K. Y.
   Egge, J. K.
   Heldal, M.
   Larsen, A.
   Neill, C.
   Nejstgaard, J.
   Norland, S.
   Sandaa, R. -A.
   Skjoldal, E. F.
   Tanaka, T.
   Thyrhaug, R.
   Topper, B.
TI Counterintuitive carbon-to-nutrient coupling in an Arctic pelagic ecosystem
SO NATURE
LA English
DT Article
ID algal-bacterial competition; organic-carbon; spring bloom; rates; phosphorus; limitation; marine; growth; accumulation; respiration
AB Predicting the ocean's role in the global carbon cycle requires an understanding of the stoichiometric coupling between carbon and growth- limiting elements in biogeochemical processes. A recent addition to such knowledge is that the carbon/nitrogen ratio of inorganic consumption and release of dissolved organic matter may increase in a high-CO2 world(1). This will, however, yield a negative feedback on atmospheric CO2 only if the extra organic material escapes mineralization within the photic zone. Here we show, in the context of an Arctic pelagic ecosystem, how the fate and effects of added degradable organic carbon depend critically on the state of the microbial food web. When bacterial growth rate was limited by mineral nutrients, extra organic carbon accumulated in the system. When bacteria were limited by organic carbon, however, addition of labile dissolved organic carbon reduced phytoplankton biomass and activity and also the rate at which total organic carbon accumulated, explained as the result of stimulated bacterial competition for mineral nutrients. This counterintuitive 'more organic carbon gives less organic carbon' effect was particularly pronounced in diatom- dominated systems where the carbon/ mineral nutrient ratio in phytoplankton production was high. Our results highlight how descriptions of present and future states of the oceanic carbon cycle require detailed understanding of the stoichiometric coupling between carbon and growth- limiting mineral nutrients in both autotrophic and heterotrophic processes.
C1 [Thingstad, T. F.; Bratbak, G.; Egge, J. K.; Heldal, M.; Larsen, A.; Nejstgaard, J.; Norland, S.; Sandaa, R. -A.; Skjoldal, E. F.; Thyrhaug, R.; Topper, B.] Univ Bergen, Dept Biol, N-5020 Bergen, Norway.
   [Bellerby, R. G. J.; Neill, C.] Bjerknes Ctr Climate Res, N-5007 Bergen, Norway.
   [Bellerby, R. G. J.] Univ Bergen, Inst Geophys, N-5007 Bergen, Norway.
   [Borsheim, K. Y.] Inst Marine Res, N-5817 Bergen, Norway.
   [Tanaka, T.] CNRS, Lab Oceanog & Biogeochim, UMR6535, F-13288 Marseille 09, France.
C3 University of Bergen; Bjerknes Centre for Climate Research; University of Bergen; Institute of Marine Research - Norway; Centre National de la Recherche Scientifique (CNRS)
RP Thingstad, TF (corresponding author), Univ Bergen, Dept Biol, Jahnebakken 5,POB 7800, N-5020 Bergen, Norway.
EM frede.thingstad@bio.uib.no
FU Research Council of Norway [175939/S30]; strategic institution project [158936/I10]; Bjerknes Centre of Climate Research Centre of Excellence [146003/V30, 178441/S40 Interact, 184860/S30 MERCLIM]; Norsk Hydro Produksjon AS [5404889]; Svalbard Science Forum as Arktisstipend
NR 32
TC 145
Z9 158
U1 3
U2 152
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 387
EP U37
DI 10.1038/nature07235
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200044
PM 18716617
DA 2026-03-09
ER

PT J
AU Santos, FC
   Santos, MD
   Pacheco, JM
AF Santos, Francisco C.
   Santos, Marta D.
   Pacheco, Jorge M.
TI Social diversity promotes the emergence of cooperation in public goods games
SO NATURE
LA English
DT Article
ID evolutionary dynamics; indirect reciprocity; networks; punishment; dilemmas; graphs
AB Humans often cooperate in public goods games(1-3) and situations ranging from family issues to global warming(4,5). However, evolutionary game theory predicts(4,6) that the temptation to forgo the public good mostly wins over collective cooperative action, and this is often also seen in economic experiments(7). Here we show how social diversity provides an escape from this apparent paradox. Up to now, individuals have been treated as equivalent in all respects(4,8), in sharp contrast with real- life situations, where diversity is ubiquitous. We introduce social diversity by means of heterogeneous graphs and show that cooperation is promoted by the diversity associated with the number and size of the public goods game in which each individual participates and with the individual contribution to each such game. When social ties follow a scale- free distribution(9), cooperation is enhanced whenever all individuals are expected to contribute a fixed amount irrespective of the plethora of public goods games in which they engage. Our results may help to explain the emergence of cooperation in the absence of mechanisms based on individual reputation and punishment(10-12). Combining social diversity with reputation and punishment will provide instrumental clues on the self- organization of social communities and their economical implications.
C1 [Santos, Marta D.; Pacheco, Jorge M.] Univ Lisbon, CFTC, ATP Grp, P-1649003 Lisbon, Portugal.
   [Santos, Francisco C.] Univ Libre Brussels, Comp & Decis Engn Dept, IRIDIA, B-1050 Brussels, Belgium.
   [Santos, Marta D.; Pacheco, Jorge M.] Univ Lisbon, Dept Fis, P-1649003 Lisbon, Portugal.
C3 Universidade de Lisboa; Universite Libre de Bruxelles; Universidade de Lisboa
RP Pacheco, JM (corresponding author), Univ Lisbon, CFTC, ATP Grp, Complexo Interdisciplinar,Av Prof Gama Pinto 2, P-1649003 Lisbon, Portugal.
EM pacheco@cii.fc.ul.pt
NR 30
TC 1218
Z9 1303
U1 11
U2 519
PU NATURE PUBLISHING 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 10
PY 2008
VL 454
IS 7201
BP 213
EP U49
DI 10.1038/nature06940
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900043
PM 18615084
DA 2026-03-09
ER

PT J
AU Chen, ZC
   Yang, HJ
   Pavletich, NP
AF Chen, Zhucheng
   Yang, Haijuan
   Pavletich, Nikola P.
TI Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structures
SO NATURE
LA English
DT Article
ID double-strand breaks; amino-acid-residues; dna-binding site; subunit interface; crystal-structure; protein; filaments; repair; rad51; complexes
AB The RecA family of ATPases mediates homologous recombination, a reaction essential for maintaining genomic integrity and for generating genetic diversity. RecA, ATP and single-stranded DNA (ssDNA) form a helical filament that binds to double-stranded DNA (dsDNA), searches for homology, and then catalyses the exchange of the complementary strand, producing a new heteroduplex. Here we have solved the crystal structures of the Escherichia coli RecA-ssDNA and RecA-heteroduplex filaments. They show that ssDNA and ATP bind to RecA-RecA interfaces cooperatively, explaining the ATP dependency of DNA binding. The ATP c-phosphate is sensed across the RecA-RecA interface by two lysine residues that also stimulate ATP hydrolysis, providing a mechanism for DNA release. The DNA is underwound and stretched globally, but locally it adopts a B-DNA-like conformation that restricts the homology search to Watson - Crick- type base pairing. The complementary strand interacts primarily through base pairing, making heteroduplex formation strictly dependent on complementarity. The underwound, stretched filament conformation probably evolved to destabilize the donor duplex, freeing the complementary strand for homology sampling.
C1 [Chen, Zhucheng; Yang, Haijuan; Pavletich, Nikola P.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10021 USA.
   [Pavletich, Nikola P.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA.
   [Chen, Zhucheng] Cornell Univ, Weill Med Coll, Dept Biochem & Struct Biol, New York, NY 10021 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute; Cornell University; Weill Cornell Medicine
RP Pavletich, NP (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, 1275 York Ave, New York, NY 10021 USA.
EM pavletin@mskcc.org
FU Howard Hughes Medical Institute Funding Source: Medline
NR 50
TC 578
Z9 738
U1 3
U2 125
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 489
EP U3
DI 10.1038/nature06971
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700035
PM 18497818
DA 2026-03-09
ER

PT J
AU Roati, G
   D'Errico, C
   Fallani, L
   Fattori, M
   Fort, C
   Zaccanti, M
   Modugno, G
   Modugno, M
   Inguscio, M
AF Roati, Giacomo
   D'Errico, Chiara
   Fallani, Leonardo
   Fattori, Marco
   Fort, Chiara
   Zaccanti, Matteo
   Modugno, Giovanni
   Modugno, Michele
   Inguscio, Massimo
TI Anderson localization of a non-interacting Bose-Einstein condensate
SO NATURE
LA English
DT Article
ID quantum diffusion; lattices; light; absence
AB Anderson localization of waves in disordered media was originally predicted(1) fifty years ago, in the context of transport of electrons in crystals(2). The phenomenon is much more general(3) and has been observed in a variety of systems, including light waves(4,5). However, Anderson localization has not been observed directly for matter waves. Owing to the high degree of control over most of the system parameters ( in particular the interaction strength), ultracold atoms offer opportunities for the study of disorder- induced localization(6). Here we use a non- interacting Bose - Einstein condensate to study Anderson localization. The experiment is performed with a one- dimensional quasi- periodic lattice - a system that features a crossover between extended and exponentially localized states, as in the case of purely random disorder in higher dimensions. Localization is clearly demonstrated through investigations of the transport properties and spatial and momentum distributions. We characterize the crossover, finding that the critical disorder strength scales with the tunnelling energy of the atoms in the lattice. This controllable system may be used to investigate the interplay of disorder and interaction ( ref. 7 and references therein), and to explore exotic quantum phases(8,9).
C1 [Roati, Giacomo; D'Errico, Chiara; Fallani, Leonardo; Fattori, Marco; Fort, Chiara; Zaccanti, Matteo; Modugno, Giovanni; Modugno, Michele; Inguscio, Massimo] Univ Florence, LENS, I-50019 Sesto Fiorentino, Italy.
   [Roati, Giacomo; D'Errico, Chiara; Fallani, Leonardo; Fattori, Marco; Fort, Chiara; Zaccanti, Matteo; Modugno, Giovanni; Modugno, Michele; Inguscio, Massimo] Univ Florence, Dept Fis, I-50019 Sesto Fiorentino, Italy.
   [Roati, Giacomo; D'Errico, Chiara; Fallani, Leonardo; Fattori, Marco; Fort, Chiara; Zaccanti, Matteo; Modugno, Giovanni; Inguscio, Massimo] INFM CNR, I-50019 Sesto Fiorentino, Italy.
   [Fattori, Marco] Ctr Studi Ric E Fermi, Museo Storico Fis, I-00184 Rome, Italy.
   [Modugno, Michele] Univ Florence, Dipartimento Matemat Applicata, I-50139 Florence, Italy.
   [Modugno, Michele] Univ Trent, BEC INFM Ctr, I-38050 Trento, Italy.
C3 University of Florence; University of Florence; Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale per la Fisica della Materia (INFM-CNR); University of Florence; University of Trento
RP Inguscio, M (corresponding author), Univ Florence, LENS, I-50019 Sesto Fiorentino, Italy.
EM inguscio@lens.unifi.it
NR 32
TC 1523
Z9 1645
U1 5
U2 157
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 895
EP U36
DI 10.1038/nature07071
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000037
PM 18548066
DA 2026-03-09
ER

PT J
AU Caro, G
   Bourdon, B
   Halliday, AN
   Quitté, G
AF Caro, Guillaume
   Bourdon, Bernard
   Halliday, Alex N.
   Quitte, Ghylaine
TI Super-chondritic Sm/Nd ratios in Mars, the Earth and the Moon
SO NATURE
LA English
DT Article
ID early differentiation; isotope systematics; martian meteorites; core formation; magma ocean; neodymium; evolution; samarium; heterogeneity; chronology
AB Small isotopic differences in the atomic abundance of neodymium-142 (Nd-142) in silicate rocks represent the time- averaged effect of decay of formerly live samarium- 146 (Sm-146) and provide constraints on the timescales and mechanisms by which planetary mantles first differentiated(1-4). This chronology, however, assumes that the composition of the total planet is identical to that of primitive undifferentiated meteorites called chondrites. The difference in the Nd-142/Nd-144 ratio between chondrites and terrestrial samples may therefore indicate very early isolation (<30Myr from the formation of the Solar System) of the upper mantle or a slightly non- chondritic bulk Earth composition(5,6). Here we present high-precision Nd-142 data for 16 martian meteorites and show that Mars also has a non- chondritic composition. Meteorites belonging to the shergottite subgroup define a planetary isochron yielding an age of differentiation of 40 +/- 18 Myr for the martian mantle. This isochron does not pass through the chondritic reference value ( 100 x epsilon Nd-142 = -21 +/- 3; Sm-147/Nd-144 = 0.1966)(6). The Earth, Moon and Mars all seem to have accreted in a portion of the inner Solar System with similar to 5 per cent higher Sm/Nd ratios than material accreted in the asteroid belt. Such chemical heterogeneities may have arisen from sorting of nebular solids or from impact erosion of crustal reservoirs in planetary precursors. The Nd-143 composition of the primitive mantle so defined by Nd-142 is strikingly similar to the putative endmember component 'FOZO' characterized by high He-3/He-4 ratios(7,8).
C1 [Caro, Guillaume] Univ Paris 07, Lab Geochim & Cosmochimie, Inst Phys Globe, F-75252 Paris 05, France.
   [Bourdon, Bernard] ETH, Inst Isotope Geochem & Mineral Resources, CH-8092 Zurich, Switzerland.
   [Halliday, Alex N.] Univ Oxford, Dept Earth Sci, Oxford OX1 3PR, England.
   [Quitte, Ghylaine] Ecole Normale Super Lyon, Lab Sci Terre, F-69364 Lyon 7, France.
C3 Universite Paris Cite; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Oxford; Ecole Normale Superieure de Lyon (ENS de LYON)
RP Caro, G (corresponding author), Univ Paris 07, Lab Geochim & Cosmochimie, Inst Phys Globe, 4 Pl Jussieu, F-75252 Paris 05, France.
EM caro@crpg.cnrs-nancy.fr
FU STFC [PP/D001250/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/D001250/1] Funding Source: researchfish
NR 30
TC 136
Z9 153
U1 1
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 336
EP 339
DI 10.1038/nature06760
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400043
PM 18354479
DA 2026-03-09
ER

PT J
AU Hopkins, M
   Harrison, TM
   Manning, CE
AF Hopkins, Michelle
   Harrison, T. Mark
   Manning, Craig E.
TI Low heat flow inferred from &gt;4 Gyr zircons suggests Hadean plate boundary interactions
SO NATURE
LA English
DT Article
ID jack-hills; western-australia; detrital zircons; ancient zircons; crust; ga; delta-o-18; tectonics; evolution; diamonds
AB The first similar to 600 million years of Earth history ( the 'Hadean' eon) remain poorly understood, largely because there is no rock record dating from that era. Detrital Hadean igneous zircons from the Jack Hills(1), Western Australia, however, can potentially provide insights into the conditions extant on our planet at that time. Results of geochemical investigations(2-13) using these ancient grains have been interpreted to suggest the presence of a hydrosphere(2-4,7,8) and continental crust(9,10) before 4Gyr. An underexploited characteristic of the >4 Gyr zircons is their diverse assemblage of mineral inclusions(14-17). Here we present an examination of over 400 Hadean zircons from Jack Hills, which shows that some inclusion assemblages are conducive to thermobarometry. Our thermobarometric analyses of 4.02 - 4.19- Gyr- old inclusion- bearing zircons constrain their magmatic formation conditions to about 700 degrees C and 7 kbar. This result implies a near- surface heat flow of similar to 75 mW m(-2), about three to five times lower than estimates of Hadean global heat flow. As the only site of magmatism on modern Earth that is characterized by heat flow of about one- quarter of the global average is above subduction zones, we suggest that the magmas from which the Jack Hills Hadean zircons crystallized were formed largely in an under thrust environment, perhaps similar to modern convergent margins.
C1 [Hopkins, Michelle; Harrison, T. Mark; Manning, Craig E.] Univ Calif Los Angeles, Inst Geophys & Planetary Phys, Los Angeles, CA 90095 USA.
   [Hopkins, Michelle; Harrison, T. Mark; Manning, Craig E.] Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Harrison, TM (corresponding author), Univ Calif Los Angeles, Inst Geophys & Planetary Phys, Los Angeles, CA 90095 USA.
EM tmh@oro.ess.ucla.edu
FU NSF [EAR-0635969]; ARC [DP0666497]; Instrumentation and Facilities Program of the National Science Foundation; Australian Research Council [DP0666497] Funding Source: Australian Research Council
NR 32
TC 250
Z9 297
U1 1
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 493
EP 496
DI 10.1038/nature07465
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500036
PM 19037314
DA 2026-03-09
ER

PT J
AU Swain, MR
   Vasisht, G
   Tinetti, G
AF Swain, Mark R.
   Vasisht, Gautam
   Tinetti, Giovanna
TI The presence of methane in the atmosphere of an extrasolar planet
SO NATURE
LA English
DT Article
ID light curves; spectra; dynamics; transit
AB Molecules present in the atmospheres of extrasolar planets are expected to influence strongly the balance of atmospheric radiation, to trace dynamical and chemical processes, and to indicate the presence of disequilibrium effects. As molecules have the potential to reveal atmospheric conditions and chemistry, searching for them is a high priority. The rotational - vibrational transition bands of water, carbon monoxide and methane are anticipated to be the primary sources of non- continuum opacity in hot- Jupiter planets(1-3). As these bands can overlap in wavelength, and the corresponding signatures from them are weak, decisive identification requires precision infrared spectroscopy. Here we report a near- infrared transmission spectrum of the planet HD 189733b that shows the presence of methane. Additionally, a resolved water vapour band at 1.9 mu m confirms the recent claim(4) of water in this object. On thermochemical grounds, carbon monoxide is expected to be abundant in the upper atmosphere of hot- Jupiter planets, but is not identifiable here; therefore the detection of methane rather than carbon monoxide in such a hot planet(5,6) could signal the presence of a horizontal chemical gradient away from the permanent dayside, or it may imply an ill- understood photochemical mechanism that leads to an enhancement of methane.
C1 [Swain, Mark R.; Vasisht, Gautam] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Tinetti, Giovanna] UCL, Dept Phys & Astron, London WC1E 6BT, England.
C3 National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of London; University College London
RP Swain, MR (corresponding author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
EM Mark.R.Swain@jpl.nasa.gov
NR 25
TC 473
Z9 535
U1 0
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 329
EP 331
DI 10.1038/nature06823
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400041
PM 18354477
DA 2026-03-09
ER

PT J
AU Christofk, HR
   Vander Heiden, MG
   Harris, MH
   Ramanathan, A
   Gerszten, RE
   Wei, R
   Fleming, MD
   Schreiber, SL
   Cantley, LC
AF Christofk, Heather R.
   Vander Heiden, Matthew G.
   Harris, Marian H.
   Ramanathan, Arvind
   Gerszten, Robert E.
   Wei, Ru
   Fleming, Mark D.
   Schreiber, Stuart L.
   Cantley, Lewis C.
TI The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
SO NATURE
LA English
DT Article
ID allosteric regulation; aerobic glycolysis; inhibition; cells
AB Many tumour cells have elevated rates of glucose uptake but reduced rates of oxidative phosphorylation. This persistence of high lactate production by tumours in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto Warburg more than 75 yr ago(1). How tumour cells establish this altered metabolic phenotype and whether it is essential for tumorigenesis is as yet unknown. Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase(2). Here we use short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell lines and replace it with pyruvate kinase M1. Switching pyruvate kinase expression to the M1 ( adult) isoform leads to reversal of the Warburg effect, as judged by reduced lactate production and increased oxygen consumption, and this correlates with a reduced ability to form tumours in nude mouse xenografts. These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo.
C1 [Christofk, Heather R.; Vander Heiden, Matthew G.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Harris, Marian H.; Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Ramanathan, Arvind; Gerszten, Robert E.; Wei, Ru; Schreiber, Stuart L.] Harvard Univ, Broad Inst, Chem Biol Program, Cambridge, MA 02142 USA.
   [Ramanathan, Arvind; Gerszten, Robert E.; Wei, Ru; Schreiber, Stuart L.] MIT, Cambridge, MA 02142 USA.
   [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA.
   [Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA.
   [Gerszten, Robert E.] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA 02115 USA.
   [Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
RP Cantley, LC (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM lcantley@hms.harvard.edu
FU National Cancer Institute [T32CA009172] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [T32 CA009172] Funding Source: Medline; NIGMS NIH HHS [R01 GM056203] Funding Source: Medline
NR 19
TC 2319
Z9 2753
U1 9
U2 400
PU 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 13
PY 2008
VL 452
IS 7184
BP 230
EP U74
DI 10.1038/nature06734
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600043
PM 18337823
DA 2026-03-09
ER

PT J
AU Nogués-Bravo, D
   Araújo, MB
   Romdal, T
   Rahbek, C
AF Nogues-Bravo, D.
   Araujo, M. B.
   Romdal, T.
   Rahbek, C.
TI Scale effects and human impact on the elevational species richness gradients
SO NATURE
LA English
DT Article
ID latitudinal gradients; spatial scale; diversity; patterns; area; biodiversity
AB Despite two centuries of effort in characterizing environmental gradients of species richness in search of universal patterns, surprisingly few of these patterns have been widely acknowledged(1-3). Species richness along altitudinal gradients was previously assumed to increase universally from cool highlands to warm lowlands, mirroring the latitudinal increase in species richness from cool to warm latitudes(1,4,5). However, since the more recent general acceptance of altitudinal gradients as model templates for testing hypotheses behind large- scale patterns of diversity(5-9), these gradients have been used in support of all the main diversity hypotheses, although little consensus has been achieved. Here we show that when resampling a data set comprising 400,000 records for 3,046 Pyrenean floristic species at different scales of analysis ( achieved by varying grain size and the extent of the gradients sampled), the derived species richness pattern changed progressively from hump- shaped to a monotonic pattern as the scale of extent diminished. Scale effects alone gave rise to as many conflicting patterns of species richness as had previously been reported in the literature, and scale effects lent significantly different statistical support to competing diversity hypotheses. Effects of scale on current studies may be affected by human activities, because montane ecosystems and human activities are intimately connected(10). This interdependence has led to a global reduction in natural lowland habitats, hampering our ability to detect universal patterns and impeding the search for universal diversity gradients to discover the mechanisms determining the distribution of biological diversity on Earth.
C1 [Nogues-Bravo, D.; Araujo, M. B.] CSIC, Museo Nacl Ciencias Nat, Dept Biodivers & Evolutionary Biol, E-28006 Madrid, Spain.
   [Nogues-Bravo, D.; Araujo, M. B.; Romdal, T.; Rahbek, C.] Univ Copenhagen, Inst Biol, Ctr Macroecol, DK-2100 Copenhagen O, Denmark.
   [Nogues-Bravo, D.] CSIC, Pyrenean Inst Ecol, E-50080 Zaragoza, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Museo Nacional de Ciencias Naturales (MNCN); University of Copenhagen; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto Pirenaico de Ecologia (IPE)
RP Nogués-Bravo, D (corresponding author), CSIC, Museo Nacl Ciencias Nat, Dept Biodivers & Evolutionary Biol, C Jose Gutierrez Abascal 2, E-28006 Madrid, Spain.
EM davidnogues@mncn.csic.es
NR 28
TC 466
Z9 548
U1 6
U2 203
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 216
EP U8
DI 10.1038/nature06812
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400038
PM 18464741
DA 2026-03-09
ER

PT J
AU Hajkova, P
   Ancelin, K
   Waldmann, T
   Lacoste, N
   Lange, UC
   Cesari, F
   Lee, C
   Almouzni, G
   Schneider, R
   Surani, MA
AF Hajkova, Petra
   Ancelin, Katia
   Waldmann, Tanja
   Lacoste, Nicolas
   Lange, Ulrike C.
   Cesari, Francesca
   Lee, Caroline
   Almouzni, Genevieve
   Schneider, Robert
   Surani, M. Azim
TI Chromatin dynamics during epigenetic reprogramming in the mouse germ line
SO NATURE
LA English
DT Article
ID histone arginine methylation; repair; nap1; specification; demeter; blimp1
AB A unique feature of the germ cell lineage is the generation of totipotency. A critical event in this context is DNA demethylation and the erasure of parental imprints in mouse primordial germ cells ( PGCs) on embryonic day 11.5 ( E11.5) after they enter into the developing gonads(1,2). Little is yet known about the mechanism involved, except that it is apparently an active process. We have examined the associated changes in the chromatin to gain further insights into this reprogramming event. Here we show that the chromatin changes occur in two steps. The first changes in nascent PGCs at E8.5 establish a distinctive chromatin signature that is reminiscent of pluripotency. Next, when PGCs are residing in the gonads, major changes occur in nuclear architecture accompanied by an extensive erasure of several histone modifications and exchange of histone variants. Furthermore, the histone chaperones HIRA and NAP- 1 ( NAP111), which are implicated in histone exchange, accumulate in PGC nuclei undergoing reprogramming. We therefore suggest that the mechanism of histone replacement is critical for these chromatin rearrangements to occur. The marked chromatin changes are intimately linked with genome- wide DNA demethylation. On the basis of the timing of the observed events, we propose that if DNA demethylation entails a DNA repair- based mechanism, the evident histone replacement would represent a repair- induced response event rather than being a prerequisite.
C1 [Hajkova, Petra; Ancelin, Katia; Lange, Ulrike C.; Cesari, Francesca; Lee, Caroline; Surani, M. Azim] Univ Cambridge, Welcome Trust Canc Res UK Gordon Inst Canc & Dev, Cambridge CB2 1QN, England.
   [Schneider, Robert] Max Planck Inst Immunobiol, D-79108 Freiburg, Germany.
   [Almouzni, Genevieve] Inst Curie, CNRS, F-75248 Paris 05, France.
C3 University of Cambridge; Max Planck Society; Centre National de la Recherche Scientifique (CNRS); UNICANCER; Universite PSL; Institut Curie
RP Surani, MA (corresponding author), Univ Cambridge, Welcome Trust Canc Res UK Gordon Inst Canc & Dev, Tennis Court Rd, Cambridge CB2 1QN, England.
EM as10021@mole.bio.cam.ac.uk
FU Medical Research Council [G0300723B] Funding Source: researchfish; Wellcome Trust [083089] Funding Source: Medline
NR 30
TC 500
Z9 581
U1 0
U2 63
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 17
PY 2008
VL 452
IS 7189
BP 877
EP U6
DI 10.1038/nature06714
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000049
PM 18354397
DA 2026-03-09
ER

PT J
AU Mimitou, EP
   Symington, LS
AF Mimitou, Eleni P.
   Symington, Lorraine S.
TI Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; homologous recombination; syndrome helicase; mre11 complex; repair; checkpoint; proteins; damage; yeast; interacts
AB DNA ends exposed after introduction of double- strand breaks ( DSBs) undergo 5 '-3 ' nucleolytic degradation to generate single- stranded DNA, the substrate for binding by the Rad51 protein to initiate homologous recombination. This process is poorly understood in eukaryotes, but several factors have been implicated, including the Mre11 complex ( Mre11 - Rad50 - Xrs2/ NBS1), Sae2/ CtIP/ Ctp1 and Exo1. Here we demonstrate that yeast Exo1 nuclease and Sgs1 helicase function in alternative pathways for DSB processing. Novel, partially resected intermediates accumulate in a double mutant lacking Exo1 and Sgs1, which are poor substrates for homologous recombination. The early processing step that generates partly resected intermediates is dependent on Sae2. When Sae2 is absent, in addition to Exo1 and Sgs1, unprocessed DSBs accumulate and homology- dependent repair fails. These results suggest a two- step mechanism for DSB processing during homologous recombination. First, the Mre11 complex and Sae2 remove a small oligonucleotide( s) from the DNA ends to form an early intermediate. Second, Exo1 and/ or Sgs1 rapidly process this intermediate to generate extensive tracts of single- stranded DNA that serve as substrate for Rad51.
C1 [Mimitou, Eleni P.; Symington, Lorraine S.] Columbia Univ, Med Ctr, Dept Microbiol, New York, NY 10032 USA.
C3 Columbia University
RP Symington, LS (corresponding author), Columbia Univ, Med Ctr, Dept Microbiol, 701 W 168th St, New York, NY 10032 USA.
EM lss5@columbia.edu
FU National Institutes of Health
NR 37
TC 825
Z9 1079
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 9
PY 2008
VL 455
IS 7214
BP 770
EP U3
DI 10.1038/nature07312
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900040
PM 18806779
DA 2026-03-09
ER

PT J
AU Manyala, N
   DiTusa, JF
   Aeppli, G
   Ramirez, AP
AF Manyala, N.
   DiTusa, J. F.
   Aeppli, G.
   Ramirez, A. P.
TI Doping a semiconductor to create an unconventional metal
SO NATURE
LA English
DT Article
ID insulator-transition; behavior; superconductivity; state
AB Landau - Fermi liquid theory, with its pivotal assertion that electrons in metals can be simply understood as independent particles with effective masses replacing the free electron mass, has been astonishingly successful. This is true despite the Coulomb interactions an electron experiences from the host crystal lattice, lattice defects and the other similar to 10(22) cm(-3) electrons. An important extension to the theory accounts for the behaviour of doped semiconductors(1,2). Because little in the vast literature on materials contradicts Fermi liquid theory and its extensions, exceptions have attracted great attention, and they include the high- temperature superconductors(3), silicon- based field- effect transistors that host two- dimensional metals(4), and certain rare- earth compounds at the threshold of magnetism(5-8). The origin of the non- Fermi liquid behaviour in all of these systems remains controversial. Here we report that an entirely different and exceedingly simple class of materials - doped small- bandgap semiconductors near a metal - insulator transition - can also display a non- Fermi liquid state. Remarkably, a modest magnetic field functions as a switch which restores the ordinary disordered Fermi liquid. Our data suggest that we have found a physical realization of the only mathematically rigorous route to a non- Fermi liquid, namely the 'undercompensated Kondo effect', where there are too few mobile electrons to compensate for the spins of unpaired electrons localized on impurity atoms(9-12).
C1 [Manyala, N.; DiTusa, J. F.] Louisiana State Univ, Dept Phys & Astron, Baton Rouge, LA 70803 USA.
   [Aeppli, G.] UCL, London Ctr Nanotechnol, London WC1E 6BT, England.
   [Aeppli, G.] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Manyala, N.] Natl Univ Lesotho, Dept Phys & Elect, Maseru 100, Lesotho.
   [Ramirez, A. P.] Alcatel Lucent, Bell Labs, Murray Hill, NJ 07974 USA.
C3 Louisiana State University System; Louisiana State University; University of London; University College London; University of London; University College London; Alcatel-Lucent; AT&T
RP DiTusa, JF (corresponding author), Louisiana State Univ, Dept Phys & Astron, Baton Rouge, LA 70803 USA.
EM ditusa@phys.lsu.edu
FU National Science Foundation; Wolfson-Royal Society Research Merit Award; Basic Technologies Programme of the UK Research Councils
NR 32
TC 75
Z9 88
U1 0
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 21
PY 2008
VL 454
IS 7207
BP 976
EP 980
DI 10.1038/nature07137
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000034
PM 18719585
DA 2026-03-09
ER

PT J
AU Dreber, A
   Rand, DG
   Fudenberg, D
   Nowak, MA
AF Dreber, Anna
   Rand, David G.
   Fudenberg, Drew
   Nowak, Martin A.
TI Winners don't punish
SO NATURE
LA English
DT Article
ID altruistic punishment; repeated games; cooperation; evolution; reciprocity
AB A key aspect of human behaviour is cooperation(1-7). We tend to help others even if costs are involved. We are more likely to help when the costs are small and the benefits for the other person significant. Cooperation leads to a tension between what is best for the individual and what is best for the group. A group does better if everyone cooperates, but each individual is tempted to defect. Recently there has been much interest in exploring the effect of costly punishment on human cooperation(8-23). Costly punishment means paying a cost for another individual to incur a cost. It has been suggested that costly punishment promotes cooperation even in non- repeated games and without any possibility of reputation effects(10). But most of our interactions are repeated and reputation is always at stake. Thus, if costly punishment is important in promoting cooperation, it must do so in a repeated setting. We have performed experiments in which, in each round of a repeated game, people choose between cooperation, defection and costly punishment. In control experiments, people could only cooperate or defect. Here we show that the option of costly punishment increases the amount of cooperation but not the average payoff of the group. Furthermore, there is a strong negative correlation between total payoff and use of costly punishment. Those people who gain the highest total payoff tend not to use costly punishment: winners don't punish. This suggests that costly punishment behaviour is maladaptive in cooperation games and might have evolved for other reasons.
C1 [Dreber, Anna; Rand, David G.; Nowak, Martin A.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Rand, David G.] Harvard Univ, Dept Syst Biol, Cambridge, MA 02138 USA.
   [Fudenberg, Drew] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA.
   [Nowak, Martin A.] Harvard Univ, Dept Math, Cambridge, MA 02138 USA.
   [Nowak, Martin A.] Harvard Univ, Dept Organism & Evolut Biol, Cambridge, MA 02138 USA.
   [Dreber, Anna] Stockholm Sch Econ, Dept Econ, S-11358 Stockholm, Sweden.
C3 Harvard University; Harvard University; Harvard University; Harvard University; Harvard University; Stockholm School of Economics
RP Nowak, MA (corresponding author), Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
EM martin_nowak@harvard.edu
FU NIGMS NIH HHS [R01 GM078986] Funding Source: Medline
NR 30
TC 529
Z9 602
U1 2
U2 140
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 348
EP 351
DI 10.1038/nature06723
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400046
PM 18354481
DA 2026-03-09
ER

PT J
AU Jankaew, K
   Atwater, BF
   Sawai, Y
   Choowong, M
   Charoentitirat, T
   Martin, ME
   Prendergast, A
AF Jankaew, Kruawun
   Atwater, Brian F.
   Sawai, Yuki
   Choowong, Montri
   Charoentitirat, Thasinee
   Martin, Maria E.
   Prendergast, Amy
TI Medieval forewarning of the 2004 Indian Ocean tsunami in Thailand
SO NATURE
LA English
DT Article
ID western coast; earthquake; diatoms; heights; rupture; hazard
AB Recent centuries provide no precedent for the 2004 Indian Ocean tsunami, either on the coasts it devastated or within its source area. The tsunami claimed nearly all of its victims on shores that had gone 200 years or more without a tsunami disaster(1). The associated earthquake of magnitude 9.2 defied a Sumatra-Andaman catalogue that contains no nineteenth- century or twentieth- century earthquake larger than magnitude 7.9 ( ref. 2). The tsunami and the earthquake together resulted from a fault rupture 1,500 km long that expended centuries' worth of plate convergence(2-5). Here, using sedimentary evidence for tsunamis(6), we identify probable precedents for the 2004 tsunami at a grassy beach- ridge plain 125 km north of Phuket. The 2004 tsunami, running 2 km across this plain, coated the ridges and intervening swales with a sheet of sand commonly 5-20 cm thick. The peaty soils of two marshy swales preserve the remains of several earlier sand sheets less than 2,800 years old. If responsible for the youngest of these pre-2004 sand sheets, the most recent full- size predecessor to the 2004 tsunami occurred about 550 - 700 years ago.
C1 [Jankaew, Kruawun; Choowong, Montri; Charoentitirat, Thasinee] Chulalongkorn Univ, Fac Sci, Dept Geol, Bangkok 10330, Thailand.
   [Atwater, Brian F.] Univ Washington, US Geol Survey, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Sawai, Yuki] Natl Inst Adv Ind Sci & Technol, Geol Survey Japan, Tsukuba, Ibaraki 3058567, Japan.
   [Martin, Maria E.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Prendergast, Amy] Geosci Australia, Canberra, ACT 2601, Australia.
C3 Chulalongkorn University; United States Department of the Interior; United States Geological Survey; University of Washington; University of Washington Seattle; National Institute of Advanced Industrial Science & Technology (AIST); University of Washington; University of Washington Seattle; Geoscience Australia
RP Jankaew, K (corresponding author), Chulalongkorn Univ, Fac Sci, Dept Geol, Phayathai Rd, Bangkok 10330, Thailand.
EM kjankaew@yahoo.co.uk
FU Ministry of Natural Resources and Environment (Thailand); National Science Foundation ( USA); US Agency for International Development; Japan Society for the Promotion of Science; Thailand Research Fund; Chulalongkorn University
NR 29
TC 286
Z9 311
U1 1
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1228
EP 1231
DI 10.1038/nature07373
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100041
DA 2026-03-09
ER

PT J
AU Tsaousis, AD
   Kunji, ERS
   Goldberg, AV
   Lucocq, JM
   Hirt, RP
   Embley, TM
AF Tsaousis, Anastasios D.
   Kunji, Edmund R. S.
   Goldberg, Alina V.
   Lucocq, John M.
   Hirt, Robert P.
   Embley, T. Martin
TI A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi
SO NATURE
LA English
DT Article
ID rickettsia-prowazekii; atp/adp translocases; microsporidia; transport; proteins; evolution; protozoa; arabidopsis; chlamydiae; biology
AB Mitochondria use transport proteins of the eukaryotic mitochondrial carrier family (MCF) to mediate the exchange of diverse substrates, including ATP, with the host cell cytosol. According to classical endosymbiosis theory, insertion of a host-nuclear-encoded MCF transporter into the protomitochondrion was the key step that allowed the host cell to harvest ATP from the enslaved endosymbiont(1). Notably the genome of the microsporidian Encephalitozoon cuniculi has lost all of its genes for MCF proteins(2). This raises the question of how the recently discovered microsporidian remnant mitochondrion, called a mitosome, acquires ATP to support protein import and other predicted ATP-dependent activities(2-4). The E. cuniculi genome does contain four genes for an unrelated type of nucleotide transporter used by plastids and bacterial intracellular parasites, such as Rickettsia and Chlamydia, to import ATP from the cytosol of their eukaryotic host cells(5-7). The inference is that E. cuniculi also uses these proteins to steal ATP from its eukaryotic host to sustain its lifestyle as an obligate intracellular parasite. Here we show that, consistent with this hypothesis, all four E. cuniculi transporters can transport ATP, and three of them are expressed on the surface of the parasite when it is living inside host cells. The fourth transporter co-locates with mitochondrial Hsp70 to the E. cuniculi mitosome. Thus, uniquely among eukaryotes, the traditional relationship between mitochondrion and host has been subverted in E. cuniculi, by reductive evolution and analogous gene replacement. Instead of the mitosome providing the parasite cytosol with ATP, the parasite cytosol now seems to provide ATP for the organelle.
C1 [Tsaousis, Anastasios D.; Goldberg, Alina V.; Hirt, Robert P.; Embley, T. Martin] Univ Newcastle, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Tsaousis, Anastasios D.] Univ Newcastle, Sch Biol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Kunji, Edmund R. S.] MRC, Dunn Human Nutr Unit, Cambridge CB2 2XY, England.
   [Lucocq, John M.] Univ Dundee, Sch Life Sci, Dundee DD1 5EH, Scotland.
C3 Newcastle University - UK; Newcastle University - UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); MRC Human Nutrition Research; University of Dundee
RP Hirt, RP (corresponding author), Univ Newcastle, Inst Cell & Mol Biosci, Catherine Cookson Bldg,Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM r.p.hirt@ncl.ac.uk; ek@mrc-dunn.cam.ac.uk
FU Medical Research Council [MC_U105663139] Funding Source: researchfish; Medical Research Council [MC_U105663139] Funding Source: Medline; MRC [MC_U105663139] Funding Source: UKRI
NR 26
TC 212
Z9 258
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 22
PY 2008
VL 453
IS 7194
BP 553
EP U11
DI 10.1038/nature06903
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700049
PM 18449191
DA 2026-03-09
ER

PT J
AU Bitterman, Y
   Mukamel, R
   Malach, R
   Fried, I
   Nelken, I
AF Bitterman, Y.
   Mukamel, R.
   Malach, R.
   Fried, I.
   Nelken, I.
TI Ultra-fine frequency tuning revealed in single neurons of human auditory cortex
SO NATURE
LA English
DT Article
ID receptive-fields; discrimination; responses; model; organization; tones; cues
AB Just- noticeable differences of physical parameters are often limited by the resolution of the peripheral sensory apparatus. Thus, two- point discrimination in vision is limited by the size of individual photoreceptors. Frequency selectivity is a basic property of neurons in the mammalian auditory pathway(1,2). However, just- noticeable differences of frequency are substantially smaller than the bandwidth of the peripheral sensors(3). Here we report that frequency tuning in single neurons recorded from human auditory cortex in response to random- chord stimuli is far narrower than that typically described in any other mammalian species ( besides bats), and substantially exceeds that attributed to the human auditory periphery. Interestingly, simple spectral filter models failed to predict the neuronal responses to natural stimuli, including speech and music. Thus, natural sounds engage additional processing mechanisms beyond the exquisite frequency tuning probed by the random- chord stimuli.
C1 [Bitterman, Y.; Nelken, I.] Hebrew Univ Jerusalem, Inst Life Sci, Dept Neurobiol, IL-91904 Jerusalem, Israel.
   [Bitterman, Y.; Nelken, I.] Hebrew Univ Jerusalem, Interdisciplinary Ctr Neural Computat, IL-91904 Jerusalem, Israel.
   [Mukamel, R.] Univ Calif Los Angeles, David Geffen Sch Med, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA 90095 USA.
   [Mukamel, R.; Fried, I.] Univ Calif Los Angeles, David Geffen Sch Med, Div Neurosurg, Los Angeles, CA 90095 USA.
   [Mukamel, R.; Fried, I.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
   [Malach, R.] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
   [Fried, I.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Funct Neurosurg Unit, IL-69978 Tel Aviv, Israel.
   [Fried, I.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
C3 Hebrew University of Jerusalem; Hebrew University of Jerusalem; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; Weizmann Institute of Science; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center; Tel Aviv University; Sackler Faculty of Medicine
RP Nelken, I (corresponding author), Hebrew Univ Jerusalem, Inst Life Sci, Dept Neurobiol, IL-91904 Jerusalem, Israel.
EM ifried@mednet.ucla.edu; israel@cc.huji.ac.il
FU NINDS NIH HHS [R01 NS033221] Funding Source: Medline
NR 29
TC 135
Z9 151
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 10
PY 2008
VL 451
IS 7175
BP 197
EP U9
DI 10.1038/nature06476
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400044
PM 18185589
DA 2026-03-09
ER

PT J
AU Herbst, W
   Hamilton, CM
   Leduc, K
   Winn, JN
   Johns-Krull, CM
   Mundt, R
   Ibrahimov, M
AF Herbst, William
   Hamilton, Catrina M.
   LeDuc, Katherine
   Winn, Joshua N.
   Johns-Krull, Christopher M.
   Mundt, Reinhard
   Ibrahimov, Mansur
TI Reflected light from sand grains in the terrestrial zone of a protoplanetary disk
SO NATURE
LA English
DT Article
ID kh 15d; mysterious eclipses; region; star; history; asiago
AB In the standard model of terrestrial planet formation, the first step in the process is for interstellar dust to coagulate within a protoplanetary disk surrounding a young star, forming large grains that settle towards the disk plane(1). Interstellar grains of typical size similar to 0.1 mm are expected to grow to millimetre- ( sand), centimetre( pebble) or even metre- sized ( boulder) objects rather quickly(2). Unfortunately, such evolved disks are hard to observe because the ratio of surface area to volume of their constituents is small. We readily detect dust around young objects known as 'classical' T Tauri stars, but there is little or no evidence of it in the slightly more evolved 'weak- line' systems(3). Here we report observations of a 3-Myr- old star, which show that grains have grown to about millimetre size or larger in the terrestrial zone ( within similar to 3 AU) of this star. The fortuitous geometry of the KH 15D binary star system allows us to infer that, when both stars are occulted by the surrounding disk, it appears as a nearly edge- on ring illuminated by one of the central binary components. This work complements the study of terrestrial zones of younger disks that have been recently resolved by interferometry(4-6).
C1 [Herbst, William; LeDuc, Katherine] Wesleyan Univ, Dept Astron, Middletown, CT 06459 USA.
   [Hamilton, Catrina M.] Dickinson Coll, Dept Phys & Astron, Carlisle, PA 17013 USA.
   [Winn, Joshua N.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Johns-Krull, Christopher M.] Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.
   [Mundt, Reinhard] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Ibrahimov, Mansur] Uzbek Acad Sci, Ulugh Beg Astron Inst, Tashkent 700052, Uzbekistan.
C3 Wesleyan University; Dickinson College; Massachusetts Institute of Technology (MIT); Rice University; Max Planck Society; Academy of Sciences of Uzbekistan; Ulugh Beg Astronomical Institute (UBAI)
RP Herbst, W (corresponding author), Wesleyan Univ, Dept Astron, Middletown, CT 06459 USA.
EM wherbst@wesleyan.edu
NR 24
TC 19
Z9 20
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 13
PY 2008
VL 452
IS 7184
BP 194
EP 197
DI 10.1038/nature06671
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600035
PM 18337817
DA 2026-03-09
ER

PT J
AU Müller, FJ
   Laurent, LC
   Kostka, D
   Ulitsky, I
   Williams, R
   Lu, C
   Park, IH
   Rao, MS
   Shamir, R
   Schwartz, PH
   Schmidt, NO
   Loring, JF
AF Mueller, Franz-Josef
   Laurent, Louise C.
   Kostka, Dennis
   Ulitsky, Igor
   Williams, Roy
   Lu, Christina
   Park, In-Hyun
   Rao, Mahendra S.
   Shamir, Ron
   Schwartz, Philip H.
   Schmidt, Nils O.
   Loring, Jeanne F.
TI Regulatory networks define phenotypic classes of human stem cell lines
SO NATURE
LA English
DT Article
ID gene-expression profiles; class discovery; biological networks; progenitor cells; genome-wide; pluripotency; differentiation; cancer
AB Stem cells are defined as self- renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells - typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation - to adult stem cell lines, which can generate a far more limited repertoire of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine(1,2) has highlighted the need for a general, reproducible method for classification of these cells(3). We report here the creation and analysis of a database of global gene expression profiles ( which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method(4,5) to categorize a collection of similar to 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis(6) we uncovered a protein - protein network (PluriNet) that is shared by the pluripotent cells ( embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the PluriNet seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self- renewal are under tight control by specific molecular networks.
C1 [Mueller, Franz-Josef; Laurent, Louise C.; Lu, Christina; Loring, Jeanne F.] Scripps Res Inst, Ctr Regenerat Med, La Jolla, CA 92037 USA.
   [Mueller, Franz-Josef] Univ Hosp Schleswig Holstein, Ctr Psychiat, ZIP Kiel, D-24105 Kiel, Germany.
   [Laurent, Louise C.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92035 USA.
   [Kostka, Dennis] Max Planck Inst Mol Genet, Dept Computat Mol Biol, D-14195 Berlin, Germany.
   [Ulitsky, Igor; Shamir, Ron] Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel.
   [Williams, Roy; Loring, Jeanne F.] Burnham Inst, La Jolla, CA 92037 USA.
   [Park, In-Hyun] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [Park, In-Hyun] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Rao, Mahendra S.] Invitrogen Co, Frederick, MD 21704 USA.
   [Rao, Mahendra S.] Buck Inst Aging, Ctr Stem Cell Biol, Novato, CA 94945 USA.
   [Schwartz, Philip H.] Childrens Hosp Orange Cty, Res Inst, Ctr Res Neurosci, Orange, CA 92868 USA.
   [Schwartz, Philip H.] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA.
   [Schmidt, Nils O.] Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, D-20246 Hamburg, Germany.
C3 Scripps Research Institute; University of Kiel; Schleswig Holstein University Hospital; University of California System; University of California San Diego; Max Planck Society; Tel Aviv University; Sanford Burnham Prebys Medical Discovery Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Thermo Fisher Scientific; Buck Institute for Research on Aging; Childrens Hospital of Orange County; University of California System; University of California Irvine; University of Hamburg; University Medical Center Hamburg-Eppendorf
RP Müller, FJ (corresponding author), Scripps Res Inst, Ctr Regenerat Med, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM fj.mueller@zip-kiel.de; jloring@scripps.edu
FU Christian- Abrechts University Young Investigator Award; Hamburger Krebsgesellschaft Grant; Edmond J. Safra Bioinformatics program fellowship at Tel- Aviv University (I.U.); Converging Technologies Program of The Israel Science Foundation [1767.07]; Raymond and Beverly Sackler Chair in Bioinformatics; Reproductive Scientist Development Program Scholar Award [K12 5K12HD000849-20]; California Institute for Regenerative Medicine Clinical Scholar Award [NIH P20 GM075059-01]; Alzheimer's Association;  [SFB-654/C5]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12HD000849] Funding Source: NIH RePORTER
NR 41
TC 283
Z9 325
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 401
EP U55
DI 10.1038/nature07213
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200047
PM 18724358
DA 2026-03-09
ER

PT J
AU Andrews, ZB
   Liu, ZW
   Walllingford, N
   Erion, DM
   Borok, E
   Friedman, JM
   Tschöp, MH
   Shanabrough, M
   Cline, G
   Shulman, GI
   Coppola, A
   Gao, XB
   Horvath, TL
   Diano, S
AF Andrews, Zane B.
   Liu, Zhong-Wu
   Walllingford, Nicholas
   Erion, Derek M.
   Borok, Erzsebet
   Friedman, Jeffery M.
   Tschop, Matthias H.
   Shanabrough, Marya
   Cline, Gary
   Shulman, Gerald I.
   Coppola, Anna
   Gao, Xiao-Bing
   Horvath, Tamas L.
   Diano, Sabrina
TI UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals
SO NATURE
LA English
DT Article
ID growth-hormone secretagogue; activated protein-kinase; beta-cell dysfunction; fatty-acid oxidation; arcuate nucleus; uncoupling protein-2; mitochondrial biogenesis; gene-expression; messenger-rna; pomc neurons
AB The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.
C1 [Andrews, Zane B.; Horvath, Tamas L.] Yale Univ, Sch Med, Comparat Med Sect, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Andrews, Zane B.; Liu, Zhong-Wu; Walllingford, Nicholas; Erion, Derek M.; Borok, Erzsebet; Shanabrough, Marya; Coppola, Anna; Gao, Xiao-Bing; Horvath, Tamas L.; Diano, Sabrina] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06520 USA.
   [Cline, Gary; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Horvath, Tamas L.; Diano, Sabrina] Yale Univ, Sch Med, Dept Neurobiol, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Liu, Zhong-Wu] Yunyang Med Coll, Dept Neurobiol, Shiyan 442000, Hubei, Peoples R China.
   [Friedman, Jeffery M.] Rockefeller Univ, Genet Mol Lab, Howard Hughes Med Inst, New York, NY 10021 USA.
   [Tschop, Matthias H.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45237 USA.
C3 Howard Hughes Medical Institute; Yale University; Yale University; Howard Hughes Medical Institute; Yale University; Yale University; Howard Hughes Medical Institute; Rockefeller University; Howard Hughes Medical Institute; University System of Ohio; University of Cincinnati
RP Horvath, TL (corresponding author), Yale Univ, Sch Med, Comparat Med Sect, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06520 USA.
EM tamas.horvath@yale.edu; sabrina.diano@yale.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIA NIH HHS [R01 AG022880] Funding Source: Medline; NIDDK NIH HHS [R01 DK040936] Funding Source: Medline
NR 39
TC 595
Z9 674
U1 3
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 14
PY 2008
VL 454
IS 7206
BP 846
EP 851
DI 10.1038/nature07181
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600027
PM 18668043
DA 2026-03-09
ER

PT J
AU Faccenda, M
   Burlini, L
   Gerya, TV
   Mainprice, D
AF Faccenda, Manuele
   Burlini, Luigi
   Gerya, Taras V.
   Mainprice, David
TI Fault-induced seismic anisotropy by hydration in subducting oceanic plates
SO NATURE
LA English
DT Article
ID shear-wave anisotropy; middle america trench; upper-mantle; active deformation; elastic-constants; crustal rocks; zones; serpentinization; olivine; beneath
AB The variation of elastic- wave velocities as a function of the direction of propagation through the Earth's interior is a widely documented phenomenon called seismic anisotropy. The geometry and amount of seismic anisotropy is generally estimated by measuring shearwave splitting, which consists of determining the polarization direction of the fast shear- wave component and the time delay between the fast and slow, orthogonally polarized, waves. In subduction zones, the teleseismic fast shear- wave component is oriented generally parallel to the strike of the trench(1), although a few exceptions have been reported (Cascadia(2) and restricted areas of South America(3,4)). The interpretation of shear- wave splitting above subduction zones has been controversial and none of the inferred models seems to be sufficiently complete to explain the entire range of anisotropic patterns registered worldwide(1). Here we show that the amount and the geometry of seismic anisotropies measured in the forearc regions of subduction zones strongly depend on the preferred orientation of hydrated faults in the subducting oceanic plate. The anisotropy originates from the crystallographic preferred orientation of highly anisotropic hydrous minerals (serpentine and talc) formed along steeply dipping faults and from the larger- scale vertical layering consisting of dry and hydrated crust - mantle sections whose spacing is several times smaller than teleseismic wavelengths. Fault orientations and estimated delay times are consistent with the observed shear- wave splitting patterns in most subduction zones.
C1 [Faccenda, Manuele; Gerya, Taras V.] ETH, Inst Geophys, CH-8093 Zurich, Switzerland.
   [Burlini, Luigi] ETH, Inst Geol, CH-8092 Zurich, Switzerland.
   [Mainprice, David] Univ Montpellier 2, F-34090 Montpellier, France.
   [Mainprice, David] CNRS, F-34090 Montpellier, France.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS)
RP Faccenda, M (corresponding author), ETH, Inst Geophys, Schafmattstr 30, CH-8093 Zurich, Switzerland.
EM faccenda@erdw.ethz.ch
FU ETH Research Grant [TH-12/05-3]; SNF Research Grant [200021-113672/1, 200021-116153]
NR 59
TC 258
Z9 286
U1 2
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1097
EP U8
DI 10.1038/nature07376
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600042
DA 2026-03-09
ER

PT J
AU Hasselmann, M
   Gempe, T
   Schiott, M
   Nunes-Silva, CG
   Otte, M
   Beye, M
AF Hasselmann, Martin
   Gempe, Tanja
   Schiott, Morten
   Nunes-Silva, Carlos Gustavo
   Otte, Marianne
   Beye, Martin
TI Evidence for the evolutionary nascence of a novel sex determination pathway in honeybees
SO NATURE
LA English
DT Article
ID transformer gene; apis-mellifera; drosophila; selection; rna; recombination; diversity; proteins; insights; insects
AB Sex determination in honeybees (Apis mellifera) is governed by heterozygosity at a single locus harbouring the complementary sex determiner (csd) gene(1), in contrast to the well-studied sex chromosome system of Drosophila melanogaster(2). Bees heterozygous at csd are females, whereas homozygotes and hemizygotes (haploid individuals) are males. Although at least 15 different csd alleles are known among natural bee populations(3), the mechanisms linking allelic interactions to switching of the sexual development programme are still obscure. Here we report a new component of the sex-determining pathway in honeybees, encoded 12 kilobases upstream of csd. The gene feminizer (fem) is the ancestrally conserved progenitor gene from which csd arose and encodes an SR-type protein, harbouring an Arg/Ser-rich domain. Fem shares the same arrangement of Arg/Ser- and proline-rich-domain with the Drosophila principal sex-determining gene transformer (tra), but lacks conserved motifs except for a 30-amino-acid motif that Fem shares only with Tra of another fly, Ceratitis capitata(4). Like tra, the fem transcript is alternatively spliced. The male-specific splice variant contains a premature stop codon and yields no functional product, whereas the female-specific splice variant encodes the functional protein. We show that RNA interference (RNAi)-induced knockdowns of the female-specific fem splice variant result in male bees, indicating that the fem product is required for entire female development. Furthermore, RNAi- induced knockdowns of female allelic csd transcripts result in the male-specific fem splice variant, suggesting that the fem gene implements the switch of developmental pathways controlled by heterozygosity at csd. Comparative analysis of fem and csd coding sequences from five bee species indicates a recent origin of csd in the honeybee lineage from the fem progenitor and provides evidence for positive selection at csd accompanied by purifying selection at fem. The fem locus in bees uncovers gene duplication and positive selection as evolutionary mechanisms underlying the origin of a novel sex determination pathway.
C1 [Hasselmann, Martin; Gempe, Tanja; Schiott, Morten; Otte, Marianne; Beye, Martin] Univ Dusseldorf, Dept Genet, D-40225 Dusseldorf, Germany.
   [Schiott, Morten] Univ Copenhagen, Ctr Social Evolut, Dept Biol, DK-2100 Copenhagen, Denmark.
   [Nunes-Silva, Carlos Gustavo] INPA, GPA, BR-69060001 Manaus, Amazonas, Brazil.
C3 Heinrich Heine University Dusseldorf; University of Copenhagen; Institute Nacional de Pesquisas da Amazonia
RP Beye, M (corresponding author), Univ Dusseldorf, Dept Genet, Universitaetsstr 1, D-40225 Dusseldorf, Germany.
EM martin.beye@uni-duesseldorf.de
NR 30
TC 204
Z9 235
U1 2
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 519
EP U7
DI 10.1038/nature07052
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300052
PM 18594516
DA 2026-03-09
ER

PT J
AU Voss, R
   Nelemans, G
AF Voss, Rasmus
   Nelemans, Gijs
TI Discovery of the progenitor of the type Ia supernova 2007on
SO NATURE
LA English
DT Article
ID white-dwarf models; x-ray sources; binary; evolution; colors
AB Type Ia supernovae are exploding stars that are used to measure the accelerated expansion of the Universe(1,2) and are responsible for most of the iron ever produced(3). Although there is general agreement that the exploding star is a white dwarf in a binary system, the exact configuration and trigger of the explosion is unclear(4), which could hamper their use for precision cosmology. Two families of progenitor models have been proposed. In the first, a white dwarf accretes material from a companion until it exceeds the Chandrasekhar mass, collapses and explodes(5,6). Alternatively, two white dwarfs merge, again causing catastrophic collapse and an explosion(7,8). It has hitherto been impossible to determine if either model is correct. Here we report the discovery of an object in pre- supernova archival X- ray images at the position of the recent type Ia supernova ( 2007on) in the elliptical galaxy NGC 1404. Deep optical images ( also archival) show no sign of this object. From this we conclude that the X- ray source is the progenitor of the supernova, which favours the accretion model for this supernova, although the host galaxy is older ( 6 - 9 Gyr) than the age at which the explosions are predicted in the accreting models.
C1 [Voss, Rasmus] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Voss, Rasmus] Excellence Cluster Universe, D-85748 Garching, Germany.
   [Nelemans, Gijs] Radboud Univ Nijmegen, Dept Astrophys, IMAPP, NL-6525 ED Nijmegen, Netherlands.
C3 Max Planck Society; University of Munich; Radboud University Nijmegen
RP Voss, R (corresponding author), Max Planck Inst Extraterr Phys, Giessenbach Str, D-85748 Garching, Germany.
EM rvoss@mpe.mpg.de; nelemans@astro.ru.nl
NR 29
TC 64
Z9 68
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 14
PY 2008
VL 451
IS 7180
BP 802
EP 804
DI 10.1038/nature06602
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400036
PM 18273013
DA 2026-03-09
ER

PT J
AU Harrington, LE
   Janowski, KM
   Oliver, JR
   Zajac, AJ
   Weaver, CT
AF Harrington, Laurie E.
   Janowski, Karen M.
   Oliver, James R.
   Zajac, Allan J.
   Weaver, Casey T.
TI Memory CD4 T cells emerge from effector T-cell progenitors
SO NATURE
LA English
DT Article
ID class-ii; lineage relationship; vaccine development; escherichia-coli; virus-infection; cutting edge; in-vivo; expression; generation; distinct
AB A hallmark of adaptive immunity is the generation of memory T cells that confer long- lived, antigen- specific protection against repeat challenges by pathogens(1-5). Understanding the mechanisms by which memory T cells arise is important for rational vaccination strategies and improved therapeutic interventions for chronic infections and autoimmune disorders. The large clonal expansion of CD8 T cells in response to some infections has made the development of CD8 T- cell memory more amenable to study, giving rise to a model of memory cell differentiation in which a fraction of fully competent effector T cells transition into long-lived memory T cells(4,6,7). Delineation of CD4 T- cell memory development has proved more difficult as a result of limitations on tracking the smaller populations of CD4 effector T cells generated during a pathogenic challenge(8-10), complicating efforts to determine whether CD4 memory T cells are direct descendants of effector T cells or whether they develop by alternative pathways(3,4). Here, using two complementary cytokine reporter mouse models to identify interferon ( IFN)- gamma-positive effector T cells and track their fate, we show that the lineage relationship between effector and memory CD4 T cells resembles that for CD8 T cells responding to the same pathogen. We find that, in parallel with effector CD8 T cells, IFN-gamma-positive effector CD4 T cells give rise to long- lived memory T cells capable of anamnestic responses to antigenic rechallenge.
C1 [Harrington, Laurie E.; Janowski, Karen M.; Oliver, James R.; Weaver, Casey T.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
   [Zajac, Allan J.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
C3 University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham
RP Weaver, CT (corresponding author), Univ Alabama, Dept Pathol, 845 19th St S, Birmingham, AL 35294 USA.
EM cweaver@uab.edu
NR 35
TC 203
Z9 279
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 356
EP U8
DI 10.1038/nature06672
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400048
PM 18322463
DA 2026-03-09
ER

PT J
AU Yu, XC
   Tsibane, T
   McGraw, PA
   House, FS
   Keefer, CJ
   Hicar, MD
   Tumpey, TM
   Pappas, C
   Perrone, LA
   Martinez, O
   Stevens, J
   Wilson, IA
   Aguilar, PV
   Altschuler, EL
   Basler, CF
   Crowe, JE
AF Yu, Xiaocong
   Tsibane, Tshidi
   McGraw, Patricia A.
   House, Frances S.
   Keefer, Christopher J.
   Hicar, Mark D.
   Tumpey, Terrence M.
   Pappas, Claudia
   Perrone, Lucy A.
   Martinez, Osvaldo
   Stevens, James
   Wilson, Ian A.
   Aguilar, Patricia V.
   Altschuler, Eric L.
   Basler, Christopher F.
   Crowe, James E., Jr.
TI Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors
SO NATURE
LA English
DT Article
ID virus hemagglutinin; humoral immunity; memory; infection; duration
AB Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era(1). Recent work has recovered the gene sequences of this unusual strain(2), so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes(3,4). However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin ( HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross- reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross- react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus- neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus- neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure - well into the tenth decade of life.
C1 [Yu, Xiaocong; McGraw, Patricia A.; House, Frances S.; Keefer, Christopher J.; Hicar, Mark D.; Crowe, James E., Jr.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
   [Yu, Xiaocong; McGraw, Patricia A.; House, Frances S.; Keefer, Christopher J.; Hicar, Mark D.; Crowe, James E., Jr.] Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA.
   [Tsibane, Tshidi; Pappas, Claudia; Martinez, Osvaldo; Aguilar, Patricia V.; Basler, Christopher F.] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
   [Tumpey, Terrence M.; Pappas, Claudia; Perrone, Lucy A.; Stevens, James] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA.
   [Stevens, James; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Stevens, James; Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Altschuler, Eric L.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA.
C3 Vanderbilt University; Vanderbilt University; Icahn School of Medicine at Mount Sinai; Centers for Disease Control & Prevention - USA; Scripps Research Institute; Scripps Research Institute; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences
RP Crowe, JE  (corresponding author), Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
EM altschel@umdnj.edu; Chris.Basler@mssm.edu
FU University of Medicine and Dentistry of New Jersey; Institute for the Elimination of Health Disparities; National Institutes of Health [U54 AI057157, CA55896, AI42266]; Southeast Regional Center of Excellence for Emerging Infections and Biodefense [U19 AI057229]; Northeast Biodefense Center [U54 AI57158, U19 AI62623, AI057158]; Center for Investigating Viral Immunity and Antagonism [P01AI058113)]
NR 30
TC 337
Z9 433
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 SEP 25
PY 2008
VL 455
IS 7212
BP 532
EP U41
DI 10.1038/nature07231
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600046
PM 18716625
DA 2026-03-09
ER

PT J
AU Long, MA
   Fee, MS
AF Long, Michael A.
   Fee, Michale S.
TI Using temperature to analyse temporal dynamics in the songbird motor pathway
SO NATURE
LA English
DT Article
ID zebra finch song; nucleus robustus-archistriatalis; central pattern generator; vocal control; brain-stem; sequence generation; membrane-property; forebrain; birdsong; system
AB Many complex behaviours, like speech or music, have a hierarchical organization with structure on many timescales, but it is not known how the brain controls the timing of behavioural sequences, or whether different circuits control different timescales of the behaviour. Here we address these issues by using temperature to manipulate the biophysical dynamics in different regions of the songbird forebrain involved in song production. We find that cooling the premotor nucleus HVC ( formerly known as the high vocal centre) slows song speed across all timescales by up to 45 per cent but only slightly alters the acoustic structure, whereas cooling the downstream motor nucleus RA ( robust nucleus of the arcopallium) has no observable effect on song timing. Our observations suggest that dynamics within HVC are involved in the control of song timing, perhaps through a chain- like organization. Local manipulation of brain temperature should be broadly applicable to the identification of neural circuitry that controls the timing of behavioural sequences and, more generally, to the study of the origin and role of oscillatory and other forms of brain dynamics in neural systems.
C1 [Long, Michael A.; Fee, Michale S.] MIT, McGovern Inst Brain Res, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Fee, MS (corresponding author), MIT, McGovern Inst Brain Res, Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM fee@mit.edu
FU US National Institutes of Health [MH067105, DC009280]; Human Frontiers Science Project
NR 45
TC 361
Z9 486
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 NOV 13
PY 2008
VL 456
IS 7219
BP 189
EP 194
DI 10.1038/nature07448
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300030
PM 19005546
DA 2026-03-09
ER

PT J
AU Majo, F
   Rochat, A
   Nicolas, M
   Abou Jaoude, G
   Barrandon, Y
AF Majo, Francois
   Rochat, Ariane
   Nicolas, Michael
   Abou Jaoude, Georges
   Barrandon, Yann
TI Oligopotent stem cells are distributed throughout the mammalian ocular surface
SO NATURE
LA English
DT Article
ID hair-follicles; corneal epithelium; basal cells; renewal; location; keratinocyte; culture; repair
AB The integrity of the cornea, the most anterior part of the eye, is indispensable for vision. Forty- five million individuals worldwide are bilaterally blind and another 135 million have severely impaired vision in both eyes because of loss of corneal transparency(1); treatments range from local medications to corneal transplants, and more recently to stem cell therapy(2). The corneal epithelium is a squamous epithelium that is constantly renewing, with a vertical turnover of 7 to 14 days in many mammals(3). Identification of slow cycling cells ( label- retaining cells) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long- term renewal of the cornea(4); hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in marked opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium(5,6). Here we show that the corneal epithelium of the mouse can be serially transplanted, is self- maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. Furthermore, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones)(7,8) with the capacity to generate individual colonies of corneal and conjunctival cells. Therefore, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. We propose a model that unifies our observations with the literature and explains why the limbal region is enriched in stem cells.
C1 [Majo, Francois; Rochat, Ariane; Nicolas, Michael; Barrandon, Yann] Ecole Polytech Fed Lausanne, Lab Stem Cell Dynam, CH-1015 Lausanne, Switzerland.
   [Abou Jaoude, Georges] Ecole Polytech Fed Lausanne, Lab Informat & Visualizat, CH-1015 Lausanne, Switzerland.
   [Majo, Francois; Rochat, Ariane; Nicolas, Michael; Barrandon, Yann] Univ Lausanne Hosp, CHU Vaudois, Dept Expt Surg, CH-1011 Lausanne, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV)
RP Barrandon, Y (corresponding author), Ecole Polytech Fed Lausanne, Lab Stem Cell Dynam, CH-1015 Lausanne, Switzerland.
EM yann.barrandon@epfl.ch
FU Swiss National Science Foundation [3100A0-104160]; EPFL; CHUV; EuroStemCell; Institut National de la Sante et de la Recherche Medicale (INSERM); Association pour la Recherche contre le Cancer; Association Francaise contre les Myopathies; Federation des Aveugles et Handicapes Visuels de France; INSERM
NR 35
TC 343
Z9 382
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 NOV 13
PY 2008
VL 456
IS 7219
BP 250
EP U51
DI 10.1038/nature07406
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300042
PM 18830243
DA 2026-03-09
ER

PT J
AU Hovhannisyan, Z
   Weiss, A
   Martin, A
   Wiesner, M
   Tollefsen, S
   Yoshida, K
   Ciszewski, C
   Curran, SA
   Murray, JA
   David, CS
   Sollid, LM
   Koning, F
   Teyton, L
   Jabri, B
AF Hovhannisyan, Zaruhi
   Weiss, Angela
   Martin, Alexandra
   Wiesner, Martina
   Tollefsen, Stig
   Yoshida, Kenji
   Ciszewski, Cezary
   Curran, Shane A.
   Murray, Joseph A.
   David, Chella S.
   Sollid, Ludvig M.
   Koning, Frits
   Teyton, Luc
   Jabri, Bana
TI The role of HLA-DQ8 β57 polymorphism in the anti-gluten T-cell response in coeliac disease
SO NATURE
LA English
DT Article
ID major histocompatibility complex; class-ii molecules; small-intestinal mucosa; gliadin; susceptibility; recognition; repertoire; peptides; mouse; gene
AB Major histocompatibility complex ( MHC) class II alleles HLA-DQ8 and the mouse homologue I-A(g7) lacking a canonical aspartic acid residue at position beta 57 are associated with coeliac disease(1,2) and type I diabetes(3,4). However, the role of this single polymorphism in disease initiation and progression remains poorly understood. The lack of Asp 57 creates a positively charged P9 pocket, which confers a preference for negatively charged peptides. Gluten lacks such peptides, but tissue transglutaminase ( TG2) introduces negatively charged residues at defined positions into gluten T- cell epitopes by deamidating specific glutamine residues(5,6) on the basis of their spacing to proline residues(7). The commonly accepted model, proposing that HLA-DQ8 simply favours binding of negatively charged peptides, does not take into account the fact that TG2 requires inflammation for activation(8) and that T- cell responses against native gluten peptides are found(9,10), particularly in children(11). Here we show that beta 57 polymorphism promotes the recruitment of T- cell receptors bearing a negative signature charge in the complementary determining region 3 beta (CDR3 beta) during the response against native gluten peptides presented by HLA-DQ8 in coeliac disease. These T cells showed a crossreactive and heteroclitic ( stronger) response to deamidated gluten peptides. Furthermore, gluten peptide deamidation extended the T- cell- receptor repertoire by relieving the requirement for a charged residue in CDR3 beta. Thus, the lack of a negative charge at position beta 57 in MHC class II was met by negatively charged residues in the T- cell receptor or in the peptide, the combination of which might explain the role of HLA-DQ8 in amplifying the T- cell response against dietary gluten.
C1 [Hovhannisyan, Zaruhi; Martin, Alexandra; Ciszewski, Cezary; Curran, Shane A.; Jabri, Bana] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Hovhannisyan, Zaruhi; Martin, Alexandra; Ciszewski, Cezary; Curran, Shane A.; Jabri, Bana] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
   [Hovhannisyan, Zaruhi; Martin, Alexandra; Ciszewski, Cezary; Curran, Shane A.; Jabri, Bana] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
   [Hovhannisyan, Zaruhi; Martin, Alexandra; Ciszewski, Cezary; Curran, Shane A.; Jabri, Bana] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA.
   [Weiss, Angela] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Wiesner, Martina; Koning, Frits] Leiden Univ, Dept Immunohematol & Blood Transfus, NL-2300 RC Leiden, Netherlands.
   [Tollefsen, Stig; Sollid, Ludvig M.] Natl Hosp Norway, Ctr Immune Regulat, Inst Immunol, N-0027 Oslo, Norway.
   [Yoshida, Kenji; Teyton, Luc] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Murray, Joseph A.; David, Chella S.] Mayo Clin, Coll Med, Dept Immunol, Rochester, MN 55905 USA.
   [Sollid, Ludvig M.] Univ Oslo, Ctr Immune Regulat, Inst Immunol, N-0027 Oslo, Norway.
C3 University of Chicago; University of Chicago; University of Chicago; University of Chicago; Princeton University; Leiden University; Leiden University - Excl LUMC; University of Oslo; National Hospital Norway; Scripps Research Institute; Mayo Clinic; University of Oslo
RP Jabri, B (corresponding author), Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM bjabri@bsd.uchicago.edu
FU Digestive Disease Research Core Center of the University of Chicago [DK42086]; NIH [DK67180, DK55037]; Celiac Disease Consortium; EU MC-RTN [512385]; Research Council of Norway; University of Oslo; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK067180, P30DK042086] Funding Source: NIH RePORTER
NR 30
TC 73
Z9 90
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 534
EP 538
DI 10.1038/nature07524
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500045
PM 19037317
DA 2026-03-09
ER

PT J
AU Christofk, HR
   Vander Heiden, MG
   Wu, N
   Asara, JM
   Cantley, LC
AF Christofk, Heather R.
   Vander Heiden, Matthew G.
   Wu, Ning
   Asara, John M.
   Cantley, Lewis C.
TI Pyruvate kinase M2 is a phosphotyrosine-binding protein
SO NATURE
LA English
DT Article
ID allosteric regulation; receptor kinase; cell-growth; phosphorylation; inhibition; enzymes
AB Growth factors stimulate cells to take up excess nutrients and to use them for anabolic processes. The biochemical mechanism by which this is accomplished is not fully understood but it is initiated by phosphorylation of signalling proteins on tyrosine residues. Using a novel proteomic screen for phosphotyrosine- binding proteins, we have made the observation that an enzyme involved in glycolysis, the human M2 ( fetal) isoform of pyruvate kinase ( PKM2), binds directly and selectively to tyrosine- phosphorylated peptides. We show that binding of phosphotyrosine peptides to PKM2 results in release of the allosteric activator fructose- 1,6- bisphosphate, leading to inhibition of PKM2 enzymatic activity. We also provide evidence that this regulation of PKM2 by phosphotyrosine signalling diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Collectively, our results indicate that expression of this phosphotyrosine- binding form of pyruvate kinase is critical for rapid growth in cancer cells.
C1 [Christofk, Heather R.; Vander Heiden, Matthew G.; Wu, Ning; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Asara, John M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
RP Cantley, LC (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM lcantley@hms.harvard.edu
FU National Cancer Institute [T32CA009172] Funding Source: NIH RePORTER; NCI NIH HHS [T32 CA009172] Funding Source: Medline; NIGMS NIH HHS [R01 GM056203] Funding Source: Medline
NR 17
TC 829
Z9 1004
U1 1
U2 158
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 13
PY 2008
VL 452
IS 7184
BP 181
EP U27
DI 10.1038/nature06667
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600033
PM 18337815
DA 2026-03-09
ER

PT J
AU Poulet, JFA
   Petersen, CCH
AF Poulet, James F. A.
   Petersen, Carl C. H.
TI Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice
SO NATURE
LA English
DT Article
ID cat visual-cortex; motor cortex; somatosensory cortex; rhythmic whisking; in-vivo; neurons; rat; oscillations; responses; awake
AB Internal brain states form key determinants for sensory perception, sensorimotor coordination and learning(1,2). A prominent reflection of different brain states in the mammalian central nervous system is the presence of distinct patterns of cortical synchrony, as revealed by extracellular recordings of the electroencephalogram, local field potential and action potentials. Such temporal correlations of cortical activity are thought to be fundamental mechanisms of neuronal computation(3-11). However, it is unknown how cortical synchrony is reflected in the intracellular membrane potential (V(m)) dynamics of behaving animals. Here we show, using dual whole-cell recordings from layer 2/3 primary somatosensory barrel cortex in behaving mice, that the Vm of nearby neurons is highly correlated during quiet wakefulness. However, when the mouse is whisking, an internally generated state change reduces the Vm correlation, resulting in a desynchronized local field potential and electroencephalogram. Action potential activity was sparse during both quiet wakefulness and active whisking. Single action potentials were driven by a large, brief and specific excitatory input that was not present in the Vm of neighbouring cells. Action potential initiation occurs with a higher signal-to-noise ratio during active whisking than during quiet periods. Therefore, we show that an internal brain state dynamically regulates cortical membrane potential synchrony during behaviour and defines different modes of cortical processing.
C1 [Poulet, James F. A.; Petersen, Carl C. H.] Ecole Polytech Fed Lausanne, Lab Sensory Proc, Brain Mind Inst, Fac Life Sci, CH-1015 Lausanne, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne
RP Petersen, CCH (corresponding author), Ecole Polytech Fed Lausanne, Lab Sensory Proc, Brain Mind Inst, Fac Life Sci, CH-1015 Lausanne, Switzerland.
EM carl.petersen@epfl.ch
NR 34
TC 617
Z9 751
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 14
PY 2008
VL 454
IS 7206
BP 881
EP U36
DI 10.1038/nature07150
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600035
PM 18633351
DA 2026-03-09
ER

PT J
AU Heng, JIT
   Nguyen, L
   Castro, DS
   Zimmer, C
   Wildner, H
   Armant, O
   Skowronska-Krawczyk, D
   Bedogni, F
   Matter, JM
   Hevner, R
   Guillemot, F
AF Heng, Julian Ik-Tsen
   Nguyen, Laurent
   Castro, Diogo S.
   Zimmer, Celine
   Wildner, Hendrik
   Armant, Olivier
   Skowronska-Krawczyk, Dorota
   Bedogni, Francesco
   Matter, Jean-Marc
   Hevner, Robert
   Guillemot, Francois
TI Neurogenin 2 controls cortical neuron migration through regulation of Rnd2
SO NATURE
LA English
DT Article
ID cerebral-cortex; pyramidal neurons; cell-migration; proneural bhlh; rho family; differentiation; neocortex; proteins; specification; hippocampus
AB Motility is a universal property of newly generated neurons. How cell migration is coordinately regulated with other aspects of neuron production is not well understood. Here we show that the proneural protein neurogenin 2 ( Neurog2), which controls neurogenesis in the embryonic cerebral cortex(1,2), directly induces the expression of the small GTP- binding protein Rnd2 ( ref. 3) in newly generated mouse cortical neurons before they initiate migration. Rnd2 silencing leads to a defect in radial migration of cortical neurons similar to that observed when the Neurog2 gene is deleted. Remarkably, restoring Rnd2 expression in Neurog2- mutant neurons is sufficient to rescue their ability to migrate. Our results identify Rnd2 as a novel essential regulator of neuronal migration in the cerebral cortex and demonstrate that Rnd2 is a major effector of Neurog2 function in the promotion of migration. Thus, a proneural protein controls the complex cellular behaviour of cell migration through a remarkably direct pathway involving the transcriptional activation of a small GTP- binding protein.
C1 [Heng, Julian Ik-Tsen; Nguyen, Laurent; Castro, Diogo S.; Zimmer, Celine; Wildner, Hendrik; Armant, Olivier; Guillemot, Francois] Natl Inst Med Res, Div Mol Neurobiol, London NW7 1AA, England.
   [Skowronska-Krawczyk, Dorota; Matter, Jean-Marc] Univ Geneva, Dept Biochem, CH-1211 Geneva 4, Switzerland.
   [Bedogni, Francesco; Hevner, Robert] Univ Washington, Harborview Med Ctr, Sch Med, Dept Pathol, Seattle, WA 98104 USA.
C3 MRC National Institute for Medical Research; University of Geneva; Harborview Medical Center; University of Washington; University of Washington Seattle
RP Guillemot, F (corresponding author), Natl Inst Med Res, Div Mol Neurobiol, Mill Hill, London NW7 1AA, England.
EM fguille@nimr.mrc.ac.uk
FU Australian CJ Martin Fellowship [310616]; Medical Research Council career development fellowship; European Molecular Biology Organization; Medical Research Council career development fellowships; European Commission 6th Framework Programme for Research and Technological Development; Medical Research Council; MRC [MC_U117570528] Funding Source: UKRI; Medical Research Council [MC_U117570528] Funding Source: researchfish; National Health and Medical Research Council (NHMRC) [310616] Funding Source: National Health and Medical Research Council (NHMRC)
NR 30
TC 221
Z9 250
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 SEP 4
PY 2008
VL 455
IS 7209
BP 114
EP U82
DI 10.1038/nature07198
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200048
PM 18690213
DA 2026-03-09
ER

PT J
AU Fabian, AC
   Johnstone, RM
   Sanders, JS
   Conselice, CJ
   Crawford, CS
   Gallagher, JS
   Zweibel, E
AF Fabian, A. C.
   Johnstone, R. M.
   Sanders, J. S.
   Conselice, C. J.
   Crawford, C. S.
   Gallagher, J. S., III
   Zweibel, E.
TI Magnetic support of the optical emission line filaments in NGC 1275
SO NATURE
LA English
DT Article
ID perseus cluster; x-ray; excitation; core; discovery; software; fields
AB The giant elliptical galaxy NGC 1275, at the centre of the Perseus cluster, is surrounded by a well- known giant nebulosity of emission-line filaments(1,2), which are plausibly in excess of 10(8) years old(3). The filaments are dragged out from the centre of the galaxy by radio-emitting 'bubbles' rising buoyantly in the hot intracluster gas(4), before later falling back. They act as markers of the feedback process by which energy is transferred from the central massive black hole to the surrounding gas. The mechanism by which the filaments are stabilized against tidal shear and dissipation into the surrounding extremely hot (4 x 10(7) K) gas has been unclear. Here we report observations that resolve thread- like structures in the filaments. Some threads extend over 6 kpc, yet are only 70 pc wide. We conclude that magnetic fields in the threads, in pressure balance with the surrounding gas, stabilize the filaments, so allowing a large mass of cold gas to accumulate and delay star formation.
C1 [Fabian, A. C.; Johnstone, R. M.; Sanders, J. S.; Crawford, C. S.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Conselice, C. J.] Univ Nottingham, Sch Phys & Astron, Nottingham NG7 2RD, England.
   [Gallagher, J. S., III; Zweibel, E.] Univ Wisconsin, Dept Astron, Madison, WI 53706 USA.
   [Zweibel, E.] Univ Wisconsin, Dept Phys, Madison, WI 53706 USA.
C3 University of Cambridge; University of Nottingham; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
RP Fabian, AC (corresponding author), Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
EM acf@ast.cam.ac.uk
FU Royal Society; NSF [AST 0507367];  [HST-GO-11207.07-A]; STFC [ST/F00298X/1, ST/F001967/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/F001967/1, ST/F00298X/1] Funding Source: researchfish
NR 20
TC 143
Z9 158
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 AUG 21
PY 2008
VL 454
IS 7207
BP 968
EP 970
DI 10.1038/nature07169
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000032
PM 18719583
DA 2026-03-09
ER

PT J
AU Yapici, N
   Kim, YJ
   Ribeiro, C
   Dickson, BJ
AF Yapici, Nilay
   Kim, Young-Joon
   Ribeiro, Carlos
   Dickson, Barry J.
TI A receptor that mediates the post-mating switch in Drosophila reproductive behaviour
SO NATURE
LA English
DT Article
ID melanogaster sex-peptide; male courtship behavior; functional expression; helicoverpa-armigera; fmrfamide receptor; molecular-cloning; seminal peptides; neural circuitry; female; identification
AB Mating in many species induces a dramatic switch in female reproductive behaviour. In most insects, this switch is triggered by factors present in the male's seminal fluid. How these factors exert such profound effects in females is unknown. Here we identify a receptor for the Drosophila melanogaster sex peptide (SP, also known as Acp70A), the primary trigger of post- mating responses in this species. Females that lack the sex peptide receptor (SPR, also known as CG16752), either entirely or only in the nervous system, fail to respond to SP and continue to show virgin behaviours even after mating. SPR is expressed in the female's reproductive tract and central nervous system. The behavioural functions of SPR map to the subset of neurons that also express the fruitless gene, a key determinant of sex- specific reproductive behaviour. SPR is highly conserved across insects, opening up the prospect of new strategies to control the reproductive and host- seeking behaviours of agricultural pests and human disease vectors.
C1 [Yapici, Nilay; Kim, Young-Joon; Ribeiro, Carlos; Dickson, Barry J.] Res Inst Mol Pathol, A-1030 Vienna, Austria.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP)
RP Dickson, BJ (corresponding author), Res Inst Mol Pathol, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
EM dickson@imp.ac.at
NR 45
TC 415
Z9 503
U1 5
U2 168
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 33
EP U1
DI 10.1038/nature06483
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300026
PM 18066048
DA 2026-03-09
ER

PT J
AU Kohsaka, Y
   Taylor, C
   Wahl, P
   Schmidt, A
   Lee, J
   Fujita, K
   Alldredge, JW
   McElroy, K
   Lee, J
   Eisaki, H
   Uchida, S
   Lee, DH
   Davis, JC
AF Kohsaka, Y.
   Taylor, C.
   Wahl, P.
   Schmidt, A.
   Lee, Jhinhwan
   Fujita, K.
   Alldredge, J. W.
   McElroy, K.
   Lee, Jinho
   Eisaki, H.
   Uchida, S.
   Lee, D. -H.
   Davis, J. C.
TI How cooper pairs vanish approaching the Mott insulator in Bi2Sr2CaCu2O8+δ
SO NATURE
LA English
DT Article
ID quasi-particles; physics; pseudogap; evolution
AB The antiferromagnetic ground state of copper oxide Mott insulators is achieved by localizing an electron at each copper atom in real space (r-space). Removing a small fraction of these electrons ( hole doping) transforms this system into a superconducting fluid of delocalized Cooper pairs in momentum space ( k- space). During this transformation, two distinctive classes of electronic excitations appear. At high energies, the mysterious 'pseudogap' excitations are found, whereas, at lower energies, Bogoliubov quasi- particles - the excitations resulting from the breaking of Cooper pairs should exist. To explore this transformation, and to identify the two excitation types, we have imaged the electronic structure of Bi2Sr2CaCu2O8+delta in r- space and k- space simultaneously. We find that although the low- energy excitations are indeed Bogoliubov quasi- particles, they occupy only a restricted region of k- space that shrinks rapidly with diminishing hole density. Concomitantly, spectral weight is transferred to higher energy r- space states that lack the characteristics of excitations from delocalized Cooper pairs. Instead, these states break translational and rotational symmetries locally at the atomic scale in an energy- independent way. We demonstrate that these unusual r- space excitations are, in fact, the pseudogap states. Thus, as the Mott insulating state is approached by decreasing the hole density, the delocalized Cooper pairs vanish from k- space, to be replaced by locally translational- and rotational- symmetry- breaking pseudogap states in r- space.
C1 [Kohsaka, Y.; Taylor, C.; Wahl, P.; Schmidt, A.; Lee, Jhinhwan; Fujita, K.; Alldredge, J. W.; Lee, Jinho; Davis, J. C.] Cornell Univ, Dept Phys, LASSP, Ithaca, NY 14853 USA.
   [Kohsaka, Y.] RIKEN, Wako, Saitama 3510198, Japan.
   [Fujita, K.] Univ Tokyo, Dept Phys, Bunkyo Ku, Tokyo 1130033, Japan.
   [Alldredge, J. W.; McElroy, K.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
   [Lee, Jinho] Univ St Andrews, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
   [Lee, Jinho; Davis, J. C.] Brookhaven Natl Lab, CMPMS Dept, Upton, NY 11973 USA.
   [Eisaki, H.] Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki 3058568, Japan.
   [Lee, D. -H.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
C3 Cornell University; RIKEN; University of Tokyo; University of Colorado System; University of Colorado Boulder; University of St Andrews; United States Department of Energy (DOE); Brookhaven National Laboratory; National Institute of Advanced Industrial Science & Technology (AIST); University of California System; University of California Berkeley
RP Davis, JC (corresponding author), Cornell Univ, Dept Phys, LASSP, Ithaca, NY 14853 USA.
EM jcdavis@ccmr.cornell.edu
FU US National Science Foundation through the Cornell Center for Material Research; Brookhaven National Laboratory; US Department of Energy; US Office of Naval Research; Ministry of Science and Education (Japan); 21st Century COE Program of the Japan Society for the Promotion of Science.; Humboldt Foundation; US Army Research Office
NR 50
TC 311
Z9 351
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 AUG 28
PY 2008
VL 454
IS 7208
BP 1072
EP 1078
DI 10.1038/nature07243
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600028
PM 18756248
DA 2026-03-09
ER

PT J
AU Byres, E
   Paton, AW
   Paton, JC
   Löfling, JC
   Smith, DF
   Wilce, MCJ
   Talbot, UM
   Chong, DC
   Yu, H
   Huang, SS
   Chen, X
   Varki, NM
   Varki, A
   Rossjohn, J
   Beddoe, T
AF Byres, Emma
   Paton, Adrienne W.
   Paton, James C.
   Lofling, Jonas C.
   Smith, David F.
   Wilce, Matthew C. J.
   Talbot, Ursula M.
   Chong, Damien C.
   Yu, Hai
   Huang, Shengshu
   Chen, Xi
   Varki, Nissi M.
   Varki, Ajit
   Rossjohn, Jamie
   Beddoe, Travis
TI Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin
SO NATURE
LA English
DT Article
ID subtilase cytotoxin; cholera-toxin; ab(5) toxin; model; mice; targets; binding; potent; site
AB AB(5) toxins comprise an A subunit that corrupts essential eukaryotic cell functions, and pentameric B subunits that direct targetcell uptake after binding surface glycans. Subtilase cytotoxin (SubAB) is an AB5 toxin secreted by Shiga toxigenic Escherichia coli (STEC)(1), which causes serious gastrointestinal disease in humans(2). SubAB causes haemolytic uraemic syndrome- like pathology in mice(3) through SubA- mediated cleavage of BiP/GRP78, an essential endoplasmic reticulum chaperone(4). Here we show that SubB has a strong preference for glycans terminating in the sialic acid N- glycolylneuraminic acid (Neu5Gc), a monosaccharide not synthesized in humans. Structures of SubB - Neu5Gc complexes revealed the basis for this specificity, and mutagenesis of key SubB residues abrogated in vitro glycan recognition, cell binding and cytotoxicity. SubAB specificity for Neu5Gc was confirmed using mouse tissues with a human- like deficiency of Neu5Gc and human cell lines fed with Neu5Gc. Despite lack of Neu5Gc biosynthesis in humans, assimilation of dietary Neu5Gc creates high- affinity receptors on human gut epithelia and kidney vasculature. This, and the lack of Neu5Gc- containing body fluid competitors in humans, confers susceptibility to the gastrointestinal and systemic toxicities of SubAB. Ironically, foods rich in Neu5Gc are the most common source of STEC contamination. Thus a bacterial toxin's receptor is generated by metabolic incorporation of an exogenous factor derived from food.
C1 [Lofling, Jonas C.; Varki, Nissi M.; Varki, Ajit] Univ Calif San Diego, Glycobiol Res & Training Ctr, La Jolla, CA 92093 USA.
   [Byres, Emma; Wilce, Matthew C. J.; Rossjohn, Jamie; Beddoe, Travis] Monash Univ, Prot Crystallog Unit, Clayton, Vic 3800, Australia.
   [Byres, Emma; Wilce, Matthew C. J.; Rossjohn, Jamie; Beddoe, Travis] Monash Univ, ARC Ctr Excellence Struct & Funct Microbial Genom, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [Paton, Adrienne W.; Paton, James C.; Talbot, Ursula M.; Chong, Damien C.] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia.
   [Smith, David F.] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
   [Yu, Hai; Huang, Shengshu; Chen, Xi] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA.
C3 University of California System; University of California San Diego; Monash University; Monash University; Adelaide University; University of Adelaide; Emory University; University of California System; University of California Davis
RP Varki, A (corresponding author), Univ Calif San Diego, Glycobiol Res & Training Ctr, La Jolla, CA 92093 USA.
EM a1varki@ucsd.edu; jamie.rossjohn@med.monash.edu.au; travis.beddoe@med.monash.edu.au
FU Program Grant from the National Health; Medical Research Council of Australia; NHMRC Project Grant; National Institute of General Medical Sciences to the Consortium for Functional Glycomics; National Institutes of Health [RO1]; ARC Centre of Excellence in Structural and Functional Microbial Genomics; Australian Research Council Federation Fellowship; NHMRC Career Development Award; NHMRC Australia Fellowship
NR 30
TC 196
Z9 217
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 4
PY 2008
VL 456
IS 7222
BP 648
EP U75
DI 10.1038/nature07428
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000043
PM 18971931
DA 2026-03-09
ER

PT J
AU Vinokur, VM
   Baturina, TI
   Fistul, MV
   Mironov, AY
   Baklanov, MR
   Strunk, C
AF Vinokur, Valerii M.
   Baturina, Tatyana I.
   Fistul, Mikhail V.
   Mironov, Aleksey Yu.
   Baklanov, Mikhail R.
   Strunk, Christoph
TI Superinsulator and quantum synchronization
SO NATURE
LA English
DT Article
ID tunnel-junctions; arrays; charge
AB Synchronized oscillators are ubiquitous in nature(1), and synchronization plays a key part in various classical and quantum phenomena. Several experiments(2-4) have shown that in thin superconducting films, disorder enforces the droplet- like electronic texture - superconducting islands immersed into a normal matrix - and that tuning disorder drives the system from superconducting to insulating behaviour. In the vicinity of the transition, a distinct state(4) forms: a Cooper- pair insulator, with thermally activated conductivity. It results from synchronization of the phase of the superconducting order parameter at the islands across the whole system(5). Here we show that at a certain finite temperature, a Cooper- pair insulator undergoes a transition to a superinsulating state with infinite resistance. We present experimental evidence of this transition in titanium nitride films and show that the superinsulating state is dual to the superconducting state: it is destroyed by a sufficiently strong critical magnetic field, and breaks down at some critical voltage that is analogous to the critical current in superconductors.
C1 [Vinokur, Valerii M.; Baturina, Tatyana I.] Argonne Natl Lab, Div Mat Sci, Argonne, IL 60439 USA.
   [Baturina, Tatyana I.; Mironov, Aleksey Yu.] Russian Acad Sci, Inst Semicond Phys, Novosibirsk 630090, Russia.
   [Baturina, Tatyana I.; Mironov, Aleksey Yu.; Strunk, Christoph] Univ Regensburg, Inst Expt Angew Phys, D-93040 Regensburg, Germany.
   [Fistul, Mikhail V.] Ruhr Univ Bochum, D-44801 Bochum, Germany.
   [Baklanov, Mikhail R.] IMEC, B-3001 Louvain, Belgium.
C3 United States Department of Energy (DOE); Argonne National Laboratory; Russian Academy of Sciences; Rzhanov Institute of Semiconductor Physics, Siberian Branch, Russian Academy of Sciences; University of Regensburg; Ruhr University Bochum; Interuniversity Microelectronics Centre
RP Vinokur, VM (corresponding author), Argonne Natl Lab, Div Mat Sci, 9700 S Cass Ave, Argonne, IL 60439 USA.
EM vinokour@anl.gov
NR 21
TC 202
Z9 214
U1 1
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 613
EP U5
DI 10.1038/nature06837
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200041
PM 18385735
DA 2026-03-09
ER

PT J
AU Kleinman, ME
   Yamada, K
   Takeda, A
   Chandrasekaran, V
   Nozaki, M
   Baffi, JZ
   Albuquerque, RJC
   Yamasaki, S
   Itaya, M
   Pan, YZ
   Appukuttan, B
   Gibbs, D
   Yang, ZL
   Karikó, K
   Ambati, BK
   Wilgus, TA
   DiPietro, LA
   Sakurai, E
   Zhang, K
   Smith, JR
   Taylor, EW
   Ambati, J
AF Kleinman, Mark E.
   Yamada, Kiyoshi
   Takeda, Atsunobu
   Chandrasekaran, Vasu
   Nozaki, Miho
   Baffi, Judit Z.
   Albuquerque, Romulo J. C.
   Yamasaki, Satoshi
   Itaya, Masahiro
   Pan, Yuzhen
   Appukuttan, Binoy
   Gibbs, Daniel
   Yang, Zhenglin
   Kariko, Katalin
   Ambati, Balamurali K.
   Wilgus, Traci A.
   DiPietro, Luisa A.
   Sakurai, Eiji
   Zhang, Kang
   Smith, Justine R.
   Taylor, Ethan W.
   Ambati, Jayakrishna
TI Sequence- and target-independent angiogenesis suppression by siRNA via TLR3
SO NATURE
LA English
DT Article
ID toll-like receptor-3; double-stranded-rna; small interfering rnas; in-vivo delivery; nf-kappa-b; choroidal neovascularization; ocular neovascularization; negative regulator; endothelial-cells; signaling pathway
AB Clinical trials of small interfering RNA ( siRNA) targeting vascular endothelial growth factor-A ( VEGFA) or its receptor VEGFR1 ( also called FLT1), in patients with blinding choroidal neovascularization ( CNV) from age- related macular degeneration, are premised on gene silencing by means of intracellular RNA interference ( RNAi). Weshow instead that CNV inhibition is a siRNA- class effect: 21- nucleotide or longer siRNAs targeting non- mammalian genes, non- expressed genes, non- genomic sequences, pro- and anti- angiogenic genes, and RNAi- incompetent siRNAs all suppressed CNV in mice comparably to siRNAs targeting Vegfa or Vegfr1 without off- target RNAi or interferon-alpha/beta activation. Non- targeted ( against non- mammalian genes) and targeted ( against Vegfa or Vegfr1) siRNA suppressed CNV via cell- surface toll- like receptor 3 ( TLR3), its adaptor TRIF, and induction of interferon-gamma and interleukin- 12. Non- targeted siRNA suppressed dermal neovascularization in mice as effectively as Vegfa siRNA. siRNA- induced inhibition of neovascularization required a minimum length of 21 nucleotides, a bridging necessity in a modelled 2: 1 TLR3 - RNA complex. Choroidal endothelial cells from people expressing the TLR3 coding variant 412FF were refractory to extracellular siRNA- induced cytotoxicity, facilitating individualized pharmacogenetic therapy. Multiple human endothelial cell types expressed surface TLR3, indicating that generic siRNAs might treat angiogenic disorders that affect 8% of the world's population, and that siRNAs might induce unanticipated vascular or immune effects.
C1 [Kleinman, Mark E.; Yamada, Kiyoshi; Takeda, Atsunobu; Nozaki, Miho; Baffi, Judit Z.; Albuquerque, Romulo J. C.; Ambati, Jayakrishna] Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
   [Albuquerque, Romulo J. C.; Ambati, Jayakrishna] Univ Kentucky, Dept Physiol, Lexington, KY 40506 USA.
   [Chandrasekaran, Vasu] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
   [Yamasaki, Satoshi; Itaya, Masahiro; Sakurai, Eiji] Nagoya City Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 4678601, Japan.
   [Pan, Yuzhen; Appukuttan, Binoy; Smith, Justine R.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA.
   [Gibbs, Daniel; Yang, Zhenglin; Ambati, Balamurali K.; Zhang, Kang] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   [Gibbs, Daniel; Yang, Zhenglin; Zhang, Kang] Univ Utah, Sch Med, Program Human Mol Biol & Genet, Eccles Inst Human Genet, Salt Lake City, UT 84132 USA.
   [Kariko, Katalin] Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA.
   [Ambati, Balamurali K.] Vet Affairs Salt Lake City Healthcare Syst, Salt Lake City, UT 84148 USA.
   [Wilgus, Traci A.; DiPietro, Luisa A.] Univ Illinois, Coll Dent, Ctr Wound Healing & Tissue Regenerat, Chicago, IL 60612 USA.
   [Taylor, Ethan W.] Univ N Carolina, Mol Med Lab, Greensboro, NC 27402 USA.
C3 University of Kentucky; University of Kentucky; University of North Carolina; University of North Carolina Chapel Hill; Nagoya City University; Oregon Health & Science University; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; University of Pennsylvania; US Department of Veterans Affairs; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of North Carolina; University of North Carolina Greensboro
RP Ambati, J (corresponding author), Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
EM jamba2@email.uky.edu
FU NEI NIH HHS [R01 EY018836, R01 EY018350, R01 EY015422] Funding Source: Medline; NIGMS NIH HHS [R01 GM050875] Funding Source: Medline
NR 55
TC 785
Z9 953
U1 4
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 APR 3
PY 2008
VL 452
IS 7187
BP 591
EP U1
DI 10.1038/nature06765
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200037
PM 18368052
DA 2026-03-09
ER

PT J
AU Umehara, M
   Hanada, A
   Yoshida, S
   Akiyama, K
   Arite, T
   Takeda-Kamiya, N
   Magome, H
   Kamiya, Y
   Shirasu, K
   Yoneyama, K
   Kyozuka, J
   Yamaguchi, S
AF Umehara, Mikihisa
   Hanada, Atsushi
   Yoshida, Satoko
   Akiyama, Kohki
   Arite, Tomotsugu
   Takeda-Kamiya, Noriko
   Magome, Hiroshi
   Kamiya, Yuji
   Shirasu, Ken
   Yoneyama, Koichi
   Kyozuka, Junko
   Yamaguchi, Shinjiro
TI Inhibition of shoot branching by new terpenoid plant hormones
SO NATURE
LA English
DT Article
ID arbuscular mycorrhizal fungi; germination stimulants; phosphorus deficiency; apical-dominance; gibberellic-acid; parasitic plants; root parasites; arabidopsis; rice; strigol
AB Shoot branching is a major determinant of plant architecture and is highly regulated by endogenous and environmental cues. Two classes of hormones, auxin and cytokinin, have long been known to have an important involvement in controlling shoot branching. Previous studies using a series of mutants with enhanced shoot branching suggested the existence of a third class of hormone( s) that is derived from carotenoids, but its chemical identity has been unknown. Here we show that levels of strigolactones, a group of terpenoid lactones, are significantly reduced in some of the branching mutants. Furthermore, application of strigolactones inhibits shoot branching in these mutants. Strigolactones were previously found in root exudates acting as communication chemicals with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Thus, we propose that strigolactones act as a new hormone class - or their biosynthetic precursors - in regulating above- ground plant architecture, and also have a function in underground communication with other neighbouring organisms.
C1 [Umehara, Mikihisa; Hanada, Atsushi; Yoshida, Satoko; Takeda-Kamiya, Noriko; Magome, Hiroshi; Kamiya, Yuji; Shirasu, Ken; Yamaguchi, Shinjiro] RIKEN, Plant Sci Ctr, Yokohama, Kanagawa 2300045, Japan.
   [Akiyama, Kohki] Osaka Prefecture Univ, Grad Sch Life & Environm Sci, Naka Ku, Osaka 5998531, Japan.
   [Arite, Tomotsugu; Kyozuka, Junko] Univ Tokyo, Grad Sch Agr & Life Sci, Bunkyo Ku, Tokyo 1138652, Japan.
   [Yoneyama, Koichi] Utsunomiya Univ, Weed Sci Ctr, Utsunomiya, Tochigi 3218505, Japan.
C3 RIKEN; University of Tokyo; Utsunomiya University
RP Yamaguchi, S (corresponding author), RIKEN, Plant Sci Ctr, Yokohama, Kanagawa 2300045, Japan.
EM shinjiro@postman.riken.jp
FU MEXT of Japan [1820810, 19678001, 19780040]; MAFF of Japan (Genomics for Agricultural Innovation) [IPG0001]; RIKEN Special Postdoctoral Researchers Program; Grants-in-Aid for Scientific Research [19780040, 19678001] Funding Source: KAKEN
NR 44
TC 1665
Z9 1926
U1 26
U2 791
PU 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 11
PY 2008
VL 455
IS 7210
BP 195
EP U29
DI 10.1038/nature07272
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800040
PM 18690207
DA 2026-03-09
ER

PT J
AU Czech, B
   Malone, CD
   Zhou, R
   Stark, A
   Schlingeheyde, C
   Dus, M
   Perrimon, N
   Kellis, M
   Wohlschlegel, JA
   Sachidanandam, R
   Hannon, GJ
   Brennecke, J
AF Czech, Benjamin
   Malone, Colin D.
   Zhou, Rui
   Stark, Alexander
   Schlingeheyde, Catherine
   Dus, Monica
   Perrimon, Norbert
   Kellis, Manolis
   Wohlschlegel, James A.
   Sachidanandam, Ravi
   Hannon, Gregory J.
   Brennecke, Julius
TI An endogenous small interfering RNA pathway in Drosophila
SO NATURE
LA English
DT Article
ID c-elegans; microrna maturation; argonaute proteins; distinct roles; biogenesis; initiation; germline; elements; reveals; virus
AB Drosophila endogenous small RNAs are categorized according to their mechanisms of biogenesis and the Argonaute protein to which they bind. MicroRNAs are a class of ubiquitously expressed RNAs of 22 nucleotides in length, which arise from structured precursors through the action of Drosha - Pasha and Dicer- 1-Loquacious complexes(1-7). These join Argonaute-1 to regulate gene expression(8,9). A second endogenous small RNA class, the Piwi-interacting RNAs, bind Piwi proteins and suppress transposons(10,11). Piwi- interacting RNAs are restricted to the gonad, and at least a subset of these arises by Piwi- catalysed cleavage of single-stranded RNAs(12,13). Here we show that Drosophila generates a third small RNA class, endogenous small interfering RNAs, in both gonadal and somatic tissues. Production of these RNAs requires Dicer- 2, but a subset depends preferentially on Loquacious(1,4,5) rather than the canonical Dicer- 2 partner, R2D2 ( ref. 14). Endogenous small interfering RNAs arise both from convergent transcription units and from structured genomic loci in a tissue- specific fashion. They predominantly join Argonaute- 2 and have the capacity, as a class, to target both protein- coding genes and mobile elements. These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles.
C1 [Czech, Benjamin; Malone, Colin D.; Schlingeheyde, Catherine; Dus, Monica; Sachidanandam, Ravi; Hannon, Gregory J.; Brennecke, Julius] Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Zhou, Rui; Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Stark, Alexander; Kellis, Manolis] MIT, Broad Inst, Cambridge, MA 02141 USA.
   [Stark, Alexander; Kellis, Manolis] Harvard Univ, Broad Inst, Cambridge, MA 02141 USA.
   [Stark, Alexander] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Wohlschlegel, James A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA.
C3 Howard Hughes Medical Institute; Cold Spring Harbor Laboratory; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
RP Hannon, GJ (corresponding author), Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM hannon@cshl.edu; brenneck@cshl.edu
FU Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF); NHGRI NIH HHS [U54 HG004570, U54 HG004555, U01 HG004264] Funding Source: Medline
NR 32
TC 558
Z9 686
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 JUN 5
PY 2008
VL 453
IS 7196
BP 798
EP U7
DI 10.1038/nature07007
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300047
PM 18463631
DA 2026-03-09
ER

PT J
AU Li, L
   Weidner, DJ
AF Li, Li
   Weidner, Donald J.
TI Effect of phase transitions on compressional-wave velocities in the Earth's mantle
SO NATURE
LA English
DT Article
ID high-pressures; transformation; discontinuity; temperatures; perovskite; diffusion; kinetics; olivine; spinel
AB The velocities of seismic waves in the Earth are governed by the response of the constituent mineral assemblage to perturbations in pressure and stress. The effective bulk modulus is significantly lowered if the pressure of the seismic wave drives a volume- reducing phase transformation(1,2). A comparison between the amount of time required by phase transitions to reach equilibrium and the sampling period thus becomes crucial in defining the softening and attenuation of compressional waves within such a two- phase zone(3). These phenomena are difficult to assess experimentally, however, because data at conditions appropriate to the Earth's deep interior are required. Here we present synchrotron- based experimental data that demonstrate softening of the bulk modulus within the two- phase loop of olivine - ringwoodite on a timescale of 100 s. If the amplitude of the pressure perturbation and the grain size are scaled to those expected in the Earth, the compressional-wave velocities within the discontinuities at 410, 520 and, possibly, 660 km are likely to be significantly lower than otherwise expected. The generalization of these observations to aluminium- controlled phase transitions raises the possibility of large velocity perturbations throughout the upper 1,000 km of the mantle.
C1 [Li, Li; Weidner, Donald J.] SUNY Stony Brook, Inst Mineral Phys, Dept Geosci, Stony Brook, NY 11794 USA.
C3 State University of New York (SUNY) System; Stony Brook University
RP Li, L (corresponding author), SUNY Stony Brook, Inst Mineral Phys, Dept Geosci, Stony Brook, NY 11794 USA.
EM lilli@ic.sunysb.edu
FU National Synchrotron Light Source; Consortium for Materials Properties in Earth Sciences; US Department of Energy [DE-AC02_ 98CH10886]; US National Science Foundation [EAR-0711365, EAR652887, EAR 01-35554]
NR 20
TC 50
Z9 56
U1 1
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 21
PY 2008
VL 454
IS 7207
BP 984
EP 986
DI 10.1038/nature07230
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000036
PM 18719587
DA 2026-03-09
ER

PT J
AU Chen, ST
   Lin, YL
   Huang, MT
   Wu, MF
   Cheng, SC
   Lei, HY
   Lee, CK
   Chiou, TW
   Wong, CH
   Hsieh, SL
AF Chen, Szu-Ting
   Lin, Yi-Ling
   Huang, Ming-Ting
   Wu, Ming-Fang
   Cheng, Shih-Chin
   Lei, Huan-Yao
   Lee, Chien-Kuo
   Chiou, Tzyy-Wen
   Wong, Chi-Huey
   Hsieh, Shie-Liang
TI CLEC5A is critical for dengue-virus-induced lethal disease
SO NATURE
LA English
DT Article
ID c-type lectins; dc-sign; dendritic cells; carbohydrate-recognition; decoy receptor-3; innate immunity; infection; enhancement; activation; antibody
AB Dengue haemorrhagic fever and dengue shock syndrome, the most severe responses to dengue virus ( DV) infection, are characterized by plasma leakage ( due to increased vascular permeability) and low platelet counts(1,2). CLEC5A ( C- type lectin domain family 5, member A; also known as myeloid DAP12- associating lectin ( MDL-1))(3) contains a C- type lectin- like fold similar to the natural- killer T- cell C- type lectin domains and associates with a 12- kDa DNAX- activating protein ( DAP12)(4) on myeloid cells. Here we show that CLEC5A interacts with the dengue virion directly and thereby brings about DAP12 phosphorylation. The CLEC5A DV interaction does not result in viral entry but stimulates the release of proinflammatory cytokines. Blockade of CLEC5A - DV interaction suppresses the secretion of proinflammatory cytokines without affecting the release of interferon-alpha, supporting the notion that CLEC5A acts as a signalling receptor for proinflammatory cytokine release. Moreover, anti- CLEC5A monoclonal antibodies inhibit DV- induced plasma leakage, as well as subcutaneous and vital- organ haemorrhaging, and reduce the mortality of DV infection by about 50% in STAT1- deficient mice. Our observation that blockade of CLEC5A- mediated signalling attenuates the production of proinflammatory cytokines by macrophages infected with DV ( either alone or complexed with an enhancing antibody) offers a promising strategy for alleviating tissue damage and increasing the survival of patients suffering from dengue haemorrhagic fever and dengue shock syndrome, and possibly even other virus- induced inflammatory diseases.
C1 [Chen, Szu-Ting; Huang, Ming-Ting; Wu, Ming-Fang; Cheng, Shih-Chin; Hsieh, Shie-Liang] Natl Yang Ming Univ, Dept Microbiol & Immunol, Taipei 112, Taiwan.
   [Chen, Szu-Ting; Huang, Ming-Ting; Wu, Ming-Fang; Cheng, Shih-Chin; Hsieh, Shie-Liang] Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 112, Taiwan.
   [Lin, Yi-Ling] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan.
   [Lin, Yi-Ling; Wong, Chi-Huey; Hsieh, Shie-Liang] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
   [Lei, Huan-Yao] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Tainan 70101, Taiwan.
   [Lee, Chien-Kuo] Natl Taiwan Univ, Inst Immunol, Taipei 100, Taiwan.
   [Chiou, Tzyy-Wen] Natl Dong Hwa Univ, Dept Life Sci, Hualien 974, Taiwan.
   [Chiou, Tzyy-Wen] Natl Dong Hwa Univ, Inst Biotechnol, Hualien 974, Taiwan.
   [Hsieh, Shie-Liang] Natl Yang Ming Univ, Immunol Res Ctr, Taipei 112, Taiwan.
   [Hsieh, Shie-Liang] Taipei Vet Gen Hosp, Taipei 112, Taiwan.
C3 National Yang Ming Chiao Tung University; National Yang Ming Chiao Tung University; Academia Sinica - Taiwan; Academia Sinica - Taiwan; National Cheng Kung University; National Taiwan University; National Dong Hwa University; National Dong Hwa University; National Yang Ming Chiao Tung University; Taipei Veterans General Hospital
RP Hsieh, SL (corresponding author), Natl Yang Ming Univ, Dept Microbiol & Immunol, Taipei 112, Taiwan.
EM slhsieh@ym.edu.tw
FU NIGMS NIH HHS [GM62116] Funding Source: Medline
NR 30
TC 334
Z9 382
U1 1
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 29
PY 2008
VL 453
IS 7195
BP 672
EP U12
DI 10.1038/nature07013
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200048
PM 18496526
DA 2026-03-09
ER

PT J
AU Lee, S
   Pirogov, A
   Kang, MS
   Jang, KH
   Yonemura, M
   Kamiyama, T
   Cheong, SW
   Gozzo, F
   Shin, N
   Kimura, H
   Noda, Y
   Park, JG
AF Lee, Seongsu
   Pirogov, A.
   Kang, Misun
   Jang, Kwang-Hyun
   Yonemura, M.
   Kamiyama, T.
   Cheong, S. -W.
   Gozzo, F.
   Shin, Namsoo
   Kimura, H.
   Noda, Y.
   Park, J. -G.
TI Giant magneto-elastic coupling in multiferroic hexagonal manganites
SO NATURE
LA English
DT Article
AB The motion of atoms in a solid always responds to cooling or heating in a way that is consistent with the symmetry of the given space group of the solid to which they belong(1,2). When the atoms move, the electronic structure of the solid changes, leading to different physical properties. Therefore, the determination of where atoms are and what atoms do is a cornerstone of modern solid- state physics. However, experimental observations of atomic displacements measured as a function of temperature are very rare, because those displacements are, in almost all cases, exceedingly small(3-5). Here we show, using a combination of diffraction techniques, that the hexagonal manganites RMnO3 ( where R is a rare- earth element) undergo an isostructural transition with exceptionally large atomic displacements: two orders of magnitude larger than those seen in any other magnetic material, resulting in an unusually strong magneto- elastic coupling. We follow the exact atomic displacements of all the atoms in the unit cell as a function of temperature and find consistency with theoretical predictions based on group theories. We argue that this gigantic magneto- elastic coupling in RMnO3 holds the key to the recently observed magneto- electric phenomenon in this intriguing class of materials(6).
C1 [Lee, Seongsu; Pirogov, A.; Kang, Misun; Jang, Kwang-Hyun; Park, J. -G.] Sungkyunkwan Univ, Dept Phys, Suwon 440746, South Korea.
   [Lee, Seongsu; Pirogov, A.; Park, J. -G.] Seoul Natl Univ, Ctr Strongly Correlated Mat Res, Seoul 151742, South Korea.
   [Kamiyama, T.; Park, J. -G.] KEK, Inst Mat Struct Sci, Tsukuba, Ibaraki 3050801, Japan.
   [Cheong, S. -W.] Rutgers State Univ, Rutgers Ctr Emergent Mat, Piscataway, NJ 08854 USA.
   [Cheong, S. -W.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [Gozzo, F.] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Shin, Namsoo] Pohang Univ Sci & Technol, Pohang Accelerator Lab, Pohang 790784, South Korea.
   [Kimura, H.; Noda, Y.] Tohoku Univ, Inst Multidisciplinary Res Adv Mat, Sendai, Miyagi 9808577, Japan.
C3 Sungkyunkwan University (SKKU); Seoul National University (SNU); High Energy Accelerator Research Organization (KEK); Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Pohang University of Science & Technology (POSTECH); Tohoku University
RP Park, JG (corresponding author), Sungkyunkwan Univ, Dept Phys, Suwon 440746, South Korea.
EM jgpark@skku.edu
NR 28
TC 366
Z9 384
U1 2
U2 218
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 805
EP U4
DI 10.1038/nature06507
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400037
PM 18273014
DA 2026-03-09
ER

PT J
AU Huang, J
   Lesser, CF
   Lory, S
AF Huang, Jin
   Lesser, Cammie F.
   Lory, Stephen
TI The essential role of the CopN protein in Chlamydia pneumoniae intracellular growth
SO NATURE
LA English
DT Article
ID iii secretion; saccharomyces-cerevisiae; infected cells; hela-cells; yeast; expression; bacterial; identification; translocation; apoptosis
AB Bacterial virulence determinants can be identified, according to the molecular Koch's postulates(1), if inactivation of a gene associated with a suspected virulence trait results in a loss in pathogenicity. This approach is commonly used with genetically tractable organisms. However, the current lack of tools for targeted gene disruptions in obligate intracellular microbial pathogens seriously hampers the identification of their virulence factors. Here we demonstrate an approach to studying potential virulence factors of genetically intractable organisms, such as Chlamydia. Heterologous expression of Chlamydia pneumoniae CopN in yeast and mammalian cells resulted in a cell cycle arrest, presumably owing to alterations in the microtubule cytoskeleton. A screen of a small molecule library identified two compounds that alleviated CopN-induced growth inhibition in yeast. These compounds interfered with C. pneumoniae replication in mammalian cells, presumably by 'knocking out' CopN function, revealing an essential role of CopN in the support of C. pneumoniae growth during infection. This work demonstrates the role of a specific chlamydial protein in virulence. The chemical biology approach described here can be used to identify virulence factors, and the reverse chemical genetic strategy can result in the identification of lead compounds for the development of novel therapeutics.
C1 [Huang, Jin; Lesser, Cammie F.; Lory, Stephen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
   [Lesser, Cammie F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Lory, S (corresponding author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
EM stephen_lory@hms.harvard.edu
FU NIAID NIH HHS [R01 AI064285] Funding Source: Medline
NR 38
TC 58
Z9 80
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 NOV 6
PY 2008
VL 456
IS 7218
BP 112
EP U10
DI 10.1038/nature07355
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000051
PM 18830244
DA 2026-03-09
ER

PT J
AU Johnson, PA
   Savage, H
   Knuth, M
   Gomberg, J
   Marone, C
AF Johnson, Paul A.
   Savage, Heather
   Knuth, Matt
   Gomberg, Joan
   Marone, Chris
TI Effects of acoustic waves on stick-slip in granular media and implications for earthquakes
SO NATURE
LA English
DT Article
ID seismicity; california; friction; stress
AB It remains unknown how the small strains induced by seismic waves can trigger earthquakes at large distances, in some cases thousands of kilometres from the triggering earthquake, with failure often occurring long after the waves have passed(1-6). Earthquake nucleation is usually observed to take place at depths of 10 - 20 km, and so static overburden should be large enough to inhibit triggering by seismic- wave stress perturbations. To understand the physics of dynamic triggering better, as well as the influence of dynamic stressing on earthquake recurrence, we have conducted laboratory studies of stick - slip in granular media with and without applied acoustic vibration. Glass beads were used to simulate granular fault zone material, sheared under constant normal stress, and subject to transient or continuous perturbation by acoustic waves. Here we show that small- magnitude failure events, corresponding to triggered aftershocks, occur when applied sound- wave amplitudes exceed several microstrain. These events are frequently delayed or occur as part of a cascade of small events. Vibrations also cause large slip events to be disrupted in time relative to those without wave perturbation. The effects are observed for many large- event cycles after vibrations cease, indicating a strain memory in the granular material. Dynamic stressing of tectonic faults may play a similar role in determining the complexity of earthquake recurrence.
C1 [Johnson, Paul A.] Los Alamos Natl Lab, Geophys Grp EES11, Los Alamos, NM 87545 USA.
   [Savage, Heather; Knuth, Matt; Marone, Chris] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Savage, Heather] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Knuth, Matt] Univ Wisconsin, Dept Geol & Geophys, Madison, WI 53706 USA.
   [Gomberg, Joan] Univ Washington, Dept Earth & Space Sci, US Geol Survey, Seattle, WA 98195 USA.
C3 United States Department of Energy (DOE); Los Alamos National Laboratory; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of California System; University of California Santa Cruz; University of Wisconsin System; University of Wisconsin Madison; United States Department of the Interior; United States Geological Survey; University of Washington; University of Washington Seattle
RP Johnson, PA (corresponding author), Los Alamos Natl Lab, Geophys Grp EES11, MS D443, Los Alamos, NM 87545 USA.
EM paj@lanl.gov
NR 17
TC 186
Z9 212
U1 4
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 3
PY 2008
VL 451
IS 7174
BP 57
EP U5
DI 10.1038/nature06440
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300032
PM 18172496
DA 2026-03-09
ER

PT J
AU Guo, Y
   Walther, TC
   Rao, M
   Stuurman, N
   Goshima, G
   Terayama, K
   Wong, JS
   Vale, RD
   Walter, P
   Farese, RV
AF Guo, Yi
   Walther, Tobias C.
   Rao, Meghana
   Stuurman, Nico
   Goshima, Gohta
   Terayama, Koji
   Wong, Jinny S.
   Vale, Ronald D.
   Walter, Peter
   Farese, Robert V., Jr.
TI Functional genomic screen reveals genes involved in lipid-droplet formation and utilization
SO NATURE
LA English
DT Article
ID drosophila; proteins; roles; phosphorylation; endocytosis; perilipin; receptor; rna
AB Eukaryotic cells store neutral lipids in cytoplasmic lipid droplets(1,2) enclosed in a monolayer of phospholipids and associated proteins(3,4). These dynamic organelles(5) serve as the principal reservoirs for storing cellular energy and for the building blocks for membrane lipids. Excessive lipid accumulation in cells is a central feature of obesity, diabetes and atherosclerosis, yet remarkably little is known about lipid- droplet cell biology. Here we show, by means of a genome- wide RNA interference ( RNAi) screen in Drosophila S2 cells that about 1.5% of all genes function in lipid- droplet formation and regulation. The phenotypes of the gene knockdowns sorted into five distinct phenotypic classes. Genes encoding enzymes of phospholipid biosynthesis proved to be determinants of lipid- droplet size and number, suggesting that the phospholipid composition of the monolayer profoundly affects droplet morphology and lipid utilization. A subset of the Arf1 - COPI vesicular transport proteins also regulated droplet morphology and lipid utilization, thereby identifying a previously unrecognized function for this machinery. These phenotypes are conserved in mammalian cells, suggesting that insights from these studies are likely to be central to our understanding of human diseases involving excessive lipid storage.
C1 [Guo, Yi; Walther, Tobias C.; Walter, Peter; Farese, Robert V., Jr.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Stuurman, Nico; Goshima, Gohta; Vale, Ronald D.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Farese, Robert V., Jr.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA.
   [Guo, Yi; Rao, Meghana; Terayama, Koji; Wong, Jinny S.; Farese, Robert V., Jr.] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Walther, Tobias C.] Max Planck Inst Biochem, D-12852 Martinsried, Germany.
   [Vale, Ronald D.; 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; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; The J David Gladstone Institutes; Max Planck Society; University of California System; University of California San Francisco; Howard Hughes Medical Institute
RP Farese, RV (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM twalther@biochem.mpg.de; bfarese@gladstone.ucsf.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIDDK NIH HHS [R21 DK078254, R21 DK078254-01] Funding Source: Medline
NR 30
TC 614
Z9 719
U1 0
U2 144
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2008
VL 453
IS 7195
BP 657
EP 661
DI 10.1038/nature06928
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200045
PM 18408709
DA 2026-03-09
ER

PT J
AU Decker, RB
   Krimigis, SM
   Roelof, EC
   Hill, ME
   Armstrong, TP
   Gloeckler, G
   Hamilton, DC
   Lanzerotti, LJ
AF Decker, R. B.
   Krimigis, S. M.
   Roelof, E. C.
   Hill, M. E.
   Armstrong, T. P.
   Gloeckler, G.
   Hamilton, D. C.
   Lanzerotti, L. J.
TI Mediation of the solar wind termination shock by non-thermal ions
SO NATURE
LA English
DT Article
ID interstellar magnetic-field; voyager-1; acceleration
AB Broad regions on both sides of the solar wind termination shock are populated by high intensities of non- thermal ions and electrons. The pre- shock particles in the solar wind have been measured by the spacecraft Voyager 1 ( refs 1 - 5) and Voyager 2 ( refs 3, 6). The post- shock particles in the heliosheath have also been measured by Voyager 1 ( refs 3 - 5). It was not clear, however, what effect these particles might have on the physics of the shock transition until Voyager 2 crossed the shock on 31 August - 1 September 2007 ( refs 7 - 9). Unlike Voyager 1, Voyager 2 is making plasma measurements(7). Data from the plasma(7) and magnetic field(8) instruments on Voyager 2 indicate that non- thermal ion distributions probably have key roles in mediating dynamical processes at the termination shock and in the heliosheath. Here we report that intensities of low- energy ions measured by Voyager 2 produce non- thermal partial ion pressures in the heliosheath that are comparable to ( or exceed) both the thermal plasma pressures and the scalar magnetic field pressures. We conclude that these ions are the >0.028 MeV portion of the non- thermal ion distribution that determines the termination shock structure(8) and the acceleration of which extracts a large fraction of bulk- flow kinetic energy from the incident solar wind(7).
C1 [Decker, R. B.; Krimigis, S. M.; Roelof, E. C.; Hill, M. E.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Krimigis, S. M.] Acad Athens, Athens 11527, Greece.
   [Armstrong, T. P.] Fundamental Technol, Lawrence, KS 66046 USA.
   [Gloeckler, G.] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Hamilton, D. C.] Univ Maryland, College Pk, MD 20742 USA.
   [Lanzerotti, L. J.] New Jersey Inst Technol, Newark, NJ 07102 USA.
   [Lanzerotti, L. J.] Alcatel Lucent, Murray Hill, NJ 07974 USA.
C3 Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; Academy of Athens; University of Michigan System; University of Michigan; University System of Maryland; University of Maryland College Park; New Jersey Institute of Technology; Alcatel-Lucent
RP Decker, RB (corresponding author), Johns Hopkins Univ, Appl Phys Lab, Johns Hopkins Rd, Laurel, MD 20723 USA.
EM robert.decker@jhuapl.edu
NR 19
TC 246
Z9 257
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 3
PY 2008
VL 454
IS 7200
BP 67
EP 70
DI 10.1038/nature07030
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300036
PM 18596801
DA 2026-03-09
ER

PT J
AU Cheng, J
   Türkel, N
   Hemati, N
   Fuller, MT
   Hunt, AJ
   Yamashita, YM
AF Cheng, Jun
   Turkel, Nezaket
   Hemati, Nahid
   Fuller, Margaret T.
   Hunt, Alan J.
   Yamashita, Yukiko M.
TI Centrosome misorientation reduces stem cell division during ageing
SO NATURE
LA English
DT Article
ID self-renewal; drosophila spermatogenesis; germline; niche; melanogaster; orientation; cancer
AB Asymmetric division of adult stem cells generates one self- renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila. Throughout the cell cycle, centrosomes in germline stem cells ( GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re- enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia.
C1 [Turkel, Nezaket; Hemati, Nahid; Yamashita, Yukiko M.] Univ Michigan, Inst Life Sci, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA.
   [Cheng, Jun; Hunt, Alan J.] Univ Michigan, Dept Biomed Engn, Ctr Ultrafast Opt Sci, Ann Arbor, MI 48109 USA.
   [Yamashita, Yukiko M.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
   [Fuller, Margaret T.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
   [Fuller, Margaret T.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Stanford University; Stanford University
RP Yamashita, YM (corresponding author), Univ Michigan, Inst Life Sci, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA.
EM yukikomy@umich.edu
FU University of Michigan; March of Dimes Basil O'Conner Starter Scholar Research Award; Searle Scholar Program; NIH [P01 DK53074, R01GM072006]
NR 27
TC 255
Z9 309
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 4
PY 2008
VL 456
IS 7222
BP 599
EP U40
DI 10.1038/nature07386
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000032
PM 18923395
DA 2026-03-09
ER

PT J
AU Bornholdt, ZA
   Prasad, BVV
AF Bornholdt, Zachary A.
   Prasad, B. V. Venkataram
TI X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus
SO NATURE
LA English
DT Article
ID antiviral cytokine responses; double-stranded-rna; pre-messenger-rnas; a virus; effector domain; protein; binding; interferon; activation; infection
AB The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns(1,2). Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains(3,4). NS1, which consists of two domains a double-stranded RNA (dsRNA) binding domain(5,6) and the effector domain(7), separated through a linker - is an antagonist of antiviral type-I interferon response in the host(8,9). Here we report the X-ray structure of the full- length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60% of human deaths in an outbreak in Vietnam(1,2). Compared to the individually determined structures of the RNA binding domain and the effector domain from non- H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full- length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo- electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-angstrom-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.
C1 [Bornholdt, Zachary A.; Prasad, B. V. Venkataram] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
   [Prasad, B. V. Venkataram] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine
RP Prasad, BVV (corresponding author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA.
EM vprasad@bcm.tmc.edu
FU NIH [AI36040, AI07471, RR002250]; Robert Welch Foundation; US Department of Energy,; Basic Energy Sciences; Office of Science [W-31-109-Eng-38]; National Institute of Allergy and Infectious Diseases [R37AI036040, R01AI036040] Funding Source: NIH RePORTER
NR 33
TC 128
Z9 165
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 18
PY 2008
VL 456
IS 7224
BP 985
EP U85
DI 10.1038/nature07444
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300053
PM 18987632
DA 2026-03-09
ER

PT J
AU Balasubramanian, G
   Chan, IY
   Kolesov, R
   Al-Hmoud, M
   Tisler, J
   Shin, C
   Kim, C
   Wojcik, A
   Hemmer, PR
   Krueger, A
   Hanke, T
   Leitenstorfer, A
   Bratschitsch, R
   Jelezko, F
   Wrachtrup, J
AF Balasubramanian, Gopalakrishnan
   Chan, I. Y.
   Kolesov, Roman
   Al-Hmoud, Mohannad
   Tisler, Julia
   Shin, Chang
   Kim, Changdong
   Wojcik, Aleksander
   Hemmer, Philip R.
   Krueger, Anke
   Hanke, Tobias
   Leitenstorfer, Alfred
   Bratschitsch, Rudolf
   Jelezko, Fedor
   Wrachtrup, Joerg
TI Nanoscale imaging magnetometry with diamond spins under ambient conditions
SO NATURE
LA English
DT Article
ID magnetic-resonance; single spin; optical microscopy; coherent dynamics; resolution; centers
AB Magnetic resonance imaging and optical microscopy are key technologies in the life sciences. For microbiological studies, especially of the inner workings of single cells, optical microscopy is normally used because it easily achieves resolution close to the optical wavelength. But in conventional microscopy, diffraction limits the resolution to about half the wavelength. Recently, it was shown that this limit can be partly overcome by nonlinear imaging techniques(1,2), but there is still a barrier to reaching the molecular scale. In contrast, in magnetic resonance imaging the spatial resolution is not determined by diffraction; rather, it is limited by magnetic field sensitivity, and so can in principle go well below the optical wavelength. The sensitivity of magnetic resonance imaging has recently been improved enough to image single cells(3,4), and magnetic resonance force microscopy(5) has succeeded in detecting single electrons(6) and small nuclear spin ensembles(7). However, this technique currently requires cryogenic temperatures, which limit most potential biological applications(8). Alternatively, single-electron spin states can be detected optically(9,10), even at room temperature in some systems(11-14). Here we show how magneto- optical spin detection can be used to determine the location of a spin associated with a single nitrogen- vacancy centre in diamond with nanometre resolution under ambient conditions. By placing these nitrogen- vacancy spins in functionalized diamond nanocrystals, biologically specific magnetofluorescent spin markers can be produced. Significantly, we show that this nanometre- scale resolution can be achieved without any probes located closer than typical cell dimensions. Furthermore, we demonstrate the use of a single diamond spin as a scanning probe magnetometer to map nanoscale magnetic field variations. The potential impact of single- spin imaging at room temperature is far- reaching. It could lead to the capability to probe biologically relevant spins in living cells.
C1 [Balasubramanian, Gopalakrishnan; Kolesov, Roman; Al-Hmoud, Mohannad; Tisler, Julia; Jelezko, Fedor; Wrachtrup, Joerg] Univ Stuttgart, Inst Phys 3, D-70550 Stuttgart, Germany.
   [Chan, I. Y.] Brandeis Univ, Dept Chem, Waltham, MA 02454 USA.
   [Shin, Chang; Kim, Changdong; Wojcik, Aleksander; Hemmer, Philip R.] Texas A&M Univ, Dept Elect & Comp Engn, College Stn, TX 77843 USA.
   [Krueger, Anke] Univ Kiel, Otto Diels Inst Organ Chem, D-24098 Kiel, Germany.
   [Hanke, Tobias; Leitenstorfer, Alfred; Bratschitsch, Rudolf] Univ Konstanz, D-78457 Constance, Germany.
   [Hanke, Tobias; Leitenstorfer, Alfred; Bratschitsch, Rudolf] Ctr Appl Photon, D-78457 Constance, Germany.
C3 University of Stuttgart; Brandeis University; Texas A&M University System; Texas A&M University College Station; University of Kiel; University of Konstanz
RP Jelezko, F (corresponding author), Univ Stuttgart, Inst Phys 3, D-70550 Stuttgart, Germany.
EM f.jelezko@physik.uni-stuttgart.de
FU EU (QAP, EQUIND, NANO4DRUGS, NEDQIT); DFG (SFB/TR21 and FOR730); Landesstiftung BW
NR 21
TC 1699
Z9 1989
U1 15
U2 692
PU 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 2
PY 2008
VL 455
IS 7213
BP 648
EP U46
DI 10.1038/nature07278
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700043
PM 18833276
DA 2026-03-09
ER

PT J
AU Herrero, JL
   Roberts, MJ
   Delicato, LS
   Gieselmann, MA
   Dayan, P
   Thiele, A
AF Herrero, J. L.
   Roberts, M. J.
   Delicato, L. S.
   Gieselmann, M. A.
   Dayan, P.
   Thiele, A.
TI Acetylcholine contributes through muscarinic receptors to attentional modulation in V1
SO NATURE
LA English
DT Article
ID primary visual-cortex; cholinergic modulation; selective attention; parietal cortex; macaque monkey; areas v1; performance; release; cells; v4
AB Attention exerts a strong influence over neuronal processing in cortical areas(1,2). It selectively increases firing rates(2-4) and affects tuning properties(1,5), including changing receptive field locations and sizes(3,6). Although these effects are well studied, their cellular mechanisms are poorly understood. To study the cellular mechanisms, we combined iontophoretic pharmacological analysis of cholinergic receptors with single cell recordings in V1 while rhesus macaque monkeys ( Macaca mulatta) performed a task that demanded top- down spatial attention. Attending to the receptive field of the V1 neuron under study caused an increase in firing rates. Here we show that this attentional modulation was enhanced by low doses of acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had no systematic effect. These results demonstrate that muscarinic cholinergic mechanisms play a central part in mediating the effects of attention in V1.
C1 [Herrero, J. L.; Roberts, M. J.; Delicato, L. S.; Gieselmann, M. A.; Thiele, A.] Univ Newcastle, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Dayan, P.] UCL, Gatsby Computat Neurosci Unit, London WC1N 3AR, England.
C3 Newcastle University - UK; University of London; University College London
RP Thiele, A (corresponding author), Univ Newcastle, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM alex.thiele@ncl.ac.uk
FU BBSRC [BBS/B/09325]; Wellcome Trust [070380/Z/03/Z]; Gatsby Charitable Foundation; Biotechnology and Biological Sciences Research Council [BBS/B/09325, BB/F021399/1] Funding Source: researchfish; BBSRC [BB/F021399/1] Funding Source: UKRI
NR 30
TC 375
Z9 450
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1110
EP 1114
DI 10.1038/nature07141
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600036
PM 18633352
DA 2026-03-09
ER

PT J
AU Smith, RP
   Sutherland, M
   Lonzarich, GG
   Saxena, SS
   Kimura, N
   Takashima, S
   Nohara, M
   Takagi, H
AF Smith, R. P.
   Sutherland, M.
   Lonzarich, G. G.
   Saxena, S. S.
   Kimura, N.
   Takashima, S.
   Nohara, M.
   Takagi, H.
TI Marginal breakdown of the Fermi-liquid state on the border of metallic ferromagnetism
SO NATURE
LA English
DT Article
ID quantum phase-transition; critical-points; electron; behavior; mnsi; superconductors; fluctuations; temperature; pressure; systems
AB For the past half century, our understanding of how the interactions between electrons affect the low-temperature properties of metals has been based on the Landau theory of a Fermi liquid(1). In recent times, however, there have been an increasingly large number of examples in which the predictions of the Fermi-liquid theory appear to be violated(2). Although the qualitative reasons for the breakdown are generally understood, the specific quantum states that replace the Fermi liquid remain in many cases unclear. Here we describe an example of such a breakdown where the non- Fermi- liquid properties can be interpreted. We show that the thermal and electrical resistivities in high- purity samples of the d-electron metal ZrZn2 at low temperatures have T and T-5/3 temperature dependences, respectively: these are the signatures of the 'marginal' Fermi- liquid state(3-7), expected to arise from effective long-range spin- spin interactions in a metal on the border of metallic ferromagnetism in three dimensions(3,5). The marginal Fermi liquid provides a link between the conventional Fermi liquid and more exotic non- Fermi- liquid states that are of growing interest in condensed matter physics. The idea of a marginal Fermi liquid has also arisen in other contexts for example, in the phenomenology of the normal state of the copper oxide superconductors(7), and in studies of relativistic plasmas and of nuclear matter(3,4,6).
C1 [Smith, R. P.; Sutherland, M.; Lonzarich, G. G.; Saxena, S. S.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Kimura, N.] Tohoku Univ, Ctr Low Temp Sci, Sendai, Miyagi 9808578, Japan.
   [Takashima, S.; Nohara, M.; Takagi, H.] Univ Tokyo, Dept Adv Mat Sci, Tokyo 2778561, Japan.
   [Takagi, H.] RIKEN, Wako, Saitama 3510198, Japan.
C3 University of Cambridge; Tohoku University; University of Tokyo; RIKEN
RP Smith, RP (corresponding author), Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM rps24@cam.ac.uk
FU Royal Society; EPSRC; St Catharine's College, Cambridge; Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Scientific Research on Priority Areas; MEXT, Japan; Engineering and Physical Sciences Research Council [EP/C009487/1, EP/C511778/1, GR/A11717/01] Funding Source: researchfish
NR 33
TC 90
Z9 100
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1220
EP 1223
DI 10.1038/nature07401
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100039
DA 2026-03-09
ER

PT J
AU Moldoveanu, T
   Gehring, K
   Green, DR
AF Moldoveanu, Tudor
   Gehring, Kalle
   Green, Douglas R.
TI Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains
SO NATURE
LA English
DT Article
ID girdle muscular-dystrophy; crystal-structure; structural basis; active-site; domain-vi; activation; reveals; peptide; enzyme; complexes
AB The Ca2+-dependent cysteine proteases, calpains, regulate cell migration(1), cell death(2), insulin secretion(3), synaptic function(4) and muscle homeostasis(5). Their endogenous inhibitor, calpastatin, consists of four inhibitory repeats, each of which neutralizes an activated calpain with exquisite specificity and potency(6). Despite the physiological importance of this interaction, the structural basis of calpain inhibition by calpastatin is unknown(7). Here we report the 3.0 angstrom structure of Ca2+-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity. The structure highlights the complexity of calpain activation by Ca2+ illustrating key residues in a peripheral domain that serve to stabilize the protease core on Ca2+ binding. Fully activated calpain binds ten Ca2+ atoms, resulting in several conformational changes allowing recognition by calpastatin. Calpain inhibition is mediated by the intimate contact with three critical regions of calpastatin. Two regions target the penta- EF- hand domains of calpain and the third occupies the substrate- binding cleft, projecting a loop around the active site thiol to evade proteolysis.
C1 [Moldoveanu, Tudor; Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Gehring, Kalle] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.
C3 St Jude Children's Research Hospital; McGill University
RP Green, DR (corresponding author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM douglas.green@stjude.org
FU US National Institute of Health; National Cancer Institute; Canadian Institute of Health Research; American Lebanese Syrian Associated Charities; National Institute of Allergy and Infectious Diseases [R01AI040646] Funding Source: NIH RePORTER
NR 37
TC 118
Z9 149
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 NOV 20
PY 2008
VL 456
IS 7220
BP 404
EP U73
DI 10.1038/nature07353
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600047
PM 19020622
DA 2026-03-09
ER

PT J
AU Mossé, YP
   Laudenslager, M
   Longo, L
   Cole, KA
   Wood, A
   Attiyeh, EF
   Laquaglia, MJ
   Sennett, R
   Lynch, JE
   Perri, P
   Laureys, G
   Speleman, F
   Kim, C
   Hou, CP
   Hakonarson, H
   Torkamani, A
   Schork, NJ
   Brodeur, GM
   Tonini, GP
   Rappaport, E
   Devoto, M
   Maris, JM
AF Mosse, Yael P.
   Laudenslager, Marci
   Longo, Luca
   Cole, Kristina A.
   Wood, Andrew
   Attiyeh, Edward F.
   Laquaglia, Michael J.
   Sennett, Rachel
   Lynch, Jill E.
   Perri, Patrizia
   Laureys, Genevieve
   Speleman, Frank
   Kim, Cecilia
   Hou, Cuiping
   Hakonarson, Hakon
   Torkamani, Ali
   Schork, Nicholas J.
   Brodeur, Garrett M.
   Tonini, Gian P.
   Rappaport, Eric
   Devoto, Marcella
   Maris, John M.
TI Identification of ALK as a major familial neuroblastoma predisposition gene
SO NATURE
LA English
DT Article
ID anaplastic lymphoma kinase; functional-analysis; homeobox gene; b-raf; mutations; expression; phox2b; receptor; cancer; activation
AB Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23-24 using a whole- genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high- risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild- type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell- surface kinase is a tractable therapeutic target for this lethal paediatric malignancy.
C1 [Mosse, Yael P.; Laudenslager, Marci; Cole, Kristina A.; Wood, Andrew; Attiyeh, Edward F.; Laquaglia, Michael J.; Sennett, Rachel; Lynch, Jill E.; Hou, Cuiping; Brodeur, Garrett M.; Rappaport, Eric; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Div Oncol, Philadelphia, PA 19104 USA.
   [Mosse, Yael P.; Laudenslager, Marci; Cole, Kristina A.; Wood, Andrew; Attiyeh, Edward F.; Laquaglia, Michael J.; Sennett, Rachel; Lynch, Jill E.; Hou, Cuiping; Brodeur, Garrett M.; Rappaport, Eric; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Ctr Childhood Canc Res, Philadelphia, PA 19104 USA.
   [Longo, Luca; Perri, Patrizia; Tonini, Gian P.] Natl Inst Canc Res, Italian Neuroblastoma Fdn, I-16132 Genoa, Italy.
   [Perri, Patrizia] Adv Biotechnol Ctr, I-16132 Genoa, Italy.
   [Laureys, Genevieve; Speleman, Frank] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
   [Kim, Cecilia; Hou, Cuiping; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Torkamani, Ali; Schork, Nicholas J.] Scripps Genom Med, La Jolla, CA 92037 USA.
   [Torkamani, Ali; Schork, Nicholas J.] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Hakonarson, Hakon; Devoto, Marcella] Univ Penn, Sch Med, Div Genet, Childrens Hosp Philadelphia,Dept Pediat, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon; Devoto, Marcella] Univ Penn, Sch Med, CCEB, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Devoto, Marcella] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy.
   [Maris, John M.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Genoa; IRCCS AOU San Martino IST; Ghent University; Ghent University Hospital; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Scripps Research Institute; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Sapienza University Rome; University of Pennsylvania
RP Maris, JM (corresponding author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Div Oncol, Philadelphia, PA 19104 USA.
EM maris@chop.edu
FU National Institutes of Health [K08-111733, R01-CA78454, R01-CA87847]; American Society of Clinical Oncology Career Development Award; Foerderer-Murray Fund; Carly Hillman Fund; Alex's Lemonade Stand Foundation; Andrew's Army Foundation; Giulio D'Angio Endowed Chair; Italian Neuroblastoma Foundation; Center for Applied Genomics at the Joseph Stokes Research Institute; Scripps Genomic Medicine; Scripps Dickinson Scholarship; Abramson Family Cancer Research Institute
NR 50
TC 1064
Z9 1293
U1 2
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 16
PY 2008
VL 455
IS 7215
BP 930
EP U22
DI 10.1038/nature07261
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300042
PM 18724359
DA 2026-03-09
ER

PT J
AU Monné, M
   Han, L
   Schwend, T
   Burendahl, S
   Jovine, L
AF Monne, Magnus
   Han, Ling
   Schwend, Thomas
   Burendahl, Sofia
   Jovine, Luca
TI Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats
SO NATURE
LA English
DT Article
ID protein-structure alignment; zona-pellucida proteins; sperm receptors; binding; prediction; model; tool; crystallography; fertilization; glycoprotein
AB Species- specific recognition between the egg extracellular matrix ( zona pellucida) and sperm is the first, crucial step of mammalian fertilization(1). Zona pellucida filament components ZP3 and ZP2 act as sperm receptors, and mice lacking either of the corresponding genes produce oocytes without a zona pellucida and are completely infertile(2). Like their counterparts in the vitelline envelope of non- mammalian eggs and many other secreted eukaryotic proteins, zona pellucida subunits polymerize using a 'zona pellucida ( ZP) domain' module(3-5), whose conserved amino- terminal part (ZP-N) was suggested to constitute a domain of its own(6). No atomic structure has been reported for ZP domain proteins, and there is no structural information on any conserved vertebrate protein that is essential for fertilization and directly involved in egg - sperm binding. Here we describe the 2.3 angstrom (angstrom) resolution structure of the ZP-N fragment of mouse primary sperm receptor ZP3. The ZP- N fold defines a new immunoglobulin superfamily subtype with a beta-sheet extension characterized by an E' strand and an invariant tyrosine residue implicated in polymerization. The structure strongly supports the presence of ZP- N repeats within the N- terminal region of ZP2 and other vertebrate zona pellucida/ vitelline envelope proteins, with implications for overall egg coat architecture, the post- fertilization block to polyspermy and speciation. Moreover, it provides an important framework for understanding human diseases caused by mutations in ZP domain proteins and developing new methods of non- hormonal contraception.
C1 [Monne, Magnus; Han, Ling; Schwend, Thomas; Burendahl, Sofia; Jovine, Luca] Karolinska Inst, Dept Biosci & Nutr, SE-14157 Huddinge, Sweden.
C3 Karolinska Institutet
RP Jovine, L (corresponding author), Karolinska Inst, Dept Biosci & Nutr, Halsovagen 7, SE-14157 Huddinge, Sweden.
EM luca.jovine@ki.se
FU Karolinska Institutet; Swedish Research Council [2005-5102]; European Community [Marie Curie ERG 31055]; Medical Research Council [G0500367] Funding Source: researchfish; MRC [G0500367] Funding Source: UKRI
NR 68
TC 109
Z9 133
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 DEC 4
PY 2008
VL 456
IS 7222
BP 653
EP U82
DI 10.1038/nature07599
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000044
PM 19052627
DA 2026-03-09
ER

PT J
AU Stayrook, S
   Jaru-Ampornpan, P
   Ni, J
   Hochschild, A
   Lewis, M
AF Stayrook, Steven
   Jaru-Ampornpan, Peera
   Ni, Jenny
   Hochschild, Ann
   Lewis, Mitchell
TI Crystal structure of the λ repressor and a model for pairwise cooperative operator binding
SO NATURE
LA English
DT Article
ID bacteriophage-lambda; lexa; cleavage; domain; crystallography; recognition; protein; dimers
AB Bacteriophage lambda has for many years been a model system for understanding mechanisms of gene regulation(1). A 'genetic switch' enables the phage to transition from lysogenic growth to lytic development when triggered by specific environmental conditions. The key component of the switch is the cI repressor, which binds to two sets of three operator sites on the lambda chromosome that are separated by about 2,400 base pairs (bp)(2,3). A hallmark of the lambda system is the pairwise cooperativity of repressor binding(4). In the absence of detailed structural information, it has been difficult to understand fully how repressor molecules establish the cooperativity complex. Here we present the X- ray crystal structure of the intact lambda cI repressor dimer bound to a DNA operator site. The structure of the repressor, determined by multiple isomorphous replacement methods, reveals an unusual overall architecture that allows it to adopt a conformation that appears to facilitate pairwise cooperative binding to adjacent operator sites.
C1 [Stayrook, Steven; Jaru-Ampornpan, Peera; Ni, Jenny; Lewis, Mitchell] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19102 USA.
   [Hochschild, Ann] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
C3 University of Pennsylvania; Harvard University; Harvard Medical School
RP Lewis, M (corresponding author), Univ Penn, Sch Med, Dept Biochem & Biophys, 37th & Hamilton Walk, Philadelphia, PA 19102 USA.
EM lewis@mail.med.upenn.edu
FU NIGMS NIH HHS [R01 GM044025] Funding Source: Medline
NR 23
TC 86
Z9 111
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 APR 24
PY 2008
VL 452
IS 7190
BP 1022
EP U12
DI 10.1038/nature06831
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600045
PM 18432246
DA 2026-03-09
ER

PT J
AU Rajagopal, A
   Rao, AU
   Amigo, J
   Tian, M
   Upadhyay, SK
   Hall, C
   Uhm, S
   Mathew, MK
   Fleming, MD
   Paw, BH
   Krause, M
   Hamza, I
AF Rajagopal, Abbhirami
   Rao, Anita U.
   Amigo, Julio
   Tian, Meng
   Upadhyay, Sanjeev K.
   Hall, Caitlin
   Uhm, Suji
   Mathew, M. K.
   Fleming, Mark D.
   Paw, Barry H.
   Krause, Michael
   Hamza, Iqbal
TI Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins
SO NATURE
LA English
DT Article
ID transporter; zebrafish; biosynthesis; disorders; sensor
AB Haems are metalloporphyrins that serve as prosthetic groups for various biological processes including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing(1-4). With a few exceptions, haem is synthesized by a multistep biosynthetic pathway comprising defined intermediates that are highly conserved throughout evolution(5). Despite our extensive knowledge of haem biosynthesis and degradation, the cellular pathways and molecules that mediate intracellular haem trafficking are unknown. The experimental setback in identifying haem trafficking pathways has been the inability to dissociate the highly regulated cellular synthesis and degradation of haem from intracellular trafficking events(6). Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins, which have vertebrate orthologues(7). Here we show, by exploiting this auxotrophy to identify HRG-1 proteins in C. elegans, that these proteins are essential for haem homeostasis and normal development in worms and vertebrates. Depletion of hrg-1, or its paralogue hrg-4, in worms results in the disruption of organismal haem sensing and an abnormal response to haem analogues. HRG-1 and HRG-4 are previously unknown transmembrane proteins, which reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and, most strikingly, profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins localize together, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1. These findings reveal conserved pathways for cellular haem trafficking in animals that define the model for eukaryotic haem transport. Thus, uncovering the mechanisms of haem transport in C. elegans may provide insights into human disorders of haem metabolism and reveal new drug targets for developing anthelminthics to combat worm infestations.
C1 [Rajagopal, Abbhirami; Rao, Anita U.; Uhm, Suji; Hamza, Iqbal] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
   [Rajagopal, Abbhirami; Rao, Anita U.; Hall, Caitlin; Uhm, Suji; Hamza, Iqbal] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
   [Amigo, Julio; Paw, Barry H.] Harvard Univ, Sch Med, Div Hematol, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Tian, Meng; Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Upadhyay, Sanjeev K.; Mathew, M. K.] Univ Agr Sci Bangalore, Natl Ctr Biol Sci, Tata Inst Fundamental Res, Bangalore 560065, Karnataka, India.
   [Krause, Michael] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
C3 University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Tata Institute of Fundamental Research (TIFR); National Centre for Biological Sciences (NCBS); University of Agricultural Sciences Bangalore; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Hamza, I (corresponding author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
EM hamza@umd.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIDDK NIH HHS [R01 DK074797] Funding Source: Medline; Intramural NIH HHS Funding Source: Medline; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK074797] Funding Source: NIH RePORTER
NR 23
TC 272
Z9 349
U1 1
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 19
PY 2008
VL 453
IS 7198
BP 1127
EP 1131
DI 10.1038/nature06934
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900062
PM 18418376
DA 2026-03-09
ER

PT J
AU Kausrud, KL
   Mysterud, A
   Steen, H
   Vik, JO
   Ostbye, E
   Cazelles, B
   Framstad, E
   Eikeset, AM
   Mysterud, I
   Solhoy, T
   Stenseth, NC
AF Kausrud, Kyrre L.
   Mysterud, Atle
   Steen, Harald
   Vik, Jon Olav
   Ostbye, Eivind
   Cazelles, Bernard
   Framstad, Erik
   Eikeset, Anne Maria
   Mysterud, Ivar
   Solhoy, Torstein
   Stenseth, Nils Chr.
TI Linking climate change to lemming cycles
SO NATURE
LA English
DT Article
ID north-atlantic oscillation; population-cycles; long-term; norwegian lemmings; phase-dependence; voles; dynamics; density; time; norway
AB The population cycles of rodents at northern latitudes have puzzled people for centuries(1,2), and their impact is manifest throughout the alpine ecosystem(2,3). Climate change is known to be able to drive animal population dynamics between stable and cyclic phases(4,5), and has been suggested to cause the recent changes in cyclic dynamics of rodents and their predators(3,6-9). But although predator - rodent interactions are commonly argued to be the cause of the Fennoscandian rodent cycles(1,10-13), the role of the environment in the modulation of such dynamics is often poorly understood in natural systems(8,9,14). Hence, quantitative links between climate-driven processes and rodent dynamics have so far been lacking. Here we show that winter weather and snow conditions, together with density dependence in the net population growth rate, account for the observed population dynamics of the rodent community dominated by lemmings ( Lemmus lemmus) in an alpine Norwegian core habitat between 1970 and 1997, and predict the observed absence of rodent peak years after 1994. These local rodent dynamics are coherent with alpine bird dynamics both locally and over all of southern Norway, consistent with the influence of large- scale fluctuations in winter conditions. The relationship between commonly available meteorological data and snow conditions indicates that changes in temperature and humidity, and thus conditions in the subnivean space, seem to markedly affect the dynamics of alpine rodents and their linked groups. The pattern of less regular rodent peaks, and corresponding changes in the overall dynamics of the alpine ecosystem, thus seems likely to prevail over a growing area under projected climate change.
C1 [Kausrud, Kyrre L.; Mysterud, Atle; Vik, Jon Olav; Eikeset, Anne Maria; Stenseth, Nils Chr.] Univ Oslo, Ctr Ecol & Evolutionary Synth, N-0316 Oslo, Norway.
   [Steen, Harald; Ostbye, Eivind; Mysterud, Ivar] Univ Oslo, Dept Biol, N-0316 Oslo, Norway.
   [Cazelles, Bernard] Ecole Normale Super, CNRS, UMR 7625, F-75230 Paris, France.
   [Cazelles, Bernard] IRD GEODES, F-93142 Bondy, France.
   [Framstad, Erik] Norwegian Inst Nat Res, N-0349 Oslo, Norway.
   [Solhoy, Torstein] Univ Bergen, Dept Biol, N-5007 Bergen, Norway.
C3 University of Oslo; University of Oslo; Sorbonne Universite; Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Norwegian Institute Nature Research; University of Bergen
RP Stenseth, NC (corresponding author), Univ Oslo, Ctr Ecol & Evolutionary Synth, POB 1066 Blindern, N-0316 Oslo, Norway.
EM n.c.stenseth@bio.uio.no
FU Norwegian Institute for Nature Research; University of Oslo; Nansen Fund; Research Council of Norway; Centre for Ecological and Evolutionary Synthesis, Oslo.
NR 41
TC 371
Z9 431
U1 7
U2 342
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 93
EP U3
DI 10.1038/nature07442
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000047
PM 18987742
DA 2026-03-09
ER

PT J
AU Südhof, TC
AF Sudhof, Thomas C.
TI Neuroligins and neurexins link synaptic function to cognitive disease
SO NATURE
LA English
DT Article
ID alpha-neurexins; cell-adhesion; transmitter release; structural variants; variable phenotype; deletion syndrome; autism; protein; genes; complex
AB The brain processes information by transmitting signals at synapses, which connect neurons into vast networks of communicating cells. In these networks, synapses not only transmit signals but also transform and refine them. Neurexins and neuroligins are synaptic cell- adhesion molecules that connect presynaptic and postsynaptic neurons at synapses, mediate signalling across the synapse, and shape the properties of neural networks by specifying synaptic functions. In humans, alterations in genes encoding neurexins or neuroligins have recently been implicated in autism and other cognitive diseases, linking synaptic cell adhesion to cognition and its disorders.
C1 [Sudhof, Thomas C.] Stanford Univ, Inst Neurosci, Dept Mol & Cellular Physiol, Palo Alto, CA 94304 USA.
   [Sudhof, Thomas C.] Stanford Univ, Howard Hughes Med Inst, Palo Alto, CA 94304 USA.
C3 Stanford University; Howard Hughes Medical Institute; Stanford University
RP Südhof, TC (corresponding author), Stanford Univ, Inst Neurosci, Dept Mol & Cellular Physiol, 1050 Arastradero Rd B249, Palo Alto, CA 94304 USA.
EM tcs1@stanford.edu
FU National Institute of Mental Health; Simon Foundation
NR 91
TC 1407
Z9 1714
U1 4
U2 165
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 903
EP 911
DI 10.1038/nature07456
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300038
PM 18923512
DA 2026-03-09
ER

PT J
AU Kuris, AM
   Hechinger, RF
   Shaw, JC
   Whitney, KL
   Aguirre-Macedo, L
   Boch, CA
   Dobson, AP
   Dunham, EJ
   Fredensborg, BL
   Huspeni, TC
   Lorda, J
   Mababa, L
   Mancini, FT
   Mora, AB
   Pickering, M
   Talhouk, NL
   Torchin, ME
   Lafferty, KD
AF Kuris, Armand M.
   Hechinger, Ryan F.
   Shaw, Jenny C.
   Whitney, Kathleen L.
   Aguirre-Macedo, Leopoldina
   Boch, Charlie A.
   Dobson, Andrew P.
   Dunham, Eleca J.
   Fredensborg, Brian L.
   Huspeni, Todd C.
   Lorda, Julio
   Mababa, Luzviminda
   Mancini, Frank T.
   Mora, Adrienne B.
   Pickering, Maria
   Talhouk, Nadia L.
   Torchin, Mark E.
   Lafferty, Kevin D.
TI Ecosystem energetic implications of parasite and free-living biomass in three estuaries
SO NATURE
LA English
DT Article
ID reproductive effort
AB Parasites can have strong impacts but are thought to contribute little biomass to ecosystems(1-3). We quantified the biomass of free-living and parasitic species in three estuaries on the Pacific coast of California and Baja California. Here we show that parasites have substantial biomass in these ecosystems. We found that parasite biomass exceeded that of top predators. The biomass of trematodes was particularly high, being comparable to that of the abundant birds, fishes, burrowing shrimps and polychaetes. Trophically transmitted parasites and parasitic castrators subsumed more biomass than did other parasitic functional groups. The extended phenotype biomass controlled by parasitic castrators sometimes exceeded that of their uninfected hosts. The annual production of free-swimming trematode transmission stages was greater than the combined biomass of all quantified parasites and was also greater than bird biomass. This biomass and productivity of parasites implies a profound role for infectious processes in these estuaries.
C1 [Kuris, Armand M.; Hechinger, Ryan F.; Shaw, Jenny C.; Whitney, Kathleen L.; Boch, Charlie A.; Lorda, Julio; Mababa, Luzviminda; Talhouk, Nadia L.] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [Aguirre-Macedo, Leopoldina] IPN, Ctr Invest & Estud Avanzados, Merida 97310, Mexico.
   [Dobson, Andrew P.] Princeton Univ, Princeton, NJ 08544 USA.
   [Dunham, Eleca J.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
   [Fredensborg, Brian L.] Univ Texas Pan Amer, Dept Biol, Edinburg, TX 78539 USA.
   [Huspeni, Todd C.] Univ Wisconsin, Dept Biol, Stevens Point, WI 54481 USA.
   [Mancini, Frank T.] NOAA, Natl Marine Fisheries Serv, Pacific Isl Fisheries Res Ctr, Honolulu, HI 96822 USA.
   [Mora, Adrienne B.] Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA.
   [Pickering, Maria] Univ Connecticut, Unit 3043, Storrs, CT 06269 USA.
   [Torchin, Mark E.] Smithsonian Trop Res Inst, Balboa 03092, Panama.
   [Lafferty, Kevin D.] Univ Calif Santa Barbara, Western Ecol Res Ctr, US Geol Survey, Inst Marine Sci, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara; Instituto Politecnico Nacional - Mexico; Princeton University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Texas System; University of Texas Rio Grande Valley; University of Wisconsin System; University of Wisconsin Stevens Point; National Aeronautics & Space Administration (NASA); National Oceanic Atmospheric Admin (NOAA) - USA; University of California System; University of California Riverside; University of Connecticut; Smithsonian Institution; Smithsonian Tropical Research Institute; United States Department of the Interior; United States Geological Survey; University of California System; University of California Santa Barbara
RP Kuris, AM (corresponding author), Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
EM kuris@lifesci.ucsb.edu
NR 30
TC 502
Z9 602
U1 3
U2 221
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 515
EP 518
DI 10.1038/nature06970
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300051
PM 18650923
DA 2026-03-09
ER

PT J
AU Makita, T
   Sucov, HM
   Gariepy, CE
   Yanagisawa, M
   Ginty, DD
AF Makita, Takako
   Sucov, Henry M.
   Gariepy, Cheryl E.
   Yanagisawa, Masashi
   Ginty, David D.
TI Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons
SO NATURE
LA English
DT Article
ID cardiac neural crest; b-receptor; gene; expression; disruption; antagonist; profile; cloning; potent; ece-1
AB During development, sympathetic neurons extend axons along a myriad of distinct trajectories, often consisting of arteries, to innervate one of a large variety of distinct final target tissues. Whether or not subsets of neurons within complex sympathetic ganglia are predetermined to innervate select end-organs is unknown. Here we demonstrate in mouse embryos that the endothelin family member Edn3 (ref. 1), acting through the endothelin receptor EdnrA (refs 2, 3), directs extension of axons of a subset of sympathetic neurons from the superior cervical ganglion to a preferred intermediate target, the external carotid artery, which serves as the gateway to select targets, including the salivary glands. These findings establish a previously unknown mechanism of axonal pathfinding involving vascular-derived endothelins, and have broad implications for endothelins as general mediators of axonal growth and guidance in the developing nervous system. Moreover, they suggest a model in which newborn sympathetic neurons distinguish and choose between distinct vascular trajectories to innervate their appropriate end organs.
C1 [Makita, Takako; Ginty, David D.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
   [Sucov, Henry M.] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA.
   [Gariepy, Cheryl E.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
   [Yanagisawa, Masashi] Univ Texas Dallas, SW Med Ctr, Dept Mol Genet, Howard Hughes Med Inst, Dallas, TX 75235 USA.
C3 Johns Hopkins University; Howard Hughes Medical Institute; University of Southern California; University of Michigan System; University of Michigan; University of Texas System; University of Texas Dallas; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute
RP Ginty, DD (corresponding author), Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
EM dginty@jhmi.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NHLBI NIH HHS [R01 HL078891] Funding Source: Medline; NINDS NIH HHS [R37 NS034814] Funding Source: Medline
NR 19
TC 155
Z9 185
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 10
PY 2008
VL 452
IS 7188
BP 759
EP U8
DI 10.1038/nature06859
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500047
PM 18401410
DA 2026-03-09
ER

PT J
AU Zarivach, R
   Deng, WY
   Vuckovic, M
   Felise, HB
   Nguyen, HV
   Miller, SI
   Finlay, BB
   Strynadka, NCJ
AF Zarivach, Raz
   Deng, Wanyin
   Vuckovic, Marija
   Felise, Heather B.
   Nguyen, Hai V.
   Miller, Samuel I.
   Finlay, B. Brett
   Strynadka, Natalie C. J.
TI Structural analysis of the essential self-cleaving type III secretion proteins EscU and SpaS
SO NATURE
LA English
DT Article
ID succinimide formation; escherichia-coli; asparaginyl; salmonella; aspartyl; export; flhb; degradation; components; mechanism
AB During infection by Gram- negative pathogenic bacteria, the type III secretion system ( T3SS) is assembled to allow for the direct transmission of bacterial virulence effectors into the host cell(1). The T3SS system is characterized by a series of prominent multicomponent rings in the inner and outer bacterial membranes, as well as a translocation pore in the host cell membrane. These are all connected by a series of polymerized tubes that act as the direct conduit for the T3SS proteins to pass through to the host cell. During assembly of the T3SS, as well as the evolutionarily related flagellar apparatus(2), a post- translational cleavage event within the inner membrane proteins EscU/FlhB is required to promote a secretion- competent state. These proteins have long been proposed to act as a part of a molecular switch, which would regulate the appropriate chronological secretion of the various T3SS apparatus components during assembly and subsequently the transported virulence effectors. Here we show that a surface type II beta- turn in the Escherichia coli protein EscU undergoes auto-cleavage by a mechanism involving cyclization of a strictly conserved asparagine residue(3). Structural and in vivo analysis of point and deletion mutations illustrates the subtle conformational effects of auto- cleavage in modulating the molecular features of a highly conserved surface region of EscU, a potential point of interaction with other T3SS components at the inner membrane. In addition, this work provides new structural insight into the distinct conformational requirements for a large class of self-cleaving reactions involving asparagine cyclization.
C1 [Zarivach, Raz; Vuckovic, Marija; Strynadka, Natalie C. J.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
   [Zarivach, Raz; Vuckovic, Marija; Strynadka, Natalie C. J.] Univ British Columbia, Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada.
   [Deng, Wanyin; Finlay, B. Brett] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada.
   [Felise, Heather B.; Nguyen, Hai V.; Miller, Samuel I.] Dept Microbiol & Med, Seattle, WA 98195 USA.
C3 University of British Columbia; University of British Columbia; University of British Columbia
RP Strynadka, NCJ (corresponding author), Univ British Columbia, Dept Biochem & Mol Biol, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada.
EM natalie@byron.biochem.ubc.ca
FU NIAID NIH HHS [U54 AI057141, U19 AI107775, R01 AI030479, 5R01 AI030479] Funding Source: Medline
NR 28
TC 119
Z9 136
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 1
PY 2008
VL 453
IS 7191
BP 124
EP +
DI 10.1038/nature06832
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800052
PM 18451864
DA 2026-03-09
ER

PT J
AU González-Maeso, J
   Ang, RL
   Yuen, T
   Chan, P
   Weisstaub, NV
   López-Giménez, JF
   Zhou, MM
   Okawa, Y
   Callado, LF
   Milligan, G
   Gingrich, JA
   Filizola, M
   Meana, JJ
   Sealfon, SC
AF Gonzalez-Maeso, Javier
   Ang, Rosalind L.
   Yuen, Tony
   Chan, Pokman
   Weisstaub, Noelia V.
   Lopez-Gimenez, Juan F.
   Zhou, Mingming
   Okawa, Yuuya
   Callado, Luis F.
   Milligan, Graeme
   Gingrich, Jay A.
   Filizola, Marta
   Meana, J. Javier
   Sealfon, Stuart C.
TI Identification of a serotonin/glutamate receptor complex implicated in psychosis
SO NATURE
LA English
DT Article
ID metabotropic glutamate receptors; crystal-structure; schizophrenia; model; rhodopsin; agonist; psilocybin; oligomerization; alignment; binding
AB The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception(1,2). Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR)(3,4). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia(5-7). The effects of hallucinogenic drugs, such as psilocybin and lysergic acid diethylamide, require the 2AR(8-10) and resemble some of the core symptoms of schizophrenia(10-12). Here we show that the mGluR2 interacts through specific transmembrane helix domains with the 2AR, a member of an unrelated G- protein- coupled receptor family, to form functional complexes in brain cortex. The 2AR - mGluR2 complex triggers unique cellular responses when targeted by hallucinogenic drugs, and activation of mGluR2 abolishes hallucinogen- specific signalling and behavioural responses. In post- mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis. These regulatory changes indicate that the 2AR mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis.
C1 [Gonzalez-Maeso, Javier; Ang, Rosalind L.; Yuen, Tony; Chan, Pokman; Okawa, Yuuya; Sealfon, Stuart C.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
   [Gonzalez-Maeso, Javier] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
   [Filizola, Marta] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA.
   [Sealfon, Stuart C.] Mt Sinai Sch Med, Ctr Translat Syst Biol, New York, NY 10029 USA.
   [Weisstaub, Noelia V.; Zhou, Mingming; Gingrich, Jay A.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
   [Weisstaub, Noelia V.; Gingrich, Jay A.] Columbia Univ, Sackler Inst Labs, New York, NY 10032 USA.
   [Gingrich, Jay A.] Columbia Univ, Lieber Ctr Schizophrenia Res, New York, NY 10032 USA.
   New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
   [Lopez-Gimenez, Juan F.; Milligan, Graeme] Univ Glasgow, Div Biochem & Mol Biol, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
   [Callado, Luis F.; Meana, J. Javier] Univ Basque Country, CIBER Mental Hlth, E-48940 Leioa, Spain.
   [Callado, Luis F.; Meana, J. Javier] Univ Basque Country, Dept Pharmacol, E-48940 Leioa, Spain.
C3 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; Columbia University; Columbia University; Columbia University; New York State Psychiatry Institute; University of Glasgow; CIBER - Centro de Investigacion Biomedica en Red; CIBERSAM; University of Basque Country; University of Basque Country
RP González-Maeso, J (corresponding author), Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
EM javier.maeso@mssm.edu; stuart.sealfon@mssm.edu
FU Medical Research Council [G9811527] Funding Source: researchfish; Medical Research Council [G9811527] Funding Source: Medline; NIDA NIH HHS [P01 DA012923, T32 DA007135] Funding Source: Medline; NIGMS NIH HHS [T32 GM062754] Funding Source: Medline; NIMH NIH HHS [U01 MH083545] Funding Source: Medline; National Institute of General Medical Sciences [T32GM062754] Funding Source: NIH RePORTER; MRC [G9811527] Funding Source: UKRI
NR 44
TC 691
Z9 800
U1 0
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 MAR 6
PY 2008
VL 452
IS 7183
BP 93
EP U9
DI 10.1038/nature06612
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900053
PM 18297054
DA 2026-03-09
ER

PT J
AU Cao, Q
   Kim, HS
   Pimparkar, N
   Kulkarni, JP
   Wang, CJ
   Shim, M
   Roy, K
   Alam, MA
   Rogers, JA
AF Cao, Qing
   Kim, Hoon-sik
   Pimparkar, Ninad
   Kulkarni, Jaydeep P.
   Wang, Congjun
   Shim, Moonsub
   Roy, Kaushik
   Alam, Muhammad A.
   Rogers, John A.
TI Medium-scale carbon nanotube thin-film integrated circuits on flexible plastic substrates
SO NATURE
LA English
DT Article
ID field-effect transistors; large-area; organic transistors; high-resolution; aligned arrays; logic gates; electronics; dielectrics; networks; polymers
AB The ability to form integrated circuits on flexible sheets of plastic enables attributes (for example conformal and flexible formats and lightweight and shock resistant construction) in electronic devices that are difficult or impossible to achieve with technologies that use semiconductor wafers or glass plates as substrates(1). Organic small-molecule and polymer-based materials represent the most widely explored types of semiconductors for such flexible circuitry(2). Although these materials and those that use films or nanostructures of inorganics have promise for certain applications, existing demonstrations of them in circuits on plastic indicate modest performance characteristics that might restrict the application possibilities. Here we report implementations of a comparatively high-performance carbon-based semiconductor consisting of sub-monolayer, random networks of single-walled carbon nanotubes to yield small-to medium-scale integrated digital circuits, composed of up to nearly 100 transistors on plastic substrates. Transistors in these integrated circuits have excellent properties: mobilities as high as 80 cm(2)V(-1) s(-1), subthreshold slopes as low as 140 m V dec(-1), operating voltages less than 5 V together with deterministic control over the threshold voltages, on/off ratios as high as 10(5), switching speeds in the kilohertz range even for coarse (similar to 100-mu m) device geometries, and good mechanical flexibility - all with levels of uniformity and reproducibility that enable high- yield fabrication of integrated circuits. Theoretical calculations, in contexts ranging from heterogeneous percolative transport through the networks to compact models for the transistors to circuit level simulations, provide quantitative and predictive understanding of these systems. Taken together, these results suggest that sub-monolayer films of single-walled carbon nanotubes are attractive materials for flexible integrated circuits, with many potential areas of application in consumer and other areas of electronics.
C1 [Cao, Qing; Rogers, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Kim, Hoon-sik; Wang, Congjun; Shim, Moonsub; Rogers, John A.] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA.
   [Rogers, John A.] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA.
   [Rogers, John A.] Univ Illinois, Dept Mech Sci & Engn, Urbana, IL 61801 USA.
   [Rogers, John A.] Univ Illinois, Frederick Seitz Mat Res Lab, Urbana, IL 61801 USA.
   [Rogers, John A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA.
   [Pimparkar, Ninad; Kulkarni, Jaydeep P.; Roy, Kaushik; Alam, Muhammad A.] Purdue Univ, Sch Elect & Comp Engn, Network Computat Nanotechnol, W Lafayette, IN 47907 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Purdue University System; Purdue University
RP Rogers, JA (corresponding author), Univ Illinois, Dept Chem, 1209 W Calif St, Urbana, IL 61801 USA.
EM jrogers@uiuc.edu
NR 43
TC 1000
Z9 1241
U1 11
U2 797
PU 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 24
PY 2008
VL 454
IS 7203
BP 495
EP U4
DI 10.1038/nature07110
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300046
PM 18650920
DA 2026-03-09
ER

PT J
AU Berns, DM
   Rudner, MS
   Valenzuela, SO
   Berggren, KK
   Oliver, WD
   Levitov, LS
   Orlando, TP
AF Berns, David M.
   Rudner, Mark S.
   Valenzuela, Sergio O.
   Berggren, Karl K.
   Oliver, William D.
   Levitov, Leonid S.
   Orlando, Terry P.
TI Amplitude spectroscopy of a solid-state artificial atom
SO NATURE
LA English
DT Article
ID macroscopic quantum states; superconducting qubit; magnetization; superposition; dynamics
AB The energy- level structure of a quantum system, which has a fundamental role in its behaviour, can be observed as discrete lines and features in absorption and emission spectra. Conventionally, spectra are measured using frequency spectroscopy, whereby the frequency of a harmonic electromagnetic driving field is tuned into resonance with a particular separation between energy levels. Although this technique has been successfully employed in a variety of physical systems, including natural and artificial atoms and molecules, its application is not universally straightforward and becomes extremely challenging for frequencies in the range of tens to hundreds of gigahertz. Here we introduce a complementary approach, amplitude spectroscopy, whereby a harmonic driving field sweeps an artificial atom through the avoided crossings between energy levels at a fixed frequency. Spectroscopic information is obtained from the amplitude dependence of the system's response, thereby overcoming many of the limitations of a broadband- frequency- based approach. The resulting 'spectroscopy diamonds', the regions in parameter space where transitions between specific pairs of levels can occur, exhibit interference patterns and population inversion that serve to distinguish the atom's spectrum. Amplitude spectroscopy provides a means of manipulating and characterizing systems over an extremely broad bandwidth, using only a single driving frequency that may be orders of magnitude smaller than the energy scales being probed.
C1 [Berns, David M.; Oliver, William D.; Orlando, Terry P.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
   [Berns, David M.; Rudner, Mark S.; Levitov, Leonid S.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Valenzuela, Sergio O.] MIT, Francis Bitter Natl Magnet Lab, Cambridge, MA 02139 USA.
   [Berggren, Karl K.; Oliver, William D.] MIT, Lincoln Lab, Lexington, MA 02420 USA.
   [Orlando, Terry P.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Lincoln Laboratory; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Oliver, WD (corresponding author), MIT, Elect Res Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM oliver@ll.mit.edu
FU Air Force Office of Scientific Research and the Laboratory for Physical Sciences [F49620-01-1-0457]; Defense University Research Initiative in Nanotechnology; US government; US Department of Defence under Air Force Contract [FA8721-05-C-0002]
NR 50
TC 139
Z9 148
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 SEP 4
PY 2008
VL 455
IS 7209
BP 51
EP U32
DI 10.1038/nature07262
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200035
PM 18769433
DA 2026-03-09
ER

PT J
AU de Brito, OM
   Scorrano, L
AF de Brito, Olga Martins
   Scorrano, Luca
TI Mitofusin 2 tethers endoplasmic reticulum to mitochondria
SO NATURE
LA English
DT Article
ID mammalian-cells; ca2+; apoptosis; fusion; determinants; oscillations; microdomains; muscle; bax; er
AB Juxtaposition between endoplasmic reticulum ( ER) and mitochondria is a common structural feature, providing the physical basis for intercommunication during Ca(2+) signalling; yet, the molecular mechanisms controlling this interaction are unknown. Here we show that mitofusin 2, a mitochondrial dynamin- related protein mutated in the inherited motor neuropathy Charcot - Marie - Tooth type IIa, is enriched at the ER - mitochondria interface. Ablation or silencing of mitofusin 2 in mouse embryonic fibroblasts and HeLa cells disrupts ER morphology and loosens ER - mitochondria interactions, thereby reducing the efficiency of mitochondrial Ca(2+) uptake in response to stimuli that generate inositol-1,4,5-trisphosphate. An in vitro assay as well as genetic and biochemical evidences support a model in which mitofusin 2 on the ER bridges the two organelles by engaging in homotypic and heterotypic complexes with mitofusin 1 or 2 on the surface of mitochondria. Thus, mitofusin 2 tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca(2+) uptake.
C1 [de Brito, Olga Martins; Scorrano, Luca] Venetian Inst Mol Med, Dulbecco Telethon Inst, I-35129 Padua, Italy.
   [Scorrano, Luca] Univ Geneva, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland.
C3 Fondazione Telethon; Dulbecco Telethon Institute (DTI); Veneto Institute Molecular Medicine; University of Geneva
RP Scorrano, L (corresponding author), Venetian Inst Mol Med, Dulbecco Telethon Inst, Via Orus 2, I-35129 Padua, Italy.
EM lscorrano@dti.telethon.it
FU Telethon Italy; Compagnia di San Paolo Italy; United Mitochondrial Disease Foundation USA; Muscular Distrophy Association USA; Swiss National Science Foundation [3100A0-118171]
NR 35
TC 2048
Z9 2297
U1 6
U2 187
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 4
PY 2008
VL 456
IS 7222
BP 605
EP U47
DI 10.1038/nature07534
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000033
PM 19052620
DA 2026-03-09
ER

PT J
AU Gosse, NJ
   Nevin, LM
   Baier, H
AF Gosse, Nathan J.
   Nevin, Linda M.
   Baier, Herwig
TI Retinotopic order in the absence of axon competition
SO NATURE
LA English
DT Article
ID retinotectal projection; retinal axons; neural map; in-vivo; zebrafish retina; ephrin-as; gradients; growth; model; connections
AB The retinotectal projection has long been studied experimentally and theoretically, as a model for the formation of topographic brain maps(1-3). Neighbouring retinal ganglion cells ( RGCs) project their axons to neighbouring positions in the optic tectum, thus reestablishing a continuous neural representation of visual space. Mapping along this axis requires chemorepellent signalling from tectal cells, expressing ephrin- A ligands, to retinal growth cones, expressing EphA receptors(4). High concentrations of ephrin A, increasing from anterior to posterior, prevent temporal axons from invading the posterior tectum. However, the force that drives nasal axons to extend past the anterior tectum and terminate in posterior regions remains to be identified. We tested whether axon - axon interactions, such as competition, are required for posterior tectum innervation. By transplanting blastomeres from a wild- type ( WT) zebrafish into a lakritz ( lak) mutant, which lacks all RGCs(5), we created chimaeras with eyes that contained single RGCs. These solitary RGCs often extended axons into the tectum, where they branched to form a terminal arbor. Here we show that the distal tips of these arbors were positioned at retinotopically appropriate positions, ruling out an essential role for competition in innervation of the ephrin- A- rich posterior tectum. However, solitary arbors were larger and more complex than under normal, crowded conditions, owing to a lack of pruning of proximal branches during refinement of the retinotectal projection. We conclude that dense innervation is not required for targeting of retinal axons within the zebrafish tectum but serves to restrict arbor size and shape.
C1 [Gosse, Nathan J.; Baier, Herwig] Univ Calif San Francisco, Program Dev Biol, San Francisco, CA 94158 USA.
   [Nevin, Linda M.; Baier, Herwig] Univ Calif San Francisco, Neurosci Program, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Baier, H (corresponding author), Univ Calif San Francisco, Program Dev Biol, 1550 4th St, San Francisco, CA 94158 USA.
EM herwig.baier@ucsf.edu
FU NEI NIH HHS [R01 EY012406, R01 EY013855] Funding Source: Medline
NR 31
TC 68
Z9 84
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 APR 17
PY 2008
VL 452
IS 7189
BP 892
EP U9
DI 10.1038/nature06816
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000052
PM 18368050
DA 2026-03-09
ER

PT J
AU Burke, KA
   Franz, TM
   Miller, DN
   Schoenbaum, G
AF Burke, Kathryn A.
   Franz, Theresa M.
   Miller, Danielle N.
   Schoenbaum, Geoffrey
TI The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards
SO NATURE
LA English
DT Article
ID nucleus-accumbens core; conditioned reinforcement; unconditioned stimulus; basolateral amygdala; d-amphetamine; lesions; representation; complex; dissociation; potentiation
AB Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways(1), and drug- associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction(2,3). Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome- specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making(4), was critical for the former but not for the latter form of conditioned reinforcement.
C1 [Franz, Theresa M.; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
   [Burke, Kathryn A.] Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA.
   [Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
   [Miller, Danielle N.] Baltimore Polytech Inst, Ingenu Project, Baltimore, MD 21209 USA.
C3 University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore
RP Schoenbaum, G (corresponding author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
EM schoenbg@schoenbaumlab.org
FU NIDA NIH HHS [R01 DA015718] Funding Source: Medline
NR 30
TC 132
Z9 172
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 17
PY 2008
VL 454
IS 7202
BP 340
EP U45
DI 10.1038/nature06993
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300040
PM 18563088
DA 2026-03-09
ER

PT J
AU Okamura, K
   Chung, WJ
   Ruby, JG
   Guo, HL
   Bartel, DP
   Lai, EC
AF Okamura, Katsutomo
   Chung, Wei-Jen
   Ruby, J. Graham
   Guo, Huili
   Bartel, David P.
   Lai, Eric C.
TI The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs
SO NATURE
LA English
DT Article
ID double-stranded-rna; passenger-strand; distinct roles; micrornas; expression; germline; cleavage; complexes; dicer-1; plants
AB In contrast to microRNAs and Piwi- associated RNAs, short interfering RNAs ( siRNAs) are seemingly dispensable for host- directed gene regulation in Drosophila. This notion is based on the fact that mutants lacking the core siRNA- generating enzyme Dicer- 2 or the predominant siRNA effector Argonaute 2 are viable, fertile and of relatively normal morphology(1,2). Moreover, endogenous Drosophila siRNAs have not yet been identified. Here we report that siRNAs derived from long hairpin RNA genes ( hpRNAs) programme Slicer complexes that can repress endogenous target transcripts. The Drosophila hpRNA pathway is a hybrid mechanism that combines canonical RNA interference factors ( Dicer- 2, Hen1 ( known as CG12367) and Argonaute 2) with a canonical microRNA factor ( Loquacious) to generate similar to 21- nucleotide siRNAs. These novel regulatory RNAs reveal unexpected complexity in the sorting of small RNAs, and open a window onto the biological usage of endogenous RNA interference in Drosophila.
C1 [Okamura, Katsutomo; Chung, Wei-Jen; Lai, Eric C.] Sloan Kettering Inst, Dept Dev Biol, Rockefeller Res Labs 521, New York, NY 10065 USA.
   [Ruby, J. Graham; Guo, Huili; Bartel, David P.] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA.
   [Ruby, J. Graham; Guo, Huili; Bartel, David P.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Ruby, J. Graham; Guo, Huili; Bartel, David P.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
C3 Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Whitehead Institute
RP Lai, EC (corresponding author), Sloan Kettering Inst, Dept Dev Biol, Rockefeller Res Labs 521, 1275 York Ave,Box 252, New York, NY 10065 USA.
EM laie@mskcc.org
FU Howard Hughes Medical Institute Funding Source: Medline; NIGMS NIH HHS [GM067031, GM083300, R01 GM083300, R01 GM067031] Funding Source: Medline; National Institute of General Medical Sciences [R01GM083300] Funding Source: NIH RePORTER
NR 28
TC 311
Z9 393
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 JUN 5
PY 2008
VL 453
IS 7196
BP 803
EP U8
DI 10.1038/nature07015
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300048
PM 18463630
DA 2026-03-09
ER

PT J
AU Boisvert, CA
   Mark-Kurik, E
   Ahlberg, PE
AF Boisvert, Catherine A.
   Mark-Kurik, Elga
   Ahlberg, Per E.
TI The pectoral fin of Panderichthys and the origin of digits
SO NATURE
LA English
DT Article
ID tetrapod limb; evolution; fish; expression
AB One of the identifying characteristics of tetrapods ( limbed vertebrates) is the presence of fingers and toes. Whereas the proximal part of the tetrapod limb skeleton can easily be homologized with the paired fin skeletons of sarcopterygian ( lobe- finned) fish, there has been much debate about the origin of digits. Early hypotheses(1) interpreted digits as derivatives of fin radials, but during the 1990s the idea gained acceptance that digits are evolutionary novelties without direct equivalents in fish fin skeletons. This was partly based on developmental genetic data(2), but also substantially on the pectoral fin skeleton of the elpistostegid ( transitional fish/ tetrapod) Panderichthys, which appeared to lack distal digit- like radials(3). Here we present a CT scan study of an undisturbed pectoral fin of Panderichthys demonstrating that the plate- like 'ulnare' of previous reconstructions is an artefact and that distal radials are in fact present. This distal portion is more tetrapod- like than that found in Tiktaalik(4) and, in combination with new data about fin development in basal actinopterygians(5), sharks(6) and lungfish(7), makes a strong case for fingers not being a novelty of tetrapods but derived from pre- existing distal radials present in all sarcopterygian fish.
C1 [Boisvert, Catherine A.; Ahlberg, Per E.] Uppsala Univ, Subdept Evolutionary Organismal Biol, Dept Physiol & Dev Biol, Evolutionary Biol Ctr, S-75236 Uppsala, Sweden.
   [Mark-Kurik, Elga] Tallinn Univ Technol, Inst Geol, EE-19086 Tallinn, Estonia.
C3 Uppsala University; Tallinn University of Technology
RP Boisvert, CA (corresponding author), Uppsala Univ, Subdept Evolutionary Organismal Biol, Dept Physiol & Dev Biol, Evolutionary Biol Ctr, Norbyvagen 18A, S-75236 Uppsala, Sweden.
EM catherine.boisvert@ebc.uu.se
FU Vetenskapsradet
NR 21
TC 105
Z9 118
U1 3
U2 129
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 4
PY 2008
VL 456
IS 7222
BP 636
EP 638
DI 10.1038/nature07339
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000040
PM 18806778
DA 2026-03-09
ER

PT J
AU Wang, ET
   Sandberg, R
   Luo, SJ
   Khrebtukova, I
   Zhang, L
   Mayr, C
   Kingsmore, SF
   Schroth, GP
   Burge, CB
AF Wang, Eric T.
   Sandberg, Rickard
   Luo, Shujun
   Khrebtukova, Irina
   Zhang, Lu
   Mayr, Christine
   Kingsmore, Stephen F.
   Schroth, Gary P.
   Burge, Christopher B.
TI Alternative isoform regulation in human tissue transcriptomes
SO NATURE
LA English
DT Article
ID messenger-rna; splicing regulation; microrna targets; protein; genome; expression; binding; fox-1; microarrays; homologs
AB Through alternative processing of pre- messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in- depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon - exon junctions indicated that 92 - 94% of human genes undergo alternative splicing,, 86% with a minor isoform frequency of 15% or more. Differences in isoform- specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full- length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 39 untranslated regions suggested common involvement of specific factors in tissue- level regulation of both splicing and polyadenylation.
C1 [Wang, Eric T.; Sandberg, Rickard; Burge, Christopher B.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Wang, Eric T.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Sandberg, Rickard] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
   [Luo, Shujun; Khrebtukova, Irina; Zhang, Lu; Schroth, Gary P.] Illumina Inc, Hayward, CA 94545 USA.
   [Mayr, Christine] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Kingsmore, Stephen F.] Natl Ctr Genome Resources, Santa Fe, NM 87505 USA.
C3 Massachusetts Institute of Technology (MIT); Harvard University; Karolinska Institutet; Illumina; Massachusetts Institute of Technology (MIT); Whitehead Institute; National Center for Genome Resources (NCGR)
RP Burge, CB (corresponding author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM cburge@mit.edu
FU NIH; Knut & Alice Wallenberg Foundation; Swedish Foundation for Strategic Research; National Human Genome Research Institute [R01HG002439] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM085319] Funding Source: NIH RePORTER
NR 41
TC 3956
Z9 4971
U1 4
U2 438
PU 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 27
PY 2008
VL 456
IS 7221
BP 470
EP 476
DI 10.1038/nature07509
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500031
PM 18978772
DA 2026-03-09
ER

PT J
AU Schaefer, AL
   Greenberg, EP
   Oliver, CM
   Oda, Y
   Huang, JJ
   Bittan-Banin, G
   Peres, CM
   Schmidt, S
   Juhaszova, K
   Sufrin, JR
   Harwood, CS
AF Schaefer, Amy L.
   Greenberg, E. P.
   Oliver, Colin M.
   Oda, Yasuhiro
   Huang, Jean J.
   Bittan-Banin, Gili
   Peres, Caroline M.
   Schmidt, Silke
   Juhaszova, Katarina
   Sufrin, Janice R.
   Harwood, Caroline S.
TI A new class of homoserine lactone quorum-sensing signals
SO NATURE
LA English
DT Article
ID identification; autoinducer; genes
AB Quorum sensing is a term used to describe cell- to- cell communication that allows cell- density- dependent gene expression. Many bacteria use acyl- homoserine lactone ( acyl- HSL) synthases to generate fatty acyl- HSL quorum- sensing signals, which function with signal receptors to control expression of specific genes. The fatty acyl group is derived from fatty acid biosynthesis and provides signal specificity, but the variety of signals is limited. Here we show that the photosynthetic bacterium Rhodopseudomonas palustris uses an acyl- HSL synthase to produce p- coumaroyl- HSL by using environmental p- coumaric acid rather than fatty acids from cellular pools. The bacterium has a signal receptor with homology to fatty acyl- HSL receptors that responds to p- coumaroyl- HSL to regulate global gene expression. We also found that p- coumaroyl- HSL is made by other bacteria including Bradyrhizobium sp. and Silicibacter pomeroyi. This discovery extends the range of possibilities for acyl- HSL quorum sensing and raises fundamental questions about quorum sensing within the context of environmental signalling.
C1 [Schaefer, Amy L.; Greenberg, E. P.; Oda, Yasuhiro; Huang, Jean J.; Bittan-Banin, Gili; Juhaszova, Katarina; Harwood, Caroline S.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
   [Oliver, Colin M.; Sufrin, Janice R.] SUNY Buffalo, Roswell Pk Canc Inst, Mol Pharmacol & Canc Therapeut Program, Buffalo, NY 14263 USA.
   [Peres, Caroline M.] Danisco Genencor, Palo Alto, CA 94304 USA.
   [Schmidt, Silke] Goethe Univ Frankfurt, Inst Mol Biosci, D-60438 Frankfurt, Germany.
C3 University of Washington; University of Washington Seattle; State University of New York (SUNY) System; University at Buffalo, SUNY; Roswell Park Comprehensive Cancer Center; Goethe University Frankfurt
RP Harwood, CS (corresponding author), Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
EM csh5@u.washington.edu
NR 30
TC 304
Z9 380
U1 5
U2 178
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 595
EP U6
DI 10.1038/nature07088
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500037
PM 18563084
DA 2026-03-09
ER

PT J
AU Metzger, RJ
   Klein, OD
   Martin, GR
   Krasnow, MA
AF Metzger, Ross J.
   Klein, Ophir D.
   Martin, Gail R.
   Krasnow, Mark A.
TI The branching programme of mouse lung development
SO NATURE
LA English
DT Article
ID 3-dimensional model; morphogenesis; architecture; epithelium; mechanisms; evolution; patterns; origin; genes
AB Mammalian lungs are branched networks containing thousands to millions of airways arrayed in intricate patterns that are crucial for respiration. How such trees are generated during development, and how the developmental patterning information is encoded, have long fascinated biologists and mathematicians. However, models have been limited by a lack of information on the normal sequence and pattern of branching events. Here we present the complete three- dimensional branching pattern and lineage of the mouse bronchial tree, reconstructed from an analysis of hundreds of developmental intermediates. The branching process is remarkably stereotyped and elegant: the tree is generated by three geometrically simple local modes of branching used in three different orders throughout the lung. We propose that each mode of branching is controlled by a genetically encoded subroutine, a series of local patterning and morphogenesis operations, which are themselves controlled by a more global master routine. We show that this hierarchical and modular programme is genetically tractable, and it is ideally suited to encoding and evolving the complex networks of the lung and other branched organs.
C1 [Metzger, Ross J.; Krasnow, Mark A.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
   [Metzger, Ross J.; Krasnow, Mark A.] Stanford Univ, Sch Med, HHMI, Stanford, CA 94305 USA.
   [Metzger, Ross J.; Klein, Ophir D.; Martin, Gail R.] Univ Calif San Francisco, Sch Med, Dept Anat, San Francisco, CA 94158 USA.
   [Klein, Ophir D.; Martin, Gail R.] Univ Calif San Francisco, Sch Med, Program Dev Biol, San Francisco, CA 94158 USA.
C3 Stanford University; Howard Hughes Medical Institute; Stanford University; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Metzger, RJ (corresponding author), Univ Calif San Francisco, Sch Med, Dept Anat, San Francisco, CA 94158 USA.
EM ross.metzger@ucsf.edu; krasnow@cmgm.stanford.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [R01 CA078711] Funding Source: Medline; NHLBI NIH HHS [R01 HL075769] Funding Source: Medline
NR 42
TC 597
Z9 743
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 JUN 5
PY 2008
VL 453
IS 7196
BP 745
EP U1
DI 10.1038/nature07005
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300035
PM 18463632
DA 2026-03-09
ER

PT J
AU Carmona-Fontaine, C
   Matthews, HK
   Kuriyama, S
   Moreno, M
   Dunn, GA
   Parsons, M
   Stern, CD
   Mayor, R
AF Carmona-Fontaine, Carlos
   Matthews, Helen K.
   Kuriyama, Sei
   Moreno, Mauricio
   Dunn, Graham A.
   Parsons, Maddy
   Stern, Claudio D.
   Mayor, Roberto
TI Contact inhibition of locomotion in vivo controls neural crest directional migration
SO NATURE
LA English
DT Article
ID planar cell-polarity; gastrulation; xenopus; morphogenesis; chemotaxis; zebrafish; movements; behavior; wnt11
AB Contact inhibition of locomotion was discovered by Abercrombie more than 50 years ago and describes the behaviour of fibroblast cells confronting each other in vitro, where they retract their protrusions and change direction on contact(1,2). Its failure was suggested to contribute to malignant invasion(3-6). However, the molecular basis of contact inhibition of locomotion and whether it also occurs in vivo are still unknown. Here we show that neural crest cells, a highly migratory and multipotent embryonic cell population, whose behaviour has been likened to malignant invasion(6-8), demonstrate contact inhibition of locomotion both in vivo and in vitro, and that this accounts for their directional migration. When two migrating neural crest cells meet, they stop, collapse their protrusions and change direction. In contrast, when a neural crest cell meets another cell type, it fails to display contact inhibition of locomotion; instead, it invades the other tissue, in the same manner as metastatic cancer cells(3,5,9). We show that inhibition of non-canonical Wnt signalling abolishes both contact inhibition of locomotion and the directionality of neural crest migration. Wnt- signalling members localize at the site of cell contact, leading to activation of RhoA in this region. These results provide the first example of contact inhibition of locomotion in vivo, provide an explanation for coherent directional migration of groups of cells and establish a previously unknown role for noncanonical Wnt signalling.
C1 [Carmona-Fontaine, Carlos; Matthews, Helen K.; Kuriyama, Sei; Moreno, Mauricio; Stern, Claudio D.; Mayor, Roberto] UCL, Dept Anat & Dev Biol, London WC1E 6BT, England.
   [Dunn, Graham A.; Parsons, Maddy] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England.
C3 University of London; University College London; University of London; King's College London
RP Mayor, R (corresponding author), UCL, Dept Anat & Dev Biol, Mortimer St, London WC1E 6BT, England.
EM r.mayor@ucl.ac.uk
FU Medical Research Council; Biotechnology and Biological Sciences Research Council; MRC; Boehringer Ingelheim Fonds; BBSRC [BB/D017521/1] Funding Source: UKRI; MRC [G0401026, G0400559, G117/506, G0100152] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/D017521/1] Funding Source: researchfish; Medical Research Council [G0100152, G0400559, G0401026, G117/506] Funding Source: researchfish
NR 29
TC 474
Z9 586
U1 0
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 957
EP 961
DI 10.1038/nature07441
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300047
PM 19078960
DA 2026-03-09
ER

PT J
AU Algra, RE
   Verheijen, MA
   Borgström, MT
   Feiner, LF
   Immink, G
   van Enckevort, WJP
   Vlieg, E
   Bakkers, EPAM
AF Algra, Rienk E.
   Verheijen, Marcel A.
   Borgstrom, Magnus T.
   Feiner, Lou-Fe
   Immink, George
   van Enckevort, Willem J. P.
   Vlieg, Elias
   Bakkers, Erik P. A. M.
TI Twinning superlattices in indium phosphide nanowires
SO NATURE
LA English
DT Article
ID zincblende-type semiconductors; optical-property; diamond-type; growth; inp; layers; gaas
AB Semiconducting nanowires offer the possibility of nearly unlimited complex bottom- up design(1,2), which allows for new device concepts(3,4). However, essential parameters that determine the electronic quality of the wires, and which have not been controlled yet for the III-V compound semiconductors, are the wire crystal structure and the stacking fault density(5). In addition, a significant feature would be to have a constant spacing between rotational twins in the wires such that a twinning superlattice is formed, as this is predicted to induce a direct bandgap in normally indirect bandgap semiconductors(6,7), such as silicon and gallium phosphide. Optically active versions of these technologically relevant semiconductors could have a significant impact on the electronics(8) and optics(9) industry. Here we show first that we can control the crystal structure of indium phosphide (InP) nanowires by using impurity dopants. We have found that zinc decreases the activation barrier for two- dimensional nucleation growth of zinc- blende InP and therefore promotes crystallization of the InP nanowires in the zinc- blende, instead of the commonly found wurtzite, crystal structure(10). More importantly, we then demonstrate that we can, once we have enforced the zinc- blende crystal structure, induce twinning superlattices with long-range order in InP nanowires. We can tune the spacing of the superlattices by changing the wire diameter and the zinc concentration, and we present a model based on the distortion of the catalyst droplet in response to the evolution of the cross- sectional shape of the nanowires to quantitatively explain the formation of the periodic twinning.
C1 [Algra, Rienk E.; Verheijen, Marcel A.; Borgstrom, Magnus T.; Feiner, Lou-Fe; Immink, George] Philips Res Labs, NL-5656 AE Eindhoven, Netherlands.
   [Algra, Rienk E.] Mat Innovat Inst M2i, NL-2628 CD Delft, Netherlands.
   [Algra, Rienk E.; van Enckevort, Willem J. P.; Vlieg, Elias] Radboud Univ Nijmegen, IMM, NL-6525 AJ Nijmegen, Netherlands.
C3 Philips; Philips Research; Radboud University Nijmegen
RP Bakkers, EPAM (corresponding author), Philips Res Labs, High Tech Campus 11, NL-5656 AE Eindhoven, Netherlands.
EM erik.bakkers@philips.com
NR 27
TC 616
Z9 684
U1 1
U2 304
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 20
PY 2008
VL 456
IS 7220
BP 369
EP 372
DI 10.1038/nature07570
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600039
PM 19020617
DA 2026-03-09
ER

PT J
AU Tuffen, H
   Smith, R
   Sammonds, PR
AF Tuffen, Hugh
   Smith, Rosanna
   Sammonds, Peter R.
TI Evidence for seismogenic fracture of silicic magma
SO NATURE
LA English
DT Article
ID soufriere hills volcano; mount-st-helens; acoustic-emission; unzen volcano; lava dome; earthquakes; montserrat; seismicity; eruptions; andesite
AB It has long been assumed that seismogenic faulting is confined to cool, brittle rocks, with a temperature upper limit of similar to 600 degrees C (ref. 1). This thinking underpins our understanding of volcanic earthquakes, which are assumed to occur in cold rocks surrounding moving magma. However, the recent discovery of abundant brittle-ductile fault textures in silicic lavas(2-4) has led to the counter-intuitive hypothesis that seismic events may be triggered by fracture and faulting within the erupting magma itself. This hypothesis is supported by recent observations of growing lava domes, where microearthquake swarms have coincided with the emplacement of gouge-covered lava spines(5,6), leading to models of seismogenic stick-slip along shallow shear zones in the magma(7). But can fracturing or faulting in high-temperature, eruptible magma really generate measurable seismic events? Here we deform high-temperature silica-rich magmas under simulated volcanic conditions in order to test the hypothesis that hightemperature magma fracture is seismogenic. The acoustic emissions recorded during experiments show that seismogenic rupture may occur in both crystal- rich and crystal-free silicic magmas at eruptive temperatures, extending the range of known conditions for seismogenic faulting.
C1 [Tuffen, Hugh] Univ Lancaster, Dept Environm Sci, Lancaster LA1 4YQ, England.
   [Tuffen, Hugh; Smith, Rosanna; Sammonds, Peter R.] UCL, Dept Earth Sci, London WC1E 6BT, England.
C3 Lancaster University; University of London; University College London
RP Tuffen, H (corresponding author), Univ Lancaster, Dept Environm Sci, Lancaster LA1 4YQ, England.
EM h.tuffen@lancaster.ac.uk
FU NERC [NE/E013740/1, NE/D012910/1] Funding Source: UKRI; Natural Environment Research Council [NE/E013740/1, NE/D012910/1] Funding Source: researchfish
NR 30
TC 116
Z9 122
U1 1
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 511
EP 514
DI 10.1038/nature06989
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700040
PM 18497823
DA 2026-03-09
ER

PT J
AU Merico, A
   Tyrrell, T
   Wilson, PA
AF Merico, Agostino
   Tyrrell, Toby
   Wilson, Paul A.
TI Eocene/oligocene ocean de-acidification linked to Antarctic glaciation by sea-level fall
SO NATURE
LA English
DT Article
ID eocene-oligocene transition; atmospheric carbon-dioxide; calcite compensation; cenozoic glaciation; bipolar glaciation; oxygen isotopes; cycle; paleoceanography; accumulation; initiation
AB One of the most dramatic perturbations to the Earth system during the past 100 million years was the rapid onset of Antarctic glaciation near the Eocene/ Oligocene epoch boundary(1-3) (similar to 34 million years ago). This climate transition was accompanied(3) by a deepening of the calcite compensation depth - the ocean depth at which the rate of calcium carbonate input from surface waters equals the rate of dissolution. Changes in the global carbon cycle(4), rather than changes in continental configuration(5), have recently been proposed as the most likely root cause of Antarctic glaciation, but the mechanism linking glaciation to the deepening of calcite compensation depth remains unclear. Here we use a global biogeochemical box model to test competing hypotheses put forward to explain the Eocene/ Oligocene transition. We find that, of the candidate hypotheses, only shelf to deep sea carbonate partitioning is capable of explaining the observed changes in both carbon isotope composition and calcium carbonate accumulation at the sea floor. In our simulations, glacioeustatic sea- level fall associated with the growth of Antarctic ice sheets permanently reduces global calcium carbonate accumulation on the continental shelves, leading to an increase in pelagic burial via permanent deepening of the calcite compensation depth. At the same time, fresh limestones are exposed to erosion, thus temporarily increasing global river inputs of dissolved carbonate and increasing seawater delta(13) C. Our work sheds new light on the mechanisms linking glaciation and ocean acidity change across arguably the most important climate transition of the Cenozoic era.
C1 [Merico, Agostino; Tyrrell, Toby; Wilson, Paul A.] Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
   [Merico, Agostino] GKSS Forschungszentrum Geesthacht GmbH, Inst Coastal Res, D-21502 Geesthacht, Germany.
C3 NERC National Oceanography Centre; Helmholtz Association; Helmholtz-Zentrum Hereon
RP Merico, A (corresponding author), Natl Oceanog Ctr, European Way, Southampton SO14 3ZH, Hants, England.
EM agostino.merico@gkss.de
FU NERC [soc010008] Funding Source: UKRI; Natural Environment Research Council [NER/A/S/2003/00377, soc010008] Funding Source: researchfish
NR 39
TC 89
Z9 106
U1 0
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 24
PY 2008
VL 452
IS 7190
BP 979
EP U6
DI 10.1038/nature06853
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600036
PM 18432242
DA 2026-03-09
ER

PT J
AU Tay, S
   Blanche, PA
   Voorakaranam, R
   Tunç, AV
   Lin, W
   Rokutanda, S
   Gu, T
   Flores, D
   Wang, P
   Li, G
   St Hilaire, P
   Thomas, J
   Norwood, RA
   Yamamoto, M
   Peyghambarian, N
AF Tay, Savas
   Blanche, P. -A.
   Voorakaranam, R.
   Tunc, A. V.
   Lin, W.
   Rokutanda, S.
   Gu, T.
   Flores, D.
   Wang, P.
   Li, G.
   St Hilaire, P.
   Thomas, J.
   Norwood, R. A.
   Yamamoto, M.
   Peyghambarian, N.
TI An updatable holographic three-dimensional display
SO NATURE
LA English
DT Article
ID 3d; system; polymers; design
AB Holographic three- dimensional ( 3D) displays(1,2) provide realistic images without the need for special eyewear, making them valuable tools for applications that require situational awareness, such as medical, industrial and military imaging. Currently commercially available holographic 3D displays(3) use photopolymers that lack image- updating capability, resulting in restricted use and high cost. Photorefractive polymers(4-9) are dynamic holographic recording materials that allow updating of images and have a wide range of applications, including optical correlation(10), imaging through scattering media(11) and optical communication(12,13). To be suitable for 3D displays, photorefractive polymers need to have nearly 100% diffraction efficiency, fast writing time, hours of image persistence, rapid erasure, and large area - a combination of properties that has not been shown before. Here, we report an updatable holographic 3D display based on photorefractive polymers with such properties, capable of recording and displaying new images every few minutes. This is the largest photorefractive 3D display to date ( 4x4 inches in size); it can be recorded within a few minutes, viewed for several hours without the need for refreshing, and can be completely erased and updated with new images when desired.
C1 [Tay, Savas; Blanche, P. -A.; Voorakaranam, R.; Tunc, A. V.; Li, G.; St Hilaire, P.; Thomas, J.; Norwood, R. A.; Peyghambarian, N.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA.
   [Lin, W.; Rokutanda, S.; Gu, T.; Flores, D.; Wang, P.; Yamamoto, M.] Nitto Denko Tech Corp, Oceanside, CA 92054 USA.
C3 University of Arizona; Nitto Denko Corporation
RP Tay, S (corresponding author), Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA.
EM savas.tay@optics.arizona.edu; nnp@u.arizona.edu
NR 29
TC 380
Z9 442
U1 3
U2 179
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 694
EP 698
DI 10.1038/nature06596
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500036
PM 18256667
DA 2026-03-09
ER

PT J
AU Johnnidis, JB
   Harris, MH
   Wheeler, RT
   Stehling-Sun, S
   Lam, MH
   Kirak, O
   Brummelkamp, TR
   Fleming, MD
   Camargo, FD
AF Johnnidis, Jonathan B.
   Harris, Marian H.
   Wheeler, Robert T.
   Stehling-Sun, Sandra
   Lam, Michael H.
   Kirak, Oktay
   Brummelkamp, Thijn R.
   Fleming, Mark D.
   Camargo, Fernando D.
TI Regulation of progenitor cell proliferation and granulocyte function by microRNA-223
SO NATURE
LA English
DT Article
ID growth-factor-i; respiratory burst; neutrophils; inflammation; expression; mechanism; capacity; hormone
AB MicroRNAs are abundant in animal genomes and have been predicted to have important roles in a broad range of gene expression programmes(1,2). Despite this prominence, there is a dearth of functional knowledge regarding individual mammalian microRNAs. Using a loss- of- function allele in mice, we report here that the myeloid- specific microRNA- 223 ( miR- 223) negatively regulates progenitor proliferation and granulocyte differentiation and activation. miR- 223 ( also called Mirn223) mutant mice have an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors. We show that Mef2c, a transcription factor that promotes myeloid progenitor proliferation, is a target of miR- 223, and that genetic ablation of Mef2c suppresses progenitor expansion and corrects the neutrophilic phenotype in miR- 223 null mice. In addition, granulocytes lacking miR- 223 are hypermature, hypersensitive to activating stimuli and display increased fungicidal activity. As a consequence of this neutrophil hyperactivity, miR- 223 mutant mice spontaneously develop inflammatory lung pathology and exhibit exaggerated tissue destruction after endotoxin challenge. Our data support a model in which miR- 223 acts as a fine- tuner of granulocyte production and the inflammatory response.
C1 [Johnnidis, Jonathan B.; Wheeler, Robert T.; Stehling-Sun, Sandra; Lam, Michael H.; Kirak, Oktay; Brummelkamp, Thijn R.; Camargo, Fernando D.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Harris, Marian H.; Fleming, Mark D.] Harvard Univ, Sch Med, Dept Pathol, Childrens Hosp, Boston, MA 02115 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital
RP Camargo, FD (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM camargo@wi.mit.edu
NR 26
TC 1021
Z9 1197
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 FEB 28
PY 2008
VL 451
IS 7182
BP 1125
EP U11
DI 10.1038/nature06607
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600046
PM 18278031
DA 2026-03-09
ER

PT J
AU Kanasaki, K
   Palmsten, K
   Sugimoto, H
   Ahmad, S
   Hamano, Y
   Xie, L
   Parry, S
   Augustin, HG
   Gattone, VH
   Folkman, J
   Strauss, JF
   Kalluri, R
AF Kanasaki, Keizo
   Palmsten, Kristin
   Sugimoto, Hikaru
   Ahmad, Shakil
   Hamano, Yuki
   Xie, Liang
   Parry, Samuel
   Augustin, Hellmut G.
   Gattone, Vincent H., Jr.
   Folkman, Judah
   Strauss, Jerome F.
   Kalluri, Raghu
TI Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia
SO NATURE
LA English
DT Article
ID growth-factor receptor-1; inhibits angiogenesis; tumor-growth; in-vitro; pregnancy; placenta; 2-hydroxyestradiol; 2-methoxyestradiol; differentiation; proteinuria
AB Despite intense investigation, mechanisms that facilitate the emergence of the pre-eclampsia phenotype in women are still unknown. Placental hypoxia, hypertension, proteinuria and oedema are the principal clinical features of this disease. It is speculated that hypoxia-driven disruption of the angiogenic balance involving vascular endothelial growth factor (VEGF)/ placenta-derived growth factor (PLGF) and soluble Fms-like tyrosine kinase-1 (sFLT-1, the soluble form of VEGF receptor 1) might contribute to some of the maternal symptoms of pre-eclampsia(1-5). However, pre-eclampsia does not develop in all women with high sFLT-1 or low PLGF levels, and it also occurs in some women with low sFLT-1 and high PLGF levels(5,6). Moreover, recent experiments strongly suggest that several soluble factors affecting the vasculature are probably elevated because of placental hypoxia in the pre-eclamptic women, indicating that upstream molecular defect(s) may contribute to pre-eclampsia. Here we show that pregnant mice deficient in catechol-O-methyltransferase (COMT) show a pre-eclampsia-like phenotype resulting from an absence of 2-methoxyoestradiol (2-ME), a natural metabolite of oestradiol that is elevated during the third trimester of normal human pregnancy. 2-ME ameliorates all pre-eclampsia-like features without toxicity in the Comt(-/-) pregnant mice and suppresses placental hypoxia, hypoxia-inducible factor-1 alpha expression and sFLT-1 elevation. The levels of COMT and 2-ME are significantly lower in women with severe pre-eclampsia. Our studies identify a genetic mouse model for pre-eclampsia and suggest that 2-ME may have utility as a plasma and urine diagnostic marker for this disease, and may also serve as a therapeutic supplement to prevent or treat this disorder.
C1 [Kanasaki, Keizo; Palmsten, Kristin; Sugimoto, Hikaru; Hamano, Yuki; Xie, Liang; Kalluri, Raghu] Beth Israel Deaconess Med Ctr, Div Matrix Biol, Dept Med, Boston, MA 02215 USA.
   [Kanasaki, Keizo; Palmsten, Kristin; Sugimoto, Hikaru; Hamano, Yuki; Xie, Liang; Kalluri, Raghu] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Ahmad, Shakil] Univ Birmingham, Sch Med, Dept Reprod Biol, Biomed Res Inst, Birmingham B15 2TT, W Midlands, England.
   [Ahmad, Shakil] Univ Birmingham, Sch Med, Dept Vasc Biol, Biomed Res Inst, Birmingham B15 2TT, W Midlands, England.
   [Ahmad, Shakil] Birmingham Womens Hosp, Birmingham B15 2TG, W Midlands, England.
   [Parry, Samuel] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
   [Augustin, Hellmut G.] Univ Heidelberg, Joint Res Div Vasc Biol, Med Fac Mannheim, D-69120 Heidelberg, Germany.
   [Augustin, Hellmut G.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
   [Gattone, Vincent H., Jr.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA.
   [Folkman, Judah] Childrens Hosp, Program Vasc Biol, Dept Surg Res, Boston, MA 02215 USA.
   [Strauss, Jerome F.] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23298 USA.
   [Kalluri, Raghu] Harvard Mit Div Hlth Sci & Technol, Boston, MA 02215 USA.
   [Kalluri, Raghu] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; University of Birmingham; University of Birmingham; Birmingham Women's Hospital; University of Pennsylvania; Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Indiana University System; Indiana University Indianapolis; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Virginia Commonwealth University; Harvard University; Harvard University; Harvard Medical School
RP Kalluri, R (corresponding author), Beth Israel Deaconess Med Ctr, Div Matrix Biol, Dept Med, Boston, MA 02215 USA.
EM rkalluri@bidmc.harvard.edu
FU MRC [G0700288] Funding Source: UKRI; Medical Research Council [G0700288] Funding Source: researchfish; British Heart Foundation Funding Source: Medline; Medical Research Council [G0700288] Funding Source: Medline; NIDDK NIH HHS [DK 61688, DK 55001, DK 62987, DK 13193, R01 DK061688, R01 DK055001] Funding Source: Medline
NR 33
TC 328
Z9 382
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 19
PY 2008
VL 453
IS 7198
BP 1117
EP U12
DI 10.1038/nature06951
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900060
PM 18469803
DA 2026-03-09
ER

PT J
AU Grillmair, CJ
   Burrows, A
   Charbonneau, D
   Armus, L
   Stauffer, J
   Meadows, V
   van Cleve, J
   von Braun, K
   Levine, D
AF Grillmair, Carl J.
   Burrows, Adam
   Charbonneau, David
   Armus, Lee
   Stauffer, John
   Meadows, Victoria
   van Cleve, Jeffrey
   von Braun, Kaspar
   Levine, Deborah
TI Strong water absorption in the dayside emission spectrum of the planet HD189733b
SO NATURE
LA English
DT Article
ID extrasolar planet; infrared-emission; giant planets; light curves; hd 209458b; atmosphere; contrast; search
AB Recent observations of the extrasolar planet HD189733b did not reveal the presence of water in the emission spectrumof the planet(1). Yet models of such 'hot- Jupiter' planets predict an abundance of atmospheric water vapour(2). Validating and constraining these models is crucial to understanding the physics and chemistry of planetary atmospheres in extreme environments. Indications of the presence of water in the atmosphere of HD189733b have recently been found in transmission spectra(3,4), where the planet's atmosphere selectively absorbs the light of the parent star, and in broadband photometry(5). Here we report the detection of strong water absorption in a high- signal- to- noise, mid- infrared emission spectrumof the planet itself. We find both a strong downturn in the flux ratio below 10 mu m and discrete spectral features that are characteristic of strong absorption by water vapour. The differences between these and previous observations are significant and admit the possibility that predicted planetary- scale dynamical weather structures(6) may alter the emission spectrum over time. Models that match the observed spectrum and the broadband photometry suggest that heat redistribution from the dayside to the nightside is weak. Reconciling this with the high nightside temperature(7) will require a better understanding of atmospheric circulation or possible additional energy sources.
C1 [Grillmair, Carl J.; Armus, Lee; Stauffer, John; Levine, Deborah] Spitzer Sci Ctr, Pasadena, CA 91125 USA.
   [Burrows, Adam] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Charbonneau, David] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Meadows, Victoria] Univ Washington, Dept Astron, Seattle, WA 98195 USA.
   [van Cleve, Jeffrey] Ball Aerosp & Technol Corp, Boulder, CO 80306 USA.
   [von Braun, Kaspar] CALTECH, Michelson Sci Ctr, Pasadena, CA 91125 USA.
C3 Princeton University; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; University of Washington; University of Washington Seattle; Ball Aerospace & Technologies; California Institute of Technology
RP Grillmair, CJ (corresponding author), Spitzer Sci Ctr, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM carl@ipac.caltech.edu
FU NASA [NNGO4GL22G]; JPL/Caltech
NR 25
TC 215
Z9 249
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 11
PY 2008
VL 456
IS 7223
BP 767
EP 769
DI 10.1038/nature07574
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900043
PM 19079054
DA 2026-03-09
ER

PT J
AU Gaspard, N
   Bouschet, T
   Hourez, R
   Dimidschstein, J
   Naeije, G
   van den Ameele, J
   Espuny-Camacho, I
   Herpoel, A
   Passante, L
   Schiffmann, SN
   Gaillard, A
   Vanderhaeghen, P
AF Gaspard, Nicolas
   Bouschet, Tristan
   Hourez, Raphael
   Dimidschstein, Jordane
   Naeije, Gilles
   van den Ameele, Jelle
   Espuny-Camacho, Ira
   Herpoel, Adele
   Passante, Lara
   Schiffmann, Serge N.
   Gaillard, Afsaneh
   Vanderhaeghen, Pierre
TI An intrinsic mechanism of corticogenesis from embryonic stem cells
SO NATURE
LA English
DT Article
ID developing cerebral-cortex; directed differentiation; cortical development; projection neuron; radial glia; specification; fate; neocortex; transplantation; precursors
AB The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases.
C1 [Gaspard, Nicolas; Bouschet, Tristan; Dimidschstein, Jordane; Naeije, Gilles; van den Ameele, Jelle; Espuny-Camacho, Ira; Herpoel, Adele; Passante, Lara; Vanderhaeghen, Pierre] Univ Libre Bruxelles, IRIBHN, Inst Interdisciplinary Res, B-1070 Brussels, Belgium.
   [Hourez, Raphael; Schiffmann, Serge N.] Univ Libre Bruxelles, Neurophysiol Lab, B-1070 Brussels, Belgium.
   [Gaillard, Afsaneh] Univ Poitiers, CNRS, Inst Physiol & Biol Cellulaires, F-86022 Poitiers, France.
C3 Universite Libre de Bruxelles; Universite Libre de Bruxelles; Centre National de la Recherche Scientifique (CNRS); Universite de Poitiers
RP Vanderhaeghen, P (corresponding author), Univ Libre Bruxelles, IRIBHN, Inst Interdisciplinary Res, 808 Route Lennik, B-1070 Brussels, Belgium.
EM pierre.vanderhaeghen@ulb.ac.be
FU Belgian FNRS, the Action de Recherches Concertees (ARC) Programs; Interuniversity Attraction Poles Program (IUAP); Belgian State; Federal Office; Walloon Region Excellence Program CIBLES; Belgian Queen Elizabeth Medical Foundation; UCB Neuroscience Award; Tournesol FNRS/CNRS Program; Televie; Marie Curie Grant; Research Fellows of the FNRS
NR 45
TC 513
Z9 607
U1 1
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 351
EP U10
DI 10.1038/nature07287
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200036
PM 18716623
DA 2026-03-09
ER

PT J
AU Zimmer, J
   Nam, YS
   Rapoport, TA
AF Zimmer, Jochen
   Nam, Yunsun
   Rapoport, Tom A.
TI Structure of a complex of the ATPase SecA and the protein-translocation channel
SO NATURE
LA English
DT Article
ID signal-sequence recognition; x-ray-structure; escherichia-coli; membrane-protein; dimeric seca; density-modification; crystal-structures; secyeg; mediate; export
AB Most proteins are secreted from bacteria by the interaction of the cytoplasmic SecA ATPase with a membrane channel, formed by the heterotrimeric SecY complex. Here we report the crystal structure of SecA bound to the SecY complex, with a maximum resolution of 4.5 angstrorm ( A), obtained for components from Thermotoga maritima. One copy of SecA in an intermediate state of ATP hydrolysis is bound to one molecule of the SecY complex. Both partners undergo important conformational changes on interaction. The polypeptide- cross- linking domain of SecA makes a large conformational change that could capture the translocation substrate in a 'clamp'. Polypeptide movement through the SecY channel could be achieved by the motion of a 'two-helix finger' of SecA inside the cytoplasmic funnel of SecY, and by the coordinated tightening and widening of SecA's clamp above the SecY pore. SecA binding generates a 'window' at the lateral gate of the SecY channel and it displaces the plug domain, preparing the channel for signal sequence binding and channel opening.
C1 [Zimmer, Jochen; Nam, Yunsun; Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Zimmer, Jochen; Nam, Yunsun; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School
RP Rapoport, TA (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 240 Longwood Ave, Boston, MA 02115 USA.
EM tom_rapoport@hms.harvard.edu
FU National Institutes of Health; Damon Runyon Cancer Research Foundation [DRG-#1953-07]
NR 62
TC 365
Z9 464
U1 2
U2 52
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 936
EP U32
DI 10.1038/nature07335
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300043
PM 18923516
DA 2026-03-09
ER

PT J
AU Mulholland, PJ
   Helton, AM
   Poole, GC
   Hall, RO
   Hamilton, SK
   Peterson, BJ
   Tank, JL
   Ashkenas, LR
   Cooper, LW
   Dahm, CN
   Dodds, WK
   Findlay, SEG
   Gregory, SV
   Grimm, NB
   Johnson, SL
   McDowell, WH
   Meyer, JL
   Valett, HM
   Webster, JR
   Arango, CP
   Beaulieu, JJ
   Bernot, MJ
   Burgin, AJ
   Crenshaw, CL
   Johnson, LT
   Niederlehner, BR
   O'Brien, JM
   Potter, JD
   Sheibley, RW
   Sobota, DJ
   Thomas, SM
AF Mulholland, Patrick J.
   Helton, Ashley M.
   Poole, Geoffrey C.
   Hall, Robert O., Jr.
   Hamilton, Stephen K.
   Peterson, Bruce J.
   Tank, Jennifer L.
   Ashkenas, Linda R.
   Cooper, Lee W.
   Dahm, Clifford N.
   Dodds, Walter K.
   Findlay, Stuart E. G.
   Gregory, Stanley V.
   Grimm, Nancy B.
   Johnson, Sherri L.
   McDowell, William H.
   Meyer, Judy L.
   Valett, H. Maurice
   Webster, Jackson R.
   Arango, Clay P.
   Beaulieu, Jake J.
   Bernot, Melody J.
   Burgin, Amy J.
   Crenshaw, Chelsea L.
   Johnson, Laura T.
   Niederlehner, B. R.
   O'Brien, Jonathan M.
   Potter, Jody D.
   Sheibley, Richard W.
   Sobota, Daniel J.
   Thomas, Suzanne M.
TI Stream denitrification across biomes and its response to anthropogenic nitrate loading
SO NATURE
LA English
DT Article
ID nitrogen; watersheds; land; size
AB Anthropogenic addition of bioavailable nitrogen to the biosphere is increasing(1,2) and terrestrial ecosystems are becoming increasingly nitrogen- saturated(3), causing more bioavailable nitrogen to enter groundwater and surface waters(4-6). Large- scale nitrogen budgets show that an average of about 20 - 25 per cent of the nitrogen added to the biosphere is exported from rivers to the ocean or inland basins(7,8), indicating that substantial sinks for nitrogen must exist in the landscape(9). Streams and rivers may themselves be important sinks for bioavailable nitrogen owing to their hydrological connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favour microbial denitrification(6,10,11). Here we present data from nitrogen stable isotope tracer experiments across 72 streams and 8 regions representing several biomes. We show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of in- stream nitrate that is removed from transport. Our data suggest that the total uptake of nitrate is related to ecosystem photosynthesis and that denitrification is related to ecosystem respiration. In addition, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.
C1 [Mulholland, Patrick J.] Oak Ridge Natl Lab, Div Environm Sci, Oak Ridge, TN 37831 USA.
   [Mulholland, Patrick J.; Cooper, Lee W.] Univ Tennessee, Dept Ecol & Evolutionary Biol, Knoxville, TN 37996 USA.
   [Helton, Ashley M.; Poole, Geoffrey C.; Meyer, Judy L.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
   [Poole, Geoffrey C.] Ecometr Inc, Tucker, GA 30084 USA.
   [Hall, Robert O., Jr.] Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82071 USA.
   [Hamilton, Stephen K.; Burgin, Amy J.; O'Brien, Jonathan M.] Michigan State Univ, Kellogg Biol Stn, Hickory Corners, MI 49060 USA.
   [Peterson, Bruce J.; Thomas, Suzanne M.] Marine Biol Lab, Ctr Ecosyst, Woods Hole, MA 02543 USA.
   [Tank, Jennifer L.; Arango, Clay P.; Beaulieu, Jake J.; Johnson, Laura T.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
   [Ashkenas, Linda R.; Gregory, Stanley V.; Sobota, Daniel J.] Oregon State Univ, Dept Fisheries & Wildlife, Corvallis, OR 97331 USA.
   [Dahm, Clifford N.; Crenshaw, Chelsea L.] Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA.
   [Dodds, Walter K.] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA.
   [Findlay, Stuart E. G.] Inst Ecosyst Studies, Millbrook, NY 12545 USA.
   [Grimm, Nancy B.; Sheibley, Richard W.] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA.
   [Johnson, Sherri L.] US Forest Serv, Pacific NW Res Stn, Corvallis, OR 97331 USA.
   [McDowell, William H.; Potter, Jody D.] Univ New Hampshire, Dept Nat Resources, Durham, NH 03824 USA.
   [Valett, H. Maurice; Webster, Jackson R.; Niederlehner, B. R.] Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA.
   [Bernot, Melody J.] Ball State Univ, Dept Biol, Muncie, IN 47306 USA.
C3 United States Department of Energy (DOE); Oak Ridge National Laboratory; University of Tennessee System; University of Tennessee Knoxville; University System of Georgia; University of Georgia; University of Wyoming; Michigan State University; Marine Biological Laboratory - Woods Hole; University of Notre Dame; Oregon State University; University of New Mexico; Kansas State University; Cary Institute of Ecosystem Studies; Arizona State University; Arizona State University-Tempe; United States Department of Agriculture (USDA); United States Forest Service; University System Of New Hampshire; University of New Hampshire; Virginia Polytechnic Institute & State University; Ball State University
RP Mulholland, PJ (corresponding author), Oak Ridge Natl Lab, Div Environm Sci, POB 2008, Oak Ridge, TN 37831 USA.
EM mulhollandpj@ornl.gov
FU Directorate For Geosciences; Division Of Ocean Sciences [1058747] Funding Source: National Science Foundation
NR 32
TC 1074
Z9 1340
U1 8
U2 897
PU NATURE PUBLISHING 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 13
PY 2008
VL 452
IS 7184
BP 202
EP U46
DI 10.1038/nature06686
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600037
PM 18337819
DA 2026-03-09
ER

PT J
AU Kepecs, A
   Uchida, N
   Zariwala, HA
   Mainen, ZF
AF Kepecs, Adam
   Uchida, Naoshige
   Zariwala, Hatim A.
   Mainen, Zachary F.
TI Neural correlates, computation and behavioural impact of decision confidence
SO NATURE
LA English
DT Article
ID orbitofrontal cortex; prefrontal cortex; matching behavior; reward preference; neuronal-activity; uncertainty; representation; models; performance; amygdala
AB Humans and other animals must often make decisions on the basis of imperfect evidence(1,2). Statisticians use measures such as P values to assign degrees of confidence to propositions, but little is known about how the brain computes confidence estimates about decisions. We explored this issue using behavioural analysis and neural recordings in rats in combination with computational modelling. Subjects were trained to perform an odour categorization task that allowed decision confidence to be manipulated by varying the distance of the test stimulus to the category boundary. To understand how confidence could be computed along with the choice itself, using standard models of decision-making(3-6), we defined a simple measure that quantified the quality of the evidence contributing to a particular decision. Here we show that the firing rates of many single neurons in the orbitofrontal cortex match closely to the predictions of confidence models and cannot be readily explained by alternative mechanisms, such as learning stimulus - outcome associations(7-10). Moreover, when tested using a delayed reward version of the task, we found that rats' willingness to wait for rewards increased with confidence, as predicted by the theoretical model. These results indicate that confidence estimates, previously suggested to require 'metacognition'(11,12) and conscious awareness(13,14), are available even in the rodent brain, can be computed with relatively simple operations, and can drive adaptive behaviour. We suggest that confidence estimation may be a fundamental and ubiquitous component of decision- making.
C1 [Kepecs, Adam; Uchida, Naoshige; Zariwala, Hatim A.; Mainen, Zachary F.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Uchida, Naoshige] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Uchida, Naoshige] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
   [Zariwala, Hatim A.] Allen Inst Brain Sci, Seattle, WA 98103 USA.
   [Mainen, Zachary F.] Gulbenkian Inst Sci, Champalimaud Neurosci Programme, P-2780901 Oeiras, Portugal.
C3 Cold Spring Harbor Laboratory; Harvard University; Harvard University; Allen Institute for Brain Science; Fundacao Champalimaud
RP Kepecs, A (corresponding author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM kepecs@cshl.edu; zmainen@igc.gulbenkian.pt
FU National Institutes of Health (NIDCD); Center for the Neural Mechanisms of Cognition at Cold Spring Harbor Laboratory; Swartz Foundation
NR 43
TC 608
Z9 736
U1 0
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 11
PY 2008
VL 455
IS 7210
BP 227
EP U55
DI 10.1038/nature07200
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800048
PM 18690210
DA 2026-03-09
ER

PT J
AU Fuerst, PG
   Koizumi, A
   Masland, RH
   Burgess, RW
AF Fuerst, Peter G.
   Koizumi, Amane
   Masland, Richard H.
   Burgess, Robert W.
TI Neurite arborization and mosaic spacing in the mouse retina require DSCAM
SO NATURE
LA English
DT Article
ID cell-adhesion molecule; homophilic intercellular-adhesion; axon guidance; drosophila dscam; self-avoidance; diversity; neurons; specificity; binding; system
AB To establish functional circuitry, retinal neurons occupy spatial domains by arborizing their processes, which requires the self-avoidance of neurites from an individual cell, and by spacing their cell bodies, which requires positioning the soma and establishing a zone within which other cells of the same type are excluded(1). The mosaic patterns of distinct cell types form independently and overlap. The cues that direct these processes in the vertebrate retina are not known(2,3). Here we show that some types of retinal amacrine cells from mice with a spontaneous mutation in Down syndrome cell adhesion molecule ( Dscam), a gene encoding an immunoglobulin- superfamily member adhesion molecule(4,5), have defects in the arborization of processes and in the spacing of cell bodies. In the mutant retina, cells that would normally express Dscam have hyperfasciculated processes, preventing them from creating an orderly arbor. Also, their cell bodies are randomly distributed or pulled into clumps rather than being regularly spaced mosaics. Our results indicate that mouse DSCAM mediates isoneuronal self- avoidance for arborization and heteroneuronal self- avoidance within specific cell types to prevent fasciculation and to preserve mosaic spacing. These functions are analogous to those of Drosophila DSCAM ( ref. 6) and DSCAM2 ( ref. 7). DSCAM may function similarly in other regions of the mammalian nervous system, and this role may extend to other members of the mammalian Dscam gene family.
C1 [Fuerst, Peter G.; Burgess, Robert W.] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Koizumi, Amane; Masland, Richard H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
C3 Jackson Laboratory; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Burgess, RW (corresponding author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM robert.burgess@jax.org
FU NEI NIH HHS [R03 EY016031, F32 EY015966] Funding Source: Medline
NR 28
TC 232
Z9 309
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 JAN 24
PY 2008
VL 451
IS 7177
BP 470
EP U8
DI 10.1038/nature06514
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100046
PM 18216855
DA 2026-03-09
ER

PT J
AU Chen, YY
   Takita, J
   Choi, YL
   Kato, M
   Ohira, M
   Sanada, M
   Wang, LL
   Soda, M
   Kikuchi, A
   Igarashi, T
   Nakagawara, A
   Hayashi, Y
   Mano, H
   Ogawa, S
AF Chen, Yuyan
   Takita, Junko
   Choi, Young Lim
   Kato, Motohiro
   Ohira, Miki
   Sanada, Masashi
   Wang, Lili
   Soda, Manabu
   Kikuchi, Akira
   Igarashi, Takashi
   Nakagawara, Akira
   Hayashi, Yasuhide
   Mano, Hiroyuki
   Ogawa, Seishi
TI Oncogenic mutations of ALK kinase in neuroblastoma
SO NATURE
LA English
DT Article
ID anaplastic lymphoma kinase; caspase-8 gene; lung-cancer; protein; fusion; system; arrays; dna
AB Neuroblastoma in advanced stages is one of the most intractable paediatric cancers, even with recent therapeutic advances(1). Neuroblastoma harbours a variety of genetic changes, including a high frequency of MYCN amplification, loss of heterozygosity at 1p36 and 11q, and gain of genetic material from 17q, all of which have been implicated in the pathogenesis of neuroblastoma(2-5). However, the scarcity of reliable molecular targets has hampered the development of effective therapeutic agents targeting neuroblastoma. Here we show that the anaplastic lymphoma kinase (ALK), originally identified as a fusion kinase in a subtype of non- Hodgkin's lymphoma (NPM-ALK)(6-8) and more recently in adenocarcinoma of lung (EML4-ALK)(9,10), is also a frequent target of genetic alteration in advanced neuroblastoma. According to our genome- wide scans of genetic lesions in 215 primary neuroblastoma samples using high- density single- nucleotide polymorphism genotyping microarrays(11-14), the ALK locus, centromeric to the MYCN locus, was identified as a recurrent target of copy number gain and gene amplification. Furthermore, DNA sequencing of ALK revealed eight novel missense mutations in 13 out of 215 (6.1%) fresh tumours and 8 out of 24 ( 33%) neuroblastoma- derived cell lines. All but one mutation in the primary samples ( 12 out of 13) were found in stages 3 - 4 of the disease and were harboured in the kinase domain. The mutated kinases were autophosphorylated and displayed increased kinase activity compared with the wild- type kinase. They were able to transform NIH3T3 fibroblasts as shown by their colony formation ability in soft agar and their capacity to form tumours in nude mice. Furthermore, we demonstrate that downregulation of ALK through RNA interference suppresses proliferation of neuroblastoma cells harbouring mutated ALK. We anticipate that our findings will provide new insights into the pathogenesis of advanced neuroblastoma and that ALK- specific kinase inhibitors might improve its clinical outcome.
C1 [Takita, Junko; Choi, Young Lim; Sanada, Masashi; Wang, Lili; Ogawa, Seishi] Univ Tokyo, Cell Therapy & Transplantat Med, Tokyo 1138655, Japan.
   [Chen, Yuyan; Takita, Junko; Kato, Motohiro; Igarashi, Takashi] Univ Tokyo, Dept Pediat, Tokyo 1138655, Japan.
   [Chen, Yuyan; Takita, Junko; Kato, Motohiro; Sanada, Masashi; Wang, Lili; Ogawa, Seishi] Univ Tokyo, Canc Genom Project, Grad Sch Med, Tokyo 1138655, Japan.
   [Choi, Young Lim; Soda, Manabu; Mano, Hiroyuki] Jichi Med Univ, Div Funct Genom, Toguchi 3290498, Japan.
   [Ohira, Miki; Nakagawara, Akira] Chiba Canc Ctr, Res Inst, Div Biochem, Chiba 2608717, Japan.
   [Sanada, Masashi; Wang, Lili; Mano, Hiroyuki; Ogawa, Seishi] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan.
   [Kikuchi, Akira] Saitama Childrens Med Ctr, Div Hematol Oncol, Saitama 3398551, Japan.
   [Hayashi, Yasuhide] Gunma Childrens Med Ctr, Shibukawa 3778577, Japan.
C3 University of Tokyo; University of Tokyo; University of Tokyo; Jichi Medical University; Chiba Cancer Center; Japan Science & Technology Agency (JST); Saitama Children's Medical Center; Gunma Children's Medical Centre
RP Ogawa, S (corresponding author), Univ Tokyo, Cell Therapy & Transplantat Med, Tokyo 1138655, Japan.
EM hayashiy-tky@umin.ac.jp; sogawa-tky@umin.net
FU Core Research for Evolutional Science and Technology; Japan Science and Technology Agency; Ministry of Health, Labor and Welfare of Japan
NR 26
TC 716
Z9 844
U1 0
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 971
EP U56
DI 10.1038/nature07399
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300051
PM 18923524
DA 2026-03-09
ER

PT J
AU Qin, Y
   Wang, XD
   Wang, ZL
AF Qin, Yong
   Wang, Xudong
   Wang, Zhong Lin
TI Microfibre-nanowire hybrid structure for energy scavenging
SO NATURE
LA English
DT Article
ID piezoelectric nanogenerators; power sources
AB A self- powering nanosystem that harvests its operating energy from the environment is an attractive proposition for sensing, personal electronics and defence technologies(1). This is in principle feasible for nanodevices owing to their extremely low power consumption(2-5). Solar, thermal and mechanical ( wind, friction, body movement) energies are common and may be scavenged from the environment, but the type of energy source to be chosen has to be decided on the basis of specific applications. Military sensing/ surveillance node placement, for example, may involve difficult- to- reach locations, may need to be hidden, and may be in environments that are dusty, rainy, dark and/ or in deep forest. In a moving vehicle or aeroplane, harvesting energy from a rotating tyre or wind blowing on the body is a possible choice to power wireless devices implanted in the surface of the vehicle. Nanowire nanogenerators built on hard substrates were demonstrated for harvesting local mechanical energy produced by high- frequency ultrasonic waves(6,7). To harvest the energy from vibration or disturbance originating from footsteps, heartbeats, ambient noise and air flow, it is important to explore innovative technologies that work at low frequencies ( such as < 10 Hz) and that are based on flexible soft materials. Here we present a simple, low- cost approach that converts low- frequency vibration/ friction energy into electricity using piezoelectric zinc oxide nanowires grown radially around textile fibres. By entangling two fibres and brushing the nanowires rooted on them with respect to each other, mechanical energy is converted into electricity owing to a coupled piezoelectric - semiconductor process(8,9). This work establishes a methodology for scavenging light- wind energy and body- movement energy using fabrics.
C1 [Qin, Yong; Wang, Xudong; Wang, Zhong Lin] Georgia Inst Technol, Sch Mat Sci & Engn, Atlanta, GA 30332 USA.
C3 University System of Georgia; Georgia Institute of Technology
RP Wang, ZL (corresponding author), Georgia Inst Technol, Sch Mat Sci & Engn, Atlanta, GA 30332 USA.
EM zlwang@gatech.edu
NR 14
TC 1456
Z9 1619
U1 16
U2 1247
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 809
EP U5
DI 10.1038/nature06601
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400038
PM 18273015
DA 2026-03-09
ER

PT J
AU Arnold, PL
   Patel, D
   Wilson, C
   Love, JB
AF Arnold, Polly L.
   Patel, Dipti
   Wilson, Claire
   Love, Jason B.
TI Reduction and selective oxo group silylation of the uranyl dication
SO NATURE
LA English
DT Article
ID pentavalent-uranyl; oxygenation reactions; active-sites; complexes; uranium; coordination; reactivity; chemistry; ligands; base
AB Uranium occurs in the environment predominantly as the uranyl dication [UO2](2+). Its solubility renders this species a problematic contaminant(1-3) which is, moreover, chemically extraordinarily robust owing to strongly covalent U-O bonds(4). This feature manifests itself in the uranyl dication showing little propensity to partake in the many oxo group functionalizations and redox reactions typically seen with [CrO2](2+), [MoO2](2+) and other transition metal analogues(5-9). As a result, only a few examples of [UO2](2+) with functionalized oxo groups are known. Similarly, it is only very recently that the isolation and characterization of the singly reduced, pentavalent uranyl cation [UO2](+) has been reported(10-12). Here we show that placing the uranyl dication within a rigid and well-defined molecular framework while keeping the environment anaerobic allows simultaneous single- electron reduction and selective covalent bond formation at one of the two uranyl oxo groups. The product of this reaction is a pentavalent and monofunctionalized [O = U = OR](+) cation that can be isolated in the presence of transition metal cations. This finding demonstrates that under appropriate reaction conditions, the uranyl oxo group will readily undergo radical reactions commonly associated only with transition metal oxo groups. We expect that this work might also prove useful in probing the chemistry of the related but highly radioactive plutonyl and neptunyl analogues found in nuclear waste.
C1 [Arnold, Polly L.; Patel, Dipti; Love, Jason B.] Univ Edinburgh, Sch Chem, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Wilson, Claire] Rigaku Europe, Sevenoaks TN15 6QY, Kent, England.
C3 University of Edinburgh; Rigaku Corporation
RP Arnold, PL (corresponding author), Univ Edinburgh, Sch Chem, W Mains Rd, Edinburgh EH9 3JJ, Midlothian, Scotland.
EM Polly.Arnold@ed.ac.uk; Jason.Love@ed.ac.uk
FU EPSRC [EP/D050782/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/D050782/1] Funding Source: researchfish
NR 30
TC 262
Z9 298
U1 1
U2 123
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 315
EP U3
DI 10.1038/nature06467
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100045
PM 18202653
DA 2026-03-09
ER

PT J
AU Kang, RJ
   Wan, JM
   Arstikaitis, P
   Takahashi, H
   Huang, K
   Bailey, AO
   Thompson, JX
   Roth, AF
   Drisdel, RC
   Mastro, R
   Green, WN
   Yates, JR
   Davis, NG
   El-Husseini, A
AF Kang, Rujun
   Wan, Junmei
   Arstikaitis, Pamela
   Takahashi, Hideto
   Huang, Kun
   Bailey, Aaron O.
   Thompson, James X.
   Roth, Amy F.
   Drisdel, Renaldo C.
   Mastro, Ryan
   Green, William N.
   Yates, John R., III
   Davis, Nicholas G.
   El-Husseini, Alaa
TI Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation
SO NATURE
LA English
DT Article
ID dendritic spine development; rho-family gtpases; protein palmitoylation; neuronal excitability; morphogenesis; cdc42; synapses; trafficking; plasticity; stability
AB Palmitoylation regulates diverse aspects of neuronal protein trafficking and function. Here a global characterization of rat neural palmitoyl- proteomes identifies most of the known neural palmitoyl proteins - 68 in total, plus more than 200 new palmitoyl- protein candidates, with further testing confirming palmitoylation for 21 of these candidates. The new palmitoyl proteins include neurotransmitter receptors, transporters, adhesion molecules, scaffolding proteins, as well as SNAREs and other vesicular trafficking proteins. Of particular interest is the finding of palmitoylation for a brain- specific Cdc42 splice variant. The palmitoylated Cdc42 isoform ( Cdc42- palm) differs from the canonical, prenylated form ( Cdc42- prenyl), both with regard to localization and function: Cdc42- palm concentrates in dendritic spines and has a special role in inducing these post- synaptic structures. Furthermore, assessing palmitoylation dynamics in drug- induced activity models identifies rapidly induced changes for Cdc42 as well as for other synaptic palmitoyl proteins, suggesting that palmitoylation may participate broadly in the activity- driven changes that shape synapse morphology and function.
C1 [Wan, Junmei; Roth, Amy F.; Davis, Nicholas G.] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA.
   [Kang, Rujun; Arstikaitis, Pamela; Takahashi, Hideto; Huang, Kun; El-Husseini, Alaa] Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC V6T 1Z3, Canada.
   [Bailey, Aaron O.; Thompson, James X.; Yates, John R., III] Scripps Res Inst, Dept Cell Biol, La Jolla, CA USA.
   [Drisdel, Renaldo C.; Mastro, Ryan; Green, William N.] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA.
C3 Wayne State University; University of British Columbia; Scripps Research Institute; University of Chicago
RP Davis, NG (corresponding author), Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA.
EM rkang@interchange.ubc.ca; ndavis@med.wayne.edu
FU Canadian Institutes for Health Research [A.E.H-20R90479, A.E.H-20R91909]; Michael Smith foundation for Health Research [A.E.-H., 20R52464]; EJLB Foundation and Neuroscience Canada [A.E.-H., 20R61933]; National Institutes of Health [GM65525, RR011823, NS043782, DA13602, DA019695]; Peter F. McManus Trust; Uehara Memorial Foundation
NR 32
TC 465
Z9 543
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 DEC 18
PY 2008
VL 456
IS 7224
BP 904
EP 909
DI 10.1038/nature07605
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300035
PM 19092927
DA 2026-03-09
ER

PT J
AU Wendt, KS
   Yoshida, K
   Itoh, T
   Bando, M
   Koch, B
   Schirghuber, E
   Tsutsumi, S
   Nagae, G
   Ishihara, K
   Mishiro, T
   Yahata, K
   Imamoto, F
   Aburatani, H
   Nakao, M
   Imamoto, N
   Maeshima, K
   Shirahige, K
   Peters, JM
AF Wendt, Kerstin S.
   Yoshida, Keisuke
   Itoh, Takehiko
   Bando, Masashige
   Koch, Birgit
   Schirghuber, Erika
   Tsutsumi, Shuichi
   Nagae, Genta
   Ishihara, Ko
   Mishiro, Tsuyoshi
   Yahata, Kazuhide
   Imamoto, Fumio
   Aburatani, Hiroyuki
   Nakao, Mitsuyoshi
   Imamoto, Naoko
   Maeshima, Kazuhiro
   Shirahige, Katsuhiko
   Peters, Jan-Michael
TI Cohesin mediates transcriptional insulation by CCCTC-binding factor
SO NATURE
LA English
DT Article
ID sister-chromatid cohesion; de-lange-syndrome; enhancer-blocking activity; human genome; nipped-b; ctcf-binding; saccharomyces-cerevisiae; drosophila-melanogaster; roberts-syndrome; gene-expression
AB Cohesin complexes mediate sister- chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin- binding sites in the human genome and show that most of these are associated with the CCCTC- binding factor ( CTCF), a zinc- finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 ( insulin- like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.
C1 [Yoshida, Keisuke; Bando, Masashige; Shirahige, Katsuhiko] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Midori Ku, Kanagawa 2268501, Japan.
   [Wendt, Kerstin S.; Koch, Birgit; Schirghuber, Erika; Peters, Jan-Michael] Res Inst Mol Pathol, A-1030 Vienna, Austria.
   [Itoh, Takehiko] Mitsubishi Res Inst Inc, Adv Sci & Technol Res Ctr, Chiyoda Ku, Tokyo 1008141, Japan.
   [Tsutsumi, Shuichi; Aburatani, Hiroyuki] Univ Tokyo, Genome Sci Div, Adv Sci & Technol Res Ctr, Tokyo 1538904, Japan.
   [Yahata, Kazuhide; Imamoto, Fumio] Osaka Univ, Dept Mol Biol, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan.
   [Ishihara, Ko; Mishiro, Tsuyoshi; Nakao, Mitsuyoshi] Kumamoto Univ, Dept Regenerat Med, Inst Mol Embryol & Genet, Kumamoto 8600811, Japan.
   [Imamoto, Naoko; Maeshima, Kazuhiro] RIKEN, Cellular Dynam Lab, Wako, Saitama 3510198, Japan.
C3 Institute of Science Tokyo; Tokyo Institute of Technology; Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); Mitsubishi International Corporation (MIC); Mitsubishi Research Institute; University of Tokyo; University of Osaka; Kumamoto University; RIKEN
RP Shirahige, K (corresponding author), Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Midori Ku, B2C4259, Kanagawa 2268501, Japan.
EM kshirahi@bio.titech.ac.jp; peters@imp.univie.ac.at
FU Austrian Science Fund FWF [F 3407] Funding Source: Medline
NR 55
TC 937
Z9 1159
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 FEB 14
PY 2008
VL 451
IS 7180
BP 796
EP U3
DI 10.1038/nature06634
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400035
PM 18235444
DA 2026-03-09
ER

PT J
AU Husnjak, K
   Elsasser, S
   Zhang, NX
   Chen, X
   Randles, L
   Shi, Y
   Hofmann, K
   Walters, KJ
   Finley, D
   Dikic, I
AF Husnjak, Koraljka
   Elsasser, Suzanne
   Zhang, Naixia
   Chen, Xiang
   Randles, Leah
   Shi, Yuan
   Hofmann, Kay
   Walters, Kylie J.
   Finley, Daniel
   Dikic, Ivan
TI Proteasome subunit Rpn13 is a novel ubiquitin receptor
SO NATURE
LA English
DT Article
ID deubiquitinating enzyme; 26s proteasome; polyubiquitin chains; protein interactome; uba domains; degradation; proteolysis; rad23; binds; uch37
AB Proteasomal receptors that recognize ubiquitin chains attached to substrates are key mediators of selective protein degradation in eukaryotes. Here we report the identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome. Rpn13 binds ubiquitin through a conserved amino-terminal region termed the pleckstrin-like receptor for ubiquitin (Pru) domain, which binds K48-linked diubiquitin with an affinity of approximately 90 nM. Like proteasomal ubiquitin receptor Rpn10/S5a, Rpn13 also binds ubiquitin-like (UBL) domains of UBL- ubiquitin- associated (UBA) proteins. In yeast, a synthetic phenotype results when specific mutations of the ubiquitin binding sites of Rpn10 and Rpn13 are combined, indicating functional linkage between these ubiquitin receptors. Because Rpn13 is also the proteasomal receptor for Uch37, a deubiquitinating enzyme, our findings suggest a coupling of chain recognition and disassembly at the proteasome.
C1 [Husnjak, Koraljka; Dikic, Ivan] Univ Frankfurt, Inst Biochem 2, D-60590 Frankfurt, Germany.
   [Husnjak, Koraljka; Dikic, Ivan] Mediterranean Inst Life Sci, Tumor Biol Program, Split 21000, Croatia.
   [Elsasser, Suzanne; Shi, Yuan; Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Zhang, Naixia; Chen, Xiang; Randles, Leah; Walters, Kylie J.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
   [Hofmann, Kay] Miltenyi Biotec GmbH, D-50829 Cologne, Germany.
   [Dikic, Ivan] Univ Split, Sch Med, Dept Immunol, Split 21000, Croatia.
C3 Goethe University Frankfurt; University of Split; Harvard University; Harvard Medical School; University of Minnesota System; University of Minnesota Twin Cities; Miltenyi Biotec; University of Split
RP Dikic, I (corresponding author), Univ Frankfurt, Inst Biochem 2, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
EM walte048@umn.edu; daniel_finley@hms.harvard.edu; Ivan.Dikic@biochem2.de
FU NCI NIH HHS [CA097004, R01 CA097004] Funding Source: Medline; NIGMS NIH HHS [R37 GM043601, GM043601, GM008700, T32 GM008700, R01 GM043601] Funding Source: Medline
NR 36
TC 538
Z9 704
U1 2
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 481
EP 488
DI 10.1038/nature06926
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700034
PM 18497817
DA 2026-03-09
ER

PT J
AU Joh, NH
   Min, A
   Faham, S
   Whitelegge, JP
   Yang, D
   Woods, VL
   Bowie, JU
AF Joh, Nathan HyunJoong
   Min, Andrew
   Faham, Salem
   Whitelegge, Julian P.
   Yang, Duan
   Woods, Virgil L., Jr.
   Bowie, James U.
TI Modest stabilization by most hydrogen-bonded side-chain interactions in membrane proteins
SO NATURE
LA English
DT Article
ID exchange mass-spectrometry; transmembrane helices; crystal-structure; polar residues; stability; mutations; nmr; bacteriorhodopsin; association; resolution
AB Understanding the energetics of molecular interactions is fundamental to all of the central quests of structural biology including structure prediction and design, mapping evolutionary pathways, learning how mutations cause disease, drug design, and relating structure to function. Hydrogen- bonding is widely regarded as an important force in a membrane environment because of the low dielectric constant of membranes and a lack of competition from water(1-6). Indeed, polar residue substitutions are the most common disease- causing mutations in membrane proteins(6,7). Because of limited structural information and technical challenges, however, there have been few quantitative tests of hydrogen- bond strength in the context of large membrane proteins. Here we show, by using a double- mutant cycle analysis, that the average contribution of eight interhelical side- chain hydrogen- bonding interactions throughout bacteriorhodopsin is only 0.6 kcal mol(-1). In agreement with these experiments, we find that 4% of polar atoms in the non- polar core regions of membrane proteins have no hydrogen- bond partner and the lengths of buried hydrogen bonds in soluble proteins and membrane protein transmembrane regions are statistically identical. Our results indicate that most hydrogen- bond interactions in membrane proteins are only modestly stabilizing. Weak hydrogen-bonding should be reflected in considerations of membrane protein folding, dynamics, design, evolution and function.
C1 [Joh, Nathan HyunJoong; Min, Andrew; Yang, Duan; Bowie, James U.] Univ Calif Los Angeles, Inst Mol Biol, Dept Chem & Biochem, UCLA DOE Ctr Genom & Proteom, Los Angeles, CA 90095 USA.
   [Faham, Salem] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA.
   [Whitelegge, Julian P.] Univ Calif Los Angeles, NPI Semel Inst, Pasarow Mass Spec Lab, Los Angeles, CA 90095 USA.
   [Woods, Virgil L., Jr.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Woods, Virgil L., Jr.] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
C3 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 System; University of California Los Angeles; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Bowie, JU (corresponding author), Univ Calif Los Angeles, Inst Mol Biol, Dept Chem & Biochem, UCLA DOE Ctr Genom & Proteom, Los Angeles, CA 90095 USA.
EM bowie@mbi.ucla.edu
FU NCI NIH HHS [R01 CA081000] Funding Source: Medline; NIGMS NIH HHS [R01 GM063919] Funding Source: Medline; National Institute of General Medical Sciences [R01GM063919] Funding Source: NIH RePORTER
NR 40
TC 224
Z9 266
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 JUN 26
PY 2008
VL 453
IS 7199
BP 1266
EP U73
DI 10.1038/nature06977
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800049
PM 18500332
DA 2026-03-09
ER

PT J
AU Kobayashi, YM
   Rader, EP
   Crawford, RW
   Iyengar, NK
   Thedens, DR
   Faulkner, JA
   Parikh, SV
   Weiss, RM
   Chamberlain, JS
   Moore, SA
   Campbell, KP
AF Kobayashi, Yvonne M.
   Rader, Erik P.
   Crawford, Robert W.
   Iyengar, Nikhil K.
   Thedens, Daniel R.
   Faulkner, John A.
   Parikh, Swapnesh V.
   Weiss, Robert M.
   Chamberlain, Jeffrey S.
   Moore, Steven A.
   Campbell, Kevin P.
TI Sarcolemma-localized nNOS is required to maintain activity after mild exercise
SO NATURE
LA English
DT Article
ID nitric-oxide synthase; duchenne muscular-dystrophy; skeletal-muscle; alpha-sarcoglycan; neuromuscular disorders; mice; deficient; fatigue; therapy; complex
AB Many neuromuscular conditions are characterized by an exaggerated exercise- induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients(1), and some patients experience severe fatigue without any demonstrable somatic disease(2). Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown(2). With no treatment available, this form of inactivity is a major determinant of disability(3). Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase ( nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS- null mice do not have muscle pathology and have no loss of muscle- specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction- induced signalling from sarcolemma- localized nNOS, which decreases cGMP- mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise- induced signalling.
C1 [Kobayashi, Yvonne M.; Rader, Erik P.; Crawford, Robert W.; Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA.
   [Kobayashi, Yvonne M.; Rader, Erik P.; Crawford, Robert W.; Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA.
   [Kobayashi, Yvonne M.; Rader, Erik P.; Crawford, Robert W.; Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Neurol, Iowa City, IA 52242 USA.
   [Kobayashi, Yvonne M.; Rader, Erik P.; Crawford, Robert W.; Iyengar, Nikhil K.; Parikh, Swapnesh V.; Weiss, Robert M.; Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
   [Thedens, Daniel R.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Radiol, Iowa City, IA 52242 USA.
   [Moore, Steven A.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA.
   [Faulkner, John A.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
   [Chamberlain, Jeffrey S.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA.
C3 University of Iowa; Howard Hughes Medical Institute; University of Iowa; University of Iowa; University of Iowa; University of Iowa; University of Iowa; University of Michigan System; University of Michigan; University of Washington; University of Washington Seattle
RP Campbell, KP (corresponding author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Howard Hughes Med Inst, 4283 Carver Biomed Res Bldg,285 Newton Rd, Iowa City, IA 52242 USA.
EM kevin-campbell@uiowa.edu
FU Paul D. Wellstone Muscular Dystrophy Cooperative Research Center Grant; University of Iowa Cardiovascular Interdisciplinary Research; National Research Service Award; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health; Senator Paul D. Wellstone Fellowship; Muscular Dystrophy Association Development Grant; Howard Hughes Medical Institute
NR 25
TC 233
Z9 284
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 511
EP 515
DI 10.1038/nature07414
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500040
PM 18953332
DA 2026-03-09
ER

PT J
AU Soengas, MS
AF Soengas, Maria S.
TI Cancer - Ins and outs of tumour control
SO NATURE
LA English
DT Article
ID cellular senescence; cells
C1 Spanish Natl Canc Res Ctr, Melanoma Grp, Mol Pathol Programme, Madrid 28029, Spain.
C3 Centro Nacional de Investigaciones Oncologicas (CNIO)
RP Soengas, MS (corresponding author), Spanish Natl Canc Res Ctr, Melanoma Grp, Mol Pathol Programme, Madrid 28029, Spain.
EM msoengas@cnio.es
NR 11
TC 3
Z9 5
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 586
EP 587
DI 10.1038/454586a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500029
PM 18668094
DA 2026-03-09
ER

PT J
AU Sohn, RA
   Willis, C
   Humphris, S
   Shank, TM
   Singh, H
   Edmonds, HN
   Kunz, C
   Hedman, U
   Helmke, E
   Jakuba, M
   Liljebladh, B
   Linder, J
   Murphy, C
   Nakamura, KI
   Sato, T
   Schlindwein, V
   Stranne, C
   Tausenfreund, M
   Upchurch, L
   Winsor, P
   Jakobsson, M
   Soule, A
AF Sohn, Robert A.
   Willis, Claire
   Humphris, Susan
   Shank, Timothy M.
   Singh, Hanumant
   Edmonds, Henrietta N.
   Kunz, Clayton
   Hedman, Ulf
   Helmke, Elisabeth
   Jakuba, Michael
   Liljebladh, Bengt
   Linder, Julia
   Murphy, Christopher
   Nakamura, Ko-ichi
   Sato, Taichi
   Schlindwein, Vera
   Stranne, Christian
   Tausenfreund, Maria
   Upchurch, Lucia
   Winsor, Peter
   Jakobsson, Martin
   Soule, Adam
TI Explosive volcanism on the ultraslow-spreading Gakkel ridge, Arctic Ocean
SO NATURE
LA English
DT Article
ID mid-atlantic ridge
AB Roughly 60% of the Earth's outer surface is composed of oceanic crust formed by volcanic processes at mid- ocean ridges. Although only a small fraction of this vast volcanic terrain has been visually surveyed or sampled, the available evidence suggests that explosive eruptions are rare on mid- ocean ridges, particularly at depths below the critical point for seawater ( 3,000 m)(1). A pyroclastic deposit has never been observed on the sea floor below 3,000 m, presumably because the volatile content of mid- ocean- ridge basalts is generally too low to produce the gas fractions required for fragmenting a magma at such high hydrostatic pressure. We employed new deep submergence technologies during an International Polar Year expedition to the Gakkel ridge in the Arctic Basin at 856 E, to acquire photographic and video images of 'zero- age' volcanic terrain on this remote, ice- covered ridge. Here we present images revealing that the axial valley at 4,000 m water depth is blanketed with unconsolidated pyroclastic deposits, including bubble wall fragments (limu o Pele)(2), covering a large ( > 10 km(2)) area. At least 13.5 wt% CO2 is necessary to fragment magma at these depths(3), which is about tenfold the highest values previously measured in a mid- ocean- ridge basalt(4). These observations raise important questions about the accumulation and discharge of magmatic volatiles at ultraslow spreading rates on the Gakkel ridge(5) and demonstrate that large- scale pyroclastic activity is possible along even the deepest portions of the global mid- ocean ridge volcanic system.
C1 [Sohn, Robert A.; Willis, Claire; Humphris, Susan; Shank, Timothy M.; Singh, Hanumant; Kunz, Clayton; Murphy, Christopher; Winsor, Peter; Soule, Adam] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
   [Edmonds, Henrietta N.; Upchurch, Lucia] Univ Texas Austin, Inst Marine Sci, Port Aransas, TX 78373 USA.
   [Hedman, Ulf] Swedish Polar Secretariat, S-10405 Stockholm, Sweden.
   [Helmke, Elisabeth; Linder, Julia; Schlindwein, Vera; Tausenfreund, Maria] Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany.
   [Jakuba, Michael] Johns Hopkins Univ, Baltimore, MD 21218 USA.
   [Liljebladh, Bengt; Stranne, Christian] Univ Gothenburg, S-40530 Gothenburg, Sweden.
   [Nakamura, Ko-ichi] AIST, Higashi, Tokyo, Japan.
   [Sato, Taichi] Univ Tokyo, Ocean Res Inst, Tokyo 1648639, Japan.
   [Jakobsson, Martin] Stockholm Univ, Dept Geol & Geochem, S-10691 Stockholm, Sweden.
C3 Woods Hole Oceanographic Institution; University of Texas System; University of Texas Austin; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; Johns Hopkins University; University of Gothenburg; National Institute of Advanced Industrial Science & Technology (AIST); University of Tokyo; Stockholm University
RP Sohn, RA (corresponding author), Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
EM rsohn@whoi.edu
NR 23
TC 118
Z9 133
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 JUN 26
PY 2008
VL 453
IS 7199
BP 1236
EP 1238
DI 10.1038/nature07075
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800042
PM 18580949
DA 2026-03-09
ER

PT J
AU Palopoli, MF
   Rockman, MV
   TinMaung, A
   Ramsay, C
   Curwen, S
   Aduna, A
   Laurita, J
   Kruglyak, L
AF Palopoli, Michael F.
   Rockman, Matthew V.
   TinMaung, Aye
   Ramsay, Camden
   Curwen, Stephen
   Aduna, Andrea
   Laurita, Jason
   Kruglyak, Leonid
TI Molecular basis of the copulatory plug polymorphism in Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID c-elegans; natural-populations; temporal dynamics; mating-behavior; evolution; mucins; rnai; prediction; phylogeny
AB Heritable variation is the raw material for evolutionary change, and understanding its genetic basis is one of the central problems in modern biology. We investigated the genetic basis of a classic phenotypic dimorphism in the nematode Caenorhabditis elegans. Males from many natural isolates deposit a copulatory plug after mating, whereas males from other natural isolates - including the standard wild- type strain ( N2 Bristol) that is used in most research laboratories - do not deposit plugs(1). The copulatory plug is a gelatinous mass that covers the hermaphrodite vulva, and its deposition decreases the mating success of subsequent males(2). We show that the plugging polymorphism results from the insertion of a retrotransposon into an exon of a novel mucin- like gene, plg-1, whose product is a major structural component of the copulatory plug. The gene is expressed in a subset of secretory cells of the male somatic gonad, and its loss has no evident effects beyond the loss of male mate- guarding. Although C. elegans descends from an obligate- outcrossing, male - female ancestor(3,4), it occurs primarily as self- fertilizing hermaphrodites(5-7). The reduced selection on male - male competition associated with the origin of hermaphroditism may have permitted the global spread of a loss-of-function mutation with restricted pleiotropy.
C1 [Palopoli, Michael F.; TinMaung, Aye; Ramsay, Camden; Curwen, Stephen; Aduna, Andrea; Laurita, Jason] Bowdoin Coll, Dept Biol, Brunswick, ME 04011 USA.
   [Rockman, Matthew V.; Kruglyak, Leonid] Princeton Univ, Carl Icahn Lab, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Rockman, Matthew V.; Kruglyak, Leonid] Princeton Univ, Carl Icahn Lab, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
C3 Bowdoin College; Princeton University; Princeton University
RP Palopoli, MF (corresponding author), Bowdoin Coll, Dept Biol, 6500 Coll Stn, Brunswick, ME 04011 USA.
EM mpalopol@bowdoin.edu
FU NIH [P20 RR-016463, R01 HG004321, P50 GM071508]; INBRE Program of the National Center for Research Resources; NSF [0110994]; Howard Hughes Medical Institute under the Undergraduate Science Education Program; James S. McDonnell Foundation Centennial Fellowship; Jane Coffin Childs Fellowship; Division Of Environmental Biology; Direct For Biological Sciences [0110994] Funding Source: National Science Foundation
NR 32
TC 106
Z9 146
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 AUG 21
PY 2008
VL 454
IS 7207
BP 1019
EP U66
DI 10.1038/nature07171
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000044
PM 18633349
DA 2026-03-09
ER

PT J
AU Giustino, F
   Cohen, ML
   Louie, SG
AF Giustino, Feliciano
   Cohen, Marvin L.
   Louie, Steven G.
TI Small phonon contribution to the photoemission kink in the copper oxide superconductors
SO NATURE
LA English
DT Article
ID high-temperature superconductors; cuprate superconductors; energy; dispersion; state
AB Despite over two decades of intense research efforts, the origin of high- temperature superconductivity in the copper oxides remains elusive. Angle- resolved photoemission spectroscopy experiments(1,2) have revealed a kink in the dispersion relations ( energy versus wavevector) of electronic states in the copper oxides at binding energies of 50-80 meV, raising the hope that this anomaly could be a key to understanding high- temperature superconductivity. The kink is often interpreted in terms of interactions between the electrons and a bosonic field. Although there is no consensus on the nature of the bosons ( or even whether a boson model is appropriate), both phonons(1) and spin fluctuations(2) have been proposed as possible candidates. Here we report first- principles calculations of the role of phonons and the electron - phonon interaction in the photoemission spectra of La2-xSrxCuO4. Our calculations within the standard formalism demonstrate that the phonon- induced renormalization of the electron energies and the Fermi velocity is almost one order of magnitude smaller than the effect observed in photoemission experiments. Therefore, our result rules out electron - phonon interaction in bulk La2-xSrxCuO4 as the exclusive origin of the measured kink. Our conclusions are consistent with those reached independently in a recent study(3) of the related compound YBa2Cu3O7.
C1 [Giustino, Feliciano; Cohen, Marvin L.; Louie, Steven G.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Giustino, Feliciano; Cohen, Marvin L.; Louie, Steven G.] 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; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Louie, SG (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
EM sglouie@berkeley.edu
NR 29
TC 163
Z9 175
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 24
PY 2008
VL 452
IS 7190
BP 975
EP 978
DI 10.1038/nature06874
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600035
PM 18432241
DA 2026-03-09
ER

PT J
AU Bredemeyer, AL
   Helmink, BA
   Innes, CL
   Calderon, B
   McGinnis, LM
   Mahowald, GK
   Gapud, EJ
   Walker, LM
   Collins, JB
   Weaver, BK
   Mandik-Nayak, L
   Schreiber, RD
   Allen, PM
   May, MJ
   Paules, RS
   Bassing, CH
   Sleckman, BP
AF Bredemeyer, Andrea L.
   Helmink, Beth A.
   Innes, Cynthia L.
   Calderon, Boris
   McGinnis, Lisa M.
   Mahowald, Grace K.
   Gapud, Eric J.
   Walker, Laura M.
   Collins, Jennifer B.
   Weaver, Brian K.
   Mandik-Nayak, Laura
   Schreiber, Robert D.
   Allen, Paul M.
   May, Michael J.
   Paules, Richard S.
   Bassing, Craig H.
   Sleckman, Barry P.
TI DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes
SO NATURE
LA English
DT Article
ID nf-kappa-b; leaky scid phenotype; v(d)j recombination; lymphoid organs; ionizing-radiation; bone-marrow; atm; expression; damage; differentiation
AB DNA double- strand breaks are generated by genotoxic agents and by cellular endonucleases as intermediates of several important physiological processes. The cellular response to genotoxic DNA breaks includes the activation of transcriptional programs known primarily to regulate cell- cycle checkpoints and cell survival(1-5). DNA double- strand breaks are generated in all developing lymphocytes during the assembly of antigen receptor genes, a process that is essential for normal lymphocyte development. Here we show that in murine lymphocytes these physiological DNA breaks activate a broad transcriptional program. This program transcends the canonical DNA double- strand break response and includes many genes that regulate diverse cellular processes important for lymphocyte development. Moreover, the expression of several of these genes is regulated similarly in response to genotoxic DNA damage. Thus, physiological DNA double- strand breaks provide cues that can regulate cell- type- specific processes not directly involved in maintaining the integrity of the genome, and genotoxic DNA breaks could disrupt normal cellular functions by corrupting these processes.
C1 [Bredemeyer, Andrea L.; Helmink, Beth A.; Calderon, Boris; McGinnis, Lisa M.; Mahowald, Grace K.; Gapud, Eric J.; Walker, Laura M.; Weaver, Brian K.; Mandik-Nayak, Laura; Schreiber, Robert D.; Allen, Paul M.; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Innes, Cynthia L.; Collins, Jennifer B.; Paules, Richard S.] NIEHS, Environm Stress & Canc Grp, Res Triangle Pk, NC 27709 USA.
   [Innes, Cynthia L.; Collins, Jennifer B.; Paules, Richard S.] NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA.
   [May, Michael J.] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
   [Bassing, Craig H.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Ctr Childhood Canc Res,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Bassing, Craig H.] Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
C3 Washington University (WUSTL); National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania
RP Sleckman, BP (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
EM Sleckman@immunology.wustl.edu
FU National Institutes of Health [AI47829]; Washington University Department of Pathology and Immunology; Department of Pathology and Center for Childhood Cancer Research of the Children's Hospital of Philadelphia; Abramson Family Cancer Research Institute; National Institute of Environmental Health Sciences; Research Scholar Award from the American Cancer Society; National Institute of Allergy and Infectious Diseases [R01AI047829] Funding Source: NIH RePORTER
NR 38
TC 122
Z9 164
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 DEC 11
PY 2008
VL 456
IS 7223
BP 819
EP U113
DI 10.1038/nature07392
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900055
PM 18849970
DA 2026-03-09
ER

PT J
AU Muruve, DA
   Pétrilli, V
   Zaiss, AK
   White, LR
   Clark, SA
   Ross, PJ
   Parks, RJ
   Tschopp, J
AF Muruve, Daniel A.
   Petrilli, Virginie
   Zaiss, Anne K.
   White, Lindsay R.
   Clark, Sharon A.
   Ross, P. Joel
   Parks, Robin J.
   Tschopp, Jurg
TI The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response
SO NATURE
LA English
DT Article
ID adenovirus vectors; caspase-1 activation; nalp3 inflammasome; gene-therapy; in-vivo; infection; expression; receptor; disease; asc
AB The innate immune system recognizes nucleic acids during infection and tissue damage. Whereas viral RNA is detected by endosomal toll- like receptors ( TLR3, TLR7, TLR8) and cytoplasmic RIG-I and MDA5, endosomal TLR9 and cytoplasmic DAI bind DNA(1), resulting in the activation of nuclear factor-kappa B and interferon regulatory factor transcription factors. However, viruses also trigger pro- inflammatory responses(2), which remain poorly defined. Here we show that internalized adenoviral DNA induces maturation of pro- interleukin-1 beta in macrophages, which is dependent on NALP3 and ASC, components of the innate cytosolic molecular complex termed the inflammasome. Correspondingly, NALP3- and ASC- deficient mice display reduced innate inflammatory responses to adenovirus particles. Inflammasome activation also occurs as a result of transfected cytosolic bacterial, viral and mammalian ( host) DNA, but in this case sensing is dependent on ASC but not NALP3. The DNA- sensing pro- inflammatory pathway functions independently of TLRs and interferon regulatory factors. Thus, in addition to viral and bacterial components or danger signals in general, inflammasomes sense potentially dangerous cytoplasmic DNA, strengthening their central role in innate immunity.
C1 [Petrilli, Virginie; Tschopp, Jurg] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
   [Muruve, Daniel A.; White, Lindsay R.; Clark, Sharon A.] Univ Calgary, Dept Med, Calgary, AB T2N 4N1, Canada.
   [Zaiss, Anne K.] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada.
   [Ross, P. Joel; Parks, Robin J.] Ottawa Hlth Res Inst, Program Mol Med, Ottawa, ON K1Y 4E9, Canada.
C3 University of Lausanne; University of Calgary; University of Calgary; University of Ottawa; Ottawa Hospital Research Institute
RP Tschopp, J (corresponding author), Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
EM Jurg.Tschopp@unil.ch
NR 30
TC 787
Z9 949
U1 0
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 6
PY 2008
VL 452
IS 7183
BP 103
EP U11
DI 10.1038/nature06664
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900055
PM 18288107
DA 2026-03-09
ER

PT J
AU Zhou, ZF
   Zhu, GS
   Hariri, AR
   Enoch, MA
   Scott, D
   Sinha, R
   Virkkunen, M
   Mash, DC
   Lipsky, RH
   Hu, XZ
   Hodgkinson, CA
   Xu, K
   Buzas, B
   Yuan, QP
   Shen, PH
   Ferrell, RE
   Manuck, SB
   Brown, SM
   Hauger, RL
   Stohler, CS
   Zubieta, JK
   Goldman, D
AF Zhou, Zhifeng
   Zhu, Guanshan
   Hariri, Ahmad R.
   Enoch, Mary-Anne
   Scott, David
   Sinha, Rajita
   Virkkunen, Matti
   Mash, Deborah C.
   Lipsky, Robert H.
   Hu, Xian-Zhang
   Hodgkinson, Colin A.
   Xu, Ke
   Buzas, Beata
   Yuan, Qiaoping
   Shen, Pei-Hong
   Ferrell, Robert E.
   Manuck, Stephen B.
   Brown, Sarah M.
   Hauger, Richard L.
   Stohler, Christian S.
   Zubieta, Jon-Kar
   Goldman, David
TI Genetic variation in human NPY expression affects stress response and emotion
SO NATURE
LA English
DT Article
ID neuropeptide-y distribution; human amygdala; serotonin transporter; polymorphism; brain; genotype; disease; anxiety; pain; association
AB Understanding inter- individual differences in stress response requires the explanation of genetic influences at multiple phenotypic levels, including complex behaviours and the metabolic responses of brain regions to emotional stimuli. Neuropeptide Y ( NPY) is anxiolytic(1,2) and its release is induced by stress(3). NPY is abundantly expressed in regions of the limbic system that are implicated in arousal and in the assignment of emotional valences to stimuli and memories(4-6). Here we show that haplotype- driven NPY expression predicts brain responses to emotional and stress challenges and also inversely correlates with trait anxiety. NPY haplotypes predicted levels of NPY messenger RNA in postmortem brain and lymphoblasts, and levels of plasma NPY. Lower haplotype- driven NPY expression predicted higher emotion- induced activation of the amygdala, as well as diminished resiliency as assessed by pain/ stress- induced activations of endogenous opioid neurotransmission in various brain regions. A single nucleotide polymorphism ( SNP rs16147) located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter- individual variation in resiliency to stress, a risk factor for many diseases.
C1 [Zhou, Zhifeng; Zhu, Guanshan; Enoch, Mary-Anne; Lipsky, Robert H.; Hu, Xian-Zhang; Hodgkinson, Colin A.; Xu, Ke; Buzas, Beata; Yuan, Qiaoping; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Hariri, Ahmad R.; Ferrell, Robert E.; Manuck, Stephen B.; Brown, Sarah M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA.
   [Hariri, Ahmad R.; Ferrell, Robert E.; Manuck, Stephen B.; Brown, Sarah M.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA.
   [Hariri, Ahmad R.; Ferrell, Robert E.; Manuck, Stephen B.; Brown, Sarah M.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15261 USA.
   [Scott, David; Zubieta, Jon-Kar] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA.
   [Scott, David; Zubieta, Jon-Kar] Univ Michigan, Sch Med, Dept Radiol, Ann Arbor, MI 48109 USA.
   [Sinha, Rajita] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA.
   [Virkkunen, Matti] Univ Helsinki, Dept Psychiat, Helsinki 00014, Finland.
   [Mash, Deborah C.] Univ Miami, Sch Med, Dept Neurol, Miami, FL 33124 USA.
   [Hauger, Richard L.] San Diego VA Healthcare Syst, Dept Psychiat, San Diego, CA 92161 USA.
   [Hauger, Richard L.] Univ Calif San Diego, San Diego, CA 92161 USA.
   [Stohler, Christian S.] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Yale University; University of Helsinki; University of Miami; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA San Diego Healthcare System; University of California System; University of California San Diego; University System of Maryland; University of Maryland Baltimore
RP Goldman, D (corresponding author), NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM davidgoldman@mail.nih.gov
FU NHLBI NIH HHS [R01 HL065137, P01 HL040962] Funding Source: Medline; NIAAA NIH HHS [R01-AA13892, R01 AA013892] Funding Source: Medline; NIDA NIH HHS [PL1 DA024859, K02-DA17232, K02 DA017232, P50 DA016556, R01 DA 016423, R01 DA016423, P50-DA16556] Funding Source: Medline; NIDCR NIH HHS [R01 DE 15396, R01 DE015396] Funding Source: Medline; NIMH NIH HHS [R01 MH074697, K01 MH072837] Funding Source: Medline; Intramural NIH HHS [Z99 AA999999, Z01 AA000301] Funding Source: Medline; National Heart Lung and Blood Institute [P01HL040962] Funding Source: NIH RePORTER; National Institute on Alcohol Abuse and Alcoholism [R01AA013892] Funding Source: NIH RePORTER
NR 35
TC 354
Z9 411
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 24
PY 2008
VL 452
IS 7190
BP 997
EP U8
DI 10.1038/nature06858
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600040
PM 18385673
DA 2026-03-09
ER

PT J
AU Klein, DE
   Stayrook, SE
   Shi, FM
   Narayan, K
   Lemmon, MA
AF Klein, Daryl E.
   Stayrook, Steven E.
   Shi, Fumin
   Narayan, Kartik
   Lemmon, Mark A.
TI Structural basis for EGFR ligand sequestration by Argos
SO NATURE
LA English
DT Article
ID epidermal-growth-factor; crystal-structure; plasminogen-activator; erbb receptors; complex; domain; superfamily; inhibition; expression; alignment
AB Members of the epidermal growth factor receptor ( EGFR) or ErbB/ HER family and their activating ligands are essential regulators of diverse developmental processes(1,2). Inappropriate activation of these receptors is a key feature of many human cancers(3), and its reversal is an important clinical goal. A natural secreted antagonist of EGFR signalling, called Argos, was identified in Drosophila(4). We showed previously that Argos functions by directly binding ( and sequestering) growth factor ligands that activate EGFR(5). Here we describe the 1.6-angstrom resolution crystal structure of Argos bound to an EGFR ligand. Contrary to expectations(4,6), Argos contains no EGF- like domain. Instead, a trio of closely related domains ( resembling a three- finger toxin fold(7)) form a clamp- like structure around the bound EGF ligand. Although structurally unrelated to the receptor, Argos mimics EGFR by using a bipartite binding surface to entrap EGF. The individual Argos domains share unexpected structural similarities with the extracellular ligand- binding regions of transforming growth factor-beta family receptors(8). The three- domain clamp of Argos also resembles the urokinase- type plasminogen activator ( uPA) receptor, which uses a similar mechanism to engulf the EGF- like module of uPA(9). Our results indicate that undiscovered mammalian counterparts of Argos may exist among other poorly characterized structural homologues. In addition, the structures presented here define requirements for the design of artificial EGF- sequestering proteins that would be valuable anti- cancer therapeutics.
C1 [Klein, Daryl E.; Stayrook, Steven E.; Shi, Fumin; Narayan, Kartik; Lemmon, Mark A.] Univ Penn, Sch Med, Dept Biochem & Biophys, Stellar Chance Labs 809C, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania
RP Lemmon, MA (corresponding author), Univ Penn, Sch Med, Dept Biochem & Biophys, Stellar Chance Labs 809C, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM mlemmon@mail.med.upenn.edu
FU NCI NIH HHS [R01 CA079992, R01 CA125432] Funding Source: Medline
NR 38
TC 46
Z9 60
U1 0
U2 13
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1271
EP U79
DI 10.1038/nature06978
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800050
PM 18500331
DA 2026-03-09
ER

PT J
AU Conrad, S
   Renninger, M
   Hennenlotter, J
   Wiesner, T
   Just, L
   Bonin, M
   Aicher, W
   Bühring, HJ
   Mattheus, U
   Mack, A
   Wagner, HJ
   Minger, S
   Matzkies, M
   Reppel, M
   Hescheler, J
   Sievert, KD
   Stenzl, A
   Skutella, T
AF Conrad, Sabine
   Renninger, Markus
   Hennenlotter, Joerg
   Wiesner, Tina
   Just, Lothar
   Bonin, Michael
   Aicher, Wilhelm
   Buehring, Hans-Joerg
   Mattheus, Ulrich
   Mack, Andreas
   Wagner, Hans-Joachim
   Minger, Stephen
   Matzkies, Matthias
   Reppel, Michael
   Hescheler, Juergen
   Sievert, Karl-Dietrich
   Stenzl, Arnulf
   Skutella, Thomas
TI RETRACTED: Generation of pluripotent stem cells from adult human testis (Retracted article. See vol. 512, pg. 338, 2014)
SO NATURE
LA English
DT Article; Retracted Publication
ID primordial germ-cells; in-vitro; differentiation; fibroblasts; culture; cardiomyocytes; derivation; markers
AB Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non- controversial access to individual cell- based therapy without the ethical and immunological problems associated with human embryonic stem cells.
C1 [Conrad, Sabine; Wiesner, Tina; Just, Lothar; Skutella, Thomas] Inst Anat, Dept Expt Embryol, D-72074 Tubingen, Germany.
   [Mattheus, Ulrich; Mack, Andreas; Wagner, Hans-Joachim] Inst Anat, Dept Cellular Neurobiol, D-72074 Tubingen, Germany.
   [Renninger, Markus; Hennenlotter, Joerg; Sievert, Karl-Dietrich; Stenzl, Arnulf] Univ Clin Tubingen, Dept Urol, D-72076 Tubingen, Germany.
   [Bonin, Michael] Univ Clin Tubingen, Inst Anthropol & Human Genet, Microarray Facil, D-72076 Tubingen, Germany.
   [Aicher, Wilhelm] Univ Clin Tubingen, ZMF Res Labs, D-72072 Tubingen, Germany.
   [Aicher, Wilhelm; Skutella, Thomas] Ctr Regenerat Biol & Med ZRM, D-72076 Tubingen, Germany.
   [Buehring, Hans-Joerg] Univ Clin Tubingen, Dept Internal Med 2, D-72076 Tubingen, Germany.
   [Minger, Stephen] Kings Coll London, Stem Cell Biol Lab, Wolfson Ctr Age Related Dis, London SE1 1UL, England.
   [Matzkies, Matthias; Reppel, Michael; Hescheler, Juergen] Univ Cologne, Inst Neurophysiol, D-50931 Cologne, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; University of London; King's College London; University of Cologne
RP Skutella, T (corresponding author), Inst Anat, Dept Expt Embryol, Osterbergstr 3, D-72074 Tubingen, Germany.
EM Thomas.Skutella@regmed.uni-tuebingen.de
FU Department of Urology; Institute of Anatomy; ZRM (University Clinic Tubingen)
NR 37
TC 371
Z9 451
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 20
PY 2008
VL 456
IS 7220
BP 344
EP U25
DI 10.1038/nature07404
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600034
PM 18849962
DA 2026-03-09
ER

PT J
AU Idnurm, A
   Walton, FJ
   Floyd, A
   Heitman, J
AF Idnurm, Alexander
   Walton, Felicia J.
   Floyd, Anna
   Heitman, Joseph
TI Identification of the sex genes in an early diverged fungus
SO NATURE
LA English
DT Article
ID mating-type region; phycomyces-blakesleeanus; neurospora-crassa; evolution; locus; recombination; chromosm; phylogeny
AB Sex determination in fungi is controlled by a small, specialized region of the genome in contrast to the large sex- specific chromosomes of animals and some plants. Different gene combinations reside at these mating- type ( MAT) loci and confer sexual identity; invariably they encode homeodomain, alpha-box, or high mobility group ( HMG)- domain transcription factors(1). So far, MAT loci have been characterized from a single monophyletic clade of fungi, the Dikarya ( the ascomycetes and basidiomycetes)(2), and the ancestral state and evolutionary history of these loci have remained a mystery. Mating in the basal members of the kingdom has been less well studied, and even their precise taxonomic interrelationships are still obscure(3,4). Here we apply bioinformatic and genetic mapping to identify the sex- determining ( sex) region in Phycomyces blakesleeanus ( Zygomycota), which represents an early branch within the fungi. Each sex allele contains a single gene that encodes an HMG- domain protein, implicating the HMG- domain proteins as an earlier form of fungal MAT loci. Additionally, one allele also contains a copy of a unique, chromosome- specific repetitive element, suggesting a generalized mechanism for the earliest steps in the evolution of sex determination and sex chromosome structure in eukaryotes.
C1 [Idnurm, Alexander; Walton, Felicia J.; Floyd, Anna; Heitman, Joseph] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
   [Idnurm, Alexander] Univ Missouri, Sch Biol Sci, Kansas City, MO 64110 USA.
C3 Duke University; University of Missouri System; University of Missouri Kansas City
RP Heitman, J (corresponding author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM heitm001@mc.duke.edu
NR 29
TC 123
Z9 139
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 10
PY 2008
VL 451
IS 7175
BP 193
EP U8
DI 10.1038/nature06453
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400043
PM 18185588
DA 2026-03-09
ER

PT J
AU Sah, P
   Westbrook, RF
AF Sah, Pankaj
   Westbrook, R. Frederick
TI Behavioural neuroscience - The circuit of fear
SO NATURE
LA English
DT Article
ID lateral amygdala neurons; responses; rat
C1 [Sah, Pankaj] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia.
   [Westbrook, R. Frederick] Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia.
C3 University of Queensland; University of New South Wales Sydney
RP Sah, P (corresponding author), Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia.
EM pankaj.sah@uq.edu.au
NR 14
TC 53
Z9 64
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 JUL 31
PY 2008
VL 454
IS 7204
BP 589
EP 590
DI 10.1038/454589a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500031
PM 18668096
DA 2026-03-09
ER

PT J
AU Pettifer, RF
   Collins, SP
   Laundy, D
AF Pettifer, Robert F.
   Collins, Stephen P.
   Laundy, David
TI Quadrupole transitions revealed by Borrmann spectroscopy
SO NATURE
LA English
DT Article
ID x-ray-scattering; absorption-spectra; crystal optics; diffraction; reflection; density; edge
AB The Borrmann effect(1,2) - a dramatic increase in transparency to X- ray beams - is observed when X- rays satisfying Bragg's law diffract through a perfect crystal. The minimization of absorption seen in the Borrmann effect has been explained by noting that the electric field of the X- ray beam approaches zero amplitude at the crystal planes, thus avoiding the atoms. Here we show experimentally that under conditions of absorption suppression, the weaker electric quadrupole absorption transitions are effectively enhanced to such a degree that they can dominate the absorption spectrum. This effect can be exploited as an atomic spectroscopy technique; we show that quadrupole transitions give rise to additional structure at the L(1), L(2) and L(3) absorption edges of gadolinium in gadolinium gallium garnet, which mark the onset of excitations from 2s, 2p(1/2) and 2p(3/2) atomic core levels, respectively. Although the Borrmann effect served to underpin the development of the theory of X- ray diffraction(3-6), this is potentially the most important experimental application of the phenomenon since its first observation seven decades ago. Identifying quadrupole features in X- ray absorption spectroscopy is central to the interpretation of 'pre- edge' spectra, which are often taken to be indicators of local symmetry, valence and atomic environment(7). Quadrupolar absorption isolates states of different symmetries to that of the dominant dipole spectrum, and typically reveals orbitals that dominate the electronic ground- state properties of lanthanides and 3d transition metals, including magnetism. Results from our Borrmann spectroscopy technique feed into contemporary discussions regarding resonant X- ray diffraction(8) and the nature of pre-edge lines identified by inelastic X- ray scattering(7). Furthermore, because the Borrmann effect has been observed in photonic materials, it seems likely that the quadrupole enhancement reported here will play an important role in modern optics.
C1 [Collins, Stephen P.] Diamond Light Source Ltd, Didcot O11 0DE, Oxon, England.
   [Pettifer, Robert F.; Collins, Stephen P.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Laundy, David] STFC Daresbury Lab, Warrington WA4 4AD, Cheshire, England.
C3 Diamond Light Source; University of Warwick; STFC Daresbury Laboratory
RP Collins, SP (corresponding author), Diamond Light Source Ltd, Diamond House,Harwell Sci & Innovat Campus, Didcot O11 0DE, Oxon, England.
EM steve.collins@diamond.ac.uk
NR 30
TC 33
Z9 33
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 196
EP 199
DI 10.1038/nature07099
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900039
PM 18615080
DA 2026-03-09
ER

PT J
AU Park, IH
   Zhao, R
   West, JA
   Yabuuchi, A
   Huo, HG
   Ince, TA
   Lerou, PH
   Lensch, MW
   Daley, GQ
AF Park, In-Hyun
   Zhao, Rui
   West, Jason A.
   Yabuuchi, Akiko
   Huo, Hongguang
   Ince, Tan A.
   Lerou, Paul H.
   Lensch, M. William
   Daley, George Q.
TI Reprogramming of human somatic cells to pluripotency with defined factors
SO NATURE
LA English
DT Article
ID embryonic stem-cells; fibroblasts; generation; differentiation; induction; selection; survival; regions; nanog; lines
AB Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo- derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors ( Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem ( iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune- deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient- specific cells might be established in culture.
C1 [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lerou, Paul H.; Lensch, M. William; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA.
   [Ince, Tan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Lerou, Paul H.] Brigham & Womens Hosp, Div Newborn Med, 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; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Daley, GQ (corresponding author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
NR 24
TC 2277
Z9 2979
U1 2
U2 767
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 141
EP U1
DI 10.1038/nature06534
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400032
PM 18157115
DA 2026-03-09
ER

PT J
AU Li, Y
   Balédent, V
   Barisic, N
   Cho, Y
   Fauqué, B
   Sidis, Y
   Yu, G
   Zhao, X
   Bourges, P
   Greven, M
AF Li, Y.
   Baledent, V.
   Barisic, N.
   Cho, Y.
   Fauque, B.
   Sidis, Y.
   Yu, G.
   Zhao, X.
   Bourges, P.
   Greven, M.
TI Unusual magnetic order in the pseudogap region of the superconductor HgBa2CuO4+δ
SO NATURE
LA English
DT Article
ID states; model
AB The pseudogap region of the phase diagram is an important unsolved puzzle in the field of high- transition- temperature (high-T-c) superconductivity, characterized by anomalous physical properties(1,2). There are open questions about the number of distinct phases and the possible presence of a quantum- critical point underneath the superconducting dome(3-5). The picture has remained unclear because there has not been conclusive evidence for a new type of order. Neutron scattering measurements for YBa2Cu3O6+delta (YBCO) resulted in contradictory claims of no(6,7) and weak(8,9) magnetic order, and the interpretation of muon spin relaxation measurements on YBCO10,11 and of circularly polarized photoemission experiments on Bi2Sr2CaCu2O8+delta ( refs 12, 13) has been controversial. Here we use polarized neutron diffraction to demonstrate for the model superconductor HgBa2CuO4+delta (Hg1201) that the characteristic temperature T* marks the onset of an unusual magnetic order. Together with recent results for YBCO14,15, this observation constitutes a demonstration of the universal existence of such a state. The findings appear to rule out theories that regard T* as a crossover temperature(16-18) rather than a phase transition temperature(19-21). Instead, they are consistent with a variant of previously proposed charge- current- loop order(19,20) that involves apical oxygen orbitals(22), and with the notion that many of the unusual properties arise from the presence of a quantum- critical point(3-5,19).
C1 [Barisic, N.; Cho, Y.; Zhao, X.; Greven, M.] Stanford Synchrotron Radiat Lab, Stanford, CA 94309 USA.
   [Li, Y.; Yu, G.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Baledent, V.; Fauque, B.; Sidis, Y.; Bourges, P.] CEA Saclay, CNRS, Leon Brillouin Lab, F-91191 Gif Sur Yvette, France.
   [Barisic, N.] Univ Stuttgart, Inst Phys 1, D-70550 Stuttgart, Germany.
   [Cho, Y.] Pusan Natl Univ, BK21 Team Nano Fus Technol, Pusan 609735, South Korea.
   [Zhao, X.] Jilin Univ, State Key Lab Inorgan Synth & Preparat Chem, Coll Chem, Changchun 130012, Peoples R China.
   [Greven, M.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
C3 Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); University of Stuttgart; Pusan National University; Jilin University; Stanford University
RP Greven, M (corresponding author), Stanford Synchrotron Radiat Lab, Stanford, CA 94309 USA.
EM greven@stanford.edu
FU US Department of Energy; National Science Foundation
NR 30
TC 252
Z9 292
U1 5
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 SEP 18
PY 2008
VL 455
IS 7211
BP 372
EP 375
DI 10.1038/nature07251
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200040
PM 18800135
DA 2026-03-09
ER

PT J
AU Wicher, D
   Schäfer, R
   Bauernfeind, R
   Stensmyr, MC
   Heller, R
   Heinemann, SH
   Hansson, BS
AF Wicher, Dieter
   Schaefer, Ronny
   Bauernfeind, Rene
   Stensmyr, Marcus C.
   Heller, Regine
   Heinemann, Stefan H.
   Hansson, Bill S.
TI Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels
SO NATURE
LA English
DT Article
ID neurosecretory insect neurons; olfactory receptor; molecular-basis; functional expression; in-vivo; camp; transduction; melanogaster; proteins; antenna
AB From worm to man, many odorant signals are perceived by the binding of volatile ligands to odorant receptors(1) that belong to the G- protein- coupled receptor ( GPCR) family(2). They couple to heterotrimeric G- proteins, most of which induce cAMP production(3). This second messenger then activates cyclic- nucleotide-gated ion channels to depolarize the olfactory receptor neuron, thus providing a signal for further neuronal processing. Recent findings, however, have challenged this concept of odorant signal transduction in insects, because their odorant receptors, which lack any sequence similarity to other GPCRs(4), are composed of conventional odorant receptors ( for example, Or22a), dimerized with a ubiquitously expressed chaperone protein(5), such as Or83b in Drosophila(6). Or83b has a structure akin to GPCRs, but has an inverted orientation in the plasma membrane(4,7). However, G proteins are expressed in insect olfactory receptor neurons(8), and olfactory perception is modified by mutations affecting the cAMP transduction pathway(9). Here we show that application of odorants to mammalian cells co- expressing Or22a and Or83b results in non- selective cation currents activated by means of an ionotropic and a metabotropic pathway, and a subsequent increase in the intracellular Ca2+ concentration. Expression of Or83b alone leads to functional ion channels not directly responding to odorants, but being directly activated by intracellular cAMP or cGMP. Insect odorant receptors thus form ligand- gated channels as well as complexes of odorant- sensing units and cyclic- nucleotide- activated non- selective cation channels. Thereby, they provide rapid and transient as well as sensitive and prolonged odorant signalling.
C1 [Wicher, Dieter; Schaefer, Ronny; Bauernfeind, Rene; Stensmyr, Marcus C.; Hansson, Bill S.] Max Planck Inst Chem Ecol, Dept Evolutionary Neuroethol, D-07745 Jena, Germany.
   [Heller, Regine] Univ Jena, Inst Mol Cell Biol, Ctr Mol Biomed, D-07743 Jena, Germany.
   [Heinemann, Stefan H.] Univ Jena, Dept Biophys, Ctr Mol Biomed, D-07745 Jena, Germany.
C3 Max Planck Society; Friedrich Schiller University of Jena; Friedrich Schiller University of Jena
RP Wicher, D (corresponding author), Max Planck Inst Chem Ecol, Dept Evolutionary Neuroethol, Hans Knoll St 8, D-07745 Jena, Germany.
EM dwicher@ice.mpg.de
NR 28
TC 695
Z9 854
U1 6
U2 193
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 24
PY 2008
VL 452
IS 7190
BP 1007
EP U10
DI 10.1038/nature06861
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600042
PM 18408711
DA 2026-03-09
ER

PT J
AU Sprecher, SG
   Desplan, C
AF Sprecher, Simon G.
   Desplan, Claude
TI Switch of rhodopsin expression in terminally differentiated Drosophila sensory neurons
SO NATURE
LA English
DT Article
ID finger transcription factor; visual-system; single cones; clock neurons; photoreceptors; retina; adult; light; melanogaster; senseless
AB Specificity of sensory neurons requires restricted expression of one sensory receptor gene and the exclusion of all others within a given cell. In the Drosophila retina, functional identity of photoreceptors depends on light-sensitive Rhodopsins (Rhs). The much simpler larval eye (Bolwig organ) is composed of about 12 photoreceptors, eight of which are green-sensitive (Rh6) and four bluesensitive (Rh5)(1). The larval eye becomes the adult extraretinal 'eyelet' composed of four green-sensitive (Rh6) photoreceptors(2,3). Here we show that, during metamorphosis, all Rh6 photoreceptors die, whereas the Rh5 photoreceptors switch fate by turning off Rh5 and then turning on Rh6 expression. This switch occurs without apparent changes in the programme of transcription factors that specify larval photoreceptor subtypes. We also show that the transcription factor Senseless (Sens) mediates the very different cellular behaviours of Rh5 and Rh6 photoreceptors. Sens is restricted to Rh5 photoreceptors and must be excluded from Rh6 photoreceptors to allow them to die at metamorphosis. Finally, we show that Ecdysone receptor (EcR) functions autonomously both for the death of larval Rh6 photoreceptors and for the sensory switch of Rh5 photoreceptors to express Rh6. This fate switch of functioning, terminally differentiated neurons provides a novel, unexpected example of hard-wired sensory plasticity.
C1 [Sprecher, Simon G.; Desplan, Claude] NYU, Ctr Dev Genet, Dept Biol, Silver Ctr 1090, New York, NY 10003 USA.
C3 New York University
RP Desplan, C (corresponding author), NYU, Ctr Dev Genet, Dept Biol, Silver Ctr 1090, 100 Washington Sq E, New York, NY 10003 USA.
EM cd38@nyu.edu
FU National Eye Institute [R01EY013010] Funding Source: NIH RePORTER; NCRR NIH HHS [C06 RR-15518-01, C06 RR015518] Funding Source: Medline; NEI NIH HHS [R01 EY013010, EY013010] Funding Source: Medline
NR 30
TC 93
Z9 104
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 533
EP 537
DI 10.1038/nature07062
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300055
PM 18594514
DA 2026-03-09
ER

PT J
AU Harvey, THP
   Butterfield, NJ
AF Harvey, Thomas H. P.
   Butterfield, Nicholas J.
TI Sophisticated particle-feeding in a large Early Cambrian crustacean
SO NATURE
LA English
DT Article
ID fossil record; phylogeny; evolution; arthropods; appendages; morphology; bearing; china; setae
AB Most Cambrian arthropods employed simple feeding mechanisms requiring only low degrees of appendage differentiation(1-3). In contrast, post- Cambrian crustaceans exhibit a wide diversity of feeding specializations and possess a vast ecological repertoire. Crustaceans are evident in the Cambrian fossil record, but have hitherto been known exclusively from small individuals with limited appendage differentiation(4). Here we describe a sophisticated feeding apparatus from an Early Cambrian arthropod that had a body length of several centimetres. Details of the mouthparts resolve this taxon as a probable crown- group ( pan) crustacean, while its feeding style, which allowed it to generate and handle fine food particles, significantly expands the known ecological capabilities of Cambrian arthropods. This Early Cambrian record predates the major expansions of large- bodied, particle- handling crustaceans by at least one hundred million years(5,6), emphasizing the importance of ecological context in driving adaptive radiations.
C1 [Harvey, Thomas H. P.; Butterfield, Nicholas J.] Univ Cambridge, Dept Earth Sci, Cambridge CB2 3EQ, England.
C3 University of Cambridge
RP Harvey, THP (corresponding author), Univ Cambridge, Dept Earth Sci, Downing St, Cambridge CB2 3EQ, England.
EM thar04@esc.cam.ac.uk
NR 30
TC 75
Z9 83
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 17
PY 2008
VL 452
IS 7189
BP 868
EP 871
DI 10.1038/nature06724
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000047
PM 18337723
DA 2026-03-09
ER

PT J
AU Orton, GS
   Yanamandra-Fisher, PA
   Fisher, BM
   Friedson, AJ
   Parrish, PD
   Nelson, JF
   Bauermeister, AS
   Fletcher, L
   Gezari, DY
   Varosi, F
   Tokunaga, AT
   Caldwell, J
   Baines, KH
   Hora, JL
   Ressler, ME
   Fujiyoshi, T
   Fuse, T
   Hagopian, H
   Martin, TZ
   Bergstralh, JT
   Howett, C
   Hoffmann, WF
   Deutsch, LK
   Van Cleve, JE
   Noe, E
   Adams, JD
   Kassis, M
   Tollestrup, E
AF Orton, Glenn S.
   Yanamandra-Fisher, Padma A.
   Fisher, Brendan M.
   Friedson, A. James
   Parrish, Paul D.
   Nelson, Jesse F.
   Bauermeister, Amber Swenson
   Fletcher, Leigh
   Gezari, Daniel Y.
   Varosi, Frank
   Tokunaga, Alan T.
   Caldwell, John
   Baines, Kevin H.
   Hora, Joseph L.
   Ressler, Michael E.
   Fujiyoshi, Takuya
   Fuse, Tetsuharu
   Hagopian, Hagop
   Martin, Terry Z.
   Bergstralh, Jay T.
   Howett, Carly
   Hoffmann, William F.
   Deutsch, Lynne K.
   Van Cleve, Jeffrey E.
   Noe, Eldar
   Adams, Joseph D.
   Kassis, Marc
   Tollestrup, Eric
TI Semi-annual oscillations in Saturn's low-latitude stratospheric temperatures
SO NATURE
LA English
DT Article
ID jupiters stratosphere
AB Observations of oscillations of temperature and wind in planetary atmospheres provide a means of generalizing models for atmospheric dynamics in a diverse set of planets in the Solar System and elsewhere. An equatorial oscillation similar to one in the Earth's atmosphere(1,2) has been discovered in Jupiter(3-6). Here we report the existence of similar oscillations in Saturn's atmosphere, from an analysis of over two decades of spatially resolved observations of its 7.8-mu m methane and 12.2-mu m ethane stratospheric emissions, where we compare zonal- mean stratospheric brightness temperatures at planetographic latitudes of 3.6 degrees and 15.5 degrees in both the northern and the southern hemispheres. These results support the interpretation of vertical and meridional variability of temperatures in Saturn's stratosphere(7) as a manifestation of a wave phenomenon similar to that on the Earth and in Jupiter. The period of this oscillation is 14.8+/-1.2 terrestrial years, roughly half of Saturn's year, suggesting the influence of seasonal forcing, as is the case with the Earth's semi- annual oscillation(1).
C1 [Orton, Glenn S.; Yanamandra-Fisher, Padma A.; Fisher, Brendan M.; Friedson, A. James; Fletcher, Leigh; Baines, Kevin H.; Ressler, Michael E.; Martin, Terry Z.; Noe, Eldar] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Parrish, Paul D.] Univ Edinburgh, Sch Geosci, Edinburgh EH9 3JN, Midlothian, Scotland.
   [Nelson, Jesse F.] Univ Maine, Dept Phys & Astron, Orono, ME 04469 USA.
   [Bauermeister, Amber Swenson] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Gezari, Daniel Y.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Varosi, Frank] Univ Florida, Dept Astron, Bryant Space Sci Ctr 211, Gainesville, FL 32611 USA.
   [Tokunaga, Alan T.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Caldwell, John] York Univ, Dept Phys & Astron, Toronto, ON M3J 1P3, Canada.
   [Hora, Joseph L.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Fujiyoshi, Takuya; Fuse, Tetsuharu] Natl Inst Nat Sci, Natl Astron Observ Japan, Subaru Telescope, Hilo, HI 96720 USA.
   [Hagopian, Hagop] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA.
   [Bergstralh, Jay T.] Langley Res Ctr, Hampton, VA 23681 USA.
   [Howett, Carly] Univ Oxford, Clarendon Lab, Oxford OX1 3PU, England.
   [Hoffmann, William F.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Van Cleve, Jeffrey E.] Ball Aerosp & Technol Corp, Civil Space Syst, Boulder, CO 80306 USA.
   [Adams, Joseph D.] Dept Radiophys & Space Res, Ithaca, NY 14853 USA.
   [Kassis, Marc] WM Keck Observ, Kamuela, HI 96743 USA.
   [Tollestrup, Eric] NASA, Infrared Telescope Facil, Inst Astron, Hilo, HI 96822 USA.
C3 California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of Edinburgh; University of Maine System; University of Maine Orono; University of California System; University of California Berkeley; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; State University System of Florida; University of Florida; University of Hawaii System; York University - Canada; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); University of California System; University of California Los Angeles; National Aeronautics & Space Administration (NASA); NASA Langley Research Center; University of Oxford; University of Arizona; Ball Aerospace & Technologies; National Aeronautics & Space Administration (NASA)
RP Orton, GS (corresponding author), CALTECH, Jet Prop Lab, MS 169-237,4800 Oak Grove Dr, Pasadena, CA 91109 USA.
EM glenn.orton@jpl.nasa.gov
NR 12
TC 79
Z9 83
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 196
EP 199
DI 10.1038/nature06897
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400033
PM 18464736
DA 2026-03-09
ER

PT J
AU Melbourne, BA
   Hastings, A
AF Melbourne, Brett A.
   Hastings, Alan
TI Extinction risk depends strongly on factors contributing to stochasticity
SO NATURE
LA English
DT Article
ID demographic stochasticity; small populations; mating system; survival; dynamics; time
AB Extinction risk in natural populations depends on stochastic factors that affect individuals, and is estimated by incorporating such factors into stochastic models(1-9). Stochasticity can be divided into four categories, which include the probabilistic nature of birth and death at the level of individuals ( demographic stochasticity(2)), variation in population- level birth and death rates among times or locations ( environmental stochasticity(1,3)), the sex of individuals(6,8) and variation in vital rates among individuals within a population ( demographic heterogeneity(7,9)). Mechanistic stochastic models that include all of these factors have not previously been developed to examine their combined effects on extinction risk. Here we derive a family of stochastic Ricker models using different combinations of all these stochastic factors, and show that extinction risk depends strongly on the combination of factors that contribute to stochasticity. Furthermore, we show that only with the full stochastic model can the relative importance of environmental and demographic variability, and therefore extinction risk, be correctly determined. Using the full model, we find that demographic sources of stochasticity are the prominent cause of variability in a laboratory population of Tribolium castaneum ( red flour beetle), whereas using only the standard simpler models would lead to the erroneous conclusion that environmental variability dominates. Our results demonstrate that current estimates of extinction risk for natural populations could be greatly underestimated because variability has been mistakenly attributed to the environment rather than the demographic factors described here that entail much higher extinction risk for the same variability level.
C1 [Melbourne, Brett A.] Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
   [Hastings, Alan] Univ Calif Davis, Dept Environm Sci & Policy, Davis, CA 95616 USA.
C3 University of Colorado System; University of Colorado Boulder; University of California System; University of California Davis
RP Melbourne, BA (corresponding author), Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
EM brett.melbourne@colorado.edu
NR 30
TC 464
Z9 531
U1 3
U2 308
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 100
EP 103
DI 10.1038/nature06922
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300045
PM 18596809
DA 2026-03-09
ER

PT J
AU Atsumi, S
   Hanai, T
   Liao, JC
AF Atsumi, Shota
   Hanai, Taizo
   Liao, James C.
TI Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; escherichia-coli; amino-acids; clostridium-acetobutylicum; molecular characterization; isoleucine biosynthesis; decarboxylase; metabolism; gene; 1,3-propanediol
AB Global energy and environmental problems have stimulated increased efforts towards synthesizing biofuels from renewable resources(1-3). Compared to the traditional biofuel, ethanol, higher alcohols offer advantages as gasoline substitutes because of their higher energy density and lower hygroscopicity. In addition, branched- chain alcohols have higher octane numbers compared with their straight- chain counterparts. However, these alcohols cannot be synthesized economically using native organisms. Here we present a metabolic engineering approach using Escherichia coli to produce higher alcohols including isobutanol, 1-butanol, 2- methyl- 1- butanol, 3- methyl- 1- butanol and 2- phenylethanol from glucose, a renewable carbon source. This strategy uses the host's highly active amino acid biosynthetic pathway and diverts its 2- keto acid intermediates for alcohol synthesis. In particular, we have achieved high- yield, high- specificity production of isobutanol from glucose. The strategy enables the exploration of biofuels beyond those naturally accumulated to high quantities in microbial fermentation.
C1 [Atsumi, Shota; Hanai, Taizo; Liao, James C.] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Los Angeles, CA 90095 USA.
   [Liao, James C.] Univ Calif Los Angeles, UCLA DOE Inst Genom & Proteom, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; United States Department of Energy (DOE); University of California System; University of California Los Angeles
RP Liao, JC (corresponding author), Univ Calif Los Angeles, Dept Chem & Biomol Engn, 5531 Boelter Hall,420 Westwood Plaza, Los Angeles, CA 90095 USA.
EM liaoj@seas.ucla.edu
NR 30
TC 1530
Z9 2091
U1 7
U2 857
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 86
EP U13
DI 10.1038/nature06450
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300039
PM 18172501
DA 2026-03-09
ER

PT J
AU Quintana, FJ
   Basso, AS
   Iglesias, AH
   Korn, T
   Farez, MF
   Bettelli, E
   Caccamo, M
   Oukka, M
   Weiner, HL
AF Quintana, Francisco J.
   Basso, Alexandre S.
   Iglesias, Antonio H.
   Korn, Thomas
   Farez, Mauricio F.
   Bettelli, Estelle
   Caccamo, Mario
   Oukka, Mohamed
   Weiner, Howard L.
TI Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor
SO NATURE
LA English
DT Article
ID tgf-beta; independent regulation; microarray analysis; ah receptor; activation; expression; induction; dioxin; t(h)17; ligand
AB Regulatory T cells (T-reg) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of T-reg cells is reciprocally related to that of pro- inflammatory T cells producing interleukin- 17 ( T(H)17). Although T-reg cell dysfunction and/ or T(H)17 cell dysregulation are thought to contribute to the development of autoimmune disorders, little is known about the physiological pathways that control the generation of these cell lineages. Here we report the identification of the ligand- activated transcription factor aryl hydrocarbon receptor ( AHR) as a regulator of T-reg and T(H)17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8- tetrachlorodibenzo- p- dioxin induced functional Treg cells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6- formylindolo[ 3,2- b] carbazole interfered with T-reg cell development, boosted T(H)17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both T-reg and T(H)17 cell differentiation in a ligand- specific fashion, constituting a unique target for therapeutic immunomodulation.
C1 [Quintana, Francisco J.; Basso, Alexandre S.; Iglesias, Antonio H.; Korn, Thomas; Farez, Mauricio F.; Bettelli, Estelle; Weiner, Howard L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
   [Caccamo, Mario] European Bioinformat Inst, EMBL Outstn Hinxton, Cambridge CB10 1SD, England.
   [Oukka, Mohamed] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Weiner, HL (corresponding author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM hweiner@rics.bwh.harvard.edu
FU NIAID NIH HHS [R01AI073542-01, R01 AI073542, AI435801] Funding Source: Medline; NINDS NIH HHS [NS38037, P01 NS038037, R01 NS059996] Funding Source: Medline
NR 41
TC 1508
Z9 1801
U1 3
U2 167
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 1
PY 2008
VL 453
IS 7191
BP 65
EP +
DI 10.1038/nature06880
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800039
PM 18362915
DA 2026-03-09
ER

PT J
AU Greenberg, JI
   Shields, DJ
   Barillas, SG
   Acevedo, LM
   Murphy, E
   Huang, JH
   Scheppke, L
   Stockmann, C
   Johnson, RS
   Angle, N
   Cheresh, DA
AF Greenberg, Joshua I.
   Shields, David J.
   Barillas, Samuel G.
   Acevedo, Lisette M.
   Murphy, Eric
   Huang, Jianhua
   Scheppke, Lea
   Stockmann, Christian
   Johnson, Randall S.
   Angle, Niren
   Cheresh, David A.
TI A role for VEGF as a negative regulator of pericyte function and vessel maturation
SO NATURE
LA English
DT Article
ID growth-factor pdgf; induced angiogenesis; endothelial-cells; in-situ; beta; bb; differentiation; recruitment; inhibition; promotes
AB Angiogenesis does not only depend on endothelial cell invasion and proliferation: it alsorequires pericyte coverage of vascular sprouts for vessel stabilization(1,2). These processes are coordinated by vascular endothelial growth factor ( VEGF) and platelet- derived growth factor ( PDGF) through their cognate receptors on endothelial cells and vascular smooth muscle cells ( VSMCs), respectively(3,4). PDGF induces neovascularization by priming VSMCs/pericytes to release proangiogenic mediators(5-7). Although VEGF directly stimulates endothelial cell proliferation and migration, its role in pericyte biology is less clear. Here we define a role for VEGF as an inhibitor of neovascularization on the basis of its capacity to disrupt VSMC function. Specifically, under conditions of PDGF- mediated angiogenesis, VEGF ablates pericyte coverage of nascent vascular sprouts, leading to vessel destabilization. At the molecular level, VEGF- mediated activation of VEGF- R2 suppresses PDGF- R beta signalling in VSMCs through the assembly of a previously undescribed receptor complex consisting of PDGF- Rb and VEGF- R2. Inhibition of VEGF- R2 not only prevents assembly of this receptor complex but also restores angiogenesis in tissues exposed to both VEGF and PDGF. Finally, genetic deletion of tumour cell VEGF disrupts PDGF-R beta/VEGF-R2 complex formation and increases tumour vessel maturation. These findings underscore the importance of VSMCs/ pericytes in neovascularization(8,9) and reveal a dichotomous role forVEGF and VEGF-R2 signalling as both a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation.
C1 [Shields, David J.; Acevedo, Lisette M.; Murphy, Eric; Huang, Jianhua; Scheppke, Lea; Cheresh, David A.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
   [Greenberg, Joshua I.; Barillas, Samuel G.; Angle, Niren] Univ Calif San Diego, Sch Med, Dept Surg, La Jolla, CA 92093 USA.
   [Shields, David J.; Acevedo, Lisette M.; Murphy, Eric; Huang, Jianhua; Scheppke, Lea; Cheresh, David A.] Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA.
   [Stockmann, Christian; Johnson, Randall S.] Univ Calif San Diego, Div Biol, Mol Biol Sect, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Cheresh, DA (corresponding author), Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
EM dcheresh@ucsd.edu
FU National Institutes of Health [R37-CA50286, CA082515, GM 68524]; University of California Academic Senate Grant; Deutsche Forschungsgemeinschaft [DFG STO 787/1-1]; Institutional Research and Academic Career Development Award; National Institute of General Medical Sciences [K12GM068524] Funding Source: NIH RePORTER
NR 27
TC 539
Z9 655
U1 1
U2 71
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 809
EP U101
DI 10.1038/nature07424
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900053
PM 18997771
DA 2026-03-09
ER

PT J
AU Depine, GV
   Andronicos, CL
   Phipps-Morgan, J
AF Depine, Gabriela V.
   Andronicos, Christopher L.
   Phipps-Morgan, Jason
TI Near-isothermal conditions in the middle and lower crust induced by melt migration
SO NATURE
LA English
DT Article
ID thermal-processes; metamorphism; granite; emplacement; mountains; solidus; complex; flow
AB The thermal structure of the crust strongly influences deformation, metamorphism and plutonism(1-3). Models for the geothermal gradient in stable crust predict a steady increase of temperature with depth. This thermal structure, however, is incompatible with observations from high- temperature metamorphic terranes exhumed in orogens(1,4,5,6). Global compilations(7) of peak conditions in high- temperature metamorphic terranes define relatively narrow ranges of peak temperatures over a wide range in pressure, for both isothermal decompression and isobaric cooling paths. Here we develop simple one- dimensional thermal models that include the effects of melt migration. These models show that long- lived plutonism results in a quasi- steady- state geotherm with a rapid temperature increase in the upper crust and nearly isothermal conditions in the middle and lower crust. The models also predict that the upward advection of heat by melt generates granulite facies metamorphism, and widespread andalusite - sillimanite metamorphism in the upper crust. Once the quasi- steady- state thermal profile is reached, the middle and lower crust are greatly weakened due to high temperatures and anatectic conditions, thus setting the stage for gravitational collapse(8), exhumation and isothermal decompression after the onset of plutonism. Near- iso-thermal conditions in the middle and lower crust result from the thermal buffering effect of dehydration melting reactions that, in part, control the shape of the geotherm.
C1 [Depine, Gabriela V.; Andronicos, Christopher L.; Phipps-Morgan, Jason] Cornell Univ, Dept Earth & Atmospher Sci, Ithaca, NY 14853 USA.
C3 Cornell University
RP Depine, GV (corresponding author), Cornell Univ, Dept Earth & Atmospher Sci, Snee Hall, Ithaca, NY 14853 USA.
EM gvd2@cornell.edu
NR 34
TC 75
Z9 84
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 6
PY 2008
VL 452
IS 7183
BP 80
EP 83
DI 10.1038/nature06689
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900050
PM 18322532
DA 2026-03-09
ER

PT J
AU Nowacki, M
   Vijayan, V
   Zhou, Y
   Schotanus, K
   Doak, TG
   Landweber, LF
AF Nowacki, Mariusz
   Vijayan, Vikram
   Zhou, Yi
   Schotanus, Klaas
   Doak, Thomas G.
   Landweber, Laura F.
TI RNA-mediated epigenetic programming of a genome-rearrangement pathway
SO NATURE
LA English
DT Article
ID internal eliminated segments; non-mendelian inheritance; dna-polymerase-alpha; double-strand breaks; paramecium-tetraurelia; binding-protein; gene; evolution; recombination; information
AB Genome- wide DNA rearrangements occur in many eukaryotes but are most exaggerated in ciliates, making them ideal model systems for epigenetic phenomena. During development of the somatic macronucleus, Oxytricha trifallax destroys 95% of its germ line, severely fragmenting its chromosomes, and then unscrambles hundreds of thousands of remaining fragments by permutation or inversion. Here we demonstrate that DNA or RNA templates can orchestrate these genome rearrangements in Oxytricha, supporting an epigenetic model for sequence- dependent comparison between germline and somatic genomes. A complete RNA cache of the maternal somatic genome may be available at a specific stage during development to provide a template for correct and precise DNA rearrangement. We show the existence of maternal RNA templates that could guide DNA assembly, and that disruption of specific RNA molecules disables rearrangement of the corresponding gene. Injection of artificial templates reprogrammes the DNA rearrangement pathway, suggesting that RNA molecules guide genome rearrangement.
C1 [Nowacki, Mariusz; Zhou, Yi; Schotanus, Klaas; Doak, Thomas G.; Landweber, Laura F.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [Vijayan, Vikram] Princeton Univ, Dept Elect Engn, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University
RP Landweber, LF (corresponding author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM lfl@princeton.edu
FU NIGMS NIH HHS [R01 GM059708] Funding Source: Medline
NR 37
TC 221
Z9 266
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 JAN 10
PY 2008
VL 451
IS 7175
BP 153
EP U4
DI 10.1038/nature06452
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400034
PM 18046331
DA 2026-03-09
ER

PT J
AU Mudd, JO
   Kass, DA
AF Mudd, James O.
   Kass, David A.
TI Tackling heart failure in the twenty-first century
SO NATURE
LA English
DT Article
ID left-ventricular function; channel ryanodine receptor; cardiac-hypertrophy; gene-expression; myocardial-infarction; assist device; fatty-acid; in-vivo; inhibition; kinase
AB Heart failure, or congestive heart failure, is a condition in which the heart cannot supply the body's tissues with enough blood. The result is a cascade of changes that lead to severe fatigue, breathlessness and, ultimately, death. In the past quarter century, much progress has been made in understanding the molecular and cellular processes that contribute to heart failure, leading to the development of effective therapies. Despite this, chronic heart failure remains a major cause of illness and death. And because the condition becomes more common with increasing age, the number of affected individuals is rising with the rapidly ageing global population. New treatments that target disease mechanisms at the cellular and whole-organ level are needed to halt and reverse the devastating consequences of this disease.
C1 [Mudd, James O.; Kass, David A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Kass, DA (corresponding author), Johns Hopkins Med Inst, Ross 835,720 Rutland Ave, Baltimore, MD 21205 USA.
EM dkass@jhmi.edu
NR 100
TC 329
Z9 407
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 FEB 21
PY 2008
VL 451
IS 7181
BP 919
EP 928
DI 10.1038/nature06798
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100032
PM 18288181
DA 2026-03-09
ER

PT J
AU Jakobsson, M
   Scholz, SW
   Scheet, P
   Gibbs, JR
   VanLiere, JM
   Fung, HC
   Szpiech, ZA
   Degnan, JH
   Wang, K
   Guerreiro, R
   Bras, JM
   Schymick, JC
   Hernandez, DG
   Traynor, BJ
   Simon-Sanchez, J
   Matarin, M
   Britton, A
   van de Leemput, J
   Rafferty, I
   Bucan, M
   Cann, HM
   Hardy, JA
   Rosenberg, NA
   Singleton, AB
AF Jakobsson, Mattias
   Scholz, Sonja W.
   Scheet, Paul
   Gibbs, J. Raphael
   VanLiere, Jenna M.
   Fung, Hon-Chung
   Szpiech, Zachary A.
   Degnan, James H.
   Wang, Kai
   Guerreiro, Rita
   Bras, Jose M.
   Schymick, Jennifer C.
   Hernandez, Dena G.
   Traynor, Bryan J.
   Simon-Sanchez, Javier
   Matarin, Mar
   Britton, Angela
   van de Leemput, Joyce
   Rafferty, Ian
   Bucan, Maja
   Cann, Howard M.
   Hardy, John A.
   Rosenberg, Noah A.
   Singleton, Andrew B.
TI Genotype, haplotype and copy-number variation in worldwide human populations
SO NATURE
LA English
DT Article
ID human genome; linkage disequilibrium; genetic-structure; polymorphisms; distance; africa; model
AB Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups(1-3). Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms ( SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected-including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas-the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.
C1 [Jakobsson, Mattias; Scheet, Paul; VanLiere, Jenna M.; Szpiech, Zachary A.; Degnan, James H.; Rosenberg, Noah A.] Univ Michigan, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA.
   [Jakobsson, Mattias; Degnan, James H.; Rosenberg, Noah A.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Scheet, Paul; Rosenberg, Noah A.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Scholz, Sonja W.; Gibbs, J. Raphael; Fung, Hon-Chung; Guerreiro, Rita; Bras, Jose M.; Schymick, Jennifer C.; Hernandez, Dena G.; Traynor, Bryan J.; Simon-Sanchez, Javier; Matarin, Mar; Britton, Angela; van de Leemput, Joyce; Rafferty, Ian; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Scholz, Sonja W.; Gibbs, J. Raphael; van de Leemput, Joyce; Hardy, John A.] UCL, Dept Mol Neurosci, London WC1N 3BG, England.
   [Scholz, Sonja W.; Gibbs, J. Raphael; van de Leemput, Joyce; Hardy, John A.] UCL, Reta Lila Weston Inst Neurol Studies, Inst Neurol, London WC1N 3BG, England.
   [Fung, Hon-Chung] Chang Gung Mem Hosp, Dept Neurol, Taipei 10591, Taiwan.
   [Fung, Hon-Chung] Chang Gung Univ, Coll Med, Taipei 10591, Taiwan.
   [Wang, Kai; Bucan, Maja] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
   [Guerreiro, Rita; Bras, Jose M.] Univ Coimbra, Fac Med, Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal.
   [Schymick, Jennifer C.] Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England.
   [Traynor, Bryan J.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
   [Simon-Sanchez, Javier] CSIC, Unidad Genet Mol, Dept Genom & Proteom, Inst Biomed Valencia, Valencia 46010, Spain.
   [Cann, Howard M.] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France.
   [Singleton, Andrew B.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of London; University College London; University of London; University College London; Chang Gung Memorial Hospital; Chang Gung University; University of Pennsylvania; Universidade de Coimbra; University of Oxford; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Biomedicina de Valencia (IBV); Foundation Jean Dausset-CEPH; University of Virginia
RP Rosenberg, NA (corresponding author), Univ Michigan, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA.
EM rnoah@umich.edu; singleta@mail.nih.gov
FU Medical Research Council [G0701075] Funding Source: researchfish; National Institute on Aging [ZIAAG000932] Funding Source: NIH RePORTER; MRC [G0701075] Funding Source: UKRI; Medical Research Council [G0701075, MR/K01417X/1] Funding Source: Medline; NHGRI NIH HHS [T32 HG000040] Funding Source: Medline; Intramural NIH HHS Funding Source: Medline
NR 30
TC 653
Z9 793
U1 0
U2 125
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 998
EP 1003
DI 10.1038/nature06742
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100050
PM 18288195
DA 2026-03-09
ER

PT J
AU Stallard, T
   Miller, S
   Lystrup, M
   Achilleos, N
   Bunce, EJ
   Arridge, CS
   Dougherty, MK
   Cowley, SWH
   Badman, SV
   Talboys, DL
   Brown, RH
   Baines, KH
   Buratti, BJ
   Clark, RN
   Sotin, C
   Nicholson, PD
   Drossart, P
AF Stallard, Tom
   Miller, Steve
   Lystrup, Makenzie
   Achilleos, Nicholas
   Bunce, Emma J.
   Arridge, Christopher S.
   Dougherty, Michele K.
   Cowley, Stan W. H.
   Badman, Sarah V.
   Talboys, Dean L.
   Brown, Robert H.
   Baines, Kevin H.
   Buratti, Bonnie J.
   Clark, Roger N.
   Sotin, Christophe
   Nicholson, Phil D.
   Drossart, Pierre
TI Complex structure within Saturn's infrared aurora
SO NATURE
LA English
DT Article
ID jovian ionosphere; emission; dynamics
AB The majority of planetary aurorae are produced by electrical currents flowing between the ionosphere and the magnetosphere which accelerate energetic charged particles that hit the upper atmosphere. At Saturn, these processes collisionally excite hydrogen, causing ultraviolet emission(1-8), and ionize the hydrogen, leading to H-3(+) infrared emission(9-15). Although the morphology of these aurorae is affected by changes in the solar wind(6,11), the source of the currents which produce them is a matter of debate(16,17). Recent models predict only weak emission away from the main auroral oval(18). Here we report images that show emission both poleward and equatorward of the main oval (separated by a region of low emission). The extensive polar emission is highly variable with time, and disappears when the main oval has a spiral morphology; this suggests that although the polar emission may be associated with minor increases in the dynamic pressure from the solar wind, it is not directly linked to strong magnetospheric compressions. This aurora appears to be unique to Saturn and cannot be explained using our current understanding of Saturn's magnetosphere. The equatorward arc of emission exists only on the nightside of the planet, and arises from internal magnetospheric processes that are currently unknown.
C1 [Stallard, Tom; Bunce, Emma J.; Cowley, Stan W. H.; Badman, Sarah V.; Talboys, Dean L.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Miller, Steve; Lystrup, Makenzie; Achilleos, Nicholas] UCL, Atmospher Phys Lab, Dept Phys & Astron, London WC1E 6BT, England.
   [Arridge, Christopher S.] Univ Coll London, Mullard Space Sci Lab, Dept Space & Climate Phys, Dorking RH5 6NT, Surrey, England.
   [Dougherty, Michele K.] Univ London Imperial Coll Sci Technol & Med, Dept Phys, Space & Atmospher Phys Grp, London SW7 2AZ, England.
   [Brown, Robert H.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Brown, Robert H.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Baines, Kevin H.; Buratti, Bonnie J.; Sotin, Christophe] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Clark, Roger N.] US Geol Survey, Lakewood, CO 80225 USA.
   [Nicholson, Phil D.] Cornell Univ, Dept Astron, Ithaca, NY 14853 USA.
   [Drossart, Pierre] Observ Paris, F-92195 Meudon, France.
C3 University of Leicester; University of London; University College London; University of London; University College London; Imperial College London; University of Arizona; University of Arizona; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); United States Department of the Interior; United States Geological Survey; Cornell University; Universite PSL; Observatoire de Paris
RP Stallard, T (corresponding author), Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
EM tss@ion.le.ac.uk
FU Research Councils UK Fellowship; UK Science and Technology Facilities Council; European Union's Sixth Framework Programme; Science and Technology Facilities Council [PP/E001076/1, PP/D000912/1, PP/E000983/1, PP/E001173/1] Funding Source: researchfish; STFC [PP/E001076/1, PP/E000983/1, PP/E001173/1, PP/D000912/1] Funding Source: UKRI
NR 26
TC 42
Z9 45
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 NOV 13
PY 2008
VL 456
IS 7219
BP 214
EP 217
DI 10.1038/nature07440
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300034
PM 19005549
DA 2026-03-09
ER

PT J
AU Gozar, A
   Logvenov, G
   Kourkoutis, LF
   Bollinger, AT
   Giannuzzi, LA
   Muller, DA
   Bozovic, I
AF Gozar, A.
   Logvenov, G.
   Kourkoutis, L. Fitting
   Bollinger, A. T.
   Giannuzzi, L. A.
   Muller, D. A.
   Bozovic, I.
TI High-temperature interface superconductivity between metallic and insulating copper oxides
SO NATURE
LA English
DT Article
ID critical current-density
AB The realization of high- transition- temperature ( high- T-c) superconductivity confined to nanometre- sized interfaces has been a long- standing goal because of potential applications(1,2) and the opportunity to study quantum phenomena in reduced dimensions(3,4). This has been, however, a challenging target: in conventional metals, the high electron density restricts interface effects ( such as carrier depletion or accumulation) to a region much narrower than the coherence length, which is the scale necessary for superconductivity to occur. By contrast, in copper oxides the carrier density is low whereas T-c is high and the coherence length very short, which provides an opportunity - but at a price: the interface must be atomically perfect. Here we report superconductivity in bilayers consisting of an insulator ( La2CuO4) and a metal ( La1.55Sr0.45CuO4), neither of which is superconducting in isolation. In these bilayers, T-c is either similar to 15 K or similar to 30 K, depending on the layering sequence. This highly robust phenomenon is confined within 2 - 3nm of the interface. If such a bilayer is exposed to ozone, T-c exceeds 50 K, and this enhanced superconductivity is also shown to originate from an interface layer about 1 - 2 unit cells thick. Enhancement of T-c in bilayer systems was observed previously(5) but the essential role of the interface was not recognized at the time.
C1 [Gozar, A.; Logvenov, G.; Bollinger, A. T.; Bozovic, I.] Brookhaven Natl Lab, Upton, NY 11973 USA.
   [Kourkoutis, L. Fitting; Muller, D. A.] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
   [Giannuzzi, L. A.] FEI Co, Hillsboro, OR 97124 USA.
C3 United States Department of Energy (DOE); Brookhaven National Laboratory; Cornell University; Thermo Fisher Scientific; FEI Company
RP Bozovic, I (corresponding author), Brookhaven Natl Lab, Upton, NY 11973 USA.
EM bozovic@bnl.gov
FU US DOE; ONR EMMA MURI; Cornell Center for Materials Research; Applied Materials
NR 27
TC 461
Z9 529
U1 10
U2 337
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 782
EP 785
DI 10.1038/nature07293
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900043
PM 18843365
DA 2026-03-09
ER

PT J
AU Arany, Z
   Foo, SY
   Ma, YH
   Ruas, JL
   Bommi-Reddy, A
   Girnun, G
   Cooper, M
   Laznik, D
   Chinsomboon, J
   Rangwala, SM
   Baek, KH
   Rosenzweig, A
   Spiegelman, BM
AF Arany, Zoltan
   Foo, Shi-Yin
   Ma, Yanhong
   Ruas, Jorge L.
   Bommi-Reddy, Archana
   Girnun, Geoffrey
   Cooper, Marcus
   Laznik, Dina
   Chinsomboon, Jessica
   Rangwala, Shamina M.
   Baek, Kwan Hyuck
   Rosenzweig, Anthony
   Spiegelman, Bruce M.
TI HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α
SO NATURE
LA English
DT Article
ID proliferator-activated receptor; controlling mitochondrial biogenesis; skeletal-muscle; gene-expression; err-alpha; pgc-1; metabolism; fibers; drives; cells
AB Ischaemia of the heart, brain and limbs is a leading cause of morbidity and mortality worldwide. Hypoxia stimulates the secretion of vascular endothelial growth factor ( VEGF) and other angiogenic factors, leading to neovascularization and protection against ischaemic injury(1). Here we show that the transcriptional coactivator PGC-1 alpha ( peroxisome- proliferator- activated receptor-gamma coactivator-1 alpha), a potent metabolic sensor and regulator(2), is induced by a lack of nutrients and oxygen, and PGC-1 alpha powerfully regulates VEGF expression and angiogenesis in cultured muscle cells and skeletal muscle in vivo. PGC-1 alpha(-/-) mice show a striking failure to reconstitute blood flow in a normal manner to the limb after an ischaemic insult, whereas transgenic expression of PGC-1 alpha in skeletal muscle is protective. Surprisingly, the induction of VEGF by PGC-1 alpha does not involve the canonical hypoxia response pathway and hypoxia inducible factor ( HIF). Instead, PGC-1 alpha coactivates the orphan nuclear receptor ERR-alpha ( oestrogen- related receptor- alpha) on conserved binding sites found in the promoter and in a cluster within the first intron of the VEGF gene. Thus, PGC-1 alpha and ERR-alpha, major regulators of mitochondrial function in response to exercise and other stimuli, also control a novel angiogenic pathway that delivers needed oxygen and substrates. PGC-1 alpha may provide a novel therapeutic target for treating ischaemic diseases.
C1 [Arany, Zoltan; Ma, Yanhong; Ruas, Jorge L.; Bommi-Reddy, Archana; Girnun, Geoffrey; Cooper, Marcus; Laznik, Dina; Chinsomboon, Jessica; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Arany, Zoltan; Ma, Yanhong; Ruas, Jorge L.; Bommi-Reddy, Archana; Girnun, Geoffrey; Cooper, Marcus; Laznik, Dina; Chinsomboon, Jessica; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Arany, Zoltan; Foo, Shi-Yin; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
   [Arany, Zoltan; Foo, Shi-Yin; Rosenzweig, Anthony] Harvard Stem Cell Inst, Boston, MA 02215 USA.
   [Rangwala, Shamina M.] Novartis Inst Biomed Res Diabet & Metab, Cambridge, MA 02139 USA.
   [Baek, Kwan Hyuck] Harvard Univ, Sch Med, Vasc Biol Program, Dept Surg,Childrens Hosp, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Novartis; Novartis USA; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital
RP Arany, Z (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM zarany1@partners.org; bruce_spiegelman@dfci.harvard.edu
FU NIDDK NIH HHS [P30 DK040561, R01 DK054477] Funding Source: Medline; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK040561] Funding Source: NIH RePORTER
NR 23
TC 903
Z9 1075
U1 1
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 1008
EP U8
DI 10.1038/nature06613
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100052
PM 18288196
DA 2026-03-09
ER

PT J
AU Beebe, K
   Mock, M
   Merriman, E
   Schimmel, P
AF Beebe, Kirk
   Mock, Marissa
   Merriman, Eve
   Schimmel, Paul
TI Distinct domains of tRNA synthetase recognize the same base pair
SO NATURE
LA English
DT Article
ID haemophilus-influenzae ybak; amino-acid; escherichia-coli; major determinant; crystal-structure; cell viability; genetic-code; discrimination; identity; mistranslation
AB Synthesis of proteins containing errors ( mistranslation) is prevented by aminoacyl transfer RNA synthetases through their accurate aminoacylation of cognate tRNAs and their ability to correct occasional errors of aminoacylation by editing reactions(1-5). A principal source of mistranslation comes from mistaking glycine or serine for alanine, which can lead to serious cell and animal pathologies, including neurodegeneration(3). A single specific GNU base pair ( G3 center dot U70) marks a tRNA for aminoacylation by alanyl-tRNA synthetase(6-9). Mistranslation occurs when glycine or serine is joined to the G3 center dot U70- containing tRNAs, and is prevented by the editing activity that clears the mischarged amino acid. Previously it was assumed that the specificity for recognition of tRNA(Ala) for editing was provided by the same structural determinants as used for aminoacylation. Here we show that the editing site of alanyl-tRNA synthetase, as an artificial recombinant fragment, targets mischarged tRNA(Ala) using a structural motif unrelated to that for aminoacylation so that, remarkably, two motifs ( one for aminoacylation and one for editing) in the same enzyme independently can provide determinants for tRNA(Ala) recognition. The structural motif for editing is also found naturally in genome-encoded protein fragments that are widely distributed in evolution(10-12). These also recognize mischarged tRNA(Ala). Thus, through evolution, three different complexes with the same tRNA can guard against mistaking glycine or serine for alanine.
C1 [Beebe, Kirk; Mock, Marissa; Merriman, Eve; Schimmel, Paul] Scripps Res Inst, Dept Mol Biol & Chem, La Jolla, CA 92037 USA.
   [Beebe, Kirk; Mock, Marissa; Merriman, Eve; Schimmel, Paul] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; Scripps Research Institute
RP Schimmel, P (corresponding author), Scripps Res Inst, Dept Mol Biol & Chem, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM schimmel@scripps.edu
NR 29
TC 71
Z9 93
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 JAN 3
PY 2008
VL 451
IS 7174
BP 90
EP U14
DI 10.1038/nature06454
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300040
PM 18172502
DA 2026-03-09
ER

PT J
AU Sánchez-Lavega, A
   Orton, GS
   Hueso, R
   García-Melendo, E
   Pérez-Hoyos, S
   Simon-Miller, A
   Rojas, JF
   Gómez, JM
   Yanamandra-Fisher, P
   Fletcher, L
   Joels, J
   Kemerer, J
   Hora, J
   Karkoschka, E
   de Pater, I
   Wong, MH
   Marcus, PS
   Pinilla-Alonso, N
   Carvalho, F
   Go, C
   Parker, D
   Salway, M
   Valimberti, M
   Wesley, A
   Pujic, Z
AF Sanchez-Lavega, A.
   Orton, G. S.
   Hueso, R.
   Garcia-Melendo, E.
   Perez-Hoyos, S.
   Simon-Miller, A.
   Rojas, J. F.
   Gomez, J. M.
   Yanamandra-Fisher, P.
   Fletcher, L.
   Joels, J.
   Kemerer, J.
   Hora, J.
   Karkoschka, E.
   de Pater, I.
   Wong, M. H.
   Marcus, P. S.
   Pinilla-Alonso, N.
   Carvalho, F.
   Go, C.
   Parker, D.
   Salway, M.
   Valimberti, M.
   Wesley, A.
   Pujic, Z.
TI Depth of a strong jovian jet from a planetary-scale disturbance driven by storms
SO NATURE
LA English
DT Article
ID deep zonal winds; moist convection; nonlinear simulations; 3-dimensional model; jupiters atmosphere; giant planets; stability; dynamics; cassini; galileo
AB The atmospheres of the gas giant planets ( Jupiter and Saturn) contain jets that dominate the circulation at visible levels(1,2). The power source for these jets ( solar radiation, internal heat, or both) and their vertical structure below the upper cloud are major open questions in the atmospheric circulation and meteorology of giant planets(1-3). Several observations(1) and in situ measurements(4) found intense winds at a depth of 24 bar, and have been interpreted as supporting an internal heat source. This issue remains controversial(5), in part because of effects from the local meteorology(6). Here we report observations and modelling of two plumes in Jupiter's atmosphere that erupted at the same latitude as the strongest jet ( 23 degrees N). The plumes reached a height of 30 km above the surrounding clouds, moved faster than any other feature ( 169 m s(-1)), and left in their wake a turbulent planetary- scale disturbance containing red aerosols. On the basis of dynamical modelling, we conclude that the data are consistent only with a wind that extends well below the level where solar radiation is deposited.
C1 [Sanchez-Lavega, A.; Hueso, R.; Perez-Hoyos, S.] Univ Basque Country, ETS Ingenieros, Dept Fis Aplicada 1, Bilbao 48013, Spain.
   [Orton, G. S.; Yanamandra-Fisher, P.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Garcia-Melendo, E.; Gomez, J. M.] Esteve Duran Observ Fdn, Seva 085330, Spain.
   [Simon-Miller, A.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Rojas, J. F.] Univ Basque Country, EUITI, Dept Fis Aplicada 1, Bilbao 48013, Spain.
   [Fletcher, L.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
   [Joels, J.] Principia Coll, Elsah, IL 62028 USA.
   [Kemerer, J.] Calif State Polytech Univ Pomona, Pomona, CA 91768 USA.
   [Hora, J.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Karkoschka, E.] Univ Arizona, Tucson, AZ 85721 USA.
   [de Pater, I.; Wong, M. H.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Marcus, P. S.] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA.
   [Pinilla-Alonso, N.] Telescopio Nazl Galileo Galilei, Santa Cruz De La Palma 38700, Spain.
   [Carvalho, F.] Ctr Estudos Universo, BR-17380000 Brotas, Brazil.
   [Go, C.] Univ San Carlos, Dept Phys, Cebu 6000, Philippines.
   [Parker, D.] Assoc Lunar & Planetary Observers, Coral Gables, FL 33156 USA.
   [Salway, M.] IcelnSpace, Wyoming, NSW 2250, Australia.
   [Valimberti, M.] Astron Soc Victoria, Melbourne, Vic 3001, Australia.
   [Wesley, A.] Math & Comp Sci, Murrumbateman 2582, Australia.
C3 University of Basque Country; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Basque Country; University of Oxford; California State University System; California State Polytechnic University Pomona; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; University of Arizona; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of San Carlos
RP Sánchez-Lavega, A (corresponding author), Univ Basque Country, ETS Ingenieros, Dept Fis Aplicada 1, Alameda Urquijo S-N, Bilbao 48013, Spain.
EM agustin.sanchez@ehu.es
FU Direct For Mathematical & Physical Scien [0808200] Funding Source: National Science Foundation; Division Of Astronomical Sciences [0808200] Funding Source: National Science Foundation
NR 25
TC 83
Z9 90
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 24
PY 2008
VL 451
IS 7177
BP 437
EP 440
DI 10.1038/nature06533
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100038
PM 18216848
DA 2026-03-09
ER

PT J
AU Koerich, LB
   Wang, XY
   Clark, AG
   Carvalho, AB
AF Koerich, Leonardo B.
   Wang, Xiaoyun
   Clark, Andrew G.
   Carvalho, Antonio Bernardo
TI Low conservation of gene content in the Drosophila Y chromosome
SO NATURE
LA English
DT Article
ID sex-chromosome; melanogaster; genome; evolution; sequence; degeneration; elements; region; scale
AB Chromosomal organization is sufficiently evolutionarily stable that large syntenic blocks of genes can be recognized even between species as distantly related as mammals and puffer fish ( 450 million years (Myr) of divergence)(1-7). In Diptera, the gene content of the X chromosome and the autosomes is well conserved: in Drosophila more than 95% of the genes have remained on the same chromosome arm in the 12 sequenced species ( 63 Myr of divergence, traversing 400 Myr of evolution) 2,4,6, and the same linkage groups are clearly recognizable in mosquito genomes (260 Myr of divergence)(3,5,7). Here we investigate the conservation of Y- linked gene content among the 12 sequenced Drosophila species. We found that only a quarter of the Drosophila melanogaster Y- linked genes ( 3 out of 12) are Y- linked in all sequenced species, and that most of them ( 7 out of 12) were acquired less than 63 Myr ago. Hence, whereas the organization of other Drosophila chromosomes traces back to the common ancestor with mosquitoes, the gene content of the D. melanogaster Y chromosome is much younger. Gene losses are known to have an important role in the evolution of Y chromosomes(8-10), and we indeed found two such cases. However, the rate of gene gain in the Drosophila Y chromosomes investigated is 10.9 times higher than the rate of gene loss ( 95% confidence interval: 2.3 - 52.5), indicating a clear tendency of the Y chromosomes to increase in gene content. In contrast with the mammalian Y chromosome, gene gains have a prominent role in the evolution of the Drosophila Y chromosome.
C1 [Koerich, Leonardo B.; Carvalho, Antonio Bernardo] Univ Fed Rio de Janeiro, Dept Genet, BR-21944970 Rio De Janeiro, Brazil.
   [Wang, Xiaoyun; Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
C3 Universidade Federal do Rio de Janeiro; Cornell University
RP Carvalho, AB (corresponding author), Univ Fed Rio de Janeiro, Dept Genet, Caixa Postal 68011, BR-21944970 Rio De Janeiro, Brazil.
EM bernardo@biologia.ufrj.br
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq; Coordenacao de Aperfeicoamento do Pessoal de Ensino Superior-CAPES; FAPERJ; FIC-NIH [TW007604-02]; NIH [GM64590]
NR 30
TC 120
Z9 144
U1 2
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 DEC 18
PY 2008
VL 456
IS 7224
BP 949
EP 951
DI 10.1038/nature07463
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300045
PM 19011613
DA 2026-03-09
ER

PT J
AU Lin, GN
   Xu, N
   Xi, RW
AF Lin, Guonan
   Xu, Na
   Xi, Rongwen
TI Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells
SO NATURE
LA English
DT Article
ID expression; armadillo; niche; protein; midgut; shaggy; roles; fates
AB In the Drosophila midgut, multipotent intestinal stem cells (ISCs) that are scattered along the epithelial basement membrane maintain tissue homeostasis by their ability to steadily produce daughters that differentiate into either enterocytes or enteroendocrine cells, depending on the levels of Notch activity(1-3). However, the mechanisms controlling ISC self- renewal remain elusive. Here we show that a canonical Wnt signalling pathway controls ISC self-renewal. The ligand Wingless (Wg) is specifically expressed in the circular muscles next to ISCs, separated by a thin layer of basement membrane. Reduced function of wg causes ISC quiescence and differentiation, whereas wg overexpression produces excessive ISC- like cells that express high levels of the Notch ligand, Delta. Clonal analysis shows that the main downstream components of the Wg pathway, including Frizzled, Dishevelled and Armadillo, are autonomously required for ISC self- renewal. Furthermore, epistatic analysis suggests that Notch acts downstream of the Wg pathway and a hierarchy of Wg/Notch signalling pathways controls the balance between self- renewal and differentiation of ISCs. These data suggest that the underlying circular muscle constitutes the ISC niche, which produce Wg signals that act directly on ISCs to promote ISC self-renewal. This study demonstrates markedly conserved mechanisms regulating ISCs from Drosophila to mammals. The identification of the Drosophila ISC niche and the principal self- renewal signal will facilitate further understanding of intestinal homeostasis control and tumorigenesis.
C1 [Lin, Guonan; Xu, Na; Xi, Rongwen] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Lin, Guonan] Peking Union Med Coll, Grad Program, Beijing 100730, Peoples R China.
   [Lin, Guonan] Chinese Acad Med Sci, Beijing 100730, Peoples R China.
C3 National Institute of Biological Sciences, Beijing; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College
RP Xi, RW (corresponding author), Natl Inst Biol Sci, 7 Sci Pk Rd,Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China.
EM xirongwen@nibs.ac.cn
FU Chinese Ministry of Science and Technology [2007AA02Z1A2]
NR 24
TC 277
Z9 318
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1119
EP U11
DI 10.1038/nature07329
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600047
PM 18806781
DA 2026-03-09
ER

PT J
AU Ito, K
   Bernardi, R
   Morotti, A
   Matsuoka, S
   Saglio, G
   Ikeda, Y
   Rosenblatt, J
   Avigan, DE
   Teruya-Feldstein, J
   Pandolfi, PP
AF Ito, Keisuke
   Bernardi, Rosa
   Morotti, Alessandro
   Matsuoka, Sahoko
   Saglio, Giuseppe
   Ikeda, Yasuo
   Rosenblatt, Jacalyn
   Avigan, David E.
   Teruya-Feldstein, Julie
   Pandolfi, Pier Paolo
TI PML targeting eradicates quiescent leukaemia-initiating cells
SO NATURE
LA English
DT Article
ID chronic myelogenous leukemia; acute promyelocytic leukemia; hematopoietic stem-cells; imatinib mesylate; retinoic acid; myeloid-leukemia; arsenic trioxide; cancer; discontinuation; remission
AB The existence of a small population of 'cancer-initiating cells' responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells, particularly those that are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies, resulting in disease relapse. Chronic myeloid leukaemia is a paradigmatic haematopoietic stem cell disease in which the leukaemia-initiating-cell pool is not eradicated by current therapy, leading to disease relapse on drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in haematopoietic stem cell maintenance, and present a new therapeutic approach for targeting quiescent leukaemia-initiating cells and possibly cancer-initiating cells by pharmacological inhibition of PML.
C1 [Ito, Keisuke; Bernardi, Rosa; Morotti, Alessandro; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Canc Genet Program, Beth Israel Deaconess Canc Ctr,Dept Med, Boston, MA 02215 USA.
   [Ito, Keisuke; Bernardi, Rosa; Morotti, Alessandro; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Canc Genet Program, Beth Israel Deaconess Canc Ctr,Dept Pathol, Boston, MA 02215 USA.
   [Rosenblatt, Jacalyn; Avigan, David E.] Harvard Univ, Sch Med, Div Hematol & Oncol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Ito, Keisuke; Bernardi, Rosa; Morotti, Alessandro; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA.
   [Ito, Keisuke; Bernardi, Rosa; Morotti, Alessandro; Teruya-Feldstein, Julie; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
   [Matsuoka, Sahoko; Ikeda, Yasuo] Keio Univ, Sch Med, Div Hematol, Dept Internal Med,Shinjuku Ku, Tokyo 1608582, Japan.
   [Saglio, Giuseppe] Univ Turin, Div Hematol & Internal Med, Dept Clin & Biol Sci, I-10043 Turin, Italy.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Keio University; University of Turin
RP Pandolfi, PP (corresponding author), Harvard Univ, Sch Med, Canc Genet Program, Beth Israel Deaconess Canc Ctr,Dept Med, New Res Bldg,330 Brookline Ave, Boston, MA 02215 USA.
EM ppandolf@bidmc.harvard.edu
FU NCI NIH HHS [R37 CA071692, R00 CA139009, K99 CA139009] Funding Source: Medline
NR 45
TC 465
Z9 522
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 19
PY 2008
VL 453
IS 7198
BP 1072
EP U4
DI 10.1038/nature07016
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900050
PM 18469801
DA 2026-03-09
ER

PT J
AU Sakai, W
   Swisher, EM
   Karlan, BY
   Agarwal, MK
   Higgins, J
   Friedman, C
   Villegas, E
   Jacquemont, C
   Farrugia, DJ
   Couch, FJ
   Urban, N
   Taniguchi, T
AF Sakai, Wataru
   Swisher, Elizabeth M.
   Karlan, Beth Y.
   Agarwal, Mukesh K.
   Higgins, Jake
   Friedman, Cynthia
   Villegas, Emily
   Jacquemont, Celine
   Farrugia, Daniel J.
   Couch, Fergus J.
   Urban, Nicole
   Taniguchi, Toshiyasu
TI Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
SO NATURE
LA English
DT Article
ID homology-directed repair; brca mutant-cells; fanconi-anemia; ovarian-cancer; breast-cancer; in-vivo; pathway; gene; inhibitors; defect
AB Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds(1). However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown(2). Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wildtype BRCA2 reading frame. First, in a cisplatin- resistant BRCA2-mutated breast- cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2- mutated pancreatic cancer cell line, Capan- 1 ( refs 3, 4), led to five different secondary mutations that restored the wild- type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly( ADP- ribose) polymerase ( PARP) inhibitor ( AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2- mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild- type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum- based chemotherapy.
C1 [Sakai, Wataru; Friedman, Cynthia; Villegas, Emily; Jacquemont, Celine; Taniguchi, Toshiyasu] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
   [Sakai, Wataru; Villegas, Emily; Jacquemont, Celine; Urban, Nicole; Taniguchi, Toshiyasu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
   [Swisher, Elizabeth M.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
   [Swisher, Elizabeth M.; Higgins, Jake] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Karlan, Beth Y.] Cedars Sinai Med Ctr, Womens Canc Res Inst, Los Angeles, CA 90048 USA.
   [Agarwal, Mukesh K.; Farrugia, Daniel J.; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
   [Higgins, Jake] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
C3 Fred Hutchinson Cancer Center; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Cedars Sinai Medical Center; Mayo Clinic; University of Washington; University of Washington Seattle
RP Taniguchi, T (corresponding author), Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
EM ttaniguc@fhcrc.org
FU NCI NIH HHS [R01 CA125636, K08 CA096610, P50 CA083636] Funding Source: Medline
NR 39
TC 911
Z9 1037
U1 0
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1116
EP U9
DI 10.1038/nature06633
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600044
PM 18264087
DA 2026-03-09
ER

PT J
AU Segal, E
   Raveh-Sadka, T
   Schroeder, M
   Unnerstall, U
   Gaul, U
AF Segal, Eran
   Raveh-Sadka, Tali
   Schroeder, Mark
   Unnerstall, Ulrich
   Gaul, Ulrike
TI Predicting expression patterns from regulatory sequence in Drosophila segmentation
SO NATURE
LA English
DT Article
ID transcription-factor binding; cooperative dna-binding; gene-expression; morphogen gradient; direct repression; dependent manner; in-vivo; embryo; melanogaster; polarity
AB The establishment of complex expression patterns at precise times and locations is key to metazoan development, yet a mechanistic understanding of the underlying transcription control networks is still missing. Here we describe a novel thermodynamic model that computes expression patterns as a function of cis- regulatory sequence and of the binding- site preferences and expression of participating transcription factors. We apply this model to the segmentation gene network of Drosophila melanogaster and find that it predicts expression patterns of cis- regulatory modules with remarkable accuracy, demonstrating that positional information is encoded in the regulatory sequence and input factor distribution. Our analysis reveals that both strong and weaker binding sites contribute, leading to high occupancy of the module DNA, and conferring robustness against mutation; short- range homotypic clustering of weaker sites facilitates cooperative binding, which is necessary to sharpen the patterns. Our computational framework is generally applicable to most protein - DNA interaction systems.
C1 [Segal, Eran; Raveh-Sadka, Tali] Weizmann Inst Sci, Dept Appl Math & Comp Sci, IL-76100 Rehovot, Israel.
   [Schroeder, Mark; Unnerstall, Ulrich; Gaul, Ulrike] Rockefeller Univ, Lab Dev Neurogenet, New York, NY 10065 USA.
C3 Weizmann Institute of Science; Rockefeller University
RP Segal, E (corresponding author), Weizmann Inst Sci, Dept Appl Math & Comp Sci, IL-76100 Rehovot, Israel.
EM eran@weizmann.ac.il; gaul@mail.rockefeller.edu
NR 48
TC 367
Z9 468
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 JAN 31
PY 2008
VL 451
IS 7178
BP 535
EP U1
DI 10.1038/nature06496
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900033
PM 18172436
DA 2026-03-09
ER

PT J
AU Wille, M
   Nägler, TF
   Lehmann, B
   Schröder, S
   Kramers, JD
AF Wille, Martin
   Naegler, Thomas F.
   Lehmann, Bernd
   Schroeder, Stefan
   Kramers, Jan D.
TI Hydrogen sulphide release to surface waters at the Precambrian/Cambrian boundary
SO NATURE
LA English
DT Article
ID cambrian black shales; northwestern hunan; south china; re-os; record; carbon; geochemistry; transition; anoxia; margin
AB Animal- like multicellular fossils appeared towards the end of the Precambrian, followed by a rapid increase in the abundance and diversity of fossils during the Early Cambrian period, an event also known as the 'Cambrian explosion'(1-3). Changes in the environmental conditions at the Precambrian/ Cambrian transition ( about 542 Myr ago) have been suggested as a possible explanation for this event, but are still a matter of debate(1-3). Here we report molybdenum isotope signatures of black shales from two stratigraphically correlated sample sets with a depositional age of around 542 Myr. We find a transient molybdenum isotope signal immediately after the Precambrian/ Cambrian transition. Using a box model of the oceanic molybdenum cycle, we find that intense upwelling of hydrogen sulphide- rich deep ocean water best explains the observed Early Cambrian molybdenum isotope signal. Our findings suggest that the Early Cambrian animal radiation may have been triggered by a major change in ocean circulation, terminating a long period during which the Proterozoic ocean was stratified, with sulphidic deep water.
C1 [Wille, Martin; Naegler, Thomas F.; Kramers, Jan D.] Univ Bern, Inst Geol Sci, CH-3012 Bern, Switzerland.
   [Lehmann, Bernd] Tech Univ Clausthal, Inst Mineral & Mineral Resources, D-38678 Clausthal Zellerfeld, Germany.
   [Schroeder, Stefan] MIT, Cambridge, MA 02139 USA.
C3 University of Bern; TU Clausthal; Massachusetts Institute of Technology (MIT)
RP Wille, M (corresponding author), Univ Bern, Inst Geol Sci, Baltzerstr 3, CH-3012 Bern, Switzerland.
EM martin.wille@anu.edu.au
NR 28
TC 229
Z9 276
U1 2
U2 92
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2008
VL 453
IS 7196
BP 767
EP 769
DI 10.1038/nature07072
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300040
PM 18509331
DA 2026-03-09
ER

PT J
AU Knesel, KM
   Cohen, BE
   Vasconcelos, PM
   Thiede, DS
AF Knesel, Kurt M.
   Cohen, Benjamin E.
   Vasconcelos, Paulo M.
   Thiede, David S.
TI Rapid change in drift of the Australian plate records collision with Ontong Java plateau
SO NATURE
LA English
DT Article
ID solomon-islands; oceanic plateaus; earths mantle; k-ar; hotspots; pacific; motion; geochronology; seamounts; volcanism
AB The subduction of oceanic plateaux, which contain extraordinarily thick basaltic crust and are the marine counterparts of continental flood-basalt provinces, is an important factor in many current models of plate motion(1-4) and provides a potential mechanism for triggering plate reorganization(5). To evaluate such models, it is essential to decipher the history of the collision between the largest and thickest of the world's oceanic plateaux, the Ontong Java plateau, and the Australian plate, but this has been hindered by poor constraints for the arrival of the plateau at the Melanesian trench. Here we present (40)Ar-(39)Ar geochronological data on hotspot volcanoes in eastern Australian that reveal a strong link between collision of the Greenland-sized Ontong Java plateau with the Melanesian arc and motion of the Australian plate. The new ages define a short-lived period of reduced northward plate motion between 26 and 23 Myr ago, coincident with an eastward offset in the contemporaneous tracks of seamount chains in the Tasman Sea east of Australia. These features record a brief westward deflection of the Australian plate as the plateau entered and choked the Melanesian trench 26 Myr ago. From 23 Myr ago, Australia returned to a rapid northerly trajectory at roughly the same time that southwest-directed subduction began along the Trobriand trough(6). The timing and brevity of this collisional event correlate well with offsets in hotspot seamount tracks on the Pacific plate, including the archetypal Hawaiian chain(7), and thus provide strong evidence that immense oceanic plateaux, like the Ontong Java, can contribute to initiating rapid change in plate boundaries and motions on a global scale.
C1 [Knesel, Kurt M.; Cohen, Benjamin E.; Vasconcelos, Paulo M.; Thiede, David S.] Univ Queensland, St Lucia, Qld 4072, Australia.
C3 University of Queensland
RP Knesel, KM (corresponding author), Univ Queensland, St Lucia, Qld 4072, Australia.
EM k.knesel@uq.edu.au; b.cohen@uq.edu.au
NR 40
TC 107
Z9 117
U1 1
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 754
EP U75
DI 10.1038/nature07138
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000042
PM 18685705
DA 2026-03-09
ER

PT J
AU Bosmans, F
   Martin-Eauclaire, MF
   Swartz, KJ
AF Bosmans, Frank
   Martin-Eauclaire, Marie-France
   Swartz, Kenton J.
TI Deconstructing voltage sensor function and pharmacology in sodium channels
SO NATURE
LA English
DT Article
ID alpha-scorpion toxin; dependent k+ channel; potassium channel; gating modifier; skeletal-muscle; molecular determinants; tarantula toxins; ionic currents; rat-brain; domain iv
AB Voltage- activated sodium (Na-v) channels are crucial for the generation and propagation of nerve impulses, and as such are widely targeted by toxins and drugs. The four voltage sensors in Na-v channels have distinct amino acid sequences, raising fundamental questions about their relative contributions to the function and pharmacology of the channel. Here we use four- fold symmetric voltage- activated potassium ( K-v) channels as reporters to examine the contributions of individual S3b-S4 paddle motifs within Na-v channel voltage sensors to the kinetics of voltage sensor activation and to forming toxin receptors. Our results uncover binding sites for toxins from tarantula and scorpion venom on each of the four paddle motifs in Nav channels, and reveal how paddle- specific interactions can be used to reshape Na-v channel activity. One paddle motif is unique in that it slows voltage sensor activation, and toxins selectively targeting this motif impede Na-v channel inactivation. This reporter approach and the principles that emerge will be useful in developing new drugs for treating pain and Na-v channelopathies.
C1 [Bosmans, Frank; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Bosmans, Frank] Catholic Univ Louvain, Toxicol Lab, B-3000 Louvain, Belgium.
   [Martin-Eauclaire, Marie-France] Univ Mediterranee, CNRS, Inst Jean Roche, UMR 6231,CRN2M, Marseille, France.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); Universite Catholique Louvain; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS)
RP Swartz, KJ (corresponding author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM swartzk@ninds.nih.gov
FU Intramural Research Program; NINDS; NIH; NIH- FWO postdoctoral fellowship
NR 62
TC 236
Z9 273
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 NOV 13
PY 2008
VL 456
IS 7219
BP 202
EP U28
DI 10.1038/nature07473
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300032
PM 19005548
DA 2026-03-09
ER

PT J
AU Tottey, S
   Waldron, KJ
   Firbank, SJ
   Reale, B
   Bessant, C
   Sato, K
   Cheek, TR
   Gray, J
   Banfield, MJ
   Dennison, C
   Robinson, NJ
AF Tottey, Steve
   Waldron, Kevin J.
   Firbank, Susan J.
   Reale, Brian
   Bessant, Conrad
   Sato, Katsuko
   Cheek, Timothy R.
   Gray, Joe
   Banfield, Mark J.
   Dennison, Christopher
   Robinson, Nigel J.
TI Protein-folding location can regulate manganese-binding versus copper- or zinc-binding
SO NATURE
LA English
DT Article
ID oxalate decarboxylase; quercetin 2,3-dioxygenase; bacillus-subtilis; sensitivity; expression; chaperone; pathway; yeast; epr
AB Metals are needed by at least one-quarter of all proteins(1,2). Although metallochaperones(3-8) insert the correct metal into some proteins, they have not been found for the vast majority, and the view is that most metalloproteins acquire their metals directly from cellular pools. However, some metals form more stable complexes with proteins than do others. For instance, as described in the Irving Williams series(9), Cu2+ and Zn2+ typically form more stable complexes than Mn2+. Thus it is unclear what cellular mechanisms manage metal acquisition by most nascent proteins. To investigate this question, we identified the most abundant Cu2+-protein, CucA (Cu2+- cupin A), and the most abundant Mn2+- protein, MncA (Mn2+- cupin A), in the periplasm of the cyanobacterium Synechocystis PCC 6803. Each of these newly identified proteins binds its respective metal via identical ligands within a cupin fold. Consistent with the Irving - Williams series, MncA only binds Mn2+ after folding in solutions containing at least a 10(4) times molar excess of Mn2+ over Cu2+ or Zn2+. However once MncA has bound Mn2+, the metal does not exchange with Cu2+. MncA and CucA have signal peptides for different export pathways into the periplasm, Tat and Sec respectively. Export by the Tat pathway allows MncA to fold in the cytoplasm, which contains only tightly bound copper or Zn2+ ( refs 10-12) but micromolar Mn2+ ( ref. 13). In contrast, CucA folds in the periplasm to acquire Cu2+. These results reveal a mechanism whereby the compartment in which a protein folds overrides its binding preference to control its metal content. They explain why the cytoplasm must contain only tightly bound and buffered copper and Zn2+.
C1 [Tottey, Steve; Waldron, Kevin J.; Firbank, Susan J.; Reale, Brian; Sato, Katsuko; Cheek, Timothy R.; Gray, Joe; Banfield, Mark J.; Dennison, Christopher; Robinson, Nigel J.] Univ Newcastle, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Bessant, Conrad] Cranfield Univ, Cranfield Bioinformat Grp, Cranfield MK43 0AL, Beds, England.
C3 Newcastle University - UK; Cranfield University
RP Robinson, NJ (corresponding author), Univ Newcastle, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM n.j.robinson@ncl.ac.uk
FU BBSRC PMS committee [BBS/B/02576, BB/E001688/1]; J. Gitlin and the Children's Discovery Institute; Royal Society University Research Fellow; Biotechnology and Biological Sciences Research Council [BBS/B/02576, BB/E001688/1] Funding Source: researchfish; Medical Research Council [G0600759, G0500367] Funding Source: researchfish; BBSRC [BB/E001688/1] Funding Source: UKRI; MRC [G0600759, G0500367] Funding Source: UKRI
NR 42
TC 260
Z9 313
U1 1
U2 140
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1138
EP U17
DI 10.1038/nature07340
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600051
PM 18948958
DA 2026-03-09
ER

PT J
AU Stark, DP
   Swinbank, AM
   Ellis, RS
   Dye, S
   Smail, IR
   Richard, J
AF Stark, Daniel P.
   Swinbank, A. Mark
   Ellis, Richard S.
   Dye, Simon
   Smail, Ian R.
   Richard, Johan
TI The formation and assembly of a typical star-forming galaxy at redshift z≈3
SO NATURE
LA English
DT Article
ID gas; z-similar-to-2; constraints
AB Recent studies of galaxies similar to 2-3 Gyr after the Big Bang have revealed large, rotating disks, similar to those of galaxies today(1,2). The existence of well- ordered rotation in galaxies during this peak epoch of cosmic star formation indicates that gas accretion is likely to be the dominant mode by which galaxies grow, because major mergers of galaxies would completely disrupt the observed velocity fields. But poor spatial resolution and sensitivity have hampered this interpretation; such studies have been limited to the largest and most luminous galaxies, which may have fundamentally different modes of assembly from those of more typical galaxies ( which are thought to grow into the spheroidal components at the centres of galaxies similar to the Milky Way). Here we report observations of a typical star- forming galaxy at z = 3.07, with a linear resolution of similar to 100 parsecs. We find a well- ordered compact source in which molecular gas is being converted efficiently into stars, likely to be assembling a spheroidal bulge similar to those seen in spiral galaxies at the present day. The presence of undisrupted rotation may indicate that galaxies such as the Milky Way gain much of their mass by accretion rather than major mergers.
C1 [Stark, Daniel P.; Ellis, Richard S.; Richard, Johan] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Swinbank, A. Mark; Smail, Ian R.] Univ Durham, Inst Computat Cosmol, Durham DH1 3LE, England.
   [Dye, Simon] Cardiff Univ, Sch Phys & Astron, Cardiff CF24 3AA, Wales.
C3 California Institute of Technology; Durham University; Cardiff University
RP Stark, DP (corresponding author), CALTECH, Dept Astron, Pasadena, CA 91125 USA.
EM dps@astro.caltech.edu
FU W. M. Keck Foundation; STFC; Royal Society; Science and Technology Facilities Council [ST/F002963/1] Funding Source: researchfish; STFC [ST/F002963/1] Funding Source: UKRI
NR 23
TC 144
Z9 164
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 OCT 9
PY 2008
VL 455
IS 7214
BP 775
EP 777
DI 10.1038/nature07294
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900041
PM 18843363
DA 2026-03-09
ER

PT J
AU Chandra, V
   Huang, PX
   Hamuro, Y
   Raghuram, S
   Wang, YJ
   Burris, TP
   Rastinejad, F
AF Chandra, Vikas
   Huang, Pengxiang
   Hamuro, Yoshitomo
   Raghuram, Srilatha
   Wang, Yongjun
   Burris, Thomas P.
   Rastinejad, Fraydoon
TI Structure of the intact PPAR-γ-RXR-α nuclear receptor complex on DNA
SO NATURE
LA English
DT Article
ID proliferator-activated receptors; retinoid-x-receptor; rev-erb-alpha; ligand-binding; allosteric control; domain; identification; mechanism; polarity; agonists
AB Nuclear receptors are multi- domain transcription factors that bind to DNA elements from which they regulate gene expression. The peroxisome proliferator- activated receptors ( PPARs) form heterodimers with the retinoid X receptor ( RXR), and PPAR-gamma has been intensively studied as a drug target because of its link to insulin sensitization. Previous structural studies have focused on isolated DNA or ligand- binding segments, with no demonstration of how multiple domains cooperate to modulate receptor properties. Here we present structures of intact PPAR-gamma and RXR-alpha as a heterodimer bound to DNA, ligands and coactivator peptides. PPAR-gamma and RXR-alpha form a non- symmetric complex, allowing the ligand- binding domain ( LBD) of PPAR-gamma to contact multiple domains in both proteins. Three interfaces link PPAR-gamma and RXR-alpha, including some that are DNA dependent. The PPAR-gamma LBD cooperates with both DNA- binding domains ( DBDs) to enhance response- element binding. The A/B segments are highly dynamic, lacking folded substructures despite their gene- activation properties.
C1 [Chandra, Vikas; Huang, Pengxiang; Raghuram, Srilatha; Rastinejad, Fraydoon] Univ Virginia Hlth Syst, Dept Pharmacol, Charlottesville, VA 22908 USA.
   [Chandra, Vikas; Huang, Pengxiang; Raghuram, Srilatha; Rastinejad, Fraydoon] Univ Virginia Hlth Syst, Ctr Mol Design, Charlottesville, VA 22908 USA.
   [Hamuro, Yoshitomo] ExSAR Corp, Monmouth Jct, NJ 08852 USA.
   [Wang, Yongjun; Burris, Thomas P.] Louisiana State Univ, Pennington Biomed Res Ctr, Nucl Receptor Biol Lab, Baton Rouge, LA 70808 USA.
C3 University of Virginia; University of Virginia (UVA) Health System; University of Virginia; University of Virginia (UVA) Health System; Louisiana State University System; Louisiana State University; Pennington Biomedical Research Center
RP Rastinejad, F (corresponding author), Univ Virginia Hlth Syst, Dept Pharmacol, 1300 Jefferson Pk Ave, Charlottesville, VA 22908 USA.
EM fr9c@virginia.edu
FU NIGMS NIH HHS [R01 GM055217] Funding Source: Medline
NR 49
TC 664
Z9 801
U1 5
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 NOV 20
PY 2008
VL 456
IS 7220
BP 350
EP U33
DI 10.1038/nature07413
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600035
PM 19043829
DA 2026-03-09
ER

PT J
AU Stricker, J
   Cookson, S
   Bennett, MR
   Mather, WH
   Tsimring, LS
   Hasty, J
AF Stricker, Jesse
   Cookson, Scott
   Bennett, Matthew R.
   Mather, William H.
   Tsimring, Lev S.
   Hasty, Jeff
TI A fast, robust and tunable synthetic gene oscillator
SO NATURE
LA English
DT Article
ID escherichia-coli; toggle switch; expression; networks; circuits; biology; protein; cells
AB One defining goal of synthetic biology is the development of engineering- based approaches that enable the construction of gene- regulatory networks according to 'design specifications' generated from computational modelling(1-6). This approach provides a systematic framework for exploring how a given regulatory network generates a particular phenotypic behaviour. Several fundamental gene circuits have been developed using this approach, including toggle switches(7) and oscillators(8-10), and these have been applied in new contexts such as triggered biofilm development(11) and cellular population control(12). Here we describe an engineered genetic oscillator in Escherichia coli that is fast, robust and persistent, with tunable oscillatory periods as fast as 13 min. The oscillator was designed using a previously modelled network architecture comprising linked positive and negative feedback loops(1,13). Using a microfluidic platform tailored for single- cell microscopy, we precisely control environmental conditions and monitor oscillations in individual cells through multiple cycles. Experiments reveal remarkable robustness and persistence of oscillations in the designed circuit; almost every cell exhibited large- amplitude fluorescence oscillations throughout observation runs. The oscillatory period can be tuned by altering inducer levels, temperature and the media source. Computational modelling demonstrates that the key design principle for constructing a robust oscillator is a time delay in the negative feedback loop, which can mechanistically arise from the cascade of cellular processes involved in forming a functional transcription factor. The positive feedback loop increases the robustness of the oscillations and allows for greater tunability. Examination of our refined model suggested the existence of a simplified oscillator design without positive feedback, and we construct an oscillator strain confirming this computational prediction.
C1 [Stricker, Jesse; Cookson, Scott; Bennett, Matthew R.; Mather, William H.; Hasty, Jeff] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Bennett, Matthew R.; Tsimring, Lev S.; Hasty, Jeff] Univ Calif San Diego, Inst Nonlinear Sci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego
RP Hasty, J (corresponding author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
EM hasty@bioeng.ucsd.edu
FU National Institutes of Health [GM69811-01]; US Department of Defense; National Institute of General Medical Sciences [R01GM069811] Funding Source: NIH RePORTER
NR 30
TC 844
Z9 1097
U1 4
U2 333
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 516
EP U39
DI 10.1038/nature07389
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500041
PM 18971928
DA 2026-03-09
ER

PT J
AU Thakur, JK
   Arthanari, H
   Yang, FJ
   Pan, SJ
   Fan, XC
   Breger, J
   Frueh, DP
   Gulshan, K
   Li, DK
   Mylonakis, E
   Struhl, K
   Moye-Rowley, WS
   Cormack, BP
   Wagner, G
   Näär, AM
AF Thakur, Jitendra K.
   Arthanari, Haribabu
   Yang, Fajun
   Pan, Shih-Jung
   Fan, Xiaochun
   Breger, Julia
   Frueh, Dominique P.
   Gulshan, Kailash
   Li, Darrick K.
   Mylonakis, Eleftherios
   Struhl, Kevin
   Moye-Rowley, W. Scott
   Cormack, Brendan P.
   Wagner, Gerhard
   Naar, Anders M.
TI A nuclear receptor-like pathway regulating multidrug resistance in fungi
SO NATURE
LA English
DT Article
ID transcription-factor-binding; drug-resistance; saccharomyces-cerevisiae; transactivation domain; cassette transporter; secondary structure; candida-glabrata; nmr-spectroscopy; azole resistance; kix domain
AB Multidrug resistance ( MDR) is a serious complication during treatment of opportunistic fungal infections that frequently afflict immunocompromised individuals, such as transplant recipients and cancer patients undergoing cytotoxic chemotherapy. Improved knowledge of the molecular pathways controlling MDR in pathogenic fungi should facilitate the development of novel therapies to combat these intransigent infections. MDR is often caused by upregulation of drug efflux pumps by members of the fungal zinc- cluster transcription- factor family ( for example Pdr1p orthologues). However, the molecular mechanisms are poorly understood. Here we show that Pdr1p family members in Saccharomyces cerevisiae and the human pathogen Candida glabrata directly bind to structurally diverse drugs and xenobiotics, resulting in stimulated expression of drug efflux pumps and induction of MDR. Notably, this is mechanistically similar to regulation of MDR in vertebrates by the PXR nuclear receptor, revealing an unexpected functional analogy of fungal and metazoan regulators of MDR. We have also uncovered a critical and specific role of the Gal11p/ MED15 subunit of the Mediator co- activator and its activator- targeted KIX domain in antifungal/ xenobiotic- dependent regulation of MDR. This detailed mechanistic understanding of a fungal nuclear receptor- like gene regulatory pathway provides novel therapeutic targets for the treatment of multidrug- resistant fungal infections.
C1 [Thakur, Jitendra K.; Yang, Fajun; Li, Darrick K.; Naar, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
   [Thakur, Jitendra K.; Yang, Fajun; Naar, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Arthanari, Haribabu; Fan, Xiaochun; Frueh, Dominique P.; Struhl, Kevin; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Pan, Shih-Jung; Cormack, Brendan P.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
   [Breger, Julia; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
   [Gulshan, Kailash; Moye-Rowley, W. Scott] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Johns Hopkins University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Iowa
RP Näär, AM (corresponding author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM naar@helix.mgh.harvard.edu
FU NCI NIH HHS [CA127990, R01 CA127990] Funding Source: Medline; NIBIB NIH HHS [EB2026] Funding Source: Medline; NIGMS NIH HHS [GM47467, GM30186, GM49825, GM071449] Funding Source: Medline; PHS HHS [A1046223] Funding Source: Medline
NR 60
TC 278
Z9 345
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 APR 3
PY 2008
VL 452
IS 7187
BP 604
EP U4
DI 10.1038/nature06836
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200039
PM 18385733
DA 2026-03-09
ER

PT J
AU Pillow, JW
   Shlens, J
   Paninski, L
   Sher, A
   Litke, AM
   Chichilnisky, EJ
   Simoncelli, EP
AF Pillow, Jonathan W.
   Shlens, Jonathon
   Paninski, Liam
   Sher, Alexander
   Litke, Alan M.
   Chichilnisky, E. J.
   Simoncelli, Eero P.
TI Spatio-temporal correlations and visual signalling in a complete neuronal population
SO NATURE
LA English
DT Article
ID ganglion-cells; information; connectivity; spikes; code
AB Statistical dependencies in the responses of sensory neurons govern both the amount of stimulus information conveyed and the means by which downstream neurons can extract it. Although a variety of measurements indicate the existence of such dependencies(1-3), their origin and importance for neural coding are poorly understood. Here we analyse the functional significance of correlated firing in a complete population of macaque parasol retinal ganglion cells using a model of multi-neuron spikeresponses(4,5). The model, with parameters fit directly to physiological data, simultaneously captures both the stimulus dependence and detailed spatio-temporal correlations in population responses, and provides two insights into the structure of the neural code. First, neural encoding at the population level is less noisy than one would expect from the variability of individual neurons: spike times are more precise, and can be predicted more accurately when the spiking of neighbouring neurons is taken into account. Second, correlations provide additional sensory information: optimal, model- based decoding that exploits the response correlation structure extracts 20% more information about the visual scene than decoding under the assumption of independence, and preserves 40% more visual information than optimal linear decoding(6). This model- based approach reveals the role of correlated activity in the retinal coding of visual stimuli, and provides a general framework for understanding the importance of correlated activity in populations of neurons.
C1 [Pillow, Jonathan W.] UCL, Gatsby Computat Neurosci Unit, London WC1N 3AR, England.
   [Shlens, Jonathon; Chichilnisky, E. J.] Salk Inst, San Diego, CA 92037 USA.
   [Paninski, Liam] Columbia Univ, Dept Stat, New York, NY 10027 USA.
   [Paninski, Liam] Columbia Univ, Ctr Theoret Neurosci, New York, NY 10027 USA.
   [Sher, Alexander; Litke, Alan M.] Univ Calif Santa Cruz, Santa Cruz Inst Particle Phys, Santa Cruz, CA 95064 USA.
   [Simoncelli, Eero P.] NYU, Howard Hughes Med Inst, Ctr Neural Sci, New York, NY 10003 USA.
   [Simoncelli, Eero P.] NYU, Courant Inst Math Sci, New York, NY 10003 USA.
C3 University of London; University College London; Salk Institute; Columbia University; Columbia University; University of California System; University of California Santa Cruz; Howard Hughes Medical Institute; New York University; New York University
RP Pillow, JW (corresponding author), UCL, Gatsby Computat Neurosci Unit, 17 Queen Sq, London WC1N 3AR, England.
EM pillow@gatsby.ucl.ac.uk
FU Royal Society USA/Canada Research Fellowship; NSF IGERT [DGE-03345]; NEI [EY018003]; Gatsby Foundation Pilot Grant; Burroughs Wellcome Fund Career Award at the Scientific Interface; US National Science Foundation [PHY-0417175]; McKnight Foundation; HHMI
NR 30
TC 965
Z9 1197
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 AUG 21
PY 2008
VL 454
IS 7207
BP 995
EP U37
DI 10.1038/nature07140
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000039
PM 18650810
DA 2026-03-09
ER

PT J
AU Jékely, G
   Colombelli, J
   Hausen, H
   Guy, K
   Stelzer, E
   Nédélec, F
   Arendt, D
AF Jekely, Gaspar
   Colombelli, Julien
   Hausen, Harald
   Guy, Keren
   Stelzer, Ernst
   Nedelec, Francois
   Arendt, Detlev
TI Mechanism of phototaxis in marine zooplankton
SO NATURE
LA English
DT Article
ID platynereis-dumerilii; chlamydomonas-reinhardtii; sponge larva; behavior; annelida; eye; nanosurgery; polychaeta; organisms; evolution
AB The simplest animal eyes are eyespots composed of two cells only: a photoreceptor and a shading pigment cell. They resemble Darwin's 'proto-eyes', considered to be the first eyes to appear in animal evolution(1-4). Eyespots cannot form images but enable the animal to sense the direction of light. They are characteristic for the zooplankton larvae of marine invertebrates and are thought to mediate larval swimming towards the light. Phototaxis of invertebrate larvae contributes to the vertical migration of marine plankton(5), which is thought to represent the biggest biomass transport on Earth(6,7). Yet, despite its ecological and evolutionary importance, the mechanism by which eyespots regulate phototaxis is poorly understood. Here we show how simple eyespots in marine zooplankton mediate phototactic swimming, using the marine annelid Platynereis dumerilii as a model(8). We find that the selective illumination of one eyespot changes the beating of adjacent cilia by direct cholinergic innervation resulting in locally reduced water flow. Computer simulations of larval swimming show that these local effects are sufficient to direct the helical swimming trajectories towards the light. The computer model also shows that axial rotation of the larval body is essential for phototaxis and that helical swimming increases the precision of navigation. These results provide, to our knowledge, the first mechanistic understanding of phototaxis in a marine zooplankton larva and show how simple eyespots regulate it. We propose that the underlying direct coupling of light sensing and ciliary locomotor control was a principal feature of the proto- eye and an important landmark in the evolution of animal eyes.
C1 [Jekely, Gaspar; Guy, Keren; Arendt, Detlev] European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany.
   [Colombelli, Julien; Stelzer, Ernst; Nedelec, Francois] European Mol Biol Lab, Cell Biol & Biophys Unit, D-69117 Heidelberg, Germany.
   [Hausen, Harald] Free Univ Berlin, Inst Biol Systemat & Evolut Tiere, D-14195 Berlin, Germany.
C3 European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); Free University of Berlin
RP Jékely, G (corresponding author), Max Planck Inst Dev Biol, D-72076 Tubingen, Germany.
EM gaspar.jekely@tuebingen.mpg.de; arendt@embl.de
FU Center for Modelling and Simulation in the Biosciences; Deutsche Forschungsgemeinschaft [HA 4443/1-1, DA Ar387/1-1]; FEBS Long Term Fellowship
NR 29
TC 239
Z9 256
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 NOV 20
PY 2008
VL 456
IS 7220
BP 395
EP U62
DI 10.1038/nature07590
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600045
PM 19020621
DA 2026-03-09
ER

PT J
AU Pomerantz, RT
   O'Donnell, M
AF Pomerantz, Richard T.
   O'Donnell, Mike
TI The replisome uses mRNA as a primer after colliding with RNA polymerase
SO NATURE
LA English
DT Article
ID stalled replication forks; discontinuous dna-replication; escherichia-coli; lagging-strand; leading-strand; chain growth; transcription; repair; organization; elongation
AB Replication forks are impeded by DNA damage and protein - nucleic acid complexes such as transcribing RNA polymerase. For example, head- on collision of the replisome with RNA polymerase results in replication fork arrest. However, co- directional collision of the replisome with RNA polymerase has little or no effect on fork progression. Here we examine co- directional collisions between a replisome and RNA polymerase in vitro. We show that the Escherichia coli replisome uses the RNAtranscript as a primer to continue leading- strand synthesis after the collision with RNA polymerase that is displaced from the DNA. This action results in a discontinuity in the leading strand, yet the replisome remains intact and bound to DNA during the entire process. These findings underscore the notable plasticity by which the replisome operates to circumvent obstacles in its path and may explain why the leading strand is synthesized discontinuously in vivo.
C1 [Pomerantz, Richard T.; O'Donnell, Mike] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA.
C3 Rockefeller University; Howard Hughes Medical Institute
RP O'Donnell, M (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, 1230 York Ave, New York, NY 10021 USA.
EM odonnell@mail.rockefeller.edu
FU National Institutes of Health; Marie-Josee and Henry Kravis Fellowship at the Rockefeller University
NR 50
TC 162
Z9 193
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 762
EP U51
DI 10.1038/nature07527
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900042
PM 19020502
DA 2026-03-09
ER

PT J
AU Schmidt, J
   Brilliantov, N
   Spahn, F
   Kempf, S
AF Schmidt, Juergen
   Brilliantov, Nikolai
   Spahn, Frank
   Kempf, Sascha
TI Slow dust in Enceladus' plume from condensation and wall collisions in tiger stripe fractures
SO NATURE
LA English
DT Article
ID saturns e-ring; water; origin
AB One of the spectacular discoveries of the Cassini spacecraft was the plume of water vapour and icy particles ( dust) originating near the south pole of Saturn's moon Enceladus(1-5). The data imply considerably smaller velocities for the grains(2,5,6) than for the vapour(4,7), which has been difficult to understand. The gas and dust are too dilute in the plume to interact, so the difference must arise below the surface. Here we report a model for grain condensation and growth in channels of variable width. We show that repeated wall collisions of grains, with re- acceleration by the gas, induce an effective friction, offering a natural explanation for the reduced grain velocity. We derive particle speed and size distributions that reproduce the observed and inferred properties of the dust plume. The gas seems to form near the triple point of water; gas densities corresponding to sublimation from ice at temperatures less than 260K are generally too low to support the measured particle fluxes(2). This in turn suggests liquid water below Enceladus' south pole.
C1 [Schmidt, Juergen; Brilliantov, Nikolai; Spahn, Frank] Univ Potsdam, Neuen Palais 10, D-14469 Potsdam, Germany.
   [Brilliantov, Nikolai] Univ Leicester, Dept Math, Leicester LE1 7RH, Leics, England.
   [Brilliantov, Nikolai] Moscow MV Lomonosov State Univ, Dept Phys, Moscow 119991, Russia.
   [Kempf, Sascha] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Kempf, Sascha] Tech Univ Carolo Wilhelmina Braunschweig, IGEP, D-38106 Braunschweig, Germany.
C3 University of Potsdam; University of Leicester; Lomonosov Moscow State University; Max Planck Society; Braunschweig University of Technology
RP Schmidt, J (corresponding author), Univ Potsdam, Neuen Palais 10, D-14469 Potsdam, Germany.
EM jschmidt@agnld.uni-potsdam.de
NR 28
TC 172
Z9 195
U1 2
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 685
EP 688
DI 10.1038/nature06491
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500034
PM 18256665
DA 2026-03-09
ER

PT J
AU Rigol, M
   Dunjko, V
   Olshanii, M
AF Rigol, Marcos
   Dunjko, Vanja
   Olshanii, Maxim
TI Thermalization and its mechanism for generic isolated quantum systems
SO NATURE
LA English
DT Article
ID eigenfunctions; chaos; atoms; gas
AB An understanding of the temporal evolution of isolated many-body quantum systems has long been elusive. Recently, meaningful experimental studies(1,2) of the problem have become possible, stimulating theoretical interest(3-7). In generic isolated systems, non- equilibrium dynamics is expected(8,9) to result in thermalization: a relaxation to states in which the values of macroscopic quantities are stationary, universal with respect to widely differing initial conditions, and predictable using statistical mechanics. However, it is not obvious what feature of many- body quantum mechanics makes quantum thermalization possible in a sense analogous to that in which dynamical chaos makes classical thermalization possible(10). For example, dynamical chaos itself cannot occur in an isolated quantum system, in which the time evolution is linear and the spectrum is discrete(11). Some recent studies(4,5) even suggest that statistical mechanics may give incorrect predictions for the outcomes of relaxation in such systems. Here we demonstrate that a generic isolated quantum many- body system does relax to a state well described by the standard statistical- mechanical prescription. Moreover, we show that time evolution itself plays a merely auxiliary role in relaxation, and that thermalization instead happens at the level of individual eigenstates, as first proposed by Deutsch(12) and Srednicki(13). A striking consequence of this eigenstate- thermalization scenario, confirmed for our system, is that knowledge of a single many- body eigenstate is sufficient to compute thermal averages - any eigenstate in the microcanonical energy window will do, because they all give the same result.
C1 [Rigol, Marcos; Dunjko, Vanja] Univ So Calif, Dept Phys & Astron, Los Angeles, CA 90089 USA.
   [Rigol, Marcos; Dunjko, Vanja; Olshanii, Maxim] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA.
C3 University of Southern California; University of Massachusetts System; University of Massachusetts Boston
RP Olshanii, M (corresponding author), Univ So Calif, Dept Phys & Astron, Los Angeles, CA 90089 USA.
EM maxim.olchanyi@umb.edu
NR 30
TC 2523
Z9 2715
U1 6
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 APR 17
PY 2008
VL 452
IS 7189
BP 854
EP 858
DI 10.1038/nature06838
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000044
PM 18421349
DA 2026-03-09
ER

PT J
AU Kummamuru, RK
   Soh, YA
AF Kummamuru, Ravi K.
   Soh, Yeong-Ah
TI Electrical effects of spin density wave quantization and magnetic domain walls in chromium
SO NATURE
LA English
DT Article
ID field dependence; cr(001) films; layers; antiferromagnetism; magnetoresistance; temperature; multilayers
AB The role of magnetic domains ( and the walls between domains) in determining the electrical properties of ferromagnetic materials(1) has been investigated in great detail for many years, not least because control over domains offers a means of manipulating electron spin to control charge transport in 'spintronic' devices(2). In contrast, much less attention has been paid to the effects of domains and domain walls on the electrical properties of antiferromagnets: antiferromagnetic domains show no net external magnetic moment, and so are difficult to manipulate or probe. Here we describe electrical measurements on chromium - a simple metal and quintessential spin density wave antiferromagnet(3) - that show behaviour directly related to spin density wave formation and the presence of antiferromagnetic domains. Two types of thermal hysteresis are seen in both longitudinal and Hall resistivity: the first can be explained by the quantization of spin density waves due to the finite film thickness ( confirmed by X- ray diffraction measurements) and the second by domain- wall scattering of electrons(4,5). We also observe the striking influence of the electrical lead configuration ( a mesoscopic effect) on the resistivity of macroscopic samples in the spin density wave state. Our results are potentially of practical importance, in that they reveal tunable electrical effects of film thickness and domain walls that are as large as the highest seen for ferromagnets(6,7).
C1 [Kummamuru, Ravi K.; Soh, Yeong-Ah] Dartmouth Coll, Dept Phys & Astron, Hanover, NH 03755 USA.
C3 Dartmouth College
RP Soh, YA (corresponding author), Univ Illinois, Dept Mat Sci & Engn, 1304 W Green St, Urbana, IL 61801 USA.
EM yeong-ah.soh@dartmouth.edu
NR 32
TC 47
Z9 56
U1 3
U2 69
PU 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 17
PY 2008
VL 452
IS 7189
BP 859
EP U4
DI 10.1038/nature06826
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000045
PM 18421350
DA 2026-03-09
ER

PT J
AU de Riedmatten, H
   Afzelius, M
   Staudt, MU
   Simon, C
   Gisin, N
AF de Riedmatten, Hugues
   Afzelius, Mikael
   Staudt, Matthias U.
   Simon, Christoph
   Gisin, Nicolas
TI A solid-state light-matter interface at the single-photon level
SO NATURE
LA English
DT Article
AB Coherent and reversible mapping of quantum information between light and matter is an important experimental challenge in quantum information science. In particular, it is an essential requirement for the implementation of quantum networks and quantum repeaters(1-3). So far, quantum interfaces between light and atoms have been demonstrated with atomic gases(4-9), and with single trapped atoms in cavities(10). Here we demonstrate the coherent and reversible mapping of a light field with less than one photon per pulse onto an ensemble of similar to 10(7) atoms naturally trapped in a solid. This is achieved by coherently absorbing the light field in a suitably prepared solid- state atomic medium(11). The state of the light is mapped onto collective atomic excitations at an optical transition and stored for a pre- determined time of up to 1 mu s before being released in a well- defined spatio- temporal mode as a result of a collective interference. The coherence of the process is verified by performing an interference experiment with two stored weak pulses with a variable phase relation. Visibilities of more than 95 per cent are obtained, demonstrating the high coherence of the mapping process at the single- photon level. In addition, we show experimentally that our interface makes it possible to store and retrieve light fields in multiple temporal modes. Our results open the way to multimode solid- state quantum memories as a promising alternative to atomic gases.
C1 [de Riedmatten, Hugues; Afzelius, Mikael; Staudt, Matthias U.; Simon, Christoph; Gisin, Nicolas] Univ Geneva, Appl Phys Grp, CH-1211 Geneva 4, Switzerland.
C3 University of Geneva
RP de Riedmatten, H (corresponding author), Univ Geneva, Appl Phys Grp, CH-1211 Geneva 4, Switzerland.
EM hugues.deriedmatten@unige.ch
FU Swiss NCCR Quantum Photonics; European Commission
NR 30
TC 431
Z9 469
U1 2
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 773
EP 777
DI 10.1038/nature07607
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900045
PM 19079056
DA 2026-03-09
ER

PT J
AU Bao, HM
   Lyons, JR
   Zhou, CM
AF Bao, Huiming
   Lyons, J. R.
   Zhou, Chuanming
TI Triple oxygen isotope evidence for elevated CO2 levels after a Neoproterozoic glaciation
SO NATURE
LA English
DT Article
ID atmospheric carbon-dioxide; oligocene ash bed; sulfate; oxidation; ozone; earth; fractionation; productivity; delta-o-18; exchange
AB Understanding the composition of the atmosphere over geological time is critical to understanding the history of the Earth system, as the atmosphere is closely linked to the lithosphere, hydrosphere and biosphere. Although much of the history of the lithosphere and hydrosphere is contained in rock and mineral records, corresponding information about the atmosphere is scarce and elusive owing to the lack of direct records. Geologists have used sedimentary minerals, fossils and geochemical models to place constraints on the concentrations of carbon dioxide, oxygen or methane in the past(1-4). Here we show that the triple oxygen isotope composition of sulphate from ancient evaporites and barites shows variable negative oxygen-17 isotope anomalies over the past 750 million years. We propose that these anomalies track those of atmospheric oxygen and in turn reflect the partial pressure of carbon dioxide (p(CO2)) in the past through a photochemical reaction network linking stratospheric ozone to carbon dioxide and to oxygen(5,6). Our results suggest that p(CO2) was much higher in the early Cambrian than in younger eras, agreeing with previous modelling results(2). We also find that the (17)O isotope anomalies of barites from Marinoan (similar to 635 million years ago) cap carbonates display a distinct negative spike (around 20.70%), suggesting that by the time barite was precipitating in the immediate aftermath of a Neoproterozoic global glaciation, the p(CO2) was at its highest level in the past 750 million years. Our finding is consistent with the 'snowball Earth' hypothesis(7,8) and/or a massive methane release(9) after the Marinoan glaciation.
C1 [Bao, Huiming] Louisiana State Univ, Dept Geol & Geophys, Baton Rouge, LA 70803 USA.
   [Lyons, J. R.] Univ Calif Los Angeles, Inst Geophys & Planetary Phys, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
   [Zhou, Chuanming] Chinese Acad Sci, State Key Lab Palaeobiol & Stratig, Nanjing Inst Geol & Palaeontol, Nanjing 210008, Peoples R China.
C3 Louisiana State University System; Louisiana State University; University of California System; University of California Los Angeles; Chinese Academy of Sciences
RP Bao, HM (corresponding author), Louisiana State Univ, Dept Geol & Geophys, E235 Howe Russell Geosci Complex, Baton Rouge, LA 70803 USA.
EM bao@lsu.edu
NR 30
TC 217
Z9 264
U1 12
U2 197
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 504
EP 506
DI 10.1038/nature06959
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700038
PM 18497821
DA 2026-03-09
ER

PT J
AU Yamagishi, Y
   Sakuno, T
   Shimura, M
   Watanabe, Y
AF Yamagishi, Yuya
   Sakuno, Takeshi
   Shimura, Mari
   Watanabe, Yoshinori
TI Heterochromatin links to centromeric protection by recruiting shugoshin
SO NATURE
LA English
DT Article
ID protein phosphatase 2a; fission yeast; cell-cycle; meiosis-i; cohesion; hp1; phosphorylation; localization; chromosome; methylation
AB The centromere of a chromosome is composed mainly of two domains, a kinetochore assembling core centromere and pericentromeric heterochromatin regions(1,2). The crucial role of centromeric heterochromatin is still unknown, because even in simpler unicellular organisms such as the fission yeast Schizosaccharomyces pombe, the heterochromatin protein Swi6 ( HP1 homologue) has several functions at centromeres, including silencing gene expression and recombination, enriching cohesin, promoting kinetochore assembly, and, ultimately, preventing erroneous microtubule attachment to the kinetochores(1,3-6). Here we show that the requirement of heterochromatin for mitotic chromosome segregation is largely replaced by forcibly enriching cohesin at centromeres in fission yeast. However, this enrichment of cohesin is not sufficient to replace the meiotic requirement for heterochromatin. We find that the heterochromatin protein Swi6 associates directly with meiosis- specific shugoshin Sgo1, a protector of cohesin at centromeres. A point mutation of Sgo1 (V242E), which abolishes the interaction with Swi6, impairs the centromeric localization and function of Sgo1. The forced centromeric localization of Sgo1 restores proper meiotic chromosome segregation in swi6 Delta cells. We also show that the direct link between HP1 and shugoshin is conserved in human cells. Taken together, our findings suggest that the recruitment of shugoshin is the important primary role for centromeric heterochromatin in ensuring eukaryotic chromosome segregation.
C1 [Yamagishi, Yuya; Sakuno, Takeshi; Watanabe, Yoshinori] Univ Tokyo, Lab Chromosome Dynam, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan.
   [Yamagishi, Yuya; Sakuno, Takeshi; Watanabe, Yoshinori] Univ Tokyo, Grad Program Biophys & Biochem, Grad Sch Sci, Tokyo 1130032, Japan.
   [Shimura, Mari] Int Med Ctr Japan, Dept Intractable Dis, Tokyo 1628655, Japan.
C3 University of Tokyo; University of Tokyo; Japan Institute for Health Security (JIHS); National Center for Global Health & Medicine - Japan
RP Watanabe, Y (corresponding author), Univ Tokyo, Lab Chromosome Dynam, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan.
EM ywatanab@iam.u-tokyo.ac.jp
FU Global COE programme (Integrative life Science Based on the Study of Biosignaling Mechanisms); MEXT, Japan; Toray Science Foundation; Grants-in-Aid for Research on Advanced Medical Technology; Ministry of Health, Labour and Welfare
NR 29
TC 157
Z9 189
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 SEP 11
PY 2008
VL 455
IS 7210
BP 251
EP U79
DI 10.1038/nature07217
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800053
PM 18716626
DA 2026-03-09
ER

PT J
AU Steinberger, B
   Torsvik, TH
AF Steinberger, Bernhard
   Torsvik, Trond H.
TI Absolute plate motions and true polar wander in the absence of hotspot tracks
SO NATURE
LA English
DT Article
ID axis
AB The motion of continents relative to the Earth's spin axis may be due either to rotation of the entire Earth relative to its spin axis true polar wander(1,2) - or to the motion of individual plates(3). In order to distinguish between these over the past 320 Myr ( since the formation of the Pangaea supercontinent), we present here computations of the global average of continental motion and rotation through time(4) in a palaeomagnetic reference frame. Two components are identified: a steady northward motion and, during certain time intervals, clockwise and anticlockwise rotations, interpreted as evidence for true polar wander. We find 186 anti-clockwise rotation about 250-220 Myr ago and the same amount of clockwise rotation about 195-145 Myr ago. In both cases the rotation axis is located at about 10-20 degrees W, 0 degrees N, near the site that became the North American - South American - African triple junction at the break- up of Pangaea. This was followed by 106 clockwise rotation about 145-135 Myr ago, followed again by the same amount of anticlockwise rotation about 110-100 Myr ago, with a rotation axis in both cases similar to 25-50 degrees E in the reconstructed area of North Africa and Arabia. These rotation axes mark the maxima of the degree- two non- hydrostatic geoid during those time intervals, and the fact that the overall net rotation since 320 Myr ago is nearly zero is an indication of long- term stability of the degree- two geoid and related mantle structure(5,6). We propose a new reference frame, based on palaeomagnetism, but corrected for the true polar wander identified in this study, appropriate for relating surface to deep mantle processes from 320 Myr ago until hotspot tracks can be used ( about 130 Myr ago).
C1 [Steinberger, Bernhard; Torsvik, Trond H.] Geol Survey Norway, Ctr Geodynam, N-7491 Trondheim, Norway.
   [Torsvik, Trond H.] Univ Oslo, N-0316 Oslo, Norway.
   [Torsvik, Trond H.] Univ Witwatersrand, Sch Geosci, ZA-2050 Johannesburg, South Africa.
C3 Geological Survey of Norway; University of Oslo; University of Witwatersrand
RP Steinberger, B (corresponding author), Geol Survey Norway, Ctr Geodynam, Leiv Eirikssons Vei 39, N-7491 Trondheim, Norway.
EM bernhard.steinberger@ngu.no
NR 32
TC 211
Z9 227
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 3
PY 2008
VL 452
IS 7187
BP 620
EP U6
DI 10.1038/nature06824
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200043
PM 18385737
DA 2026-03-09
ER

PT J
AU Kelly, BT
   McCoy, AJ
   Späte, K
   Miller, SE
   Evans, PR
   Höning, S
   Owen, DJ
AF Kelly, Bernard T.
   McCoy, Airlie J.
   Spaete, Kira
   Miller, Sharon E.
   Evans, Philip R.
   Hoening, Stefan
   Owen, David J.
TI A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex
SO NATURE
LA English
DT Article
ID sorting-signal recognition; clathrin-coated vesicles; di-leucine motif; adapter; phosphorylation; subunit; protein; cluster; software; receptor
AB Most transmembrane proteins are selected as transport- vesicle cargo through the recognition of short, linear amino- acid motifs in their cytoplasmic portions by vesicle coat proteins. For clathrin-coated vesicles, the motifs are recognized by clathrin adaptors. The AP2 adaptor complex (subunits alpha, beta 2, mu 2 and sigma 2) recognizes both major endocytic motifs: Yxx Phi motifs(1) ( where Phi can be F, I, L, Mor V) and [ED] xxxL[ LI] acidic dileucine motifs. Here we describe the binding of AP2 to the endocytic dileucine motif from CD4 ( ref. 2). The major recognition events are the two leucine residues binding in hydrophobic pockets on sigma 2. The hydrophilic residue four residues upstream from the first leucine sits on a positively charged patch made from residues on the sigma 2 and a subunits. Mutations in key residues inhibit the binding of AP2 to 'acidic dileucine' motifs displayed in liposomes containing phosphatidylinositol-4,5-bisphosphate,but do not affect binding to Yxx Phi motifs through mu 2. In the 'inactive' AP2 core structure(3) both motif- binding sites are blocked by different parts of the beta 2 subunit. To allow a dileucine motif to bind, the beta 2 amino terminus is displaced and becomes disordered; however, in this structure the Yxx Phi-binding site on mu 2 remains blocked.
C1 [Kelly, Bernard T.; McCoy, Airlie J.; Miller, Sharon E.; Owen, David J.] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
   [Kelly, Bernard T.; McCoy, Airlie J.; Miller, Sharon E.; Owen, David J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 0XY, England.
   [Spaete, Kira; Hoening, Stefan] Univ Cologne, Inst Biochem 1, D-50931 Cologne, Germany.
   [Spaete, Kira; Hoening, Stefan] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany.
   [Evans, Philip R.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
C3 University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cologne; University of Cologne; MRC Laboratory Molecular Biology
RP Owen, DJ (corresponding author), Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Hills Rd, Cambridge CB2 0XY, England.
EM djo30@cam.ac.uk
FU Wellcome Trust Senior Research Fellowship; Deutsche Forschungsgemeinschaft [SFB635, SFB670]; Medical Research Council [MC_U105178845] Funding Source: researchfish; MRC [MC_U105178845] Funding Source: UKRI
NR 27
TC 267
Z9 340
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 DEC 18
PY 2008
VL 456
IS 7224
BP 976
EP U81
DI 10.1038/nature07422
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300051
PM 19140243
DA 2026-03-09
ER

PT J
AU Mansy, SS
   Schrum, JP
   Krishnamurthy, M
   Tobé, S
   Treco, DA
   Szostak, JW
AF Mansy, Sheref S.
   Schrum, Jason P.
   Krishnamurthy, Mathangi
   Tobe, Sylvia
   Treco, Douglas A.
   Szostak, Jack W.
TI Template-directed synthesis of a genetic polymer in a model protocell
SO NATURE
LA English
DT Article
ID monocarboxylic acids; membrane; growth; oligomerization; encapsulation; stability; bilayers; water; rna
AB Contemporary phospholipid- based cell membranes are formidable barriers to the uptake of polar and charged molecules ranging from metal ions to complex nutrients. Modern cells therefore require sophisticated protein channels and pumps to mediate the exchange of molecules with their environment. The strong barrier function of membranes has made it difficult to understand the origin of cellular life and has been thought to preclude a heterotrophic lifestyle for primitive cells. Although nucleotides can cross dimyristoyl phosphatidylcholine membranes through defects formed at the gel- to- liquid transition temperature(1,2), phospholipid membranes lack the dynamic properties required for membrane growth. Fatty acids and their corresponding alcohols and glycerol monoesters are attractive candidates for the components of protocell membranes because they are simple amphiphiles that form bilayer membrane vesicles(3-5) that retain encapsulated oligonucleotides(3,6) and are capable of growth and division(7-9). Here we show that such membranes allow the passage of charged molecules such as nucleotides, so that activated nucleotides added to the outside of a model protocell spontaneously cross the membrane and take part in efficient template copying in the protocell interior. The permeability properties of prebiotically plausible membranes suggest that primitive protocells could have acquired complex nutrients from their environment in the absence of any macromolecular transport machinery; that is, they could have been obligate heterotrophs.
C1 [Mansy, Sheref S.; Schrum, Jason P.; Krishnamurthy, Mathangi; Tobe, Sylvia; Treco, Douglas A.; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA.
   [Mansy, Sheref S.; Schrum, Jason P.; Krishnamurthy, Mathangi; Tobe, Sylvia; Treco, Douglas A.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Szostak, JW (corresponding author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIGMS NIH HHS [F32 GM074506, F32 GM07450601] Funding Source: Medline
NR 34
TC 539
Z9 610
U1 4
U2 285
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 122
EP U10
DI 10.1038/nature07018
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300050
PM 18528332
DA 2026-03-09
ER

PT J
AU Richard, DJ
   Bolderson, E
   Cubeddu, L
   Wadsworth, RIM
   Savage, K
   Sharma, GG
   Nicolette, ML
   Tsvetanov, S
   McIlwraith, MJ
   Pandita, RK
   Takeda, S
   Hay, RT
   Gautier, J
   West, SC
   Paull, TT
   Pandita, TK
   White, MF
   Khanna, KK
AF Richard, Derek J.
   Bolderson, Emma
   Cubeddu, Liza
   Wadsworth, Ross I. M.
   Savage, Kienan
   Sharma, Girdhar G.
   Nicolette, Matthew L.
   Tsvetanov, Sergie
   McIlwraith, Michael J.
   Pandita, Raj K.
   Takeda, Shunichi
   Hay, Ronald T.
   Gautier, Jean
   West, Stephen C.
   Paull, Tanya T.
   Pandita, Tej K.
   White, Malcolm F.
   Khanna, Kum Kum
TI Single-stranded DNA-binding protein hSSB1 is critical for genomic stability
SO NATURE
LA English
DT Article
ID mammalian-cells; rad52 protein; break repair; s-phase; damage; atm; phosphorylation; recombination; activation; checkpoint
AB Single- strand DNA ( ssDNA)- binding proteins ( SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair(1). SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand- exchange proteins, activating transcription and mediating protein - protein interactions. In eukaryotes, the major SSB, replication protein A ( RPA), is a heterotrimer(1). Here we describe a second human SSB ( hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated ( ATM) kinase phosphorylates hSSB1 in response to DNA double- strand breaks ( DSBs). This phosphorylation event is required for DNA damage- induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell- cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S- phase cells and hSSB1 deficiency does not influence S- phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse end-points in the cellular DNA damage response.
C1 [Richard, Derek J.; Bolderson, Emma; Savage, Kienan; Tsvetanov, Sergie; Khanna, Kum Kum] Queensland Inst Med Res, Signal Transduct Lab, Brisbane, Qld 4029, Australia.
   [Cubeddu, Liza; Wadsworth, Ross I. M.; White, Malcolm F.] Univ St Andrews, Ctr Biomol Sci, St Andrews KY16 9ST, Fife, Scotland.
   [Cubeddu, Liza] Univ Sydney, Sch Mol & Microbial Biosci, Sydney, NSW 2006, Australia.
   [Savage, Kienan] Univ Queensland, Cent Clin Div, Sch Med, Brisbane, Qld 4072, Australia.
   [Sharma, Girdhar G.; Pandita, Raj K.; Pandita, Tej K.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA.
   [Nicolette, Matthew L.; Paull, Tanya T.] Univ Texas Austin, Dept Mol Genet & Microbiol, Austin, TX 78712 USA.
   [McIlwraith, Michael J.; West, Stephen C.] Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
   [Takeda, Shunichi] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Kyoto 6068501, Japan.
   [Hay, Ronald T.] Univ Dundee, Div Gene Regulat & Express, Wellcome Bioctr, Dundee DD1 5EH, Scotland.
   [Gautier, Jean] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA.
C3 QIMR Berghofer Medical Research Institute; University of St Andrews; University of Sydney; University of Queensland; Washington University (WUSTL); University of Texas System; University of Texas Austin; Cancer Research UK; Kyoto University; University of Dundee; Columbia University
RP Khanna, KK (corresponding author), Queensland Inst Med Res, Signal Transduct Lab, Brisbane, Qld 4029, Australia.
EM mfw2@st-and.ac.uk; kumkumK@qimr.edu.au
FU Biotechnology and Biological Sciences Research Council [BB/C000110/1] Funding Source: researchfish; Biotechnology and Biological Sciences Research Council [BB/C000110/1] Funding Source: Medline; NCI NIH HHS [CA10445, CA92245, CA123232] Funding Source: Medline
NR 27
TC 213
Z9 257
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 29
PY 2008
VL 453
IS 7195
BP 677
EP U13
DI 10.1038/nature06883
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200049
PM 18449195
DA 2026-03-09
ER

PT J
AU Zhou, B
   Ma, Q
   Rajagopal, S
   Wu, SM
   Domian, I
   Rivera-Feliciano, J
   Jiang, DW
   von Gise, A
   Ikeda, S
   Chien, KR
   Pu, WT
AF Zhou, Bin
   Ma, Qing
   Rajagopal, Satish
   Wu, Sean M.
   Domian, Ibrahim
   Rivera-Feliciano, Jose
   Jiang, Dawei
   von Gise, Alexander
   Ikeda, Sadakatsu
   Chien, Kenneth R.
   Pu, William T.
TI Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart
SO NATURE
LA English
DT Article
ID smooth-muscle-cells; cardiovascular progenitors; pericardial mesoderm; reporter strain; expression; origin; mouse; neovascularization; differentiation; population
AB The heart is formed from cardiogenic progenitors expressing the transcription factors Nkx2-5 and Isl1 ( refs 1 and 2). These multipotent progenitors give rise to cardiomyocyte, smooth muscle and endothelial cells, the major lineages of the mature heart(3,4). Here we identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium - an epithelial sheet overlying the heart. During normal murine heart development, a subset of these Wt1(+) precursors differentiated into fully functional cardiomyocytes. Wt1(+) proepicardial cells arose from progenitors that express Nkx2-5 and Isl1, suggesting that they share a developmental origin with multipotent Nkx2-5(+) and Isl1(+) progenitors. These results identify Wt1(+) epicardial cells as previously unrecognized cardiomyocyte progenitors, and lay the foundation for future efforts to harness the cardiogenic potential of these progenitors for cardiac regeneration and repair.
C1 [Zhou, Bin; Ma, Qing; Rajagopal, Satish; Jiang, Dawei; von Gise, Alexander; Ikeda, Sadakatsu; Pu, William T.] Childrens Hosp, Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Zhou, Bin; Ma, Qing; Rajagopal, Satish; Jiang, Dawei; von Gise, Alexander; Ikeda, Sadakatsu; Pu, William T.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
   [Zhou, Bin; Ma, Qing; Rajagopal, Satish; Rivera-Feliciano, Jose; von Gise, Alexander; Ikeda, Sadakatsu; Pu, William T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Wu, Sean M.; Domian, Ibrahim; Chien, Kenneth R.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA.
   [Wu, Sean M.; Domian, Ibrahim; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   [von Gise, Alexander] Charite Univ Med Berlin, Clin Neonatol, D-10117 Berlin, Germany.
C3 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; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
RP Pu, WT (corresponding author), Childrens Hosp, Harvard Stem Cell Inst, 300 Longwood Ave, Boston, MA 02115 USA.
EM wpu@enders.tch.harvard.edu
FU NHLBI NIH HHS [P50 HL074734] Funding Source: Medline
NR 36
TC 796
Z9 969
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 JUL 3
PY 2008
VL 454
IS 7200
BP 109
EP U5
DI 10.1038/nature07060
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300047
PM 18568026
DA 2026-03-09
ER

PT J
AU Holt, LJ
   Krutchinsky, AN
   Morgan, DO
AF Holt, Liam J.
   Krutchinsky, Andrew N.
   Morgan, David O.
TI Positive feedback sharpens the anaphase switch
SO NATURE
LA English
DT Article
ID mitotic exit; phosphatase cdc14; budding yeast; dna-damage; phosphorylation; separase; mitosis; apc; destruction; dynamics
AB At the onset of anaphase, sister- chromatid cohesion is dissolved abruptly and irreversibly, ensuring that all chromosome pairs disjoin almost simultaneously. The regulatory mechanisms that generate this switch- like behaviour are unclear. Anaphase is initiated when a ubiquitin ligase, the anaphase- promoting complex ( APC), triggers the destruction of securin, thereby allowing separase, a protease, to disrupt sister- chromatid cohesion(1-4). Here we demonstrate that the cyclin- dependent kinase 1 ( Cdk1)- dependent phosphorylation of securin near its destruction- box motif inhibits securin ubiquitination by the APC. The phosphatase Cdc14 reverses securin phosphorylation, thereby increasing the rate of securin ubiquitination. Because separase is known to activate Cdc14 ( refs 5 and 6), our results support the existence of a positive feedback loop that increases the abruptness of anaphase. Consistent with this model, we show that mutations that disrupt securin phosphoregulation decrease the synchrony of chromosome segregation. Our results also suggest that coupling securin degradation with changes in Cdk1 and Cdc14 activities helps coordinate the initiation of sister- chromatid separation with changes in spindle dynamics.
C1 [Holt, Liam J.; Morgan, David O.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Holt, Liam J.; Morgan, David O.] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94158 USA.
   [Holt, Liam J.; Morgan, David O.] Univ Calif San Francisco, Dept Biophys, San Francisco, CA 94158 USA.
   [Krutchinsky, Andrew N.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Morgan, DO (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
EM david.morgan@ucsf.edu
FU NIGMS NIH HHS [R01 GM069901] Funding Source: Medline
NR 30
TC 152
Z9 192
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 353
EP 357
DI 10.1038/nature07050
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300043
PM 18552837
DA 2026-03-09
ER

PT J
AU Guardavaccaro, D
   Frescas, D
   Dorrello, NV
   Peschiaroli, A
   Multani, AS
   Cardozo, T
   Lasorella, A
   Iavarone, A
   Chang, S
   Hernando, E
   Pagano, M
AF Guardavaccaro, Daniele
   Frescas, David
   Dorrello, N. Valerio
   Peschiaroli, Angelo
   Multani, Asha S.
   Cardozo, Timothy
   Lasorella, Anna
   Iavarone, Antonio
   Chang, Sandy
   Hernando, Eva
   Pagano, Michele
TI Control of chromosome stability by the β-TrCP-REST-Mad2 axis
SO NATURE
LA English
DT Article
ID restrictive silencer factor; cell lung-cancer; trcp-mediated degradation; box protein beta-trcp1; beta-trcp; glycine receptor; rest; transcription; repressor; differentiation
AB REST/NRSF ( repressor-element-1-silencing transcription factor/ neuron- restrictive silencing factor) negatively regulates the transcription of genes containing RE1 sites(1,2). REST is expressed in non- neuronal cells and stem/ progenitor neuronal cells, in which it inhibits the expression of neuron- specific genes. Overexpression of REST is frequently found in human medulloblastomas and neuroblastomas(3-7), in which it is thought to maintain the stem character of tumour cells. Neural stem cells forced to express REST and c- Myc fail to differentiate and give rise to tumours in the mouse cerebellum(3). Expression of a splice variant of REST that lacks the carboxy terminus has been associated with neuronal tumours and small- cell lung carcinomas(8-10), and a frameshift mutant ( REST- FS), which is also truncated at the C terminus, has oncogenic properties(11). Here we show, by using an unbiased screen, that REST is an interactor of the F- box protein beta-TrCP. REST is degraded by means of the ubiquitin ligase SCF beta-TrCP during the G2 phase of the cell cycle to allow transcriptional derepression of Mad2, an essential component of the spindle assembly checkpoint. The expression in cultured cells of a stable REST mutant, which is unable to bind beta-TrCP, inhibited Mad2 expression and resulted in a phenotype analogous to that observed in Mad2(+/-) cells. In particular, we observed defects that were consistent with faulty activation of the spindle checkpoint, such as shortened mitosis, premature sister- chromatid separation, chromosome bridges and mis- segregation in anaphase, tetraploidy, and faster mitotic slippage in the presence of a spindle inhibitor. An indistinguishable phenotype was observed by expressing the oncogenic REST- FS mutant(11), which does not bind beta-TrCP. Thus, SCF beta-TrCP-dependent degradation of REST during G2 permits the optimal activation of the spindle checkpoint, and consequently it is required for the fidelity of mitosis. The high levels of REST or its truncated variants found in certain human tumours may contribute to cellular transformation by promoting genomic instability.
C1 [Guardavaccaro, Daniele; Frescas, David; Dorrello, N. Valerio; Peschiaroli, Angelo; Hernando, Eva; Pagano, Michele] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Cardozo, Timothy] NYU, Sch Med, Dept Pharmacol, NYU Canc Inst, New York, NY 10016 USA.
   [Multani, Asha S.; Chang, Sandy] Univ Texas Houston, MD Anderson Canc Ctr, Dept Canc Genet, Houston, TX 77030 USA.
   [Lasorella, Anna; Iavarone, Antonio] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA.
C3 New York University; New York University; University of Texas System; University of Texas Health Science Center Houston; UTMD Anderson Cancer Center; Columbia University
RP Pagano, M (corresponding author), NYU, Sch Med, Dept Pathol, 550 1st Ave, MSB 599, New York, NY 10016 USA.
EM michele.pagano@nyumc.org
FU Howard Hughes Medical Institute Funding Source: Medline; NIGMS NIH HHS [R01 GM057587] Funding Source: Medline
NR 32
TC 170
Z9 205
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 365
EP U10
DI 10.1038/nature06641
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400050
PM 18354482
DA 2026-03-09
ER

PT J
AU Saal, AE
   Hauri, EH
   Lo Cascio, M
   Van Orman, JA
   Rutherford, MC
   Cooper, RF
AF Saal, Alberto E.
   Hauri, Erik H.
   Lo Cascio, Mauro
   Van Orman, James A.
   Rutherford, Malcolm C.
   Cooper, Reid F.
TI Volatile content of lunar volcanic glasses and the presence of water in the Moon's interior
SO NATURE
LA English
DT Article
ID detrital zircons; upper-mantle; evolution; surface; impact; crust; earth; ftir
AB The Moon is generally thought to have formed and evolved through a single or a series of catastrophic heating events(1), during which most of the highly volatile elements were lost. Hydrogen, being the lightest element, is believed to have been completely lost during this period(2). Here we make use of considerable advances in secondary ion mass spectrometry(3) to obtain improved limits on the indigenous volatile (CO(2), H(2)O, F, S and Cl) contents of the most primitive basalts in the Moon - the lunar volcanic glasses. Although the pre- eruptive water content of the lunar volcanic glasses cannot be precisely constrained, numerical modelling of diffusive degassing of the very- low- Ti glasses provides a best estimate of 745 p. p. m. water, with a minimum of 260 p. p. m. at the 95 per cent confidence level. Our results indicate that, contrary to prevailing ideas, the bulk Moon might not be entirely depleted in highly volatile elements, including water. Thus, the presence of water must be considered in models constraining the Moon's formation and its thermal and chemical evolution.
C1 [Saal, Alberto E.; Lo Cascio, Mauro; Rutherford, Malcolm C.; Cooper, Reid F.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Hauri, Erik H.] Carnegie Inst Washington, Dept Terr Magnetism, Washington, DC 20015 USA.
   [Van Orman, James A.] Case Western Reserve Univ, Dept Geol Sci, Cleveland, OH 44106 USA.
C3 Brown University; Carnegie Institution for Science; University System of Ohio; Case Western Reserve University
RP Saal, AE (corresponding author), Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
EM asaal@brown.edu
NR 33
TC 568
Z9 664
U1 2
U2 223
PU 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 10
PY 2008
VL 454
IS 7201
BP 192
EP U38
DI 10.1038/nature07047
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900038
PM 18615079
DA 2026-03-09
ER

PT J
AU Gomez, C
   Özbudak, EM
   Wunderlich, J
   Baumann, D
   Lewis, J
   Pourquié, O
AF Gomez, Celine
   Ozbudak, Ertugrul M.
   Wunderlich, Joshua
   Baumann, Diana
   Lewis, Julian
   Pourquie, Olivier
TI Control of segment number in vertebrate embryos
SO NATURE
LA English
DT Article
ID somite boundary formation; paraxial mesoderm; chick-embryo; mouse embryo; clock; expression; gene; somitogenesis; activation; morphogenesis
AB The vertebrate body axis is subdivided into repeated segments, best exemplified by the vertebrae that derive from embryonic somites. The number of somites is precisely defined for any given species but varies widely from one species to another. To determine the mechanism controlling somite number, we have compared somitogenesis in zebrafish, chicken, mouse and corn snake embryos. Here we present evidence that in all of these species a similar 'clock-and-wavefront'(1-3) mechanism operates to control somitogenesis; in all of them, somitogenesis is brought to an end through a process in which the presomitic mesoderm, having first increased in size, gradually shrinks until it is exhausted, terminating somite formation. In snake embryos, however, the segmentation clock rate is much faster relative to developmental rate than in other amniotes, leading to a greatly increased number of smaller-sized somites.
C1 [Gomez, Celine; Ozbudak, Ertugrul M.; Wunderlich, Joshua; Baumann, Diana; Pourquie, Olivier] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Lewis, Julian] London Res Inst, Canc Res UK, Vertebrate Dev Lab, London WC2A 3PX, England.
   [Pourquie, Olivier] Howard Hughes Med Inst, Kansas City, MO 64110 USA.
C3 Stowers Institute for Medical Research; Cancer Research UK; Howard Hughes Medical Institute
RP Pourquié, O (corresponding author), Stowers Inst Med Res, Kansas City, MO 64110 USA.
EM olp@stowers-institute.org
FU Cancer Research UK Funding Source: Medline; Howard Hughes Medical Institute Funding Source: Medline
NR 30
TC 349
Z9 407
U1 3
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 17
PY 2008
VL 454
IS 7202
BP 335
EP 339
DI 10.1038/nature07020
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300039
PM 18563087
DA 2026-03-09
ER

PT J
AU Kishimoto, M
   Antonucci, R
   Blaes, O
   Lawrence, A
   Boisson, C
   Albrecht, M
   Leipski, C
AF Kishimoto, Makoto
   Antonucci, Robert
   Blaes, Omer
   Lawrence, Andy
   Boisson, Catherine
   Albrecht, Marcus
   Leipski, Christian
TI The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared
SO NATURE
LA English
DT Article
ID active galactic nuclei; continuum energy-distributions; seyfert-galaxy; polarization; ultraviolet; models; edge; bump; emission; stellar
AB Quasars are thought to be powered by supermassive black holes accreting surrounding gas(1-3). Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output(2-4). It is well known, however, that the most extensively studied disk model(5) - an optically thick disk which is heated locally by the dissipation of gravitational binding energy is apparently contradicted by observations in a few major respects(6,7). In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared(5,8), but this is not generally seen in the visible wavelength region where the disk spectrum is observable(9-13). A crucial difficulty has been that, towards the infrared, the disk spectrum starts to be hidden under strong, hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emitting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct.
C1 [Kishimoto, Makoto] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Kishimoto, Makoto; Lawrence, Andy] Univ Edinburgh, Royal Observ, Scottish Univ Phys Alliance, Astron Inst, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Antonucci, Robert; Blaes, Omer; Leipski, Christian] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Boisson, Catherine] Univ Paris 07, LUTH, FRE 2462, CNRS,Observ Paris,Sect Meudon, F-92195 Meudon, France.
   [Albrecht, Marcus] Univ Catolica Norte, Inst Astron, Antofagasta 1270709, Chile.
C3 Max Planck Society; University of Edinburgh; University of California System; University of California Santa Barbara; Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universidad Catolica del Norte
RP Kishimoto, M (corresponding author), Max Planck Inst Radioastron, Hugel 69, D-53121 Bonn, Germany.
EM mk@mpifr-bonn.mpg.de
NR 30
TC 120
Z9 131
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 24
PY 2008
VL 454
IS 7203
BP 492
EP 494
DI 10.1038/nature07114
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300045
PM 18650919
DA 2026-03-09
ER

PT J
AU Omran, H
   Kobayashi, D
   Olbrich, H
   Tsukahara, T
   Loges, NT
   Hagiwara, H
   Zhang, Q
   Leblond, G
   O'Toole, E
   Hara, C
   Mizuno, H
   Kawano, H
   Fliegauf, M
   Yagi, T
   Koshida, S
   Miyawaki, A
   Zentgraf, H
   Seithe, H
   Reinhardt, R
   Watanabe, Y
   Kamiya, R
   Mitchell, DR
   Takeda, H
AF Omran, Heymut
   Kobayashi, Daisuke
   Olbrich, Heike
   Tsukahara, Tatsuya
   Loges, Niki T.
   Hagiwara, Haruo
   Zhang, Qi
   Leblond, Gerard
   O'Toole, Eileen
   Hara, Chikako
   Mizuno, Hideaki
   Kawano, Hiroyuki
   Fliegauf, Manfred
   Yagi, Toshiki
   Koshida, Sumito
   Miyawaki, Atsushi
   Zentgraf, Hanswalter
   Seithe, Horst
   Reinhardt, Richard
   Watanabe, Yoshinori
   Kamiya, Ritsu
   Mitchell, David R.
   Takeda, Hiroyuki
TI Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins
SO NATURE
LA English
DT Article
ID primary ciliary dyskinesia; chlamydomonas-reinhardtii; kupffers vesicle; fluid-flow; arm dynein; mutations; medaka; protein; chain; mutant
AB Cilia and flagella are highly conserved organelles that have diverse roles in cell motility and sensing extracellular signals. Motility defects in cilia and flagella often result in primary ciliary dyskinesia. However, the mechanisms underlying cilia formation and function, and in particular the cytoplasmic assembly of dyneins that power ciliary motility, are only poorly understood. Here we report a new gene, kintoun ( ktu), involved in this cytoplasmic process. This gene was first identified in a medaka mutant, and found to be mutated in primary ciliary dyskinesia patients from two affected families as well as in the pf13 mutant of Chlamydomonas. In the absence of Ktu/ PF13, both outer and inner dynein arms are missing or defective in the axoneme, leading to a loss of motility. Biochemical and immunohistochemical studies show that Ktu/ PF13 is one of the long- sought proteins involved in pre- assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment.
C1 [Omran, Heymut; Olbrich, Heike; Loges, Niki T.; Fliegauf, Manfred] Univ Hosp Freiburg, Dept Pediat & Adolescent Med, D-79106 Freiburg, Germany.
   [Kobayashi, Daisuke; Yagi, Toshiki; Koshida, Sumito; Kamiya, Ritsu; Takeda, Hiroyuki] Univ Tokyo, Dept Biol Sci, Grad Sch Sci, Tokyo 1130033, Japan.
   [Tsukahara, Tatsuya; Watanabe, Yoshinori] Univ Tokyo, Inst Mol & Cellular Biosci, Grad Sch Sci, Tokyo 1130033, Japan.
   [Tsukahara, Tatsuya; Watanabe, Yoshinori] Univ Tokyo, Grad Program Biophys & Biochem, Grad Sch Sci, Tokyo 1130033, Japan.
   [Hagiwara, Haruo] Gunma Univ, Grad Sch Med, Dept Anat & Cell Biol, Gunma 3718511, Japan.
   [Zhang, Qi; Leblond, Gerard; Mitchell, David R.] SUNY Upstate Med Univ, Dept Cell & Dev Biol, Syracuse, NY 13210 USA.
   [O'Toole, Eileen] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
   [Hara, Chikako; Mizuno, Hideaki; Kawano, Hiroyuki; Miyawaki, Atsushi] RIKEN, Brain Sci Inst, Adv Technol Dev Grp, Lab Cell Funct Dynam, Wako, Saitama 3510198, Japan.
   [Zentgraf, Hanswalter] German Canc Res Ctr, Dept Tumor Virol, D-69120 Heidelberg, Germany.
   [Seithe, Horst] Klinikum Nurnberg Sud, Klin Kinder & Jugendliche, D-90471 Nurnberg, Germany.
   [Reinhardt, Richard] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
C3 University of Freiburg; University of Tokyo; University of Tokyo; University of Tokyo; Gunma University; State University of New York (SUNY) System; SUNY Upstate Medical University; University of Colorado System; University of Colorado Boulder; RIKEN; Helmholtz Association; German Cancer Research Center (DKFZ); Max Planck Society
RP Omran, H (corresponding author), Univ Hosp Freiburg, Dept Pediat & Adolescent Med, Mathildenstr 1, D-79106 Freiburg, Germany.
EM heymut.omran@uniklinik-freiburg.de; MitchelD@upstate.edu; htakeda@biol.s.u-tokyo.ac.jp
FU NIG Cooperative Research Program; Grants-in-Aid for Scientific Research Priority Area Genome Science and Scientific Research (A and B); Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms); Ministry of Education, Culture, Sports, Science and Technology ( MEXT) of Japan; Yamada Science Foundation; Bio-Design Project of the Ministry of Agriculture, Forestry and Fisheries of Japan; University of Tokyo; MEXT, Japan; ' Deutsche Forschungsgemeinschaft' [DFG Om 6/4, GRK1104]; BIOSS; NIH [GM44228]; German Ministry of Science and Education ( BMBF) [NGFN-2:01GR0414-PDN-S02T17]; 'Primare Ciliaere Dyskinesie and Kartagener Syndrom e. V.';  [SFB592]; Grants-in-Aid for Scientific Research [20247030] Funding Source: KAKEN
NR 47
TC 294
Z9 338
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 DEC 4
PY 2008
VL 456
IS 7222
BP 611
EP U54
DI 10.1038/nature07471
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000034
PM 19052621
DA 2026-03-09
ER

PT J
AU Evershed, RP
   Payne, S
   Sherratt, AG
   Copley, MS
   Coolidge, J
   Urem-Kotsu, D
   Kotsakis, K
   Özdogan, M
   Özdogan, AE
   Nieuwenhuyse, O
   Akkermans, PMMG
   Bailey, D
   Andeescu, RR
   Campbell, S
   Farid, S
   Hodder, I
   Yalman, N
   Özbasaran, M
   Biçakci, E
   Garfinkel, Y
   Levy, T
   Burton, MM
AF Evershed, Richard P.
   Payne, Sebastian
   Sherratt, Andrew G.
   Copley, Mark S.
   Coolidge, Jennifer
   Urem-Kotsu, Duska
   Kotsakis, Kostas
   Ozdogan, Mehmet
   Ozdogan, Asly E.
   Nieuwenhuyse, Olivier
   Akkermans, Peter M. M. G.
   Bailey, Douglass
   Andeescu, Radian-Romus
   Campbell, Stuart
   Farid, Shahina
   Hodder, Ian
   Yalman, Nurcan
   Ozbasaran, Mihriban
   Bicakci, Erhan
   Garfinkel, Yossef
   Levy, Thomas
   Burton, Margie M.
TI Earliest date for milk use in the Near East and southeastern Europe linked to cattle herding
SO NATURE
LA English
DT Article
ID pottery vessels; potsherds; products
AB The domestication of cattle, sheep and goats had already taken place in the Near East by the eighth millennium BC(1-3). Although there would have been considerable economic and nutritional gains from using these animals for their milk and other products from living animals - that is, traction and wool - the first clear evidence for these appears much later, from the late fifth and fourth millennia BC(4,5). Hence, the timing and region in which milking was first practised remain unknown. Organic residues preserved in archaeological pottery(6,7) have provided direct evidence for the use of milk in the fourth millennium in Britain(7-9), and in the sixth millennium in eastern Europe(10), based on the delta(13)C values of the major fatty acids of milk fat(6,7). Here we apply this approach to more than 2,200 pottery vessels from sites in the Near East and southeastern Europe dating from the fifth to the seventh millennia BC. We show that milk was in use by the seventh millennium; this is the earliest direct evidence to date. Milking was particularly important in northwestern Anatolia, pointing to regional differences linked with conditions more favourable to cattle compared to other regions, where sheep and goats were relatively common and milk use less important. The latter is supported by correlations between the fat type and animal bone evidence.
C1 [Evershed, Richard P.; Copley, Mark S.] Univ Bristol, Sch Chem, Organ Geochem Unit, Bristol Biogeochem Res Ctr, Bristol BS8 1TS, Avon, England.
   [Payne, Sebastian] English Heritage, London EC1N 2ST, England.
   [Sherratt, Andrew G.] Univ Sheffield, Dept Archaeol, Sheffield S10 2TN, S Yorkshire, England.
   [Coolidge, Jennifer] Univ Oxford, Archaeol & Hist Art Res Lab, Oxford OX1 3QJ, England.
   [Urem-Kotsu, Duska; Kotsakis, Kostas] Aristotle Univ Thessaloniki, Dept Archaeol, Thessaloniki 54124, Greece.
   [Ozdogan, Mehmet; Ozbasaran, Mihriban; Bicakci, Erhan] Istanbul Univ, Prehist Dept, TR-34134 Istanbul, Turkey.
   [Ozdogan, Asly E.] Canakkale Onsekiz Mart Univ, Dept Archaeol, TR-17020 Canakkale, Turkey.
   [Nieuwenhuyse, Olivier; Akkermans, Peter M. M. G.] Netherlands Natl Museum Antiqu, NL-2301 EC Leiden, Netherlands.
   [Nieuwenhuyse, Olivier; Akkermans, Peter M. M. G.] Leiden Univ, NL-2301 EC Leiden, Netherlands.
   [Bailey, Douglass] Cardiff Univ, Sch Hist & Archaeol, Cardiff CF10 3EU, Wales.
   [Andeescu, Radian-Romus] Romanian Natl Museum Hist, Bucharest 030026, Romania.
   [Campbell, Stuart] Univ Manchester, Sch Arts Hist & Cultures, Manchester M13 9PL, Lancs, England.
   [Farid, Shahina] UCL, Inst Archaeol, London WC1H 0PY, England.
   [Hodder, Ian] Stanford Univ, Archaeol Ctr, Stanford, CA 94305 USA.
   [Yalman, Nurcan; Garfinkel, Yossef] Hebrew Univ Jerusalem, Inst Archaeol, IL-91905 Jerusalem, Israel.
   [Levy, Thomas; Burton, Margie M.] Univ Calif San Diego, Dept Anthropol, La Jolla, CA 92093 USA.
C3 University of Bristol; English Heritage; University of Sheffield; University of Oxford; Aristotle University of Thessaloniki; Istanbul University; Canakkale Onsekiz Mart University; Leiden University; Leiden University - Excl LUMC; Cardiff University; University of Manchester; University of London; University College London; Stanford University; Hebrew University of Jerusalem; University of California System; University of California San Diego
RP Evershed, RP (corresponding author), Univ Bristol, Sch Chem, Organ Geochem Unit, Bristol Biogeochem Res Ctr, Cantocks Close, Bristol BS8 1TS, Avon, England.
EM r.p.evershed@bristol.ac.uk
FU Leverhulme Trust [F/00182/T]; UK Natural Environment Research Council
NR 30
TC 453
Z9 534
U1 4
U2 154
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 528
EP 531
DI 10.1038/nature07180
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600045
PM 18690215
DA 2026-03-09
ER

PT J
AU Turgeon, SC
   Creaser, RA
AF Turgeon, Steven C.
   Creaser, Robert A.
TI Cretaceous oceanic anoxic event 2 triggered by a massive magmatic episode
SO NATURE
LA English
DT Article
ID cenomanian-turonian boundary; isotope stratigraphy; dysoxic events; volcanism; extinctions; madagascar; atlantic; end
AB Oceanic anoxic events ( OAEs) were episodes of widespread marine anoxia during which large amounts of organic carbon were buried on the ocean floor under oxygen- deficient bottom waters(1,2). OAE2, occurring at the Cenomanian/ Turonian boundary ( about 93.5 Myr ago)(3), is the most widespread and best defined OAE of the mid-Cretaceous. Although the enhanced burial of organic matter can be explained either through increased primary productivity or enhanced preservation scenarios(1,2), the actual trigger mechanism, corresponding closely to the onset of these episodes of increased carbon sequestration, has not been clearly identified. It has been postulated that large- scale magmatic activity initially triggered OAE2 ( refs 4, 5), but a direct proxy of magmatism preserved in the sedimentary record coinciding closely with the onset of OAE2 has not yet been found. Here we report seawater osmium isotope ratios in organic- rich sediments from two distant sites. We find that at both study sites the marine osmium isotope record changes abruptly just at or before the onset of OAE2. Using a simple two-component mixing equation, we calculate that over 97 per cent of the total osmium content in contemporaneous seawater at both sites is magmatic in origin, a similar to 30-50-fold increase relative to pre-OAE conditions. Furthermore, the magmatic osmium isotope signal appears slightly before the OAE2 - as indicated by carbon isotope ratios - suggesting a time- lag of up to similar to 23 kyr between magmatism and the onset of significant organic carbon burial, which may reflect the reaction time of the global ocean system. Our marine osmium isotope data are indicative of a widespread magmatic pulse at the onset of OAE2, which may have triggered the subsequent deposition of large amounts of organic matter.
C1 [Turgeon, Steven C.; Creaser, Robert A.] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T2G 2E2, Canada.
C3 University of Alberta
RP Turgeon, SC (corresponding author), Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T2G 2E2, Canada.
EM turgeonsc@ualberta.ca
NR 30
TC 418
Z9 494
U1 5
U2 100
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 323
EP U29
DI 10.1038/nature07076
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300036
PM 18633415
DA 2026-03-09
ER

PT J
AU Luik, RM
   Wang, B
   Prakriya, M
   Wu, MM
   Lewis, RS
AF Luik, Riina M.
   Wang, Bin
   Prakriya, Murali
   Wu, Minnie M.
   Lewis, Richard S.
TI Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation
SO NATURE
LA English
DT Article
ID stromal interaction molecule-1; operated ca2+ entry; plasma-membrane; endoplasmic-reticulum; store depletion; protein; orai1; mechanism; domain; sensor
AB Ca(2+)-release-activated Ca(2+) (CRAC) channels generate sustained Ca(2+) signals that are essential for a range of cell functions, including antigen-stimulated T lymphocyte activation and proliferation(1,2). Recent studies(3) have revealed that the depletion of Ca(2+) from the endoplasmic reticulum (ER) triggers the oligomerization of stromal interaction molecule 1 (STIM1), the ER Ca(2+) sensor, and its redistribution to ER-plasma membrane (ER-PM) junctions(4-8) where the CRAC channel subunit ORAI1 accumulates in the plasma membrane and CRAC channels open(9-12). However, how the loss of ER Ca(2+) sets into motion these coordinated molecular rearrangements remains unclear. Here we define the relationships among [Ca(2+)](ER), STIM1 redistribution and CRAC channel activation and identify STIM1 oligomerization as the critical [Ca(2+)](ER)-dependent event that drives store-operated Ca(2+) entry. In human Jurkat leukaemic T cells expressing an ER-targeted Ca(2+) indicator, CRAC channel activation and STIM1 redistribution follow the same function of [Ca(2+)](ER), reaching half-maximum at similar to 200 mu M with a Hill coefficient of similar to 4. Because STIM1 binds only a single Ca(2+) ion(5), the high apparent cooperativity suggests that STIM1 must first oligomerize to enable its accumulation at ER-PM junctions. To assess directly the causal role of STIM1 oligomerization in store-operated Ca(2+) entry, we replaced the luminal Ca(2+)-sensing domain of STIM1 with the 12-kDa FK506- and rapamycin-binding protein (FKBP12, also known as FKBP1A) or the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR, also known as FRAP1). A rapamycin analogue oligomerizes the fusion proteins and causes them to accumulate at ER-PM junctions and activate CRAC channels without depleting Ca(2+) from the ER. Thus, STIM1 oligomerization is the critical transduction event through which Ca(2+) store depletion controls store-operated Ca(2+) entry, acting as a switch that triggers the self-organization and activation of STIM1-ORAI1 clusters at ER-PM junctions.
C1 [Luik, Riina M.; Wang, Bin; Prakriya, Murali; Wu, Minnie M.; Lewis, Richard S.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
C3 Stanford University
RP Lewis, RS (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
EM rslewis@stanford.edu
FU National Institute of Allergy and Infectious Diseases [T32AI007290] Funding Source: NIH RePORTER; NIAID NIH HHS [T32 AI007290] Funding Source: Medline; NIGMS NIH HHS [R01 GM045374] Funding Source: Medline
NR 31
TC 459
Z9 544
U1 1
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 538
EP U11
DI 10.1038/nature07065
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300056
PM 18596693
DA 2026-03-09
ER

PT J
AU Nordborg, M
   Weigel, D
AF Nordborg, Magnus
   Weigel, Detlef
TI Next-generation genetics in plants
SO NATURE
LA English
DT Article
ID quantitative trait locus; genome-wide association; arabidopsis-thaliana; flowering time; complex traits; structural variation; haplotype map; maize; disequilibrium; recombination
AB Natural variation presents one of the fundamental challenges of modern biology. Soon, the genome sequences of thousands of individuals will be known for each of several species. But how does the genotypic variation that will be observed among these individuals translate into phenotypic variation? Plants are in many ways ideal for addressing this question, and resources that are unmatched, except in humans, have now been developed.
C1 [Nordborg, Magnus] Univ So Calif, Los Angeles, CA 90089 USA.
   [Weigel, Detlef] Max Planck Inst Dev Biol, Dept Mol Biol, D-72076 Tubingen, Germany.
C3 University of Southern California; Max Planck Society
RP Nordborg, M (corresponding author), Univ So Calif, Los Angeles, CA 90089 USA.
EM magnus@usc.edu; weigel@weigelworld.org
FU National Science Foundation; National Institutes of Health; German Research Foundation; German Federal Ministry of Education and Research; European Union's Sixth Framework Programme; Human Frontier Science Program; Max Planck Society
NR 35
TC 332
Z9 407
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 DEC 11
PY 2008
VL 456
IS 7223
BP 720
EP 723
DI 10.1038/nature07629
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900034
PM 19079047
DA 2026-03-09
ER

PT J
AU Michishita, E
   McCord, RA
   Berber, E
   Kioi, M
   Padilla-Nash, H
   Damian, M
   Cheung, P
   Kusumoto, R
   Kawahara, TLA
   Barrett, JC
   Chang, HY
   Bohr, VA
   Ried, T
   Gozani, O
   Chua, KF
AF Michishita, Eriko
   McCord, Ronald A.
   Berber, Elisabeth
   Kioi, Mitomu
   Padilla-Nash, Hesed
   Damian, Mara
   Cheung, Peggie
   Kusumoto, Rika
   Kawahara, Tiara L. A.
   Barrett, J. Carl
   Chang, Howard Y.
   Bohr, Vilhelm A.
   Ried, Thomas
   Gozani, Or
   Chua, Katrin F.
TI SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin
SO NATURE
LA English
DT Article
ID protects human telomeres; werner-syndrome cells; s-phase; dysfunctional telomeres; syndrome fibroblasts; genomic instability; mammalian telomeres; dna-damage; senescence; trf2
AB The Sir2 deacetylase regulates chromatin silencing and lifespan in Saccharomycescerevisiae(1,2). In mice, deficiency for the Sir2 family member SIRT6 leads to a shortened lifespan and a premature ageing- like phenotype(3). However, the molecular mechanisms of SIRT6 function are unclear. SIRT6 is a chromatin- associated protein(3), but no enzymatic activity of SIRT6 at chromatin has yet been detected, and the identity of physiological SIRT6 substrates is unknown. Here we show that the human SIRT6 protein is an NAD(+)-dependent, histone H3 lysine 9 ( H3K9) deacetylase that modulates telomeric chromatin. SIRT6 associates specifically with telomeres, and SIRT6 depletion leads to telomere dysfunction with end- to- end chromosomal fusions and premature cellular senescence. Moreover, SIRT6- depleted cells exhibit abnormal telomere structures that resemble defects observed in Werner syndrome, a premature ageing disorder(4,5). At telomeric chromatin, SIRT6 deacetylates H3K9 and is required for the stable association of WRN, the factor that is mutated in Werner syndrome(4,5). We propose that SIRT6 contributes to the propagation of a specialized chromatin state at mammalian telomeres, which in turn is required for proper telomere metabolism and function. Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome.
C1 [Michishita, Eriko; McCord, Ronald A.; Berber, Elisabeth; Damian, Mara; Chua, Katrin F.] Stanford Univ, Dept Med, Div Endocrinol Gerontol & Metab, Sch Med, Stanford, CA 94305 USA.
   [Kioi, Mitomu] Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA.
   [Cheung, Peggie; Gozani, Or] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA.
   [Kawahara, Tiara L. A.; Chang, Howard Y.] Stanford Univ, Program Epithelial Biol, Sch Med, Stanford, CA 94305 USA.
   [Michishita, Eriko; McCord, Ronald A.; Berber, Elisabeth; Damian, Mara; Chua, Katrin F.] VA Palo Alto Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Palo Alto, CA 94304 USA.
   [Padilla-Nash, Hesed; Ried, Thomas] NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Barrett, J. Carl] NCI, Lab Biosyst & Canc, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Kusumoto, Rika; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Geriatric Research Education & Clinical Center; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
RP Chua, KF (corresponding author), Stanford Univ, Dept Med, Div Endocrinol Gerontol & Metab, Sch Med, Stanford, CA 94305 USA.
EM kfchua@stanford.edu
FU NIA NIH HHS [R01 AG028867, K08 AG028961] Funding Source: Medline; NIGMS NIH HHS [R01 GM079641] Funding Source: Medline
NR 32
TC 891
Z9 1079
U1 3
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 492
EP U16
DI 10.1038/nature06736
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300036
PM 18337721
DA 2026-03-09
ER

PT J
AU Eliades, SJ
   Wang, XQ
AF Eliades, Steven J.
   Wang, Xiaoqin
TI Neural substrates of vocalization feedback monitoring in primate auditory cortex
SO NATURE
LA English
DT Article
ID speech production; responses; voice; schizophrenia; modulation; marmosets; monkey; sign; fmri
AB Vocal communication involves both speaking and hearing, often taking place concurrently. Vocal production, including human speech and animal vocalization, poses a number of unique challenges for the auditory system. It is important for the auditory system to monitor external sounds continuously from the acoustic environment during speaking despite the potential for sensory masking by self-generated sounds(1). It is also essential for the auditory system to monitor feedback of one's own voice. This self-monitoring may play a part in distinguishing between self-generated or externally generated(2,3) auditory inputs and in detecting errors in our vocal production(4). Previous work in humans(5-10) and other animals(11-13) has demonstrated that the auditory cortex is largely suppressed during speaking or vocalizing. Despite the importance of self-monitoring, the underlying neural mechanisms in the mammalian brain, in particular the role of vocalization-induced suppression, remain virtually unknown. Here we show that neurons in the auditory cortex of marmoset monkeys (Callithrix jacchus) are sensitive to auditory feedback during vocal production, and that changes in the feedback alter the coding properties of these neurons. Furthermore, we found that the previously described cortical suppression during vocalization actually increased the sensitivity of these neurons to vocal feedback. This heightened sensitivity to vocal feedback suggests that these neurons may have an important role in auditory self-monitoring.
C1 [Eliades, Steven J.; Wang, Xiaoqin] Johns Hopkins Univ, Sch Med, Lab Auditory Neurophysiol, Dept Biomed Engn, Baltimore, MD 21205 USA.
C3 Johns Hopkins University
RP Eliades, SJ (corresponding author), Johns Hopkins Univ, Sch Med, Lab Auditory Neurophysiol, Dept Biomed Engn, Baltimore, MD 21205 USA.
EM seliades@jhu.edu; xiaoqin.wang@jhu.edu
NR 30
TC 335
Z9 392
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 JUN 19
PY 2008
VL 453
IS 7198
BP 1102
EP U8
DI 10.1038/nature06910
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900057
PM 18454135
DA 2026-03-09
ER

PT J
AU Gegear, RJ
   Casselman, A
   Waddell, S
   Reppert, SM
AF Gegear, Robert J.
   Casselman, Amy
   Waddell, Scott
   Reppert, Steven M.
TI Cryptochrome mediates light-dependent magnetosensitivity in Drosophila
SO NATURE
LA English
DT Article
ID magnetic-field detection; magnetoreception; mechanism; model; photoreceptor; orientation; animals; birds
AB Although many animals use the Earth's magnetic field for orientation and navigation(1,2), the precise biophysical mechanisms underlying magnetic sensing have been elusive. One theoretical model proposes that geomagnetic fields are perceived by chemical reactions involving specialized photoreceptors(3). However, the specific photoreceptor involved in such magnetoreception has not been demonstrated conclusively in any animal. Here we show that the ultraviolet-A/blue-light photoreceptor cryptochrome ( Cry) is necessary for light- dependent magnetosensitive responses in Drosophila melanogaster. In a binary- choice behavioural assay for magnetosensitivity, wild- type flies show significant naive and trained responses to a magnetic field under full- spectrum light (similar to 300-700 nm) but do not respond to the field when wavelengths in the Cry- sensitive, ultraviolet- A/ blue- light part of the spectrum (<420 nm) are blocked. Notably, Cry- deficient cry(0) and cry(b) flies do not show either naive or trained responses to a magnetic field under full- spectrum light. Moreover, Cry- dependent magnetosensitivity does not require a functioning circadian clock. Our work provides, to our knowledge, the first genetic evidence for a Cry-based magnetosensitive system in any animal.
C1 [Gegear, Robert J.; Casselman, Amy; Waddell, Scott; Reppert, Steven M.] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester
RP Reppert, SM (corresponding author), Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA.
EM steven.reppert@umassmed.edu
FU NIH
NR 30
TC 337
Z9 396
U1 3
U2 176
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 21
PY 2008
VL 454
IS 7207
BP 1014
EP U61
DI 10.1038/nature07183
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000043
PM 18641630
DA 2026-03-09
ER

PT J
AU Conrad, KL
   Tseng, KY
   Uejima, JL
   Reimers, JM
   Heng, LJ
   Shaham, Y
   Marinelli, M
   Wolf, ME
AF Conrad, Kelly L.
   Tseng, Kuei Y.
   Uejima, Jamie L.
   Reimers, Jeremy M.
   Heng, Li-Jun
   Shaham, Yavin
   Marinelli, Michela
   Wolf, Marina E.
TI Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving
SO NATURE
LA English
DT Article
ID cultured hippocampal-neurons; nucleus-accumbens; surface expression; synaptic plasticity; behavioral sensitization; dopamine-receptors; seeking behavior; nmda receptors; rat; addiction
AB Relapse to cocaine use after prolonged abstinence is an important clinical problem. This relapse is often induced by exposure to cues associated with cocaine use. To account for the persistent propensity for relapse, it has been suggested(1) that cue- induced cocaine craving increases over the first several weeks of abstinence and remains high for extended periods. We and others identified an analogous phenomenon in rats that was termed 'incubation of cocaine craving': time- dependent increases in cue- induced cocaine- seeking over the first months after withdrawal from self- administered cocaine(2-4). Cocaine- seeking requires the activation of glutamate projections that excite receptors for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ( AMPA) in the nucleus accumbens(5-7). Here we show that the number of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor 2 ( GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine craving. Our results indicate that GluR2- lacking AMPA receptors could be a new target for drug development for the treatment of cocaine addiction. We propose that after prolonged withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the higher conductance of GluR2- lacking AMPA receptors(8,9) causes increased reactivity of accumbens neurons to cocaine- related cues, leading to an intensification of drug craving and relapse.
C1 [Conrad, Kelly L.; Reimers, Jeremy M.; Wolf, Marina E.] Rosalind Franklin Univ Med & Sci, Dept Neurosci, N Chicago, IL 60064 USA.
   [Tseng, Kuei Y.; Heng, Li-Jun; Marinelli, Michela] Rosalind Franklin Univ Med & Sci, Dept Mol & Cellular Pharmacol, N Chicago, IL 60064 USA.
   [Uejima, Jamie L.; Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA.
C3 Rosalind Franklin University of Medicine & Science; Rosalind Franklin University of Medicine & Science; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); NIH National Institute on Drug Abuse (NIDA)
RP Wolf, ME (corresponding author), Rosalind Franklin Univ Med & Sci, Dept Neurosci, 3333 Green Bay Rd, N Chicago, IL 60064 USA.
EM marina.wolf@rosalindfranklin.edu
FU NIDA NIH HHS [DA020654, R01 DA020654, R01 DA015835, DA09621, K02 DA000453, R37 DA015835, R01 DA009621, DA015835, DA00453] Funding Source: Medline; Intramural NIH HHS [Z01 DA000434] Funding Source: Medline; National Institute on Drug Abuse [ZIADA000434, R01DA009621] Funding Source: NIH RePORTER
NR 50
TC 718
Z9 860
U1 0
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 118
EP U9
DI 10.1038/nature06995
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300049
PM 18500330
DA 2026-03-09
ER

PT J
AU Yoo, SD
   Cho, YH
   Tena, G
   Xiong, Y
   Sheen, J
AF Yoo, Sang-Dong
   Cho, Young-Hee
   Tena, Guillaume
   Xiong, Yan
   Sheen, Jen
TI Dual control of nuclear EIN3 by bifurcate MAPK cascades in C2H4 signalling
SO NATURE
LA English
DT Article
ID activated protein-kinase; ethylene-response pathway; f-box proteins; functional-analysis; arabidopsis; stress; ubiquitin; ctr1; etr1; ethylene-insensitive3
AB A principal question in MAP kinase ( MAPK/ MPK) cascade signalling is how similar components dictate different specificity in the information- processing machineries from yeast to humans and plants. In Arabidopsis, how MPK3/ 6modulates distinct outputs in diverse signal transduction pathways remains elusive. By combining systematic cellular and genetic screens, here we uncover a previously unexpected MKK9 - MPK3/ MPK6 cascade promoting ethylene- insensitive 3 ( EIN3)- mediated transcription in ethylene signalling. The mkk9 mutant exhibits a broad spectrum of moderate ethylene- insensitive phenotypes, and translocated MKK9 governs nuclear signalling downstream of receptors. Breaking a linear model and conventional MAPK signalling, ethylene inactivates the negative regulator constitutive triple response 1 ( CTR1, a Raf- like MAPK kinase kinase ( MAPKKK)) to activate the positive MKK9 - MPK3/ 6 cascade. The bifurcate and antagonistic CTR1 and MKK9 pathways are both critical in determining ethylene- signalling specificity through two MAPK phosphorylation sites with opposite effects on EIN3 stability. The results suggest a new paradigm for linking intertwined MAPK cascades to control quantitative responses and specificity in signalling networks.
C1 [Yoo, Sang-Dong; Cho, Young-Hee; Tena, Guillaume; Xiong, Yan; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Yoo, Sang-Dong; Cho, Young-Hee; Tena, Guillaume; Xiong, Yan; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
RP Sheen, J (corresponding author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM yoo@molbio.mgh.harvard.edu; sheen@molbio.mgh.harvard.edu
FU NIGMS NIH HHS [R01 GM070567, R01 GM060493] Funding Source: Medline
NR 50
TC 408
Z9 493
U1 5
U2 121
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 789
EP U1
DI 10.1038/nature06543
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400034
PM 18273012
DA 2026-03-09
ER

PT J
AU Stefansson, H
   Rujescu, D
   Cichon, S
   Pietiläinen, OPH
   Ingason, A
   Steinberg, S
   Fossdal, R
   Sigurdsson, E
   Sigmundsson, T
   Buizer-Voskamp, JE
   Hansen, T
   Jakobsen, KD
   Muglia, P
   Francks, C
   Matthews, PM
   Gylfason, A
   Halldorsson, BV
   Gudbjartsson, D
   Thorgeirsson, TE
   Sigurdsson, A
   Jonasdottir, A
   Jonasdottir, A
   Bjornsson, A
   Mattiasdottir, S
   Blondal, T
   Haraldsson, M
   Magnusdottir, BB
   Giegling, I
   Möller, HJ
   Hartmann, A
   Shianna, KV
   Ge, DL
   Need, AC
   Crombie, C
   Fraser, G
   Walker, N
   Lonnqvist, J
   Suvisaari, J
   Tuulio-Henriksson, A
   Paunio, T
   Toulopoulou, T
   Bramon, E
   Di Forti, M
   Murray, R
   Ruggeri, M
   Vassos, E
   Tosato, S
   Walshe, M
   Li, T
   Vasilescu, C
   Mühleisen, TW
   Wang, AG
   Ullum, H
   Djurovic, S
   Melle, I
   Olesen, J
   Kiemeney, LA
   Franke, B
   Sabatti, C
   Freimer, NB
   Gulcher, JR
   Thorsteinsdottir, U
   Kong, A
   Andreassen, OA
   Ophoff, RA
   Georgi, A
   Rietschel, M
   Werge, T
   Petursson, H
   Goldstein, DB
   Nöthen, MM
   Peltonen, L
   Collier, DA
   St Clair, D
   Stefansson, K
AF Stefansson, Hreinn
   Rujescu, Dan
   Cichon, Sven
   Pietilainen, Olli P. H.
   Ingason, Andres
   Steinberg, Stacy
   Fossdal, Ragnheidur
   Sigurdsson, Engilbert
   Sigmundsson, Thordur
   Buizer-Voskamp, Jacobine E.
   Hansen, Thomas
   Jakobsen, Klaus D.
   Muglia, Pierandrea
   Francks, Clyde
   Matthews, Paul M.
   Gylfason, Arnaldur
   Halldorsson, Bjarni V.
   Gudbjartsson, Daniel
   Thorgeirsson, Thorgeir E.
   Sigurdsson, Asgeir
   Jonasdottir, Adalbjorg
   Jonasdottir, Aslaug
   Bjornsson, Asgeir
   Mattiasdottir, Sigurborg
   Blondal, Thorarinn
   Haraldsson, Magnus
   Magnusdottir, Brynja B.
   Giegling, Ina
   Moeller, Hans-Juergen
   Hartmann, Annette
   Shianna, Kevin V.
   Ge, Dongliang
   Need, Anna C.
   Crombie, Caroline
   Fraser, Gillian
   Walker, Nicholas
   Lonnqvist, Jouko
   Suvisaari, Jaana
   Tuulio-Henriksson, Annamarie
   Paunio, Tiina
   Toulopoulou, Timi
   Bramon, Elvira
   Di Forti, Marta
   Murray, Robin
   Ruggeri, Mirella
   Vassos, Evangelos
   Tosato, Sarah
   Walshe, Muriel
   Li, Tao
   Vasilescu, Catalina
   Muehleisen, Thomas W.
   Wang, August G.
   Ullum, Henrik
   Djurovic, Srdjan
   Melle, Ingrid
   Olesen, Jes
   Kiemeney, Lambertus A.
   Franke, Barbara
   Sabatti, Chiara
   Freimer, Nelson B.
   Gulcher, Jeffrey R.
   Thorsteinsdottir, Unnur
   Kong, Augustine
   Andreassen, Ole A.
   Ophoff, Roel A.
   Georgi, Alexander
   Rietschel, Marcella
   Werge, Thomas
   Petursson, Hannes
   Goldstein, David B.
   Noethen, Markus M.
   Peltonen, Leena
   Collier, David A.
   St Clair, David
   Stefansson, Kari
TI Large recurrent microdeletions associated with schizophrenia
SO NATURE
LA English
DT Article
ID fragile-x-syndrome; genomic disorders; linkage analysis; deletion; genes; amplification; chromosm; impairment; phenotype; deficit
AB Reduced fecundity, associated with severe mental disorders(1), places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism(2), schizophrenia(3) and mental retardation(4). Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations ( CNVs) can be detected using genome- wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation(4,5) and autism(2). In a genome- wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample ( phase I) were followed up in a second sample of 3,285 cases and 7,951 controls ( phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.
C1 [Crombie, Caroline; Fraser, Gillian; St Clair, David] Univ Aberdeen, Royal Cornhill Hosp, Dept Mental Hlth, Aberdeen AB25 2ZD, Scotland.
   [Stefansson, Hreinn; Ingason, Andres; Steinberg, Stacy; Fossdal, Ragnheidur; Gylfason, Arnaldur; Halldorsson, Bjarni V.; Gudbjartsson, Daniel; Thorgeirsson, Thorgeir E.; Sigurdsson, Asgeir; Jonasdottir, Adalbjorg; Jonasdottir, Aslaug; Bjornsson, Asgeir; Mattiasdottir, Sigurborg; Blondal, Thorarinn; Gulcher, Jeffrey R.; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari] deCODE Genet, CNS Div, IS-101 Reykjavik, Iceland.
   [Rujescu, Dan; Giegling, Ina; Moeller, Hans-Juergen; Hartmann, Annette] Univ Munich, Div Mol & Clin Neurobiol, Dept Psychiat, Genet Res Ctr, D-80336 Munich, Germany.
   [Cichon, Sven; Vasilescu, Catalina; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-53127 Bonn, Germany.
   [Cichon, Sven; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-53111 Bonn, Germany.
   [Pietilainen, Olli P. H.; Paunio, Tiina; Peltonen, Leena] Natl Publ Hlth Inst, Dept Mol Med, Biomedicum, Helsinki 00290, Finland.
   [Sigurdsson, Engilbert; Sigmundsson, Thordur; Haraldsson, Magnus; Magnusdottir, Brynja B.; Petursson, Hannes] Natl Univ Hosp Reykjavik, Dept Psychiat, IS-101 Reykjavik, Iceland.
   [Buizer-Voskamp, Jacobine E.; Ophoff, Roel A.] Univ Med Ctr Utrecht, Netherlands Dept Med Genet, NL-3584 CG Utrecht, Netherlands.
   [Buizer-Voskamp, Jacobine E.; Ophoff, Roel A.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands.
   [Hansen, Thomas; Jakobsen, Klaus D.; Werge, Thomas] Univ Copenhagen Hosp, Res Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, DK-4000 Roskilde, Denmark.
   [Hansen, Thomas; Jakobsen, Klaus D.] Univ Copenhagen, Ctr Pharmacogenom, DK-2200 Copenhagen N, Denmark.
   [Muglia, Pierandrea; Francks, Clyde] GlaxoSmithKline R&D, Med Genet, I-37135 Verona, Italy.
   [Matthews, Paul M.] Hammersmith Hosp, GlaxoSmithKline, Clin Imaging Ctr, London W12 0NN, England.
   [Shianna, Kevin V.; Ge, Dongliang; Need, Anna C.; Goldstein, David B.] Duke Univ, Inst Genome Sci & Policy, Ctr Populat Genom & Pharmacogenet, Durham, NC 27708 USA.
   [Walker, Nicholas] Ravenscraig Hosp, Greenock PA16 9HA, Scotland.
   [Lonnqvist, Jouko; Suvisaari, Jaana; Tuulio-Henriksson, Annamarie; Paunio, Tiina] Natl Publ Hlth Inst, Dept Mental Hlth & Addict, FIN-00300 Helsinki, Finland.
   [Toulopoulou, Timi; Bramon, Elvira; Di Forti, Marta; Murray, Robin; Vassos, Evangelos; Walshe, Muriel; Li, Tao; Collier, David A.] Kings Coll London, Div Psychol Med & Social, Genet & Dev Psychiat Ctr, Inst Psychiat, London SE5 8AF, England.
   [Ruggeri, Mirella; Tosato, Sarah] Univ Verona, Sect Psychiat & Clin Psychol, I-37134 Verona, Italy.
   [Li, Tao; Collier, David A.] Sichuan Univ, W China Hosp, Dept Psychiat, Psychiat Lab, Chengdu 610041, Peoples R China.
   [Wang, August G.] Copenhagen Univ Hosp, Dept Clin Immunol, DK-2200 Copenhagen N, Denmark.
   [Ullum, Henrik] Copenhagen Univ Hosp, Mental Hlth Ctr Amager, DK-2300 Copenhagen S, Denmark.
   [Djurovic, Srdjan; Andreassen, Ole A.] Univ Oslo, Inst Psychiat, N-0318 Oslo, Norway.
   [Djurovic, Srdjan; Melle, Ingrid; Andreassen, Ole A.] Ullevaal Univ Hosp, Dept Med Genet, N-0407 Oslo, Norway.
   [Djurovic, Srdjan; Melle, Ingrid; Andreassen, Ole A.] Ullevaal Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway.
   [Olesen, Jes] Glostrup Cty Hosp, Dept Neurol, DK-2600 Glostrup, Denmark.
   [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat EPIB 133, NL-6500 HB Nijmegen, Netherlands.
   [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol URO 659, NL-6500 HB Nijmegen, Netherlands.
   [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
   [Sabatti, Chiara] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Sabatti, Chiara] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA.
   [Freimer, Nelson B.; Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA.
   [Georgi, Alexander; Rietschel, Marcella] Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Germany.
   [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Peltonen, Leena] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [St Clair, David; Stefansson, Kari] Univ Iceland, Sch Med, IS-101 Reykjavik, Iceland.
C3 University of Aberdeen; Decode Genetics; University of Munich; University of Bonn; University of Bonn; Finland National Institute for Health & Welfare; University of Helsinki; Landspitali National University Hospital; Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; University of Copenhagen; Copenhagen University Hospital; University of Copenhagen; GlaxoSmithKline; GlaxoSmithKline Italy; GlaxoSmithKline; Glaxosmithkline United Kingdom; Imperial College London; Duke University; Finland National Institute for Health & Welfare; University of London; King's College London; University of Verona; Sichuan University; University of Copenhagen; Copenhagen University Hospital; University of Copenhagen; Copenhagen University Hospital; University of Oslo; University of Oslo; University of Oslo; University of Copenhagen; Radboud University Nijmegen; Radboud University Nijmegen; Radboud University Nijmegen; 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; Ruprecht Karls University Heidelberg; Central Institute of Mental Health; Wellcome Trust Sanger Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Iceland
RP St Clair, D (corresponding author), Univ Aberdeen, Royal Cornhill Hosp, Dept Mental Hlth, Aberdeen AB25 2ZD, Scotland.
EM d.stclair@abdn.ac.uk; kari.stefansson@decode.is
FU EU grant [LSHM-CT-2006-037761 ( Project SGENE)]; Simons Foundation; NIMH [R01 MH078075]; Chinese National Natural Science Foundation; National Genomic Network (NGFN-2) of the German Federal Ministry of Education and Research (BMBF); Alfried Krupp von Bohlen und Halbach-Stiftung;  [R01MH71425-01A1]; National Institute for Health Research [PDA/02/06/016] Funding Source: researchfish
NR 30
TC 1381
Z9 1602
U1 0
U2 191
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 11
PY 2008
VL 455
IS 7210
BP 232
EP U61
DI 10.1038/nature07229
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800049
PM 18668039
DA 2026-03-09
ER

PT J
AU Yi, R
   Poy, MN
   Stoffel, M
   Fuchs, E
AF Yi, Rui
   Poy, Matthew N.
   Stoffel, Markus
   Fuchs, Elaine
TI A skin microRNA promotes differentiation by repressing 'stemness'
SO NATURE
LA English
DT Article
ID gene-expression; p53 homolog; in-vivo; p63; keratinocyte; cells; proliferation; morphogenesis; commitment; zebrafish
AB In stratified epithelial tissues, homeostasis relies on the self-renewing capacity of stem cells located within the innermost basal layer(1). As basal cells become suprabasal, they lose proliferative potential and embark on a terminal differentiation programme(2,3). Here, we show that microRNA- 203 is induced in the skin concomitantly with stratification and differentiation. By alteringmiR- 203' s spatiotemporal expression in vivo, we show that miR- 203 promotes epidermal differentiation by restricting proliferative potential and inducing cell- cycle exit. We identify p63 as one of the conserved targets of miR- 203 across vertebrates. Notably, p63 is an essential regulator of stem- cell maintenance in stratified epithelial tissues(4-9). We show that miR- 203 directly represses the expression of p63: it fails to switch off suprabasally when either Dicer1 or miR- 203 is absent and it becomes repressed basally when miR- 203 is prematurely expressed. Our findings suggest that miR- 203 defines a molecular boundary between proliferative basal progenitors and terminally differentiating suprabasal cells, ensuring proper identity of neighbouring layers.
C1 [Yi, Rui; Fuchs, Elaine] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Yi, Rui; Fuchs, Elaine] Rockefeller Univ, Lab Mammalian Cell Biol & Dev, New York, NY 10065 USA.
   [Poy, Matthew N.; Stoffel, Markus] ETH, Swiss Fed Inst Technol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
C3 Howard Hughes Medical Institute; Rockefeller University; Rockefeller University; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Fuchs, E (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
EM fuchslb@rockefeller.edu
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR050452] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NIAMS NIH HHS [R01 AR050452] Funding Source: Medline
NR 30
TC 640
Z9 763
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 13
PY 2008
VL 452
IS 7184
BP 225
EP U69
DI 10.1038/nature06642
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600042
PM 18311128
DA 2026-03-09
ER

PT J
AU Heimann, M
   Reichstein, M
AF Heimann, Martin
   Reichstein, Markus
TI Terrestrial ecosystem carbon dynamics and climate feedbacks
SO NATURE
LA English
DT Article
ID temperature; soil; decomposition
AB Recent evidence suggests that, on a global scale, terrestrial ecosystems will provide a positive feedback in a warming world, albeit of uncertain magnitude.
C1 [Heimann, Martin; Reichstein, Markus] Max Planck Inst Biogeochem, D-07745 Jena, Germany.
C3 Max Planck Society
RP Heimann, M (corresponding author), Max Planck Inst Biogeochem, Hans Knoll Str 10, D-07745 Jena, Germany.
EM martin.heimann@bgc-jena.mpg.de
NR 18
TC 1237
Z9 1523
U1 13
U2 945
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 289
EP 292
DI 10.1038/nature06591
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100038
PM 18202646
DA 2026-03-09
ER

PT J
AU Simonetti, A
   Marzi, S
   Myasnikov, AG
   Fabbretti, A
   Yusupov, M
   Gualerzi, CO
   Klaholz, BP
AF Simonetti, Angelita
   Marzi, Stefano
   Myasnikov, Alexander G.
   Fabbretti, Attilio
   Yusupov, Marat
   Gualerzi, Claudio O.
   Klaholz, Bruno P.
TI Structure of the 30S translation initiation complex
SO NATURE
LA English
DT Article
ID messenger-rna translation; ribosomal-subunit; crystal-structure; binding; fmet-trna(fmet); termination; bootstrap; movement; reveals; events
AB Translation initiation, the rate- limiting step of the universal process of protein synthesis, proceeds through sequential, tightly regulated steps. In bacteria, the correct messenger RNA start site and the reading frame are selected when, with the help of initiation factors IF1, IF2 and IF3, the initiation codon is decoded in the peptidyl site of the 30S ribosomal subunit by the fMet-tRNA(fMet) anticodon. This yields a 30S initiation complex (30SIC) that is an intermediate in the formation of the 70S initiation complex (70SIC) that occurs on joining of the 50S ribosomal subunit to the 30SIC and release of the initiation factors(1-3). The localization of IF2 in the 30SIC has proved to be difficult so far using biochemical approaches, but could now be addressed using cryo- electron microscopy and advanced particle separation techniques on the basis of three- dimensional statistical analysis. Here we report the direct visualization of a 30SIC containing mRNA, fMet-tRNA(fMet) and initiation factors IF1 and GTP-bound IF2. We demonstrate that the fMet-tRNA(fMet) is held in a characteristic and precise position and conformation by two interactions that contribute to the formation of a stable complex: one involves the transfer RNA decoding stem which is buried in the 30S peptidyl site, and the other occurs between the carboxy- terminal domain of IF2 and the tRNA acceptor end. The structure provides insights into the mechanism of 70SIC assembly and rationalizes the rapid activation of GTP hydrolysis triggered on 30SIC-50S joining(2,3) by showing that the GTP- binding domain of IF2 would directly face the GTPase-activated centre of the 50S subunit.
C1 [Simonetti, Angelita; Marzi, Stefano; Myasnikov, Alexander G.; Yusupov, Marat; Klaholz, Bruno P.] Inst Genet & Mol & Cellular Biol, Dept Struct Biol & Genom, F-67404 Illkirch Graffenstaden, France.
   [Simonetti, Angelita; Marzi, Stefano; Myasnikov, Alexander G.; Yusupov, Marat; Klaholz, Bruno P.] INSERM, U596, F-67404 Illkirch Graffenstaden, France.
   [Simonetti, Angelita; Marzi, Stefano; Myasnikov, Alexander G.; Yusupov, Marat; Klaholz, Bruno P.] CNRS, UMR7104, F-67404 Illkirch Graffenstaden, France.
   [Simonetti, Angelita; Marzi, Stefano; Myasnikov, Alexander G.; Yusupov, Marat; Klaholz, Bruno P.] Univ Strasbourg, F-67070 Strasbourg, France.
   [Marzi, Stefano] CNRS, Inst Biol Mol & Cellulaire, Architecture & React ARN, UPR 9002, F-67084 Strasbourg, France.
   [Fabbretti, Attilio; Gualerzi, Claudio O.] Univ Camerino, Dept Biol, Genet Lab, MCA, I-62032 Camerino, MC, Italy.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Camerino
RP Klaholz, BP (corresponding author), Inst Genet & Mol & Cellular Biol, Dept Struct Biol & Genom, F-67404 Illkirch Graffenstaden, France.
EM klaholz@igbmc.u-strasbg.fr
FU Centre National pour la Recherche Scientifique; Ministere de la Recherche et de la Technologie; European Molecular Biology Organization Young Investigator Programme; Institut du Developpement et des Ressources en Informatique Scientifique; European Commission [LSHG-CT-2006-031220]; SPINE2; Institut National de la Sante et de la Recherche Medicale; Fondation de la Recherche Medicale; ULP,; CNRS; FRM; Alsace Regio; Association pour la Recherche sur le Cancer
NR 37
TC 177
Z9 214
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 416
EP U73
DI 10.1038/nature07192
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200050
PM 18758445
DA 2026-03-09
ER

PT J
AU Spalding, KL
   Arner, E
   Westermark, PO
   Bernard, S
   Buchholz, BA
   Bergmann, O
   Blomqvist, L
   Hoffstedt, J
   Näslund, E
   Britton, T
   Concha, H
   Hassan, M
   Rydén, M
   Frisén, J
   Arner, P
AF Spalding, Kirsty L.
   Arner, Erik
   Westermark, Pal O.
   Bernard, Samuel
   Buchholz, Bruce A.
   Bergmann, Olaf
   Blomqvist, Lennart
   Hoffstedt, Johan
   Naslund, Erik
   Britton, Tom
   Concha, Hernan
   Hassan, Moustapha
   Ryden, Mikael
   Frisen, Jonas
   Arner, Peter
TI Dynamics of fat cell turnover in humans
SO NATURE
LA English
DT Article
ID adipose-tissue cellularity; mechanisms linking obesity; nuclear tests; adipocytes; disease; number; size; c-14; age
AB Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes(1,2). Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history(3). The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells ( adipocytes) is thought to be most important(4,5). Here we show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese individuals, even after marked weight loss, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analysing the integration of C-14 derived from nuclear bomb tests in genomic DNA(6). Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in early onset obesity, suggesting a tight regulation of fat cell number in this condition during adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.
C1 [Spalding, Kirsty L.; Arner, Erik; Bergmann, Olaf; Frisen, Jonas] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
   [Westermark, Pal O.] Humboldt Univ, ITB, D-10115 Berlin, Germany.
   [Westermark, Pal O.] Charite, D-10115 Berlin, Germany.
   [Bernard, Samuel] Fdn Res & Technol, Inst Appl & Computat Math, Iraklion 71110, Greece.
   [Buchholz, Bruce A.] Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94551 USA.
   [Blomqvist, Lennart; Hoffstedt, Johan; Concha, Hernan; Hassan, Moustapha; Ryden, Mikael; Arner, Peter] Karolinska Univ Hosp, Dept Med, SE-14186 Stockholm, Sweden.
   [Naslund, Erik] Karolinska Inst, Div Surg, Dept Clin Sci, Danderyd Hosp, SE-18288 Stockholm, Sweden.
   [Britton, Tom] Stockholm Univ, Dept Math, S-10691 Stockholm, Sweden.
C3 Karolinska Institutet; Humboldt University of Berlin; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Karolinska Institutet; Karolinska University Hospital; Karolinska Institutet; Danderyds Hospital; Stockholm University
RP Spalding, KL (corresponding author), Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
EM kirsty.spalding@ki.se; jonas.frisen@ki.se; peter.arner@ki.se
FU NCRR NIH HHS [P41 RR013461, RR13461] Funding Source: Medline
NR 30
TC 1748
Z9 2114
U1 1
U2 212
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2008
VL 453
IS 7196
BP 783
EP 787
DI 10.1038/nature06902
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300044
PM 18454136
DA 2026-03-09
ER

PT J
AU Cavey, M
   Rauzi, M
   Lenne, PF
   Lecuit, T
AF Cavey, Matthieu
   Rauzi, Matteo
   Lenne, Pierre-Francois
   Lecuit, Thomas
TI A two-tiered mechanism for stabilization and immobilization of E-cadherin
SO NATURE
LA English
DT Article
ID single-particle tracking; cell-cell adhesion; adherens junctions; epithelial-cells; alpha-catenin; drosophila embryo; actin; polarity; endocytosis; membrane
AB Epithelial tissues maintain a robust architecture which is important for their barrier function, but they are also remodelled through the reorganization of cell - cell contacts. Tissue stability requires intercellular adhesion mediated by E- cadherin, in particular its trans- association in homophilic complexes supported by actin filaments through beta- and alpha- catenin. How alpha- catenin dynamic interactions between E- cadherin/ beta- catenin and cortical actin control both stability and remodelling of adhesion is unclear. Here we focus on Drosophila homophilic E- cadherin complexes rather than total E- cadherin, including diffusing 'free' E- cadherin, because these complexes are a better proxy for adhesion. We find that E- cadherin complexes partition in very stable microdomains ( that is, bona fide adhesive foci which are more stable than remodelling contacts). Furthermore, we find that stability and mobility of these microdomains depend on two actin populations: small, stable actin patches concentrate at homophilic E- cadherin clusters, whereas a rapidly turning over, contractile network constrains their lateral movement by a tethering mechanism. alpha- Catenin controls epithelial architecture mainly through regulation of the mobility of homophilic clusters and it is largely dispensable for their stability. Uncoupling stability and mobility of E- cadherin complexes suggests that stable epithelia may remodel through the regulated mobility of very stable adhesive foci.
C1 [Cavey, Matthieu; Rauzi, Matteo; Lecuit, Thomas] Univ Aix Marseille 2, CNRS, Inst Biol Dev Marseille Luminy, UMR 6216, F-13288 Marseille 09, France.
   [Rauzi, Matteo; Lenne, Pierre-Francois] Univ Aix Marseille 3, CNRS, Inst Fresnel, UMR 6133, F-13397 Marseille 20, France.
C3 Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite
RP Lecuit, T (corresponding author), Univ Aix Marseille 2, CNRS, Inst Biol Dev Marseille Luminy, UMR 6216, Campus Luminy Case 907, F-13288 Marseille 09, France.
EM lenne@fresnel.fr; lecuit@ibdm.univ-mrs.fr
NR 42
TC 326
Z9 391
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 JUN 5
PY 2008
VL 453
IS 7196
BP 751
EP U2
DI 10.1038/nature06953
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300036
PM 18480755
DA 2026-03-09
ER

PT J
AU Calais, E
   d'Oreye, N
   Albaric, J
   Deschamps, A
   Delvaux, D
   Déverchère, J
   Ebinger, C
   Ferdinand, RW
   Kervyn, F
   Macheyeki, AS
   Oyen, A
   Perrot, J
   Saria, E
   Smets, B
   Stamps, DS
   Wauthier, C
AF Calais, Eric
   d'Oreye, Nicolas
   Albaric, Julie
   Deschamps, Anne
   Delvaux, Damien
   Deverchere, Jacques
   Ebinger, Cynthia
   Ferdinand, Richard W.
   Kervyn, Francois
   Macheyeki, Athanas S.
   Oyen, Anneleen
   Perrot, Julie
   Saria, Elifuraha
   Smets, Benoit
   Stamps, D. Sarah
   Wauthier, Christelle
TI Strain accommodation by slow slip and dyking in a youthful continental rift, East Africa
SO NATURE
LA English
DT Article
ID southern kenya rift; magma accumulation; surface uplift; 1960 collapse; volcano; deformation; subsidence; volume; mantle
AB Continental rifts begin and develop through repeated episodes of faulting and magmatism, but strain partitioning between faulting and magmatism during discrete rifting episodes remains poorly documented. In highly evolved rifts, tensile stresses from far-field plate motions accumulate over decades before being released during relatively short time intervals by faulting and magmatic intrusions(1-3). These rifting crises are rarely observed in thick lithosphere during the initial stages of rifting. Here we show that most of the strain during the July - August 2007 seismic crisis in the weakly extended Natron rift, Tanzania, was released aseismically. Deformation was achieved by slow slip on a normal fault that promoted subsequent dyke intrusion by stress unclamping. This event provides compelling evidence for strain accommodation by magma intrusion, in addition to slip along normal faults, during the initial stages of continental rifting and before significant crustal thinning.
C1 [Calais, Eric; Stamps, D. Sarah] Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47906 USA.
   [d'Oreye, Nicolas; Oyen, Anneleen] Natl Museum Nat Hist, Dept Geophys Astrophys, L-2160 Luxembourg, Luxembourg.
   [Albaric, Julie; Deverchere, Jacques; Perrot, Julie] Univ Bretagne Occidentale, Inst Univ Europeen Mer, F-29280 Plouzane, France.
   [Deschamps, Anne] Geosci Azur, CNRS, UNS, F-06560 Valbonne, France.
   [Delvaux, Damien; Kervyn, Francois; Smets, Benoit; Wauthier, Christelle] Royal Museum Cent Africa, B-3080 Tervuren, Belgium.
   [Ebinger, Cynthia] Univ Rochester, Dept Earth & Environm Sci, New York, NY 14627 USA.
   [Ferdinand, Richard W.] Univ Dar Es Salaam, Dept Geol, Dar Es Salaam, Tanzania.
   [Macheyeki, Athanas S.] Univ Ghent, Dept Soil Sci & Geol, Renard Ctr Marine Geol, B-9000 Ghent, Belgium.
   [Macheyeki, Athanas S.] Mineral Resources Madini Inst, Dodoma, Tanzania.
   [Oyen, Anneleen] Delft Univ Technol, NL-2600 Delft, Netherlands.
   [Saria, Elifuraha] Ardhi Univ, Dept Geomatics, Dar Es Salaam, Tanzania.
   [Wauthier, Christelle] Univ Liege, B-4000 Liege, Belgium.
C3 Purdue University System; Purdue University; Universite de Bretagne Occidentale; Institut Universitaire Europeen de la Mer (IUEM); Universite Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Royal Museum for Central Africa; University of Rochester; University of Dar es Salaam; Ghent University; Delft University of Technology; University of Liege
RP Calais, E (corresponding author), Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47906 USA.
EM ecalais@purdue.edu
FU US National Science Foundation [EAR-0801801, EAR-0538119]; French INSU-CNRS DyETI programme; Belgian Science Policy; SAMAAV and Rukwa; Division Of Earth Sciences; Directorate For Geosciences [0801801] Funding Source: National Science Foundation
NR 28
TC 177
Z9 191
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 783
EP U67
DI 10.1038/nature07478
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900047
PM 19079058
DA 2026-03-09
ER

PT J
AU Chang, HH
   Hemberg, M
   Barahona, M
   Ingber, DE
   Huang, S
AF Chang, Hannah H.
   Hemberg, Martin
   Barahona, Mauricio
   Ingber, Donald E.
   Huang, Sui
TI Transcriptome-wide noise controls lineage choice in mammalian progenitor cells
SO NATURE
LA English
DT Article
ID eukaryotic gene-expression; single-cell; stem-cells; dynamics; hematopoiesis; stochasticity
AB Phenotypic cell-to-cell variability within clonal populations may be a manifestation of 'gene expression noise'(1-6), or it may reflect stable phenotypic variants(7). Such 'non-genetic cell individuality'(7) can arise from the slow fluctuations of protein levels(8) in mammalian cells. These fluctuations produce persistent cell individuality, thereby rendering a clonal population heterogeneous. However, it remains unknown whether this heterogeneity may account for the stochasticity of cell fate decisions in stem cells. Here we show that in clonal populations of mouse haematopoietic progenitor cells, spontaneous 'outlier' cells with either extremely high or low expression levels of the stem cell marker Sca-1 (also known as Ly6a; ref. 9) reconstitute the parental distribution of Sca-1 but do so only after more than one week. This slow relaxation is described by a gaussian mixture model that incorporates noise- driven transitions between discrete subpopulations, suggesting hidden multi-stability within one cell type. Despite clonality, the Sca-1 outliers had distinct transcriptomes. Although their unique gene expression profiles eventually reverted to that of the median cells, revealing an attractor state, they lasted long enough to confer a greatly different proclivity for choosing either the erythroid or the myeloid lineage. Preference in lineage choice was associated with increased expression of lineage-specific transcription factors, such as a > 200-fold increase in Gata1 (ref. 10) among the erythroid-prone cells, or a > 15-fold increased PU.1 (Sfpi1) (ref. 11) expression among myeloid-prone cells. Thus, clonal heterogeneity of gene expression level is not due to independent noise in the expression of individual genes, but reflects metastable states of a slowly fluctuating transcriptome that is distinct in individual cells and may govern the reversible, stochastic priming of multipotent progenitor cells in cell fate decision.
C1 [Chang, Hannah H.; Ingber, Donald E.; Huang, Sui] Childrens Hosp, Vasc Biol Programme, Dept Pathol & Surg, Boston, MA 02115 USA.
   [Chang, Hannah H.; Ingber, Donald E.; Huang, Sui] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Chang, Hannah H.] Harvard Univ, Sch Med, Program Biophys, Boston, MA 02115 USA.
   [Chang, Hannah H.] Harvard Univ, Sch Med, MD PhD Programme, Boston, MA 02115 USA.
   [Hemberg, Martin; Barahona, Mauricio] Univ London Imperial Coll Sci Technol & Med, Dept Bioengn, London SW7 2AZ, England.
   [Hemberg, Martin; Barahona, Mauricio] Univ London Imperial Coll Sci Technol & Med, Inst Math Sci, London SW7 2AZ, England.
   [Ingber, Donald E.] Harvard Inst Biol Inspired Engn, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Imperial College London; Imperial College London; Harvard University
RP Huang, S (corresponding author), Univ Calgary, Inst Biocomplex & Informat, Calgary, AB T2N 1N4, Canada.
EM sui.huang@ucalgary.ca
FU NCI NIH HHS [R21 CA123284, P01 CA045548] Funding Source: Medline
NR 25
TC 878
Z9 1035
U1 0
U2 100
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 544
EP U10
DI 10.1038/nature06965
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700047
PM 18497826
DA 2026-03-09
ER

PT J
AU Wookey, J
   Helffrich, G
AF Wookey, James
   Helffrich, George
TI Inner-core shear-wave anisotropy and texture from an observation of PKJKP waves
SO NATURE
LA English
DT Article
ID elastic-anisotropy; travel-times; model; earth; iron; heterogeneity; constraints; attenuation; network; phases
AB Since the discovery of the Earth's core a century ago(1), and the subsequent discovery(2) of a solid inner core (postulated to have formed by the freezing of iron(3)) seismologists have striven to understand this most remote part of the deep Earth. The most direct evidence for a solid inner core would be the observation of shear-mode body waves that traverse it, but these phases are extremely difficult to observe. Two reported observations in short-period data(4,5) have proved controversial(6). Arguably more successful have been studies of longer-period data(6,7), but such averaging limits the usefulness of the observations to reported sightings. We present two observations of an inner-core shear-wave phase at higher frequencies in stacked data from the Japanese High-Sensitivity Array, Hi-Net(8). From an analysis of timing, amplitude and waveform of the 'PKJKP' phase we derive constraints on inner-core compressional-wave velocity and shear attenuation at about 0.3 Hz which differ from standard isotropic core models(9). We can explain waveform features and can partially reconcile the otherwise large differences between core wavespeed and attenuation models that our observations apparently suggest if we invoke shear-wave anisotropy in the inner core. A simple model of an inner core composed of hexagonal close-packed iron with its c axis aligned perpendicular to the rotation axis(10) yields anisotropy that is compatible with both the shear-wave anisotropy that we observe and the well-established 3 per cent compressional-wave anisotropy.
C1 [Wookey, James; Helffrich, George] Univ Bristol, Dept Earth Sci, Bristol BS8 1RJ, Avon, England.
C3 University of Bristol
RP Wookey, J (corresponding author), Univ Bristol, Dept Earth Sci, Wills Mem Bldg,Queens Rd, Bristol BS8 1RJ, Avon, England.
EM j.wookey@bristol.ac.uk
FU Natural Environment Research Council [NE/C518030/1] Funding Source: researchfish
NR 34
TC 47
Z9 55
U1 2
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 14
PY 2008
VL 454
IS 7206
BP 873
EP U24
DI 10.1038/nature07131
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600033
PM 18704084
DA 2026-03-09
ER

PT J
AU Mastepanov, M
   Sigsgaard, C
   Dlugokencky, EJ
   Houweling, S
   Ström, L
   Tamstorf, MP
   Christensen, TR
AF Mastepanov, Mikhail
   Sigsgaard, Charlotte
   Dlugokencky, Edward J.
   Houweling, Sander
   Strom, Lena
   Tamstorf, Mikkel P.
   Christensen, Torben R.
TI Large tundra methane burst during onset of freezing
SO NATURE
LA English
DT Article
ID trace gas-exchange; atmospheric methane; northeast greenland; arctic tundra; ch4; emission; climate; thaw; co2
AB Terrestrial wetland emissions are the largest single source of the greenhouse gas methane(1). Northern high- latitude wetlands contribute significantly to the overall methane emissions from wetlands, but the relative source distribution between tropical and high- latitude wetlands remains uncertain(2,3). As a result, not all the observed spatial and seasonal patterns of atmospheric methane concentrations can be satisfactorily explained, particularly for high northern latitudes. For example, a late- autumn shoulder is consistently observed in the seasonal cycles of atmospheric methane at high- latitude sites(4), but the sources responsible for these increased methane concentrations remain uncertain. Here we report a data set that extends hourly methane flux measurements from a high Arctic setting into the late autumn and early winter, during the onset of soil freezing. We find that emissions fall to a low steady level after the growing season but then increase significantly during the freeze- in period. The integral of emissions during the freeze- in period is approximately equal to the amount of methane emitted during the entire summer season. Three- dimensional atmospheric chemistry and transport model simulations of global atmospheric methane concentrations indicate that the observed early winter emission burst improves the agreement between the simulated seasonal cycle and atmospheric data from latitudes north of 60 degrees N. Our findings suggest that permafrost- associated freeze- in bursts of methane emissions from tundra regions could be an important and so far unrecognized component of the seasonal distribution of methane emissions from high latitudes.
C1 [Mastepanov, Mikhail; Strom, Lena; Christensen, Torben R.] Lund Univ, Geobiosphere Sci Ctr, S-22362 Lund, Sweden.
   [Sigsgaard, Charlotte] Univ Copenhagen, Inst Geog & Geol, DK-1350 Copenhagen, Denmark.
   [Dlugokencky, Edward J.] NOAA, Earth Syst Res Lab, Boulder, CO 80305 USA.
   [Houweling, Sander] SRON, Netherlands Inst Space Res, NL-3584 CA Utrecht, Netherlands.
   [Houweling, Sander] Univ Utrecht, Inst Marine & Atmospher Res Utrecht IMAU, NL-3584 CC Utrecht, Netherlands.
   [Tamstorf, Mikkel P.] Univ Aarhus, Natl Environm Res Inst, DK-4000 Roskilde, Denmark.
C3 Lund University; University of Copenhagen; National Oceanic Atmospheric Admin (NOAA) - USA; Utrecht University; Aarhus University; Danish National Environmental Research Institute
RP Christensen, TR (corresponding author), Lund Univ, Geobiosphere Sci Ctr, Solvegatan 12, S-22362 Lund, Sweden.
EM Torben.Christensen@nateko.lu.se
FU Danish Ministry of the Environment; Commission for Scientific Research in Greenland (KVUG); Swedish Research Councils VR; FORMAS
NR 22
TC 250
Z9 303
U1 0
U2 218
PU 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 4
PY 2008
VL 456
IS 7222
BP 628
EP U58
DI 10.1038/nature07464
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000038
PM 19052625
DA 2026-03-09
ER

PT J
AU Maze, JR
   Stanwix, PL
   Hodges, JS
   Hong, S
   Taylor, JM
   Cappellaro, P
   Jiang, L
   Dutt, MVG
   Togan, E
   Zibrov, AS
   Yacoby, A
   Walsworth, RL
   Lukin, MD
AF Maze, J. R.
   Stanwix, P. L.
   Hodges, J. S.
   Hong, S.
   Taylor, J. M.
   Cappellaro, P.
   Jiang, L.
   Dutt, M. V. Gurudev
   Togan, E.
   Zibrov, A. S.
   Yacoby, A.
   Walsworth, R. L.
   Lukin, M. D.
TI Nanoscale magnetic sensing with an individual electronic spin in diamond
SO NATURE
LA English
DT Article
ID coherent dynamics; quantum; qubits
AB Detection of weak magnetic fields with nanoscale spatial resolution is an outstanding problem in the biological and physical sciences(1-5). For example, at a distance of 10 nm, the spin of a single electron produces a magnetic field of about 1 mu T, and the corresponding field from a single proton is a few nanoteslas. A sensor able to detect such magnetic fields with nanometre spatial resolution would enable powerful applications, ranging from the detection of magnetic resonance signals from individual electron or nuclear spins in complex biological molecules(5,6) to readout of classical or quantum bits of information encoded in an electron or nuclear spin memory(7). Here we experimentally demonstrate an approach to such nanoscale magnetic sensing, using coherent manipulation of an individual electronic spin qubit associated with a nitrogen- vacancy impurity in diamond at room temperature(8). Using an ultra- pure diamond sample, we achieve detection of 3 nT magnetic fields at kilohertz frequencies after 100 s of averaging. In addition, we demonstrate a sensitivity of 0.5 mu THz(-1/2) for a diamond nanocrystal with a diameter of 30 nm.
C1 [Maze, J. R.; Hodges, J. S.; Hong, S.; Cappellaro, P.; Jiang, L.; Togan, E.; Zibrov, A. S.; Yacoby, A.; Walsworth, R. L.; Lukin, M. D.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Stanwix, P. L.; Cappellaro, P.; Walsworth, R. L.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Hodges, J. S.] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA.
   [Taylor, J. M.] MIT, Dept Phys, Cambridge, MA 02138 USA.
   [Dutt, M. V. Gurudev] Univ Pittsburgh, Dept Phys & Astron, Pittsburgh, PA 15260 USA.
C3 Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Lukin, MD (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM lukin@fas.harvard.edu
FU NSF; DARPA; Packard Foundation; Harvard CNS
NR 24
TC 1688
Z9 2065
U1 15
U2 640
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 644
EP U41
DI 10.1038/nature07279
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700042
PM 18833275
DA 2026-03-09
ER

PT J
AU Eisenbarth, SC
   Colegio, OR
   O'Connor, W
   Sutterwala, FS
   Flavell, RA
AF Eisenbarth, Stephanie C.
   Colegio, Oscar R.
   O'Connor, William, Jr.
   Sutterwala, Fayyaz S.
   Flavell, Richard A.
TI Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
SO NATURE
LA English
DT Article
ID immune-response; dying cells; t-cells; induction; antigen; activation; recognition; caspase-1; hydroxide; receptor
AB Aluminium adjuvants, typically referred to as 'alum', are the most commonly used adjuvants in human and animal vaccines worldwide, yet the mechanism underlying the stimulation of the immune system by alum remains unknown. Toll-like receptors are critical in sensing infections and are therefore common targets of various adjuvants used in immunological studies. Although alum is known to induce the production of proinflammatory cytokines in vitro, it has been repeatedly demonstrated that alum does not require intact Toll-like receptor signalling to activate the immune system(1,2). Here we show that aluminium adjuvants activate an intracellular innate immune response system called the Nalp3 (also known as cryopyrin, CIAS1 or NLRP3) inflammasome. Production of the pro-inflammatory cytokines interleukin-1 beta and interleukin-18 by macrophages in response to alum in vitro required intact inflammasome signalling. Furthermore, in vivo, mice deficient in Nalp3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) or caspase-1 failed to mount a significant antibody response to an antigen administered with aluminium adjuvants, whereas the response to complete Freund's adjuvant remained intact. We identify the Nalp3 inflammasome as a crucial element in the adjuvant effect of aluminium adjuvants; in addition, we show that the innate inflammasome pathway can direct a humoral adaptive immune response. This is likely to affect how we design effective, but safe, adjuvants in the future.
C1 [Eisenbarth, Stephanie C.; Colegio, Oscar R.; O'Connor, William, Jr.; Sutterwala, Fayyaz S.; Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Eisenbarth, Stephanie C.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA.
   [Colegio, Oscar R.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA.
   [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Sutterwala, Fayyaz S.] Univ Iowa, Dept Med, Inflammat Program, Iowa City, IA 52241 USA.
C3 Yale University; Yale University; Yale University; Yale University; Howard Hughes Medical Institute; University of Iowa
RP Flavell, RA (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.
EM richard.flavell@yale.edu
FU National Heart Lung and Blood Institute [T32HL007974] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32AR007016] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NHLBI NIH HHS [T32 HL007974] Funding Source: Medline; NIAID NIH HHS [K08 AI065517] Funding Source: Medline; NIAMS NIH HHS [T32 AR007016] Funding Source: Medline
NR 30
TC 1231
Z9 1459
U1 5
U2 187
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 19
PY 2008
VL 453
IS 7198
BP 1122
EP U13
DI 10.1038/nature06939
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900061
PM 18496530
DA 2026-03-09
ER

PT J
AU Engelkes, T
   Morriën, E
   Verhoeven, KJF
   Bezemer, TM
   Biere, A
   Harvey, JA
   McIntyre, LM
   Tamis, WLM
   van der Putten, WH
AF Engelkes, Tim
   Morrien, Elly
   Verhoeven, Koen J. F.
   Bezemer, T. Martijn
   Biere, Arjen
   Harvey, Jeffrey A.
   McIntyre, Lauren M.
   Tamis, Wil L. M.
   van der Putten, Wim H.
TI Successful range-expanding plants experience less above-ground and below-ground enemy impact
SO NATURE
LA English
DT Article
ID climate-change; soil biota; british butterfly; natural enemy; invasive plants; feedback; herbivores; release; community; pathogens
AB Many species are currently moving to higher latitudes and altitudes(1-3). However, little is known about the factors that influence the future performance of range- expanding species in their new habitats. Here we show that range- expanding plant species from a riverine area were better defended against shoot and root enemies than were related native plant species growing in the same area. We grew fifteen plant species with and without non- coevolved polyphagous locusts and cosmopolitan, polyphagous aphids. Contrary to our expectations, the locusts performed more poorly on the range- expanding plant species than on the congeneric native plant species, whereas the aphids showed no difference. The shoot herbivores reduced the biomass of the native plants more than they did that of the congeneric range expanders. Also, the range- expanding plants developed fewer pathogenic effects(4,5) in their root- zone soil than did the related native species. Current predictions forecast biodiversity loss due to limitations in the ability of species to adjust to climate warming conditions in their range(6-8). Our results strongly suggest that the plants that shift ranges towards higher latitudes and altitudes may include potential invaders, as the successful range expanders may experience less control by above- ground or below-ground enemies than the natives.
C1 [Engelkes, Tim; Morrien, Elly; Verhoeven, Koen J. F.; Bezemer, T. Martijn; Biere, Arjen; Harvey, Jeffrey A.; van der Putten, Wim H.] Netherlands Inst Ecol, NIOO KNAW, Dept Multitroph Interact, NL-6666 ZG Heteren, Netherlands.
   [Bezemer, T. Martijn; van der Putten, Wim H.] Univ Wageningen & Res Ctr, Nematol Lab, NL-6700 ES Wageningen, Netherlands.
   [McIntyre, Lauren M.] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
   [McIntyre, Lauren M.] Univ Florida, Dept Stat, Gainesville, FL 32610 USA.
   [Tamis, Wil L. M.] Natl Herbarium Nederland, Leiden Univ Branch, NL-2300 RA Leiden, Netherlands.
C3 Royal Netherlands Academy of Arts & Sciences; Netherlands Institute of Ecology (NIOO-KNAW); Wageningen University & Research; State University System of Florida; University of Florida; State University System of Florida; University of Florida; Leiden University; Leiden University - Excl LUMC
RP van der Putten, WH (corresponding author), Netherlands Inst Ecol, NIOO KNAW, Dept Multitroph Interact, POB 40, NL-6666 ZG Heteren, Netherlands.
EM w.vanderputten@nioo.knaw.nl
FU ALW-VICI
NR 28
TC 239
Z9 281
U1 2
U2 235
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 946
EP 948
DI 10.1038/nature07474
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300044
PM 19020504
DA 2026-03-09
ER

PT J
AU Prucca, CG
   Slavin, I
   Quiroga, R
   Elías, EV
   Rivero, FD
   Saura, A
   Carranza, PG
   Luján, HD
AF Prucca, Cesar G.
   Slavin, Ileana
   Quiroga, Rodrigo
   Elias, Eliana V.
   Rivero, Fernando D.
   Saura, Alicia
   Carranza, Pedro G.
   Lujan, Hugo D.
TI Antigenic variation in Giardia lamblia is regulated by RNA interference
SO NATURE
LA English
DT Article
ID gene; protein; identification; mechanisms; transcripts; expression; eukaryote; plants; fungi; sense
AB Giardia lamblia ( also called Giardia intestinalis) is one of the most common intestinal parasites of humans. To evade the host's immune response, Giardia undergoes antigenic variation - a process that allows the parasite to develop chronic and recurrent infections. From a repertoire of similar to 190 variant- specific surface protein ( VSP)- coding genes, Giardia expresses only one VSP on the surface of each parasite at a particular time, but spontaneously switches to a different VSP by unknown mechanisms. Here we show that regulation of VSP expression involves a system comprising RNA- dependent RNA polymerase, Dicer and Argonaute, known components of the RNA interference machinery. Clones expressing a single surface antigen efficiently transcribe several VSP genes but only accumulate transcripts encoding the VSP to be expressed. Detection of antisense RNAs corresponding to the silenced VSP genes and small RNAs from the silenced but not for the expressed vsp implicate the RNA interference pathway in antigenic variation. Remarkably, silencing of Dicer and RNA- dependent RNA polymerase leads to a change from single to multiple VSP expression in individual parasites.
C1 [Prucca, Cesar G.; Slavin, Ileana; Quiroga, Rodrigo; Elias, Eliana V.; Rivero, Fernando D.; Saura, Alicia; Carranza, Pedro G.; Lujan, Hugo D.] Univ Catolica Cordoba, Fac Med, Lab Bioquim & Biol Mol, Cordoba, Argentina.
C3 Catholic University of Cordoba
RP Luján, HD (corresponding author), Univ Catolica Cordoba, Fac Med, Lab Bioquim & Biol Mol, X5004ASK, Cordoba, Argentina.
EM hlujan@ucc.edu.ar
FU Agencia Nacional para la Promocion de la Ciencia y la Tecnologia; Consejo Nacional de Investigaciones Cientificas y Tecnicas; Universidad Catolica de Cordoba; Howard Hughes Medical Institute; European Union CONTENT
NR 38
TC 167
Z9 210
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 DEC 11
PY 2008
VL 456
IS 7223
BP 750
EP 754
DI 10.1038/nature07585
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900040
PM 19079052
DA 2026-03-09
ER

PT J
AU Atarashi, K
   Nishimura, J
   Shima, T
   Umesaki, Y
   Yamamoto, M
   Onoue, M
   Yagita, H
   Ishii, N
   Evans, R
   Honda, K
   Takeda, K
AF Atarashi, Koji
   Nishimura, Junichi
   Shima, Tatsuichiro
   Umesaki, Yoshinori
   Yamamoto, Masahiro
   Onoue, Masaharu
   Yagita, Hideo
   Ishii, Naoto
   Evans, Richard
   Honda, Kenya
   Takeda, Kiyoshi
TI ATP drives lamina propria TH17 cell differentiation
SO NATURE
LA English
DT Article
ID inflammatory-bowel-disease; dendritic cells; t-cells; tgf-beta; p2x receptors; generation; immunity; pathway; il-21; mice
AB Interleukin ( IL)- 17- producing CD4 1 T lymphocytes ( T(H)17 cells) constitute a subset of T- helper cells involved in host defence and several immune disorders(1,2). An intriguing feature of T(H)17 cells is their selective and constitutive presence in the intestinal lamina propria(3). Here we show that adenosine 5 '- triphosphate ( ATP) that can be derived from commensal bacteria activates a unique subset of lamina propria cells, CD70(high) CD11c(low) cells, leading to the differentiation of T(H)17 cells. Germ- free mice exhibit much lower concentrations of luminal ATP, accompanied by fewer lamina propria T(H)17 cells, compared to specific- pathogen- free mice. Systemic or rectal administration of ATP into these germ- free mice results in a marked increase in the number of lamina propria T(H)17 cells. A CD70(high) CD11c(low) subset of the lamina propria cells expresses T(H)17- prone molecules, such as IL- 6, IL- 23p19 and trans-forming-growth- factor-beta-activating integrin-alpha V and -beta 8, in response to ATP stimulation, and preferentially induces T(H)17 differentiation of co- cultured naive CD4(+) T cells. The critical role of ATP is further underscored by the observation that administration of ATP exacerbates a T- cell- mediated colitis model with enhanced T(H)17 differentiation. These observations highlight the importance of commensal bacteria and ATP for T(H)17 differentiation in health and disease, and offer an explanation of why T(H)17 cells specifically present in the intestinal lamina propria.
C1 [Atarashi, Koji; Nishimura, Junichi; Yamamoto, Masahiro; Honda, Kenya; Takeda, Kiyoshi] Osaka Univ, Lab Immune Regulat, Grad Sch Med, Suita, Osaka 5650871, Japan.
   [Shima, Tatsuichiro; Umesaki, Yoshinori; Onoue, Masaharu] Yakult Cent Inst Microbiol Res, Tokyo 1868650, Japan.
   [Yamamoto, Masahiro; Honda, Kenya; Takeda, Kiyoshi] Osaka Univ, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan.
   [Yagita, Hideo] Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 1138421, Japan.
   [Ishii, Naoto] Tohoku Univ, Grad Sch Med, Dept Microbiol & Immunol, Aoba Ku, Sendai, Miyagi 9808575, Japan.
   [Evans, Richard] Univ Leicester, Dept Cell Physiol & Pharmacol, Leicester LE1 9HN, Leics, England.
C3 University of Osaka; Yakult Honsha Company, Limited; University of Osaka; Juntendo University; Tohoku University; University of Leicester
RP Honda, K (corresponding author), Osaka Univ, Lab Immune Regulat, Grad Sch Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM honda@ongene.med.osaka-u.ac.jp; ktakeda@ongene.med.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology; Ministry of Health, Labour and Welfare; Osaka Foundation for the Promotion of Clinical Immunology; Ichiro Kanehara Foundation; Sumitomo Foundation; Senri Life Science Foundation; Naito Foundation
NR 32
TC 889
Z9 1017
U1 4
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 808
EP U10
DI 10.1038/nature07240
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900049
PM 18716618
DA 2026-03-09
ER

PT J
AU Baek, D
   Villén, J
   Shin, C
   Camargo, FD
   Gygi, SP
   Bartel, DP
AF Baek, Daehyun
   Villen, Judit
   Shin, Chanseok
   Camargo, Fernando D.
   Gygi, Steven P.
   Bartel, David P.
TI The impact of microRNAs on protein output
SO NATURE
LA English
DT Article
ID growth-factor-i; messenger-rnas; mirna targets; cell-culture; cathepsin-b; amino-acids; c. elegans; identification; expression; determinants
AB MicroRNAs are endogenous similar to 23-nucleotide RNAs that can pair to sites in the messenger RNAs of protein- coding genes to downregulate the expression from these messages. MicroRNAs are known to influence the evolution and stability of many mRNAs, but their global impact on protein output had not been examined. Here we use quantitative mass spectrometry to measure the response of thousands of proteins after introducing microRNAs into cultured cells and after deleting mir- 223 in mouse neutrophils. The identities of the responsive proteins indicate that targeting is primarily through seed- matched sites located within favourable predicted contexts in 39 untranslated regions. Hundreds of genes were directly repressed, albeit each to a modest degree, by individual microRNAs. Although some targets were repressed without detectable changes in mRNA levels, those translationally repressed by more than a third also displayed detectable mRNA destabilization, and, for the more highly repressed targets, mRNA destabilization usually comprised the major component of repression. The impact of microRNAs on the proteome indicated that for most interactions microRNAs act as rheostats to make fine- scale adjustments to protein output.
C1 [Villen, Judit; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Baek, Daehyun; Shin, Chanseok; Camargo, Fernando D.; Bartel, David P.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Baek, Daehyun; Shin, Chanseok; Bartel, David P.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Baek, Daehyun; Shin, Chanseok; Bartel, David P.] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Gygi, SP (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM steven_gygi@hms.harvard.edu; dbartel@wi.mit.edu
FU Damon Runyon postdoctoral fellowship; NIH
NR 48
TC 3030
Z9 3578
U1 2
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 SEP 4
PY 2008
VL 455
IS 7209
BP 64
EP U38
DI 10.1038/nature07242
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200037
PM 18668037
DA 2026-03-09
ER

PT J
AU Carlson, ME
   Hsu, M
   Conboy, IM
AF Carlson, Morgan E.
   Hsu, Michael
   Conboy, Irina M.
TI Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells
SO NATURE
LA English
DT Article
ID skeletal-muscle; proliferation; p16(ink4a); arrest; mice
AB Adult skeletal muscle robustly regenerates throughout an organism's life, but as the muscle ages, its ability to repair diminishes and eventually fails(1,2). Previous work suggests that the regenerative potential of muscle stem cells (satellite cells) is not triggered in the old muscle because of a decline in Notch activation, and that it can be rejuvenated by forced local activation of Notch(3). Here we report that, in addition to the loss of Notch activation, old muscle produces excessive transforming growth factor (TGF)-beta (but not myostatin), which induces unusually high levels of TGF-beta pSmad3 in resident satellite cells and interferes with their regenerative capacity. Importantly, endogenous Notch and pSmad3 antagonize each other in the control of satellite-cell proliferation, such that activation of Notch blocks the TGF-beta-dependent upregulation of the cyclin-dependent kinase (CDK) inhibitors p15, p16, p21 and p27, whereas inhibition of Notch induces them. Furthermore, in muscle stem cells, Notch activity determines the binding of pSmad3 to the promoters of these negative regulators of cell-cycle progression. Attenuation of TGF-beta/pSmad3 in old, injured muscle restores regeneration to satellite cells in vivo. Thus a balance between endogenous pSmad3 and active Notch controls the regenerative competence of muscle stem cells, and deregulation of this balance in the old muscle microniche interferes with regeneration.
C1 [Carlson, Morgan E.; Hsu, Michael; Conboy, Irina M.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Conboy, IM (corresponding author), Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
EM iconboy@berkeley.edu
FU NIA NIH HHS [R21 AG27892, R21 AG027892, R01 AG027252] Funding Source: Medline
NR 30
TC 392
Z9 447
U1 1
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 528
EP U9
DI 10.1038/nature07034
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300054
PM 18552838
DA 2026-03-09
ER

PT J
AU Holmström, M
   Ekenbäck, A
   Selsis, F
   Penz, T
   Lammer, H
   Wurz, P
AF Holmstroem, M.
   Ekenbaeck, A.
   Selsis, F.
   Penz, T.
   Lammer, H.
   Wurz, P.
TI Energetic neutral atoms as the explanation for the high-velocity hydrogen around HD 209458b
SO NATURE
LA English
DT Article
ID extrasolar planets; upper-atmosphere; hd209458b; aeronomy; mars
AB Absorption in the stellar Lyman-alpha (Ly alpha) line observed during the transit of the extrasolar planet HD 209458b in front of its host star reveals high-velocity atomic hydrogen at great distances from the planet(1,2). This has been interpreted as hydrogen atoms escaping from the planet's exosphere(1,3), possibly undergoing hydrodynamic blow-off(4), and being accelerated by stellar radiation pressure. Energetic neutral atoms around Solar System planets have been observed to form from charge exchange between solar wind protons and neutral hydrogen from the planetary exospheres(5-7), however, and this process also should occur around extrasolar planets. Here we show that the measured transit-associated Ly alpha absorption can be explained by the interaction between the exosphere of HD 209458b and the stellar wind, and that radiation pressure alone cannot explain the observations. As the stellar wind protons are the source of the observed energetic neutral atoms, this provides a way of probing stellar wind conditions, and our model suggests a slow and hot stellar wind near HD 209458b at the time of the observations.
C1 [Holmstroem, M.; Ekenbaeck, A.] Swedish Inst Space Phys, SE-98128 Kiruna, Sweden.
   [Selsis, F.] Univ Bordeaux 1, Astrophys Lab, CNRS, F-33270 Floirac, France.
   [Selsis, F.] Univ Lyon 1, Ecole Normale Super Lyon, CNRS, Ctr Rech Astrophys Lyon, F-69007 Lyon, France.
   [Penz, T.] INAF Osserv Astron Palermo, I-90134 Palermo, Italy.
   [Lammer, H.] Austrian Acad Sci, Inst Space Res, A-8042 Graz, Austria.
   [Wurz, P.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
C3 Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Universite Lyon 1; Ecole Normale Superieure de Lyon (ENS de LYON); Istituto Nazionale Astrofisica (INAF); Austrian Academy of Sciences; University of Bern
RP Holmström, M (corresponding author), Swedish Inst Space Phys, POB 812, SE-98128 Kiruna, Sweden.
EM matsh@irf.se
NR 18
TC 139
Z9 153
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 21
PY 2008
VL 451
IS 7181
BP 970
EP 972
DI 10.1038/nature06600
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100043
PM 18288189
DA 2026-03-09
ER

PT J
AU Raulin, F
AF Raulin, Francois
TI Planetary science - Organic lakes on Titan
SO NATURE
LA English
DT Article
ID surface; ethane; ocean
C1 [Raulin, Francois] Univ Paris 12, F-94010 Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC)
RP Raulin, F (corresponding author), Univ Paris 12, 61 Ave Gen de Gaulle, F-94010 Creteil, France.
EM raulin@lisa.univ-paris12.fr
NR 10
TC 24
Z9 29
U1 1
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 JUL 31
PY 2008
VL 454
IS 7204
BP 587
EP 589
DI 10.1038/454587a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500030
PM 18668095
DA 2026-03-09
ER

PT J
AU Raebiger, H
   Lany, S
   Zunger, A
AF Raebiger, Hannes
   Lany, Stephan
   Zunger, Alex
TI Charge self-regulation upon changing the oxidation state of transition metals in insulators
SO NATURE
LA English
DT Article
ID impurity; system
AB Transition- metal atoms embedded in an ionic or semiconducting crystal can exist in various oxidation states that have distinct signatures in X- ray photoemission spectroscopy and 'ionic radii' which vary with the oxidation state of the atom. These oxidation states are often tacitly associated with a physical ionization of the transition- metal atoms(1,2) - that is, a literal transfer of charge to or from the atoms. Physical models have been founded on this charge- transfer paradigm(3-6), but first- principles quantum mechanical calculations show only negligible changes in the local transition-metal charge(7-12) as the oxidation state is altered. Here we explain this peculiar tendency of transition- metal atoms to maintain a constant local charge under external perturbations in terms of an inherent, homeostasis- like negative feedback. We show that signatures of oxidation states and multivalence - such as X- ray photoemission core- level shifts, ionic radii and variations in local magnetization - that have often been interpreted as literal charge transfer(3,4,13-16) are instead a consequence of the negative- feedback charge regulation.
C1 [Raebiger, Hannes; Lany, Stephan; Zunger, Alex] Natl Renewable Energy Lab, Golden, CO 80401 USA.
C3 United States Department of Energy (DOE); National Renewable Energy Laboratory - USA
RP Raebiger, H (corresponding author), Natl Renewable Energy Lab, Golden, CO 80401 USA.
EM hannes_raebiger@nrel.gov; alex_zunger@nrel.gov
NR 23
TC 248
Z9 271
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 JUN 5
PY 2008
VL 453
IS 7196
BP 763
EP 766
DI 10.1038/nature07009
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300039
PM 18528391
DA 2026-03-09
ER

PT J
AU Zheng, XW
   Pontes, O
   Zhu, JH
   Miki, D
   Zhang, F
   Li, WX
   Iida, K
   Kapoor, A
   Pikaard, CS
   Zhu, JK
AF Zheng, Xianwu
   Pontes, Olga
   Zhu, Jianhua
   Miki, Daisuke
   Zhang, Fei
   Li, Wen-Xue
   Iida, Kei
   Kapoor, Avnish
   Pikaard, Craig S.
   Zhu, Jian-Kang
TI ROS3 is an RNA-binding protein required for DNA demethylation in Arabidopsis
SO NATURE
LA English
DT Article
ID glycosylase/lyase ros1; methylation patterns; abscisic-acid; human-cells; plants; pathways; replication; micrornas; demeter; targets
AB DNA methylation is an important epigenetic mark for transcriptional gene silencing ( TGS) in diverse organisms(1-6). Recent studies suggest that the methylation status of a number of genes is dynamically regulated by methylation and demethylation(7-10). In Arabidopsis, active DNA demethylation is mediated by the ROS1 ( repressor of silencing 1) subfamily of 5- methylcytosine DNA glycosylases through a base excision repair pathway(8,10-13). These demethylases have critical roles in erasing DNA methylation and preventing TGS of target genes(7,8,10). However, it is not known how the demethylases are targeted to specific sequences. Here we report the identification of ROS3, an essential regulator of DNA demethylation that contains an RNA recognition motif. Analysis of ros3 mutants and ros1ros3 double mutants suggests that ROS3 acts in the same genetic pathway as ROS1 to prevent DNA hypermethylation and TGS. Gel mobility shift assays and analysis of ROS3 immunoprecipitate from plant extracts shows that ROS3 binds to small RNAs in vitro and in vivo. Immunostaining shows that ROS3 and ROS1 proteins co-localize in discrete foci dispersed throughout the nucleus. These results demonstrate a critical role for ROS3 in preventing DNA hypermethylation and suggest that DNA demethylation by ROS1 may be guided by RNAs bound to ROS3.
C1 [Zheng, Xianwu; Miki, Daisuke; Zhang, Fei; Li, Wen-Xue; Iida, Kei; Kapoor, Avnish; Zhu, Jian-Kang] Univ Calif Riverside, Ctr Plant Cell Biol, Riverside, CA 92521 USA.
   [Zheng, Xianwu; Miki, Daisuke; Zhang, Fei; Li, Wen-Xue; Iida, Kei; Kapoor, Avnish; Zhu, Jian-Kang] Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
   [Pontes, Olga; Pikaard, Craig S.] Washington Univ, Dept Biol, St Louis, MO 63130 USA.
   [Zhu, Jianhua] Univ Maryland, Dept Plant Sci & Landscape Architecture, College Pk, MD 20742 USA.
   [Zhang, Fei] Shanghai Jiao Tong Univ, Plant Biotechnol Res Ctr, Sch Agr & Biol, Shanghai 200240, Peoples R China.
C3 University of California System; University of California Riverside; University of California System; University of California Riverside; Washington University (WUSTL); University System of Maryland; University of Maryland College Park; Shanghai Jiao Tong University
RP Zhu, JK (corresponding author), Univ Calif Riverside, Ctr Plant Cell Biol, Riverside, CA 92521 USA.
EM jian-kang.zhu@ucr.edu
FU National Institutes of Health [R01GM070795, R01GM059138, R01GM077590, 1R01GM060380]; Edward Mallinckrodt Foundation; China Scholarship Council [2007104542]
NR 34
TC 122
Z9 152
U1 1
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1259
EP U70
DI 10.1038/nature07305
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100049
PM 18815596
DA 2026-03-09
ER

PT J
AU Yang, JW
   Chandler, C
   Stadler, M
   Kampen, D
   List, B
AF Yang, Jung Woon
   Chandler, Carley
   Stadler, Michael
   Kampen, Daniela
   List, Benjamin
TI Proline-catalysed Mannich reactions of acetaldehyde
SO NATURE
LA English
DT Article
ID beta-amino acids; enantioselective synthesis; asymmetric-synthesis; aldol reactions; aldehydes; uk-427,857; inhibitor; maraviroc; imines; potent
AB Small organic molecules recently emerged as a third class of broadly useful asymmetric catalysts that direct reactions to yield predominantly one chiral product, complementing enzymes and metal complexes(1). For instance, the amino acid proline and its derivatives are useful for the catalytic activation of carbonyl compounds via nucleophilic enamine intermediates. Several important carbon carbon bond- forming reactions, including the Mannich reaction, have been developed using this approach(2), all of which are useful for making chiral, biologically relevant compounds. Remarkably, despite attempts(3,4), the simplest of all nucleophiles, acetaldehyde, could not be used in this way. Here we show that acetaldehyde is a powerful nucleophile in asymmetric, proline- catalysed Mannich reactions with N- tert- butoxycarbonyl ( N- Boc)- imines, yielding beta- amino aldehydes with extremely high enantioselectivities- desirable products as drug intermediates and in the synthesis of other biologically active molecules. Although acetaldehyde has been used as a nucleophile in reactions with biological catalysts such as aldolases(5) and thiamine- dependent enzymes(6), and has also been employed indirectly(7-9), its use as an inexpensive and versatile two- carbon nucleophile in asymmetric, small- molecule catalysis will find many practical applications.
C1 [Yang, Jung Woon; Chandler, Carley; Stadler, Michael; Kampen, Daniela; List, Benjamin] Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany.
C3 Max Planck Society
RP List, B (corresponding author), Max Planck Inst Kohlenforsch, Kaiser Wilhelm Pl 1, D-45470 Mulheim, Germany.
EM list@mpi-muelheim.mpg.de
NR 24
TC 264
Z9 276
U1 3
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 453
EP 455
DI 10.1038/nature06740
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300027
PM 18288105
DA 2026-03-09
ER

PT J
AU Adilakshmi, T
   Bellur, DL
   Woodson, SA
AF Adilakshmi, Tadepalli
   Bellur, Deepti L.
   Woodson, Sarah A.
TI Concurrent nucleation of 16S folding and induced fit in 30S ribosome assembly
SO NATURE
LA English
DT Article
ID escherichia-coli ribosm; parallel pathways; rna; subunit; protein; vitro; domains; s4
AB Rapidly growing cells produce thousands of new ribosomes each minute, in a tightly regulated process that is essential to cell growth(1,2). How the Escherichia coli 16S ribosomal RNA and the 20 proteins that make up the 30S ribosomal subunit can assemble correctly in a few minutes remains a challenging problem, partly because of the lack of real- time data on the earliest stages of assembly. By providing snapshots of individual RNA and protein interactions as they emerge in real time, here we show that 30S assembly nucleates concurrently from different points along the rRNA. Time- resolved hydroxyl radical footprinting(3) was used to map changes in the structure of the rRNA within 20 milliseconds after the addition of total 30S proteins. Helical junctions in each domain fold within 100 ms. In contrast, interactions surrounding the decoding site and between the 5', the central and the 3' domains require 2 - 200 seconds to form. Unexpectedly, nucleotides contacted by the same protein are protected at different rates, indicating that initial RNA - protein encounter complexes refold during assembly. Although early steps in assembly are linked to intrinsically stable rRNA structure, later steps correspond to regions of induced fit between the proteins and the rRNA.
C1 [Adilakshmi, Tadepalli; Woodson, Sarah A.] Johns Hopkins Univ, TC Jenkins Dept Biophys, Baltimore, MD 21218 USA.
   [Bellur, Deepti L.] Johns Hopkins Univ, Program Cell Mol & Dev Biol & Biophys, Baltimore, MD 21218 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Woodson, SA (corresponding author), Johns Hopkins Univ, TC Jenkins Dept Biophys, 3400 N Charles St, Baltimore, MD 21218 USA.
EM swoodson@jhu.edu
FU National Institutes of Health [GM60819, P41-EB0001979.]
NR 28
TC 151
Z9 202
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1268
EP 1272
DI 10.1038/nature07298
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100051
PM 18784650
DA 2026-03-09
ER

PT J
AU Escartín, J
   Smith, DK
   Cann, J
   Schouten, H
   Langmuir, CH
   Escrig, S
AF Escartin, J.
   Smith, D. K.
   Cann, J.
   Schouten, H.
   Langmuir, C. H.
   Escrig, S.
TI Central role of detachment faults in accretion of slow-spreading oceanic lithosphere
SO NATURE
LA English
DT Article
ID mid-atlantic ridge; microearthquake characteristics; hydrothermal field; complexes; beneath; valley; modes
AB The formation of oceanic detachment faults is well established from inactive, corrugated fault planes exposed on sea floor formed along ridges spreading at less than 80 km Myr(-1) ( refs 1 - 4). These faults can accommodate extension for up to 1 - 3 Myr ( ref. 5), and are associated with one of the two contrasting modes of accretion operating along the northern Mid- Atlantic Ridge. The first mode is asymmetrical accretion involving an active detachment fault(6) along one ridge flank. The second mode is the well- known symmetrical accretion, dominated by magmatic processes with subsidiary high- angle faulting and the formation of abyssal hills on both flanks. Here we present an examination of similar to 2,500 km of the Mid- Atlantic Ridge between 12.5 and 35 degrees N, which reveals asymmetrical accretion along almost half of the ridge. Hydrothermal activity identified so far in the study region is closely associated with asymmetrical accretion, which also shows high levels of near-continuous hydroacoustically and teleseismically recorded seismicity. Increased seismicity is probably generated along detachment faults that accommodate a sizeable proportion of the total plate separation. In contrast, symmetrical segments have lower levels of seismicity, which occurs primarily at segment ends. Basalts erupted along asymmetrical segments have compositions that are consistent with crystallization at higher pressures than basalts from symmetrical segments, and with lower extents of partial melting of the mantle. Both seismic evidence and geochemical evidence indicate that the axial lithosphere is thicker and colder at asymmetrical sections of the ridge, either because associated hydrothermal circulation efficiently penetrates to greater depths or because the rising mantle is cooler. We suggest that much of the variability in sea- floor morphology, seismicity and basalt chemistry found along slow- spreading ridges can be thus attributed to the frequent involvement of detachment faults in oceanic lithospheric accretion.
C1 [Escartin, J.] Inst Phys Globe, CNRS, Marine Geosci Grp, F-75252 Paris 05, France.
   [Smith, D. K.; Schouten, H.] Woods Hole Oceanog Inst, Geol & Geophys Dept, Woods Hole, MA 02543 USA.
   [Cann, J.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Langmuir, C. H.; Escrig, S.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Woods Hole Oceanographic Institution; University of Leeds; Harvard University
RP Escartín, J (corresponding author), Inst Phys Globe, CNRS, Marine Geosci Grp, 4 Pl Jussieu, F-75252 Paris 05, France.
EM escartin@ipgp.jussieu.fr
FU CNRS; NSF; WHOI; Harvard University; University of Leeds; MIT
NR 43
TC 427
Z9 465
U1 1
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 790
EP U5
DI 10.1038/nature07333
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900045
PM 18843367
DA 2026-03-09
ER

PT J
AU Behrens, TEJ
   Hunt, LT
   Woolrich, MW
   Rushworth, MFS
AF Behrens, Timothy E. J.
   Hunt, Laurence T.
   Woolrich, Mark W.
   Rushworth, Matthew F. S.
TI Associative learning of social value
SO NATURE
LA English
DT Article
ID prediction; reward; cortex; brain; error; trust; pay
AB Our decisions are guided by information learnt from our environment. This information may come via personal experiences of reward, but also from the behaviour of social partners(1,2). Social learning is widely held to be distinct from other forms of learning in its mechanism and neural implementation; it is often assumed to compete with simpler mechanisms, such as reward- based associative learning, to drive behaviour(3). Recently, neural signals have been observed during social exchange reminiscent of signals seen in studies of associative learning(4). Here we demonstrate that social information may be acquired using the same associative processes assumed to underlie reward- based learning. We find that key computational variables for learning in the social and reward domains are processed in a similar fashion, but in parallel neural processing streams. Two neighbouring divisions of the anterior cingulate cortex were central to learning about social and reward- based information, and for determining the extent to which each source of information guides behaviour. When making a decision, however, the information learnt using these parallel streams was combined within ventromedial prefrontal cortex. These findings suggest that human social valuation can be realized by means of the same associative processes previously established for learning other, simpler, features of the environment.
C1 [Behrens, Timothy E. J.; Hunt, Laurence T.; Woolrich, Mark W.; Rushworth, Matthew F. S.] Univ Oxford, John Radcliffe Hosp, FMRIB Ctr, Oxford OX3 9DU, England.
   [Behrens, Timothy E. J.; Hunt, Laurence T.; Rushworth, Matthew F. S.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
C3 University of Oxford; University of Oxford
RP Behrens, TEJ (corresponding author), Univ Oxford, John Radcliffe Hosp, FMRIB Ctr, Oxford OX3 9DU, England.
EM behrens@fmrib.ox.ac.uk
FU UK MRC; Wellcome Trust; UK EPSRC; MRC [G0501316, G0600994] Funding Source: UKRI; Medical Research Council [G0501316, G0600994] Funding Source: researchfish
NR 32
TC 726
Z9 785
U1 2
U2 191
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 13
PY 2008
VL 456
IS 7219
BP 245
EP U45
DI 10.1038/nature07538
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300041
PM 19005555
DA 2026-03-09
ER

PT J
AU Ley, TJ
   Mardis, ER
   Ding, L
   Fulton, B
   McLellan, MD
   Chen, K
   Dooling, D
   Dunford-Shore, BH
   McGrath, S
   Hickenbotham, M
   Cook, L
   Abbott, R
   Larson, DE
   Koboldt, DC
   Pohl, C
   Smith, S
   Hawkins, A
   Abbott, S
   Locke, D
   Hillier, LW
   Miner, T
   Fulton, L
   Magrini, V
   Wylie, T
   Glasscock, J
   Conyers, J
   Sander, N
   Shi, XQ
   Osborne, JR
   Minx, P
   Gordon, D
   Chinwalla, A
   Zhao, Y
   Ries, RE
   Payton, JE
   Westervelt, P
   Tomasson, MH
   Watson, M
   Baty, J
   Ivanovich, J
   Heath, S
   Shannon, WD
   Nagarajan, R
   Walter, MJ
   Link, DC
   Graubert, TA
   DiPersio, JF
   Wilson, RK
AF Ley, Timothy J.
   Mardis, Elaine R.
   Ding, Li
   Fulton, Bob
   McLellan, Michael D.
   Chen, Ken
   Dooling, David
   Dunford-Shore, Brian H.
   McGrath, Sean
   Hickenbotham, Matthew
   Cook, Lisa
   Abbott, Rachel
   Larson, David E.
   Koboldt, Dan C.
   Pohl, Craig
   Smith, Scott
   Hawkins, Amy
   Abbott, Scott
   Locke, Devin
   Hillier, LaDeana W.
   Miner, Tracie
   Fulton, Lucinda
   Magrini, Vincent
   Wylie, Todd
   Glasscock, Jarret
   Conyers, Joshua
   Sander, Nathan
   Shi, Xiaoqi
   Osborne, John R.
   Minx, Patrick
   Gordon, David
   Chinwalla, Asif
   Zhao, Yu
   Ries, Rhonda E.
   Payton, Jacqueline E.
   Westervelt, Peter
   Tomasson, Michael H.
   Watson, Mark
   Baty, Jack
   Ivanovich, Jennifer
   Heath, Sharon
   Shannon, William D.
   Nagarajan, Rakesh
   Walter, Matthew J.
   Link, Daniel C.
   Graubert, Timothy A.
   DiPersio, John F.
   Wilson, Richard K.
TI DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome
SO NATURE
LA English
DT Article
ID adult patients; mutations; aml; nucleophosmin; cancer; genes; flt3
AB Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole- genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour- specific somatic mutations that alter the protein- coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole- genome sequencing as an unbiased method for discovering cancer- initiating mutations in previously unidentified genes that may respond to targeted therapies.
C1 [Ley, Timothy J.; Mardis, Elaine R.; Ding, Li; Magrini, Vincent; Wilson, Richard K.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA.
   [Ley, Timothy J.; Zhao, Yu; Ries, Rhonda E.; Westervelt, Peter; Tomasson, Michael H.; Heath, Sharon; Shannon, William D.; Walter, Matthew J.; Link, Daniel C.; Graubert, Timothy A.; DiPersio, John F.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63108 USA.
   [Ley, Timothy J.; Mardis, Elaine R.; Ding, Li; Fulton, Bob; McLellan, Michael D.; Chen, Ken; Dooling, David; Dunford-Shore, Brian H.; McGrath, Sean; Hickenbotham, Matthew; Cook, Lisa; Abbott, Rachel; Larson, David E.; Koboldt, Dan C.; Pohl, Craig; Smith, Scott; Hawkins, Amy; Abbott, Scott; Locke, Devin; Hillier, LaDeana W.; Miner, Tracie; Fulton, Lucinda; Magrini, Vincent; Wylie, Todd; Glasscock, Jarret; Conyers, Joshua; Sander, Nathan; Shi, Xiaoqi; Osborne, John R.; Minx, Patrick; Chinwalla, Asif; Watson, Mark; Wilson, Richard K.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
   [Ley, Timothy J.; Westervelt, Peter; Tomasson, Michael H.; Watson, Mark; Ivanovich, Jennifer; Heath, Sharon; Shannon, William D.; Nagarajan, Rakesh; Walter, Matthew J.; Link, Daniel C.; Graubert, Timothy A.; DiPersio, John F.; Wilson, Richard K.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63108 USA.
   [Payton, Jacqueline E.; Watson, Mark; Nagarajan, Rakesh] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63108 USA.
   [Baty, Jack] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63108 USA.
   [Ivanovich, Jennifer] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63108 USA.
   [Hillier, LaDeana W.; Gordon, David] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); University of Washington; University of Washington Seattle
RP Mardis, ER (corresponding author), Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA.
EM emardis@wustl.edu
FU National Cancer Institute; National Human Genome Research Institute; Barnes-Jewish Hospital Foundation
NR 29
TC 962
Z9 1226
U1 0
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 66
EP 72
DI 10.1038/nature07485
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000041
PM 18987736
DA 2026-03-09
ER

PT J
AU Chesson, P
   Kuang, JJ
AF Chesson, Peter
   Kuang, Jessica J.
TI The interaction between predation and competition
SO NATURE
LA English
DT Article
ID apparent competition; ecological community; top predators; resource; coexistence; prey; diversity; systems; models
AB Competition and predation are the most heavily investigated species interactions in ecology, dominating studies of species diversity maintenance. However, these two interactions are most commonly viewed highly asymmetrically. Competition for resources is seen as the primary interaction limiting diversity, with predation modifying what competition does(1), although theoretical models have long supported diverse views(1-5). Here we show, using a comprehensive three- trophic- level model, that competition and predation should be viewed symmetrically: these two interactions are equally able to either limit or promote diversity. Diversity maintenance requires within- species density feedback loops to be stronger than between- species feedback loops. We quantify the contributions of predation and competition to these loops in a simple, interpretable form, showing their equivalent potential to strengthen or weaken diversity maintenance. Moreover, we show that competition and predation can undermine each other, with the tendency of the stronger interaction to promote or limit diversity prevailing. The past failure to appreciate the symmetrical effects and interactions of competition and predation has unduly restricted diversity maintenance studies. A multitrophic perspective should be adopted to examine a greater variety of possible effects of predation than generally considered in the past. Conservation and management strategies need to be much more concerned with the implications of changes in the strengths of trophic interactions.
C1 [Chesson, Peter; Kuang, Jessica J.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
C3 University of Arizona
RP Chesson, P (corresponding author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
EM pchesson@u.arizona.edu; jjkuang@u.arizona.edu
FU National Science Foundation [DEB-0542991, DEB-0717222]
NR 24
TC 412
Z9 516
U1 10
U2 322
PU 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 13
PY 2008
VL 456
IS 7219
BP 235
EP 238
DI 10.1038/nature07248
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300039
PM 19005554
DA 2026-03-09
ER

PT J
AU Helliker, BR
   Richter, SL
AF Helliker, Brent R.
   Richter, Suzanna L.
TI Subtropical to boreal convergence of tree-leaf temperatures
SO NATURE
LA English
DT Article
ID oxygen-isotope ratios; relative-humidity; cellulose; carbon; water; hydrogen; forest; plants; model; rings
AB The oxygen isotope ratio (delta(18)O) of cellulose is thought to provide a record of ambient temperature and relative humidity during periods of carbon assimilation(1,2). Here we introduce a method to resolve tree-canopy leaf temperature with the use of delta(18)O of cellulose in 39 tree species. We show a remarkably constant leaf temperature of 21.4 +/- 2.2 degrees C across 50 degrees of latitude, from subtropical to boreal biomes. This means that when carbon assimilation is maximal, the physiological and morphological properties of tree branches serve to raise leaf temperature above air temperature to a much greater extent in more northern latitudes. A main assumption underlying the use of delta(18)O to reconstruct climate history is that the temperature and relative humidity of an actively photosynthesizing leaf are the same as those of the surrounding air(3,4). Our data are contrary to that assumption and show that plant physiological ecology must be considered when reconstructing climate through isotope analysis. Furthermore, our results may explain why climate has only a modest effect on leaf economic traits(5) in general.
C1 [Helliker, Brent R.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Richter, Suzanna L.] Univ Penn, Dept Earth & Environm Sci, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania
RP Helliker, BR (corresponding author), Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
EM helliker@sas.upenn.edu
NR 35
TC 211
Z9 247
U1 4
U2 144
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 511
EP U6
DI 10.1038/nature07031
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300050
PM 18548005
DA 2026-03-09
ER

PT J
AU Xu, Y
   Feng, L
   Jeffrey, PD
   Shi, YG
   Morel, FMM
AF Xu, Yan
   Feng, Liang
   Jeffrey, Philip D.
   Shi, Yigong
   Morel, Francois M. M.
TI Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms
SO NATURE
LA English
DT Article
ID active-site; crystal-structure; proton-transfer; enzyme; zinc; binding; phytoplankton; waters; co2; identification
AB Carbonic anhydrase, a zinc enzyme found in organisms from all kingdoms, catalyses the reversible hydration of carbon dioxide and is used for inorganic carbon acquisition by phytoplankton. In the oceans, where zinc is nearly depleted, diatoms use cadmium as a catalytic metal atom in cadmium carbonic anhydrase ( CDCA). Here we report the crystal structures of CDCA in four distinct forms: cadmium- bound, zinc- bound, metal- free and acetate- bound. Despite lack of sequence homology, CDCA is a structural mimic of a functional beta- carbonic anhydrase dimer, with striking similarity in the spatial organization of the active site residues. CDCA readily exchanges cadmium and zinc at its active site - an apparently unique adaptation to oceanic life that is explained by a stable opening of the metal coordinating site in the absence of metal. Given the central role of diatoms in exporting carbon to the deep sea, their use of cadmium in an enzyme critical for carbon acquisition establishes a remarkable link between the global cycles of cadmium and carbon.
C1 [Morel, Francois M. M.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
   [Xu, Yan] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
   [Feng, Liang; Jeffrey, Philip D.; Shi, Yigong] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Princeton University
RP Morel, FMM (corresponding author), Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
EM yshi@princeton.edu; morel@princeton.edu
NR 47
TC 451
Z9 511
U1 3
U2 253
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 6
PY 2008
VL 452
IS 7183
BP 56
EP U3
DI 10.1038/nature06636
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900045
PM 18322527
DA 2026-03-09
ER

PT J
AU Goes, S
   Capitanio, FA
   Morra, G
AF Goes, Saskia
   Capitanio, Fabio A.
   Morra, Gabriele
TI Evidence of lower-mantle slab penetration phases in plate motions
SO NATURE
LA English
DT Article
ID trench migration; subduction zones; lithosphere; transition; convection; tectonics; mechanism; buoyancy; stresses; strength
AB It is well accepted that subduction of the cold lithosphere is a crucial component of the Earth's plate tectonic style of mantle convection. But whether and how subducting plates penetrate into the lower mantle is the subject of continuing debate, which has substantial implications for the chemical and thermal evolution of the mantle(1,2). Here we identify lower-mantle slab penetration events by comparing Cenozoic plate motions at the Earth's main subduction zones(3) with motions predicted by fully dynamic models of the upper- mantle phase of subduction, driven solely by downgoing plate density(4). Whereas subduction of older, intrinsically denser, lithosphere occurs at rates consistent with the model, younger lithosphere (of ages less than about 60 Myr) often subducts up to two times faster, while trench motions are very low. We conclude that the most likely explanation is that older lithosphere, subducting under significant trench retreat, tends to lie down flat above the transition to the high- viscosity lower mantle, whereas younger lithosphere, which is less able to drive trench retreat and deforms more readily, buckles and thickens. Slab thickening enhances buoyancy (volume times density) and thereby Stokes sinking velocity, thus facilitating fast lowermantle penetration. Such an interpretation is consistent with seismic images of the distribution of subducted material in upper and lower mantle(5,6). Thus we identify a direct expression of time- dependent flow between the upper and lower mantle.
C1 [Goes, Saskia] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
   [Capitanio, Fabio A.; Morra, Gabriele] ETH, Inst Geophys, CH-8093 Zurich, Switzerland.
C3 Imperial College London; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Goes, S (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
EM s.goes@imperial.ac.uk
NR 30
TC 124
Z9 137
U1 0
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 981
EP 984
DI 10.1038/nature06691
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100046
PM 18288192
DA 2026-03-09
ER

PT J
AU Wilhelm, BT
   Marguerat, S
   Watt, S
   Schubert, F
   Wood, V
   Goodhead, I
   Penkett, CJ
   Rogers, J
   Bähler, J
AF Wilhelm, Brian T.
   Marguerat, Samuel
   Watt, Stephen
   Schubert, Falk
   Wood, Valerie
   Goodhead, Ian
   Penkett, Christopher J.
   Rogers, Jane
   Bahler, Jurg
TI Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution
SO NATURE
LA English
DT Article
ID genome-wide transcription; gene-expression; fission yeast; meiosis; identification; program; network; ter1; map
AB Recent data from several organisms indicate that the transcribed portions of genomes are larger and more complex than expected, and that many functional properties of transcripts are based not on coding sequences but on regulatory sequences in untranslated regions or non- coding RNAs1-9. Alternative start and polyadenylation sites and regulation of intron splicing add additional dimensions to the rich transcriptional output(10,11). This transcriptional complexity has been sampled mainly using hybridization- based methods under one or few experimental conditions. Here we applied direct high- throughput sequencing of complementary DNAs ( RNA- Seq), supplemented with data from high- density tiling arrays, to globally sample transcripts of the fission yeast Schizosaccharomyces pombe, independently from available gene annotations. We interrogated transcriptomes under multiple conditions, including rapid proliferation, meiotic differentiation and environmental stress, as well as in RNA processing mutants to reveal the dynamic plasticity of the transcriptional landscape as a function of environmental, developmental and genetic factors. High- throughput sequencing proved to be a powerful and quantitative method to sample transcriptomes deeply at maximal resolution. In contrast to hybridization, sequencing showed little, if any, background noise and was sensitive enough to detect widespread transcription in >90% of the genome, including traces of RNAs that were not robustly transcribed or rapidly degraded. The combined sequencing and strand- specific array data provide rich condition- specific information on novel, mostly non- coding transcripts, untranslated regions and gene structures, thus improving the existing genome annotation. Sequence reads spanning exon-exon or exon - intron junctions give unique insight into a surprising variability in splicing efficiency across introns, genes and conditions. Splicing efficiency was largely coordinated with transcript levels, and increased transcription led to increased splicing in test genes. Hundreds of introns showed such regulated splicing during cellular proliferation or differentiation.
C1 [Wilhelm, Brian T.; Marguerat, Samuel; Watt, Stephen; Schubert, Falk; Wood, Valerie; Goodhead, Ian; Penkett, Christopher J.; Rogers, Jane; Bahler, Jurg] Wellcome Trust Sanger Inst, Canc Res UK Fiss Yeast Funct Genom Grp, Cambridge CB10 1HH, England.
C3 Wellcome Trust Sanger Institute
RP Bähler, J (corresponding author), UCL, Dept Genet Evolut & Environm, Mortimer St, London WC1E 6BT, England.
EM jurg@sanger.ac.uk
FU Cancer Research UK [C9546/A6517, A6517] Funding Source: Medline; Wellcome Trust [077118] Funding Source: Medline
NR 31
TC 785
Z9 1016
U1 2
U2 222
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1239
EP U39
DI 10.1038/nature07002
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800043
PM 18488015
DA 2026-03-09
ER

PT J
AU Velliste, M
   Perel, S
   Spalding, MC
   Whitford, AS
   Schwartz, AB
AF Velliste, Meel
   Perel, Sagi
   Spalding, M. Chance
   Whitford, Andrew S.
   Schwartz, Andrew B.
TI Cortical control of a prosthetic arm for self-feeding
SO NATURE
LA English
DT Article
ID population representation; drawing movements; computer; neurons; restoration; interfaces; direction; signals
AB Arm movement is well represented in populations of neurons recorded from the motor cortex(1-7). Cortical activity patterns have been used in the new field of brain-machine interfaces(8-11) to show how cursors on computer displays can be moved in two- and three-dimensional space(12-22). Although the ability to move a cursor can be useful in its own right, this technology could be applied to restore arm and hand function for amputees and paralysed persons. However, the use of cortical signals to control a multi-jointed prosthetic device for direct real-time interaction with the physical environment ('embodiment') has not been demonstrated. Here we describe a system that permits embodied prosthetic control; we show how monkeys (Macaca mulatta) use their motor cortical activity to control a mechanized arm replica in a self-feeding task. In addition to the three dimensions of movement, the subjects' cortical signals also proportionally controlled a gripper on the end of the arm. Owing to the physical interaction between the monkey, the robotic arm and objects in the workspace, this new task presented a higher level of difficulty than previous virtual (cursor-control) experiments. Apart from an example of simple one-dimensional control(23), previous experiments have lacked physical interaction even in cases where a robotic arm(16,19,24) or hand(20) was included in the control loop, because the subjects did not use it to interact with physical objects - an interaction that cannot be fully simulated. This demonstration of multi-degree-of-freedom embodied prosthetic control paves the way towards the development of dexterous prosthetic devices that could ultimately achieve arm and hand function at a near-natural level.
C1 [Velliste, Meel; Schwartz, Andrew B.] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15213 USA.
   [Perel, Sagi; Spalding, M. Chance; Whitford, Andrew S.; Schwartz, Andrew B.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA.
   [Perel, Sagi; Spalding, M. Chance; Whitford, Andrew S.; Schwartz, Andrew B.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA.
   [Perel, Sagi; Spalding, M. Chance; Whitford, Andrew S.; Schwartz, Andrew B.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
   [Schwartz, Andrew B.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA.
   [Schwartz, Andrew B.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15219 USA.
   [Schwartz, Andrew B.] Carnegie Mellon Univ, Inst Robot, Pittsburgh, PA 15213 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Carnegie Mellon University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Carnegie Mellon University
RP Schwartz, AB (corresponding author), Univ Pittsburgh, Sch Med, Dept Neurobiol, E1440 BST,Lothrop St, Pittsburgh, PA 15213 USA.
EM abs21@pitt.edu
FU NINDS NIH HHS [NS050256] Funding Source: Medline; PHS HHS [N01-2-2346] Funding Source: Medline
NR 30
TC 1155
Z9 1463
U1 6
U2 475
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2008
VL 453
IS 7198
BP 1098
EP 1101
DI 10.1038/nature06996
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900056
PM 18509337
DA 2026-03-09
ER

PT J
AU Castro-Tirado, AJ
   Postigo, AD
   Gorosabel, J
   Jelínek, M
   Fatkhullin, TA
   Sokolov, VV
   Ferrero, P
   Kann, DA
   Klose, S
   Sluse, D
   Bremer, M
   Winters, JM
   Nuernberger, D
   Pérez-Ramírez, D
   Guerrero, MA
   French, J
   Melady, G
   Hanlon, L
   McBreen, B
   Leventis, K
   Markoff, SB
   Leon, S
   Kraus, A
   Aceituno, FJ
   Cunniffe, R
   Kubánek, P
   Vítek, S
   Schulze, S
   Wilson, AC
   Hudec, R
   Durant, M
   González-Pérez, JM
   Shahbaz, T
   Guziy, S
   Pandey, SB
   Pavlenko, L
   Sonbas, E
   Trushkin, SA
   Bursov, NN
   Nizhelskij, NA
   Sánchez-Fernández, C
   Sabau-Graziati, L
AF Castro-Tirado, A. J.
   de Ugarte Postigo, A.
   Gorosabel, J.
   Jelinek, M.
   Fatkhullin, T. A.
   Sokolov, V. V.
   Ferrero, P.
   Kann, D. A.
   Klose, S.
   Sluse, D.
   Bremer, M.
   Winters, J. M.
   Nuernberger, D.
   Perez-Ramirez, D.
   Guerrero, M. A.
   French, J.
   Melady, G.
   Hanlon, L.
   McBreen, B.
   Leventis, K.
   Markoff, S. B.
   Leon, S.
   Kraus, A.
   Aceituno, F. J.
   Cunniffe, R.
   Kubanek, P.
   Vitek, S.
   Schulze, S.
   Wilson, A. C.
   Hudec, R.
   Durant, M.
   Gonzalez-Perez, J. M.
   Shahbaz, T.
   Guziy, S.
   Pandey, S. B.
   Pavlenko, L.
   Sonbas, E.
   Trushkin, S. A.
   Bursov, N. N.
   Nizhelskij, N. A.
   Sanchez-Fernandez, C.
   Sabau-Graziati, L.
TI Flares from a candidate Galactic magnetar suggest a missing link to dim isolated neutron stars
SO NATURE
LA English
DT Article
ID xmm-newton observations; soft gamma repeaters; x-ray; v4641 sagittarii; transient; sgr; discovery; emission; sgr1806-20; outburst
AB Magnetars(1) are young neutron stars with very strong magnetic fields of the order of 10(14)-10(15) G. They are detected in our Galaxy either as soft gamma-ray repeaters or anomalous X-ray pulsars. Soft gamma-ray repeaters are a rare type of gamma-ray transient sources that are occasionally detected as bursters in the high-energy sky(2-4). No optical counterpart to the gamma-ray flares or the quiescent source has yet been identified. Here we report multi-wavelength observations of a puzzling source, SWIFT J195509+261406. We detected more than 40 flaring episodes in the optical band over a time span of three days, and a faint infrared flare 11 days later, after which the source returned to quiescence. Our radio observations confirm a Galactic nature and establish a lower distance limit of similar to 3.7 kpc. We suggest that SWIFT J195509+261406 could be an isolated magnetar whose bursting activity has been detected at optical wavelengths, and for which the long- term X- ray emission is short- lived. In this case, a new manifestation of magnetar activity has been recorded and we can consider SWIFT J195509+261406 to be a link between the 'persistent' soft gamma-ray repeaters/anomalous X- ray pulsars and dim isolated neutron stars.
C1 [Castro-Tirado, A. J.; de Ugarte Postigo, A.; Gorosabel, J.; Jelinek, M.; Guerrero, M. A.; Aceituno, F. J.; Cunniffe, R.; Kubanek, P.; Vitek, S.] CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain.
   [de Ugarte Postigo, A.; Nuernberger, D.] European So Observ, Santiago 19, Chile.
   [Fatkhullin, T. A.; Sokolov, V. V.; Sonbas, E.; Trushkin, S. A.; Bursov, N. N.; Nizhelskij, N. A.] Russian Acad Sci, Special Astrophys Observ, Nizhnii Arkhyz 369167, Russia.
   [Ferrero, P.; Kann, D. A.; Klose, S.; Schulze, S.] Thuringer Landessternwarte Tautenburg, D-07778 Tautenburg, Germany.
   [Sluse, D.] EPFL Observ, Lab Astrophys, CH-1290 Sauverny, Switzerland.
   [Bremer, M.; Winters, J. M.] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Perez-Ramirez, D.] Univ Jaen, Fac Ciencias Expt, E-23071 Jaen, Spain.
   [Perez-Ramirez, D.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [French, J.; Melady, G.; Hanlon, L.; McBreen, B.] Univ Coll Dublin, Sch Phys, Dublin 4, Ireland.
   [Leventis, K.; Markoff, S. B.] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1098 SJ Amsterdam, Netherlands.
   [Leon, S.] IRAM, E-18012 Granada, Spain.
   [Kraus, A.] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Cunniffe, R.] Cork Inst Technol, Cork, Ireland.
   [Kubanek, P.] Univ Valencia, Edif Inst Invest, GACE ICMOL, E-46980 Valencia, Spain.
   [Wilson, A. C.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Hudec, R.] Acad Sci Czech Republic, Inst Astron, CS-25165 Ondrejov, Czech Republic.
   [Durant, M.; Gonzalez-Perez, J. M.; Shahbaz, T.] Inst Astrofis Canarias, E-38205 Tenerife, Spain.
   [Guziy, S.] Nikolaev State Univ, UA-54030 Nikolayev, Ukraine.
   [Pandey, S. B.] Aryabhatta Res Inst Observ Sci ARIES, Naini Tal 263129, India.
   [Pavlenko, L.] Crimean Astrophys Observ, UA-98409 Nauchnyi, Ukraine.
   [Sonbas, E.] Cukurova Univ, Dept Phys, TR-01330 Adana, Turkey.
   [Sanchez-Fernandez, C.] ESAC, E-28691 Madrid, Spain.
   [Sabau-Graziati, L.] INTA, E-28750 Madrid, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); European Southern Observatory; Russian Academy of Sciences; Special Astrophysics Observatory of the Russian Academy of Sciences; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Universidad de Jaen; University of Leicester; University College Dublin; University of Amsterdam; Max Planck Society; Munster Technological University (MTU); University of Valencia; University of Texas System; University of Texas Austin; Czech Academy of Sciences; Astronomical Institute of the Czech Academy of Sciences; Instituto de Astrofisica de Canarias; V.O. Sukhomlynskyi Mykolaiv National University; Ministry of Education & Science of Ukraine; Mykolayiv National Agrarian University (MNAU); Department of Science & Technology (India); Aryabhatta Research Institute of Observational Sciences (ARIES); Crimean Astrophysical Observatory; Cukurova University; European Space Agency; European Space Astronomy Center; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA)
RP Castro-Tirado, AJ (corresponding author), CSIC, Inst Astrofis Andalucia, POB 03004, E-18080 Granada, Spain.
EM ajct@iaa.es
FU INSU/CNRS (France); MPG (Germany); IGN (Spain); DFG; D.P.R; IRCSET; SFI; PECs; GACR; Spanish Ministry of Science and Innovation
NR 29
TC 34
Z9 37
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 SEP 25
PY 2008
VL 455
IS 7212
BP 506
EP 509
DI 10.1038/nature07328
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600040
PM 18818652
DA 2026-03-09
ER

PT J
AU Friedman, WE
AF Friedman, William E.
TI Hydatellaceae are water lilies with gymnospermous tendencies
SO NATURE
LA English
DT Article
ID female gametophyte; endosperm; phylogeny; evolution; nymphaeaceae; angiosperms; genes; seed
AB The flowering plant family Hydatellaceae was recently discovered to be allied to the ancient angiosperm lineage Nymphaeales ( water lilies)(1). Because of its critical phylogenetic position, members of the Hydatellaceae have the potential to provide insights into the origin and early diversification of angiosperms(2). Here I report that Hydatella expresses several rare embryological features that, in combination, are found only in members of the Nymphaeales. At maturity, the female gametophyte is four- celled, four- nucleate and will produce a diploid endosperm, as is characteristic of most early divergent angiosperm lineages(3,4). As with all members of the Nymphaeales, endosperm in Hydatella is minimally developed and perisperm is the major embryo- nourishing tissue within the seed(5,6). Remarkably, Hydatella exhibits a maternal seed-provisioning strategy that is unique among flowering plants, but common to all gymnosperms(7): pre- fertilization allocation of nutrients to the embryo- nourishing tissue. This exceptional case of pre- fertilization maternal provisioning of a seed in Hydatella may well be an apomorphic feature of Hydatellaceae alone but, given the newly discovered phylogenetic position of this family, potentially represents a plesiomorphic and transitional condition associated with the origin of flowering plants from gymnospermous ancestors.
C1 Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
C3 University of Colorado System; University of Colorado Boulder
RP Friedman, WE (corresponding author), Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
EM ned@colorado.edu
NR 30
TC 59
Z9 66
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 1
PY 2008
VL 453
IS 7191
BP 94
EP 97
DI 10.1038/nature06733
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800045
PM 18354395
DA 2026-03-09
ER

PT J
AU Lambert, F
   Delmonte, B
   Petit, JR
   Bigler, M
   Kaufmann, PR
   Hutterli, MA
   Stocker, TF
   Ruth, U
   Steffensen, JP
   Maggi, V
AF Lambert, F.
   Delmonte, B.
   Petit, J. R.
   Bigler, M.
   Kaufmann, P. R.
   Hutterli, M. A.
   Stocker, T. F.
   Ruth, U.
   Steffensen, J. P.
   Maggi, V.
TI Dust-climate couplings over the past 800,000 years from the EPICA Dome C ice core
SO NATURE
LA English
DT Article
ID last glacial maximum; east antarctica; southern-ocean; productivity; transport; record; reconstruction; temperature; cycle
AB Dust can affect the radiative balance of the atmosphere by absorbing or reflecting incoming solar radiation(1); it can also be a source of micronutrients, such as iron, to the ocean(2). It has been suggested that production, transport and deposition of dust is influenced by climatic changes on glacial-interglacial timescales(3-6). Here we present a high- resolution record of aeolian dust from the EPICA Dome C ice core in East Antarctica, which provides an undisturbed climate sequence over the past eight climatic cycles(7,8). We find that there is a significant correlation between dust flux and temperature records during glacial periods that is absent during interglacial periods. Our data suggest that dust flux is increasingly correlated with Antarctic temperature as the climate becomes colder. We interpret this as progressive coupling of the climates of Antarctic and lower latitudes. Limited changes in glacial-interglacial atmospheric transport time(4,9,10) suggest that the sources and lifetime of dust are the main factors controlling the high glacial dust input. We propose that the observed similar to 25-fold increase in glacial dust flux over all eight glacial periods can be attributed to a strengthening of South American dust sources, together with a longer lifetime for atmospheric dust particles in the upper troposphere resulting from a reduced hydrological cycle during the ice ages.
C1 [Petit, J. R.] Univ Grenoble 1, CNRS, Lab Glaciol & Geophys Environm, F-38402 St Martin Dheres, France.
   [Lambert, F.; Bigler, M.; Kaufmann, P. R.; Stocker, T. F.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
   [Lambert, F.; Kaufmann, P. R.; Stocker, T. F.] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Delmonte, B.; Maggi, V.] Univ Milano Bicocca, Dept Environm Sci, I-20126 Milan, Italy.
   [Bigler, M.; Steffensen, J. P.] Univ Copenhagen, Niels Bohr Inst, Ctr Ice & Climate, DK-2100 Copenhagen OE, Denmark.
   [Hutterli, M. A.] British Antarctic Survey, Cambridge CB3 0ET, England.
   [Ruth, U.] Alfred Wegener Inst Polar & Marine Res, D-27568 Bremerhaven, Germany.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); University of Bern; University of Bern; University of Milano-Bicocca; University of Copenhagen; Niels Bohr Institute; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research
RP Petit, JR (corresponding author), Univ Grenoble 1, CNRS, Lab Glaciol & Geophys Environm, BP96, F-38402 St Martin Dheres, France.
EM petit@lgge.obs.ujf-grenoble.fr
FU Natural Environment Research Council [bas010016] Funding Source: researchfish; NERC [bas010016] Funding Source: UKRI
NR 29
TC 549
Z9 637
U1 9
U2 208
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 616
EP 619
DI 10.1038/nature06763
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200042
PM 18385736
DA 2026-03-09
ER

PT J
AU Park, T
   Sidorov, VA
   Ronning, F
   Zhu, JX
   Tokiwa, Y
   Lee, H
   Bauer, ED
   Movshovich, R
   Sarrao, JL
   Thompson, JD
AF Park, T.
   Sidorov, V. A.
   Ronning, F.
   Zhu, J. -X.
   Tokiwa, Y.
   Lee, H.
   Bauer, E. D.
   Movshovich, R.
   Sarrao, J. L.
   Thompson, J. D.
TI Isotropic quantum scattering and unconventional superconductivity
SO NATURE
LA English
DT Article
ID phase-transitions; critical-point; heavy; metals; criticality; disorder; cerhin5; spin
AB Superconductivity without phonons has been proposed for strongly correlated electron materials that are tuned close to a zero- temperature magnetic instability of itinerant charge carriers(1). Near this boundary, quantum fluctuations of magnetic degrees of freedom assume the role of phonons in conventional superconductors, creating an attractive interaction that 'glues' electrons into superconducting pairs. Here we show that superconductivity can arise from a very different spectrum of fluctuations associated with a local (or Kondo-breakdown) quantum critical point(2-5) that is revealed in isotropic scattering of charge carriers and a sublinear, temperature-dependent electrical resistivity. At this critical point, accessed by applying pressure to the strongly correlated, local- moment antiferromagnet CeRhIn5, magnetic and charge fluctuations coexist and produce electronic scattering that is maximal at the optimal pressure for superconductivity. This previously unanticipated source of pairing glue(6) opens possibilities for understanding and discovering new unconventional forms of superconductivity.
C1 [Park, T.; Sidorov, V. A.; Ronning, F.; Zhu, J. -X.; Tokiwa, Y.; Lee, H.; Bauer, E. D.; Movshovich, R.; Sarrao, J. L.; Thompson, J. D.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Park, T.] Sungkyunkwan Univ, Dept Phys, Suwon 440746, South Korea.
   [Sidorov, V. A.] RAS, Vereshchagin Inst High Pressure Phys, Troitsk 142190, Russia.
C3 United States Department of Energy (DOE); Los Alamos National Laboratory; Sungkyunkwan University (SKKU); Russian Academy of Sciences; Vereshchagin Institute of High Pressure Physics, Russian Academy of Sciences
RP Park, T (corresponding author), Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87545 USA.
EM tuson@lanl.gov; jdt@lanl.gov
FU Los Alamos Directed Research and Developmental; Russian Foundation for Basic Research [06-02-16590]; Program of the Presidium of RAS on Physics of Strongly Compressed Matter
NR 24
TC 97
Z9 104
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 NOV 20
PY 2008
VL 456
IS 7220
BP 366
EP 368
DI 10.1038/nature07431
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600038
PM 19020616
DA 2026-03-09
ER

PT J
AU Guzzo, L
   Pierleoni, M
   Meneux, B
   Branchini, E
   Le Fèvre, O
   Marinoni, C
   Garilli, B
   Blaizot, J
   De Lucia, G
   Pollo, A
   McCracken, HJ
   Bottini, D
   Le Brun, V
   Maccagni, D
   Picat, JP
   Scaramella, R
   Scodeggio, M
   Tresse, L
   Vettolani, G
   Zanichelli, A
   Adami, C
   Arnouts, S
   Bardelli, S
   Bolzonella, M
   Bongiorno, A
   Cappi, A
   Charlot, S
   Ciliegi, P
   Contini, T
   Cucciati, O
   de la Torre, S
   Dolag, K
   Foucaud, S
   Franzetti, P
   Gavignaud, I
   Ilbert, O
   Iovino, A
   Lamareille, F
   Marano, B
   Mazure, A
   Memeo, P
   Merighi, R
   Moscardini, L
   Paltani, S
   Pellò, R
   Perez-Montero, E
   Pozzetti, L
   Radovich, M
   Vergani, D
   Zamorani, G
   Zucca, E
AF Guzzo, L.
   Pierleoni, M.
   Meneux, B.
   Branchini, E.
   Le Fevre, O.
   Marinoni, C.
   Garilli, B.
   Blaizot, J.
   De Lucia, G.
   Pollo, A.
   McCracken, H. J.
   Bottini, D.
   Le Brun, V.
   Maccagni, D.
   Picat, J. P.
   Scaramella, R.
   Scodeggio, M.
   Tresse, L.
   Vettolani, G.
   Zanichelli, A.
   Adami, C.
   Arnouts, S.
   Bardelli, S.
   Bolzonella, M.
   Bongiorno, A.
   Cappi, A.
   Charlot, S.
   Ciliegi, P.
   Contini, T.
   Cucciati, O.
   de la Torre, S.
   Dolag, K.
   Foucaud, S.
   Franzetti, P.
   Gavignaud, I.
   Ilbert, O.
   Iovino, A.
   Lamareille, F.
   Marano, B.
   Mazure, A.
   Memeo, P.
   Merighi, R.
   Moscardini, L.
   Paltani, S.
   Pello, R.
   Perez-Montero, E.
   Pozzetti, L.
   Radovich, M.
   Vergani, D.
   Zamorani, G.
   Zucca, E.
TI A test of the nature of cosmic acceleration using galaxy redshift distortions
SO NATURE
LA English
DT Article
ID vlt deep survey; cluster abundance; density; constraints; evolution; omega(m); models; space; bias
AB Observations of distant supernovae indicate that the Universe is now in a phase of accelerated expansion(1,2) the physical cause of which is a mystery(3). Formally, this requires the inclusion of a term acting as a negative pressure in the equations of cosmic expansion, accounting for about 75 per cent of the total energy density in the Universe. The simplest option for this 'dark energy' corresponds to a 'cosmological constant', perhaps related to the quantum vacuum energy. Physically viable alternatives invoke either the presence of a scalar field with an evolving equation of state, or extensions of general relativity involving higher- order curvature terms or extra dimensions(4-8). Although they produce similar expansion rates, different models predict measurable differences in the growth rate of large- scale structure with cosmic time(9). A fingerprint of this growth is provided by coherent galaxy motions, which introduce a radial anisotropy in the clustering pattern reconstructed by galaxy redshift surveys(10). Here we report a measurement of this effect at a redshift of 0.8. Using a new survey of more than 10,000 faint galaxies(11,12), we measure the anisotropy parameter beta=0.70 +/- 0.26, which corresponds to a growth rate of structure at that time of f = 0.9 +/- 0.36. This is consistent with the standard cosmological- constant model with low matter density and flat geometry, although the error bars are still too large to distinguish among alternative origins for the accelerated expansion. The correct origin could be determined with a further factor-of-ten increase in the sampled volume at similar redshift.
C1 [Guzzo, L.; Cucciati, O.; Iovino, A.] INAF, Osservatorio Astron Brera, I-23807 Merate, LC, Italy.
   [Guzzo, L.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Guzzo, L.; Pierleoni, M.; Blaizot, J.; De Lucia, G.; Dolag, K.] Max Planck Inst Astrophys, D-85748 Garching, Germany.
   [Guzzo, L.] European So Observ, D-85748 Garching, Germany.
   [Meneux, B.; Garilli, B.; Bottini, D.; Maccagni, D.; Scodeggio, M.; Franzetti, P.; Memeo, P.; Vergani, D.] INAF, IASF, I-20133 Milan, Italy.
   [Branchini, E.] Univ Roma 3, Dipartimento Fis, I-00146 Rome, Italy.
   [Le Fevre, O.; Pollo, A.; Le Brun, V.; Tresse, L.; Adami, C.; Arnouts, S.; de la Torre, S.; Mazure, A.] Univ Aix Marseille 1, Lab Astrophys Marseille, CNRS, UMR6110, F-13376 Marseille 12, France.
   [Marinoni, C.] Univ Aix Marseille 1, Ctr Phys Theor, CNRS, UMR 6207, F-13288 Marseille, France.
   [Pollo, A.] Andrzej Soltan Inst Nucl Res, PL-00681 Warsaw, Poland.
   [McCracken, H. J.; Charlot, S.] Inst Astrophys, UMR 7095, F-75014 Paris, France.
   [McCracken, H. J.] LERMA, Observ Paris, F-75014 Paris, France.
   [Picat, J. P.; Contini, T.; Pello, R.; Perez-Montero, E.] Observ Midi Pyrenees, Astrophys Lab, UMR 5572, F-31400 Toulouse, France.
   [Scaramella, R.; Vettolani, G.; Zanichelli, A.] INAF, IRA, I-40129 Bologna, Italy.
   [Scaramella, R.] INAF, Osservatorio Astron Roma, I-00040 Monte Porzio Catone, Italy.
   [Bardelli, S.; Bolzonella, M.; Cappi, A.; Ciliegi, P.; Lamareille, F.; Merighi, R.; Pozzetti, L.; Zamorani, G.; Zucca, E.] INAF, Osservatorio Astron Bologna, I-40127 Bologna, Italy.
   [Bongiorno, A.; Marano, B.; Moscardini, L.] Univ Bologna, Dipartimento Astron, I-40127 Bologna, Italy.
   [Cucciati, O.] Univ Milano Bicocca, Dipartimento Fis, I-20126 Milan, Italy.
   [Foucaud, S.] Univ Nottingham, Sch Phys & Astron, Nottingham NG7 2RD, England.
   [Gavignaud, I.] Astrophys Inst Potsdam, D-14482 Potsdam, Germany.
   [Ilbert, O.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Moscardini, L.] Ist Nazl Fis Nucl, Sez Bologna, I-40127 Bologna, Italy.
   [Paltani, S.] Observ Geneva, CH-1290 Sauverny, Switzerland.
   [Paltani, S.] Integral Sci Data Ctr, CH-1290 Versoix, Switzerland.
   [Radovich, M.] INAF, Osservatorio Astron Capodimonte, I-80131 Naples, Italy.
C3 Istituto Nazionale Astrofisica (INAF); Max Planck Society; Max Planck Society; European Southern Observatory; Istituto Nazionale Astrofisica (INAF); Roma Tre University; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Soltan Institute for Nuclear Studies; National Centre for Nuclear Research; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Universite PSL; Observatoire de Paris; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); University of Bologna; University of Milano-Bicocca; University of Nottingham; University of Hawaii System; Istituto Nazionale di Fisica Nucleare (INFN); University of Geneva; University of Geneva; Istituto Nazionale Astrofisica (INAF)
RP Guzzo, L (corresponding author), INAF, Osservatorio Astron Brera, Via Bianchi 46, I-23807 Merate, LC, Italy.
EM luigi.guzzo@brera.inaf.it
NR 28
TC 584
Z9 612
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 31
PY 2008
VL 451
IS 7178
BP 541
EP 544
DI 10.1038/nature06555
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900034
PM 18235494
DA 2026-03-09
ER

PT J
AU Huber, D
   Petreanu, L
   Ghitani, N
   Ranade, S
   Hromádka, T
   Mainen, Z
   Svoboda, K
AF Huber, Daniel
   Petreanu, Leopoldo
   Ghitani, Nima
   Ranade, Sachin
   Hromadka, Tomas
   Mainen, Zach
   Svoboda, Karel
TI Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice
SO NATURE
LA English
DT Article
ID light-induced activation; electrical-stimulation; neurons; channelrhodopsin-2; photostimulation; representation
AB Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions(1-6). However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain(7,8). To address these issues we introduced the light- gated algal channel channelrhodopsin- 2 (ChR2)(9) specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus- locked action potentials(10-13) at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials ( five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons ( approximately 60) were required for longer stimuli ( five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.
C1 [Huber, Daniel; Petreanu, Leopoldo; Ghitani, Nima; Svoboda, Karel] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Huber, Daniel; Petreanu, Leopoldo; Ranade, Sachin; Hromadka, Tomas; Mainen, Zach; Svoboda, Karel] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 Howard Hughes Medical Institute; Cold Spring Harbor Laboratory
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 30
TC 398
Z9 479
U1 0
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 61
EP U7
DI 10.1038/nature06445
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300033
PM 18094685
DA 2026-03-09
ER

PT J
AU Olsen, SM
   Hansen, B
   Quadfasel, D
   Osterhus, S
AF Olsen, Steffen M.
   Hansen, Bogi
   Quadfasel, Detlef
   Osterhus, Svein
TI Observed and modelled stability of overflow across the Greenland-Scotland ridge
SO NATURE
LA English
DT Article
ID meridional overturning circulation; north-atlantic; deep-water; faroe; variability
AB Across the Greenland - Scotland ridge there is a continuous flow of cold dense water, termed 'overflow', from the Nordic seas to the Atlantic Ocean(1). This is a main contributor to the production of North Atlantic Deep Water(2) that feeds the lower limb of the Atlantic meridional overturning circulation, which has been predicted to weaken as a consequence of climate change(3,4). The two main overflow branches pass the Denmark Strait and the Faroe Bank channel. Here we combine results from direct current measurements in the Faroe Bank channel(5) for 1995 - 2005 with an ensemble hindcast experiment(6) for 1948 - 2005 using an ocean general circulation model. For the overlapping period we find a convincing agreement between model simulations and observations on monthly to interannual timescales. Both observations and model data show no significant trend in volume transport. In addition, for the whole 1948 - 2005 period, the model indicates no persistent trend in the Faroe Bank channel overflow or in the total overflow transport, in agreement with the few available historical observations. Deepening isopycnals in the Norwegian Sea have tended to decrease the pressure difference across the Greenland - Scotland ridge(7), but this has been compensated for by the effect of changes in sea level. In contrast with earlier studies(7,8), we therefore conclude that the Faroe Bank channel overflow, and also the total overflow, did not decrease consistently from 1950 to 2005, although the model does show a weakening total Atlantic meridional overturning circulation as a result of changes south of the Greenland - Scotland ridge.
C1 [Olsen, Steffen M.] Danish Meteorol Inst, DK-2100 Copenhagen, Denmark.
   [Hansen, Bogi] Faroese Fisheries Lab, FO-110 Torshavn, Faroe Islands, Denmark.
   [Quadfasel, Detlef] Univ Hamburg, Zentrum Meeres & Klimaforsch, D-20146 Hamburg, Germany.
   [Osterhus, Svein] Univ Bergen, Bjerknes Ctr Climate Res, NO-5014 Bergen, Norway.
C3 Danish Meteorological Institute DMI; University of Hamburg; University of Bergen; Bjerknes Centre for Climate Research
RP Olsen, SM (corresponding author), Danish Meteorol Inst, Lyngbyvej 100, DK-2100 Copenhagen, Denmark.
EM smo@dmi.dk
FU European Commission; Danish Environmental Ministry; Nordic Council in the project Arctic-Atlantic Exchanges (ARATEX); German Federal Ministry of Education and Research ( BMBF); North Atlantic Project; Research Council of Norway; POCAHONTAS; CNES
NR 25
TC 83
Z9 87
U1 2
U2 30
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 519
EP U35
DI 10.1038/nature07302
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600043
PM 18818655
DA 2026-03-09
ER

PT J
AU Sato, Y
   Yoshikawa, A
   Yamagata, A
   Mimura, H
   Yamashita, M
   Ookata, K
   Nureki, O
   Iwai, K
   Komada, M
   Fukai, S
AF Sato, Yusuke
   Yoshikawa, Azusa
   Yamagata, Atsushi
   Mimura, Hisatoshi
   Yamashita, Masami
   Ookata, Kayoko
   Nureki, Osamu
   Iwai, Kazuhiro
   Komada, Masayuki
   Fukai, Shuya
TI Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains
SO NATURE
LA English
DT Article
ID splicing factor prp8; crystal-structure; ubiquitin; domain; deubiquitination; recognition; protein; degradation; binding; refinement
AB Deubiquitinating enzymes ( DUBs) remove ubiquitin from conjugated substrates to regulate various cellular processes. The Zn2+-dependent DUBs AMSH and AMSH- LP regulate receptor trafficking by specifically cleaving Lys 63- linked polyubiquitin chains from internalized receptors. Here we report the crystal structures of the human AMSH- LP DUB domain alone and in complex with a Lys 63- linked di- ubiquitin at 1.2 angstrom and 1.6 angstrom resolutions, respectively. The AMSH- LP DUB domain consists of a Zn2+-coordinating catalytic core and two characteristic insertions, Ins- 1 and Ins- 2. The distal ubiquitin interacts with Ins- 1 and the core, whereas the proximal ubiquitin interacts with Ins- 2 and the core. The core and Ins- 1 form a catalytic groove that accommodates the Lys 63 side chain of the proximal ubiquitin and the isopeptide- linked carboxy- terminal tail of the distal ubiquitin. This is the first reported structure of a DUB in complex with an isopeptide- linked ubiquitin chain, which reveals the mechanism for Lys 63- linkage- specific deubiquitination by AMSH family members.
C1 [Sato, Yusuke; Yoshikawa, Azusa; Yamagata, Atsushi; Mimura, Hisatoshi; Yamashita, Masami; Fukai, Shuya] Univ Tokyo, Struct Biol Lab, Div Life Sci, Synchrotron Radiat Res Org, Tokyo 1130032, Japan.
   [Sato, Yusuke; Yoshikawa, Azusa; Yamagata, Atsushi; Mimura, Hisatoshi; Yamashita, Masami; Fukai, Shuya] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan.
   [Sato, Yusuke; Yoshikawa, Azusa; Ookata, Kayoko; Nureki, Osamu] Tokyo Inst Technol, Dept Biol Informat, Yokohama, Kanagawa 2268501, Japan.
   [Komada, Masayuki] Tokyo Inst Technol, Dept Biol Sci, Grad Sch Biosci & Biotechnol, Yokohama, Kanagawa 2268501, Japan.
   [Yamashita, Masami; Fukai, Shuya] Univ Tokyo, Dept Med Genome Sci, Grad Sch Frontier Sci, Chiba 2778501, Japan.
   [Iwai, Kazuhiro] Osaka Univ, Dept Biophys & Biochem, Grad Sch Med, Suita, Osaka 5650871, Japan.
C3 University of Tokyo; University of Tokyo; Institute of Science Tokyo; Tokyo Institute of Technology; Institute of Science Tokyo; Tokyo Institute of Technology; University of Tokyo; University of Osaka
RP Fukai, S (corresponding author), Univ Tokyo, Struct Biol Lab, Div Life Sci, Synchrotron Radiat Res Org, Tokyo 1130032, Japan.
EM fukai@iam.u-tokyo.ac.jp
FU MEXT; JSPS research fellowships
NR 49
TC 278
Z9 342
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 SEP 18
PY 2008
VL 455
IS 7211
BP 358
EP U19
DI 10.1038/nature07254
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200037
PM 18758443
DA 2026-03-09
ER

PT J
AU Wheeler, DA
   Srinivasan, M
   Egholm, M
   Shen, Y
   Chen, L
   McGuire, A
   He, W
   Chen, YJ
   Makhijani, V
   Roth, GT
   Gomes, X
   Tartaro, K
   Niazi, F
   Turcotte, CL
   Irzyk, GP
   Lupski, JR
   Chinault, C
   Song, XZ
   Liu, Y
   Yuan, Y
   Nazareth, L
   Qin, X
   Muzny, DM
   Margulies, M
   Weinstock, GM
   Gibbs, RA
   Rothberg, JM
AF Wheeler, David A.
   Srinivasan, Maithreyan
   Egholm, Michael
   Shen, Yufeng
   Chen, Lei
   McGuire, Amy
   He, Wen
   Chen, Yi-Ju
   Makhijani, Vinod
   Roth, G. Thomas
   Gomes, Xavier
   Tartaro, Karrie
   Niazi, Faheem
   Turcotte, Cynthia L.
   Irzyk, Gerard P.
   Lupski, James R.
   Chinault, Craig
   Song, Xing-zhi
   Liu, Yue
   Yuan, Ye
   Nazareth, Lynne
   Qin, Xiang
   Muzny, Donna M.
   Margulies, Marcel
   Weinstock, George M.
   Gibbs, Richard A.
   Rothberg, Jonathan M.
TI The complete genome of an individual by massively parallel DNA sequencing
SO NATURE
LA English
DT Article
ID structural variation; gene
AB The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of 'genomic medicine'. However, the formidable size of the diploid human genome(1), approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4- fold redundancy in two months using massively parallel sequencing in picolitre- size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino- acid substitution within the coding sequence. In addition, we accurately identified small-scale ( 2 - 40,000 base pair ( bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large- scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual(2) by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell- free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next- generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome sequencing'.
C1 [Wheeler, David A.; Chen, Lei; Song, Xing-zhi; Liu, Yue; Yuan, Ye; Nazareth, Lynne; Qin, Xiang; Muzny, Donna M.; Weinstock, George M.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [McGuire, Amy] Baylor Coll Med, Ctr Eth & Hlth Policy, Houston, TX 77030 USA.
   [Lupski, James R.; Chinault, Craig; Weinstock, George M.; Gibbs, Richard A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [Lupski, James R.] Texas Childrens Hosp, Texas Med Ctr, Houston, TX 77030 USA.
   [Srinivasan, Maithreyan; Egholm, Michael; He, Wen; Chen, Yi-Ju; Makhijani, Vinod; Roth, G. Thomas; Gomes, Xavier; Tartaro, Karrie; Niazi, Faheem; Turcotte, Cynthia L.; Irzyk, Gerard P.; Margulies, Marcel; Rothberg, Jonathan M.] Roche Diagnost, Bradford, CT 06405 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; Roche Holding; Roche Holding USA
RP Rothberg, JM (corresponding author), Roche Diagnost, 454 Life Sci,20 Commercial St, Bradford, CT 06405 USA.
EM agibbs@bcm.tmc.edu; jonathan.rothberg@gmail.com
NR 21
TC 1296
Z9 1713
U1 2
U2 261
PU NATURE PUBLISHING 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 17
PY 2008
VL 452
IS 7189
BP 872
EP U5
DI 10.1038/nature06884
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000048
PM 18421352
DA 2026-03-09
ER

PT J
AU Röthlisberger, D
   Khersonsky, O
   Wollacott, AM
   Jiang, L
   DeChancie, J
   Betker, J
   Gallaher, JL
   Althoff, EA
   Zanghellini, A
   Dym, O
   Albeck, S
   Houk, KN
   Tawfik, DS
   Baker, D
AF Rothlisberger, Daniela
   Khersonsky, Olga
   Wollacott, Andrew M.
   Jiang, Lin
   DeChancie, Jason
   Betker, Jamie
   Gallaher, Jasmine L.
   Althoff, Eric A.
   Zanghellini, Alexandre
   Dym, Orly
   Albeck, Shira
   Houk, Kendall N.
   Tawfik, Dan S.
   Baker, David
TI Kemp elimination catalysts by computational enzyme design
SO NATURE
LA English
DT Article
ID physical organic-chemistry; proton-transfer; evolution; antibody; proteins; benzisoxazoles; decomposition; prediction; selection; pcr
AB The design of new enzymes for reactions not catalysed by naturally occurring biocatalysts is a challenge for protein engineering and is a critical test of our understanding of enzyme catalysis. Here we describe the computational design of eight enzymes that use two different catalytic motifs to catalyse the Kemp elimination - a model reaction for proton transfer from carbon - with measured rate enhancements of up to 10 5 and multiple turnovers. Mutational analysis confirms that catalysis depends on the computationally designed active sites, and a high- resolution crystal structure suggests that the designs have close to atomic accuracy. Application of in vitro evolution to enhance the computational designs produced a >200-fold increase in k(cat)/K-m (k(cat)/K-m of 2,600 M(-1)s(-1) and k(cat)/k(uncat) of >10(6)). These results demonstrate the power of combining computational protein design with directed evolution for creating new enzymes, and we anticipate the creation of a wide range of useful new catalysts in the future.
C1 [Rothlisberger, Daniela; Wollacott, Andrew M.; Jiang, Lin; Althoff, Eric A.; Zanghellini, Alexandre; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Betker, Jamie; Gallaher, Jasmine L.; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Khersonsky, Olga; Tawfik, Dan S.] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
   [Dym, Orly; Albeck, Shira] Weizmann Inst Sci, Israel Struct Proteom Ctr, IL-76100 Rehovot, Israel.
   [DeChancie, Jason; Houk, Kendall N.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Weizmann Institute of Science; Weizmann Institute of Science; University of California System; University of California Los Angeles
RP Baker, D (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
EM dan.tawfik@weizmann.ac.il; dabaker@u.washington.edu
FU Howard Hughes Medical Institute Funding Source: Medline
NR 34
TC 1043
Z9 1367
U1 15
U2 428
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 190
EP U4
DI 10.1038/nature06879
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400032
PM 18354394
DA 2026-03-09
ER

PT J
AU Minobe, S
   Kuwano-Yoshida, A
   Komori, N
   Xie, SP
   Small, RJ
AF Minobe, Shoshiro
   Kuwano-Yoshida, Akira
   Komori, Nobumasa
   Xie, Shang-Ping
   Small, Richard Justin
TI Influence of the Gulf Stream on the troposphere
SO NATURE
LA English
DT Article
ID sea-surface temperature; satellite-observations; numerical-simulation; ocean; climate; convergence; circulation; winds
AB The Gulf Stream transports large amounts of heat from the tropics to middle and high latitudes, and thereby affects weather phenomena such as cyclogenesis(1,2) and low cloud formation(3). But its climatic influence, on monthly and longer timescales, remains poorly understood. In particular, it is unclear how the warm current affects the free atmosphere above the marine atmospheric boundary layer. Here we consider the Gulf Stream's influence on the troposphere, using a combination of operational weather analyses, satellite observations and an atmospheric general circulation model(4). Our results reveal that the Gulf Stream affects the entire troposphere. In the marine boundary layer, atmospheric pressure adjustments to sharp sea surface temperature gradients lead to surface wind convergence, which anchors a narrow band of precipitation along the Gulf Stream. In this rain band, upward motion and cloud formation extend into the upper troposphere, as corroborated by the frequent occurrence of very low cloud- top temperatures. These mechanisms provide a pathway by which the Gulf Stream can affect the atmosphere locally, and possibly also in remote regions by forcing planetary waves(5,6). The identification of this pathway may have implications for our understanding of the processes involved in climate change, because the Gulf Stream is the upper limb of the Atlantic meridional overturning circulation, which has varied in strength in the past(7) and is predicted to weaken in response to human- induced global warming in the future(8).
C1 [Minobe, Shoshiro] Hokkaido Univ, Dept Nat Hist Sci, Grad Sch Sci, Sapporo, Hokkaido 0600810, Japan.
   [Kuwano-Yoshida, Akira; Komori, Nobumasa] Japan Agcy Marine Earth Sci & Technol, Earth Simulator Ctr, Yokohama, Kanagawa 2360001, Japan.
   [Xie, Shang-Ping; Small, Richard Justin] Univ Hawaii Manoa, Int Pacific Res Ctr, Honolulu, HI 96822 USA.
   [Xie, Shang-Ping] Univ Hawaii Manoa, Dept Meteorol, Honolulu, HI 96822 USA.
C3 Hokkaido University; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); University of Hawaii System; University of Hawaii Manoa; University of Hawaii System; University of Hawaii Manoa
RP Minobe, S (corresponding author), Hokkaido Univ, Dept Nat Hist Sci, Grad Sch Sci, Sapporo, Hokkaido 0600810, Japan.
EM minobe@sci.hokudai.ac.jp
NR 33
TC 650
Z9 748
U1 4
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 MAR 13
PY 2008
VL 452
IS 7184
BP 206
EP U51
DI 10.1038/nature06690
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600038
PM 18337820
DA 2026-03-09
ER

PT J
AU Métivier, R
   Gallais, R
   Tiffoche, C
   Le Péron, C
   Jurkowska, RZ
   Carmouche, RP
   Ibberson, D
   Barath, P
   Demay, F
   Reid, G
   Benes, V
   Jeltsch, A
   Gannon, F
   Salbert, G
AF Metivier, Raphael
   Gallais, Rozenn
   Tiffoche, Christophe
   Le Peron, Christine
   Jurkowska, Renata Z.
   Carmouche, Richard P.
   Ibberson, David
   Barath, Peter
   Demay, Florence
   Reid, George
   Benes, Vladimir
   Jeltsch, Albert
   Gannon, Frank
   Salbert, Gilles
TI Cyclical DNA methylation of a transcriptionally active promoter
SO NATURE
LA English
DT Article
ID estrogen-receptor-alpha; regulated transcription; nuclear receptor; gene activation; genomic dna; demethylation; glycosylase; dnmt3a; organization; complex
AB Processes that regulate gene transcription are directly under the influence of the genome organization. The epigenome contains additional information that is not brought by DNA sequence, and generates spatial and functional constraints that complement genetic instructions. DNA methylation on CpGs constitutes an epigenetic mark generally correlated with transcriptionally silent condensed chromatin. Replication of methylation patterns by DNA methyltransferases maintains genome stability through cell division. Here we present evidence of an unanticipated dynamic role for DNA methylation in gene regulation in human cells. Periodic, strand- specific methylation/ demethylation occurs during transcriptional cycling of the pS2/TFF1 gene promoter on activation by oestrogens. DNA methyltransferases exhibit dual actions during these cycles, being involved in CpG methylation and active demethylation of (5m)CpGs through deamination. Inhibition of this process precludes demethylation of the pS2 gene promoter and its subsequent transcriptional activation. Cyclical changes in the methylation status of promoter CpGs may thus represent a critical event in transcriptional achievement.
C1 [Metivier, Raphael; Gallais, Rozenn; Tiffoche, Christophe; Le Peron, Christine; Barath, Peter; Demay, Florence; Salbert, Gilles] Univ Rennes 1, CNRS, Equipe SPARTE,GFAS IFR 140, UMR 6026, F-35042 Rennes, France.
   [Jurkowska, Renata Z.; Jeltsch, Albert] Jacobs Univ Bremen, D-28759 Bremen, Germany.
   [Carmouche, Richard P.; Ibberson, David; Reid, George; Benes, Vladimir; Gannon, Frank] European Mol Biol Lab, D-69117 Heidelberg, Germany.
C3 Centre National de la Recherche Scientifique (CNRS); Universite de Rennes; Constructor University; European Molecular Biology Laboratory (EMBL)
RP Métivier, R (corresponding author), Univ Rennes 1, CNRS, Equipe SPARTE,GFAS IFR 140, UMR 6026, Campus Beaulieu, F-35042 Rennes, France.
EM Raphael.Metivier@univ-rennes1.fr
NR 47
TC 726
Z9 855
U1 0
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 6
PY 2008
VL 452
IS 7183
BP 45
EP U2
DI 10.1038/nature06544
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900043
PM 18322525
DA 2026-03-09
ER

PT J
AU Sacco, A
   Doyonnas, R
   Kraft, P
   Vitorovic, S
   Blau, HM
AF Sacco, Alessandra
   Doyonnas, Regis
   Kraft, Peggy
   Vitorovic, Stefan
   Blau, Helen M.
TI Self-renewal and expansion of single transplanted muscle stem cells
SO NATURE
LA English
DT Article
ID skeletal-muscle; satellite cells; myoblasts; fate; reconstitution; heterogeneity; expression
AB Adult muscle satellite cells have a principal role in postnatal skeletal muscle growth and regeneration(1). Satellite cells reside as quiescent cells underneath the basal lamina that surrounds muscle fibres(2) and respond to damage by giving rise to transient amplifying cells ( progenitors) and myoblasts that fuse with myofibres. Recent experiments showed that, in contrast to cultured myoblasts, satellite cells freshly isolated(3-5) or satellite cells derived from the transplantation of one intact myofibre(6) contribute robustly to muscle repair. However, because satellite cells are known to be heterogeneous(4,6,7), clonal analysis is required to demonstrate stem cell function. Here we show that when a single luciferase- expressing muscle stem cell is transplanted into the muscle of mice it is capable of extensive proliferation, contributes to muscle fibres, and Pax7(+) luciferase(+) mononucleated cells can be readily re- isolated, providing evidence of muscle stem cell self- renewal. In addition, we show using in vivo bioluminescence imaging that the dynamics of muscle stem cell behaviour during muscle repair can be followed in a manner not possible using traditional retrospective histological analyses. By imaging luciferase activity, real- time quantitative and kinetic analyses show that donor- derived muscle stem cells proliferate and engraft rapidly after injection until homeostasis is reached. On injury, donor- derived mononucleated cells generate massive waves of cell proliferation. Together, these results show that the progeny of a single luciferase- expressing muscle stem cell can both self- renew and differentiate after transplantation in mice, providing new evidence at the clonal level that self- renewal is an autonomous property of a single adult muscle stem cell.
C1 [Sacco, Alessandra; Doyonnas, Regis; Kraft, Peggy; Vitorovic, Stefan; Blau, Helen M.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Baxter Lab Genet Pharmacol,Stem Cell Inst, Stanford, CA 94305 USA.
C3 Stanford University
RP Blau, HM (corresponding author), Stanford Univ, Sch Med, Dept Microbiol & Immunol, Baxter Lab Genet Pharmacol,Stem Cell Inst, Stanford, CA 94305 USA.
EM hblau@stanford.edu
FU NIH [AG009521, AG024987]; Baxter Foundation
NR 26
TC 693
Z9 874
U1 1
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 NOV 27
PY 2008
VL 456
IS 7221
BP 502
EP 506
DI 10.1038/nature07384
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500038
PM 18806774
DA 2026-03-09
ER

PT J
AU Shcheprova, Z
   Baldi, S
   Frei, SB
   Gonnet, G
   Barral, Y
AF Shcheprova, Zhanna
   Baldi, Sandro
   Frei, Stephanie Buvelot
   Gonnet, Gaston
   Barral, Yves
TI A mechanism for asymmetric segregation of age during yeast budding
SO NATURE
LA English
DT Article
ID nuclear-pore complex; saccharomyces-cerevisiae; life-span; gene deletion; protein; localization; dynamics; compartmentalization; plasmid; mother
AB Ageing and the mortality that ensues are sustainable for the species only if age is reset in newborns. In budding yeast, buds are made young whereas ageing factors, such as carbonylated proteins and DNA circles, remain confined to the ageing mother cell. The mechanisms of this confinement and their relevance are poorly understood. Here we show that a septin-dependent, lateral diffusion barrier forms in the nuclear envelope and limits the translocation of pre-existing nuclear pores into the bud. The retention of DNA circles within the mother cell depends on the presence of the diffusion barrier and on the anchorage of the circles to pores mediated by the nuclear basket. In accordance with the diffusion barrier ensuring the asymmetric segregation of nuclear age-determinants, the barrier mutant bud6 Delta fails to properly reset age in buds. Our data involve septin-dependent diffusion barriers in the confinement of ageing factors to one daughter cell during asymmetric cell division.
C1 [Shcheprova, Zhanna; Baldi, Sandro; Frei, Stephanie Buvelot; Barral, Yves] ETH, Inst Biochem, Dept Biol, CH-8093 Zurich, Switzerland.
   [Gonnet, Gaston] ETH, Inst Computat Sci, Dept Comp Sci, CH-8092 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Barral, Y (corresponding author), ETH, Inst Biochem, Dept Biol, Schafmattstr 18, CH-8093 Zurich, Switzerland.
EM yves.barral@bc.biol.ethz.ch
NR 47
TC 262
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 AUG 7
PY 2008
VL 454
IS 7205
BP 728
EP U64
DI 10.1038/nature07212
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000037
PM 18660802
DA 2026-03-09
ER

PT J
AU Warren, WC
   Hillier, LW
   Graves, JAM
   Birney, E
   Ponting, CP
   Grützner, F
   Belov, K
   Miller, W
   Clarke, L
   Chinwalla, AT
   Yang, SP
   Heger, A
   Locke, DP
   Miethke, P
   Waters, PD
   Veyrunes, F
   Fulton, L
   Fulton, B
   Graves, T
   Wallis, J
   Puente, XS
   López-Otín, C
   Ordóñez, GR
   Eichler, EE
   Chen, L
   Cheng, Z
   Deakin, JE
   Alsop, A
   Thompson, K
   Kirby, P
   Papenfuss, AT
   Wakefield, MJ
   Olender, T
   Lancet, D
   Huttley, GA
   Smit, AFA
   Pask, A
   Temple-Smith, P
   Batzer, MA
   Walker, JA
   Konkel, MK
   Harris, RS
   Whittington, CM
   Wong, ESW
   Gemmell, NJ
   Buschiazzo, E
   Jentzsch, IMV
   Merkel, A
   Schmitz, J
   Zemann, A
   Churakov, G
   Kriegs, JO
   Brosius, J
   Murchison, EP
   Sachidanandam, R
   Smith, C
   Hannon, GJ
   Tsend-Ayush, E
   McMillan, D
   Attenborough, R
   Rens, W
   Ferguson-Smith, M
   Lefèvre, CM
   Sharp, JA
   Nicholas, KR
   Ray, DA
   Kube, M
   Reinhardt, R
   Pringle, TH
   Taylor, J
   Jones, RC
   Nixon, B
   Dacheux, JL
   Niwa, H
   Sekita, Y
   Huang, XQ
   Stark, A
   Kheradpour, P
   Kellis, M
   Flicek, P
   Chen, Y
   Webber, C
   Hardison, R
   Nelson, J
   Hallsworth-Pepin, K
   Delehaunty, K
   Markovic, C
   Minx, P
   Feng, YC
   Kremitzki, C
   Mitreva, M
   Glasscock, J
   Wylie, T
   Wohldmann, P
   Thiru, P
   Nhan, MN
   Pohl, CS
   Smith, SM
   Hou, SF
   Renfree, MB
   Mardis, ER
   Wilson, RK
AF Warren, Wesley C.
   Hillier, LaDeana W.
   Graves, Jennifer A. Marshall
   Birney, Ewan
   Ponting, Chris P.
   Grutzner, Frank
   Belov, Katherine
   Miller, Webb
   Clarke, Laura
   Chinwalla, Asif T.
   Yang, Shiaw-Pyng
   Heger, Andreas
   Locke, Devin P.
   Miethke, Pat
   Waters, Paul D.
   Veyrunes, Frederic
   Fulton, Lucinda
   Fulton, Bob
   Graves, Tina
   Wallis, John
   Puente, Xose S.
   Lopez-Otin, Carlos
   Ordonez, Gonzalo R.
   Eichler, Evan E.
   Chen, Lin
   Cheng, Ze
   Deakin, Janine E.
   Alsop, Amber
   Thompson, Katherine
   Kirby, Patrick
   Papenfuss, Anthony T.
   Wakefield, Matthew J.
   Olender, Tsviya
   Lancet, Doron
   Huttley, Gavin A.
   Smit, Arian F. A.
   Pask, Andrew
   Temple-Smith, Peter
   Batzer, Mark A.
   Walker, Jerilyn A.
   Konkel, Miriam K.
   Harris, Robert S.
   Whittington, Camilla M.
   Wong, Emily S. W.
   Gemmell, Neil J.
   Buschiazzo, Emmanuel
   Jentzsch, Iris M. Vargas
   Merkel, Angelika
   Schmitz, Juergen
   Zemann, Anja
   Churakov, Gennady
   Kriegs, Jan Ole
   Brosius, Juergen
   Murchison, Elizabeth P.
   Sachidanandam, Ravi
   Smith, Carly
   Hannon, Gregory J.
   Tsend-Ayush, Enkhjargal
   McMillan, Daniel
   Attenborough, Rosalind
   Rens, Willem
   Ferguson-Smith, Malcolm
   Lefevre, Christophe M.
   Sharp, Julie A.
   Nicholas, Kevin R.
   Ray, David A.
   Kube, Michael
   Reinhardt, Richard
   Pringle, Thomas H.
   Taylor, James
   Jones, Russell C.
   Nixon, Brett
   Dacheux, Jean-Louis
   Niwa, Hitoshi
   Sekita, Yoko
   Huang, Xiaoqiu
   Stark, Alexander
   Kheradpour, Pouya
   Kellis, Manolis
   Flicek, Paul
   Chen, Yuan
   Webber, Caleb
   Hardison, Ross
   Nelson, Joanne
   Hallsworth-Pepin, Kym
   Delehaunty, Kim
   Markovic, Chris
   Minx, Pat
   Feng, Yucheng
   Kremitzki, Colin
   Mitreva, Makedonka
   Glasscock, Jarret
   Wylie, Todd
   Wohldmann, Patricia
   Thiru, Prathapan
   Nhan, Michael N.
   Pohl, Craig S.
   Smith, Scott M.
   Hou, Shunfeng
   Renfree, Marilyn B.
   Mardis, Elaine R.
   Wilson, Richard K.
TI Genome analysis of the platypus reveals unique signatures of evolution
SO NATURE
LA English
DT Article
ID monodelphis-domestica; phylogenetic analysis; monotreme; chromosm; insights; family; electroreception; cathelicidins; arrangement; expression
AB We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co- opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non- protein- coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.
C1 [Warren, Wesley C.; Hillier, LaDeana W.; Chinwalla, Asif T.; Yang, Shiaw-Pyng; Locke, Devin P.; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N.; Pohl, Craig S.; Smith, Scott M.; Hou, Shunfeng; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA.
   [Graves, Jennifer A. Marshall; Miethke, Pat; Waters, Paul D.; Veyrunes, Frederic; Deakin, Janine E.; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Huttley, Gavin A.; Attenborough, Rosalind] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 0200, Australia.
   [Birney, Ewan; Flicek, Paul; Chen, Yuan] EBI, EMBL, Cambridge CB10 1SD, England.
   [Ponting, Chris P.; Heger, Andreas; Webber, Caleb] Univ Oxford, Dept Human Physiol Anat & Genet, MRC, Funct Genet Unit, Oxford OX1 3QX, England.
   [Grutzner, Frank; Tsend-Ayush, Enkhjargal] Univ Adelaide, Sch Mol & Biomed Sci, Discipline Genet, Adelaide, SA 5005, Australia.
   [Belov, Katherine; Whittington, Camilla M.; Wong, Emily S. W.] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia.
   [Miller, Webb; Harris, Robert S.; Hardison, Ross] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Clarke, Laura] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Veyrunes, Frederic; Rens, Willem; Ferguson-Smith, Malcolm] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England.
   [Puente, Xose S.; Lopez-Otin, Carlos; Ordonez, Gonzalo R.] Univ Oviedo, Dept Bioquim & Biol Mol, Inst Univ Oncol, E-33006 Oviedo, Spain.
   [Eichler, Evan E.; Chen, Lin; Cheng, Ze] Univ Washington, Howard Hughes Med Inst, Dept Genome Sci, Seattle, WA 98195 USA.
   [Papenfuss, Anthony T.; Wakefield, Matthew J.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
   [Olender, Tsviya; Lancet, Doron] Weizmann Inst Sci, Dept Mol Genet, Crown Human Genome Ctr, IL-76100 Rehovot, Israel.
   [Smit, Arian F. A.] Inst Syst Biol, Seattle, WA 98103 USA.
   [Pask, Andrew; Temple-Smith, Peter; Lefevre, Christophe M.; Sharp, Julie A.; Nicholas, Kevin R.; Renfree, Marilyn B.] Univ Melbourne, Dept Zool, CRC Innovat Dairy Prod, Parkville, Vic 3010, Australia.
   [Temple-Smith, Peter] Monash Inst Med Res, Clayton, Vic 3168, Australia.
   [Batzer, Mark A.; Walker, Jerilyn A.; Konkel, Miriam K.] Louisiana State Univ, Dept Biol Sci, Ctr Biomodular Multiscale Syst, Baton Rouge, LA 70803 USA.
   [Gemmell, Neil J.; Buschiazzo, Emmanuel; Jentzsch, Iris M. Vargas; Merkel, Angelika] Univ Canterbury, Sch Biol Sci, Christchurch 8140, New Zealand.
   [Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen] Univ Munster, Inst Expt Pathol, D-48149 Munster, Germany.
   [Murchison, Elizabeth P.; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
   [Lefevre, Christophe M.] Monash Univ, Victorian Bioinformat Consortium, Clayton, Vic 3080, Australia.
   [Ray, David A.] W Virginia Univ, Dept Biol, Morgantown, WV 26505 USA.
   [Kube, Michael; Reinhardt, Richard] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Pringle, Thomas H.] Sperling Fdn, Eugene, OR 97405 USA.
   [Taylor, James] NYU, Courant Inst, New York, NY 10012 USA.
   [Jones, Russell C.; Nixon, Brett] Univ Newcastle, Sch Environm & Life Sci, Discipline Biol Sci, Newcastle, NSW 2308, Australia.
   [Dacheux, Jean-Louis] INRA, CNRS, UMR 6073, F-37380 Nouzilly, France.
   [Niwa, Hitoshi; Sekita, Yoko] RIKEN, CDB, Lab Pluripotent Cell Studies, Chuo Ku, Kobe, Hyogo 6500047, Japan.
   [Huang, Xiaoqiu] Iowa State Univ, Dept Comp Sci, Ames, IA 50011 USA.
   [Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis] MIT, Broad Inst, Cambridge, MA 02139 USA.
   [Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis] Harvard Univ, Broad Inst, Cambridge, MA 02139 USA.
C3 Washington University (WUSTL); Australian National University; John Curtin School of Medical Research; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Oxford; Adelaide University; University of Adelaide; University of Sydney; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Wellcome Trust Sanger Institute; University of Cambridge; University of Oviedo; Instituto Universitario de Oncologia de Asturias; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Walter & Eliza Hall Institute; Melbourne Health; Royal Melbourne Hospital; Weizmann Institute of Science; Institute for Systems Biology (ISB); University of Melbourne; Hudson Institute of Medical Research; Monash University; Louisiana State University System; Louisiana State University; University of Canterbury; University of Munster; Howard Hughes Medical Institute; Cold Spring Harbor Laboratory; Monash University; West Virginia University; Max Planck Society; New York University; University of Newcastle; Centre National de la Recherche Scientifique (CNRS); Universite de Tours; INRAE; RIKEN; Iowa State University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Warren, WC (corresponding author), Washington Univ, Sch Med, Genome Sequencing Ctr, Campus Box 8501,4444 Forest Pk Ave, St Louis, MO 63108 USA.
EM wwarren@wustl.edu; rwilson@wustl.edu
FU Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF); National Cancer Institute [P01CA013106] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG002385, R01HG002939] Funding Source: NIH RePORTER; Medical Research Council [MC_U137761446] Funding Source: researchfish; MRC [MC_U137761446] Funding Source: UKRI; Medical Research Council [MC_U137761446] Funding Source: Medline; NCI NIH HHS [P01 CA013106] Funding Source: Medline; NHGRI NIH HHS [R01 HG002939, R01 HG002385, R01HG02385, R01 HG004037, HG002238, R01 HG002238] Funding Source: Medline; NIGMS NIH HHS [R01 GM059290, R01 GM59290] Funding Source: Medline; Wellcome Trust [062023] Funding Source: Medline
NR 79
TC 546
Z9 620
U1 7
U2 347
PU NATURE PUBLISHING 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 8
PY 2008
VL 453
IS 7192
BP 175
EP U1
DI 10.1038/nature06936
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400030
PM 18464734
DA 2026-03-09
ER

PT J
AU Lin, SW
   Unno, Y
   Hou, WS
   Chang, P
   Adachi, I
   Aihara, H
   Akai, K
   Arinstein, K
   Aulchenko, V
   Aushev, T
   Aziz, T
   Bakich, AM
   Balagura, V
   Barberio, E
   Bay, A
   Bedny, I
   Bitenc, U
   Bondar, A
   Bozek, A
   Bracko, M
   Browder, TE
   Chang, MC
   Chao, Y
   Chen, A
   Chen, KF
   Chen, WT
   Cheon, BG
   Chiang, CC
   Chistov, R
   Cho, IS
   Choi, SK
   Choi, Y
   Choi, YK
   Cole, S
   Dalseno, J
   Danilov, M
   Dash, M
   Drutskoy, A
   Eidelman, S
   Epifanov, D
   Fratina, S
   Fujikawa, M
   Furukawa, K
   Gabyshev, N
   Goldenzweig, P
   Golob, B
   Ha, H
   Haba, J
   Hara, T
   Hayasaka, K
   Hayashii, H
   Hazumi, M
   Heffernan, D
   Hokuue, T
   Hoshi, Y
   Hsiung, YB
   Hyun, HJ
   Iijima, T
   Ikado, K
   Inami, K
   Ishikawa, A
   Ishino, H
   Itoh, R
   Iwabuchi, M
   Iwasaki, M
   Iwasaki, Y
   Kah, DH
   Kaji, H
   Kataoka, SU
   Kawai, H
   Kawasaki, T
   Kibayashi, A
   Kichimi, H
   Kikutani, E
   Kim, HJ
   Kim, SK
   Kim, YJ
   Kinoshita, K
   Korpar, S
   Kozakai, Y
   Krizan, P
   Krokovny, P
   Kumar, R
   Kuo, CC
   Kuzmin, A
   Kwon, YJ
   Lee, MJ
   Lee, SE
   Lesiak, T
   Li, J
   Liu, Y
   Liventsev, D
   Mandl, F
   Marlow, D
   McOnie, S
   Medvedeva, T
   Mimashi, T
   Mitaroff, W
   Miyabayashi, K
   Miyake, H
   Miyazaki, Y
   Mizuk, R
   Mori, T
   Nakamura, TT
   Nakano, E
   Nakao, M
   Nakazawa, H
   Nishida, S
   Nitoh, O
   Noguchi, S
   Nozaki, T
   Ogawa, S
   Ogawa, Y
   Ohshima, T
   Okuno, S
   Olsen, SL
   Ozaki, H
   Pakhlova, G
   Park, CW
   Park, H
   Peak, LS
   Pestotnik, R
   Peters, M
   Piilonen, LE
   Poluektov, A
   Sahoo, H
   Sakai, Y
   Schneider, O
   Schümann, J
   Schwartz, AJ
   Seidl, R
   Senyo, K
   Sevior, ME
   Shapkin, M
   Shen, CP
   Shibuya, H
   Shidara, T
   Shinomiya, S
   Shiu, JG
   Shwartz, B
   Singh, JB
   Sokolov, A
   Somov, A
   Stanic, S
   Staric, M
   Sumisawa, K
   Sumiyoshi, T
   Suzuki, S
   Tajima, O
   Takasaki, F
   Tamura, N
   Tanaka, M
   Tawada, M
   Taylor, GN
   Teramoto, Y
   Tikhomirov, I
   Trabelsi, K
   Uehara, S
   Ueno, K
   Uglov, T
   Uno, S
   Urquijo, P
   Ushiroda, Y
   Usov, Y
   Varner, G
   Varvell, KE
   Vervink, K
   Villa, S
   Wang, CC
   Wang, CH
   Wang, MZ
   Watanabe, Y
   Wedd, R
   Wicht, J
   Won, E
   Yabsley, BD
   Yamaguchi, A
   Yamashita, Y
   Yamauchi, M
   Yoshida, M
   Yuan, CZ
   Yusa, Y
   Zhang, CC
   Zhang, ZP
   Zhilich, V
   Zhulanov, V
   Zupanc, A
AF Lin, S. -W.
   Unno, Y.
   Hou, W. -S.
   Chang, P.
   Adachi, I.
   Aihara, H.
   Akai, K.
   Arinstein, K.
   Aulchenko, V.
   Aushev, T.
   Aziz, T.
   Bakich, A. M.
   Balagura, V.
   Barberio, E.
   Bay, A.
   Bedny, I.
   Bitenc, U.
   Bondar, A.
   Bozek, A.
   Bracko, M.
   Browder, T. E.
   Chang, M. -C.
   Chao, Y.
   Chen, A.
   Chen, K. -F.
   Chen, W. T.
   Cheon, B. G.
   Chiang, C. -C.
   Chistov, R.
   Cho, I. -S.
   Choi, S. -K.
   Choi, Y.
   Choi, Y. K.
   Cole, S.
   Dalseno, J.
   Danilov, M.
   Dash, M.
   Drutskoy, A.
   Eidelman, S.
   Epifanov, D.
   Fratina, S.
   Fujikawa, M.
   Furukawa, K.
   Gabyshev, N.
   Goldenzweig, P.
   Golob, B.
   Ha, H.
   Haba, J.
   Hara, T.
   Hayasaka, K.
   Hayashii, H.
   Hazumi, M.
   Heffernan, D.
   Hokuue, T.
   Hoshi, Y.
   Hsiung, Y. B.
   Hyun, H. J.
   Iijima, T.
   Ikado, K.
   Inami, K.
   Ishikawa, A.
   Ishino, H.
   Itoh, R.
   Iwabuchi, M.
   Iwasaki, M.
   Iwasaki, Y.
   Kah, D. H.
   Kaji, H.
   Kataoka, S. U.
   Kawai, H.
   Kawasaki, T.
   Kibayashi, A.
   Kichimi, H.
   Kikutani, E.
   Kim, H. J.
   Kim, S. K.
   Kim, Y. J.
   Kinoshita, K.
   Korpar, S.
   Kozakai, Y.
   Krizan, P.
   Krokovny, P.
   Kumar, R.
   Kuo, C. C.
   Kuzmin, A.
   Kwon, Y. -J.
   Lee, M. J.
   Lee, S. E.
   Lesiak, T.
   Li, J.
   Liu, Y.
   Liventsev, D.
   Mandl, F.
   Marlow, D.
   McOnie, S.
   Medvedeva, T.
   Mimashi, T.
   Mitaroff, W.
   Miyabayashi, K.
   Miyake, H.
   Miyazaki, Y.
   Mizuk, R.
   Mori, T.
   Nakamura, T. T.
   Nakano, E.
   Nakao, M.
   Nakazawa, H.
   Nishida, S.
   Nitoh, O.
   Noguchi, S.
   Nozaki, T.
   Ogawa, S.
   Ogawa, Y.
   Ohshima, T.
   Okuno, S.
   Olsen, S. L.
   Ozaki, H.
   Pakhlova, G.
   Park, C. W.
   Park, H.
   Peak, L. S.
   Pestotnik, R.
   Peters, M.
   Piilonen, L. E.
   Poluektov, A.
   Sahoo, H.
   Sakai, Y.
   Schneider, O.
   Schuemann, J.
   Schwartz, A. J.
   Seidl, R.
   Senyo, K.
   Sevior, M. E.
   Shapkin, M.
   Shen, C. P.
   Shibuya, H.
   Shidara, T.
   Shinomiya, S.
   Shiu, J. -G.
   Shwartz, B.
   Singh, J. B.
   Sokolov, A.
   Somov, A.
   Stanic, S.
   Staric, M.
   Sumisawa, K.
   Sumiyoshi, T.
   Suzuki, S.
   Tajima, O.
   Takasaki, F.
   Tamura, N.
   Tanaka, M.
   Tawada, M.
   Taylor, G. N.
   Teramoto, Y.
   Tikhomirov, I.
   Trabelsi, K.
   Uehara, S.
   Ueno, K.
   Uglov, T.
   Uno, S.
   Urquijo, P.
   Ushiroda, Y.
   Usov, Y.
   Varner, G.
   Varvell, K. E.
   Vervink, K.
   Villa, S.
   Wang, C. C.
   Wang, C. H.
   Wang, M. -Z.
   Watanabe, Y.
   Wedd, R.
   Wicht, J.
   Won, E.
   Yabsley, B. D.
   Yamaguchi, A.
   Yamashita, Y.
   Yamauchi, M.
   Yoshida, M.
   Yuan, C. Z.
   Yusa, Y.
   Zhang, C. C.
   Zhang, Z. P.
   Zhilich, V.
   Zhulanov, V.
   Zupanc, A.
TI Difference in direct charge-parity violation between charged and neutral B meson decays
SO NATURE
LA English
DT Article
ID direct cp violation; asymmetry; belle
AB Equal amounts of matter and antimatter are predicted to have been produced in the Big Bang, but our observable Universe is clearly matter- dominated. One of the prerequisites(1) for understanding this elimination of antimatter is the nonconservation of charge- parity ( CP) symmetry. So far, two types of CP violation have been observed in the neutral K meson ( K-0) and B meson ( B-0) systems: CP violation involving the mixing(2) between K-0 and its antiparticle (K) over bar (0) ( and likewise(3,4) for B-0 and (B) over bar (0)), and direct CP violation in the decay of each meson(5-8). The observed effects for both types of CP violation are substantially larger for the B-0 meson system. However, they are still consistent with the standard model of particle physics, which has a unique source(9) of CP violation that is known to be too small(10) to account for the matter-dominated Universe. Here we report that the direct CP violation in charged B-+/- --> K-+/- pi(0) decay is different from that in the neutral B-0 counterpart. The direct CP- violating decay rate asymmetry, A(K)+/- (pi 0) ( that is, the difference between the number of observed B- --> K- pi(0) event versus B+ --> K+ pi(0) events, normalized to the sum of these events) is measured to be about +7%, with an uncertainty that is reduced by a factor of 1.7 from a previous measurement(7). However, the asymmetry A(K+/-) p(-/+) for B-0 --> K- pi(+) versus B-0 --> K+ pi(-) is at the -10% level(7,8). Although it is susceptible to strong interaction effects that need further clarification, this large deviation in direct CP violation between charged and neutral B meson decays could be an indication of new sources of CP violation - which would help to explain the dominance of matter in the Universe.
C1 [Lin, S. -W.; Hou, W. -S.; Chang, P.; Chao, Y.; Chen, K. -F.; Chiang, C. -C.; Wang, C. C.] Natl Taiwan Univ, Dept Phys, Taipei 106, Taiwan.
   [Unno, Y.; Cheon, B. G.] Hanyang Univ, Seoul 133791, South Korea.
   [Adachi, I.; Akai, K.; Furukawa, K.; Haba, J.; Hazumi, M.; Itoh, R.; Iwasaki, Y.; Kibayashi, A.; Kichimi, H.; Kikutani, E.; Krokovny, P.; Mimashi, T.; Nakamura, T. T.; Nakao, M.; Nishida, S.; Nozaki, T.; Ogawa, Y.; Ozaki, H.; Sakai, Y.; Schuemann, J.; Shidara, T.; Sumisawa, K.; Tajima, O.; Takasaki, F.; Tanaka, M.; Tawada, M.; Trabelsi, K.; Uehara, S.; Uno, S.; Ushiroda, Y.; Yamauchi, M.; Yoshida, M.] High Energy Accelerator Res Org, KEK, Tsukuba, Ibaraki 3050801, Japan.
   [Aihara, H.] Univ Tokyo, Dept Phys, Tokyo 1130033, Japan.
   [Arinstein, K.; Aulchenko, V.; Aushev, T.; Bedny, I.; Bondar, A.; Eidelman, S.; Epifanov, D.; Gabyshev, N.; Kuzmin, A.; Poluektov, A.; Shwartz, B.; Usov, Y.; Zhulanov, V.] Budker Inst Nucl Phys, Novosibirsk 630090, Russia.
   [Aushev, T.; Bay, A.; Vervink, K.; Villa, S.; Wicht, J.] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, CH-1015 Lausanne, Switzerland.
   [Aushev, T.; Balagura, V.; Chistov, R.; Danilov, M.; Liventsev, D.; Medvedeva, T.; Mizuk, R.; Pakhlova, G.; Tikhomirov, I.; Uglov, T.] State Atom Energy Commiss, Inst Theoret & Expt Phys, Moscow 117218, Russia.
   [Aziz, T.] Tata Inst Fundamental Res, Bombay 400005, Maharashtra, India.
   [Bakich, A. M.; Cole, S.; McOnie, S.; Peak, L. S.; Yabsley, B. D.] Univ Sydney, Sydney, NSW 2006, Australia.
   [Barberio, E.; Dalseno, J.; Taylor, G. N.; Urquijo, P.; Wedd, R.] Univ Melbourne, Sch Phys, Melbourne, Vic 3010, Australia.
   [Bracko, M.; Fratina, S.; Golob, B.; Korpar, S.; Pestotnik, R.; Staric, M.; Zupanc, A.] Jozef Stefan Inst, SI-1001 Ljubljana, Slovenia.
   [Bozek, A.] H Niewodniczanski Inst Nucl Phys, PL-31342 Krakow, Poland.
   [Bracko, M.] Univ Maribor, SI-2000 Maribor, Slovenia.
   [Browder, T. E.; Li, J.; Olsen, S. L.; Peters, M.; Sahoo, H.; Varner, G.] Univ Hawaii, Honolulu, HI 96822 USA.
   [Chang, M. -C.] Fu Jen Catholic Univ, Dept Phys, Taipei 242, Taiwan.
   [Chen, A.; Chen, W. T.; Kuo, C. C.] Natl Cent Univ, Chungli 32054, Taiwan.
   [Cho, I. -S.; Kwon, Y. -J.] Yonsei Univ, Seoul 120749, South Korea.
   [Choi, S. -K.] Gyeongsang Natl Univ, Jinju 660701, South Korea.
   [Choi, Y.; Choi, Y. K.; Park, C. W.] Sungkyunkwan Univ, Suwon 440746, South Korea.
   [Dash, M.; Piilonen, L. E.; Yusa, Y.] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA.
   [Drutskoy, A.; Goldenzweig, P.; Kinoshita, K.; Schwartz, A. J.; Somov, A.] Univ Cincinnati, Cincinnati, OH 45221 USA.
   [Fujikawa, M.; Hayashii, H.; Kataoka, S. U.; Miyabayashi, K.; Noguchi, S.] Nara Womens Univ, Nara 6308506, Japan.
   [Golob, B.; Krizan, P.] Univ Ljubljana, Fac Math & Phys, SI-1001 Ljubljana, Slovenia.
   [Ha, H.; Won, E.] Korea Univ, Seoul 136701, South Korea.
   [Hara, T.; Heffernan, D.; Miyake, H.; Shinomiya, S.] Osaka Univ, Osaka 5600043, Japan.
   [Hayasaka, K.; Hokuue, T.; Iijima, T.; Ikado, K.; Inami, K.; Kaji, H.; Kozakai, Y.; Miyazaki, Y.; Mori, T.; Ohshima, T.; Senyo, K.] Nagoya Univ, Nagoya, Aichi 4648602, Japan.
   [Hoshi, Y.] Tohoku Gakuin Univ, Tagajo, Miyagi 9858537, Japan.
   [Hyun, H. J.; Kah, D. H.; Kim, H. J.; Park, H.] Kyungpook Natl Univ, Taegu 702701, South Korea.
   [Ishikawa, A.; Suzuki, S.] Saga Univ, Saga 8408502, Japan.
   [Ishino, H.] Tokyo Inst Technol, Tokyo 1528551, Japan.
   [Kim, Y. J.; Liu, Y.] Grad Univ Adv Studies, Hayama 2400193, Japan.
   [Kawai, H.] Chiba Univ, Chiba 2638522, Japan.
   [Kawasaki, T.; Tamura, N.] Niigata Univ, Niigata 9502181, Japan.
   [Kim, S. K.; Lee, M. J.] Seoul Natl Univ, Seoul 151742, South Korea.
   [Kumar, R.; Singh, J. B.] Panjab Univ, Chandigarh 160014, India.
   [Mandl, F.; Mitaroff, W.] Austrian Acad Sci, Inst Hochenergiephys, A-1050 Vienna, Austria.
   [Marlow, D.] Princeton Univ, Princeton, NJ 08544 USA.
   [Nakano, E.; Teramoto, Y.] Osaka City Univ, Osaka 5588585, Japan.
   [Nitoh, O.] Tokyo Univ Agr & Technol, Koganei, Tokyo 1848588, Japan.
   [Ogawa, S.; Shibuya, H.] Toho Univ, Chiba 2748510, Japan.
   [Okuno, S.; Watanabe, Y.] Kanagawa Univ, Yokohama, Kanagawa 2218686, Japan.
   [Olsen, S. L.; Shen, C. P.; Yuan, C. Z.; Zhang, C. C.] Chinese Acad Sci, Inst High Energy Phys, Beijing 100049, Peoples R China.
   [Seidl, R.] Univ Illinois, Urbana, IL 61801 USA.
   [Seidl, R.] RIKEN BNL Res Ctr, Upton, NY 11973 USA.
   [Shapkin, M.; Sokolov, A.] Inst High Energy Phys, Protvino 142281, Russia.
   [Stanic, S.] Univ Nova Gorica, SL-5000 Nova Gorica, Slovenia.
   [Sumiyoshi, T.] Tokyo Metropolitan Univ, Tokyo 1920397, Japan.
   [Wang, C. H.] Natl United Univ, Miaoli 36003, Taiwan.
   [Yamaguchi, A.] Tohoku Univ, Sendai, Miyagi 9808578, Japan.
   [Yamashita, Y.] Nippon Dent Univ, Niigata 9518580, Japan.
   [Zhang, Z. P.] Univ Sci & Technol China, Anhua 230026, Peoples R China.
C3 National Taiwan University; Hanyang University; High Energy Accelerator Research Organization (KEK); University of Tokyo; Russian Academy of Sciences; Budker Institute of Nuclear Physics; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; National Research Centre - Kurchatov Institute; Alikhanov Institute for Theoretical & Experimental Physics; Tata Institute of Fundamental Research (TIFR); Tata Institute of Fundamental Research (TIFR), Mumbai; University of Sydney; University of Melbourne; Slovenian Academy of Sciences & Arts (SASA); Jozef Stefan Institute; Polish Academy of Sciences; Institute of Nuclear Physics - Polish Academy of Sciences; University of Maribor; University of Hawaii System; Fu Jen Catholic University; National Central University; Yonsei University; Gyeongsang National University; Sungkyunkwan University (SKKU); Virginia Polytechnic Institute & State University; University System of Ohio; University of Cincinnati; Nara Womens University; University of Ljubljana; Korea University; University of Osaka; Nagoya University; Tohoku Gakuin University; Kyungpook National University (KNU); Saga University; Institute of Science Tokyo; Tokyo Institute of Technology; Graduate University for Advanced Studies - Japan; Chiba University; Niigata University; Seoul National University (SNU); Panjab University; Austrian Academy of Sciences; Institute of High Energy Physics of the Austrian Academy of Sciences; Princeton University; Osaka Metropolitan University; Tokyo University of Agriculture & Technology; Toho University; Kanagawa University; Chinese Academy of Sciences; Institute of High Energy Physics, CAS; University of Illinois System; University of Illinois Urbana-Champaign; RIKEN; National Research Centre - Kurchatov Institute; Institute of High Energy Physics - IHEP; University of Nova Gorica; Tokyo Metropolitan University; National United University; Tohoku University; Nippon Dental University; Chinese Academy of Sciences; University of Science & Technology of China, CAS
RP Chang, P (corresponding author), Natl Taiwan Univ, Dept Phys, Taipei 106, Taiwan.
EM pchang@phys.ntu.edu.tw
FU Science and Technology Facilities Council [ST/F002289/1] Funding Source: researchfish; STFC [ST/F002289/1] Funding Source: UKRI
NR 30
TC 107
Z9 115
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 MAR 20
PY 2008
VL 452
IS 7185
BP 332
EP U3
DI 10.1038/nature06827
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400042
PM 18354478
DA 2026-03-09
ER

PT J
AU Pitsouli, C
   Perrimon, N
AF Pitsouli, Chrysoula
   Perrimon, Norbert
TI Developmental biology - Our fly cousins' gut
SO NATURE
LA English
DT Article
ID stem-cells; midgut
C1 [Pitsouli, Chrysoula; Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Pitsouli, C (corresponding author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM perrimon@receptor.med.harvard.edu
NR 8
TC 22
Z9 30
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 JUL 31
PY 2008
VL 454
IS 7204
BP 592
EP 593
DI 10.1038/454592a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500033
PM 18668098
DA 2026-03-09
ER

PT J
AU Edwards, SL
   Brough, R
   Lord, CJ
   Natrajan, R
   Vatcheva, R
   Levine, DA
   Boyd, J
   Reis, JS
   Ashworth, A
AF Edwards, Stacey L.
   Brough, Rachel
   Lord, Christopher J.
   Natrajan, Rachael
   Vatcheva, Radost
   Levine, Douglas A.
   Boyd, Jeff
   Reis-Filho, Jorge S.
   Ashworth, Alan
TI Resistance to therapy caused by intragenic deletion in BRCA2
SO NATURE
LA English
DT Article
ID homology-directed repair; adp-ribose polymerase; genomic stability; improved survival; mutant-cells; cancer; mutations; protein; breaks; defect
AB Cells with loss of BRCA2 function are defective in homologous recombination ( HR) and are highly sensitive to inhibitors of poly( ADP- ribose) polymerase ( PARP)(1,2), which provides the basis for a new therapeutic approach. Here we show that resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. We derived PARP- inhibitor- resistant ( PIR) clones from the human CAPAN1 pancreatic cancer cell line, which carries the protein- truncating c.6174delT frameshift mutation. PIR clones could form DNA- damage- induced RAD51 nuclear foci and were able to limit genotoxin- induced genomic instability, both hallmarks of a competent HR pathway. New BRCA2 isoforms were expressed in the resistant lines as a result of intragenic deletion of the c.6174delT mutation and restoration of the open reading frame ( ORF). Reconstitution of BRCA2- deficient cells with these revertant BRCA2 alleles rescued PARP inhibitor sensitivity and HR deficiency. Most of the deletions in BRCA2 were associated with small tracts of homology, and possibly arose from error-prone repair caused by BRCA2 deficiency(3,4). Similar ORF-restoring mutations were present in carboplatin- resistant ovarian tumours from c.6174delT mutation carriers. These observations have implications for understanding drug resistance in BRCA mutation carriers as well as in defining functionally important domains within BRCA2.
C1 [Edwards, Stacey L.; Brough, Rachel; Lord, Christopher J.; Natrajan, Rachael; Vatcheva, Radost; Reis-Filho, Jorge S.; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
   [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
   [Boyd, Jeff] Mem Hlth Univ Med Ctr, Anderson Canc Inst, Savannah, GA 31404 USA.
C3 Royal Marsden NHS Foundation Trust; University of London; Institute of Cancer Research - UK; Memorial Sloan Kettering Cancer Center
RP Ashworth, A (corresponding author), Inst Canc Res, Breakthrough Breast Canc Res Ctr, Fulham Rd, London SW3 6JB, England.
EM alan.ashworth@icr.ac.uk
FU Cancer Research UK [A8363] Funding Source: Medline; Breast Cancer Now [BREAST CANCER NOW RESEARCH CENTRE] Funding Source: Medline
NR 30
TC 871
Z9 990
U1 2
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1111
EP U8
DI 10.1038/nature06548
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600043
PM 18264088
DA 2026-03-09
ER

PT J
AU Titov, DV
   Taylor, FW
   Svedhem, H
   Ignatiev, NI
   Markiewicz, WJ
   Piccioni, G
   Drossart, P
AF Titov, Dmitry V.
   Taylor, Fredric W.
   Svedhem, Hakan
   Ignatiev, Nikolay I.
   Markiewicz, Wojciech J.
   Piccioni, Giuseppe
   Drossart, Pierre
TI Atmospheric structure and dynamics as the cause of ultraviolet markings in the clouds of Venus
SO NATURE
LA English
DT Article
ID middle atmosphere; express; mission
AB When seen in ultraviolet light, Venus has contrast features that arise from the non- uniform distribution of unknown absorbers within the sulphuric acid clouds(1-3) and seem to trace dynamical activity in the middle atmosphere(4). It has long been unclear whether the global pattern arises from differences in cloud top altitude (which was earlier(3) estimated to be 66-72 km), compositional variations or temperature contrasts. Here we report multiwavelength imaging that reveals that the dark low latitudes are dominated by convective mixing which brings the ultraviolet absorbers up from depth. The bright and uniform mid- latitude clouds reside in the 'cold collar', an annulus of cold air characterized by similar to 30K lower temperatures with a positive lapse rate, which suppresses vertical mixing and cuts off the supply of ultraviolet absorbers from below. In low and middle latitudes, the visible cloud top is located at a remarkably constant altitude of 72 +/- 1 km in both the ultraviolet dark and bright regions, indicating that the brightness variations result from compositional differences caused by the colder environment rather than by elevation changes. The cloud top descends to similar to 64 km in the eye of the hemispheric vortex, which appears as a depression in the upper cloud deck. The ultraviolet dark circular streaks enclose the vortex eye and are dynamically connected to it.
C1 [Titov, Dmitry V.; Ignatiev, Nikolay I.; Markiewicz, Wojciech J.] Max Planck Inst Sonnensyst Forsch, D-37191 Katlenburg Lindau, Germany.
   [Taylor, Fredric W.] Univ Oxford, Clarendon Lab, Subdept Atmospher Ocean & Planetary Phys, Oxford OX1 3PU, England.
   [Svedhem, Hakan] European Space Agcy, Estec, NL-2200 AG Noordwijk, Netherlands.
   [Titov, Dmitry V.; Ignatiev, Nikolay I.] Space Res Inst IKI, Moscow 117997, Russia.
   [Piccioni, Giuseppe] Ist Astrofis Spaziale & Fis Cosmica INAF IASF, I-00133 Rome, Italy.
   [Drossart, Pierre] Observ Paris, LESIA, F-92195 Meudon, France.
C3 Max Planck Society; University of Oxford; European Space Agency; European Space Research & Technology Centre; Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences; Istituto Nazionale Astrofisica (INAF); Universite PSL; Observatoire de Paris
RP Titov, DV (corresponding author), Max Planck Inst Sonnensyst Forsch, Max Planck Str 2, D-37191 Katlenburg Lindau, Germany.
EM Titov@mps.mpg.de
FU UK Science and Technology Facilities Council; Italian (ASI); French (CNES); Russian Foundation for Basic Research
NR 22
TC 71
Z9 74
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 4
PY 2008
VL 456
IS 7222
BP 620
EP 623
DI 10.1038/nature07466
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000036
PM 19052623
DA 2026-03-09
ER

PT J
AU Erlandson, KJ
   Miller, SBM
   Nam, Y
   Osborne, AR
   Zimmer, J
   Rapoport, TA
AF Erlandson, Karl J.
   Miller, Stephanie B. M.
   Nam, Yunsun
   Osborne, Andrew R.
   Zimmer, Jochen
   Rapoport, Tom A.
TI A role for the two-helix finger of the SecA ATPase in protein translocation
SO NATURE
LA English
DT Article
ID escherichia-coli; pore residues; channel; membrane; complex; mediate; recognition; proteolysis; hydrolysis; peptidase
AB An important step in the biosynthesis of many proteins is their partial or complete translocation across the plasma membrane in prokaryotes or the endoplasmic reticulum membrane in eukaryotes(1). In bacteria, secretory proteins are generally translocated after completion of their synthesis by the interaction of the cytoplasmic ATPase SecA and a protein- conducting channel formed by the SecY complex(2). How SecA moves substrates through the SecY channel is unclear. However, a recent structure of a SecA - SecY complex raises the possibility that the polypeptide chain is moved by a two- helix finger domain of SecA that is inserted into the cytoplasmic opening of the SecY channel(3). Here we have used disulphide- bridge cross-linking to show that the loop at the tip of the two- helix finger of Escherichia coli SecA interacts with a polypeptide chain right at the entrance into the SecY pore. Mutagenesis demonstrates that a tyrosine in the loop is particularly important for translocation, but can be replaced by some other bulky, hydrophobic residues. We propose that the two- helix finger of SecA moves a polypeptide chain into the SecY channel with the tyrosine providing the major contact with the substrate, a mechanism analogous to that suggested for hexameric, protein- translocating ATPases.
C1 [Erlandson, Karl J.; Miller, Stephanie B. M.; Nam, Yunsun; Osborne, Andrew R.; Zimmer, Jochen; Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Erlandson, Karl J.; Miller, Stephanie B. M.; Nam, Yunsun; Osborne, Andrew R.; Zimmer, Jochen; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School
RP Rapoport, TA (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 240 Longwood Ave, Boston, MA 02115 USA.
EM tom_rapoport@hms.harvard.edu
FU NIH; Damon Runyon Cancer Research Foundation [DRG 1953-07]; National Institute of General Medical Sciences [R01GM052586] Funding Source: NIH RePORTER
NR 27
TC 108
Z9 139
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 984
EP U67
DI 10.1038/nature07439
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300054
PM 18923526
DA 2026-03-09
ER

PT J
AU Peters, SE
AF Peters, Shanan E.
TI Environmental determinants of extinction selectivity in the fossil record
SO NATURE
LA English
DT Article
ID marine; diversity; dynamics; history
AB The causes of mass extinctions and the nature of biological selectivity during extinction events remain central questions in palaeobiology. Although many different environmental perturbations have been invoked as extinction mechanisms(1-3), it has long been recognized that fluctuations in sea level coincide with many episodes of biotic turnover(4-6). Recent work supports the hypothesis that changes in the areas of epicontinental seas have influenced the macroevolution of marine animals(7,8), but the extent to which differential environmental turnover has contributed to extinction selectivity remains unknown. Here I use a new compilation of the temporal durations of sedimentary rock packages to show that carbonate and terrigenous clastic marine shelf environments have different spatio- temporal dynamics and that these dynamics predict patterns of genus- level extinction, extinction selectivity and diversity among Sepkoski's Palaeozoic and modern evolutionary faunae(9). These results do not preclude a role for biological interactions or unusual physical events as drivers of macroevolution, but they do suggest that the turnover of marine shelf habitats and correlated environmental changes have been consistent determinants of extinction, extinction selectivity and the shifting composition of the marine biota during the Phanerozoic eon.
C1 [Peters, Shanan E.] Univ Wisconsin, Dept Geol & Geophys, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison
RP Peters, SE (corresponding author), Univ Wisconsin, Dept Geol & Geophys, 1215 W Dayton St, Madison, WI 53706 USA.
EM peters@geology.wisc.edu
NR 30
TC 118
Z9 143
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 JUL 31
PY 2008
VL 454
IS 7204
BP 626
EP U38
DI 10.1038/nature07032
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500044
PM 18552839
DA 2026-03-09
ER

PT J
AU Miller, W
   Drautz, DI
   Ratan, A
   Pusey, B
   Qi, J
   Lesk, AM
   Tomsho, LP
   Packard, MD
   Zhao, FQ
   Sher, A
   Tikhonov, A
   Raney, B
   Patterson, N
   Lindblad-Toh, K
   Lander, ES
   Knight, JR
   Irzyk, GP
   Fredrikson, KM
   Harkins, TT
   Sheridan, S
   Pringle, T
   Schuster, SC
AF Miller, Webb
   Drautz, Daniela I.
   Ratan, Aakrosh
   Pusey, Barbara
   Qi, Ji
   Lesk, Arthur M.
   Tomsho, Lynn P.
   Packard, Michael D.
   Zhao, Fangqing
   Sher, Andrei
   Tikhonov, Alexei
   Raney, Brian
   Patterson, Nick
   Lindblad-Toh, Kerstin
   Lander, Eric S.
   Knight, James R.
   Irzyk, Gerard P.
   Fredrikson, Karin M.
   Harkins, Timothy T.
   Sheridan, Sharon
   Pringle, Tom
   Schuster, Stephan C.
TI Sequencing the nuclear genome of the extinct woolly mammoth
SO NATURE
LA English
DT Article
ID dna; humans; size
AB In 1994, two independent groups extracted DNA from several Pleistocene epoch mammoths and noted differences among individual specimens(1,2). Subsequently, DNA sequences have been published for a number of extinct species. However, such ancient DNA is often fragmented and damaged(3), and studies to date have typically focused on short mitochondrial sequences, never yielding more than a fraction of a per cent of any nuclear genome. Here we describe 4.17 billion bases ( Gb) of sequence from several mammoth specimens, 3.3 billion ( 80%) of which are from the woolly mammoth ( Mammuthus primigenius) genome and thus comprise an extensive set of genome- wide sequence from an extinct species. Our data support earlier reports(4) that elephantid genomes exceed 4 Gb. The estimated divergence rate between mammoth and African elephant is half of that between human and chimpanzee. The observed number of nucleotide differences between two particular mammoths was approximately one- eighth of that between one of them and the African elephant, corresponding to a separation between the mammoths of 1.5 - 2.0 Myr. The estimated probability that orthologous elephant and mammoth amino acids differ is 0.002, corresponding to about one residue per protein. Differences were discovered between mammoth and African elephant in amino- acid positions that are otherwise invariant over several billion years of combined mammalian evolution. This study shows that nuclear genome sequencing of extinct species can reveal population differences not evident from the fossil record, and perhaps even discover genetic factors that affect extinction.
C1 [Miller, Webb; Drautz, Daniela I.; Ratan, Aakrosh; Pusey, Barbara; Qi, Ji; Lesk, Arthur M.; Tomsho, Lynn P.; Packard, Michael D.; Zhao, Fangqing; Schuster, Stephan C.] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Sher, Andrei] Russian Acad Sci, Severtsov Inst Ecol & Evolut, Moscow 119071, Russia.
   [Tikhonov, Alexei] Russian Acad Sci, Inst Zool, St Petersburg 199034, Russia.
   [Raney, Brian] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Patterson, Nick; Lindblad-Toh, Kerstin; Lander, Eric S.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Fredrikson, Karin M.; Harkins, Timothy T.; Sheridan, Sharon] Roche Diagnost Corp, Indianapolis, IN 46250 USA.
   [Pringle, Tom] Sperling Fdn, Eugene, OR 97405 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Russian Academy of Sciences; Saratov Scientific Center of the Russian Academy of Sciences; Severtsov Institute of Ecology & Evolution; Russian Academy of Sciences; Zoological Institute of the Russian Academy of Sciences; University of California System; University of California Santa Cruz; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Roche Holding; Roche Holding USA
RP Miller, W (corresponding author), Penn State Univ, Ctr Comparat Genom & Bioinformat, 310 Wartik Bldg, University Pk, PA 16802 USA.
EM webb@bx.psu.edu; scs@bx.psu.edu
FU National Human Genome Research Institute [HG002238]; Gordon and Betty Moore Foundation; Pennsylvania Department of Health using Tobacco Settlement Funds appropriated by the US legislature
NR 38
TC 230
Z9 269
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 NOV 20
PY 2008
VL 456
IS 7220
BP 387
EP U51
DI 10.1038/nature07446
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600043
PM 19020620
DA 2026-03-09
ER

PT J
AU Hyman, SE
AF Hyman, Steven E.
TI A glimmer of light for neuropsychiatric disorders
SO NATURE
LA English
DT Article
ID genome-wide association; national comorbidity survey; alzheimers-disease; rett-syndrome; copy number; genetics; schizophrenia; genes; loci; translocation
C1 [Hyman, Steven E.] Harvard Univ, Sch Med, Off Provost, Dept Neurobiol, Cambridge, MA 02138 USA.
C3 Harvard University
RP Hyman, SE (corresponding author), Harvard Univ, Sch Med, Off Provost, Dept Neurobiol, Massachusetts Hall, Cambridge, MA 02138 USA.
EM seh@harvard.edu
NR 48
TC 98
Z9 115
U1 0
U2 12
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 890
EP 893
DI 10.1038/nature07454
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300036
PM 18923510
DA 2026-03-09
ER

PT J
AU Lutz, W
   Sanderson, W
   Scherbov, S
AF Lutz, Wolfgang
   Sanderson, Warren
   Scherbov, Sergei
TI The coming acceleration of global population ageing
SO NATURE
LA English
DT Article
ID demography; limits
AB The future paths of population ageing result from specific combinations of declining fertility and increasing life expectancies in different parts of the world(1). Here we measure the speed of population ageing by using conventional measures and new ones that take changes in longevity into account for the world as a whole and for 13 major regions. We report on future levels of indicators of ageing and the speed at which they change. We show how these depend on whether changes in life expectancy are taken into account. We also show that the speed of ageing is likely to increase over the coming decades and to decelerate in most regions by mid-century. All our measures indicate a continuous ageing of the world's population throughout the century. The median age of the world's population increases from 26.6 years in 2000 to 37.3 years in 2050 and then to 45.6 years in 2100, when it is not adjusted for longevity increase. When increases in life expectancy are taken into account(2,3), the adjusted median age rises from 26.6 in 2000 to 31.1 in 2050 and only to 32.9 in 2100, slightly less than what it was in the China region in 2005. There are large differences in the regional patterns of ageing. In North America, the median age adjusted for life expectancy change falls throughout almost the entire century, whereas the conventional median age increases significantly. Our assessment of trends in ageing is based on new probabilistic population forecasts. The probability that growth in the world's population will end during this century is 88%, somewhat higher than previously assessed(4). After mid- century, lower rates of population growth are likely to coincide with slower rates of ageing.
C1 [Lutz, Wolfgang; Sanderson, Warren; Scherbov, Sergei] Int Inst Appl Syst Anal, World Populat Program, A-2361 Laxenburg, Austria.
   [Lutz, Wolfgang; Scherbov, Sergei] Austrian Acad Sci, Vienna Inst Demog, A-1040 Vienna, Austria.
   [Sanderson, Warren] SUNY Stony Brook, Dept Econ, Stony Brook, NY 11794 USA.
   [Sanderson, Warren] SUNY Stony Brook, Dept Hist, Stony Brook, NY 11794 USA.
C3 International Institute for Applied Systems Analysis (IIASA); Austrian Academy of Sciences; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University
RP Lutz, W (corresponding author), Int Inst Appl Syst Anal, World Populat Program, Schlosspl 1, A-2361 Laxenburg, Austria.
EM lutz@iiasa.ac.at
NR 19
TC 1019
Z9 1205
U1 9
U2 270
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 716
EP 719
DI 10.1038/nature06516
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500041
PM 18204438
DA 2026-03-09
ER

PT J
AU Zilberman, D
   Coleman-Derr, D
   Ballinger, T
   Henikoff, S
AF Zilberman, Daniel
   Coleman-Derr, Devin
   Ballinger, Tracy
   Henikoff, Steven
TI Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks
SO NATURE
LA English
DT Article
ID genome-wide; variant; arabidopsis; nucleosome; promoters; genes; euchromatin; dynamics; yeast
AB Eukaryotic chromatin is separated into functional domains differentiated by post- translational histone modifications, histone variants and DNA methylation(1-6). Methylation is associated with repression of transcriptional initiation in plants and animals, and is frequently found in transposable elements. Proper methylation patterns are crucial for eukaryotic development(4,5), and aberrant methylation- induced silencing of tumour suppressor genes is a common feature of human cancer(7). In contrast to methylation, the histone variant H2A. Z is preferentially deposited by the Swr1 ATPase complex near 59 ends of genes where it promotes transcriptional competence(8-20). How DNA methylation and H2A.Z influence transcription remains largely unknown. Here we show that in the plant Arabidopsis thaliana regions of DNA methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at sites of DNA methylation in the bodies of actively transcribed genes and in methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes both losses and gains of DNA methylation(4,5), engenders opposite changes ( gains and losses) in H2A.Z deposition, whereas mutation of the PIE1 subunit of the Swr1 complex that deposits H2A.Z(17) leads to genome- wide hypermethylation. Our findings indicate that DNA methylation can influence chromatin structure and effect gene silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation.
C1 [Zilberman, Daniel; Coleman-Derr, Devin] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [Ballinger, Tracy; Henikoff, Steven] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Ballinger, Tracy; Henikoff, Steven] Howard Hughes Med Inst, Seattle, WA 98109 USA.
C3 University of California System; University of California Berkeley; Fred Hutchinson Cancer Center; Howard Hughes Medical Institute
RP Zilberman, D (corresponding author), Univ Calif Berkeley, 211 Koshland Hall, Berkeley, CA 94720 USA.
EM daniel.zilberman@nature.berkely.edu; steveh@fhcrc.org
FU NSF
NR 30
TC 452
Z9 557
U1 0
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 125
EP U14
DI 10.1038/nature07324
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000054
PM 18815594
DA 2026-03-09
ER

PT J
AU McKay, D
   White, M
   Pasienski, M
   DeMarco, B
AF McKay, D.
   White, M.
   Pasienski, M.
   DeMarco, B.
TI Phase-slip-induced dissipation in an atomic Bose-Hubbard system
SO NATURE
LA English
DT Article
ID superconducting nanowires; einstein condensate; insulator; transition; superfluid
AB Phase- slips control dissipation in many bosonic systems, determining the critical velocity of superfluid helium(1) and the generation of resistance in thin superconducting wires(2). Technological interest has been largely motivated by applications involving nanoscale superconducting circuit elements, such as standards based on quantum phase- slip junctions(3). Although phase slips caused by thermal fluctuations at high temperatures are well understood(4), controversy remains over the role of phase slips in small- scale superconductors(5) - in solids, problems such as uncontrolled noise sources and disorder complicate their study and application(6). Here we show that phase slips can lead to dissipation in a clean and well- characterized Bose - Hubbard system, by experimentally studying the transport of ultracold atoms trapped in an optical lattice. In contrast to previous work, we explore a low- velocity regime described by the three- dimensional Bose Hubbard model that is unaffected by instabilities, and we measure the effect of temperature on the dissipation strength. The damping rate of atomic motion ( the analogue of electrical resistance in a solid) in the confining parabolic potential is well fitted by a model that includes finite damping at zero temperature. The low- temperature behaviour is consistent with the theory of quantum tunnelling of phase slips, whereas at higher temperatures a crossover consistent with a transition to thermal activation of phase slips is evident. Motion- induced features reminiscent of vortices and vortex rings associated with phase slips are also observed in time- of- flight imaging. These results clarify the role of phase slips in superfluid systems. They may also be of relevance in understanding the source of metallic phases observed in thin films(7,8), or serve as a test bed for theories of bosonic dissipation based upon variants of the Bose - Hubbard model(9).
C1 [McKay, D.; White, M.; Pasienski, M.; DeMarco, B.] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign
RP DeMarco, B (corresponding author), Univ Illinois, Dept Phys, 1110 W Green St, Urbana, IL 61801 USA.
EM bdemarco@uiuc.edu
NR 35
TC 69
Z9 81
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 MAY 1
PY 2008
VL 453
IS 7191
BP 76
EP +
DI 10.1038/nature06920
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800041
PM 18451857
DA 2026-03-09
ER

PT J
AU Barthelemy, P
   Bertolotti, J
   Wiersma, DS
AF Barthelemy, Pierre
   Bertolotti, Jacopo
   Wiersma, Diederik S.
TI A Levy flight for light
SO NATURE
LA English
DT Article
ID anomalous diffusion; fluctuations
AB A random walk is a stochastic process in which particles or waves travel along random trajectories. The first application of a random walk was in the description of particle motion in a fluid (brownian motion); now it is a central concept in statistical physics, describing transport phenomena such as heat, sound and light diffusion(1). Levy flights are a particular class of generalized random walk in which the step lengths during the walk are described by a 'heavy-tailed' probability distribution. They can describe all stochastic processes that are scale invariant(2,3). Levy flights have accordingly turned out to be applicable to a diverse range of fields, describing animal foraging patterns(4), the distribution of human travel(5) and even some aspects of earthquake behaviour(6). Transport based on Levy flights has been extensively studied numerically(7-9), but experimental work has been limited(10,11) and, to date, it has not seemed possible to observe and study Levy transport in actual materials. For example, experimental work on heat, sound, and light diffusion is generally limited to normal, brownian, diffusion. Here we show that it is possible to engineer an optical material in which light waves perform a Levy flight. The key parameters that determine the transport behaviour can be easily tuned, making this an ideal experimental system in which to study Levy flights in a controlled way. The development of a material in which the diffusive transport of light is governed by Levy statistics might even permit the development of new optical functionalities that go beyond normal light diffusion.
C1 [Barthelemy, Pierre; Bertolotti, Jacopo; Wiersma, Diederik S.] European Lab Nonlinear Spect, I-50019 Florence, Italy.
   [Barthelemy, Pierre; Bertolotti, Jacopo; Wiersma, Diederik S.] INFM BEC, I-50019 Florence, Italy.
RP Wiersma, DS (corresponding author), European Lab Nonlinear Spect, Via Nello Carrara 1, I-50019 Florence, Italy.
EM wiersma@lens.unifi.it
NR 29
TC 655
Z9 682
U1 2
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 495
EP 498
DI 10.1038/nature06948
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700036
PM 18497819
DA 2026-03-09
ER

PT J
AU King, AA
   Ionides, EL
   Pascual, M
   Bouma, MJ
AF King, Aaron A.
   Ionides, Edward L.
   Pascual, Mercedes
   Bouma, Menno J.
TI Inapparent infections and cholera dynamics
SO NATURE
LA English
DT Article
ID vibrio-cholerae; endemic cholera; climate; environment; bangladesh; epidemics; disease
AB In many infectious diseases, an unknown fraction of infections produce symptoms mild enough to go unrecorded, a fact that can seriously compromise the interpretation of epidemiological records. This is true for cholera, a pandemic bacterial disease, where estimates of the ratio of asymptomatic to symptomatic infections have ranged from 3 to 100 (refs 1-5). In the absence of direct evidence, understanding of fundamental aspects of cholera transmission, immunology and control has been based on assumptions about this ratio and about the immunological consequences of inapparent infections. Here we show that a model incorporating high asymptomatic ratio and rapidly waning immunity, with infection both from human and environmental sources, explains 50 yr of mortality data from 26 districts of Bengal, the pathogen's endemic home. We find that the asymptomatic ratio in cholera is far higher than had been previously supposed and that the immunity derived from mild infections wanes much more rapidly than earlier analyses have indicated. We find, too, that the environmental reservoir(5,6) (free-living pathogen) is directly responsible for relatively few infections but that it may be critical to the disease's endemicity. Our results demonstrate that inapparent infections can hold the key to interpreting the patterns of disease outbreaks. New statistical methods(7), which allow rigorous maximum likelihood inference based on dynamical models incorporating multiple sources and outcomes of infection, seasonality, process noise, hidden variables and measurement error, make it possible to test more precise hypotheses and obtain unexpected results. Our experience suggests that the confrontation of time-series data with mechanistic models is likely to revise our understanding of the ecology of many infectious diseases.
C1 [King, Aaron A.; Pascual, Mercedes] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
   [King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
   [Ionides, Edward L.] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA.
   [Pascual, Mercedes] Santa Fe Inst, Santa Fe, NM 87501 USA.
   [Bouma, Menno J.] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; The Santa Fe Institute; University of London; London School of Hygiene & Tropical Medicine
RP King, AA (corresponding author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM kingaa@umich.edu
NR 36
TC 341
Z9 393
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 AUG 14
PY 2008
VL 454
IS 7206
BP 877
EP U29
DI 10.1038/nature07084
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600034
PM 18704085
DA 2026-03-09
ER

PT J
AU Parisien, M
   Major, F
AF Parisien, Marc
   Major, Francois
TI The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data
SO NATURE
LA English
DT Article
ID secondary structure; messenger-rna; induced fit; prediction; protein; iron; recognition; loop
AB The classical RNA secondary structure model considers A.U and G.U Watson - Crick as well as G.U wobble base pairs. Here we substitute it for a new one, in which sets of nucleotide cyclic motifs define RNA structures. This model allows us to unify all base pairing energetic contributions in an effective scoring function to tackle the problem of RNA folding. We show how pipelining two computer algorithms based on nucleotide cyclic motifs, MC- Fold and MC- Sym, reproduces a series of experimentally determined RNA three- dimensional structures from the sequence. This demonstrates how crucial the consideration of all base- pairing interactions is in filling the gap between sequence and structure. We use the pipeline to define rules of precursor microRNA folding in double helices, despite the presence of a number of presumed mismatches and bulges, and to propose a new model of the human immunodeficiency virus- 1-1 frame- shifting element.
C1 [Parisien, Marc; Major, Francois] Univ Montreal, IRIC, Dept Comp Sci & Operat Res, Montreal, PQ H3C 3J7, Canada.
C3 Universite de Montreal
RP Major, F (corresponding author), Univ Montreal, IRIC, Dept Comp Sci & Operat Res, POB 6128,Downtown Stn, Montreal, PQ H3C 3J7, Canada.
EM francois.major@umontreal.ca
NR 40
TC 655
Z9 819
U1 0
U2 48
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 6
PY 2008
VL 452
IS 7183
BP 51
EP 55
DI 10.1038/nature06684
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900044
PM 18322526
DA 2026-03-09
ER

PT J
AU Bruneau, BG
AF Bruneau, Benoit G.
TI The developmental genetics of congenital heart disease
SO NATURE
LA English
DT Article
ID of-function mutations; holt-oram-syndrome; smooth-muscle; cause noonan; cardiovascular-disease; scientific statement; alagille-syndrome; current knowledge; progenitor cells; okihiro-syndrome
AB Congenital heart disease is the leading cause of infant morbidity in the Western world, but only in the past ten years has its aetiology been understood. Recent studies have uncovered the genetic basis for some common forms of the disease and provide new insight into how the heart develops and how dysregulation of heart development leads to disease.
C1 [Bruneau, Benoit G.] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Bruneau, Benoit G.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco
RP Bruneau, BG (corresponding author), Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, 1650 Owens St, San Francisco, CA 94158 USA.
EM bbruneau@gladstone.ucsf.edu
NR 68
TC 609
Z9 764
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 FEB 21
PY 2008
VL 451
IS 7181
BP 943
EP 948
DI 10.1038/nature06801
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100035
PM 18288184
DA 2026-03-09
ER

PT J
AU Guelen, L
   Pagie, L
   Brasset, E
   Meuleman, W
   Faza, MB
   Talhout, W
   Eussen, BH
   de Klein, A
   Wessels, L
   de Laat, W
   van Steensel, B
AF Guelen, Lars
   Pagie, Ludo
   Brasset, Emilie
   Meuleman, Wouter
   Faza, Marius B.
   Talhout, Wendy
   Eussen, Bert H.
   de Klein, Annelies
   Wessels, Lodewyk
   de Laat, Wouter
   van Steensel, Bas
TI Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions
SO NATURE
LA English
DT Article
ID gene-expression; membrane protein; human genome; cells; architecture; localization; emerin; transcription; mechanisms; periphery
AB The architecture of human chromosomes in interphase nuclei is still largely unknown. Microscopy studies have indicated that specific regions of chromosomes are located in close proximity to the nuclear lamina (NL)(1-3). This has led to the idea that certain genomic elements may be attached to the NL, which may contribute to the spatial organization of chromosomes inside the nucleus. However, sequences in the human genome that interact with the NL in vivo have not been identified. Here we construct a high-resolution map of the interaction sites of the entire genome with NL components in human fibroblasts. This map shows that genome - lamina interactions occur through more than 1,300 sharply defined large domains 0.1 - 10 megabases in size. These lamina-associated domains ( LADs) are typified by low gene- expression levels, indicating that LADs represent a repressive chromatin environment. The borders of LADs are demarcated by the insulator protein CTCF, by promoters that are oriented away from LADs, or by CpG islands, suggesting possible mechanisms of LAD confinement. Taken together, these results demonstrate that the human genome is divided into large, discrete domains that are units of chromosome organization within the nucleus.
C1 [Guelen, Lars; Pagie, Ludo; Meuleman, Wouter; Faza, Marius B.; Talhout, Wendy; Wessels, Lodewyk; van Steensel, Bas] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands.
   [Brasset, Emilie; de Laat, Wouter] Erasmus MC, Dept Cell Biol & Genet, NL-3000 CA Rotterdam, Netherlands.
   [Eussen, Bert H.; de Klein, Annelies] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands.
   [Meuleman, Wouter; Wessels, Lodewyk] Delft Univ Technol, Fac Elect Engn Math & Comp Sci, NL-2628 CD Delft, Netherlands.
C3 Netherlands Cancer Institute; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Delft University of Technology
RP van Steensel, B (corresponding author), Netherlands Canc Inst, Div Mol Biol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM b.v.steensel@nki.nl
NR 35
TC 1476
Z9 1773
U1 1
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 948
EP U83
DI 10.1038/nature06947
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000050
PM 18463634
DA 2026-03-09
ER

PT J
AU Nakao, N
   Ono, H
   Yamamura, T
   Anraku, T
   Takagi, T
   Higashi, K
   Yasuo, S
   Katou, Y
   Kageyama, S
   Uno, Y
   Kasukawa, T
   Iigo, M
   Sharp, PJ
   Iwasawa, A
   Suzuki, Y
   Sugano, S
   Niimi, T
   Mizutani, M
   Namikawa, T
   Ebihara, S
   Ueda, HR
   Yoshimura, T
AF Nakao, Nobuhiro
   Ono, Hiroko
   Yamamura, Takashi
   Anraku, Tsubasa
   Takagi, Tsuyoshi
   Higashi, Kumiko
   Yasuo, Shinobu
   Katou, Yasuhiro
   Kageyama, Saburo
   Uno, Yumiko
   Kasukawa, Takeya
   Iigo, Masayuki
   Sharp, Peter J.
   Iwasawa, Atsushi
   Suzuki, Yutaka
   Sugano, Sumio
   Niimi, Teruyuki
   Mizutani, Makoto
   Namikawa, Takao
   Ebihara, Shizufumi
   Ueda, Hiroki R.
   Yoshimura, Takashi
TI Thyrotrophin in the pars tuberalis triggers photoperiodic response
SO NATURE
LA English
DT Article
ID ii iodothyronine deiodinase; coturnix-coturnix-japonica; japanese-quail; chicken thyrotropin; gene-expression; circadian clock; beta-subunit; hormone; receptor; brain
AB Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid- hormone- activating enzyme ( type 2 deiodinase, DIO2) in the mediobasal hypothalamus ( MBH) of the Japanese quail ( Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin ( TSH) beta- subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular ( ICV) administration of TSH to short- day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor - cyclic AMP ( cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long- day photoinduced seasonal breeding.
C1 [Nakao, Nobuhiro; Ono, Hiroko; Yamamura, Takashi; Anraku, Tsubasa; Takagi, Tsuyoshi; Higashi, Kumiko; Yasuo, Shinobu; Katou, Yasuhiro; Kageyama, Saburo; Uno, Yumiko; Ebihara, Shizufumi; Yoshimura, Takashi] Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Div Biomodelling, Nagoya, Aichi 4648601, Japan.
   [Kasukawa, Takeya; Ueda, Hiroki R.] RIKEN, Funct Genom Subunit, Ctr Dev Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan.
   [Iigo, Masayuki] Utsunomiya Univ, Fac Agr, Dept Appl Biochem, Utsunomiya, Tochigi 3218505, Japan.
   [Sharp, Peter J.] Univ Edinburgh, Div Genet & Genom, Roslin Inst, Roslin EH25 9PS, Midlothian, Scotland.
   [Sharp, Peter J.] Univ Edinburgh, Div Genet & Genom, Royal Dick Sch Vet Studies, Roslin EH25 9PS, Midlothian, Scotland.
   [Iwasawa, Atsushi] Gifu Univ, Lab Comparat Biochem, Grad Sch Appl Biol Sci, Gifu 5011193, Japan.
   [Suzuki, Yutaka; Sugano, Sumio] Univ Tokyo, Dept Med Genome Sci, Grad Sch Frontier Sci, Minato Ku, Tokyo 1088639, Japan.
   [Niimi, Teruyuki] Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Div Biofunct Dev, Nagoya, Aichi 4648601, Japan.
   [Mizutani, Makoto; Namikawa, Takao; Ebihara, Shizufumi; Yoshimura, Takashi] Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Avian Biosci Res Ctr, Nagoya, Aichi 4648601, Japan.
   [Ueda, Hiroki R.] RIKEN, Lab Syst Biol, Ctr Dev Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan.
   [Yoshimura, Takashi] Nagoya Univ, Chikusa Ku, Inst Adv Res, Nagoya, Aichi 4648601, Japan.
C3 Nagoya University; RIKEN; Utsunomiya University; University of Edinburgh; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; Gifu University; University of Tokyo; Nagoya University; Nagoya University; RIKEN; Nagoya University
RP Yoshimura, T (corresponding author), Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Div Biomodelling, Furo Cho, Nagoya, Aichi 4648601, Japan.
EM takashiy@agr.nagoya-u.ac.jp
NR 39
TC 422
Z9 476
U1 0
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 317
EP U1
DI 10.1038/nature06738
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400039
PM 18354476
DA 2026-03-09
ER

PT J
AU Paukstelis, PJ
   Chen, JH
   Chase, E
   Lambowitz, AM
   Golden, BL
AF Paukstelis, Paul J.
   Chen, Jui-Hui
   Chase, Elaine
   Lambowitz, Alan M.
   Golden, Barbara L.
TI Structure of a tyrosyl-tRNA synthetase splicing factor bound to a group I intron RNA
SO NATURE
LA English
DT Article
ID neurospora-crassa; catalytic core; crystal-structure; cyt-18 protein; tetrahymena ribozyme; tertiary structure; p4-p6 domain; binding; defects; program
AB The 'RNA world' hypothesis holds that during evolution the structural and enzymatic functions initially served by RNA were assumed by proteins, leading to the latter's domination of biological catalysis. This progression can still be seen in modern biology, where ribozymes, such as the ribosome and RNase P, have evolved into protein- dependent RNA catalysts ('RNPzymes'). Similarly, group I introns use RNA- catalysed splicing reactions, but many function as RNPzymes bound to proteins that stabilize their catalytically active RNA structure(1,2). One such protein, the Neurospora crassa mitochondrial tyrosyl- tRNA synthetase ( TyrRS; CYT- 18), is bifunctional and both aminoacylates mitochondrial tRNA(Tyr) and promotes the splicing of mitochondrial group I introns(3). Here we determine a 4.5-angstrom co-crystal structure of the Twort orf142-I2 group I intron ribozyme bound to splicing-active, carboxy- terminally truncated CYT- 18. The structure shows that the group I intron binds across the two subunits of the homodimeric protein with a newly evolved RNA- binding surface distinct from that which binds tRNA(Tyr). This RNA binding surface provides an extended scaffold for the phosphodiester backbone of the conserved catalytic core of the intron RNA, allowing the protein to promote the splicing of a wide variety of group I introns. The group I intron- binding surface includes three small insertions and additional structural adaptations relative to non- splicing bacterial TyrRSs, indicating a multistep adaptation for splicing function. The co- crystal structure provides insight into how CYT- 18 promotes group I intron splicing, how it evolved to have this function, and how proteins could have incrementally replaced RNA structures during the transition from an RNA world to an RNP world.
C1 [Paukstelis, Paul J.; Lambowitz, Alan M.] Univ Texas Austin, Sch Biol Sci, Dept Chem & Biochem, Inst Mol & Cellular Biol, Austin, TX 78712 USA.
   [Paukstelis, Paul J.; Lambowitz, Alan M.] Univ Texas Austin, Sch Biol Sci, Sect Mol Genet & Microbiol, Austin, TX 78712 USA.
   [Chen, Jui-Hui; Chase, Elaine; Golden, Barbara L.] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA.
C3 University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; Purdue University System; Purdue University
RP Lambowitz, AM (corresponding author), Univ Texas Austin, Sch Biol Sci, Dept Chem & Biochem, Inst Mol & Cellular Biol, Austin, TX 78712 USA.
EM lambowitz@mail.utexas.edu; barbgolden@purdue.edu
NR 34
TC 70
Z9 99
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 JAN 3
PY 2008
VL 451
IS 7174
BP 94
EP U15
DI 10.1038/nature06413
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300041
PM 18172503
DA 2026-03-09
ER

PT J
AU Shen, JX
   Feng, AS
   Xu, ZM
   Yu, ZL
   Arch, VS
   Yu, XJ
   Narins, PM
AF Shen, Jun-Xian
   Feng, Albert S.
   Xu, Zhi-Min
   Yu, Zu-Lin
   Arch, Victoria S.
   Yu, Xin-Jian
   Narins, Peter M.
TI Ultrasonic frogs show hyperacute phonotaxis to female courtship calls
SO NATURE
LA English
DT Article
ID communication; signals; vocalizations
AB Sound communication plays a vital role in frog reproduction(1,2), in which vocal advertisement is generally the domain of males. Females are typically silent, but in a few anuran species they can produce a feeble reciprocal call(3) or rapping sounds(4) during courtship. Males of concave- eared torrent frogs ( Odorrana tormota) have demonstrated ultrasonic communication capacity(5). Although females of O. tormota have an unusually well- developed vocal production system(6), it is unclear whether or not they produce calls or are only passive partners in a communication system dominated by males. Here we show that before ovulation, gravid females of O. tormota emit calls that are distinct from males' advertisement calls, having higher fundamental frequencies and harmonics and shorter call duration. In the field and in a quiet, darkened indoor arena, these female calls evoke vocalizations and extraordinarily precise positive phonotaxis ( a localization error of <1 degrees), rivalling that of vertebrates with the highest localization acuity ( barn owls(7,8), dolphins, elephants and humans(9)). The localization accuracy of O. tormota is remarkable in light of their small head size ( interaural distance of <1 cm), and suggests an additional selective advantage of high- frequency hearing beyond the ability to avoid masking by low- frequency background noise(5).
C1 [Shen, Jun-Xian; Xu, Zhi-Min; Yu, Zu-Lin] Chinese Acad Sci, State Key Lab Brain & Cognit Sci, Inst Biophys, Beijing 100101, Peoples R China.
   [Feng, Albert S.] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
   [Feng, Albert S.] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA.
   [Arch, Victoria S.; Narins, Peter M.] Univ Calif Los Angeles, Dept Ecol & Evolut Biol, Los Angeles, CA 90095 USA.
   [Narins, Peter M.] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA.
   [Yu, Xin-Jian] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200032, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Biophysics, CAS; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Chinese Academy of Sciences
RP Shen, JX (corresponding author), Chinese Acad Sci, State Key Lab Brain & Cognit Sci, Inst Biophys, Beijing 100101, Peoples R China.
EM shenjx@sun5.ibp.ac.cn
NR 25
TC 90
Z9 115
U1 5
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 JUN 12
PY 2008
VL 453
IS 7197
BP 914
EP U46
DI 10.1038/nature06719
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000042
PM 18469804
DA 2026-03-09
ER

PT J
AU Gong, Y
   Cao, P
   Yu, HJ
   Jiang, T
AF Gong, Yong
   Cao, Peng
   Yu, Hong-jun
   Jiang, Tao
TI Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex
SO NATURE
LA English
DT Article
ID nerve growth-factor; receptor; binding; trka
AB Neurotrophins (NTs) are important regulators for the survival, differentiation and maintenance of different peripheral and central neurons. NTs bind to two distinct classes of glycosylated receptor: the p75 neurotrophin receptor (p75(NTR)) and tyrosine kinase receptors (Trks). Whereas p75(NTR) binds to all NTs, the Trk subtypes are specific for each NT1,2. The question of whether NTs stimulate p75(NTR) by inducing receptor homodimerization is still under debate. Here we report the 2.6-angstrom resolution crystal structure of neurotrophin-3 (NT-3) complexed to the ectodomain of glycosylated p75(NTR). In contrast to the previously reported asymmetric complex structure, which contains a dimer of nerve growth factor (NGF) bound to a single ectodomain of deglycosylated p75(NTR) (ref. 3), we show that NT-3 forms a central homodimer around which two glycosylated p75(NTR) molecules bind symmetrically. Symmetrical binding occurs along the NT-3 interfaces, resulting in a 2:2 ligand-receptor cluster. A comparison of the symmetrical and asymmetric structures reveals significant differences in ligand receptor interactions and p75(NTR) conformations. Biochemical experiments indicate that both NT-3 and NGF bind to p75(NTR) with 2:2 stoichiometry in solution, whereas the 2:1 complexes are the result of artificial deglycosylation. We therefore propose that the symmetrical 2:2 complex reflects a native state of p75(NTR) activation at the cell surface. These results provide a model for NTs-p75(NTR) recognition and signal generation, as well as insights into coordination between p75(NTR) and Trks.
C1 [Gong, Yong; Cao, Peng; Yu, Hong-jun; Jiang, Tao] Chinese Acad Sci, Natl Key Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Biophysics, CAS
RP Jiang, T (corresponding author), Chinese Acad Sci, Natl Key Lab Biomacromol, Inst Biophys, 15 Datun Rd, Beijing 100101, Peoples R China.
EM tjiang@ibp.ac.cn
NR 28
TC 98
Z9 131
U1 1
U2 34
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 789
EP U114
DI 10.1038/nature07089
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000050
PM 18596692
DA 2026-03-09
ER

PT J
AU Lim, J
   Crespo-Barreto, J
   Jafar-Nejad, P
   Bowman, AB
   Richman, R
   Hill, DE
   Orr, HT
   Zoghbi, HY
AF Lim, Janghoo
   Crespo-Barreto, Juan
   Jafar-Nejad, Paymaan
   Bowman, Aaron B.
   Richman, Ronald
   Hill, David E.
   Orr, Harry T.
   Zoghbi, Huda Y.
TI Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1
SO NATURE
LA English
DT Article
ID bulbar muscular-atrophy; motor-neuron degeneration; transgenic mouse model; huntingtons-disease; mutant huntingtin; in-vivo; trinucleotide repeat; interaction network; mice; ataxin-1
AB Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a glutamine-encoding repeat in ataxin 1 (ATXN1). In all known polyglutamine diseases, the glutamine expansion confers toxic functions onto the protein; however, the mechanism by which this occurs remains enigmatic, in light of the fact that the mutant protein apparently maintains interactions with its usual partners. Here we show that the expanded polyglutamine tract differentially affects the function of the host protein in the context of different endogenous protein complexes. Polyglutamine expansion in ATXN1 favours the formation of a particular protein complex containing RBM17, contributing to SCA1 neuropathology by means of a gain-of-function mechanism. Concomitantly, polyglutamine expansion attenuates the formation and function of another protein complex containing ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism. This model provides mechanistic insight into the molecular pathogenesis of SCA1 as well as other polyglutamine diseases.
C1 [Lim, Janghoo; Jafar-Nejad, Paymaan; Bowman, Aaron B.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Crespo-Barreto, Juan; Zoghbi, Huda Y.] Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA.
   [Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
   [Richman, Ronald; Zoghbi, Huda Y.] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA.
   [Hill, David E.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
   [Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Hill, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Orr, Harry T.] Univ Minnesota, Inst Human Genet, Dept Biochem Biophys & Mol Biol, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Howard Hughes Medical Institute; Baylor College of Medicine; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; University of Minnesota System; University of Minnesota Twin Cities
RP Zoghbi, HY (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM hzoghbi@bcm.tmc.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NICHD NIH HHS [P30 HD024064] Funding Source: Medline; NINDS NIH HHS [R01 NS027699] Funding Source: Medline; National Institute of Neurological Disorders and Stroke [R01NS027699] Funding Source: NIH RePORTER
NR 43
TC 249
Z9 309
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 10
PY 2008
VL 452
IS 7188
BP 713
EP U1
DI 10.1038/nature06731
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500037
PM 18337722
DA 2026-03-09
ER

PT J
AU Hÿtch, M
   Houdellier, F
   Hüe, F
   Snoeck, E
AF Hytch, Martin
   Houdellier, Florent
   Hue, Florian
   Snoeck, Etienne
TI Nanoscale holographic interferometry for strain measurements in electronic devices
SO NATURE
LA English
DT Article
ID silicon; diffraction; displacement; si; performance; relaxation; microscopy; resolution; system; layers
AB Strained silicon is now an integral feature of the latest generation of transistors and electronic devices(1-3) because of the associated enhancement in carrier mobility(4,5). Strain is also expected to have an important role in future devices based on nanowires(6) and in optoelectronic components(7). Different strategies have been used to engineer strain in devices, leading to complex strain distributions in two and three dimensions(8,9). Developing methods of strain measurement at the nanoscale has therefore been an important objective in recent years but has proved elusive in practice(1,10): none of the existing techniques combines the necessary spatial resolution, precision and field of view. For example, Raman spectroscopy or X-ray diffraction techniques can map strain at the micrometre scale, whereas transmission electron microscopy allows strain measurement at the nanometre scale but only over small sample areas. Here we present a technique capable of bridging this gap and measuring strain to high precision, with nanometre spatial resolution and for micrometre fields of view(11). Our method combines the advantages of moire techniques(12) with the flexibility of off-axis electron holography(13) and is also applicable to relatively thick samples, thus reducing the influence of thin-film relaxation effects.
C1 [Hytch, Martin; Houdellier, Florent; Hue, Florian; Snoeck, Etienne] nMat Grp, CEMES CNRS, F-31055 Toulouse, France.
C3 Centre National de la Recherche Scientifique (CNRS)
RP Hÿtch, M (corresponding author), nMat Grp, CEMES CNRS, 29 Rue Jeanne Marvig, F-31055 Toulouse, France.
EM hytch@cemes.fr
NR 35
TC 387
Z9 425
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 JUN 19
PY 2008
VL 453
IS 7198
BP 1086
EP U5
DI 10.1038/nature07049
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900053
PM 18563161
DA 2026-03-09
ER

PT J
AU Hamzah, J
   Jugold, M
   Kiessling, F
   Rigby, P
   Manzur, M
   Marti, HH
   Rabie, T
   Kaden, S
   Gröne, HJ
   Hämmerling, GJ
   Arnold, B
   Ganss, R
AF Hamzah, Juliana
   Jugold, Manfred
   Kiessling, Fabian
   Rigby, Paul
   Manzur, Mitali
   Marti, Hugo H.
   Rabie, Tamer
   Kaden, Sylvia
   Groene, Hermann-Josef
   Haemmerling, Guenter J.
   Arnold, Bernd
   Ganss, Ruth
TI Vascular normalization in Rgs5-deficient tumours promotes immune destruction
SO NATURE
LA English
DT Article
ID hepatocellular-carcinoma; antiangiogenic therapy; blood-vessels; pericytes; protein; cells; model; rgs5; edema; tumorigenesis
AB The vasculature of solid tumours is morphologically aberrant and characterized by dilated and fragile vessels, intensive vessel sprouting and loss of hierarchical architecture(1). Constant vessel remodelling leads to spontaneous haemorrhages(2) and increased interstitial fluid pressure in the tumour environment(3,4). Tumour-related angiogenesis supports tumour growth and is also a major obstacle for successful immune therapy as it prevents migration of immune effector cells into established tumour parenchyma(2,5,6). The molecular mechanisms for these angiogenic alterations are largely unknown. Here we identify regulator of G-protein signalling 5 (Rgs5) as a master gene responsible for the abnormal tumour vascular morphology in mice. Loss of Rgs5 results in pericyte maturation, vascular normalization and consequent marked reductions in tumour hypoxia and vessel leakiness. These vascular and intratumoral changes enhance influx of immune effector cells into tumour parenchyma and markedly prolong survival of tumour-bearing mice. This is the first demonstration, to our knowledge, of reduced tumour angiogenesis and improved immune therapeutic outcome on loss of a vascular gene function and establishes a previously unrecognized role of G-protein signalling in tumour angiogenesis.
C1 [Hamzah, Juliana; Manzur, Mitali; Ganss, Ruth] Univ Western Australia, Med Res Ctr, Western Australian Inst Med Res, Perth, WA 6000, Australia.
   [Jugold, Manfred; Kiessling, Fabian] German Canc Res Ctr, Juniorgrp Mol Imaging, Dept Med Phys Radiol, D-69120 Heidelberg, Germany.
   [Kaden, Sylvia; Groene, Hermann-Josef] German Canc Res Ctr, Dept Cellular & Mol Pathol, D-69120 Heidelberg, Germany.
   [Haemmerling, Guenter J.; Arnold, Bernd] German Canc Res Ctr, Dept Mol Immunol, D-69120 Heidelberg, Germany.
   [Rigby, Paul] Univ Western Australia, Ctr Microscopy Characterisat & Anal, Perth, WA 6000, Australia.
   [Marti, Hugo H.; Rabie, Tamer] Univ Heidelberg, Inst Physiol & Pathophysiol, D-69120 Heidelberg, Germany.
C3 University of Western Australia; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); University of Western Australia; Ruprecht Karls University Heidelberg
RP Ganss, R (corresponding author), Univ Western Australia, Med Res Ctr, Western Australian Inst Med Res, Perth, WA 6000, Australia.
EM ganss@waimr.uwa.edu.au
NR 30
TC 476
Z9 539
U1 0
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 15
PY 2008
VL 453
IS 7193
BP 410
EP U67
DI 10.1038/nature06868
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400056
PM 18418378
DA 2026-03-09
ER

PT J
AU Tam, OH
   Aravin, AA
   Stein, P
   Girard, A
   Murchison, EP
   Cheloufi, S
   Hodges, E
   Anger, M
   Sachidanandam, R
   Schultz, RM
   Hannon, GJ
AF Tam, Oliver H.
   Aravin, Alexei A.
   Stein, Paula
   Girard, Angelique
   Murchison, Elizabeth P.
   Cheloufi, Sihem
   Hodges, Emily
   Anger, Martin
   Sachidanandam, Ravi
   Schultz, Richard M.
   Hannon, Gregory J.
TI Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes
SO NATURE
LA English
DT Article
ID piwi; protein; mili; biogenesis; micrornas; mechanism
AB Pseudogenes populate the mammalian genome as remnants of artefactual incorporation of coding messenger RNAs into transposon pathways(1). Here we show that a subset of pseudogenes generates endogenous small interfering RNAs (endo-siRNAs) in mouse oocytes. These endo-siRNAs are often processed from double-stranded RNAs formed by hybridization of spliced transcripts from protein-coding genes to antisense transcripts from homologous pseudogenes. An inverted repeat pseudogene can also generate abundant small RNAs directly. A second class of endosiRNAs may enforce repression of mobile genetic elements, acting together with Piwi-interacting RNAs. Loss of Dicer, a protein integral to small RNA production, increases expression of endosiRNA targets, demonstrating their regulatory activity. Our findings indicate a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonautemediated catalysis in mammals.
C1 [Tam, Oliver H.; Aravin, Alexei A.; Girard, Angelique; Murchison, Elizabeth P.; Cheloufi, Sihem; Hodges, Emily; Sachidanandam, Ravi; Hannon, Gregory J.] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Tam, Oliver H.; Aravin, Alexei A.; Girard, Angelique; Murchison, Elizabeth P.; Cheloufi, Sihem; Hodges, Emily; Sachidanandam, Ravi; Hannon, Gregory J.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
   [Stein, Paula; Anger, Martin; Schultz, Richard M.] Univ Penn, Dept Biol, Lynch Labs 205, Philadelphia, PA 19104 USA.
C3 Cold Spring Harbor Laboratory; Cold Spring Harbor Laboratory; Howard Hughes Medical Institute; University of Pennsylvania
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
FU National Cancer Institute [P01CA013106] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [P01 CA013106] Funding Source: Medline; NIGMS NIH HHS [R01 GM062534] Funding Source: Medline
NR 29
TC 841
Z9 1009
U1 1
U2 92
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 534
EP U8
DI 10.1038/nature06904
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700045
PM 18404147
DA 2026-03-09
ER

PT J
AU Read, KA
   Mahajan, AS
   Carpenter, LJ
   Evans, MJ
   Faria, BVE
   Heard, DE
   Hopkins, JR
   Lee, JD
   Moller, SJ
   Lewis, AC
   Mendes, L
   McQuaid, JB
   Oetjen, H
   Saiz-Lopez, A
   Pilling, MJ
   Plane, JMC
AF Read, Katie A.
   Mahajan, Anoop S.
   Carpenter, Lucy J.
   Evans, Mathew J.
   Faria, Bruno V. E.
   Heard, Dwayne E.
   Hopkins, James R.
   Lee, James D.
   Moller, Sarah J.
   Lewis, Alastair C.
   Mendes, Luis
   McQuaid, James B.
   Oetjen, Hilke
   Saiz-Lopez, Alfonso
   Pilling, Michael J.
   Plane, John M. C.
TI Extensive halogen-mediated ozone destruction over the tropical Atlantic Ocean
SO NATURE
LA English
DT Article
ID marine boundary-layer; tropospheric chemistry; bromine chemistry; model; simulation; bro; oh
AB Increasing tropospheric ozone levels over the past 150 years have led to a significant climate perturbation(1); the prediction of future trends in tropospheric ozone will require a full understanding of both its precursor emissions and its destruction processes. A large proportion of tropospheric ozone loss occurs in the tropical marine boundary layer(2,3) and is thought to be driven primarily by high ozone photolysis rates in the presence of high concentrations of water vapour. A further reduction in the tropospheric ozone burden through bromine and iodine emitted from open- ocean marine sources has been postulated by numerical models(4-7), but thus far has not been verified by observations. Here we report eight months of spectroscopic measurements at the Cape Verde Observatory indicative of the ubiquitous daytime presence of bromine monoxide and iodine monoxide in the tropical marine boundary layer. A year- round data set of co- located in situ surface trace gas measurements made in conjunction with low- level aircraft observations shows that the mean daily observed ozone loss is similar to 50 per cent greater than that simulated by a global chemistry model using a classical photochemistry scheme that excludes halogen chemistry. We perform box model calculations that indicate that the observed halogen concentrations induce the extra ozone loss required for the models to match observations. Our results show that halogen chemistry has a significant and extensive influence on photochemical ozone loss in the tropical Atlantic Ocean boundary layer. The omission of halogen sources and their chemistry in atmospheric models may lead to significant errors in calculations of global ozone budgets, tropospheric oxidizing capacity and methane oxidation rates, both historically and in the future.
C1 [Read, Katie A.; Carpenter, Lucy J.; Moller, Sarah J.] Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England.
   [Mahajan, Anoop S.; Heard, Dwayne E.; Oetjen, Hilke; Pilling, Michael J.; Plane, John M. C.] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England.
   [Evans, Mathew J.; McQuaid, James B.] Univ Leeds, SEE, Leeds LS2 9JT, W Yorkshire, England.
   [Faria, Bruno V. E.; Mendes, Luis] INMG, Mindelo, Cape Verde.
   [Hopkins, James R.; Lee, James D.; Lewis, Alastair C.] Univ York, NCAS, York YO10 5DD, N Yorkshire, England.
   [Saiz-Lopez, Alfonso] CALTECH, Jet Prop Lab, Div Earth & Space Sci, Pasadena, CA 91109 USA.
C3 University of York - UK; University of Leeds; University of Leeds; University of York - UK; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL)
RP Carpenter, LJ (corresponding author), Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England.
EM ljc4@york.ac.uk; j.m.c.plane@leeds.ac.uk
FU NERC [NE/E011330/1, ncas10008, NE/D006562/1, NE/D006570/1, NE/E01111X/1] Funding Source: UKRI; Natural Environment Research Council [ncas10008, NE/D006562/1, NE/E01111X/1, NER/J/S/2002/00641, NE/D006570/1, NE/E011330/1] Funding Source: researchfish
NR 26
TC 359
Z9 400
U1 6
U2 202
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1232
EP 1235
DI 10.1038/nature07035
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800041
PM 18580948
DA 2026-03-09
ER

PT J
AU Reddy, KL
   Zullo, JM
   Bertolino, E
   Singh, H
AF Reddy, K. L.
   Zullo, J. M.
   Bertolino, E.
   Singh, H.
TI Transcriptional repression mediated by repositioning of genes to the nuclear lamina
SO NATURE
LA English
DT Article
ID cell differentiation; membrane protein; genome; locus; emerin; compartmentalization; organization; architecture; association; expression
AB Nuclear compartmentalization seems to have an important role in regulating metazoan genes(1,2). Although studies on immunoglobulin and other loci have shown a correlation between positioning at the nuclear lamina and gene repression, the functional consequences of this compartmentalization remain untested(2,3). We devised an approach for inducible tethering of genes to the inner nuclear membrane ( INM), and tested the consequences of such repositioning on gene activity in mouse fibroblasts. Here, using three- dimensional DNA- immunoFISH, we demonstrate repositioning of chromosomal regions to the nuclear lamina that is dependent on breakdown and reformation of the nuclear envelope during mitosis. Moreover, tethering leads to the accumulation of lamin and INM proteins, but not to association with pericentro-meric heterochromatin or nuclear pore complexes. Recruitment of genes to the INM can result in their transcriptional repression. Finally, we use targeted adenine methylation ( DamID) to show that, as is the case for our model system, inactive immunoglobulin loci at the nuclear periphery are contacted by INM and lamina proteins. We propose that these molecular interactions may be used to compartmentalize and to limit the accessibility of immunoglobulin loci to transcription and recombination factors.
C1 [Reddy, K. L.; Zullo, J. M.; Singh, H.] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
   [Reddy, K. L.; Zullo, J. M.; Bertolino, E.; Singh, H.] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA.
C3 University of Chicago; Howard Hughes Medical Institute; University of Chicago
RP Singh, H (corresponding author), Univ Chicago, Howard Hughes Med Inst, GCIS W522,929 E 57th St, Chicago, IL 60637 USA.
EM hsingh@uchicago.edu
FU Howard Hughes Medical Institute Funding Source: Medline
NR 28
TC 610
Z9 750
U1 1
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 13
PY 2008
VL 452
IS 7184
BP 243
EP 247
DI 10.1038/nature06727
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600046
PM 18272965
DA 2026-03-09
ER

PT J
AU Fink, JM
   Göppl, M
   Baur, M
   Bianchetti, R
   Leek, PJ
   Blais, A
   Wallraff, A
AF Fink, J. M.
   Goeppl, M.
   Baur, M.
   Bianchetti, R.
   Leek, P. J.
   Blais, A.
   Wallraff, A.
TI Climbing the Jaynes-Cummings ladder and observing its √n nonlinearity in a cavity QED system
SO NATURE
LA English
DT Article
ID single quantum-dot; photon number states; electrodynamics; spectroscopy; field; coherence; circuit; atom
AB The field of cavity quantum electrodynamics ( QED), traditionally studied in atomic systems(1-3), has gained new momentum by recent reports of quantum optical experiments with solid- state semiconducting(4-8) and superconducting(9-11) systems. In cavity QED, the observation of the vacuum Rabi mode splitting is used to investigate the nature of matter - light interaction at a quantum-mechanical level. However, this effect can, at least in principle, be explained classically as the normal mode splitting of two coupled linear oscillators(12). It has been suggested that an observation of the scaling of the resonant atom - photon coupling strength in the Jaynes - Cummings energy ladder(13) with the square root of photon number n is sufficient to prove that the system is quantum mechanical in nature(14). Here we report a direct spectroscopic observation of this characteristic quantum nonlinearity. Measuring the photonic degree of freedom of the coupled system, our measurements provide unambiguous spectroscopic evidence for the quantum nature of the resonant atom - field interaction in cavity QED. We explore atom - photon superposition states involving up to two photons, using a spectroscopic pump and probe technique. The experiments have been performed in a circuit QED set- up(15), in which very strong coupling is realized by the large dipole coupling strength and the long coherence time of a superconducting qubit embedded in a high- quality on- chip microwave cavity. Circuit QED systems also provide a natural quantum interface between flying qubits ( photons) and stationary qubits for applications in quantum information processing and communication(16).
C1 [Fink, J. M.; Goeppl, M.; Baur, M.; Bianchetti, R.; Leek, P. J.; Wallraff, A.] ETH, Dept Phys, CH-8093 Zurich, Switzerland.
   [Blais, A.] Univ Sherbrooke, Dept Phys, Sherbrooke, PQ J1K 2R1, Canada.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Sherbrooke
RP Fink, JM (corresponding author), ETH, Dept Phys, CH-8093 Zurich, Switzerland.
EM jfink@phys.ethz.ch; andreas.wallraff@phys.ethz.ch
NR 30
TC 440
Z9 485
U1 3
U2 109
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 315
EP 318
DI 10.1038/nature07112
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300034
PM 18633413
DA 2026-03-09
ER

PT J
AU Wang, YL
   Juranek, S
   Li, HT
   Sheng, G
   Tuschl, T
   Patel, DJ
AF Wang, Yanli
   Juranek, Stefan
   Li, Haitao
   Sheng, Gang
   Tuschl, Thomas
   Patel, Dinshaw J.
TI Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex
SO NATURE
LA English
DT Article
ID crystal-structure; recognition; risc; sirnas; slicer; interference; cleavage; insights; disease
AB Here we report on a 3.0 angstrom crystal structure of a ternary complex of wild- type Thermus thermophilus argonaute bound to a 5 '- phosphorylated 21- nucleotide guide DNA and a 20- nucleotide target RNA containing cleavage- preventing mismatches at the 10 - 11 step. The seed segment ( positions 2 to 8) adopts an A- helical- like Watson - Crick paired duplex, with both ends of the guide strand anchored in the complex. An arginine, inserted between guide- strand bases 10 and 11 in the binary complex, locking it in an inactive conformation, is released on ternary complex formation. The nucleic- acid- binding channel between the PAZ- and PIWI- containing lobes of argonaute widens on formation of a more open ternary complex. The relationship of structure to function was established by determining cleavage activity of ternary complexes containing position- dependent base mismatch, bulge and 2 '- O- methyl modifications. Consistent with the geometry of the ternary complex, bulges residing in the seed segments of the target, but not the guide strand, were better accommodated and their complexes were catalytically active.
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; 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; Starr Foundation; US Department of Energy
NR 41
TC 471
Z9 596
U1 1
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 DEC 18
PY 2008
VL 456
IS 7224
BP 921
EP U72
DI 10.1038/nature07666
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300038
PM 19092929
DA 2026-03-09
ER

PT J
AU Lohmueller, KE
   Indap, AR
   Schmidt, S
   Boyko, AR
   Hernandez, RD
   Hubisz, MJ
   Sninsky, JJ
   White, TJ
   Sunyaev, SR
   Nielsen, R
   Clark, AG
   Bustamante, CD
AF Lohmueller, Kirk E.
   Indap, Amit R.
   Schmidt, Steffen
   Boyko, Adam R.
   Hernandez, Ryan D.
   Hubisz, Melissa J.
   Sninsky, John J.
   White, Thomas J.
   Sunyaev, Shamil R.
   Nielsen, Rasmus
   Clark, Andrew G.
   Bustamante, Carlos D.
TI Proportionally more deleterious genetic variation in European than in African populations
SO NATURE
LA English
DT Article
ID brain size; mutations; selection; evolution; genome
AB Quantifying the number of deleterious mutations per diploid human genome is of crucial concern to both evolutionary and medical geneticists(1-3). Here we combine genome- wide polymorphism data from PCR- based exon resequencing, comparative genomic data across mammalian species, and protein structure predictions to estimate the number of functionally consequential singlenucleotide polymorphisms (SNPs) carried by each of 15 African American (AA) and 20 European American (EA) individuals. We find that AAs show significantly higher levels of nucleotide heterozygosity than do EAs for all categories of functional SNPs considered, including synonymous, non- synonymous, predicted 'benign', predicted 'possibly damaging' and predicted 'probably damaging' SNPs. This result is wholly consistent with previous work showing higher overall levels of nucleotide variation in African populations than in Europeans(4). EA individuals, in contrast, have significantly more genotypes homozygous for the derived allele at synonymous and non- synonymous SNPs and for the damaging allele at ` probably damaging' SNPs than AAs do. For SNPs segregating only in one population or the other, the proportion of non-synonymous SNPs is significantly higher in the EA sample (55.4%) than in the AA sample (47.0%; P < 2.33 X 10(-37)). We observe a similar proportional excess of SNPs that are inferred to be 'probably damaging' (15.9% in EA; 12.1% in AA; P < 3.33 X 10(-11)). Using extensive simulations, we show that this excess proportion of segregating damaging alleles in Europeans is probably a consequence of a bottleneck that Europeans experienced at about the time of the migration out of Africa.
C1 [Lohmueller, Kirk E.; Indap, Amit R.; Boyko, Adam R.; Hernandez, Ryan D.; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
   [Lohmueller, Kirk E.; Boyko, Adam R.; Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
   [Schmidt, Steffen] Max Planck Inst Dev Biol, Dept Biochem, D-72076 Tubingen, Germany.
   [Hubisz, Melissa J.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Sninsky, John J.; White, Thomas J.] Celera Diagnost, Alameda, CA 94592 USA.
   [Sunyaev, Shamil R.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA.
   [Sunyaev, Shamil R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Nielsen, Rasmus] Univ Copenhagen, Ctr Comparat Genom, Dept Biol, DK-2100 Copenhagen O, Denmark.
C3 Cornell University; Cornell University; Max Planck Society; University of Chicago; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Copenhagen
RP Bustamante, CD (corresponding author), Cornell Univ, Dept Biol Stat & Computat Biol, Biotechnol Bldg, Ithaca, NY 14853 USA.
EM cdb28@cornell.edu
FU NHGRI NIH HHS [R01 HG003229] Funding Source: Medline; NHLBI NIH HHS [R01 HL072904] Funding Source: Medline; NIGMS NIH HHS [P50 GM065509] Funding Source: Medline
NR 30
TC 314
Z9 383
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 994
EP U5
DI 10.1038/nature06611
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100049
PM 18288194
DA 2026-03-09
ER

PT J
AU Hirata, A
   Klein, BJ
   Murakami, KS
AF Hirata, Akira
   Klein, Brianna J.
   Murakami, Katsuhiko S.
TI The X-ray crystal structure of RNA polymerase from Archaea
SO NATURE
LA English
DT Article
ID transcription factors; angstrom resolution; initiation; subunit; translation; machinery; mechanism; complex; system; enzyme
AB The transcription apparatus in Archaea can be described as a simplified version of its eukaryotic RNA polymerase ( RNAP) II counterpart, comprising an RNAPII- like enzyme as well as two general transcription factors, the TATA- binding protein ( TBP) and the eukaryotic TFIIB orthologue TFB1,2. It has been widely understood that precise comparisons of cellular RNAP crystal structures could reveal structural elements common to all enzymes and that these insights would be useful in analysing components of each enzyme that enable it to perform domain- specific gene expression. However, the structure of archaeal RNAP has been limited to individual subunits(3,4). Here we report the first crystal structure of the archaeal RNAP from Sulfolobus solfataricus at 3.4 angstrom resolution, completing the suite of multi- subunit RNAP structures from all three domains of life. We also report the high-resolution ( at 1.76 angstrom) crystal structure of the D/ L subcomplex of archaeal RNAP and provide the first experimental evidence of any RNAP possessing an iron - sulphur ( Fe - S) cluster, which may play a structural role in a key subunit of RNAP assembly. The striking structural similarity between archaeal RNAP and eukaryotic RNAPII highlights the simpler archaeal RNAP as an ideal model system for dissecting the molecular basis of eukaryotic transcription.
C1 [Hirata, Akira; Klein, Brianna J.; Murakami, Katsuhiko S.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Murakami, KS (corresponding author), Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
EM kum14@psu.edu
FU NIGMS NIH HHS [R01 GM071897] Funding Source: Medline
NR 35
TC 169
Z9 238
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 851
EP U12
DI 10.1038/nature06530
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400047
PM 18235446
DA 2026-03-09
ER

PT J
AU Fischer, H
   Behrens, M
   Bock, M
   Richter, U
   Schmitt, J
   Loulergue, L
   Chappellaz, J
   Spahni, R
   Blunier, T
   Leuenberger, M
   Stocker, TF
AF Fischer, Hubertus
   Behrens, Melanie
   Bock, Michael
   Richter, Ulrike
   Schmitt, Jochen
   Loulergue, Laetitia
   Chappellaz, Jerome
   Spahni, Renato
   Blunier, Thomas
   Leuenberger, Markus
   Stocker, Thomas F.
TI Changing boreal methane sources and constant biomass burning during the last termination
SO NATURE
LA English
DT Article
ID atmospheric ch4 gradient; greenland; climate; antarctica; oxidation; record
AB Past atmospheric methane concentrations show strong fluctuations in parallel to rapid glacial climate changes in the Northern Hemisphere(1,2) superimposed on a glacial - interglacial doubling of methane concentrations(3-5). The processes driving the observed fluctuations remain uncertain but can be constrained using methane isotopic information from ice cores(6,7). Here we present an ice core record of carbon isotopic ratios in methane over the entire last glacial - interglacial transition. Our data show that the carbon in atmospheric methane was isotopically much heavier in cold climate periods. With the help of a box model constrained by the present data and previously published results(6,8), we are able to estimate the magnitude of past individual methane emission sources and the atmospheric lifetime of methane. We find that methane emissions due to biomass burning were about 45 Tg methane per year, and that these remained roughly constant throughout the glacial termination. The atmospheric lifetime of methane is reduced during cold climate periods. We also show that boreal wetlands are an important source of methane during warm events, but their methane emissions are essentially shut down during cold climate conditions.
C1 [Fischer, Hubertus; Behrens, Melanie; Bock, Michael; Richter, Ulrike; Schmitt, Jochen] Alfred Wegener Inst Polar & Marine Res, D-27568 Bremerhaven, Germany.
   [Loulergue, Laetitia; Chappellaz, Jerome] UJF, CNRS, Lab Glaciol & Geophys Environm, F-38400 Grenoble, France.
   [Spahni, Renato; Blunier, Thomas; Leuenberger, Markus; Stocker, Thomas F.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
C3 Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); University of Bern
RP Fischer, H (corresponding author), Alfred Wegener Inst Polar & Marine Res, Columbusstr, D-27568 Bremerhaven, Germany.
EM hubertus.fischer@awi.de
NR 30
TC 143
Z9 161
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 APR 17
PY 2008
VL 452
IS 7189
BP 864
EP 867
DI 10.1038/nature06825
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000046
PM 18421351
DA 2026-03-09
ER

PT J
AU Dhonukshe, P
   Tanaka, H
   Goh, T
   Ebine, K
   Mähönen, AP
   Prasad, K
   Blilou, I
   Geldner, N
   Xu, J
   Uemura, T
   Chory, J
   Ueda, T
   Nakano, A
   Scheres, B
   Friml, J
AF Dhonukshe, Pankaj
   Tanaka, Hirokazu
   Goh, Tatsuaki
   Ebine, Kazuo
   Mahonen, Ari Pekka
   Prasad, Kalika
   Blilou, Ikram
   Geldner, Niko
   Xu, Jian
   Uemura, Tomohiro
   Chory, Joanne
   Ueda, Takashi
   Nakano, Akihiko
   Scheres, Ben
   Friml, Jiri
TI RETRACTED: Generation of cell polarity in plants links endocytosis, auxin distribution and cell fate decisions (Retracted Article)
SO NATURE
LA English
DT Article; Retracted Publication
ID arabidopsis-thaliana; h+-atpase; efflux; transport; root; trafficking; gradients; distinct; stem; biosynthesis
AB Dynamically polarized membrane proteins define different cell boundaries and have an important role in intercellular communication - a vital feature of multicellular development. Efflux carriers for the signalling molecule auxin from the PIN family(1) are landmarks of cell polarity in plants and have a crucial involvement in auxin distribution- dependent development including embryo patterning, organogenesis and tropisms(2-7). Polar PIN localization determines the direction of intercellular auxin flow(8), yet the mechanisms generating PIN polarity remain unclear. Here we identify an endocytosis- dependent mechanism of PIN polarity generation and analyse its developmental implications. Real- time PIN tracking showed that after synthesis, PINs are initially delivered to the plasma membrane in a non- polar manner and their polarity is established by subsequent endocytic recycling. Interference with PIN endocytosis either by auxin or by manipulation of the Arabidopsis Rab5 GTPase pathway prevents PIN polarization. Failure of PIN polarization transiently alters asymmetric auxin distribution during embryogenesis and increases the local auxin response in apical embryo regions. This results in ectopic expression of auxin pathway- associated root- forming master regulators in embryonic leaves and promotes homeotic transformation of leaves to roots. Our results indicate a two- step mechanism for the generation of PIN polar localization and the essential role of endocytosis in this process. It also highlights the link between endocytosis- dependent polarity of individual cells and auxin distribution- dependent cell fate establishment for multicellular patterning.
C1 [Dhonukshe, Pankaj; Mahonen, Ari Pekka; Prasad, Kalika; Blilou, Ikram; Xu, Jian; Scheres, Ben] Univ Utrecht, Dept Biol, Fac Sci, NL-3584 CH Utrecht, Netherlands.
   [Tanaka, Hirokazu; Friml, Jiri] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Tanaka, Hirokazu; Friml, Jiri] Univ Ghent, Dept Mol Genet, B-9052 Ghent, Belgium.
   [Goh, Tatsuaki; Ebine, Kazuo; Uemura, Tomohiro; Ueda, Takashi; Nakano, Akihiko] Univ Tokyo, Dept Biol Sci, Grad Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Geldner, Niko] Univ Lausanne, Dept Plant Mol Biol DBMV, UNIL Sorge, CH-1015 Lausanne, Switzerland.
   [Geldner, Niko; Chory, Joanne] Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA.
   [Nakano, Akihiko] RIKEN Adv Sci Inst, Mol Membrane Biol Lab, Wako, Saitama 3510198, Japan.
C3 Utrecht University; Ghent University; Flanders Institute for Biotechnology (VIB); Ghent University; University of Tokyo; University of Lausanne; Salk Institute; RIKEN
RP Dhonukshe, P (corresponding author), Univ Utrecht, Dept Biol, Fac Sci, Padualaan 8, NL-3584 CH Utrecht, Netherlands.
EM P.B.Dhonukshe@uu.nl; jiri.friml@psb.ugent.be
FU VolkswagenStiftung; EMBO Long Term Fellowship; Netherlands Organization for Scientific Research (NWO)-VENI; EMBO Young Investigator Program; Odysseus program; HFSP fellowship; NWO-VIDI; Swiss National Science Foundation; HHMI; USDA; NIH; NWO-Spinoza; Ministry of Education, Culture, Sports, Science and Technology of Japan
NR 44
TC 193
Z9 223
U1 1
U2 88
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 962
EP U75
DI 10.1038/nature07409
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300048
PM 18953331
DA 2026-03-09
ER

PT J
AU Petrovic, M
   Hummel, T
AF Petrovic, Milan
   Hummel, Thomas
TI Temporal identity in axonal target layer recognition
SO NATURE
LA English
DT Article
ID zinc-finger protein; lamina-specific connectivity; n-cadherin; transcription factors; gene-function; drosophila; receptor; expression; system; regulator
AB The segregation of axon and dendrite projections into distinct synaptic layers is a fundamental principle of nervous system organization and the structural basis for information processing in the brain(1). Layer- specific recognition molecules that allow projecting neurons to stabilize transient contacts and initiate synaptogenesis(2,3) have been identified. However, most of the neuronal cell- surface molecules critical for layer organization are expressed broadly in the developing nervous system(4,5), raising the question of how these so- called permissive adhesion molecules support synaptic specificity. Here we show that the temporal expression dynamics of the zinc- finger protein sequoia is the major determinant of Drosophila photoreceptor connectivity into distinct synaptic layers. Neighbouring R8 and R7 photoreceptors show consecutive peaks of elevated sequoia expression, which correspond to their sequential target- layer innervation. Loss of sequoia in R7 leads to a projection switch into the R8 recipient layer, whereas a prolonged expression in R8 induces a redirection of their axons into the R7 layer. The sequoia- induced axon targeting is mediated through the ubiquitously expressed Cadherin- N cell adhesion molecule. Our data support a model in which recognition specificity during synaptic layer formation is generated through a temporally restricted axonal competence to respond to broadly expressed adhesion molecules. Because developing neurons innervating the same target area often project in a distinct, birth- order- dependent sequence, temporal identity seems to contain crucial information in generating not only cell type diversity during neuronal division(6) but also connection diversity of projecting neurons.
C1 [Petrovic, Milan; Hummel, Thomas] Univ Munster, Inst Neurobiol, D-48149 Munster, Germany.
C3 University of Munster
RP Hummel, T (corresponding author), Univ Munster, Inst Neurobiol, Badestr 9, D-48149 Munster, Germany.
EM hummel@uni-muenster.de
FU Deutsche Forschungsgemeinschaft [SFB629]; EMBO Young Investigator Programme
NR 42
TC 62
Z9 78
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 800
EP U87
DI 10.1038/nature07407
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900051
PM 18978776
DA 2026-03-09
ER

PT J
AU Pain, A
   Böhme, U
   Berry, AE
   Mungall, K
   Finn, RD
   Jackson, AP
   Mourier, T
   Mistry, J
   Pasini, EM
   Aslett, MA
   Balasubrammaniam, S
   Borgwardt, K
   Brooks, K
   Carret, C
   Carver, TJ
   Cherevach, I
   Chillingworth, T
   Clark, TG
   Galinski, MR
   Hall, N
   Harper, D
   Harris, D
   Hauser, H
   Ivens, A
   Janssen, CS
   Keane, T
   Larke, N
   Lapp, S
   Marti, M
   Moule, S
   Meyer, IM
   Ormond, D
   Peters, N
   Sanders, M
   Sanders, S
   Sargeant, TJ
   Simmonds, M
   Smith, F
   Squares, R
   Thurston, S
   Tivey, AR
   Walker, D
   White, B
   Zuiderwijk, E
   Churcher, C
   Quail, MA
   Cowman, AF
   Turner, CMR
   Rajandream, MA
   Kocken, CHM
   Thomas, AW
   Newbold, CI
   Barrell, BG
   Berriman, M
AF Pain, A.
   Bohme, U.
   Berry, A. E.
   Mungall, K.
   Finn, R. D.
   Jackson, A. P.
   Mourier, T.
   Mistry, J.
   Pasini, E. M.
   Aslett, M. A.
   Balasubrammaniam, S.
   Borgwardt, K.
   Brooks, K.
   Carret, C.
   Carver, T. J.
   Cherevach, I.
   Chillingworth, T.
   Clark, T. G.
   Galinski, M. R.
   Hall, N.
   Harper, D.
   Harris, D.
   Hauser, H.
   Ivens, A.
   Janssen, C. S.
   Keane, T.
   Larke, N.
   Lapp, S.
   Marti, M.
   Moule, S.
   Meyer, I. M.
   Ormond, D.
   Peters, N.
   Sanders, M.
   Sanders, S.
   Sargeant, T. J.
   Simmonds, M.
   Smith, F.
   Squares, R.
   Thurston, S.
   Tivey, A. R.
   Walker, D.
   White, B.
   Zuiderwijk, E.
   Churcher, C.
   Quail, M. A.
   Cowman, A. F.
   Turner, C. M. R.
   Rajandream, M. A.
   Kocken, C. H. M.
   Thomas, A. W.
   Newbold, C. I.
   Barrell, B. G.
   Berriman, M.
TI The genome of the simian and human malaria parasite Plasmodium knowlesi
SO NATURE
LA English
DT Article
ID antigenic variation; variant antigen; sequence; protein; expression; virulence; signal; identification; erythrocytes; infections
AB Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis ( the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia(1,2). Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated(3), and it has a close phylogenetic relationship to Plasmodium vivax(4), the second most important species of human malaria parasite ( reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle ( reviewed in ref. 4). Here we present an analysis of the P. knowlesi ( H strain, Pk1( A+) clone(5)) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome(4) and other sequenced Plasmodium genomes(6-8). In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs(9), contains sequences that collectively match over one- half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.
C1 [Pain, A.; Bohme, U.; Berry, A. E.; Mungall, K.; Finn, R. D.; Jackson, A. P.; Mistry, J.; Aslett, M. A.; Balasubrammaniam, S.; Brooks, K.; Carret, C.; Carver, T. J.; Cherevach, I.; Chillingworth, T.; Clark, T. G.; Harper, D.; Harris, D.; Hauser, H.; Ivens, A.; Keane, T.; Larke, N.; Moule, S.; Ormond, D.; Peters, N.; Sanders, M.; Sanders, S.; Simmonds, M.; Smith, F.; Squares, R.; Thurston, S.; Tivey, A. R.; Walker, D.; White, B.; Zuiderwijk, E.; Churcher, C.; Quail, M. A.; Rajandream, M. A.; Newbold, C. I.; Barrell, B. G.; Berriman, M.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
   [Mourier, T.] Univ Copenhagen, Dept Biol, Ancient DNA & Evolut Grp, DK-2100 Copenhagen, Denmark.
   [Pasini, E. M.; Kocken, C. H. M.; Thomas, A. W.] Biomed Primate Res Ctr, Dept Parasitol, NL-2280 GH Rijswijk, Netherlands.
   [Borgwardt, K.] Univ Cambridge, Dept Engn, Machine Learning Grp, Cambridge CB2 1PZ, England.
   [Clark, T. G.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 9BN, England.
   [Galinski, M. R.; Lapp, S.] Emory Univ, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Hall, N.] Univ Liverpool, Sch Biol Sci, Liverpool L69 3BX, Merseyside, England.
   [Janssen, C. S.; Turner, C. M. R.] Univ Glasgow, Inst Biomed & Life Sci, Glasgow G12 8TA, Lanark, Scotland.
   [Marti, M.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   [Meyer, I. M.] Univ British Columbia, UBC Bioinformat Ctr, Vancouver, BC V6T 1Z4, Canada.
   [Meyer, I. M.] Univ British Columbia, Dept Comp Sci, Vancouver, BC V6T 1Z4, Canada.
   [Meyer, I. M.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z4, Canada.
   [Sargeant, T. J.; Cowman, A. F.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia.
   [Sargeant, T. J.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
   [Newbold, C. I.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
C3 Wellcome Trust Sanger Institute; University of Copenhagen; University of Cambridge; University of Oxford; Wellcome Centre for Human Genetics; Emory University; University of Liverpool; University of Glasgow; Harvard University; Harvard T.H. Chan School of Public Health; University of British Columbia; University of British Columbia; University of British Columbia; Melbourne Health; Royal Melbourne Hospital; Walter & Eliza Hall Institute; University of Melbourne; University of Oxford
RP Pain, A (corresponding author), Wellcome Trust Sanger Inst, Genome Campus, Hinxton CB10 1SA, Cambs, England.
EM ap2@sanger.ac.uk
FU Wellcome Trust; Netherlands Organization for Scientific Research; NIH; BioMalPar; Virimal contract
NR 39
TC 296
Z9 368
U1 0
U2 27
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 799
EP U7
DI 10.1038/nature07306
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900047
PM 18843368
DA 2026-03-09
ER

PT J
AU Foster, MA
   Salem, R
   Geraghty, DF
   Turner-Foster, AC
   Lipson, M
   Gaeta, AL
AF Foster, Mark A.
   Salem, Reza
   Geraghty, David F.
   Turner-Foster, Amy C.
   Lipson, Michal
   Gaeta, Alexander L.
TI Silicon-chip-based ultrafast optical oscilloscope
SO NATURE
LA English
DT Article
ID conversion time microscope; group-velocity dispersion; wave-guides; wavelength conversion; pulse; interferometry; magnification; generation; systems; phase
AB With the realization of faster telecommunication data rates and an expanding interest in ultrafast chemical and physical phenomena, it has become important to develop techniques that enable simple measurements of optical waveforms with subpicosecond resolution(1). State- of- the- art oscilloscopes with high- speed photodetectors provide single- shot waveform measurement with 30- ps resolution. Although multiple- shot sampling techniques can achieve few- picosecond resolution, single- shot measurements are necessary to analyse events that are rapidly varying in time, asynchronous, or may occur only once. Further improvements in single- shot resolution are challenging, owing to microelectronic bandwidth limitations. To overcome these limitations, researchers have looked towards all- optical techniques because of the large processing bandwidths that photonics allow. This has generated an explosion of interest in the integration of photonics on standard electronics platforms, which has spawned the field of silicon photonics(2) and promises to enable the next generation of computer processing units and advances in high- bandwidth communications. For the success of silicon photonics in these areas, on- chip optical signal- processing for optical performance monitoring will prove critical. Beyond next- generation communications, siliconcompatible ultrafast metrology would be of great utility to many fundamental research fields, as evident from the scientific impact that ultrafast measurement techniques continue to make(3-5). Here, using time- to- frequency conversion(6) via the nonlinear process of four- wave mixing on a silicon chip, we demonstrate a waveform measurement technology within a silicon- photonic platform. We measure optical waveforms with 220- fs resolution over lengths greater than 100 ps, which represent the largest record- length- to-resolution ratio (> 450) of any single- shot- capable picosecond waveform measurement technique(6-16). Our implementation allows for single- shot measurements and uses only highly developed electronic and optical materials of complementary metal- oxide-semiconductor (CMOS)- compatible silicon- on- insulator technology and single- mode optical fibre. The mature silicon- on- insulator platform and the ability to integrate electronics with these CMOS-compatible photonics offer great promise to extend this technology into commonplace bench- top and chip- scale instruments.
C1 [Foster, Mark A.; Salem, Reza; Geraghty, David F.; Gaeta, Alexander L.] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
   [Turner-Foster, Amy C.; Lipson, Michal] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA.
C3 Cornell University; Cornell University
RP Gaeta, AL (corresponding author), Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
EM a.gaeta@cornell.edu
FU DARPA; NSF; New York State Office of Science, Technology and Academic Research
NR 30
TC 398
Z9 451
U1 3
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 81
EP U2
DI 10.1038/nature07430
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000044
PM 18987739
DA 2026-03-09
ER

PT J
AU Stallard, T
   Miller, S
   Melin, H
   Lystrup, M
   Cowley, SWH
   Bunce, EJ
   Achilleos, N
   Dougherty, M
AF Stallard, Tom
   Miller, Steve
   Melin, Henrik
   Lystrup, Makenzie
   Cowley, Stan W. H.
   Bunce, Emma J.
   Achilleos, Nicholas
   Dougherty, Michele
TI Jovian-like aurorae on Saturn
SO NATURE
LA English
DT Article
ID h-3(+) infrared-emission; ionosphere; field; oval; magnetosphere; thermosphere; temperature; dynamics
AB Planetary aurorae are formed by energetic charged particles streaming along the planet's magnetic field lines into the upper atmosphere from the surrounding space environment. Earth's main auroral oval is formed through interactions with the solar wind(1), whereas that at Jupiter is formed through interactions with plasma from the moon Io inside its magnetic field (although other processes form aurorae at both planets(2,3)). At Saturn, only the main auroral oval has previously been observed and there remains much debate over its origin. Here we report the discovery of a secondary oval at Saturn that is similar to 25 per cent as bright as the main oval, and we show this to be caused by interaction with the middle magnetosphere around the planet. This is a weak equivalent of Jupiter's main oval, its relative dimness being due to the lack of as large a source of ions as Jupiter's volcanic moon Io. This result suggests that differences seen in the auroral emissions from Saturn and Jupiter are due to scaling differences in the conditions at each of these two planets, whereas the underlying formation processes are the same.
C1 [Stallard, Tom; Cowley, Stan W. H.; Bunce, Emma J.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Miller, Steve; Lystrup, Makenzie; Achilleos, Nicholas] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Melin, Henrik] Space Environm Technol, Planetary & Space Sci Div, Pasadena, CA 91107 USA.
   [Dougherty, Michele] Univ London Imperial Coll Sci Technol & Med, Dept Phys, Space & Atmospher Phys Grp, London SW7 2BW, England.
C3 University of Leicester; University of London; University College London; Imperial College London
RP Stallard, T (corresponding author), Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
EM tss@ion.le.ac.uk
FU Science and Technology Facilities Council [PP/E000983/1] Funding Source: researchfish; STFC [PP/E000983/1] Funding Source: UKRI
NR 23
TC 44
Z9 48
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 JUN 19
PY 2008
VL 453
IS 7198
BP 1083
EP 1085
DI 10.1038/nature07077
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900052
PM 18563160
DA 2026-03-09
ER

PT J
AU Vinther, J
   Van Roy, P
   Briggs, DEG
AF Vinther, Jakob
   Van Roy, Peter
   Briggs, Derek E. G.
TI Machaeridians are Palaeozoic armoured annelids
SO NATURE
LA English
DT Article
AB The systematic affinities of several Palaeozoic skeletal taxa were only resolved when their soft- tissue morphology was revealed by the discovery of exceptionally preserved specimens. The conodonts provide a classic example, their tooth- like elements having been assigned to various invertebrate and vertebrate groups for more than 125 years until the discovery of their soft tissues revealed them to be crown- group vertebrates(1). Machaeridians, which are virtually ubiquitous as shell plates in benthic marine shelly assemblages ranging from Early Ordovician ( Late Tremadoc) to Carboniferous(2), have proved no less enigmatic. The Machaeridia comprise three distinct families of worm- like animals, united by the possession of a dorsal skeleton of calcite plates that is rarely found articulated. Since they were first described 150 years ago(3) machaeridians have been allied with barnacles(4,5), echinoderms(6,7), molluscs(3,8-10) or annelids(9,11,12). Here we describe a new machaeridian with preserved soft parts, including parapodia and chaetae, from the Upper Tremadoc of Morocco, demonstrating the annelid affinity of the group. This discovery shows that a lineage of annelids evolved a dorsal skeleton of calcareous plates early in their history; it also resolves the affinities of a group of problematic Palaeozoic invertebrates previously known only from isolated elements and occasional skeletal assemblages.
C1 [Vinther, Jakob; Briggs, Derek E. G.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Van Roy, Peter] Univ Ghent, Dept Soil Sci & Geol, B-9000 Ghent, Belgium.
C3 Yale University; Ghent University
RP Briggs, DEG (corresponding author), Yale Univ, Dept Geol & Geophys, POB 208109, New Haven, CT 06520 USA.
EM derek.briggs@yale.edu
NR 30
TC 98
Z9 106
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 JAN 10
PY 2008
VL 451
IS 7175
BP 185
EP 188
DI 10.1038/nature06474
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400041
PM 18185586
DA 2026-03-09
ER

PT J
AU Lim, KH
   Ancrile, BB
   Kashatus, DF
   Counter, CM
AF Lim, Kian-Huat
   Ancrile, Brooke B.
   Kashatus, David F.
   Counter, Christopher M.
TI Tumour maintenance is mediated by eNOS
SO NATURE
LA English
DT Article
ID nitric-oxide synthase; kappa-b kinase; protein s-nitrosylation; k-ras; n-ras; cell-lines; in-vivo; ha-ras; activation; cancer
AB Tumour cells become addicted to the expression of initiating oncogenes like Ras, such that loss of oncogene expression in established tumours leads to tumour regression(1). HRas, NRas or KRas are mutated to remain in the active GTP- bound oncogenic state in many cancers(2). Although Ras activates several proteins to initiate human tumour growth, only PI3K, through activation of protein kinase B ( PKB; also known as AKT), must remain activated by oncogenic Ras to maintain this growth63. Here we show that blocking phosphorylation of the AKT substrate, endothelial nitric oxide synthase ( eNOS or NOS3), inhibits tumour initiation and maintenance. Moreover, eNOS enhances the nitrosylation and activation of endogenous wild- type Ras proteins, which are required throughout tumorigenesis. We suggest that activation of the PI3K - AKT - eNOS -( wild- type) Ras pathway by oncogenic Ras in cancer cells is required to initiate and maintain tumour growth.
C1 [Lim, Kian-Huat; Ancrile, Brooke B.; Kashatus, David F.; Counter, Christopher M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Dept Radiat Oncol, Durham, NC 27710 USA.
C3 Duke University
RP Counter, CM (corresponding author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Dept Radiat Oncol, Durham, NC 27710 USA.
EM count004@mc.duke.edu
FU NCI NIH HHS [R01 CA123031, R01 CA094184] Funding Source: Medline
NR 34
TC 251
Z9 313
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 646
EP U11
DI 10.1038/nature06778
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200049
PM 18344980
DA 2026-03-09
ER

PT J
AU Lefèvre, F
   Bertaux, JL
   Clancy, RT
   Encrenaz, T
   Fast, K
   Forget, F
   Lebonnois, S
   Montmessin, F
   Perrier, S
AF Lefevre, Franck
   Bertaux, Jean-Loup
   Clancy, R. Todd
   Encrenaz, Therese
   Fast, Kelly
   Forget, Francois
   Lebonnois, Sebastien
   Montmessin, Franck
   Perrier, Severine
TI Heterogeneous chemistry in the atmosphere of Mars
SO NATURE
LA English
DT Article
ID martian atmosphere; water-vapor; interannual variability; ozone; spectroscopy; stability; aphelion; h2o2; photochemistry; abundance
AB Hydrogen radicals are produced in the martian atmosphere by the photolysis of water vapour and subsequently initiate catalytic cycles that recycle carbon dioxide from its photolysis product carbon monoxide(1,2). These processes provide a qualitative explanation for the stability of the atmosphere of Mars, which contains 95 per cent carbon dioxide. Balancing carbon dioxide production and loss based on our current understanding of the gas-phase chemistry in the martian atmosphere has, however, proven to be difficult(3-5). Interactions between gaseous chemical species and ice cloud particles have been shown to be key factors in the loss of polar ozone observed in the Earth's stratosphere(6), and may significantly perturb the chemistry of the Earth's upper troposphere(7). Water-ice clouds are also commonly observed in the atmosphere of Mars(8-10) and it has been suggested previously that heterogeneous chemistry could have an important impact on the composition of the martian atmosphere(3-5,11). Here we use a state-of-the- art general circulation model together with new observations of the martian ozone layer(12-15) to show that model simulations to much improved quantitative agreement with observed martian ozone levels in comparison with model simulations based on gas-phase chemistry alone. Ozone is readily destroyed by hydrogen radicals and is therefore a sensitive tracer of the chemistry that regulates the atmosphere of Mars. Our results suggest that heterogeneous chemistry on ice clouds plays an important role in controlling the stability and composition of the martian atmosphere.
C1 [Lefevre, Franck] Univ Paris 06, UPMC, Serv Aeron, F-75005 Paris, France.
   [Lefevre, Franck; Bertaux, Jean-Loup; Encrenaz, Therese; Forget, Francois; Lebonnois, Sebastien; Montmessin, Franck; Perrier, Severine] CNRS, INSU, F-75700 Paris, France.
   [Bertaux, Jean-Loup; Montmessin, Franck; Perrier, Severine] Univ Versailles St Quentin, Serv Aeron, F-91371 Verrieres Le Buisson, France.
   [Clancy, R. Todd] Space Sci Inst, Boulder, CO 80301 USA.
   [Encrenaz, Therese] Observ Paris, LESIA, F-92195 Meudon, France.
   [Fast, Kelly] NASA, Goddard Space Flight Ctr, Planetary Syst Lab, Greenbelt, MD 20771 USA.
   [Forget, Francois; Lebonnois, Sebastien] Univ Paris 06, UPMC, Meteorol Dynam Lab, F-75005 Paris, France.
C3 Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Saclay; Universite PSL; Observatoire de Paris; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Institut Polytechnique de Paris; Ecole Polytechnique; Sorbonne Universite
RP Lefèvre, F (corresponding author), Univ Paris 06, UPMC, Serv Aeron, F-75005 Paris, France.
EM franck.lefevre@aero.jussieu.fr
NR 30
TC 114
Z9 115
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 21
PY 2008
VL 454
IS 7207
BP 971
EP 975
DI 10.1038/nature07116
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000033
PM 18719584
DA 2026-03-09
ER

PT J
AU Yoshino, T
   Manthilake, G
   Matsuzaki, T
   Katsura, T
AF Yoshino, Takashi
   Manthilake, Geeth
   Matsuzaki, Takuya
   Katsura, Tomoo
TI Dry mantle transition zone inferred from the conductivity of wadsleyite and ringwoodite
SO NATURE
LA English
DT Article
ID electrical-conductivity; pacific-ocean; c-responses; beneath; water; olivine; hydrogen; region; phase
AB The Earth's mantle transition zone could potentially store a large amount of water, as the minerals wadsleyite and ringwoodite incorporate a significant amount of water in their crystal structure(1,2). The water content in the transition zone can be estimated from the electrical conductivities of hydrous wadsleyite and ringwoodite, although such estimates depend on accurate knowledge of the two conduction mechanisms in these minerals ( small polaron and proton conductions), which early studies have failed to distinguish between(3,4). Here we report the electrical conductivity of these two minerals obtained by high- pressure multi- anvil experiments. We found that the small polaron conductions of these minerals are substantially lower than previously estimated. The contributions of proton conduction are small at temperatures corresponding to the mantle transition zone and the conductivity of wadsleyite is considerably lower than that of ringwoodite for both mechanisms. The dry model mantle shows considerable conductivity jumps associated with the olivine- wadsleyite, wadsleyite- ringwoodite and post- spinel transitions. Such a dry model explains well the currently available conductivity- depth profiles(5) obtained from geoelectromagnetic studies. We therefore conclude that there is no need to introduce a significant amount of water in the mantle transition to satisfy electrical conductivity constraints.
C1 [Yoshino, Takashi; Manthilake, Geeth; Matsuzaki, Takuya; Katsura, Tomoo] Okayama Univ, Inst Study Earths Interior, Tottori 6820193, Japan.
C3 Okayama University
RP Yoshino, T (corresponding author), Okayama Univ, Inst Study Earths Interior, Tottori 6820193, Japan.
EM tyoshino@misasa.okayama-u.ac.jp
NR 24
TC 197
Z9 234
U1 6
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 326
EP 329
DI 10.1038/nature06427
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100048
PM 18202656
DA 2026-03-09
ER

PT J
AU Sytina, OA
   Heyes, DJ
   Hunter, CN
   Alexandre, MT
   van Stokkum, IHM
   van Grondelle, R
   Groot, ML
AF Sytina, Olga A.
   Heyes, Derren J.
   Hunter, C. Neil
   Alexandre, Maxime T.
   van Stokkum, Ivo H. M.
   van Grondelle, Rienk
   Groot, Marie Louise
TI Conformational changes in an ultrafast light-driven enzyme determine catalytic activity
SO NATURE
LA English
DT Article
ID protochlorophyllide oxidoreductase; dihydrofolate-reductase; dynamics; spectroscopy; chlorophyllide; identification; mutagenesis; complex; protein; nadph
AB The role of conformational changes in explaining the huge catalytic power of enzymes is currently one of the most challenging questions in biology(1-7). Although it is now widely regarded that enzymes modulate reaction rates by means of short- and long- range protein motions(3-7), it is almost impossible to distinguish between conformational changes and catalysis. We have solved this problem using the chlorophyll biosynthetic enzyme NADPH: protochlorophyllide ( Pchlide) oxidoreductase, which catalyses a unique light- driven reaction involving hydride and proton transfers(8). Here we report that prior excitation of the enzyme- substrate complex with a laser pulse induces a more favourable conformation of the active site, enabling the coupled hydride and proton transfer reactions to occur. This effect, which is triggered during the Pchlide excited-state lifetime and persists on a long timescale, switches the enzyme into an active state characterized by a high rate and quantum yield of formation of a catalytic intermediate. The corresponding spectral changes in the mid- infrared following the absorption of one photon reveal significant conformational changes in the enzyme, illustrating the importance of flexibility and dynamics in the structure of enzymes for their function.
C1 [Hunter, C. Neil] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England.
   [Sytina, Olga A.; Alexandre, Maxime T.; van Stokkum, Ivo H. M.; van Grondelle, Rienk; Groot, Marie Louise] Vrije Univ Amsterdam, Dept Phys & Astron, Fac Sci, NL-1081 HV Amsterdam, Netherlands.
   [Heyes, Derren J.] Univ Manchester, Manchester Interdisciplinary Bioctr, Manchester M1 7DN, Lancs, England.
C3 University of Sheffield; Vrije Universiteit Amsterdam; University of Manchester
RP Hunter, CN (corresponding author), Univ Sheffield, Dept Mol Biol & Biotechnol, Firth Court, Sheffield S10 2TN, S Yorkshire, England.
EM c.n.hunter@sheffield.ac.uk
FU The Netherlands Organization for Scientific Research; Dutch Foundation for Earth and Life Sciences [834.01.002]; NWO-ALW [831.00.004]; NWO-CW [700.53.307]; Biotechnology and Biological Sciences Research Council, UK
NR 31
TC 117
Z9 127
U1 0
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 1001
EP U89
DI 10.1038/nature07354
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300057
PM 19092933
DA 2026-03-09
ER

PT J
AU Lin, YX
   Bloodgood, BL
   Hauser, JL
   Lapan, AD
   Koon, AC
   Kim, TK
   Hu, LS
   Malik, AN
   Greenberg, ME
AF Lin, Yingxi
   Bloodgood, Brenda L.
   Hauser, Jessica L.
   Lapan, Ariya D.
   Koon, Alex C.
   Kim, Tae-Kyung
   Hu, Linda S.
   Malik, Athar N.
   Greenberg, Michael E.
TI Activity-dependent regulation of inhibitory synapse development by Npas4
SO NATURE
LA English
DT Article
ID neurotrophic factor; critical period; mice deficient; 65-kda isoform; visual-cortex; plasticity; transcription; expression; genes; mouse
AB Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity- dependent development of GABA (gamma-aminobutyric acid)- releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity- dependent genes, which in turn control the number of GABA- releasing synapses that form on excitatory neurons. These findings demonstrate that the activity- dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.
C1 [Lin, Yingxi; Bloodgood, Brenda L.; Hauser, Jessica L.; Koon, Alex C.; Kim, Tae-Kyung; Hu, Linda S.; Malik, Athar N.; Greenberg, Michael E.] Harvard Univ, Sch Med, FM Kirby Neurobiol Ctr, Childrens Hosp, Boston, MA 02115 USA.
   [Lin, Yingxi; Bloodgood, Brenda L.; Hauser, Jessica L.; Koon, Alex C.; Kim, Tae-Kyung; Hu, Linda S.; Malik, Athar N.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
   [Lin, Yingxi; Bloodgood, Brenda L.; Hauser, Jessica L.; Koon, Alex C.; Kim, Tae-Kyung; Hu, Linda S.; Malik, Athar N.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Lapan, Ariya D.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA.
   [Malik, Athar N.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP Greenberg, ME (corresponding author), Harvard Univ, Sch Med, FM Kirby Neurobiol Ctr, Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
EM meg@hms.harvard.edu
FU F. M. Kirby Foundation to the Neurobiology Program of the Children's Hospital; Nancy Lurie Marks Family Foundation; Lefler Foundation postdoctoral fellowship; Ruth L. Kirschstein National Research Service Award; Helen Hay Whitney postdoctoral fellowship; National Science Foundation Graduate Research Fellowship; Jane Coffin Childs Memorial Fund; Mental Retardation Research Center [HD18655]; National Institutes of Health [NS27572, NS48276]; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 50
TC 487
Z9 619
U1 1
U2 61
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1198
EP U23
DI 10.1038/nature07319
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100035
PM 18815592
DA 2026-03-09
ER

PT J
AU Towers, M
   Mahood, R
   Yin, YL
   Tickle, C
AF Towers, Matthew
   Mahood, Ruth
   Yin, Yili
   Tickle, Cheryll
TI Integration of growth and specification in chick wing digit-patterning
SO NATURE
LA English
DT Article
ID sonic-hedgehog; cell-cycle; limb bud; positional information; anteroposterior axis; valproic acid
AB In the classical model of chick wing digit- patterning(1), the polarizing region - a group of cells at the posterior margin of the early bud - produces a morphogen gradient, now known to be based on Sonic hedgehog (Shh)(2,3), that progressively specifies anteroposterior positional identities in the posterior digit- forming region(4). Here we add an integral growth component to this model by showing that Shh- dependent proliferation of prospective digit progenitor cells is essential for specifying the complete pattern of digits across the anteroposterior axis. Inhibiting Shh signalling in early wing buds reduced anteroposterior expansion, and posterior digits were lost because all prospective digit precursors formed anterior structures. Inhibiting proliferation also irreversibly reduced anteroposterior expansion, but instead anterior digits were lost because all prospective digit precursors formed posterior structures. When proliferation recovered in such wings, Shh transcription was maintained for longer than normal, suggesting that duration of Shh expression is controlled by a mechanism that measures proliferation. Rescue experiments confirmed that Shh- dependent proliferation controls digit number during a discrete time- window in which Shh- dependent specification normally occurs. Our findings that Shh signalling has dual functions that can be temporally uncoupled have implications for understanding congenital and evolutionary digit reductions.
C1 [Towers, Matthew; Mahood, Ruth; Yin, Yili; Tickle, Cheryll] Univ Dundee, Dept Dev & Cell Biol, Dundee DD1 5EH, Scotland.
C3 University of Dundee
RP Tickle, C (corresponding author), Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England.
EM cat24@bath.ac.uk
FU MRC [G9806660] Funding Source: UKRI; Medical Research Council [G9806660] Funding Source: researchfish; Medical Research Council [G9806660] Funding Source: Medline
NR 30
TC 174
Z9 205
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 APR 17
PY 2008
VL 452
IS 7189
BP 882
EP U7
DI 10.1038/nature06718
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000050
PM 18354396
DA 2026-03-09
ER

PT J
AU Zerrouki, D
   Baudry, J
   Pine, D
   Chaikin, P
   Bibette, J
AF Zerrouki, D.
   Baudry, J.
   Pine, D.
   Chaikin, P.
   Bibette, J.
TI Chiral colloidal clusters
SO NATURE
LA English
DT Article
ID particles; growth
AB Chirality is an important element of biology, chemistry and physics. Once symmetry is broken and a handedness is established, biochemical pathways are set. In DNA, the double helix arises from the existence of two competing length scales, one set by the distance between monomers in the sugar backbone, and the other set by the stacking of the base pairs(1). Here we use a colloidal system to explore a simple forcing route to chiral structures. To do so we have designed magnetic colloids that, depending on both their shape and induced magnetization, self- assemble with controlled helicity. We model the two length scales with asymmetric colloidal dumbbells linked by a magnetic belt at their waist. In the presence of a magnetic field the belts assemble into a chain and the steric constraints imposed by the asymmetric spheres force the chain to coil. We show that if the size ratio between the spheres is large enough, a single helicity is adopted, right or left. The realization of chiral colloidal clusters opens up a new link between colloidal science and chemistry. These colloidal clusters may also find use as mesopolymers, as optical and light- activated structures(2), and as models for enantiomeric separation.
C1 [Zerrouki, D.; Baudry, J.; Bibette, J.] UPMC, CNRS, ESPCI, Lab Colloides & Mat Divises, F-75005 Paris, France.
   [Pine, D.; Chaikin, P.] NYU, Dept Phys, Ctr Soft Matter Res, New York, NY 10003 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); New York University
RP Bibette, J (corresponding author), UPMC, CNRS, ESPCI, Lab Colloides & Mat Divises, 10 Rue Vauquelin, F-75005 Paris, France.
EM jerome.bibette@espci.fr
NR 15
TC 323
Z9 382
U1 3
U2 238
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 380
EP 382
DI 10.1038/nature07237
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200042
PM 18800136
DA 2026-03-09
ER

PT J
AU Moore, CB
   Bergstralh, DT
   Duncan, JA
   Lei, Y
   Morrison, TE
   Zimmermann, AG
   Accavitti-Loper, MA
   Madden, VJ
   Sun, LJ
   Ye, ZM
   Lich, JD
   Heise, MT
   Chen, ZJ
   Ting, JPY
AF Moore, Chris B.
   Bergstralh, Daniel T.
   Duncan, Joseph A.
   Lei, Yu
   Morrison, Thomas E.
   Zimmermann, Albert G.
   Accavitti-Loper, Mary A.
   Madden, Victoria J.
   Sun, Lijun
   Ye, Zhengmao
   Lich, John D.
   Heise, Mark T.
   Chen, Zhijian
   Ting, Jenny P-Y.
TI NLRX1 is a regulator of mitochondrial antiviral immunity
SO NATURE
LA English
DT Article
ID nf-kappa-b; rig-i; adapter protein; lrr proteins; responses; caterpiller; family; defense; pathway; signals
AB The RIG- like helicase ( RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS ( also known as Cardif, VISA and IPS- 1) during a viral infection(1-6). MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interferons. Although MAVS is vital to antiviral immunity, its regulation from within the mitochondria remains unknown. Here we describe human NLRX1, a highly conserved nucleotide- binding domain ( NBD)- and leucine- rich- repeat ( LRR)- containing family member ( known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS- mediated interferon-beta promoter activity and in the disruption of virus- induced RLH-MAVS interactions. Depletion of NLRX1 with small interference RNA promotes virus- induced type I interferon production and decreases viral replication. This work identifies NLRX1 as a check against mitochondrial antiviral responses and represents an intersection of three ancient cellular processes: NLR signalling, intracellular virus detection and the use of mitochondria as a platform for anti- pathogen signalling. This represents a conceptual advance, in that NLRX1 is a modulator of pathogen- associated molecular pattern receptors rather than a receptor, and identifies a key therapeutic target for enhancing antiviral responses.
C1 [Moore, Chris B.; Lei, Yu; Zimmermann, Albert G.; Ye, Zhengmao; Lich, John D.; Ting, Jenny P-Y.] Univ N Carolina, Dept Microbiol Immunol, Chapel Hill, NC 27599 USA.
   [Moore, Chris B.; Bergstralh, Daniel T.; Lei, Yu; Zimmermann, Albert G.; Ye, Zhengmao; Lich, John D.; Ting, Jenny P-Y.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Duncan, Joseph A.] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC 27599 USA.
   [Morrison, Thomas E.; Heise, Mark T.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Morrison, Thomas E.; Heise, Mark T.] Univ N Carolina, Carolina Vaccine Inst, Chapel Hill, NC 27599 USA.
   [Madden, Victoria J.] Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA.
   [Accavitti-Loper, Mary A.] Univ Alabama, Birmingham, AL 35294 USA.
   [Sun, Lijun; Chen, Zhijian] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Howard Hughes Med Inst, Dallas, TX 75390 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of Alabama System; University of Alabama Birmingham; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute
RP Ting, JPY (corresponding author), Univ N Carolina, Dept Microbiol Immunol, Chapel Hill, NC 27599 USA.
EM jenny_ting@med.unc.edu
NR 25
TC 486
Z9 577
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 573
EP U8
DI 10.1038/nature06501
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900042
PM 18200010
DA 2026-03-09
ER

PT J
AU Sandoval, H
   Thiagarajan, P
   Dasgupta, SK
   Schumacher, A
   Prchal, JT
   Chen, M
   Wang, J
AF Sandoval, Hector
   Thiagarajan, Perumal
   Dasgupta, Swapan K.
   Schumacher, Armin
   Prchal, Josef T.
   Chen, Min
   Wang, Jin
TI Essential role for Nix in autophagic maturation of erythroid cells
SO NATURE
LA English
DT Article
ID in-vitro; mice; apoptosis; survival; reticulocytes; erythroblasts; mitochondria; phosphatidylserine; erythropoiesis; inhibitor
AB Erythroid cells undergo enucleation and the removal of organelles during terminal differentiation(1-3). Although autophagy has been suggested to mediate the elimination of organelles for erythroid maturation(2-6), the molecular mechanisms underlying this process remain undefined. Here we report a role for a Bcl- 2 family member, Nix ( also called Bnip3L)(7-9), in the regulation of erythroid maturation through mitochondrial autophagy. Nix(-/-) mice developed anaemia with reduced mature erythrocytes and compensatory expansion of erythroid precursors. Erythrocytes in the peripheral blood of Nix(-/-) mice exhibited mitochondrial retention and reduced lifespan in vivo. Although the clearance of ribosomes proceeded normally in the absence of Nix, the entry of mitochondria into autophagosomes for clearance was defective. Deficiency in Nix inhibited the loss of mitochondrial membrane potential (Delta Psi(m)), and treatment with uncoupling chemicals or a BH3 mimetic induced the loss of Delta Psi(m) and restored the sequestration of mitochondria into autophagosomes in Nix(-/-) erythroid cells. These results suggest that Nix- dependent loss of Delta Psi(m) is important for targeting the mitochondria into autophagosomes for clearance during erythroid maturation, and interference with this function impairs erythroid maturation and results in anaemia. Our study may also provide insights into molecular mechanisms underlying mitochondrial quality control involving mitochondrial autophagy.
C1 [Sandoval, Hector; Chen, Min; Wang, Jin] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA.
   [Thiagarajan, Perumal; Dasgupta, Swapan K.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
   [Schumacher, Armin] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Prchal, Josef T.] Univ Utah, Sch Med, Div Hematol, Salt Lake City, UT 84132 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Utah System of Higher Education; University of Utah
RP Chen, M (corresponding author), Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA.
EM minc@bcm.tmc.edu; jinwang@bcm.tmc.edu
FU NIAID NIH HHS [F31 AI058932, R01 AI074949, R01 AI056210] Funding Source: Medline; NIGMS NIH HHS [R01 GM087710] Funding Source: Medline
NR 32
TC 991
Z9 1152
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 JUL 10
PY 2008
VL 454
IS 7201
BP 232
EP U66
DI 10.1038/nature07006
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900047
PM 18454133
DA 2026-03-09
ER

PT J
AU Koglin, A
   Löhr, F
   Bernhard, F
   Rogov, VV
   Frueh, DP
   Strieter, ER
   Mofid, MR
   Güntert, P
   Wagner, G
   Walsh, CT
   Marahiel, MA
   Dötsch, V
AF Koglin, Alexander
   Loehr, Frank
   Bernhard, Frank
   Rogov, Vladimir V.
   Frueh, Dominique P.
   Strieter, Eric R.
   Mofid, Mohammad R.
   Guentert, Peter
   Wagner, Gerhard
   Walsh, Christopher T.
   Marahiel, Mohamed A.
   Doetsch, Volker
TI Structural basis for the selectivity of the external thioesterase of the surfactin synthetase
SO NATURE
LA English
DT Article
ID acyl carrier protein; peptide synthetases; chemical-shift; polyketide; biosynthesis; macrocyclization; restraints; dynamics; synthase; database
AB Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) found in bacteria, fungi and plants use two different types of thioesterases for the production of highly active biological compounds(1,2). Type I thioesterases (TEI) catalyse the release step from the assembly line(3) of the final product where it is transported from one reaction centre to the next as a thioester linked to a 4 '-phosphopantetheine (4 '-PP) cofactor that is covalently attached to thiolation (T) domains(4-9). The second enzyme involved in the synthesis of these secondary metabolites, the type II thioesterase (TEII), is a crucial repair enzyme for the regeneration of functional 4 '-PP cofactors of holo-T domains of NRPS and PKS systems(10-12). Mispriming of 4 '-PP cofactors by acetyl- and short-chain acyl-residues interrupts the biosynthetic system. This repair reaction is very important, because roughly 80% of CoA, the precursor of the 4 '-PP cofactor, is acetylated in bacteria(13). Here we report the three-dimensional structure of a type II thioesterase from Bacillus subtilis free and in complex with a T domain. Comparison with structures of TEI enzymes(3,14) shows the basis for substrate selectivity and the different modes of interaction of TEII and TEI enzymes with T domains. Furthermore, we show that the TEII enzyme exists in several conformations of which only one is selected on interaction with its native substrate, a modified holo-T domain.
C1 [Koglin, Alexander; Loehr, Frank; Bernhard, Frank; Rogov, Vladimir V.; Guentert, Peter; Doetsch, Volker] Goethe Univ Frankfurt, Inst Biophys Chem, D-60438 Frankfurt, Germany.
   [Koglin, Alexander; Loehr, Frank; Bernhard, Frank; Rogov, Vladimir V.; Guentert, Peter; Doetsch, Volker] Goethe Univ Frankfurt, Ctr Biomol Magnet Resonance & Cluster Excellence, D-60438 Frankfurt, Germany.
   [Koglin, Alexander; Frueh, Dominique P.; Strieter, Eric R.; Wagner, Gerhard; Walsh, Christopher T.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Rogov, Vladimir V.] Russian Acad Sci, Inst Prot Res, Pushchino 142290, Russia.
   [Mofid, Mohammad R.; Marahiel, Mohamed A.] Univ Marburg, Dept Chem Biochem, D-35032 Marburg, Germany.
   [Guentert, Peter] Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany.
C3 Goethe University Frankfurt; Goethe University Frankfurt; Harvard University; Harvard Medical School; Russian Academy of Sciences; Philipps University Marburg
RP Dötsch, V (corresponding author), Goethe Univ Frankfurt, Inst Biophys Chem, D-60438 Frankfurt, Germany.
EM Christopher_Walsh@hms.harvard.edu; Marahiel@chemie.uni-marburg.de; VDoetsch@em.uni-frankfurt.de
FU NIAID NIH HHS [R01 AI042738] Funding Source: Medline; NIBIB NIH HHS [P41 EB002026] Funding Source: Medline; NIGMS NIH HHS [P01 GM047467, R01 GM020011, R01 GM049338] Funding Source: Medline
NR 40
TC 119
Z9 155
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 AUG 14
PY 2008
VL 454
IS 7206
BP 907
EP U68
DI 10.1038/nature07161
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600041
PM 18704089
DA 2026-03-09
ER

PT J
AU González-José, R
   Escapa, I
   Neves, WA
   Cúneo, R
   Pucciarelli, HM
AF Gonzalez-Jose, Rolando
   Escapa, Ignacio
   Neves, Walter A.
   Cuneo, Ruben
   Pucciarelli, Hector M.
TI Cladistic analysis of continuous modularized traits provides phylogenetic signals in Homo evolution
SO NATURE
LA English
DT Article
ID integration; characters
AB Evolutionary novelties in the skeleton are usually expressed as changes in the timing of growth of features intrinsically integrated at different hierarchical levels of development(1). As a consequence, most of the shape- traits observed across species do vary quantitatively rather than qualitatively(2), in a multivariate space(3) and in a modularized way(4,5). Because most phylogenetic analyses normally use discrete, hypothetically independent characters(6), previous attempts have disregarded the phylogenetic signals potentially enclosed in the shape of morphological structures. When analysing low taxonomic levels, where most variation is quantitative in nature, solving basic requirements like the choice of characters and the capacity of using continuous, integrated traits is of crucial importance in recovering wider phylogenetic information. This is particularly relevant when analysing extinct lineages, where available data are limited to fossilized structures. Here we show that when continuous, multivariant and modularized characters are treated as such, cladistic analysis successfully solves relationships among main Homo taxa. Our attempt is based on a combination of cladistics, evolutionary- development- derived selection of characters, and geometric morphometrics methods. In contrast with previous cladistic analyses of hominid phylogeny, our method accounts for the quantitative nature of the traits, and respects their morphological integration patterns. Because complex phenotypes are observable across different taxonomic groups and are potentially informative about phylogenetic relationships, future analyses should point strongly to the incorporation of these types of trait.
C1 [Gonzalez-Jose, Rolando] Consejo Nacl Invest Cient & Tecn, Unidad Invest Divers Sistemat & Evoluc, Ctr Nacl Patagonico, Consejo Nacl Invest Cient & Tecn, Puerto Madryn, Argentina.
   [Escapa, Ignacio; Cuneo, Ruben] Consejo Nacl Invest Cient & Tecn, Museo Paleontol Egidio Feruglio, Consejo Nacl Invest Cient & Tecn, Trelew, Argentina.
   [Neves, Walter A.] Univ Sao Paulo, Lab Estud Evolut Humanos, Dept Genet & Biol Evolut, Inst Biociencias, BR-05422970 Sao Paulo, Brazil.
   [Pucciarelli, Hector M.] Natl Univ La Plata, Consejo Nacl Invest Cient & Tecn, CONICET, Dept Cientifico Antropol Museo La Plata, RA-1900 La Plata, Argentina.
C3 Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Centro Nacional Patagonico (CENPAT); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Universidade de Sao Paulo; National University of La Plata; Museo La Plata; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
RP González-José, R (corresponding author), Consejo Nacl Invest Cient & Tecn, Unidad Invest Divers Sistemat & Evoluc, Ctr Nacl Patagonico, Consejo Nacl Invest Cient & Tecn, Blvd Brown 2825,U9120ACF, Puerto Madryn, Argentina.
EM rolando@cenpat.edu.ar
NR 31
TC 79
Z9 101
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2008
VL 453
IS 7196
BP 775
EP U4
DI 10.1038/nature06891
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300042
PM 18454137
DA 2026-03-09
ER

PT J
AU Dong, XP
   Cheng, XP
   Mills, E
   Delling, M
   Wang, FD
   Kurz, T
   Xu, HX
AF Dong, Xian-Ping
   Cheng, Xiping
   Mills, Eric
   Delling, Markus
   Wang, Fudi
   Kurz, Tino
   Xu, Haoxing
TI The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel
SO NATURE
LA English
DT Article
ID receptor potential channel; membrane-protein; mutations; metabolism; pathway; disease; mice; skin
AB TRPML1 ( mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential ( TRP) proteins(1-3). Mutations in the human TRPML1 gene cause mucolipidosis type IV disease ( ML4)4,5.ML4 patients have motor impairment, mental retardation, retinal degeneration and iron- deficiency anaemia. Because aberrant iron metabolism may cause neural and retinal degeneration(6,7), it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes after iron uptake by endocytosis of Fe(3+)- bound transferrin receptors(6), or after lysosomal degradation of ferritin - iron complexes and autophagic ingestion of iron-containing macromolecules(6,8), is the chief source of cellular iron. The divalent metal transporter protein DMT1 ( also known as SLC11A2) is the only endosomal Fe(2+) transporter known at present and it is highly expressed in erythroid precursors(6,9). Genetic studies, however, suggest the existence of a DMT1-independent endosomal and lysosomal Fe(2+) transport protein(9). By measuring radiolabelled iron uptake, by monitoring the levels of cytosolic and intralysosomal iron and by directly patch- clamping the late endosomal and lysosomal membrane, here we show that TRPML1 functions as a Fe(2+) permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair the ability of TRPML1 to permeate Fe(2+) at varying degrees, which correlate well with the disease severity. A comparison of TRPML1(-/-) ML4 and control human skin fibroblasts showed a reduction in cytosolic Fe(2+) levels, an increase in intralysosomal Fe(2+) levels and an accumulation of lipofuscin- like molecules in TRPML1(-/-) cells. We propose that TRPML1 mediates a mechanism by which Fe(2+) is released from late endosomes and lysosomes. Our results indicate that impaired iron transportmay contribute to both haematological and degenerative symptoms of ML4 patients.
C1 [Dong, Xian-Ping; Cheng, Xiping; Mills, Eric; Xu, Haoxing] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA.
   [Delling, Markus] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
   [Wang, Fudi] Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
   [Kurz, Tino] Linkoping Univ, Dept Pharmacol, Fac Hlth Sci, S-58185 Linkoping, Sweden.
C3 University of Michigan System; University of Michigan; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Chinese Academy of Sciences; Linkoping University
RP Xu, HX (corresponding author), Univ Michigan, Dept Mol Cellular & Dev Biol, 3089 Nat Sci Bldg Kraus,830 N Univ, Ann Arbor, MI 48109 USA.
EM haoxingx@umich.edu
FU Department of Molecular, Cellular; Developmental Biology and Biological Science Scholar Program; University of Michigan; National Heart Lung and Blood Institute [T32HL007572] Funding Source: NIH RePORTER
NR 25
TC 482
Z9 561
U1 0
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 992
EP U78
DI 10.1038/nature07311
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300056
PM 18794901
DA 2026-03-09
ER

PT J
AU Takashima, S
   Mkrtchyan, M
   Younossi-Hartenstein, A
   Merriam, JR
   Hartenstein, V
AF Takashima, Shigeo
   Mkrtchyan, Marianna
   Younossi-Hartenstein, Amelia
   Merriam, John R.
   Hartenstein, Volker
TI The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling
SO NATURE
LA English
DT Article
ID small-intestine; expression; hedgehog; differentiation; epithelium; pattern; midgut; fates
AB The intestinal tract maintains proper function by replacing aged cells with freshly produced cells that arise from a population of self-renewing intestinal stem cells ( ISCs). In the mammalian intestine, ISC self renewal, amplification and differentiation take place along the crypt - villus axis, and are controlled by the Wnt and hedgehog ( Hh) signalling pathways(1). However, little is known about the mechanisms that specify ISCs within the developing intestinal epithelium, or about the signalling centres that help maintain them in their self- renewing stem cell state. Here we show that in adult Drosophila melanogaster, ISCs of the posterior intestine ( hindgut) are confined to an anterior narrow segment, which we name the hindgut proliferation zone ( HPZ). Within the HPZ, self renewal of ISCs, as well as subsequent proliferation and differentiation of ISC descendants, are controlled by locally emanating Wingless ( Wg, a Drosophila Wnt homologue) and Hh signals. The anteriorly restricted expression of Wg in the HPZ acts as a niche signal that maintains cells in a slow- cycling, self- renewing mode. As cells divide and move posteriorly away from the Wg source, they enter a phase of rapid proliferation. During this phase, Hh signal is required for exiting the cell cycle and the onset of differentiation. The HPZ, with its characteristic proliferation dynamics and signalling properties, is set up during the embryonic phase and becomes active in the larva, where it generates all adult hindgut cells including ISCs. The mechanism and genetic control of cell renewal in the Drosophila HPZ exhibits a large degree of similarity with what is seen in the mammalian intestine. Our analysis of the Drosophila HPZ provides an insight into the specification and control of stem cells, highlighting the way in which the spatial pattern of signals that promote self renewal, growth and differentiation is set up within a genetically tractable model system.
C1 [Takashima, Shigeo; Mkrtchyan, Marianna; Younossi-Hartenstein, Amelia; Merriam, John R.; Hartenstein, Volker] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles
RP Hartenstein, V (corresponding author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
EM volkerh@mcdb.ucla.edu
NR 20
TC 156
Z9 194
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 651
EP U58
DI 10.1038/nature07156
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500050
PM 18633350
DA 2026-03-09
ER

PT J
AU Boukai, AI
   Bunimovich, Y
   Tahir-Kheli, J
   Yu, JK
   Goddard, WA
   Heath, JR
AF Boukai, Akram I.
   Bunimovich, Yuri
   Tahir-Kheli, Jamil
   Yu, Jen-Kan
   Goddard, William A., III
   Heath, James R.
TI Silicon nanowires as efficient thermoelectric materials
SO NATURE
LA English
DT Article
ID thermal-conductivity; phonon drag; power; transport; figure
AB Thermoelectric materials interconvert thermal gradients and electric fields for power generation or for refrigeration(1,2). Thermoelectrics currently find only niche applications because of their limited efficiency, which is measured by the dimensionless parameter ZT - a function of the Seebeck coefficient or thermoelectric power, and of the electrical and thermal conductivities. Maximizing ZT is challenging because optimizing one physical parameter often adversely affects another(3). Several groups have achieved significant improvements in ZT through multi- component nanostructured thermoelectrics(4-6), such as Bi2Te3/Sb2Te3 thin- film superlattices, or embedded PbSeTe quantum dot superlattices. Here we report efficient thermoelectric performance from the single- component system of silicon nanowires for cross- sectional areas of 10 nm x 20 nm and 20 nm x 20 nm. By varying the nanowire size and impurity doping levels, ZT values representing an approximately 100- fold improvement over bulk Si are achieved over a broad temperature range, including ZT approximate to 1 at 200 K. Independent measurements of the Seebeck coefficient, the electrical conductivity and the thermal conductivity, combined with theory, indicate that the improved efficiency originates from phonon effects. These results are expected to apply to other classes of semiconductor nanomaterials.
C1 [Boukai, Akram I.; Bunimovich, Yuri; Tahir-Kheli, Jamil; Yu, Jen-Kan; Goddard, William A., III; Heath, James R.] CALTECH, Div Chem & Chem Engn, MC 127-72,1200 E Calif Blvd, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Heath, JR (corresponding author), CALTECH, Div Chem & Chem Engn, MC 127-72,1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM heath@caltech.edu
NR 30
TC 2481
Z9 2864
U1 9
U2 1602
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 168
EP 171
DI 10.1038/nature06458
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400037
PM 18185583
DA 2026-03-09
ER

PT J
AU Elmen, J
   Lindow, M
   Schütz, S
   Lawrence, M
   Petri, A
   Obad, S
   Lindholm, M
   Hedtjärn, M
   Hansen, HF
   Berger, U
   Gullans, S
   Kearney, P
   Sarnow, P
   Straarup, EM
   Kauppinen, S
AF Elmen, Joacim
   Lindow, Morten
   Schutz, Sylvia
   Lawrence, Matthew
   Petri, Andreas
   Obad, Susanna
   Lindholm, Marie
   Hedtjarn, Maj
   Hansen, Henrik Frydenlund
   Berger, Urs
   Gullans, Steven
   Kearney, Phil
   Sarnow, Peter
   Straarup, Ellen Marie
   Kauppinen, Sakari
TI LNA-mediated microRNA silencing in non-human primates
SO NATURE
LA English
DT Article
ID animal development; in-vivo; specificity; modulation; expression
AB microRNAs ( miRNAs) are small regulatory RNAs that are important in development and disease(1-3) and therefore represent a potential new class of targets for therapeutic intervention(4). Despite recent progress in silencing of miRNAs in rodents(5,6), the development of effective and safe approaches for sequence-specific antagonism of miRNAs in vivo remains a significant scientific and therapeutic challenge. Moreover, there are no reports of miRNA antagonism in primates. Here we show that the simple systemic delivery of a unconjugated, PBS- formulated locked- nucleic- acid- modified oligonucleotide ( LNA- antimiR) effectively antagonizes the liver- expressed miR- 122 in non- human primates. Acute administration by intravenous injections of 3 or 10 mg kg(-1) LNA- antimiR to African green monkeys resulted in uptake of the LNA- antimiR in the cytoplasm of primate hepatocytes and formation of stable heteroduplexes between the LNA-antimiR and miR- 122. This was accompanied by depletion of mature miR- 122 and dose- dependent lowering of plasma cholesterol. Efficient silencing of miR- 122 was achieved in primates by three doses of 10 mg kg(-1) LNA- antimiR, leading to a long- lasting and reversible decrease in total plasma cholesterol without any evidence for LNA- associated toxicities or histopathological changes in the study animals. Our findings demonstrate the utility of systemically administered LNA- antimiRs in exploring miRNA function in rodents and primates, and support the potential of these compounds as a new class of therapeutics for disease-associated miRNAs.
C1 [Elmen, Joacim; Lindow, Morten; Petri, Andreas; Obad, Susanna; Lindholm, Marie; Hedtjarn, Maj; Kearney, Phil; Straarup, Ellen Marie; Kauppinen, Sakari] Santaris Pharma, DK-2970 Horsholm, Denmark.
   [Schutz, Sylvia; Sarnow, Peter] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
   [Lawrence, Matthew; Gullans, Steven] RxGen Inc, Hamden, CT 06517 USA.
   [Berger, Urs] UB In situ, Natick, MA 01760 USA.
   [Kauppinen, Sakari] Univ Copenhagen, Dept Cellular & Mol Med, Wilhelm Johannsen Ctr Funct Genome Res, DK-2200 Copenhagen N, Denmark.
C3 Stanford University; University of Copenhagen
RP Kauppinen, S (corresponding author), Santaris Pharma, Boge Allee 3, DK-2970 Horsholm, Denmark.
EM sk@santaris.com
NR 25
TC 1373
Z9 1641
U1 1
U2 165
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 17
PY 2008
VL 452
IS 7189
BP 896
EP U10
DI 10.1038/nature06783
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000053
PM 18368051
DA 2026-03-09
ER

PT J
AU Gutnisky, DA
   Dragoi, V
AF Gutnisky, Diego A.
   Dragoi, Valentin
TI Adaptive coding of visual information in neural populations
SO NATURE
LA English
DT Article
ID orientation discrimination; rapid adaptation; firing rate; cortex; transmission; variability; statistics; synchrony; dynamics; macaque
AB Our perception of the environment relies on the capacity of neural networks to adapt rapidly to changes in incoming stimuli(1-4). It is increasingly being realized that the neural code is adaptive(5), that is, sensory neurons change their responses and selectivity in a dynamic manner to match the changes in input stimuli(1,2,5). Understanding how rapid exposure, or adaptation, to a stimulus of fixed structure changes information processing by cortical networks is essential for understanding the relationship between sensory coding and behaviour(5-8). Physiological investigations of adaptation have contributed greatly to our understanding of how individual sensory neurons change their responses to influence stimulus coding(2,9-12), yet whether and how adaptation affects information coding in neural populations is unknown. Here we examine how brief adaptation ( on the timescale of visual fixation)(2,9,10) influences the structure of interneuronal correlations and the accuracy of population coding in the macaque ( Macaca mulatta) primary visual cortex ( V1). We find that brief adaptation to a stimulus of fixed structure reorganizes the distribution of correlations across the entire network by selectively reducing their mean and variability. The post- adaptation changes in neuronal correlations are associated with specific, stimulus- dependent changes in the efficiency of the population code, and are consistent with changes in perceptual performance after adaptation(2,13,14). Our results have implications beyond the predictions of current theories of sensory coding, suggesting that brief adaptation improves the accuracy of population coding to optimize neuronal performance during natural viewing.
C1 [Gutnisky, Diego A.; Dragoi, Valentin] Univ Texas Houston, Sch Med, Dept Neurobiol & Anat, Houston, TX 77030 USA.
C3 University of Texas System; University of Texas Health Science Center Houston
RP Dragoi, V (corresponding author), Univ Texas Houston, Sch Med, Dept Neurobiol & Anat, Houston, TX 77030 USA.
EM v.dragoi@uth.tmc.edu
NR 32
TC 241
Z9 302
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 13
PY 2008
VL 452
IS 7184
BP 220
EP U63
DI 10.1038/nature06563
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600041
PM 18337822
DA 2026-03-09
ER

PT J
AU Likhtik, E
   Popa, D
   Apergis-Schoute, J
   Fidacaro, GA
   Paré, D
AF Likhtik, Ekaterina
   Popa, Daniela
   Apergis-Schoute, John
   Fidacaro, George A., Jr.
   Pare, Denis
TI Amygdala intercalated neurons are required for expression of fear extinction
SO NATURE
LA English
DT Article
ID medial prefrontal cortex; dopamine d1 receptor; potentiated startle; nmda receptors; facilitation; mechanisms; mu
AB Congruent findings from studies of fear learning in animals and humans indicate that research on the circuits mediating fear constitutes our best hope of understanding human anxiety disorders(1-4). In mammals, repeated presentations of a conditioned stimulus that was previously paired to a noxious stimulus leads to the gradual disappearance of conditioned fear responses. Although much evidence suggests that this extinction process depends on plastic events in the amygdala(1-7), the underlying mechanisms remain unclear. Intercalated ( ITC) amygdala neurons constitute probable mediators of extinction because they receive information about the conditioned stimulus from the basolateral amygdala ( BLA)(8,9), and contribute inhibitory projections to the central nucleus ( CEA)(10,11), the main output station of the amygdala for conditioned fear responses(12). Thus, after extinction training, ITC cells could reduce the impact of conditioned- stimulus- related BLA inputs to the CEA by means of feed- forward inhibition. Here we test the hypothesis that ITC neurons mediate extinction by lesioning them with a toxin that selectively targets cells expressing mu- opioid receptors (mu ORs). Electron microscopic observations revealed that the incidence of mu OR- immunoreactive synapses is much higher in ITC cell clusters than in the BLA or CEA and that mORs typically have a post- synaptic location in ITC cells. In keeping with this, bilateral infusions of the mu OR agonist dermorphin conjugated to the toxin saporin in the vicinity of ITC neurons caused a 34% reduction in the number of ITC cells but no significant cell loss in surrounding nuclei. Moreover, ITC lesions caused a marked deficit in the expression of extinction that correlated negatively with the number of surviving ITC neurons but not CEA cells. Because ITC cells exhibit an unusual pattern of receptor expression, these findings open new avenues for the treatment of anxiety disorders.
C1 [Likhtik, Ekaterina; Popa, Daniela; Apergis-Schoute, John; Fidacaro, George A., Jr.; Pare, Denis] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA.
C3 Rutgers University System; Rutgers University New Brunswick; Rutgers University Newark
RP Paré, D (corresponding author), Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA.
EM pare@andromeda.rutgers.edu
FU NIMH NIH HHS [F31 MH076415, R01MH-073610, R01 MH073610, F31 MH76415] Funding Source: Medline
NR 30
TC 379
Z9 490
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 31
PY 2008
VL 454
IS 7204
BP 642
EP U48
DI 10.1038/nature07167
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500048
PM 18615014
DA 2026-03-09
ER

PT J
AU Kroner, M
   Govorov, AO
   Remi, S
   Biedermann, B
   Seidl, S
   Badolato, A
   Petroff, PM
   Zhang, W
   Barbour, R
   Gerardot, BD
   Warburton, RJ
   Karrai, K
AF Kroner, M.
   Govorov, A. O.
   Remi, S.
   Biedermann, B.
   Seidl, S.
   Badolato, A.
   Petroff, P. M.
   Zhang, W.
   Barbour, R.
   Gerardot, B. D.
   Warburton, R. J.
   Karrai, K.
TI The nonlinear Fano effect
SO NATURE
LA English
DT Article
ID single quantum-dot; interference; emission
AB The Fano effect(1) is ubiquitous in the spectroscopy of, for instance, atoms(1,2), bulk solids(3,4) and semiconductor heterostructures(5-7). It arises when quantum interference takes place between two competing optical pathways, one connecting the energy ground state and an excited discrete state, the other connecting the ground state with a continuum of energy states. The nature of the interference changes rapidly as a function of energy, giving rise to characteristically asymmetric lineshapes. The Fano effect is particularly important in the interpretation of electronic transport(5,6) and optical spectra(7,8) in semiconductors. Whereas Fano's original theory(1) applies to the linear regime at low power, at higher power a laser field strongly admixes the states and the physics becomes rich, leading, for example, to a remarkable interplay of coherent nonlinear transitions(9). Despite the general importance of Fano physics, this nonlinear regime has received very little attention experimentally, presumably because the classic autoionization processes(2), the original test-bed of Fano's ideas(1), occur in an inconvenient spectral region, the deep ultraviolet. Here we report experiments that access the nonlinear Fano regime by using semiconductor quantum dots, which allow both the continuum states to be engineered and the energies to be rescaled to the near infrared. We measure the absorption cross- section of a single quantum dot and discover clear Fano resonances that we can tune with the device design or even in situ with a voltage bias. In parallel, we develop a nonlinear theory applicable to solid- state systems with fast relaxation of carriers. In the nonlinear regime, the visibility of the Fano quantum interferences increases dramatically, affording a sensitive probe of continuum coupling. This could be a unique method to detect weak couplings of a two- level quantum system ( qubits), which should ideally be decoupled from all other states.
C1 [Govorov, A. O.; Zhang, W.] Ohio Univ, Dept Phys & Astron, Athens, OH 45701 USA.
   [Kroner, M.; Remi, S.; Biedermann, B.; Seidl, S.; Karrai, K.] Univ Munich, Ctr Nanosci, D-80539 Munich, Germany.
   [Kroner, M.; Remi, S.; Biedermann, B.; Seidl, S.; Karrai, K.] Univ Munich, Dept Phys, D-80539 Munich, Germany.
   [Badolato, A.; Petroff, P. M.] Univ Calif Santa Barbara, Dept Mat, Santa Barbara, CA 93106 USA.
   [Barbour, R.; Gerardot, B. D.; Warburton, R. J.] Heriot Watt Univ, Sch Engn & Phys Sci, Edinburgh EH14 4AS, Midlothian, Scotland.
C3 University System of Ohio; Ohio University; University of Munich; University of Munich; University of California System; University of California Santa Barbara; Heriot Watt University
RP Govorov, AO (corresponding author), Ohio Univ, Dept Phys & Astron, Athens, OH 45701 USA.
EM govorov@helios.phy.ohiou.edu
FU EPSRC [EP/E037992/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/E037992/1] Funding Source: researchfish
NR 28
TC 218
Z9 240
U1 0
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 311
EP 314
DI 10.1038/nature06506
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100044
PM 18202652
DA 2026-03-09
ER

PT J
AU Hamilton, DP
   Krüger, H
AF Hamilton, Douglas P.
   Krueger, Harald
TI The sculpting of Jupiter's gossamer rings by its shadow
SO NATURE
LA English
DT Article
ID dust grains; galileo; ejection; dynamics; voyager; system
AB Dust near Jupiter is produced when interplanetary impactors collide energetically with small inner moons, and is organized into a main ring, an inner halo, and two fainter and more distant gossamer rings(1,2). Most of these structures are constrained by the orbits of the moons(3) Adrastea, Metis, Amalthea and Thebe, but a faint outward protrusion called the Thebe extension behaves differently and has eluded understanding. Here we report on dust impacts detected during the Galileo spacecraft's traversal of the outer ring region(4): we find a gap in the rings interior to Thebe's orbit(5), grains on highly inclined paths, and a strong excess of submicrometre- sized dust just inside Amalthea's orbit. We present detailed modelling that shows that the passage of ring particles through Jupiter's shadow creates the Thebe extension and fully accounts for these Galileo results. Dust grains alternately charge and discharge when traversing shadow boundaries, allowing the planet's powerful magnetic field to excite orbital eccentricities(6) and, when conditions are right, inclinations as well.
C1 [Hamilton, Douglas P.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Krueger, Harald] Max Planck Inst Sonnensyst Forsch, D-37191 Katlenburg Lindau, Germany.
   [Krueger, Harald] Max Planck Inst Kernphys, D-69029 Heidelberg, Germany.
C3 University System of Maryland; University of Maryland College Park; Max Planck Society; Max Planck Society
RP Hamilton, DP (corresponding author), Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
EM dphamil@umd.edu
NR 19
TC 30
Z9 34
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 1
PY 2008
VL 453
IS 7191
BP 72
EP 75
DI 10.1038/nature06886
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800040
PM 18451856
DA 2026-03-09
ER

PT J
AU Yang, SH
   Cheng, PH
   Banta, H
   Piotrowska-Nitsche, K
   Yang, JJ
   Cheng, ECH
   Snyder, B
   Larkin, K
   Liu, J
   Orkin, J
   Fang, ZH
   Smith, Y
   Bachevalier, J
   Zola, SM
   Li, SH
   Li, XJ
   Chan, AWS
AF Yang, Shang-Hsun
   Cheng, Pei-Hsun
   Banta, Heather
   Piotrowska-Nitsche, Karolina
   Yang, Jin-Jing
   Cheng, Eric C. H.
   Snyder, Brooke
   Larkin, Katherine
   Liu, Jun
   Orkin, Jack
   Fang, Zhi-Hui
   Smith, Yoland
   Bachevalier, Jocelyne
   Zola, Stuart M.
   Li, Shi-Hua
   Li, Xiao-Jiang
   Chan, Anthony W. S.
TI Towards a transgenic model of Huntington's disease in a non-human primate
SO NATURE
LA English
DT Article
ID neuronal intranuclear inclusions; gene; mice
AB Non- human primates are valuable for modelling human disorders and for developing therapeutic strategies; however, little work has been reported in establishing transgenic non- human primate models of human diseases. Huntington's disease ( HD) is an autosomal dominant neurodegenerative disorder characterized by motor impairment, cognitive deterioration and psychiatric disturbances followed by death within 10 - 15 years of the onset of the symptoms(1-4). HD is caused by the expansion of cytosine-adenine-guanine ( CAG, translated into glutamine) trinucleotide repeats in the first exon of the human huntingtin ( HTT) gene(5). Mutant HTT with expanded polyglutamine ( polyQ) is widely expressed in the brain and peripheral tissues(2,6), but causes selective neurodegeneration that is most prominent in the striatum and cortex of the brain. Although rodent models of HD have been developed, these models do not satisfactorily parallel the brain changes and behavioural features observed in HD patients. Because of the close physiological(7), neurological and genetic similarities(8,9) between humans and higher primates, monkeys can serve as very useful models for understanding human physiology and diseases(10,11). Here we report our progress in developing a transgenic model of HD in a rhesus macaque that expresses polyglutamine- expanded HTT. Hallmark features of HD, including nuclear inclusions and neuropil aggregates, were observed in the brains of the HD transgenic monkeys. Additionally, the transgenic monkeys showed important clinical features of HD, including dystonia and chorea. A transgenic HD monkey model may open the way to understanding the underlying biology of HD better, and to the development of potential therapies. Moreover, our data suggest that it will be feasible to generate valuable non-human primate models of HD and possibly other human genetic diseases.
C1 [Yang, Shang-Hsun; Cheng, Pei-Hsun; Banta, Heather; Piotrowska-Nitsche, Karolina; Yang, Jin-Jing; Cheng, Eric C. H.; Snyder, Brooke; Larkin, Katherine; Liu, Jun; Orkin, Jack; Smith, Yoland; Bachevalier, Jocelyne; Zola, Stuart M.; Chan, Anthony W. S.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Yang, Shang-Hsun; Cheng, Pei-Hsun; Piotrowska-Nitsche, Karolina; Yang, Jin-Jing; Cheng, Eric C. H.; Snyder, Brooke; Liu, Jun; Fang, Zhi-Hui; Li, Shi-Hua; Li, Xiao-Jiang; Chan, Anthony W. S.] Emory Univ, Dept Human Genet, Atlanta, GA 30329 USA.
   [Yang, Shang-Hsun; Li, Xiao-Jiang; Chan, Anthony W. S.] Emory Univ, Genet & Mol Biol Program, Atlanta, GA 30329 USA.
   [Liu, Jun; Smith, Yoland; Zola, Stuart M.; Li, Xiao-Jiang; Chan, Anthony W. S.] Emory Univ, Neurosci Program, Atlanta, GA 30329 USA.
   [Smith, Yoland] Emory Univ, Dept Neurol, Atlanta, GA 30329 USA.
   [Bachevalier, Jocelyne] Emory Univ, Dept Psychol, Atlanta, GA 30329 USA.
   [Bachevalier, Jocelyne; Zola, Stuart M.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30329 USA.
   [Piotrowska-Nitsche, Karolina] Polish Acad Sci, Dept Expt Embryol, Inst Genet & Anim Breeding, PL-05552 Wolka Kosowska, Poland.
   [Zola, Stuart M.] Vet Affairs Med Ctr, Atlanta, GA 30033 USA.
C3 Emory University; Emory University; Emory University; Emory University; Emory University; Emory University; Emory University; Institute of Genetics & Animal Biotechnology, Polish Academy of Sciences; Polish Academy of Sciences; US Department of Veterans Affairs; Veterans Health Administration (VHA); Atlanta VA Health Care System
RP Chan, AWS (corresponding author), Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
EM achan@genetics.emory.edu
FU National Institute of Neurological Disorders and Stroke [R01NS036232] Funding Source: NIH RePORTER; NIA NIH HHS [R01 AG019206] Funding Source: Medline; NIH HHS [R24 OD010930] Funding Source: Medline; NINDS NIH HHS [R01 NS041669, R01 NS036232] Funding Source: Medline
NR 21
TC 381
Z9 451
U1 1
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 921
EP U56
DI 10.1038/nature06975
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000044
PM 18488016
DA 2026-03-09
ER

PT J
AU Ayoub, N
   Jeyasekharan, AD
   Bernal, JA
   Venkitaraman, AR
AF Ayoub, Nabieh
   Jeyasekharan, Anand D.
   Bernal, Juan A.
   Venkitaraman, Ashok R.
TI HP1-β mobilization promotes chromatin changes that initiate the DNA damage response
SO NATURE
LA English
DT Article
ID protein-kinase ck2; double-strand breaks; heterochromatin protein-1; mammalian-cells; histone h2ax; phosphorylation; hp1; dynamics; atm; mobility
AB Minutes after DNA damage, the variant histone H2AX is phosphorylated by protein kinases of the phosphoinositide kinase family, including ATM, ATR or DNA- PK1. Phosphorylated (gamma)-H2AX - which recruits molecules that sense or signal the presence of DNA breaks, activating the response that leads to repair(2,3) - is the earliest known marker of chromosomal DNA breakage. Here we identify a dynamic change in chromatin that promotes H2AX phosphorylation in mammalian cells. DNA breaks swiftly mobilize heterochromatin protein 1 (HP1)-beta ( also called CBX1), a chromatin factor bound to histone H3 methylated on lysine 9 ( H3K9me). Local changes in histone- tail modifications are not apparent. Instead, phosphorylation of HP1-beta on amino acid Thr 51 accompanies mobilization, releasing HP1-beta from chromatin by disrupting hydrogen bonds that fold its chromodomain around H3K9me. Inhibition of casein kinase 2 ( CK2), an enzyme implicated in DNA damage sensing and repair(4-6), suppresses Thr 51 phosphorylation and HP1-beta mobilization in living cells. CK2 inhibition, or a constitutively chromatin- bound HP1-beta mutant, diminishes H2AX phosphorylation. Our findings reveal an unrecognized signalling cascade that helps to initiate the DNA damage response, altering chromatin by modifying a histone- code mediator protein, HP1, but not the code itself.
C1 [Ayoub, Nabieh; Jeyasekharan, Anand D.; Bernal, Juan A.; Venkitaraman, Ashok R.] Hutchison MRC Res Ctr, Med Res Council Canc Cell Unit, Cambridge CB2 0XZ, England.
RP Venkitaraman, AR (corresponding author), Hutchison MRC Res Ctr, Med Res Council Canc Cell Unit, Hills Rd, Cambridge CB2 0XZ, England.
EM arv22@cam.ac.uk
FU MRC [G0700651, G0600332, MC_U105359877, G9900064] Funding Source: UKRI; Medical Research Council [G0600332, G0700651, MC_U105359877, G9900064] Funding Source: Medline; Medical Research Council [G0700651, MC_U105359877, G0600332, G9900064] Funding Source: researchfish
NR 26
TC 353
Z9 401
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 MAY 29
PY 2008
VL 453
IS 7195
BP 682
EP U14
DI 10.1038/nature06875
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200050
PM 18438399
DA 2026-03-09
ER

PT J
AU Santelli, CM
   Orcutt, BN
   Banning, E
   Bach, W
   Moyer, CL
   Sogin, ML
   Staudigel, H
   Edwards, KJ
AF Santelli, Cara M.
   Orcutt, Beth N.
   Banning, Erin
   Bach, Wolfgang
   Moyer, Craig L.
   Sogin, Mitchell L.
   Staudigel, Hubert
   Edwards, Katrina J.
TI Abundance and diversity of microbial life in ocean crust
SO NATURE
LA English
DT Article
ID dissolved organic-carbon; bacterial; community; geomicrobiology; quantification; hybridization; program
AB Oceanic lithosphere exposed at the sea floor undergoes seawater rock alteration reactions involving the oxidation and hydration of glassy basalt. Basalt alteration reactions are theoretically capable of supplying sufficient energy for chemolithoautotrophic growth(1). Such reactions have been shown to generate microbial biomass in the laboratory(2), but field- based support for the existence of microbes that are supported by basalt alteration is lacking. Here, using quantitative polymerase chain reaction, in situ hybridization and microscopy, we demonstrate that prokaryotic cell abundances on seafloor- exposed basalts are 3 - 4 orders of magnitude greater than in overlying deep sea water. Phylogenetic analyses of basaltic lavas from the East Pacific Rise ( 9 degrees N) and around Hawaii reveal that the basalt- hosted biosphere harbours high bacterial community richness and that community membership is shared between these sites. We hypothesize that alteration reactions fuel chemolithoautotrophic microorganisms, which constitute a trophic base of the basalt habitat, with important implications for deep- sea carbon cycling and chemical exchange between basalt and sea water.
C1 [Santelli, Cara M.; Bach, Wolfgang; Edwards, Katrina J.] Woods Hole Oceanog Inst, Dept Marine Chem & Geochem, Woods Hole, MA 02543 USA.
   [Santelli, Cara M.; Banning, Erin] Woods Hole Oceanog Inst, MIT WHOI Joint Program Oceanog & Ocean Engn, Woods Hole, MA 02543 USA.
   [Orcutt, Beth N.; Edwards, Katrina J.] Univ So Calif, Geomicrobiol Grp, Dept Biol Sci, Los Angeles, CA 90089 USA.
   [Bach, Wolfgang] Univ Bremen, Fachbereich Geowissensch, D-28334 Bremen, Germany.
   [Moyer, Craig L.] Western Washington Univ, Dept Biol, Bellingham, WA 98225 USA.
   [Sogin, Mitchell L.] Marine Biol Lab, Josephine Bay Paul Ctr, Woods Hole, MA 02543 USA.
   [Staudigel, Hubert] Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92037 USA.
C3 Woods Hole Oceanographic Institution; Woods Hole Oceanographic Institution; Massachusetts Institute of Technology (MIT); University of Southern California; University of Bremen; Western Washington University; Marine Biological Laboratory - Woods Hole; University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Edwards, KJ (corresponding author), Woods Hole Oceanog Inst, Dept Marine Chem & Geochem, Woods Hole, MA 02543 USA.
EM kje@usc.edu
NR 37
TC 294
Z9 345
U1 0
U2 189
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2008
VL 453
IS 7195
BP 653
EP U7
DI 10.1038/nature06899
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200044
PM 18509444
DA 2026-03-09
ER

PT J
AU Schatton, T
   Murphy, GF
   Frank, NY
   Yamaura, K
   Waaga-Gasser, AM
   Gasser, M
   Zhan, Q
   Jordan, S
   Duncan, LM
   Weishaupt, C
   Fuhlbrigge, RC
   Kupper, TS
   Sayegh, MH
   Frank, MH
AF Schatton, Tobias
   Murphy, George F.
   Frank, Natasha Y.
   Yamaura, Kazuhiro
   Waaga-Gasser, Ana Maria
   Gasser, Martin
   Zhan, Qian
   Jordan, Stefan
   Duncan, Lyn M.
   Weishaupt, Carsten
   Fuhlbrigge, Robert C.
   Kupper, Thomas S.
   Sayegh, Mohamed H.
   Frank, Markus H.
TI Identification of cells initiating human melanomas
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; malignant-melanoma; stem-cells; cancer-cells; expression; chemoresistance; gene
AB Tumour- initiating cells capable of self- renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies(1,2) and solid cancers(3-6). If such minority populations are associated with tumour progression in human patients, specific targeting of tumour- initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant- melanoma- initiating cells ( MMIC) defined by expression of the chemoresistance mediator ABCB5 ( refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5(+) tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human- to-mouse xenotransplantation experiments, ABCB5(+) melanoma cells possess greater tumorigenic capacity than ABCB5(-) bulk populations and re- establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5(+) sub-populations for self- renewal and differentiation, because ABCB5(+) cancer cells generate both ABCB5(+) and ABCB5(-) progeny, whereas ABCB5(-) tumour populations give rise, at lower rates, exclusively to ABCB5(-) cells. In an initial proof- of- principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody- dependent cell- mediated cytotoxicity in ABCB5(+) MMIC, exerted tumour- inhibitory effects. Identification of tumour- initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.
C1 [Schatton, Tobias; Frank, Natasha Y.; Yamaura, Kazuhiro; Jordan, Stefan; Sayegh, Mohamed H.; Frank, Markus H.] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA.
   [Schatton, Tobias; Murphy, George F.; Frank, Natasha Y.; Yamaura, Kazuhiro; Zhan, Qian; Jordan, Stefan; Sayegh, Mohamed H.; Frank, Markus H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Frank, Natasha Y.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Waaga-Gasser, Ana Maria; Gasser, Martin] Univ Wurzburg, Dept Surg, D-97080 Wurzburg, Germany.
   [Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Weishaupt, Carsten; Fuhlbrigge, Robert C.; Kupper, Thomas S.] Brigham & Womens Hosp, Dept Dermatol, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; 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; University of Wurzburg; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School
RP Frank, MH (corresponding author), Childrens Hosp, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA.
EM mfrank@rics.bwh.harvard.edu
FU NCI NIH HHS [R01 CA113796] Funding Source: Medline; NHLBI NIH HHS [R01 HL084815] Funding Source: Medline; NIAMS NIH HHS [P30 AR042689] Funding Source: Medline; NINDS NIH HHS [K08 NS051349] Funding Source: Medline
NR 30
TC 1144
Z9 1334
U1 2
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 345
EP U11
DI 10.1038/nature06489
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100052
PM 18202660
DA 2026-03-09
ER

PT J
AU Toggweiler, JR
   Russell, J
AF Toggweiler, J. R.
   Russell, Joellen
TI Ocean circulation in a warming climate
SO NATURE
LA English
DT Article
ID atmospheric co2; stratification; cycle; wind
AB Climate models predict that the ocean's circulation will weaken in response to global warming, but the warming at the end of the last ice age suggests a different outcome.
C1 [Toggweiler, J. R.] NOAA, Geophys Fluid Dynam Lab, Princeton, NJ 08542 USA.
   [Russell, Joellen] Univ Arizona, Dept Geosci, Tucson, AZ 85721 USA.
C3 National Oceanic Atmospheric Admin (NOAA) - USA; University of Arizona
RP Toggweiler, JR (corresponding author), NOAA, Geophys Fluid Dynam Lab, Princeton, NJ 08542 USA.
EM robbie.toggweiler@noaa.gov
NR 25
TC 300
Z9 351
U1 6
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 286
EP 288
DI 10.1038/nature06590
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100037
PM 18202645
DA 2026-03-09
ER

PT J
AU Chen, ES
   Zhang, K
   Nicolas, E
   Cam, HP
   Zofall, M
   Grewal, SIS
AF Chen, Ee Sin
   Zhang, Ke
   Nicolas, Estelle
   Cam, Hugh P.
   Zofall, Martin
   Grewal, Shiv I. S.
TI Cell cycle control of centromeric repeat transcription and heterochromatin assembly
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; fission yeast; chromosome condensation; lysine-9 methylation; epigenetic control; ubiquitin ligase; chromatin; phosphorylation; rits; maintenance
AB Heterochromatin in eukaryotic genomes regulates diverse chromosomal processes including transcriptional silencing(1). However, in Schizosaccharomyces pombe RNA polymerase II ( RNAPII) transcription of centromeric repeats is essential for RNA- interference- mediated heterochromatin assembly(2-5). Here we study heterochromatin dynamics during the cell cycle and its effect on RNAPII transcription. We describe a brief period during the S phase of the cell cycle in which RNAPII preferentially transcribes centromeric repeats. This period is enforced by heterochromatin, which restricts RNAPII accessibility at centromeric repeats for most of the cell cycle. RNAPII transcription during S phase is linked to loading of RNA interference and heterochromatin factors such as the Ago1 subunit of the RITS complex(6) and the Clr4 methyltransferase complex subunit Rik1 ( ref. 7). Moreover, Set2, an RNAPII- associated methyltransferase(8) that methylates histone H3 lysine 36 at repeat loci during S phase, acts in a pathway parallel to Clr4 to promote heterochromatin assembly. We also show that phosphorylation of histone H3 serine 10 alters heterochromatin during mitosis, correlating with recruitment of condensin that affects silencing of centromeric repeats. Our analyses suggest at least two distinct modes of heterochromatin targeting to centromeric repeats, whereby RNAPII transcription of repeats and chromodomain proteins bound to methylated histone H3 lysine 9 mediate recruitment of silencing factors. Together, these processes probably facilitate heterochromatin maintenance through successive cell divisions.
C1 [Chen, Ee Sin; Zhang, Ke; Nicolas, Estelle; Cam, Hugh P.; Zofall, Martin; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Grewal, SIS (corresponding author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
FU Intramural NIH HHS Funding Source: Medline; National Cancer Institute [ZIABC011208, ZIABC010523] Funding Source: NIH RePORTER
NR 30
TC 312
Z9 375
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 FEB 7
PY 2008
VL 451
IS 7179
BP 734
EP 737
DI 10.1038/nature06561
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500045
PM 18216783
DA 2026-03-09
ER

PT J
AU Gaucher, EA
   Govindarajan, S
   Ganesh, OK
AF Gaucher, Eric A.
   Govindarajan, Sridhar
   Ganesh, Omjoy K.
TI Palaeotemperature trend for Precambrian life inferred from resurrected proteins
SO NATURE
LA English
DT Article
ID oxygen-isotope geochemistry; 3.4 billion years; western-australia; south-africa; evolution; cherts; origin; reconstruction; bacteria; seawater
AB Biosignatures and structures in the geological record indicate that microbial life has inhabited Earth for the past 3.5 billion years or so(1,2). Research in the physical sciences has been able to generate statements about the ancient environment that hosted this life(3-6). These include the chemical compositions and temperatures of the early ocean and atmosphere. Only recently have the natural sciences been able to provide experimental results describing the environments of ancient life. Our previous work with resurrected proteins indicated that ancient life lived in a hot environment(7,8). Here we expand the timescale of resurrected proteins to provide a palaeotemperature trend of the environments that hosted life from 3.5 to 0.5 billion years ago. The thermostability of more than 25 phylogenetically dispersed ancestral elongation factors suggest that the environment supporting ancient life cooled progressively by 30 degrees C during that period. Here we show that our results are robust to potential statistical bias associated with the posterior distribution of inferred character states, phylogenetic ambiguity, and uncertainties in the amino- acid equilibrium frequencies used by evolutionary models. Our results are further supported by a nearly identical cooling trend for the ancient ocean as inferred from the deposition of oxygen isotopes. The convergence of results from natural and physical sciences suggest that ancient life has continually adapted to changes in environmental temperatures throughout its evolutionary history.
C1 [Gaucher, Eric A.] Fdn Appl Mol Evolut, Gainesville, FL 32601 USA.
   [Govindarajan, Sridhar] DNA2 0 Inc, Menlo Pk, CA 94025 USA.
   [Ganesh, Omjoy K.] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
C3 State University System of Florida; University of Florida
RP Gaucher, EA (corresponding author), Fdn Appl Mol Evolut, Gainesville, FL 32601 USA.
EM egaucher@ffame.org
NR 30
TC 292
Z9 359
U1 2
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 FEB 7
PY 2008
VL 451
IS 7179
BP 704
EP U2
DI 10.1038/nature06510
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500038
PM 18256669
DA 2026-03-09
ER

PT J
AU González, MC
   Hidalgo, CA
   Barabási, AL
AF Gonzalez, Marta C.
   Hidalgo, Cesar A.
   Barabasi, Albert-Laszlo
TI Understanding individual human mobility patterns
SO NATURE
LA English
DT Article
ID flight search patterns; scaling laws
AB Despite their importance for urban planning(1), traffic forecasting(2) and the spread of biological(3-5) and mobile viruses(6), our understanding of the basic laws governing human motion remains limited owing to the lack of tools to monitor the time- resolved location of individuals. Here we study the trajectory of 100,000 anonymized mobile phone users whose position is tracked for a six- month period. We find that, in contrast with the random trajectories predicted by the prevailing Levy flight and random walk models(7), human trajectories show a high degree of temporal and spatial regularity, each individual being characterized by a time-independent characteristic travel distance and a significant probability to return to a few highly frequented locations. After correcting for differences in travel distances and the inherent anisotropy of each trajectory, the individual travel patterns collapse into a single spatial probability distribution, indicating that, despite the diversity of their travel history, humans follow simple reproducible patterns. This inherent similarity in travel patterns could impact all phenomena driven by human mobility, from epidemic prevention to emergency response, urban planning and agent- based modelling.
C1 [Gonzalez, Marta C.; Hidalgo, Cesar A.; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
   [Gonzalez, Marta C.; Hidalgo, Cesar A.; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Biol & Comp Sci, Boston, MA 02115 USA.
   [Hidalgo, Cesar A.; Barabasi, Albert-Laszlo] Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA.
   [Hidalgo, Cesar A.; Barabasi, Albert-Laszlo] Univ Notre Dame, Dept Phys & Comp Sci, Notre Dame, IN 46556 USA.
   [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
C3 Northeastern University; Northeastern University; University of Notre Dame; University of Notre Dame; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Barabási, AL (corresponding author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
EM alb@neu.edu
FU Direct For Mathematical & Physical Scien; Division Of Materials Research [0837678] Funding Source: National Science Foundation
NR 30
TC 4340
Z9 5077
U1 37
U2 1308
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2008
VL 453
IS 7196
BP 779
EP 782
DI 10.1038/nature06958
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300043
PM 18528393
DA 2026-03-09
ER

PT J
AU Murray-Rust, P
AF Murray-Rust, Peter
TI Chemistry for everyone
SO NATURE
LA English
DT Article
C1 Univ Cambridge, Dept Chem, Unilever Ctr Mol Sci Informat, Cambridge CB2 1EW, England.
C3 University of Cambridge
RP Murray-Rust, P (corresponding author), Univ Cambridge, Dept Chem, Unilever Ctr Mol Sci Informat, Lensfield Rd, Cambridge CB2 1EW, England.
EM pm286@cam.ac.uk
NR 0
TC 35
Z9 43
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 FEB 7
PY 2008
VL 451
IS 7179
BP 648
EP 651
DI 10.1038/451648a
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500028
PM 18256659
DA 2026-03-09
ER

PT J
AU Méndez-Ferrer, S
   Lucas, D
   Battista, M
   Frenette, PS
AF Mendez-Ferrer, Simon
   Lucas, Daniel
   Battista, Michela
   Frenette, Paul S.
TI Haematopoietic stem cell release is regulated by circadian oscillations
SO NATURE
LA English
DT Article
ID sympathetic-nervous-system; myeloid progenitor cells; bone-marrow; targeted disruption; protein-kinase; stromal cells; receptor gene; e-selectin; mobilization; niche
AB Haematopoietic stem cells ( HSCs) circulate in the bloodstream under steady- state conditions, but the mechanisms controlling their physiological trafficking are unknown. Here we show that circulating HSCs and their progenitors exhibit robust circadian fluctuations, peaking 5 h after the initiation of light and reaching a nadir 5 h after darkness. Circadian oscillations are markedly altered when mice are subjected to continuous light or to a 'jet lag' ( defined as a shift of 12 h). Circulating HSCs and their progenitors fluctuate in antiphase with the expression of the chemokine CXCL12 in the bone marrow microenvironment. The cyclical release of HSCs and expression of Cxcl12 are regulated by core genes of the molecular clock through circadian noradrenaline secretion by the sympathetic nervous system. These adrenergic signals are locally delivered by nerves in the bone marrow, transmitted to stromal cells by the beta(3)- adrenergic receptor, leading to a decreased nuclear content of Sp1 transcription factor and the rapid downregulation of Cxcl12. These data indicate that a circadian, neurally driven release of HSC during the animal's resting period may promote the regeneration of the stem cell niche and possibly other tissues.
C1 [Mendez-Ferrer, Simon; Lucas, Daniel; Battista, Michela; Frenette, Paul S.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
   [Mendez-Ferrer, Simon; Lucas, Daniel; Battista, Michela; Frenette, Paul S.] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA.
   [Frenette, Paul S.] Black Family Stem Cell Inst, New York, NY 10029 USA.
   [Frenette, Paul S.] Inst Immunol, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Frenette, PS (corresponding author), Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
EM paul.frenette@mssm.edu
NR 48
TC 1041
Z9 1204
U1 1
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 442
EP U4
DI 10.1038/nature06685
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300025
PM 18256599
DA 2026-03-09
ER

PT J
AU Kageyama, A
   Miyagoshi, T
   Sato, T
AF Kageyama, Akira
   Miyagoshi, Takehiro
   Sato, Tetsuya
TI Formation of current coils in geodynamo simulations
SO NATURE
LA English
DT Article
ID rotating spherical-shell; magnetohydrodynamic dynamo; geomagnetic-field; computer-simulation; polarity reversals; dipole field; convection; visualization; equations
AB Computer simulations have been playing an important role in the development of our understanding of the geodynamo(1-3), but direct numerical simulation of the geodynamo with a realistic parameter regime is still beyond the power of today's supercomputers. Difficulties in simulating the geodynamo arise from the extreme conditions of the core, which are characterized by very large or very small values of the non- dimensional parameters of the system. Among them, the Ekman number, E, has been adopted as a barometer of the distance of simulations from real core conditions, in which E is of the order of 10(-15). Following the initial computer simulations of the geodynamo(4,5), the Ekman number achieved has been steadily decreasing, with recent geodynamo simulations(6-8) performed with E of the order of 10(-6). Here we present a geodynamo simulation with an Ekman number of the order of 10(-7)-the highest-resolution simulation yet achieved, making use of 4,096 processors of the Earth Simulator. We have found that both the convection flow and magnetic field structures are qualitatively different from those found in larger- Ekman- number dynamos. The convection takes the form of sheet plumes or radial sheet jets(9), rather than the columnar cell structures(10) that are usually found. We have found that this sheet plume convection is an effective dynamo and the generated current is organized as a set of coils in the shape of helical springs or at times as a torus.
C1 [Kageyama, Akira; Miyagoshi, Takehiro; Sato, Tetsuya] Japan Agcy Marine Earth Sci & Technol, Earth Simulator Ctr, Yokohama, Kanagawa 2360001, Japan.
C3 Japan Agency for Marine-Earth Science & Technology (JAMSTEC)
RP Kageyama, A (corresponding author), Japan Agcy Marine Earth Sci & Technol, Earth Simulator Ctr, Yokohama, Kanagawa 2360001, Japan.
EM kage@jamstec.go.jp
FU KAKENHI [17540404]; The Mitsubishi Foundation; Grants-in-Aid for Scientific Research [17540404] Funding Source: KAKEN
NR 29
TC 81
Z9 92
U1 2
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1106
EP 1109
DI 10.1038/nature07227
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600035
PM 18756255
DA 2026-03-09
ER

PT J
AU Stone, EC
   Cummings, AC
   McDonald, FB
   Heikkila, BC
   Lal, N
   Webber, WR
AF Stone, Edward C.
   Cummings, Alan C.
   McDonald, Frank B.
   Heikkila, Bryant C.
   Lal, Nand
   Webber, William R.
TI An asymmetric solar wind termination shock
SO NATURE
LA English
DT Article
ID interstellar magnetic-field; energetic particles; voyager-1; acceleration; heliosheath; heliosphere; anisotropy; intensity; spacecraft; upstream
AB Voyager 2 crossed the solar wind termination shock at 83.7 AU in the southern hemisphere, 10 AU closer to the Sun than found by Voyager 1 in the north(1-4). This asymmetry could indicate an asymmetric pressure from an interstellar magnetic field(5,6), from transient-induced shock motion(7), or from the solar wind dynamic pressure. Here we report that the intensity of 4 - 5 MeV protons accelerated by the shock near Voyager 2 was three times that observed concurrently by Voyager 1, indicating differences in the shock at the two locations. ( Companion papers report on the plasma(8), magnetic field(9), plasma- wave(10) and lower energy particle(11) observations at the shock.) Voyager 2 did not find the source of anomalous cosmic rays at the shock, suggesting that the source is elsewhere on the shock(12-14) or in the heliosheath(15-19). The small intensity gradient of Galactic cosmic ray helium indicates that either the gradient is further out in the heliosheath(20) or the local interstellar Galactic cosmic ray intensity is lower than expected(21).
C1 [Stone, Edward C.; Cummings, Alan C.] CALTECH, Pasadena, CA 91125 USA.
   [McDonald, Frank B.] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA.
   [Heikkila, Bryant C.; Lal, Nand] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Webber, William R.] New Mexico State Univ, Dept Phys & Astron, Las Cruces, NM 88003 USA.
C3 California Institute of Technology; University System of Maryland; University of Maryland College Park; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; New Mexico State University
RP Stone, EC (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM ecs@srl.caltech.edu
NR 26
TC 344
Z9 367
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 71
EP 74
DI 10.1038/nature07022
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300037
PM 18596802
DA 2026-03-09
ER

PT J
AU Kwiatkowski, D
AF Kwiatkowski, Dominic
TI A global network for investigating the genomic epidemiology of malaria
SO NATURE
LA English
DT Article
ID parasite plasmodium-falciparum; wide association; insecticide resistance; genetic-association; anopheles-gambiae; african children; sequence; collaboration; population; diversity
AB Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.
EM dominic@sanger.ac.uk
FU Medical Research Council [G0600718, G0600230, G0200454, G19/9] Funding Source: researchfish; Medical Research Council [G0600718, G0200454, G0600230, G0600230(77610), G0200454(62635), G19/9] Funding Source: Medline; Wellcome Trust [077383/Z/05/Z, 077383, 076934] Funding Source: Medline; MRC [G0200454, G0600718, G19/9, G0600230] Funding Source: UKRI
NR 34
TC 120
Z9 137
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 DEC 11
PY 2008
VL 456
IS 7223
BP 732
EP U39
DI 10.1038/nature07632
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900037
PM 19079050
DA 2026-03-09
ER

PT J
AU Bingel-Erlenmeyer, R
   Kohler, R
   Kramer, G
   Sandikci, A
   Antolic, S
   Maier, T
   Schaffitzel, C
   Wiedmann, B
   Bukau, B
   Ban, N
AF Bingel-Erlenmeyer, Rouven
   Kohler, Rebecca
   Kramer, Guenter
   Sandikci, Arzu
   Antolic, Snjezana
   Maier, Timm
   Schaffitzel, Christiane
   Wiedmann, Brigitte
   Bukau, Bernd
   Ban, Nenad
TI A peptide deformylase-ribosome complex reveals mechanism of nascent chain processing
SO NATURE
LA English
DT Article
ID escherichia-coli; protein-synthesis; trigger factor; in-vitro; initiation; translation; excision; residue; domain; agents
AB Messenger- RNA- directed protein synthesis is accomplished by the ribosome(1-3). In eubacteria, this complex process is initiated by a specialized transfer RNA charged with formylmethionine ( tRNA(fMet))(4-6). The amino- terminal formylated methionine of all bacterial nascent polypeptides blocks the reactive amino group to prevent unfavourable side- reactions and to enhance the efficiency of translation initiation(7,8). The first enzymatic factor that processes nascent chains is peptide deformylase ( PDF)(5,9-11); it removes this formyl group as polypeptides emerge from the ribosomal tunnel(12,13) and before the newly synthesized proteins can adopt their native fold, which may bury the N terminus. Next, the N-terminal methionine is excised by methionine aminopeptidase(14). Bacterial PDFs are metalloproteases sharing a conserved N- terminal catalytic domain. All Gram- negative bacteria, including Escherichia coli, possess class- 1 PDFs characterized by a carboxy- terminal alpha- helical extension(15). Studies focusing on PDF as a target for antibacterial drugs(14,16) have not revealed the mechanism of its co- translational mode of action despite indications in early work that it co- purifies with ribosomes(17). Here we provide biochemical evidence that E. coli PDF interacts directly with the ribosome via its C- terminal extension. Crystallographic analysis of the complex between the ribosome- interacting helix of PDF and the ribosome at 3.7 angstrom resolution reveals that the enzyme orients its active site towards the ribosomal tunnel exit for efficient co- translational processing of emerging nascent chains. Furthermore, we have found that the interaction of PDF with the ribosome enhances cell viability. These results provide the structural basis for understanding the coupling between protein synthesis and enzymatic processing of nascent chains, and offer insights into the interplay of PDF with the ribosome- associated chaperone trigger factor.
C1 [Bingel-Erlenmeyer, Rouven; Kohler, Rebecca; Antolic, Snjezana; Maier, Timm; Schaffitzel, Christiane; Ban, Nenad] ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
   [Kramer, Guenter; Sandikci, Arzu; Bukau, Bernd] Univ Heidelberg, Zentrum Mol Biol ZMBH, D-69120 Heidelberg, Germany.
   [Wiedmann, Brigitte] Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Ruprecht Karls University Heidelberg; Novartis; Novartis USA
RP Ban, N (corresponding author), ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
EM ban@mol.biol.ethz.ch
NR 37
TC 95
Z9 113
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 6
PY 2008
VL 452
IS 7183
BP 108
EP U13
DI 10.1038/nature06683
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900056
PM 18288106
DA 2026-03-09
ER

PT J
AU Maeda, K
   Henbest, KB
   Cintolesi, F
   Kuprov, I
   Rodgers, CT
   Liddell, PA
   Gust, D
   Timmel, CR
   Hore, PJ
AF Maeda, Kiminori
   Henbest, Kevin B.
   Cintolesi, Filippo
   Kuprov, Ilya
   Rodgers, Christopher T.
   Liddell, Paul A.
   Gust, Devens
   Timmel, Christiane R.
   Hore, P. J.
TI Chemical compass model of avian magnetoreception
SO NATURE
LA English
DT Article
ID radical-pair mechanism; weak magnetic-fields; arabidopsis-thaliana; charge separation; epr spectroscopy; migratory birds; european robins; recombination; cryptochrome; orientation
AB Approximately 50 species, including birds, mammals, reptiles, amphibians, fish, crustaceans and insects, are known to use the Earth's magnetic field for orientation and navigation(1). Birds in particular have been intensively studied, but the biophysical mechanisms that underlie the avian magnetic compass are still poorly understood. One proposal, based on magnetically sensitive free radical reactions(2,3), is gaining support(4-11) despite the fact that no chemical reaction in vitro has been shown to respond to magnetic fields as weak as the Earth's (similar to 50 mu T) or to be sensitive to the direction of such a field. Here we use spectroscopic observation of a carotenoid-porphyrin-fullerene model system to demonstrate that the lifetime of a photochemically formed radical pair is changed by application of <= 50 mu T magnetic fields, and to measure the anisotropic chemical response that is essential for its operation as a chemical compass sensor. These experiments establish the feasibility of chemical magnetoreception and give insight into the structural and dynamic design features required for optimal detection of the direction of the Earth's magnetic field.
C1 [Cintolesi, Filippo; Kuprov, Ilya; Rodgers, Christopher T.; Hore, P. J.] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England.
   [Maeda, Kiminori; Henbest, Kevin B.; Timmel, Christiane R.] Univ Oxford, Inorgan Chem Lab, Dept Chem, Oxford OX1 3QR, England.
   [Liddell, Paul A.; Gust, Devens] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
C3 University of Oxford; University of Oxford; Arizona State University; Arizona State University-Tempe
RP Hore, PJ (corresponding author), Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, S Parks Rd, Oxford OX1 3QZ, England.
EM christiane.timmel@chem.ox.ac.uk; peter.hore@chem.ox.ac.uk
FU Engineering and Physical Sciences Research Council [EP/F065205/1, GR/T05424/01, EP/D048559/1] Funding Source: researchfish; EPSRC [EP/F065205/1, EP/D048559/1] Funding Source: UKRI
NR 29
TC 418
Z9 475
U1 7
U2 381
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 15
PY 2008
VL 453
IS 7193
BP 387
EP U38
DI 10.1038/nature06834
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400051
PM 18449197
DA 2026-03-09
ER

PT J
AU Clark, CM
   Tilman, D
AF Clark, Christopher M.
   Tilman, David
TI Loss of plant species after chronic low-level nitrogen deposition to prairie grasslands
SO NATURE
LA English
DT Article
ID nutrient-enrichment; ecosystem recovery; vegetation; diversity; heathland; fertilization; acidification; productivity; community; limitation
AB Rates of atmospheric deposition of biologically active nitrogen ( N) are two to seven times the pre- industrial rates in many developed nations because of combustion of fossil fuels and agricultural fertilization(1,2). They are expected to increase similarly over the next 50 years in industrializing nations of Asia and South America(2). Although the environmental impacts of high rates of nitrogen addition have been well studied(3-8), this is not so for the lower, chronic rates that characterize much of the globe. Here we present results of the first multi- decadal experiment to examine the impacts of chronic, experimental nitrogen addition as low as 10 kg N ha(-1) yr(-1) above ambient atmospheric nitrogen deposition ( 6 kg N ha(-1) yr(-1) at our site). This total input rate is comparable to terrestrial nitrogen deposition in many industrialized nations(2). We found that this chronic low- level nitrogen addition rate reduced plant species numbers by 17% relative to controls receiving ambient N deposition. Moreover, species numbers were reduced more per unit of added nitrogen at lower addition rates, suggesting that chronic but low- level nitrogen deposition may have a greater impact on diversity than previously thought. A second experiment showed that a decade after cessation of nitrogen addition, relative plant species number, although not species abundances, had recovered, demonstrating that some effects of nitrogen addition are reversible.
C1 [Clark, Christopher M.; Tilman, David] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities
RP Clark, CM (corresponding author), Univ Minnesota, Dept Ecol Evolut & Behav, 100 Ecol,1987 Upper Buford Circle, St Paul, MN 55108 USA.
EM clark134@umn.edu
NR 28
TC 859
Z9 1118
U1 16
U2 962
PU 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 7
PY 2008
VL 451
IS 7179
BP 712
EP 715
DI 10.1038/nature06503
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500040
PM 18256670
DA 2026-03-09
ER

PT J
AU Goldstein, SL
   Soffer, G
   Langmuir, CH
   Lehnert, KA
   Graham, DW
   Michael, PJ
AF Goldstein, Steven L.
   Soffer, Gad
   Langmuir, Charles H.
   Lehnert, Kerstin A.
   Graham, David W.
   Michael, Peter J.
TI Origin of a 'Southern Hemisphere' geochemical signature in the Arctic upper mantle
SO NATURE
LA English
DT Article
ID mid-atlantic ridge; southwest indian ridge; heterogeneity beneath; peridotite xenoliths; enriched mantle; gakkel ridge; ocean-ridge; trace; morb; isotope
AB The Gakkel ridge, which extends under the Arctic ice cap for similar to 1,800 km, is the slowest spreading ocean ridge on Earth. Its spreading created the Eurasian basin, which is isolated from the rest of the oceanic mantle by North America, Eurasia and the Lomonosov ridge. The Gakkel ridge thus provides unique opportunities to investigate the composition of the sub- Arctic mantle and mantle heterogeneity and melting at the lower limits of seafloor spreading. The first results of the 2001 Arctic Mid- Ocean Ridge Expedition ( ref. 1) divided the Gakkel ridge into three tectonic segments, composed of robust western and eastern volcanic zones separated by a `sparsely magmatic zone'. On the basis of Sr - Nd - Pb isotope ratios and trace elements in basalts from the spreading axis, we show that the sparsely magmatic zone contains an abrupt mantle compositional boundary. Basalts to the west of the boundary display affinities to the Southern Hemisphere 'Dupal' isotopic province(2), whereas those to the east - closest to the Eurasian continent and where the spreading rate is slowest display affinities to 'Northern Hemisphere' ridges. The western zone is the only known spreading ridge outside the Southern Hemisphere that samples a significant upper- mantle region with Dupal- like characteristics. Although the cause of Dupal mantle has been long debated, we show that the source of this signature beneath the western Gakkel ridge was subcontinental lithospheric mantle that delaminated and became integrated into the convecting Arctic asthenosphere. This occurred as North Atlantic mantle propagated north into the Arctic during the separation of Svalbard and Greenland.
C1 [Goldstein, Steven L.; Soffer, Gad; Lehnert, Kerstin A.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Goldstein, Steven L.; Soffer, Gad] Columbia Univ, Dept Earth & Environm Sci, Palisades, NY 10964 USA.
   [Langmuir, Charles H.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Graham, David W.] Oregon State Univ, Coll Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [Michael, Peter J.] Univ Tulsa, Dept Geosci, Tulsa, OK 74104 USA.
C3 Columbia University; Columbia University; Harvard University; Oregon State University; University of Tulsa
RP Goldstein, SL (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, 61 Route 9W, Palisades, NY 10964 USA.
EM steveg@ldeo.columbia.edu
NR 34
TC 104
Z9 118
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 MAY 1
PY 2008
VL 453
IS 7191
BP 89
EP +
DI 10.1038/nature06919
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800044
PM 18451860
DA 2026-03-09
ER

PT J
AU Liu, CZ
   Snow, JE
   Hellebrand, E
   Brügmann, G
   von der Handt, A
   Büchl, A
   Hofmann, AW
AF Liu, Chuan-Zhou
   Snow, Jonathan E.
   Hellebrand, Eric
   Bruegmann, Gerhard
   von der Handt, Anette
   Buechl, Anette
   Hofmann, Albrecht W.
TI Ancient, highly heterogeneous mantle beneath Gakkel ridge, Arctic Ocean
SO NATURE
LA English
DT Article
ID mid-atlantic ridge; osmium isotopic composition; abyssal peridotites; midocean ridge; os isotopes; melt extraction; indian ridge; morb mantle; systematics; basalts
AB The Earth's mantle beneath ocean ridges is widely thought to be depleted by previous melt extraction, but well homogenized by convective stirring. This inference of homogeneity has been complicated by the occurrence of portions enriched in incompatible elements. Here we show that some refractory abyssal peridotites from the ultraslow- spreading Gakkel ridge ( Arctic Ocean) have very depleted Os-187/Os-188 ratios with model ages up to 2 billion years, implying the long- term preservation of refractory domains in the asthenospheric mantle rather than their erasure by mantle convection. The refractory domains would not be sampled by mid- ocean- ridge basalts because they contribute little to the genesis of magmas. We thus suggest that the upwelling mantle beneath mid- ocean ridges is highly heterogeneous, which makes it difficult to constrain its composition by mid- ocean- ridge basalts alone. Furthermore, the existence of ancient domains in oceanic mantle suggests that using osmium model ages to constrain the evolution of continental lithosphere should be approached with caution.
C1 [Liu, Chuan-Zhou] Chinese Acad Sci, State Key Lab Lithospher Evolut, Inst Geol & Geophys, Beijing 100029, Peoples R China.
   [Liu, Chuan-Zhou; Snow, Jonathan E.; Hellebrand, Eric; Bruegmann, Gerhard; von der Handt, Anette; Buechl, Anette; Hofmann, Albrecht W.] Max Planck Inst Chem, Abt Geochem, D-55020 Mainz, Germany.
   [Liu, Chuan-Zhou] Grad Univ Chinese Acad Sci, Coll Earth Sci, Beijing 100039, Peoples R China.
   [Snow, Jonathan E.] Univ Houston, Dept Geosci, Houston, TX 77204 USA.
   [Hellebrand, Eric; von der Handt, Anette] Univ Hawaii, Dept Geol & Geophys, Honolulu, HI 96822 USA.
C3 Chinese Academy of Sciences; Institute of Geology & Geophysics, CAS; Max Planck Society; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; University of Houston System; University of Houston; University of Hawaii System
RP Liu, CZ (corresponding author), Chinese Acad Sci, State Key Lab Lithospher Evolut, Inst Geol & Geophys, Beijing 100029, Peoples R China.
EM chzliu@mail.iggcas.ac.cn
NR 50
TC 309
Z9 338
U1 5
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 311
EP 316
DI 10.1038/nature06688
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400038
PM 18354475
DA 2026-03-09
ER

PT J
AU Fischer, SEJ
   Butler, MD
   Pan, Q
   Ruvkun, G
AF Fischer, Sylvia E. J.
   Butler, Maurice D.
   Pan, Qi
   Ruvkun, Gary
TI Trans-splicing in C. elegans generates the negative RNAi regulator ERI-6/7
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; genetic interference; drosophila; protein; argonaute; helicase; identification; pathways; reveals; encodes
AB Mutations that enhance the response to double- stranded RNA ( dsRNA) have revealed components of the RNA interference ( RNAi) pathway or related small RNA pathways. To explore these small RNA pathways, we screened for Caenorhabditis elegans mutants displaying an enhanced response to exogenous dsRNAs. Here we describe the isolation of mutations in two adjacent, divergently transcribed open reading frames ( eri-6 and eri-7) that fail to complement. eri-6 and eri- 7 produce separate pre- messenger RNAs ( pre- mRNAs) that are trans- spliced to form a functional mRNA, eri- 6/ 7. Trans- splicing of eri6/7 is mediated by a direct repeat that flanks the eri- 6 gene. Adenosine to inosine editing within untranslated regions of eri- 6 and eri- 7 pre- mRNAs reveals a double- stranded pre- mRNA intermediate, forming in the nucleus before splicing occurs. The ERI-6/7 protein is a superfamily I helicase that both negatively regulates the exogenous RNAi pathway and functions in an endogenous RNAi pathway.
C1 [Fischer, Sylvia E. J.; Butler, Maurice D.; Pan, Qi; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Fischer, Sylvia E. J.; Butler, Maurice D.; Pan, Qi; 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 Leukemia and Lymphoma Society; EMBO; National Institute of General Medical Sciences [R01GM044619] Funding Source: NIH RePORTER
NR 43
TC 80
Z9 107
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 491
EP U23
DI 10.1038/nature07274
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600037
PM 18784652
DA 2026-03-09
ER

PT J
AU Friedlingstein, P
AF Friedlingstein, Pierre
TI A steep road to climate stabilization
SO NATURE
LA English
DT Article
C1 CEA Saclay, Inst Pierre Simon Laplace, Lab Climate & Environm Sci, F-91191 Gif Sur Yvette, France.
C3 Universite Paris Saclay; CEA
RP Friedlingstein, P (corresponding author), CEA Saclay, Inst Pierre Simon Laplace, Lab Climate & Environm Sci, F-91191 Gif Sur Yvette, France.
EM pierre.friedlingstein@lsce.ipsl.fr
NR 4
TC 33
Z9 36
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 17
PY 2008
VL 451
IS 7176
BP 297
EP 298
DI 10.1038/nature06593
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100040
PM 18202648
DA 2026-03-09
ER

PT J
AU Arnone, JA
   Verburg, PSJ
   Johnson, DW
   Larsen, JD
   Jasoni, RL
   Lucchesi, AJ
   Batts, CM
   von Nagy, C
   Coulombe, WG
   Schorran, DE
   Buck, PE
   Braswell, BH
   Coleman, JS
   Sherry, RA
   Wallace, LL
   Luo, YQ
   Schimel, DS
AF Arnone, John A., III
   Verburg, Paul S. J.
   Johnson, Dale W.
   Larsen, Jessica D.
   Jasoni, Richard L.
   Lucchesi, Annmarie J.
   Batts, Candace M.
   von Nagy, Christopher
   Coulombe, William G.
   Schorran, David E.
   Buck, Paul E.
   Braswell, Bobby H.
   Coleman, James S.
   Sherry, Rebecca A.
   Wallace, Linda L.
   Luo, Yiqi
   Schimel, David S.
TI Prolonged suppression of ecosystem carbon dioxide uptake after an anomalously warm year
SO NATURE
LA English
DT Article
ID water-vapor exchange; temperate grassland; terrestrial ecosystems; tallgrass prairie; plant-growth; co2; variability; fluxes; productivity; respiration
AB Terrestrial ecosystems control carbon dioxide fluxes to and from the atmosphere(1,2) through photosynthesis and respiration, a balance between net primary productivity and heterotrophic respiration, that determines whether an ecosystem is sequestering carbon or releasing it to the atmosphere. Global(1,3-5) and site-specific(6) data sets have demonstrated that climate and climate variability influence biogeochemical processes that determine net ecosystem carbon dioxide exchange (NEE) at multiple timescales. Experimental data necessary to quantify impacts of a single climate variable, such as temperature anomalies, on NEE and carbon sequestration of ecosystems at interannual timescales have been lacking. This derives from an inability of field studies to avoid the confounding effects of natural intra- annual and interannual variability in temperature and precipitation. Here we present results from a four-year study using replicate 12,000-kg intact tallgrass prairie monoliths located in four 184-m(3) enclosed lysimeters(7). We exposed 6 of 12 monoliths to an anomalously warm year in the second year of the study(8) and continuously quantified rates of ecosystem processes, including NEE. We find that warming decreases NEE in both the extreme year and the following year by inducing drought that suppresses net primary productivity in the extreme year and by stimulating heterotrophic respiration of soil biota in the subsequent year. Our data indicate that two years are required for NEE in the previously warmed experimental ecosystems to recover to levels measured in the control ecosystems. This time lag caused net ecosystem carbon sequestration in previously warmed ecosystems to be decreased threefold over the study period, compared with control ecosystems. Our findings suggest that more frequent anomalously warm years(9), a possible consequence of increasing anthropogenic carbon dioxide levels(10), may lead to a sustained decrease in carbon dioxide uptake by terrestrial ecosystems.
C1 [Arnone, John A., III; Verburg, Paul S. J.; Larsen, Jessica D.; Jasoni, Richard L.; Lucchesi, Annmarie J.; Batts, Candace M.; von Nagy, Christopher; Coulombe, William G.; Schorran, David E.; Buck, Paul E.] Univ Nevada, Desert Res Inst, Reno, NV 89512 USA.
   [Johnson, Dale W.] Univ Nevada, Dept Nat Resources & Environm Sci, Reno, NV 89557 USA.
   [Braswell, Bobby H.] Univ New Hampshire, Inst Study Earth Oceans & Space, Durham, NH 03824 USA.
   [Coleman, James S.] Rice Univ, Res Off, Houston, TX 77251 USA.
   [Coleman, James S.] Rice Univ, Dept Ecol & Evolutionary Biol, Houston, TX 77251 USA.
   [Sherry, Rebecca A.; Wallace, Linda L.; Luo, Yiqi] Univ Oklahoma, Dept Bot & Microbiol, Norman, OK 73019 USA.
   [Schimel, David S.] Natl Ctr Atmospher Res, Boulder, CO 80305 USA.
C3 Nevada System of Higher Education (NSHE); University of Nevada Reno; Desert Research Institute NSHE; Nevada System of Higher Education (NSHE); University of Nevada Reno; University System Of New Hampshire; University of New Hampshire; Rice University; Rice University; University of Oklahoma System; University of Oklahoma - Norman; National Center Atmospheric Research (NCAR) - USA
RP Arnone, JA (corresponding author), Univ Nevada, Desert Res Inst, Reno, NV 89512 USA.
EM jarnone@dri.edu
FU US National Science Foundation's Integrated Research Challenges in Environmental Biology program; Desert Research Institute (DRI)
NR 26
TC 137
Z9 156
U1 2
U2 164
PU 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 18
PY 2008
VL 455
IS 7211
BP 383
EP 386
DI 10.1038/nature07296
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200043
PM 18800137
DA 2026-03-09
ER

PT J
AU Ives, AR
   Einarsson, A
   Jansen, VAA
   Gardarsson, A
AF Ives, Anthony R.
   Einarsson, Arni
   Jansen, Vincent A. A.
   Gardarsson, Arnthor
TI High-amplitude fluctuations and alternative dynamical states of midges in Lake Myvatn
SO NATURE
LA English
DT Article
ID population-dynamics; diptera; chaos; predators; stability; systems; limits
AB Complex dynamics are often shown by simple ecological models(1,2) and have been clearly demonstrated in laboratory(3,4) and natural systems(5-9). Yet many classes of theoretically possible dynamics are still poorly documented in nature. Here we study long- term time- series data of a midge, Tanytarsus gracilentus ( Diptera: Chironomidae), in Lake Myvatn, Iceland. The midge undergoes density fluctuations of almost six orders of magnitude. Rather than regular cycles, however, these fluctuations have irregular periods of 4 - 7 years, indicating complex dynamics. We fit three consumer - resource models capable of qualitatively distinct dynamics to the data. Of these, the best- fitting model shows alternative dynamical states in the absence of environmental variability; depending on the initial midge densities, the model shows either fluctuations around a fixed point or high- amplitude cycles. This explains the observed complex population dynamics: high-amplitude but irregular fluctuations occur because stochastic variability causes the dynamics to switch between domains of attraction to the alternative states. In the model, the amplitude of fluctuations depends strongly on minute resource subsidies into the midge habitat. These resource subsidies may be sensitive to human- caused changes in the hydrology of the lake, with human impacts such as dredging leading to higher- amplitude fluctuations. Tanytarsus gracilentus is a key component of the Myvatn ecosystem, representing two- thirds of the secondary productivity of the lake(10) and providing vital food resources to fish and to breeding bird populations(11,12). Therefore the high- amplitude, irregular fluctuations in midge densities generated by alternative dynamical states dominate much of the ecology of the lake.
C1 [Ives, Anthony R.] Univ Wisconsin, Dept Zool, Madison, WI 53706 USA.
   [Einarsson, Arni; Gardarsson, Arnthor] Univ Iceland, Myvatn Res Stn, IS-101 Reykjavik, Iceland.
   [Einarsson, Arni; Gardarsson, Arnthor] Univ Iceland, Inst Biol, IS-101 Reykjavik, Iceland.
   [Jansen, Vincent A. A.] Univ London Royal Holloway & Bedford New Coll, Sch Biol Sci, Egham TW20 0EX, Surrey, England.
C3 University of Wisconsin System; University of Wisconsin Madison; University of Iceland; Natural Science Institute of Iceland; University of Iceland; University of London; Royal Holloway University London
RP Ives, AR (corresponding author), Univ Wisconsin, Dept Zool, Madison, WI 53706 USA.
EM arives@wisc.edu
NR 30
TC 93
Z9 116
U1 2
U2 98
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 6
PY 2008
VL 452
IS 7183
BP 84
EP 87
DI 10.1038/nature06610
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900051
PM 18322533
DA 2026-03-09
ER

PT J
AU Colaluca, IN
   Tosoni, D
   Nuciforo, P
   Senic-Matuglia, F
   Galimberti, V
   Viale, G
   Pece, S
   Di Fiore, PP
AF Colaluca, Ivan N.
   Tosoni, Daniela
   Nuciforo, Paolo
   Senic-Matuglia, Francesca
   Galimberti, Viviana
   Viale, Giuseppe
   Pece, Salvatore
   Di Fiore, Pier Paolo
TI NUMB controls p53 tumour suppressor activity
SO NATURE
LA English
DT Article
ID asymmetric cell-division; breast-cancer; negative regulation; endocytic protein; alpha-adaptin; histone h2ax; stem-cells; mdm2; expression; gene
AB NUMB is a cell fate determinant, which, by asymmetrically partitioning at mitosis, controls cell fate choices by antagonising the activity of the plasma membrane receptor of the NOTCH family(1). NUMB is also an endocytic protein(2), and the NOTCH-NUMB counteraction has been linked to this function(3,4). There might be, however, additional functions of NUMB, as witnessed by its proposed role as a tumour suppressor in breast cancer(5). Here we describe a previously unknown function for human NUMB as a regulator of tumour protein p53 ( also known as TP53). NUMB enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2( also known as MDM2), thereby preventing ubiquitination and degradation of p53. This results in increased p53 protein levels and activity, and in regulation of p53- dependent phenotypes. In breast cancers there is frequent loss of NUMB expression(5). We show that, in primary breast tumour cells, this event causes decreased p53 levels and increased chemoresistance. In breast cancers, loss of NUMB expression causes increased activity of the receptor NOTCH5. Thus, in these cancers, a single event - loss of NUMB expression - determines activation of an oncogene ( NOTCH) and attenuation of the p53 tumour suppressor pathway. Biologically, this results in an aggressive tumour phenotype, as witnessed by findings that NUMB- defective breast tumours display poor prognosis. Our results uncover a previously unknown tumour suppressor circuitry.
C1 [Colaluca, Ivan N.; Tosoni, Daniela; Nuciforo, Paolo; Senic-Matuglia, Francesca; Pece, Salvatore; Di Fiore, Pier Paolo] FIRC Inst Mol Oncol Fdn, IFOM, I-20139 Milan, Italy.
   [Colaluca, Ivan N.; Tosoni, Daniela; Galimberti, Viviana; Viale, Giuseppe; Pece, Salvatore; Di Fiore, Pier Paolo] European Inst Oncol, I-20141 Milan, Italy.
   [Viale, Giuseppe; Pece, Salvatore; Di Fiore, Pier Paolo] Univ Milan, Dipartimento Med Chirurg & Odontoiatria, I-20122 Milan, Italy.
C3 IFOM - FIRC Institute of Molecular Oncology; IRCCS European Institute of Oncology (IEO); University of Milan
RP Pece, S (corresponding author), FIRC Inst Mol Oncol Fdn, IFOM, Via Adamello 16, I-20139 Milan, Italy.
EM salvatore.pece@ifom-ieo-campus.it; pierpaolo.difiore@ifom-ieo-campus.it
FU Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
NR 32
TC 323
Z9 423
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 76
EP U11
DI 10.1038/nature06412
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300037
PM 18172499
DA 2026-03-09
ER

PT J
AU Lunt, DJ
   Foster, GL
   Haywood, AM
   Stone, EJ
AF Lunt, Daniel J.
   Foster, Gavin L.
   Haywood, Alan M.
   Stone, Emma J.
TI Late Pliocene Greenland glaciation controlled by a decline in atmospheric CO2 levels
SO NATURE
LA English
DT Article
ID carbon-dioxide concentrations; north-atlantic; late neogene; climate; panama; eocene; uplift; ice; closure; warmth
AB It is thought(1,2) that the Northern Hemisphere experienced only ephemeral glaciations from the Late Eocene to the Early Pliocene epochs ( about 38 to 4 million years ago), and that the onset of extensive glaciations did not occur until about 3 million years ago(3,4). Several hypotheses have been proposed to explain this increase in Northern Hemisphere glaciation during the Late Pliocene(5-11). Here we use a fully coupled atmosphere - ocean general circulation model and an ice- sheet model to assess the impact of the proposed driving mechanisms for glaciation and the influence of orbital variations on the development of the Greenland ice sheet in particular. We find that Greenland glaciation is mainly controlled by a decrease in atmospheric carbon dioxide during the Late Pliocene. By contrast, our model results suggest that climatic shifts associated with the tectonically driven closure of the Panama seaway(5,6), with the termination of a permanent El Nino state(7-9) or with tectonic uplift(10) are not large enough to contribute significantly to the growth of the Greenland ice sheet; moreover, we find that none of these processes acted as a priming mechanism for glacial inception triggered by variations in the Earth's orbit.
C1 [Lunt, Daniel J.; Stone, Emma J.] Univ Bristol, BRIDGE, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
   [Lunt, Daniel J.] British Antarctic Survey, Geol Sci Div, Cambridge CB3 0ET, England.
   [Foster, Gavin L.] Univ Bristol, Dept Earth Sci, Bristol Isotope Grp, Bristol BS8 1RJ, Avon, England.
   [Haywood, Alan M.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
C3 University of Bristol; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; University of Bristol; University of Leeds
RP Lunt, DJ (corresponding author), Univ Bristol, BRIDGE, Sch Geog Sci, Univ Rd, Bristol BS8 1SS, Avon, England.
EM d.j.lunt@bristol.ac.uk
FU GEACEP (Greenhouse to ice-house: Evolution of the Antarctic Cryosphere and Palaeoenvironment) programme; BAS fellowship; RCUK fellowship; NERC research fellowship; NERC [bas010019] Funding Source: UKRI; Natural Environment Research Council [bas010019, NER/I/S/2002/00720] Funding Source: researchfish
NR 30
TC 218
Z9 263
U1 3
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1102
EP U41
DI 10.1038/nature07223
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600034
PM 18756254
DA 2026-03-09
ER

PT J
AU Zachos, JC
   Dickens, GR
   Zeebe, RE
AF Zachos, James C.
   Dickens, Gerald R.
   Zeebe, Richard E.
TI An early Cenozoic perspective on greenhouse warming and carbon-cycle dynamics
SO NATURE
LA English
DT Article
ID eocene thermal maximum; climate system; global carbon; paleocene; methane; ocean; mechanism; hydrate
C1 [Zachos, James C.] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95060 USA.
   [Dickens, Gerald R.] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Zeebe, Richard E.] Univ Hawaii Manoa, Sch Ocean & Earth Sci & Technol, Honolulu, HI 96822 USA.
C3 University of California System; University of California Santa Cruz; Rice University; University of Hawaii System; University of Hawaii Manoa
RP Zachos, JC (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95060 USA.
EM jzachos@es.ucsc.edu; zeebe@hawaii.edu
NR 27
TC 2753
Z9 3203
U1 30
U2 988
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 279
EP 283
DI 10.1038/nature06588
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100035
PM 18202643
DA 2026-03-09
ER

PT J
AU Koentges, G
AF Koentges, Georgy
TI Evolution of anatomy and gene control
SO NATURE
LA English
DT Article
ID transgenic analysis; high-throughput; expression; patterns; origins; noise
C1 [Koentges, Georgy] Univ Warwick, Warwick Syst Biol Ctr, Coventry CV4 7AL, W Midlands, England.
C3 University of Warwick
RP Koentges, G (corresponding author), Univ Warwick, Warwick Syst Biol Ctr, Coventry CV4 7AL, W Midlands, England.
EM g.koentges@warwick.ac.uk
FU Wellcome Trust Funding Source: Medline
NR 60
TC 22
Z9 24
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 FEB 7
PY 2008
VL 451
IS 7179
BP 658
EP 663
DI 10.1038/451658a
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500030
PM 18256661
DA 2026-03-09
ER

PT J
AU McCauley, E
   Nelson, WA
   Nisbet, RM
AF McCauley, Edward
   Nelson, William A.
   Nisbet, Roger M.
TI Small-amplitude cycles emerge from stage-structured interactions in Daphnia-algal systems
SO NATURE
LA English
DT Article
ID prey; population; dynamics; model; environments; zooplankton; mechanisms; plankton
AB A long-standing issue in ecology is reconciling the apparent stability of many populations with robust predictions of large-amplitude population cycles from general theory on consumer resource interactions(1). Even when consumers are decoupled from dynamic resources, large- amplitude cycles can theoretically emerge from delayed feedback processes found in many consumers(2,3). Here we show that resource- dependent mortality and a dynamic developmental delay in consumers produces a new type of small- amplitude cycle that coexists with large- amplitude fluctuations in coupled consumer - resource systems. A distinctive characteristic of the small- amplitude cycles is slow juvenile development for consumers, leading to a developmental delay that is longer than the cycle period. By contrast, the period exceeds the delay in large-amplitude cycles. These theoretical predictions may explain previous empirical results on coexisting attractors found in Daphnia algal systems(4,5). To test this, we used bioassay experiments that measure the growth rates of individuals in populations exhibiting each type of cycle. The results were consistent with predictions. Together, the new theory and experiments establish that two very general features of consumers - a resource- dependent juvenile stage duration and resource- dependent mortality - combine to produce small- amplitude resource - consumer cycles. This phenomenon may contribute to the prevalence of small- amplitude fluctuations in many other consumer - resource populations(6,7).
C1 [McCauley, Edward] Univ Calgary, Dept Biol Sci, Ecol & Evolut Grp, Calgary, AB T2N 1N4, Canada.
   [Nelson, William A.] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada.
   [Nisbet, Roger M.] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
C3 University of Calgary; Queens University - Canada; University of California System; University of California Santa Barbara
RP McCauley, E (corresponding author), Univ Calgary, Dept Biol Sci, Ecol & Evolut Grp, 2500 Univ Dr 1 NW, Calgary, AB T2N 1N4, Canada.
EM mccauley@ucalgary.ca
FU NSERC ( Discovery Grants and Accelerator Award); Canada Foundation for Innovation; Canada Research Chairs Program; Alberta Ingenuity; US National Science Foundation [DEB- 0717259]
NR 24
TC 65
Z9 78
U1 2
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1240
EP 1243
DI 10.1038/nature07220
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100044
PM 18972019
DA 2026-03-09
ER

PT J
AU Stassun, KG
   Mathieu, RD
   Cargile, PA
   Aarnio, AN
   Stempels, E
   Geller, A
AF Stassun, Keivan G.
   Mathieu, Robert D.
   Cargile, Phillip A.
   Aarnio, Alicia N.
   Stempels, Eric
   Geller, Aaron
TI Surprising dissimilarities in a newly formed pair of 'identical twin' stars
SO NATURE
LA English
DT Article
ID orion nebula cluster; sequence eclipsing binary; low-mass; absolute calibration; forming region; brown dwarfs; system; 2mass; temperatures; photometry
AB The mass and chemical composition of a star are the primary determinants of its basic physical properties - radius, temperature and luminosity - and how those properties evolve with time(1). Accordingly, two stars born at the same time, from the same natal material and with the same mass, are 'identical twins,' and as such might be expected to possess identical physical attributes. We have discovered in the Orion nebula a pair of stellar twins in a newborn binary star system(2). Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to within 2 per cent. Here we report that these twin stars have surface temperatures differing by similar to 300 K (similar to 10 per cent) and luminosities differing by similar to 50 per cent, both at high confidence level. Preliminary results indicate that the stars' radii also differ, by 5 - 10 per cent. These surprising dissimilarities suggest that one of the twins may have been delayed by several hundred thousand years in its formation relative to its sibling. Such a delay could only have been detected in a very young, definitively equal-mass binary system(3). Our findings reveal cosmic limits on the age synchronization of young binary stars, often used as tests for the age calibrations of star-formation models(4).
C1 [Stassun, Keivan G.; Cargile, Phillip A.; Aarnio, Alicia N.] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA.
   [Mathieu, Robert D.; Geller, Aaron] Univ Wisconsin, Dept Astron, Madison, WI 53706 USA.
   [Stempels, Eric] Univ St Andrews, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
C3 Vanderbilt University; University of Wisconsin System; University of Wisconsin Madison; University of St Andrews
RP Stassun, KG (corresponding author), Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA.
EM keivan.stassun@vanderbilt.edu
NR 29
TC 47
Z9 53
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 19
PY 2008
VL 453
IS 7198
BP 1079
EP 1082
DI 10.1038/nature07069
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900051
PM 18563159
DA 2026-03-09
ER

PT J
AU Rius, J
   Guma, M
   Schachtrup, C
   Akassoglou, K
   Zinkernagel, AS
   Nizet, V
   Johnson, RS
   Haddad, GG
   Karin, M
AF Rius, Jordi
   Guma, Monica
   Schachtrup, Christian
   Akassoglou, Katerina
   Zinkernagel, Annelies S.
   Nizet, Victor
   Johnson, Randall S.
   Haddad, Gabriel G.
   Karin, Michael
TI NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α
SO NATURE
LA English
DT Article
ID ikk-beta; cutting edge; cells; expression; oxygen; hypoxia-inducible-factor-1-alpha; carcinogenesis; inflammation; inhibition; prevention
AB The hypoxic response is an ancient stress response triggered by low ambient oxygen ( O(2)) ( ref. 1) and controlled by hypoxia-inducible transcription factor- 1 ( HIF- 1), whose a subunit is rapidly degraded under normoxia but stabilized when O(2)- dependent prolyl hydroxylases ( PHDs) that target its O(2)- dependent degradation domain are inhibited(2-4). Thus, the amount of HIF-1 alpha, which controls genes involved in energy metabolism and angiogenesis, is regulated post- translationally. Another ancient stress response is the innate immune response, regulated by several transcription factors, among which NF-kappa B plays a central role(5,6). NF-kappa B activation is controlled by I kappa B kinases ( IKK), mainly IKK-beta, needed for phosphorylation- induced degradation of I kappa B inhibitors in response to infection and inflammation(7). IKK-beta is modestly activated in hypoxic cell cultures when PHDs that attenuate its activation are inhibited(8). However, defining the relationship between NF-kappa B and HIF-1 alpha has proven elusive. Using in vitro systems, it was reported that HIF-1 alpha activates NF- kappa B(9), that NF-kappa B controls HIF-1 alpha transcription(10) and that HIF-1 alpha activation may be concurrent with inhibition of NF-kappa B(11). Here we show, with the use of mice lacking IKK-beta in different cell types, that NF-kappa B is a critical transcriptional activator of HIF-1 alpha and that basal NF-kappa B activity is required for HIF-1 alpha protein accumulation under hypoxia in cultured cells and in the liver and brain of hypoxic animals. IKK-beta deficiency results in defective induction of HIF-1 alpha target genes including vascular endothelial growth factor. IKK-beta is also essential for HIF-1 alpha accumulation in macrophages experiencing a bacterial infection. Hence, IKK-beta is an important physiological contributor to the hypoxic response, linking it to innate immunity and inflammation.
C1 [Rius, Jordi; Guma, Monica; Karin, Michael] Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA.
   [Rius, Jordi; Guma, Monica; Schachtrup, Christian; Akassoglou, Katerina; Karin, Michael] Univ Calif San Diego, Dept Pharmacol, Sch Med, La Jolla, CA 92093 USA.
   [Rius, Jordi; Guma, Monica; Karin, Michael] Univ Calif San Diego, Dept Pathol, Sch Med, La Jolla, CA 92093 USA.
   [Zinkernagel, Annelies S.; Nizet, Victor; Haddad, Gabriel G.] Univ Calif San Diego, Dept Pediat, Sch Med, La Jolla, CA 92093 USA.
   [Nizet, Victor] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
   [Johnson, Randall S.] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Karin, M (corresponding author), Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM karinoffice@ucsd.edu
FU NCI NIH HHS [R01 CA118165] Funding Source: Medline; NCRR NIH HHS [P41 RR004050] Funding Source: Medline; NIAID NIH HHS [R01 AI043477] Funding Source: Medline
NR 30
TC 1318
Z9 1540
U1 3
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 JUN 5
PY 2008
VL 453
IS 7196
BP 807
EP U9
DI 10.1038/nature06905
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300049
PM 18432192
DA 2026-03-09
ER

PT J
AU Colina, R
   Costa-Mattioli, M
   Dowling, RJO
   Jaramillo, M
   Tai, LH
   Breitbach, CJ
   Martineau, Y
   Larsson, O
   Rong, LW
   Svitkin, YV
   Makrigiannis, AP
   Bell, JC
   Sonenberg, N
AF Colina, Rodney
   Costa-Mattioli, Mauro
   Dowling, Ryan J. O.
   Jaramillo, Maritza
   Tai, Lee-Hwa
   Breitbach, Caroline J.
   Martineau, Yvan
   Larsson, Ola
   Rong, Liwei
   Svitkin, Yuri V.
   Makrigiannis, Andrew P.
   Bell, John C.
   Sonenberg, Nahum
TI Translational control of the innate immune response through IRF-7
SO NATURE
LA English
DT Article
ID double-stranded-rna; targeted disruption; initiation-factors; rig-i; interferon; recognition; gene; phosphorylation; kinase; cells
AB Transcriptional activation of cytokines, such as type-I interferons ( interferon ( IFN)- alpha and IFN- beta), constitutes the first line of antiviral defence. Here we show that translational control is critical for induction of type- I IFN production. In mouse embryonic fibroblasts lacking the translational repressors 4E- BP1 and 4E- BP2, the threshold for eliciting type- I IFN production is lowered. Consequently, replication of encephalomyocarditis virus, vesicular stomatitis virus, influenza virus and Sindbis virus is markedly suppressed. Furthermore, mice with both 4E- BP1 and 4E- BP2 genes ( also known as Eif4ebp1 and Eif4ebp2, respectively) knocked out are resistant to vesicular stomatitis virus infection, and this correlates with an enhanced type- I IFN production in plasmacytoid dendritic cells and the expression of IFN- regulated genes in the lungs. The enhanced type- I IFN response in 4E-BP1(-/-) 4E-BP2(-/-) double knockout mouse embryonic fibroblasts is caused by upregulation of interferon regulatory factor 7 ( Irf7) messenger RNA translation. These findings highlight the role of 4E- BPs as negative regulators of type- I IFN production, via translational repression of Irf7 mRNA.
C1 [Colina, Rodney; Costa-Mattioli, Mauro; Dowling, Ryan J. O.; Jaramillo, Maritza; Martineau, Yvan; Larsson, Ola; Rong, Liwei; Svitkin, Yuri V.; Sonenberg, Nahum] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.
   [Tai, Lee-Hwa; Makrigiannis, Andrew P.] Univ Montreal, Inst Rech Clin Montreal, Lab Mol Immunol, Montreal, PQ H2W 1R7, Canada.
   [Breitbach, Caroline J.; Bell, John C.] Ottawa Hlth Res Inst, Ottawa, ON K1H 8L6, Canada.
C3 McGill University; Institut de Recherche Clinique de Montreal (IRCM); Universite de Montreal; University of Ottawa; Ottawa Hospital Research Institute
RP Sonenberg, N (corresponding author), McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.
EM mauro.costa-mattioli@mail.mcgill.ca; nahum.sonenberg@mcgill.ca
FU Howard Hughes Medical Institute Funding Source: Medline
NR 44
TC 264
Z9 313
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 20
PY 2008
VL 452
IS 7185
BP 323
EP U2
DI 10.1038/nature06730
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400040
PM 18272964
DA 2026-03-09
ER

PT J
AU Ahlberg, PE
   Clack, JA
   Luksevics, E
   Blom, H
   Zupins, I
AF Ahlberg, Per E.
   Clack, Jennifer A.
   Luksevics, Ervins
   Blom, Henning
   Zupins, Ivars
TI Ventastega curonica and the origin of tetrapod morphology
SO NATURE
LA English
DT Article
ID crassigyrinus-scoticus lydekker; acanthostega-gunnari jarvik; earliest known tetrapod; devonian tetrapod; evolution; fish; skeleton; interrelationships; braincase; anatomy
AB The gap in our understanding of the evolutionary transition from fish to tetrapod is beginning to close thanks to the discovery of new intermediate forms such as Tiktaalik roseae. Here we narrow it further by presenting the skull, exceptionally preserved braincase, shoulder girdle and partial pelvis of Ventastega curonica from the Late Devonian of Latvia, a transitional intermediate form between the 'elpistostegids' Panderichthys and Tiktaalik and the Devonian tetrapods ( limbed vertebrates) Acanthostega and Ichthyostega. Ventastega is the most primitive Devonian tetrapod represented by extensive remains, and casts light on a part of the phylogeny otherwise only represented by fragmentary taxa: it illuminates the origin of principal tetrapod structures and the extent of morphological diversity among the transitional forms.
C1 [Ahlberg, Per E.; Blom, Henning] Uppsala Univ, Subdept Evolutionary Organismal Biol, Dept Physiol & Dev Biol, S-75236 Uppsala, Sweden.
   [Clack, Jennifer A.] Univ Cambridge, Museum Zool, Cambridge CB2 3EJ, England.
   [Luksevics, Ervins] Univ Latvia, Dept Geol, LV-1586 Riga, Latvia.
   [Zupins, Ivars] Nat Hist Museum Latvia, LV-1712 Riga, Latvia.
C3 Uppsala University; University of Cambridge; University of Latvia
RP Ahlberg, PE (corresponding author), Uppsala Univ, Subdept Evolutionary Organismal Biol, Dept Physiol & Dev Biol, Norbyvagen 18A, S-75236 Uppsala, Sweden.
EM per.ahlberg@ebc.uu.se
NR 46
TC 74
Z9 86
U1 1
U2 105
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1199
EP 1204
DI 10.1038/nature06991
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800034
PM 18580942
DA 2026-03-09
ER

PT J
AU Mookherjee, M
   Stixrude, L
   Karki, B
AF Mookherjee, Mainak
   Stixrude, Lars
   Karki, Bijaya
TI Hydrous silicate melt at high pressure
SO NATURE
LA English
DT Article
ID upper-mantle; molecular-dynamics; united-states; water; h2o; density; glasses; system; earth; speciation
AB The structure and physical properties of hydrous silicate melts and the solubility of water in melts over most of the pressure regime of Earth's mantle ( up to 136 GPa) remain unknown. At low pressure ( up to a few gigapascals) the solubility of water increases rapidly with increasing pressure(1), and water has a large influence on the solidus temperature, density(2), viscosity(3) and electrical conductivity. Here we report the results of first- principles molecular dynamics simulations of hydrous MgSiO(3) melt. These show that pressure has a profound influence on speciation of the water component, which changes from being dominated by hydroxyls and water molecules at low pressure(4) to extended structures at high pressure. We link this change in structure to our finding that the water - silicate system becomes increasingly ideal at high pressure: we find complete miscibility of water and silicate melt throughout almost the entire mantle pressure regime. On the basis of our results, we argue that a buoyantly stable melt at the base of the upper mantle would contain approximately 3 wt% water and have an electrical conductivity of 18 S m(-1), and should therefore be detectable by means of electromagnetic sounding.
C1 [Stixrude, Lars] UCL, Dept Earth Sci, London WC1E 6BT, England.
   [Mookherjee, Mainak] Yale Univ, Dept Geol & Geophys, New Haven, CT 06511 USA.
   [Karki, Bijaya] Louisiana State Univ, Dept Comp Sci, Baton Rouge, LA 70803 USA.
   [Karki, Bijaya] Louisiana State Univ, Dept Geol & Geophys, Baton Rouge, LA 70803 USA.
C3 University of London; University College London; Yale University; Louisiana State University System; Louisiana State University; Louisiana State University System; Louisiana State University
RP Stixrude, L (corresponding author), UCL, Dept Earth Sci, Gower St, London WC1E 6BT, England.
EM stixrude@umich.edu
NR 30
TC 129
Z9 144
U1 1
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 24
PY 2008
VL 452
IS 7190
BP 983
EP 986
DI 10.1038/nature06918
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600037
PM 18432243
DA 2026-03-09
ER

PT J
AU Srinivasan, J
   Kaplan, F
   Ajredini, R
   Zachariah, C
   Alborn, HT
   Teal, PEA
   Malik, RU
   Edison, AS
   Sternberg, PW
   Schroeder, FC
AF Srinivasan, Jagan
   Kaplan, Fatma
   Ajredini, Ramadan
   Zachariah, Cherian
   Alborn, Hans T.
   Teal, Peter E. A.
   Malik, Rabia U.
   Edison, Arthur S.
   Sternberg, Paul W.
   Schroeder, Frank C.
TI A blend of small molecules regulates both mating and development in Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID dauer-inducing pheromone; gene; longevity; sex
AB In many organisms, population- density sensing and sexual attraction rely on small- molecule- based signalling systems(1,2). In the nematode Caenorhabditis elegans, population density is monitored through specific glycosides of the dideoxysugar ascarylose ( the 'ascarosides') that promote entry into an alternative larval stage, the non- feeding and highly persistent dauer stage(3,4). In addition, adult C. elegans males are attracted to hermaphrodites by a previously unidentified small- molecule signal(5,6). Here we show, by means of combinatorial activity- guided fractionation of the C. elegans metabolome, that the mating signal consists of a synergistic blend of three dauer- inducing ascarosides, which we call ascr#2, ascr#3 and ascr#4. This blend of ascarosides acts as a potent male attractant at very low concentrations, whereas at the higher concentrations required for dauer formation the compounds no longer attract males and instead deter hermaphrodites. The ascarosides ascr#2 and ascr# 3 carry different, but overlapping, information, as ascr# 3 is more potent as a male attractant than ascr#2 , whereas ascr# 2 is slightly more potent than ascr# 3 in promoting dauer formation(7). We demonstrate that ascr# 2, ascr# 3 and ascr# 4 are strongly synergistic, and that two types of neuron, the amphid single- ciliated sensory neuron type K ( ASK) and the male- specific cephalic companion neuron ( CEM), are required for male attraction by ascr#3. On the basis of these results, male attraction and dauer formation in C. elegans appear as alternative behavioural responses to a common set of signalling molecules. The ascaroside signalling system thus connects reproductive and developmental pathways and represents a unique example of structure- and concentration-dependent differential activity of signalling molecules.
C1 [Srinivasan, Jagan; Sternberg, Paul W.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [Srinivasan, Jagan; Sternberg, Paul W.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Kaplan, Fatma; Ajredini, Ramadan; Zachariah, Cherian; Edison, Arthur S.] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
   [Kaplan, Fatma; Ajredini, Ramadan; Zachariah, Cherian; Edison, Arthur S.] Univ Florida, McKnight Brain Inst, Gainesville, FL 32610 USA.
   [Kaplan, Fatma; Ajredini, Ramadan; Zachariah, Cherian; Edison, Arthur S.] Univ Florida, Natl High Magnet Field Lab, Gainesville, FL 32610 USA.
   [Alborn, Hans T.; Teal, Peter E. A.] USDA ARS, Ctr Med Agr & Vet Entomol, Gainesville, FL 32604 USA.
   [Malik, Rabia U.; Schroeder, Frank C.] Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA.
C3 Howard Hughes Medical Institute; California Institute of Technology; California Institute of Technology; State University System of Florida; University of Florida; State University System of Florida; University of Florida; State University System of Florida; University of Florida; United States Department of Agriculture (USDA); Cornell University; Boyce Thompson Institute for Plant Research
RP Sternberg, PW (corresponding author), CALTECH, Howard Hughes Med Inst, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM art@mbi.ufl.edu; pws@caltech.edu; fs31@cornell.edu
FU Human Frontiers Science Program; US National Institutes of Health [P41 GM079571]; Howard Hughes Medical Institute
NR 23
TC 302
Z9 396
U1 3
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1115
EP U46
DI 10.1038/nature07168
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600037
PM 18650807
DA 2026-03-09
ER

PT J
AU Pflamm-Altenburg, J
   Kroupa, P
AF Pflamm-Altenburg, Jan
   Kroupa, Pavel
TI Clustered star formation as a natural explanation for the Hα cut-off in disk galaxies
SO NATURE
LA English
DT Article
ID initial mass function; extreme outer disk; spiral galaxy; formation rates; galactic disks; formation law; gas; regions; continuum; density
AB The rate of star formation in a galaxy is often determined by the observation of emission in the H alpha line, which is related to the presence of short- lived massive stars. Disk galaxies show a strong cut- off in H alpha radiation at a certain galactocentric distance, which has led to the conclusion that star formation is suppressed in the outer regions of disk galaxies. This is seemingly in contradiction to recent observations(1) in the ultraviolet which imply that disk galaxies have star formation beyond the H alpha cut- off, and that the star-formation-rate surface density is linearly related to the underlying gas surface density, which is a shallower relationship than that derived from H alpha luminosities(2). In a galaxy- wide formulation, the clustered nature of star formation has recently led to the insight that the total galactic H alpha luminosity is nonlinearly related to the galaxy- wide star formation rate(3). Here we show that a local formulation of the concept of clustered star formation naturally leads to a steeper radial decrease in the H alpha surface luminosity than in the star-formation-rate surface density, in quantitative agreement with the observations, and that the observed H alpha cut- off arises naturally.
C1 [Pflamm-Altenburg, Jan; Kroupa, Pavel] Univ Bonn, Argelander Inst Astron, D-53121 Bonn, Germany.
C3 University of Bonn
RP Pflamm-Altenburg, J (corresponding author), Univ Bonn, Argelander Inst Astron, D-53121 Bonn, Germany.
EM jpflamm@astro.uni-bonn.de
NR 30
TC 79
Z9 85
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 OCT 2
PY 2008
VL 455
IS 7213
BP 641
EP 643
DI 10.1038/nature07266
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700041
PM 18833274
DA 2026-03-09
ER

PT J
AU Bortnik, J
   Thorne, RM
   Meredith, NP
AF Bortnik, Jacob
   Thorne, Richard M.
   Meredith, Nigel P.
TI The unexpected origin of plasmaspheric hiss from discrete chorus emissions
SO NATURE
LA English
DT Article
ID magnetospherically reflecting whistlers; radiation belt electrons; frequency; satellite
AB Plasmaspheric hiss(1) is a type of electromagnetic wave found ubiquitously in the dense plasma region that encircles the Earth, known as the plasmasphere(2). This important wave is known to remove(3-5) the high- energy electrons that are trapped along the Earth's magnetic field lines(6), and therefore helps to reduce the radiation hazards to satellites and humans in space. Numerous theories to explain the origin of hiss have been proposed over the past four decades, but none have been able to account fully for its observed properties. Here we show that a different wave type called chorus(7,8), previously thought to be unrelated to hiss, can propagate into the plasmasphere from tens of thousands of kilometres away, and evolve into hiss. Our new model naturally accounts for the observed frequency band of hiss, its incoherent nature, its day - night asymmetry in intensity, its association with solar activity and its spatial distribution. The connection between chorus and hiss is very interesting because chorus is instrumental in the formation of high- energy electrons outside the plasmasphere(9), whereas hiss depletes these electrons at lower equatorial altitudes(3,4).
C1 [Bortnik, Jacob; Thorne, Richard M.] Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA 90095 USA.
   [Meredith, Nigel P.] British Antarctic Survey, NERC, Cambridge CB3 0ET, England.
C3 University of California System; University of California Los Angeles; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey
RP Bortnik, J (corresponding author), Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, 405 Hilgard Ave, Los Angeles, CA 90095 USA.
EM jbortnik@gmail.com
FU Natural Environment Research Council [bas010022] Funding Source: researchfish; NERC [bas010022] Funding Source: UKRI
NR 30
TC 351
Z9 373
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 MAR 6
PY 2008
VL 452
IS 7183
BP 62
EP 66
DI 10.1038/nature06741
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900046
PM 18322528
DA 2026-03-09
ER

PT J
AU Feng, J
   Hennig, RG
   Ashcroft, NW
   Hoffmann, R
AF Feng, Ji
   Hennig, Richard G.
   Ashcroft, N. W.
   Hoffmann, Roald
TI Emergent reduction of electronic state dimensionality in dense ordered Li-Be alloys
SO NATURE
LA English
DT Article
ID crystal-structures; high-pressure; metals; potassium; behavior; elements; lithium; phases
AB High pressure is known to influence electronic structure and crystal packing, and can in some cases even induce compound formation between elements that do not bond under ambient conditions(1-3). Here we present a computational study showing that high pressure fundamentally alters the reactivity of the light elements lithium ( Li) and beryllium ( Be), which are the first of the metals in the condensed state and immiscible under normal conditions(4,5). We identify four stoichiometric LixBe1-x compounds that are stable over a range of pressures, and find that the electronic density of states of one of them displays a remarkable step-like feature near the bottom of the valence band and then remains almost constant with increasing energy. These characteristics are typical of a quasi- two- dimensional electronic structure, the emergence of which in a three- dimensional environment is rather unexpected. We attribute this observation to large size differences between the ionic cores of Li and Be: as the density increases, the Li cores start to overlap and thereby expel valence electrons into quasi- two- dimensional layers characterized by delocalized free- particle- like states in the vicinity of Be ions.
C1 [Ashcroft, N. W.] Cornell Univ, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA.
   [Feng, Ji; Hoffmann, Roald] Cornell Univ, Baker Lab, Dept Chem & Biol Chem, Ithaca, NY 14853 USA.
   [Hennig, Richard G.] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
   [Ashcroft, N. W.] Cornell Univ, Cornell Ctr Mat Res, Ithaca, NY 14853 USA.
C3 Cornell University; Cornell University; Cornell University; Cornell University
RP Ashcroft, NW (corresponding author), Cornell Univ, Atom & Solid State Phys Lab, Clark Hall, Ithaca, NY 14853 USA.
EM nwa@ccmr.cornell.edu; rh34@cornell.edu
NR 26
TC 110
Z9 135
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 24
PY 2008
VL 451
IS 7177
BP 445
EP 448
DI 10.1038/nature06442
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100040
PM 18216850
DA 2026-03-09
ER

PT J
AU Danovaro, R
   Dell'Anno, A
   Corinaldesi, C
   Magagnini, M
   Noble, R
   Tamburini, C
   Weinbauer, M
AF Danovaro, Roberto
   Dell'Anno, Antonio
   Corinaldesi, Cinzia
   Magagnini, Mirko
   Noble, Rachel
   Tamburini, Christian
   Weinbauer, Markus
TI Major viral impact on the functioning of benthic deep-sea ecosystems
SO NATURE
LA English
DT Article
ID marine virus; hydrostatic-pressure; organic-matter; key role; mortality; sediments; bacterioplankton; waters; dna; infection
AB Viruses are the most abundant biological organisms of the world's oceans. Viral infections are a substantial source of mortality in a range of organisms - including autotrophic and heterotrophic plankton - but their impact on the deep ocean and benthic biosphere is completely unknown. Here we report that viral production in deep- sea benthic ecosystems worldwide is extremely high, and that viral infections are responsible for the abatement of 80% of prokaryotic heterotrophic production. Virus- induced prokaryotic mortality increases with increasing water depth, and beneath a depth of 1,000 m nearly all of the prokaryotic heterotrophic production is transformed into organic detritus. The viral shunt, releasing on a global scale similar to 0.37 - 0.63 gigatonnes of carbon per year, is an essential source of labile organic detritus in the deep- sea ecosystems. This process sustains a high prokaryotic biomass and provides an important contribution to prokaryotic metabolism, allowing the system to cope with the severe organic resource limitation of deep- sea ecosystems. Our results indicate that viruses have an important role in global biogeochemical cycles, in deep- sea metabolism and the overall functioning of the largest ecosystem of our biosphere.
C1 [Danovaro, Roberto; Dell'Anno, Antonio; Corinaldesi, Cinzia; Magagnini, Mirko] Polytech Univ Marche, Dept Marine Sci, Fac Sci, I-60131 Ancona, Italy.
   [Noble, Rachel] Univ N Carolina, Inst Marine Sci, Morehead City, NC 28557 USA.
   [Tamburini, Christian] Univ Aix Marseille 2, Ctr Oceanol Marseille, CNRS, UMR 6117, F-13288 Marseille 9, France.
   [Weinbauer, Markus] CNRS, F-06234 Villefranche Sur Mer, France.
   [Weinbauer, Markus] Lab Oceanog Villefranche, Microbial Ecol & Biogeochem Grp, F-06234 Villefranche Sur Mer, France.
   [Weinbauer, Markus] Univ Paris 06, Lab Oceanog Villefranche, F-06234 Villefranche Sur Mer, France.
C3 Marche Polytechnic University; University of North Carolina; University of North Carolina Chapel Hill; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Sorbonne Universite
RP Danovaro, R (corresponding author), Polytech Univ Marche, Dept Marine Sci, Fac Sci, Via Brecce Bianche, I-60131 Ancona, Italy.
EM r.danovaro@univpm.it
FU project HERMES; ANR POTES
NR 39
TC 309
Z9 371
U1 7
U2 206
PU 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 28
PY 2008
VL 454
IS 7208
BP 1084
EP U27
DI 10.1038/nature07268
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600030
PM 18756250
DA 2026-03-09
ER

PT J
AU Donnelly, P
AF Donnelly, Peter
TI Progress and challenges in genome-wide association studies in humans
SO NATURE
LA English
DT Article
ID susceptibility loci; prostate-cancer; breast-cancer; variants; disease; risk; replication; height
AB After more than a decade of hope and hype, researchers are finally making inroads into understanding the genetic basis of many common human diseases. The use of genome- wide association studies has broken the logjam, enabling genetic variants at specific loci to be associated with particular diseases. Genetic association data are now providing new routes to understanding the aetiology of disease, as well as new footholds on the long and difficult path to better treatment and disease prevention.
C1 Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
C3 University of Oxford; Wellcome Centre for Human Genetics
RP Donnelly, P (corresponding author), Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
EM peter.donnelly@well.ox.ac.uk
NR 20
TC 256
Z9 322
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 DEC 11
PY 2008
VL 456
IS 7223
BP 728
EP 731
DI 10.1038/nature07631
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900036
PM 19079049
DA 2026-03-09
ER

PT J
AU Crowley, TJ
   Hyde, WT
AF Crowley, Thomas J.
   Hyde, William T.
TI Transient nature of late Pleistocene climate variability
SO NATURE
LA English
DT Article
ID ice-age cycle; carbon-dioxide; snowball earth; model; trends; record; ma; temperature; instability; glaciation
AB Climate in the early Pleistocene(1) varied with a period of 41 kyr and was related to variations in Earth's obliquity. About 900 kyr ago, variability increased and oscillated primarily at a period of similar to 100 kyr, suggesting that the link was then with the eccentricity of Earth's orbit. This transition has often(2-5) been attributed to a non-linear response to small changes in external boundary conditions. Here we propose that increasing variablility within the past million years may indicate that the climate system was approaching a second climate bifurcation point, after which it would transition again to a new stable state characterized by permanent mid- latitude Northern Hemisphere glaciation. From this perspective the past million years can be viewed as a transient interval in the evolution of Earth's climate. We support our hypothesis using a coupled energy balance/ ice- sheet model, which furthermore predicts that the future transition would involve a large expansion of the Eurasian ice sheet. The process responsible for the abrupt change seems to be the albedo discontinuity at the snow - ice edge. The best- fit model run, which explains almost 60% of the variance in global ice volume(6) during the past 400 kyr, predicts a rapid transition in the geologically near future to the proposed glacial state. Should it be attained, this state would be more 'symmetric' than the present climate, with comparable areas of ice/ sea- ice cover in each hemisphere, and would represent the culmination of 50 million years of evolution from bipolar nonglacial climates to bipolar glacial climates.
C1 [Crowley, Thomas J.] Univ Edinburgh, Sch Geosci, Edinburgh EH9 3JW, Midlothian, Scotland.
   [Hyde, William T.] Univ Toronto, Dept Phys, Toronto, ON M5S 1A7, Canada.
C3 University of Edinburgh; University of Toronto
RP Crowley, TJ (corresponding author), Univ Edinburgh, Sch Geosci, Edinburgh EH9 3JW, Midlothian, Scotland.
EM thomas.crowley@ed.ac.uk
FU Scottish Alliance for Geoscience, the Environment, and Society ( SAGES); US National Science Foundation
NR 30
TC 50
Z9 59
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 NOV 13
PY 2008
VL 456
IS 7219
BP 226
EP 230
DI 10.1038/nature07365
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300037
PM 19005552
DA 2026-03-09
ER

PT J
AU Skotheim, JM
   Di Talia, S
   Siggia, ED
   Cross, FR
AF Skotheim, Jan M.
   Di Talia, Stefano
   Siggia, Eric D.
   Cross, Frederick R.
TI Positive feedback of G1 cyclins ensures coherent cell cycle entry
SO NATURE
LA English
DT Article
ID yeast saccharomyces-cerevisiae; transcription factors; g1-specific transcription; fluorescent protein; gene-expression; budding yeast; cdk activity; cln3; start; division
AB In budding yeast, Saccharomyces cerevisiae, the Start checkpoint integrates multiple internal and external signals into an all- or- none decision to enter the cell cycle. Here we show that Start behaves like a switch due to systems- level feedback in the regulatory network. In contrast to current models proposing a linear cascade of Start activation, transcriptional positive feedback of the G1 cyclins Cln1 and Cln2 induces the near- simultaneous expression of the similar to 200- gene G1/ S regulon. Nuclear Cln2 drives coherent regulon expression, whereas cytoplasmic Cln2 drives efficient budding. Cells with the CLN1 and CLN2 genes deleted frequently arrest as unbudded cells, incurring a large fluctuation- induced fitness penalty due to both the lack of cytoplasmic Cln2 and insufficient G1/ S regulon expression. Thus, positive- feedback- amplified expression of Cln1 and Cln2 simultaneously drives robust budding and rapid, coherent regulon expression. A similar G1/ S regulatory network in mammalian cells, comprised of non- orthologous genes, suggests either conservation of regulatory architecture or convergent evolution.
C1 [Skotheim, Jan M.; Di Talia, Stefano; Siggia, Eric D.; Cross, Frederick R.] Rockefeller Univ, Ctr Studies Phys & Biol, New York, NY 10065 USA.
C3 Rockefeller University
RP Skotheim, JM (corresponding author), Rockefeller Univ, Ctr Studies Phys & Biol, 1230 York Ave, New York, NY 10065 USA.
EM skotheim@stanford.edu
FU NIGMS NIH HHS [R01 GM078153, F32 GM078769] Funding Source: Medline
NR 43
TC 275
Z9 357
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 291
EP U12
DI 10.1038/nature07118
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300029
PM 18633409
DA 2026-03-09
ER

PT J
AU Krumholz, MR
   McKee, CF
AF Krumholz, Mark R.
   McKee, Christopher F.
TI A minimum column density of 1 g cm-2 for massive star formation
SO NATURE
LA English
DT Article
ID protostellar cores; molecular clouds; cluster formation; water masers; gas; fragmentation; turbulence; galaxy; disks; time
AB Massive stars are very rare, but their extreme luminosities make them both the only type of young star we can observe in distant galaxies and the dominant energy sources in the Universe today. They form rarely because efficient radiative cooling keeps most star- forming gas clouds close to isothermal as they collapse, and this favours fragmentation into stars of one solar mass or lower(1-3). Heating of a cloud by accreting low- mass stars within it can prevent fragmentation and allow formation of massive stars(4,5), but the necessary properties for a cloud to form massive stars - and therefore where massive stars form in a galaxy - have not yet been determined. Here we show that only clouds with column densities of at least 1 g cm(-2) can avoid fragmentation and form massive stars. This threshold, and the environmental variation of the stellar initial mass function that it implies, naturally explain the characteristic column densities associated with massive star clusters(6-9) and the difference between the radial profiles of Ha and ultraviolet emission in galactic disks(10,11). The existence of a threshold also implies that the initial mass function should show detectable variation with environment within the Galaxy, that the characteristic column densities of clusters containing massive stars should vary between galaxies, and that star formation rates in some galactic environments may have been systematically underestimated.
C1 [Krumholz, Mark R.] Princeton Univ, Dept Astrophys, Princeton, NJ 08544 USA.
   [Krumholz, Mark R.] Univ Calif Santa Cruz, Dept Astrophys, Santa Cruz, CA 95064 USA.
   [McKee, Christopher F.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [McKee, Christopher F.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
C3 Princeton University; University of California System; University of California Santa Cruz; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Krumholz, MR (corresponding author), Princeton Univ, Dept Astrophys, Princeton, NJ 08544 USA.
EM krumholz@astro.princeton.edu
NR 30
TC 277
Z9 310
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1082
EP 1084
DI 10.1038/nature06620
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600036
PM 18305539
DA 2026-03-09
ER

PT J
AU Ewald, SE
   Lee, BL
   Lau, L
   Wickliffe, KE
   Shi, GP
   Chapman, HA
   Barton, GM
AF Ewald, Sarah E.
   Lee, Bettina L.
   Lau, Laura
   Wickliffe, Katherine E.
   Shi, Guo-Ping
   Chapman, Harold A.
   Barton, Gregory M.
TI The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor
SO NATURE
LA English
DT Article
ID antigen presentation; stranded-rna; cpg-dna; tlr9; er; toll-like-receptor-9; recognition; cathepsins; responses; membrane
AB Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids(1,2); however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids(3). The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood(4-6). Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full- length protein is detectable in the compartment where ligand is recognized. Notably, although both the full- length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full- length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non- functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids.
C1 [Ewald, Sarah E.; Lee, Bettina L.; Lau, Laura; Wickliffe, Katherine E.; Barton, Gregory M.] Univ Calif Berkeley, Div Immunol & Pathogenesis, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Shi, Guo-Ping] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Chapman, Harold A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
   [Chapman, Harold A.] Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA.
C3 University of California System; University of California Berkeley; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Barton, GM (corresponding author), Univ Calif Berkeley, Div Immunol & Pathogenesis, Dept Mol & Cell Biol, 405 Life Sci Addit, Berkeley, CA 94720 USA.
EM barton@berkeley.edu
FU Novel Research Grant; The Lupus Research Institute; Hellman Faculty Fund; NIH [HL67204, CA009179, AI072429]; National Institute of Allergy and Infectious Diseases [R01AI072429] Funding Source: NIH RePORTER
NR 23
TC 497
Z9 598
U1 2
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 4
PY 2008
VL 456
IS 7222
BP 658
EP U88
DI 10.1038/nature07405
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000045
PM 18820679
DA 2026-03-09
ER

PT J
AU Neil, SJD
   Zang, T
   Bieniasz, PD
AF Neil, Stuart J. D.
   Zang, Trinity
   Bieniasz, Paul D.
TI Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu
SO NATURE
LA English
DT Article
ID virus type-1 vpu; protein; raft; cd4; endocytosis; expression; cells; gene; nef; gag
AB Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV- 1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha, and it consists of protein- based tethers, which we term 'tetherins', that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317 ( also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV- 1 and murine leukaemia virus particle release. Furthermore, in cells where HIV- 1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317- positive compartments. Vpu co- localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin's antiviral activity is a potential therapeutic strategy in HIV/AIDS.
C1 [Neil, Stuart J. D.; Zang, Trinity; Bieniasz, Paul D.] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA.
   [Neil, Stuart J. D.; Zang, Trinity; Bieniasz, Paul D.] Rockefeller Univ, Lab Retrovirol, New York, NY 10016 USA.
C3 Rockefeller University; Rockefeller University
RP Bieniasz, PD (corresponding author), Rockefeller Univ, Aaron Diamond AIDS Res Ctr, 455 1st Ave, New York, NY 10016 USA.
EM pbienias@adarc.org
NR 22
TC 1514
Z9 1985
U1 1
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 24
PY 2008
VL 451
IS 7177
BP 425
EP U1
DI 10.1038/nature06553
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100036
PM 18200009
DA 2026-03-09
ER

PT J
AU Srivastava, M
   Begovic, E
   Chapman, J
   Putnam, NH
   Hellsten, U
   Kawashima, T
   Kuo, A
   Mitros, T
   Salamov, A
   Carpenter, ML
   Signorovitch, AY
   Moreno, MA
   Kamm, K
   Grimwood, J
   Schmutz, J
   Shapiro, H
   Grigoriev, IV
   Buss, LW
   Schierwater, B
   Dellaporta, SL
   Rokhsar, DS
AF Srivastava, Mansi
   Begovic, Emina
   Chapman, Jarrod
   Putnam, Nicholas H.
   Hellsten, Uffe
   Kawashima, Takeshi
   Kuo, Alan
   Mitros, Therese
   Salamov, Asaf
   Carpenter, Meredith L.
   Signorovitch, Ana Y.
   Moreno, Maria A.
   Kamm, Kai
   Grimwood, Jane
   Schmutz, Jeremy
   Shapiro, Harris
   Grigoriev, Igor V.
   Buss, Leo W.
   Schierwater, Bernd
   Dellaporta, Stephen L.
   Rokhsar, Daniel S.
TI The Trichoplax genome and the nature of placozoans
SO NATURE
LA English
DT Article
ID multiple sequence alignment; origin; gene; expression; phylum; diversity; evolution; cnidarian; position; field
AB As arguably the simplest free- living animals, placozoans may represent a primitive metazoan form, yet their biology is poorly understood. Here we report the sequencing and analysis of the similar to 98 million base pair nuclear genome of the placozoan Trichoplax adhaerens. Whole- genome phylogenetic analysis suggests that placozoans belong to a 'eumetazoan' clade that includes cnidarians and bilaterians, with sponges as the earliest diverging animals. The compact genome shows conserved gene content, gene structure and synteny in relation to the human and other complex eumetazoan genomes. Despite the apparent cellular and organismal simplicity of Trichoplax, its genome encodes a rich array of transcription factor and signalling pathway genes that are typically associated with diverse cell types and developmental processes in eumetazoans, motivating further searches for cryptic cellular complexity and/ or as yet unobserved life history stages.
C1 [Srivastava, Mansi; Begovic, Emina; Kawashima, Takeshi; Mitros, Therese; Carpenter, Meredith L.; Rokhsar, Daniel S.] Univ Calif Berkeley, Ctr Integrat Genom, Berkeley, CA 94720 USA.
   [Srivastava, Mansi; Begovic, Emina; Kawashima, Takeshi; Mitros, Therese; Carpenter, Meredith L.; Rokhsar, Daniel S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Begovic, Emina; Chapman, Jarrod; Putnam, Nicholas H.; Hellsten, Uffe; Kuo, Alan; Salamov, Asaf; Shapiro, Harris; Grigoriev, Igor V.; Rokhsar, Daniel S.] Dept Energy Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Kawashima, Takeshi] Okinawa Inst Sci & Technol, Okinawa 9042234, Japan.
   [Signorovitch, Ana Y.; Moreno, Maria A.; Schierwater, Bernd; Dellaporta, Stephen L.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Signorovitch, Ana Y.; Buss, Leo W.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
   [Buss, Leo W.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Kamm, Kai; Schierwater, Bernd] Stiftung Tieraerztliche Hochsch Hannover, Div Ecol & Evolut, Inst Tierokol & Zellbiol, D-30559 Hannover, Germany.
   [Grimwood, Jane; Schmutz, Jeremy] Stanford Univ, Stanford Human Genome Ctr, Palo Alto, CA 94304 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Okinawa Institute of Science & Technology Graduate University; Yale University; Yale University; Yale University; Stanford University
RP Srivastava, M (corresponding author), Univ Calif Berkeley, Ctr Integrat Genom, Berkeley, CA 94720 USA.
EM msrivast@berkeley.edu; dsrokhsar@yahoo.com
FU USA Department of Energy's Office of Science, Biological and Environmental Research Program; Gordon and Betty Moore Foundation; National Science Foundation; German Science Foundation
NR 56
TC 676
Z9 817
U1 0
U2 98
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 21
PY 2008
VL 454
IS 7207
BP 955
EP U19
DI 10.1038/nature07191
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000030
PM 18719581
DA 2026-03-09
ER

PT J
AU Zhou, L
   Lopes, JE
   Chong, MMW
   Ivanov, II
   Min, R
   Victora, GD
   Shen, YL
   Du, JG
   Rubtsov, YP
   Rudensky, AY
   Ziegler, SF
   Littman, DR
AF Zhou, Liang
   Lopes, Jared E.
   Chong, Mark M. W.
   Ivanov, Ivaylo I.
   Min, Roy
   Victora, Gabriel D.
   Shen, Yuelei
   Du, Jianguang
   Rubtsov, Yuri P.
   Rudensky, Alexander Y.
   Ziegler, Steven F.
   Littman, Dan R.
TI TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function
SO NATURE
LA English
DT Article
ID autoimmune inflammation; generation; cytokine; il-21; interleukin-17; transcription; activation; repressor; responses; pathways
AB T helper cells that produce IL- 17 (T(H)17 cells) promote autoimmunity in mice and have been implicated in the pathogenesis of human inflammatory diseases. At mucosal surfaces, T(H)17 cells are thought to protect the host from infection, whereas regulatory T ( T-reg) cells control immune responses and inflammation triggered by the resident microflora(1-5). Differentiation of both cell types requires transforming growth factor-beta (TGF-beta), but depends on distinct transcription factors: ROR gamma t ( encoded by Rorc(gamma t)) for T(H)17 cells and Foxp3 for T-reg cells(6-8). How TGF-beta regulates the differentiation of T cells with opposing activities has been perplexing. Here we demonstrate that, together with pro- inflammatory cytokines, TGF-beta orchestrates T(H)17 cell differentiation in a concentration-dependent manner. At low concentrations, TGF-b synergizes with interleukin ( IL)- 6 and IL- 21 ( refs 9 - 11) to promote IL- 23 receptor (Il23r) expression, favouring T(H)17 cell differentiation. High concentrations of TGF-beta repress IL23r expression and favour Foxp3(+) T-reg cells. ROR gamma t and Foxp3 are co- expressed in naive CD4(+) T cells exposed to TGF-beta and in a subset of T cells in the small intestinal lamina propria of the mouse. In vitro, TGF-beta-induced Foxp3 inhibits ROR gamma t function, at least in part through their interaction. Accordingly, lamina propria T cells that co-express both transcription factors produce less IL- 17 ( also known as IL-17a) than those that express ROR gamma t alone. IL- 6, IL- 21 and IL- 23 relieve Foxp3- mediated inhibition of ROR gamma t, thereby promoting TH17 cell differentiation. Therefore, the decision of antigen- stimulated cells to differentiate into either T(H)17 or T-reg cells depends on the cytokine- regulated balance of ROR gamma t and Foxp3.
C1 [Zhou, Liang; Chong, Mark M. W.; Ivanov, Ivaylo I.; Min, Roy; Victora, Gabriel D.; Shen, Yuelei; Littman, Dan R.] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Min, Roy; Littman, Dan R.] NYU, Sch Med, Dept Microbiol, Howard Hughes Med Inst, New York, NY 10016 USA.
   [Min, Roy; Littman, Dan R.] NYU, Sch Med, Dept Pathol, Howard Hughes Med Inst, New York, NY 10016 USA.
   [Lopes, Jared E.; Du, Jianguang; Ziegler, Steven F.] Benaroya Res Inst, Program Immunol, Seattle, WA 98101 USA.
   [Lopes, Jared E.; Du, Jianguang; Ziegler, Steven F.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA USA.
   [Rubtsov, Yuri P.; Rudensky, Alexander Y.] Univ Washington, Dept Immunol, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 New York University; New York University; Howard Hughes Medical Institute; New York University; Howard Hughes Medical Institute; Benaroya Research Institute; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
RP Littman, DR (corresponding author), NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA.
EM littman@saturn.med.nyu.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIAID NIH HHS [R01 AI048779, AI48779] Funding Source: Medline
NR 30
TC 1607
Z9 2020
U1 5
U2 131
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 236
EP U14
DI 10.1038/nature06878
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400043
PM 18368049
DA 2026-03-09
ER

PT J
AU Sebastian, SE
   Harrison, N
   Palm, E
   Murphy, TP
   Mielke, CH
   Liang, RX
   Bonn, DA
   Hardy, WN
   Lonzarich, GG
AF Sebastian, Suchitra E.
   Harrison, N.
   Palm, E.
   Murphy, T. P.
   Mielke, C. H.
   Liang, Ruixing
   Bonn, D. A.
   Hardy, W. N.
   Lonzarich, G. G.
TI A multi-component Fermi surface in the vortex state of an underdoped high-Tc superconductor
SO NATURE
LA English
DT Article
ID quantum oscillations; phase
AB To understand the origin of superconductivity, it is crucial to ascertain the nature and origin of the primary carriers available to participate in pairing(1-6). Recent quantum oscillation experiments on high- transition- temperature ( high- T-c) copper oxide superconductors(7-10) have revealed the existence of a Fermi surface akin to that in normal metals, comprising fermionic carriers that undergo orbital quantization(11). The unexpectedly small size of the observed carrier pocket, however, leaves open a variety of possibilities for the existence or form of any underlying magnetic order, and its relation to d- wave superconductivity(12-15). Here we report experiments on quantum oscillations in the magnetization ( the de Haas- van Alphen effect) in superconducting YBa2Cu3O6.51 that reveal more than one carrier pocket. In particular, we find evidence for the existence of a much larger pocket of heavier mass carriers playing a thermodynamically dominant role in this hole- doped superconductor. Importantly, characteristics of the multiple pockets within this more complete Fermi surface impose constraints on the wavevector of any underlying order and the location of the carriers in momentum space. These constraints enable us to construct a possible density- wave model with spiral or related modulated magnetic order, consistent with experimental observations.
C1 [Sebastian, Suchitra E.; Lonzarich, G. G.] Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
   [Harrison, N.; Mielke, C. H.] Los Alamos Natl Lab, Natl High Magnet Field Lab, Los Alamos, NM 87545 USA.
   [Palm, E.; Murphy, T. P.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA.
   [Liang, Ruixing; Bonn, D. A.; Hardy, W. N.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z4, Canada.
   [Liang, Ruixing; Bonn, D. A.; Hardy, W. N.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
C3 University of Cambridge; United States Department of Energy (DOE); Los Alamos National Laboratory; State University System of Florida; Florida State University; University of British Columbia; Canadian Institute for Advanced Research (CIFAR)
RP Sebastian, SE (corresponding author), Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM suchitra@phy.cam.ac.uk
FU Engineering and Physical Sciences Research Council [EP/C511778/1] Funding Source: researchfish
NR 31
TC 217
Z9 241
U1 0
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 200
EP 203
DI 10.1038/nature07095
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900040
PM 18615081
DA 2026-03-09
ER

PT J
AU Murakami, M
   Kouyama, T
AF Murakami, Midori
   Kouyama, Tsutomu
TI Crystal structure of squid rhodopsin
SO NATURE
LA English
DT Article
ID protein-coupled receptors; activation; vertebrate; system; light; photoisomerization; opsin; suite
AB Invertebrate phototransduction uses an inositol-1,4,5-trisphosphate signalling cascade in which photoactivated rhodopsin stimulates a G(q)-type G protein, that is, a class of G protein that stimulates membrane-bound phospholipase C beta. The same cascade is used by many G-protein-coupled receptors, indicating that invertebrate rhodopsin is a prototypical member. Here we report the crystal structure of squid (Todarodes pacificus) rhodopsin at 2.5 angstrom resolution. Among seven transmembrane alpha-helices, helices V and VI extend into the cytoplasmic medium and, together with two cytoplasmic helices, they form a rigid protrusion from the membrane surface. This peculiar structure, which is not seen in bovine rhodopsin, seems to be crucial for the recognition of G(q)-type G proteins. The retinal Schiff base forms a hydrogen bond to Asn 87 or Tyr 111; it is far from the putative counterion Glu 180. In the crystal, a tight association is formed between the amino-terminal polypeptides of neighbouring monomers; this intermembrane dimerization may be responsible for the organization of hexagonally packed microvillar membranes in the photoreceptor rhabdom.
C1 [Murakami, Midori; Kouyama, Tsutomu] Nagoya Univ, Dept Phys, Grad Sch Sci, Nagoya, Aichi 4648602, Japan.
   [Kouyama, Tsutomu] RIKEN Harima Inst, SPring 8, Sayo, Hyogo 6795148, Japan.
C3 Nagoya University; RIKEN; Japan Synchrotron Radiation Research Institute
RP Kouyama, T (corresponding author), Nagoya Univ, Dept Phys, Grad Sch Sci, Nagoya, Aichi 4648602, Japan.
EM kouyama@bio.phys.nagoya-u.ac.jp
NR 40
TC 414
Z9 494
U1 0
U2 71
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 15
PY 2008
VL 453
IS 7193
BP 363
EP U33
DI 10.1038/nature06925
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400045
PM 18480818
DA 2026-03-09
ER

PT J
AU Springel, V
   White, SDM
   Frenk, CS
   Navarro, JF
   Jenkins, A
   Vogelsberger, M
   Wang, J
   Ludlow, A
   Helmi, A
AF Springel, V.
   White, S. D. M.
   Frenk, C. S.
   Navarro, J. F.
   Jenkins, A.
   Vogelsberger, M.
   Wang, J.
   Ludlow, A.
   Helmi, A.
TI Prospects for detecting supersymmetric dark matter in the Galactic halo
SO NATURE
LA English
DT Article
ID gamma-rays; galaxy
AB Dark matter is the dominant form of matter in the Universe, but its nature is unknown. It is plausibly an elementary particle, perhaps the lightest supersymmetric partner of known particle species(1). In this case, annihilation of dark matter in the halo of the Milky Way should produce gamma-rays at a level that may soon be observable(2,3). Previous work has argued that the annihilation signal will be dominated by emission from very small clumps(4,5) ( perhaps smaller even than the Earth), which would be most easily detected where they cluster together in the dark matter haloes of dwarf satellite galaxies(6). Here we report that such small- scale structure will, in fact, have a negligible impact on dark matter detectability. Rather, the dominant and probably most easily detectable signal will be produced by diffuse dark matter in the main halo of the MilkyWay(7,8). If the main halo is strongly detected, then small dark matter clumps should also be visible, but may well contain no stars, thereby confirming a key prediction of the cold dark matter model.
C1 [Springel, V.; White, S. D. M.; Vogelsberger, M.; Wang, J.] Max Planck Inst Astrophys, D-85740 Garching, Germany.
   [Frenk, C. S.; Jenkins, A.] Univ Durham, Dept Phys, Inst Computat Cosmol, Durham DH1 3LE, England.
   [Navarro, J. F.; Ludlow, A.] Univ Victoria, Dept Phys & Astron, Victoria, BC V8P 5C2, Canada.
   [Navarro, J. F.] Univ Massachusetts, Dept Astron, Amherst, MA 01003 USA.
   [Helmi, A.] Univ Groningen, Kapteyn Astron Inst, NL-9700 AV Groningen, Netherlands.
C3 Max Planck Society; Durham University; University of Victoria; University of Massachusetts System; University of Massachusetts Amherst; University of Groningen; Kapteyn Astronomical Institute
RP Springel, V (corresponding author), Max Planck Inst Astrophys, Karl Schwarzschild Str 1, D-85740 Garching, Germany.
EM vspringel@mpa-garching.mpg.de
FU STFC Rolling Grant; STFC [ST/F002289/1, ST/F002300/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/F002289/1, ST/F002300/1] Funding Source: researchfish
NR 30
TC 209
Z9 230
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 NOV 6
PY 2008
VL 456
IS 7218
BP 73
EP 76
DI 10.1038/nature07411
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000042
PM 18987737
DA 2026-03-09
ER

PT J
AU Kim, J
   Darley, DJ
   Buckel, W
   Pierik, AJ
AF Kim, Jihoe
   Darley, Daniel J.
   Buckel, Wolfgang
   Pierik, Antonio J.
TI An allylic ketyl radical intermediate in clostridial amino-acid fermentation
SO NATURE
LA English
DT Article
ID iron-sulfur clusters; lysine 2,3-aminomutase; mechanistic proposal; anaerobic-bacteria; difficile; dehydratase; leucine; genome; analog
AB The human pathogenic bacterium Clostridium difficile thrives by the fermentation of L- leucine toammonia, CO2, 3-methylbutanoate and 4-methylpentanoate under anaerobic conditions(1). The reductive branch to 4- methylpentanoate proceeds by means of the dehydration of ( R)- 2- hydroxy- 4- methylpentanoyl- CoA to 4- methylpent-2- enoyl- CoA, which is chemically the most demanding step. Ketyl radicals have been proposed(2) to mediate this reaction catalysed by an iron - sulphur- cluster- containing dehydratase, which requires activation by ATP- dependent electron transfer from a second iron - sulphur protein functionally similar to the iron protein of nitrogenase. Here we identify a kinetically competent product-related allylic ketyl radical bound to the enzyme by electron paramagnetic resonance spectroscopy employing isotope- labelled ( R)- 2- hydroxy- 4- methylpentanoyl- CoA species. We also found that the enzyme generated the stabilized pentadienoyl ketyl radical from the substrate analogue 2- hydroxypent- 4- enoyl- CoA, supporting the proposed mechanism. Our results imply that also other 2- hydroxyacyl- CoA dehydratases(3) and the related benzoyl- CoA reductases(4) - present in anaerobically living bacteria - employ ketyl radical intermediates. The absence of radical generators such as coenzyme B-12, S- adenosylmethionine or oxygen makes these enzymes unprecedented in biochemistry.
C1 [Kim, Jihoe; Darley, Daniel J.; Buckel, Wolfgang; Pierik, Antonio J.] Univ Marburg, Fachbereich Biol, Mikrobiol Lab, D-35032 Marburg, Germany.
C3 Philipps University Marburg
RP Pierik, AJ (corresponding author), Univ Marburg, Fachbereich Biol, Mikrobiol Lab, D-35032 Marburg, Germany.
EM pierik@staff.uni-marburg.de
NR 26
TC 59
Z9 70
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 13
PY 2008
VL 452
IS 7184
BP 239
EP U85
DI 10.1038/nature06637
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600045
PM 18337824
DA 2026-03-09
ER

PT J
AU Ding, L
   Getz, G
   Wheeler, DA
   Mardis, ER
   McLellan, MD
   Cibulskis, K
   Sougnez, C
   Greulich, H
   Muzny, DM
   Morgan, MB
   Fulton, L
   Fulton, RS
   Zhang, QY
   Wendl, MC
   Lawrence, MS
   Larson, DE
   Chen, K
   Dooling, DJ
   Sabo, A
   Hawes, AC
   Shen, H
   Jhangiani, SN
   Lewis, LR
   Hall, O
   Zhu, YM
   Mathew, T
   Ren, YR
   Yao, JQ
   Scherer, SE
   Clerc, K
   Metcalf, GA
   Ng, B
   Milosavljevic, A
   Gonzalez-Garay, ML
   Osborne, JR
   Meyer, R
   Shi, XQ
   Tang, YZ
   Koboldt, DC
   Lin, L
   Abbott, R
   Miner, TL
   Pohl, C
   Fewell, G
   Haipek, C
   Schmidt, H
   Dunford-Shore, BH
   Kraja, A
   Crosby, SD
   Sawyer, CS
   Vickery, T
   Sander, S
   Robinson, J
   Winckler, W
   Baldwin, J
   Chirieac, LR
   Dutt, A
   Fennell, T
   Hanna, M
   Johnson, BE
   Onofrio, RC
   Thomas, RK
   Tonon, G
   Weir, BA
   Zhao, XJ
   Ziaugra, L
   Zody, MC
   Giordano, T
   Orringer, MB
   Roth, JA
   Spitz, MR
   Wistuba, II
   Ozenberger, B
   Good, PJ
   Chang, AC
   Beer, DG
   Watson, MA
   Ladanyi, M
   Broderick, S
   Yoshizawa, A
   Travis, WD
   Pao, W
   Province, MA
   Weinstock, GM
   Varmus, HE
   Gabriel, SB
   Lander, ES
   Gibbs, RA
   Meyerson, M
   Wilson, RK
AF Ding, Li
   Getz, Gad
   Wheeler, David A.
   Mardis, Elaine R.
   McLellan, Michael D.
   Cibulskis, Kristian
   Sougnez, Carrie
   Greulich, Heidi
   Muzny, Donna M.
   Morgan, Margaret B.
   Fulton, Lucinda
   Fulton, Robert S.
   Zhang, Qunyuan
   Wendl, Michael C.
   Lawrence, Michael S.
   Larson, David E.
   Chen, Ken
   Dooling, David J.
   Sabo, Aniko
   Hawes, Alicia C.
   Shen, Hua
   Jhangiani, Shalini N.
   Lewis, Lora R.
   Hall, Otis
   Zhu, Yiming
   Mathew, Tittu
   Ren, Yanru
   Yao, Jiqiang
   Scherer, Steven E.
   Clerc, Kerstin
   Metcalf, Ginger A.
   Ng, Brian
   Milosavljevic, Aleksandar
   Gonzalez-Garay, Manuel L.
   Osborne, John R.
   Meyer, Rick
   Shi, Xiaoqi
   Tang, Yuzhu
   Koboldt, Daniel C.
   Lin, Ling
   Abbott, Rachel
   Miner, Tracie L.
   Pohl, Craig
   Fewell, Ginger
   Haipek, Carrie
   Schmidt, Heather
   Dunford-Shore, Brian H.
   Kraja, Aldi
   Crosby, Seth D.
   Sawyer, Christopher S.
   Vickery, Tammi
   Sander, Sacha
   Robinson, Jody
   Winckler, Wendy
   Baldwin, Jennifer
   Chirieac, Lucian R.
   Dutt, Amit
   Fennell, Tim
   Hanna, Megan
   Johnson, Bruce E.
   Onofrio, Robert C.
   Thomas, Roman K.
   Tonon, Giovanni
   Weir, Barbara A.
   Zhao, Xiaojun
   Ziaugra, Liuda
   Zody, Michael C.
   Giordano, Thomas
   Orringer, Mark B.
   Roth, Jack A.
   Spitz, Margaret R.
   Wistuba, Ignacio I.
   Ozenberger, Bradley
   Good, Peter J.
   Chang, Andrew C.
   Beer, David G.
   Watson, Mark A.
   Ladanyi, Marc
   Broderick, Stephen
   Yoshizawa, Akihiko
   Travis, William D.
   Pao, William
   Province, Michael A.
   Weinstock, George M.
   Varmus, Harold E.
   Gabriel, Stacey B.
   Lander, Eric S.
   Gibbs, Richard A.
   Meyerson, Matthew
   Wilson, Richard K.
TI Somatic mutations affect key pathways in lung adenocarcinoma
SO NATURE
LA English
DT Article
ID human breast; mendelian-inheritance; homozygous deletions; colorectal cancers; egfr mutations; tobacco-smoke; kras mutation; never smokers; receptor gene; gefitinib
AB Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
C1 [Ding, Li; Mardis, Elaine R.; McLellan, Michael D.; Fulton, Lucinda; Fulton, Robert S.; Wendl, Michael C.; Larson, David E.; Chen, Ken; Dooling, David J.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
   [Getz, Gad; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Lawrence, Michael S.; Winckler, Wendy; Baldwin, Jennifer; Dutt, Amit; Fennell, Tim; Hanna, Megan; Onofrio, Robert C.; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Gabriel, Stacey B.; Lander, Eric S.; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Genome Biol Program, Cambridge, MA 02142 USA.
   [Wheeler, David A.; Muzny, Donna M.; Morgan, Margaret B.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Greulich, Heidi; Winckler, Wendy; Dutt, Amit; Hanna, Megan; Johnson, Bruce E.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Zhang, Qunyuan; Kraja, Aldi; Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA.
   [Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Chirieac, Lucian R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Chirieac, Lucian R.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Thomas, Roman K.] Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany.
   [Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany.
   [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.
   [Giordano, Thomas] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Orringer, Mark B.; Chang, Andrew C.; Beer, David G.] Univ Michigan, Thorac Surg Sect, Dept Surg, Ann Arbor, MI 48109 USA.
   [Roth, Jack A.; Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA.
   [Spitz, Margaret R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Ozenberger, Bradley; Good, Peter J.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Watson, Mark A.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63108 USA.
   [Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
   [Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Computat Biol, New York, NY 10065 USA.
   [Ladanyi, Marc; Pao, William] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Varmus, Harold E.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
C3 Washington University (WUSTL); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Baylor College of Medicine; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Washington University (WUSTL); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Max Planck Society; University of Cologne; University of Cologne; University of Cologne; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Texas System; UTMD Anderson Cancer Center; University of Texas Health Science Center Houston; University of Texas System; UTMD Anderson Cancer Center; University of Texas Health Science Center Houston; University of Texas System; University of Texas Health Science Center Houston; UTMD Anderson Cancer Center; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Washington University (WUSTL); 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; Memorial Sloan Kettering Cancer Center
RP Wilson, RK (corresponding author), Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
EM matthew_meyerson@dfci.harvard.edu; rwilson@wustl.edu
FU National Human Genome Research Institute; National Cancer Institute [P50CA070907] Funding Source: NIH RePORTER
NR 50
TC 2181
Z9 2540
U1 1
U2 263
PU 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 23
PY 2008
VL 455
IS 7216
BP 1069
EP 1075
DI 10.1038/nature07423
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600036
PM 18948947
DA 2026-03-09
ER

PT J
AU Chen, KM
   Harjes, E
   Gross, PJ
   Fahmy, A
   Lu, YJ
   Shindo, K
   Harris, RS
   Matsuo, H
AF Chen, Kuan-Ming
   Harjes, Elena
   Gross, Phillip J.
   Fahmy, Amr
   Lu, Yongjian
   Shindo, Keisuke
   Harris, Reuben S.
   Matsuo, Hiroshi
TI Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G
SO NATURE
LA English
DT Article
ID 3-dimensional nmr-spectroscopy; cytidine deaminase; crystal-structure; sedimentation-velocity; retroviral infection; high-sensitivity; protein; resonance; assignment; complex
AB The human APOBEC3G ( apolipoprotein B messenger- RNA-editing enzyme, catalytic polypeptide- like 3G) protein is a single-strand DNA deaminase that inhibits the replication of human immunodeficiency virus-1 (HIV-1), other retroviruses and retrotransposons(1-6). APOBEC3G anti- viral activity is circumvented by most retroelements, such as through degradation by HIV-1 Vif(7). APOBEC3G is a member of a family of polynucleotide cytosine deaminases, several of which also target distinct physiological substrates. For instance, APOBEC1 edits APOB mRNA and AID deaminates antibody gene DNA(8-10). Although structures of other family members exist, none of these proteins has elicited polynucleotide cytosine deaminase or anti- viral activity(11-16). Here we report a solution structure of the human APOBEC3G catalytic domain. Five alpha- helices, including two that form the zinc- coordinating active site, are arranged over a hydrophobic platform consisting of five beta-strands. NMR DNA titration experiments, computational modelling, phylogenetic conservation and Escherichia coli- based activity assays combine to suggest a DNA-binding model in which a brim of positively charged residues positions the target cytosine for catalysis. The structure of the APOBEC3G catalytic domain will help us to understand functions of other family members and interactions that occur with pathogenic proteins such as HIV- 1 Vif.
C1 [Chen, Kuan-Ming; Harjes, Elena; Gross, Phillip J.; Lu, Yongjian; Shindo, Keisuke; Harris, Reuben S.; Matsuo, Hiroshi] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
   [Chen, Kuan-Ming; Harjes, Elena; Gross, Phillip J.; Lu, Yongjian; Shindo, Keisuke; Harris, Reuben S.; Matsuo, Hiroshi] Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA.
   [Gross, Phillip J.; Shindo, Keisuke; Harris, Reuben S.] Univ Minnesota, Arnold & Mabel Beckman Ctr Genome Engn, Minneapolis, MN 55455 USA.
   [Fahmy, Amr] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Harvard University; Harvard Medical School
RP Matsuo, H (corresponding author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
EM rsh@umn.edu; matsu029@umn.edu
FU NIAID NIH HHS [R21 AI073167] Funding Source: Medline
NR 53
TC 186
Z9 266
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 MAR 6
PY 2008
VL 452
IS 7183
BP 116
EP U16
DI 10.1038/nature06638
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900058
PM 18288108
DA 2026-03-09
ER

PT J
AU Jia, SD
   Liu, ZN
   Zhang, S
   Liu, PX
   Zhang, L
   Lee, SH
   Zhang, J
   Signoretti, S
   Loda, M
   Roberts, TM
   Zhao, JJ
AF Jia, Shidong
   Liu, Zhenning
   Zhang, Sen
   Liu, Pixu
   Zhang, Lei
   Lee, Sang Hyun
   Zhang, Jing
   Signoretti, Sabina
   Loda, Massimo
   Roberts, Thomas M.
   Zhao, Jean J.
TI Essential roles of PI(3)K-p110β in cell growth, metabolism and tumorigenesis (Publication with Expression of Concern. See APR, 2025)
SO NATURE
LA English
DT Article; Publication with Expression of Concern
ID phosphoinositide 3-kinase; phosphatidylinositol 3-kinases; embryonic lethality; p110-alpha subunit; catalytic subunit; beta-gamma; gene; activation; insulin; pten
AB On activation by receptors, the ubiquitously expressed class IA isoforms (p110 alpha and p110 beta) of phosphatidylinositol-3-OH kinase (PI(3)K) generate lipid second messengers, which initiate multiple signal transduction cascades(1-5). Recent studies have demonstrated specific functions for p110 alpha in growth factor and insulin signalling(6-8). To probe for distinct functions of p110 beta, we constructed conditional knockout mice. Here we show that ablation of p110 beta in the livers of the resulting mice leads to impaired insulin sensitivity and glucose homeostasis, while having little effect on phosphorylation of Akt, suggesting the involvement of a kinase-independent role of p110 beta in insulin metabolic action. Using established mouse embryonic fibroblasts, we found that removal of p110 beta also had little effect on Akt phosphorylation in response to stimulation by insulin and epidermal growth factor, but resulted in retarded cell proliferation. Reconstitution of p110 beta-null cells with a wild-type or kinase-dead allele of p110 beta demonstrated that p110 beta possesses kinase-independent functions in regulating cell proliferation and trafficking. However, the kinase activity of p110 beta was required for G-protein-coupled receptor signalling triggered by lysophosphatidic acid and had a function in oncogenic transformation. Most strikingly, in an animal model of prostate tumour formation induced by Pten loss, ablation of p110 beta (also known as Pik3cb), but not that of p110 alpha (also known as Pik3ca), impeded tumorigenesis with a concomitant diminution of Akt phosphorylation. Taken together, our findings demonstrate both kinase-dependent and kinase-independent functions for p110 beta, and strongly indicate the kinase-dependent functions of p110 beta as a promising target in cancer therapy.
C1 [Jia, Shidong; Liu, Zhenning; Zhang, Sen; Liu, Pixu; Zhang, Lei; Lee, Sang Hyun; Zhang, Jing; Roberts, Thomas M.; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Signoretti, Sabina; Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Jia, Shidong; Liu, Zhenning; Zhang, Sen; Liu, Pixu; Zhang, Lei; Lee, Sang Hyun; Zhang, Jing; Signoretti, Sabina; Loda, Massimo; Roberts, Thomas M.; Zhao, Jean J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Zhao, Jean J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, 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; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School
RP Roberts, TM (corresponding author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM thomas_roberts@dfci.harvard.edu; jean_zhao@dfci.harvard.edu
FU NCI NIH HHS [P01 CA089021, R01 CA131945, R01 CA030002, P01 CA050661, P50 CA089393, R01 CA134502, P50 CA090381] Funding Source: Medline
NR 34
TC 603
Z9 720
U1 1
U2 60
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 776
EP U102
DI 10.1038/nature07091
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000047
PM 18594509
DA 2026-03-09
ER

PT J
AU Anderson, JS
   Reisz, RR
   Scott, D
   Fröbisch, NB
   Sumida, SS
AF Anderson, Jason S.
   Reisz, Robert R.
   Scott, Diane
   Frobisch, Nadia B.
   Sumida, Stuart S.
TI A stem batrachian from the Early Permian of Texas and the origin of frogs and salamanders
SO NATURE
LA English
DT Article
ID phylogeny; ancestry
AB The origin of extant amphibians (Lissamphibia: frogs, salamanders and caecilians) is one of the most controversial questions in vertebrate evolution, owing to large morphological and temporal gaps in the fossil record(1-3). Current discussions focus on three competing hypotheses: a monophyletic origin within either Temnospondyli(4-7) or Lepospondyli(8-10), or a polyphyletic origin with frogs and salamanders arising among temnospondyls and caecilians among the lepospondyls(11-16). Recent molecular analyses are also controversial, with estimations for the batrachian (frog salamander) divergence significantly older than the palaeontological evidence supports(17,18). Here we report the discovery of an amphibamid temnospondyl from the Early Permian of Texas that bridges the gap between other Palaeozoic amphibians and the earliest known salientians(19,20) and caudatans(21) from the Mesozoic. The presence of a mosaic of salientian and caudatan characters in this small fossil makes it a key taxon close to the batrachian (frog and salamander) divergence. Phylogenetic analysis suggests that the batrachian divergence occurred in the Middle Permian, rather than the late Carboniferous as recently estimated using molecular clocks(18,22), but the divergence with caecilians corresponds to the deep split between temnospondyls and lepospondyls, which is congruent with themolecular estimates.
C1 [Anderson, Jason S.] Univ Calgary, Dept Comparat Biol & Expt Med, Fac Vet Med, Calgary, AB T2N 4N1, Canada.
   [Reisz, Robert R.; Scott, Diane] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
   [Frobisch, Nadia B.] McGill Univ, Redpath Museum, Montreal, PQ H3A 2K6, Canada.
   [Sumida, Stuart S.] Calif State Univ San Bernardino, Dept Biol, San Bernardino, CA 92407 USA.
C3 University of Calgary; University of Toronto; University Toronto Mississauga; McGill University; California State University System; California State University San Bernardino
RP Anderson, JS (corresponding author), Univ Calgary, Dept Comparat Biol & Expt Med, Fac Vet Med, 3330 Hosp Dr, Calgary, AB T2N 4N1, Canada.
EM janders@ucalgary.ca
NR 30
TC 181
Z9 201
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 MAY 22
PY 2008
VL 453
IS 7194
BP 515
EP 518
DI 10.1038/nature06865
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700041
PM 18497824
DA 2026-03-09
ER

PT J
AU Mazmanian, SK
   Round, JL
   Kasper, DL
AF Mazmanian, Sarkis K.
   Round, June L.
   Kasper, Dennis L.
TI A microbial symbiosis factor prevents intestinal inflammatory disease
SO NATURE
LA English
DT Article
ID regulatory t-cells; bowel-disease; bacteria; suppress; colitis; gut; flora; interleukin-10; pathogenesis; microflora
AB Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule ( polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro- inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro- inflammatory interleukin- 17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin- 10- producing CD4(+) T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.
C1 [Mazmanian, Sarkis K.; Round, June L.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Kasper, Dennis L.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Kasper, Dennis L.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
C3 California Institute of Technology; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard Medical School
RP Mazmanian, SK (corresponding author), CALTECH, Div Biol, Pasadena, CA 91125 USA.
EM sarkis@caltech.edu; dennis_kasper@hms.harvard.edu
FU NIAID NIH HHS [R01 AI039576] Funding Source: Medline
NR 38
TC 1887
Z9 2315
U1 15
U2 654
PU NATURE PUBLISHING 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 29
PY 2008
VL 453
IS 7195
BP 620
EP 625
DI 10.1038/nature07008
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200036
PM 18509436
DA 2026-03-09
ER

PT J
AU Tammela, T
   Zarkada, G
   Wallgard, E
   Murtomäki, A
   Suchting, S
   Wirzenius, M
   Waltari, M
   Hellström, M
   Schomber, T
   Peltonen, R
   Freitas, C
   Duarte, A
   Isoniemi, H
   Laakkonen, P
   Christofori, G
   Ylä-Herttuala, S
   Shibuya, M
   Pytowski, B
   Eichmann, A
   Betsholtz, C
   Alitalo, K
AF Tammela, Tuomas
   Zarkada, Georgia
   Wallgard, Elisabet
   Murtomaki, Aino
   Suchting, Steven
   Wirzenius, Maria
   Waltari, Marika
   Hellstrom, Mats
   Schomber, Tibor
   Peltonen, Reetta
   Freitas, Catarina
   Duarte, Antonio
   Isoniemi, Helena
   Laakkonen, Pirjo
   Christofori, Gerhard
   Yla-Herttuala, Seppo
   Shibuya, Masabumi
   Pytowski, Bronislaw
   Eichmann, Anne
   Betsholtz, Christer
   Alitalo, Kari
TI Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation
SO NATURE
LA English
DT Article
ID growth-factor receptor-3; inhibits tumor-growth; endothelial-cells; factor-c; lymphatic endothelium; lymphangiogenesis; expression; mouse; mice; cancer
AB Angiogenesis, the growth of new blood vessels from pre- existing vasculature, is a key process in several pathological conditions, including tumour growth and age- related macular degeneration(1). Vascular endothelial growth factors ( VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor ( VEGFR) tyrosine kinases in endothelial cells(2). VEGFR- 3 ( also known as FLT- 4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium(3). However, VEGFR- 3 is upregulated in the microvasculature of tumours and wounds(4,5). Here we demonstrate that VEGFR- 3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR- 3 or blocking of VEGFR- 3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR- 3 augmented VEGF- induced angiogenesis and sustained angiogenesis even in the presence of VEGFR- 2 ( also known as KDR or FLK- 1) inhibitors, whereas antibodies against VEGFR- 3 and VEGFR- 2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR- 3 expression and excessive sprouting, which was inhibited by blocking VEGFR- 3 signals. Our results implicate VEGFR- 3 as a regulator of vascular network formation. Targeting VEGFR- 3 may provide additional efficacy for anti- angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR- 2 inhibitors.
C1 [Tammela, Tuomas; Zarkada, Georgia; Murtomaki, Aino; Wirzenius, Maria; Waltari, Marika; Laakkonen, Pirjo; Alitalo, Kari] Univ Helsinki, Lab Mol Canc Biol, FIN-00014 Helsinki, Finland.
   [Tammela, Tuomas; Zarkada, Georgia; Murtomaki, Aino; Wirzenius, Maria; Waltari, Marika; Laakkonen, Pirjo; Alitalo, Kari] Univ Helsinki, Ludwig Inst Canc Res, Biomedicum Helsinki, FIN-00014 Helsinki, Finland.
   [Tammela, Tuomas; Zarkada, Georgia; Murtomaki, Aino; Wirzenius, Maria; Waltari, Marika; Laakkonen, Pirjo; Alitalo, Kari] Univ Helsinki, Haartman Inst, FIN-00014 Helsinki, Finland.
   [Wallgard, Elisabet; Hellstrom, Mats; Betsholtz, Christer] Karolinska Inst, Div Matrix Biol, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden.
   [Suchting, Steven; Freitas, Catarina; Eichmann, Anne] Coll France, INSERM, U833, F-75005 Paris, France.
   [Schomber, Tibor; Christofori, Gerhard] Univ Basel, Ctr Biomed, Dept Clin Biol Sci, CH-4058 Basel, Switzerland.
   [Peltonen, Reetta; Isoniemi, Helena] Univ Helsinki, Cent Hosp, Dept Transplantat & Hepat Surg, Helsinki 00029, Finland.
   [Duarte, Antonio] Univ Tecn Lisbon, Fac Vet Med, Interdisciplinary Ctr Res Anim Hlth CIISA, P-1300474 Lisbon, Portugal.
   [Yla-Herttuala, Seppo] Univ Kuopio, AI Virtanen Inst, FIN-70211 Kuopio, Finland.
   [Shibuya, Masabumi] Tokyo Med & Dent Univ, Dept Mol Oncol, Bunkyo Ku, Tokyo 1138519, Japan.
   [Pytowski, Bronislaw] ImClone Syst, New York, NY 10014 USA.
C3 University of Helsinki; University of Helsinki; Ludwig Institute for Cancer Research; University of Helsinki; Karolinska Institutet; Universite PSL; College de France; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Basel; University of Helsinki; Helsinki University Central Hospital; Universidade de Lisboa; University of Eastern Finland; Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Eli Lilly; Imclone Systems Inc
RP Alitalo, K (corresponding author), Univ Helsinki, Lab Mol Canc Biol, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland.
EM kari.alitalo@helsinki.fi
FU NHLBI NIH HHS [5 R01 HL075183-02] Funding Source: Medline
NR 50
TC 671
Z9 803
U1 0
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 656
EP U68
DI 10.1038/nature07083
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500051
PM 18594512
DA 2026-03-09
ER

PT J
AU Hertlein, C
   Helden, L
   Gambassi, A
   Dietrich, S
   Bechinger, C
AF Hertlein, C.
   Helden, L.
   Gambassi, A.
   Dietrich, S.
   Bechinger, C.
TI Direct measurement of critical Casimir forces
SO NATURE
LA English
DT Article
ID spherical-particles; light-scattering; liquid-mixtures; spheres; aggregation; suspensions; fluids; wall
AB When fluctuating fields are confined between two surfaces, long- range forces arise. A famous example is the quantum electrodynamical Casimir force that results from zero- point vacuum fluctuations confined between two conducting metal plates(1). A thermodynamic analogue is the critical Casimir force: it acts between surfaces immersed in a binary liquid mixture close to its critical point and arises from the confinement of concentration fluctuations within the thin film of fluid separating the surfaces(2). So far, all experimental evidence for the existence of this effect has been indirect(3-5). Here we report the direct measurement of critical Casimir force between a single colloidal sphere and a flat silica surface immersed in a mixture of water and 2,6- lutidine near its critical point. We use total internal reflection microscopy to determine in situ the forces between the sphere and the surface, with femtonewton resolution(6). Depending on whether the adsorption preferences of the sphere and the surface for water and 2,6- lutidine are identical or opposite, we measure attractive and repulsive forces, respectively, that agree quantitatively with theoretical predictions and exhibit exquisite dependence on the temperature of the system. We expect that these features of critical Casimir forces may result in novel uses of colloids as model systems.
C1 [Hertlein, C.; Helden, L.; Bechinger, C.] Univ Stuttgart, Inst Phys 2, D-70569 Stuttgart, Germany.
   [Gambassi, A.; Dietrich, S.] Max Planck Inst Met Res, D-70569 Stuttgart, Germany.
   [Gambassi, A.; Dietrich, S.] Univ Stuttgart, Inst Theoret & Angew Phys, D-70569 Stuttgart, Germany.
C3 University of Stuttgart; Max Planck Society; University of Stuttgart
RP Bechinger, C (corresponding author), Univ Stuttgart, Inst Phys 2, Pfaffenwaldring 57, D-70569 Stuttgart, Germany.
EM c.bechinger@physik.uni-stuttgart.de
NR 24
TC 505
Z9 532
U1 4
U2 175
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 172
EP 175
DI 10.1038/nature06443
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400038
PM 18185584
DA 2026-03-09
ER

PT J
AU Armand, M
   Tarascon, JM
AF Armand, M.
   Tarascon, J. -M.
TI Building better batteries
SO NATURE
LA English
DT Article
ID electrode materials
C1 [Armand, M.; Tarascon, J. -M.] Univ Picardie, LRCS, CNRS, UMR 6007, Amiens, France.
C3 Universite de Picardie Jules Verne (UPJV); Centre National de la Recherche Scientifique (CNRS)
RP Tarascon, JM (corresponding author), Univ Picardie, LRCS, CNRS, UMR 6007, Amiens, France.
EM jean-marie.tarascon@sc.u-picardie.fr
NR 27
TC 17908
Z9 19513
U1 190
U2 11016
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 652
EP 657
DI 10.1038/451652a
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500029
PM 18256660
DA 2026-03-09
ER

PT J
AU Keren, K
   Pincus, Z
   Allen, GM
   Barnhart, EL
   Marriott, G
   Mogilner, A
   Theriot, JA
AF Keren, Kinneret
   Pincus, Zachary
   Allen, Greg M.
   Barnhart, Erin L.
   Marriott, Gerard
   Mogilner, Alex
   Theriot, Julie A.
TI Mechanism of shape determination in motile cells
SO NATURE
LA English
DT Article
ID fish keratocytes; retrograde flow; leading-edge; actin; dynamics; lamellipodia; cytoskeleton; locomotion; fragments; migration
AB The shape of motile cells is determined by many dynamic processes spanning several orders of magnitude in space and time, from local polymerization of actin monomers at subsecond timescales to global, cell-scale geometry that may persist for hours. Understanding the mechanism of shape determination in cells has proved to be extremely challenging due to the numerous components involved and the complexity of their interactions. Here we harness the natural phenotypic variability in a large population of motile epithelial keratocytes from fish (Hypsophrys nicaraguensis) to reveal mechanisms of shape determination. We find that the cells inhabit a low-dimensional, highly correlated spectrum of possible functional states. We further show that a model of actin network treadmilling in an inextensible membrane bag can quantitatively recapitulate this spectrum and predict both cell shape and speed. Our model provides a simple biochemical and biophysical basis for the observed morphology and behaviour of motile cells.
C1 [Keren, Kinneret; Pincus, Zachary; Allen, Greg M.; Barnhart, Erin L.; Theriot, Julie A.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
   [Theriot, Julie A.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
   [Keren, Kinneret] Technion Israel Inst Technol, Dept Phys, IL-32000 Haifa, Israel.
   [Pincus, Zachary] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Marriott, Gerard] Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA.
   [Mogilner, Alex] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Davis, CA 95616 USA.
   [Mogilner, Alex] Univ Calif Davis, Dept Math, Davis, CA 95616 USA.
C3 Stanford University; Stanford University; Technion Israel Institute of Technology; Yale University; University of Wisconsin System; University of Wisconsin Madison; University of California System; University of California Davis; University of California System; University of California Davis
RP Theriot, JA (corresponding author), Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
EM theriot@stanford.edu
FU NIGMS NIH HHS [U54 GM64346, U54 GM064346] Funding Source: Medline
NR 36
TC 594
Z9 691
U1 2
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 MAY 22
PY 2008
VL 453
IS 7194
BP 475
EP U1
DI 10.1038/nature06952
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700033
PM 18497816
DA 2026-03-09
ER

PT J
AU Krause, O
   Tanaka, M
   Usuda, T
   Hattori, T
   Goto, M
   Birkmann, S
   Nomoto, K
AF Krause, Oliver
   Tanaka, Masaomi
   Usuda, Tomonori
   Hattori, Takashi
   Goto, Miwa
   Birkmann, Stephan
   Nomoto, Ken'ichi
TI Tycho Brahe's 1572 supernova as a standard type Ia as revealed by its light-echo spectrum
SO NATURE
LA English
DT Article
ID high-velocity features; cassiopeia-a; white-dwarf; sn 2001el; models; progenitor; constant; remnant
AB Type Ia supernovae are thermonuclear explosions of white dwarf stars in close binary systems(1). They play an important role as cosmological distance indicators and have led to the discovery of the accelerated expansion of the Universe(2,3). Among the most important unsolved questions(4) about supernovae are how the explosion actually proceeds and whether accretion occurs from a companion or by the merging of two white dwarfs. Tycho Brahe's supernova of 1572 ( SN 1572) is thought to be one of the best candidates for a type Ia supernova in the Milky Way(5). The proximity of the SN 1572 remnant has allowed detailed studies, such as the possible identification of the binary companion(6), and provides a unique opportunity to test theories of the explosion mechanism and the nature of the progenitor. The determination of the hitherto unknown(7-9) spectroscopic type of this supernova is crucial in relating these results to the diverse population of type Ia supernovae(10). Here we report an optical spectrum of Tycho's supernova near maximum brightness, obtained from a scattered- light echo more than four centuries after the direct light from the explosion swept past the Earth. We find that SN 1572 belongs to the majority class of normal type Ia supernovae.
C1 [Krause, Oliver; Goto, Miwa; Birkmann, Stephan] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Tanaka, Masaomi; Nomoto, Ken'ichi] Univ Tokyo, Inst Phys & Math Universe, Chiba 2778568, Japan.
   [Tanaka, Masaomi; Nomoto, Ken'ichi] Univ Tokyo, Dept Astron, Grad Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Usuda, Tomonori; Hattori, Takashi] Natl Inst Nat Sci, Natl Astron Observ Japan, Subaru Telescope, Hilo, HI 96720 USA.
   [Birkmann, Stephan] European Space Agcy, Dept Space Sci, NL-2200 AG Noordwijk, Netherlands.
C3 Max Planck Society; University of Tokyo; University of Tokyo; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); European Space Agency
RP Krause, O (corresponding author), Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
EM krause@mpia.de; nomoto@astron.s.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science Research Fellowship for Young Scientists; World Premier International Research Center Initiative, MEXT, Japan
NR 30
TC 149
Z9 175
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 DEC 4
PY 2008
VL 456
IS 7222
BP 617
EP 619
DI 10.1038/nature07608
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000035
PM 19052622
DA 2026-03-09
ER

PT J
AU Leong, KG
   Wang, BE
   Johnson, L
   Gao, WQ
AF Leong, Kevin G.
   Wang, Bu-Er
   Johnson, Leisa
   Gao, Wei-Qiang
TI Generation of a prostate from a single adult stem cell
SO NATURE
LA English
DT Article
ID proximal region; mouse prostate; c-kit; murine prostate; marker; expression; identification; regeneration; cancer; tissue
AB The existence of prostate stem cells ( PSCs) was first postulated from the observation that normal prostate regeneration can occur after repeated cycles of androgen deprivation and replacement in rodents(1). Given the critical role of PSCs in maintaining prostate tissue integrity and their potential involvement in prostate tumorigenesis(2), it is important to define specific markers for normal PSCs. Several cell- surface markers have been reported to identify candidate PSCs, including stem cell antigen-1 ( Sca-1, also known as Ly6a), CD133 (Prom1) and CD44 ( refs 3-10). However, many non- PSCs in the mouse prostate also express these markers and thus identification of a more defined PSC population remains elusive. Here we identify CD117 ( c- kit, stem cell factor receptor) as a new marker of a rare adult mouse PSC population, and demonstrate that a single stem cell defined by the phenotype Lin(-) Sca-1(+)CD133(+)CD44(+)CD117(+) can generate a prostate after transplantation in vivo. CD117 expression is predominantly localized to the region of the mouse prostate proximal to the urethra and is upregulated after castration- induced prostate involution - two characteristics consistent with that of a PSC marker. CD117(+) PSCs can generate functional, secretion- producing prostates when transplanted in vivo. Moreover, CD117(+) PSCs have long- term self-renewal capacity, as evidenced by serial isolation and transplantation in vivo. Our data establish that single cells in the adult mouse prostate with multipotent, self- renewal capacity are defined by a Lin(-)Sca-1(+) CD133(+) CD44(+) CD117(+) phenotype.
C1 [Leong, Kevin G.; Wang, Bu-Er; Johnson, Leisa; Gao, Wei-Qiang] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
C3 Roche Holding; Roche Holding USA; Genentech
RP Gao, WQ (corresponding author), Genentech Inc, Dept Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA.
EM gao@gene.com
FU Genentech Laboratory Animal Resources
NR 30
TC 334
Z9 416
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 DEC 11
PY 2008
VL 456
IS 7223
BP 804
EP 808
DI 10.1038/nature07427
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900052
PM 18946470
DA 2026-03-09
ER

PT J
AU Weiler, CN
   Neely, TW
   Scherer, DR
   Bradley, AS
   Davis, MJ
   Anderson, BP
AF Weiler, Chad N.
   Neely, Tyler W.
   Scherer, David R.
   Bradley, Ashton S.
   Davis, Matthew J.
   Anderson, Brian P.
TI Spontaneous vortices in the formation of Bose-Einstein condensates
SO NATURE
LA English
DT Article
ID gross-pitaevskii equation; cosmological experiments; vortex formation; superfluid he-3; gas; symmetry; dynamics; kinetics; strings; analog
AB Phase transitions are ubiquitous in nature, and can be arranged into universality classes such that systems having unrelated microscopic physics show identical scaling behaviour near the critical point. One prominent universal element of many continuous phase transitions is the spontaneous formation of topological defects during a quench through the critical point(1-3). The microscopic dynamics of defect formation in such transitions are generally difficult to investigate, particularly for superfluids(4-7). However, Bose - Einstein condensates ( BECs) offer unique experimental and theoretical opportunities for probing these details. Here we present an experimental and theoretical study of the BEC phase transition of a trapped atomic gas, in which we observe and statistically characterize the spontaneous formation of vortices during condensation(8,9). Using microscopic theories(10-17) that incorporate atomic interactions and quantum and thermal fluctuations of a finite-temperature Bose gas, we simulate condensation and observe vortex formation in close quantitative agreement with our experimental results. Our studies provide further understanding of the development of coherence in superfluids, and may allow for direct investigation of universal phase transition dynamics.
C1 [Weiler, Chad N.; Neely, Tyler W.; Scherer, David R.; Anderson, Brian P.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA.
   [Bradley, Ashton S.; Davis, Matthew J.] Univ Queensland, ARC Ctr Excellence Quantum Atom Opt, Sch Phys Sci, Brisbane, Qld 4072, Australia.
C3 University of Arizona; University of Queensland
RP Anderson, BP (corresponding author), Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA.
EM bpa@optics.arizona.edu
FU US National Science Foundation [0354977]; Army Research Office; Australian Research Council Centre of Excellence for Quantum-Atom Optics; University of Queensland; Direct For Mathematical & Physical Scien; Division Of Physics [0354977] Funding Source: National Science Foundation
NR 33
TC 471
Z9 503
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 948
EP U37
DI 10.1038/nature07334
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300045
DA 2026-03-09
ER

PT J
AU Jiang, W
   Baker, ML
   Jakana, J
   Weigele, PR
   King, J
   Chiu, W
AF Jiang, Wen
   Baker, Matthew L.
   Jakana, Joanita
   Weigele, Peter R.
   King, Jonathan
   Chiu, Wah
TI Backbone structure of the infectious ε15 virus capsid revealed by electron cryomicroscopy
SO NATURE
LA English
DT Article
ID density maps; protein; virus; bacteriophages; microscopy; particles; algorithm; evolution; topology; binding
AB A half- century after the determination of the first three-dimensional crystal structure of a protein(1), more than 40,000 structures ranging from single polypeptides to large assemblies have been reported(2). The challenge for crystallographers, however, remains the growing of a diffracting crystal. Here we report the 4.5- angstrom resolution structure of a 22-MDa macromolecular assembly, the capsid of the infectious epsilon15 ( epsilon 15) particle, by single-particle electron cryomicroscopy. From this density map we constructed a complete backbone trace of its major capsid protein, gene product 7 ( gp7). The structure reveals a similar protein architecture to that of other tailed double- stranded DNA viruses, even in the absence of detectable sequence similarity(3,4). However, the connectivity of the secondary structure elements ( topology) in gp7 is unique. Protruding densities are observed around the two- fold axes that cannot be accounted for by gp7. A subsequent proteomic analysis of the whole virus identifies these densities as gp10, a 12- kDa protein. Its structure, location and high binding affinity to the capsid indicate that the gp10 dimer functions as a molecular staple between neighbouring capsomeres to ensure the particle's stability. Beyond epsilon 15, this method potentially offers a new approach for modelling the backbone conformations of the protein subunits in other macromolecular assemblies at near- native solution states.
C1 [Baker, Matthew L.; Jakana, Joanita; Chiu, Wah] Baylor Coll Med, Natl Ctr Macromol Imaging, Verna & Marrs Mclean Dept Biochem, Houston, TX 77030 USA.
   [Jiang, Wen] Purdue Univ, Markey Ctr Struct Biol, Dept Biol Sci, W Lafayette, IN 47907 USA.
   [Weigele, Peter R.; King, Jonathan] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Baylor College of Medicine; Purdue University System; Purdue University; Massachusetts Institute of Technology (MIT)
RP Chiu, W (corresponding author), Baylor Coll Med, Natl Ctr Macromol Imaging, Verna & Marrs Mclean Dept Biochem, Houston, TX 77030 USA.
EM jiang12@purdue.edu; wah@bcm.edu
NR 35
TC 180
Z9 225
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1130
EP U12
DI 10.1038/nature06665
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600047
PM 18305544
DA 2026-03-09
ER

PT J
AU Nurse, P
AF Nurse, Paul
TI Life, logic and information
SO NATURE
LA English
DT Article
C1 [Nurse, Paul] Rockefeller Univ, New York, NY 10065 USA.
C3 Rockefeller University
RP Nurse, P (corresponding author), Rockefeller Univ, 1230 York Ave, New York, NY 10065 USA.
EM nurse@mail.rockefeller.edu
NR 0
TC 162
Z9 176
U1 0
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 424
EP 426
DI 10.1038/454424a
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300035
PM 18650911
DA 2026-03-09
ER

PT J
AU Güler, AD
   Ecker, JL
   Lall, GS
   Haq, S
   Altimus, CM
   Liao, HW
   Barnard, AR
   Cahill, H
   Badea, TC
   Zhao, HQ
   Hankins, MW
   Berson, DM
   Lucas, RJ
   Yau, KW
   Hattar, S
AF Gueler, Ali D.
   Ecker, Jennifer L.
   Lall, Gurprit S.
   Haq, Shafiqul
   Altimus, Cara M.
   Liao, Hsi-Wen
   Barnard, Alun R.
   Cahill, Hugh
   Badea, Tudor C.
   Zhao, Haiqing
   Hankins, Mark W.
   Berson, David M.
   Lucas, Robert J.
   Yau, King-Wai
   Hattar, Samer
TI Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision
SO NATURE
LA English
DT Article
ID retinal ganglion-cells; responses; projections; light
AB Rod and cone photoreceptors detect light and relay this information through a multisynaptic pathway to the brain by means of retinal ganglion cells (RGCs)(1). These retinal outputs support not only pattern vision but also non- image- forming ( NIF) functions, which include circadian photoentrainment and pupillary light reflex ( PLR). In mammals, NIF functions are mediated by rods, cones and the melanopsin- containing intrinsically photosensitive retinal ganglion cells (ipRGCs)(2,3). Rod - cone photoreceptors and ipRGCs are complementary in signalling light intensity for NIF functions(4-12). The ipRGCs, in addition to being directly photosensitive, also receive synaptic input from rod - cone networks(13,14). To determine how the ipRGCs relay rod - cone light information for both image- forming and non- image- forming functions, we genetically ablated ipRGCs in mice. Here we show that animals lacking ipRGCs retain pattern vision but have deficits in both PLR and circadian photoentrainment that are more extensive than those observed in melanopsin knockouts(8,10,11). The defects in PLR and photoentrainment resemble those observed in animals that lack phototransduction in all three photoreceptor classes(6). These results indicate that light signals for irradiance detection are dissociated from pattern vision at the retinal ganglion cell level, and animals that cannot detect light for NIF functions are still capable of image formation.
C1 [Gueler, Ali D.; Ecker, Jennifer L.; Altimus, Cara M.; Zhao, Haiqing; Hattar, Samer] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
   [Lall, Gurprit S.; Barnard, Alun R.; Lucas, Robert J.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
   [Haq, Shafiqul; Liao, Hsi-Wen; Cahill, Hugh; Yau, King-Wai] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
   [Hankins, Mark W.] Univ Oxford, Oxford OX3 7BN, England.
   [Berson, David M.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
C3 Johns Hopkins University; University of Manchester; Johns Hopkins University; University of Oxford; Brown University
RP Hattar, S (corresponding author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
EM robert.lucas@manchester.ac.uk; shattar@jhu.edu
FU NEI NIH HHS [R01 EY014596, R01 EY017137, R01 EY006837] Funding Source: Medline; NIDCD NIH HHS [R01 DC006904] Funding Source: Medline; NIGMS NIH HHS [R01 GM076430] Funding Source: Medline; National Eye Institute [R01EY014596] Funding Source: NIH RePORTER
NR 26
TC 692
Z9 821
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 MAY 1
PY 2008
VL 453
IS 7191
BP 102
EP +
DI 10.1038/nature06829
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800047
PM 18432195
DA 2026-03-09
ER

PT J
AU Saunders, MA
   Lea, AS
AF Saunders, Mark A.
   Lea, Adam S.
TI Large contribution of sea surface warming to recent increase in Atlantic hurricane activity
SO NATURE
LA English
DT Article
ID north-atlantic; climate; meteorology; intensity
AB Atlantic hurricane activity has increased significantly since 1995 ( refs 1 - 4), but the underlying causes of this increase remain uncertain(2,5) (-15). It is widely thought that rising Atlantic sea surface temperatures have had a role in this(16,17), but the magnitude of this contribution is not known. Here we quantify this contribution for storms that formed in the tropical North Atlantic, Caribbean Sea and Gulf of Mexico; these regions together account for most of the hurricanes that make landfall in the United States. We show that a statistical model based on two environmental variables local sea surface temperature and an atmospheric wind field - can replicate a large proportion of the variance in tropical Atlantic hurricane frequency and activity between 1965 and 2005. We then remove the influence of the atmospheric wind field to assess the contribution of sea surface temperature. Our results indicate that the sensitivity of tropical Atlantic hurricane activity to August September sea surface temperature over the period we consider is such that a 0.5 degrees C increase in sea surface temperature is associated with a similar to 40% increase in hurricane frequency and activity. The results also indicate that local sea surface warming was responsible for similar to 40% of the increase in hurricane activity relative to the 1950 2000 average between 1996 and 2005. Our analysis does not identify whether warming induced by greenhouse gases contributed to the increase in hurricane activity, but the ability of climate models to reproduce the observed relationship between hurricanes and sea surface temperature will serve as a useful means of assessing whether they are likely to provide reliable projections of future changes in Atlantic hurricane activity.
C1 [Saunders, Mark A.; Lea, Adam S.] UCL, Dept Space & Climate Phys, Benfield UCL Hazard Res Ctr, Dorking RH5 6NT, Surrey, England.
C3 University of London; University College London
RP Saunders, MA (corresponding author), UCL, Dept Space & Climate Phys, Benfield UCL Hazard Res Ctr, Holmbury St Mary, Dorking RH5 6NT, Surrey, England.
EM mas@mssl.ucl.ac.uk
NR 31
TC 165
Z9 220
U1 1
U2 69
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 557
EP U3
DI 10.1038/nature06422
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900038
PM 18235498
DA 2026-03-09
ER

PT J
AU Roch, N
   Florens, S
   Bouchiat, V
   Wernsdorfer, W
   Balestro, F
AF Roch, Nicolas
   Florens, Serge
   Bouchiat, Vincent
   Wernsdorfer, Wolfgang
   Balestro, Franck
TI Quantum phase transition in a single-molecule quantum dot
SO NATURE
LA English
DT Article
ID kondo; fabrication; field
AB Quantum criticality is the intriguing possibility offered by the laws of quantum mechanics when the wave function of a many- particle physical system is forced to evolve continuously between two distinct, competing ground states(1). This phenomenon, often related to a zero- temperature magnetic phase transition, is believed to govern many of the fascinating properties of strongly correlated systems such as heavy- fermion compounds or high- temperature superconductors(1). In contrast to bulk materials with very complex electronic structures, artificial nanoscale devices could offer a new and simpler means of understanding quantum phase transitions(2,3). Here we demonstrate this possibility in a single- molecule quantum dot, where a gate voltage induces a crossing of two different types of electron spin state ( singlet and triplet) at zero magnetic field. The quantum dot is operated in the Kondo regime, where the electron spin on the quantum dot is partially screened by metallic electrodes. This strong electronic coupling between the quantum dot and the metallic contacts provides the strong electron correlations necessary to observe quantum critical behaviour. The quantum magnetic phase transition between two different Kondo regimes is achieved by tuning gate voltages and is fundamentally different from previously observed Kondo transitions in semiconductor and nanotube quantum dots(4,5). Our work may offer new directions in terms of control and tunability for molecular spintronics(6).
C1 [Roch, Nicolas; Florens, Serge; Bouchiat, Vincent; Wernsdorfer, Wolfgang; Balestro, Franck] CNRS, Inst Neel, F-38042 Grenoble 9, France.
   [Roch, Nicolas; Florens, Serge; Bouchiat, Vincent; Wernsdorfer, Wolfgang; Balestro, Franck] Univ Grenoble 1, F-38042 Grenoble 9, France.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA)
RP Balestro, F (corresponding author), CNRS, Inst Neel, BP 166, F-38042 Grenoble 9, France.
EM franck.balestro@grenoble.cnrs.fr
NR 39
TC 258
Z9 276
U1 3
U2 138
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2008
VL 453
IS 7195
BP 633
EP U3
DI 10.1038/nature06930
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200039
PM 18509439
DA 2026-03-09
ER

PT J
AU Korup, O
   Montgomery, DR
AF Korup, Oliver
   Montgomery, David R.
TI Tibetan plateau river incision inhibited by glacial stabilization of the Tsangpo gorge
SO NATURE
LA English
DT Article
ID landslide; himalayas; erosion; moraine; growth; ice
AB A considerable amount of research has focused on how and when the Tibetan plateau formed in the wake of tectonic convergence between India and Asia(1). Although far less enquiry has addressed the controls on river incision into the plateau itself(2), widely accepted theory(3) predicts that steep fluvial knick points ( river reaches with very steep gradients) in the eastern Himalayan syntaxis at the southeastern plateau margin should erode rapidly(4), driving a wave of incision back into the plateau. Preservation of the plateau edge thus presents something of a conundrum that may be resolved by invoking either differential rock uplift matching erosional decay(5-7), or other mechanisms for retarding bedrock river incision(8,9) in this region where high stream power excludes the potential for aridity as a simple limit to dissection of the plateau(10). Here we report morphologic evidence showing that Quaternary depression of the regional equilibrium line altitude, where long-term glacier mass gain equals mass loss, was sufficient to repeatedly form moraine dams on major rivers: such damming substantially impeded river incision into the southeastern edge of the Tibetan plateau through the coupled effects of upstream impoundment and interglacial aggradation. Such glacial stabilization of the resulting highly focused river incision centred on the Tsangpo gorge could further contribute to initiating and accentuating a locus of rapid exhumation, known as tectonic anaeurysm(6).
C1 [Korup, Oliver] Swiss Fed Res Inst WSL SLF, CH-7260 Davos, Switzerland.
   [Montgomery, David R.] Univ Washington, Quaternary Res Ctr, Dept Earth & Space Sci, Seattle, WA 98195 USA.
C3 Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Washington; University of Washington Seattle
RP Korup, O (corresponding author), Swiss Fed Res Inst WSL SLF, Fluelastr 11, CH-7260 Davos, Switzerland.
EM korup@slf.ch
FU EU-FP6 [081412 IRASMOS]; Continental Dynamics Program of the US National Science Foundation [EAR-0003561]
NR 32
TC 210
Z9 273
U1 6
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 9
PY 2008
VL 455
IS 7214
BP 786
EP U4
DI 10.1038/nature07322
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900044
PM 18843366
DA 2026-03-09
ER

PT J
AU Moldón, A
   Malapeira, J
   Gabrielli, N
   Gogol, M
   Gómez-Escoda, B
   Ivanova, T
   Seidel, C
   Ayté, J
AF Moldon, Alberto
   Malapeira, Jordi
   Gabrielli, Natalia
   Gogol, Madelaine
   Gomez-Escoda, Blanca
   Ivanova, Tsvetomira
   Seidel, Chris
   Ayte, Jose
TI Promoter-driven splicing regulation in fission yeast
SO NATURE
LA English
DT Article
ID forkhead transcription factors; dna-binding-domain; rna-polymerase-ii; schizosaccharomyces-pombe; budding yeasts; meiosis; program; sporulation; proteins; encodes
AB The meiotic cell cycle is modified from the mitotic cell cycle by having a pre- meiotic S phase that leads to high levels of recombination, two rounds of nuclear division with no intervening DNA synthesis and a reductional pattern of chromosome segregation. Rem1 is a cyclin that is only expressed during meiosis in the fission yeast Schizosaccharomyces pombe. Cells in which rem1 has been deleted show decreased intragenic meiotic recombination and a delay at the onset of meiosis I ( ref. 1). When ectopically expressed in mitotically growing cells, Rem1 induces a G1 arrest followed by severe mitotic catastrophes. Here we show that rem1 expression is regulated at the level of both transcription and splicing, encoding two proteins with different functions depending on the intron retention. We have determined that the regulation of rem1 splicing is not dependent on any transcribed region of the gene. Furthermore, when the rem1 promoter is fused to other intron-containing genes, the chimaeras show a meiotic- specific regulation of splicing, exactly the same as endogenous rem1. This regulation is dependent on two transcription factors of the forkhead family, Mei4 ( ref. 2) and Fkh2 ( ref. 3). Whereas Mei4 induces both transcription and splicing of rem1, Fkh2 is responsible for the intron retention of the transcript during vegetative growth and the pre- meiotic S phase.
C1 [Moldon, Alberto; Malapeira, Jordi; Gabrielli, Natalia; Gomez-Escoda, Blanca; Ivanova, Tsvetomira; Ayte, Jose] Univ Pompeu Fabra, Oxidat Stress & Cell Cycle Grp, Barcelona 08003, Spain.
   [Gogol, Madelaine] Stowers Inst, Kansas City, MO 64110 USA.
C3 Pompeu Fabra University; Stowers Institute for Medical Research
RP Ayté, J (corresponding author), Univ Pompeu Fabra, Oxidat Stress & Cell Cycle Grp, C Doctor Aiguader 88, Barcelona 08003, Spain.
EM jose.ayte@upf.edu
FU Ministerio de Ciencia y Tecnologia [BFU2006-01785]; Consolider-Ingenio
NR 29
TC 69
Z9 83
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 997
EP U83
DI 10.1038/nature07325
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300057
PM 18815595
DA 2026-03-09
ER

PT J
AU Greaves, SJ
   Wrede, E
   Goldberg, NT
   Zhang, JY
   Miller, DJ
   Zare, RN
AF Greaves, Stuart J.
   Wrede, Eckart
   Goldberg, Noah T.
   Zhang, Jianyang
   Miller, Daniel J.
   Zare, Richard N.
TI Vibrational excitation through tug-of-war inelastic collisions
SO NATURE
LA English
DT Article
ID differential cross-sections; hydrogen-exchange reaction; energy-transfer; scattering-amplitudes; molecular-collisions; nearside-farside; resonances; dynamics; atoms; co2
AB Vibrationally inelastic scattering is a fundamental collision process that converts some of the kinetic energy of the colliding partners into vibrational excitation(1,2). The conventional wisdom is that collisions with high impact parameters ( where the partners only 'graze' each other) are forward scattered and essentially elastic, whereas collisions with low impact parameters transfer a large amount of energy into vibrations and are mainly back scattered(3). Here we report experimental observations of exactly the opposite behaviour for the simplest and most studied of all neutral - neutral collisions: we find that the inelastic scattering process H + D-2 (nu = 0, j = 0, 2) --> H + D-2 (nu' = 3, j' = 0, 2, 4, 6, 8) leads dominantly to forward scattering (nu and j respectively refer to the vibrational and rotational quantum numbers of the D-2 molecule). Quasi- classical trajectory calculations show that the vibrational excitation is caused by extension, not compression, of the D - D bond through interaction with the passing H atom. However, the H - D interaction never becomes strong enough for capture of the H atom before it departs with diminished kinetic energy; that is, the inelastic scattering process is essentially a frustrated reaction in which the collision typically excites the outward- going half of the H - D - D symmetric stretch before the H - D-2 complex dissociates. We suggest that this 'tug of war' between H and D-2 is a new mechanism for vibrational excitation that should play a role in all neutral - neutral collisions where strong attraction can develop between the collision partners.
C1 [Goldberg, Noah T.; Zhang, Jianyang; Miller, Daniel J.; Zare, Richard N.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Greaves, Stuart J.] Univ Bristol, Sch Chem, Laser Chem Spect & Dynam Grp, Bristol BS8 1TS, Avon, England.
   [Wrede, Eckart] Univ Durham, Dept Chem, Durham DH1 3LE, England.
C3 Stanford University; University of Bristol; Durham University
RP Zare, RN (corresponding author), Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
EM zare@stanford.edu
NR 28
TC 53
Z9 57
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 JUL 3
PY 2008
VL 454
IS 7200
BP 88
EP 91
DI 10.1038/nature07079
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300042
PM 18596807
DA 2026-03-09
ER

PT J
AU Rambaut, A
   Pybus, OG
   Nelson, MI
   Viboud, C
   Taubenberger, JK
   Holmes, EC
AF Rambaut, Andrew
   Pybus, Oliver G.
   Nelson, Martha I.
   Viboud, Cecile
   Taubenberger, Jeffery K.
   Holmes, Edward C.
TI The genomic and epidemiological dynamics of human influenza A virus
SO NATURE
LA English
DT Article
ID phylogenetic analysis; membrane association; genetic evolution; matrix protein; m(2) protein; h3n2 virus; hemagglutinin; reassortment; h1n1; glycoproteins
AB The evolutionary interaction between influenza A virus and the human immune system, manifest as 'antigenic drift' of the viral haemagglutinin, is one of the best described patterns in molecular evolution. However, little is known about the genome- scale evolutionary dynamics of this pathogen. Similarly, how genomic processes relate to global influenza epidemiology, in which the A/ H3N2 and A/ H1N1 subtypes co- circulate, is poorly understood. Here through an analysis of 1,302 complete viral genomes sampled from temperate populations in both hemispheres, we show that the genomic evolution of influenza A virus is characterized by a complex interplay between frequent reassortment and periodic selective sweeps. The A/ H3N2 and A/ H1N1 subtypes exhibit different evolutionary dynamics, with diverse lineages circulating in A/ H1N1, indicative of weaker antigenic drift. These results suggest a sink - source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions.
C1 [Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Nelson, Martha I.; Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA.
   [Viboud, Cecile; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Taubenberger, Jeffery K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
C3 University of Edinburgh; University of Oxford; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; National Institutes of Health (NIH) - USA; NIH Fogarty International Center (FIC); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Rambaut, A (corresponding author), Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh EH9 3JT, Midlothian, Scotland.
EM a.rambaut@ed.ac.uk; ech15@psu.edu
FU Intramural NIH HHS [Z01 AI000996] Funding Source: Medline
NR 49
TC 758
Z9 902
U1 2
U2 138
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2008
VL 453
IS 7195
BP 615
EP U2
DI 10.1038/nature06945
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200035
PM 18418375
DA 2026-03-09
ER

PT J
AU McGinty, RK
   Kim, J
   Chatterjee, C
   Roeder, RG
   Muir, TW
AF McGinty, Robert K.
   Kim, Jaehoon
   Chatterjee, Champak
   Roeder, Robert G.
   Muir, Tom W.
TI Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation
SO NATURE
LA English
DT Article
ID h3 methylation; ubiquitination; cysteine; dot1p; yeast; core; monoubiquitination; ligation; proteins; domain
AB Numerous post- translational modifications of histones have been described in organisms ranging from yeast to humans(1). Growing evidence for dynamic regulation of these modifications, position- and modification- specific protein interactions, and biochemical crosstalk between modifications has strengthened the 'histone code' hypothesis, in which histone modifications are integral to choreographing the expression of the genome(1,2). One such modification, ubiquitylation of histone H2B ( uH2B) on lysine 120 ( K120) in humans(3), and lysine 123 in yeast(4), has been correlated with enhanced methylation of lysine 79 ( K79) of histone H3 ( refs 5 - 8), by K79- specific methyltransferase Dot1 ( KMT4)(9-11). However, the specific function of uH2B in this crosstalk pathway is not understood. Here we demonstrate, using chemically ubiquitylated H2B, a direct stimulation of hDot1L- mediated intranucleosomal methylation of H3 K79. Two traceless orthogonal expressed protein ligation ( EPL) reactions were used to ubiquitylate H2B site- specifically. This strategy, using a photolytic ligation auxiliary and a desulphurization reaction, should be generally applicable to the chemical ubiquitylation of other proteins. Reconstitution of our uH2B into chemically defined nucleosomes, followed by biochemical analysis, revealed that uH2B directly activates methylation of H3 K79 by hDot1L. This effect is mediated through the catalytic domain of hDot1L, most likely through allosteric mechanisms. Furthermore, asymmetric incorporation of uH2B into dinucleosomes showed that the enhancement of methylation was limited to nucleosomes bearing uH2B. This work demonstrates a direct biochemical crosstalk between two modifications on separate histone proteins within a nucleosome.
C1 [McGinty, Robert K.; Chatterjee, Champak; Muir, Tom W.] Rockefeller Univ, Lab Synth Prot Chem, New York, NY 10065 USA.
   [Kim, Jaehoon; Roeder, Robert G.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10065 USA.
C3 Rockefeller University; Rockefeller University
RP Muir, TW (corresponding author), Rockefeller Univ, Lab Synth Prot Chem, New York, NY 10065 USA.
EM muirt@rockefeller.edu
FU NCI NIH HHS [R01 CA129325] Funding Source: Medline; NIGMS NIH HHS [T32 GM007739, GM07739, R01 GM086868] Funding Source: Medline; National Institute of General Medical Sciences [T32GM007739, R01GM086868] Funding Source: NIH RePORTER
NR 37
TC 459
Z9 558
U1 2
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2008
VL 453
IS 7196
BP 812
EP U12
DI 10.1038/nature06906
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300050
PM 18449190
DA 2026-03-09
ER

PT J
AU Kay, KN
   Naselaris, T
   Prenger, RJ
   Gallant, JL
AF Kay, Kendrick N.
   Naselaris, Thomas
   Prenger, Ryan J.
   Gallant, Jack L.
TI Identifying natural images from human brain activity
SO NATURE
LA English
DT Article
ID human visual-cortex; bold fmri; orientation; striate; areas; reconstruction; representation; frequency; responses; patterns
AB A challenging goal in neuroscience is to be able to read out, or decode, mental content from brain activity. Recent functional magnetic resonance imaging ( fMRI) studies have decoded orientation(1,2), position(3) and object category(4,5) from activity in visual cortex. However, these studies typically used relatively simple stimuli ( for example, gratings) or images drawn from fixed categories ( for example, faces, houses), and decoding was based on previous measurements of brain activity evoked by those same stimuli or categories. To overcome these limitations, here we develop a decoding method based on quantitative receptive- field models that characterize the relationship between visual stimuli and fMRI activity in early visual areas. These models describe the tuning of individual voxels for space, orientation and spatial frequency, and are estimated directly from responses evoked by natural images. We show that these receptive- field models make it possible to identify, from a large set of completely novel natural images, which specific image was seen by an observer. Identification is not a mere consequence of the retinotopic organization of visual areas; simpler receptive- field models that describe only spatial tuning yield much poorer identification performance. Our results suggest that it may soon be possible to reconstruct a picture of a person's visual experience from measurements of brain activity alone.
C1 [Kay, Kendrick N.; Gallant, Jack L.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA.
   [Naselaris, Thomas; Gallant, Jack L.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
   [Prenger, Ryan J.] Univ Calif Berkeley, Dept Phys, 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 Gallant, JL (corresponding author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA.
EM gallant@berkeley.edu
FU NEI NIH HHS [R01 EY019684] Funding Source: Medline
NR 30
TC 927
Z9 1148
U1 5
U2 187
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 352
EP U7
DI 10.1038/nature06713
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400047
PM 18322462
DA 2026-03-09
ER

PT J
AU Cordier, P
   Tournilhac, F
   Soulié-Ziakovic, C
   Leibler, L
AF Cordier, Philippe
   Tournilhac, Francois
   Soulie-Ziakovic, Corinne
   Leibler, Ludwik
TI Self-healing and thermoreversible rubber from supramolecular assembly
SO NATURE
LA English
DT Article
ID hydrogen-bonding networks; thermoplastic elastomers; polymers; dynamics; polybutadiene; copolymers
AB Rubbers exhibit enormous extensibility up to several hundred per cent, compared with a few per cent for ordinary solids, and have the ability to recover their original shape and dimensions on release of stress(1,2). Rubber elasticity is a property of macromolecules that are either covalently cross- linked(1,2) or connected in a network by physical associations such as small glassy or crystalline domains(3-5), ionic aggregates(6) or multiple hydrogen bonds(7-16). Covalent cross-links or strong physical associations prevent flow and creep. Here we design and synthesize molecules that associate together to form both chains and cross-links via hydrogen bonds. The system shows recoverable extensibility up to several hundred per cent and little creep under load. In striking contrast to conventional cross-linked or thermoreversible rubbers made of macromolecules, these systems, when broken or cut, can be simply repaired by bringing together fractured surfaces to self- heal at room temperature. Repaired samples recuperate their enormous extensibility. The process of breaking and healing can be repeated many times. These materials can be easily processed, re- used and recycled. Their unique self-repairing properties, the simplicity of their synthesis, their availability from renewable resources and the low cost of raw ingredients (fatty acids and urea) bode well for future applications.
C1 [Cordier, Philippe; Tournilhac, Francois; Soulie-Ziakovic, Corinne; Leibler, Ludwik] Ecole Super Phys & Chim Ind Ville Paris, CNRS ESPCI, UMR 7167, F-75005 Paris, France.
C3 Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC)
RP Leibler, L (corresponding author), Ecole Super Phys & Chim Ind Ville Paris, CNRS ESPCI, UMR 7167, 10 Rue Vauquelin, F-75005 Paris, France.
EM ludwik.leibler@espci.fr
NR 30
TC 2587
Z9 2942
U1 50
U2 3370
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 977
EP 980
DI 10.1038/nature06669
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100045
PM 18288191
DA 2026-03-09
ER

PT J
AU Thompson, DWJ
   Kennedy, JJ
   Wallace, JM
   Jones, PD
AF Thompson, David W. J.
   Kennedy, John J.
   Wallace, John M.
   Jones, Phil D.
TI A large discontinuity in the mid-twentieth century in observed global-mean surface temperature
SO NATURE
LA English
DT Article
AB Data sets used to monitor the Earth's climate indicate that the surface of the Earth warmed from 1910 to 1940, cooled slightly from 1940 to 1970, and then warmed markedly from 1970 onward(1). The weak cooling apparent in the middle part of the century has been interpreted in the context of a variety of physical factors, such as atmosphere - ocean interactions and anthropogenic emissions of sulphate aerosols(2). Here we call attention to a previously overlooked discontinuity in the record at 1945, which is a prominent feature of the cooling trend in the midtwentieth century. The discontinuity is evident in published versions of the global- mean temperature time series(1), but stands out more clearly after the data are filtered for the effects of internal climate variability. We argue that the abrupt temperature drop of similar to 0.3 degrees C in 1945 is the apparent result of uncorrected instrumental biases in the sea surface temperature record. Corrections for the discontinuity are expected to alter the character of mid- twentieth century temperature variability but not estimates of the century-long trend in global- mean temperatures.
C1 [Thompson, David W. J.] Colorado State Univ, Dept Atmospher Sci, Ft Collins, CO 80523 USA.
   [Kennedy, John J.] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [Wallace, John M.] Univ Washington, Dept Atmospher Sci, Seattle, WA 98195 USA.
   [Jones, Phil D.] Univ E Anglia, Climat Res Unit, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
C3 Colorado State University System; Colorado State University Fort Collins; Met Office - UK; Hadley Centre; University of Washington; University of Washington Seattle; University of East Anglia
RP Thompson, DWJ (corresponding author), Colorado State Univ, Dept Atmospher Sci, Ft Collins, CO 80523 USA.
EM davet@atmos.colostate.edu
NR 13
TC 218
Z9 244
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 MAY 29
PY 2008
VL 453
IS 7195
BP 646
EP U5
DI 10.1038/nature06982
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200042
PM 18509442
DA 2026-03-09
ER

PT J
AU Chen, TY
   Tesanovic, Z
   Liu, RH
   Chen, XH
   Chien, CL
AF Chen, T. Y.
   Tesanovic, Z.
   Liu, R. H.
   Chen, X. H.
   Chien, C. L.
TI A BCS-like gap in the superconductor SmFeAsO0.85F0.15
SO NATURE
LA English
DT Article
ID tunneling spectroscopy
AB Since the discovery of superconductivity in the high- transition-temperature ( high-T-c) copper oxides two decades ago, it has been firmly established that the CuO2 plane is essential for superconductivity and gives rise to a host of other very unusual properties. A new family of superconductors with the general composition of LaFeAsO1-xFx has recently been discovered(1-8) and the conspicuous lack of the CuO2 planes raises the tantalizing question of a different pairing mechanism in these oxypnictides. The superconducting gap ( its magnitude, structure, and temperature dependence) is intimately related to pairing. Here we report the observation of a single gap in the superconductor SmFeAsO0.85F0.15 with T-c= 42 K as measured by Andreev spectroscopy. The gap value of 2 Delta = 13.34 +/- 0.3meV gives 2 Delta/k(B)T(c) = 3.68 ( where k(B) is the Boltzmann constant), close to the Bardeen Cooper - Schrieffer ( BCS) prediction of 3.53. The gap decreases with temperature and vanishes at T-c in a manner consistent with the BCS prediction, but dramatically different from that of the pseudogap behaviour in the copper oxide superconductors. Our results clearly indicate a nodeless gap order parameter, which is nearly isotropic in size across different sections of the Fermi surface, and are not compatible with models involving antiferromagnetic fluctuations, strong correlations, the t- J model, and the like, originally designed for the high- T-c copper oxides.
C1 [Chen, T. Y.; Tesanovic, Z.; Chien, C. L.] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Liu, R. H.; Chen, X. H.] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Anhua 230026, Peoples R China.
   [Liu, R. H.; Chen, X. H.] Univ Sci & Technol China, Dept Phys, Anhua 230026, Peoples R China.
C3 Johns Hopkins University; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS
RP Chien, CL (corresponding author), Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
EM clc@pha.jhu.edu
NR 21
TC 288
Z9 316
U1 0
U2 102
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1224
EP 1227
DI 10.1038/nature07081
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800039
PM 18528330
DA 2026-03-09
ER

PT J
AU Cam, HP
   Noma, K
   Ebina, H
   Levin, HL
   Grewal, SIS
AF Cam, Hugh P.
   Noma, Ken-ichi
   Ebina, Hirotaka
   Levin, Henry L.
   Grewal, Shiv I. S.
TI Host genome surveillance for retrotransposons by transposon-derived proteins
SO NATURE
LA English
DT Article
ID human centromere protein; fission yeast; cenp-b; schizosaccharomyces-pombe; chromosome segregation; molecular-cloning; dna methylation; heterochromatin; sequence; elements
AB Transposable elements and their remnants constitute a substantial fraction of eukaryotic genomes. Host genomes have evolved defence mechanisms, including chromatin modifications and RNA interference, to regulate transposable elements. Here we describe a genome surveillance mechanism for retrotransposons by transposase- derived centromeric protein CENP- B homologues of the fission yeast Schizosaccharomyces pombe. CENP- B homologues of S. pombe localize at and recruit histone deacetylases to silence Tf2 retrotransposons. CENP- Bs also repress solo long terminal repeats ( LTRs) and LTR- associated genes. Tf2 elements are clustered into 'Tf' bodies, the organization of which depends on CENP- Bs that display discrete nuclear structures. Furthermore, CENP- Bs prevent an 'extinct' Tf1 retrotransposon from re- entering the host genome by blocking its recombination with extant Tf2, and silence and immobilize a Tf1 integrant that becomes sequestered into Tf bodies. Our results reveal a probable ancient retrotransposon surveillance pathway important for host genome integrity, and highlight potential conflicts between DNA transposons and retrotransposons, major transposable elements believed to have greatly moulded the evolution of genomes.
C1 [Cam, Hugh P.; Noma, Ken-ichi; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Ebina, Hirotaka; Levin, Henry L.] NICHHD, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
RP Grewal, SIS (corresponding author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [ZIAHD001009] Funding Source: NIH RePORTER; National Cancer Institute [ZIABC011208, ZIABC010523] Funding Source: NIH RePORTER; Intramural NIH HHS Funding Source: Medline
NR 50
TC 141
Z9 166
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 24
PY 2008
VL 451
IS 7177
BP 431
EP U2
DI 10.1038/nature06499
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100037
PM 18094683
DA 2026-03-09
ER

PT J
AU Ramocki, MB
   Zoghbi, HY
AF Ramocki, Melissa B.
   Zoghbi, Huda Y.
TI Failure of neuronal homeostasis results in common neuropsychiatric phenotypes
SO NATURE
LA English
DT Article
ID expressive-language delay; severe mental-retardation; williams-beuren-syndrome; fragile-x-syndrome; gene copy-number; rett-syndrome; mouse model; messenger-rnas; homologous recombination; neurological symptoms
AB Failure of normal brain development leads to mental retardation or autism in about 3% of children. Many genes integral to pathways by which synaptic modification and the remodelling of neuronal networks mediate cognitive and social development have been identified, usually through loss of function. Evidence is accumulating, however, that either loss or gain of molecular functions can be deleterious to the nervous system. Copy- number variation, regulation of gene expression by non- coding RNAs and epigenetic changes are all mechanisms by which altered gene dosage can cause the failure of neuronal homeostasis.
C1 [Ramocki, Melissa B.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Sect Pediat Neurol & Dev Neurosci, Houston, TX 77030 USA.
   [Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Sect Human & Mol Genet, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine
RP Ramocki, MB (corresponding author), Baylor Coll Med, Dept Pediat, Sect Pediat Neurol & Dev Neurosci, 1 Baylor Plaza,MS 225,BCMT-T807, Houston, TX 77030 USA.
EM mramocki@bcm.tmc.edu; hzoghbi@bcm.tmc.edu
FU Howard Hughes Medical Institute; National Institute of Neurological Disorders and Stroke [1R01 NS057819-01, T32 NS43124, 1K08 NS062711-01]; Simons Foundation; National Institute of Neurological Disorders and Stroke [R01NS057819, T32NS043124] Funding Source: NIH RePORTER
NR 69
TC 318
Z9 376
U1 2
U2 30
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 912
EP 918
DI 10.1038/nature07457
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300039
PM 18923513
DA 2026-03-09
ER

PT J
AU Miller, EJ
   Li, J
   Leng, L
   McDonald, C
   Atsumi, T
   Bucala, R
   Young, LH
AF Miller, Edward J.
   Li, Ji
   Leng, Lin
   McDonald, Courtney
   Atsumi, Toshiya
   Bucala, Richard
   Young, Lawrence H.
TI Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart
SO NATURE
LA English
DT Article
ID factor mif gene; glucose-uptake; cardiac dysfunction; disease severity; regulatory role; cytokine; injury; translocation; polymorphism; binding
AB Understanding cellular response to environmental stress has broad implications for human disease. AMP- activated protein kinase ( AMPK) orchestrates the regulation of energy- generating and - consuming pathways, and protects the heart against ischaemic injury and apoptosis(1). A role for circulating hormones such as adiponectin(2) and leptin(3) in the activation of AMPK has received recent attention. Whether local autocrine and paracrine factors within target organs such as the heart modulate AMPK is unknown. Here we show that macrophage migration inhibitory factor ( MIF), an upstream regulator of inflammation(4), is released in the ischaemic heart, where it stimulates AMPK activation through CD74, promotes glucose uptake and protects the heart during ischaemia- reperfusion injury. Germline deletion of the Mif gene impairs ischaemic AMPK signalling in the mouse heart. Human fibroblasts with a low- activity MIF promoter polymorphism(5) have diminished MIF release and AMPK activation during hypoxia. Thus, MIF modulates the activation of the cardioprotective AMPK pathway during ischaemia, functionally linking inflammation and metabolism in the heart. We anticipate that genetic variation in MIF expression may impact on the response of the human heart to ischaemia by the AMPK pathway, and that diagnostic MIF genotyping might predict risk in patients with coronary artery disease.
C1 [Miller, Edward J.; Li, Ji; Young, Lawrence H.] Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Med Sect, New Haven, CT 06520 USA.
   [Leng, Lin; McDonald, Courtney; Bucala, Richard] Yale Univ, Sch Med, Dept Internal Med, Rheumatol Sect, New Haven, CT 06520 USA.
   [Bucala, Richard] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
   [Young, Lawrence H.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA.
   [Atsumi, Toshiya] Hokkaido Univ, Dept Med 2, Sapporo, Hokkaido 0608638, Japan.
C3 Yale University; Yale University; Yale University; Yale University; Hokkaido University
RP Young, LH (corresponding author), Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Med Sect, 333 Cedar St, New Haven, CT 06520 USA.
EM lawrence.young@yale.edu
NR 32
TC 385
Z9 417
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 578
EP U9
DI 10.1038/nature06504
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900043
PM 18235500
DA 2026-03-09
ER

PT J
AU Enquist, JA
   Stoltz, BM
AF Enquist, John A., Jr.
   Stoltz, Brian M.
TI The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation
SO NATURE
LA English
DT Article
ID sponge myrmekioderma-styx; quaternary stereocenters; organic-synthesis; allylation; ac
AB Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation(1,2). In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation(3-6). Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre- existing chiral centres that are proximal to the reactive site(1). Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized(2). Here we report the use of a double stereoablative(7) enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid ( -)-cyanthiwigin F ( ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product.
C1 [Enquist, John A., Jr.; Stoltz, Brian M.] CALTECH, Arnold & Mabel Beckman Labs Chem Synth, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Stoltz, BM (corresponding author), CALTECH, Arnold & Mabel Beckman Labs Chem Synth, Div Chem & Chem Engn, 1200 E Calif Blvd,MC164-30, Pasadena, CA 91125 USA.
EM stoltz@caltech.edu
FU NIGMS NIH HHS [R01GM080269-01, R01 GM080269] Funding Source: Medline; National Institute of General Medical Sciences [R01GM080269] Funding Source: NIH RePORTER
NR 30
TC 226
Z9 282
U1 0
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1228
EP 1231
DI 10.1038/nature07046
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800040
PM 18580947
DA 2026-03-09
ER

PT J
AU Ben-Zvi, D
   Shilo, BZ
   Fainsod, A
   Barkai, N
AF Ben-Zvi, Danny
   Shilo, Ben-Zion
   Fainsod, Abraham
   Barkai, Naama
TI Scaling of the BMP activation gradient in Xenopus embryos
SO NATURE
LA English
DT Article
ID dorsalizing-morphogenetic-protein; drosophila embryo; twisted gastrulation; spemann organizer; neural induction; amphibian embryos; ventral mesoderm; marginal zone; chordin; antagonist
AB In groundbreaking experiments, Hans Spemann demonstrated that the dorsal part of the amphibian embryo can generate a well- proportioned tadpole, and that a small group of dorsal cells, the 'organizer', can induce a complete and well- proportioned twinned axis when transplanted into a host embryo. Key to organizer function is the localized secretion of inhibitors of bone morphogenetic protein ( BMP), which defines a graded BMP activation profile. Although the central proteins involved in shaping this gradient are well characterized, their integrated function, and in particular how pattern scales with size, is not understood. Here we present evidence that in Xenopus, the BMP activity gradient is defined by a 'shuttling- based' mechanism, whereby the BMP ligands are translocated ventrally through their association with the BMP inhibitor Chordin. This shuttling, with feedback repression of the BMP ligand Admp, offers a quantitative explanation to Spemann's observations, and accounts naturally for the scaling of embryo pattern with its size.
C1 [Ben-Zvi, Danny; Shilo, Ben-Zion; Barkai, Naama] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
   [Fainsod, Abraham] Hebrew Univ Jerusalem, Dept Cellular Biochem & Human Genet, Fac Med, IL-91120 Jerusalem, Israel.
   [Barkai, Naama] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science; Hebrew University of Jerusalem; Weizmann Institute of Science
RP Barkai, N (corresponding author), Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
EM fainsod@cc.huji.ac.il; Naama.barkai@weizmann.ac.il
NR 49
TC 197
Z9 233
U1 1
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1205
EP U22
DI 10.1038/nature07059
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800035
PM 18580943
DA 2026-03-09
ER

PT J
AU Groll, M
   Schellenberg, B
   Bachmann, AS
   Archer, CR
   Huber, R
   Powell, TK
   Lindow, S
   Kaiser, M
   Dudler, R
AF Groll, Michael
   Schellenberg, Barbara
   Bachmann, Andre S.
   Archer, Crystal R.
   Huber, Robert
   Powell, Tracy K.
   Lindow, Steven
   Kaiser, Markus
   Dudler, Robert
TI A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism
SO NATURE
LA English
DT Article
ID syringae pv.-syringae; cerulenin-mediated apoptosis; hypersensitive cell-death; iii effector proteins; pseudomonas-syringae; 20s proteasome; bacterial virulence; innate immunity; powdery mildew; key role
AB Pathogenic bacteria often use effector molecules to increase virulence. In most cases, the mode of action of effectors remains unknown. Strains of Pseudomonas syringae pv. syringae (Pss) secrete syringolin A (SylA), a product of a mixed non-ribosomal peptide/polyketide synthetase, in planta(1). Here we identify SylA as a virulence factor because a SylA-negative mutant in Pss strain B728a obtained by gene disruption was markedly less virulent on its host, Phaseolus vulgaris (bean). We show that SylA irreversibly inhibits all three catalytic activities of eukaryotic proteasomes, thus adding proteasome inhibition to the repertoire of modes of action of virulence factors. The crystal structure of the yeast proteasome in complex with SylA revealed a novel mechanism of covalent binding to the catalytic subunits. Thus, SylA defines a new class of proteasome inhibitors that includes glidobactin A (GlbA), a structurally related compound from an unknown species of the order Burkholderiales(2), for which we demonstrate a similar proteasome inhibition mechanism. As proteasome inhibitors are a promising class of anti-tumour agents, the discovery of a novel family of inhibitory natural products, which we refer to as syrbactins, may also have implications for the development of anti-cancer drugs(3). Homologues of SylA and GlbA synthetase genes are found in some other pathogenic bacteria, including the human pathogen Burkholderia pseudomallei, the causative agent of melioidosis(4). It is thus possible that these bacteria are capable of producing proteasome inhibitors of the syrbactin class.
C1 [Schellenberg, Barbara; Dudler, Robert] Univ Zurich, Inst Plant Biol, Zurich Basel Plant Sci Ctr, CH-8008 Zurich, Switzerland.
   [Groll, Michael] Tech Univ Munich, Ctr Integrated Prot Sci, Dept Chem, Lehrstuhl Biochem, D-85747 Garching, Germany.
   [Bachmann, Andre S.; Archer, Crystal R.] Univ Hawaii Manoa, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
   [Bachmann, Andre S.; Archer, Crystal R.] Univ Hawaii Manoa, Cell & Mol Biol Grad Program, John A Burns Sch Med, Honolulu, HI 96813 USA.
   [Huber, Robert] Max Planck Inst Biochem, D-82152 Martinsried, Germany.
   [Huber, Robert] Cardiff Univ, Sch Biosci, Cardiff CF10 3US, Wales.
   [Huber, Robert] Univ Duisburg Essen, Zentrum Med Biotechnol, D-45117 Essen, Germany.
   [Powell, Tracy K.; Lindow, Steven] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
   [Kaiser, Markus] Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany.
C3 University of Zurich; Technical University of Munich; Cancer Research Center of Hawaii; University of Hawaii System; University of Hawaii Manoa; University of Hawaii System; University of Hawaii Manoa; Max Planck Society; Cardiff University; University of Duisburg Essen; University of California System; University of California Berkeley; Max Planck Society
RP Dudler, R (corresponding author), Univ Zurich, Inst Plant Biol, Zurich Basel Plant Sci Ctr, Zollikerstr 107, CH-8008 Zurich, Switzerland.
EM abachmann@crch.hawaii.edu; markus.kaiser@cgc.mpg.de; rdudler@botinst.uzh.ch
NR 36
TC 259
Z9 315
U1 2
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 10
PY 2008
VL 452
IS 7188
BP 755
EP U7
DI 10.1038/nature06782
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500046
PM 18401409
DA 2026-03-09
ER

PT J
AU Tsai, SY
   Opavsky, R
   Sharma, N
   Wu, LZ
   Naidu, S
   Nolan, E
   Feria-Arias, E
   Timmers, C
   Opavska, J
   de Bruin, A
   Chong, JL
   Trikha, P
   Fernandez, SA
   Stromberg, P
   Rosol, TJ
   Leone, G
AF Tsai, Shih-Yin
   Opavsky, Rene
   Sharma, Nidhi
   Wu, Lizhao
   Naidu, Shan
   Nolan, Eric
   Feria-Arias, Enrique
   Timmers, Cynthia
   Opavska, Jana
   de Bruin, Alain
   Chong, Jean-Leon
   Trikha, Prashant
   Fernandez, Soledad A.
   Stromberg, Paul
   Rosol, Thomas J.
   Leone, Gustavo
TI Mouse development with a single E2F activator
SO NATURE
LA English
DT Article
ID transcription factor; cell-cycle; proliferation; mice; rb; identification; specificity; maturation; mechanism; binding
AB The E2F family is conserved from Caenorhabditis elegans to mammals, with some family members having transcription activation functions and others having repressor functions(1,2). Whereas C. elegans(3) and Drosophila melanogaster(4,5) have a single E2F activator protein and repressor protein, mammals have at least three activator and five repressor proteins(1,2,6). Why such genetic complexity evolved in mammals is not known. To begin to evaluate this genetic complexity, we targeted the inactivation of the entire subset of activators, E2f1, E2f2, E2f3a and E2f3b, singly or in combination in mice. We demonstrate that E2f3a is sufficient to support mouse embryonic and postnatal development. Remarkably, expression of E2f3b or E2f1 from the E2f3a locus ( E2f3a(3bki) or E2f3a(1ki), respectively) suppressed all the postnatal phenotypes associated with the inactivation of E2f3a. We conclude that there is significant functional redundancy among activators and that the specific requirement for E2f3a during postnatal development is dictated by regulatory sequences governing its selective spatiotemporal expression and not by its intrinsic protein functions. These findings provide a molecular basis for the observed specificity among E2F activators during development.
C1 [Tsai, Shih-Yin; Opavsky, Rene; Sharma, Nidhi; Wu, Lizhao; Nolan, Eric; Feria-Arias, Enrique; Timmers, Cynthia; Opavska, Jana; de Bruin, Alain; Chong, Jean-Leon; Trikha, Prashant; Leone, Gustavo] Ohio State Univ, Dept Mol Genet, Coll Biol Sci, Columbus, OH 43210 USA.
   [Tsai, Shih-Yin; Opavsky, Rene; Sharma, Nidhi; Wu, Lizhao; Naidu, Shan; Nolan, Eric; Feria-Arias, Enrique; Timmers, Cynthia; Opavska, Jana; de Bruin, Alain; Chong, Jean-Leon; Trikha, Prashant; Leone, Gustavo] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA.
   [Tsai, Shih-Yin; Opavsky, Rene; Sharma, Nidhi; Wu, Lizhao; Naidu, Shan; Nolan, Eric; Feria-Arias, Enrique; Timmers, Cynthia; Opavska, Jana; de Bruin, Alain; Chong, Jean-Leon; Trikha, Prashant; Leone, Gustavo] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Coll Med, Columbus, OH 43210 USA.
   [Naidu, Shan; Stromberg, Paul; Rosol, Thomas J.] Ohio State Univ, Dept Vet Biosci, Coll Vet Med, Columbus, OH 43210 USA.
   [Fernandez, Soledad A.] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University; James Cancer Hospital & Solove Research Institute; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University
RP Leone, G (corresponding author), Ohio State Univ, Dept Mol Genet, Coll Biol Sci, 484 W 12Th Ave, Columbus, OH 43210 USA.
EM Gustavo.Leone@osumc.edu
FU NIH [R01CA85619, R01HD042619, R01CA121275, R01HD047470, P01CA097189, K01CA102328]; DoD awards [BC0300893, BC061730]; T32 fellowship [CA106196]; Pew Charitable Trusts Scholar Award; Leukemia and Lymphoma Society Scholar Award
NR 26
TC 82
Z9 109
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1137
EP U69
DI 10.1038/nature07066
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600042
PM 18594513
DA 2026-03-09
ER

PT J
AU Nadler, JW
   Angelaki, DE
   DeAngelis, GC
AF Nadler, Jacob W.
   Angelaki, Dora E.
   DeAngelis, Gregory C.
TI A neural representation of depth from motion parallax in macaque visual cortex
SO NATURE
LA English
DT Article
ID middle temporal area; binocular disparity; stereoscopic depth; cortical area; functional-property; eye-movements; mt neurons; perception; monkey; discrimination
AB Perception of depth is a fundamental challenge for the visual system, particularly for observers moving through their environment. The brain makes use of multiple visual cues to reconstruct the three- dimensional structure of a scene. One potent cue, motion parallax, frequently arises during translation of the observer because the images of objects at different distances move across the retina with different velocities. Human psychophysical studies have demonstrated that motion parallax can be a powerful depth cue(1-5), and motion parallax seems to be heavily exploited by animal species that lack highly developed binocular vision(6-8). However, little is known about the neural mechanisms that underlie this capacity. Here we show, by using a virtual- reality system to translate macaque monkeys ( Macaca mulatta) while they viewed motion parallax displays that simulated objects at different depths, that many neurons in the middle temporal area ( area MT) signal the sign of depth ( near versus far) from motion parallax in the absence of other depth cues. To achieve this, neurons must combine visual motion with extra- retinal ( non- visual) signals related to the animal's movement. Our findings suggest a new neural substrate for depth perception and demonstrate a robust interaction of visual and non- visual cues in area MT. Combined with previous studies that implicate area MT in depth perception based on binocular disparities(9-12), our results suggest that area MT contains a more general representation of three- dimensional space that makes use of multiple cues.
C1 [Nadler, Jacob W.; Angelaki, Dora E.; DeAngelis, Gregory C.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
   [DeAngelis, Gregory C.] Univ Rochester, Dept Brain & Cognit Sci, Rochester, NY 14627 USA.
C3 Washington University (WUSTL); University of Rochester
RP DeAngelis, GC (corresponding author), Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
EM gdeangelis@cvs.rochester.edu
FU NEI NIH HHS [R01 EY013644, T32 EY013360, R01 EY017866] Funding Source: Medline; National Eye Institute [T32EY013360] Funding Source: NIH RePORTER
NR 30
TC 85
Z9 104
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 APR 3
PY 2008
VL 452
IS 7187
BP 642
EP U10
DI 10.1038/nature06814
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200048
PM 18344979
DA 2026-03-09
ER

PT J
AU Hsieh, D
   Qian, D
   Wray, L
   Xia, Y
   Hor, YS
   Cava, RJ
   Hasan, MZ
AF Hsieh, D.
   Qian, D.
   Wray, L.
   Xia, Y.
   Hor, Y. S.
   Cava, R. J.
   Hasan, M. Z.
TI A topological Dirac insulator in a quantum spin Hall phase
SO NATURE
LA English
DT Article
ID magnetic susceptibility; band-structure; graphene; bismuth; transition; wells; model; gas
AB When electrons are subject to a large external magnetic field, the conventional charge quantum Hall effect(1,2) dictates that an electronic excitation gap is generated in the sample bulk, but metallic conduction is permitted at the boundary. Recent theoretical models suggest that certain bulk insulators with large spin - orbit interactions may also naturally support conducting topological boundary states in the quantum limit(3-5), which opens up the possibility for studying unusual quantum Hall- like phenomena in zero external magnetic fields(6). Bulk Bi1-xSbx single crystals are predicted to be prime candidates(7,8) for one such unusual Hall phase of matter known as the topological insulator(9-11). The hallmark of a topological insulator is the existence of metallic surface states that are higher- dimensional analogues of the edge states that characterize a quantum spin Hall insulator(3-13). In addition to its interesting boundary states, the bulk of Bi1-xSbx is predicted to exhibit three- dimensional Dirac particles(14-17), another topic of heightened current interest following the new findings in two-dimensional graphene(18-20) and charge quantum Hall fractionalization observed in pure bismuth(21). However, despite numerous transport and magnetic measurements on the Bi1-xSbx family since the 1960s(17), no direct evidence of either topological Hall states or bulk Dirac particles has been found. Here, using incident- photon- energy- modulated angle- resolved photoemission spectroscopy ( IPEM- ARPES), we report the direct observation of massive Dirac particles in the bulk of Bi0.9Sb0.1, locate the Kramers points at the sample's boundary and provide a comprehensive mapping of the Dirac insulator's gapless surface electron bands. These findings taken together suggest that the observed surface state on the boundary of the bulk insulator is a realization of the 'topological metal'(9-11). They also suggest that this material has potential application in developing next- generation quantum computing devices that may incorporate 'light- like' bulk carriers and spin- textured surface currents.
C1 [Hsieh, D.; Qian, D.; Wray, L.; Xia, Y.; Hasan, M. Z.] Princeton Univ, Dept Phys, Joseph Henry Labs Phys, Princeton, NJ 08544 USA.
   [Hor, Y. S.; Cava, R. J.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
   [Hasan, M. Z.] Princeton Univ, Princeton Inst Sci & Technol Mat, Princeton Ctr Complex Mat, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Princeton University
RP Hasan, MZ (corresponding author), Princeton Univ, Dept Phys, Joseph Henry Labs Phys, Princeton, NJ 08544 USA.
EM mzhasan@princeton.edu
NR 36
TC 3034
Z9 3444
U1 13
U2 1480
PU NATURE PUBLISHING 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 24
PY 2008
VL 452
IS 7190
BP 970
EP U5
DI 10.1038/nature06843
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600034
PM 18432240
DA 2026-03-09
ER

PT J
AU Jouvenet, N
   Bieniasz, PD
   Simon, SM
AF Jouvenet, Nolwenn
   Bieniasz, Paul D.
   Simon, Sanford M.
TI Imaging the biogenesis of individual HIV-1 virions in live cells
SO NATURE
LA English
DT Article
ID plasma-membrane; fluorescent proteins; living cells; virus; microscopy; release; visualization; replication; macrophages; clathrin
AB Observations of individual virions in live cells have led to the characterization of their attachment, entry and intracellular transport(1). However, the assembly of individual virions has never been observed in real time. Insights into this process have come primarily from biochemical analyses of populations of virions or from microscopic studies of fixed infected cells. Thus, some assembly properties, such as kinetics and location, are either unknown or controversial(2-5). Here we describe quantitatively the genesis of individual virions in real time, from initiation of assembly to budding and release. We studied fluorescently tagged derivatives of Gag, the major structural component of HIV-1-which is sufficient to drive the assembly of virus- like particles(6) - with the use of fluorescence resonance energy transfer, fluorescence recovery after photobleaching and total- internal- reflection fluorescent microscopy in living cells. Virions appeared individually at the plasma membrane, their assembly rate accelerated as Gag protein accumulated in cells, and typically 5 - 6 min was required to complete the assembly of a single virion. These approaches allow a previously unobserved view of the genesis of individual virions and the determination of parameters of viral assembly that are inaccessible with conventional techniques.
C1 [Jouvenet, Nolwenn; Bieniasz, Paul D.] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10065 USA.
   [Jouvenet, Nolwenn; Bieniasz, Paul D.] Rockefeller Univ, Lab Retrovirol, New York, NY 10065 USA.
   [Simon, Sanford M.] Rockefeller Univ, Lab Cellular Biophys, New York, NY 10065 USA.
C3 Rockefeller University; Rockefeller University; Rockefeller University
RP Bieniasz, PD (corresponding author), Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10065 USA.
EM pbienias@adarc.org; simon@rockefeller.edu
FU NIAID NIH HHS [R01 AI089844] Funding Source: Medline; NIGMS NIH HHS [R01 GM087977, P20 GM072015] Funding Source: Medline
NR 27
TC 265
Z9 320
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 236
EP 240
DI 10.1038/nature06998
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900048
PM 18500329
DA 2026-03-09
ER

PT J
AU Ko, HC
   Stoykovich, MP
   Song, JZ
   Malyarchuk, V
   Choi, WM
   Yu, CJ
   Geddes, JB
   Xiao, JL
   Wang, SD
   Huang, YG
   Rogers, JA
AF Ko, Heung Cho
   Stoykovich, Mark P.
   Song, Jizhou
   Malyarchuk, Viktor
   Choi, Won Mook
   Yu, Chang-Jae
   Geddes, Joseph B., III
   Xiao, Jianliang
   Wang, Shuodao
   Huang, Yonggang
   Rogers, John A.
TI A hemispherical electronic eye camera based on compressible silicon optoelectronics
SO NATURE
LA English
DT Article
ID spherical surfaces; soft lithography; stamp collapse; fabrication; microstructures; arrays
AB The human eye is a remarkable imaging device, with many attractive design features(1,2). Prominent among these is a hemispherical detector geometry, similar to that found in many other biological systems, that enables a wide field of view and low aberrations with simple, few-component imaging optics(3-5). This type of configuration is extremely difficult to achieve using established optoelectronics technologies, owing to the intrinsically planar nature of the patterning, deposition, etching, materials growth and doping methods that exist for fabricating such systems. Here we report strategies that avoid these limitations, and implement them to yield high-performance, hemispherical electronic eye cameras based on single-crystalline silicon. The approach uses wafer-scale optoelectronics formed in unusual, two-dimensionally compressible configurations and elastomeric transfer elements capable of transforming the planar layouts in which the systems are initially fabricated into hemispherical geometries for their final implementation. In a general sense, these methods, taken together with our theoretical analyses of their associated mechanics, provide practical routes for integrating well-developed planar device technologies onto the surfaces of complex curvilinear objects, suitable for diverse applications that cannot be addressed by conventional means.
C1 [Ko, Heung Cho; Stoykovich, Mark P.; Choi, Won Mook; Yu, Chang-Jae; Rogers, John A.] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA.
   [Song, Jizhou; Rogers, John A.] Univ Illinois, Dept Mech Sci & Engn, Urbana, IL 61801 USA.
   [Malyarchuk, Viktor; Rogers, John A.] Univ Illinois, Frederick Seitz Mat Res Lab, Urbana, IL 61801 USA.
   [Geddes, Joseph B., III; Rogers, John A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA.
   [Rogers, John A.] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA.
   [Rogers, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Xiao, Jianliang; Wang, Shuodao; Huang, Yonggang] Northwestern Univ, Dept Mech Engn, Evanston, IL 60208 USA.
   [Huang, Yonggang] Northwestern Univ, Dept Civil & Environm Engn, Evanston, IL 60208 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Northwestern University; Northwestern University
RP Rogers, JA (corresponding author), Univ Illinois, Dept Mat Sci & Engn, 1304 W Green St, Urbana, IL 61801 USA.
EM y-huang@northwestern.edu; jrogers@uiuc.edu
NR 25
TC 1193
Z9 1494
U1 15
U2 729
PU 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 7
PY 2008
VL 454
IS 7205
BP 748
EP 753
DI 10.1038/nature07113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000041
PM 18685704
DA 2026-03-09
ER

PT J
AU Soukup, V
   Epperlein, HH
   Horácek, I
   Cerny, R
AF Soukup, Vladimir
   Epperlein, Hans-Henning
   Horacek, Ivan
   Cerny, Robert
TI Dual epithelial origin of vertebrate oral teeth
SO NATURE
LA English
DT Article
ID cranial neural crest; evolutionary origins; tooth; dentitions; endoderm; genes; mouth; jaws
AB The oral cavity of vertebrates is generally thought to arise as an ectodermal invagination(1,2). Consistent with this, oral teeth are proposed to arise exclusively from ectoderm, contributing to tooth enamel epithelium, and from neural crest derived mesenchyme, contributing to dentin and pulp(3-5). Yet in many vertebrate groups, teeth are not restricted only to the oral cavity(6-9), but extend posteriorly as pharyngeal teeth that could be derived either directly from the endodermal epithelium, or from the ectodermal epithelium that reached this location through the mouth or through the pharyngeal slits(6). However, when the oropharyngeal membrane, which forms a sharp ecto/ endodermal border(10), is broken, the fate of these cells is poorly known. Here, using transgenic axolotls with a combination of fate- mapping approaches, we present reliable evidence of oral teeth derived from both the ectoderm and endoderm and, moreover, demonstrate teeth with a mixed ecto/ endodermal origin. Despite the enamel epithelia having a different embryonic source, oral teeth in the axolotl display striking developmental uniformities and are otherwise identical. This suggests a dominant role for the neural crest mesenchyme over epithelia in tooth initiation and, from an evolutionary point of view, that an essential factor in teeth evolution was the odontogenic capacity of neural crest cells, regardless of possible 'outside-in'(11) or 'inside-out'(12) influx of the epithelium.
C1 [Soukup, Vladimir; Horacek, Ivan; Cerny, Robert] Charles Univ Prague, Dept Zool, CR-12844 Prague, Czech Republic.
   [Epperlein, Hans-Henning] Tech Univ Dresden, Dept Anat, D-01307 Dresden, Germany.
C3 Charles University Prague; Technische Universitat Dresden
RP Cerny, R (corresponding author), Charles Univ Prague, Dept Zool, Vinicna 7, CR-12844 Prague, Czech Republic.
EM cerny8@natur.cuni.cz
FU Ministry of Youth, Education and Sport of the Czech Republic [MSMT 0021620828]; SMWK (Dresden); COST Action B23
NR 31
TC 79
Z9 100
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 795
EP U6
DI 10.1038/nature07304
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900046
PM 18794902
DA 2026-03-09
ER

PT J
AU Des Marais, DL
   Rausher, MD
AF Des Marais, David L.
   Rausher, Mark D.
TI Escape from adaptive conflict after duplication in an anthocyanin pathway gene
SO NATURE
LA English
DT Article
ID dihydroflavonol 4-reductase; positive selection; substrate-specificity; zea-mays; evolution; preservation; consequences; probability; metabolism; flavonoids
AB Gene duplications have been recognized as an important source of evolutionary innovation and adaptation since at least Haldane(1), and their varying fates may partly explain the vast disparity in observed genome sizes(2). The expected fates of most gene duplications involve primarily non-adaptive substitutions leading to either non-functionalization of one duplicate copy or subfunctionalization(3), neither of which yields novel function. A significant evolutionary problem is thus elucidating the mechanisms of adaptive evolutionary change leading to evolutionary novelty. Currently, the most widely recognized adaptive process involving gene duplication is neo-functionalization (NEO-F), in which one copy undergoes directional selection to perform a novel function after duplication(4). An alternative, but understudied, adaptive fate that has been proposed is escape from adaptive conflict (EAC), in which a single-copy gene is selected to perform a novel function while maintaining its ancestral function(5,6). This gene is constrained from improving either novel or ancestral function because of detrimental pleiotropic effects on the other function. After duplication, one copy is free to improve novel function, whereas the other is selected to improve ancestral function. Here we first present two criteria that can be used to distinguish NEO-F from EAC. Using both tests for positive selection and assays of enzyme function, we then demonstrate that adaptive evolutionary change in a duplicated gene of the anthocyanin biosynthetic pathway in morning glories (Ipomoea) is best interpreted as EAC. Finally, we argue that this phenomenon likely occurs more often than has been previously believed and may thus represent an important mechanism in generating evolutionary novelty.
C1 [Des Marais, David L.; Rausher, Mark D.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
   [Des Marais, David L.; Rausher, Mark D.] Duke Univ, Univ Program Genet & Genom, Durham, NC 27708 USA.
C3 Duke University; Duke University
RP Des Marais, DL (corresponding author), Duke Univ, Dept Biol, Box 90338, Durham, NC 27708 USA.
EM dld3@duke.edu; mrausher@duke.edu
NR 30
TC 309
Z9 364
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 AUG 7
PY 2008
VL 454
IS 7205
BP 762
EP U85
DI 10.1038/nature07092
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000044
PM 18594508
DA 2026-03-09
ER

PT J
AU Lavallée, Y
   Meredith, PG
   Dingwell, DB
   Hess, KU
   Wassermann, J
   Cordonnier, B
   Gerik, A
   Kruhl, JH
AF Lavallee, Y.
   Meredith, P. G.
   Dingwell, D. B.
   Hess, K. -U.
   Wassermann, J.
   Cordonnier, B.
   Gerik, A.
   Kruhl, J. H.
TI Seismogenic lavas and explosive eruption forecasting
SO NATURE
LA English
DT Article
ID mount-st-helens; volcanic-eruptions; magma fragmentation; acoustic-emission; material-failure; earthquakes; seismicity; montserrat; rheology; fracture
AB Volcanic dome-building episodes commonly exhibit acceleration in both effusive discharge rate and seismicity before explosive eruptions(1). This should enable the application of material failure forecasting methods to eruption forecasting(2,3). To date, such methods have been based exclusively on the seismicity of the country rock(4). It is clear, however, that the rheology and deformation rate of the lava ultimately dictate eruption style(5). The highly crystalline lavas involved in these eruptions are pseudoplastic fluids that exhibit a strong component of shear thinning as their deformation accelerates across the ductile to brittle transition(6). Thus, understanding the nature of the ductile-brittle transition in dome lavas may well hold the key to an accurate description of dome growth and stability. Here we present the results of rheological experiments with continuous microseismic monitoring, which reveal that dome lavas are seismogenic and that the character of the seismicity changes markedly across the ductile-brittle transition until complete brittle failure occurs at high strain rates. We conclude that magma seismicity, combined with failure forecasting methods, could potentially be applied successfully to dome-building eruptions for volcanic forecasting.
C1 [Lavallee, Y.; Dingwell, D. B.; Hess, K. -U.; Wassermann, J.; Cordonnier, B.; Gerik, A.] Univ Munich, Dept Earth & Environm Sci, D-80333 Munich, Germany.
   [Meredith, P. G.] UCL, Dept Earth Sci, London WC1E 6BT, England.
   [Gerik, A.; Kruhl, J. H.] Tech Univ Munich, Fac Civil & Geodet Engn, D-80333 Munich, Germany.
C3 University of Munich; University of London; University College London; Technical University of Munich
RP Lavallée, Y (corresponding author), Univ Munich, Dept Earth & Environm Sci, D-80333 Munich, Germany.
EM lavallee@min.uni-muenchen.de
FU Natural Environment Research Council [NE/D012910/1] Funding Source: researchfish; NERC [NE/D012910/1] Funding Source: UKRI
NR 30
TC 157
Z9 171
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 507
EP 510
DI 10.1038/nature06980
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700039
PM 18497822
DA 2026-03-09
ER

PT J
AU Kraal, ER
   van Dijk, M
   Postma, G
   Kleinhans, MG
AF Kraal, Erin R.
   van Dijk, Maurits
   Postma, George
   Kleinhans, Maarten G.
TI Martian stepped-delta formation by rapid water release
SO NATURE
LA English
DT Article
ID model; flow
AB Deltas and alluvial fans preserved on the surface of Mars provide an important record of surface water flow(1-3). Understanding how surface water flow could have produced the observed morphology is fundamental to understanding the history of water on Mars. To date, morphological studies have provided only minimum time estimates for the longevity of martian hydrologic events, which range from decades to millions of years(4-7). Here we use sand flume studies to show that the distinct morphology of martian stepped (terraced) deltas(8-11) could only have originated from a single basin- filling event on a timescale of tens of years. Stepped deltas therefore provide a minimum and maximum constraint on the duration and magnitude of some surface flows on Mars. We estimate that the amount of water required to fill the basin and deposit the delta is comparable to the amount of water discharged by large terrestrial rivers, such as the Mississippi. The massive discharge, short timescale, and the associated short canyon lengths favour the hypothesis that stepped fans are terraced delta deposits draped over an alluvial fan and formed by water released suddenly from subsurface storage.
C1 [Kraal, Erin R.; van Dijk, Maurits; Postma, George; Kleinhans, Maarten G.] Univ Utrecht, Fac Geosci, NL-3508 TC Utrecht, Netherlands.
C3 Utrecht University
RP Kraal, ER (corresponding author), Virginia Polytech Inst & State Univ, Dept Geosci, 4044 Derring Hall 0420, Blacksburg, VA 24061 USA.
EM ekraal@vt.edu
NR 25
TC 76
Z9 87
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 973
EP U2
DI 10.1038/nature06615
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100044
PM 18288190
DA 2026-03-09
ER

PT J
AU Moore, RB
   Oborník, M
   Janouskovec, J
   Chrudimsky, T
   Vancová, M
   Green, DH
   Wright, SW
   Davies, NW
   Bolch, CJS
   Heimann, K
   Slapeta, J
   Hoegh-Guldberg, O
   Logsdon, JM
   Carter, DA
AF Moore, Robert B.
   Obornik, Miroslav
   Janouskovec, Jan
   Chrudimsky, Tomas
   Vancova, Marie
   Green, David H.
   Wright, Simon W.
   Davies, Noel W.
   Bolch, Christopher J. S.
   Heimann, Kirsten
   Slapeta, Jan
   Hoegh-Guldberg, Ove
   Logsdon, John M., Jr.
   Carter, Dee A.
TI A photosynthetic alveolate closely related to apicomplexan parasites
SO NATURE
LA English
DT Article
ID cryptosporidium-parvum; toxoplasma-gondii; common origin; dinoflagellate; phylogeny; diversity; sporozoan; plastids; taxonomy; protein
AB Many parasitic Apicomplexa, such as Plasmodium falciparum, contain an unpigmented chloroplast remnant termed the apicoplast, which is a target for malaria treatment. However, no close relative of apicomplexans with a functional photosynthetic plastid has yet been described. Here we describe a newly cultured organism that has ultrastructural features typical for alveolates, is phylogenetically related to apicomplexans, and contains a photosynthetic plastid. The plastid is surrounded by four membranes, is pigmented by chlorophyll a, and uses the codon UGA to encode tryptophan in the psbA gene. This genetic feature has been found only in coccidian apicoplasts and various mitochondria. The UGA-Trp codon and phylogenies of plastid and nuclear ribosomal RNA genes indicate that the organism is the closest known photosynthetic relative to apicomplexan parasites and that its plastid shares an origin with the apicoplasts. The discovery of this organism provides a powerful model with which to study the evolution of parasitism in Apicomplexa.
C1 [Moore, Robert B.; Carter, Dee A.] Univ Sydney, Sch Mol & Microbial Biosci, Darlington, NSW 2006, Australia.
   [Moore, Robert B.; Logsdon, John M., Jr.] Univ Iowa, Roy J Carver Ctr Comparat Genom, Dept Biol Sci, Iowa City, IA 52242 USA.
   [Obornik, Miroslav; Janouskovec, Jan; Chrudimsky, Tomas; Vancova, Marie] Acad Sci Czech Republ, Ctr Biol, Inst Parasitol, Ceske Budejovice 37005, Czech Republic.
   [Obornik, Miroslav; Janouskovec, Jan; Chrudimsky, Tomas; Vancova, Marie] Univ S Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
   [Green, David H.] Dunstaffnage Marine Lab Oban, Scottish Assoc Marine Sci, Argyll PA37 1QA, Scotland.
   [Wright, Simon W.] Australian Antarctic Div, Kingston, Tas 7050, Australia.
   [Davies, Noel W.] Univ Tasmania, Cent Sci Lab, Hobart, Tas 7001, Australia.
   [Bolch, Christopher J. S.] Univ Tasmania, Sch Aquaculture, Launceston, Tas 7250, Australia.
   [Heimann, Kirsten] James Cook Univ N Queensland, Sch Marine & Trop Biol, Townsville, Qld 4811, Australia.
   [Slapeta, Jan] Univ Sydney, Fac Vet Sci, Camperdown, NSW 2006, Australia.
   [Hoegh-Guldberg, Ove] Univ Queensland, Ctr Marine Studies, St Lucia, Qld 4072, Australia.
C3 University of Sydney; University of Iowa; Czech Academy of Sciences; Biology Centre of the Czech Academy of Sciences; University of South Bohemia Ceske Budejovice; Australian Antarctic Division; University of Tasmania; University of Tasmania; James Cook University; University of Sydney; University of Queensland
RP Carter, DA (corresponding author), Univ Sydney, Sch Mol & Microbial Biosci, Darlington, NSW 2006, Australia.
EM d.carter@mmb.usyd.edu.au
FU Natural Environment Research Council [dml010007] Funding Source: researchfish; NERC [dml010007] Funding Source: UKRI
NR 30
TC 361
Z9 413
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 FEB 21
PY 2008
VL 451
IS 7181
BP 959
EP 963
DI 10.1038/nature06635
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100041
PM 18288187
DA 2026-03-09
ER

PT J
AU Gierlinski, M
   Middleton, M
   Ward, M
   Done, C
AF Gierlinski, Marek
   Middleton, Matthew
   Ward, Martin
   Done, Chris
TI A periodicity of ∼1 hour in X-ray emission from the active galaxy RE J1034+396
SO NATURE
LA English
DT Article
ID galactic nuclei; seyfert-1 galaxy; red noise; spectrum; mass
AB Active galactic nuclei and quasars are thought to be scaled- up versions of Galactic black hole binaries, powered by accretion onto supermassive black holes with masses of 10(6)-10(9) M., as opposed to the similar to 10 M. in binaries (here M. is the solar mass). One example of the similarities between these two types of systems is the characteristic rapid X- ray variability seen from the accretion flow(1). The power spectrum of this variability in black hole binaries consists of a broad noise with multiple quasi- periodic oscillations superimposed on it. Although the broad noise component has been observed in many active galactic nuclei(2,3), there have hitherto been no significant detections of quasi- periodic oscillations(4-6). Here we report the discovery of an similar to 1- hour X- ray periodicity in a bright active galaxy, RE J1034+396. The signal is highly statistically significant ( at the 5.6 sigma level) and very coherent, with quality factorQ > 16. The X- ray modulation arises from the direct vicinity of the black hole.
C1 [Gierlinski, Marek; Middleton, Matthew; Ward, Martin; Done, Chris] Univ Durham, Dept Phys, Durham DH1 3LE, England.
C3 Durham University
RP Gierlinski, M (corresponding author), Univ Durham, Dept Phys, South Rd, Durham DH1 3LE, England.
EM marek.gierlinski@durham.ac.uk
FU Polish MNiSW [NN203065933]; PPARC senior fellowship; Science and Technology Facilities Council [ST/F002963/1] Funding Source: researchfish; STFC [ST/F002963/1] Funding Source: UKRI
NR 22
TC 272
Z9 294
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 SEP 18
PY 2008
VL 455
IS 7211
BP 369
EP 371
DI 10.1038/nature07277
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200039
PM 18800134
DA 2026-03-09
ER

PT J
AU Mikkelsen, TS
   Hanna, J
   Zhang, XL
   Ku, MC
   Wernig, M
   Schorderet, P
   Bernstein, BE
   Jaenisch, R
   Lander, ES
   Meissner, A
AF Mikkelsen, Tarjei S.
   Hanna, Jacob
   Zhang, Xiaolan
   Ku, Manching
   Wernig, Marius
   Schorderet, Patrick
   Bernstein, Bradley E.
   Jaenisch, Rudolf
   Lander, Eric S.
   Meissner, Alexander
TI Dissecting direct reprogramming through integrative genomic analysis
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; generation; fibroblasts; mouse; myc; expression; mice
AB Somatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report an integrative genomic analysis of reprogramming of mouse fibroblasts and B lymphocytes. Lineage- committed cells show a complex response to the ectopic expression involving induction of genes downstream of individual reprogramming factors. Fully reprogrammed cells show gene expression and epigenetic states that are highly similar to embryonic stem cells. In contrast, stable partially reprogrammed cell lines show reactivation of a distinctive subset of stem- cell- related genes, incomplete repression of lineage- specifying transcription factors, and DNA hypermethylation at pluripotency- related loci. These observations suggest that some cells may become trapped in partially reprogrammed states owing to incomplete repression of transcription factors, and that DNA de- methylation is an inefficient step in the transition to pluripotency. We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process.
C1 [Mikkelsen, Tarjei S.; Zhang, Xiaolan; Bernstein, Bradley E.; Lander, Eric S.; Meissner, Alexander] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Mikkelsen, Tarjei S.; Zhang, Xiaolan; Bernstein, Bradley E.; Lander, Eric S.; Meissner, Alexander] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
   [Mikkelsen, Tarjei S.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Jaenisch, Rudolf; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Hanna, Jacob; Wernig, Marius; Schorderet, Patrick; Jaenisch, Rudolf; Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.
   [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
   [Bernstein, Bradley E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA.
   [Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); 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 Medical School; Harvard University; Harvard Medical School; Harvard University
RP Meissner, A (corresponding author), MIT, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA.
EM alex@broad.mit.edu
FU NHGRI NIH HHS [U54 HG003067] Funding Source: Medline
NR 33
TC 1151
Z9 1451
U1 0
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 49
EP U1
DI 10.1038/nature07056
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300033
PM 18509334
DA 2026-03-09
ER

PT J
AU Holland, MD
   Hastings, A
AF Holland, Matthew D.
   Hastings, Alan
TI Strong effect of dispersal network structure on ecological dynamics
SO NATURE
LA English
DT Article
ID persistence; synchronization; landscapes; predators; corridors; stability
AB A central question in ecology with great importance for management, conservation and biological control is how changing connectivity affects the persistence and dynamics of interacting species. Researchers in many disciplines have used large systems of coupled oscillators to model the behaviour of a diverse array of fluctuating systems in nature(1-4). In the well- studied regime of weak coupling, synchronization is favoured by increases in coupling strength and large- scale network structures ( for example 'small worlds') that produce short cuts and clustering(5-9). Here we show that, by contrast, randomizing the structure of dispersal networks in a model of predators and prey tends to favour asynchrony and prolonged transient dynamics, with resulting effects on the amplitudes of population fluctuations. Our results focus on synchronization and dynamics of clusters in models, and on time-scales, more appropriate for ecology, namely smaller systems with strong interactions outside the weak- coupling regime, rather than the better- studied cases of large, weakly coupled systems. In these smaller systems, the dynamics of transients and the effects of changes in connectivity can be well understood using a set of methods including numerical reconstructions of phase dynamics, examinations of cluster formation and the consideration of important aspects of cyclic dynamics, such as amplitude.
C1 [Holland, Matthew D.; Hastings, Alan] Univ Calif Davis, Dept Environm Sci & Policy, Davis, CA 95616 USA.
C3 University of California System; University of California Davis
RP Holland, MD (corresponding author), Univ Calif Davis, Dept Environm Sci & Policy, 1 Shields Ave, Davis, CA 95616 USA.
EM mdholland@ucdavis.edu
FU Quantitative Environmental and Integrative Biology; National Science Foundation; Direct For Biological Sciences [0827460] Funding Source: National Science Foundation; Emerging Frontiers [0827460] Funding Source: National Science Foundation
NR 30
TC 168
Z9 184
U1 3
U2 118
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 792
EP U76
DI 10.1038/nature07395
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900049
PM 18931656
DA 2026-03-09
ER

PT J
AU Moritz, CT
   Perlmutter, SI
   Fetz, EE
AF Moritz, Chet T.
   Perlmutter, Steve I.
   Fetz, Eberhard E.
TI Direct control of paralysed muscles by cortical neurons
SO NATURE
LA English
DT Article
ID motor cortex cells; intraspinal microstimulation; arm muscles; movement; computer; monkeys; neuroprosthesis; stimulation; prosthesis; plasticity
AB A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury by artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralysed limbs(1-3). In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms(4-10), and paralysed muscles have been activated by functional electrical stimulation(11-13). Here we show that Macaca nemestrina monkeys can directly control stimulation of muscles using the activity of neurons in the motor cortex, thereby restoring goal-directed movements to a transiently paralysed arm. Moreover, neurons could control functional stimulation equally well regardless of any previous association to movement, a finding that considerably expands the source of control signals for brain- machine interfaces. Monkeys learned to use these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron - muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralysed limbs.
C1 [Moritz, Chet T.; Perlmutter, Steve I.; Fetz, Eberhard E.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
   [Moritz, Chet T.; Perlmutter, Steve I.; Fetz, Eberhard E.] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Moritz, CT (corresponding author), Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
EM ctmoritz@u.washington.edu
FU National Institutes of Health
NR 33
TC 430
Z9 554
U1 0
U2 135
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 4
PY 2008
VL 456
IS 7222
BP 639
EP U63
DI 10.1038/nature07418
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000041
PM 18923392
DA 2026-03-09
ER

PT J
AU Neuser, K
   Triphan, T
   Mronz, M
   Poeck, B
   Strauss, R
AF Neuser, Kirsa
   Triphan, Tilman
   Mronz, Markus
   Poeck, Burkhard
   Strauss, Roland
TI Analysis of a spatial orientation memory in Drosophila
SO NATURE
LA English
DT Article
ID working-memory; expression; gene; melanogaster; mutants; operant; dunce; fly; rsk
AB Flexible goal- driven orientation requires that the position of a target be stored, especially in case the target moves out of sight. The capability to retain, recall and integrate such positional information into guiding behaviour has been summarized under the term spatial working memory(1). This kind of memory contains specific details of the presence that are not necessarily part of a long- term memory. Neurophysiological studies in primates(2) indicate that sustained activity of neurons encodes the sensory information even though the object is no longer present. Furthermore they suggest that dopamine transmits the respective input to the prefrontal cortex, and simultaneous suppression by GABA spatially restricts this neuronal activity(3). Here we show that Drosophila melanogaster possesses a similar spatial memory during locomotion. Using a new detour setup, we show that flies can remember the position of an object for several seconds after it has been removed from their environment. In this setup, flies are temporarily lured away from the direction towards their hidden target, yet they are thereafter able to aim for their former target. Furthermore, we find that the GABAergic ( stainable with antibodies against GABA) ring neurons(4) of the ellipsoid body in the central brain are necessary and their plasticity is sufficient for a functional spatial orientation memory in flies. We also find that the protein kinase S6KII ( ignorant)(5) is required in a distinct subset of ring neurons to display this memory. Conditional expression of S6KII in these neurons only in adults can restore the loss of the orientation memory of the ignorant mutant. The S6KII signalling pathway therefore seems to be acutely required in the ring neurons for spatial orientation memory in flies.
C1 [Neuser, Kirsa; Triphan, Tilman; Mronz, Markus; Poeck, Burkhard; Strauss, Roland] Univ Wurzburg, Lehrstuhl Genet & Neurobiol, Biozentrum, D-97074 Wurzburg, Germany.
C3 University of Wurzburg
RP Strauss, R (corresponding author), Johannes Gutenberg Univ Mainz, Inst Zool Neurobiol 3, Col Kleinmann Weg 2, D-55099 Mainz, Germany.
EM rstrauss@uni-mainz.de
NR 30
TC 286
Z9 333
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 JUN 26
PY 2008
VL 453
IS 7199
BP 1244
EP U44
DI 10.1038/nature07003
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800044
PM 18509336
DA 2026-03-09
ER

PT J
AU Scheerer, P
   Park, JH
   Hildebrand, PW
   Kim, YJ
   Krauss, N
   Choe, HW
   Hofmann, KP
   Ernst, OP
AF Scheerer, Patrick
   Park, Jung Hee
   Hildebrand, Peter W.
   Kim, Yong Ju
   Krauss, Norbert
   Choe, Hui-Woog
   Hofmann, Klaus Peter
   Ernst, Oliver P.
TI Crystal structure of opsin in its G-protein-interacting conformation
SO NATURE
LA English
DT Article
ID heterotrimeric g-protein; catalyzed transducin activation; carboxylic-acid group; alpha-subunit; nucleotide exchange; coupled receptor; squid rhodopsin; dark-adaptation; proton uptake; binding-site
AB Opsin, the ligand- free form of the G- protein- coupled receptor rhodopsin, at low pH adopts a conformationally distinct, active G- protein- binding state known as Ops*. A synthetic peptide derived from the main binding site of the heterotrimeric G protein - the carboxy terminus of the alpha-subunit (G alpha CT) - stabilizes Ops*. Here we present the 3.2 angstrom crystal structure of the bovine Ops* - G alpha CT peptide complex. G alpha CT binds to a site in opsin that is opened by an outward tilt of transmembrane helix ( TM) 6, a pairing of TM5 and TM6, and a restructured TM7 - helix 8 kink. Contacts along the inner surface of TM5 and TM6 induce an alpha- helical conformation in G alpha CT with a C- terminal reverse turn. Main- chain carbonyl groups in the reverse turn constitute the centre of a hydrogen- bonded network, which links the two receptor regions containing the conserved E( D) RY and NPxxY(x)(5,6)F motifs. On the basis of the Ops* - G alpha CT structure and known conformational changes in G alpha, we discuss signal transfer from the receptor to the G protein nucleotide- binding site.
C1 [Scheerer, Patrick; Park, Jung Hee; Hildebrand, Peter W.; Kim, Yong Ju; Choe, Hui-Woog; Hofmann, Klaus Peter; Ernst, Oliver P.] Charite Univ Med Berlin, Inst Med Phys & Biophys CC2, D-10117 Berlin, Germany.
   [Krauss, Norbert] Univ London Queen Mary Coll, Sch Biol & Chem Sci, London E1 4NS, England.
   [Choe, Hui-Woog] Chonbuk Natl Univ, Dept Chem, Coll Nat Sci, Chonju 561756, South Korea.
   [Hofmann, Klaus Peter] Humboldt Univ, Zentrum Biophys & Bioinformat, D-10115 Berlin, Germany.
C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; University of London; Queen Mary University London; Jeonbuk National University; Humboldt University of Berlin
RP Ernst, OP (corresponding author), Charite Univ Med Berlin, Inst Med Phys & Biophys CC2, Charitepl 1, D-10117 Berlin, Germany.
EM hwchoe@chonbuk.ac.kr; klaus_peter.hofmann@charite.de; oliver.ernst@charite.de
FU Protein Structure Factory; Freie Universitat Berlin [BL 14.1, BL 14.2]; Deutsche Forschungsgemeinschaft [Sfb449, Sfb740]; DFG-KOSEF international cooperation [ER 294/1-1, F01-2004-000-10054-0]; CBNU; Leibniz Graduate School of Molecular Biophysics, Berlin
NR 58
TC 930
Z9 1075
U1 1
U2 176
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 497
EP U30
DI 10.1038/nature07330
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600038
PM 18818650
DA 2026-03-09
ER

PT J
AU Kangaspeska, S
   Stride, B
   Métivier, R
   Polycarpou-Schwarz, M
   Ibberson, D
   Carmouche, RP
   Benes, V
   Gannon, F
   Reid, G
AF Kangaspeska, Sara
   Stride, Brenda
   Metivier, Raphael
   Polycarpou-Schwarz, Maria
   Ibberson, David
   Carmouche, Richard Paul
   Benes, Vladimir
   Gannon, Frank
   Reid, George
TI Transient cyclical methylation of promoter DNA
SO NATURE
LA English
DT Article
ID estrogen-receptor-alpha; chromatin modification; nuclear receptor; gene-regulation; transcription; organization; mechanisms; dynamics
AB Methylation of CpG dinucleotides is generally associated with epigenetic silencing of transcription and is maintained through cellular division(1-3). Multiple CpG sequences are rare in mammalian genomes, but frequently occur at the transcriptional start site of active genes, with most clusters of CpGs being hypomethylated(4). We reported previously that the proximal region of the trefoil factor 1 ( TFF1, also known as pS2) and oestrogen receptor alpha ( ER alpha) promoters could be partially methylated by treatment with deacetylase inhibitors(5), suggesting the possibility of dynamic changes in DNA methylation. Here we show that cyclical methylation and demethylation of CpG dinucleotides, with a periodicity of around 100 min, is characteristic for five selected promoters, including the oestrogen ( E2)- responsive pS2 gene, in human cells. When the pS2 gene is actively transcribed, DNA methylation occurs after the cyclical occupancy of ER alpha and RNA polymerase II ( polII). Moreover, we report conditions that provoke methylation cycling of the pS2 promoter in cell lines in which pS2 expression is quiescent and the proximal promoter is methylated. This coincides with a low- level re- expression of ER alpha and of pS2 transcripts.
C1 [Kangaspeska, Sara; Stride, Brenda; Polycarpou-Schwarz, Maria; Ibberson, David; Carmouche, Richard Paul; Benes, Vladimir; Gannon, Frank; Reid, George] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Metivier, Raphael] Univ Rennes 1, SPARTE, CNRS, UMR 6026, F-35042 Rennes, France.
C3 European Molecular Biology Laboratory (EMBL); Universite de Rennes; Centre National de la Recherche Scientifique (CNRS)
RP Reid, G (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM george.reid@embl.de
NR 23
TC 528
Z9 637
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 MAR 6
PY 2008
VL 452
IS 7183
BP 112
EP U14
DI 10.1038/nature06640
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900057
PM 18322535
DA 2026-03-09
ER

PT J
AU Ziegenfuss, JS
   Biswas, R
   Avery, MA
   Hong, K
   Sheehan, AE
   Yeung, YG
   Stanley, ER
   Freeman, MR
AF Ziegenfuss, Jennifer S.
   Biswas, Romi
   Avery, Michelle A.
   Hong, Kyoungja
   Sheehan, Amy E.
   Yeung, Yee-Guide
   Stanley, E. Richard
   Freeman, Marc R.
TI Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling
SO NATURE
LA English
DT Article
ID embryonic dorsal closure; cell corpse engulfment; apoptotic cells; c-elegans; drosophila metamorphosis; tyrosine kinase; receptor; protein; removal; ced-1
AB The cellular machinery promoting phagocytosis of corpses of apoptotic cells is well conserved from worms to mammals. An important component is the Caenorhabditis elegans engulfment receptor CED- 1 ( ref. 1) and its Drosophila orthologue, Draper(2). The CED- 1/ Draper signalling pathway is also essential for the phagocytosis of other types of 'modified self' including necrotic cells(3), developmentally pruned axons(4,5) and dendrites(6), and axons undergoing Wallerian degeneration(7). Here we show that Drosophila Shark, a non- receptor tyrosine kinase similar to mammalian Syk and Zap- 70, binds Draper through an immunoreceptor tyrosine- based activation motif ( ITAM) in the Draper intracellular domain. We show that Shark activity is essential for Draper-mediated signalling events in vivo, including the recruitment of glial membranes to severed axons and the phagocytosis of axonal debris and neuronal cell corpses by glia. We also show that the Src family kinase ( SFK) Src42A can markedly increase Draper phosphorylation and is essential for glial phagocytic activity. We propose that ligand- dependent Draper receptor activation initiates the Src42A- dependent tyrosine phosphorylation of Draper, the association of Shark and the activation of the Draper pathway. These Draper - Src42A - Shark interactions are strikingly similar to mammalian immunoreceptor - SFK - Syk signalling events in mammalian myeloid and lymphoid cells(8,9). Thus, Draper seems to be an ancient immunoreceptor with an extracellular domain tuned to modified self, and an intracellular domain promoting phagocytosis through an ITAM- domain - SFK - Syk- mediated signalling cascade.
C1 [Ziegenfuss, Jennifer S.; Avery, Michelle A.; Sheehan, Amy E.; Freeman, Marc R.] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA.
   [Biswas, Romi; Hong, Kyoungja; Yeung, Yee-Guide; Stanley, E. Richard] Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Freeman, MR (corresponding author), Univ Massachusetts, Sch Med, Dept Neurobiol, 364 Plantat St, Worcester, MA 01605 USA.
EM rstanley@aecom.yu.edu; marc.freeman@umassmed.edu
FU National Institute of Neurological Disorders and Stroke [R01NS053538] Funding Source: NIH RePORTER; NCI NIH HHS [1R01CA26504, R37 CA026504, R01 CA026504] Funding Source: Medline; NIGMS NIH HHS [1R01GM55293] Funding Source: Medline; NINDS NIH HHS [1R01NS053538, R01 NS053538] Funding Source: Medline
NR 32
TC 163
Z9 200
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 935
EP U68
DI 10.1038/nature06901
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000047
PM 18432193
DA 2026-03-09
ER

PT J
AU Stevenson, DJ
AF Stevenson, David J.
TI A planetary perspective on the deep Earth
SO NATURE
LA English
DT Article
ID accretion
AB Earth is an engine, tending to obliterate some of the evidence of events that are distant in time, but a memory is retained in its chemistry, its isotopes, the presence of the Moon, perhaps also in geophysical observables such as the temperature of the core and the nature of the mantle immediately above the core, and maybe even in the existence of plate tectonics and life. The remarkable growth in the study and understanding of Earth has happened in parallel with a spectacular era of planetary exploration, relevant astronomical discoveries and computational and theoretical advances, all of which help us to place Earth and its interior in a perspective that integrates the Earth sciences with extraterrestrial studies and basic sciences such as condensed- matter physics. However, progress on the biggest challenges in understanding the deep Earth continues to rely mainly on looking down rather than looking up.
C1 CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Stevenson, DJ (corresponding author), CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
EM djs@gps.caltech.edu
NR 17
TC 41
Z9 54
U1 1
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 261
EP 265
DI 10.1038/nature06582
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100029
PM 18202637
DA 2026-03-09
ER

PT J
AU Richardson, SH
   Shirey, SB
AF Richardson, Stephen H.
   Shirey, Steven B.
TI Continental mantle signature of Bushveld magmas and coeval diamonds
SO NATURE
LA English
DT Article
ID re-os isotope; kaapvaal craton; south-africa; crustal contamination; lithospheric mantle; osmium isotopes; merensky reef; sr isotope; complex; systematics
AB The emplacement of the 2.05- billion- year- old Bushveld complex, the world's largest layered intrusion and platinum- group element ( PGE) repository(1), is a singular event in the history of the Kaapvaal craton of southern Africa(2-4), one of Earth's earliest surviving continental nuclei. In the prevailing model for the complex's mineralization, the radiogenic strontium and osmium isotope signatures of Bushveld PGE ores are attributed to continental crustal contamination of the host magmas(5-11). The scale of the intrusion and lateral homogeneity of the PGE- enriched layers(1), however, have long been problematical for the crustal contamination model, given the typically heterogeneous nature of continental crust. Furthermore, the distribution of Bushveld magmatism matches that of seismically anomalous underlying mantle(3,12), implying significant interaction before emplacement in the crust. Mineral samples of the ancient 200- km- deep craton keel, encapsulated in macrodiamonds and entrained by proximal kimberlites, reveal the nature of continental mantle potentially incorporated by Bushveld magmas(13,14). Here we show that sulphide inclusions in 2- billion- year- old diamonds from the 0.5- billion- year- old Venetia and 1.2- billion- year- old Premier kimberlites ( on opposite sides of the complex) have initial osmium isotope ratios even more radiogenic than those of Bushveld sulphide ore minerals(6,15). Sulphide Re - Os and silicate Sm - Nd and Rb - Sr isotope compositions indicate that continental mantle harzburgite and eclogite components, in addition to the original convecting mantle magma, most probably contributed to the genesis of both the diamonds and the Bushveld complex. Coeval diamonds provide key evidence that the main source of Bushveld PGEs is the mantle rather than the crust.
C1 [Richardson, Stephen H.] Univ Cape Town, Dept Geol Sci, ZA-7701 Rondebosch, South Africa.
   [Shirey, Steven B.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
C3 University of Cape Town; Carnegie Institution for Science
RP Richardson, SH (corresponding author), Univ Cape Town, Dept Geol Sci, ZA-7701 Rondebosch, South Africa.
EM steve.richardson@uct.ac.za
NR 33
TC 132
Z9 143
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 910
EP 913
DI 10.1038/nature07073
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000041
PM 18548068
DA 2026-03-09
ER

PT J
AU Difilippantonio, S
   Gapud, E
   Wong, N
   Huang, CY
   Mahowald, G
   Chen, HT
   Kruhlak, MJ
   Callen, E
   Livak, F
   Nussenzweig, MC
   Sleckman, BP
   Nussenzweig, A
AF Difilippantonio, Simone
   Gapud, Eric
   Wong, Nancy
   Huang, Ching-Yu
   Mahowald, Grace
   Chen, Hua Tang
   Kruhlak, Michael J.
   Callen, Elsa
   Livak, Ferenc
   Nussenzweig, Michel C.
   Sleckman, Barry P.
   Nussenzweig, Andre
TI 53BP1 facilitates long-range DNA end-joining during V(D)J recombination
SO NATURE
LA English
DT Article
ID switch region recombination; genomic instability; chromosome breaks; in-vivo; damage; atm; h2ax; p53; methylation; prevents
AB Variable, diversity and joining (V(D)J) recombination and class-switch recombination use overlapping but distinct non- homologous end joining pathways to repair DNA double- strand- break intermediates. 53BP1 is a DNA- damage- response protein that is rapidly recruited to sites of chromosomal double- strand breaks, where it seems to function in a subset of ataxia telangiectasia mutated ( ATM) kinase-, H2A histone family member X ( H2AX, also known as H2AFX)- and mediator of DNA damage checkpoint 1 (MDC1)- dependent events(1,2). A 53BP1- dependent end- joining pathway has been described that is dispensable for V( D) J recombination but essential for class- switch recombination(3,4). Here we report a previously unrecognized defect in the joining phase of V( D) J recombination in 53BP1- deficient lymphocytes that is distinct from that found in classical non- homologous- end- joining-, H2ax-, Mdc1- and Atm- deficient mice. Absence of 53BP1 leads to impairment of distal V - DJ joining with extensive degradation of unrepaired coding ends and episomal signal joint reintegration at V( D) J junctions. This results in apoptosis, loss of T- cell receptor a locus integrity and lymphopenia. Further impairment of the apoptotic checkpoint causes propagation of lymphocytes that have antigen receptor breaks. These data suggest a more general role for 53BP1 in maintaining genomic stability during long- range joining of DNA breaks.
C1 [Difilippantonio, Simone; Wong, Nancy; Chen, Hua Tang; Kruhlak, Michael J.; Callen, Elsa; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Gapud, Eric; Huang, Ching-Yu; Mahowald, Grace; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Livak, Ferenc] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
   [Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA.
   [Nussenzweig, Michel C.] Howard Hughes Med Inst, New York, NY 10021 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Washington University (WUSTL); University System of Maryland; University of Maryland Baltimore; Rockefeller University; Howard Hughes Medical Institute
RP Nussenzweig, A (corresponding author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
FU NIH [R01AI074953]; Cancer Research Institute; Intramural Research Program; National Cancer Institute; Center for Cancer Research; National Cancer Institute [ZIABC010283, ZICBC009255, ZICBC010915] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI074953] Funding Source: NIH RePORTER
NR 30
TC 247
Z9 299
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 NOV 27
PY 2008
VL 456
IS 7221
BP 529
EP U57
DI 10.1038/nature07476
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500044
PM 18931658
DA 2026-03-09
ER

PT J
AU Dulcis, D
   Spitzer, NC
AF Dulcis, Davide
   Spitzer, Nicholas C.
TI Illumination controls differentiation of dopamine neurons regulating behaviour
SO NATURE
LA English
DT Article
ID activity-dependent regulation; seasonal affective-disorder; xenopus-laevis; melanotrope cells; tyrosine-hydroxylase; suprachiasmatic nucleus; expression; plasticity; zebrafish; system
AB Specification of the appropriate neurotransmitter is a crucial step in neuronal differentiation because it enables signalling among populations of neurons. Experimental manipulations demonstrate that both autonomous and activity- dependent genetic programs contribute to this process during development, but whether natural environmental stimuli specify transmitter expression in a neuronal population is unknown. We investigated neurons of the ventral suprachiasmatic nucleus that regulate neuroendocrine pituitary function in response to light in teleosts, amphibia and primates. Here we show that altering light exposure, which changes the sensory input to the circuit controlling adaptation of skin pigmentation to background, changes the number of neurons expressing dopamine in larvae of the amphibian Xenopus laevis in a circuit- specific and activity- dependent manner. Neurons newly expressing dopamine then regulate changes in camouflage colouration in response to illumination. Thus, physiological activity alters the numbers of behaviourally relevant amine- transmitter- expressing neurons in the brain at postembryonic stages of development. The results may be pertinent to changes in cognitive states that are regulated by biogenic amines.
C1 [Dulcis, Davide; Spitzer, Nicholas C.] Univ Calif San Diego, Neurobiol Sect, Div Biol Sci, La Jolla, CA 92093 USA.
   [Dulcis, Davide; Spitzer, Nicholas C.] Univ Calif San Diego, Ctr Mol Genet, Kavli Inst Brain & Mind, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego
RP Dulcis, D (corresponding author), Univ Calif San Diego, Neurobiol Sect, Div Biol Sci, La Jolla, CA 92093 USA.
EM ddulcis@biomail.ucsd.edu
FU N.C.S.; National Institutes of Health
NR 46
TC 101
Z9 120
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 13
PY 2008
VL 456
IS 7219
BP 195
EP U20
DI 10.1038/nature07569
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300031
PM 19005547
DA 2026-03-09
ER

PT J
AU Ratcliffe, JM
   Nydam, ML
AF Ratcliffe, John M.
   Nydam, Marie L.
TI Multimodal warning signals for a multiple predator world
SO NATURE
LA English
DT Article
ID arctiid moths; evolution; lepidoptera; gene; bats; discrimination; mitochondrial; defenses; utility
AB Aposematism is an anti- predator defence, dependent on a predator's ability to associate unprofitable prey with a prey- borne signal(1). Multimodal signals should vary in efficacy according to the sensory systems of different predators; however, until now, the impact of multiple predator classes on the evolution of these signals had not been investigated(2,3). Here, using a community- level molecular phylogeny to generate phylogenetically independent contrasts, we show that warning signals of tiger moths vary according to the seasonal and daily activity patterns of birds and bats - predators with divergent sensory capacities. Many tiger moths advertise chemical defence(4,5) using conspicuous colouration and/ or ultrasonic clicks(3,6). During spring, when birds are active and bats less so, we found that tiger moths did not produce ultrasonic clicks. Throughout both spring and summer, tiger moths most active during the day were visually conspicuous. Those species emerging later in the season produced ultrasonic clicks; those that were most nocturnal were visually cryptic. Our results indicate that selective pressures from multiple predator classes have distinct roles in the evolution of multimodal warning displays now effective against a single predator class. We also suggest that the evolution of acoustic warning signals may lack the theoretical difficulties associated with the origination of conspicuous colouration.
C1 [Nydam, Marie L.] Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA.
   [Ratcliffe, John M.] Univ So Denmark, Ctr Sound Commun, Inst Biol, DK-5230 Odense M, Denmark.
C3 Cornell University; University of Southern Denmark
RP Nydam, ML (corresponding author), Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA.
EM jmr@biology.sdu.dk; mln32@cornell.edu
FU NSERC; NIDCD; DNSRC
NR 40
TC 94
Z9 109
U1 3
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 96
EP U59
DI 10.1038/nature07087
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200044
PM 18769439
DA 2026-03-09
ER

PT J
AU Arita, K
   Ariyoshi, M
   Tochio, H
   Nakamura, Y
   Shirakawa, M
AF Arita, Kyohei
   Ariyoshi, Mariko
   Tochio, Hidehito
   Nakamura, Yusuke
   Shirakawa, Masahiro
TI Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism
SO NATURE
LA English
DT Article
ID binding; domain; dnmt1
AB DNA methylation of CpG dinucleotides is an important epigenetic modification of mammalian genomes and is essential for the regulation of chromatin structure, of gene expression and of genome stability(1,2). Differences in DNA methylation patterns underlie a wide range of biological processes, such as genomic imprinting, inactivation of the X chromosome, embryogenesis, and carcinogenesis(3-6). Inheritance of the epigenetic methylation pattern is mediated by the enzyme DNA methyltransferase 1 ( Dnmt1), which methylates newly synthesized CpG sequences during DNA replication, depending on the methylation status of the template strands(7,8). The protein UHRF1 ( also known as Np95 and ICBP90) recognizes hemi- methylation sites via a SET and RING- associated ( SRA) domain and directs Dnmt1 to these sites(9-11). Here we report the crystal structures of the SRA domain in free and hemi- methylated DNA- bound states. The SRA domain folds into a globular structure with a basic concave surface formed by highly conserved residues. Binding of DNA to the concave surface causes a loop and an amino- terminal tail of the SRA domain to fold into DNA interfaces at the major and minor grooves of the methylation site. In contrast to fully methylated CpG sites recognized by the methyl- CpG- binding domain(12,13), the methylcytosine base at the hemi- methylated site is flipped out of the DNA helix in the SRA - DNA complex and fits tightly into a protein pocket on the concave surface. The complex structure suggests that the successive flip out of the pre- existing methylated cytosine and the target cytosine to be methylated is associated with the coordinated transfer of the hemi- methylated CpG site from UHRF1 to Dnmt1.
C1 [Arita, Kyohei; Ariyoshi, Mariko; Tochio, Hidehito; Shirakawa, Masahiro] Kyoto Univ, Grad Sch Engn, Kyoto 6158510, Japan.
   [Tochio, Hidehito; Shirakawa, Masahiro] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
   [Nakamura, Yusuke] Univ Tokyo, Mol Med Lab, Ctr Human Genome, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan.
   [Shirakawa, Masahiro] RIKEN, Yokohama Inst, Yokohama, Kanagawa 2300045, Japan.
C3 Kyoto University; Japan Science & Technology Agency (JST); University of Tokyo; RIKEN
RP Shirakawa, M (corresponding author), Kyoto Univ, Grad Sch Engn, Kyoto 6158510, Japan.
EM ma4@eng.mbox.media.kyoto-u.ac.jp; shirakawa@moleng.kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; Japan Science and Technology Agency; Japan Society for the Promotion of Science; Global COE Program 'Integrated Materials Science' of MEXT of Japan
NR 27
TC 403
Z9 471
U1 0
U2 53
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 818
EP U12
DI 10.1038/nature07249
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900051
PM 18772891
DA 2026-03-09
ER

PT J
AU Gomez-Roldan, V
   Fermas, S
   Brewer, PB
   Puech-Pagès, V
   Dun, EA
   Pillot, JP
   Letisse, F
   Matusova, R
   Danoun, S
   Portais, JC
   Bouwmeester, H
   Bécard, G
   Beveridge, CA
   Rameau, C
   Rochange, SF
AF Gomez-Roldan, Victoria
   Fermas, Soraya
   Brewer, Philip B.
   Puech-Pages, Virginie
   Dun, Elizabeth A.
   Pillot, Jean-Paul
   Letisse, Fabien
   Matusova, Radoslava
   Danoun, Saida
   Portais, Jean-Charles
   Bouwmeester, Harro
   Becard, Guillaume
   Beveridge, Christine A.
   Rameau, Catherine
   Rochange, Soizic F.
TI Strigolactone inhibition of shoot branching
SO NATURE
LA English
DT Article
ID arbuscular-mycorrhizal fungi; root parasitic plants; germination stimulants; phosphorus deficiency; seed-germination; apical dominance; rms1 mutant; arabidopsis; pea; signal
AB A carotenoid- derived hormonal signal that inhibits shoot branching in plants has long escaped identification. Strigolactones are compounds thought to be derived from carotenoids and are known to trigger the germination of parasitic plant seeds and stimulate symbiotic fungi. Here we present evidence that carotenoid cleavage dioxygenase 8 shoot branching mutants of pea are strigolactone deficient and that strigolactone application restores the wild- type branching phenotype to ccd8 mutants. Moreover, we show that other branching mutants previously characterized as lacking a response to the branching inhibition signal also lack strigolactone response, and are not deficient in strigolactones. These responses are conserved in Arabidopsis. In agreement with the expected properties of the hormonal signal, exogenous strigolactone can be transported in shoots and act at low concentrations. We suggest that endogenous strigolactones or related compounds inhibit shoot branching in plants. Furthermore, ccd8 mutants demonstrate the diverse effects of strigolactones in shoot branching, mycorrhizal symbiosis and parasitic weed interaction.
C1 [Fermas, Soraya; Pillot, Jean-Paul; Rameau, Catherine] Inst JP Bourgin, Genet & Ameliorat Plantes Stn, INRA, UR254, F-78000 Versailles, France.
   [Gomez-Roldan, Victoria; Puech-Pages, Virginie; Danoun, Saida; Becard, Guillaume; Rochange, Soizic F.] Univ Toulouse 1, F-31326 Castanet Tolosan, France.
   [Gomez-Roldan, Victoria; Puech-Pages, Virginie; Danoun, Saida; Becard, Guillaume; Rochange, Soizic F.] UPS, F-31326 Castanet Tolosan, France.
   [Gomez-Roldan, Victoria; Puech-Pages, Virginie; Danoun, Saida; Becard, Guillaume; Rochange, Soizic F.] CNRS, F-31326 Castanet Tolosan, France.
   [Brewer, Philip B.; Dun, Elizabeth A.; Beveridge, Christine A.] Univ Queensland, ARC Ctr Excellence Integrat Legume Res, Brisbane, Qld 4072, Australia.
   [Letisse, Fabien; Portais, Jean-Charles] INSA Toulouse, CNRS, UMR5504, UMR792,INRA, F-31400 Toulouse, France.
   [Matusova, Radoslava; Bouwmeester, Harro] Plant Res Int, NL-6700 AA Wageningen, Netherlands.
   [Bouwmeester, Harro] Univ Wageningen & Res Ctr, Lab Plant Physiol, NL-6703 BD Wageningen, Netherlands.
   [Beveridge, Christine A.] Univ Queensland, Sch Integrat Biol, Brisbane, Qld 4072, Australia.
C3 INRAE; Universite Paris Saclay; Universite de Toulouse; Universite Toulouse 1 Capitole; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); University of Queensland; INRAE; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite de Toulouse; Institut National des Sciences Appliquees de Toulouse; Wageningen University & Research; University of Queensland
RP Rameau, C (corresponding author), Inst JP Bourgin, Genet & Ameliorat Plantes Stn, INRA, UR254, F-78000 Versailles, France.
EM becard@scsv.ups-tlse.fr; rameau@versailles.inra.fr
FU French Ministry of Research and Higher Education; ANR; The Netherlands Organisation for Scientific Research (NWO; VICI-grant)
NR 51
TC 1792
Z9 2078
U1 22
U2 897
PU 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 11
PY 2008
VL 455
IS 7210
BP 189
EP U22
DI 10.1038/nature07271
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800039
PM 18690209
DA 2026-03-09
ER

PT J
AU Yang, CG
   Yi, CQ
   Duguid, EM
   Sullivan, CT
   Jian, X
   Rice, PA
   He, C
AF Yang, Cai-Guang
   Yi, Chengqi
   Duguid, Erica M.
   Sullivan, Christopher T.
   Jian, Xing
   Rice, Phoebe A.
   He, Chuan
TI Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA
SO NATURE
LA English
DT Article
ID oxidative demethylation; alkylation damage; dna; bacterial; lesions; 3-methylthymine; protein; iron; 1-methylguanine; 8-oxoguanine
AB Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/ RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1- meA damage by repairing this lesion in double- stranded DNA ( dsDNA), whereas AlkB and ABH3 preferentially repair single- stranded DNA ( ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB - dsDNA and ABH2 - dsDNA complexes, stabilized by a chemical cross- linking strategy. This study reveals that AlkB uses an unprecedented base- flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped- out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.
C1 [Yang, Cai-Guang; Yi, Chengqi; Duguid, Erica M.; Sullivan, Christopher T.; Jian, Xing; He, Chuan] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
   [Rice, Phoebe A.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP He, C (corresponding author), Univ Chicago, Dept Chem, 929 E 57th St, Chicago, IL 60637 USA.
EM chuanhe@uchicago.edu
FU NIGMS NIH HHS [R01 GM071440, GM071440] Funding Source: Medline
NR 44
TC 220
Z9 281
U1 2
U2 77
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 24
PY 2008
VL 452
IS 7190
BP 961
EP U4
DI 10.1038/nature06889
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600032
PM 18432238
DA 2026-03-09
ER

PT J
AU Xu, SZ
   Sukumar, P
   Zeng, FN
   Li, J
   Jairaman, A
   English, A
   Naylor, J
   Ciurtin, C
   Majeed, Y
   Milligan, CJ
   Bahnasi, YM
   Al-Shawaf, E
   Porter, KE
   Jiang, LH
   Emery, P
   Sivaprasadarao, A
   Beech, DJ
AF Xu, Shang-Zhong
   Sukumar, Piruthivi
   Zeng, Fanning
   Li, Jing
   Jairaman, Amit
   English, Anne
   Naylor, Jacqueline
   Ciurtin, Coziana
   Majeed, Yasser
   Milligan, Carol J.
   Bahnasi, Yahya M.
   Al-Shawaf, Eman
   Porter, Karen E.
   Jiang, Lin-Hua
   Emery, Paul
   Sivaprasadarao, Asipu
   Beech, David J.
TI TRPC channel activation by extracellular thioredoxin
SO NATURE
LA English
DT Article
ID rheumatoid-arthritis; oxidative stress; cation channels; reductase; cell; subunit; disease; brain
AB Mammalian homologues of Drosophila melanogaster transient receptor potential ( TRP) are a large family of multimeric cation channels that act, or putatively act, as sensors of one or more chemical factor(1,2). Major research objectives are the identification of endogenous activators and the determination of cellular and tissue functions of these channels. Here we show the activation of TRPC5 ( canonical TRP 5) homomultimeric and TRPC5-TRPC1 heteromultimeric channels(3-5) by extracellular reduced thioredoxin, which acts by breaking a disulphide bridge in the predicted extracellular loop adjacent to the ion- selectivity filter of TRPC5. Thioredoxin is an endogenous redox protein with established intracellular functions, but it is also secreted and its extracellular targets are largely unknown(6-9). Particularly high extracellular concentrations of thioredoxin are apparent in rheumatoid arthritis(8,10-12), an inflammatory joint disease that disables millions of people worldwide(13). We show that TRPC5 and TRPC1 are expressed in secretory fibroblast- like synoviocytes from patients with rheumatoid arthritis, that endogenous TRPC5 - TRPC1 channels of the cells are activated by reduced thioredoxin, and that blockade of the channels enhances secretory activity and prevents the suppression of secretion by thioredoxin. The data indicate the presence of a previously unrecognized ion- channel activation mechanism that couples extracellular thioredoxin to cell function.
C1 [Xu, Shang-Zhong; Sukumar, Piruthivi; Zeng, Fanning; Li, Jing; Jairaman, Amit; Naylor, Jacqueline; Ciurtin, Coziana; Majeed, Yasser; Milligan, Carol J.; Bahnasi, Yahya M.; Al-Shawaf, Eman; Jiang, Lin-Hua; Sivaprasadarao, Asipu; Beech, David J.] Univ Leeds, Fac Biol Sci, Inst Membrane & Syst Biol, Leeds LS2 9JT, W Yorkshire, England.
   [Porter, Karen E.] Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England.
   [English, Anne; Emery, Paul] Chapel Allerton Hosp, Acad Unit Musculoskeletal Dis, Leeds LS7 4SA, W Yorkshire, England.
C3 University of Leeds; University of Leeds; Chapel Allerton Hospital; University of Leeds
RP Beech, DJ (corresponding author), Univ Leeds, Fac Biol Sci, Inst Membrane & Syst Biol, Garstang Bldg, Leeds LS2 9JT, W Yorkshire, England.
EM d.j.beech@leeds.ac.uk
FU Biotechnology and Biological Sciences Research Council [BB/D524875/1] Funding Source: researchfish; Arthritis Research UK [18475] Funding Source: Medline; Biotechnology and Biological Sciences Research Council [BB/D524875/1] Funding Source: Medline; Wellcome Trust [077424, 083857] Funding Source: Medline; BBSRC [BB/D524875/1] Funding Source: UKRI
NR 27
TC 241
Z9 274
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 3
PY 2008
VL 451
IS 7174
BP 69
EP U9
DI 10.1038/nature06414
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300035
PM 18172497
DA 2026-03-09
ER

PT J
AU Kurz, WA
   Dymond, CC
   Stinson, G
   Rampley, GJ
   Neilson, ET
   Carroll, AL
   Ebata, T
   Safranyik, L
AF Kurz, W. A.
   Dymond, C. C.
   Stinson, G.
   Rampley, G. J.
   Neilson, E. T.
   Carroll, A. L.
   Ebata, T.
   Safranyik, L.
TI Mountain pine beetle and forest carbon feedback to climate change
SO NATURE
LA English
DT Article
ID disturbance; outbreak; ecosystem
AB The mountain pine beetle ( Dendroctonus ponderosae Hopkins, Coleoptera: Curculionidae, Scolytinae) is a native insect of the pine forests of western North America, and its populations periodically erupt into large- scale outbreaks(1-3). During outbreaks, the resulting widespread tree mortality reduces forest carbon uptake and increases future emissions from the decay of killed trees. The impacts of insects on forest carbon dynamics, however, are generally ignored in large- scale modelling analyses. The current outbreak in British Columbia, Canada, is an order of magnitude larger in area and severity than all previous recorded outbreaks(4). Here we estimate that the cumulative impact of the beetle outbreak in the affected region during 2000 - 2020 will be 270 megatonnes ( Mt) carbon ( or 36 g carbon m(-2) yr(-1) on average over 374,000 km 2 of forest). This impact converted the forest from a small net carbon sink to a large net carbon source both during and immediately after the outbreak. In the worst year, the impacts resulting from the beetle outbreak in British Columbia were equivalent to similar to 75% of the average annual direct forest fire emissions from all of Canada during 1959 - 1999. The resulting reduction in net primary production was of similar magnitude to increases observed during the 1980s and 1990s as a result of global change(5). Climate change has contributed to the unprecedented extent and severity of this outbreak(6). Insect outbreaks such as this represent an important mechanism by which climate change may undermine the ability of northern forests to take up and store atmospheric carbon, and such impacts should be accounted for in large- scale modelling analyses.
C1 [Kurz, W. A.; Dymond, C. C.; Stinson, G.; Rampley, G. J.; Neilson, E. T.; Carroll, A. L.; Safranyik, L.] Nat Resources Canada, Canadian Forest Serv, Pacific Forestry Ctr, Victoria, BC V8Z 1M5, Canada.
   [Ebata, T.] British Columbia Minist Forests & Range, Victoria, BC V8W 9C2, Canada.
C3 Natural Resources Canada; Canadian Forest Service
RP Kurz, WA (corresponding author), Nat Resources Canada, Canadian Forest Serv, Pacific Forestry Ctr, Victoria, BC V8Z 1M5, Canada.
EM wkurz@nrcan.gc.ca
NR 30
TC 1449
Z9 1709
U1 11
U2 903
PU NATURE PUBLISHING 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 24
PY 2008
VL 452
IS 7190
BP 987
EP 990
DI 10.1038/nature06777
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600038
PM 18432244
DA 2026-03-09
ER

PT J
AU Frueh, DP
   Arthanari, H
   Koglin, A
   Vosburg, DA
   Bennett, AE
   Walsh, CT
   Wagner, G
AF Frueh, Dominique P.
   Arthanari, Haribabu
   Koglin, Alexander
   Vosburg, David A.
   Bennett, Andrew E.
   Walsh, Christopher T.
   Wagner, Gerhard
TI Dynamic thiolation-thioesterase structure of a non-ribosomal peptide synthetase
SO NATURE
LA English
DT Article
ID acyl carrier protein; fatty-acid synthase; triple-resonance experiments; escherichia-coli; macromolecular structure; c-13 magnetization; nmr-spectroscopy; chemical-shift; swiss-model; resolution
AB Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) produce numerous secondary metabolites with various therapeutic/antibiotic properties(1). Like fatty acid synthases (FAS), these enzymes are organized in modular assembly lines in which each module, made of conserved domains, incorporates a given monomer unit into the growing chain. Knowledge about domain or module interactions may enable reengineering of this assembly line enzymatic organization and open avenues for the design of new bioactive compounds with improved therapeutic properties. So far, little structural information has been available on how the domains interact and communicate. This may be because of inherent interdomain mobility hindering crystallization, or because crystallized molecules may not represent the active domain orientations(2). In solution, the large size and internal dynamics of multidomain fragments (> 35 kilodaltons) make structure determination by nuclear magnetic resonance a challenge and require advanced technologies. Here we present the solution structure of the apo-thiolation-thioesterase (T-TE) di-domain fragment of the Escherichia coli enterobactin synthetase EntF NRPS subunit. In the holoenzyme, the T domain carries the growing chain tethered to a 4 '-phosphopantetheine whereas the TE domain catalyses hydrolysis and cyclization of the iron chelator enterobactin. The T-TE di-domain forms a compact but dynamic structure with a well-defined domain interface; the two active sites are at a suitable distance for substrate transfer from T to TE. We observe extensive interdomain and intradomain motions forwell-defined regions and show that these are modulated by interactions with proteins that participate in the biosynthesis. The T-TE interaction described here provides a model for NRPS, PKS and FAS function in general as T-TE-like di-domains typically catalyse the last step in numerous assembly-line chain-termination machineries.
C1 [Frueh, Dominique P.; Arthanari, Haribabu; Koglin, Alexander; Vosburg, David A.; Bennett, Andrew E.; Walsh, Christopher T.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Wagner, G (corresponding author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM dominique_frueh@hms.harvard.edu; christopher_walsh@hms.harvard.edu; gerhard_wagner@hms.harvard.edu
FU NIBIB NIH HHS [P41 EB002026, EB 002026] Funding Source: Medline; NIGMS NIH HHS [GM47467, P01 GM047467, P41 GM066360, GM066360] Funding Source: Medline
NR 46
TC 140
Z9 186
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 AUG 14
PY 2008
VL 454
IS 7206
BP 903
EP U62
DI 10.1038/nature07162
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600040
PM 18704088
DA 2026-03-09
ER

PT J
AU Poverenov, E
   Efremenko, I
   Frenkel, AI
   Ben-David, Y
   Shimon, LJW
   Leitus, G
   Konstantinovski, L
   Martin, JML
   Milstein, D
AF Poverenov, Elena
   Efremenko, Irena
   Frenkel, Anatoly I.
   Ben-David, Yehoshoa
   Shimon, Linda J. W.
   Leitus, Gregory
   Konstantinovski, Leonid
   Martin, Jan M. L.
   Milstein, David
TI Evidence for a terminal Pt(IV)-oxo complex exhibiting diverse reactivity
SO NATURE
LA English
DT Article
ID water oxidation; oxo complex; bond activation; mechanism; chemistry; catalysts; dioxygen; energy
AB Terminal oxo complexes of transition metals have critical roles in various biological and chemical processes(1,2). For example, the catalytic oxidation of organic molecules(3,4), some oxidative enzymatic transformations(5-7), and the activation of dioxygen on metal surfaces(8) are all thought to involve oxo complexes. Moreover, they are believed to be key intermediates in the photocatalytic oxidation of water to give molecular oxygen, a topic of intensive global research aimed at artificial photosynthesis and water splitting(9-13). The terminal oxo ligand is a strong pi-electron donor, so it readily forms stable complexes with high-valent early transition metals. As the d orbitals are filled up with valence electrons, the terminal oxo ligand becomes destabilized(2). Here we present evidence for a d(n) (n > 5) terminal oxo complex that is not stabilized by an electron withdrawing ligand framework. This d(6) Pt( IV) complex exhibits reactivity as an inter- and intramolecular oxygen donor and as an electrophile. In addition, it undergoes a water activation process leading to a terminal dihydroxo complex, which may be relevant to the mechanism of catalytic reactions such as water oxidation.
C1 [Poverenov, Elena; Efremenko, Irena; Ben-David, Yehoshoa; Martin, Jan M. L.; Milstein, David] Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel.
   [Shimon, Linda J. W.; Leitus, Gregory; Konstantinovski, Leonid] Weizmann Inst Sci, Unit Chem Res Support, IL-76100 Rehovot, Israel.
   [Frenkel, Anatoly I.] Yeshiva Univ, Dept Phys, New York, NY 10016 USA.
C3 Weizmann Institute of Science; Weizmann Institute of Science; Yeshiva University
RP Milstein, D (corresponding author), Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel.
EM david.milstein@weizmann.ac.il
FU Israeli Science Foundation; US Department of Energy [DE-FG02-03ER15476]; NSLS; US DOE [DE-FG02-05ER15688]; U.S. Department of Energy (DOE) [DE-FG02-03ER15476] Funding Source: U.S. Department of Energy (DOE)
NR 30
TC 165
Z9 201
U1 1
U2 128
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1093
EP 1096
DI 10.1038/nature07356
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600041
DA 2026-03-09
ER

PT J
AU Courbet, S
   Gay, S
   Arnoult, N
   Wronka, G
   Anglana, M
   Brison, O
   Debatisse, M
AF Courbet, Sylvain
   Gay, Sophie
   Arnoult, Nausica
   Wronka, Gerd
   Anglana, Mauro
   Brison, Olivier
   Debatisse, Michelle
TI Replication fork movement sets chromatin loop size and origin choice in mammalian cells
SO NATURE
LA English
DT Article
ID site-specific initiation; common fragile sites; dna-replication; nuclear-matrix; chromosomal dna; replicon; transcription; orignai3; dynamics; domains
AB Genome stability requires one, and only one, DNA duplication at each S phase. The mechanisms preventing origin firing on newly replicated DNA are well documented(1), but much less is known about the mechanisms controlling the spacing of initiation events 2,3, namely the completion of DNA replication. Here we show that origin use in Chinese hamster cells depends on both the movement of the replication forks and the organization of chromatin loops. We found that slowing the replication speed triggers the recruitment of latent origins within minutes, allowing the completion of S phase in a timely fashion. When slowly replicating cells are shifted to conditions of fast fork progression, although the decrease in the overall number of active origins occurs within 2 h, the cells still have to go through a complete cell cycle before the efficiency specific to each origin is restored. We observed a strict correlation between replication speed during a given S phase and the size of chromatin loops in the next G1 phase. Furthermore, we found that origins located at or near sites of anchorage of chromatin loops in G1 are activated preferentially in the following S phase. These data suggest a mechanism of origin programming in which replication speed determines the spacing of anchorage regions of chromatin loops, that, in turn, controls the choice of initiation sites.
C1 [Courbet, Sylvain; Gay, Sophie; Arnoult, Nausica; Wronka, Gerd; Anglana, Mauro; Brison, Olivier; Debatisse, Michelle] Inst Curie, F-75248 Paris, France.
   [Courbet, Sylvain; Gay, Sophie; Arnoult, Nausica; Wronka, Gerd; Anglana, Mauro; Brison, Olivier; Debatisse, Michelle] Univ Paris 06, UPMC, F-75005 Paris, France.
   [Courbet, Sylvain; Gay, Sophie; Arnoult, Nausica; Wronka, Gerd; Anglana, Mauro; Brison, Olivier; Debatisse, Michelle] CNRS, UMR 7147, F-75700 Paris, France.
C3 UNICANCER; Universite PSL; Institut Curie; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS)
RP Debatisse, M (corresponding author), Inst Curie, 26 Rue Ulm, F-75248 Paris, France.
EM michelle.debatisse@curie.fr
FU ARC; Ministere de la Recherche; La Ligue Nationale contre le Cancer; Agence Nationale de la Recherche
NR 27
TC 182
Z9 203
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 557
EP 560
DI 10.1038/nature07233
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600051
PM 18716622
DA 2026-03-09
ER

PT J
AU Fehr, E
   Bernhard, H
   Rockenbach, B
AF Fehr, Ernst
   Bernhard, Helen
   Rockenbach, Bettina
TI Egalitarianism in young children
SO NATURE
LA English
DT Article
ID altruistic punishment; parochial altruism; chimpanzees; behavior; preferences; heritability; advantage; outcm; impact; trust
AB Human social interaction is strongly shaped by other- regarding preferences, that is, a concern for the welfare of others. These preferences are important for a unique aspect of human sociality - large scale cooperation with genetic strangers but little is known about their developmental roots. Here we show that young children's other- regarding preferences assume a particular form, inequality aversion that develops strongly between the ages of 3 and 8. At age 3 - 4, the overwhelming majority of children behave selfishly, whereas most children at age 7 - 8 prefer resource allocations that remove advantageous or disadvantageous inequality. Moreover, inequality aversion is strongly shaped by parochialism, a preference for favouring the members of one's own social group. These results indicate that human egalitarianism and parochialism have deep developmental roots, and the simultaneous emergence of altruistic sharing and parochialism during childhood is intriguing in view of recent evolutionary theories which predict that the same evolutionary process jointly drives both human altruism and parochialism.
C1 [Fehr, Ernst; Bernhard, Helen] Univ Zurich, Inst Empir Res Econ, CH-8006 Zurich, Switzerland.
   [Fehr, Ernst] Coll Helveticum, CH-8092 Zurich, Switzerland.
   [Rockenbach, Bettina] Univ Erfurt, D-99089 Erfurt, Germany.
C3 University of Zurich; University of Erfurt
RP Fehr, E (corresponding author), Univ Zurich, Inst Empir Res Econ, Blumlisalpstr 10, CH-8006 Zurich, Switzerland.
EM efehr@iew.uzh.ch; bettina.rockenbach@uni-erfurt.de
FU Foundations of Human Social Behaviour-Altruism versus Egoism' at the University of Zurich; Swiss National Science Foundation
NR 50
TC 1035
Z9 1233
U1 10
U2 352
PU NATURE PUBLISHING 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 28
PY 2008
VL 454
IS 7208
BP 1079
EP U22
DI 10.1038/nature07155
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600029
PM 18756249
DA 2026-03-09
ER

PT J
AU Brunetti, G
   Giacintucci, S
   Cassano, R
   Lane, W
   Dallacasa, D
   Venturi, T
   Kassim, NE
   Setti, G
   Cotton, WD
   Markevitch, M
AF Brunetti, G.
   Giacintucci, S.
   Cassano, R.
   Lane, W.
   Dallacasa, D.
   Venturi, T.
   Kassim, N. E.
   Setti, G.
   Cotton, W. D.
   Markevitch, M.
TI A low-frequency radio halo associated with a cluster of galaxies
SO NATURE
LA English
DT Article
ID x-ray-emission; coma cluster; alfvenic reacceleration; particle reacceleration; relativistic-particles; cosmic-rays; sky survey; gamma-ray; electrons; origin
AB Clusters of galaxies are the largest gravitationally bound objects in the Universe, containing about 10(15) solar masses of hot (10(8) K) gas, galaxies and dark matter in a typical volume of 10 Mpc(3). Magnetic fields and relativistic particles are mixed with the gas as revealed by giant 'radio haloes', which arise from diffuse, megaparsec- scale synchrotron radiation at cluster centre(1,2). Radio haloes require that the emitting electrons are accelerated in situ ( by turbulence)(3-6), or are injected ( as secondary particles) by proton collisions into the intergalactic medium(7-10). They are found only in a fraction of massive clusters that have complex dynamics(11-14), which suggests a connection between these mechanisms and cluster mergers. Here we report a radio halo at low frequencies associated with the merging cluster Abell 521. This halo has an extremely steep radio spectrum, which implies a high frequency cut- off; this makes the halo difficult to detect with observations at 1.4 GHz ( the frequency at which all other known radio haloes have been best studied). The spectrum of the halo is inconsistent with a secondary origin of the relativistic electrons, but instead supports turbulent acceleration, which suggests that many radio haloes in the Universe should emit mainly at low frequencies.
C1 [Brunetti, G.; Giacintucci, S.; Cassano, R.; Venturi, T.; Setti, G.] Ist Radioastron, INAF, I-40129 Bologna, Italy.
   [Giacintucci, S.; Markevitch, M.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Lane, W.; Kassim, N. E.] USN, Res Lab, Code 7213, Washington, DC 20375 USA.
   [Dallacasa, D.; Setti, G.] Univ Bologna, Dipartimento Astron, I-40127 Bologna, Italy.
   [Cotton, W. D.] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
C3 Istituto Nazionale Astrofisica (INAF); Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; United States Department of Defense; United States Navy; United States Naval Research Laboratory; NRL Chesapeake; University of Bologna; National Radio Astronomy Observatory (NRAO)
RP Brunetti, G (corresponding author), Ist Radioastron, INAF, Via P Gobetti 101, I-40129 Bologna, Italy.
EM brunetti@ira.inaf.it
FU PRIN-INAF; Harvard-Smithsonian Center for Astrophysics; US Naval Research Laboratory; National Radio Astronomy Observatory; 6.1 base funding;  [ASI-INAFI/088/06/0]
NR 30
TC 205
Z9 218
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 944
EP 947
DI 10.1038/nature07379
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300044
DA 2026-03-09
ER

PT J
AU Tang, C
   Louis, JM
   Aniana, A
   Suh, JY
   Clore, GM
AF Tang, Chun
   Louis, John M.
   Aniana, Annie
   Suh, Jeong-Yong
   Clore, G. Marius
TI Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease
SO NATURE
LA English
DT Article
ID encounter complexes; nmr; binding; kinetics; enhancement; precursor; dynamics; cleavage; association; inhibitors
AB HIV- 1 protease processes the Gag and Gag- Pol polyproteins into mature structural and functional proteins, including itself, and is therefore indispensable for viral maturation(1,2). The mature protease is active only as a dimer(3-5) with each subunit contributing catalytic residues(6). The full- length transframe region protease precursor appears to be monomeric yet undergoes maturation via intramolecular cleavage of a putative precursor dimer(5,7-11), concomitant with the appearance of mature- like catalytic activity(7,9). How such intramolecular cleavage can occur when the amino and carboxy termini of the mature protease are part of an intersubunit beta-sheet located distal from the active site is unclear. Here we visualize the early events in N- terminal autoprocessing using an inactive mini- precursor with a four- residue N- terminal extension that mimics the transframe region protease precursor(5,12). Using paramagnetic relaxation enhancement, a technique that is exquisitely sensitive to the presence of minor species(13-16), we show that the mini- precursor forms highly transient, lowly populated (3-5%) dimeric encounter complexes that involve the mature dimer interface but occupy a wide range of subunit orientations relative to the mature dimer. Furthermore, the occupancy of the mature dimer configuration constitutes a very small fraction of the self- associated species ( accounting for the very low enzymatic activity of the protease precursor), and the N- terminal extension makes transient intra- and intersubunit contacts with the substrate binding site and is therefore available for autocleavage when the correct dimer orientation is sampled within the encounter complex ensemble.
C1 [Tang, Chun; Louis, John M.; Aniana, Annie; Suh, Jeong-Yong; Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Clore, GM (corresponding author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
FU Intramural Program of the NIH; NIDDK; AIDS Targeted Antiviral program
NR 40
TC 106
Z9 138
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 OCT 2
PY 2008
VL 455
IS 7213
BP 693
EP U92
DI 10.1038/nature07342
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700053
PM 18833280
DA 2026-03-09
ER

PT J
AU Knabl, J
   Witschi, R
   Hösl, K
   Reinold, H
   Zeilhofer, UB
   Ahmadi, S
   Brockhaus, J
   Sergejeva, M
   Hess, A
   Brune, K
   Fritschy, JM
   Rudolph, U
   Möhler, H
   Zeilhofer, HU
AF Knabl, Julia
   Witschi, Robert
   Hoesl, Katharina
   Reinold, Heiko
   Zeilhofer, Ulrike B.
   Ahmadi, Seifollah
   Brockhaus, Johannes
   Sergejeva, Marina
   Hess, Andreas
   Brune, Kay
   Fritschy, Jean-Marc
   Rudolph, Uwe
   Moehler, Hanns
   Zeilhofer, Hanns Ulrich
TI Reversal of pathological pain through specific spinal GABAA receptor subtypes
SO NATURE
LA English
DT Article
ID superficial dorsal horn; peripheral-nerve injury; neuropathic pain; anion gradient; rat; hyperalgesia; cord; inhibition; neurons; benzodiazepines
AB Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment(1,2). A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology(3-7). Facilitation of spinal gamma-aminobutyric acid ( GABA) ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss(8,9). With the use of GABA(A)-receptor point- mutated knock- in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine- site ligands(10-12), we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha 2 and/ or alpha 3 subunits. We show that their selective activation by the non- sedative ('alpha 1- sparing') benzodiazepine- site ligand L- 838,417 ( ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L- 838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative- emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype- selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.
C1 [Knabl, Julia; Hoesl, Katharina; Reinold, Heiko; Zeilhofer, Ulrike B.; Ahmadi, Seifollah; Sergejeva, Marina; Hess, Andreas; Brune, Kay; Zeilhofer, Hanns Ulrich] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, D-91054 Erlangen, Germany.
   [Witschi, Robert; Brockhaus, Johannes; Fritschy, Jean-Marc; Rudolph, Uwe; Moehler, Hanns; Zeilhofer, Hanns Ulrich] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland.
   [Moehler, Hanns; Zeilhofer, Hanns Ulrich] ETH, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland.
   [Rudolph, Uwe] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat,Lab Genet Neuropharmacol, Belmont, MA 02478 USA.
   [Moehler, Hanns] Collegium Helveticum, CH-8092 Zurich, Switzerland.
C3 University of Erlangen Nuremberg; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Harvard University; Harvard University Medical Affiliates; McLean Hospital
RP Zeilhofer, HU (corresponding author), Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, D-91054 Erlangen, Germany.
EM zeilhofer@pharma.uzh.ch
NR 38
TC 375
Z9 428
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 330
EP U6
DI 10.1038/nature06493
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100049
PM 18202657
DA 2026-03-09
ER

PT J
AU Vannucchi, P
   Remitti, F
   Bettelli, G
AF Vannucchi, Paola
   Remitti, Francesca
   Bettelli, Giuseppe
TI Geological record of fluid flow and seismogenesis along an erosive subducting plate boundary
SO NATURE
LA English
DT Article
ID northern apennines; sediment subduction; seamount subduction; melange formation; accretion; zones; fault; succession; dilatancy; margins
AB Tectonic erosion of the overriding plate by the downgoing slab is believed to occur at half the Earth's subduction zones(1,2). In situ investigation of the geological processes at active erosive margins is extremely difficult owing to the deep marine environment and the net loss of forearc crust to deeper levels in the subduction zone. Until now, a fossil erosive subduction channel - the shear zone marking the plate boundary(3) - has not been recognized in the field, so that seismic observations have provided the only information on plate boundary processes at erosive margins. Here we show that a fossil erosive margin is preserved in the Northern Apennines of Italy. It formed during the Tertiary transition from oceanic subduction to continental collision, and was preserved by the late deactivation and fossilization of the plate boundary. The outcropping erosive subduction channel is similar to 500 m thick. It is representative of the first 5 km of depth, with its deeper portions reaching similar to 150 degrees C. The fossil zone records several surprises. Two decollements were simultaneously active at the top and base of the subduction channel. Both deeper basal erosion and near- surface frontal erosion occurred. At shallow depths extension was a key deformation component within this erosive convergent plate boundary, and slip occurred without an observable fluid pressure cycle. At depths greater than about 3 km a fluid cycle is clearly shown by the development of veins and the alternation of fast ( co- seismic) and slow ( inter- seismic) slip. In the deepest portions of the outcropping subduction channel, extension is finally overprinted by compressional structures. In modern subduction zones the onset of seismic activity is believed to occur at similar to 150 degrees C, but in the fossil channel the onset occurred at cooler palaeo- temperatures.
C1 [Vannucchi, Paola] Univ Florence, Dipartimento Sci Terra, I-50121 Florence, Italy.
   [Remitti, Francesca; Bettelli, Giuseppe] Univ Modena, Dipartimento Sci Terra, I-41100 Modena, Italy.
C3 University of Florence; Universita di Modena e Reggio Emilia
RP Vannucchi, P (corresponding author), Univ Florence, Dipartimento Sci Terra, Via Pira 4, I-50121 Florence, Italy.
EM paola.vannucchi@unifi.it
NR 28
TC 136
Z9 148
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 7
PY 2008
VL 451
IS 7179
BP 699
EP 703
DI 10.1038/nature06486
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500037
PM 18256668
DA 2026-03-09
ER

PT J
AU Watanabe, T
   Totoki, Y
   Toyoda, A
   Kaneda, M
   Kuramochi-Miyagawa, S
   Obata, Y
   Chiba, H
   Kohara, Y
   Kono, T
   Nakano, T
   Surani, MA
   Sakaki, Y
   Sasaki, H
AF Watanabe, Toshiaki
   Totoki, Yasushi
   Toyoda, Atsushi
   Kaneda, Masahiro
   Kuramochi-Miyagawa, Satomi
   Obata, Yayoi
   Chiba, Hatsune
   Kohara, Yuji
   Kono, Tomohiro
   Nakano, Toru
   Surani, M. Azim
   Sakaki, Yoshiyuki
   Sasaki, Hiroyuki
TI Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes
SO NATURE
LA English
DT Article
ID small rnas; c-elegans; micrornas; gene; antisense; germline; genome; testes; piwi; retrotransposon
AB RNA interference (RNAi) is a mechanism by which doublestranded RNAs (dsRNAs) suppress specific transcripts in a sequence-dependent manner. dsRNAs are processed by Dicer to 21-24-nucleotide small interfering RNAs (siRNAs) and then incorporated into the argonaute (Ago) proteins(1-4). Gene regulation by endogenous siRNAs has been observed only in organisms possessing RNA- dependent RNA polymerase (RdRP)(5-10). In mammals, where no RdRP activity has been found, biogenesis and function of endogenous siRNAs remain largely unknown. Here we show, using mouse oocytes, that endogenous siRNAs are derived from naturally occurring dsRNAs and have roles in the regulation of gene expression. By means of deep sequencing, we identify a large number of both similar to 25-27-nucleotide Piwi-interacting RNAs (piRNAs) and similar to 21-nucleotide siRNAs corresponding to messenger RNAs or retrotransposons in growing oocytes. piRNAs are bound to Mili and have a role in the regulation of retrotransposons. siRNAs are exclusively mapped to retrotransposons or other genomic regions that produce transcripts capable of forming dsRNA structures. Inverted repeat structures, bidirectional transcription and antisense transcripts from various loci are sources of the dsRNAs. Some precursor transcripts of siRNAs are derived from expressed pseudogenes, indicating that one role of pseudogenes is to adjust the level of the founding source mRNA through RNAi. Loss of Dicer or Ago2 results in decreased levels of siRNAs and increased levels of retrotransposon and protein-coding transcripts complementary to the siRNAs. Thus, the RNAi pathway regulates both protein-coding transcripts and retrotransposons in mouse oocytes. Our results reveal a role for endogenous siRNAs in mammalian oocytes and show that organisms lacking RdRP activity can produce functional endogenous siRNAs from naturally occurring dsRNAs.
C1 [Watanabe, Toshiaki; Chiba, Hatsune; Sasaki, Hiroyuki] Res Org Informat & Syst, Div Human Genet, Dept Integrated Genet, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
   [Watanabe, Toshiaki; Chiba, Hatsune; Kohara, Yuji; Sasaki, Hiroyuki] Grad Univ Adv Studies, SOKENDAI, Dept Genet, Sch Life Sci, Mishima, Shizuoka 4118540, Japan.
   [Totoki, Yasushi; Sakaki, Yoshiyuki] RIKEN, Genome Sci Ctr, Genome Annotat & Comparat Anal Team, Computat & Expt Syst Biol Grp, Yokohama, Kanagawa 2300045, Japan.
   [Toyoda, Atsushi; Sakaki, Yoshiyuki] RIKEN, Genome Sci Ctr, Sequence Technol Team, Yokohama, Kanagawa 2300045, Japan.
   [Kaneda, Masahiro] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst Canc Dev B, Cambridge CB2 1QN, England.
   [Kaneda, Masahiro] Natl Agr & Food Res Org, Reprod Biol & Technol Res Team, Natl Inst Livestock & Grassland Sci, Tsukuba, Ibaraki 3050901, Japan.
   [Kuramochi-Miyagawa, Satomi; Nakano, Toru] Osaka Univ, Dept Pathol, Grad Sch Med & Frontier Biosci, Suita, Osaka 5650871, Japan.
   [Obata, Yayoi; Kono, Tomohiro; Surani, M. Azim] Tokyo Univ Agr, Dept Biosci, Tokyo 1568502, Japan.
   [Kohara, Yuji] Res Org Informat & Syst, Genome Biol Lab, Ctr Genet Resources Informat, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
C3 Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Graduate University for Advanced Studies - Japan; RIKEN; RIKEN; University of Cambridge; National Agriculture & Food Research Organization - Japan; University of Osaka; Tokyo University of Agriculture; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan
RP Watanabe, T (corresponding author), Res Org Informat & Syst, Div Human Genet, Dept Integrated Genet, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
EM toshwata@lab.nig.ac.jp; hisasaki@lab.nig.ac.jp
FU Grants-in-Aid for Scientific Research [19061001] Funding Source: KAKEN
NR 29
TC 876
Z9 1102
U1 0
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 539
EP U9
DI 10.1038/nature06908
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700046
PM 18404146
DA 2026-03-09
ER

PT J
AU Minamino, T
   Namba, K
AF Minamino, Tohru
   Namba, Keiichi
TI Distinct roles of the FliI ATPase and proton motive force in bacterial flagellar protein export
SO NATURE
LA English
DT Article
ID iii secretion; salmonella-typhimurium; escherichia-coli; catalytic cycle; components; apparatus; oligomerization; specificity; similarity; regulator
AB Translocation of many soluble proteins across cell membranes occurs in an ATPase- driven manner. For construction of the bacterial flagellum responsible for motility, most of the components are exported by the flagellar protein export apparatus(1,2). The FliI ATPase is required for this export(3), and its ATPase activity is regulated by FliH(4); however, it is unclear how the chemical energy derived from ATP hydrolysis is used for the export process. Here we report that flagellar proteins of Salmonella enterica serovar Typhimurium are exported even in the absence of FliI. A fliH fliI double null mutant was weakly motile. Certain mutations in FlhA or FlhB, which form the core of the export gate, substantially improved protein export and motility of the double null mutant. Furthermore, proton motive force was essential for the export process. These results suggest that the FliH - FliI complex facilitates only the initial entry of export substrates into the gate, with the energy of ATP hydrolysis being used to disassemble and release the FliH - FliI complex from the protein about to be exported. The rest of the successive unfolding/ translocation process of the substrates is driven by proton motive force.
C1 [Minamino, Tohru; Namba, Keiichi] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
   [Minamino, Tohru; Namba, Keiichi] JST, ICORP, Dynam NanoMachine Project, Suita, Osaka 5650871, Japan.
C3 University of Osaka; Japan Science & Technology Agency (JST)
RP Namba, K (corresponding author), Osaka Univ, Grad Sch Frontier Biosci, 1-3 Yamadaoka, Suita, Osaka 5650871, Japan.
EM keiichi@fbs.osaka-u.ac.jp
NR 34
TC 249
Z9 286
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 24
PY 2008
VL 451
IS 7177
BP 485
EP U12
DI 10.1038/nature06449
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100049
PM 18216858
DA 2026-03-09
ER

PT J
AU Parsons, T
   Ji, C
   Kirby, E
AF Parsons, Tom
   Ji, Chen
   Kirby, Eric
TI Stress changes from the 2008 Wenchuan earthquake and increased hazard in the Sichuan basin
SO NATURE
LA English
DT Article
ID seismic hazard
AB On 12 May 2008, the devastating magnitude 7.9 (Wenchuan) earthquake struck the eastern edge of the Tibetan plateau, collapsing buildings and killing thousands in major cities aligned along the western Sichuan basin in China. After such a large-magnitude earthquake, rearrangement of stresses in the crust commonly leads to subsequent damaging earthquakes(1-5). The mainshock of the 12 May earthquake ruptured with as much as 9m of slip along the boundary between the Longmen Shan and Sichuan basin, and demonstrated the complex strike-slip and thrust motion(6) that characterizes the region(7,8). The Sichuan basin and surroundings are also crossed by other active strike-slip and thrust faults. Here we present calculations of the coseismic stress changes that resulted from the 12 May event using models of those faults, and show that many indicate significant stress increases. Rapid mapping of such stress changes can help to locate fault sections with relatively higher odds of producing large aftershocks.
C1 [Parsons, Tom] US Geol Survey, Menlo Pk, CA 94025 USA.
   [Ji, Chen] Univ Calif Santa Barbara, Dept Geol Sci, Santa Barbara, CA 93106 USA.
   [Kirby, Eric] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
C3 United States Department of the Interior; United States Geological Survey; University of California System; University of California Santa Barbara; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Parsons, T (corresponding author), US Geol Survey, MS-999,345 Middlefield Rd, Menlo Pk, CA 94025 USA.
EM tparsons@usgs.gov
NR 13
TC 451
Z9 560
U1 3
U2 283
PU 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 24
PY 2008
VL 454
IS 7203
BP 509
EP 510
DI 10.1038/nature07177
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300049
PM 18600260
DA 2026-03-09
ER

PT J
AU Bintanja, R
   van de Wal, RSW
AF Bintanja, R.
   van de Wal, R. S. W.
TI North American ice-sheet dynamics and the onset of 100,000-year glacial cycles
SO NATURE
LA English
DT Article
ID middle pleistocene transition; hemisphere glaciation; climate; volume; temperatures; deglaciation; evolution
AB The onset of major glaciations in the Northern Hemisphere about 2.7 million years ago(1) was most probably induced by climate cooling during the late Pliocene epoch(2,3). These glaciations, during which the Northern Hemisphere ice sheets successively expanded and retreated, are superimposed on this long-term climate trend, and have been linked to variations in the Earth's orbital parameters(4). One intriguing problem associated with orbitally driven glacial cycles is the transition from 41,000-year to 100,000-year climatic cycles that occurred without an apparent change in insolation forcing(5). Several hypotheses have been proposed to explain the transition, both including and excluding ice-sheet dynamics(6-10). Difficulties in finding a conclusive answer to this palaeoclimatic problem are related to the lack of sufficiently long records of ice-sheet volume or sea level. Here we use a comprehensive ice-sheet model and a simple ocean-temperature model(11) to extract three-million-year mutually consistent records of surface air temperature, ice volume and sea level from marine benthic oxygen isotopes(12). Although these records and their relative phasings are subject to considerable uncertainty owing to limited availability of palaeoclimate constraints, the results suggest that the gradual emergence of the 100,000-year cycles can be attributed to the increased ability of the merged North American ice sheets to survive insolation maxima and reach continental-scale size. The oversized, wet-based ice sheet probably responded to the subsequent insolation maximum by rapid thinning through increased basal-sliding(13,14), thereby initiating a glacial termination. Based on our assessment of the temporal changes in air temperature and ice volume during individual glacials, we demonstrate the importance of ice dynamics and ice-climate interactions in establishing the 100,000-year glacial cycles, with enhanced North American ice-sheet growth and the subsequent merging of the ice sheets being key elements.
C1 [Bintanja, R.] Royal Netherlands Meteorol Inst, KNMI, NL-3732 GK De Bilt, Netherlands.
   [van de Wal, R. S. W.] Univ Utrecht, Inst Marine & Atmospher Res Utrecht IMAU, NL-3584 CC Utrecht, Netherlands.
C3 Royal Netherlands Meteorological Institute; Utrecht University
RP Bintanja, R (corresponding author), Royal Netherlands Meteorol Inst, KNMI, Wilhelminalaan 10, NL-3732 GK De Bilt, Netherlands.
EM bintanja@knmi.nl
NR 29
TC 375
Z9 424
U1 1
U2 115
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 14
PY 2008
VL 454
IS 7206
BP 869
EP 872
DI 10.1038/nature07158
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600032
PM 18704083
DA 2026-03-09
ER

PT J
AU Berry, AJ
   Danyushevsky, LV
   O'Neill, HSC
   Newville, M
   Sutton, SR
AF Berry, Andrew J.
   Danyushevsky, Leonid V.
   O'Neill, Hugh St C.
   Newville, Matt
   Sutton, Stephen R.
TI Oxidation state of iron in komatiitic melt inclusions indicates hot Archaean mantle
SO NATURE
LA English
DT Article
ID ferric iron; glass inclusions; cooling history; silicate glass; redox states; k-edge; xanes; magmas; fe; ratios
AB Komatiites are volcanic rocks mainly of Archaean age that formed by unusually high degrees of melting of mantle peridotite. Their origin is controversial and has been attributed to either anhydrous melting of anomalously hot mantle(1-3) or hydrous melting at temperatures only modestly greater than those found today(4,5). Here we determine the original Fe(3+)/Sigma Fe ratio of 2.7- Gyr- old komatiitic magma from Belingwe, Zimbabwe(6), preserved as melt inclusions in olivine, to be 0.10+/-0.02, using iron K- edge X- ray absorption near- edge structure spectroscopy. This value is consistent with near- anhydrous melting of a source with a similar oxidation state to the source of present- day mid- ocean- ridge basalt. Furthermore, this low Fe(3+)/Sigma Fe value, together with a water content of only 0.2-0.3 wt% ( ref. 7), excludes the possibility that the trapped melt contained significantly more water that was subsequently lost from the inclusions by reduction to H(2) and diffusion. Loss of only 1.5 wt% water by this mechanism would have resulted in complete oxidation of iron ( that is, the Fe(3+)/Sigma Fe ratio would be similar to 1). There is also no petrographic evidence for the loss of molecular water. Our results support the identification of the Belingwe komatiite as a product of high mantle temperatures (similar to 1,700 degrees C), rather than melting under hydrous conditions ( 3-5-wt% water), confirming the existence of anomalously hot mantle in the Archaean era.
C1 [Berry, Andrew J.] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
   [Danyushevsky, Leonid V.] Univ Tasmania, CODES, Hobart, Tas 7001, Australia.
   [O'Neill, Hugh St C.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
   [Newville, Matt; Sutton, Stephen R.] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA.
   [Sutton, Stephen R.] Univ Chicago, Dept Geophys Sci, Chicago, IL 60637 USA.
C3 Imperial College London; University of Tasmania; Australian National University; University of Chicago; University of Chicago
RP Berry, AJ (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
EM a.berry@imperial.ac.uk
FU Commonwealth of Australia; Natural Environment Research Council; US National Science Foundation [EAR-0622171]; US Department of Energy [DE-FG02-94ER14466]; Office of Science; Office of Basic Energy Sciences [W-31-109-Eng-38]; Natural Environment Research Council [NE/E001106/1] Funding Source: researchfish; NERC [NE/E001106/1] Funding Source: UKRI
NR 33
TC 172
Z9 186
U1 1
U2 101
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 960
EP U42
DI 10.1038/nature07377
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300048
DA 2026-03-09
ER

PT J
AU Murayama, Y
   Kurokawa, Y
   Mayanagi, K
   Iwasaki, H
AF Murayama, Yasuto
   Kurokawa, Yumiko
   Mayanagi, Kouta
   Iwasaki, Hiroshi
TI Formation and branch migration of Holliday junctions mediated by eukaryotic recombinases
SO NATURE
LA English
DT Article
ID dna strand exchange; escherichia-coli reca; human rad51 protein; homologous recombination; meiotic recombination; heteroduplex formation; atp hydrolysis; break repair; duplex dna; in-vitro
AB Holliday junctions ( HJs) are key intermediates in homologous recombination and are especially important for the production of crossover recombinants(1-4). Bacterial RecA family proteins promote the formation and branch migration of HJs in vitro by catalysing a reciprocal DNA- strand exchange reaction between two duplex DNA molecules, one of which contains a single- stranded DNA region that is essential for initial nucleoprotein filament formation(5). This activity has been reported only for prokaryotic RecA family recombinases(5), although eukaryotic homologues are also essential for HJ production in vivo(6,7). Here we show that fission yeast ( Rhp51) and human ( hRad51) RecA homologues promote duplex - duplex DNA- strand exchange in vitro. As with RecA, a HJ is formed between the two duplex DNA molecules, and reciprocal strand exchange proceeds through branch migration of the HJ. In contrast to RecA, however, strand exchange mediated by eukaryotic recombinases proceeds in the 3 '-->5 ' direction relative to the single- stranded DNA region of the substrate DNA. The opposite polarity of Rhp51 makes it especially suitable for the repair of DNA double- strand breaks, whose repair is initiated at the processed ends of breaks that have protruding 3 ' termini(1,2).
C1 [Murayama, Yasuto; Kurokawa, Yumiko; Iwasaki, Hiroshi] Yokohama City Univ, Div Mol & Cellular Biol, Int Grad Sch Arts & Sci, Kanagawa 2300045, Japan.
   [Mayanagi, Kouta] Nagahama Inst Biosci & Technol, Dept Biosci, Shiga 5260829, Japan.
   [Mayanagi, Kouta] JST, BIRD, Shiga 5260829, Japan.
C3 Yokohama City University; Nagahama Institute of Bio-Science & Technology; Japan Science & Technology Agency (JST)
RP Iwasaki, H (corresponding author), Yokohama City Univ, Div Mol & Cellular Biol, Int Grad Sch Arts & Sci, 1-7-29 Suehirocho, Kanagawa 2300045, Japan.
EM iwasaki@tsurumi.yokohama-cu.ac.jp
NR 33
TC 44
Z9 55
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 1018
EP U10
DI 10.1038/nature06609
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100054
PM 18256600
DA 2026-03-09
ER

PT J
AU Kuemmeth, F
   Ilani, S
   Ralph, DC
   McEuen, PL
AF Kuemmeth, F.
   Ilani, S.
   Ralph, D. C.
   McEuen, P. L.
TI Coupling of spin and orbital motion of electrons in carbon nanotubes
SO NATURE
LA English
DT Article
ID quantum dots; transport
AB Electrons in atoms possess both spin and orbital degrees of freedom. In non- relativistic quantum mechanics, these are independent, resulting in large degeneracies in atomic spectra. However, relativistic effects couple the spin and orbital motion, leading to the well- known fine structure in their spectra. The electronic states in defect- free carbon nanotubes are widely believed to be four- fold degenerate(1-10), owing to independent spin and orbital symmetries, and also to possess electron - hole symmetry(11). Here we report measurements demonstrating that in clean nanotubes the spin and orbital motion of electrons are coupled, thereby breaking all of these symmetries. This spin - orbit coupling is directly observed as a splitting of the four- fold degeneracy of a single electron in ultra- clean quantum dots. The coupling favours parallel alignment of the orbital and spin magnetic moments for electrons and antiparallel alignment for holes. Our measurements are consistent with recent theories(12,13) that predict the existence of spin - orbit coupling in curved graphene and describe it as a spin-dependent topological phase in nanotubes. Our findings have important implications for spin- based applications in carbon-based systems, entailing new design principles for the realization of quantum bits ( qubits) in nanotubes and providing a mechanism for all- electrical control of spins(14) in nanotubes.
C1 [Kuemmeth, F.; Ilani, S.; Ralph, D. C.; McEuen, P. L.] Cornell Univ, Atom & Solid State Phys Lab, Dept Phys, Ithaca, NY 14853 USA.
C3 Cornell University
RP McEuen, PL (corresponding author), Cornell Univ, Atom & Solid State Phys Lab, Dept Phys, Ithaca, NY 14853 USA.
EM mceuen@ccmr.cornell.edu
NR 27
TC 513
Z9 546
U1 1
U2 178
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 448
EP 452
DI 10.1038/nature06822
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300026
PM 18368113
DA 2026-03-09
ER

PT J
AU Tye, KM
   Stuber, GD
   de Ridder, B
   Bonci, A
   Janak, PH
AF Tye, Kay M.
   Stuber, Garret D.
   de Ridder, Bram
   Bonci, Antonello
   Janak, Patricia H.
TI Rapid strengthening of thalamo-amygdala synapses mediates cue-reward learning
SO NATURE
LA English
DT Article
ID long-term potentiation; lateral amygdala; prefrontal cortex; ventral striatum; fear; plasticity; neurons; stimuli; rat; projections
AB What neural changes underlie individual differences in goal-directed learning? The lateral amygdala ( LA) is important for assigning emotional and motivational significance to discrete environmental cues(1-4), including those that signal rewarding events(5-8). Recognizing that a cue predicts a reward enhances an animal's ability to acquire that reward; however, the cellular and synaptic mechanisms that underlie cue - reward learning are unclear. Here we show that marked changes in both cue- induced neuronal firing and input- specific synaptic strength occur with the successful acquisition of a cue - reward association within a single training session. We performed both in vivo and ex vivo electrophysiological recordings in the LA of rats trained to self- administer sucrose. We observed that reward- learning success increased in proportion to the number of amygdala neurons that responded phasically to a reward- predictive cue. Furthermore, cue - reward learning induced an AMPA (alpha-amino- 3- hydroxy- 5- methyl-isoxazole propionic acid)- receptor- mediated increase in the strength of thalamic, but not cortical, synapses in the LA that was apparent immediately after the first training session. The level of learning attained by individual subjects was highly correlated with the degree of synaptic strength enhancement. Importantly, intra-LA NMDA ( N- methyl- D- aspartate)- receptor blockade impaired reward- learning performance and attenuated the associated increase in synaptic strength. These findings provide evidence of a connection between LA synaptic plasticity and cue - reward learning, potentially representing a key mechanism underlying goal-directed behaviour.
C1 [Tye, Kay M.; Stuber, Garret D.; de Ridder, Bram; Bonci, Antonello; Janak, Patricia H.] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA.
   [Stuber, Garret D.; Bonci, Antonello; Janak, Patricia H.] Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94143 USA.
   [Bonci, Antonello; Janak, Patricia H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Bonci, Antonello; Janak, Patricia H.] Univ Calif San Francisco, Wheeler Ctr Neurobiol Addict, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; Ernest Gallo Clinic & Research Center; 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 Janak, PH (corresponding author), Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA.
EM pjanak@gallo.ucsf.edu
FU NIDA NIH HHS [R01DA115096, R01 DA015096] Funding Source: Medline; NIDDK NIH HHS [DP2 DK102256] Funding Source: Medline
NR 30
TC 169
Z9 213
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1253
EP U56
DI 10.1038/nature06963
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800046
PM 18469802
DA 2026-03-09
ER

PT J
AU Jones, KE
   Patel, NG
   Levy, MA
   Storeygard, A
   Balk, D
   Gittleman, JL
   Daszak, P
AF Jones, Kate E.
   Patel, Nikkita G.
   Levy, Marc A.
   Storeygard, Adam
   Balk, Deborah
   Gittleman, John L.
   Daszak, Peter
TI Global trends in emerging infectious diseases
SO NATURE
LA English
DT Article
ID public-health; risk-factors; host-range; emergence; ecology
AB Emerging infectious diseases (EIDs) are a significant burden on global economies and public health(1-3). Their emergence is thought to be driven largely by socio- economic, environmental and ecological factors(1-9), but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID 'events' (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large number of drug- resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio- economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease 'hotspots'). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries from where the next important EID is least likely to originate.
C1 [Patel, Nikkita G.; Daszak, Peter] Wildlife Trust, Consortium Conservat Med, Beijing 100011, Peoples R China.
   [Jones, Kate E.] Zool Soc London, Inst Zool, London NW1 4RY, England.
   [Levy, Marc A.; Storeygard, Adam; Balk, Deborah] Columbia Univ, Ctr Int Earth Sci Informat Network, Palisades, NY 10964 USA.
   [Gittleman, John L.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
C3 Zoological Society of London; Columbia University; University System of Georgia; University of Georgia
RP Daszak, P (corresponding author), Wildlife Trust, Consortium Conservat Med, 460 W 34th St,17th Floor, Beijing 100011, Peoples R China.
EM daszak@conservationmedicine.org
FU FIC NIH HHS [R01 TW005869] Funding Source: Medline; NIAID NIH HHS [R01 AI079231] Funding Source: Medline; NICHD NIH HHS [T32 HD007338] Funding Source: Medline; Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32HD007338] Funding Source: NIH RePORTER; Direct For Biological Sciences [0914866] Funding Source: National Science Foundation; Division Of Environmental Biology [0914866] Funding Source: National Science Foundation
NR 29
TC 5597
Z9 6799
U1 23
U2 2848
PU 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 21
PY 2008
VL 451
IS 7181
BP 990
EP U4
DI 10.1038/nature06536
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100048
PM 18288193
DA 2026-03-09
ER

PT J
AU Forde, SE
   Beardmore, RE
   Gudelj, I
   Arkin, SS
   Thompson, JN
   Hurst, LD
AF Forde, Samantha E.
   Beardmore, Robert E.
   Gudelj, Ivana
   Arkin, Sinan S.
   Thompson, John N.
   Hurst, Laurence D.
TI Understanding the limits to generalizability of experimental evolutionary models
SO NATURE
LA English
DT Article
ID host-parasitoid interaction; escherichia-coli; bacteria; coevolution; phage; community; adaptation; resistance; genetics; virus
AB Given the difficulty of testing evolutionary and ecological theory in situ, in vitro model systems are attractive alternatives(1); however, can we appraise whether an experimental result is particular to the in vitro model, and, if so, characterize the systems likely to behave differently and understand why? Here we examine these issues using the relationship between phenotypic diversity and resource input in the T7 - Escherichia coli co- evolving system as a case history. We establish a mathematical model of this interaction, framed as one instance of a super- class of host - parasite co- evolutionary models, and show that it captures experimental results. By tuning this model, we then ask how diversity as a function of resource input could behave for alternative co- evolving partners ( for example, E. coli with lambda bacteriophages). In contrast to populations lacking bacteriophages, variation in diversity with differences in resources is always found for co- evolving populations, supporting the geographic mosaic theory of co- evolution(2). The form of this variation is not, however, universal. Details of infectivity are pivotal: in T7 - E. coli with a modified gene- for- gene interaction, diversity is low at high resource input, whereas, for matching- allele interactions, maximal diversity is found at high resource input. A combination of in vitro systems and appropriately configured mathematical models is an effective means to isolate results particular to the in vitro system, to characterize systems likely to behave differently and to understand the biology underpinning those alternatives.
C1 [Hurst, Laurence D.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England.
   [Forde, Samantha E.; Thompson, John N.] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
   [Beardmore, Robert E.; Gudelj, Ivana; Arkin, Sinan S.] Univ London Imperial Coll Sci Technol & Med, Dept Math, London SW7 2AZ, England.
   [Gudelj, Ivana] Univ Bath, Dept Math Sci, Bath BA2 7AY, Avon, England.
C3 University of Bath; University of California System; University of California Santa Cruz; Imperial College London; University of Bath
RP Hurst, LD (corresponding author), Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England.
EM l.d.hurst@bath.ac.uk
FU NERC Advanced Fellowship; ORS award; Department of Mathematics at Imperial College London; National Science Foundation [DEB 0515598]; EPSRC [EP/F037856/1] Funding Source: UKRI; NERC [NE/B501998/2, NE/E013007/2] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/F037856/1] Funding Source: researchfish; Natural Environment Research Council [NE/B501998/2, NE/E013007/2, NE/B501998/1] Funding Source: researchfish
NR 21
TC 36
Z9 44
U1 1
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 11
PY 2008
VL 455
IS 7210
BP 220
EP U44
DI 10.1038/nature07152
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800046
PM 18784724
DA 2026-03-09
ER

PT J
AU Diemand, J
   Kuhlen, M
   Madau, P
   Zemp, M
   Moore, B
   Potter, D
   Stadel, J
AF Diemand, J.
   Kuhlen, M.
   Madau, P.
   Zemp, M.
   Moore, B.
   Potter, D.
   Stadel, J.
TI Clumps and streams in the local dark matter distribution
SO NATURE
LA English
DT Article
ID density profiles; substructure; haloes; satellites; galaxy; simulations; evolution; scatter; cluster; probe
AB In cold dark matter cosmological models(1,2), structures form and grow through the merging of smaller units(3). Numerical simulations have shown that such merging is incomplete; the inner cores of haloes survive and orbit as 'subhaloes' within their hosts(4,5). Here we report a simulation that resolves such substructure even in the very inner regions of the Galactic halo. We find hundreds of very concentrated dark matter clumps surviving near the solar circle, as well as numerous cold streams. The simulation also reveals the fractal nature of dark matter clustering: isolated haloes and subhaloes contain the same relative amount of substructure and both have cusped inner density profiles. The inner mass and phase-space densities of subhaloes match those of recently discovered faint, dark-matter-dominated dwarf satellite galaxies(6-8), and the overall amount of substructure can explain the anomalous flux ratios seen in strong gravitational lenses(9,10). Subhaloes boost gamma-ray production from dark matter annihilation by factors of 4 to 15 relative to smooth galactic models. Local cosmic ray production is also enhanced, typically by a factor of 1.4 but by a factor of more than 10 in one per cent of locations lying sufficiently close to a large subhalo. (These estimates assume that the gravitational effects of baryons on dark matter substructure are small.).
C1 [Diemand, J.; Madau, P.; Zemp, M.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Kuhlen, M.] Inst Adv Study, Princeton, NJ 08540 USA.
   [Moore, B.; Potter, D.; Stadel, J.] Univ Zurich, Inst Theoret Phys, CH-8057 Zurich, Switzerland.
C3 University of California System; University of California Santa Cruz; Institute for Advanced Study - USA; University of Zurich
RP Diemand, J (corresponding author), Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
EM diemand@ucolick.org
NR 30
TC 734
Z9 820
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 735
EP 738
DI 10.1038/nature07153
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000038
PM 18685701
DA 2026-03-09
ER

PT J
AU Krojer, T
   Sawa, J
   Schäfer, E
   Saibil, HR
   Ehrmann, M
   Clausen, T
AF Krojer, Tobias
   Sawa, Justyna
   Schaefer, Eva
   Saibil, Helen R.
   Ehrmann, Michael
   Clausen, Tim
TI Structural basis for the regulated protease and chaperone function of DegP
SO NATURE
LA English
DT Article
ID escherichia-coli; outer-membrane; crystal-structure; stress-response; pdz domains; periplasmic protein; electron-microscopy; ompf; skp; visualization
AB All organisms have to monitor the folding state of cellular proteins precisely. The heat- shock protein DegP is a protein quality control factor in the bacterial envelope that is involved in eliminating misfolded proteins and in the biogenesis of outer- membrane proteins. Here we describe the molecular mechanisms underlying the regulated protease and chaperone function of DegP from Escherichia coli. We show that binding of misfolded proteins transforms hexameric DegP into large, catalytically active 12- meric and 24- meric multimers. A structural analysis of these particles revealed that DegP represents a protein packaging device whose central compartment is adaptable to the size and concentration of substrate. Moreover, the inner cavity serves antagonistic functions. Whereas the encapsulation of folded protomers of outer- membrane proteins is protective and might allow safe transit through the periplasm, misfolded proteins are eliminated in the molecular reaction chamber. Oligomer reassembly and concomitant activation on substrate binding may also be critical in regulating other HtrA proteases implicated in protein- folding diseases.
C1 [Krojer, Tobias; Sawa, Justyna; Clausen, Tim] Inst Mol Pathol, Res Inst Mol Pathol, A-1030 Vienna, Austria.
   [Schaefer, Eva; Saibil, Helen R.] Univ London Birkbeck Coll, Dept Crystallog, London WC1E 7HX, England.
   [Schaefer, Eva; Saibil, Helen R.] Univ London Birkbeck Coll, Inst Struct Mol Biol, London WC1E 7HX, England.
   [Ehrmann, Michael] Univ Duisburg Essen, Ctr Med Biotechnol, FB Biol & Geog, D-45117 Essen, Germany.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); University of London; Birkbeck University London; University of London; Birkbeck University London; University of Duisburg Essen
RP Clausen, T (corresponding author), Inst Mol Pathol, Res Inst Mol Pathol, Dr Bohrgasse 7, A-1030 Vienna, Austria.
EM clausen@imp.univie.ac.at
FU Biotechnology and Biological Sciences Research Council [BB/C516179/1, BBS/B/03955, BB/C516144/1, BB/F010281/1] Funding Source: researchfish; BBSRC [BB/C516144/1, BB/F010281/1, BB/C516179/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/C516179/1, BB/C516144/1, BB/F010281/1, BBS/B/03955] Funding Source: Medline; Wellcome Trust [079605, 070776] Funding Source: Medline
NR 55
TC 318
Z9 380
U1 0
U2 52
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 885
EP U31
DI 10.1038/nature07004
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000035
PM 18496527
DA 2026-03-09
ER

PT J
AU Hofheinz, M
   Weig, EM
   Ansmann, M
   Bialczak, RC
   Lucero, E
   Neeley, M
   O'Connell, AD
   Wang, H
   Martinis, JM
   Cleland, AN
AF Hofheinz, Max
   Weig, E. M.
   Ansmann, M.
   Bialczak, Radoslaw C.
   Lucero, Erik
   Neeley, M.
   O'Connell, A. D.
   Wang, H.
   Martinis, John M.
   Cleland, A. N.
TI Generation of Fock states in a superconducting quantum circuit
SO NATURE
LA English
DT Article
ID photon number states; trapped atom; radiation; cavity; field; collapse; qubits
AB Spin systems and harmonic oscillators comprise two archetypes in quantum mechanics(1). The spin-1/2 system, with two quantum energy levels, is essentially the most nonlinear system found in nature, whereas the harmonic oscillator represents the most linear, with an infinite number of evenly spaced quantum levels. A significant difference between these systems is that a two- level spin can be prepared in an arbitrary quantum state using classical excitations, whereas classical excitations applied to an oscillator generate a coherent state, nearly indistinguishable from a classical state(2). Quantum behaviour in an oscillator is most obvious in Fock states, which are states with specific numbers of energy quanta, but such states are hard to create(3-7). Here we demonstrate the controlled generation of multi- photon Fock states in a solid- state system. We use a superconducting phase qubit(8), which is a close approximation to a two- level spin system, coupled to a microwave resonator, which acts as a harmonic oscillator, to prepare and analyse pure Fock states with up to six photons. We contrast the Fock states with coherent states generated using classical pulses applied directly to the resonator.
C1 [Hofheinz, Max; Weig, E. M.; Ansmann, M.; Bialczak, Radoslaw C.; Lucero, Erik; Neeley, M.; O'Connell, A. D.; Wang, H.; 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
NR 30
TC 471
Z9 539
U1 2
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 JUL 17
PY 2008
VL 454
IS 7202
BP 310
EP 314
DI 10.1038/nature07136
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300033
PM 18633412
DA 2026-03-09
ER

PT J
AU Zubkov, MV
   Tarran, GA
AF Zubkov, Mikhail V.
   Tarran, Glen A.
TI High bacterivory by the smallest phytoplankton in the North Atlantic Ocean
SO NATURE
LA English
DT Article
ID amino-acid-uptake; planktonic protists; surface waters; flow-cytometry; food webs; mixotrophy; bacterioplankton; cyanobacteria; assimilation; enumeration
AB Planktonic algae, <5 mu m in size are major fixers of inorganic carbon in the ocean(1). They dominate phytoplankton biomass in post-bloom, stratified oceanic temperate waters(2). Traditionally, large and small algae are viewed as having a critical growth dependence on inorganic nutrients, which the latter can better acquire at lower ambient concentrations owing to their higher surface area to volume ratios(3,4). Nonetheless, recent phosphate tracer experiments in the oligotrophic ocean(5) have suggested that small algae obtain inorganic phosphate indirectly, possibly through feeding on bacterioplankton. There have been numerous microscopy- based studies of algae feeding mixotrophically(6,7) in the laboratory(8-10) and field(11-14), as well as mathematical modelling of the ecological importance of mixotrophy(15). However, because of methodological limitations(16) there has not been a direct comparison of obligate heterotrophic and mixotrophic bacterivory. Here we present direct evidence that small algae carry out 40 - 95% of the bacterivory in the euphotic layer of the temperate North Atlantic Ocean in summer. A similar range of 37 - 70% was determined in the surface waters of the tropical North- East Atlantic Ocean, suggesting the global significance of mixotrophy. This finding reveals that even the smallest algae have less dependence on dissolved inorganic nutrients than previously thought, obtaining a quarter of their biomass from bacterivory. This has important implications for how we perceive nutrient acquisition and limitation of carbon- fixing protists as well as control of bacterioplankton in the ocean.
C1 [Zubkov, Mikhail V.] Natl Ocean Ctr, Southampton SO14 3ZH, Hants, England.
   [Tarran, Glen A.] Plymouth Marine Lab, Plymouth PL1 3DH, Devon, England.
C3 NERC National Oceanography Centre; Plymouth Marine Laboratory
RP Zubkov, MV (corresponding author), Natl Ocean Ctr, Southampton SO14 3ZH, Hants, England.
EM mvz@noc.soton.ac.uk
FU UK Natural Environment Research Council (NERC); Oceans 2025 core programmes of the National Oceanography Centre; Southampton and Plymouth Marine Laboratory; NERC thematic programme Surface Ocean Low Atmosphere Study (SOLAS); Natural Environment Research Council [pml010002, soc010012, NE/C001931/1, NE/E016138/1, soc010008] Funding Source: researchfish; NERC [soc010008, NE/E016138/1, soc010012, pml010002] Funding Source: UKRI
NR 28
TC 313
Z9 345
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 SEP 11
PY 2008
VL 455
IS 7210
BP 224
EP U48
DI 10.1038/nature07236
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800047
PM 18690208
DA 2026-03-09
ER

PT J
AU Shaffer, AL
   Emre, NCT
   Lamy, L
   Ngo, VN
   Wright, G
   Xiao, WM
   Powell, J
   Dave, S
   Yu, X
   Zhao, H
   Zeng, YX
   Chen, BZ
   Epstein, J
   Staudt, LM
AF Shaffer, Arthur L.
   Emre, N. C. Tolga
   Lamy, Laurence
   Ngo, Vu N.
   Wright, George
   Xiao, Wenming
   Powell, John
   Dave, Sandeep
   Yu, Xin
   Zhao, Hong
   Zeng, Yuxin
   Chen, Bangzheng
   Epstein, Joshua
   Staudt, Louis M.
TI IRF4 addiction in multiple myeloma
SO NATURE
LA English
DT Article
ID plasma-cell differentiation; lymphoma-cells; myc; expression; cancer; activation; profiles; survival
AB The transcription factor IRF4 ( interferon regulatory factor 4) is required during an immune response for lymphocyte activation and the generation of immunoglobulin- secreting plasma cells(1-3). Multiple myeloma, a malignancy of plasma cells, has a complex molecular aetiology with several subgroups defined by gene expression profiling and recurrent chromosomal translocations(4,5). Moreover, the malignant clone can sustain multiple oncogenic lesions, accumulating genetic damage as the disease progresses(6,7). Current therapies for myeloma can extend survival but are not curative(8,9). Hence, new therapeutic strategies are needed that target molecular pathways shared by all subtypes of myeloma. Here we show, using a loss- of- function, RNA- interference- based genetic screen, that IRF4 inhibition is toxic to myeloma cell lines, regardless of transforming oncogenic mechanism. Gene expression profiling and genome- wide chromatin immunoprecipitation analysis uncovered an extensive network of IRF4 target genes and identified MYC as a direct target of IRF4 in activated B cells and myeloma. Unexpectedly, IRF4 was itself a direct target of MYC transactivation, generating an autoregulatory circuit in myeloma cells. Although IRF4 is not genetically altered in most myelomas, they are nonetheless addicted to an aberrant IRF4 regulatory network that fuses the gene expression programmes of normal plasma cells and activated B cells.
C1 [Shaffer, Arthur L.; Emre, N. C. Tolga; Lamy, Laurence; Ngo, Vu N.; Dave, Sandeep; Yu, Xin; Zhao, Hong; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Wright, George] NCI, Biometr Res Branch, Rockville, MD 20892 USA.
   [Xiao, Wenming; Powell, John] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
   [Zeng, Yuxin; Chen, Bangzheng; Epstein, Joshua] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72212 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH Center for Information Technology (CIT); University of Arkansas System; University of Arkansas Medical Sciences
RP Staudt, LM (corresponding author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
FU National Cancer Institute [ZIABC011007, ZIABC011010] Funding Source: NIH RePORTER; NCI NIH HHS [CA97513, R33 CA097513, R01 CA113992, CA113992] Funding Source: Medline; Intramural NIH HHS [Z99 CA999999] Funding Source: Medline
NR 29
TC 590
Z9 674
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 226
EP 231
DI 10.1038/nature07064
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900046
PM 18568025
DA 2026-03-09
ER

PT J
AU Jaillon, O
   Bouhouche, K
   Gout, JF
   Aury, JM
   Noel, B
   Saudemont, B
   Nowacki, M
   Serrano, V
   Porcel, BM
   Ségurens, B
   Le Mouël, A
   Lepere, G
   Schächter, V
   Bétermier, M
   Cohen, J
   Wincker, P
   Sperling, L
   Duret, L
   Meyer, E
AF Jaillon, Olivier
   Bouhouche, Khaled
   Gout, Jean-Francois
   Aury, Jean-Marc
   Noel, Benjamin
   Saudemont, Baptiste
   Nowacki, Mariusz
   Serrano, Vincent
   Porcel, Betina M.
   Segurens, Beatrice
   Le Mouel, Anne
   Lepere, Gersende
   Schachter, Vincent
   Betermier, Mireille
   Cohen, Jean
   Wincker, Patrick
   Sperling, Linda
   Duret, Laurent
   Meyer, Eric
TI Translational control of intron splicing in eukaryotes
SO NATURE
LA English
DT Article
ID messenger-rna decay; nonsense-mediated decay; protein-synthesis; genome browser; interference; recognition
AB Most eukaryotic genes are interrupted by non- coding introns that must be accurately removed from pre- messenger RNAs to produce translatable mRNAs(1). Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poorly understood. In most organisms, short introns recognized by the intron definition mechanism(2) cannot be efficiently predicted solely on the basis of sequence motifs(3). In multicellular eukaryotes, long introns are recognized through exon definition(2) and most genes produce multiple mRNA variants through alternative splicing(4). The nonsense- mediated mRNA decay(5,6) ( NMD) pathway may further shape the observed sets of variants by selectively degrading those containing premature termination codons, which are frequently produced in mammals(7,8). Here we show that the tiny introns of the ciliate Paramecium tetraurelia are under strong selective pressure to cause premature termination of mRNA translation in the event of intron retention, and that the same bias is observed among the short introns of plants, fungi and animals. By knocking down the two P. tetraurelia genes encoding UPF1, a protein that is crucial in NMD, we show that the intrinsic efficiency of splicing varies widely among introns and that NMD activity can significantly reduce the fraction of unspliced mRNAs. The results suggest that, independently of alternative splicing, species with large intron numbers universally rely on NMD to compensate for suboptimal splicing efficiency and accuracy.
C1 [Bouhouche, Khaled; Saudemont, Baptiste; Nowacki, Mariusz; Serrano, Vincent; Le Mouel, Anne; Lepere, Gersende; Meyer, Eric] Ecole Normale Super, Genet Mol Lab, F-75005 Paris, France.
   [Jaillon, Olivier; Aury, Jean-Marc; Noel, Benjamin; Porcel, Betina M.; Segurens, Beatrice; Schachter, Vincent; Wincker, Patrick] Genoscope CEA, F-91057 Evry, France.
   [Jaillon, Olivier; Aury, Jean-Marc; Noel, Benjamin; Porcel, Betina M.; Schachter, Vincent; Wincker, Patrick] CNRS, UMR 8030, F-91057 Evry, France.
   [Jaillon, Olivier; Aury, Jean-Marc; Noel, Benjamin; Porcel, Betina M.; Schachter, Vincent; Wincker, Patrick] Univ Evry, F-91057 Evry, France.
   [Bouhouche, Khaled; Saudemont, Baptiste; Nowacki, Mariusz; Serrano, Vincent; Le Mouel, Anne; Lepere, Gersende; Meyer, Eric] CNRS, UMR 8541, F-75005 Paris, France.
   [Bouhouche, Khaled; Betermier, Mireille; Cohen, Jean; Sperling, Linda] CNRS, Ctr Genet Mol, UPR 2167, F-91198 Gif Sur Yvette, France.
   [Bouhouche, Khaled; Betermier, Mireille; Cohen, Jean; Sperling, Linda] Univ Paris 11, F-91405 Orsay, France.
   [Bouhouche, Khaled; Betermier, Mireille; Cohen, Jean; Sperling, Linda] Univ Paris 06, F-75005 Paris, France.
   [Gout, Jean-Francois; Duret, Laurent] Univ Lyon 1, CNRS, UMR 5558, Lab Biometrie & Biol Evolut, F-69622 Villeurbanne, France.
C3 Universite PSL; Ecole Normale Superieure (ENS); CEA; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); CEA; Universite Paris Saclay; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Universite Paris Saclay; Sorbonne Universite; Universite Lyon 1; VetAgro Sup; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE)
RP Meyer, E (corresponding author), Ecole Normale Super, Genet Mol Lab, 46 Rue Ulm, F-75005 Paris, France.
EM emeyer@biologie.ens.fr
NR 39
TC 181
Z9 215
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 359
EP U15
DI 10.1038/nature06495
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100055
PM 18202663
DA 2026-03-09
ER

PT J
AU Graversen, RG
   Mauritsen, T
   Tjernström, M
   Källén, E
   Svensson, G
AF Graversen, Rune G.
   Mauritsen, Thorsten
   Tjernstrom, Michael
   Kallen, Erland
   Svensson, Gunilla
TI Vertical structure of recent Arctic warming
SO NATURE
LA English
DT Article
ID surface air-temperature; climate-change; polar amplification; circulation
AB Near- surface warming in the Arctic has been almost twice as large as the global average over recent decades(1-5) - a phenomenon that is known as the 'Arctic amplification'. The underlying causes of this temperature amplification remain uncertain. The reduction in snow and ice cover that has occurred over recent decades(6,7) may have played a role(5,8). Climate model experiments indicate that when global temperature rises, Arctic snow and ice cover retreats, causing excessive polar warming(9-11). Reduction of the snow and ice cover causes albedo changes, and increased refreezing of sea ice during the cold season and decreases in sea- ice thickness both increase heat flux from the ocean to the atmosphere. Changes in oceanic and atmospheric circulation, as well as cloud cover, have also been proposed to cause Arctic temperature amplification(12-17). Here we examine the vertical structure of temperature change in the Arctic during the late twentieth century using reanalysis data. We find evidence for temperature amplification well above the surface. Snow and ice feedbacks cannot be the main cause of the warming aloft during the greater part of the year, because these feedbacks are expected to primarily affect temperatures in the lowermost part of the atmosphere, resulting in a pattern of warming that we only observe in spring. A significant proportion of the observed temperature amplification must therefore be explained by mechanisms that induce warming above the lowermost part of the atmosphere. We regress the Arctic temperature field on the atmospheric energy transport into the Arctic and find that, in the summer half- year, a significant proportion of the vertical structure of warming can be explained by changes in this variable. We conclude that changes in atmospheric heat transport may be an important cause of the recent Arctic temperature amplification.
C1 [Graversen, Rune G.; Mauritsen, Thorsten; Tjernstrom, Michael; Kallen, Erland; Svensson, Gunilla] Univ Stockholm, Dept Meteorol, S-10691 Stockholm, Sweden.
C3 Stockholm University
RP Graversen, RG (corresponding author), Univ Stockholm, Dept Meteorol, S-10691 Stockholm, Sweden.
EM rune@misu.su.se
NR 26
TC 491
Z9 571
U1 2
U2 170
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 53
EP U4
DI 10.1038/nature06502
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300031
PM 18172495
DA 2026-03-09
ER

PT J
AU Akala, OO
   Park, IK
   Qian, DL
   Pihalja, M
   Becker, MW
   Clarke, MF
AF Akala, Omobolaji O.
   Park, In-Kyung
   Qian, Dalong
   Pihalja, Michael
   Becker, Michael W.
   Clarke, Michael F.
TI Long-term haematopoietic reconstitution by Trp53-/-p16Ink4a-/-p19Arf-/- multipotent progenitors
SO NATURE
LA English
DT Article
ID slam family receptors; leukemic stem-cells; ex-vivo expansion; self-renewal; bmi-1; p53; p16(ink4a); proliferation; senescence; expression
AB Haematopoiesis is maintained by a hierarchical system where haematopoietic stem cells ( HSCs) give rise to multipotent progenitors, which in turn differentiate into all types of mature blood cells1. HSCs maintain themselves for the lifetime of the organism because of their ability to self- renew. However, multipotent progenitors lack the ability to self- renew, therefore their mitotic capacity and expansion potential are limited and they are destined to eventually stop proliferating after a finite number of cell divisions(1,2). The molecular mechanisms that limit the proliferation capacity of multipotent progenitors and other more mature progenitors are not fully understood(2,3). Here we show that bone marrow cells from mice deficient in three genes genetically downstream of Bmi1-p16(Ink4a), p19(Arf) and Trp53 ( triple mutant mice; p16(Ink4a) and p19(Arf) are alternative reading frames of the same gene ( also called Cdkn2a) that encode different proteins) - have an approximately 10-fold increase in cells able to reconstitute the blood long term. This increase is associated with the acquisition of long- term reconstitution capacity by cells of the phenotype c-kit(+)Sca-1(+)Flt3(+)CD150(-)CD48(-)Lin(-), which defines multipotent progenitors in wild- type mice(4-6). The pattern of triple mutant multipotent progenitor response to growth factors resembles that of wild- type multipotent progenitors but not wild- type HSCs. These results demonstrate that p16(Ink4a)/p19(Arf) and Trp53 have a central role in limiting the expansion potential of multipotent progenitors. These pathways are commonly repressed in cancer, suggesting a mechanism by which early progenitor cells could gain the ability to self- renew and become malignant with further oncogenic mutations.
C1 [Akala, Omobolaji O.; Qian, Dalong; Clarke, Michael F.] Stanford Univ, Stanford Inst Stem Cell Biol & Regenerat Med, Palo Alto, CA 94304 USA.
   [Akala, Omobolaji O.] Univ Michigan, Cellular & Mol Biol Grad Program, Taubman Med Lib 2966, Ann Arbor, MI 48109 USA.
   [Akala, Omobolaji O.; Qian, Dalong; Clarke, Michael F.] Stanford Univ, Div Hematol Oncol, Palo Alto, CA 94304 USA.
   [Park, In-Kyung; Pihalja, Michael] Univ Michigan, Dept Hematol Oncol, Ann Arbor, MI 48109 USA.
   [Becker, Michael W.] Univ Rochester, Div Hematol Oncol, Rochester, NY 14642 USA.
C3 Stanford University; University of Michigan System; University of Michigan; Stanford University; University of Michigan System; University of Michigan; University of Rochester
RP Clarke, MF (corresponding author), Stanford Univ, Stanford Inst Stem Cell Biol & Regenerat Med, 1050 Arastradero Rd, Palo Alto, CA 94304 USA.
EM mfclarke@stanford.edu
NR 27
TC 136
Z9 165
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 228
EP U12
DI 10.1038/nature06869
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400041
PM 18418377
DA 2026-03-09
ER

PT J
AU Harper, GR
   Pfennig, DW
AF Harper, George R., Jr.
   Pfennig, David W.
TI Selection overrides gene flow to break down maladaptive mimicry
SO NATURE
LA English
DT Article
ID biased dispersal; model; snake; populations; patterns; predators; tools
AB Predators typically avoid dangerous species, and batesian mimicry evolves when a palatable species ( the 'mimic') co- opts a warning signal from a dangerous species ( the 'model') and thereby deceives its potential predators(1,2). Because predators would not be under selection to avoid the model and any of its look- alikes in areas where the model is absent ( that is, allopatry)(2-5), batesian mimics should occur only in sympatry with their model. However, contrary to this expectation, batesian mimics often occur in allopatry(6-8). Here we focus on one such example - a coral snake mimic(3,8). Using indirect DNA- based methods, we provide evidence suggesting that mimics migrate from sympatry, where mimicry is favoured(3,9), to allopatry, where it is disfavoured(10). Such gene flow is much stronger in nuclear genes than in maternally inherited mitochondrial genes, indicating that dispersal by males may explain the presence of mimetic phenotypes in allopatry. Despite this gene flow, however, individuals from allopatry resemble the model less than do individuals from sympatry. We show that this breakdown of mimicry probably reflects predator- mediated selection acting against individuals expressing the more conspicuous mimetic phenotype in allopatry. Thus, although gene flow may explain why batesian mimics occur in allopatry, natural selection may often override such gene flow and promote the evolution of non- mimetic phenotypes in such areas.
C1 [Harper, George R., Jr.; Pfennig, David W.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill
RP Pfennig, DW (corresponding author), Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
EM dpfennig@unc.edu
NR 29
TC 51
Z9 59
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 28
PY 2008
VL 451
IS 7182
BP 1103
EP U6
DI 10.1038/nature06532
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600041
PM 18305543
DA 2026-03-09
ER

PT J
AU Dinsdale, EA
   Edwards, RA
   Hall, D
   Angly, F
   Breitbart, M
   Brulc, JM
   Furlan, M
   Desnues, C
   Haynes, M
   Li, LL
   McDaniel, L
   Moran, MA
   Nelson, KE
   Nilsson, C
   Olson, R
   Paul, J
   Brito, BR
   Ruan, YJ
   Swan, BK
   Stevens, R
   Valentine, DL
   Thurber, RV
   Wegley, L
   White, BA
   Rohwer, F
AF Dinsdale, Elizabeth A.
   Edwards, Robert A.
   Hall, Dana
   Angly, Florent
   Breitbart, Mya
   Brulc, Jennifer M.
   Furlan, Mike
   Desnues, Christelle
   Haynes, Matthew
   Li, Linlin
   McDaniel, Lauren
   Moran, Mary Ann
   Nelson, Karen E.
   Nilsson, Christina
   Olson, Robert
   Paul, John
   Brito, Beltran Rodriguez
   Ruan, Yijun
   Swan, Brandon K.
   Stevens, Rick
   Valentine, David L.
   Thurber, Rebecca Vega
   Wegley, Linda
   White, Bryan A.
   Rohwer, Forest
TI Functional metagenomic profiling of nine biomes
SO NATURE
LA English
DT Article
ID microbial ecology; genome; diversity; evolution; community; database; virus; bacteriophages; bacteria; archaea
AB Microbial activities shape the biogeochemistry of the planet(1,2) and macroorganism health(3). Determining the metabolic processes performed by microbes is important both for understanding and for manipulating ecosystems ( for example, disruption of key processes that lead to disease, conservation of environmental services, and so on). Describing microbial function is hampered by the inability to culture most microbes and by high levels of genomic plasticity. Metagenomic approaches analyse microbial communities to determine the metabolic processes that are important for growth and survival in any given environment. Here we conduct a metagenomic comparison of almost 15 million sequences from 45 distinct microbiomes and, for the first time, 42 distinct viromes and show that there are strongly discriminatory metabolic profiles across environments. Most of the functional diversity was maintained in all of the communities, but the relative occurrence of metabolisms varied, and the differences between metagenomes predicted the biogeochemical conditions of each environment. The magnitude of the microbial metabolic capabilities encoded by the viromes was extensive, suggesting that they serve as a repository for storing and sharing genes among their microbial hosts and influence global evolutionary and metabolic processes.
C1 [Dinsdale, Elizabeth A.; Edwards, Robert A.; Hall, Dana; Angly, Florent; Furlan, Mike; Desnues, Christelle; Haynes, Matthew; Li, Linlin; Brito, Beltran Rodriguez; Thurber, Rebecca Vega; Wegley, Linda; Rohwer, Forest] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
   [Edwards, Robert A.; Rohwer, Forest] San Diego State Univ, Ctr Microbial Sci, San Diego, CA 92182 USA.
   [Edwards, Robert A.] San Diego State Univ, Dept Comp Sci, San Diego, CA 92182 USA.
   [Angly, Florent; Brito, Beltran Rodriguez] San Diego State Univ, Computat Sci Res Ctr, San Diego, CA 92182 USA.
   [Dinsdale, Elizabeth A.] Flinders Univ S Australia, Sch Biol Sci, Bedford Pk, SA 5042, Australia.
   [Edwards, Robert A.; Olson, Robert; Stevens, Rick] Argonne Natl Lab, Div Math & Comp Sci, Argonne, IL 60439 USA.
   [Breitbart, Mya; McDaniel, Lauren; Paul, John] Univ S Florida, Coll Marine Sci, St Petersburg, FL 33701 USA.
   [Brulc, Jennifer M.; White, Bryan A.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA.
   [White, Bryan A.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Moran, Mary Ann] Univ Georgia, Dept Marine Sci, Athens, GA 30602 USA.
   [Nelson, Karen E.] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Nilsson, Christina; Ruan, Yijun] Genome Inst Singapore, Singapore 138672, Singapore.
   [Swan, Brandon K.; Valentine, David L.] Univ Calif Santa Barbara, Dept Earth Sci, Santa Barbara, CA 93106 USA.
C3 California State University System; San Diego State University; California State University System; San Diego State University; California State University System; San Diego State University; California State University System; San Diego State University; Flinders University; United States Department of Energy (DOE); Argonne National Laboratory; State University System of Florida; University of South Florida; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University System of Georgia; University of Georgia; J. Craig Venter Institute; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); University of California System; University of California Santa Barbara
RP Dinsdale, EA (corresponding author), San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
EM elizabeth_dinsdale@hotmail.com
NR 36
TC 686
Z9 833
U1 4
U2 343
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 629
EP U8
DI 10.1038/nature06810
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200045
PM 18337718
DA 2026-03-09
ER

PT J
AU Abbondanzieri, EA
   Bokinsky, G
   Rausch, JW
   Zhang, JX
   Le Grice, SFJ
   Zhuang, XW
AF Abbondanzieri, Elio A.
   Bokinsky, Gregory
   Rausch, Jason W.
   Zhang, Jennifer X.
   Le Grice, Stuart F. J.
   Zhuang, Xiaowei
TI Dynamic binding orientations direct activity of HIV reverse transcriptase
SO NATURE
LA English
DT Article
ID human-immunodeficiency-virus; dependent dna-polymerase; rnase-h-function; angstrom resolution; primed initiation; crystal-structure; energy-transfer; rna/dna hybrid; mechanism; complex
AB The reverse transcriptase of human immunodeficiency virus ( HIV) catalyses a series of reactions to convert the single- stranded RNA genome of HIV into double- stranded DNA for host- cell integration. This task requires the reverse transcriptase to discriminate a variety of nucleic- acid substrates such that active sites of the enzyme are correctly positioned to support one of three catalytic functions: RNA- directed DNA synthesis, DNA- directed DNA synthesis and DNA- directed RNA hydrolysis. However, the mechanism by which substrates regulate reverse transcriptase activities remains unclear. Here we report distinct orientational dynamics of reverse transcriptase observed on different substrates with a single- molecule assay. The enzyme adopted opposite binding orientations on duplexes containing DNA or RNA primers, directing its DNA synthesis or RNA hydrolysis activity, respectively. On duplexes containing the unique polypurine RNA primers for plus- strand DNA synthesis, the enzyme can rapidly switch between the two orientations. The switching kinetics were regulated by cognate nucleotides and non- nucleoside reverse transcriptase inhibitors, a major class of anti- HIV drugs. These results indicate that the activities of reverse transcriptase are determined by its binding orientation on substrates.
C1 [Abbondanzieri, Elio A.; Bokinsky, Gregory; Zhang, Jennifer X.; Zhuang, Xiaowei] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA.
   [Zhuang, Xiaowei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
   [Rausch, Jason W.; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
C3 Harvard University; Harvard University; Harvard University; Howard Hughes Medical Institute; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Zhuang, XW (corresponding author), Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA.
EM zhuang@chemistry.harvard.edu
FU National Cancer Institute [ZIABC010493] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NIGMS NIH HHS [R01 GM068518, GM 068518] Funding Source: Medline; Intramural NIH HHS [Z01 BC010493] Funding Source: Medline
NR 41
TC 147
Z9 191
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 MAY 8
PY 2008
VL 453
IS 7192
BP 184
EP U2
DI 10.1038/nature06941
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400031
PM 18464735
DA 2026-03-09
ER

PT J
AU Han, HJ
   Russo, J
   Kohwi, Y
   Kohwi-Shigematsu, T
AF Han, Hye-Jung
   Russo, Jose
   Kohwi, Yoshinori
   Kohwi-Shigematsu, Terumi
TI SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis
SO NATURE
LA English
DT Article
ID epithelial-mesenchymal transitions; cancer metastasis; signal-transduction; binding protein; in-vivo; chromatin; cells; progression; architecture; apoptosis
AB Mechanisms underlying global changes in gene expression during tumour progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin- remodelling enzymes to regulate chromatin structure and gene expression. Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance ( P < 0.0001), independent of lymph- node status. RNA- interference- mediated knockdown of SATB1 in highly aggressive ( MDA- MB- 231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast- like acinar polarity and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non- aggressive ( SKBR3) cells led to gene expression patterns consistent with aggressive- tumour phenotypes, acquiring metastatic activity in vivo. SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis- associated genes while downregulating tumour- suppressor genes. SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.
C1 [Han, Hye-Jung; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi] Univ Calif Berkeley, Div Life Sci, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Russo, Jose] Fox Chase Canc Ctr, Breast Canc Res Lab, Philadelphia, PA 19111 USA.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Fox Chase Cancer Center
RP Kohwi-Shigematsu, T (corresponding author), Univ Calif Berkeley, Div Life Sci, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
EM YKohwi@lbl.gov; Terumiks@lbl.gov
NR 50
TC 446
Z9 536
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 13
PY 2008
VL 452
IS 7184
BP 187
EP 193
DI 10.1038/nature06781
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600034
PM 18337816
DA 2026-03-09
ER

PT J
AU Liang, HL
   Nien, CY
   Liu, HY
   Metzstein, MM
   Kirov, N
   Rushlow, C
AF Liang, Hsiao-Lan
   Nien, Chung-Yi
   Liu, Hsiao-Yun
   Metzstein, Mark M.
   Kirov, Nikolai
   Rushlow, Christine
TI The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila
SO NATURE
LA English
DT Article
ID polarized membrane growth; repression; binding; cellularization; insertions; transition; regulator; cleavage; encodes; targets
AB In all animals, the initial events of embryogenesis are controlled by maternal gene products that are deposited into the developing oocyte. At some point after fertilization, control of embryogenesis is transferred to the zygotic genome in a process called the maternal- to-zygotic transition. During this time, many maternal RNAs are degraded and transcription of zygotic RNAs ensues(1). There is a long-standing question as to which factors regulate these events. The recent findings that microRNAs(2,3) and Smaug(4) mediate maternal transcript degradation have shed new light on this aspect of the problem. However, the transcription factor(s) that activate the zygotic genomeremain elusive. The discovery that many of the early transcribed genes in Drosophila share a cis- regulatory heptamer motif, CAGGTAG and related sequences(5,6), collectively referred to as TAGteam sites(5) raised the possibility that a dedicated transcription factor could interact with these sites to activate transcription. Here we report that the zinc- finger protein Zelda ( Zld; Zinc- finger early Drosophila activator) binds specifically to these sites and is capable of activating transcription in transient transfection assays. Mutant embryos lacking zld are defective in cellular blastoderm formation, and fail to activate many genes essential for cellularization, sex determination and pattern formation. Global expression profiling confirmed that Zld has an important role in the activation of the early zygotic genome and suggests that Zld may also regulate maternal RNA degradation during the maternal- to- zygotic transition.
C1 [Liang, Hsiao-Lan; Nien, Chung-Yi; Liu, Hsiao-Yun; Kirov, Nikolai; Rushlow, Christine] NYU, Dept Biol, New York, NY 10003 USA.
   [Metzstein, Mark M.] Univ Utah, Inst Human Genet, Salt Lake City, UT 84112 USA.
C3 New York University; Utah System of Higher Education; University of Utah
RP Rushlow, C (corresponding author), NYU, Dept Biol, 100 Washington Sq E, New York, NY 10003 USA.
EM chris.rushlow@nyu.edu
FU National Institutes of Health [GM63024]
NR 28
TC 383
Z9 493
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 NOV 20
PY 2008
VL 456
IS 7220
BP 400
EP U67
DI 10.1038/nature07388
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600046
PM 18931655
DA 2026-03-09
ER

PT J
AU Hanna, RA
   Campbell, RL
   Davies, PL
AF Hanna, Rachel A.
   Campbell, Robert L.
   Davies, Peter L.
TI Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin
SO NATURE
LA English
DT Article
ID crystal-structures; active-site; mu-calpain; activation; peptide; binding; model; complexes
AB Calpains are non-lysosomal calcium-dependent cysteine proteinases that selectively cleave proteins in response to calcium signals(1) and thereby control cellular functions such as cytoskeletal remodelling, cell cycle progression, gene expression and apoptotic cell death(2-4). In mammals, the two best-characterized members of the calpain family, calpain 1 and calpain 2 ( mu-calpain and m-calpain, respectively), are ubiquitously expressed. The activity of calpains is tightly controlled by the endogenous inhibitor calpastatin, which is an intrinsically unstructured protein capable of reversibly binding and inhibiting four molecules of calpain, but only in the presence of calcium(5,6). To date, the mechanism of inhibition by calpastatin and the basis for its absolute specificity have remained speculative(7-9). It was not clear how this unstructured protein inhibits calpains without being cleaved itself, nor was it known how calcium induced changes that facilitated the binding of calpastatin to calpain. Here we report the 2.4-angstrom-resolution crystal structure of the calcium-bound calpain 2 heterodimer bound by one of the four inhibitory domains of calpastatin. Calpastatin is seen to inhibit calpain by occupying both sides of the active site cleft. Although the inhibitor passes through the active site cleft it escapes cleavage in a novel manner by looping out and around the active site cysteine. The inhibitory domain of calpastatin recognizes multiple lower affinity sites present only in the calcium-bound form of the enzyme, resulting in an interaction that is tight, specific and calcium dependent. This crystal structure, and that of a related complex(10), also reveal the conformational changes that calpain undergoes on binding calcium, which include opening of the active site cleft and movement of the domains relative to each other to produce a more compact enzyme.
C1 [Hanna, Rachel A.; Campbell, Robert L.; Davies, Peter L.] Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada.
C3 Queens University - Canada
RP Davies, PL (corresponding author), Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada.
EM peter.davies@queensu.ca
FU Canadian Institutes for Health Research; Bauman Fellowship; R. J. Wilson Fellowship
NR 32
TC 266
Z9 336
U1 1
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 20
PY 2008
VL 456
IS 7220
BP 409
EP U78
DI 10.1038/nature07451
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600048
PM 19020623
DA 2026-03-09
ER

PT J
AU Sussan, TE
   Yang, AN
   Li, F
   Ostrowski, MC
   Reeves, RH
AF Sussan, Thomas E.
   Yang, Annan
   Li, Fu
   Ostrowski, Michael C.
   Reeves, Roger H.
TI Trisomy represses ApcMin-mediated tumours in mouse models of Down's syndrome
SO NATURE
LA English
DT Article
ID intestinal neoplasia; cancer incidence; major modifier; mortality; growth; gene; angiogenesis; locus
AB Epidemiological studies spanning more than 50 yr reach conflicting conclusions as to whether there is a lower incidence of solid tumours in people with trisomy 21 ( Down's syndrome)(1,2). We used mouse models of Down's syndrome and of cancer in a biological approach to investigate the relationship between trisomy and the incidence of intestinal tumours. Apc(Min)-mediated tumour number was determined in aneuploid mouse models Ts65Dn, Ts1Rhr and Ms1Rhr. Trisomy for orthologues of about half of the genes on chromosome 21 ( Hsa21) in Ts65Dn mice or just 33 of these genes in Ts1Rhr mice resulted in a significant reduction in the number of intestinal tumours. In Ms1Rhr, segmental monosomy for the same 33 genes that are triplicated in Ts1Rhr resulted in an increased number of tumours. Further studies demonstrated that the Ets2 gene contributed most of the dosage- sensitive effect on intestinal tumour number. The action of Ets2 as a repressor when it is overexpressed differs from tumour suppression, which requires normal gene function to prevent cellular transformation. Upregulation of Ets2 and, potentially, other genes involved in this kind of protective effect may provide a prophylactic effect in all individuals, regardless of ploidy.
C1 [Sussan, Thomas E.; Yang, Annan; Reeves, Roger H.] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA.
   [Sussan, Thomas E.; Yang, Annan; Reeves, Roger H.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA.
   [Li, Fu; Ostrowski, Michael C.] Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA.
C3 Johns Hopkins University; Johns Hopkins University; University System of Ohio; Ohio State University
RP Reeves, RH (corresponding author), Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA.
EM rreeves@jhmi.edu
FU NCI NIH HHS [P01 CA097189, R01 CA053271] Funding Source: Medline
NR 21
TC 135
Z9 161
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 JAN 3
PY 2008
VL 451
IS 7174
BP 73
EP U10
DI 10.1038/nature06446
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300036
PM 18172498
DA 2026-03-09
ER

PT J
AU Desnues, C
   Rodriguez-Brito, B
   Rayhawk, S
   Kelley, S
   Tran, T
   Haynes, M
   Liu, H
   Furlan, M
   Wegley, L
   Chau, B
   Ruan, YJ
   Hall, D
   Angly, FE
   Edwards, RA
   Li, LL
   Thurber, RV
   Reid, RP
   Siefert, J
   Souza, V
   Valentine, DL
   Swan, BK
   Breitbart, M
   Rohwer, F
AF Desnues, Christelle
   Rodriguez-Brito, Beltran
   Rayhawk, Steve
   Kelley, Scott
   Tran, Tuong
   Haynes, Matthew
   Liu, Hong
   Furlan, Mike
   Wegley, Linda
   Chau, Betty
   Ruan, Yijun
   Hall, Dana
   Angly, Florent E.
   Edwards, Robert A.
   Li, Linlin
   Thurber, Rebecca Vega
   Reid, R. Pamela
   Siefert, Janet
   Souza, Valeria
   Valentine, David L.
   Swan, Brandon K.
   Breitbart, Mya
   Rohwer, Forest
TI Biodiversity and biogeography of phages in modern stromatolites and thrombolites
SO NATURE
LA English
DT Article
ID online tool; virus; marine; diversity; alignment
AB Viruses, and more particularly phages ( viruses that infect bacteria), represent one of the most abundant living entities in aquatic and terrestrial environments. The biogeography of phages has only recently been investigated and so far reveals a cosmopolitan distribution of phage genetic material ( or genotypes)(1-4). Here we address this cosmopolitan distribution through the analysis of phage communities in modern microbialites, the living representatives of one of the most ancient life forms on Earth. On the basis of a comparative metagenomic analysis of viral communities associated with marine ( Highborne Cay, Bahamas) and freshwater ( Pozas Azules II and Rio Mesquites, Mexico) microbialites, we show that some phage genotypes are geographically restricted. The high percentage of unknown sequences recovered from the three metagenomes (>97%), the low percentage similarities with sequences from other environmental viral ( n = 42) and microbial ( n = 36) metagenomes, and the absence of viral genotypes shared among microbialites indicate that viruses are genetically unique in these environments. Identifiable sequences in the Highborne Cay metagenome were dominated by single- stranded DNA microphages that were not detected in any other samples examined, including sea water, fresh water, sediment, terrestrial, extreme, metazoan- associated and marine microbial mats. Finally, a marine signature was present in the phage community of the Pozas Azules II microbialites, even though this environment has not been in contact with the ocean for tens of millions of years. Taken together, these results prove that viruses in modern microbialites display biogeographical variability and suggest that they may be derived from an ancient community.
C1 [Desnues, Christelle; Rodriguez-Brito, Beltran; Rayhawk, Steve; Kelley, Scott; Tran, Tuong; Haynes, Matthew; Liu, Hong; Furlan, Mike; Wegley, Linda; Chau, Betty; Hall, Dana; Angly, Florent E.; Edwards, Robert A.; Li, Linlin; Thurber, Rebecca Vega; Rohwer, Forest] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
   [Rodriguez-Brito, Beltran; Rayhawk, Steve; Edwards, Robert A.] San Diego State Univ, Computat Sci Res Ctr, San Diego, CA 92182 USA.
   [Kelley, Scott; Edwards, Robert A.; Rohwer, Forest] San Diego State Univ, Ctr Microbial Sci, San Diego, CA 92182 USA.
   [Ruan, Yijun] Genome Inst Singapore, Singapore 138672, Singapore.
   [Edwards, Robert A.] Argonne Natl Lab, Div Math & Comp Sci, Argonne, IL 60439 USA.
   [Reid, R. Pamela] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33149 USA.
   [Siefert, Janet] Rice Univ, Dept Stat, Houston, TX 77251 USA.
   [Souza, Valeria] Univ Nacl Autonoma Mexico, Dept Ecol Evolut, Inst Ecol, Mexico City 04510, DF, Mexico.
   [Valentine, David L.; Swan, Brandon K.] Univ Calif Santa Barbara, Dept Earth Sci, Santa Barbara, CA 93106 USA.
   [Breitbart, Mya] Univ S Florida, Coll Marine Sci, St Petersburg, FL 33701 USA.
C3 California State University System; San Diego State University; California State University System; San Diego State University; California State University System; San Diego State University; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); United States Department of Energy (DOE); Argonne National Laboratory; University of Miami; Rice University; Universidad Nacional Autonoma de Mexico; University of California System; University of California Santa Barbara; State University System of Florida; University of South Florida
RP Desnues, C (corresponding author), San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
EM cdesnues@yahoo.fr
NR 30
TC 193
Z9 230
U1 1
U2 89
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 340
EP U5
DI 10.1038/nature06735
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400044
PM 18311127
DA 2026-03-09
ER

PT J
AU Got, JL
   Monteiller, V
   Monteux, J
   Hassani, R
   Okubo, P
AF Got, Jean-Luc
   Monteiller, Vadim
   Monteux, Julien
   Hassani, Riad
   Okubo, Paul
TI Deformation and rupture of the oceanic crust may control growth of Hawaiian volcanoes
SO NATURE
LA English
DT Article
ID beneath kilauea volcano; mauna-loa; south flank; islands; mantle; landslides; insights; stress; field
AB Hawaiian volcanoes are formed by the eruption of large quantities of basaltic magma related to hot- spot activity below the Pacific Plate(1,2). Despite the apparent simplicity of the parent process emission of magma onto the oceanic crust - the resulting edifices display some topographic complexity(3-5). Certain features, such as rift zones and large flank slides, are common to all Hawaiian volcanoes, indicating similarities in their genesis; however, the underlying mechanism controlling this process remains unknown(6,7). Here we use seismological investigations and finite-element mechanical modelling to show that the load exerted by large Hawaiian volcanoes can be sufficient to rupture the oceanic crust. This intense deformation, combined with the accelerated subsidence of the oceanic crust and the weakness of the volcanic edifice/ oceanic crust interface, may control the surface morphology of Hawaiian volcanoes, especially the existence of their giant flank instabilities(8-10). Further studies are needed to determine whether such processes occur in other active intraplate volcanoes.
C1 [Got, Jean-Luc; Monteiller, Vadim; Hassani, Riad] Univ Savoie, Lab Geophys Interne & Tectonophys, F-73376 Le Bourget Du Lac, France.
   [Monteux, Julien] Ecole Normale Super Lyon, Lab Sci Terre, F-69364 Lyon, France.
   [Okubo, Paul] US Geol Survey, Hawaiian Volcano Observ, Hawaii Natl Pk, HI USA.
C3 Universite Savoie Mont Blanc; Ecole Normale Superieure de Lyon (ENS de LYON); United States Department of the Interior; United States Geological Survey
RP Got, JL (corresponding author), Univ Savoie, Lab Geophys Interne & Tectonophys, F-73376 Le Bourget Du Lac, France.
EM jlgot@univ-savoie.fr
NR 29
TC 32
Z9 40
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 JAN 24
PY 2008
VL 451
IS 7177
BP 453
EP 456
DI 10.1038/nature06481
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100042
PM 18216852
DA 2026-03-09
ER

PT J
AU Mellman, DL
   Gonzales, ML
   Song, CH
   Barlow, CA
   Wang, P
   Kendziorski, C
   Anderson, RA
AF Mellman, David L.
   Gonzales, Michael L.
   Song, Chunhua
   Barlow, Christy A.
   Wang, Ping
   Kendziorski, Christina
   Anderson, Richard A.
TI A PtdIns4,5P2-regulatednuclear poly(A) polymerase controls expression of select mRNAs
SO NATURE
LA English
DT Article
ID polyadenylation; complex; family; mechanism; kinases; binding; region; domain; gamma; ends
AB Phosphoinositides are a family of lipid signalling molecules that regulate many cellular functions in eukaryotes. Phosphatidylinositol-4,5- bisphosphate ( PtdIns4,5P(2)), the central component in the phosphoinositide signalling circuitry, is generated primarily by type I phosphatidylinositol 4- phosphate 5- kinases ( PIPKI alpha, PIPKI beta and PIPKI gamma)(1). In addition to functions in the cytosol, phosphoinositides are present in the nucleus(2,3), where they modulate several functions(4-6); however, the mechanism by which they directly regulate nuclear functions remains unknown. PIPKIs regulate cellular functions through interactions with protein partners, often PtdIns4,5P(2) effectors, that target PIPKIs to discrete subcellular compartments, resulting in the spatial and temporal generation of PtdIns4,5P(2) required for the regulation of specific signalling pathways(1,7). Therefore, to determine roles for nuclear PtdIns4,5P(2) we set out to identify proteins that interacted with the nuclear PIPK, PIPKI alpha. Here we show that PIPKI alpha co- localizes at nuclear speckles and interacts with a newly identified non- canonical poly( A) polymerase, which we have termed Star- PAP ( nuclear speckle targeted PIPKIa regulated- poly( A) polymerase) and that the activity of Star- PAP can be specifically regulated by PtdIns4,5P(2). Star- PAP and PIPKIa function together in a complex to control the expression of select mRNAs, including the transcript encoding the key cytoprotective enzyme haem oxygenase- 1 ( refs 8, 9) and other oxidative stress response genes by regulating the 3 '-end formation of their mRNAs. Taken together, the data demonstrate a model by which phosphoinositide signalling works in tandem with complement pathways to regulate the activity of Star- PAP and the subsequent biosynthesis of its target mRNA. The results reveal a mechanism for the integration of nuclear phosphoinositide signals and a method for regulating gene expression.
C1 [Mellman, David L.; Gonzales, Michael L.; Anderson, Richard A.] Univ Wisconsin, Sch Med, Mol & Cellular Biol Program, Madison, WI 53706 USA.
   [Song, Chunhua; Barlow, Christy A.; Anderson, Richard A.] Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA.
   [Wang, Ping; Kendziorski, Christina] Univ Wisconsin, Sch Med, Dept Biostat & Med Informat, 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 Anderson, RA (corresponding author), Univ Wisconsin, Sch Med, Mol & Cellular Biol Program, 1300 Univ Ave, Madison, WI 53706 USA.
EM raanders@wisc.edu
FU NIGMS NIH HHS [R01 GM051968, R01 GM114386] Funding Source: Medline
NR 32
TC 212
Z9 253
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 1013
EP U9
DI 10.1038/nature06666
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100053
PM 18288197
DA 2026-03-09
ER

PT J
AU Han, MH
   Hwang, SI
   Roy, DB
   Lundgren, DH
   Price, JV
   Ousman, SS
   Fernald, GH
   Gerlitz, B
   Robinson, WH
   Baranzini, SE
   Grinnell, BW
   Raine, CS
   Sobel, RA
   Han, DK
   Steinman, L
AF Han, May H.
   Hwang, Sun-Il
   Roy, Dolly B.
   Lundgren, Deborah H.
   Price, Jordan V.
   Ousman, Shalina S.
   Fernald, Guy Haskin
   Gerlitz, Bruce
   Robinson, William H.
   Baranzini, Sergio E.
   Grinnell, Brian W.
   Raine, Cedric S.
   Sobel, Raymond A.
   Han, David K.
   Steinman, Lawrence
TI Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets
SO NATURE
LA English
DT Article
ID central-nervous-system; alpha-b-crystallin; protein-c; plaque; chromatography; pathogenesis; astrocytes; activation; antibody; sepsis
AB Understanding the neuropathology of multiple sclerosis ( MS) is essential for improved therapies. Therefore, identification of targets specific to pathological types of MS may have therapeutic benefits. Here we identify, by laser- capture microdissection and proteomics, proteins unique to three major types of MS lesions: acute plaque, chronic active plaque and chronic plaque. Comparative proteomic profiles identified tissue factor and protein C inhibitor within chronic active plaque samples, suggesting dysregulation of molecules associated with coagulation. In vivo administration of hirudin or recombinant activated protein C reduced disease severity in experimental autoimmune encephalomyelitis and suppressed Th1 and Th17 cytokines in astrocytes and immune cells. Administration of mutant forms of recombinant activated protein C showed that both its anticoagulant and its signalling functions were essential for optimal amelioration of experimental autoimmune encephalomyelitis. A proteomic approach illuminated potential therapeutic targets selective for specific pathological stages of MS and implicated participation of the coagulation cascade.
C1 [Han, May H.; Price, Jordan V.; Ousman, Shalina S.; Steinman, Lawrence] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
   [Robinson, William H.] Stanford Univ, Sch Med, Div Immunol & Rheumatol, Stanford, CA 94305 USA.
   [Hwang, Sun-Il; Lundgren, Deborah H.; Han, David K.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Ctr Vasc Biol, Farmington, CT 06030 USA.
   [Roy, Dolly B.] Northridge Neurol Ctr, Northridge, CA 91325 USA.
   [Fernald, Guy Haskin; Baranzini, Sergio E.] Univ Calif San Francisco, Sch Dent, Dept Neurol, San Francisco, CA 94143 USA.
   [Gerlitz, Bruce; Grinnell, Brian W.] Eli Lilly & Co, Lilly Res Lab, Lilly Corp Ctr, Biotechnol Discovery Res, Indianapolis, IN 46285 USA.
   [Raine, Cedric S.] Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA.
   [Sobel, Raymond A.] Dept Pathol Neuropathol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; University of Connecticut; University of California System; University of California San Francisco; Eli Lilly; Lilly Research Laboratories; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University
RP Steinman, L (corresponding author), Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
EM steinman@stanford.edu
FU NIAID NIH HHS [T32 AI007290] Funding Source: Medline; NLM NIH HHS [T15 LM007033] Funding Source: Medline; National Institute of Allergy and Infectious Diseases [T32AI007290] Funding Source: NIH RePORTER; National Library of Medicine; National Institute of Allergy and Infectious Diseases [T15LM007033] Funding Source: NIH RePORTER
NR 38
TC 467
Z9 523
U1 0
U2 48
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1076
EP U2
DI 10.1038/nature06559
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600035
PM 18278032
DA 2026-03-09
ER

PT J
AU Gurnett, DA
   Kurth, WS
AF Gurnett, D. A.
   Kurth, W. S.
TI Intense plasma waves at and near the solar wind termination shock
SO NATURE
LA English
DT Article
ID earths bow shock; voyager mission; oscillations; neptune
AB Plasma waves are a characteristic feature of shocks in plasmas, and are produced by non- thermal particle distributions that develop in the shock transition layer. The electric fields of these waves have a key role in dissipating energy in the shock and driving the particle distributions back towards thermal equilibrium(1). Here we report the detection of intense plasma- wave electric fields at the solar wind termination shock. The observations were obtained from the plasma- wave instrument on the Voyager 2 spacecraft(2). The first evidence of the approach to the shock was the detection of upstream electron plasma oscillations on 1 August 2007 at a heliocentric radial distance of 83.4 AU ( 1 AU is the Earth - Sun distance). These narrowband oscillations continued intermittently for about a month until, starting on 31 August 2007 and ending on 1 September 2007, a series of intense bursts of broadband electrostatic waves signalled a series of crossings of the termination shock at a heliocentric radial distance of 83.7 AU. The spectrum of these waves is quantitatively similar to those observed at bow shocks upstream of Jupiter, Saturn, Uranus and Neptune.
C1 [Gurnett, D. A.; Kurth, W. S.] Univ Iowa, Dept Phys & Astron, Iowa City, IA 52242 USA.
C3 University of Iowa
RP Gurnett, DA (corresponding author), Univ Iowa, Dept Phys & Astron, Iowa City, IA 52242 USA.
EM donald-gurnett@uiowa.edu
NR 17
TC 54
Z9 57
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 JUL 3
PY 2008
VL 454
IS 7200
BP 78
EP 80
DI 10.1038/nature07023
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300039
PM 18596804
DA 2026-03-09
ER

PT J
AU Alenghat, T
   Meyers, K
   Mullican, SE
   Leitner, K
   Adeniji-Adele, A
   Avila, J
   Bucan, M
   Ahima, RS
   Kaestner, KH
   Lazar, MA
AF Alenghat, Theresa
   Meyers, Katherine
   Mullican, Shannon E.
   Leitner, Kirstin
   Adeniji-Adele, Adetoun
   Avila, Jacqueline
   Bucan, Maja
   Ahima, Rexford S.
   Kaestner, Klaus H.
   Lazar, Mitchell A.
TI Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology
SO NATURE
LA English
DT Article
ID rev-erb-alpha; thyroid-hormone receptor; gene-expression; glucose-homeostasis; clock; transcription; repression; promoter; deletion; elements
AB Rhythmic changes in histone acetylation at circadian clock genes suggest that temporal modulation of gene expression is regulated by chromatin modifications(1-3). Furthermore, recent studies demonstrate a critical relationship between circadian and metabolic physiology(4-7). The nuclear receptor corepressor 1 (Ncor1) functions as an activating subunit for the chromatin modifying enzyme histone deacetylase 3 (Hdac3)(8). Lack of Ncor1 is incompatible with life, and hence it is unknown whether Ncor1, and particularly its regulation of Hdac3, is critical for adult mammalian physiology(9). Here we show that specific, genetic disruption of the Ncor1-Hdac3 interaction in mice causes aberrant regulation of clock genes and results in abnormal circadian behaviour. These mice are also leaner and more insulin- sensitive owing to increased energy expenditure. Unexpectedly, loss of a functional Ncor1-Hdac3 complex in vivo does not lead to sustained increases in known catabolic genes, but instead significantly alters the oscillatory patterns of several metabolic genes, demonstrating that circadian regulation of metabolism is critical for normal energy balance. These findings indicate that activation of Hdac3 by Ncor1 is a nodal point in the epigenetic regulation of circadian and metabolic physiology.
C1 [Alenghat, Theresa; Meyers, Katherine; Mullican, Shannon E.; Leitner, Kirstin; Avila, Jacqueline; Ahima, Rexford S.; Lazar, Mitchell A.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Philadelphia, PA 19104 USA.
   [Alenghat, Theresa; Meyers, Katherine; Mullican, Shannon E.; Leitner, Kirstin; Avila, Jacqueline; Ahima, Rexford S.; Kaestner, Klaus H.; Lazar, Mitchell A.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
   [Adeniji-Adele, Adetoun; Bucan, Maja; Kaestner, Klaus H.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania
RP Lazar, MA (corresponding author), Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Philadelphia, PA 19104 USA.
EM lazar@mail.med.upenn.edu
FU National Institutes of Health [DK43806]; National Research Training Grant in Developmental Biology; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK050306, P30DK019525, R01DK043806] Funding Source: NIH RePORTER
NR 34
TC 231
Z9 279
U1 1
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 997
EP U88
DI 10.1038/nature07541
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300056
PM 19037247
DA 2026-03-09
ER

PT J
AU Qi, H
   Cannons, JL
   Klauschen, F
   Schwartzberg, PL
   Germain, RN
AF Qi, Hai
   Cannons, Jennifer L.
   Klauschen, Frederick
   Schwartzberg, Pamela L.
   Germain, Ronald N.
TI SAP-controlled T-B cell interactions underlie germinal centre formation
SO NATURE
LA English
DT Article
ID linked lymphoproliferative-disease; humoral immunity; dendritic cells; in-vivo; lymph-nodes; cytokine regulation; antibody-responses; gene-product; activation; infection
AB Generation of long- term antibody- mediated immunity depends on the germinal centre reaction, which requires cooperation between antigen- specific T and B lymphocytes. In human X- linked lymphoproliferative disease and its gene- targeted mouse model, loss- of- function mutations in signalling lymphocyte activation molecule- associated protein ( SAP, encoded by SH2D1a) cause a profound defect in germinal centre formation by an as yet unknown mechanism. Here, using two- photon intravital imaging, we show that SAP deficiency selectively impairs the ability of CD4(+) T cells to stably interact with cognate B cells but not antigen- presenting dendritic cells. This selective defect results in a failure of antigen- specific B cells to receive adequate levels of contact- dependent T- cell help to expand normally, despite Sap(-/-) T cells exhibiting the known characteristics of otherwise competent helper T cells. Furthermore, the lack of stable interactions with B cells renders Sap(-/-) T cells unable to be efficiently recruited to and retained in a nascent germinal centre to sustain the germinal centre reaction. These results offer an explanation for the germinal centre defect due to SAP deficiency and provide new insights into the bi- directional communication between cognate T and B cells in vivo.
C1 [Qi, Hai; Klauschen, Frederick; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Germain, RN (corresponding author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pams@nhgri.nih.gov; rgermain@niaid.nih.gov
FU National Institute of Allergy and Infectious Disease; National Human Genome Research Institute; National Institutes of Health, USA.; National Institute of Allergy and Infectious Diseases [ZIAAI000545] Funding Source: NIH RePORTER
NR 44
TC 515
Z9 631
U1 1
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 764
EP U2
DI 10.1038/nature07345
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900039
PM 18843362
DA 2026-03-09
ER

PT J
AU Weidenspointner, G
   Skinner, G
   Jean, P
   Knödlseder, J
   von Ballmoos, P
   Bignami, G
   Diehl, R
   Strong, AW
   Cordier, B
   Schanne, S
   Winkler, C
AF Weidenspointner, Georg
   Skinner, Gerry
   Jean, Pierre
   Knoedlseder, Juergen
   von Ballmoos, Peter
   Bignami, Giovanni
   Diehl, Roland
   Strong, Andrew W.
   Cordier, Bertrand
   Schanne, Stephane
   Winkler, Christoph
TI An asymmetric distribution of positrons in the Galactic disk revealed by γ-rays
SO NATURE
LA English
DT Article
ID annihilation radiation; sky distribution; inner galaxy; black-hole; milky-way; emission; al-26; search
AB Gamma- ray line radiation at 511 keV is the signature of electron positron annihilation. Such radiation has been known for 30 years to come from the general direction of the Galactic Centre(1), but the origin of the positrons has remained a mystery. Stellar nucleosynthesis(2-4), accreting compact objects(5-8), and even the annihilation of exotic dark- matter particles(9) have all been suggested. Here we report a distinct asymmetry in the 511- keV line emission coming from the inner Galactic disk ( similar to 10-50 degrees from the Galactic Centre). This asymmetry resembles an asymmetry in the distribution of low mass X- ray binaries with strong emission at photon energies >20 keV ('hard' LMXBs), indicating that they may be the dominant origin of the positrons. Although it had long been suspected that electron - positron pair plasmas may exist in X- ray binaries, it was not evident that many of the positrons could escape to lose energy and ultimately annihilate with electrons in the interstellar medium and thus lead to the emission of a narrow 511- keV line. For these models, our result implies that up to a few times 10(41) positrons escape per second from a typical hard LMXB. Positron production at this level from hard LMXBs in the Galactic bulge would reduce ( and possibly eliminate) the need for more exotic explanations, such as those involving dark matter.
C1 [Weidenspointner, Georg; Skinner, Gerry; Jean, Pierre; Knoedlseder, Juergen; von Ballmoos, Peter; Bignami, Giovanni] UPS, CNRS, Ctr Etud Spatiale Rayonnements, Toulouse 4, France.
   [Weidenspointner, Georg; Diehl, Roland; Strong, Andrew W.] Max Planck Inst Extraterr Phys, D-85741 Garching, Germany.
   [Weidenspointner, Georg] MPI Halbleiterlab, D-81739 Munich, Germany.
   [Skinner, Gerry] NASA, CRESST, Greenbelt, MD 20771 USA.
   [Skinner, Gerry] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Skinner, Gerry] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Cordier, Bertrand; Schanne, Stephane] CEA Saclay, SAp, DAPNIA, DSM, F-91191 Gif Sur Yvette, France.
   [Winkler, Christoph] ESA, ESTEC, SCI SA, NL-2201 AZ Noordwijk, Netherlands.
   [Bignami, Giovanni] IUSS, I-27100 Pavia, Italy.
C3 Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Max Planck Society; National Aeronautics & Space Administration (NASA); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland College Park; CEA; Universite Paris Saclay; European Space Agency; European Space Research & Technology Centre; IUSS PAVIA
RP Weidenspointner, G (corresponding author), UPS, CNRS, Ctr Etud Spatiale Rayonnements, BP 44346, Toulouse 4, France.
EM Georg.Weidenspointner@hll.mpg.de
NR 29
TC 183
Z9 201
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 159
EP 162
DI 10.1038/nature06490
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400035
PM 18185581
DA 2026-03-09
ER

PT J
AU Song, C
   Wang, P
   Makse, HA
AF Song, Chaoming
   Wang, Ping
   Makse, Hernan A.
TI A phase diagram for jammed matter
SO NATURE
LA English
DT Article
ID random close packing; spheres; density
AB The problem of finding the most efficient way to pack spheres has a long history, dating back to the crystalline arrays conjectured(1) by Kepler and the random geometries explored(2) by Bernal. Apart from its mathematical interest, the problem has practical relevance(3) in a wide range of fields, from granular processing to fruit packing. There are currently numerous experiments showing that the loosest way to pack spheres ( random loose packing) gives a density of similar to 55 per cent(4-6). On the other hand, the most compact way to pack spheres ( random close packing) results in a maximum density of similar to 64 per cent(2,4,6). Although these values seem to be robust, there is as yet no physical interpretation for them. Here we present a statistical description of jammed states(7) in which random close packing can be interpreted as the ground state of the ensemble of jammed matter. Our approach demonstrates that random packings of hard spheres in three dimensions cannot exceed a density limit of similar to 63.4 per cent. We construct a phase diagram that provides a unified view of the hard- sphere packing problem and illuminates various data, including the random-loose-packed state.
C1 [Song, Chaoming; Wang, Ping; Makse, Hernan A.] CUNY City Coll, Levich Inst, New York, NY 10031 USA.
   [Song, Chaoming; Wang, Ping; Makse, Hernan A.] CUNY City Coll, Dept Phys, New York, NY 10031 USA.
   [Makse, Hernan A.] Univ Fed Ceara, Dept Fis, BR-60451970 Fortaleza, Ceara, Brazil.
C3 City University of New York (CUNY) System; City College of New York (CUNY); City University of New York (CUNY) System; City College of New York (CUNY); Universidade Federal do Ceara
RP Makse, HA (corresponding author), CUNY City Coll, Levich Inst, New York, NY 10031 USA.
EM hmakse@lev.ccny.cuny.edu
NR 28
TC 780
Z9 926
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 MAY 29
PY 2008
VL 453
IS 7195
BP 629
EP 632
DI 10.1038/nature06981
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200038
PM 18509438
DA 2026-03-09
ER

PT J
AU Cauchemez, S
   Valleron, AJ
   Boëlle, PY
   Flahault, A
   Ferguson, NM
AF Cauchemez, Simon
   Valleron, Alain-Jacques
   Boelle, Pierre-Yves
   Flahault, Antoine
   Ferguson, Neil M.
TI Estimating the impact of school closure on influenza transmission from Sentinel data
SO NATURE
LA English
DT Article
ID pandemic influenza; nonpharmaceutical interventions; communicable diseases; us city; surveillance; strategy; household
AB The threat posed by the highly pathogenic H5N1 influenza virus requires public health authorities to prepare for a human pandemic. Although pre-pandemic vaccines and antiviral drugs might significantly reduce illness rates(1,2), their stockpiling is too expensive to be practical for many countries. Consequently, alternative control strategies, based on non-pharmaceutical interventions, are a potentially attractive policy option. School closure is the measure most often considered. The high social and economic costs of closing schools for months make it an expensive and therefore controversial policy, and the current absence of quantitative data on the role of schools during influenza epidemics means there is little consensus on the probable effectiveness of school closure in reducing the impact of a pandemic. Here, from the joint analysis of surveillance data and holiday timing in France, we quantify the role of schools in influenza epidemics and predict the effect of school closure during a pandemic. We show that holidays lead to a 20 - 29% reduction in the rate at which influenza is transmitted to children, but that they have no detectable effect on the contact patterns of adults. Holidays prevent 16 - 18% of seasonal influenza cases (18 - 21% in children). By extrapolation, we find that prolonged school closure during a pandemic might reduce the cumulative number of cases by 13 - 17% (18 - 23% in children) and peak attack rates by up to 39 - 45% (47 - 52% in children). The impact of school closure would be reduced if it proved difficult to maintain low contact rates among children for a prolonged period.
C1 [Cauchemez, Simon; Ferguson, Neil M.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London W2 1PG, England.
   [Valleron, Alain-Jacques; Boelle, Pierre-Yves; Flahault, Antoine] Univ Paris 06, UMR S707, F-75012 Paris, France.
   [Valleron, Alain-Jacques; Boelle, Pierre-Yves; Flahault, Antoine] INSERM, UMR S 707, F-75012 Paris, France.
   [Valleron, Alain-Jacques; Boelle, Pierre-Yves] Hop St Antoine, AP HP, F-75012 Paris, France.
   [Flahault, Antoine] French Sch Publ Hlth EHESP, F-75004 Paris, France.
C3 Imperial College London; Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Sorbonne Universite; Hopital Universitaire Saint-Antoine - APHP
RP Cauchemez, S (corresponding author), Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, Norfolk Pl, London W2 1PG, England.
EM s.cauchemez@imperial.ac.uk
FU Medical Research Council [G0600719B] Funding Source: researchfish
NR 22
TC 517
Z9 591
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 10
PY 2008
VL 452
IS 7188
BP 750
EP U6
DI 10.1038/nature06732
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500045
PM 18401408
DA 2026-03-09
ER

PT J
AU Disson, O
   Grayo, S
   Huillet, E
   Nikitas, G
   Langa-Vives, F
   Dussurget, O
   Ragon, M
   Le Monnier, A
   Babinet, C
   Cossart, P
   Lecuit, M
AF Disson, Olivier
   Grayo, Solene
   Huillet, Eugenie
   Nikitas, Georgios
   Langa-Vives, Francina
   Dussurget, Olivier
   Ragon, Marie
   Le Monnier, Alban
   Babinet, Charles
   Cossart, Pascale
   Lecuit, Marc
TI Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis
SO NATURE
LA English
DT Article
ID surface protein; e-cadherin; monocytogenes; internalin; receptor; entry; model; inib; sufficient; pregnancy
AB The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental barriers, and causes severe maternofetal infections by an unknown mechanism(1). Several studies have helped to characterize the bacterial invasion proteins InlA and InlB(2). However, their respective species specificity has complicated investigations on their in vivo role(3,4). Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock- in mouse line ubiquitously expressing humanized E- cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier.
C1 [Disson, Olivier; Grayo, Solene; Huillet, Eugenie; Nikitas, Georgios; Dussurget, Olivier; Cossart, Pascale; Lecuit, Marc] Inst Pasteur, Grp Microorganismes & Barrieres Hote, Unite Interact Bacteries Cellules, F-75015 Paris, France.
   [Disson, Olivier; Grayo, Solene; Nikitas, Georgios; Lecuit, Marc] Inserm Avenir, U604, F-75015 Paris, France.
   [Grayo, Solene; Ragon, Marie; Le Monnier, Alban; Lecuit, Marc] Inst Pasteur, Ctr Natl Reference Listeria, F-75015 Paris, France.
   [Huillet, Eugenie; Dussurget, Olivier; Cossart, Pascale] INSERM, U604, F-75015 Paris, France.
   [Huillet, Eugenie; Dussurget, Olivier; Cossart, Pascale] INRA, USC2020, F-75015 Paris, France.
   [Langa-Vives, Francina] Inst Pasteur, Ctr Ingn Genet Murine, F-75015 Paris, France.
   [Babinet, Charles] Inst Pasteur, Dev Biol Unit, F-75015 Paris, France.
   [Lecuit, Marc] Univ Paris 05, Ctr Infectiol Necker Pasteur, Serv Malad Infect & Trop, Hop Necker Enfants Malad,Assistance Publ Hop Pari, F-75015 Paris, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); INRAE; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP
RP Lecuit, M (corresponding author), Inst Pasteur, Grp Microorganismes & Barrieres Hote, Unite Interact Bacteries Cellules, F-75015 Paris, France.
EM mlecuit@pasteur.fr
FU Institut Pasteur, Inserm; INRA; Fondation pour la Recherche Medicale; Howard Hughes Medical Institute international research scholar
NR 30
TC 204
Z9 261
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 23
PY 2008
VL 455
IS 7216
BP 1114
EP 1118
DI 10.1038/nature07303
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600046
PM 18806773
DA 2026-03-09
ER

PT J
AU Meyer, JC
   Girit, CO
   Crommie, MF
   Zettl, A
AF Meyer, Jannik C.
   Girit, C. O.
   Crommie, M. F.
   Zettl, A.
TI Imaging and dynamics of light atoms and molecules on graphene
SO NATURE
LA English
DT Article
ID field electron-microscopy; carbon nanotubes; single atoms; defects; surface; resolution; clusters; crystals; oxygen
AB Observing the individual building blocks of matter is one of the primary goals of microscopy. The invention of the scanning tunnelling microscope(1) revolutionized experimental surface science in that atomic- scale features on a solid- state surface could finally be readily imaged. However, scanning tunnelling microscopy has limited applicability due to restrictions in, for example, sample conductivity, cleanliness, and data acquisition rate. An older microscopy technique, that of transmission electron microscopy (TEM)(2,3), has benefited tremendously in recent years from subtle instrumentation advances, and individual heavy ( high-atomic-number) atoms can now be detected by TEM4-7 even when embedded within a semiconductor material(8,9). But detecting an individual low- atomic- number atom, for example carbon or even hydrogen, is still extremely challenging, if not impossible, via conventional TEM owing to the very low contrast of light elements(2,3,10) (-12). Here we demonstrate a means to observe, by conventional TEM, even the smallest atoms and molecules: on a clean single- layer graphene membrane, adsorbates such as atomic hydrogen and carbon can be seen as if they were suspended in free space. We directly image such individual adatoms, along with carbon chains and vacancies, and investigate their dynamics in real time. These techniques open a way to reveal dynamics of more complex chemical reactions or identify the atomic- scale structure of unknown adsorbates. In addition, the study of atomic- scale defects in graphene may provide insights for nanoelectronic applications of this interesting material.
C1 [Meyer, Jannik C.; Girit, C. O.; Crommie, M. F.; Zettl, A.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Meyer, Jannik C.; Girit, C. O.; Crommie, M. F.; Zettl, A.] 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; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Meyer, JC (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
EM email@jannikmeyer.de; azettl@berkeley.edu
NR 30
TC 443
Z9 515
U1 3
U2 428
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 319
EP 322
DI 10.1038/nature07094
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300035
PM 18633414
DA 2026-03-09
ER

PT J
AU Saito, T
   Owen, DM
   Jiang, FG
   Marcotrigiano, J
   Gale, M
AF Saito, Takeshi
   Owen, David M.
   Jiang, Fuguo
   Marcotrigiano, Joseph
   Gale, Michael, Jr.
TI Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA
SO NATURE
LA English
DT Article
ID antiviral responses; gene-expression; replication; translation; activation; infection; ribosome; helicase; elements; protein
AB Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs)(1). Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide(2). Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-alpha/beta and antiviral/interferon-stimulated genes (ISGs) that limit infection(3-10). Here we identify the polyuridine motif of the HCV genome 3 ' non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells(8). 5 ' terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response in vivo, and triggered interferon and ISG expression to suppress HCV infection in vitro. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP-RIG-I interaction that could be used as an immune adjuvant for vaccine and immunotherapy approaches.
C1 [Saito, Takeshi; Owen, David M.; Gale, Michael, Jr.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
   [Owen, David M.] Univ Texas Dallas, SW Med Ctr, Dept Microbiol, Dallas, TX 75235 USA.
   [Jiang, Fuguo; Marcotrigiano, Joseph] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
C3 University of Washington; University of Washington Seattle; University of Texas System; University of Texas Southwestern Medical Center; University of Texas Dallas; Rutgers University System; Rutgers University New Brunswick
RP Gale, M (corresponding author), Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
EM mgale@u.washington.edu
FU NIAID NIH HHS [R56 AI060389, R01AI060389, U19AI40035, N01 AI040035, R01 AI060389, U19 AI040035] Funding Source: Medline; NIDA NIH HHS [R01DA021353, R01 DA024563] Funding Source: Medline; Wellcome Trust Funding Source: Medline
NR 30
TC 605
Z9 766
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 24
PY 2008
VL 454
IS 7203
BP 523
EP 527
DI 10.1038/nature07106
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300053
PM 18548002
DA 2026-03-09
ER

PT J
AU White, RS
   Smith, LK
   Roberts, AW
   Christie, PAF
   Kusznir, NJ
AF White, R. S.
   Smith, L. K.
   Roberts, A. W.
   Christie, P. A. F.
   Kusznir, N. J.
TI Lower-crustal intrusion on the North Atlantic continental margin
SO NATURE
LA English
DT Article
ID iceland mantle plume; greenland margin; refraction; thickness; reflectors; dimensions; magmatism; accretion; rift
AB When continents break apart, the rifting is sometimes accompanied by the production of large volumes of molten rock(1-3). The total melt volume, however, is uncertain, because only part of it has erupted at the surface. Furthermore, the cause of the magmatism is still disputed - specifically, whether or not it is due to increased mantle temperatures. We recorded deep- penetration normal-incidence and wide- angle seismic profiles across the Faroe and Hatton Bank volcanic margins in the northeast Atlantic. Here we show that near the Faroe Islands, for every 1 km along strike, 360 - 400 km(3) of basalt is extruded, while 540 - 600 km(3) is intruded into the continent - ocean transition. We find that lower- crustal intrusions are focused mainly into a narrow zone similar to 50 km wide on the transition, although extruded basalts flow more than 100 km from the rift. Seismic profiles show that the melt is intruded into the lower crust as sills, which cross- cut the continental fabric, rather than as an 'underplate' of 100 per cent melt, as has often been assumed. Evidence from the measured seismic velocities and from igneous thicknesses are consistent with the dominant control on melt production being increased mantle temperatures, with no requirement for either significant active small- scale mantle convection under the rift or the presence of fertile mantle at the time of continental break- up, as has previously been suggested for the North Atlantic Ocean(4-6).
C1 [White, R. S.; Smith, L. K.; Roberts, A. W.] Univ Cambridge, Bullard Labs, Cambridge CB3 0EZ, England.
   [Christie, P. A. F.] Schlumberger Cambridge Res Ltd, Cambridge CB3 0EL, England.
   [Kusznir, N. J.] Univ Liverpool, Dept Earth Sci, Liverpool L69 3BX, Merseyside, England.
C3 University of Cambridge; Schlumberger; University of Liverpool
RP White, RS (corresponding author), Univ Cambridge, Bullard Labs, Madingley Rd, Cambridge CB3 0EZ, England.
EM rwhite@esc.cam.ac.uk
FU Natural Environment Research Council [NER/T/S/2000/01021] Funding Source: researchfish
NR 33
TC 279
Z9 298
U1 1
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 460
EP U6
DI 10.1038/nature06687
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300029
PM 18368115
DA 2026-03-09
ER

PT J
AU Rasmussen, B
   Fletcher, IR
   Brocks, JJ
   Kilburn, MR
AF Rasmussen, Birger
   Fletcher, Ian R.
   Brocks, Jochen J.
   Kilburn, Matt R.
TI Reassessing the first appearance of eukaryotes and cyanobacteria
SO NATURE
LA English
DT Article
ID isotopic ratio measurements; proterozoic mcarthur basin; mount bruce supergroup; great oxidation event; atmospheric oxygen; molecular fossils; western-australia; northern australia; petroleum geology; fluid inclusions
AB The evolution of oxygenic photosynthesis had a profound impact on the Earth's surface chemistry, leading to a sharp rise in atmospheric oxygen between 2.45 and 2.32 billion years (Gyr) ago(1,2) and the onset of extreme ice ages(3). The oldest widely accepted evidence for oxygenic photosynthesis has come from hydrocarbons extracted from similar to 2.7-Gyr-old shales in the Pilbara Craton, Australia, which contain traces of biomarkers ( molecular fossils) indicative of eukaryotes and suggestive of oxygen- producing cyanobacteria(4-7). The soluble hydrocarbons were interpreted to be indigenous and syngenetic despite metamorphic alteration and extreme enrichment ( 10-20 parts per thousand) of (13)C relative to bulk sedimentary organic matter(5,8). Here we present micrometre-scale, in situ (13)C/(12)C measurements of pyrobitumen ( thermally altered petroleum) and kerogen from these metamorphosed shales, including samples that originally yielded biomarkers. Our results show that both kerogen and pyrobitumen are strongly depleted in (13)C, indicating that indigenous petroleum is 10-20 parts per thousand lighter than the extracted hydrocarbons(5). These results are inconsistent with an indigenous origin for the biomarkers. Whatever their origin, the biomarkers must have entered the rock after peak metamorphism 2.2 Gyr ago(9) and thus do not provide evidence for the existence of eukaryotes and cyanobacteria in the Archaeaneon. The oldest fossil evidence for eukaryotes and cyanobacteria therefore reverts to 1.78-1.68 Gyr ago and similar to 2.15 Gyr ago(10,11), respectively. Our results eliminate the evidence for oxygenic photosynthesis similar to 2.7 Gyr ago and exclude previous biomarker evidence for a long delay (similar to 300 million years) between the appearance of oxygen- producing cyanobacteria and the rise in atmospheric oxygen 2.45-2.32 Gyr ago(1).
C1 [Rasmussen, Birger; Fletcher, Ian R.] Curtin Univ Technol, Dept Appl Geol, Bentley, WA 6102, Australia.
   [Brocks, Jochen J.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
   [Brocks, Jochen J.] Australian Natl Univ, Ctr Macroevolut & Macroecol, Canberra, ACT 0200, Australia.
   [Kilburn, Matt R.] Univ Western Australia, Ctr Microscopy Characterisat & Anal, Nedlands, WA 6009, Australia.
C3 Curtin University; Australian National University; Australian National University; University of Western Australia
RP Rasmussen, B (corresponding author), Curtin Univ Technol, Dept Appl Geol, Kent St, Bentley, WA 6102, Australia.
EM B.Rasmussen@curtin.edu.au
FU Australian Microscopy and Microanalysis Research Facility at the Centre for Microscopy, Characterisation and Analysis; University of Western Australia; University, State and Commonwealth Governments
NR 33
TC 414
Z9 490
U1 3
U2 264
PU 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 23
PY 2008
VL 455
IS 7216
BP 1101
EP U9
DI 10.1038/nature07381
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600043
PM 18948954
DA 2026-03-09
ER

PT J
AU Isalan, M
   Lemerle, C
   Michalodimitrakis, K
   Horn, C
   Beltrao, P
   Raineri, E
   Garriga-Canut, M
   Serrano, L
AF Isalan, Mark
   Lemerle, Caroline
   Michalodimitrakis, Konstantinos
   Horn, Carsten
   Beltrao, Pedro
   Raineri, Emanuele
   Garriga-Canut, Mireia
   Serrano, Luis
TI Evolvability and hierarchy in rewired bacterial gene networks
SO NATURE
LA English
DT Article
ID escherichia-coli; regulatory network; transcriptional regulation; operon organization; biofilm formation; growth; expression; tolerance; rpos; phenotypes
AB Sequencing DNA from several organisms has revealed that duplication and drift of existing genes have primarily moulded the contents of a given genome. Though the effect of knocking out or overexpressing a particular gene has been studied in many organisms, no study has systematically explored the effect of adding new links in a biological network. To explore network evolvability, we constructed 598 recombinations of promoters ( including regulatory regions) with different transcription or sigma-factor genes in Escherichia coli, added over a wild- type genetic background. Here we show that similar to 95% of new networks are tolerated by the bacteria, that very few alter growth, and that expression level correlates with factor position in the wild- type network hierarchy. Most importantly, we find that certain networks consistently survive over the wild type under various selection pressures. Therefore new links in the network are rarely a barrier for evolution and can even confer a fitness advantage.
C1 [Isalan, Mark; Michalodimitrakis, Konstantinos; Raineri, Emanuele; Garriga-Canut, Mireia; Serrano, Luis] UPF, CRG, EMBL, CRG Syst Biol, Barcelona 08003, Spain.
   [Lemerle, Caroline; Horn, Carsten; Beltrao, Pedro] European Mol Biol Lab, D-69117 Heidelberg, Germany.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL)
RP Isalan, M (corresponding author), UPF, CRG, EMBL, CRG Syst Biol, Barcelona 08003, Spain.
EM isalan@crg.es
FU Wellcome Trust [066543] Funding Source: Medline
NR 45
TC 242
Z9 293
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 17
PY 2008
VL 452
IS 7189
BP 840
EP U2
DI 10.1038/nature06847
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000041
PM 18421347
DA 2026-03-09
ER

PT J
AU Houlton, BZ
   Wang, YP
   Vitousek, PM
   Field, CB
AF Houlton, Benjamin Z.
   Wang, Ying-Ping
   Vitousek, Peter M.
   Field, Christopher B.
TI A unifying framework for dinitrogen fixation in the terrestrial biosphere
SO NATURE
LA English
DT Article
ID symbiotic nitrogen-fixation; soil; phosphorus; forest; availability; temperature; acquisition; limitation; phosphatase; ecosystems
AB Dinitrogen ( N(2)) fixation is widely recognized as an important process in controlling ecosystem responses to global environmental change, both today(1) and in the past(2); however, significant discrepancies exist between theory and observations of patterns of N(2) fixation across major sectors of the land biosphere. A question remains as to why symbiotic N(2)- fixing plants are more abundant in vast areas of the tropics than in many of the mature forests that seem to be nitrogen- limited in the temperate and boreal zones(3). Here we present a unifying framework for terrestrial N(2) fixation that can explain the geographic occurrence of N(2) fixers across diverse biomes and at the global scale. By examining trade- offs inherent in plant carbon, nitrogen and phosphorus capture, we find a clear advantage to symbiotic N(2) fixers in phosphorus-limited tropical savannas and lowland tropical forests. The ability of N(2) fixers to invest nitrogen into phosphorus acquisition seems vital to sustained N(2) fixation in phosphorus- limited tropical ecosystems. In contrast, modern- day temperatures seem to constrain N(2) fixation rates and N(2)- fixing species from mature forests in the high latitudes. We propose that an analysis that couples biogeochemical cycling and biophysical mechanisms is sufficient to explain the principal geographical patterns of symbiotic N(2) fixation on land, thus providing a basis for predicting the response of nutrient- limited ecosystems to climate change and increasing atmospheric CO(2).
C1 [Houlton, Benjamin Z.; Vitousek, Peter M.] Stanford Univ, Stanford, CA 94305 USA.
   [Houlton, Benjamin Z.; Field, Christopher B.] Carnegie Inst Washington, Dept Global Ecol, Stanford, CA 94305 USA.
   [Wang, Ying-Ping] CSIRO Marine & Atmospher Res, Aspendale, Vic 3195, Australia.
   [Wang, Ying-Ping] Ctr Australian Weather & Climate Res, Aspendale, Vic 3195, Australia.
C3 Stanford University; Carnegie Institution for Science; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Commonwealth Scientific & Industrial Research Organisation (CSIRO)
RP Houlton, BZ (corresponding author), Univ Calif Davis, Dept Land Air & Water Resources, Davis, CA 95616 USA.
EM bzhoulton@ucdavis.edu
NR 41
TC 651
Z9 788
U1 15
U2 521
PU 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 17
PY 2008
VL 454
IS 7202
BP 327
EP U34
DI 10.1038/nature07028
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300037
PM 18563086
DA 2026-03-09
ER

PT J
AU Wang, XM
   Harris, RE
   Bayston, LJ
   Ashe, HL
AF Wang, Xiaomeng
   Harris, Robin E.
   Bayston, Laura J.
   Ashe, Hilary L.
TI Type IV collagens regulate BMP signalling in Drosophila
SO NATURE
LA English
DT Article
ID bone morphogenetic proteins; germline stem-cells; basement-membrane; dpp; gradient; embryo; sog; differentiation; stimulation; binding
AB Dorsal-ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic ( Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved.
C1 [Wang, Xiaomeng; Harris, Robin E.; Bayston, Laura J.; Ashe, Hilary L.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
C3 University of Manchester
RP Ashe, HL (corresponding author), Univ Manchester, Fac Life Sci, Oxford Rd, Manchester M13 9PT, Lancs, England.
EM hilary.ashe@manchester.ac.uk
FU BBSRC project grant; Biotechnology and Biological Sciences Research Council [BBS/B/11672] Funding Source: researchfish
NR 37
TC 279
Z9 356
U1 0
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 72
EP U49
DI 10.1038/nature07214
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200038
PM 18701888
DA 2026-03-09
ER

PT J
AU Park, SY
   Lytton-Jean, AKR
   Lee, B
   Weigand, S
   Schatz, GC
   Mirkin, CA
AF Park, Sung Yong
   Lytton-Jean, Abigail K. R.
   Lee, Byeongdu
   Weigand, Steven
   Schatz, George C.
   Mirkin, Chad A.
TI DNA-programmable nanoparticle crystallization
SO NATURE
LA English
DT Article
ID dissipative particle dynamics; asymmetric functionalization; colloidal crystals; gold nanoparticles; building-blocks; oligonucleotides; superlattices
AB It was first shown(1,2) more than ten years ago that DNA oligonucleotides can be attached to gold nanoparticles rationally to direct the formation of larger assemblies. Since then, oligonucleotide-functionalized nanoparticles have been developed into powerful diagnostic tools(3,4) for nucleic acids and proteins, and into intracellular probes(5) and gene regulators(6). In contrast, the conceptually simple yet powerful idea that functionalized nanoparticles might serve as basic building blocks that can be rationally assembled through programmable base- pairing interactions into highly ordered macroscopic materials remains poorly developed. So far, the approach has mainly resulted in polymerization, with modest control over the placement of, the periodicity in, and the distance between particles within the assembled material. That is, most of the materials obtained thus far are best classified as amorphous polymers(7-16), although a few examples of colloidal crystal formation exist(8,16). Here, we demonstrate that DNA can be used to control the crystallization of nanoparticle - oligonucleotide conjugates to the extent that different DNA sequences guide the assembly of the same type of inorganic nanoparticle into different crystalline states. We show that the choice of DNA sequences attached to the nanoparticle building blocks, the DNA linking molecules and the absence or presence of a non- bonding single- base flexor can be adjusted so that gold nanoparticles assemble into micrometresized face- centred- cubic or body- centred- cubic crystal structures. Our findings thus clearly demonstrate that synthetically programmable colloidal crystallization is possible, and that a single-component system can be directed to form different structures.
C1 [Park, Sung Yong; Lytton-Jean, Abigail K. R.; Schatz, George C.; Mirkin, Chad A.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
   [Park, Sung Yong; Lytton-Jean, Abigail K. R.; Schatz, George C.; Mirkin, Chad A.] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA.
   [Lee, Byeongdu] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA.
   [Weigand, Steven] Northwestern Univ, DND CAT Synchrotron Res Ctr, Argonne, IL 60439 USA.
C3 Northwestern University; Northwestern University; United States Department of Energy (DOE); Argonne National Laboratory; Northwestern University
RP Mirkin, CA (corresponding author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM chadnano@northwestern.edu
NR 30
TC 1375
Z9 1686
U1 6
U2 798
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 553
EP 556
DI 10.1038/nature06508
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900037
PM 18235497
DA 2026-03-09
ER

PT J
AU Loulergue, L
   Schilt, A
   Spahni, R
   Masson-Delmotte, V
   Blunier, T
   Lemieux, B
   Barnola, JM
   Raynaud, D
   Stocker, TF
   Chappellaz, J
AF Loulergue, Laetitia
   Schilt, Adrian
   Spahni, Renato
   Masson-Delmotte, Valerie
   Blunier, Thomas
   Lemieux, Benedicte
   Barnola, Jean-Marc
   Raynaud, Dominique
   Stocker, Thomas F.
   Chappellaz, Jerome
TI Orbital and millennial-scale features of atmospheric CH4 over the past 800,000 years
SO NATURE
LA English
DT Article
ID climate variability; terrestrial plants; methane emissions; ice cores; sensitivity; greenland
AB Atmospheric methane is an important greenhouse gas and a sensitive indicator of climate change and millennial-scale temperature variability(1). Its concentrations over the past 650,000 years have varied between similar to 350 and similar to 800 parts per 10 9 by volume ( p. p. b. v.) during glacial and interglacial periods, respectively(2). In comparison, present-day methane levels of,1,770 p. p. b. v. have been reported(3). Insights into the external forcing factors and internal feedbacks controlling atmospheric methane are essential for predicting the methane budget in a warmer world(3). Here we present a detailed atmospheric methane record from the EPICA Dome C ice core that extends the history of this greenhouse gas to 800,000 yr before present. The average time resolution of the new data is similar to 380 yr and permits the identification of orbital and millennial-scale features. Spectral analyses indicate that the long-term variability in atmospheric methane levels is dominated by,100,000 yr glacial - interglacial cycles up to,400,000 yr ago with an increasing contribution of the precessional component during the four more recent climatic cycles. We suggest that changes in the strength of tropical methane sources and sinks ( wetlands, atmospheric oxidation), possibly influenced by changes in monsoon systems and the position of the intertropical convergence zone, controlled the atmospheric methane budget, with an additional source input during major terminations as the retreat of the northern ice sheet allowed higher methane emissions from extending periglacial wetlands. Millennial-scale changes in methane levels identified in our record as being associated with Antarctic isotope maxima events(1,4) are indicative of ubiquitous millennial-scale temperature variability during the past eight glacial cycles.
C1 [Loulergue, Laetitia; Lemieux, Benedicte; Barnola, Jean-Marc; Raynaud, Dominique; Chappellaz, Jerome] Univ Grenoble 1, CNRS, Lab Glaciol & Geophys Environm, F-38402 St Martin Dheres, France.
   [Schilt, Adrian; Spahni, Renato; Blunier, Thomas; Stocker, Thomas F.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
   [Masson-Delmotte, Valerie] Univ Versailles St Quentin, Lab Sci Climat & Environm, Inst Pierre Simon Laplace, CE Saclay,CEA CNRS, F-91191 Gif Sur Yvette, France.
C3 Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); University of Bern; Universite Paris Saclay; CEA
RP Chappellaz, J (corresponding author), Univ Grenoble 1, CNRS, Lab Glaciol & Geophys Environm, 54 Rue Moliere, F-38402 St Martin Dheres, France.
EM jerome@lgge.obs.ujf-grenoble.fr
NR 27
TC 745
Z9 869
U1 4
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 MAY 15
PY 2008
VL 453
IS 7193
BP 383
EP 386
DI 10.1038/nature06950
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400050
PM 18480822
DA 2026-03-09
ER

PT J
AU Redondo, P
   Prieto, J
   Muñoz, IG
   Alibés, A
   Stricher, F
   Serrano, L
   Cabaniols, JP
   Daboussi, F
   Arnould, S
   Perez, C
   Duchateau, P
   Pâques, F
   Blanco, FJ
   Montoya, G
AF Redondo, Pilar
   Prieto, Jesus
   Munoz, Ines G.
   Alibes, Andreu
   Stricher, Francois
   Serrano, Luis
   Cabaniols, Jean-Pierre
   Daboussi, Fayza
   Arnould, Sylvain
   Perez, Christophe
   Duchateau, Philippe
   Paques, Frederic
   Blanco, Francisco J.
   Montoya, Guillermo
TI Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases
SO NATURE
LA English
DT Article
ID zinc-finger nucleases; double-strand breaks; homing endonucleases; mammalian-cells; homologous recombination; directed evolution; site-specificity; cre recombinase; gene correction; i-crei
AB Xeroderma pigmentosum is a monogenic disease characterized by hypersensitivity to ultraviolet light. The cells of xeroderma pigmentosum patients are defective in nucleotide excision repair, limiting their capacity to eliminate ultraviolet- induced DNA damage, and resulting in a strong predisposition to develop skin cancers(1). The use of rare cutting DNA endonucleases - such as homing endonucleases, also known as meganucleases - constitutes one possible strategy for repairing DNA lesions. Homing endonucleases have emerged as highly specific molecular scalpels that recognize and cleave DNA sites, promoting efficient homologous gene targeting through double- strand- break- induced homologous recombination. Here we describe two engineered heterodimeric derivatives of the homing endonuclease I- CreI, produced by a semi- rational approach. These two molecules - Amel3 - Amel4 and Ini3 - Ini4 cleave DNA from the human XPC gene ( xeroderma pigmentosum group C), in vitro and in vivo. Crystal structures of the I- CreI variants complexed with intact and cleaved XPC target DNA suggest that the mechanism of DNA recognition and cleavage by the engineered homing endonucleases is similar to that of the wild- type I- CreI. Furthermore, these derivatives induced high levels of specific gene targeting in mammalian cells while displaying no obvious genotoxicity. Thus, homing endonucleases can be designed to recognize and cleave the DNA sequences of specific genes, opening up new possibilities for genome engineering and gene therapy in xeroderma pigmentosum patients whose illness can be treated ex vivo.
C1 [Redondo, Pilar; Munoz, Ines G.; Montoya, Guillermo] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, Macromol Crystallog Grp, Madrid 28029, Spain.
   [Prieto, Jesus; Blanco, Francisco J.] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, NMR Grp, Madrid 28029, Spain.
   [Alibes, Andreu; Stricher, Francois; Serrano, Luis] UPF, European Mol Biol Lab, CRG Syst Biol Unit, CRG, Barcelona 08003, Spain.
   [Serrano, Luis] ICREA, F-93235 Romainville, France.
   [Cabaniols, Jean-Pierre; Daboussi, Fayza; Arnould, Sylvain; Perez, Christophe; Duchateau, Philippe; Paques, Frederic] CELLECTIS SA, F-93235 Romainville, France.
C3 Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); European Molecular Biology Laboratory (EMBL); Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG)
RP Blanco, FJ (corresponding author), CIC bioGUNE, Parque Tecnol Vizcaya,Edificio 800, Derio 48160, Spain.
EM fblanco@cicbiogune.es; gmontoya@cnio.es
FU EU MEGATOOL [LSHG-CT-2006-037226]; CRG-Novartis fellowship
NR 33
TC 140
Z9 166
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 NOV 6
PY 2008
VL 456
IS 7218
BP 107
EP U8
DI 10.1038/nature07343
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000050
PM 18987743
DA 2026-03-09
ER

PT J
AU Warner, DA
   Shine, R
AF Warner, D. A.
   Shine, R.
TI The adaptive significance of temperature-dependent sex determination in a reptile
SO NATURE
LA English
DT Article
ID gecko eublepharis-macularius; lizard; estradiol; evolution; ecology; growth
AB Understanding the mechanisms that determine an individual's sex remains a primary challenge for evolutionary biology. Chromosome- based systems ( genotypic sex determination) that generate roughly equal numbers of sons and daughters accord with theory(1), but the adaptive significance of environmental sex determination ( that is, when embryonic environmental conditions determine offspring sex, ESD) is a major unsolved problem(2,3). Theoretical models predict that selection should favour ESD over genotypic sex determination when the developmental environment differentially influences male versus female fitness ( that is, the Charnov - Bull model)(4), but empirical evidence for this hypothesis remains elusive in amniote vertebrates - the clade in which ESD is most prevalent(5). Here we provide the first substantial empirical support for this model by showing that incubation temperatures influence reproductive success of males differently than that of females in a short- lived lizard ( Amphibolurus muricatus, Agamidae) with temperature- dependent sex determination. We incubated eggs at a variety of temperatures, and de- confounded sex and incubation temperature by using hormonal manipulations to embryos. We then raised lizards in field enclosures and quantified their lifetime reproductive success. Incubation temperature affected reproductive success differently in males versus females in exactly the way predicted by theory: the fitness of each sex was maximized by the incubation temperature that produces that sex. Our results
C1 [Warner, D. A.; Shine, R.] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia.
C3 University of Sydney
RP Warner, DA (corresponding author), Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA 50011 USA.
EM dwarner@iastate.edu
NR 25
TC 272
Z9 327
U1 5
U2 266
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 566
EP U5
DI 10.1038/nature06519
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900040
PM 18204437
DA 2026-03-09
ER

PT J
AU Branzei, D
   Vanoli, F
   Foiani, M
AF Branzei, Dana
   Vanoli, Fabio
   Foiani, Marco
TI SUMOylation regulates Rad18-mediated template switch
SO NATURE
LA English
DT Article
ID defective postreplication repair; uv-damaged dna; saccharomyces-cerevisiae; homologous recombination; genomic instability; group genes; ubiquitin; replication; helicase; rad18
AB Replication by template switch is thought to mediate DNA damage- bypass and fillings of gaps. Gap- filling repair requires homologous recombination as well as Rad18- and Rad5- mediated proliferating cell nuclear antigen ( PCNA) polyubiquitylation. However, it is unclear whether these processes are coordinated, and the physical evidence for Rad18 - Rad5- dependent template switch at replication forks is still elusive. Here we show, using genetic and physical approaches, that in budding yeast ( Saccharomyces cerevisiae) Rad18 is required for the formation of X- shaped sister chromatid junctions ( SCJs) at damaged replication forks through a process involving PCNA polyubiquitylation and the ubiquitin- conjugating enzymes Mms2 and Ubc13. The Rad18 - Mms2- mediated damage- bypass through SCJs requires the small ubiquitin- like modifier ( SUMO)- conjugating enzyme Ubc9 and SUMOylated PCNA, and is coordinated with Rad51- dependent recombination events. We propose that the Rad18 - Rad5 - Mms2- dependent SCJs represent template switch events. Altogether, our results unmask a role for PCNA ubiquitylation and SUMOylation pathways in promoting transient damage- induced replication- coupled recombination events involving sister chromatids at replication forks.
C1 [Branzei, Dana; Vanoli, Fabio; Foiani, Marco] IFOM IEO, FIRC Inst Mol Oncol Fdn, I-20139 Milan, Italy.
   [Foiani, Marco] Univ Milan, Dipartimento Sci Biomol & Biotecnol, I-20133 Milan, Italy.
C3 IRCCS European Institute of Oncology (IEO); IFOM - FIRC Institute of Molecular Oncology; University of Milan
RP Branzei, D (corresponding author), IFOM IEO, FIRC Inst Mol Oncol Fdn, Via Adamello 16, I-20139 Milan, Italy.
EM dana.branzei@ifom-ieo-campus.it
FU Associazione Italiana per la Ricerca sul Cancro; Association for International Cancer Research; European Community GENICA; European Community DNA Repair; Telethon; MIUR; Ministry of Health; Buzzati-Traverso foundation
NR 50
TC 226
Z9 272
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 DEC 18
PY 2008
VL 456
IS 7224
BP 915
EP 920
DI 10.1038/nature07587
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300037
PM 19092928
DA 2026-03-09
ER

PT J
AU Racusin, JL
   Karpov, SV
   Sokolowski, M
   Granot, J
   Wu, XF
   Pal'shin, V
   Covino, S
   van der Horst, AJ
   Oates, SR
   Schady, P
   Smith, RJ
   Cummings, J
   Starling, RLC
   Piotrowski, LW
   Zhang, B
   Evans, PA
   Holland, ST
   Malek, K
   Page, MT
   Vetere, L
   Margutti, R
   Guidorzi, C
   Kamble, AP
   Curran, PA
   Beardmore, A
   Kouveliotou, C
   Mankiewicz, L
   Melandri, A
   O'Brien, PT
   Page, KL
   Piran, T
   Tanvir, NR
   Wrochna, G
   Aptekar, RL
   Barthelmy, S
   Bartolini, C
   Beskin, GM
   Bondar, S
   Bremer, M
   Campana, S
   Castro-Tirado, A
   Cucchiara, A
   Cwiok, M
   D'Avanzo, P
   D'Elia, V
   Della Valle, M
   Postigo, AD
   Dominik, W
   Falcone, A
   Fiore, F
   Fox, DB
   Frederiks, DD
   Fruchter, AS
   Fugazza, D
   Garrett, MA
   Gehrels, N
   Golenetskii, S
   Gomboc, A
   Gorosabel, J
   Greco, G
   Guarnieri, A
   Immler, S
   Jelinek, M
   Kasprowicz, G
   La Parola, V
   Levan, AJ
   Mangano, V
   Mazets, EP
   Molinari, E
   Moretti, A
   Nawrocki, K
   Oleynik, PP
   Osborne, JP
   Pagani, C
   Pandey, SB
   Paragi, Z
   Perri, M
   Piccioni, A
   Ramirez-Ruiz, E
   Roming, PWA
   Steele, IA
   Strom, RG
   Testa, V
   Tosti, G
   Ulanov, MV
   Wiersema, K
   Wijers, RAMJ
   Winters, JM
   Zarnecki, AF
   Zerbi, F
   Mészáros, P
   Chincarini, G
   Burrows, DN
AF Racusin, J. L.
   Karpov, S. V.
   Sokolowski, M.
   Granot, J.
   Wu, X. F.
   Pal'shin, V.
   Covino, S.
   van der Horst, A. J.
   Oates, S. R.
   Schady, P.
   Smith, R. J.
   Cummings, J.
   Starling, R. L. C.
   Piotrowski, L. W.
   Zhang, B.
   Evans, P. A.
   Holland, S. T.
   Malek, K.
   Page, M. T.
   Vetere, L.
   Margutti, R.
   Guidorzi, C.
   Kamble, A. P.
   Curran, P. A.
   Beardmore, A.
   Kouveliotou, C.
   Mankiewicz, L.
   Melandri, A.
   O'Brien, P. T.
   Page, K. L.
   Piran, T.
   Tanvir, N. R.
   Wrochna, G.
   Aptekar, R. L.
   Barthelmy, S.
   Bartolini, C.
   Beskin, G. M.
   Bondar, S.
   Bremer, M.
   Campana, S.
   Castro-Tirado, A.
   Cucchiara, A.
   Cwiok, M.
   D'Avanzo, P.
   D'Elia, V.
   Della Valle, M.
   de Ugarte Postigo, A.
   Dominik, W.
   Falcone, A.
   Fiore, F.
   Fox, D. B.
   Frederiks, D. D.
   Fruchter, A. S.
   Fugazza, D.
   Garrett, M. A.
   Gehrels, N.
   Golenetskii, S.
   Gomboc, A.
   Gorosabel, J.
   Greco, G.
   Guarnieri, A.
   Immler, S.
   Jelinek, M.
   Kasprowicz, G.
   La Parola, V.
   Levan, A. J.
   Mangano, V.
   Mazets, E. P.
   Molinari, E.
   Moretti, A.
   Nawrocki, K.
   Oleynik, P. P.
   Osborne, J. P.
   Pagani, C.
   Pandey, S. B.
   Paragi, Z.
   Perri, M.
   Piccioni, A.
   Ramirez-Ruiz, E.
   Roming, P. W. A.
   Steele, I. A.
   Strom, R. G.
   Testa, V.
   Tosti, G.
   Ulanov, M. V.
   Wiersema, K.
   Wijers, R. A. M. J.
   Winters, J. M.
   Zarnecki, A. F.
   Zerbi, F.
   Meszaros, P.
   Chincarini, G.
   Burrows, D. N.
TI Broadband observations of the naked-eye γ-ray burst GRB 080319B
SO NATURE
LA English
DT Article
ID afterglow emission; optical-emission; 2-component jet; reverse shock; light curves; grb 990123; telescope; spectra; models; flash
AB Long- duration gamma-ray bursts ( GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of massive stars. Previous early optical observations of even the most exceptional GRBs ( 990123 and 030329) lacked both the temporal resolution to probe the optical flash in detail and the accuracy needed to trace the transition from the prompt emission within the outflow to external shocks caused by interaction with the progenitor environment. Here we report observations of the extraordinarily bright prompt optical and gamma-ray emission of GRB 080319B that provide diagnostics within seconds of its formation, followed by broadband observations of the afterglow decay that continued for weeks. We show that the prompt emission stems from a single physical region, implying an extremely relativistic outflow that propagates within the narrow inner core of a two- component jet.
C1 [Racusin, J. L.; Wu, X. F.; Vetere, L.; Cucchiara, A.; Falcone, A.; Fox, D. B.; Pagani, C.; Roming, P. W. A.; Meszaros, P.; Burrows, D. N.] Penn State Univ, Dept Astron & Astrophys, University Pk, PA 16802 USA.
   [Karpov, S. V.; Beskin, G. M.] Russian Acad Sci, Special Astrophys Observ, Nizhnii Arkhyz 369167, Russia.
   [Sokolowski, M.; Wrochna, G.; Nawrocki, K.] Soltan Inst Nucl Studies, PL-05400 Otwock, Poland.
   [Granot, J.] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.
   [Wu, X. F.] Chinese Acad Sci, Purple Mt Observ, Nanjing 210008, Peoples R China.
   [Pal'shin, V.; Aptekar, R. L.; Frederiks, D. D.; Golenetskii, S.; Mazets, E. P.; Oleynik, P. P.; Ulanov, M. V.] AF Ioffe Phys Tech Inst, Expt Astrophys Lab, St Petersburg 194021, Russia.
   [Covino, S.; Guidorzi, C.; Campana, S.; D'Avanzo, P.; Fugazza, D.; Molinari, E.; Moretti, A.; Zerbi, F.; Chincarini, G.] INAF Osserv Astron Brera, I-23807 Merate, LC, Italy.
   [Oates, S. R.; Schady, P.; Page, M. T.] UCL, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Smith, R. J.; Guidorzi, C.; Melandri, A.; Steele, I. A.] Liverpool John Moores Univ, Astrophys Res Inst, Birkenhead CH41 1LD, Merseyside, England.
   [Cummings, J.; Barthelmy, S.; Gehrels, N.] NASA, Goddard Space Flight Ctr, Astrophys Sci Div, Greenbelt, MD 20771 USA.
   [Starling, R. L. C.; Evans, P. A.; Beardmore, A.; O'Brien, P. T.; Page, K. L.; Tanvir, N. R.; Osborne, J. P.; Wiersema, K.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Piotrowski, L. W.; Cwiok, M.; Dominik, W.; Zarnecki, A. F.] Univ Warsaw, Inst Expt Phys, PL-00681 Warsaw, Poland.
   [Zhang, B.] Univ Nevada, Dept Phys & Astron, Las Vegas, NV 89154 USA.
   [Holland, S. T.; Immler, S.] NASA, Goddard Space Flight Ctr, Astrophys Sci Div, Greenbelt, MD 20771 USA.
   [Holland, S. T.] Univ Space Res Assoc, Columbia, MD 21044 USA.
   [Holland, S. T.; Immler, S.] NASA, Goddard Space Flight Ctr, Ctr Res & Explorat Space Sci & Technol, Greenbelt, MD 20771 USA.
   [Malek, K.; Mankiewicz, L.] Polish Acad Sci, Ctr Theoret Phys, PL-02668 Warsaw, Poland.
   [Margutti, R.; Chincarini, G.] Univ Milano Bicocca, Dept Phys, I-20126 Milan, Italy.
   [Kamble, A. P.; Curran, P. A.; Strom, R. G.; Wijers, R. A. M. J.] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1098 SJ Amsterdam, Netherlands.
   [Kouveliotou, C.] NASA, George C Marshall Space Flight Ctr, NSSTC, Huntsville, AL 35805 USA.
   [Piran, T.] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Bartolini, C.; Greco, G.; Guarnieri, A.; Piccioni, A.] Univ Bologna, I-40126 Bologna, Italy.
   [Bondar, S.] Inst Precise Instrumentat, Nizhnii Arkhyz 369167, Russia.
   [Bremer, M.; Winters, J. M.] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Castro-Tirado, A.; Gorosabel, J.; Jelinek, M.] Inst Astrofis Andalucia, CSIC, E-18080 Granada, Spain.
   [D'Elia, V.; Fiore, F.; Testa, V.] Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, Italy.
   [Della Valle, M.] European So Observ, D-85748 Garching, Germany.
   [Della Valle, M.] Osserv Astron Capodimonte, INAF, I-80131 Naples, Italy.
   [de Ugarte Postigo, A.] European So Observ, Santiago 19, Chile.
   [Fruchter, A. S.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Garrett, M. A.; Strom, R. G.] Netherlands Inst Radio Astron ASTRON, NL-7990 AA Dwingeloo, Netherlands.
   [Garrett, M. A.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Garrett, M. A.] Swinburne Univ Technol, Ctr Astrophys & Supercomp, Hawthorn, Vic 3122, Australia.
   [Gomboc, A.] Univ Ljubljana, Fac Math & Phys, SI-1000 Ljubljana, Slovenia.
   [Kasprowicz, G.] Warsaw Univ Technol, Inst Elect Syst, PL-00665 Warsaw, Poland.
   [La Parola, V.; Mangano, V.] INAF IASF PA, I-90146 Palermo, Italy.
   [Levan, A. J.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Pandey, S. B.] Aryabhatta Res Inst Observ Sci ARIES, Naini Tal 263129, India.
   [Paragi, Z.] JIVE, NL-7990 AA Dwingeloo, Netherlands.
   [Perri, M.] ESRIN, ASI Sci Data Ctr, I-00044 Frascati, Italy.
   [Ramirez-Ruiz, E.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Tosti, G.] Univ Perugia, I-06100 Perugia, Italy.
   [Meszaros, P.] Penn State Univ, Dept Phys, Davey Lab 104, University Pk, PA 16801 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Russian Academy of Sciences; Special Astrophysics Observatory of the Russian Academy of Sciences; Soltan Institute for Nuclear Studies; University of Hertfordshire; Chinese Academy of Sciences; Nanjing Institute of Astronomical Optics & Technology, NAOC, CAS; Purple Mountain Observatory, CAS; Russian Academy of Sciences; St. Petersburg Scientific Centre of the Russian Academy of Sciences; Ioffe Physical Technical Institute; Istituto Nazionale Astrofisica (INAF); University of London; University College London; Liverpool John Moores University; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Leicester; University of Warsaw; Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Universities Space Research Association (USRA); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Polish Academy of Sciences; Center for Theoretical Physics - Polish Academy of Sciences; University of Milano-Bicocca; University of Amsterdam; National Aeronautics & Space Administration (NASA); NASA Marshall Space Flight Center; Hebrew University of Jerusalem; University of Bologna; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); Istituto Nazionale Astrofisica (INAF); European Southern Observatory; Istituto Nazionale Astrofisica (INAF); European Southern Observatory; Space Telescope Science Institute; Leiden University; Leiden University - Excl LUMC; Swinburne University of Technology; University of Ljubljana; Warsaw University of Technology; Istituto Nazionale Astrofisica (INAF); University of Warwick; Department of Science & Technology (India); Aryabhatta Research Institute of Observational Sciences (ARIES); European Space Agency; European Space Research Institute; Agenzia Spaziale Italiana (ASI); University of California System; University of California Santa Cruz; University of Perugia; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Racusin, JL (corresponding author), Penn State Univ, Dept Astron & Astrophys, 525 Davey Lab, University Pk, PA 16802 USA.
EM racusin@astro.psu.edu
FU NASA; National Science Foundation (NSF); Agenzia Spaziale Italiana, the Ministero dell'Universita` e della Ricerca ( MUR); Ministero degli Affari Esteri, the Netherlands Organization for Scientific Research; National Science Foundation of China; Russian Space Agency; Science and Technology and Facilities Council ( STFC); Slovenian Research Agency; Ministry for Higher Education, Science, and Technology, Slovenia; Polish Ministry of Science and Higher Education; STFC [PP/E001149/1, PP/D000920/1, PP/E002064/1, PP/E001173/1, PP/E003303/1, ST/F002599/1, ST/F006489/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/F006489/1, PP/E003303/1, PP/E001173/1, PP/E001149/1, ST/F002599/1, PP/D000920/1, PP/E002064/1] Funding Source: researchfish
NR 42
TC 476
Z9 504
U1 0
U2 49
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 11
PY 2008
VL 455
IS 7210
BP 183
EP 188
DI 10.1038/nature07270
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800038
PM 18784718
DA 2026-03-09
ER

PT J
AU Bennett, MR
   Pang, WL
   Ostroff, NA
   Baumgartner, BL
   Nayak, S
   Tsimring, LS
   Hasty, J
AF Bennett, Matthew R.
   Pang, Wyming Lee
   Ostroff, Natalie A.
   Baumgartner, Bridget L.
   Nayak, Sujata
   Tsimring, Lev S.
   Hasty, Jeff
TI Metabolic gene regulation in a dynamically changing environment
SO NATURE
LA English
DT Article
ID messenger-rna decay; saccharomyces-cerevisiae; fluctuating environments; glucose repression; soft lithography; yeast; expression; biology; networks; proteins
AB Natural selection dictates that cells constantly adapt to dynamically changing environments in a context- dependent manner. Gene- regulatory networks often mediate the cellular response to perturbation(1-3), and an understanding of cellular adaptation will require experimental approaches aimed at subjecting cells to a dynamic environment that mimics their natural habitat(4-9). Here we monitor the response of Saccharomyces cerevisiae metabolic gene regulation to periodic changes in the external carbon source by using a microfluidic platform that allows precise, dynamic control over environmental conditions. We show that the metabolic system acts as a low- pass filter that reliably responds to a slowly changing environment, while effectively ignoring fast fluctuations. The sensitive low- frequency response was significantly faster than in predictions arising from our computational modelling, and this discrepancy was resolved by the discovery that two key galactose transcripts possess half- lives that depend on the carbon source. Finally, to explore how induction characteristics affect frequency response, we compare two S. cerevisiae strains and show that they have the same frequency response despite having markedly different induction properties. This suggests that although certain characteristics of the complex networks may differ when probed in a static environment, the system has been optimized for a robust response to a dynamically changing environment.
C1 [Bennett, Matthew R.; Pang, Wyming Lee; Ostroff, Natalie A.; Baumgartner, Bridget L.; Nayak, Sujata; Hasty, Jeff] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Bennett, Matthew R.; Tsimring, Lev S.; Hasty, Jeff] Univ Calif San Diego, Inst Nonlinear Sci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego
RP Hasty, J (corresponding author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
EM hasty@ucsd.edu
FU National Institute of General Medical Sciences of the National Institutes of Health
NR 27
TC 243
Z9 321
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 AUG 28
PY 2008
VL 454
IS 7208
BP 1119
EP 1122
DI 10.1038/nature07211
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600038
PM 18668041
DA 2026-03-09
ER

PT J
AU Zheng, HW
   Ying, HQ
   Yan, HY
   Kimmelman, AC
   Hiller, DJ
   Chen, AJ
   Perry, SR
   Tonon, G
   Chu, GC
   Ding, ZH
   Stommel, JM
   Dunn, KL
   Wiedemeyer, R
   You, MJJ
   Brennan, C
   Wang, YA
   Ligon, KL
   Wong, WH
   Chin, L
   DePinho, RA
AF Zheng, Hongwu
   Ying, Haoqiang
   Yan, Haiyan
   Kimmelman, Alec C.
   Hiller, David J.
   Chen, An-Jou
   Perry, Samuel R.
   Tonon, Giovanni
   Chu, Gerald C.
   Ding, Zhihu
   Stommel, Jayne M.
   Dunn, Katherine L.
   Wiedemeyer, Ruprecht
   You, Mingjian J.
   Brennan, Cameron
   Wang, Y. Alan
   Ligon, Keith L.
   Wong, Wing H.
   Chin, Lynda
   DePinho, Ronald A.
TI p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation
SO NATURE
LA English
DT Article
ID stem-cell; self-renewal; c-myc; glioblastoma; receptor; pathways; biology; genes; model; akt
AB Glioblastoma ( GBM) is a highly lethal brain tumour presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as a high-grade disease that typically harbours mutations in EGFR, PTEN and INK4A/ARF ( also known as CDKN2A), and the secondary GBM subtype evolves from the slow progression of a low- grade disease that classically possesses PDGF and TP53 events(1-3). Here we show that concomitant central nervous system (CNS)- specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute- onset high- grade malignant glioma phenotype with notable clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted TP53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of TP53 as well as the expected PTEN mutations. Integrated transcriptomic profiling, in silico promoter analysis and functional studies of murine neural stem cells ( NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives increased Myc protein levels and its associated signature. Functional studies validated increased Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of NSCs doubly null for p53 and Pten (p53(-/-) Pten(-/-)) as well as tumour neurospheres (TNSs) derived from this model. Myc also serves to maintain robust tumorigenic potential of p53(-/-) Pten(-/-) TNSs. These murine modelling studies, together with confirmatory transcriptomic/ promoter studies in human primary GBM, validate a pathogenetic role of a common tumour suppressor mutation profile in human primary GBM and establish Myc as an important target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/ progenitor cell differentiation, self- renewal and tumorigenic potential.
C1 [Zheng, Hongwu; Ying, Haoqiang; Yan, Haiyan; Kimmelman, Alec C.; Chen, An-Jou; Perry, Samuel R.; Tonon, Giovanni; Chu, Gerald C.; Ding, Zhihu; Stommel, Jayne M.; Dunn, Katherine L.; Wiedemeyer, Ruprecht; You, Mingjian J.; Wang, Y. Alan; Ligon, Keith L.; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Perry, Samuel R.; Chu, Gerald C.; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Fdn Inst Innovat Canc Sci, Boston, MA 02115 USA.
   [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
   [Kimmelman, Alec C.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
   [Chu, Gerald C.; Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Ligon, Keith L.] Harvard Univ, Sch Med, Div Neuropathol, Boston, MA 02115 USA.
   [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Hiller, David J.; Wong, Wing H.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
   [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
   [Brennan, Cameron] Weill Cornell Med Coll, Dept Neurosurg, New York, NY 10065 USA.
   [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, 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 Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Stanford University; Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP DePinho, RA (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM ron_depinho@dfci.harvard.edu
FU Helen Hay Whitney Foundation; Marsha Mae Moeslein Fellowship; American Brain Tumor Association; Leonard B. Holman Research Pathway Fellowship; Damon Runyon Cancer Research Foundation; Ruth L. Kirschstein National Research Service Award Fellowship; Mildred Scheel Fellowship (Deutsche Krebshilfe); Goldhirsh Foundation; NIH [U01 CA84313, RO1CA99041, 5P01CA95616]; Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science
NR 35
TC 601
Z9 709
U1 3
U2 103
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1129
EP U13
DI 10.1038/nature07443
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600049
PM 18948956
DA 2026-03-09
ER

PT J
AU Monecke, K
   Finger, W
   Klarer, D
   Kongko, W
   McAdoo, BG
   Moore, AL
   Sudrajat, SU
AF Monecke, Katrin
   Finger, Willi
   Klarer, David
   Kongko, Widjo
   McAdoo, Brian G.
   Moore, Andrew L.
   Sudrajat, Sam U.
TI A 1,000-year sediment record of tsunami recurrence in northern Sumatra
SO NATURE
LA English
DT Article
ID deposits; storm
AB The Indian Ocean tsunami of 26 December 2004 reached maximum wave heights of 35 m in Aceh, the northernmost province of Sumatra(1,2). Both the tsunami and the associated Sumatra Andaman earthquake were unprecedented in Acehnese history(3,4). Here we use sand sheets to extend tsunami history 1,000 years into Aceh's past. The 2004 tsunami deposited a sand sheet up to 1.8 km inland on a marshy beach ridge plain. Sediment cores from these coastal marshes revealed two older extensive sand sheets with similar sediment characteristics. These sheets, deposited soon after AD 1290 - 1400 and AD 780 - 990, probably resulted from earlier tsunamis. An additional sand sheet of limited extent might correlate with a documented smaller tsunami of AD 1907. These findings, a first step towards a palaeotsunami record for northern Sumatra, suggest that damage- causing tsunamis in Aceh recur infrequently enough for entire human lifetimes to typically elapse between them. Such recurrence adds to the challenge of preparing communities along the northern Indian Ocean shorelines for future tsunamis.
C1 [Monecke, Katrin] Kent State Univ, Dept Geol, Kent, OH 44242 USA.
   [Finger, Willi] Swiss Agcy Dev & Cooperat SDC, Swiss Humanitarian Aid Unit SHA, CH-8002 Zurich, Switzerland.
   [Klarer, David] Old Woman Creek Natl Estuarine Res Reserve, Huron, OH 44839 USA.
   [Kongko, Widjo] Jalan Grafika, Badan Pengkajan Penerapan Teknol BPPT, Yogjakarta 55281, Indonesia.
   [McAdoo, Brian G.] Vassar Coll, Dept Earth Sci & Geog, Poughkeepsie, NY 12604 USA.
   [Moore, Andrew L.] Earlham Coll, Dept Geosci, Richmond, IN 47374 USA.
   [Sudrajat, Sam U.] Jalan Nasl, CRS, Meulaboh, NAD, Indonesia.
C3 University System of Ohio; Kent State University; Kent State University Kent; Kent State University Salem; Vassar College; Earlham College
RP Monecke, K (corresponding author), Univ Pittsburgh, Dept Geol & Planetary Sci, 450 Schoolhouse Rd, Johnstown, PA 15904 USA.
EM monecke@pitt.edu
FU Swiss Science Foundation; US National Science Foundation; Vassar College
NR 26
TC 231
Z9 261
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 OCT 30
PY 2008
VL 455
IS 7217
BP 1232
EP 1234
DI 10.1038/nature07374
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100042
DA 2026-03-09
ER

PT J
AU Mariani, FV
   Ahn, CP
   Martin, GR
AF Mariani, Francesca V.
   Ahn, Christina P.
   Martin, Gail R.
TI Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning
SO NATURE
LA English
DT Article
ID apical ectodermal ridge; vertebrate limb; chick limb; feedback loop; mouse embryos; bud; outgrowth; growth; axis; differentiation
AB Half a century ago, the apical ectodermal ridge (AER) at the distal tip of the tetrapod limb bud was shown to produce signals necessary for development along the proximal-distal (P-D) axis, but how these signals influence limb patterning is still much debated(1,2). Fibroblast growth factor (FGF) gene family members are key AER-derived signals(3,4), with Fgf4, Fgf8, Fgf9 and Fgf17 expressed specifically in the mouse AER(5). Here we demonstrate that mouse limbs lacking Fgf4, Fgf9 and Fgf17 have normal skeletal pattern, indicating that Fgf8 is sufficient among AER-FGFs to sustain normal limb formation. Inactivation of Fgf8 alone causes a mild skeletal phenotype(6,7); however, when we also removed different combinations of the other AER-FGF genes, we obtained unexpected skeletal phenotypes of increasing severity, reflecting the contribution that each FGF can make to the total AER-FGF signal. Analysis of the compound mutant limb buds revealed that, in addition to sustaining cell survival, AER-FGFs regulate P-D-patterning gene expression during early limb bud development, providing genetic evidence that AER-FGFs function to specify a distal domain and challenging the long-standing hypothesis that AER-FGF signalling is permissive rather than instructive for limb patterning. We discuss how a two-signal model for P-D patterning can be integrated with the concept of early specification to explain the genetic data presented here.
C1 [Mariani, Francesca V.; Ahn, Christina P.; Martin, Gail R.] Univ Calif San Francisco, Dept Anat, Sch Med, San Francisco, CA 94158 USA.
   [Mariani, Francesca V.; Ahn, Christina P.; Martin, Gail R.] Univ Calif San Francisco, Program Dev Biol, Sch Med, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Martin, GR (corresponding author), Univ Calif San Francisco, Dept Anat, Sch Med, San Francisco, CA 94158 USA.
EM gail.r.martin@ucsf.edu
FU NICHD NIH HHS [F32 HD008696, R01 HD034380, R01 HD34380] Funding Source: Medline
NR 31
TC 272
Z9 335
U1 1
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 15
PY 2008
VL 453
IS 7193
BP 401
EP U56
DI 10.1038/nature06876
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400054
PM 18449196
DA 2026-03-09
ER

PT J
AU Hanson, JA
   Chang, CB
   Graves, SM
   Li, ZB
   Mason, TG
   Deming, TJ
AF Hanson, Jarrod A.
   Chang, Connie B.
   Graves, Sara M.
   Li, Zhibo
   Mason, Thomas G.
   Deming, Timothy J.
TI Nanoscale double emulsions stabilized by single-component block copolypeptides
SO NATURE
LA English
DT Article
ID monodisperse double emulsions; multiple emulsions; curvature; delivery; release
AB Water- in- oil- in- water emulsions are examples of double emulsions, in which dispersions of small water droplets within larger oil droplets are themselves dispersed in a continuous aqueous phase(1-3). Emulsions occur in many forms of processing and are used extensively by the foods, cosmetics and coatings industries. Because of their compartmentalized internal structure, double emulsions can provide advantages over simple oil- in- water emulsions for encapsulation, such as the ability to carry both polar and non- polar cargos, and improved control over release of therapeutic molecules(4-6). The preparation of double emulsions typically requires mixtures of surfactants for stability; the formation of double nanoemulsions, where both inner and outer droplets are under 100 nm, has not yet been achieved(7-9). Here we show that water- in- oil- in- water double emulsions can be prepared in a simple process and stabilized over many months using single- component, synthetic amphiphilic diblock copolypeptide surfactants. These surfactants even stabilize droplets subjected to extreme flow, leading to direct, mass production of robust double nanoemulsions that are amenable to nanostructured encapsulation applications in foods, cosmetics and drug delivery.
C1 [Hanson, Jarrod A.; Li, Zhibo; Deming, Timothy J.] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA.
   [Chang, Connie B.; Graves, Sara M.; Mason, Thomas G.; Deming, Timothy J.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
   [Mason, Thomas G.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Mason, Thomas G.; Deming, Timothy J.] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Deming, TJ (corresponding author), Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA.
EM mason@chem.ucla.edu; demingt@seas.ucla.edu
FU National Science Foundation; Human Frontiers of Science Program; University of California; National Institutes of Health; National Center for Research Resources P41 programme
NR 30
TC 245
Z9 295
U1 6
U2 299
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 85
EP U54
DI 10.1038/nature07197
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200041
PM 18769436
DA 2026-03-09
ER

PT J
AU Mavrich, TN
   Jiang, CZ
   Ioshikhes, IP
   Li, XY
   Venters, BJ
   Zanton, SJ
   Tomsho, LP
   Qi, J
   Glaser, RL
   Schuster, SC
   Gilmour, DS
   Albert, I
   Pugh, BF
AF Mavrich, Travis N.
   Jiang, Cizhong
   Ioshikhes, Ilya P.
   Li, Xiaoyong
   Venters, Bryan J.
   Zanton, Sara J.
   Tomsho, Lynn P.
   Qi, Ji
   Glaser, Robert L.
   Schuster, Stephan C.
   Gilmour, David S.
   Albert, Istvan
   Pugh, B. Franklin
TI Nucleosome organization in the Drosophila genome
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; high-resolution map; promoter element; histone h2a.z; transcription; chromatin; replacement; variant; genes; acetylation
AB Comparative genomics of nucleosome positions provides a powerful means for understanding how the organization of chromatin and the transcription machinery co-evolve. Here we produce a high-resolution reference map of H2A.Z and bulk nucleosome locations across the genome of the fly Drosophila melanogaster and compare it to that from the yeast Saccharomyces cerevisiae. Like Saccharomyces, Drosophila nucleosomes are organized around active transcription start sites in a canonical -1, nucleosome-free region, +1 arrangement. However, Drosophila does not incorporate H2A.Z into the -1 nucleosome and does not bury its transcriptional start site in the +1 nucleosome. At thousands of genes, RNA polymerase II engages the +1 nucleosome and pauses. How the transcription initiation machinery contends with the +1 nucleosome seems to be fundamentally different across major eukaryotic lines.
C1 [Mavrich, Travis N.; Jiang, Cizhong; Venters, Bryan J.; Zanton, Sara J.; Gilmour, David S.; Pugh, B. Franklin] Penn State Univ, Ctr Gene Regulat, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
   [Mavrich, Travis N.; Jiang, Cizhong; Venters, Bryan J.; Zanton, Sara J.; Tomsho, Lynn P.; Qi, Ji; Schuster, Stephan C.; Albert, Istvan; Pugh, B. Franklin] Penn State Univ, Ctr Comparat Genom & Bioinformat, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
   [Ioshikhes, Ilya P.] Ohio State Univ, Dept Biomed Informat, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA.
   [Ioshikhes, Ilya P.] Ohio State Univ, Dept Mol & Cellular Biochem, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA.
   [Li, Xiaoyong] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley Drosophila Transcript Network Project, Genom Div, Berkeley, CA 94720 USA.
   [Glaser, Robert L.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA.
   [Glaser, Robert L.] SUNY Albany, Dept Biomed Sci, Albany, NY 12201 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 System of Ohio; Ohio State University; University System of Ohio; Ohio State University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; State University of New York (SUNY) System; Wadsworth Center; State University of New York (SUNY) System; University at Albany, SUNY
RP Pugh, BF (corresponding author), Penn State Univ, Ctr Gene Regulat, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
EM bfp2@psu.edu
FU National Human Genome Research Institute [R01HG004160] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM047477] Funding Source: NIH RePORTER; NHGRI NIH HHS [R56 HG004160, HG004160, R01 HG004160] Funding Source: Medline; NIGMS NIH HHS [GM47477, R01 GM047477] Funding Source: Medline
NR 54
TC 583
Z9 787
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 MAY 15
PY 2008
VL 453
IS 7193
BP 358
EP U27
DI 10.1038/nature06929
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400044
PM 18408708
DA 2026-03-09
ER

PT J
AU Yang, HG
   Sun, CH
   Qiao, SZ
   Zou, J
   Liu, G
   Smith, SC
   Cheng, HM
   Lu, GQ
AF Yang, Hua Gui
   Sun, Cheng Hua
   Qiao, Shi Zhang
   Zou, Jin
   Liu, Gang
   Smith, Sean Campbell
   Cheng, Hui Ming
   Lu, Gao Qing
TI Anatase TiO2 single crystals with a large percentage of reactive facets
SO NATURE
LA English
DT Article
ID total-energy calculations; wave basis-set; hydrothermal conditions; titanium-dioxide; surface; oxide; nanostructures; nanoparticles; nanocrystals; efficiency
AB Owing to their scientific and technological importance, inorganic single crystals with highly reactive surfaces have long been studied(1-13). Unfortunately, surfaces with high reactivity usually diminish rapidly during the crystal growth process as a result of the minimization of surface energy. A typical example is titanium dioxide ( TiO2), which has promising energy and environmental applications(14-17). Most available anatase TiO2 crystals are dominated by the thermodynamically stable {101} facets ( more than 94 per cent, according to the Wulff construction(10)), rather than the much more reactive {001} facets(8-13,18-20). Here we demonstrate that for fluorine- terminated surfaces this relative stability is reversed: {001} is energetically preferable to {101}. We explored this effect systematically for a range of non- metallic adsorbate atoms by first- principle quantum chemical calculations. On the basis of theoretical predictions, we have synthesized uniform anatase TiO2 single crystals with a high percentage ( 47 per cent) of {001} facets using hydrofluoric acid as a morphology controlling agent. Moreover, the fluorated surface of anatase single crystals can easily be cleaned using heat treatment to render a fluorine-
C1 [Yang, Hua Gui; Sun, Cheng Hua; Qiao, Shi Zhang; Liu, Gang; Smith, Sean Campbell; Lu, Gao Qing] Univ Queensland, ARC Ctr Excellence Funct Nanomat, Sch Engn, Brisbane, Qld 4072, Australia.
   [Yang, Hua Gui; Sun, Cheng Hua; Qiao, Shi Zhang; Liu, Gang; Smith, Sean Campbell; Lu, Gao Qing] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Ctr Computat Mol Sci, Brisbane, Qld 4072, Australia.
   [Zou, Jin] Univ Queensland, Ctr Microscopy & Microanal, Brisbane, Qld 4072, Australia.
   [Zou, Jin] Univ Queensland, Sch Engn, Brisbane, Qld 4072, Australia.
   [Liu, Gang; Cheng, Hui Ming] Chinese Acad Sci, Met Res Inst, Shenyang Natl Lab Mat sci, Shenyang 110016, Peoples R China.
C3 University of Queensland; University of Queensland; University of Queensland; University of Queensland; Chinese Academy of Sciences; Institute of Metal Research, CAS
RP Lu, GQ (corresponding author), Univ Queensland, ARC Ctr Excellence Funct Nanomat, Sch Engn, Brisbane, Qld 4072, Australia.
EM s.qiao@uq.edu.au; maxlu@uq.edu.au
NR 37
TC 3952
Z9 4215
U1 41
U2 4004
PU NATURE PUBLISHING 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 29
PY 2008
VL 453
IS 7195
BP 638
EP U4
DI 10.1038/nature06964
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200040
PM 18509440
DA 2026-03-09
ER

PT J
AU Emilsson, V
   Thorleifsson, G
   Zhang, B
   Leonardson, AS
   Zink, F
   Zhu, J
   Carlson, S
   Helgason, A
   Walters, GB
   Gunnarsdottir, S
   Mouy, M
   Steinthorsdottir, V
   Eiriksdottir, GH
   Bjornsdottir, G
   Reynisdottir, I
   Gudbjartsson, D
   Helgadottir, A
   Jonasdottir, A
   Jonasdottir, A
   Styrkarsdottir, U
   Gretarsdottir, S
   Magnusson, KP
   Stefansson, H
   Fossdal, R
   Kristjansson, K
   Gislason, HG
   Stefansson, T
   Leifsson, BG
   Thorsteinsdottir, U
   Lamb, JR
   Gulcher, JR
   Reitman, ML
   Kong, A
   Schadt, EE
   Stefansson, K
AF Emilsson, Valur
   Thorleifsson, Gudmar
   Zhang, Bin
   Leonardson, Amy S.
   Zink, Florian
   Zhu, Jun
   Carlson, Sonia
   Helgason, Agnar
   Walters, G. Bragi
   Gunnarsdottir, Steinunn
   Mouy, Magali
   Steinthorsdottir, Valgerdur
   Eiriksdottir, Gudrun H.
   Bjornsdottir, Gyda
   Reynisdottir, Inga
   Gudbjartsson, Daniel
   Helgadottir, Anna
   Jonasdottir, Aslaug
   Jonasdottir, Adalbjorg
   Styrkarsdottir, Unnur
   Gretarsdottir, Solveig
   Magnusson, Kristinn P.
   Stefansson, Hreinn
   Fossdal, Ragnheidur
   Kristjansson, Kristleifur
   Gislason, Hjortur G.
   Stefansson, Tryggvi
   Leifsson, Bjorn G.
   Thorsteinsdottir, Unnur
   Lamb, John R.
   Gulcher, Jeffrey R.
   Reitman, Marc L.
   Kong, Augustine
   Schadt, Eric E.
   Stefansson, Kari
TI Genetics of gene expression and its effect on disease
SO NATURE
LA English
DT Article
ID integrative genomics approach; segregating mouse-population; linkage analysis; adipose-tissue; obesity; networks; yeast; association; pedigrees; discovery
AB Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population- based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity- related traits. Genome- wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal ( cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity- related traits.
C1 [Emilsson, Valur; Thorleifsson, Gudmar; Zink, Florian; Helgason, Agnar; Walters, G. Bragi; Gunnarsdottir, Steinunn; Mouy, Magali; Steinthorsdottir, Valgerdur; Eiriksdottir, Gudrun H.; Bjornsdottir, Gyda; Reynisdottir, Inga; Gudbjartsson, Daniel; Helgadottir, Anna; Jonasdottir, Aslaug; Jonasdottir, Adalbjorg; Styrkarsdottir, Unnur; Gretarsdottir, Solveig; Magnusson, Kristinn P.; Stefansson, Hreinn; Fossdal, Ragnheidur; Kristjansson, Kristleifur; Thorsteinsdottir, Unnur; Gulcher, Jeffrey R.; Kong, Augustine; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland.
   [Emilsson, Valur; Zhang, Bin; Leonardson, Amy S.; Zhu, Jun; Carlson, Sonia; Lamb, John R.; Schadt, Eric E.] Rosetta Inpharmat LLC, Seattle, WA 98109 USA.
   [Gislason, Hjortur G.; Stefansson, Tryggvi; Leifsson, Bjorn G.] Natl Univ Hosp Reykjavik, Dept Surg, IS-101 Reykjavik, Iceland.
   [Reitman, Marc L.] Merck Res Labs, Rahway, NJ 07065 USA.
C3 Decode Genetics; Merck & Company; Landspitali National University Hospital; Merck & Company
RP Stefansson, K (corresponding author), deCODE Genet, IS-101 Reykjavik, Iceland.
EM eric_schadt@merck.com; kari.stefansson@decode.is
NR 40
TC 1004
Z9 1235
U1 0
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 423
EP U2
DI 10.1038/nature06758
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300022
PM 18344981
DA 2026-03-09
ER

PT J
AU Tripp, HJ
   Kitner, JB
   Schwalbach, MS
   Dacey, JWH
   Wilhelm, LJ
   Giovannoni, SJ
AF Tripp, H. James
   Kitner, Joshua B.
   Schwalbach, Michael S.
   Dacey, John W. H.
   Wilhelm, Larry J.
   Giovannoni, Stephen J.
TI SAR11 marine bacteria require exogenous reduced sulphur for growth
SO NATURE
LA English
DT Article
ID dissolved dimethylsulfoniopropionate; bacterioplankton community; north-atlantic; sulfate; reduction; ocean; microorganisms; metabolism; genomics; sequence
AB Sulphur is a universally required cell nutrient found in two amino acids and other small organic molecules. All aerobic marine bacteria are known to use assimilatory sulphate reduction to supply sulphur for biosynthesis, although many can assimilate sulphur from organic compounds that contain reduced sulphur atoms(1-3). An analysis of three complete 'Candidatus Pelagibacter ubique' genomes, and public ocean metagenomic data sets, suggested that members of the ubiquitous and abundant SAR11 alphaproteobacterial clade are deficient in assimilatory sulphate reduction genes. Here we show that SAR11 requires exogenous sources of reduced sulphur, such as methionine or 3-dimethylsulphoniopropionate (DMSP) for growth. Titrations of the algal osmolyte DMSP in seawater medium containing all other macronutrients in excess showed that 1.5 x 10(8) SAR11 cells are produced per nanomole of DMSP. Although it has been shown that other marine alphaproteobacteria use sulphur from DMSP in preference to sulphate(1,2), our results indicate that 'Cand. P. ubique' relies exclusively on reduced sulphur compounds that originate from other plankton.
C1 [Tripp, H. James; Kitner, Joshua B.; Schwalbach, Michael S.; Wilhelm, Larry J.; Giovannoni, Stephen J.] Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA.
   [Dacey, John W. H.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
C3 Oregon State University; Woods Hole Oceanographic Institution
RP Giovannoni, SJ (corresponding author), Oregon State Univ, Dept Microbiol, 220 Nash Hall, Corvallis, OR 97331 USA.
EM steve.giovannoni@oregonstate.edu
NR 30
TC 301
Z9 355
U1 2
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 APR 10
PY 2008
VL 452
IS 7188
BP 741
EP 744
DI 10.1038/nature06776
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500043
PM 18337719
DA 2026-03-09
ER

PT J
AU Walter, MJ
   Bulanova, GP
   Armstrong, LS
   Keshav, S
   Blundy, JD
   Gudfinnsson, G
   Lord, OT
   Lennie, AR
   Clark, SM
   Smith, CB
   Gobbo, L
AF Walter, M. J.
   Bulanova, G. P.
   Armstrong, L. S.
   Keshav, S.
   Blundy, J. D.
   Gudfinnsson, G.
   Lord, O. T.
   Lennie, A. R.
   Clark, S. M.
   Smith, C. B.
   Gobbo, L.
TI Primary carbonatite melt from deeply subducted oceanic crust
SO NATURE
LA English
DT Article
ID earths lower mantle; high-pressure; transition zone; phase-relations; mato-grosso; juina area; diamonds; fluids; metasomatism; subsolidus
AB Partial melting in the Earth's mantle plays an important part in generating the geochemical and isotopic diversity observed in volcanic rocks at the surface(1). Identifying the composition of these primary melts in the mantle is crucial for establishing links between mantle geochemical 'reservoirs' and fundamental geodynamic processes(2). Mineral inclusions in natural diamonds have provided a unique window into such deep mantle processes(3-8). Here we provide experimental and geochemical evidence that silicate mineral inclusions in diamonds from Juina, Brazil, crystallized from primary and evolved carbonatite melts in the mantle transition zone and deep upper mantle. The incompatible trace element abundances calculated for a melt coexisting with a calcium-titanium- silicate perovskite inclusion indicate deep melting of carbonated oceanic crust, probably at transition- zone depths. Further to perovskite, calcic- majorite garnet inclusions record crystallization in the deep upper mantle from an evolved melt that closely resembles estimates of primitive carbonatite on the basis of volcanic rocks. Small- degree melts of subducted crust can be viewed as agents of chemical mass- transfer in the upper mantle and transition zone, leaving a chemical imprint of ocean crust that can possibly endure for billions of years.
C1 [Walter, M. J.; Bulanova, G. P.; Armstrong, L. S.; Blundy, J. D.; Lord, O. T.] Univ Bristol, Dept Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Keshav, S.; Gudfinnsson, G.] Univ Bayreuth, Bayer Geoinst, D-95440 Bayreuth, Germany.
   [Lennie, A. R.] SERC, Daresbury Lab, Warrington WA4 4AD, Cheshire, England.
   [Clark, S. M.] Univ Calif Berkeley, Lawrence Berkeley Lab, Adv Light Source, Berkeley, CA 94720 USA.
   [Smith, C. B.] Rio Tinto Min & Explorat Ltd, London W2 6LG, England.
   [Gobbo, L.] Rio Tinto Desinvolvimentos Min Ltda, BR-71200020 Brasilia, DF, Brazil.
C3 University of Bristol; University of Bayreuth; STFC Daresbury Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Rio Tinto
RP Walter, MJ (corresponding author), Univ Bristol, Dept Earth Sci, Queens Rd, Bristol BS8 1RJ, Avon, England.
EM m.j.walter@bris.ac.uk
FU Natural Environment Research Council [NE/E010466/1] Funding Source: researchfish; NERC [NE/E010466/1] Funding Source: UKRI
NR 35
TC 254
Z9 287
U1 4
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 622
EP U30
DI 10.1038/nature07132
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500043
PM 18668105
DA 2026-03-09
ER

PT J
AU Yang, L
   Soonpaa, MH
   Adler, ED
   Roepke, TK
   Kattman, SJ
   Kennedy, M
   Henckaerts, E
   Bonham, K
   Abbott, GW
   Linden, RM
   Field, LJ
   Keller, GM
AF Yang, Lei
   Soonpaa, Mark H.
   Adler, Eric D.
   Roepke, Torsten K.
   Kattman, Steven J.
   Kennedy, Marion
   Henckaerts, Els
   Bonham, Kristina
   Abbott, Geoffrey W.
   Linden, R. Michael
   Field, Loren J.
   Keller, Gordon M.
TI Human cardiovascular progenitor cells develop from a KDR plus embryonic-stem-cell-derived population
SO NATURE
LA English
DT Article
ID smooth-muscle; heart; specification; differentiation; proliferation; cardiogenesis; requirement; expression
AB The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1(+) (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages(1). To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDRlow/C-KIT (CD117)(neg) population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDR low/C-KIT neg cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDRlow/C-KITneg fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colonyforming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.
C1 [Yang, Lei; Adler, Eric D.; Linden, R. Michael; Keller, Gordon M.] Mt Sinai Sch Med, Dept Gene & Cell Med, Black Family Stem Cell Inst, New York, NY 10029 USA.
   [Soonpaa, Mark H.; Field, Loren J.] Indiana Univ, Sch Med, Wells Ctr Pediat Res, Indianapolis, IN 46202 USA.
   [Roepke, Torsten K.; Abbott, Geoffrey W.] Cornell Univ, Greenberg Div Cardiol, Dept Med, Weill Med Coll, New York, NY 10021 USA.
   [Roepke, Torsten K.; Abbott, Geoffrey W.] Cornell Univ, Greenberg Div Cardiol, Dept Pharmacol, Weill Med Coll, New York, NY 10021 USA.
   [Kattman, Steven J.; Kennedy, Marion; Keller, Gordon M.] Univ Hlth Network, McEwen Ctr Regenerat Med, Toronto, ON M5G 1L7, Canada.
   [Henckaerts, Els; Linden, R. Michael] Kings Coll London, Dept Infect Dis, London SE1 9RT, England.
   [Bonham, Kristina] VistaGen Therapeut Inc, San Francisco, CA 94080 USA.
C3 Icahn School of Medicine at Mount Sinai; Indiana University System; Indiana University Indianapolis; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; University of Toronto; University Health Network Toronto; University of London; King's College London
RP Keller, GM (corresponding author), Mt Sinai Sch Med, Dept Gene & Cell Med, Black Family Stem Cell Inst, 1425 Madison Ave, New York, NY 10029 USA.
EM gkeller@uhnresearch.ca
FU NHLBI NIH HHS [R01 HL083126, R01 HL079275] Funding Source: Medline
NR 30
TC 1132
Z9 1436
U1 1
U2 126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 524
EP U6
DI 10.1038/nature06894
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700043
PM 18432194
DA 2026-03-09
ER

PT J
AU Wang, PYT
   Caspi, L
   Lam, CKL
   Chari, M
   Li, XS
   Light, PE
   Gutierrez-Juarez, R
   Ang, M
   Schwartz, GJ
   Lam, TKT
AF Wang, Penny Y. T.
   Caspi, Liora
   Lam, Carol K. L.
   Chari, Madhu
   Li, Xiaosong
   Light, Peter E.
   Gutierrez-Juarez, Roger
   Ang, Michelle
   Schwartz, Gary J.
   Lam, Tony K. T.
TI Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production
SO NATURE
LA English
DT Article
ID d-aspartate receptors; food-intake; obesity; energy; mechanisms; homeostasis; nucleus; balance; signals; weight
AB Energy and glucose homeostasis are regulated by food intake and liver glucose production, respectively. The upper intestine has a critical role in nutrient digestion and absorption. However, studies indicate that upper intestinal lipids inhibit food intake as well in rodents and humans by the activation of an intestine - brain axis(1-4). In parallel, a brain - liver axis has recently been proposed to detect blood lipids to inhibit glucose production in rodents(5). Thus, we tested the hypothesis that upper intestinal lipids activate an intestine - brain - liver neural axis to regulate glucose homeostasis. Here we demonstrate that direct administration of lipids into the upper intestine increased upper intestinal long- chain fatty acyl-coenzyme A ( LCFA- CoA) levels and suppressed glucose production. Co- infusion of the acyl- CoA synthase inhibitor triacsin C or the anaesthetic tetracaine with duodenal lipids abolished the inhibition of glucose production, indicating that upper intestinal LCFA- CoAs regulate glucose production in the preabsorptive state. Subdiaphragmatic vagotomy or gut vagal deafferentation interrupts the neural connection between the gut and the brain, and blocks the ability of upper intestinal lipids to inhibit glucose production. Direct administration of the N- methyl- D- aspartate ion channel blocker MK- 801 into the fourth ventricle or the nucleus of the solitary tract where gut sensory fibres terminate abolished the upper- intestinal- lipid- induced inhibition of glucose production. Finally, hepatic vagotomy negated the inhibitory effects of upper intestinal lipids on glucose production. These findings indicate that upper intestinal lipids activate an intestine - brain - liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis.
C1 [Wang, Penny Y. T.; Caspi, Liora; Lam, Carol K. L.; Chari, Madhu; Ang, Michelle; Lam, Tony K. T.] Univ Hlth Network, Toronto Gen Hosp, Res Inst, Toronto, ON M5G 1L7, Canada.
   [Lam, Carol K. L.; Chari, Madhu; Lam, Tony K. T.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada.
   [Lam, Tony K. T.] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada.
   [Li, Xiaosong; Gutierrez-Juarez, Roger; Schwartz, Gary J.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA.
   [Li, Xiaosong; Gutierrez-Juarez, Roger; Schwartz, Gary J.] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA.
   [Light, Peter E.] Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada.
C3 University of Toronto; University Health Network Toronto; Toronto General Hospital; University of Toronto; University of Toronto; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University of Alberta
RP Lam, TKT (corresponding author), Univ Hlth Network, Toronto Gen Hosp, Res Inst, Toronto, ON M5G 1L7, Canada.
EM tony.lam@uhnres.utoronto.ca
FU NIDDK NIH HHS [DK45024, DK47208] Funding Source: Medline
NR 30
TC 244
Z9 297
U1 3
U2 85
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 24
PY 2008
VL 452
IS 7190
BP 1012
EP 1016
DI 10.1038/nature06852
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600043
PM 18401341
DA 2026-03-09
ER

PT J
AU Wang, B
   Côté, AP
   Furukawa, H
   O'Keeffe, M
   Yaghi, OM
AF Wang, Bo
   Cote, Adrien P.
   Furukawa, Hiroyasu
   O'Keeffe, Michael
   Yaghi, Omar M.
TI Colossal cages in zeolitic imidazolate frameworks as selective carbon dioxide reservoirs
SO NATURE
LA English
DT Article
ID metal-organic frameworks; gas separation; design; polymers; nets
AB Zeolitic imidazolate frameworks ( ZIFs) are porous crystalline materials with tetrahedral networks that resemble those of zeolites: transition metals ( Zn, Co) replace tetrahedrally coordinated atoms ( for example, Si), and imidazolate links replace oxygen bridges(1). A striking feature of these materials is that the structure adopted by a given ZIF is determined by link - link interactions, rather than by the structure directing agents used in zeolite synthesis(2). As a result, systematic variations of linker substituents have yielded many different ZIFs that exhibit known or predicted zeolite topologies. The materials are chemically and thermally stable, yet have the long- sought- after design flexibility offered by functionalized organic links and a high density of transition metal ions(1-7) . Here we report the synthesis and characterization of two porous ZIFs-ZIF-95 and ZIF-100-with structures of a scale and complexity previously unknown in zeolites(8-10). The materials have complex cages that contain up to 264 vertices, and are constructed from as many as 7,524 atoms. As expected from the adsorption selectivity recently documented for other members of this materials family(3), both ZIFs selectively capture carbon dioxide from several different gas mixtures at room temperature, with ZIF-100 capable of storing 28 litres per litre of material at standard temperature and pressure. These characteristics, combined with their high thermal and chemical stability and ease of fabrication, make ZIFs promising candidate materials for strategies aimed at ameliorating increasing atmospheric carbon dioxide levels.
C1 [Wang, Bo; Cote, Adrien P.; Furukawa, Hiroyasu; Yaghi, Omar M.] Univ Calif Los Angeles, Dept Chem & Biochem, Ctr Reticular Chem, Los Angeles, CA 90095 USA.
   [O'Keeffe, Michael] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
C3 University of California System; University of California Los Angeles; Arizona State University; Arizona State University-Tempe
RP Yaghi, OM (corresponding author), Univ Calif Los Angeles, Dept Chem & Biochem, Ctr Reticular Chem, 607 E Charles E Young Dr, Los Angeles, CA 90095 USA.
EM yaghi@chem.ucla.edu
NR 28
TC 1430
Z9 1620
U1 19
U2 1413
PU NATURE PUBLISHING 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 8
PY 2008
VL 453
IS 7192
BP 207
EP U6
DI 10.1038/nature06900
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400036
PM 18464739
DA 2026-03-09
ER

PT J
AU Singh, R
   Jamieson, A
   Cresswell, P
AF Singh, Reshma
   Jamieson, Amanda
   Cresswell, Peter
TI GILT is a critical host factor for Listeria monocytogenes infection
SO NATURE
LA English
DT Article
ID thiol reductase gilt; maturation; hepatocytes; cytolysins; mutants; peptide; complex; prepore; spread; growth
AB Listeria monocytogenes is a Gram- positive, intracellular, foodborne pathogen that can cause severe illness in humans and animals. On infection, it is actively phagocytosed by macrophages(1); it then escapes from the phagosome, replicates in the cytosol, and subsequently spreads from cell to cell by a non- lytic mechanism driven by actin polymerization(2). Penetration of the phagosomal membrane is initiated by the secreted haemolysin listeriolysin O ( LLO), which is essential for vacuolar escape in vitro and for virulence in animal models of infection(3). Reduction is required to activate the lytic activity of LLO in vitro(4-6), and we show here that reduction by the enzyme gamma-interferon- inducible lysosomal thiol reductase ( GILT, also called Ifi30) is responsible for the activation of LLO in vivo. GILT is a soluble thiol reductase expressed constitutively within the lysosomes of antigen- presenting cells(7,8), and it accumulates in macrophage phagosomes as they mature into phagolysosomes(9). The enzyme is delivered by a mannose-6-phosphate receptor- dependent mechanism to the endocytic pathway, where amino- and carboxy- terminal pro- peptides are cleaved to generate a 30- kDa mature enzyme(7,8,10). The active site of GILT contains two cysteine residues in a CXXC motif that catalyses the reduction of disulphide bonds(7,8). Mice lacking GILT are deficient in generating major histocompatibility complex class- II- restricted CD4(+) T-cell responses to protein antigens that contain disulphide bonds(11,12). Here we show that these mice are resistant to L. monocytogenes infection. Replication of the organism in GILT- negative macrophages, or macrophages expressing an enzymatically inactive GILT mutant, is impaired because of delayed escape from the phagosome. GILT activates LLO within the phagosome by the thiol reductase mechanism shared by members of the thioredoxin family. In addition, purified GILT activates recombinant LLO, facilitating membrane permeabilization and red blood cell lysis. The data show that GILT is a critical host factor that facilitates L. monocytogenes infection.
C1 [Singh, Reshma; Jamieson, Amanda; Cresswell, Peter] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06250 USA.
   [Singh, Reshma; Cresswell, Peter] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06250 USA.
C3 Yale University; Yale University; Howard Hughes Medical Institute
RP Cresswell, P (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 300 Cedar St, New Haven, CT 06250 USA.
EM peter.cresswell@yale.edu
FU NIH [AI023081]; Howard Hughes Medical Institute
NR 30
TC 121
Z9 159
U1 1
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1244
EP U55
DI 10.1038/nature07344
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100045
PM 18815593
DA 2026-03-09
ER

PT J
AU Boussau, B
   Blanquart, S
   Necsulea, A
   Lartillot, N
   Gouy, M
AF Boussau, Bastien
   Blanquart, Samuel
   Necsulea, Anamaria
   Lartillot, Nicolas
   Gouy, Manolo
TI Parallel adaptations to high temperatures in the Archaean eon
SO NATURE
LA English
DT Article
ID sequence alignment; evolution; origin; bombardment; bacteria; ancestor; accurate; protein; model; time
AB Fossils of organisms dating from the origin and diversification of cellular life are scant and difficult to interpret(1), for this reason alternative means to investigate the ecology of the last universal common ancestor ( LUCA) and of the ancestors of the three domains of life are of great scientific value. It was recently recognized that the effects of temperature on ancestral organisms left 'genetic footprints' that could be uncovered in extant genomes(2-4). Accordingly, analyses of resurrected proteins predicted that the bacterial ancestor was thermophilic and that Bacteria subsequently adapted to lower temperatures(3,4). As the archaeal ancestor is also thought to have been thermophilic(5), the LUCA was parsimoniously inferred as thermophilic too. However, an analysis of ribosomal RNAs supported the hypothesis of a non- hyperthermophilic LUCA(2). Here we show that both rRNA and protein sequences analysed with advanced, realistic models of molecular evolution(6,7) provide independent support for two environmental- temperature-related phases during the evolutionary history of the tree of life. In the first period, thermotolerance increased from a mesophilic LUCA to thermophilic ancestors of Bacteria and of Archaea Eukaryota; in the second period, it decreased. Therefore, the two lineages descending from the LUCA and leading to the ancestors of Bacteria and Archaea - Eukaryota convergently adapted to high temperatures, possibly in response to a climate change of the early Earth(1,8,9), and/or aided by the transition from an RNA genome in the LUCA to organisms with more thermostable DNA genomes(10,11). This analysis unifies apparently contradictory results(2-4) into a coherent depiction of the evolution of an ecological trait over the entire tree of life.
C1 [Boussau, Bastien; Necsulea, Anamaria; Gouy, Manolo] Univ Lyon 1, CNRS, Lab Biometrie & Biol Evolut, F-69622 Villeurbanne, France.
   [Blanquart, Samuel; Lartillot, Nicolas] CNRS, LIRMM, F-34392 Montpellier, France.
C3 Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); VetAgro Sup; Centre National de la Recherche Scientifique (CNRS); Universite Paul-Valery; Universite Perpignan Via Domitia; Universite de Montpellier
RP Gouy, M (corresponding author), Univ Lyon 1, CNRS, Lab Biometrie & Biol Evolut, 32 Blvd 11 Novembre, F-69622 Villeurbanne, France.
EM mgouy@biomserv.univ-lyon1.fr
FU Action Concertee Incitative IMPBIO-MODELPHYLO; ANR PlasmoExplore
NR 45
TC 173
Z9 194
U1 2
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 942
EP U74
DI 10.1038/nature07393
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300043
PM 19037246
DA 2026-03-09
ER

PT J
AU Romani, L
   Fallarino, F
   De Luca, A
   Montagnoli, C
   D'Angelo, C
   Zelante, T
   Vacca, C
   Bistoni, F
   Fioretti, MC
   Grohmann, U
   Segal, BH
   Puccetti, P
AF Romani, Luigina
   Fallarino, Francesca
   De Luca, Antonella
   Montagnoli, Claudia
   D'Angelo, Carmen
   Zelante, Teresa
   Vacca, Carmine
   Bistoni, Francesco
   Fioretti, Maria C.
   Grohmann, Ursula
   Segal, Brahm H.
   Puccetti, Paolo
TI Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease
SO NATURE
LA English
DT Article
ID delta-t-cells; nf-kappa-b; dendritic cells; indoleamine 2,3-dioxygenase; il-17 production; host-defense; gamma; ido; tolerance; infection
AB Half a century ago, chronic granulomatous disease ( CGD) was first described as a disease fatally affecting the ability of children to survive infections. Various milestone discoveries have since been made, from an insufficient ability of patients' leucocytes to kill microbes to the underlying genetic abnormalities(1). In this inherited disorder, phagocytes lack NADPH oxidase activity and do not generate reactive oxygen species, most notably superoxide anion, causing recurrent bacterial and fungal infections. Patients with CGD also suffer from chronic inflammatory conditions, most prominently granuloma formation in hollow viscera. The precise mechanisms of the increased microbial pathogenicity have been unclear(2), and more so the reasons for the exaggerated inflammatory response(3-6). Here we show that a superoxide- dependent step in tryptophan metabolism along the kynurenine pathway is blocked in CGD mice with lethal pulmonary aspergillosis, leading to unrestrained V gamma 1(+) gamma delta T- cell reactivity, dominant production of interleukin ( IL)- 17, defective regulatory T- cell activity and acute inflammatory lung injury. Although beneficial effects are induced by IL- 17 neutralization or gamma delta T- cell contraction, complete cure and reversal of the hyperinflammatory phenotype are achieved by replacement therapy with a natural kynurenine distal to the blockade in the pathway. Effective therapy, which includes co-administration of recombinant interferon-gamma ( IFN-gamma), restores production of downstream immunoactive metabolites and enables the emergence of regulatory V gamma 4(+) gamma delta and Foxp3(+) alpha beta T cells. Therefore, paradoxically, the lack of reactive oxygen species contributes to the hyperinflammatory phenotype associated with NADPH oxidase deficiencies, through a dysfunctional kynurenine pathway of tryptophan catabolism. Yet, this condition can be reverted by reactivating the pathway downstream of the superoxide- dependent step.
C1 [Romani, Luigina; Fallarino, Francesca; De Luca, Antonella; Montagnoli, Claudia; D'Angelo, Carmen; Zelante, Teresa; Vacca, Carmine; Bistoni, Francesco; Fioretti, Maria C.; Grohmann, Ursula; Puccetti, Paolo] Univ Perugia, Dept Expt Med, I-06126 Perugia, Italy.
   [Segal, Brahm H.] Roswell Pk Canc Inst, Div Infect Dis, Buffalo, NY 14263 USA.
C3 University of Perugia; Roswell Park Comprehensive Cancer Center
RP Romani, L (corresponding author), Univ Perugia, Dept Expt Med, I-06126 Perugia, Italy.
EM iromani@unipg.it; plopcc@tin.it
NR 39
TC 469
Z9 527
U1 0
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 211
EP U12
DI 10.1038/nature06471
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400047
PM 18185592
DA 2026-03-09
ER

PT J
AU Mancera, E
   Bourgon, R
   Brozzi, A
   Huber, W
   Steinmetz, LM
AF Mancera, Eugenio
   Bourgon, Richard
   Brozzi, Alessandro
   Huber, Wolfgang
   Steinmetz, Lars M.
TI High-resolution mapping of meiotic crossovers and non-crossovers in yeast
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; gene conversion; crossing-over; hot-spots; recombination hotspots; meiosis; dna; evolution; genome; bioinformatics
AB Meiotic recombination has a central role in the evolution of sexually reproducing organisms. The two recombination outcomes, crossover and non-crossover, increase genetic diversity, but have the potential to homogenize alleles by gene conversion. Whereas crossover rates vary considerably across the genome, non-crossovers and gene conversions have only been identified in a handful of loci. To examine recombination genome wide and at high spatial resolution, we generated maps of crossovers, crossover-associated gene conversion and non-crossover gene conversion using dense genetic marker data collected from all four products of fifty-six yeast (Saccharomyces cerevisiae) meioses. Our maps reveal differences in the distributions of crossovers and non-crossovers, showing more regions where either crossovers or non-crossovers are favoured than expected by chance. Furthermore, we detect evidence for interference between crossovers and non-crossovers, a phenomenon previously only known to occur between crossovers. Up to 1% of the genome of each meiotic product is subject to gene conversion in a single meiosis, with detectable bias towards GC nucleotides. To our knowledge the maps represent the first high-resolution, genome-wide characterization of the multiple outcomes of recombination in any organism. In addition, because non-crossover hotspots create holes of reduced linkage within haplotype blocks, our results stress the need to incorporate non-crossovers into genetic linkage analysis.
C1 [Mancera, Eugenio; Steinmetz, Lars M.] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Bourgon, Richard; Brozzi, Alessandro; Huber, Wolfgang] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
C3 European Molecular Biology Laboratory (EMBL); 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 NHGRI NIH HHS [P01 HG000205] Funding Source: Medline; NIGMS NIH HHS [R01 GM068717] Funding Source: Medline
NR 49
TC 493
Z9 591
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 479
EP U1
DI 10.1038/nature07135
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300043
PM 18615017
DA 2026-03-09
ER

PT J
AU Kim, JE
   Chen, JJ
   Lou, ZK
AF Kim, Ja-Eun
   Chen, Junjie
   Lou, Zhenkun
TI DBC1 is a negative regulator of SIRT1
SO NATURE
LA English
DT Article
ID calorie restriction; cell-survival; life-span; transcription factors; tumor-suppressor; dna-damage; deacetylase; cancer; stress; nad
AB The NAD- dependent protein deacetylase Sir2 ( silent information regulator 2) regulates lifespan in several organisms(1-3). SIRT1, the mammalian orthologue of yeast Sir2, participates in various cellular functions(4-7) and possibly tumorigenesis(8). Whereas the cellular functions of SIRT1 have been extensively investigated, less is known about the regulation of SIRT1 activity. Here we show that Deleted in Breast Cancer- 1 ( DBC1), initially cloned from a region ( 8p21) homozygously deleted in breast cancers(9), forms a stable complex with SIRT1. DBC1 directly interacts with SIRT1 and inhibits SIRT1 activity in vitro and in vivo. Downregulation of DBC1 expression potentiates SIRT1- dependent inhibition of apoptosis induced by genotoxic stress. Our results shed new light on the regulation of SIRT1 and have important implications in understanding the molecular mechanism of ageing and cancer.
C1 [Kim, Ja-Eun; Chen, Junjie] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA.
   [Lou, Zhenkun] Mayo Clin, Coll Med, Div Oncol Res, Rochester, MN 55905 USA.
C3 Yale University; Mayo Clinic
RP Chen, JJ (corresponding author), Yale Univ, Sch Med, Dept Therapeut Radiol, 333 Cedar St, New Haven, CT 06520 USA.
EM Junjie.Chen@yale.edu; Lou.Zhenkun@mayo.edu
NR 30
TC 438
Z9 510
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 JAN 31
PY 2008
VL 451
IS 7178
BP 583
EP U10
DI 10.1038/nature06500
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900044
PM 18235501
DA 2026-03-09
ER

PT J
AU Laurberg, M
   Asahara, H
   Korostelev, A
   Zhu, JY
   Trakhanov, S
   Noller, HF
AF Laurberg, Martin
   Asahara, Haruichi
   Korostelev, Andrei
   Zhu, Jianyu
   Trakhanov, Sergei
   Noller, Harry F.
TI Structural basis for translation termination on the 70S ribosome
SO NATURE
LA English
DT Article
ID stop codon recognition; peptide-bond formation; transfer-rna; release factors; ggq motif; crystal-structure; escherichia-coli; chain termination; decoding center; human erf1
AB At termination of protein synthesis, type I release factors promote hydrolysis of the peptidyl-transfer RNA linkage in response to recognition of a stop codon. Here we describe the crystal structure of the Thermus thermophilus 70S ribosome in complex with the release factor RF1, tRNA and a messenger RNA containing a UAA stop codon, at 3.2 angstrom resolution. The stop codon is recognized in a pocket formed by conserved elements of RF1, including its PxT recognition motif, and 16S ribosomal RNA. The codon and the 30S subunit A site undergo an induced fit that results in stabilization of a conformation of RF1 that promotes its interaction with the peptidyl transferase centre. Unexpectedly, the main-chain amide group of Gln 230 in the universally conserved GGQ motif of the factor is positioned to contribute directly to peptidyl-tRNA hydrolysis.
C1 [Laurberg, Martin; Asahara, Haruichi; Korostelev, Andrei; Zhu, Jianyu; Trakhanov, Sergei; Noller, Harry F.] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
   [Laurberg, Martin; Asahara, Haruichi; Korostelev, Andrei; Zhu, Jianyu; Trakhanov, Sergei; Noller, Harry F.] Univ Calif Santa Cruz, Ctr Mol Biol RNA, Santa Cruz, CA 95064 USA.
C3 University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz
RP Noller, HF (corresponding author), Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
EM harry@nuvolari.ucsc.edu
NR 43
TC 288
Z9 380
U1 0
U2 28
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 14
PY 2008
VL 454
IS 7206
BP 852
EP 857
DI 10.1038/nature07115
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600028
PM 18596689
DA 2026-03-09
ER

PT J
AU Bentley, DR
   Balasubramanian, S
   Swerdlow, HP
   Smith, GP
   Milton, J
   Brown, CG
   Hall, KP
   Evers, DJ
   Barnes, CL
   Bignell, HR
   Boutell, JM
   Bryant, J
   Carter, RJ
   Cheetham, RK
   Cox, AJ
   Ellis, DJ
   Flatbush, MR
   Gormley, NA
   Humphray, SJ
   Irving, LJ
   Karbelashvili, MS
   Kirk, SM
   Li, H
   Liu, XH
   Maisinger, KS
   Murray, LJ
   Obradovic, B
   Ost, T
   Parkinson, ML
   Pratt, MR
   Rasolonjatovo, IMJ
   Reed, MT
   Rigatti, R
   Rodighiero, C
   Ross, MT
   Sabot, A
   Sankar, SV
   Scally, A
   Schroth, GP
   Smith, ME
   Smith, VP
   Spiridou, A
   Torrance, PE
   Tzonev, SS
   Vermaas, EH
   Walter, K
   Wu, XL
   Zhang, L
   Alam, MD
   Anastasi, C
   Aniebo, IC
   Bailey, DMD
   Bancarz, IR
   Banerjee, S
   Barbour, SG
   Baybayan, PA
   Benoit, VA
   Benson, KF
   Bevis, C
   Black, PJ
   Boodhun, A
   Brennan, JS
   Bridgham, JA
   Brown, RC
   Brown, AA
   Buermann, DH
   Bundu, AA
   Burrows, JC
   Carter, NP
   Castillo, N
   Catenazzi, MCE
   Chang, S
   Cooley, RN
   Crake, NR
   Dada, OO
   Diakoumakos, KD
   Dominguez-Fernandez, B
   Earnshaw, DJ
   Egbujor, UC
   Elmore, DW
   Etchin, SS
   Ewan, MR
   Fedurco, M
   Fraser, LJ
   Fajardo, KVF
   Furey, WS
   George, D
   Gietzen, KJ
   Goddard, CP
   Golda, GS
   Granieri, PA
   Green, DE
   Gustafson, DL
   Hansen, NF
   Harnish, K
   Haudenschild, CD
   Heyer, NI
   Hims, MM
   Ho, JT
   Horgan, AM
   Hoschler, K
   Hurwitz, S
   Ivanov, DV
   Johnson, MQ
   James, T
   Jones, TAH
   Kang, GD
   Kerelska, TH
   Kersey, AD
   Khrebtukova, I
   Kindwall, AP
   Kingsbury, Z
   Kokko-Gonzales, PI
   Kumar, A
   Laurent, MA
   Lawley, CT
   Lee, SE
   Lee, X
   Liao, AK
   Loch, JA
   Lok, M
   Luo, SJ
   Mammen, RM
   Martin, JW
   McCauley, PG
   McNitt, P
   Mehta, P
   Moon, KW
   Mullens, JW
   Newington, T
   Ning, ZM
   Ng, BL
   Novo, SM
   O'Neill, MJ
   Osborne, MA
   Osnowski, A
   Ostadan, O
   Paraschos, LL
   Pickering, L
   Pike, AC
   Pike, AC
   Pinkard, DC
   Pliskin, DP
   Podhasky, J
   Quijano, VJ
   Raczy, C
   Rae, VH
   Rawlings, SR
   Rodriguez, AC
   Roe, PM
   Rogers, J
   Bacigalupo, MCR
   Romanov, N
   Romieu, A
   Roth, RK
   Rourke, NJ
   Ruediger, ST
   Rusman, E
   Sanches-Kuiper, RM
   Schenker, MR
   Seoane, JM
   Shaw, RJ
   Shiver, MK
   Short, SW
   Sizto, NL
   Sluis, JP
   Smith, MA
   Sohna, JES
   Spence, EJ
   Stevens, K
   Sutton, N
   Szajkowski, L
   Tregidgo, CL
   Turcatti, G
   vandeVondele, S
   Verhovsky, Y
   Virk, SM
   Wakelin, S
   Walcott, GC
   Wang, JW
   Worsley, GJ
   Yan, JY
   Yau, L
   Zuerlein, M
   Rogers, J
   Mullikin, JC
   Hurles, ME
   McCooke, NJ
   West, JS
   Oaks, FL
   Lundberg, PL
   Klenerman, D
   Durbin, R
   Smith, AJ
AF Bentley, David R.
   Balasubramanian, Shankar
   Swerdlow, Harold P.
   Smith, Geoffrey P.
   Milton, John
   Brown, Clive G.
   Hall, Kevin P.
   Evers, Dirk J.
   Barnes, Colin L.
   Bignell, Helen R.
   Boutell, Jonathan M.
   Bryant, Jason
   Carter, Richard J.
   Cheetham, R. Keira
   Cox, Anthony J.
   Ellis, Darren J.
   Flatbush, Michael R.
   Gormley, Niall A.
   Humphray, Sean J.
   Irving, Leslie J.
   Karbelashvili, Mirian S.
   Kirk, Scott M.
   Li, Heng
   Liu, Xiaohai
   Maisinger, Klaus S.
   Murray, Lisa J.
   Obradovic, Bojan
   Ost, Tobias
   Parkinson, Michael L.
   Pratt, Mark R.
   Rasolonjatovo, Isabelle M. J.
   Reed, Mark T.
   Rigatti, Roberto
   Rodighiero, Chiara
   Ross, Mark T.
   Sabot, Andrea
   Sankar, Subramanian V.
   Scally, Aylwyn
   Schroth, Gary P.
   Smith, Mark E.
   Smith, Vincent P.
   Spiridou, Anastassia
   Torrance, Peta E.
   Tzonev, Svilen S.
   Vermaas, Eric H.
   Walter, Klaudia
   Wu, Xiaolin
   Zhang, Lu
   Alam, Mohammed D.
   Anastasi, Carole
   Aniebo, Ify C.
   Bailey, David M. D.
   Bancarz, Iain R.
   Banerjee, Saibal
   Barbour, Selena G.
   Baybayan, Primo A.
   Benoit, Vincent A.
   Benson, Kevin F.
   Bevis, Claire
   Black, Phillip J.
   Boodhun, Asha
   Brennan, Joe S.
   Bridgham, John A.
   Brown, Rob C.
   Brown, Andrew A.
   Buermann, Dale H.
   Bundu, Abass A.
   Burrows, James C.
   Carter, Nigel P.
   Castillo, Nestor
   Catenazzi, Maria Chiara E.
   Chang, Simon
   Cooley, R. Neil
   Crake, Natasha R.
   Dada, Olubunmi O.
   Diakoumakos, Konstantinos D.
   Dominguez-Fernandez, Belen
   Earnshaw, David J.
   Egbujor, Ugonna C.
   Elmore, David W.
   Etchin, Sergey S.
   Ewan, Mark R.
   Fedurco, Milan
   Fraser, Louise J.
   Fajardo, Karin V. Fuentes
   Furey, W. Scott
   George, David
   Gietzen, Kimberley J.
   Goddard, Colin P.
   Golda, George S.
   Granieri, Philip A.
   Green, David E.
   Gustafson, David L.
   Hansen, Nancy F.
   Harnish, Kevin
   Haudenschild, Christian D.
   Heyer, Narinder I.
   Hims, Matthew M.
   Ho, Johnny T.
   Horgan, Adrian M.
   Hoschler, Katya
   Hurwitz, Steve
   Ivanov, Denis V.
   Johnson, Maria Q.
   James, Terena
   Jones, T. A. Huw
   Kang, Gyoung-Dong
   Kerelska, Tzvetana H.
   Kersey, Alan D.
   Khrebtukova, Irina
   Kindwall, Alex P.
   Kingsbury, Zoya
   Kokko-Gonzales, Paula I.
   Kumar, Anil
   Laurent, Marc A.
   Lawley, Cynthia T.
   Lee, Sarah E.
   Lee, Xavier
   Liao, Arnold K.
   Loch, Jennifer A.
   Lok, Mitch
   Luo, Shujun
   Mammen, Radhika M.
   Martin, John W.
   McCauley, Patrick G.
   McNitt, Paul
   Mehta, Parul
   Moon, Keith W.
   Mullens, Joe W.
   Newington, Taksina
   Ning, Zemin
   Ng, Bee Ling
   Novo, Sonia M.
   O'Neill, Michael J.
   Osborne, Mark A.
   Osnowski, Andrew
   Ostadan, Omead
   Paraschos, Lambros L.
   Pickering, Lea
   Pike, Andrew C.
   Pike, Alger C.
   Pinkard, D. Chris
   Pliskin, Daniel P.
   Podhasky, Joe
   Quijano, Victor J.
   Raczy, Come
   Rae, Vicki H.
   Rawlings, Stephen R.
   Rodriguez, Ana Chiva
   Roe, Phyllida M.
   Rogers, John
   Bacigalupo, Maria C. Rogert
   Romanov, Nikolai
   Romieu, Anthony
   Roth, Rithy K.
   Rourke, Natalie J.
   Ruediger, Silke T.
   Rusman, Eli
   Sanches-Kuiper, Raquel M.
   Schenker, Martin R.
   Seoane, Josefina M.
   Shaw, Richard J.
   Shiver, Mitch K.
   Short, Steven W.
   Sizto, Ning L.
   Sluis, Johannes P.
   Smith, Melanie A.
   Sohna, Jean Ernest Sohna
   Spence, Eric J.
   Stevens, Kim
   Sutton, Neil
   Szajkowski, Lukasz
   Tregidgo, Carolyn L.
   Turcatti, Gerardo
   vandeVondele, Stephanie
   Verhovsky, Yuli
   Virk, Selene M.
   Wakelin, Suzanne
   Walcott, Gregory C.
   Wang, Jingwen
   Worsley, Graham J.
   Yan, Juying
   Yau, Ling
   Zuerlein, Mike
   Rogers, Jane
   Mullikin, James C.
   Hurles, Matthew E.
   McCooke, Nick J.
   West, John S.
   Oaks, Frank L.
   Lundberg, Peter L.
   Klenerman, David
   Durbin, Richard
   Smith, Anthony J.
TI Accurate whole human genome sequencing using reversible terminator chemistry
SO NATURE
LA English
DT Article
ID structural variation; chromatin; maps
AB DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long ( 400 - 800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re- sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high- quality sequence. We demonstrate application of this approach to human genome sequencing on flow- sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from. 303 average depth of paired 35- base reads. We characterize four million single- nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole- genome re- sequencing and many other biomedical applications.
C1 [Bentley, David R.; Swerdlow, Harold P.; Smith, Geoffrey P.; Milton, John; Brown, Clive G.; Hall, Kevin P.; Evers, Dirk J.; Barnes, Colin L.; Bignell, Helen R.; Boutell, Jonathan M.; Bryant, Jason; Carter, Richard J.; Cheetham, R. Keira; Cox, Anthony J.; Ellis, Darren J.; Gormley, Niall A.; Humphray, Sean J.; Irving, Leslie J.; Liu, Xiaohai; Maisinger, Klaus S.; Murray, Lisa J.; Obradovic, Bojan; Ost, Tobias; Parkinson, Michael L.; Rasolonjatovo, Isabelle M. J.; Rigatti, Roberto; Rodighiero, Chiara; Ross, Mark T.; Sabot, Andrea; Smith, Mark E.; Smith, Vincent P.; Spiridou, Anastassia; Torrance, Peta E.; Wu, Xiaolin; Anastasi, Carole; Aniebo, Ify C.; Bailey, David M. D.; Bancarz, Iain R.; Barbour, Selena G.; Benoit, Vincent A.; Benson, Kevin F.; Bevis, Claire; Black, Phillip J.; Boodhun, Asha; Brennan, Joe S.; Brown, Rob C.; Brown, Andrew A.; Bundu, Abass A.; Catenazzi, Maria Chiara E.; Cooley, R. Neil; Crake, Natasha R.; Dada, Olubunmi O.; Diakoumakos, Konstantinos D.; Dominguez-Fernandez, Belen; Earnshaw, David J.; Egbujor, Ugonna C.; Fraser, Louise J.; Fajardo, Karin V. Fuentes; Goddard, Colin P.; Green, David E.; Harnish, Kevin; Heyer, Narinder I.; Hims, Matthew M.; Horgan, Adrian M.; Hoschler, Katya; James, Terena; Jones, T. A. Huw; Kang, Gyoung-Dong; Kersey, Alan D.; Kingsbury, Zoya; Kokko-Gonzales, Paula I.; Kumar, Anil; Lee, Sarah E.; Loch, Jennifer A.; Mammen, Radhika M.; McCauley, Patrick G.; Mehta, Parul; Newington, Taksina; Novo, Sonia M.; Osborne, Mark A.; Osnowski, Andrew; Pickering, Lea; Pike, Andrew C.; Raczy, Come; Rae, Vicki H.; Rawlings, Stephen R.; Rodriguez, Ana Chiva; Roe, Phyllida M.; Rogers, John; Bacigalupo, Maria C. Rogert; Romanov, Nikolai; Rourke, Natalie J.; Ruediger, Silke T.; Sanches-Kuiper, Raquel M.; Schenker, Martin R.; Shaw, Richard J.; Smith, Melanie A.; Sohna, Jean Ernest Sohna; Stevens, Kim; Sutton, Neil; Szajkowski, Lukasz; Tregidgo, Carolyn L.; vandeVondele, Stephanie; Wang, Jingwen; Worsley, Graham J.; McCooke, Nick J.; Smith, Anthony J.] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England.
   [Balasubramanian, Shankar; Barnes, Colin L.; Liu, Xiaohai; Earnshaw, David J.; Furey, W. Scott; Osborne, Mark A.; Klenerman, David] Univ Cambridge, Dept Chem, Univ Chem Lab, Cambridge CB2 1EW, England.
   [Flatbush, Michael R.; Karbelashvili, Mirian S.; Kirk, Scott M.; Pratt, Mark R.; Reed, Mark T.; Sankar, Subramanian V.; Schroth, Gary P.; Tzonev, Svilen S.; Vermaas, Eric H.; Zhang, Lu; Alam, Mohammed D.; Banerjee, Saibal; Baybayan, Primo A.; Bridgham, John A.; Buermann, Dale H.; Burrows, James C.; Castillo, Nestor; Chang, Simon; Elmore, David W.; Etchin, Sergey S.; Ewan, Mark R.; George, David; Golda, George S.; Granieri, Philip A.; Gustafson, David L.; Haudenschild, Christian D.; Ho, Johnny T.; Hurwitz, Steve; Ivanov, Denis V.; Johnson, Maria Q.; Kerelska, Tzvetana H.; Khrebtukova, Irina; Kindwall, Alex P.; Lee, Xavier; Liao, Arnold K.; Lok, Mitch; Luo, Shujun; Martin, John W.; McNitt, Paul; Moon, Keith W.; Mullens, Joe W.; O'Neill, Michael J.; Ostadan, Omead; Paraschos, Lambros L.; Pike, Alger C.; Pinkard, D. Chris; Pliskin, Daniel P.; Podhasky, Joe; Quijano, Victor J.; Roth, Rithy K.; Rusman, Eli; Seoane, Josefina M.; Shiver, Mitch K.; Short, Steven W.; Sizto, Ning L.; Sluis, Johannes P.; Spence, Eric J.; Verhovsky, Yuli; Virk, Selene M.; Wakelin, Suzanne; Walcott, Gregory C.; Yan, Juying; Yau, Ling; Zuerlein, Mike; West, John S.; Oaks, Frank L.; Lundberg, Peter L.] Illumina Hayward, Hayward, CA 94343 USA.
   [Li, Heng; Scally, Aylwyn; Walter, Klaudia; Carter, Nigel P.; Ning, Zemin; Ng, Bee Ling; Rogers, Jane; Hurles, Matthew E.; Durbin, Richard] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Fedurco, Milan; Romieu, Anthony; Turcatti, Gerardo] Manteia Predict Med SA, CH-1267 Coinsins, Switzerland.
   [Gietzen, Kimberley J.; Laurent, Marc A.; Lawley, Cynthia T.; Ostadan, Omead] Illumina Inc, Corp Headquarters, San Diego, CA 92121 USA.
   [Hansen, Nancy F.; Mullikin, James C.] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 Illumina; University of Cambridge; Illumina; Wellcome Trust Sanger Institute; Illumina; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Bentley, DR (corresponding author), Illumina Cambridge Ltd, Chesterford Res Pk, Saffron Walden CB10 1XL, Essex, England.
EM dbentley@illumina.com
FU The Wellcome Trust; Biotechnology and Biological Sciences Research Council; BBSRC Applied Genomics LINK Programme; Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health; MRC [G0701805] Funding Source: UKRI; Medical Research Council [G0701805] Funding Source: researchfish; National Human Genome Research Institute [ZIAHG200330] Funding Source: NIH RePORTER
NR 32
TC 2585
Z9 3929
U1 10
U2 540
PU NATURE PUBLISHING 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 6
PY 2008
VL 456
IS 7218
BP 53
EP 59
DI 10.1038/nature07517
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000039
PM 18987734
DA 2026-03-09
ER

PT J
AU Deléglise, S
   Dotsenko, I
   Sayrin, C
   Bernu, J
   Brune, M
   Raimond, JM
   Haroche, S
AF Deleglise, Samuel
   Dotsenko, Igor
   Sayrin, Clement
   Bernu, Julien
   Brune, Michel
   Raimond, Jean-Michel
   Haroche, Serge
TI Reconstruction of non-classical cavity field states with snapshots of their decoherence
SO NATURE
LA English
DT Article
ID wigner function; quantum state; entanglement; tomography
AB The state of a microscopic system encodes its complete quantum description, from which the probabilities of all measurement outcomes are inferred. Being a statistical concept, the state cannot be obtained from a single system realization, but can instead be reconstructed(1) from an ensemble of copies through measurements on different realizations(2-4). Reconstructing the state of a set of trapped particles shielded from their environment is an important step in the investigation of the quantum - classical boundary(5). Although trapped- atom state reconstructions(6-8) have been achieved, it is challenging to perform similar experiments with trapped photons because cavities that can store light for very long times are required. Here we report the complete reconstruction and pictorial representation of a variety of radiation states trapped in a cavity in which several photons survive long enough to be repeatedly measured. Atoms crossing the cavity one by one are used to extract information about the field. We obtain images of coherent states(9), Fock states with a definite photon number and 'Schrodinger cat' states ( superpositions of coherent states with different phases(10)). These states are equivalently represented by their density matrices or Wigner functions(11). Quasi- classical coherent states have a Gaussian- shaped Wigner function, whereas the Wigner functions of Fock and Schrodinger cat states show oscillations and negativities revealing quantum interferences. Cavity damping induces decoherence that quickly washes out such oscillations(5). We observe this process and follow the evolution of decoherence by reconstructing snapshots of Schrodinger cat states at successive times. Our reconstruction procedure is a useful tool for further decoherence and quantum feedback studies of fields trapped in one or two cavities.
C1 [Deleglise, Samuel; Dotsenko, Igor; Sayrin, Clement; Bernu, Julien; Brune, Michel; Raimond, Jean-Michel; Haroche, Serge] Univ Paris 06, CNRS, Lab Kastler Brossel, Ecole Normale Super, F-75231 Paris 05, France.
   [Dotsenko, Igor; Haroche, Serge] Coll France, F-75231 Paris 05, France.
C3 Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite PSL; College de France
RP Haroche, S (corresponding author), Univ Paris 06, CNRS, Lab Kastler Brossel, Ecole Normale Super, 24 Rue Lhomond, F-75231 Paris 05, France.
EM haroche@lkb.ens.fr
FU Agence Nationale pour la Recherche; Japan Science and Technology Agency; European Union; Integrated Projects SCALA; CONQUEST; Delegation Generale pour l'Armement
NR 28
TC 492
Z9 544
U1 1
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 510
EP 514
DI 10.1038/nature07288
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600041
PM 18818653
DA 2026-03-09
ER

PT J
AU Liu, Y
   Dentin, R
   Chen, D
   Hedrick, S
   Ravnskjaer, K
   Schenk, S
   Milne, J
   Meyers, DJ
   Cole, P
   Yates, J
   Olefsky, J
   Guarente, L
   Montminy, M
AF Liu, Yi
   Dentin, Renaud
   Chen, Danica
   Hedrick, Susan
   Ravnskjaer, Kim
   Schenk, Simon
   Milne, Jill
   Meyers, David J.
   Cole, Phil
   Yates, John, III
   Olefsky, Jerrold
   Guarente, Leonard
   Montminy, Marc
TI A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange
SO NATURE
LA English
DT Article
ID transcription factor foxo1; glucose-homeostasis; catalytic subunit; gene-expression; factor fkhr; glucose-6-phosphatase; sirt1; p300; metabolism; starvation
AB During early fasting, increases in skeletal muscle proteolysis liberate free amino acids for hepatic gluconeogenesis in response to pancreatic glucagon. Hepatic glucose output diminishes during the late protein- sparing phase of fasting, when ketone body production by the liver supplies compensatory fuel for glucose- dependent tissues(1-4). Glucagon stimulates the gluconeogenic program by triggering the dephosphorylation and nuclear translocation of the CREB regulated transcription coactivator 2 ( CRTC2; also known as TORC2), while parallel decreases in insulin signalling augment gluconeogenic gene expression through the dephosphorylation and nuclear shuttling of forkhead box O1 (FOXO1)(5-7). Here we show that a fasting- inducible switch, consisting of the histone acetyltransferase p300 and the nutrient- sensing deacetylase sirtuin 1 ( SIRT1), maintains energy balance in mice through the sequential induction of CRTC2 and FOXO1. After glucagon induction, CRTC2 stimulated gluconeogenic gene expression by an association with p300, which we show here is also activated by dephosphorylation at Ser 89 during fasting. In turn, p300 increased hepatic CRTC2 activity by acetylating it at Lys 628, a site that also targets CRTC2 for degradation after its ubiquitination by the E3 ligase constitutive photomorphogenic protein (COP1)(8). Glucagon effects were attenuated during late fasting, when CRTC2 was downregulated owing to SIRT1- mediated deacetylation and when FOXO1 supported expression of the gluconeogenic program. Disrupting SIRT1 activity, by liver- specific knockout of the Sirt1 gene or by administration of a SIRT1 antagonist, increased CRTC2 activity and glucose output, whereas exposure to SIRT1 agonists reduced them. In view of the reciprocal activation of FOXO1 and its coactivator peroxisome proliferator- activated receptor-gamma coactivator-1 alpha (PGC-1 alpha, encoded by Ppargc1 alpha) by SIRT1 activators(9-12), our results illustrate how the exchange of two gluconeogenic regulators during fasting maintains energy balance.
C1 [Liu, Yi; Dentin, Renaud; Hedrick, Susan; Ravnskjaer, Kim; Montminy, Marc] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
   [Chen, Danica; Guarente, Leonard] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Schenk, Simon; Olefsky, Jerrold] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Milne, Jill] Sirtris Pharmaceut Inc, Cambridge, MA 02139 USA.
   [Meyers, David J.; Cole, Phil] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
   [Yates, John, III] Scripps Res Inst, La Jolla, CA 92037 USA.
C3 Salk Institute; Massachusetts Institute of Technology (MIT); University of California System; University of California San Diego; Johns Hopkins University; Scripps Research Institute
RP Montminy, M (corresponding author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM Montminy@salk.edu
FU National Institutes of Health; Clayton Medical Research Foundation, Inc; Hillblom Foundation; Kieckhefer Foundation
NR 30
TC 458
Z9 549
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 NOV 13
PY 2008
VL 456
IS 7219
BP 269
EP U74
DI 10.1038/nature07349
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300046
PM 18849969
DA 2026-03-09
ER

PT J
AU Llewellyn, ME
   Barretto, RPJ
   Delp, SL
   Schnitzer, MJ
AF Llewellyn, Michael E.
   Barretto, Robert P. J.
   Delp, Scott L.
   Schnitzer, Mark J.
TI Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans
SO NATURE
LA English
DT Article
ID in-vivo; 2nd-harmonic generation; muscle; microscopy; fluorescence; proteins; mouse; cells
AB Sarcomeres are the basic contractile units of striated muscle. Our knowledge about sarcomere dynamics has primarily come from in vitro studies of muscle fibres(1) and analysis of optical diffraction patterns obtained from living muscles(2,3). Both approaches involve highly invasive procedures and neither allows examination of individual sarcomeres in live subjects. Here we report direct visualization of individual sarcomeres and their dynamical length variations using minimally invasive optical microendoscopy(4) to observe second-harmonic frequencies of light generated in the muscle fibres(5,6) of live mice and humans. Using microendoscopes as small as 350 mm in diameter, we imaged individual sarcomeres in both passive and activated muscle. Our measurements permit in vivo characterization of sarcomere length changes that occur with alterations in body posture and visualization of local variations in sarcomere length not apparent in aggregate length determinations. High-speed data acquisition enabled observation of sarcomere contractile dynamics with millisecond-scale resolution. These experiments point the way to in vivo imaging studies demonstrating how sarcomere performance varies with physical conditioning and physiological state, as well as imaging diagnostics revealing how neuromuscular diseases affect contractile dynamics.
C1 [Llewellyn, Michael E.; Barretto, Robert P. J.; Delp, Scott L.; Schnitzer, Mark J.] Stanford Univ, Bio X Program, James H Clark Ctr Biomed Engn & Sci, Stanford, CA 94305 USA.
C3 Stanford University
RP Schnitzer, MJ (corresponding author), Stanford Univ, Bio X Program, James H Clark Ctr Biomed Engn & Sci, Stanford, CA 94305 USA.
EM mschnitz@stanford.edu
FU NINDS NIH HHS [R01 NS050533, R01NS050533] Funding Source: Medline
NR 30
TC 265
Z9 329
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 784
EP 788
DI 10.1038/nature07104
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000049
PM 18600262
DA 2026-03-09
ER

PT J
AU Nott, A
   Watson, PM
   Robinson, JD
   Crepaldi, L
   Riccio, A
AF Nott, Alexi
   Watson, P. Marc
   Robinson, James D.
   Crepaldi, Luca
   Riccio, Antonella
TI S-nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons
SO NATURE
LA English
DT Article
ID nitric-oxide; signaling pathway; expression; roles
AB Brain- derived neurotrophic factor ( BDNF) and other neurotrophins have a vital role in the development of the rat and mouse nervous system by influencing the expression of many specific genes that promote differentiation, cell survival, synapse formation and, later, synaptic plasticity(1). Although nitric oxide ( NO) is known to be an important mediator of BDNF signalling in neurons(2), the mechanisms by which neurotrophins influence gene expression during development and plasticity remain largely unknown. Here we show that BDNF triggers NO synthesis and S- nitrosylation of histone deacetylase 2 ( HDAC2) in neurons, resulting in changes to histone modifications and gene activation. S- nitrosylation of HDAC2 occurs at Cys 262 and Cys 274 and does not affect deacetylase activity. In contrast, nitrosylation of HDAC2 induces its release from chromatin, which increases acetylation of histones surrounding neurotrophin- dependent gene promoters and promotes transcription. Notably, nitrosylation of HDAC2 in embryonic cortical neurons regulates dendritic growth and branching, possibly by the activation of CREB ( cyclic- AMP-responsive-element- binding protein)- dependent genes. Thus, by stimulating NO production and S- nitrosylation of HDAC2, neurotrophic factors promote chromatin remodelling and the activation of genes that are associated with neuronal development.
C1 [Nott, Alexi; Watson, P. Marc; Robinson, James D.; Crepaldi, Luca; Riccio, Antonella] UCL, MRC, Lab Mol & Cell Biol, London WC1E 6BT, England.
   [Nott, Alexi; Watson, P. Marc; Robinson, James D.; Crepaldi, Luca; Riccio, Antonella] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England.
C3 University of London; University College London; University of London; University College London
RP Riccio, A (corresponding author), UCL, MRC, Lab Mol & Cell Biol, Mortimer St, London WC1E 6BT, England.
EM a.riccio@ucl.ac.uk
FU Medical Research Council [G0500792]; European Research Council [MIRG-CT-2005-016501]; MRC Career Development Fellowship [G117/533]; MRC Career Development Award; Medical Research Council [G120/934, G0500792, MC_U122663296] Funding Source: researchfish; MRC [MC_U122663296, G120/934, G0500792] Funding Source: UKRI
NR 33
TC 369
Z9 401
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 18
PY 2008
VL 455
IS 7211
BP 411
EP U67
DI 10.1038/nature07238
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200049
PM 18754010
DA 2026-03-09
ER

PT J
AU Lagos, M
   Ballhaus, C
   Münker, C
   Wohlgemuth-Ueberwasser, C
   Berndt, J
   Kuzmin, DV
AF Lagos, M.
   Ballhaus, C.
   Muenker, C.
   Wohlgemuth-Ueberwasser, C.
   Berndt, J.
   Kuzmin, Dmitry V.
TI The Earth's missing lead may not be in the core
SO NATURE
LA English
DT Article
ID geochemical constraints; differentiation; moon; age; accretion; pressure; origin; metal
AB Relative to the CI chondrite class of meteorites (widely thought to be the ` building blocks' of the terrestrial planets), the Earth is depleted in volatile elements. For most elements this depletion is thought to be a solar nebular signature, as chondrites show depletions qualitatively similar to that of the Earth(1). Onthe other hand, as lead is a volatile element, some Pb may also have been lost after accretion. The unique Pb-206/Pb-204 and Pb-207/Pb-204 ratios of the Earth's mantle suggest that some lead was lost about 50 to 130 Myr after Solar System formation(2-4). This has commonly been explained by lead lost via the segregation of a sulphide melt to the Earth's core(5-7), which assumes that lead has an affinity towards sulphide. Some models, however, have reconciled the Earth's lead deficit with volatilization(8). Which ever model is preferred, the broad coincidence of U-Pb model ages with the age of the Moon(9-11) suggests that lead loss may be related to the Moon- forming impact. Here we report partitioning experiments in metal - sulphide - silicate systems. We show that lead is neither siderophile nor chalcophile enough to explain the high U/Pb ratio of the Earth'smantle as being a result of lead pumping to the core. The Earth may have accreted from initially volatile- depleted material, some lead may have been lost to degassing following the Moon- forming giant impact, or a hidden reservoir exists in the deep mantle with lead isotope compositions complementary to upper- mantle values; it is unlikely though that the missing lead resides in the core.
C1 [Lagos, M.; Ballhaus, C.; Muenker, C.; Wohlgemuth-Ueberwasser, C.] Univ Bonn, Steinmann Inst, D-53115 Bonn, Germany.
   [Lagos, M.; Muenker, C.; Wohlgemuth-Ueberwasser, C.; Berndt, J.] Univ Munster, Inst Mineral, D-48149 Munster, Germany.
   [Kuzmin, Dmitry V.] Max Planck Inst Chem, Abt Geochem, D-55128 Mainz, Germany.
   [Kuzmin, Dmitry V.] Russian Acad Sci, SB, Inst Geol & Mineral, Novosibirsk 630090, Russia.
C3 University of Bonn; University of Munster; Max Planck Society; Russian Academy of Sciences; Sobolev Institute of Geology & Mineralogy of the Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences
RP Lagos, M (corresponding author), Univ Bonn, Steinmann Inst, Poppelsdorfer Schloss, D-53115 Bonn, Germany.
EM lagos@uni-bonn.de
FU German Research Council
NR 29
TC 46
Z9 51
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 89
EP 92
DI 10.1038/nature07375
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000046
PM 18987741
DA 2026-03-09
ER

PT J
AU Seehausen, O
   Terai, Y
   Magalhaes, IS
   Carleton, KL
   Mrosso, HDJ
   Miyagi, R
   van der Sluijs, I
   Schneider, MV
   Maan, ME
   Tachida, H
   Imai, H
   Okada, N
AF Seehausen, Ole
   Terai, Yohey
   Magalhaes, Isabel S.
   Carleton, Karen L.
   Mrosso, Hillary D. J.
   Miyagi, Ryutaro
   van der Sluijs, Inke
   Schneider, Maria V.
   Maan, Martine E.
   Tachida, Hidenori
   Imai, Hiroo
   Okada, Norihiro
TI Speciation through sensory drive in cichlid fish
SO NATURE
LA English
DT Article
ID lake victoria cichlids; tuning spectral sensitivity; sexual selection; molecular evolution; color-vision; opsin gene; reproductive isolation; adaptive divergence; population; polymorphism
AB Theoretically, divergent selection on sensory systems can cause speciation through sensory drive. However, empirical evidence is rare and incomplete. Here we demonstrate sensory drive speciation within island populations of cichlid fish. We identify the ecological and molecular basis of divergent evolution in the cichlid visual system, demonstrate associated divergence in male colouration and female preferences, and show subsequent differentiation at neutral loci, indicating reproductive isolation. Evidence is replicated in several pairs of sympatric populations and species. Variation in the slope of the environmental gradients explains variation in the progress towards speciation: speciation occurs on all but the steepest gradients. This is the most complete demonstration so far of speciation through sensory drive without geographical isolation. Our results also provide a mechanistic explanation for the collapse of cichlid fish species diversity during the anthropogenic eutrophication of Lake Victoria.
C1 [Seehausen, Ole; Magalhaes, Isabel S.] Univ Bern, Inst Zool, CH-3012 Bern, Switzerland.
   [Seehausen, Ole; Magalhaes, Isabel S.; Schneider, Maria V.] Ctr Ecol Evolut & Biogeochem, Dept Fish Ecol & Evolut, Eawag, Swiss Fed Inst Aquat Sci & Technol, CH-6047 Kastanienbaum, Switzerland.
   [Terai, Yohey; Miyagi, Ryutaro; Okada, Norihiro] Tokyo Inst Technol, Midori Ku, Grad Sch Biosci & Biotechnol, Yokohama, Kanagawa 2268501, Japan.
   [Carleton, Karen L.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
   [Mrosso, Hillary D. J.] Mwanza Ctr, Tanzania Fisheries Res Inst, Mwanza, Tanzania.
   [van der Sluijs, Inke; Maan, Martine E.] Leiden Univ, Dept Anim Ecol, Inst Biol, NL-2300 RA Leiden, Netherlands.
   [Tachida, Hidenori] Kyushu Univ, Fac Sci, Dept Biol, Fukuoka 8108560, Japan.
   [Imai, Hiroo] Kyoto Univ, Dept Cellular & Mol Biol, Primate Res Inst, Kyoto 4848506, Japan.
C3 University of Bern; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); Institute of Science Tokyo; Tokyo Institute of Technology; University System of Maryland; University of Maryland College Park; Leiden University; Leiden University - Excl LUMC; Kyushu University; Kyoto University
RP Seehausen, O (corresponding author), Univ Bern, Inst Zool, Baltzerstr 6, CH-3012 Bern, Switzerland.
EM ole.seehausen@aqua.unibe.ch; nokada@bio.titech.ac.jp
FU Swiss National Science Foundation [3100A0-106573]; Ministry of Education, Culture, Sports, Science and Technology of Japan
NR 49
TC 873
Z9 1033
U1 5
U2 536
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 620
EP U23
DI 10.1038/nature07285
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700037
PM 18833272
DA 2026-03-09
ER

PT J
AU Goyon, J
   Colin, A
   Ovarlez, G
   Ajdari, A
   Bocquet, L
AF Goyon, J.
   Colin, A.
   Ovarlez, G.
   Ajdari, A.
   Bocquet, L.
TI Spatial cooperativity in soft glassy flows
SO NATURE
LA English
DT Article
ID structural relaxation; transition
AB Amorphous glassy materials of diverse nature - concentrated emulsions, granular materials, pastes, molecular glasses - display complex flow properties, intermediate between solid and liquid, which are at the root of their use in many applications(1-3). A general feature of such systems, well documented yet not really understood, is the strongly nonlinear nature of the flow rule relating stresses and strain rates(4,5). Here we use a microfluidic velocimetry technique to characterize the flow of thin layers of concentrated emulsions, confined in gaps of different thicknesses by surfaces of different roughnesses. We find evidence for finite- size effects in the flow behaviour and the absence of an intrinsic local flow rule. In contrast to the classical nonlinearities of the rheological behaviour of amorphous materials, we show that a rather simple nonlocal flow rule can account for all the velocity profiles. This nonlocality of the dynamics is quantified by a length, characteristic of cooperativity within the flow at these scales, that is unobservable in the liquid state ( lower emulsion concentrations) and that increases with concentration in the jammed state. Beyond its practical importance for applications involving thin layers ( for example, coatings), these non- locality and cooperativity effects have parallels in the behaviour of other glassy, jammed and granular systems, suggesting a possible fundamental universality.
C1 [Bocquet, L.] Univ Lyon 1, Lab PMCN, CNRS, UMR 5586, F-69622 Villeurbanne, France.
   [Goyon, J.; Colin, A.] Univ Bordeaux 1, LOF, UMR CNRS Rhodia Bordeaux 1 5258, F-33608 Pessac, France.
   [Ovarlez, G.] Univ Paris Est, Inst Navier, LMSGC, F-77420 Champs Sur Marne, France.
   [Ajdari, A.] Gulliver, UMR CNRS ESPCI 7083, F-75005 Paris, France.
   [Bocquet, L.] Tech Univ Munich, Dept Phys, D-85748 Garching, Germany.
C3 Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Universite de Bordeaux; Universite Gustave-Eiffel; Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Technical University of Munich
RP Bocquet, L (corresponding author), Univ Lyon 1, Lab PMCN, CNRS, UMR 5586, F-69622 Villeurbanne, France.
EM annie.colin-exterieur@eu.rhodia.com; lyderic.bocquet@univ-lyon1.fr
NR 30
TC 352
Z9 395
U1 1
U2 167
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 84
EP 87
DI 10.1038/nature07026
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300041
PM 18596806
DA 2026-03-09
ER

PT J
AU Dolev, M
   Heiblum, M
   Umansky, V
   Stern, A
   Mahalu, D
AF Dolev, M.
   Heiblum, M.
   Umansky, V.
   Stern, Ady
   Mahalu, D.
TI Observation of a quarter of an electron charge at the ν=5/2 quantum Hall state
SO NATURE
LA English
DT Article
ID fractional charge; quasi-particle; noise
AB The fractional quantum Hall effect, where plateaus in the Hall resistance at values of h/nu e(2) coexist with zeros in the longitudinal resistance, results from electron correlations in two dimensions under a strong magnetic field. ( Here h is Planck's constant, nu the filling factor and e the electron charge.) Current flows along the sample edges and is carried by charged excitations ( quasiparticles) whose charge is a fraction of the electron charge. Although earlier research concentrated on odd denominator fractional values of nu, the observation of the even denominator nu = 5/2 state sparked much interest. This state is conjectured to be characterized by quasiparticles of charge e/4, whose statistics are 'non- abelian' - in other words, interchanging two quasiparticles may modify the state of the system into a different one, rather than just adding a phase as is the case for fermions or bosons. As such, these quasiparticles may be useful for the construction of a topological quantum computer. Here we report data on shot noise generated by partitioning edge currents in the nu = 5/2 state, consistent with the charge of the quasiparticle being e/4, and inconsistent with other possible values, such as e/2 and e. Although this finding does not prove the non- abelian nature of the nu= 5/2 state, it is the first step towards a full understanding of these new fractional charges.
C1 [Dolev, M.; Heiblum, M.; Umansky, V.; Stern, Ady; Mahalu, D.] Weizmann Inst Sci, Braun Ctr Submicron Res, Dept Condensed Matter Phys, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science
RP Dolev, M (corresponding author), Weizmann Inst Sci, Braun Ctr Submicron Res, Dept Condensed Matter Phys, IL-76100 Rehovot, Israel.
EM merav.dolev@weizmann.ac.il
NR 29
TC 303
Z9 357
U1 1
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 APR 17
PY 2008
VL 452
IS 7189
BP 829
EP U1
DI 10.1038/nature06855
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000039
PM 18421345
DA 2026-03-09
ER

PT J
AU Yang, YF
   Fisk, Z
   Lee, HO
   Thompson, JD
   Pines, D
AF Yang, Yi-feng
   Fisk, Zachary
   Lee, Han-Oh
   Thompson, J. D.
   Pines, David
TI Scaling the Kondo lattice
SO NATURE
LA English
DT Article
ID ground-state; superconductivity; behavior; system; nmr
AB The origin of magnetic order in metals has two extremes: an instability in a liquid of local magnetic moments interacting through conduction electrons, and a spin- density wave instability in a Fermi liquid of itinerant electrons. This dichotomy between 'local- moment' magnetism and 'itinerant- electron' magnetism is reminiscent of the valence bond/ molecular orbital dichotomy present in studies of chemical bonding. The class of heavy- electron intermetallic compounds of cerium, ytterbium and various 5f elements bridges the extremes, with itinerant- electron magnetic characteristics at low temperatures that grow out of a high-temperature local- moment state(1). Describing this transition quantitatively has proved difficult, and one of the main unsolved problems is finding what determines the temperature scale for the evolution of this behaviour. Here we present a simple, semi-quantitative solution to this problem that provides a basic framework for interpreting the physics of heavy- electron materials and offers the prospect of a quantitative determination of the physical origin of their magnetic ordering and superconductivity. It also reveals the difference between the temperature scales that distinguish the conduction electrons' response to a single magnetic impurity and their response to a lattice of local moments, and provides an updated version of the well- known Doniach diagram(2).
C1 [Yang, Yi-feng; Lee, Han-Oh; Thompson, J. D.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Yang, Yi-feng; Pines, David] Univ Calif Davis, Dept Phys, Davis, CA 95616 USA.
   [Fisk, Zachary] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
C3 United States Department of Energy (DOE); Los Alamos National Laboratory; University of California System; University of California Davis; University of California System; University of California Irvine
RP Yang, YF (corresponding author), Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87545 USA.
EM yifengyyf@gmail.com
NR 30
TC 203
Z9 234
U1 4
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 JUL 31
PY 2008
VL 454
IS 7204
BP 611
EP 613
DI 10.1038/nature07157
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500040
PM 18668102
DA 2026-03-09
ER

PT J
AU Cai, L
   Dalal, CK
   Elowitz, MB
AF Cai, Long
   Dalal, Chiraj K.
   Elowitz, Michael B.
TI Frequency-modulated nuclear localization bursts coordinate gene regulation
SO NATURE
LA English
DT Article
ID transcription factor; protein expression; global analysis; calcineurin; yeast; oscillations; variability; noise; cells; dependence
AB In yeast, the transcription factor Crz1 is dephosphorylated and translocates into the nucleus in response to extracellular calcium. Here we show, using time- lapse microscopy, that Crz1 exhibits short bursts of nuclear localization ( typically lasting 2 min) that occur stochastically in individual cells and propagate to the expression of downstream genes. Strikingly, calcium concentration controls the frequency, but not the duration, of localization bursts. Using an analytic model, we also show that this frequency modulation of bursts ensures proportional expression of multiple target genes across a wide dynamic range of expression levels, independent of promoter characteristics. We experimentally confirm this theory with natural and synthetic Crz1 target promoters. Another stress- response transcription factor, Msn2, exhibits similar, but largely uncorrelated, localization bursts under calcium stress suggesting that frequency- modulation regulation of localization bursts may be a general control strategy used by the cell to coordinate multi- gene responses to external signals.
C1 [Cai, Long; Dalal, Chiraj K.; Elowitz, Michael B.] CALTECH, Howard Hughes Med Inst, Div Biol, Pasadena, CA 91125 USA.
   [Cai, Long; Dalal, Chiraj K.; Elowitz, Michael B.] CALTECH, Dept Appl Phys, Pasadena, CA 91125 USA.
C3 Howard Hughes Medical Institute; California Institute of Technology; California Institute of Technology
RP Elowitz, MB (corresponding author), CALTECH, Howard Hughes Med Inst, Div Biol, M-C 114-96, Pasadena, CA 91125 USA.
EM melowitz@caltech.edu
FU Beckman Fellows Program at Caltech; National Institutes of Health [R01GM079771]; National Centers of Systems Biology, and the Packard Foundation [P50 GM068763]
NR 48
TC 405
Z9 502
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 SEP 25
PY 2008
VL 455
IS 7212
BP 485
EP U16
DI 10.1038/nature07292
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600036
PM 18818649
DA 2026-03-09
ER

PT J
AU Ishikawa, H
   Barber, GN
AF Ishikawa, Hiroki
   Barber, Glen N.
TI STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
SO NATURE
LA English
DT Article
ID rig-i; antiviral responses; protein-synthesis; rna virus; kappa-b; recognition; activation; mechanism; helicases; pathway
AB The cellular innate immune system is essential for recognizing pathogen infection and for establishing effective host defence. But critical molecular determinants responsible for facilitating an appropriate immune response - following infection with DNA and RNA viruses, for example - remain to be identified. Here we report the identification, following expression cloning, of a molecule ( STING; stimulator of interferon genes) that appears essential for effective innate immune signalling processes. It comprises five putative transmembrane regions, predominantly resides in the endoplasmic reticulum and is able to activate both NF-kappa B and IRF3 transcription pathways to induce expression of type I interferon (IFN-alpha and IFN-beta) and exert a potent anti- viral state following expression. In contrast, loss of STING rendered murine embryonic fibroblasts extremely susceptible to negative-stranded virus infection, including vesicular stomatitis virus. Further, STING ablation abrogated the ability of intracellular B-form DNA, as well as members of the herpesvirus family, to induce IFN-beta, but did not significantly affect the Toll- like receptor ( TLR) pathway. Yeast two- hybrid and co- immunoprecipitation studies indicated that STING interacts with RIG- I and with SSR2 ( also known as TRAP beta), which is a member of the translocon-associated protein ( TRAP) complex required for protein translocation across the endoplasmic reticulum membrane following translation(1,2.) Ablation by RNA interference of both TRAPb and translocon adaptor SEC61 beta was subsequently found to inhibit STING's ability to stimulate expression of IFN-beta. Thus, as well as identifying a regulator of innate immune signalling, our results imply a potential role for the translocon in innate signalling pathways activated by select viruses as well as intracellular DNA.
C1 [Ishikawa, Hiroki; Barber, Glen N.] Univ Miami, Sch Med, Dept Med, Miami, FL 33136 USA.
   [Ishikawa, Hiroki; Barber, Glen N.] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
C3 University of Miami; University of Miami
RP Barber, GN (corresponding author), Univ Miami, Sch Med, Dept Med, Miami, FL 33136 USA.
EM gbarber@med.miami.edu
FU NIAID NIH HHS [R01 AI079336] Funding Source: Medline
NR 25
TC 2915
Z9 3478
U1 22
U2 488
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 674
EP U74
DI 10.1038/nature07317
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700049
PM 18724357
DA 2026-03-09
ER

PT J
AU Putnam, NH
   Butts, T
   Ferrier, DEK
   Furlong, RF
   Hellsten, U
   Kawashima, T
   Robinson-Rechavi, M
   Shoguchi, E
   Terry, A
   Yu, JK
   Benito-Gutiérrez, E
   Dubchak, I
   Garcia-Fernàndez, J
   Gibson-Brown, JJ
   Grigoriev, IV
   Horton, AC
   de Jong, PJ
   Jurka, J
   Kapitonov, VV
   Kohara, Y
   Kuroki, Y
   Lindquist, E
   Lucas, S
   Osoegawa, K
   Pennacchio, LA
   Salamov, AA
   Satou, Y
   Sauka-Spengler, T
   Schmutz, J
   Shin-I, T
   Toyoda, A
   Bronner-Fraser, M
   Fujiyama, A
   Holland, LZ
   Holland, PWH
   Satoh, N
   Rokhsar, DS
AF Putnam, Nicholas H.
   Butts, Thomas
   Ferrier, David E. K.
   Furlong, Rebecca F.
   Hellsten, Uffe
   Kawashima, Takeshi
   Robinson-Rechavi, Marc
   Shoguchi, Eiichi
   Terry, Astrid
   Yu, Jr-Kai
   Benito-Gutierrez, Elia
   Dubchak, Inna
   Garcia-Fernandez, Jordi
   Gibson-Brown, Jeremy J.
   Grigoriev, Igor V.
   Horton, Amy C.
   de Jong, Pieter J.
   Jurka, Jerzy
   Kapitonov, Vladimir V.
   Kohara, Yuji
   Kuroki, Yoko
   Lindquist, Erika
   Lucas, Susan
   Osoegawa, Kazutoyo
   Pennacchio, Len A.
   Salamov, Asaf A.
   Satou, Yutaka
   Sauka-Spengler, Tatjana
   Schmutz, Jeremy
   Shin-I, Tadasu
   Toyoda, Atsushi
   Bronner-Fraser, Marianne
   Fujiyama, Asao
   Holland, Linda Z.
   Holland, Peter W. H.
   Satoh, Nori
   Rokhsar, Daniel S.
TI The amphioxus genome and the evolution of the chordate karyotype
SO NATURE
LA English
DT Article
ID gene duplications; reveals; vertebrates; origins; reconstruction; insights; chromosm; divergence; phylogeny; inference
AB Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic similar to 520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution.
C1 [Putnam, Nicholas H.; Hellsten, Uffe; Terry, Astrid; Dubchak, Inna; Grigoriev, Igor V.; Lindquist, Erika; Lucas, Susan; Pennacchio, Len A.; Salamov, Asaf A.; Rokhsar, Daniel S.] Dept Energy Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Putnam, Nicholas H.; Kawashima, Takeshi; Rokhsar, Daniel S.] Univ Calif Berkeley, Ctr Integrat Genom, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Butts, Thomas; Furlong, Rebecca F.; Holland, Linda Z.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Ferrier, David E. K.] Univ St Andrews, Gatty Marine Lab, St Andrews KY16 8LB, Fife, Scotland.
   [Robinson-Rechavi, Marc] Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.
   [Robinson-Rechavi, Marc] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Shoguchi, Eiichi; Satou, Yutaka; Satoh, Nori] Kyoto Univ, Dept Zool, Grad Sch Sci, Sakyo Ku, Kyoto 6068502, Japan.
   [Yu, Jr-Kai; Sauka-Spengler, Tatjana; Bronner-Fraser, Marianne] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Benito-Gutierrez, Elia] Natl Inst Med Res, London NW7 1AA, England.
   [Garcia-Fernandez, Jordi] Univ Barcelona, Dept Genet, Fac Biol, E-08028 Barcelona, Spain.
   [Gibson-Brown, Jeremy J.; Horton, Amy C.] Washington Univ, Dept Biol, St Louis, MO 63130 USA.
   [de Jong, Pieter J.; Osoegawa, Kazutoyo] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
   [Jurka, Jerzy; Kapitonov, Vladimir V.] Genet Informat Res Inst, Mountain View, CA 94043 USA.
   [Kohara, Yuji; Shin-I, Tadasu] Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
   [Kuroki, Yoko; Toyoda, Atsushi; Fujiyama, Asao] RIKEN, Genom Sci Ctr, Tsurumi Ku, Kanagawa 2300045, Japan.
   [Schmutz, Jeremy] JGI Stanford Human Genome Ctr, Palo Alto, CA 94304 USA.
   [Fujiyama, Asao] Res Org Informat & Syst, Natl Inst Informat, Chiyoda Ku, Tokyo 1018430, Japan.
   [Holland, Peter W. H.] Univ Calif San Diego, Scripps Inst Oceanog, Marine Biol Res Div, La Jolla, CA 92093 USA.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of Oxford; University of St Andrews; University of Lausanne; Swiss Institute of Bioinformatics; Kyoto University; California Institute of Technology; MRC National Institute for Medical Research; University of Barcelona; Washington University (WUSTL); University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; Children's Hospital Oakland Research Institute; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; RIKEN; Research Organization of Information & Systems (ROIS); National Institute of Informatics (NII) - Japan; University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Rokhsar, DS (corresponding author), Dept Energy Joint Genome Inst, Walnut Creek, CA 94598 USA.
EM satoh@ascidian.zool.kyoto-u.ac.jp; dsrokhsar@yahoo.com
FU Biotechnology and Biological Sciences Research Council [BBS/B/12067/2, BBS/B/12067] Funding Source: researchfish; Biotechnology and Biological Sciences Research Council [BBS/B/12067/2, BBS/B/12067] Funding Source: Medline; Wellcome Trust Funding Source: Medline; BBSRC [BBS/B/12067/2] Funding Source: UKRI
NR 79
TC 1286
Z9 1479
U1 5
U2 210
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2008
VL 453
IS 7198
BP 1064
EP U3
DI 10.1038/nature06967
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900049
PM 18563158
DA 2026-03-09
ER

PT J
AU Allen, PA
AF Allen, Philip A.
TI From landscapes into geological history
SO NATURE
LA English
DT Article
ID sediment
AB Erosional and depositional landscapes are linked by the sediment- routing system. Observations over a wide range of timescales might show how these landscapes are translated into the narrative of geological history.
C1 Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
C3 Imperial College London
RP Allen, PA (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, S Kensington Campus, London SW7 2AZ, England.
EM philip.allen@imperial.ac.uk
NR 14
TC 389
Z9 539
U1 17
U2 146
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 274
EP 276
DI 10.1038/nature06586
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100033
PM 18202641
DA 2026-03-09
ER

PT J
AU Macurek, L
   Lindqvist, A
   Lim, D
   Lampson, MA
   Klompmaker, R
   Freire, R
   Clouin, C
   Taylor, SS
   Yaffe, MB
   Medema, RH
AF Macurek, Libor
   Lindqvist, Arne
   Lim, Dan
   Lampson, Michael A.
   Klompmaker, Rob
   Freire, Raimundo
   Clouin, Christophe
   Taylor, Stephen S.
   Yaffe, Michael B.
   Medema, Rene H.
TI Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery
SO NATURE
LA English
DT Article
ID small-molecule inhibitor; protein-kinase; mammalian-cells; dna-damage; bipolar spindle; phosphorylation; reveals; cycle; plx1; polo-like-kinase-1
AB Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process(1). Activation of PLK1 requires phosphorylation of a conserved threonine residue ( Thr 210) in the T- loop of the PLK1 kinase domain, but the kinase responsible for this has not yet been affirmatively identified(2-6). Here we show that in human cells PLK1 activation occurs several hours before entry into mitosis, and requires aurora A ( AURKA, also known as STK6)- dependent phosphorylation of Thr 210. We find that aurora A can directly phosphorylate PLK1 on Thr 210, and that activity of aurora A towards PLK1 is greatly enhanced by Bora ( also known as C13orf34 and FLJ22624), a known cofactor for aurora A ( ref. 7). We show that Bora/ aurora- A- dependent phosphorylation is a prerequisite for PLK1 to promote mitotic entry after a checkpoint- dependent arrest. Importantly, expression of a PLK1- T210D phospho- mimicking mutant partially overcomes the requirement for aurora A in checkpoint recovery. Taken together, these data demonstrate that the initial activation of PLK1 is a primary function of aurora A.
C1 [Macurek, Libor; Lindqvist, Arne; Klompmaker, Rob; Medema, Rene H.] Univ Med Ctr Utrecht, Dept Med Oncol, NL-3584 CG Utrecht, Netherlands.
   [Lim, Dan; Clouin, Christophe; Yaffe, Michael B.] MIT, Ctr Canc Res, Cambridge, MA 02139 USA.
   [Lampson, Michael A.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Freire, Raimundo] Hosp Univ Canarias, Unidad Invest, La Cuesta 38320, Spain.
   [Taylor, Stephen S.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
C3 Utrecht University; Utrecht University Medical Center; Massachusetts Institute of Technology (MIT); University of Pennsylvania; Universidad de la Laguna; University Hospital of the Canary Islands; University of Manchester
RP Medema, RH (corresponding author), Univ Med Ctr Utrecht, Dept Med Oncol, NL-3584 CG Utrecht, Netherlands.
EM r.h.medema@umcutrecht.nl
FU Dutch Cancer Society [UU2006-3579]; Dutch Organisation for Scientific Research [ZonMw 918.46.616, ZonMw 916.86.083]; Association for International Cancer Research [08-0172]; NIH [GM-60594, CA112967]; Wenner-Gren foundations; Netherlands Genomic Initiative of the Netherlands Organisation for Scientific Research (NWO).
NR 32
TC 582
Z9 705
U1 1
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 119
EP U88
DI 10.1038/nature07185
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200049
PM 18615013
DA 2026-03-09
ER

PT J
AU Kidd, JM
   Cooper, GM
   Donahue, WF
   Hayden, HS
   Sampas, N
   Graves, T
   Hansen, N
   Teague, B
   Alkan, C
   Antonacci, F
   Haugen, E
   Zerr, T
   Yamada, NA
   Tsang, P
   Newman, TL
   Tüzün, E
   Cheng, Z
   Ebling, HM
   Tusneem, N
   David, R
   Gillett, W
   Phelps, KA
   Weaver, M
   Saranga, D
   Brand, A
   Tao, W
   Gustafson, E
   McKernan, K
   Chen, L
   Malig, M
   Smith, JD
   Korn, JM
   McCarroll, SA
   Altshuler, DA
   Peiffer, DA
   Dorschner, M
   Stamatoyannopoulos, J
   Schwartz, D
   Nickerson, DA
   Mullikin, JC
   Wilson, RK
   Bruhn, L
   Olson, MV
   Kaul, R
   Smith, DR
   Eichler, EE
AF Kidd, Jeffrey M.
   Cooper, Gregory M.
   Donahue, William F.
   Hayden, Hillary S.
   Sampas, Nick
   Graves, Tina
   Hansen, Nancy
   Teague, Brian
   Alkan, Can
   Antonacci, Francesca
   Haugen, Eric
   Zerr, Troy
   Yamada, N. Alice
   Tsang, Peter
   Newman, Tera L.
   Tuezuen, Eray
   Cheng, Ze
   Ebling, Heather M.
   Tusneem, Nadeem
   David, Robert
   Gillett, Will
   Phelps, Karen A.
   Weaver, Molly
   Saranga, David
   Brand, Adrianne
   Tao, Wei
   Gustafson, Erik
   McKernan, Kevin
   Chen, Lin
   Malig, Maika
   Smith, Joshua D.
   Korn, Joshua M.
   McCarroll, Steven A.
   Altshuler, David A.
   Peiffer, Daniel A.
   Dorschner, Michael
   Stamatoyannopoulos, John
   Schwartz, David
   Nickerson, Deborah A.
   Mullikin, James C.
   Wilson, Richard K.
   Bruhn, Laurakay
   Olson, Maynard V.
   Kaul, Rajinder
   Smith, Douglas R.
   Eichler, Evan E.
TI Mapping and sequencing of structural variation from eight human genomes
SO NATURE
LA English
DT Article
ID copy number polymorphism; segmental duplications; predisposes; inversion; variants; reveals; maps
AB Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale - particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone- based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high- resolution sequence map of human structural variation - a standard for genotyping platforms and a prelude to future individual genome sequencing projects.
C1 [Kidd, Jeffrey M.; Cooper, Gregory M.; Alkan, Can; Antonacci, Francesca; Zerr, Troy; Newman, Tera L.; Tuezuen, Eray; Cheng, Ze; Weaver, Molly; Chen, Lin; Malig, Maika; Smith, Joshua D.; Dorschner, Michael; Stamatoyannopoulos, John; Nickerson, Deborah A.; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Kidd, Jeffrey M.; Cooper, Gregory M.; Alkan, Can; Antonacci, Francesca; Zerr, Troy; Newman, Tera L.; Tuezuen, Eray; Cheng, Ze; Weaver, Molly; Chen, Lin; Malig, Maika; Smith, Joshua D.; Dorschner, Michael; Stamatoyannopoulos, John; Nickerson, Deborah A.; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Donahue, William F.; Ebling, Heather M.; Tusneem, Nadeem; David, Robert; Saranga, David; Brand, Adrianne; Tao, Wei; Gustafson, Erik; McKernan, Kevin; Smith, Douglas R.] Agencourt Biosci Corp, Beverly, MA 01915 USA.
   [Hayden, Hillary S.; Haugen, Eric; Gillett, Will; Phelps, Karen A.; Olson, Maynard V.; Kaul, Rajinder] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
   [Hayden, Hillary S.; Haugen, Eric; Gillett, Will; Phelps, Karen A.; Olson, Maynard V.; Kaul, Rajinder] Univ Washington, Univ Washington Genome Ctr, Seattle, WA 98195 USA.
   [Sampas, Nick; Yamada, N. Alice; Tsang, Peter; Bruhn, Laurakay] Agilent Technol, Santa Clara, CA 95051 USA.
   [Graves, Tina; Wilson, Richard K.] Washington Univ, Genome Sequencing Ctr, Sch Med, St Louis, MO 63108 USA.
   [Hansen, Nancy; Mullikin, James C.] NIH, Human Genome Res Inst, Bethesda, MD 20892 USA.
   [Teague, Brian; Schwartz, David] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
   [Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David A.] MIT, Broad Inst, Program Med & Populat Genet, Boston, MA 02114 USA.
   [Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David A.] Harvard Univ, Broad Inst, Boston, MA 02114 USA.
   [Peiffer, Daniel A.] Illumina Inc, San Diego, CA 92121 USA.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Agilent Technologies; Washington University (WUSTL); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of Wisconsin System; University of Wisconsin Madison; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Illumina
RP Eichler, EE (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM eee@gs.washington.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NHGRI NIH HHS [3 U54 HG002043, U54 HG002043, P01 HG004120, HG004120] Funding Source: Medline
NR 42
TC 849
Z9 1098
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 MAY 1
PY 2008
VL 453
IS 7191
BP 56
EP 64
DI 10.1038/nature06862
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800038
PM 18451855
DA 2026-03-09
ER

PT J
AU Carlton, JM
   Adams, JH
   Silva, JC
   Bidwell, SL
   Lorenzi, H
   Caler, E
   Crabtree, J
   Angiuoli, SV
   Merino, EF
   Amedeo, P
   Cheng, Q
   Coulson, RMR
   Crabb, BS
   del Portillo, HA
   Essien, K
   Feldblyum, TV
   Fernandez-Becerra, C
   Gilson, PR
   Gueye, AH
   Guo, X
   Kang'a, S
   Kooij, TWA
   Korsinczky, M
   Meyer, EVS
   Nene, V
   Paulsen, I
   White, O
   Ralph, SA
   Ren, QH
   Sargeant, TJ
   Salzberg, SL
   Stoeckert, CJ
   Sullivan, SA
   Yamamoto, MM
   Hoffman, SL
   Wortman, JR
   Gardner, MJ
   Galinski, MR
   Barnwell, JW
   Fraser-Liggett, CM
AF Carlton, Jane M.
   Adams, John H.
   Silva, Joana C.
   Bidwell, Shelby L.
   Lorenzi, Hernan
   Caler, Elisabet
   Crabtree, Jonathan
   Angiuoli, Samuel V.
   Merino, Emilio F.
   Amedeo, Paolo
   Cheng, Qin
   Coulson, Richard M. R.
   Crabb, Brendan S.
   del Portillo, Hernando A.
   Essien, Kobby
   Feldblyum, Tamara V.
   Fernandez-Becerra, Carmen
   Gilson, Paul R.
   Gueye, Amy H.
   Guo, Xiang
   Kang'a, Simon
   Kooij, Taco W. A.
   Korsinczky, Michael
   Meyer, Esmeralda V. -S.
   Nene, Vish
   Paulsen, Ian
   White, Owen
   Ralph, Stuart A.
   Ren, Qinghu
   Sargeant, Tobias J.
   Salzberg, Steven L.
   Stoeckert, Christian J.
   Sullivan, Steven A.
   Yamamoto, Marcio M.
   Hoffman, Stephen L.
   Wortman, Jennifer R.
   Gardner, Malcolm J.
   Galinski, Mary R.
   Barnwell, John W.
   Fraser-Liggett, Claire M.
TI Comparative genomics of the neglected human malaria parasite Plasmodium vivax
SO NATURE
LA English
DT Article
ID red-blood-cells; phenotypic variation; falciparum; proteins; binding; identification; superfamily; expression; resistance; virulence
AB The human malaria parasite Plasmodium vivax is responsible for 25 - 40% of the similar to 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non- human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.
C1 [Carlton, Jane M.; Bidwell, Shelby L.; Lorenzi, Hernan; Caler, Elisabet; Crabtree, Jonathan; Amedeo, Paolo; Guo, Xiang; Paulsen, Ian; Ren, Qinghu; Gardner, Malcolm J.] J Craig Venter Inst, Inst Genom Res, Rockville, MD 20850 USA.
   [Carlton, Jane M.; Merino, Emilio F.; Kang'a, Simon; Sullivan, Steven A.] NYU, Langone Med Ctr, Dept Med Parasitol, New York, NY 10010 USA.
   [Adams, John H.] Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Tampa, FL 33612 USA.
   [Silva, Joana C.; Nene, Vish] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
   [Silva, Joana C.; Crabtree, Jonathan; Angiuoli, Samuel V.; Feldblyum, Tamara V.; Nene, Vish; White, Owen; Wortman, Jennifer R.; Fraser-Liggett, Claire M.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
   [White, Owen] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
   [Wortman, Jennifer R.; Fraser-Liggett, Claire M.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
   [Angiuoli, Samuel V.; Salzberg, Steven L.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
   [Cheng, Qin; Korsinczky, Michael] Australian Army Malaria Inst, Enoggera, Qld 4051, Australia.
   [Coulson, Richard M. R.] European Bioinformat Inst, Microarray Grp, Cambridge CB10 1SD, England.
   [Crabb, Brendan S.; Gilson, Paul R.; Sargeant, Tobias J.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
   [Crabb, Brendan S.] Burnet Inst, Melbourne, Vic 3004, Australia.
   [del Portillo, Hernando A.; Fernandez-Becerra, Carmen] Univ Barcelona, Barcelona Ctr Int Hlth Res, Hosp Clin IDIBAPS, E-08036 Barcelona, Spain.
   [del Portillo, Hernando A.] Passeig Lluis Co, Inst Catalana Recerca & Estud Avancats, Barcelona 08010, Spain.
   [Essien, Kobby; Stoeckert, Christian J.] Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA.
   [Essien, Kobby; Stoeckert, Christian J.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
   [Essien, Kobby] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
   [Gueye, Amy H.] Hood Coll, Frederick, MD 21701 USA.
   [Kooij, Taco W. A.] Heidelberg Univ, Sch Med, Dept Parasitol, D-69120 Heidelberg, Germany.
   [Korsinczky, Michael; Galinski, Mary R.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
   [Meyer, Esmeralda V. -S.] Emory Univ, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Meyer, Esmeralda V. -S.] Emory Univ, Dept Med, Div Infect Dis, Atlanta, GA 30329 USA.
   [Paulsen, Ian] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia.
   [Ralph, Stuart A.] Univ Melbourne, Dept Biochem & Mol Biol, Bio21 Mol Sci & Biotechnol Inst, Melbourne, Vic 3010, Australia.
   [Sargeant, Tobias J.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
   [Yamamoto, Marcio M.] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, BR-05508900 Sao Paulo, Brazil.
   [Hoffman, Stephen L.] Sanaria Inc, Rockville, MD 20850 USA.
   [Barnwell, John W.] Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis, Natl Ctr Zoonot Vectorborne & Enter Dis, Atlanta, GA 30341 USA.
C3 J. Craig Venter Institute; NYU Langone Medical Center; New York University; State University System of Florida; University of South Florida; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland College Park; QIMR Berghofer Medical Research Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Walter & Eliza Hall Institute; Burnet Institute; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; ISGlobal; CRESIB; ICREA; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Ruprecht Karls University Heidelberg; University of Queensland; Emory University; Emory University; Macquarie University; University of Melbourne; University of Melbourne; Universidade de Sao Paulo; Sanaria Inc.; Centers for Disease Control & Prevention - USA
RP Carlton, JM (corresponding author), J Craig Venter Inst, Inst Genom Res, 9704 Med Res Dr, Rockville, MD 20850 USA.
EM jane.carlton@nyumc.org
FU US Department of Defense and National Institute of Allergy and Infectious Diseases; BurroughsWellcome Fund; National Institute of General Medical Sciences; ICREA Funding Source: Custom; National Institute of Allergy and Infectious Diseases [R01AI064478] Funding Source: NIH RePORTER
NR 49
TC 663
Z9 803
U1 2
U2 104
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 757
EP 763
DI 10.1038/nature07327
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900038
PM 18843361
DA 2026-03-09
ER

PT J
AU Muneepeerakul, R
   Bertuzzo, E
   Lynch, HJ
   Fagan, WF
   Rinaldo, A
   Rodriguez-Iturbe, I
AF Muneepeerakul, Rachata
   Bertuzzo, Enrico
   Lynch, Heather J.
   Fagan, William F.
   Rinaldo, Andrea
   Rodriguez-Iturbe, Ignacio
TI Neutral metacommunity models predict fish diversity patterns in Mississippi-Missouri basin
SO NATURE
LA English
DT Article
ID relative species abundance; biodiversity; community; ecology
AB River networks, seen as ecological corridors featuring connected and hierarchical dendritic landscapes for animals and plants, present unique challenges and opportunities for testing biogeographical theories and macroecological laws(1). Although local and basin- scale differences in riverine fish diversity have been analysed as functions of energy availability and habitat heterogeneity(2), scale- dependent environmental conditions(3) and river discharge(4,5), a model that predicts a comprehensive set of system-wide diversity patterns has been hard to find. Here we show that fish diversity patterns throughout the Mississippi - Missouri River System are well described by a neutral metacommunity model coupled with an appropriate habitat capacity distribution and dispersal kernel. River network structure acts as an effective template for characterizing spatial attributes of fish biodiversity. We show that estimates of average dispersal behaviour and habitat capacities, objectively calculated from average runoff production, yield reliable predictions of large- scale spatial biodiversity patterns in riverine systems. The success of the neutral theory in two- dimensional forest ecosystems(6-8) and here in dendritic riverine ecosystems suggests the possible application of neutral metacommunity models in a diverse suite of ecosystems. This framework offers direct linkage from large- scale forcing, such as global climate change, to biodiversity patterns.
C1 [Muneepeerakul, Rachata; Bertuzzo, Enrico; Rodriguez-Iturbe, Ignacio] Princeton Univ, Dept Civil & Environm Engn, Princeton, NJ 08544 USA.
   [Bertuzzo, Enrico; Rinaldo, Andrea] Ecole Polytech Fed Lausanne, Fac ENAC, Lab Ecohydrol, CH-1015 Lausanne, Switzerland.
   [Lynch, Heather J.; Fagan, William F.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
   [Rinaldo, Andrea] Univ Padua, Dipartimento Ingn Idraul Marittima Ambientale & G, I-35131 Padua, Italy.
   [Rinaldo, Andrea] Univ Padua, Ctr Int Idrol Dino Tonini, I-35131 Padua, Italy.
C3 Princeton University; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University System of Maryland; University of Maryland College Park; University of Padua; University of Padua
RP Muneepeerakul, R (corresponding author), Princeton Univ, Dept Civil & Environm Engn, E Quad, Princeton, NJ 08544 USA.
EM rmuneepe@princeton.edu; irodrigu@princeton.edu
NR 30
TC 314
Z9 355
U1 5
U2 202
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 220
EP U9
DI 10.1038/nature06813
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400039
PM 18464742
DA 2026-03-09
ER

PT J
AU Levy, ED
   Erba, EB
   Robinson, CV
   Teichmann, SA
AF Levy, Emmanuel D.
   Erba, Elisabetta Boeri
   Robinson, Carol V.
   Teichmann, Sarah A.
TI Assembly reflects evolution of protein complexes
SO NATURE
LA English
DT Article
ID macromolecular assembly; networks; symmetry; subunit
AB A homomer is formed by self- interacting copies of a protein unit. This is functionally important(1,2), as in allostery(3-5), and structurally crucial because mis- assembly of homomers is implicated in disease(6,7). Homomers are widespread, with 50 - 70% of proteins with a known quaternary state assembling into such structures(8,9). Despite their prevalence, their role in the evolution of cellular machinery(10,11) and the potential for their use in the design of new molecular machines(12,13), little is known about the mechanisms that drive formation of homomers at the level of evolution and assembly in the cell(9,14). Here we present an analysis of over 5,000 unique atomic structures and show that the quaternary structure of homomers is conserved in over 70% of protein pairs sharing as little as 30% sequence identity. Where quaternary structure is not conserved among the members of a protein family, a detailed investigation revealed well- defined evolutionary pathways by which proteins transit between different quaternary structure types. Furthermore, we show by perturbing subunit interfaces within complexes and by mass spectrometry analysis(15), that the ( dis) assembly pathway mimics the evolutionary pathway. These data represent a molecular analogy to Haeckel's evolutionary paradigm of embryonic development, where an intermediate in the assembly of a complex represents a form that appeared in its own evolutionary history. Our model of self- assembly allows reliable prediction of evolution and assembly of a complex solely from its crystal structure.
C1 [Levy, Emmanuel D.; Teichmann, Sarah A.] MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
   [Erba, Elisabetta Boeri; Robinson, Carol V.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
C3 MRC Laboratory Molecular Biology; University of Cambridge
RP Levy, ED (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England.
EM homomers@mrc-lmb.cam.ac.uk
FU Medical Research Council [MC_U105161047, U.1051.04.025(78835)] Funding Source: Medline; MRC [MC_U105161047] Funding Source: UKRI; Medical Research Council [MC_U105161047] Funding Source: researchfish
NR 28
TC 353
Z9 413
U1 0
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 26
PY 2008
VL 453
IS 7199
BP 1262
EP U66
DI 10.1038/nature06942
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800048
PM 18563089
DA 2026-03-09
ER

PT J
AU Minto, C
   Myers, RA
   Blanchard, W
AF Minto, Coilin
   Myers, Ransom A.
   Blanchard, Wade
TI Survival variability and population density in fish populations
SO NATURE
LA English
DT Article
ID marine demersal fish; dependence; recruitment; mortality; time; cod; age
AB To understand the processes that regulate the abundance and persistence of wild populations is a fundamental goal of ecology and a prerequisite for the management of living resources. Variable abundance data, however, make the demonstration of regulation processes challenging(1-3). A previously overlooked aspect in understanding how populations are regulated(4-6) is the possibility that the pattern of variability - its strength as a function of population size - may be more than 'noise', thus revealing much about the characteristics of population regulation. Here we show that patterns in survival variability do provide evidence of regulation through density. Using a large, global compilation of marine, anadromous and freshwater fisheries data, we examine the relationship between the variability of survival and population abundance. The interannual variability in progeny survival increases at low adult abundance in an inversely density- dependent fashion. This pattern is consistent with models in which density dependence enters after the larval stage. The findings are compatible with very simple forms of density dependence: even a linear increase of juvenile mortality with adult density adequately explains the results. The model predictions explain why populations with strong regulation may experience large increases in variability at low densities(7). Furthermore, the inverse relationship between survival variability and the strength of density dependence has important consequences for fisheries management and recovery, and population persistence or extinction(8-10).
C1 [Minto, Coilin] Dalhousie Univ, Dept Biol, Halifax, NS B3H 4J1, Canada.
   [Blanchard, Wade] Dalhousie Univ, Dept Math & Stat, Halifax, NS B3H 3J5, Canada.
C3 Dalhousie University; Dalhousie University
RP Minto, C (corresponding author), Dalhousie Univ, Dept Biol, Halifax, NS B3H 4J1, Canada.
EM mintoc@mathstat.dal.ca
NR 33
TC 90
Z9 104
U1 1
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 20
PY 2008
VL 452
IS 7185
BP 344
EP U6
DI 10.1038/nature06605
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 276BX
UT WOS:000254117400045
PM 18354480
DA 2026-03-09
ER

PT J
AU Kim, JB
   Zaehres, H
   Wu, GM
   Gentile, L
   Ko, K
   Sebastiano, V
   Araúzo-Bravo, MJ
   Ruau, D
   Han, DW
   Zenke, M
   Schöler, HR
AF Kim, Jeong Beom
   Zaehres, Holm
   Wu, Guangming
   Gentile, Luca
   Ko, Kinarm
   Sebastiano, Vittorio
   Arauzo-Bravo, Marcos J.
   Ruau, David
   Han, Dong Wook
   Zenke, Martin
   Schoeler, Hans R.
TI Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors
SO NATURE
LA English
DT Article
ID fibroblasts; expression; mouse; generation; genes; sox2; p53
AB Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient- specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem ( iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 ( also known as Pou5f1), Sox2, c- Myc and Klf4 ( refs 1 - 11). Considering that ectopic expression of c- Myc causes tumorigenicity in offspring(2) and that retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c- Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c- Myc is sufficient to generate iPS cells from neural stem cells. These two- factor iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimaeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.
C1 [Kim, Jeong Beom; Zaehres, Holm; Wu, Guangming; Gentile, Luca; Ko, Kinarm; Sebastiano, Vittorio; Arauzo-Bravo, Marcos J.; Han, Dong Wook; Schoeler, Hans R.] Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, Germany.
   [Ruau, David; Zenke, Martin] Univ Aachen, Sch Med, Rhein Westfal TH Aachen, Inst Biomed Engn,Dept Cell Biol, D-52074 Aachen, Germany.
C3 Max Planck Society; RWTH Aachen University
RP Schöler, HR (corresponding author), Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, Rontgenstr 20, D-48149 Munster, Germany.
EM schoeler@mpi-muenster.mpg.de
NR 26
TC 749
Z9 1039
U1 2
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 646
EP U54
DI 10.1038/nature07061
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500049
PM 18594515
DA 2026-03-09
ER

PT J
AU Olsen, SR
   Wilson, RI
AF Olsen, Shawn R.
   Wilson, Rachel I.
TI Lateral presynaptic inhibition mediates gain control in an olfactory circuit
SO NATURE
LA English
DT Article
ID drosophila antennal lobe; center-surround inhibition; bulb glomeruli; odor quality; mitral cells; neurons; representations; mechanisms; receptors; input
AB Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second- order neurons. In the Drosophila antennal lobe ( a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second- order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.
C1 [Olsen, Shawn R.; Wilson, Rachel I.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Wilson, RI (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM rachel_wilson@hms.harvard.edu
FU National Institute on Deafness and Other Communication Disorders [R01DC008174] Funding Source: NIH RePORTER; NIDCD NIH HHS [R01 DC008174] Funding Source: Medline
NR 42
TC 382
Z9 481
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 APR 24
PY 2008
VL 452
IS 7190
BP 956
EP U3
DI 10.1038/nature06864
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600031
PM 18344978
DA 2026-03-09
ER

PT J
AU Polizzotto, ML
   Kocar, BD
   Benner, SG
   Sampson, M
   Fendorf, S
AF Polizzotto, Matthew L.
   Kocar, Benjamin D.
   Benner, Shawn G.
   Sampson, Michael
   Fendorf, Scott
TI Near-surface wetland sediments as a source of arsenic release to ground water in Asia
SO NATURE
LA English
DT Article
ID reducing bacteria; organic-matter; drinking-water; bangladesh; mekong; contamination; mobility; cambodia; delta; extraction
AB Tens of millions of people in south and southeast Asia routinely consume ground water that has unsafe arsenic levels(1,2). Arsenic is naturally derived from eroded Himalayan sediments, and is believed to enter solution following reductive release from solid phases under anaerobic conditions. However, the processes governing aqueous concentrations and locations of arsenic release to pore water remain unresolved, limiting our ability to predict arsenic concentrations spatially (between wells) and temporally (future concentrations) and to assess the impact of human activities on the arsenic problem(3-9). This uncertainty is partly attributed to a poor understanding of groundwater flow paths altered by extensive irrigation pumping in the Ganges-Brahmaputra delta(10), where most research has focused. Here, using hydrologic and (bio)geochemical measurements, we show that on the minimally disturbed Mekong delta of Cambodia, arsenic is released from near-surface, river-derived sediments and transported, on a centennial timescale, through the underlying aquifer back to the river. Owing to similarities in geologic deposition, aquifer source rock and regional hydrologic gradients(11-15), our results represent a model for understanding pre-disturbance conditions for other major deltas in Asia. Furthermore, the observation of strong hydrologic influence on arsenic behaviour indicates that release and transport of arsenic are sensitive to continuing and impending anthropogenic disturbances. In particular, groundwater pumping for irrigation, changes in agricultural practices, sediment excavation, levee construction and upstream dam installations will alter the hydraulic regime and/or arsenic source material and, by extension, influence groundwater arsenic concentrations and the future of this health problem.
C1 [Polizzotto, Matthew L.; Kocar, Benjamin D.; Fendorf, Scott] Stanford Univ, Sch Earth & Atmospher Sci, Stanford, CA 94305 USA.
   [Benner, Shawn G.] Boise State Univ, Dept Geosci, Boise, ID 83705 USA.
   [Sampson, Michael] Resource Dev Int Cambodia, Phnom Penh, Cambodia.
C3 Stanford University; Boise State University
RP Fendorf, S (corresponding author), Stanford Univ, Sch Earth & Atmospher Sci, Stanford, CA 94305 USA.
EM fendorf@stanford.edu
NR 28
TC 501
Z9 588
U1 11
U2 522
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 505
EP U5
DI 10.1038/nature07093
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300048
PM 18650922
DA 2026-03-09
ER

PT J
AU de Lucas, M
   Davière, JM
   Rodríguez-Falcón, M
   Pontin, M
   Iglesias-Pedraz, JM
   Lorrain, S
   Fankhauser, C
   Blázquez, MA
   Titarenko, E
   Prat, S
AF de Lucas, Miguel
   Daviere, Jean-Michel
   Rodriguez-Falcon, Mariana
   Pontin, Mariela
   Iglesias-Pedraz, Juan Manuel
   Lorrain, Severine
   Fankhauser, Christian
   Blazquez, Miguel Angel
   Titarenko, Elena
   Prat, Salome
TI A molecular framework for light and gibberellin control of cell elongation
SO NATURE
LA English
DT Article
ID signal-transduction; phytochrome-b; transcription factors; arabidopsis-thaliana; induced degradation; protein; gene; plants; photomorphogenesis; rga
AB Cell elongation during seedling development is antagonistically regulated by light and gibberellins (GAs)(1,2). Light induces photomorphogenesis, leading to inhibition of hypocotyl growth, whereas GAs promote etiolated growth, characterized by increased hypocotyl elongation. The mechanism underlying this antagonistic interaction remains unclear. Here we report on the central role of the Arabidopsis thaliana nuclear transcription factor PIF4 ( encoded by PHYTOCHROME INTERACTING FACTOR 4)(3) in the positive control of genes mediating cell elongation and show that this factor is negatively regulated by the light photoreceptor phyB ( ref. 4) and by DELLA proteins that have a key repressor function in GA signalling(5). Our results demonstrate that PIF4 is destabilized by phyB in the light and that DELLAs block PIF4 transcriptional activity by binding the DNA- recognition domain of this factor. We show that GAs abrogate such repression by promoting DELLA destabilization, and therefore cause a concomitant accumulation of free PIF4 in the nucleus. Consistent with this model, intermediate hypocotyl lengths were observed in transgenic plants over- accumulating both DELLAs and PIF4. Destabilization of this factor by phyB, together with its inactivation by DELLAs, constitutes a protein interaction framework that explains how plants integrate both light and GA signals to optimize growth and development in response to changing environments.
C1 [de Lucas, Miguel; Daviere, Jean-Michel; Rodriguez-Falcon, Mariana; Pontin, Mariela; Iglesias-Pedraz, Juan Manuel; Titarenko, Elena; Prat, Salome] CSIC, Ctr Nacl Biotecnol, Dept Genet Mol Plantas, Madrid 28049, Spain.
   [Lorrain, Severine; Fankhauser, Christian] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Blazquez, Miguel Angel] Univ Politecn Valencia, CSIC, Inst Biol Mol & Celular Plantas, Valencia 46022, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB); University of Lausanne; Consejo Superior de Investigaciones Cientificas (CSIC); Universitat Politecnica de Valencia; CSIC-UPV - Instituto de Biologia Molecular y Celular de Plantas (IBMCP)
RP Prat, S (corresponding author), CSIC, Ctr Nacl Biotecnol, Dept Genet Mol Plantas, Campus Univ Autonoma Madrid,C Darwin 3, Madrid 28049, Spain.
EM sprat@cnb.uam.es
NR 36
TC 1042
Z9 1147
U1 5
U2 372
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 24
PY 2008
VL 451
IS 7177
BP 480
EP U11
DI 10.1038/nature06520
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100048
PM 18216857
DA 2026-03-09
ER

PT J
AU Mustard, JF
   Murchie, SL
   Pelkey, SM
   Ehlmann, BL
   Milliken, RE
   Grant, JA
   Bibring, JP
   Poulet, F
   Bishop, J
   Dobrea, EN
   Roach, L
   Seelos, F
   Arvidson, RE
   Wiseman, S
   Green, R
   Hash, C
   Humm, D
   Malaret, E
   McGovern, JA
   Seelos, K
   Clancy, T
   Clark, R
   Des Marais, D
   Izenberg, N
   Knudson, A
   Langevin, Y
   Martin, T
   McGuire, P
   Morris, R
   Robinson, M
   Roush, T
   Smith, M
   Swayze, G
   Taylor, H
   Titus, T
   Wolff, M
AF Mustard, John F.
   Murchie, S. L.
   Pelkey, S. M.
   Ehlmann, B. L.
   Milliken, R. E.
   Grant, J. A.
   Bibring, J. -P.
   Poulet, F.
   Bishop, J.
   Dobrea, E. Noe
   Roach, L.
   Seelos, F.
   Arvidson, R. E.
   Wiseman, S.
   Green, R.
   Hash, C.
   Humm, D.
   Malaret, E.
   McGovern, J. A.
   Seelos, K.
   Clancy, T.
   Clark, R.
   Des Marais, D.
   Izenberg, N.
   Knudson, A.
   Langevin, Y.
   Martin, T.
   McGuire, P.
   Morris, R.
   Robinson, M.
   Roush, T.
   Smith, M.
   Swayze, G.
   Taylor, H.
   Titus, T.
   Wolff, M.
TI Hydrated silicate minerals on mars observed by the Mars reconnaissance orbiter CRISM instrument
SO NATURE
LA English
DT Article
ID olivine; diversity; region
AB Phyllosilicates, a class of hydrous mineral first definitively identified on Mars by the OMEGA ( Observatoire pour la Mineralogie, L'Eau, les Glaces et l'Activitie') instrument(1,2), preserve a record of the interaction of water with rocks on Mars. Global mapping showed that phyllosilicates are widespread but are apparently restricted to ancient terrains and a relatively narrow range of mineralogy ( Fe/ Mg and Al smectite clays). This was interpreted to indicate that phyllosilicate formation occurred during the Noachian ( the earliest geological era of Mars), and that the conditions necessary for phyllosilicate formation ( moderate to high pH and high water activity(3)) were specific to surface environments during the earliest era of Mars's history(4). Here we report results from the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM)(5) of phyllosilicate- rich regions. We expand the diversity of phyllosilicate mineralogy with the identification of kaolinite, chlorite and illite or muscovite, and a new class of hydrated silicate ( hydrated silica). We observe diverse Fe/ Mg-OH phyllosilicates and find that smectites such as nontronite and saponite are the most common, but chlorites are also present in some locations. Stratigraphic relationships in the Nili Fossae region show olivine- rich materials overlying phyllosilicate- bearing units, indicating the cessation of aqueous alteration before emplacement of the olivine- bearing unit. Hundreds of detections of Fe/ Mg phyllosilicate in rims, ejecta and central peaks of craters in the southern highland Noachian cratered terrain indicate excavation of altered crust from depth. We also find phyllosilicate in sedimentary deposits clearly laid by water. These results point to a rich diversity of Noachian environments conducive to habitability.
C1 [Mustard, John F.; Pelkey, S. M.; Ehlmann, B. L.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Murchie, S. L.; Seelos, F.; Humm, D.; McGovern, J. A.; Seelos, K.; Izenberg, N.; Taylor, H.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Milliken, R. E.; Dobrea, E. Noe; Green, R.; Martin, T.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Grant, J. A.] Smithsonian Inst, Ctr Earth & Planetary Studies, Natl Air & Space Museum, Washington, DC 20560 USA.
   [Bibring, J. -P.; Poulet, F.; Langevin, Y.] Ctr Univ Paris Sud, Inst Astrophys Spatiale, F-91405 Orsay, France.
   [Bishop, J.; Des Marais, D.; Roush, T.] Ames Res Ctr, Natl Aeronaut & Space Adm, Mountain View, CA 94043 USA.
   [Arvidson, R. E.; Wiseman, S.; Knudson, A.; McGuire, P.] Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
   [Hash, C.; Malaret, E.] Appl Coherent Technol, Herndon, VA 22070 USA.
   [Clancy, T.; Swayze, G.; Wolff, M.] Space Sci Inst, Boulder, CO 80301 USA.
   [Clark, R.] US Geol Survey, Denver Fed Ctr, Denver, CO 80225 USA.
   [Morris, R.] NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA.
   [Robinson, M.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Smith, M.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Titus, T.] US Geol Survey, Flagstaff, AZ 86001 USA.
C3 Brown University; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Smithsonian Institution; Sorbonne Universite; Universite Paris Saclay; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Washington University (WUSTL); United States Department of the Interior; United States Geological Survey; National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; Arizona State University; Arizona State University-Tempe; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; United States Department of the Interior; United States Geological Survey
RP Mustard, JF (corresponding author), Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
EM john_mustard@brown.edu
NR 31
TC 646
Z9 768
U1 10
U2 195
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 305
EP 309
DI 10.1038/nature07097
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300032
PM 18633411
DA 2026-03-09
ER

PT J
AU King, N
   Westbrook, MJ
   Young, SL
   Kuo, A
   Abedin, M
   Chapman, J
   Fairclough, S
   Hellsten, U
   Isogai, Y
   Letunic, I
   Marr, M
   Pincus, D
   Putnam, N
   Rokas, A
   Wright, KJ
   Zuzow, R
   Dirks, W
   Good, M
   Goodstein, D
   Lemons, D
   Li, WQ
   Lyons, JB
   Morris, A
   Nichols, S
   Richter, DJ
   Salamov, A
   Bork, P
   Lim, WA
   Manning, G
   Miller, WT
   McGinnis, W
   Shapiro, H
   Tjian, R
   Grigoriev, IV
   Rokhsar, D
AF King, Nicole
   Westbrook, M. Jody
   Young, Susan L.
   Kuo, Alan
   Abedin, Monika
   Chapman, Jarrod
   Fairclough, Stephen
   Hellsten, Uffe
   Isogai, Yoh
   Letunic, Ivica
   Marr, Michael
   Pincus, David
   Putnam, Nicholas
   Rokas, Antonis
   Wright, Kevin J.
   Zuzow, Richard
   Dirks, William
   Good, Matthew
   Goodstein, David
   Lemons, Derek
   Li, Wanqing
   Lyons, Jessica B.
   Morris, Andrea
   Nichols, Scott
   Richter, Daniel J.
   Salamov, Asaf
   Bork, Peer
   Lim, Wendell A.
   Manning, Gerard
   Miller, W. Todd
   McGinnis, William
   Shapiro, Harris
   Tjian, Robert
   Grigoriev, Igor V.
   Rokhsar, Daniel
TI The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans
SO NATURE
LA English
DT Article
ID unicellular relatives; evolutionary origin; cell-adhesion; insights; conservation; architecture; proteins; family
AB Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron- rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans.
C1 [King, Nicole; Westbrook, M. Jody; Young, Susan L.; Abedin, Monika; Chapman, Jarrod; Fairclough, Stephen; Isogai, Yoh; Putnam, Nicholas; Wright, Kevin J.; Zuzow, Richard; Dirks, William; Goodstein, David; Lyons, Jessica B.; Nichols, Scott; Richter, Daniel J.; Tjian, Robert; Rokhsar, Daniel] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [King, Nicole; Westbrook, M. Jody; Young, Susan L.; Abedin, Monika; Chapman, Jarrod; Fairclough, Stephen; Isogai, Yoh; Putnam, Nicholas; Wright, Kevin J.; Zuzow, Richard; Dirks, William; Goodstein, David; Lyons, Jessica B.; Nichols, Scott; Richter, Daniel J.; Tjian, Robert; Rokhsar, Daniel] Univ Calif Berkeley, Ctr Integrat Genom, Berkeley, CA 94720 USA.
   [King, Nicole] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Kuo, Alan; Hellsten, Uffe; Salamov, Asaf; Shapiro, Harris; Grigoriev, Igor V.; Rokhsar, Daniel; JGI Sequencing] Dept Energy Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Letunic, Ivica; Bork, Peer] European Mol Biol Lab, D-69012 Heidelberg, Germany.
   [Marr, Michael] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA.
   [Pincus, David; Good, Matthew; Lim, Wendell A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Rokas, Antonis] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
   [Lemons, Derek; McGinnis, William] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
   [Li, Wanqing; Miller, W. Todd] SUNY Stony Brook, Dept Physiol & Biophys, Stony Brook, NY 11794 USA.
   [Morris, Andrea] Univ Michigan, Dept Cellular & Mol Biol, Ann Arbor, MI 48109 USA.
   [Manning, Gerard] Salk Inst Biol Studies, Razavi Newman Bioinformat Ctr, La Jolla, CA 92037 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; European Molecular Biology Laboratory (EMBL); Brandeis University; University of California System; University of California San Francisco; Vanderbilt University; University of California System; University of California San Diego; State University of New York (SUNY) System; Stony Brook University; University of Michigan System; University of Michigan; Salk Institute
RP King, N (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM nking@berkeley.edu; dsrokhsar@lbl.gov
FU NCI NIH HHS [R01 CA058530] Funding Source: Medline; NHGRI NIH HHS [R01 HG004164] Funding Source: Medline; NICHD NIH HHS [R37 HD028315] Funding Source: Medline; NIGMS NIH HHS [R01 GM077197] Funding Source: Medline
NR 48
TC 861
Z9 1054
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 FEB 14
PY 2008
VL 451
IS 7180
BP 783
EP 788
DI 10.1038/nature06617
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400033
PM 18273011
DA 2026-03-09
ER

PT J
AU Wheeler, TD
   Stroock, AD
AF Wheeler, Tobias D.
   Stroock, Abraham D.
TI The transpiration of water at negative pressures in a synthetic tree
SO NATURE
LA English
DT Article
ID system; cavitation; resistance; capillary; transport; suction; plants
AB Plant scientists believe that transpiration - the motion of water from the soil, through a vascular plant, and into the air - occurs by a passive, wicking mechanism. This mechanism is described by the cohesion- tension theory: loss of water by evaporation reduces the pressure of the liquid water within the leaf relative to atmospheric pressure; this reduced pressure pulls liquid water out of the soil and up the xylem to maintain hydration(1-3). Strikingly, the absolute pressure of the water within the xylem is often negative, such that the liquid is under tension and is thermodynamically metastable with respect to the vapour phase(1,4). Qualitatively, this mechanism is the same as that which drives fluid through the synthetic wicks that are key elements in technologies for heat transfer(5), fuel cells(6,7) and portable chemical systems(8-10). Quantitatively, the differences in pressure generated in plants to drive flow can be more than a hundredfold larger than those generated in synthetic wicks. Here we present the design and operation of a microfluidic system formed in a synthetic hydrogel. This synthetic 'tree' captures the main attributes of transpiration in plants: transduction of subsaturation in the vapour phase of water into negative pressures in the liquid phase, stabilization and flow of liquid water at large negative pressures (-1.0 MPa or lower), continuous heat transfer with the evaporation of liquid water at negative pressure, and continuous extraction of liquid water from subsaturated sources. This development opens the opportunity for technological uses of water under tension and for new experimental studies of the liquid state of water.
C1 [Wheeler, Tobias D.; Stroock, Abraham D.] Cornell Univ, Sch Chem & Biomol Engn, Ithaca, NY 14853 USA.
C3 Cornell University
RP Stroock, AD (corresponding author), Cornell Univ, Sch Chem & Biomol Engn, Ithaca, NY 14853 USA.
EM ads10@cornell.edu
FU Office of Naval Research Young Investigator Program; Camille and Henry Dreyfus Foundation; Corning Foundation; National Science Foundation (NSF); Nanobiotechnology Center; STC Program of the NSF [ECS-98767710]; Cornell Center for Materials Research; NSF [DMR- 0520404]
NR 28
TC 467
Z9 533
U1 8
U2 451
PU NATURE PUBLISHING 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 11
PY 2008
VL 455
IS 7210
BP 208
EP 212
DI 10.1038/nature07226
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800043
PM 18784721
DA 2026-03-09
ER

PT J
AU Press, D
   Ladd, TD
   Zhang, BY
   Yamamoto, Y
AF Press, David
   Ladd, Thaddeus D.
   Zhang, Bingyang
   Yamamoto, Yoshihisa
TI Complete quantum control of a single quantum dot spin using ultrafast optical pulses
SO NATURE
LA English
DT Article
ID electron-spin; manipulation
AB A basic requirement for quantum information processing systems is the ability to completely control the state of a single qubit(1-6). For qubits based on electron spin, a universal single- qubit gate is realized by a rotation of the spin by any angle about an arbitrary axis. Driven, coherent Rabi oscillations between two spin states can be used to demonstrate control of the rotation angle. Ramsey interference, produced by two coherent spin rotations separated by a variable time delay, demonstrates control over the axis of rotation. Full quantum control of an electron spin in a quantum dot has previously been demonstrated using resonant radio- frequency pulses that require many spin precession periods(7-10). However, optical manipulation of the spin allows quantum control on a picosecond or femtosecond timescale(11-18), permitting an arbitrary rotation to be completed within one spin precession period(6). Recent work in optical single-spin control has demonstrated the initialization of a spin state in a quantumdot(19-22), as well as the ultrafast manipulation of coherence in a largely unpolarized single- spin state(17). Here we demonstrate complete coherent control over an initialized electron spin state in a quantum dot using picosecond optical pulses. First we vary the intensity of a single optical pulse to observe over six Rabi oscillations between the two spin states; then we apply two sequential pulses to observe high- contrast Ramsey interference. Such a two- pulse sequence realizes an arbitrary single- qubit gate completed on a picosecond timescale. Along with the spin initialization and final projective measurement of the spin state, these results demonstrate a complete set of all- optical single- qubit operations.
C1 [Press, David; Ladd, Thaddeus D.; Zhang, Bingyang; Yamamoto, Yoshihisa] Stanford Univ, Edward L Ginzton Lab, Stanford, CA 94305 USA.
   [Ladd, Thaddeus D.; Yamamoto, Yoshihisa] Res Org Informat & Syst, Natl Inst Informat, Chiyoda Ku, Tokyo 1018403, Japan.
C3 Stanford University; Research Organization of Information & Systems (ROIS); National Institute of Informatics (NII) - Japan
RP Press, D (corresponding author), Stanford Univ, Edward L Ginzton Lab, Stanford, CA 94305 USA.
EM dlpress@stanford.edu
FU JST/SORST; NICT; MEXT; MURI [(ARMY, DAAD 19-03-1-0199)]; Special Coordination Funds for Promoting Science and Technology; Grants-in-Aid for Scientific Research [18001002] Funding Source: KAKEN
NR 29
TC 769
Z9 857
U1 5
U2 189
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 13
PY 2008
VL 456
IS 7219
BP 218
EP 221
DI 10.1038/nature07530
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300035
PM 19005550
DA 2026-03-09
ER

PT J
AU Martin, F
   Aerts, A
   Ahrén, D
   Brun, A
   Danchin, EGJ
   Duchaussoy, F
   Gibon, J
   Kohler, A
   Lindquist, E
   Pereda, V
   Salamov, A
   Shapiro, HJ
   Wuyts, J
   Blaudez, D
   Buée, M
   Brokstein, P
   Canbäck, B
   Cohen, D
   Courty, PE
   Coutinho, PM
   Delaruelle, C
   Detter, JC
   Deveau, A
   DiFazio, S
   Duplessis, S
   Fraissinet-Tachet, L
   Lucic, E
   Frey-Klett, P
   Fourrey, C
   Feussner, I
   Gay, G
   Grimwood, J
   Hoegger, PJ
   Jain, P
   Kilaru, S
   Labbé, J
   Lin, YC
   Legué, V
   Le Tacon, F
   Marmeisse, R
   Melayah, D
   Montanini, B
   Muratet, M
   Nehls, U
   Niculita-Hirzel, H
   Oudot-Le Secq, MP
   Peter, M
   Quesneville, H
   Rajashekar, B
   Reich, M
   Rouhier, N
   Schmutz, J
   Yin, T
   Chalot, M
   Henrissat, B
   Kües, U
   Lucas, S
   Van de Peer, Y
   Podila, GK
   Polle, A
   Pukkila, PJ
   Richardson, PM
   Rouzé, P
   Sanders, IR
   Stajich, JE
   Tunlid, A
   Tuskan, G
   Grigoriev, IV
AF Martin, F.
   Aerts, A.
   Ahren, D.
   Brun, A.
   Danchin, E. G. J.
   Duchaussoy, F.
   Gibon, J.
   Kohler, A.
   Lindquist, E.
   Pereda, V.
   Salamov, A.
   Shapiro, H. J.
   Wuyts, J.
   Blaudez, D.
   Buee, M.
   Brokstein, P.
   Canback, B.
   Cohen, D.
   Courty, P. E.
   Coutinho, P. M.
   Delaruelle, C.
   Detter, J. C.
   Deveau, A.
   DiFazio, S.
   Duplessis, S.
   Fraissinet-Tachet, L.
   Lucic, E.
   Frey-Klett, P.
   Fourrey, C.
   Feussner, I.
   Gay, G.
   Grimwood, J.
   Hoegger, P. J.
   Jain, P.
   Kilaru, S.
   Labbe, J.
   Lin, Y. C.
   Legue, V.
   Le Tacon, F.
   Marmeisse, R.
   Melayah, D.
   Montanini, B.
   Muratet, M.
   Nehls, U.
   Niculita-Hirzel, H.
   Oudot-Le Secq, M. P.
   Peter, M.
   Quesneville, H.
   Rajashekar, B.
   Reich, M.
   Rouhier, N.
   Schmutz, J.
   Yin, T.
   Chalot, M.
   Henrissat, B.
   Kuees, U.
   Lucas, S.
   Van de Peer, Y.
   Podila, G. K.
   Polle, A.
   Pukkila, P. J.
   Richardson, P. M.
   Rouze, P.
   Sanders, I. R.
   Stajich, J. E.
   Tunlid, A.
   Tuskan, G.
   Grigoriev, I. V.
TI The genome of Laccaria bicolor provides insights into mycorrhizal symbiosis
SO NATURE
LA English
DT Article
ID medicago-truncatula; proteins; biology
AB Mycorrhizal symbioses - the union of roots and soil fungi - are universal in terrestrial ecosystems and may have been fundamental to land colonization by plants(1,2). Boreal, temperate and montane forests all depend on ectomycorrhizae(1). Identification of the primary factors that regulate symbiotic development and metabolic activity will therefore open the door to understanding the role of ectomycorrhizae in plant development and physiology, allowing the full ecological significance of this symbiosis to be explored. Here we report the genome sequence of the ectomycorrhizal basidiomycete Laccaria bicolor ( Fig. 1) and highlight gene sets involved in rhizosphere colonization and symbiosis. This 65- megabase genome assembly contains 20,000 predicted protein- encoding genes and a very large number of transposons and repeated sequences. We detected unexpected genomic features, most notably a battery of effector- type small secreted proteins ( SSPs) with unknown function, several of which are only expressed in symbiotic tissues. The most highly expressed SSP accumulates in the proliferating hyphae colonizing the host root. The ectomycorrhizae- specific SSPs probably have a decisive role in the establishment of the symbiosis. The unexpected observation that the genome of L. bicolor lacks carbohydrate- active enzymes involved in degradation of plant cell walls, but maintains the ability to degrade non- plant cell wall polysaccharides, reveals the dual saprotrophic and biotrophic lifestyle of the mycorrhizal fungus that enables it to grow within both soil and living plant roots. The predicted gene inventory of the L. bicolor genome, therefore, points to previously unknown mechanisms of symbiosis operating in biotrophic mycorrhizal fungi. The availability of this genome provides an unparalleled opportunity to develop a deeper understanding of the processes by which symbionts interact with plants within their ecosystem to perform vital functions in the carbon and nitrogen cycles that are fundamental to sustainable plant productivity.
C1 [Martin, F.; Brun, A.; Duchaussoy, F.; Gibon, J.; Kohler, A.; Pereda, V.; Wuyts, J.; Blaudez, D.; Buee, M.; Cohen, D.; Courty, P. E.; Delaruelle, C.; Deveau, A.; Duplessis, S.; Lucic, E.; Frey-Klett, P.; Fourrey, C.; Labbe, J.; Legue, V.; Le Tacon, F.; Montanini, B.; Oudot-Le Secq, M. P.; Peter, M.; Reich, M.; Rouhier, N.; Chalot, M.] Univ Nancy 1, INRA, UMR 1136, F-54280 Champenoux, France.
   [Aerts, A.; Lindquist, E.; Salamov, A.; Shapiro, H. J.; Brokstein, P.; Detter, J. C.; Lucas, S.; Richardson, P. M.; Grigoriev, I. V.] US DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Ahren, D.; Canback, B.; Rajashekar, B.; Tunlid, A.] Lund Univ, SE-22362 Lund, Sweden.
   [Danchin, E. G. J.; Coutinho, P. M.; Henrissat, B.] Univ Aix Marseille 1, CNRS, UMR 6098, F-13288 Marseille 9, France.
   [Danchin, E. G. J.; Coutinho, P. M.; Henrissat, B.] Univ Aix Marseille 2, CNRS, UMR 6098, F-13288 Marseille 9, France.
   [Wuyts, J.; Lin, Y. C.; Van de Peer, Y.; Rouze, P.] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [DiFazio, S.] W Virginia Univ, Dept Biol, Morgantown, WV 26506 USA.
   [Feussner, I.] Univ Gottingen, Dept Plant Biochem, D-37077 Gottingen, Germany.
   [Fraissinet-Tachet, L.; Gay, G.; Marmeisse, R.; Melayah, D.] Univ Lyon 1, CNRS, UMR USC INRA Ecol Microbienne, F-69622 Villeurbanne, France.
   [Grimwood, J.; Schmutz, J.] Stanford Univ, Sch Med, Stanford Human Genome Ctr, Dept Genet, Palo Alto, CA 94304 USA.
   [Hoegger, P. J.; Kilaru, S.; Reich, M.; Kuees, U.; Polle, A.] Univ Gottingen, Inst Forest Bot, D-37077 Gottingen, Germany.
   [Jain, P.; Muratet, M.; Podila, G. K.] Univ Alabama, Dept Biol Sci, Huntsville, AL 35899 USA.
   [Nehls, U.] Univ Tubingen, D-72076 Tubingen, Germany.
   [Niculita-Hirzel, H.; Sanders, I. R.] Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.
   [Peter, M.] Swiss Fed Res Inst WSL, CH-8903 Birmensdorf, Switzerland.
   [Quesneville, H.] INRA, Unite Rech Genom Info, F-91034 Evry, France.
   [Yin, T.; Tuskan, G.] Oak Ridge Natl Lab, Div Environm Sci, Oak Ridge, TN 37831 USA.
   [Pukkila, P. J.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Rouze, P.] Univ Ghent, Lab Assoc INRA, B-9052 Ghent, Belgium.
   [Stajich, J. E.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
C3 Universite de Lorraine; INRAE; United States Department of Energy (DOE); Lund University; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Ghent University; Flanders Institute for Biotechnology (VIB); West Virginia University; University of Gottingen; INRAE; Centre National de la Recherche Scientifique (CNRS); Universite Lyon 1; Stanford University; University of Gottingen; University of Alabama System; University of Alabama Huntsville; Eberhard Karls University of Tubingen; University of Lausanne; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; INRAE; United States Department of Energy (DOE); Oak Ridge National Laboratory; University of North Carolina; University of North Carolina Chapel Hill; Ghent University; University of California System; University of California Berkeley
RP Martin, F (corresponding author), Univ Nancy 1, INRA, UMR 1136, F-54280 Champenoux, France.
EM fmartin@nancy.inra.fr
NR 27
TC 794
Z9 973
U1 4
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 6
PY 2008
VL 452
IS 7183
BP 88
EP U7
DI 10.1038/nature06556
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900052
PM 18322534
DA 2026-03-09
ER

PT J
AU Venail, PA
   MacLean, RC
   Bouvier, T
   Brockhurst, MA
   Hochberg, ME
   Mouquet, N
AF Venail, P. A.
   MacLean, R. C.
   Bouvier, T.
   Brockhurst, M. A.
   Hochberg, M. E.
   Mouquet, N.
TI Diversity and productivity peak at intermediate dispersal rate in evolving metacommunities
SO NATURE
LA English
DT Article
ID species-diversity; evolutionary diversification; ecological theory; current knowledge; escherichia-coli; plant diversity; biodiversity; populations; coexistence; heterogeneity
AB Positive relationships between species diversity and productivity have been reported for a number of ecosystems(1,2). Theoretical and experimental studies have attempted to determine the mechanisms that generate this pattern over short timescales(1,2), but little attention has been given to the problem of understanding how diversity and productivity are linked over evolutionary timescales. Here, we investigate the role of dispersal in determining both diversity and productivity over evolutionary timescales, using experimental metacommunities of the bacterium Pseudomonas fluorescens assembled by divergent natural selection. We show that both regional diversity and productivity peak at an intermediate dispersal rate. Moreover, we demonstrate that these two patterns are linked: selection at intermediate rates of dispersal leads to high niche differentiation between genotypes, allowing greater coverage of the heterogeneous environment and a higher regional productivity. We argue that processes that operate over both ecological and evolutionary timescales should be jointly considered when attempting to understand the emergence of ecosystem- level properties such as diversity - function relationships.
C1 [Venail, P. A.; Hochberg, M. E.; Mouquet, N.] Univ Montpellier 2, CNRS, Inst Sci Evolut, UMR 5554, F-34095 Montpellier 05, France.
   [Bouvier, T.] Univ Montpellier 2, CNRS, IFREMER, Ecosyst Lagunaires UMR 5119, F-34095 Montpellier, France.
   [MacLean, R. C.] Univ London Imperial Coll Sci Technol & Med, NERC Ctr Populat Biol, Ascot SL5 7PY, Berks, England.
   [Brockhurst, M. A.] Univ Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England.
C3 Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite de Montpellier; CNRS - Institute of Ecology & Environment (INEE); Universite de Montpellier; Ifremer; Centre National de la Recherche Scientifique (CNRS); Imperial College London; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); University of Liverpool
RP Venail, PA (corresponding author), Univ Montpellier 2, CNRS, Inst Sci Evolut, UMR 5554, CC065 Pl Eugene Bataillon, F-34095 Montpellier 05, France.
EM pvenail@univ-montp2.fr; nmouquet@univ-montp2.fr
FU NERC [cpb010001] Funding Source: UKRI; Natural Environment Research Council [cpb010001] Funding Source: researchfish
NR 29
TC 137
Z9 153
U1 1
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 13
PY 2008
VL 452
IS 7184
BP 210
EP U57
DI 10.1038/nature06554
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600039
PM 18337821
DA 2026-03-09
ER

PT J
AU Bessonov, S
   Anokhina, M
   Will, CL
   Urlaub, H
   Lührmann, R
AF Bessonov, Sergey
   Anokhina, Maria
   Will, Cindy L.
   Urlaub, Henning
   Luehrmann, Reinhard
TI Isolation of an active step I spliceosome and composition of its RNP core
SO NATURE
LA English
DT Article
ID bimolecular exon ligation; protein-composition; complex; u2; prp19; site
AB Formation of catalytically active RNA structures within the spliceosome requires the assistance of proteins. However, little is known about the number and nature of proteins needed to establish and maintain the spliceosome's active site. Here we affinity- purified human spliceosomal C complexes and show that they catalyse exon ligation in the absence of added factors. Comparisons of the composition of the precatalytic versus the catalytic spliceosome revealed a marked exchange of proteins during the transition from the B to the C complex, with apparent stabilization of Prp19 - CDC5 complex proteins and destabilization of SF3a/ b proteins. Disruption of purified C complexes led to the isolation of a salt- stable ribonucleoprotein ( RNP) core that contained both splicing intermediates and U2, U5 and U6 small nuclear RNA plus predominantly U5 and human Prp19 - CDC5 proteins and Prp19- related factors. Our data provide insights into the spliceosome's catalytic RNP domain and indicate a central role for the aforementioned proteins in sustaining its catalytically active structure.
C1 [Bessonov, Sergey; Anokhina, Maria; Will, Cindy L.; Luehrmann, Reinhard] Max Planck Inst Biophys Chem, Dept Cellular Biochem, D-37077 Gottingen, Germany.
   [Urlaub, Henning] Max Planck Inst Biophys Chem, Bioanalyt Mass Spectrometry Grp, D-37077 Gottingen, Germany.
C3 Max Planck Society; Max Planck Society
RP Lührmann, R (corresponding author), Max Planck Inst Biophys Chem, Dept Cellular Biochem, D-37077 Gottingen, Germany.
EM reinhard.luehrmann@mpi-bpc.mpg.de
NR 27
TC 313
Z9 388
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 APR 17
PY 2008
VL 452
IS 7189
BP 846
EP U3
DI 10.1038/nature06842
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000042
PM 18322460
DA 2026-03-09
ER

PT J
AU He, WZ
   Ladinsky, MS
   Huey-Tubman, KE
   Jensen, GJ
   McIntosh, JR
   Björkman, PJ
AF He, Wanzhong
   Ladinsky, Mark S.
   Huey-Tubman, Kathryn E.
   Jensen, Grant J.
   McIntosh, J. Richard
   Bjorkman, Pamela J.
TI FcRn-mediated antibody transport across epithelial cells revealed by electron tomography
SO NATURE
LA English
DT Article
ID clathrin-coated vesicles; rat-kidney cell; intestinal transport; freeze-substitution; immunoglobulin-g; neonatal rat; 3 dimensions; young-rat; receptor; fusion
AB The neonatal Fc receptor ( FcRn) transports maternal IgG across epithelial barriers(1,2), thereby providing the fetus or newborn with humoral immunity before its immune system is fully functional. In newborn rats, FcRn transfers IgG from milk to blood by apical-to-basolateral transcytosis across intestinal epithelial cells. The pH difference between the apical ( pH 6.0-6.5) and basolateral ( pH 7.4) sides of intestinal epithelial cells facilitates the efficient unidirectional transport of IgG, because FcRn binds IgG at pH 6.0-6.5 but not at pH 7 or more(1,2). As milk passes through the neonatal intestine, maternal IgG is removed by FcRn-expressing cells in the proximal small intestine ( duodenum and jejunum); remaining proteins are absorbed and degraded by FcRn- negative cells in the distal small intestine ( ileum)(3-6). Here we use electron tomography to make jejunal transcytosis visible directly in space and time, developing new labelling and detection methods to map individual nanogold-labelled Fc within transport vesicles(7) and simultaneously to characterize these vesicles by immunolabelling. Combining electron tomography with a nonperturbing endocytic label allowed us to conclusively identify receptor- bound ligands, resolve interconnecting vesicles, determine whether a vesicle was microtubule- associated, and accurately trace FcRn- mediated transport of IgG. Our results present a complex picture in which Fc moves through networks of entangled tubular and irregular vesicles, only some of which are microtubuleassociated, as it migrates to the basolateral surface. New features of transcytosis are elucidated, including transport involving multivesicular body inner vesicles/ tubules and exocytosis through clathrin- coated pits. Markers for early, late and recycling endosomes each labelled vesicles in different and overlapping morphological classes, revealing spatial complexity in endo- lysosomal trafficking.
C1 [He, Wanzhong; Huey-Tubman, Kathryn E.; Jensen, Grant J.; Bjorkman, Pamela J.] CALTECH, Div Biol 114 96, Pasadena, CA 91125 USA.
   [Huey-Tubman, Kathryn E.; Bjorkman, Pamela J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [He, Wanzhong] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
   [Ladinsky, Mark S.; McIntosh, J. Richard] Univ Colorado, Boulder Lab 3D Elect Microscopy Cells, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
C3 California Institute of Technology; Howard Hughes Medical Institute; California Institute of Technology; National University of Singapore; University of Colorado System; University of Colorado Boulder
RP Björkman, PJ (corresponding author), CALTECH, Div Biol 114 96, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM bjorkman@caltech.edu
FU National Institutes of Health [2 R37 AI041239-06A1, RR000592]; Max Planck Research Award; Gordon and Betty Moore Foundation; Agouron Institute; Caltech; National University of Singapore [R-154-000-339-133]
NR 37
TC 145
Z9 172
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 542
EP U53
DI 10.1038/nature07255
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600048
PM 18818657
DA 2026-03-09
ER

PT J
AU Scaillet, B
   Pichavant, M
   Cioni, R
AF Scaillet, B.
   Pichavant, M.
   Cioni, R.
TI Upward migration of Vesuvius magma chamber over the past 20,000 years
SO NATURE
LA English
DT Article
ID somma-vesuvius; plinian eruption; mt-vesuvius; volcanos; reconstruction; phenocrysts; dynamics; system
AB Forecasting future eruptions of Vesuvius is an important challenge for volcanologists, as its reawakening could threaten the lives of 700,000 people living near the volcano(1,2). Critical to the evaluation of hazards associated with the next eruption is the estimation of the depth of the magma reservoir, one of the main parameters controlling magma properties and eruptive style. Petrological studies have indicated that during past activity, magma chambers were at depths between 3 and 16 km ( refs 3-7). Geophysical surveys have imaged some levels of seismic attenuation, the shallowest of which lies at 8-9 km depth(8), and these have been tentatively interpreted as levels of preferential magma accumulation. By using experimental phase equilibria, carried out on material from four main explosive events at Vesuvius, we show here that the reservoirs that fed the eruptive activity migrated from 7-8 km to 3-4 km depth between the AD 79 ( Pompeii) and AD 472 ( Pollena) events. If data from the Pomici di Base event 18.5 kyr ago(9) and the 1944 Vesuvius eruption(7) are included, the total upward migration of the reservoir amounts to 9-11 km. The change of preferential magma ponding levels in the upper crust can be attributed to differences in the volatile content and buoyancy of ascending magmas, as well as to changes in local stress field following either caldera formation(10) or volcano spreading(11). Reservoir migration, and the possible influence on feeding rates(12), should be integrated into the parameters used for defining expected eruptive scenarios at Vesuvius.
C1 [Scaillet, B.; Pichavant, M.] CNRS, INSU, Inst Sci Terre Orleans, F-45071 Orleans 2, France.
   [Scaillet, B.; Pichavant, M.] Univ Orleans, Inst Sci Terre Orleans, F-45071 Orleans, France.
   [Cioni, R.] Dipartimento Sci Terra, I-09127 Cagliari, Italy.
   [Cioni, R.] INGV, Sez Pisa, I-56100 Pisa, Italy.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Orleans; Istituto Nazionale Geofisica e Vulcanologia (INGV)
RP Scaillet, B (corresponding author), CNRS, INSU, Inst Sci Terre Orleans, 1A Rue Ferollerie, F-45071 Orleans 2, France.
EM bscaille@cnrs-orleans.fr
FU GNV; INGV; department of the Italian Civil Defense
NR 33
TC 132
Z9 136
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 11
PY 2008
VL 455
IS 7210
BP 216
EP U39
DI 10.1038/nature07232
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800045
PM 18784723
DA 2026-03-09
ER

PT J
AU Wachter, S
   Ramirez-Ruiz, E
   Dwarkadas, VV
   Kouveliotou, C
   Granot, J
   Patel, SK
   Figer, D
AF Wachter, S.
   Ramirez-Ruiz, E.
   Dwarkadas, V. V.
   Kouveliotou, C.
   Granot, J.
   Patel, S. K.
   Figer, D.
TI An infrared ring around the magnetar SGR 1900+14
SO NATURE
LA English
DT Article
ID gamma-ray bursts; sgr 1900+14; stars; discovery; pulsar; dust; sgr-1806-20; cluster
AB Magnetars(1,2) are a special class of slowly rotating ( period similar to 5 - 12 s) neutron stars with extremely strong magnetic fields (>10(14) G) - at least an order of magnitude larger than those of the 'normal' radio pulsars. The potential evolutionary links and differences between these two types of object are still unknown; recent studies, however, have provided circumstantial evidence connecting magnetars with very massive progenitor stars(3-5). Here we report the discovery of an infrared elliptical ring or shell surrounding the magnetar SGR 1900+14. The appearance and energetics of the ring are difficult to interpret within the framework of the progenitor's stellar mass loss or the subsequent evolution of the supernova remnant. We suggest instead that a dust- free cavity was produced in the magnetar environment by the giant flare emitted by the source in August 1998. Considering the total energy released in the flare, the theoretical dust- destruction radius matches well with the observed dimensions of the ring. We conclude that SGR 1900+14 is unambiguously associated with a cluster of massive stars, thereby solidifying the link between magnetars and massive stars.
C1 [Wachter, S.] CALTECH, Spitzer Sci Ctr, Pasadena, CA 91125 USA.
   [Dwarkadas, V. V.] Univ Chicago, Dept Astron & Astrophys, Chicago, IL 60637 USA.
   [Kouveliotou, C.] NASA, George C Marshall Space Flight Ctr, NSSTC, Huntsville, AL 35805 USA.
   [Granot, J.] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.
   [Patel, S. K.] Opt Sci Corp, Huntsville, AL 35806 USA.
   [Figer, D.] Rochester Inst Technol, Chester F Carlson Ctr Imaging Sci, Rochester, NY 14623 USA.
C3 California Institute of Technology; University of Chicago; National Aeronautics & Space Administration (NASA); NASA Marshall Space Flight Center; University of Hertfordshire; Rochester Institute of Technology
RP Wachter, S (corresponding author), CALTECH, Spitzer Sci Ctr, Pasadena, CA 91125 USA.
EM wachter@ipac.caltech.edu
FU Science and Technology Facilities Council [PP/D000920/1] Funding Source: researchfish; STFC [PP/D000920/1] Funding Source: UKRI
NR 30
TC 17
Z9 19
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2008
VL 453
IS 7195
BP 626
EP 628
DI 10.1038/nature06987
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200037
PM 18509437
DA 2026-03-09
ER

PT J
AU Kaminsky, R
   Ducray, P
   Jung, M
   Clover, R
   Rufener, L
   Bouvier, J
   Weber, SS
   Wenger, A
   Wieland-Berghausen, S
   Goebel, T
   Gauvry, N
   Pautrat, F
   Skripsky, T
   Froelich, O
   Komoin-Oka, C
   Westlund, B
   Sluder, A
   Mäser, P
AF Kaminsky, Ronald
   Ducray, Pierre
   Jung, Martin
   Clover, Ralph
   Rufener, Lucien
   Bouvier, Jacques
   Weber, Sandra Schorderet
   Wenger, Andre
   Wieland-Berghausen, Susanne
   Goebel, Thomas
   Gauvry, Noelle
   Pautrat, Francois
   Skripsky, Thomas
   Froelich, Olivier
   Komoin-Oka, Clarisse
   Westlund, Bethany
   Sluder, Ann
   Maeser, Pascal
TI A new class of anthelmintics effective against drug-resistant nematodes
SO NATURE
LA English
DT Article
ID haemonchus-contortus; ivermectin; efficacy; subunits
AB Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics - the benzimidazoles, imidazothiazoles and macrocyclic lactones - has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino- acetonitrile derivatives ( AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock- pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode- specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.
C1 [Kaminsky, Ronald; Jung, Martin; Rufener, Lucien; Bouvier, Jacques; Weber, Sandra Schorderet; Wenger, Andre; Froelich, Olivier] Novartis Ctr Rech Sante Animale, CH-1566 St Aubin, Switzerland.
   [Ducray, Pierre; Wieland-Berghausen, Susanne; Goebel, Thomas; Gauvry, Noelle; Pautrat, Francois; Skripsky, Thomas] Novartis Anim Hlth Inc, CH-4002 Basel, Switzerland.
   [Clover, Ralph; Westlund, Bethany; Sluder, Ann] Cambria Biosci, Woburn, MA 01801 USA.
   [Rufener, Lucien; Maeser, Pascal] Lab Cent Vet Bingerville, Lanada, Cote Ivoire.
C3 Novartis; Novartis
RP Kaminsky, R (corresponding author), Novartis Ctr Rech Sante Animale, CH-1566 St Aubin, Switzerland.
EM ronald.kaminsky@novartis.com
NR 23
TC 405
Z9 520
U1 2
U2 128
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 13
PY 2008
VL 452
IS 7184
BP 176
EP U19
DI 10.1038/nature06722
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600032
PM 18337814
DA 2026-03-09
ER

PT J
AU Lelieveld, J
   Butler, TM
   Crowley, JN
   Dillon, TJ
   Fischer, H
   Ganzeveld, L
   Harder, H
   Lawrence, MG
   Martinez, M
   Taraborrelli, D
   Williams, J
AF Lelieveld, J.
   Butler, T. M.
   Crowley, J. N.
   Dillon, T. J.
   Fischer, H.
   Ganzeveld, L.
   Harder, H.
   Lawrence, M. G.
   Martinez, M.
   Taraborrelli, D.
   Williams, J.
TI Atmospheric oxidation capacity sustained by a tropical forest
SO NATURE
LA English
DT Article
ID isoprene; chemistry; emission; model; thermotolerance; hydrocarbons; terrestrial; simulation; ozone
AB Terrestrial vegetation, especially tropical rain forest, releases vast quantities of volatile organic compounds (VOCs) to the atmosphere(1-3), which are removed by oxidation reactions and deposition of reaction products(4-6). The oxidation is mainly initiated by hydroxyl radicals (OH), primarily formed through the photodissociation of ozone(4). Previously it was thought that, in unpolluted air, biogenic VOCs deplete OH and reduce the atmospheric oxidation capacity(5-10). Conversely, in polluted air VOC oxidation leads to noxious oxidant build-up by the catalytic action of nitrogen oxides(5-10) (NOx = NO + NO2). Here we report aircraft measurements of atmospheric trace gases performed over the pristine Amazon forest. Our data reveal unexpectedly high OH concentrations. We propose that natural VOC oxidation, notably of isoprene, recycles OH efficiently in low-NOx air through reactions of organic peroxy radicals. Computations with an atmospheric chemistry model and the results of laboratory experiments suggest that an OH recycling efficiency of 40-80 per cent in isoprene oxidation may be able to explain the high OH levels we observed in the field. Although further laboratory studies are necessary to explore the chemical mechanism responsible for OH recycling in more detail, our results demonstrate that the biosphere maintains a remarkable balance with the atmospheric environment.
C1 [Lelieveld, J.; Butler, T. M.; Crowley, J. N.; Dillon, T. J.; Fischer, H.; Ganzeveld, L.; Harder, H.; Lawrence, M. G.; Martinez, M.; Taraborrelli, D.; Williams, J.] Max Planck Inst Chem, D-55128 Mainz, Germany.
C3 Max Planck Society
RP Lelieveld, J (corresponding author), Max Planck Inst Chem, 27 Becherweg, D-55128 Mainz, Germany.
EM lelieveld@mpch-mainz.mpg.de
NR 29
TC 701
Z9 806
U1 12
U2 531
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 10
PY 2008
VL 452
IS 7188
BP 737
EP 740
DI 10.1038/nature06870
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500042
PM 18401407
DA 2026-03-09
ER

PT J
AU Malanchi, I
   Peinado, H
   Kassen, D
   Hussenet, T
   Metzger, D
   Chambon, P
   Huber, M
   Hohl, D
   Cano, A
   Birchmeier, W
   Huelsken, J
AF Malanchi, Ilaria
   Peinado, Hector
   Kassen, Deepika
   Hussenet, Thomas
   Metzger, Daniel
   Chambon, Pierre
   Huber, Marcel
   Hohl, Daniel
   Cano, Amparo
   Birchmeier, Walter
   Huelsken, Joerg
TI Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling
SO NATURE
LA English
DT Article
ID hair follicle bulge; skin tumors; expression; gene; differentiation; epidermis; mutation; ras; tumorigenesis; populations
AB Continuous turnover of epithelia is ensured by the extensive self-renewal capacity of tissue- specific stem cells(1). Similarly, epithelial tumour maintenance relies on cancer stem cells ( CSCs), which co-opt stem cell properties(2). For most tumours, the cellular origin of these CSCs and regulatory pathways essential for sustaining stemness have not been identified. In murine skin, follicular morphogenesis is driven by bulge stem cells that specifically express CD34. Here we identify a population of cells in early epidermal tumours characterized by phenotypic and functional similarities to normal bulge skin stem cells. This population contains CSCs, which are the only cells with tumour initiation properties. Transplants derived from these CSCs preserve the hierarchical organization of the primary tumour. We describe beta-catenin signalling(3) as being essential in sustaining the CSC phenotype. Ablation of the beta-catenin gene results in the loss of CSCs and complete tumour regression. In addition, we provide evidence for the involvement of increased beta-catenin signalling in malignant human squamous cell carcinomas. Because Wnt/beta-catenin signalling is not essential for normal epidermal homeostasis, such a mechanistic difference may thus be targeted to eliminate CSCs(4) and consequently eradicate squamous cell carcinomas.
C1 [Malanchi, Ilaria; Kassen, Deepika; Hussenet, Thomas; Huelsken, Joerg] EPFL, ISREC Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland.
   [Malanchi, Ilaria; Kassen, Deepika; Hussenet, Thomas; Huelsken, Joerg] NCCR Mol Oncol, CH-1066 Epalinges, Switzerland.
   [Peinado, Hector; Cano, Amparo] UAM, CSIC, Dept Bioquim, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain.
   [Metzger, Daniel; Chambon, Pierre] CU Strasbourg, IGBMC, F-67404 Illkirch Graffenstaden, France.
   [Huber, Marcel; Hohl, Daniel] CHU Vaudois, Lab Cutaneous Biol Dermatol, CH-1011 Lausanne, Switzerland.
   [Huber, Marcel; Hohl, Daniel] FBM UNIL, CH-1011 Lausanne, Switzerland.
   [Birchmeier, Walter] Max Delbruck Ctr Mol Med, D-13122 Berlin, Germany.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Institute Experimental Cancer Research; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Investigaciones Biomedicas Alberto Sols (IIBM); Autonomous University of Madrid; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Huelsken, J (corresponding author), EPFL, ISREC Swiss Inst Expt Canc Res, Chemin Boveresses 155, CH-1066 Epalinges, Switzerland.
EM joerg.huelsken@epfl.ch
NR 32
TC 491
Z9 596
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 650
EP U12
DI 10.1038/nature06835
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200050
PM 18385740
DA 2026-03-09
ER

PT J
AU Houweling, AR
   Brecht, M
AF Houweling, Arthur R.
   Brecht, Michael
TI Behavioural report of single neuron stimulation in somatosensory cortex
SO NATURE
LA English
DT Article
ID in-vivo; cortical microstimulation; neocortical neurons; whisker deflection; receptive-fields; pyramidal cells; rat; representation; discrimination; population
AB Understanding how neural activity in sensory cortices relates to perception is a central theme of neuroscience. Action potentials of sensory cortical neurons can be strongly correlated to properties of sensory stimuli(1) and reflect the subjective judgements of an individual about stimuli(2). Microstimulation experiments have established a direct link from sensory activity to behaviour(3,4), suggesting that small neuronal populations can influence sensory decisions(5). However, microstimulation does not allow identification and quantification of the stimulated cellular elements(6). The sensory impact of individual cortical neurons therefore remains unknown. Here we show that stimulation of single neurons in somatosensory cortex affects behavioural responses in a detection task. We trained rats to respond to microstimulation of barrel cortex at low current intensities. We then initiated short trains of action potentials in single neurons by juxtacellular stimulation. Animals responded significantly more often in single- cell stimulation trials than in catch trials without stimulation. Stimulation effects varied greatly between cells, and on average in 5% of trials a response was induced. Whereas stimulation of putative excitatory neurons led to weak biases towards responding, stimulation of putative inhibitory neurons led to more variable and stronger sensory effects. Reaction times for single- cell stimulation were long and variable. Our results demonstrate that single neuron activity can cause a change in the animal's detection behaviour, suggesting a much sparser cortical code for sensations than previously anticipated.
C1 [Houweling, Arthur R.; Brecht, Michael] Bernstein Ctr Computat Neurosci, D-10115 Berlin, Germany.
   [Houweling, Arthur R.; Brecht, Michael] Humboldt Univ, D-10115 Berlin, Germany.
   [Houweling, Arthur R.; Brecht, Michael] Erasmus MC, Dept Neurosci, NL-3000 CA Rotterdam, Netherlands.
C3 Humboldt University of Berlin; Erasmus University Rotterdam; Erasmus MC
RP Houweling, AR (corresponding author), Bernstein Ctr Computat Neurosci, Philippstr 13,House 6, D-10115 Berlin, Germany.
EM arthur.houweling@bccn-berlin.de; michael.brecht@bccn-berlin.de
NR 31
TC 336
Z9 391
U1 0
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 65
EP U8
DI 10.1038/nature06447
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300034
PM 18094684
DA 2026-03-09
ER

PT J
AU Gerszten, RE
   Wang, TJ
AF Gerszten, Robert E.
   Wang, Thomas J.
TI The search for new cardiovascular biomarkers
SO NATURE
LA English
DT Article
ID coronary-artery-disease; plasma-proteome; identification; chemokine; receptor; association; database; events; risk
AB Despite considerable advances in the treatment of cardiovascular disease, it remains the leading cause of death in developed countries. Assessment of classic cardiovascular risk factors-including high blood pressure, diabetes and smoking-has a central role in disease prevention. However, many individuals with coronary heart disease (a narrowing of the blood vessels that supply the heart) have only one, or none, of the classic risk factors. Thus, new biomarkers are needed to augment the information obtained from traditional indicators and to illuminate disease mechanisms.
C1 [Gerszten, Robert E.; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
   [Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Gerszten, RE (corresponding author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA.
EM rgerszten@partners.org
NR 26
TC 275
Z9 312
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 21
PY 2008
VL 451
IS 7181
BP 949
EP 952
DI 10.1038/nature06802
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100036
PM 18288185
DA 2026-03-09
ER

PT J
AU Bozec, A
   Bakiri, L
   Hoebertz, A
   Eferl, R
   Schilling, AF
   Komnenovic, V
   Scheuch, H
   Priemel, M
   Stewart, CL
   Amling, M
   Wagner, EF
AF Bozec, Aline
   Bakiri, Latifa
   Hoebertz, Astrid
   Eferl, Robert
   Schilling, Arndt F.
   Komnenovic, Vukoslav
   Scheuch, Harald
   Priemel, Matthias
   Stewart, Colin L.
   Amling, Michael
   Wagner, Erwin F.
TI Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia
SO NATURE
LA English
DT Article
ID leukemia inhibitory factor; pagets-disease; stem-cells; c-fos; mice; expression; gene; growth; bcl-2; differentiation
AB Osteoclasts are multinucleated haematopoietic cells that resorb bone. Increased osteoclast activity causes osteoporosis, a disorder resulting in a low bone mass and a high risk of fractures(1). Increased osteoclast size and numbers are also a hallmark of other disorders, such as Paget's disease and multiple myeloma(2). The protein c- Fos, a component of the AP- 1 transcription factor complex, is essential for osteoclast differentiation(3). Here we show that the Fos- related protein Fra- 2 controls osteoclast survival and size. The bones of Fra- 2- deficient newborn mice have giant osteoclasts, and signalling through leukaemia inhibitory factor ( LIF) and its receptor is impaired. Similarly, newborn animals lacking LIF have giant osteoclasts, and we show that LIF is a direct transcriptional target of Fra- 2 and c- Jun. Moreover, bones deficient in Fra- 2 and LIF are hypoxic and express increased levels of hypoxia- induced factor 1 alpha ( HIF1 alpha) and Bcl- 2. Overexpression of Bcl- 2 is sufficient to induce giant osteoclasts in vivo, whereas Fra- 2 and LIF affect HIF1a through transcriptional modulation of the HIF prolyl hydroxylase PHD2. This pathway is operative in the placenta, because specific inactivation of Fra- 2 in the embryo alone does not cause hypoxia or the giant osteoclast phenotype. Thus placenta- induced hypoxia during embryogenesis leads to the formation of giant osteoclasts in young pups. These findings offer potential targets for the treatment of syndromes associated with increased osteoclastogenesis.
C1 [Bozec, Aline; Bakiri, Latifa; Hoebertz, Astrid; Eferl, Robert; Komnenovic, Vukoslav; Scheuch, Harald; Wagner, Erwin F.] Res Inst Mol Pathol, A-1030 Vienna, Austria.
   [Schilling, Arndt F.; Priemel, Matthias; Amling, Michael] Univ Med Ctr Hamburg Eppendorf, Dept Trauma Hand & Reconstruct Surg, Ctr Biomech & Skeletal Biol, D-20246 Hamburg, Germany.
   [Stewart, Colin L.] Inst Med Biol, Dev & Regenerat Biol Lab, Singapore 138648, Singapore.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); University of Hamburg; University Medical Center Hamburg-Eppendorf; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Medical Biology (IMB)
RP Wagner, EF (corresponding author), CNIO, C Melchor Fernandez Almagro 3, E-28029 Madrid, Spain.
EM wagner@imp.ac.at
NR 34
TC 166
Z9 188
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 221
EP U61
DI 10.1038/nature07019
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900045
PM 18548006
DA 2026-03-09
ER

PT J
AU Wang, Z
   Smith, KS
   Murphy, M
   Piloto, O
   Somervaille, TCP
   Cleary, ML
AF Wang, Zhong
   Smith, Kevin S.
   Murphy, Mark
   Piloto, Obdulio
   Somervaille, Tim C. P.
   Cleary, Michael L.
TI Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy
SO NATURE
LA English
DT Article
ID glycogen-synthase kinase-3; stem-cells; beta-catenin; protein; progenitors; menin; phosphorylates; rearrangements; transformation; specification
AB Glycogen synthase kinase 3 ( GSK3) is a multifunctional serine/ threonine kinase that participates in numerous signalling pathways involved in diverse physiological processes. Several of these pathways are implicated in disease pathogenesis, which has prompted efforts to develop GSK3- specific inhibitors for therapeutic applications. However, before now, there has been no strong rationale for targeting GSK3 in malignancies. Here we report pharmacological, physiological and genetic studies that demonstrate an oncogenic requirement for GSK3 in the maintenance of a specific subtype of poor prognosis human leukaemia, genetically defined by mutations of the MLL proto- oncogene. In contrast to its previously characterized roles in suppression of neoplasia- associated signalling pathways, GSK3 paradoxically supports MLL leukaemia cell proliferation and transformation by a mechanism that ultimately involves destabilization of the cyclin- dependent kinase inhibitor p27(Kip1). Inhibition of GSK3 in a preclinical murine model of MLL leukaemia provides promising evidence of efficacy and earmarks GSK3 as a candidate cancer drug target.
C1 [Wang, Zhong; Smith, Kevin S.; Murphy, Mark; Piloto, Obdulio; Somervaille, Tim C. P.; Cleary, Michael L.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
C3 Stanford University
RP Cleary, ML (corresponding author), Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
EM mcleary@stanford.edu
FU Children's Health Initiative of the Packard Foundation; PHS [CA55029, CA116606]; Leukemia and Lymphoma Society; Williams Lawrence Foundation; Developmental Research Award from the Stanford Cancer Center
NR 43
TC 237
Z9 283
U1 0
U2 12
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1205
EP U29
DI 10.1038/nature07284
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100036
PM 18806775
DA 2026-03-09
ER

PT J
AU Stefanescu, A
   Kanbach, G
   Slowikowska, A
   Greiner, J
   McBreen, S
   Sala, G
AF Stefanescu, A.
   Kanbach, G.
   Slowikowska, A.
   Greiner, J.
   McBreen, S.
   Sala, G.
TI Very fast optical flaring from a possible new Galactic magnetar
SO NATURE
LA English
DT Article
ID ray; telescope; outburst; mission
AB Highly luminous rapid flares are characteristic of processes around compact objects like white dwarfs, neutron stars and black holes. In the high- energy regime of X- rays and gamma-rays, outbursts with variabilities on timescales of seconds or less are routinely observed, for example in gamma-ray bursts(1) or soft gamma-ray repeaters(2). At optical wavelengths, flaring activity on such timescales has not been observed, other than from the prompt phase of one exceptional gamma-ray burst(3). This is mostly due to the fact that outbursts with strong, fast flaring are usually discovered in the high- energy regime; most optical follow-up observations of such transients use instruments with integration times exceeding tens of seconds, which are therefore unable to resolve fast variability. Here we show the observation of extremely bright and rapid optical flaring in the Galactic transient(4-7) SWIFT J195509.6+261406. Our optical light curves are phenomenologically similar to high- energy light curves of soft gamma-ray repeaters and anomalous X- ray pulsars(8), which are thought to be neutron stars with extremely high magnetic fields ( magnetars). This suggests that similar processes are in operation, but with strong emission in the optical, unlike in the case of other known magnetars.
C1 [Stefanescu, A.; Kanbach, G.; Greiner, J.; McBreen, S.; Sala, G.] Max Planck Inst Extraterr Phys, D-85741 Garching, Germany.
   [Slowikowska, A.] Fdn Res & Technol Hellas, IESL, GR-71110 Iraklion, Greece.
   [Slowikowska, A.] Copernicus Astron Ctr, PL-87100 Torun, Poland.
C3 Max Planck Society; Foundation for Research & Technology - Hellas (FORTH)
RP Stefanescu, A (corresponding author), Max Planck Inst Extraterr Phys, POB 1312, D-85741 Garching, Germany.
EM astefan@mpe.mpg.de; gok@mpe.mpg.de
FU OPTICON; Marie Curie Transfer of Knowledge Fellowship; Marie Curie Intra-European Fellowship; DLR.
NR 24
TC 35
Z9 38
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 SEP 25
PY 2008
VL 455
IS 7212
BP 503
EP 505
DI 10.1038/nature07308
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600039
PM 18818651
DA 2026-03-09
ER

PT J
AU Hanyu-Nakamura, K
   Sonobe-Nojima, H
   Tanigawa, A
   Lasko, P
   Nakamura, A
AF Hanyu-Nakamura, Kazuko
   Sonobe-Nojima, Hiroko
   Tanigawa, Akie
   Lasko, Paul
   Nakamura, Akira
TI Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; heat-shock; c-elegans; transcription elongation; caenorhabditis-elegans; gene-expression; noncoding rna; hiv-1 tat; in-vivo; kinase
AB Germ cells are the only cells that transmit genetic information to the next generation, and they therefore must be prevented from differentiating inappropriately into somatic cells(1). A common mechanism by which germline progenitors are protected from differentiation- inducing signals is a transient and global repression of RNA polymerase II ( RNAPII)- dependent transcription(1). In both Drosophila and Caenorhabditis elegans embryos, the repression of messenger RNA transcription during germ cell specification correlates with an absence of phosphorylation of Ser 2 residues in the carboxy- terminal domain of RNAPII ( hereafter called CTD)(2), a critical modification for transcriptional elongation(3). Here we show that, in Drosophila embryos, a small protein encoded by polar granule component ( pgc) is essential for repressing CTD Ser 2 phosphorylation in newly formed pole cells, the germline progenitors. Ectopic Pgc expression in somatic cells is sufficient to repress CTD Ser 2 phosphorylation. Furthermore, Pgc interacts, physically and genetically, with positive transcription elongation factor b ( P- TEFb), the CTD Ser 2 kinase complex, and prevents its recruitment to transcription sites. These results indicate that Pgc is a cell- type- specific P- TEFb inhibitor that has a fundamental role in Drosophila germ cell specification. In C. elegans embryos, PIE- 1 protein segregates to germline blastomeres, and is thought to repress mRNA transcription through interaction with P- TEFb(4-7). Thus, inhibition of P- TEFb is probably a common mechanism during germ cell specification in the disparate organisms C. elegans and Drosophila.
C1 [Hanyu-Nakamura, Kazuko; Sonobe-Nojima, Hiroko; Tanigawa, Akie; Nakamura, Akira] RIKEN, Ctr Dev Biol, Lab Germline Dev, Kobe, Hyogo 6500047, Japan.
   [Lasko, Paul] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
C3 RIKEN; McGill University
RP Nakamura, A (corresponding author), RIKEN, Ctr Dev Biol, Lab Germline Dev, Kobe, Hyogo 6500047, Japan.
EM akiran@cdb.riken.jp
FU NICHD NIH HHS [R01 HD036631] Funding Source: Medline
NR 33
TC 177
Z9 226
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 730
EP U7
DI 10.1038/nature06498
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500044
PM 18200011
DA 2026-03-09
ER

PT J
AU Suzuki, H
   Thiele, TR
   Faumont, S
   Ezcurra, M
   Lockery, SR
   Schafer, WR
AF Suzuki, Hiroshi
   Thiele, Tod R.
   Faumont, Serge
   Ezcurra, Marina
   Lockery, Shawn R.
   Schafer, William R.
TI Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis
SO NATURE
LA English
DT Article
ID nucleotide-gated channel; olfactory receptor-cells; c-elegans; behavior; responses; proteins; circuit; vesicle
AB Chemotaxis in Caenorhabditis elegans, like chemotaxis in bacteria(1), involves a random walk biased by the time derivative of attractant concentration(2,3), but how the derivative is computed is unknown. Laser ablations have shown that the strongest deficits in chemotaxis to salts are obtained when the ASE chemosensory neurons ( ASEL and ASER) are ablated, indicating that this pair has a dominant role(4). Although these neurons are left - right homologues anatomically, they exhibit marked asymmetries in gene expression and ion preference(5-7). Here, using optical recordings of calcium concentration in ASE neurons in intact animals, we demonstrate an additional asymmetry: ASEL is an ON- cell, stimulated by increases in NaCl concentration, whereas ASER is an OFF-cell, stimulated by decreases in NaCl concentration. Both responses are reliable yet transient, indicating that ASE neurons report changes in concentration rather than absolute levels. Recordings from synaptic and sensory transduction mutants show that the ON - OFF asymmetry is the result of intrinsic differences between ASE neurons. Unilateral activation experiments indicate that the asymmetry extends to the level of behavioural output: ASEL lengthens bouts of forward locomotion ( runs) whereas ASER promotes direction changes ( turns). Notably, the input and output asymmetries of ASE neurons are precisely those of a simple yet novel neuronal motif for computing the time derivative of chemosensory information, which is the fundamental computation of C. elegans chemotaxis(3,8). Evidence for ON and OFF cells in other chemosensory networks(9-12) suggests that this motif may be common in animals that navigate by taste and smell.
C1 [Thiele, Tod R.; Faumont, Serge; Lockery, Shawn R.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA.
   [Suzuki, Hiroshi; Schafer, William R.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
   [Ezcurra, Marina; Schafer, William R.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
C3 University of Oregon; University of California System; University of California San Diego; MRC Laboratory Molecular Biology
RP Lockery, SR (corresponding author), Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA.
EM shawn@uoregon.edu
FU MRC [MC_U105185857] Funding Source: UKRI; Medical Research Council [MC_U105185857] Funding Source: researchfish; Medical Research Council [MC_U105185857] Funding Source: Medline; NIDA NIH HHS [R01 DA016445, DA016445] Funding Source: Medline; NIMH NIH HHS [R21 MH112105, MH051383, R29 MH051383, R01 MH051383] Funding Source: Medline
NR 32
TC 191
Z9 256
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 114
EP U6
DI 10.1038/nature06927
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300048
PM 18596810
DA 2026-03-09
ER

PT J
AU Kwon, C
   Neu, C
   Pajonk, S
   Yun, HS
   Lipka, U
   Humphry, M
   Bau, S
   Straus, M
   Kwaaitaal, M
   Rampelt, H
   El Kasmi, F
   Jürgens, G
   Parker, J
   Panstruga, R
   Lipka, V
   Schulze-Lefert, P
AF Kwon, Chian
   Neu, Christina
   Pajonk, Simone
   Yun, Hye Sup
   Lipka, Ulrike
   Humphry, Matt
   Bau, Stefan
   Straus, Marco
   Kwaaitaal, Mark
   Rampelt, Heike
   El Kasmi, Farid
   Juergens, Gerd
   Parker, Jane
   Panstruga, Ralph
   Lipka, Volker
   Schulze-Lefert, Paul
TI Co-option of a default secretory pathway for plant immune responses
SO NATURE
LA English
DT Article
ID disease-resistance; nonhost resistance; snare-protein; penetration resistance; arabidopsis-thaliana; callose synthase; membrane-fusion; complex; cells; reorganization
AB Cell- autonomous immunity is widespread in plant - fungus interactions and terminates fungal pathogenesis either at the cell surface or after pathogen entry. Although post- invasive resistance responses typically coincide with a self- contained cell death of plant cells undergoing attack by parasites, these cells survive pre- invasive defence. Mutational analysis in Arabidopsis identified PEN1 syntaxin as one component of two pre- invasive resistance pathways against ascomycete powdery mildew fungi(1-3). Here we show that plasma- membrane- resident PEN1 promiscuously forms SDS- resistant soluble N- ethylmaleimide sensitive factor attachment protein receptor ( SNARE) complexes together with the SNAP33 adaptor and a subset of vesicle- associated membrane proteins ( VAMPs). PEN1- dependent disease resistance acts in vivo mainly through two functionally redundant VAMP72 subfamily members, VAMP721 and VAMP722. Unexpectedly, the same two VAMP proteins also operate redundantly in a default secretory pathway, suggesting dual functions in separate biological processes owing to evolutionary co- option of the default pathway for plant immunity. The disease resistance function of the secretory PEN1 - SNAP33 - VAMP721/ 722 complex and the pathogen- induced subcellular dynamics of its components are mechanistically reminiscent of immunological synapse formation in vertebrates, enabling execution of immune responses through focal secretion.
C1 [Kwon, Chian; Neu, Christina; Pajonk, Simone; Yun, Hye Sup; Lipka, Ulrike; Humphry, Matt; Bau, Stefan; Straus, Marco; Kwaaitaal, Mark; Parker, Jane; Panstruga, Ralph; Lipka, Volker; Schulze-Lefert, Paul] Max Planck Inst Zuchtungsforsch, Dept Plant Microbe Interact, D-50829 Cologne, Germany.
   [Lipka, Ulrike; Rampelt, Heike; Lipka, Volker] Univ Tubingen, ZMBP, D-72076 Tubingen, Germany.
C3 Max Planck Society; Eberhard Karls University of Tubingen
RP Lipka, V (corresponding author), John Innes Inst, John Innes Ctr Plant Sci Res, Sainsbury Lab, Colney Lane, Norwich NR4 7UH, Norfolk, England.
EM panstrug@mpiz-koeln.mpg.de; Volker.Lipka@sainsbury-laboratory.ac.uk; schlef@mpiz-koeln.mpg.de
NR 28
TC 379
Z9 427
U1 5
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 835
EP U10
DI 10.1038/nature06545
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400044
PM 18273019
DA 2026-03-09
ER

PT J
AU Selbach, M
   Schwanhäusser, B
   Thierfelder, N
   Fang, Z
   Khanin, R
   Rajewsky, N
AF Selbach, Matthias
   Schwanhaeusser, Bjoern
   Thierfelder, Nadine
   Fang, Zhuo
   Khanin, Raya
   Rajewsky, Nikolaus
TI Widespread changes in protein synthesis induced by microRNAs
SO NATURE
LA English
DT Article
ID mass-spectrometry; amino-acids; rna; identification; targets; determinants; degradation; repression; proteomics; turnover
AB Animal microRNAs ( miRNAs) regulate gene expression by inhibiting translation and/ or by inducing degradation of target messenger RNAs. It is unknown how much translational control is exerted by miRNAs on a genome- wide scale. We used a new proteomic approach to measure changes in synthesis of several thousand proteins in response to miRNA transfection or endogenous miRNA knockdown. In parallel, we quantified mRNA levels using microarrays. Here we show that a single miRNA can repress the production of hundreds of proteins, but that this repression is typically relatively mild. A number of known features of the miRNA- binding site such as the seed sequence also govern repression of human protein synthesis, and we report additional target sequence characteristics. We demonstrate that, in addition to downregulating mRNA levels, miRNAs also directly repress translation of hundreds of genes. Finally, our data suggest that a miRNA can, by direct or indirect effects, tune protein synthesis from thousands of genes.
C1 [Selbach, Matthias; Schwanhaeusser, Bjoern; Thierfelder, Nadine; Fang, Zhuo; Rajewsky, Nikolaus] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Khanin, Raya] Univ Glasgow, Dept Stat, Glasgow G12 8QQ, Lanark, Scotland.
C3 Helmholtz Association; Max Delbruck Center for Molecular Medicine; University of Glasgow
RP Selbach, M (corresponding author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13125 Berlin, Germany.
EM matthias.selbach@mdc-berlin.de; rajewsky@mdc-berlin.de
FU DAAD scholarship
NR 49
TC 2871
Z9 3361
U1 2
U2 315
PU NATURE PUBLISHING 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 4
PY 2008
VL 455
IS 7209
BP 58
EP 63
DI 10.1038/nature07228
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200036
PM 18668040
DA 2026-03-09
ER

PT J
AU Ishii, KJ
   Kawagoe, T
   Koyama, S
   Matsui, K
   Kumar, H
   Kawai, T
   Uematsu, S
   Takeuchi, O
   Takeshita, F
   Coban, C
   Akira, S
AF Ishii, Ken J.
   Kawagoe, Tatsukata
   Koyama, Shohei
   Matsui, Kosuke
   Kumar, Himanshu
   Kawai, Taro
   Uematsu, Satoshi
   Takeuchi, Osamu
   Takeshita, Fumihiko
   Coban, Cevayir
   Akira, Shizuo
TI TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines
SO NATURE
LA English
DT Article
ID dendritic cells; i interferon; activation; recognition; induction; infection; mice; vaccination; influenza; pathway
AB Successful vaccines contain not only protective antigen(s) but also an adjuvant component that triggers innate immune activation and is necessary for their optimal immunogenicity(1,2). In the case of DNA vaccines(3), this consists of plasmid DNA; however, the adjuvant element( s) as well as its intra- and inter- cellular innate immune signalling pathway( s) leading to the encoded antigen- specific T- and B- cell responses remain unclear. Here we demonstrate in vivo that TANK- binding kinase 1 ( TBK1), a non- canonical I kappa B kinase, mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice. Plasmid-DNA- activated, TBK1- dependent signalling and the resultant type- I interferon receptor- mediated signalling was required for induction of antigen- specific B and T cells, which occurred even in the absence of innate immune signalling through a well known CpG DNA sensor - Toll- like receptor 9 ( TLR9) or Z- DNA binding protein 1 ( ZBP1, also known as DAI, which was recently reported as a potential B- form DNA sensor(4)). Moreover, bone- marrow-transfer experiments revealed that TBK1- mediated signalling in haematopoietic cells was critical for the induction of antigenspecific B and CD4(+) T cells, whereas in non- haematopoietic cells TBK1 was required for CD8(+) T- cell induction. These data suggest that TBK1 is a key signalling molecule for DNA- vaccine- induced immunogenicity, by differentially controlling DNA- activated innate immune signalling through haematopoietic and nonhaematopoietic cells.
C1 [Ishii, Ken J.; Kawai, Taro; Takeuchi, Osamu; Akira, Shizuo] Osaka Univ, ERATO, Japan Sci & Technol Agcy, Suita, Osaka 5650871, Japan.
   [Ishii, Ken J.] Osaka Univ, Dept Mol Protozool, Suita, Osaka 5650871, Japan.
   [Ishii, Ken J.; Kawagoe, Tatsukata; Koyama, Shohei; Kumar, Himanshu; Kawai, Taro; Uematsu, Satoshi; Takeuchi, Osamu; Coban, Cevayir; Akira, Shizuo] Osaka Univ, Host Def Lab, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan.
   [Kawagoe, Tatsukata; Koyama, Shohei; Matsui, Kosuke; Kumar, Himanshu; Kawai, Taro; Uematsu, Satoshi; Takeuchi, Osamu; Coban, Cevayir; Akira, Shizuo] Osaka Univ, Dept Host Def, Suita, Osaka 5650871, Japan.
   [Coban, Cevayir; Akira, Shizuo] Osaka Univ, Century Ctr Excellence COE 21, Combined Program Microbiol & Immunol, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan.
   [Takeshita, Fumihiko] Yokohama City Univ, Dept Mol Biodef Res, Grad Sch Med, Kanagawa 2360004, Japan.
   [Koyama, Shohei] Tohoku Univ, Inst Dev Aging & Canc, Sendai, Miyagi 9808575, Japan.
C3 Japan Science & Technology Agency (JST); University of Osaka; University of Osaka; University of Osaka; University of Osaka; University of Osaka; Yokohama City University; Tohoku University
RP Ishii, KJ (corresponding author), Osaka Univ, ERATO, Japan Sci & Technol Agcy, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM kenishii@biken.osaka-u.ac.jp; sakira@biken.osaka-u.ac.jp
NR 30
TC 520
Z9 638
U1 1
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 725
EP U6
DI 10.1038/nature06537
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500043
PM 18256672
DA 2026-03-09
ER

PT J
AU Nykypanchuk, D
   Maye, MM
   van der Lelie, D
   Gang, O
AF Nykypanchuk, Dmytro
   Maye, Mathew M.
   van der Lelie, Daniel
   Gang, Oleg
TI DNA-guided crystallization of colloidal nanoparticles
SO NATURE
LA English
DT Article
ID superlattices; assembly; hybridization; nanocrystals; protein; arrays
AB Many nanometre-sized building blocks will readily assemble into macroscopic structures. If the process is accompanied by effective control over the interactions between the blocks and all entropic effects(1,2), then the resultant structures will be ordered with a precision hard to achieve with other fabrication methods. But it remains challenging to use self- assembly to design systems comprised of different types of building blocks - to realize novel magnetic, plasmonic and photonic metamaterials(3-5), for example. A conceptually simple idea for overcoming this problem is the use of 'encodable' interactions between building blocks; this can in principle be straightforwardly implemented using biomolecules(6-10). Strategies that use DNA programmability to control the placement of nanoparticles in one and two dimensions have indeed been demonstrated(11-13). However, our theoretical understanding of how to extend this approach to three dimensions is limited(14,15), and most experiments have yielded amorphous aggregates(16-19) and only occasionally crystallites of close- packed micrometre- sized particles(9,10). Here, we report the formation of three- dimensional crystalline assemblies of gold nanoparticles mediated by interactions between complementary DNA molecules attached to the nanoparticles' surface. We find that the nanoparticle crystals form reversibly during heating and cooling cycles. Moreover, the body- centred- cubic lattice structure is temperature-tuneable and structurally open, with particles occupying only similar to 4% of the unit cell volume. We expect that our DNA-mediated crystallization approach, and the insight into DNA design requirements it has provided, will facilitate both the creation of new classes of ordered multicomponent metamaterials and the exploration of the phase behaviour of hybrid systems with addressable interactions.
C1 [Nykypanchuk, Dmytro; Maye, Mathew M.; Gang, Oleg] Brookhaven Natl Lab, Ctr Funct Nanomat, Upton, NY 11973 USA.
   [van der Lelie, Daniel] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
C3 United States Department of Energy (DOE); Brookhaven National Laboratory; United States Department of Energy (DOE); Brookhaven National Laboratory
RP Gang, O (corresponding author), Brookhaven Natl Lab, Ctr Funct Nanomat, Upton, NY 11973 USA.
EM ogang@bnl.gov
NR 28
TC 1366
Z9 1629
U1 6
U2 830
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 549
EP 552
DI 10.1038/nature06560
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900036
PM 18235496
DA 2026-03-09
ER

PT J
AU Xiao, H
   Murakami, H
   Suga, H
   Ferré-D'Amaré, AR
AF Xiao, Hong
   Murakami, Hiroshi
   Suga, Hiroaki
   Ferre-D'Amare, Adrian R.
TI Structural basis of specific tRNA aminoacylation by a small in vitro selected ribozyme
SO NATURE
LA English
DT Article
ID protein-synthesis; crystal-structure; active-site; synthetase; origin; reveals; complex
AB In modern organisms, protein enzymes are solely responsible for the aminoacylation of transfer RNA. However, the evolution of protein synthesis in the RNA world required RNAs capable of catalysing this reaction. Ribozymes that aminoacylate RNA by using activated amino acids have been discovered through selection in vitro(1-5). Flexizyme is a 45- nucleotide ribozyme capable of charging tRNA in trans with various activated L- phenylalanine derivatives. In addition to a more than 10(5) rate enhancement and more than 10(4)-fold discrimination against some non- cognate amino acids, this ribozyme achieves good regioselectivity: of all the hydroxyl groups of a tRNA, it exclusively aminoacylates the terminal 3'-OH5-7. Here we report the 2.8-angstrom resolution structure of flexizyme fused to a substrate RNA. Together with randomization of ribozyme core residues and reselection, this structure shows that very few nucleotides are needed for the aminoacylation of specific tRNAs. Although it primarily recognizes tRNA through base- pairing with the CCA terminus of the tRNA molecule, flexizyme makes numerous local interactions to position the acceptor end of tRNA precisely. A comparison of two crystallographically independent flexizyme conformations, only one of which appears capable of binding activated phenylalanine, suggests that this ribozyme may achieve enhanced specificity by coupling active- site folding to tRNA docking. Such a mechanism would be reminiscent of the mutually induced fit of tRNA and protein employed by some aminoacyl- tRNA synthetases(8,9) to increase specificity.
C1 [Xiao, Hong; Ferre-D'Amare, Adrian R.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Murakami, Hiroshi; Suga, Hiroaki] Univ Tokyo, Adv Sci & Technol Res Ctr, Tokyo 1538904, Japan.
   [Suga, Hiroaki] Univ Tokyo, Dept Chem & Biotechnol, Grad Sch Engn, Tokyo 1138656, Japan.
C3 Fred Hutchinson Cancer Center; University of Tokyo; University of Tokyo
RP Ferré-D'Amaré, AR (corresponding author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA.
EM aferre@fhcrc.org
NR 36
TC 125
Z9 145
U1 0
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 358
EP U60
DI 10.1038/nature07033
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300044
PM 18548004
DA 2026-03-09
ER

PT J
AU Nemchin, AA
   Whitehouse, MJ
   Menneken, M
   Geisler, T
   Pidgeon, RT
   Wilde, SA
AF Nemchin, Alexander A.
   Whitehouse, Martin J.
   Menneken, Martina
   Geisler, Thorsten
   Pidgeon, Robert T.
   Wilde, Simon A.
TI A light carbon reservoir recorded in zircon-hosted diamond from the Jack Hills
SO NATURE
LA English
DT Article
ID origin; crust; earth; evolution; impact; fluid; moon; ga
AB The recent discovery of diamond - graphite inclusions in the Earth's oldest zircon grains ( formed up to 4,252 Myr ago) from the Jack Hills metasediments in Western Australia(1) provides a unique opportunity to investigate Earth's earliest known carbon reservoir. Here we report ion microprobe analyses of the carbon isotope composition of these diamond - graphite inclusions. The observed delta(13) C-PDB values ( expressed using the PeeDee Belemnite standard) range between -5 per mil and -58 per mil with a median of -31 per mil. This extends beyond typical mantle values of around -6 per mil to values observed in metamorphic and some eclogitic diamonds that are interpreted to reflect deep subduction of low-delta(13) C-PDB biogenic surface carbon. Low delta(13) C-PDB values may also be produced by inorganic chemical reactions(2), and therefore are not unambiguous evidence for life on Earth as early as 4,250 Myr ago. Regardless, our results suggest that a low-delta(13) C-PDB reservoir may have existed on the early Earth.
C1 [Nemchin, Alexander A.; Pidgeon, Robert T.; Wilde, Simon A.] Curtin Univ Technol, Western Australian Sch Mines, Dept Appl Geol, Bentley, WA 6102, Australia.
   [Whitehouse, Martin J.] Swedish Museum Nat Hist, Lab Isotope Geol, SE-10405 Stockholm, Sweden.
   [Menneken, Martina; Geisler, Thorsten] Univ Munster, Inst Mineral, D-48149 Munster, Germany.
C3 Curtin University; Swedish Museum of Natural History; University of Munster
RP Nemchin, AA (corresponding author), Curtin Univ Technol, Western Australian Sch Mines, Dept Appl Geol, Bentley, WA 6102, Australia.
EM nemchina@kalg.curtin.edu.au
NR 31
TC 52
Z9 58
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 3
PY 2008
VL 454
IS 7200
BP 92
EP U3
DI 10.1038/nature07102
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300043
PM 18596808
DA 2026-03-09
ER

PT J
AU Aubert, J
   Amit, H
   Hulot, G
   Olson, P
AF Aubert, Julien
   Amit, Hagay
   Hulot, Gauthier
   Olson, Peter
TI Thermochemical flows couple the Earth's inner core growth to mantle heterogeneity
SO NATURE
LA English
DT Article
ID laboratory model; magnetic-field; convection; solidification; attenuation; geodynamo; rotation; velocity; beneath; top
AB Seismic waves sampling the top 100 km of the Earth's inner core reveal that the eastern hemisphere (40 degrees E-180 degrees E) is seismically faster(1,2), more isotropic(2,3) and more attenuating(4) than the western hemisphere. The origin of this hemispherical dichotomy is a challenging problem for our understanding of the Earth as a system of dynamically coupled layers. Previously, laboratory experiments have established that thermal control from the lower mantle can drastically affect fluid flow in the outer core(5), which in turn can induce textural heterogeneity on the inner core solidification front(6). The resulting texture should be consistent with other expected manifestations of thermal mantle control on the geodynamo, specifically magnetic flux concentrations(7,8) in the timeaverage palaeomagnetic field(9,10) over the past 5 Myr, and preferred eddy locations(11) in flows imaged below the core-mantle boundary by the analysis of historical geomagnetic secular variation(12). Here we show that a single model of thermochemical convection and dynamo action can account for all these effects by producing a large-scale, long-term outer core flow that couples the heterogeneity of the inner core with that of the lower mantle. The main feature of this thermochemical 'wind' is a cyclonic circulation below Asia, which concentrates magnetic field on the core-mantle boundary at the observed location and locally agrees with core flow images. This wind also causes anomalously high rates of light element release in the eastern hemisphere of the inner core boundary, suggesting that lateral seismic anomalies at the top of the inner core result from mantle-induced variations in its freezing rate.
C1 [Aubert, Julien; Amit, Hagay; Hulot, Gauthier] Univ Paris Diderot, Inst Phys Globe, INSU, CNRS, F-75252 Paris 05, France.
   [Olson, Peter] Johns Hopkins Univ, Dept Earth & Planetary Sci, Baltimore, MD 21218 USA.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite; Johns Hopkins University
RP Aubert, J (corresponding author), Univ Paris Diderot, Inst Phys Globe, INSU, CNRS, 4 Pl Jussieu, F-75252 Paris 05, France.
EM aubert@ipgp.jussieu.fr
NR 33
TC 216
Z9 228
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 AUG 7
PY 2008
VL 454
IS 7205
BP 758
EP U80
DI 10.1038/nature07109
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000043
PM 18685706
DA 2026-03-09
ER

PT J
AU Krishnan, MN
   Ng, A
   Sukumaran, B
   Gilfoy, FD
   Uchil, PD
   Sultana, H
   Brass, AL
   Adametz, R
   Tsui, M
   Qian, F
   Montgomery, RR
   Lev, S
   Mason, PW
   Koski, RA
   Elledge, SJ
   Xavier, RJ
   Agaisse, H
   Fikrig, E
AF Krishnan, Manoj N.
   Ng, Aylwin
   Sukumaran, Bindu
   Gilfoy, Felicia D.
   Uchil, Pradeep D.
   Sultana, Hameeda
   Brass, Abraham L.
   Adametz, Rachel
   Tsui, Melody
   Qian, Feng
   Montgomery, Ruth R.
   Lev, Sima
   Mason, Peter W.
   Koski, Raymond A.
   Elledge, Stephen J.
   Xavier, Ramnik J.
   Agaisse, Herve
   Fikrig, Erol
TI RNA interference screen for human genes associated with West Nile virus infection
SO NATURE
LA English
DT Article
ID dengue-virus; interaction network; viral spread; host-cells; protein; entry; replication; database; identification; endocytosis
AB West Nile virus ( WNV), and related flaviviruses such as tick- borne encephalitis, Japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem(1). However, our understanding of the molecular interaction of such flaviviruses with mammalian host cells is limited(1). WNV encodes only 10 proteins, implying that it may use many cellular proteins for infection(1). WNV enters the cytoplasm through pH- dependent endocytosis, undergoes cycles of translation and replication, assembles progeny virions in association with endoplasmic reticulum, and exits along the secretory pathway(1-3). RNA interference ( RNAi) presents a powerful forward genetics approach to dissect virus - host cell interactions(4-6). Here we report the identification of 305 host proteins that affect WNV infection, using a human- genome-wide RNAi screen. Functional clustering of the genes revealed a complex dependence of this virus on host cell physiology, requiring a wide variety of molecules and cellular pathways for successful infection. We further demonstrate a requirement for the ubiquitin ligase CBLL1 in WNV internalization, a post- entry role for the endoplasmic- reticulum- associated degradation pathway in viral infection, and the monocarboxylic acid transporter MCT4 as a viral replication resistance factor. By extending this study to dengue virus, we show that flaviviruses have both overlapping and unique interaction strategies with host cells. This study provides a comprehensive molecular portrait of WNV - human cell interactions that forms a model for understanding single plus- stranded RNA virus infection, and reveals potential antiviral targets.
C1 [Krishnan, Manoj N.; Sukumaran, Bindu; Sultana, Hameeda; Fikrig, Erol] Yale Univ, Sch Med, Infect Dis Sect, Dept Internal Med, New Haven, CT 06520 USA.
   [Qian, Feng; Montgomery, Ruth R.] Yale Univ, Sch Med, Rheumatol Sect, Dept Internal Med, New Haven, CT 06520 USA.
   [Uchil, Pradeep D.; Adametz, Rachel; Agaisse, Herve] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06520 USA.
   [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
   [Gilfoy, Felicia D.; Mason, Peter W.] Univ Texas Galveston, Med Branch, Dept Pathol, Galveston, TX 77555 USA.
   [Tsui, Melody] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Syst Biol, Boston, MA 02115 USA.
   [Brass, Abraham L.; Elledge, Stephen J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Genet,Ctr Genet & Genom, Boston, MA 02115 USA.
   [Lev, Sima] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
   [Koski, Raymond A.] L2 Diagnost, New Haven, CT 06511 USA.
   [Elledge, Stephen J.; Fikrig, Erol] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Yale University; Yale University; Yale University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; University of Texas System; University of Texas Medical Branch Galveston; 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; Weizmann Institute of Science; Howard Hughes Medical Institute
RP Fikrig, E (corresponding author), Yale Univ, Sch Med, Infect Dis Sect, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA.
EM erol.fikrig@yale.edu
FU New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease [U54AI057159]; NIH [AI062773, U54 AI057156]; Crohn's and Colitis Foundation of America; CCIB development funds; Emerging and Tropical Infectious Diseases [AI07526]; NIAID; National Institute of Allergy and Infectious Diseases [T32AI007526] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK040561] Funding Source: NIH RePORTER
NR 34
TC 436
Z9 517
U1 2
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 11
PY 2008
VL 455
IS 7210
BP 242
EP U67
DI 10.1038/nature07207
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800051
PM 18690214
DA 2026-03-09
ER

PT J
AU Orlando, DA
   Lin, CY
   Bernard, A
   Wang, JY
   Socolar, JES
   Iversen, ES
   Hartemink, AJ
   Haase, SB
AF Orlando, David A.
   Lin, Charles Y.
   Bernard, Allister
   Wang, Jean Y.
   Socolar, Joshua E. S.
   Iversen, Edwin S.
   Hartemink, Alexander J.
   Haase, Steven B.
TI Global control of cell-cycle transcription by coupled CDK and network oscillators
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; dependent kinase; nuclear-localization; regulated genes; yeast; phosphorylation; expression; inhibitor; genome; phase
AB A significant fraction of the Saccharomyces cerevisiae genome is transcribed periodically during the cell division cycle(1,2), indicating that properly timed gene expression is important for regulating cell- cycle events. Genomic analyses of the localization and expression dynamics of transcription factors suggest that a network of sequentially expressed transcription factors could control the temporal programme of transcription during the cell cycle(3). However, directed studies interrogating small numbers of genes indicate that their periodic transcription is governed by the activity of cyclin- dependent kinases (CDKs)(4). To determine the extent to which the global cell- cycle transcription programme is controlled by cyclin - CDK complexes, we examined genome- wide transcription dynamics in budding yeast mutant cells that do not express S- phase and mitotic cyclins. Here we show that a significant fraction of periodic genes are aberrantly expressed in the cyclin mutant. Although cells lacking cyclins are blocked at the G1/S border, nearly 70% of periodic genes continued to be expressed periodically and on schedule. Our findings reveal that although CDKs have a function in the regulation of cell- cycle transcription, they are not solely responsible for establishing the global periodic transcription programme. We propose that periodic transcription is an emergent property of a transcription factor network that can function as a cell- cycle oscillator independently of, and in tandem with, the CDK oscillator.
C1 [Orlando, David A.; Lin, Charles Y.; Wang, Jean Y.; Haase, Steven B.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
   [Orlando, David A.] Duke Univ, Program Computat Biol & Bioinformat, Durham, NC 27708 USA.
   [Bernard, Allister; Hartemink, Alexander J.] Duke Univ, Dept Comp Sci, Durham, NC 27708 USA.
   [Socolar, Joshua E. S.] Duke Univ, Dept Phys, Durham, NC 27708 USA.
   [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA.
C3 Duke University; Duke University; Duke University; Duke University; Duke University
RP Haase, SB (corresponding author), Duke Univ, Dept Biol, Durham, NC 27708 USA.
EM shaase@duke.edu
FU NIGMS NIH HHS [P50 GM081883] Funding Source: Medline
NR 32
TC 244
Z9 294
U1 1
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 944
EP U78
DI 10.1038/nature06955
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000049
PM 18463633
DA 2026-03-09
ER

PT J
AU Otero, G
   Biddau, G
   Sánchez-Sánchez, C
   Caillard, R
   López, MF
   Rogero, C
   Palomares, FJ
   Cabello, N
   Basanta, MA
   Ortega, J
   Méndez, J
   Echavarren, AM
   Pérez, R
   Gómez-Lor, B
   Martín-Gago, JA
AF Otero, Gonzalo
   Biddau, Giulio
   Sanchez-Sanchez, Carlos
   Caillard, Renaud
   Lopez, Maria F.
   Rogero, Celia
   Palomares, F. Javier
   Cabello, Noemi
   Basanta, Miguel A.
   Ortega, Jose
   Mendez, Javier
   Echavarren, Antonio M.
   Perez, Ruben
   Gomez-Lor, Berta
   Martin-Gago, Jose A.
TI Fullerenes from aromatic precursors by surface-catalysed cyclodehydrogenation
SO NATURE
LA English
DT Article
ID crushed-fullerene; c-60 adsorption; c60h30; films
AB Graphite vaporization provides an uncontrolled yet efficient means of producing fullerene molecules. However, some fullerene derivatives or unusual fullerene species might only be accessible through rational and controlled synthesis methods. Recently, such an approach has been used(1) to produce isolable amounts of the fullerene C-60 from commercially available starting materials. But the overall process required 11 steps to generate a suitable polycyclic aromatic precursor molecule, which was then dehydrogenated in the gas phase with a yield of only about one per cent. Here we report the formation of C-60 and the triazafullerene C57N3 from aromatic precursors using a highly efficient surface-catalysed cyclodehydrogenation process. We find that after deposition onto a platinum (111) surface and heating to 750 K, the precursors are transformed into the corresponding fullerene and triazafullerene molecules with about 100 per cent yield. We expect that this approach will allow the production of a range of other fullerenes and heterofullerenes(2,3), once suitable precursors are available. Also, if the process is carried out in an atmosphere containing guest species, it might even allow the encapsulation of atoms or small molecules to form endohedral fullerenes(4,5).
C1 [Otero, Gonzalo; Sanchez-Sanchez, Carlos; Caillard, Renaud; Lopez, Maria F.; Palomares, F. Javier; Mendez, Javier; Gomez-Lor, Berta; Martin-Gago, Jose A.] CSIC, Inst Ciencia Mat, Madrid 28049, Spain.
   [Biddau, Giulio; Basanta, Miguel A.; Ortega, Jose; Perez, Ruben] Univ Autonoma Madrid, Dept Fis Teor Mat Condensada, E-28049 Madrid, Spain.
   [Rogero, Celia; Martin-Gago, Jose A.] CSIC INTA, Ctr Astrobiol, Madrid 28850, Spain.
   [Cabello, Noemi; Echavarren, Antonio M.] Inst Chem Res Catalonia ICIQ, Tarragona 43007, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias Matematicas (ICMAT); Instituto de Ciencia de Materiales de Sevilla (ICMS-CSIC); CSIC - Instituto de Ciencia de Materiales de Madrid (ICMM); Autonomous University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); Barcelona Institute of Science & Technology; Universitat Rovira i Virgili; Institute of Chemical Research of Catalonia
RP Gómez-Lor, B (corresponding author), CSIC, Inst Ciencia Mat, Madrid 28049, Spain.
EM bgl@icmm.csic.es; gago@icmm.csic.es
NR 22
TC 269
Z9 297
U1 4
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 AUG 14
PY 2008
VL 454
IS 7206
BP 865
EP U19
DI 10.1038/nature07193
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600031
PM 18704082
DA 2026-03-09
ER

PT J
AU Kitano, M
   Nakaya, M
   Nakamura, T
   Nagata, S
   Matsuda, M
AF Kitano, Masahiro
   Nakaya, Michio
   Nakamura, Takeshi
   Nagata, Shigekazu
   Matsuda, Michiyuki
TI Imaging of Rab5 activity identifies essential regulators for phagosome maturation
SO NATURE
LA English
DT Article
ID apoptotic cells; proteins; macrophages; activation; dynamics; fusion; phagocytosis; recruitment; rho
AB Efficient phagocytosis of apoptotic cells is crucial for tissue homeostasis and the immune response(1,2). Rab5 is known as a key regulator of the early endocytic pathway(3) and we have recently shown that Rab5 is also implicated in apoptotic cell engulfment(4); however, the precise spatio- temporal dynamics of Rab5 activity remain unknown. Here, using a newly developed fluorescence resonance energy transfer biosensor, we describe a change in Rab5 activity during the engulfment of apoptotic thymocytes. Rab5 activity on phagosome membranes began to increase on disassembly of the actin coat encapsulating phagosomes. Rab5 activation was either continuous or repetitive for up to 10 min, but it ended before the collapse of engulfed apoptotic cells. Expression of a dominant-negative mutant of Rab5 delayed this collapse of apoptotic thymocytes, showing a role for Rab5 in phagosome maturation. Disruption of microtubules with nocodazole inhibited Rab5 activation on the phagosome membrane without perturbing the engulfment of apoptotic cells. Furthermore, we found that Gapex-5 is the guanine nucleotide exchange factor essential for Rab5 activation during the engulfment of apoptotic cells. Gapex- 5 was bound to a microtubule- tip- associating protein, EB1, whose depletion inhibited Rab5 activation during phagocytosis. We therefore propose a mechanistic model in which the recruitment of Gapex- 5 to phagosomes through the microtubule network induces the transient Rab5 activation.
C1 [Kitano, Masahiro; Nakamura, Takeshi; Matsuda, Michiyuki] Kyoto Univ, Grad Sch Biostudies, Lab Bioimaging & Cell Signaling, Sakyo Ku, Kyoto 6068501, Japan.
   [Nakaya, Michio; Nagata, Shigekazu] Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan.
   [Kitano, Masahiro] Osaka Univ, Microbial Dis Res Inst, Dept Signal Transduct, Suita, Osaka 5650871, Japan.
   [Nakaya, Michio; Nagata, Shigekazu] Japan Sci & Technol Corp, Solut Oriented Res Sci & Technol, Sakyo Ku, Kyoto 6068501, Japan.
C3 Kyoto University; Kyoto University; University of Osaka; Japan Science & Technology Agency (JST)
RP Nakamura, T (corresponding author), Kyoto Univ, Grad Sch Biostudies, Lab Bioimaging & Cell Signaling, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
EM tnakamr@path1.med.kyoto-u.ac.jp
NR 24
TC 131
Z9 168
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 MAY 8
PY 2008
VL 453
IS 7192
BP 241
EP U15
DI 10.1038/nature06857
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400044
PM 18385674
DA 2026-03-09
ER

PT J
AU Datta, SR
   Vasconcelos, ML
   Ruta, V
   Luo, S
   Wong, A
   Demir, E
   Flores, J
   Balonze, K
   Dickson, BJ
   Axel, R
AF Datta, Sandeep Robert
   Vasconcelos, Maria Luisa
   Ruta, Vanessa
   Luo, Sean
   Wong, Allan
   Demir, Ebru
   Flores, Jorge
   Balonze, Karen
   Dickson, Barry J.
   Axel, Richard
TI The Drosophila pheromone cVA activates a sexually dimorphic neural circuit
SO NATURE
LA English
DT Article
ID male courtship behavior; olfactory system; fruitless gene; neurons; protein; representation; organization; orientation; responses; brain
AB Courtship is an innate sexually dimorphic behaviour that can be observed in naive animals without previous learning or experience, suggesting that the neural circuits that mediate this behaviour are developmentally programmed(1). In Drosophila, courtship involves a complex yet stereotyped array of dimorphic behaviours that are regulated by Fru(M), a male- specific isoform of the fruitless gene(2-5). Fru(M) is expressed in about 2,000 neurons in the fly brain, including three subpopulations of olfactory sensory neurons and projection neurons ( PNs). One set of Fru(+) olfactory neurons expresses the odorant receptor Or67d and responds to the male-specific pheromone cis- vaccenyl acetate ( cVA)(6-10). These neurons converge on the DA1 glomerulus in the antennal lobe. In males, activation of Or67d 1 neurons by cVA inhibits courtship of other males, whereas in females their activation promotes receptivity to other males(7). These observations pose the question of how a single pheromone acting through the same set of sensory neurons can elicit different behaviours in male and female flies. Anatomical or functional dimorphisms in this neural circuit might be responsible for the dimorphic behaviour. We therefore developed a neural tracing procedure that employs two- photon laser scanning microscopy to activate the photoactivatable green fluorescent protein(11). Here we show, using this technique, that the projections from the DA1 glomerulus to the protocerebrum are sexually dimorphic. We observe a male- specific axonal arbor in the lateral horn whose elaboration requires the expression of the transcription factor Fru(M) in DA1 projection neurons and other Fru(+) cells. The observation that cVA activates a sexually dimorphic circuit in the protocerebrum suggests a mechanism by which a single pheromone can elicit different behaviours in males and in females.
C1 [Datta, Sandeep Robert; Vasconcelos, Maria Luisa; Ruta, Vanessa; Luo, Sean; Wong, Allan; Flores, Jorge; Balonze, Karen; Axel, Richard] Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Datta, Sandeep Robert; Vasconcelos, Maria Luisa; Ruta, Vanessa; Luo, Sean; Wong, Allan; Flores, Jorge; Balonze, Karen; Axel, Richard] Columbia Univ, Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Wong, Allan] CALTECH, Div Biol 216 76, Pasadena, CA 91125 USA.
   [Wong, Allan] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [Demir, Ebru; Dickson, Barry J.] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria.
C3 Columbia University; Columbia University; Howard Hughes Medical Institute; California Institute of Technology; California Institute of Technology; Howard Hughes Medical Institute; Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP)
RP Axel, R (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
EM ra27@columbia.edu
FU Howard Hughes Medical Institute Funding Source: Medline
NR 27
TC 297
Z9 380
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 MAR 27
PY 2008
VL 452
IS 7186
BP 473
EP 477
DI 10.1038/nature06808
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300032
PM 18305480
DA 2026-03-09
ER

PT J
AU Cokus, SJ
   Feng, SH
   Zhang, XY
   Chen, ZG
   Merriman, B
   Haudenschild, CD
   Pradhan, S
   Nelson, SF
   Pellegrini, M
   Jacobsen, SE
AF Cokus, Shawn J.
   Feng, Suhua
   Zhang, Xiaoyu
   Chen, Zugen
   Merriman, Barry
   Haudenschild, Christian D.
   Pradhan, Sriharsa
   Nelson, Stanley F.
   Pellegrini, Matteo
   Jacobsen, Steven E.
TI Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning
SO NATURE
LA English
DT Article
ID 5-methylcytosine residues; epigenetic inheritance; nucleosomal structure; genes
AB Cytosine DNA methylation is important in regulating gene expression and in silencing transposons and other repetitive sequences(1,2). Recent genomic studies in Arabidopsis thaliana have revealed that many endogenous genes are methylated either within their promoters or within their transcribed regions, and that gene methylation is highly correlated with transcription levels(3-5). However, plants have different types of methylation controlled by different genetic pathways, and detailed information on the methylation status of each cytosine in any given genome is lacking. To this end, we generated a map at single- base- pair resolution of methylated cytosines for Arabidopsis, by combining bisulphite treatment of genomic DNA with ultra- high- throughput sequencing using the Illumina 1G Genome Analyser and Solexa sequencing technology(6). This approach, termed BS- Seq, unlike previous microarray- based methods, allows one to sensitively measure cytosine methylation on a genome- wide scale within specific sequence contexts. Here we describe methylation on previously inaccessible components of the genome and analyse the DNA methylation sequence composition and distribution. We also describe the effect of various DNA methylation mutants on genome- wide methylation patterns, and demonstrate that our newly developed library construction and computational methods can be applied to large genomes such as that of mouse.
C1 [Cokus, Shawn J.; Feng, Suhua; Zhang, Xiaoyu; Pellegrini, Matteo; Jacobsen, Steven E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Feng, Suhua; Jacobsen, Steven E.] Univ Calif Los Angeles, David Geffen Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
   [Chen, Zugen; Merriman, Barry; Nelson, Stanley F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Haudenschild, Christian D.] Illumina Inc, Hayward, CA 94545 USA.
   [Pradhan, Sriharsa] New England Biolabs Inc, Ipswich, MA 01938 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; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Illumina; New England Biolabs
RP Jacobsen, SE (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
EM matteop@mcdb.ucla.edu; jacobsen@ucla.edu
FU Howard Hughes Medical Institute Funding Source: Medline
NR 26
TC 1773
Z9 2120
U1 7
U2 411
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 13
PY 2008
VL 452
IS 7184
BP 215
EP 219
DI 10.1038/nature06745
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273JG
UT WOS:000253925600040
PM 18278030
DA 2026-03-09
ER

PT J
AU Romanowicz, B
AF Romanowicz, Barbara
TI Using seismic waves to image Earth's internal structure
SO NATURE
LA English
DT Article
ID velocity structure; shear velocity; mantle; heterogeneity; tomography; dynamics; surface; beneath
C1 [Romanowicz, Barbara] Univ Calif Berkeley, Berkeley Seismol Lab, Berkeley, CA 94720 USA.
   [Romanowicz, Barbara] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Romanowicz, B (corresponding author), Univ Calif Berkeley, Berkeley Seismol Lab, 215 McCone Hall, Berkeley, CA 94720 USA.
EM barbara.romanowicz@gmail.com
NR 17
TC 59
Z9 75
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 17
PY 2008
VL 451
IS 7176
BP 266
EP 268
DI 10.1038/nature06583
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100030
PM 18202638
DA 2026-03-09
ER

PT J
AU Raizen, DM
   Zimmerman, JE
   Maycock, MH
   Ta, UD
   You, YJ
   Sundaram, MV
   Pack, AI
AF Raizen, David M.
   Zimmerman, John E.
   Maycock, Matthew H.
   Ta, Uyen D.
   You, Young-Jai
   Sundaram, Meera V.
   Pack, Allan I.
TI Lethargus is a Caenorhabditis elegans sleep-like state
SO NATURE
LA English
DT Article
ID dependent protein-kinase; c-elegans; drosophila-melanogaster; nematode; behavior; rest
AB There are fundamental similarities between sleep in mammals and quiescence in the arthropod Drosophila melanogaster, suggesting that sleep- like states are evolutionarily ancient(1-3). The nematode Caenorhabditis elegans also has a quiescent behavioural state during a period called lethargus, which occurs before each of the four moults(4). Like sleep, lethargus maintains a constant temporal relationship with the expression of the C. elegans Period homologue LIN-42 ( ref. 5). Here we show that quiescence associated with lethargus has the additional sleep- like properties of reversibility, reduced responsiveness and homeostasis. We identify the cGMP-dependent protein kinase ( PKG) gene egl- 4 as a regulator of sleep-like behaviour, and show that egl- 4 functions in sensory neurons to promote the C. elegans sleep- like state. Conserved effects on sleep- like behaviour of homologous genes in C. elegans and Drosophila suggest a common genetic regulation of sleep- like states in arthropods and nematodes. Our results indicate that C. elegans is a suitable model system for the study of sleep regulation. The association of this C. elegans sleep- like state with developmental changes that occur with larval moults suggests that sleep may have evolved to allow for developmental changes.
C1 [Raizen, David M.; Zimmerman, John E.; Maycock, Matthew H.; Ta, Uyen D.; Pack, Allan I.] Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA.
   [Raizen, David M.; Ta, Uyen D.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA.
   [Sundaram, Meera V.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
   [Pack, Allan I.] Univ Penn, Sch Med, Dept Med, Div Sleep Med, Philadelphia, PA 19104 USA.
   [You, Young-Jai] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Texas System; University of Texas Southwestern Medical Center
RP Raizen, DM (corresponding author), Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, 3400 Spruce St, Philadelphia, PA 19104 USA.
EM raizen@mail.med.upenn.edu
NR 30
TC 364
Z9 503
U1 5
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 569
EP U6
DI 10.1038/nature06535
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900041
PM 18185515
DA 2026-03-09
ER

PT J
AU Lee, JE
   Fusco, ML
   Hessell, AJ
   Oswald, WB
   Burton, DR
   Saphire, EO
AF Lee, Jeffrey E.
   Fusco, Marnie L.
   Hessell, Ann J.
   Oswald, Wendelien B.
   Burton, Dennis R.
   Saphire, Erica Ollmann
TI Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor
SO NATURE
LA English
DT Article
ID gp120 envelope glycoprotein; neutralizing human-antibody; internal fusion peptide; hemorrhagic-fever; marburg virus; virion glycoproteins; cysteines flanking; nonhuman-primates; vaccine protects; filovirus entry
AB Ebola virus ( EBOV) entry requires the surface glycoprotein ( GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre- fusion conformation ( GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin- like domain restrict access to the conserved receptor- binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre- fusion GP2 to the amino terminus of GP1. This structure provides a template for unravelling the mechanism of EBOV GP- mediated fusion and for future immunotherapeutic development.
C1 [Lee, Jeffrey E.; Fusco, Marnie L.; Hessell, Ann J.; Oswald, Wendelien B.; Burton, Dennis R.; Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Saphire, EO (corresponding author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd,Mail Drop IMM-2, La Jolla, CA 92037 USA.
EM erica@scripps.edu
FU NIAID NIH HHS [R21 AI053423, R01 AI067927] Funding Source: Medline
NR 68
TC 578
Z9 749
U1 0
U2 228
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 177
EP U27
DI 10.1038/nature07082
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900035
PM 18615077
DA 2026-03-09
ER

PT J
AU He, XJ
   Zhou, J
   Bartlam, M
   Zhang, RG
   Ma, JY
   Lou, ZY
   Li, XM
   Li, JJ
   Joachimiak, A
   Zeng, ZH
   Ge, RW
   Rao, ZH
   Liu, YF
AF He, Xiaojing
   Zhou, Jie
   Bartlam, Mark
   Zhang, Rongguang
   Ma, Jianyuan
   Lou, Zhiyong
   Li, Xuemei
   Li, Jingjing
   Joachimiak, Andrzej
   Zeng, Zonghao
   Ge, Ruowen
   Rao, Zihe
   Liu, Yingfang
TI Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus
SO NATURE
LA English
DT Article
ID amino-acid mutation; rna-polymerase; pa subunit; a virus; promoter-binding; macromolecular structures; pb1 protein; cap-binding; model; domains
AB The recent emergence of highly pathogenic avian influenza A virus strains with subtype H5N1 pose a global threat to human health(1). Elucidation of the underlying mechanisms of viral replication is critical for development of anti- influenza virus drugs(2). The influenza RNA- dependent RNA polymerase ( RdRp) heterotrimer has crucial roles in viral RNA replication and transcription. It contains three proteins: PA, PB1 and PB2. PB1 harbours polymerase and endonuclease activities and PB2 is responsible for cap binding(3,4); PA is implicated in RNA replication(5-10) and proteolytic activity(11-14), although its function is less clearly defined. Here we report the 2.9 angstrom structure of avian H5N1 influenza A virus PA ( PA(C), residues 257 - 716) in complex with the PA- binding region of PB1 ( PB1(N), residues 1 - 25). PA(C) has a fold resembling a dragon's head with PB1(N) clamped into its open 'jaws'. PB1(N) is a known inhibitor that blocks assembly of the polymerase heterotrimer and abolishes viral replication. Our structure provides details for the binding of PB1(N) to PA(C) at the atomic level, demonstrating a potential target for novel anti- influenza therapeutics. We also discuss a potential nucleotide binding site and the roles of some known residues involved in polymerase activity. Furthermore, to explore the role of PA in viral replication and transcription, we propose a model for the influenza RdRp heterotrimer by comparing PA(C) with the lambda 3 reovirus polymerase structure, and docking the PA(C) structure into an available low resolution electron microscopy map.
C1 [He, Xiaojing; Zhou, Jie; Ma, Jianyuan; Li, Xuemei; Li, Jingjing; Zeng, Zonghao; Rao, Zihe; Liu, Yingfang] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Bartlam, Mark; Rao, Zihe] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China.
   [Bartlam, Mark; Rao, Zihe] Nankai Univ, Tianjin State Lab Prot Sci, Tianjin 300071, Peoples R China.
   [Zhang, Rongguang; Joachimiak, Andrzej] Argonne Natl Lab, Midwest Ctr Struct Genom, Biosci Div, Argonne, IL 60439 USA.
   [Zhang, Rongguang; Joachimiak, Andrzej] Argonne Natl Lab, Struct Biol Ctr, Biosci Div, Argonne, IL 60439 USA.
   [Lou, Zhiyong; Li, Xuemei; Rao, Zihe] Tsinghua Univ, Struct Biol Lab, Beijing 100084, Peoples R China.
   [Ge, Ruowen] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
C3 Chinese Academy of Sciences; Institute of Biophysics, CAS; Nankai University; Nankai University; United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Argonne National Laboratory; Tsinghua University; National University of Singapore
RP Rao, ZH (corresponding author), Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
EM raozh@xtal.tsinghua.edu.cn; liuy@ibp.ac.cn
FU National Natural Science Foundation of China [30599432, 30221003]; Ministry of Science and Technology International Cooperation Project [2006DFB32420]; Ministry of Science and Technology 863 Project [2006AA02A314, 2006AA02A322]; Ministry of Science and Technology 973 Project [2006CB504300, 2007CB914300]
NR 40
TC 262
Z9 310
U1 0
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1123
EP U51
DI 10.1038/nature07120
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600039
PM 18615018
DA 2026-03-09
ER

PT J
AU Zhao, WH
   Kruse, JP
   Tang, Y
   Jung, SY
   Qin, J
   Gu, W
AF Zhao, Wenhui
   Kruse, Jan-Philipp
   Tang, Yi
   Jung, Sung Yun
   Qin, Jun
   Gu, Wei
TI Negative regulation of the deacetylase SIRT1 by DBC1
SO NATURE
LA English
DT Article
ID transcription factors; cell-survival; life-span; p53; resveratrol; activation; acetylation; pgc-1-alpha; candidate; apoptosis
AB SIRT1 is an NAD- dependent deacetylase critically involved in stress responses, cellular metabolism and, possibly, ageing(1-15). The tumour suppressor p53 represents the first non- histone substrate functionally regulated by acetylation and deacetylation(16,17); we and others previously found that SIRT1 promotes cell survival by deacetylating p53 ( refs 4-6). These results were further supported by the fact that p53 hyperacetylation and increased radiation- induced apoptosis were observed in Sirt1- deficient mice(10). Nevertheless, SIRT1-mediated deacetylase function is also implicated in p53- independent pathways under different cellular contexts, and its effects on transcriptional factors such as members of the FOXO family and PGC-1 alpha directly modulate metabolic responses(1-15). These studies validate the importance of the deacetylase activity of SIRT1, but how SIRT1 activity is regulated in vivo is not well understood. Here we show that DBC1 ( deleted in breast cancer 1) acts as a native inhibitor of SIRT1 in human cells. DBC1- mediated repression of SIRT1 leads to increasing levels of p53 acetylation and upregulation of p53-mediated function. In contrast, depletion of endogenous DBC1 by RNA interference ( RNAi) stimulates SIRT1- mediated deacetylation of p53 and inhibits p53- dependent apoptosis. Notably, these effects can be reversed in cells by concomitant knockdown of endogenous SIRT1. Our study demonstrates that DBC1 promotes p53- mediated apoptosis through specific inhibition of SIRT1.
C1 [Zhao, Wenhui; Kruse, Jan-Philipp; Tang, Yi; Gu, Wei] Columbia Univ Coll Phys & Surg, Inst Canc Genet, New York, NY 10032 USA.
   [Zhao, Wenhui; Kruse, Jan-Philipp; Tang, Yi; Gu, Wei] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA.
   [Jung, Sung Yun; Qin, Jun] Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA.
   [Jung, Sung Yun; Qin, Jun] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA.
C3 Columbia University; Columbia University; Baylor College of Medicine; Baylor College of Medicine
RP Gu, W (corresponding author), Columbia Univ Coll Phys & Surg, Inst Canc Genet, 1130 St Nicholas Ave, New York, NY 10032 USA.
EM wg8@columbia.edu
FU NCI NIH HHS [R01 CA098821, R01 CA085533] Funding Source: Medline; National Cancer Institute [R01CA085533] Funding Source: NIH RePORTER
NR 30
TC 410
Z9 492
U1 3
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 587
EP U11
DI 10.1038/nature06515
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900045
PM 18235502
DA 2026-03-09
ER

PT J
AU Sekido, R
   Lovell-Badge, R
AF Sekido, Ryohei
   Lovell-Badge, Robin
TI Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer
SO NATURE
LA English
DT Article
ID campomelic dysplasia; testis development; distinct functions; determining region; mouse; gene; mice; differentiation; activation; expression
AB The mammalian Y chromosome acts as a dominant male determinant as a result of the action of a single gene, Sry, whose role in sex determination is to initiate testis rather than ovary development from early bipotential gonads(1-3). It does so by triggering the differentiation of Sertoli cells from supporting cell precursors, which would otherwise give follicle cells. The related autosomal gene Sox9 is also known from loss- of- function mutations in mice and humans to be essential for Sertoli cell differentiation(4,5); moreover, its abnormal expression in an XX gonad can lead to male development in the absence of Sry(6,7). These genetic data, together with the finding that Sox9 is upregulated in Sertoli cell precursors just after SRY expression begins(8,9), has led to the proposal that Sox9 could be directly regulated by SRY. However, the mechanism by which SRY action might affect Sox9 expression was not understood. Here we show that SRY binds to multiple elements within a Sox9 gonad- specific enhancer in mice, and that it does so along with steroidogenic factor 1 ( SF1, encoded by the gene Nr5a1 ( Sf1)), an orphan nuclear receptor. Mutation, co- transfection and sex-reversal studies all point to a feedforward, self- reinforcing pathway in which SF1 and SRY cooperatively upregulate Sox9 and then, together with SF1, SOX9 also binds to the enhancer to help maintain its own expression after that of SRY has ceased. Our results open up the field, permitting further characterization of the molecular mechanisms regulating sex determination and how they have evolved, as well as how they fail in cases of sex reversal.
C1 [Sekido, Ryohei; Lovell-Badge, Robin] Natl Inst Med Res, MRC, Div Dev Genet, London NW7 1AA, England.
C3 MRC National Institute for Medical Research
RP Sekido, R (corresponding author), Natl Inst Med Res, MRC, Div Dev Genet, Ridgeway,Mill Hill, London NW7 1AA, England.
EM rsekido@nimr.mrc.ac.uk; rlovell@nimr.mrc.ac.uk
FU Medical Research Council [MC_U117562207] Funding Source: researchfish; MRC [MC_U117562207] Funding Source: UKRI; Medical Research Council [MC_U117562207] Funding Source: Medline
NR 30
TC 748
Z9 890
U1 4
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 12
PY 2008
VL 453
IS 7197
BP 930
EP 934
DI 10.1038/nature06944
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000046
PM 18454134
DA 2026-03-09
ER

PT J
AU Wada, H
   Masuda, K
   Satoh, R
   Kakugawa, K
   Ikawa, T
   Katsura, Y
   Kawamoto, H
AF Wada, Haruka
   Masuda, Kyoko
   Satoh, Rumi
   Kakugawa, Kiyokazu
   Ikawa, Tomokatsu
   Katsura, Yoshimoto
   Kawamoto, Hiroshi
TI Adult T-cell progenitors retain myeloid potential
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; natural-killer-cell; murine fetal liver; lymphoid progenitors; b-lineage; thymus; precursor; mouse; identification; subpopulation
AB During haematopoiesis, pluripotent haematopoietic stem cells are sequentially restricted to give rise to a variety of lineage-committed progenitors. The classical model of haematopoiesis postulates that, in the first step of differentiation, the stem cell generates common myelo-erythroid progenitors and common lymphoid progenitors (CLPs). However, our previous studies in fetal mice showed that myeloid potential persists even as the lineage branches segregate towards T and B cells(1-6). We therefore proposed the 'myeloid-based' model of haematopoiesis(7,8), in which the stem cell initially generates common myelo-erythroid progenitors and common myelo-lymphoid progenitors. T-cell and B-cell progenitors subsequently arise from common myelo-lymphoid progenitors through myeloid-T and myeloid-B stages, respectively. However, it has been unclear whether this myeloid-based model is also valid for adult haematopoiesis. Here we provide clonal evidence that the early cell populations in the adult thymus contain progenitors that have lost the potential to generate B cells but retain substantial macrophage potential as well as T-cell, natural killer (NK)-cell and dendritic-cell potential. We also show that such T-cell progenitors can give rise to macrophages in the thymic environment in vivo. Our findings argue against the classical dichotomy model in which T cells are derived from CLPs; instead, they support the validity of the 'myeloid-based' model for both adult and fetal haematopoiesis.
C1 [Wada, Haruka; Masuda, Kyoko; Satoh, Rumi; Kakugawa, Kiyokazu; Ikawa, Tomokatsu; Katsura, Yoshimoto; Kawamoto, Hiroshi] RIKEN Res Ctr Allergy & Immunol, Lab Lymphocyte Dev, Yokohama, Kanagawa 2300045, Japan.
   [Katsura, Yoshimoto] Nihon Univ, Sch Med, Div Cell Regenerat & Transplantat, Adv Med Res Ctr, Tokyo 1738610, Japan.
C3 RIKEN; Nihon University
RP Kawamoto, H (corresponding author), RIKEN Res Ctr Allergy & Immunol, Lab Lymphocyte Dev, Yokohama, Kanagawa 2300045, Japan.
EM kawamoto@rcai.riken.jp
NR 26
TC 291
Z9 375
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 APR 10
PY 2008
VL 452
IS 7188
BP 768
EP U10
DI 10.1038/nature06839
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500049
PM 18401412
DA 2026-03-09
ER

PT J
AU Tsintzos, SI
   Pelekanos, NT
   Konstantinidis, G
   Hatzopoulos, Z
   Savvidis, PG
AF Tsintzos, S. I.
   Pelekanos, N. T.
   Konstantinidis, G.
   Hatzopoulos, Z.
   Savvidis, P. G.
TI A GaAs polariton light-emitting diode operating near room temperature
SO NATURE
LA English
DT Article
ID bose-einstein condensation; semiconductor microcavity; amplifier; lasers
AB The increasing ability to control light-matter interactions at the nanometre scale has improved the performance of semiconductor lasers in the past decade. The ultimate optimization is realized in semiconductor microcavities, in which strong coupling between quantum-well excitons and cavity photons gives rise to hybrid half-light/half-matter polariton quasiparticles(1). The unique properties of polaritons - such as stimulated scattering(2,3), parametric amplification(4-6), lasing(7-10), condensation(11-13) and superfluidity(14,15) - are believed to provide the basis for a new generation of polariton emitters and semiconductor lasers. Until now, polariton lasing and nonlinearities have only been demonstrated in optical experiments, which have shown the potential to reduce lasing thresholds by two orders of magnitude compared to conventional semiconductor lasers(16). Here we report an experimental realization of an electrically pumped semiconductor polariton light-emitting device, which emits directly from polariton states at a temperature of 235 K. Polariton electroluminescence data reveal characteristic anticrossing between exciton and cavity modes, a clear signature of the strong coupling regime. These findings represent a substantial step towards the realization of ultra-efficient polaritonic devices with unprecedented characteristics.
C1 [Tsintzos, S. I.; Pelekanos, N. T.; Savvidis, P. G.] Univ Crete, Dept Mat Sci & Technol, Iraklion 71003, Greece.
   [Hatzopoulos, Z.] Univ Crete, Dept Phys, Iraklion 71003, Greece.
   [Pelekanos, N. T.; Konstantinidis, G.; Hatzopoulos, Z.; Savvidis, P. G.] Inst Elect Struct & Laser, Fdn Res & Technol Hellas, Iraklion 71110, Greece.
C3 University of Crete; University of Crete; Foundation for Research & Technology - Hellas (FORTH)
RP Savvidis, PG (corresponding author), Univ Crete, Dept Mat Sci & Technol, POB 2208, Iraklion 71003, Greece.
EM psav@materials.uoc.gr
NR 24
TC 231
Z9 247
U1 2
U2 115
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 15
PY 2008
VL 453
IS 7193
BP 372
EP 375
DI 10.1038/nature06979
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400047
PM 18480820
DA 2026-03-09
ER

PT J
AU Song, MS
   Salmena, L
   Carracedo, A
   Egia, A
   Lo-Coco, F
   Teruya-Feldstein, J
   Pandolfi, PP
AF Song, Min Sup
   Salmena, Leonardo
   Carracedo, Arkaitz
   Egia, Ainara
   Lo-Coco, Francesco
   Teruya-Feldstein, Julie
   Pandolfi, Pier Paolo
TI The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network
SO NATURE
LA English
DT Article
ID nuclear-body formation; promyelocytic leukemia; tumor suppression; ubiquitin ligase; expression; mdm2; degradation; protein; monoubiquitylation; mutation
AB Nuclear exclusion of the PTEN ( phosphatase and tensin homologue deleted in chromosome 10) tumour suppressor has been associated with cancer progression(1-6). However, the mechanisms leading to this aberrant PTEN localization in human cancers are currently unknown. We have previously reported that ubiquitinylation of PTEN at specific lysine residues regulates its nuclear cytoplasmic partitioning(7). Here we show that functional promyelocytic leukaemia protein ( PML) nuclear bodies co- ordinate PTEN localization by opposing the action of a previously unknown PTEN- deubiquitinylating enzyme, herpesvirus- associated ubiquitin- specific protease ( HAUSP, also known as USP7), and that the integrity of this molecular framework is required for PTEN to be able to enter the nucleus. We find that PTEN is aberrantly localized in acute promyelocytic leukaemia, in which PML function is disrupted by the PML - RAR alpha fusion oncoprotein. Remarkably, treatment with drugs that trigger PML - RAR alpha degradation, such as all- trans retinoic acid or arsenic trioxide, restore nuclear PTEN. We demonstrate that PML opposes the activity of HAUSP towards PTEN through a mechanism involving the adaptor protein DAXX ( death domain- associated protein). In support of this paradigm, we show that HAUSP is overexpressed in human prostate cancer and is associated with PTEN nuclear exclusion. Thus, our results delineate a previously unknown PML DAXX - HAUSP molecular network controlling PTEN deubiquitinylation and trafficking, which is perturbed by oncogenic cues in human cancer, in turn defining a new deubiquitinylation- dependent model for PTEN subcellular compartmentalization.
C1 [Song, Min Sup; Salmena, Leonardo; Carracedo, Arkaitz; Egia, Ainara; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Canc Ctr, Canc Genet Program, Boston, MA 02215 USA.
   [Song, Min Sup; Salmena, Leonardo; Carracedo, Arkaitz; Egia, Ainara; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
   [Lo-Coco, Francesco] Univ Roma Tor Vergata, Dept Biopathol, I-00133 Rome, Italy.
   [Teruya-Feldstein, Julie] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Pathol, New York, NY 10021 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; University of Rome Tor Vergata; Memorial Sloan Kettering Cancer Center
RP Pandolfi, PP (corresponding author), Harvard Univ, Sch Med, Beth Israel Deaconess Canc Ctr, Canc Genet Program, Boston, MA 02215 USA.
EM ppandolf@bidmc.harvard.edu
FU NIH; International Human Frontier Science Program Organization; European Molecular Biology Organization; National Cancer Institute [P50CA092629] Funding Source: NIH RePORTER
NR 30
TC 457
Z9 580
U1 0
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 813
EP U11
DI 10.1038/nature07290
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900050
PM 18716620
DA 2026-03-09
ER

PT J
AU Wen, JD
   Lancaster, L
   Hodges, C
   Zeri, AC
   Yoshimura, SH
   Noller, HF
   Bustamante, C
   Tinoco, I
AF Wen, Jin-Der
   Lancaster, Laura
   Hodges, Courtney
   Zeri, Ana-Carolina
   Yoshimura, Shige H.
   Noller, Harry F.
   Bustamante, Carlos
   Tinoco, Ignacio, Jr.
TI Following translation by single ribosomes one codon at a time
SO NATURE
LA English
DT Article
ID initiator transfer-rna; elongation-factor tu; messenger-rna; angstrom resolution; crystal-structure; escherichia-coli; optical tweezers; force; translocation; complexes
AB We have followed individual ribosomes as they translate single messenger RNA hairpins tethered by the ends to optical tweezers. Here we reveal that translation occurs through successive translocation- and- pause cycles. The distribution of pause lengths, with a median of 2.8 s, indicates that at least two rate- determining processes control each pause. Each translocation step measures three bases - one codon - and occurs in less than 0.1 s. Analysis of the times required for translocation reveals, surprisingly, that there are three substeps in each step. Pause lengths, and thus the overall rate of translation, depend on the secondary structure of the mRNA; the applied force destabilizes secondary structure and decreases pause durations, but does not affect translocation times. Translocation and RNA unwinding are strictly coupled ribosomal functions.
C1 [Wen, Jin-Der; Bustamante, Carlos; Tinoco, Ignacio, Jr.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Lancaster, Laura; Noller, Harry F.] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
   [Lancaster, Laura; Noller, Harry F.] Univ Calif Santa Cruz, Ctr Mol Biol RNA, Santa Cruz, CA 95064 USA.
   [Hodges, Courtney; Bustamante, Carlos] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
   [Zeri, Ana-Carolina] Brazilian Synchrotron Light Lab, BR-13083970 Campinas, SP, Brazil.
   [Yoshimura, Shige H.] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068501, Japan.
   [Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Phys & Mol & Cell Biol, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; University of California System; University of California Berkeley; Laboratorio Nacional de Luz Sincrotron (LNLS); Kyoto University; University of California System; University of California Berkeley; Howard Hughes Medical Institute
RP Tinoco, I (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM intinoco@lbl.gov
FU NIGMS NIH HHS [R01 GM010840] Funding Source: Medline
NR 44
TC 401
Z9 498
U1 1
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 598
EP 603
DI 10.1038/nature06716
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200038
PM 18327250
DA 2026-03-09
ER

PT J
AU Keitt, TH
AF Keitt, Timothy H.
TI Coherent ecological dynamics induced by large-scale disturbance
SO NATURE
LA English
DT Article
ID compensatory dynamics; community dynamics; current knowledge; biodiversity; acidification; variability; synchrony; stability; wavelets
AB Aggregate community- level response to disturbance is a principle concern in ecology because post- disturbance dynamics are integral to the ability of ecosystems to maintain function in an uncertain world. Community- level responses to disturbance can be arrayed along a spectrum ranging from synchronous oscillations where all species rise and fall together, to compensatory dynamics where total biomass remains relatively constant despite fluctuations in the densities of individual species(1). An important recent insight is that patterns of synchrony and compensation can vary with the timescale of analysis(2) and that spectral time series methods can enable detection of coherent dynamics that would otherwise be obscured by opposing patterns occurring at different scales(3). Here I show that application of wavelet analysis to experimentally manipulated plankton communities reveals strong synchrony after disturbance. The result is paradoxical because it is well established that these communities contain both disturbance- sensitive and disturbance- tolerant species leading to compensation within functional groups(4,5). Theory predicts that compensatory substitution of functionally equivalent species should stabilize ecological communities(6-10), yet I found at the whole- community level a large increase in seasonal biomass variation. Resolution of the paradox hinges on patterns of seasonality among species. The compensatory shift in community composition after disturbance resulted in a loss of cold- season dominants, which before disturbance had served to stabilize biomass throughout the year. Species dominating the disturbed community peaked coherently during the warm season, explaining the observed synchrony and increase in seasonal biomass variation. These results suggest that theory relating compensatory dynamics to ecological stability needs to consider not only complementarity in species responses to environmental change, but also seasonal complementarity among disturbance- tolerant and disturbance- sensitive species.
C1 Univ Texas Austin, Austin, TX 78712 USA.
C3 University of Texas System; University of Texas Austin
RP Keitt, TH (corresponding author), Univ Texas Austin, Austin, TX 78712 USA.
EM tkeitt@mail.utexas.edu
FU Direct For Biological Sciences; Division Of Environmental Biology [0822700] Funding Source: National Science Foundation
NR 29
TC 97
Z9 109
U1 4
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 331
EP U39
DI 10.1038/nature06935
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300038
PM 18633416
DA 2026-03-09
ER

PT J
AU Zhai, RG
   Zhang, F
   Hiesinger, PR
   Cao, Y
   Haueter, CM
   Bellen, HJ
AF Zhai, R. Grace
   Zhang, Fan
   Hiesinger, P. Robin
   Cao, Yu
   Haueter, Claire M.
   Bellen, Hugo J.
TI NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration
SO NATURE
LA English
DT Article
ID wallerian degeneration; axon degeneration; nervous-system; wld(s); mice; model; biosynthesis; aggregation; drosophila; disease
AB Neurodegeneration can be triggered by genetic or environmental factors. Although the precise cause is often unknown, many neurodegenerative diseases share common features such as protein aggregation and age dependence. Recent studies in Drosophila have uncovered protective effects of NAD synthase nicotinamide mononucleotide adenylyltransferase ( NMNAT) against activity-induced neurodegeneration and injury- induced axonal degeneration(1,2). Here we show that NMNAT overexpression can also protect against spinocerebellar ataxia 1 ( SCA1)- induced neurodegeneration, suggesting a general neuroprotective function of NMNAT. It protects against neurodegeneration partly through a proteasome-mediated pathway in a manner similar to heat- shock protein 70 ( Hsp70). NMNAT displays chaperone function both in biochemical assays and cultured cells, and it shares significant structural similarity with known chaperones. Furthermore, it is upregulated in the brain upon overexpression of poly- glutamine expanded protein and recruited with the chaperone Hsp70 into protein aggregates. Our results implicate NMNAT as a stress- response protein that acts as a chaperone for neuronal maintenance and protection. Our studies provide an entry point for understanding how normal neurons maintain activity, and offer clues for the common mechanisms underlying different neurodegenerative conditions.
C1 [Zhai, R. Grace; Zhang, Fan] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA.
   [Zhai, R. Grace; Hiesinger, P. Robin; Bellen, Hugo J.] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA.
   [Zhai, R. Grace; Cao, Yu; Bellen, Hugo J.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Bellen, Hugo J.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
C3 University of Miami; Baylor College of Medicine; Howard Hughes Medical Institute; Baylor College of Medicine; Baylor College of Medicine
RP Zhai, RG (corresponding author), Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA.
EM gzhai@med.miami.edu; hbellen@bcm.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NICHD NIH HHS [P30 HD024064] Funding Source: Medline
NR 30
TC 171
Z9 214
U1 2
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 17
PY 2008
VL 452
IS 7189
BP 887
EP U8
DI 10.1038/nature06721
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000051
PM 18344983
DA 2026-03-09
ER

PT J
AU Schmittner, A
   Galbraith, ED
AF Schmittner, Andreas
   Galbraith, Eric D.
TI Glacial greenhouse-gas fluctuations controlled by ocean circulation changes
SO NATURE
LA English
DT Article
ID atmospheric co2; carbon-cycle; ice core; climate; reorganizations; dynamics; surface; system; earth; pump
AB Earth's climate and the concentrations of the atmospheric greenhouse gases carbon dioxide (CO2) and nitrous oxide (N2O) varied strongly on millennial timescales during past glacial periods. Large and rapid warming events in Greenland and the North Atlantic were followed by more gradual cooling, and are highly correlated with fluctuations of N2O as recorded in ice cores. Antarctic temperature variations, on the other hand, were smaller and more gradual, showed warming during the Greenland cold phase and cooling while the North Atlantic was warm, and were highly correlated with fluctuations in CO2. Abrupt changes in the Atlantic meridional overturning circulation (AMOC) have often been invoked to explain the physical characteristics of these Dansgaard - Oeschger climate oscillations(1-3), but the mechanisms for the greenhouse- gas variations and their linkage to the AMOC have remained unclear(4-8). Here we present simulations with a coupled model of glacial climate and biogeochemical cycles, forced only with changes in the AMOC. The model simultaneously reproduces characteristic features of the Dansgaard - Oeschger temperature, as well as CO2 and N2O fluctuations. Despite significant changes in the land carbon inventory, CO2 variations on millennial timescales are dominated by slow changes in the deep ocean inventory of biologically sequestered carbon and are correlated with Antarctic temperature and Southern Ocean stratification. In contrast, N2O co-varies more rapidly with Greenland temperatures owing to fast adjustments of the thermocline oxygen budget. These results suggest that ocean circulation changes were the primary mechanism that drove glacial CO2 and N2O fluctuations on millennial timescales.
C1 [Schmittner, Andreas] Oregon State Univ, Coll Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [Galbraith, Eric D.] Princeton Univ, Princeton, NJ 08544 USA.
C3 Oregon State University; Princeton University
RP Schmittner, A (corresponding author), Oregon State Univ, Coll Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
EM aschmitt@coas.oregonstate.edu
FU NSF Marine Geology and Geophysics [0728315-OCE]; NSF Paleoclimate programme [0602395-ATM]; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [0602395] Funding Source: National Science Foundation
NR 30
TC 172
Z9 191
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 NOV 20
PY 2008
VL 456
IS 7220
BP 373
EP 376
DI 10.1038/nature07531
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600040
PM 19020618
DA 2026-03-09
ER

PT J
AU Walsh, KJ
   Richardson, DC
   Michel, P
AF Walsh, Kevin J.
   Richardson, Derek C.
   Michel, Patrick
TI Rotational breakup as the origin of small binary asteroids
SO NATURE
LA English
DT Article
ID collisions; model
AB Asteroids with satellites are observed throughout the Solar System, from subkilometre near-Earth asteroid pairs to systems of large and distant bodies in the Kuiper belt. The smallest and closest systems are found among the near- Earth and small inner main- belt asteroids, which typically have rapidly rotating primaries and close secondaries on circular orbits. About 15 per cent of near- Earth and main- belt asteroids with diameters under 10 km have satellites(1,2). The mechanism that forms such similar binaries in these two dynamically different populations was hitherto unclear. Here we show that these binaries are created by the slow spinup of a `rubble pile' asteroid by means of the thermal YORP ( Yarkovsky - O'Keefe - Radzievskii - Paddack) effect. We find that mass shed from the equator of a critically spinning body accretes into a satellite if the material is collisionally dissipative and the primary maintains a low equatorial elongation. The satellite forms mostly from material originating near the primary's surface and enters into a close, low- eccentricity orbit. The properties of binaries produced by our model match those currently observed in the small near- Earth and main- belt asteroid populations, including 1999 KW4 ( refs 3, 4).
C1 [Walsh, Kevin J.; Michel, Patrick] Univ Nice, UMR Cassiopee 6202, CNRS, Observ Cote Azur, F-06304 Nice 4, France.
   [Walsh, Kevin J.; Richardson, Derek C.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
C3 Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; Observatoire de la Cote d'Azur; University System of Maryland; University of Maryland College Park
RP Walsh, KJ (corresponding author), Univ Nice, UMR Cassiopee 6202, CNRS, Observ Cote Azur, BP 4229, F-06304 Nice 4, France.
EM kwalsh@oca.eu
NR 21
TC 350
Z9 387
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 JUL 10
PY 2008
VL 454
IS 7201
BP 188
EP 191
DI 10.1038/nature07078
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900037
PM 18615078
DA 2026-03-09
ER

PT J
AU Wang, XT
   Arai, S
   Song, XY
   Reichart, D
   Du, K
   Pascual, G
   Tempst, P
   Rosenfeld, MG
   Glass, CK
   Kurokawa, R
AF Wang, Xiangting
   Arai, Shigeki
   Song, Xiaoyuan
   Reichart, Donna
   Du, Kun
   Pascual, Gabriel
   Tempst, Paul
   Rosenfeld, Michael G.
   Glass, Christopher K.
   Kurokawa, Riki
TI Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription
SO NATURE
LA English
DT Article
ID pro-oncoprotein tls/fus; noncoding rnas; gene-expression; coactivator; genome; tls; identification; chromatin; complex; mice
AB With the recent recognition of non- coding RNAs ( ncRNAs) flanking many genes(1-5), a central issue is to obtain a full understanding of their potential roles in regulated gene transcription programmes, possibly through different mechanisms(6-12). Here we show that an RNA- binding protein, TLS ( for translocated in liposarcoma), serves as a key transcriptional regulatory sensor of DNA damage signals that, on the basis of its allosteric modulation by RNA, specifically binds to and inhibits CREB- binding protein ( CBP) and p300 histone acetyltransferase activities on a repressed gene target, cyclin D1 ( CCND1) in human cell lines. Recruitment of TLS to the CCND1 promoter to cause gene- specific repression is directed by single- stranded, low- copy- number ncRNA transcripts tethered to the 5' regulatory regions of CCND1 that are induced in response to DNA damage signals. Our data suggest that signal-induced ncRNAs localized to regulatory regions of transcription units can act cooperatively as selective ligands, recruiting and modulating the activities of distinct classes of RNA- binding co-regulators in response to specific signals, providing an unexpected ncRNA/RNA-binding protein-based strategy to integrate transcriptional programmes.
C1 [Arai, Shigeki; Du, Kun; Kurokawa, Riki] Saitama Med Univ, Res Ctr Genom Med, Div Gene Struct & Funct, Hidaka, Saitama 3501241, Japan.
   [Wang, Xiangting; Song, Xiaoyuan; Rosenfeld, Michael G.] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Wang, Xiangting] Univ Calif San Diego, Sch Med, Mol Pathol Grad Program, La Jolla, CA 92093 USA.
   [Reichart, Donna; Pascual, Gabriel; Glass, Christopher K.] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Pascual, Gabriel; Rosenfeld, Michael G.; Glass, Christopher K.] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.
   [Tempst, Paul] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA.
C3 Saitama Medical University; Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Memorial Sloan Kettering Cancer Center
RP Kurokawa, R (corresponding author), Saitama Med Univ, Res Ctr Genom Med, Div Gene Struct & Funct, 1397-1 Yamane, Hidaka, Saitama 3501241, Japan.
EM mgr@ucsd.edu; ckg@ucsd.edu; rkurokaw@saitama-med.ac.jp
FU National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK091183, R01DK039949] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [R01 CA052599, CA52599, P30 CA08748, CA097134, P30 CA008748] Funding Source: Medline; NHLBI NIH HHS [R01 HL059694, HL59694] Funding Source: Medline; NIDDK NIH HHS [R01 DK039949, R01 DK091183, DK074868, R37 DK039949, DK39949] Funding Source: Medline; NINDS NIH HHS [R01 NS034934, NS34934] Funding Source: Medline
NR 29
TC 826
Z9 1005
U1 6
U2 129
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 126
EP U11
DI 10.1038/nature06992
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300051
PM 18509338
DA 2026-03-09
ER

PT J
AU Morris, EJ
   Ji, JY
   Yang, FJ
   Di Stefano, L
   Herr, A
   Moon, NS
   Kwon, EJ
   Haigis, KM
   Näär, AM
   Dyson, NJ
AF Morris, Erick J.
   Ji, Jun-Yuan
   Yang, Fajun
   Di Stefano, Luisa
   Herr, Anabel
   Moon, Nam-Sung
   Kwon, Eun-Jeong
   Haigis, Kevin M.
   Naar, Anders M.
   Dyson, Nicholas J.
TI E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8
SO NATURE
LA English
DT Article
ID colon-cancer; expression; activation; protein; gene; apc; p53; specificity; drosophila; mediator
AB The E2F1 transcription factor can promote proliferation or apoptosis when activated, and is a key downstream target of the retinoblastoma tumour suppressor protein ( pRB). Here we show that E2F1 is a potent and specific inhibitor of beta-catenin/T-cell factor (TCF)- dependent transcription, and that this function contributes to E2F1- induced apoptosis. E2F1 deregulation suppresses beta-catenin activity in an adenomatous polyposis coli ( APC)/glycogen synthase kinase- 3 ( GSK3)- independent manner, reducing the expression of key beta-catenin targets including c- MYC. This interaction explains why colorectal tumours, which depend on beta- catenin transcription for their abnormal proliferation, keep RB1 intact. Remarkably, E2F1 activity is also repressed by cyclin- dependent kinase- 8 ( CDK8), a colorectal oncoprotein(1). Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1. Thus, by retaining RB1 and amplifying CDK8, colorectal tumour cells select conditions that collectively suppress E2F1 and enhance the activity of beta-catenin.
C1 [Morris, Erick J.; Ji, Jun-Yuan; Yang, Fajun; Di Stefano, Luisa; Herr, Anabel; Moon, Nam-Sung; Haigis, Kevin M.; Naar, Anders M.; Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA.
   [Morris, Erick J.; Ji, Jun-Yuan; Yang, Fajun; Di Stefano, Luisa; Herr, Anabel; Moon, Nam-Sung; Haigis, Kevin M.; Naar, Anders M.; Dyson, Nicholas J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   [Yang, Fajun; Naar, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Kwon, Eun-Jeong] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Kwon, Eun-Jeong] Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
   [Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc, Lab Mol Pathol, Charlestown, MA 02129 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Dyson, NJ (corresponding author), Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, 13th St,Bldg 149, Charlestown, MA 02129 USA.
EM dyson@helix.mgh.harvard.edu
FU Ruth L. Kirschstein Award; Tosteson Postdoctoral Fellowship; MGH ECOR Fund for Medical Discovery; Career Development award; Harvard Gastrointestinal Specialized Program of Research Excellence [P50-CA127003]; Saltonstall Foundation; National Institutes of Health [GM81607, GM053203, GM071449]; National Cancer Institute [P50CA127003] Funding Source: NIH RePORTER
NR 29
TC 268
Z9 318
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 552
EP U67
DI 10.1038/nature07310
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600050
PM 18794899
DA 2026-03-09
ER

PT J
AU Lu, DH
   Yi, M
   Mo, SK
   Erickson, AS
   Analytis, J
   Chu, JH
   Singh, DJ
   Hussain, Z
   Geballe, TH
   Fisher, IR
   Shen, ZX
AF Lu, D. H.
   Yi, M.
   Mo, S. -K.
   Erickson, A. S.
   Analytis, J.
   Chu, J. -H.
   Singh, D. J.
   Hussain, Z.
   Geballe, T. H.
   Fisher, I. R.
   Shen, Z. -X.
TI Electronic structure of the iron-based superconductor LaOFeP
SO NATURE
LA English
DT Article
ID 43 k; lao1-xfxfeas; compound
AB The recent discovery of superconductivity in the iron oxypnictide family of compounds(1-9) has generated intense interest. The layered crystal structure with transition- metal ions in planar square- lattice form and the discovery of spin- density- wave order near 130 K ( refs 10, 11) seem to hint at a strong similarity with the copper oxide superconductors. An important current issue is the nature of the ground state of the parent compounds. Two distinct classes of theories, distinguished by the underlying band structure, have been put forward: a local- moment antiferromagnetic ground state in the strong- coupling approach(12-17), and an itinerant ground state in the weak- coupling approach(18-22). The first approach stresses on-site correlations, proximity to a Mott- insulating state and, thus, the resemblance to the high- transition- temperature copper oxides, whereas the second approach emphasizes the itinerant- electron physics and the interplay between the competing ferromagnetic and antiferromagnetic fluctuations. The debate over the two approaches is partly due to the lack of conclusive experimental information on the electronic structures. Here we report angle- resolved photoemission spectroscopy ( ARPES) of LaOFeP ( superconducting transition temperature, T-c = 5.9 K), the first- reported iron- based superconductor(2). Our results favour the itinerant ground state, albeit with band renormalization. In addition, our data reveal important differences between these and copper- based superconductors.
C1 [Lu, D. H.; Yi, M.; Mo, S. -K.; Shen, Z. -X.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Lu, D. H.; Yi, M.; Mo, S. -K.; Shen, Z. -X.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Lu, D. H.; Yi, M.; Mo, S. -K.; Shen, Z. -X.] Stanford Univ, Stanford Synchrotron Radiat Lab, Stanford, CA 94305 USA.
   [Mo, S. -K.; Hussain, Z.] Univ Calif Berkeley, Lawrence Berkeley Lab, Adv Light Source, Berkeley, CA 94720 USA.
   [Erickson, A. S.; Analytis, J.; Chu, J. -H.; Geballe, T. H.; Fisher, I. R.] Stanford Univ, Geballe Lab Adv Mat, Stanford, CA 94305 USA.
   [Erickson, A. S.; Analytis, J.; Chu, J. -H.; Geballe, T. H.; Fisher, I. R.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Singh, D. J.] Oak Ridge Natl Lab, Mat Sci & Technol Div, Oak Ridge, TN 37831 USA.
C3 Stanford University; Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Stanford University; Stanford University; United States Department of Energy (DOE); Oak Ridge National Laboratory
RP Shen, ZX (corresponding author), Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
EM dhlu@slac.stanford.edu; zxshen@stanford.edu
FU Office of Basic Energy Science, Division of Materials Science and Engineering
NR 29
TC 252
Z9 280
U1 2
U2 144
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 81
EP 84
DI 10.1038/nature07263
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200040
PM 18769435
DA 2026-03-09
ER

PT J
AU Madueno, R
   Räisänen, MT
   Silien, C
   Buck, M
AF Madueno, Rafael
   Raisanen, Minna T.
   Silien, Christophe
   Buck, Manfred
TI Functionalizing hydrogen-bonded surface networks with self-assembled monolayers
SO NATURE
LA English
DT Article
ID scanning-tunneling-microscopy; underpotential deposition; systems; au(111); guests; complexation; interfaces; inclusion; template; copper
AB One of the central challenges in nanotechnology is the development of flexible and efficient methods for creating ordered structures with nanometre precision over an extended length scale. Supramolecular self- assembly on surfaces offers attractive features in this regard: it is a 'bottom- up' approach and thus allows the simple and rapid creation of surface assemblies(1,2), which are readily tuned through the choice of molecular building blocks used and stabilized by hydrogen bonding(3-8), van der Waals interactions(9), pi-pi bonding(10,11) or metal coordination(12,13) between the blocks. Assemblies in the form of two- dimensional open networks(3,9,10,13-17) are of particular interest for possible applications because well- defined pores can be used for the precise localization and confinement of guest entities such as molecules or clusters, which can add functionality to the supramolecular network. Another widely used method for producing surface structures involves self- assembled monolayers (SAMs)(18), which have introduced unprecedented flexibility in our ability to tailor interfaces and generate patterned surfaces(19-22). But SAMs are part of a top-down technology that is limited in terms of the spatial resolution that can be achieved. We therefore rationalized that a particularly powerful fabrication platform might be realized by combining non- covalent self- assembly of porous networks and SAMs, with the former providing nanometre- scale precision and the latter allowing versatile functionalization. Here we show that the two strategies can indeed be combined to create integrated network SAM hybrid systems that are sufficiently robust for further processing. We show that the supramolecular network and the SAM can both be deposited from solution, which should enable the widespread and flexible use of this combined fabrication method.
C1 [Madueno, Rafael; Raisanen, Minna T.; Silien, Christophe; Buck, Manfred] Univ St Andrews, EaStCHEM Sch Chem, St Andrews KY16 9ST, Fife, Scotland.
C3 University of St Andrews
RP Buck, M (corresponding author), Univ St Andrews, EaStCHEM Sch Chem, St Andrews KY16 9ST, Fife, Scotland.
EM rafael.madueno@uco.es; mb45@st-and.ac.uk
FU Engineering and Physical Sciences Research Council [EP/D048761/1, EP/D036828/1] Funding Source: researchfish; EPSRC [EP/D048761/1, EP/D036828/1] Funding Source: UKRI
NR 30
TC 336
Z9 354
U1 5
U2 330
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 618
EP 621
DI 10.1038/nature07096
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500042
PM 18668104
DA 2026-03-09
ER

PT J
AU Valtonen, MJ
   Lehto, HJ
   Nilsson, K
   Heidt, J
   Takalo, LO
   Sillanpää, A
   Villforth, C
   Kidger, M
   Poyner, G
   Pursimo, T
   Zola, S
   Wu, JH
   Zhou, X
   Sadakane, K
   Drozdz, M
   Koziel, D
   Marchev, D
   Ogloza, W
   Porowski, C
   Siwak, M
   Stachowski, G
   Winiarski, M
   Hentunen, VP
   Nissinen, M
   Liakos, A
   Dogru, S
AF Valtonen, M. J.
   Lehto, H. J.
   Nilsson, K.
   Heidt, J.
   Takalo, L. O.
   Sillanpaa, A.
   Villforth, C.
   Kidger, M.
   Poyner, G.
   Pursimo, T.
   Zola, S.
   Wu, J. -H.
   Zhou, X.
   Sadakane, K.
   Drozdz, M.
   Koziel, D.
   Marchev, D.
   Ogloza, W.
   Porowski, C.
   Siwak, M.
   Stachowski, G.
   Winiarski, M.
   Hentunen, V. -P.
   Nissinen, M.
   Liakos, A.
   Dogru, S.
TI A massive binary black-hole system in OJ 287 and a test of general relativity
SO NATURE
LA English
DT Article
ID bl-lacertae objects; oj 287; accretion disk; model; outburst; pulsar; oj287; lens
AB Tests of Einstein's general theory of relativity have mostly been carried out in weak gravitational fields where the space- time curvature effects are first- order deviations from Newton's theory(1-6). Binary pulsars(4) provide a means of probing the strong gravitational field around a neutron star, but strong- field effects may be best tested in systems containing black holes(7,8). Here we report such a test in a close binary system of two candidate black holes in the quasar OJ 287. This quasar shows quasi- periodic optical outbursts at 12- year intervals, with two outburst peaks per interval(9,10). The latest outburst occurred in September 2007, within a day of the time predicted by the binary black- hole model and general relativity(11). The observations confirm the binary nature of the system and also provide evidence for the loss of orbital energy in agreement ( within 10 per cent) with the emission of gravitational waves from the system(12). In the absence of gravitational wave emission the outburst would have happened 20 days later(13).
C1 [Valtonen, M. J.; Lehto, H. J.; Takalo, L. O.; Sillanpaa, A.; Villforth, C.] Univ Turku, Dept Phys, FI-21500 Piikkio, Finland.
   [Valtonen, M. J.; Lehto, H. J.; Nilsson, K.; Takalo, L. O.; Sillanpaa, A.; Villforth, C.] Univ Turku, Tuorla Observ, FI-21500 Piikkio, Finland.
   [Heidt, J.] Landessternwarte Heidelberg, D-69117 Heidelberg, Germany.
   [Kidger, M.] European Space Agcy, European Space Astron Ctr, Herschel Sci Ctr, Villafrance Castillo Satellite Tracking Stn, Madrid 28691, Spain.
   [Kidger, M.] INSA, Madrid 28008, Spain.
   [Poyner, G.] British Astron Assoc Variable Star Sect, Birmingham B44 0QE, W Midlands, England.
   [Pursimo, T.] Nord Opt Telescope, E-38700 S C La Palma, Spain.
   [Zola, S.; Koziel, D.; Porowski, C.; Siwak, M.; Winiarski, M.] Jagiellonian Univ, Astron Observ, PL-30224 Krakow, Poland.
   [Stachowski, G.] Pedagog Univ, Mt Suhora Observ, PL-30084 Krakow, Poland.
   [Wu, J. -H.; Zhou, X.] Chinese Acad Sci, Natl Astron Observ, Beijing 100012, Peoples R China.
   [Sadakane, K.] Osaka Kyoiku Univ, Inst Astron, Kashiwara, Osaka 5828582, Japan.
   [Marchev, D.] Shoumen Univ, Dept Phys, Shumen, Bulgaria.
   [Nissinen, M.] Warkauden Kassiopeia Ry, Kangaslampi 79480, Finland.
   [Liakos, A.] Univ Athens, Fac Phys, Dept Astrophys Astron & Mech, GR-15784 Athens, Greece.
   [Dogru, S.] Canakkale Onsekiz Mart Univ, Fac Phys, TR-17020 Canakkale, Turkey.
C3 University of Turku; University of Turku; Ruprecht Karls University Heidelberg; European Space Agency; European Space Astronomy Center; Jagiellonian University; University of the National Education Commission; Chinese Academy of Sciences; National Astronomical Observatory, CAS; Osaka University of Education; University of Shumen; National & Kapodistrian University of Athens; Canakkale Onsekiz Mart University
RP Valtonen, MJ (corresponding author), Univ Turku, Dept Phys, Vaisalantie 20, FI-21500 Piikkio, Finland.
EM mvaltonen2001@yahoo.com
NR 23
TC 349
Z9 386
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 APR 17
PY 2008
VL 452
IS 7189
BP 851
EP 853
DI 10.1038/nature06896
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000043
PM 18421348
DA 2026-03-09
ER

PT J
AU Flint, J
   Mott, R
AF Flint, Jonathan
   Mott, Richard
TI Applying mouse complex-trait resources to behavioural genetics
SO NATURE
LA English
DT Article
ID long-term potentiation; mutant mice; collaborative cross; interaction network; circadian behavior; genome; loci; susceptibility; association; expression
AB Studies of the genetic basis of behaviour in mice are at a turning point. Soon, new resources will enable the behavioural function of all genes to be tested and the networks of genes, messenger RNAs and proteins involved in a particular behaviour to be identified. Using these resources, scientists will be able to analyse mouse behaviour at an unprecedented level of detail. Interpreting the new data, however, will require a shift in focus from gene- based approaches to network- based approaches.
C1 [Flint, Jonathan; Mott, Richard] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
C3 University of Oxford; Wellcome Centre for Human Genetics
RP Flint, J (corresponding author), Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
EM jf@well.ox.ac.uk
FU Wellcome Trust
NR 35
TC 33
Z9 35
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 724
EP 727
DI 10.1038/nature07630
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900035
PM 19079048
DA 2026-03-09
ER

PT J
AU Penna, A
   Demuro, A
   Yeromin, AV
   Zhang, SYL
   Safrina, O
   Parker, I
   Cahalan, MD
AF Penna, Aubin
   Demuro, Angelo
   Yeromin, Andriy V.
   Zhang, Shenyuan L.
   Safrina, Olga
   Parker, Ian
   Cahalan, Michael D.
TI The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimers
SO NATURE
LA English
DT Article
ID ca2+ sensor; store; subunit; architecture; protein; pore
AB Ca2+-release- activated Ca2+ (CRAC) channels underlie sustained Ca2+ signalling in lymphocytes and numerous other cells after Ca2+ liberation from the endoplasmic reticulum (ER). RNA interference screening approaches identified two proteins, Stim(1,2) and Orai(3-5), that together form the molecular basis for CRAC channel activity(6,7). Stim senses depletion of the ER Ca2+ store and physically relays this information by translocating from the ER to junctions adjacent to the plasma membrane(1,8,9), and Orai embodies the pore of the plasma membrane calcium channel(10-12). A close interaction between Stim and Orai, identified by co-immunoprecipitation(12) and by Forster resonance energy transfer(13), is involved in the opening of the Ca2+ channel formed by Orai subunits. Most ion channels are multimers of pore- forming subunits surrounding a central channel, which are preassembled in the ER and transported in their final stoichiometry to the plasma membrane. Here we show, by biochemical analysis after cross- linking in cell lysates and intact cells and by using non- denaturing gel electrophoresis without cross- linking, that Orai is predominantly a dimer in the plasma membrane under resting conditions. Moreover, single- molecule imaging of green fluorescent protein (GFP)- tagged Orai expressed in Xenopus oocytes showed predominantly two- step photobleaching, again consistent with a dimeric basal state. In contrast, co- expression of GFP- tagged Orai with the carboxy terminus of Stim as a cytosolic protein to activate the Orai channel without inducing Ca2+ store depletion or clustering of Orai into punctae yielded mostly four- step photobleaching, consistent with a tetrameric stoichiometry of the active Orai channel. Interaction with the C terminus of Stim thus induces Orai dimers to dimerize, forming tetramers that constitute the Ca2+-selective pore. This represents a new mechanism in which assembly and activation of the functional ion channel are mediated by the same triggering molecule.
C1 [Penna, Aubin; Yeromin, Andriy V.; Zhang, Shenyuan L.; Safrina, Olga; Parker, Ian; Cahalan, Michael D.] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA.
   [Demuro, Angelo; Parker, Ian] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA.
   [Cahalan, Michael D.] Univ Calif Irvine, Ctr Immunol, Irvine, CA 92697 USA.
C3 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 Cahalan, MD (corresponding author), Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA.
EM mcahalan@uci.edu
FU National Institutes of Health; George E. Hewitt Foundation; National Cancer Institute [P30CA062203] Funding Source: NIH RePORTER
NR 31
TC 308
Z9 375
U1 1
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 116
EP U12
DI 10.1038/nature07338
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000052
PM 18820677
DA 2026-03-09
ER

PT J
AU Davis, BN
   Hilyard, AC
   Lagna, G
   Hata, A
AF Davis, Brandi N.
   Hilyard, Aaron C.
   Lagna, Giorgio
   Hata, Akiko
TI SMAD proteins control DROSHA-mediated microRNA maturation
SO NATURE
LA English
DT Article
ID tgf-beta; posttranscriptional regulation; expression signature; binding-protein; cancer; targets; genes; rna; differentiation; inhibition
AB MicroRNAs ( miRNAs) are small non- coding RNAs that participate in the spatiotemporal regulation of messenger RNA and protein synthesis. Aberrant miRNA expression leads to developmental abnormalities and diseases, such as cardiovascular disorders and cancer; however, the stimuli and processes regulating miRNA biogenesis are largely unknown. The transforming growth factor beta ( TGF-beta) and bone morphogenetic protein ( BMP) family of growth factors orchestrates fundamental biological processes in development and in the homeostasis of adult tissues, including the vasculature. Here we show that induction of a contractile phenotype in human vascular smooth muscle cells by TGF-beta and BMPs is mediated by miR- 21. miR- 21 downregulates PDCD4 ( programmed cell death 4), which in turn acts as a negative regulator of smooth muscle contractile genes. Surprisingly, TGF-beta and BMP signalling promotes a rapid increase in expression of mature miR- 21 through a post- transcriptional step, promoting the processing of primary transcripts of miR- 21 ( pri- miR- 21) into precursor miR- 21 ( pre- miR- 21) by the DROSHA ( also known as RNASEN) complex. TGF-beta- and BMP- specific SMAD signal transducers are recruited to pri- miR- 21 in a complex with the RNA helicase p68 ( also known as DDX5), a component of the DROSHA microprocessor complex. The shared cofactor SMAD4 is not required for this process. Thus, regulation of miRNA biogenesis by ligand- specific SMAD proteins is critical for control of the vascular smooth muscle cell phenotype and potentially for SMAD4- independent responses mediated by the TGF-beta and BMP signalling pathways.
C1 [Davis, Brandi N.; Hata, Akiko] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA.
   [Davis, Brandi N.; Hilyard, Aaron C.; Lagna, Giorgio; Hata, Akiko] Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA.
C3 Tufts University; Tufts Medical Center
RP Hata, A (corresponding author), Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA.
EM akiko.hata@tufts.edu
FU NHLBI NIH HHS [HL086572, R21 HL086572, R01 HL082854, HL082854] Funding Source: Medline; NICHD NIH HHS [HD042149, R01 HD042149] Funding Source: Medline
NR 50
TC 1123
Z9 1356
U1 0
U2 113
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2008
VL 454
IS 7200
BP 56
EP U2
DI 10.1038/nature07086
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 321MC
UT WOS:000257308300034
PM 18548003
DA 2026-03-09
ER

PT J
AU Negi, J
   Matsuda, O
   Nagasawa, T
   Oba, Y
   Takahashi, H
   Kawai-Yamada, M
   Uchimiya, H
   Hashimoto, M
   Iba, K
AF Negi, Juntaro
   Matsuda, Osamu
   Nagasawa, Takashi
   Oba, Yasuhiro
   Takahashi, Hideyuki
   Kawai-Yamada, Maki
   Uchimiya, Hirofumi
   Hashimoto, Mimi
   Iba, Koh
TI CO2 regulator SLAC1 and its homologues are essential for anion homeostasis in plant cells
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; plasma-membrane; protein-kinase; abscisic-acid; ion channels; conductance; protoplasts; activation; malate; gene
AB The continuing rise in atmospheric [ CO2] is predicted to have diverse and dramatic effects on the productivity of agriculture, plant ecosystems and gas exchange(1-3). Stomatal pores in the epidermis provide gates for the exchange of CO2 and water between plants and the atmosphere, processes vital to plant life(4-6). Increased [ CO2] has been shown to enhance anion channel activity(7) proposed to mediate efflux of osmoregulatory anions ( Cl- and malate(2-)) from guard cells during stomatal closure(8,9). However, the genes encoding anion efflux channels in plant plasma membranes remain unknown. Here we report the isolation of an Arabidopsis gene, SLAC1 ( SLOW ANION CHANNEL-ASSOCIATED 1, At1g12480), which mediates CO2 sensitivity in regulation of plant gas exchange. The SLAC1 protein is a distant homologue of bacterial and fungal C4- dicarboxylate transporters, and is localized specifically to the plasma membrane of guard cells. It belongs to a protein family that in Arabidopsis consists of four structurally related members that are common in their plasma membrane localization, but show distinct tissue- specific expression patterns. The loss- of- function mutation in SLAC1 was accompanied by an over- accumulation of the osmoregulatory anions in guard cell protoplasts. Guard- cell- specific expression of SLAC1 or its family members resulted in restoration of the wild- type stomatal responses, including CO2 sensitivity, and also in the dissipation of the over- accumulated anions. These results suggest that SLAC1-family proteins have an evolutionarily conserved function that is required for the maintenance of organic/ inorganic anion homeostasis on the cellular level.
C1 [Negi, Juntaro; Matsuda, Osamu; Nagasawa, Takashi; Oba, Yasuhiro; Hashimoto, Mimi; Iba, Koh] Kyushu Univ, Fac Sci, Dept Biol, Fukuoka 8128581, Japan.
   [Takahashi, Hideyuki; Uchimiya, Hirofumi] Iwate Biotechnol Ctr, Kitakami, Iwate 0240003, Japan.
   [Kawai-Yamada, Maki; Uchimiya, Hirofumi] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan.
C3 Kyushu University; University of Tokyo
RP Iba, K (corresponding author), Kyushu Univ, Fac Sci, Dept Biol, Fukuoka 8128581, Japan.
EM koibascb@mbox.nc.kyushu-u.ac.jp
NR 33
TC 505
Z9 576
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 MAR 27
PY 2008
VL 452
IS 7186
BP 483
EP U13
DI 10.1038/nature06720
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300034
PM 18305482
DA 2026-03-09
ER

PT J
AU Raymo, ME
   Huybers, P
AF Raymo, Maureen E.
   Huybers, Peter
TI Unlocking the mysteries of the ice ages
SO NATURE
LA English
DT Article
ID climate
AB Much progress has been made towards understanding what caused the waxing and the waning of the great ice sheets, but a complete theory of the ice ages is still elusive.
C1 [Raymo, Maureen E.] Boston Univ, Dept Earth Sci, Boston, MA 02215 USA.
   [Huybers, Peter] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Boston University; Harvard University
RP Raymo, ME (corresponding author), Boston Univ, Dept Earth Sci, 685 Commonwealth Ave, Boston, MA 02215 USA.
EM raymo@bu.edu
NR 8
TC 70
Z9 87
U1 4
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 284
EP 285
DI 10.1038/nature06589
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100036
PM 18202644
DA 2026-03-09
ER

PT J
AU Rehmann, H
   Arias-Palomo, E
   Hadders, MA
   Schwede, F
   Llorca, O
   Bos, JL
AF Rehmann, Holger
   Arias-Palomo, Ernesto
   Hadders, Michael A.
   Schwede, Frank
   Llorca, Oscar
   Bos, Johannes L.
TI Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B
SO NATURE
LA English
DT Article
ID nucleotide-exchange factor; dependent protein-kinase; electron-microscopy; regulatory subunit; binding proteins; activation; ras; program; family; visualization
AB Epac proteins are activated by binding of the second messenger cAMP and then act as guanine nucleotide exchange factors for Rap proteins(1,2). The Epac proteins are involved in the regulation of cell adhesion(3) and insulin secretion(4). Here we have determined the structure of Epac2 in complex with a cAMP analogue (Sp-cAMPS) and RAP1B by X- ray crystallography and single particle electron microscopy. The structure represents the cAMP activated state of the Epac2 protein with the RAP1B protein trapped in the course of the exchange reaction. Comparison with the inactive conformation reveals that cAMP binding causes conformational changes that allow the cyclic nucleotide binding domain to swing from a position blocking the Rap binding site towards a docking site at the Ras exchange motif domain.
C1 [Rehmann, Holger; Bos, Johannes L.] Univ Med Ctr, Dept Physiol Chem, Ctr Biomed Genet, NL-3584 CG Utrecht, Netherlands.
   [Rehmann, Holger; Bos, Johannes L.] Univ Med Ctr, Canc Genom Ctr, NL-3584 CG Utrecht, Netherlands.
   [Arias-Palomo, Ernesto; Llorca, Oscar] CSIC, CIB, Spanish Natl Res Council, E-28040 Madrid, Spain.
   [Hadders, Michael A.] Univ Utrecht, Bijvoet Ctr, Dept Crystal & Struct Chem, NL-3584 CH Utrecht, Netherlands.
   [Schwede, Frank] BIOLOG Life Sci Inst, D-28199 Bremen, Germany.
C3 Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Investigaciones Biologicas (CIB); Utrecht University
RP Rehmann, H (corresponding author), Univ Med Ctr, Dept Physiol Chem, Ctr Biomed Genet, Universiteitsweg 100, NL-3584 CG Utrecht, Netherlands.
EM h.rehmann@UMCutrecht.nl
FU Autonomous Region of Madrid; Bremer Innovationsagentur; Spanish Ministry of Education and Science (MEC); Red Tematica de Investigacion cooperativa en Cancer (RTICC); Chemical Sciences and the Netherlands Genomic Initiative of the Netherlands Organisation for Scientific Research (NWO)
NR 35
TC 154
Z9 177
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 124
EP U93
DI 10.1038/nature07187
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200050
PM 18660803
DA 2026-03-09
ER

PT J
AU Grunze, M
AF Grunze, Michael
TI Nanotechnology - Patterns from molecular corrals
SO NATURE
LA English
DT Article
ID porous network; surface; fullerenes
C1 Univ Heidelberg, Dept Appl Phys Chem, D-69120 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Grunze, M (corresponding author), Univ Heidelberg, Dept Appl Phys Chem, INF 253, D-69120 Heidelberg, Germany.
EM michael.grunze@urz.uni-heidelberg.de
NR 6
TC 9
Z9 9
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 31
PY 2008
VL 454
IS 7204
BP 585
EP 586
DI 10.1038/454585a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500028
PM 18668093
DA 2026-03-09
ER

PT J
AU Paul, K
   Erhardt, M
   Hirano, T
   Blair, DF
   Hughes, KT
AF Paul, Koushik
   Erhardt, Marc
   Hirano, Takanori
   Blair, David F.
   Hughes, Kelly T.
TI Energy source of flagellar type III secretion
SO NATURE
LA English
DT Article
ID proton motive force; salmonella-typhimurium; negative regulator; escherichia-coli; export apparatus; atpase; flii; flgm; components; proteins
AB Bacterial flagella contain a specialized secretion apparatus that functions to deliver the protein subunits that form the filament and other structures to outside the membrane(1). This apparatus is related to the injectisome used by many gram- negative pathogens and symbionts to transfer effector proteins into host cells; in both systems this export mechanism is termed 'type III' secretion(2,3). The flagellar secretion apparatus comprises a membrane- embedded complex of about five proteins, and soluble factors, which include export- dedicated chaperones and an ATPase, FliI, that was thought to provide the energy for export(1,4). Here we show that flagellar secretion in Salmonella enterica requires the proton motive force ( PMF) and does not require ATP hydrolysis by FliI. The export of several flagellar export substrates was prevented by treatment with the protonophore CCCP, with no accompanying decrease in cellular ATP levels. Weak swarming motility and rare flagella were observed in a mutant deleted for FliI and for the non-flagellar type- III secretion ATPases InvJ and SsaN. These findings show that the flagellar secretion apparatus functions as a proton-driven protein exporter and that ATP hydrolysis is not essential for type III secretion.
C1 [Paul, Koushik; Erhardt, Marc; Hirano, Takanori; Blair, David F.; Hughes, Kelly T.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah
RP Blair, DF (corresponding author), Univ Utah, Dept Biol, 257 South 1400 East, Salt Lake City, UT 84112 USA.
EM blair@bioscience.utah.edu; hughes@biology.utah.edu
FU NIGMS NIH HHS [R01 GM056141] Funding Source: Medline
NR 27
TC 257
Z9 303
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 24
PY 2008
VL 451
IS 7177
BP 489
EP U13
DI 10.1038/nature06497
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100050
PM 18216859
DA 2026-03-09
ER

PT J
AU Konca, AO
   Avouac, JP
   Sladen, A
   Meltzner, AJ
   Sieh, K
   Fang, P
   Li, ZH
   Galetzka, J
   Genrich, J
   Chlieh, M
   Natawidjaja, DH
   Bock, Y
   Fielding, EJ
   Ji, C
   Helmberger, DV
AF Konca, A. Ozgun
   Avouac, Jean-Philippe
   Sladen, Anthony
   Meltzner, Aron J.
   Sieh, Kerry
   Fang, Peng
   Li, Zhenhong
   Galetzka, John
   Genrich, Jeff
   Chlieh, Mohamed
   Natawidjaja, Danny H.
   Bock, Yehuda
   Fielding, Eric J.
   Ji, Chen
   Helmberger, Don V.
TI Partial rupture of a locked patch of the Sumatra megathrust during the 2007 earthquake sequence
SO NATURE
LA English
DT Article
ID andaman earthquake; zone; deformation; asperity; model; slip
AB The great Sumatra - Andaman earthquake and tsunami of 2004 was a dramatic reminder of the importance of understanding the seismic and tsunami hazards of subduction zones(1-4). In March 2005, the Sunda megathrust ruptured again, producing an event(5) of moment magnitude (M-w) 8.6 south of the 2004 rupture area, which was the site of a similar event in 1861 (ref. 6). Concern was then focused on the Mentawai area, where large earthquakes had occurred in 1797 ( M-w = 8.8) and 1833 (M-w = 9.0)(6,7). Two earthquakes, one of M-w = 8.4 and, twelve hours later, one of M-w = 7.9, indeed occurred there on 12 September 2007. Here we show that these earthquakes ruptured only a fraction of the area ruptured in 1833 and consist of distinct asperities within a patch of the megathrust that had remained locked in the interseismic period. This indicates that the same portion of a megathrust can rupture in different patterns depending on whether asperities break as isolated seismic events or cooperate to produce a larger rupture. This variability probably arises from the influence of non- permanent barriers, zones with locally lower pre- stress due to the past earthquakes. The stress state of the portion of the Sunda megathrust that had ruptured in 1833 and 1797 was probably not adequate for the development of a single large rupture in 2007. Themoment released in 2007 amounts to only a fraction both of that released in 1833 and of the deficit of moment that had accumulated as a result of interseismic strain since 1833. The potential for a large megathrust event in the Mentawai area thus remains large.
C1 [Konca, A. Ozgun; Avouac, Jean-Philippe; Sladen, Anthony; Meltzner, Aron J.; Sieh, Kerry; Galetzka, John; Genrich, Jeff; Natawidjaja, Danny H.; Helmberger, Don V.] CALTECH, Tecton Observ, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Fang, Peng; Bock, Yehuda] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Li, Zhenhong] Univ Glasgow, COMET, Dept Geog & Earth Sci, Glasgow G12 8QQ, Lanark, Scotland.
   [Chlieh, Mohamed] Univ Nice Sophia Antipolis, Inst Rech Dev, Observ Cote Azur, F-06560 Valbonne, France.
   [Fielding, Eric J.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Ji, Chen] Univ Calif Santa Barbara, Dept Geol Sci, Santa Barbara, CA 94106 USA.
C3 California Institute of Technology; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Glasgow; Universite Cote d'Azur; Observatoire de la Cote d'Azur; Institut de Recherche pour le Developpement (IRD); National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of California System; University of California Santa Barbara
RP Avouac, JP (corresponding author), CALTECH, Tecton Observ, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
EM avouac@gps.caltech.edu
FU NSF [EAR-0538333]; Gordon and Betty Moore Foundation; NERC [come20001] Funding Source: UKRI; Natural Environment Research Council [earth010007, come20001] Funding Source: researchfish
NR 29
TC 297
Z9 331
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 DEC 4
PY 2008
VL 456
IS 7222
BP 631
EP 635
DI 10.1038/nature07572
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000039
PM 19052626
DA 2026-03-09
ER

PT J
AU Yang, L
   Anderson, DE
   Baecher-Allan, C
   Hastings, WD
   Bettelli, E
   Oukka, M
   Kuchroo, VK
   Hafler, DA
AF Yang, Li
   Anderson, David E.
   Baecher-Allan, Clare
   Hastings, William D.
   Bettelli, Estelle
   Oukka, Mohamed
   Kuchroo, Vijay K.
   Hafler, David A.
TI IL-21 and TGF-β are required for differentiation of human TH17 cells
SO NATURE
LA English
DT Article
ID growth-factor-beta; t-cells; generation; pathways; lineage; context; il-17
AB The recent discovery of CD4(+) T cells characterized by secretion of interleukin ( IL)- 17 (T(H)17 cells) and the naturally occurring regulatory FOXP3(+) CD4 T cell ( nT(reg)) has had a major impact on our understanding of immune processes not readily explained by the T(H)1/T(H)2 paradigm. T(H)17 and nT(reg) cells have been implicated in the pathogenesis of human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and psoriasis(1,2). Our recent data and the work of others demonstrated that transforming growth factor-beta ( TGF-beta) and IL- 6 are responsible for the differentiation of naive mouse T cells into T(H)17 cells, and it has been proposed that IL-23 may have a critical role in stabilization of the T(H)17 phenotype(3-5). A second pathway has been discovered in which a combination of TGF-beta and IL- 21 is capable of inducing differentiation of mouse T(H)17 cells in the absence of IL- 6 ( refs 6 - 8). However, TGF-beta and IL- 6 are not capable of differentiating human T(H)17 cells(2,9) and it has been suggested that TGF-beta may in fact suppress the generation of human T(H)17 cells(10). Instead, it has been recently shown that the cytokines IL-1 beta, IL- 6 and IL- 23 are capable of driving IL- 17 secretion in short- term CD4(+) T cell lines isolated from human peripheral blood(11), although the factors required for differentiation of naive human CD4 to T(H)17 cells are still unknown. Here we confirm that whereas IL-1 beta and IL- 6 induce IL- 17A secretion from human central memory CD4(+) T cells, TGF-beta and IL- 21 uniquely promote the differentiation of human naive CD4(+) T cells into T(H)17 cells accompanied by expression of the transcription factor RORC2. These data will allow the investigation of this new population of T(H)17 cells in human inflammatory disease.
C1 [Yang, Li; Anderson, David E.; Baecher-Allan, Clare; Hastings, William D.; Bettelli, Estelle; Oukka, Mohamed; Kuchroo, Vijay K.; Hafler, David A.] Harvard Univ, Sch Med, Div Mol Immunol, Ctr Neurol Dis,Brigham & Womens Hosp, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Anderson, DE (corresponding author), Harvard Univ, Sch Med, Div Mol Immunol, Ctr Neurol Dis,Brigham & Womens Hosp, Boston, MA 02115 USA.
EM danderson@rics.bwh.harvard.edu
FU NIAID NIH HHS [P01 AI039671, R01 AI073542, U19 AI070352] Funding Source: Medline; NINDS NIH HHS [P01 NS038037, R37 NS024247] Funding Source: Medline; National Institute of Allergy and Infectious Diseases [P01AI039671] Funding Source: NIH RePORTER
NR 14
TC 792
Z9 946
U1 1
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 350
EP U55
DI 10.1038/nature07021
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300042
PM 18469800
DA 2026-03-09
ER

PT J
AU Kim, IJ
   Zhang, YF
   Yamagata, M
   Meister, M
   Sanes, JR
AF Kim, In-Jung
   Zhang, Yifeng
   Yamagata, Masahito
   Meister, Markus
   Sanes, Joshua R.
TI Molecular identification of a retinal cell type that responds to upward motion
SO NATURE
LA English
DT Article
ID ganglion-cells; adhesion molecules; selective units; mouse; morphology; parallel; receptor
AB The retina contains complex circuits of neurons that extract salient information from visual inputs. Signals from photoreceptors are processed by retinal interneurons, integrated by retinal ganglion cells ( RGCs) and sent to the brain by RGC axons. Distinct types of RGC respond to different visual features, such as increases or decreases in light intensity ( ON and OFF cells, respectively), colour or moving objects(1-5). Thus, RGCs comprise a set of parallel pathways from the eye to the brain. The identification of molecular markers for RGC subsets will facilitate attempts to correlate their structure with their function, assess their synaptic inputs and targets, and study their diversification. Here we show, by means of a transgenic marking method, that junctional adhesion molecule B ( JAM- B) marks a previously unrecognized class of OFF RGCs in mice. These cells have asymmetric dendritic arbors aligned in a dorsal- to- ventral direction across the retina. Their receptive fields are also asymmetric and respond selectively to stimuli moving in a soma- to- dendrite direction; because the lens reverses the image of the world on the retina, these cells detect upward motion in the visual field. Thus, JAM- B identifies a unique population of RGCs in which structure corresponds remarkably to function.
C1 [Kim, In-Jung; Zhang, Yifeng; Yamagata, Masahito; Meister, Markus; Sanes, Joshua R.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Kim, In-Jung; Zhang, Yifeng; Yamagata, Masahito; Meister, Markus; Sanes, Joshua R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University
RP Meister, M (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM meister@fas.harvard.edu; sanesj@mcb.harvard.edu
NR 37
TC 329
Z9 415
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 MAR 27
PY 2008
VL 452
IS 7186
BP 478
EP U11
DI 10.1038/nature06739
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300033
PM 18368118
DA 2026-03-09
ER

PT J
AU Long, JA
   Trinajstic, K
   Young, GC
   Senden, T
AF Long, John A.
   Trinajstic, Kate
   Young, Gavin C.
   Senden, Tim
TI Live birth in the Devonian period
SO NATURE
LA English
DT Article
ID x-ray tomography; viviparity; fish
AB The extinct placoderm fishes were the dominant group of vertebrates throughout the Middle Palaeozoic era(1), yet controversy about their relationships within the gnathostomes ( jawed vertebrates) is partly due to different interpretations of their reproductive biology(2-5). Here we document the oldest record of a live- bearing vertebrate in a new ptyctodontid placoderm, Materpiscis attenboroughi gen. et sp. nov., from the Late Devonian Gogo Formation of Australia ( approximately 380 million years ago)(6). The new specimen, remarkably preserved in three dimensions, contains a single, intra- uterine embryo connected by a permineralized umbilical cord. An amorphous crystalline mass near the umbilical cord possibly represents the recrystallized yolk sac. Another ptyctodont from the Gogo Formation, Austroptyctodus gardineri(7), also shows three small embryos inside it in the same position. Ptyctodontids have already provided the oldest definite evidence for vertebrate copulation(8), and the new specimens confirm that some placoderms had a remarkably advanced reproductive biology, comparable to that of some modern sharks and rays. The new discovery points to internal fertilization and viviparity in vertebrates as originating earliest within placoderms.
C1 [Long, John A.] Museum Victoria, Melbourne, Vic 3001, Australia.
   [Long, John A.; Young, Gavin C.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, 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.
   [Senden, Tim] Australian Natl Univ, Dept Appl Math, Res Sch Phys Sci & Engn, Canberra, ACT 0200, Australia.
C3 Museum Victoria; Australian National University; Monash University; University of Western Australia; Australian National University
RP Long, JA (corresponding author), Museum Victoria, POB 666, Melbourne, Vic 3001, Australia.
EM jlong@museum.vic.gov.au
NR 17
TC 93
Z9 105
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 29
PY 2008
VL 453
IS 7195
BP 650
EP U6
DI 10.1038/nature06966
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 305NN
UT WOS:000256185200043
PM 18509443
DA 2026-03-09
ER

PT J
AU Uchida, K
   Takahashi, S
   Harii, K
   Ieda, J
   Koshibae, W
   Ando, K
   Maekawa, S
   Saitoh, E
AF Uchida, K.
   Takahashi, S.
   Harii, K.
   Ieda, J.
   Koshibae, W.
   Ando, K.
   Maekawa, S.
   Saitoh, E.
TI Observation of the spin Seebeck effect
SO NATURE
LA English
DT Article
ID room-temperature; semiconductors; spintronics; electronics
AB The generation of electric voltage by placing a conductor in a temperature gradient is called the Seebeck effect(1,2). Its efficiency is represented by the Seebeck coefficient, S, which is defined as the ratio of the generated electric voltage to the temperature difference, and is determined by the scattering rate and the density of the conduction electrons. The effect can be exploited, for example, in thermal electric- power generators and for temperature sensing, by connecting two conductors with different Seebeck coefficients, a device called a thermocouple(1,2). Here we report the observation of the thermal generation of driving power, or voltage, for electron spin: the spin Seebeck effect. Using a recently developed spin-detection technique that involves the spin Hall effect(3-14), we measure the spin voltage generated from a temperature gradient in a metallic magnet. This thermally induced spin voltage persists even at distances far from the sample ends, and spins can be extracted from every position on the magnet simply by attaching a metal. The spin Seebeck effect observed here is directly applicable to the production of spin- voltage generators, which are crucial for driving spintronic(15-18) devices. The spin Seebeck effect allows us to pass a pure spin current(19), a flow of electron spins without electric currents, over a long distance. These innovative capabilities will invigorate spintronics research.
C1 [Uchida, K.; Harii, K.; Ando, K.; Saitoh, E.] Keio Univ, Dept Appl Phys & Physicoinformat, Yokohama, Kanagawa 2238522, Japan.
   [Takahashi, S.; Ieda, J.; Maekawa, S.] Tohoku Univ, Inst Mat Res, Sendai, Miyagi 9808577, Japan.
   [Takahashi, S.; Ieda, J.; Maekawa, S.] Japan Sci & Technol Agcy, CREST, Tokyo 1020075, Japan.
   [Koshibae, W.] RIKEN, Cross Correlated Mat Res Grp, Wako, Saitama 3510198, Japan.
   [Saitoh, E.] Japan Sci & Technol Agcy, PRESTO, Tokyo 1020075, Japan.
C3 Keio University; Tohoku University; Japan Science & Technology Agency (JST); RIKEN; Japan Science & Technology Agency (JST)
RP Saitoh, E (corresponding author), Keio Univ, Dept Appl Phys & Physicoinformat, Yokohama, Kanagawa 2238522, Japan.
EM saitoheiji@appi.keio.ac.jp
FU MEXT, Japan [19048028]; MIC, Japan; IMS, Japan; Grants-in-Aid for Scientific Research [19048009, 19048028] Funding Source: KAKEN
NR 28
TC 1967
Z9 2115
U1 21
U2 917
PU 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 9
PY 2008
VL 455
IS 7214
BP 778
EP 781
DI 10.1038/nature07321
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900042
PM 18843364
DA 2026-03-09
ER

PT J
AU Billy, J
   Josse, V
   Zuo, ZC
   Bernard, A
   Hambrecht, B
   Lugan, P
   Clément, D
   Sanchez-Palencia, L
   Bouyer, P
   Aspect, A
AF Billy, Juliette
   Josse, Vincent
   Zuo, Zhanchun
   Bernard, Alain
   Hambrecht, Ben
   Lugan, Pierre
   Clement, David
   Sanchez-Palencia, Laurent
   Bouyer, Philippe
   Aspect, Alain
TI Direct observation of Anderson localization of matter waves in a controlled disorder
SO NATURE
LA English
DT Article
ID lattices; diffusion; transport; light
AB In 1958, Anderson predicted the localization(1) of electronic wave-functions in disordered crystals and the resulting absence of diffusion. It is now recognized that Anderson localization is ubiquitous in wave physics(2) because it originates from the interference between multiple scattering paths. Experimentally, localization has been reported for light waves(3-7), microwaves(8,9), sound waves(10) and electron gases(11). However, there has been no direct observation of exponential spatial localization of matter waves of any type. Here we observe exponential localization of a Bose Einstein condensate released into a one- dimensional waveguide in the presence of a controlled disorder created by laser speckle(12). We operate in a regime of pure Anderson localization, that is, with weak disorder - such that localization results from many quantum reflections of low amplitude - and an atomic density low enough to render interactions negligible. We directly image the atomic density profiles as a function of time, and find that weak disorder can stop the expansion and lead to the formation of a stationary, exponentially localized wavefunction - a direct signature of Anderson localization. We extract the localization length by fitting the exponential wings of the profiles, and compare it to theoretical calculations. The power spectrum of the one- dimensional speckle potentials has a high spatial frequency cutoff, causing exponential localization to occur only when the de Broglie wavelengths of the atoms in the expanding condensate are greater than an effective mobility edge corresponding to that cutoff. In the opposite case, we find that the density profiles decay algebraically, as predicted in ref. 13. The method presented here can be extended to localization of atomic quantum gases in higher dimensions, and with controlled interactions.
C1 [Billy, Juliette; Josse, Vincent; Zuo, Zhanchun; Bernard, Alain; Hambrecht, Ben; Lugan, Pierre; Clement, David; Sanchez-Palencia, Laurent; Bouyer, Philippe; Aspect, Alain] Ecole Polytech, CNRS, Lab Charles Fabry, Inst Opt, F-91127 Palaiseau, France.
   [Billy, Juliette; Josse, Vincent; Zuo, Zhanchun; Bernard, Alain; Hambrecht, Ben; Lugan, Pierre; Clement, David; Sanchez-Palencia, Laurent; Bouyer, Philippe; Aspect, Alain] Univ Paris Sud, F-91127 Palaiseau, France.
C3 Institut Polytechnique de Paris; Ecole Polytechnique; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Universite Paris Saclay
RP Bouyer, P (corresponding author), Ecole Polytech, CNRS, Lab Charles Fabry, Inst Opt, Campus Polytech,RD 128, F-91127 Palaiseau, France.
EM philippe.bouyer@institutoptique.fr
NR 32
TC 1379
Z9 1514
U1 9
U2 253
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 891
EP 894
DI 10.1038/nature07000
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000036
PM 18548065
DA 2026-03-09
ER

PT J
AU Feng, SH
   Martinez, C
   Gusmaroli, G
   Wang, Y
   Zhou, JL
   Wang, F
   Chen, LY
   Yu, L
   Iglesias-Pedraz, JM
   Kircher, S
   Schäfer, E
   Fu, XD
   Fan, LM
   Deng, XW
AF Feng, Suhua
   Martinez, Cristina
   Gusmaroli, Giuliana
   Wang, Yu
   Zhou, Junli
   Wang, Feng
   Chen, Liying
   Yu, Lu
   Iglesias-Pedraz, Juan M.
   Kircher, Stefan
   Schaefer, Eberhard
   Fu, Xiangdong
   Fan, Liu-Min
   Deng, Xing Wang
TI Coordinated regulation of Arabidopsis thaliana development by light and gibberellins
SO NATURE
LA English
DT Article
ID phytochrome interacting factor-3; transcription factor; seed-germination; protein; pif3; affinity; degradation; receptor; pathway; binding
AB Light and gibberellins ( GAs) mediate many essential and partially overlapping plant developmental processes. DELLA proteins are GA- signalling repressors that block GA- induced development(1). GA induces degradation of DELLA proteins via the ubiquitin/ proteasome pathway(2), but light promotes accumulation of DELLA proteins by reducing GA levels(3). It was proposed that DELLA proteins restrain plant growth largely through their effect on gene expression(4,5). However, the precise mechanism of their function in coordinating GA signalling and gene expression remains unknown. Here we characterize a nuclear protein interaction cascade mediating transduction of GA signals to the activity regulation of a light- responsive transcription factor. In the absence of GA, nuclear- localized DELLA proteins accumulate to higher levels, interact with phytochrome- interacting factor 3 ( PIF3, a bHLH- type transcription factor) and prevent PIF3 from binding to its target gene promoters and regulating gene expression, and therefore abrogate PIF3- mediated light control of hypocotyl elongation. In the presence of GA, GID1 proteins ( GA receptors) elevate their direct interaction with DELLA proteins in the nucleus, trigger DELLA protein's ubiquitination and proteasome- mediated degradation, and thus release PIF3 from the negative effect of DELLA proteins.
C1 [Feng, Suhua; Martinez, Cristina; Gusmaroli, Giuliana; Deng, Xing Wang] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Feng, Suhua; Zhou, Junli; Wang, Feng; Chen, Liying; Yu, Lu; Deng, Xing Wang] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Wang, Yu; Fan, Liu-Min; Deng, Xing Wang] Peking Univ, Coll Life Sci, Peking Yale Joint Ctr Plant Mol Genet & Agrobiote, Beijing 100871, Peoples R China.
   [Wang, Yu; Fan, Liu-Min; Deng, Xing Wang] Peking Univ, Coll Life Sci, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China.
   [Iglesias-Pedraz, Juan M.] CSIC, Ctr Nacl Biotecnol, Dept Genet Mol Plantas, E-28049 Madrid, Spain.
   [Kircher, Stefan; Schaefer, Eberhard] Univ Freiburg, Inst Biol Bot 2, D-79104 Freiburg, Germany.
   [Fu, Xiangdong] Chinese Acad Sci, Inst Genet & Dev Biol, Beijing 100080, Peoples R China.
C3 Yale University; National Institute of Biological Sciences, Beijing; Peking University; Peking University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB); University of Freiburg; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS
RP Deng, XW (corresponding author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
EM xingwang.deng@yale.edu
FU NIGMS NIH HHS [R37 GM047850, R01 GM047850] Funding Source: Medline
NR 32
TC 869
Z9 1047
U1 5
U2 346
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 24
PY 2008
VL 451
IS 7177
BP 475
EP U9
DI 10.1038/nature06448
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100047
PM 18216856
DA 2026-03-09
ER

PT J
AU DeConto, RM
   Pollard, D
   Wilson, PA
   Pälike, H
   Lear, CH
   Pagani, M
AF DeConto, Robert M.
   Pollard, David
   Wilson, Paul A.
   Palike, Heiko
   Lear, Caroline H.
   Pagani, Mark
TI Thresholds for Cenozoic bipolar glaciation
SO NATURE
LA English
DT Article
ID carbon-dioxide concentrations; antarctic glaciation; ice-sheet; early miocene; oligocene; climate; transition; greenland; onset; ocean
AB The long-standing view of Earth's Cenozoic glacial history calls for the first continental-scale glaciation of Antarctica in the earliest Oligocene epoch (similar to 33.6 million years ago(1)), followed by the onset of northern- hemispheric glacial cycles in the late Pliocene epoch, about 31 million years later(2). The pivotal early Oligocene event is characterized by a rapid shift of 1.5 parts per thousand in deep- sea benthic oxygen- isotope values(3) ( Oi- 1) within a few hundred thousand years(4), reflecting a combination of terrestrial ice growth and deep- sea cooling. The apparent absence of contemporaneous cooling in deep- sea Mg/Ca records(4-6), however, has been argued to reflect the growth of more ice than can be accommodated on Antarctica; this, combined with new evidence of continental cooling(7) and ice- rafted debris(8,9) in the Northern Hemisphere during this period, raises the possibility that Oi- 1 represents a precursory bipolar glaciation. Here we test this hypothesis using an isotope-capable global climate/ ice- sheet model that accommodates both the long- term decline of Cenozoic atmospheric CO2 levels(10,11) and the effects of orbital forcing(12). We show that the CO2 threshold below which glaciation occurs in the Northern Hemisphere (similar to 280 p.p.m.v.) is much lower than that for Antarctica (similar to 750 p.p.m.v.). Therefore, the growth of ice sheets in the Northern Hemisphere immediately following Antarctic glaciation would have required rapid CO2 drawdown within the Oi- 1 time-frame, to levels lower than those estimated by geochemical proxies(10,11) and carbon- cycle models(13,14). Instead of bipolar glaciation, we find that Oi- 1 is best explained by Antarctic glaciation alone, combined with deep- sea cooling of up to 4 degrees C and Antarctic ice that is less isotopically depleted (-30 to -35 parts per thousand) than previously suggested(15,16). Proxy CO2 estimates remain above our model's northern- hemispheric glaciation threshold of similar to 280 p.p.m.v. until similar to 25 Myr ago, but have been near or below that level ever since(10,11). This implies that episodic northern- hemispheric ice sheets have been possible some 20 million years earlier than currently assumed ( although still much later than Oi- 1) and could explain some of the variability in Miocene sea- level records(17,18).
C1 [DeConto, Robert M.] Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.
   [Pollard, David] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [Wilson, Paul A.; Palike, Heiko] Univ Southampton, Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
   [Lear, Caroline H.] Cardiff Univ, Sch Earth & Ocean Sci, Cardiff CF10 3YE, Wales.
   [Pagani, Mark] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
C3 University of Massachusetts System; University of Massachusetts Amherst; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; NERC National Oceanography Centre; University of Southampton; Cardiff University; Yale University
RP DeConto, RM (corresponding author), Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.
EM deconto@geo.umass.edu
FU National Science Foundation.; NERC [NE/D000343/1] Funding Source: UKRI; STFC [PP/D002176/1] Funding Source: UKRI; Natural Environment Research Council [NE/D000343/1] Funding Source: researchfish; Science and Technology Facilities Council [PP/D002176/1] Funding Source: researchfish
NR 34
TC 319
Z9 374
U1 3
U2 175
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 652
EP U52
DI 10.1038/nature07337
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700044
PM 18833277
DA 2026-03-09
ER

PT J
AU Ravi, M
   Marimuthu, MPA
   Siddiqi, I
AF Ravi, Maruthachalam
   Marimuthu, Mohan P. A.
   Siddiqi, Imran
TI Gamete formation without meiosis in Arabidopsis
SO NATURE
LA English
DT Article
ID thaliana plants; apomixis; gene; markers; identification; progression; strategy; tripsacum; evolution; apospory
AB Apomixis, the formation of asexual seeds in plants, leads to populations that are genetically uniform maternal clones. The transfer of apomixis to crop plants holds great promise in plant breeding for fixation of heterozygosity and hybrid vigour because it would allow the propagation of hybrids over successive generations(1,2). Apomixis involves the production of unreduced ( diploid) female gametes that retain the genotype of the parent plant ( apomeiosis), followed by parthenogenetic development of the egg cell into an embryo and the formation of functional endosperm(3). The molecular mechanisms underlying apomixis are unknown. Here we show that mutation of the Arabidopsis gene DYAD/ SWITCH1 (SWI1)(4,5), a regulator of meiotic chromosome organization, leads to apomeiosis. We found that most fertile ovules in dyad plants form seeds that are triploid and that arise from the fertilization of an unreduced female gamete by a haploid male gamete. The unreduced female gametes fully retain parental heterozygosity across the genome, which is characteristic of apomeiosis. Our results show that the alteration of a single gene in a sexual plant can bring about functional apomeiosis, a major component of apomixis.
C1 [Ravi, Maruthachalam; Marimuthu, Mohan P. A.; Siddiqi, Imran] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India.
C3 Council of Scientific & Industrial Research (CSIR) - India; CSIR - Centre for Cellular & Molecular Biology (CCMB)
RP Siddiqi, I (corresponding author), Ctr Cellular & Mol Biol, Uppal Rd, Hyderabad 500007, Andhra Pradesh, India.
EM imran@ccmb.res.in
NR 33
TC 173
Z9 203
U1 5
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1121
EP U10
DI 10.1038/nature06557
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600045
PM 18272967
DA 2026-03-09
ER

PT J
AU Shin, YI
   Schunck, CH
   Schirotzek, A
   Ketterle, W
AF Shin, Yong-Il
   Schunck, Christian H.
   Schirotzek, Andre
   Ketterle, Wolfgang
TI Phase diagram of a two-component Fermi gas with resonant interactions
SO NATURE
LA English
DT Article
ID critical field; superconductors; superfluidity
AB The pairing of fermions lies at the heart of superconductivity and superfluidity. The stability of these pairs determines the robustness of the superfluid state, and the quest for superconductors with high critical temperature equates to a search for systems with strong pairing mechanisms. Ultracold atomic Fermi gases present a highly controllable model system for studying strongly interacting fermions(1). Tunable interactions ( through Feshbach collisional resonances) and the control of population or mass imbalance among the spin components provide unique opportunities to investigate the stability of pairing(2-4) - and possibly to search for exotic forms of superfluidity(5,6). A major controversy has surrounded the stability of superfluidity against an imbalance between the two spin components when the fermions interact resonantly ( that is, at unitarity). Here we present the phase diagram of a spin- polarized Fermi gas of Li-6 atoms at unitarity, experimentally mapping out the superfluid phases versus temperature and density imbalance. Using tomographic techniques, we reveal spatial discontinuities in the spin polarization; this is the signature of a first- order superfluid- to- normal phase transition, and disappears at a tricritical point where the nature of the phase transition changes from first- order to second- order. At zero temperature, there is a quantum phase transition from a fully paired superfluid to a partially polarized normal gas. These observations and the implementation of an in situ ideal gas thermometer provide quantitative tests of theoretical calculations on the stability of resonant superfluidity.
C1 [Shin, Yong-Il; Schunck, Christian H.; Schirotzek, Andre; Ketterle, Wolfgang] MIT, Dept Phys, MIT Harvard Ctr Ultracold Atoms, Cambridge, MA 02139 USA.
   [Shin, Yong-Il; Schunck, Christian H.; Schirotzek, Andre; Ketterle, Wolfgang] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Shin, YI (corresponding author), MIT, Dept Phys, MIT Harvard Ctr Ultracold Atoms, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM yishin@mit.edu
NR 30
TC 284
Z9 318
U1 1
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 689
EP U1
DI 10.1038/nature06473
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500035
PM 18256666
DA 2026-03-09
ER

PT J
AU Friedman, M
AF Friedman, Matt
TI The evolutionary origin of flatfish asymmetry
SO NATURE
LA English
DT Article
ID phylogeny; behavior; record
AB All adult flatfishes ( Pleuronectiformes), including the gastronomically familiar plaice, sole, turbot and halibut, have highly asymmetrical skulls, with both eyes placed on one side of the head. This arrangement, one of the most extraordinary anatomical specializations among vertebrates, arises through migration of one eye during late larval development. Although the transformation of symmetrical larvae into asymmetrical juveniles is well documented(1-7), the evolutionary origins of flatfish asymmetry are uncertain(1,2) because there are no transitional forms linking flatfishes with their symmetrical relatives(8,9). The supposed inviability of such intermediates gave pleuronectiforms a prominent role in evolutionary debates(10-16), leading to attacks on natural selection(11) and arguments for saltatory change(14,15). Here I show that Amphistium and the new genus Heteronectes, both extinct spiny- finned fishes from the Eocene epoch of Europe, are the most primitive pleuronectiforms known. The orbital region of the skull in both taxa is strongly asymmetrical, as in living flatfishes, but these genera retain many primitive characters unknown in extant forms. Most remarkably, orbital migration was incomplete in Amphistium and Heteronectes, with eyes remaining on opposite sides of the head in post- metamorphic individuals. This condition is intermediate between that in living pleuronectiforms and the arrangement found in other fishes. Amphistium and Heteronectes indicate that the evolution of the profound cranial asymmetry of extant flatfishes was gradual in nature.
C1 [Friedman, Matt] Univ Chicago, Comm Evolutionary Biol, Chicago, IL 60637 USA.
   [Friedman, Matt] Field Museum Nat Hist, Dept Geol, Chicago, IL 60605 USA.
C3 University of Chicago; Field Museum of Natural History (Chicago)
RP Friedman, M (corresponding author), Univ Chicago, Comm Evolutionary Biol, 1025 E 57th St, Chicago, IL 60637 USA.
EM mattf@uchicago.edu
NR 30
TC 120
Z9 139
U1 3
U2 163
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 209
EP 212
DI 10.1038/nature07108
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900042
PM 18615083
DA 2026-03-09
ER

PT J
AU Ming, R
   Hou, SB
   Feng, Y
   Yu, QY
   Dionne-Laporte, A
   Saw, JH
   Senin, P
   Wang, W
   Ly, BV
   Lewis, KLT
   Salzberg, SL
   Feng, L
   Jones, MR
   Skelton, RL
   Murray, JE
   Chen, CX
   Qian, WB
   Shen, JG
   Du, P
   Eustice, M
   Tong, E
   Tang, HB
   Lyons, E
   Paull, RE
   Michael, TP
   Wall, K
   Rice, DW
   Albert, H
   Wang, ML
   Zhu, YJ
   Schatz, M
   Nagarajan, N
   Acob, RA
   Guan, PZ
   Blas, A
   Wai, CM
   Ackerman, CM
   Ren, Y
   Liu, C
   Wang, JM
   Wang, JP
   Na, JK
   Shakirov, EV
   Haas, B
   Thimmapuram, J
   Nelson, D
   Wang, XY
   Bowers, JE
   Gschwend, AR
   Delcher, AL
   Singh, R
   Suzuki, JY
   Tripathi, S
   Neupane, K
   Wei, HR
   Irikura, B
   Paidi, M
   Jiang, N
   Zhang, WL
   Presting, G
   Windsor, A
   Navajas-Pérez, R
   Torres, MJ
   Feltus, FA
   Porter, B
   Li, YJ
   Burroughs, AM
   Luo, MC
   Liu, L
   Christopher, DA
   Mount, SM
   Moore, PH
   Sugimura, T
   Jiang, JM
   Schuler, MA
   Friedman, V
   Mitchell-Olds, T
   Shippen, DE
   dePamphilis, CW
   Palmer, JD
   Freeling, M
   Paterson, AH
   Gonsalves, D
   Wang, L
   Alam, M
AF Ming, Ray
   Hou, Shaobin
   Feng, Yun
   Yu, Qingyi
   Dionne-Laporte, Alexandre
   Saw, Jimmy H.
   Senin, Pavel
   Wang, Wei
   Ly, Benjamin V.
   Lewis, Kanako L. T.
   Salzberg, Steven L.
   Feng, Lu
   Jones, Meghan R.
   Skelton, Rachel L.
   Murray, Jan E.
   Chen, Cuixia
   Qian, Wubin
   Shen, Junguo
   Du, Peng
   Eustice, Moriah
   Tong, Eric
   Tang, Haibao
   Lyons, Eric
   Paull, Robert E.
   Michael, Todd P.
   Wall, Kerr
   Rice, Danny W.
   Albert, Henrik
   Wang, Ming-Li
   Zhu, Yun J.
   Schatz, Michael
   Nagarajan, Niranjan
   Acob, Ricelle A.
   Guan, Peizhu
   Blas, Andrea
   Wai, Ching Man
   Ackerman, Christine M.
   Ren, Yan
   Liu, Chao
   Wang, Jianmei
   Wang, Jianping
   Na, Jong-Kuk
   Shakirov, Eugene V.
   Haas, Brian
   Thimmapuram, Jyothi
   Nelson, David
   Wang, Xiyin
   Bowers, John E.
   Gschwend, Andrea R.
   Delcher, Arthur L.
   Singh, Ratnesh
   Suzuki, Jon Y.
   Tripathi, Savarni
   Neupane, Kabi
   Wei, Hairong
   Irikura, Beth
   Paidi, Maya
   Jiang, Ning
   Zhang, Wenli
   Presting, Gernot
   Windsor, Aaron
   Navajas-Perez, Rafael
   Torres, Manuel J.
   Feltus, F. Alex
   Porter, Brad
   Li, Yingjun
   Burroughs, A. Max
   Luo, Ming-Cheng
   Liu, Lei
   Christopher, David A.
   Mount, Stephen M.
   Moore, Paul H.
   Sugimura, Tak
   Jiang, Jiming
   Schuler, Mary A.
   Friedman, Vikki
   Mitchell-Olds, Thomas
   Shippen, Dorothy E.
   dePamphilis, Claude W.
   Palmer, Jeffrey D.
   Freeling, Michael
   Paterson, Andrew H.
   Gonsalves, Dennis
   Wang, Lei
   Alam, Maqsudul
TI The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus)
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; ringspot virus; y-chromosome; gene; sequence; protein; dna; evolution; family; plants
AB Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 33 draft genome sequence of 'SunUp' papaya, the first commercial virus- resistant transgenic fruit tree(1) to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease- resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far(2-5), may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree- like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit- tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho- physiological, medicinal and nutritional properties.
C1 [Hou, Shaobin; Dionne-Laporte, Alexandre; Saw, Jimmy H.; Senin, Pavel; Ly, Benjamin V.; Lewis, Kanako L. T.; Alam, Maqsudul] Univ Hawaii, Dept Microbiol, Honolulu, HI 96822 USA.
   [Ming, Ray; Yu, Qingyi; Jones, Meghan R.; Skelton, Rachel L.; Murray, Jan E.; Eustice, Moriah; Tong, Eric; Wang, Ming-Li; Zhu, Yun J.; Acob, Ricelle A.; Guan, Peizhu; Blas, Andrea; Wai, Ching Man; Ackerman, Christine M.; Singh, Ratnesh; Paidi, Maya] Hawaii Agr Res Ctr, Aiea, HI 96701 USA.
   [Ming, Ray; Murray, Jan E.; Chen, Cuixia; Wang, Jianping; Na, Jong-Kuk; Gschwend, Andrea R.; Li, Yingjun] Univ Illinois, Dept Plant Biol, Urbana, IL 61801 USA.
   [Feng, Yun; Wang, Wei; Feng, Lu; Qian, Wubin; Ren, Yan; Liu, Chao; Wang, Jianmei; Wang, Lei] Nankai Univ, TEDA Sch Biol Sci & Biotechnol, Tianjin Econ Technol Dev Area, Tianjin 300457, Peoples R China.
   [Feng, Yun; Feng, Lu; Shen, Junguo; Du, Peng; Wang, Lei] Tianjin Res Ctr Funct Genom & Biochip, Tianjin Econ Technol Dev Area, Tianjin 300457, Peoples R China.
   [Wang, Wei; Feng, Lu; Wang, Lei] Nankai Univ, Coll Life Sci, Minist Educ, Key Lab Mol Microbiol & Technol, Tianjin 300071, Peoples R China.
   [Salzberg, Steven L.; Schatz, Michael; Nagarajan, Niranjan; Delcher, Arthur L.; Burroughs, A. Max; Mount, Stephen M.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
   [Eustice, Moriah; Acob, Ricelle A.; Guan, Peizhu; Blas, Andrea; Singh, Ratnesh; Paidi, Maya; Presting, Gernot; Porter, Brad; Christopher, David A.] Univ Hawaii, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA.
   [Tang, Haibao; Wang, Xiyin; Bowers, John E.; Navajas-Perez, Rafael; Torres, Manuel J.; Feltus, F. Alex; Paterson, Andrew H.] Univ Georgia, Plant Genome Mapping Lab, Athens, GA 30602 USA.
   [Lyons, Eric; Freeling, Michael] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
   [Paull, Robert E.; Wai, Ching Man; Irikura, Beth] Univ Hawaii, Dept Trop Plant & Soil Sci, Honolulu, HI 96822 USA.
   [Michael, Todd P.] Rutgers State Univ, Waksman Inst Microbiol, Piscataway, NJ 08854 USA.
   [Michael, Todd P.] Rutgers State Univ, Dept Plant Biol & Pathol, Piscataway, NJ 08854 USA.
   [Wall, Kerr; dePamphilis, Claude W.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
   [Rice, Danny W.; Palmer, Jeffrey D.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Albert, Henrik; Suzuki, Jon Y.; Tripathi, Savarni; Moore, Paul H.; Gonsalves, Dennis] ARS, USDA, Pacific Basin Agr Res Ctr, Hilo, HI 96720 USA.
   [Shakirov, Eugene V.; Shippen, Dorothy E.] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA.
   [Haas, Brian] Inst Genom Res, Rockville, MD 20850 USA.
   [Thimmapuram, Jyothi; Liu, Lei] Univ Illinois, WM Keck Ctr Comparat & Funct Genom, Urbana, IL 61801 USA.
   [Nelson, David] Univ Tennessee, Dept Mol Sci, Memphis, TN 38163 USA.
   [Neupane, Kabi] Univ Hawaii, Leeward Community Coll, Pearl City, HI 96782 USA.
   [Wei, Hairong] Wicell Res Inst, Madison, WI 53707 USA.
   [Jiang, Ning] Michigan State Univ, Dept Hort, E Lansing, MI 48824 USA.
   [Zhang, Wenli; Jiang, Jiming] Univ Wisconsin, Dept Hort, Madison, WI 53706 USA.
   [Windsor, Aaron; Mitchell-Olds, Thomas] Duke Univ, Dept Biol, Durham, NC 27708 USA.
   [Luo, Ming-Cheng] Univ Calif Davis, Dept Plant Sci, Davis, CA 95616 USA.
   [Mount, Stephen M.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
   [Sugimura, Tak] Maui High Performance Comp Ctr, Kihei, HI 96753 USA.
   [Schuler, Mary A.] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA.
   [Schuler, Mary A.] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA.
   [Schuler, Mary A.] Univ Illinois, Dept Plant Biol, Urbana, IL 61801 USA.
   [Friedman, Vikki] Appl Biosyst Inc, Foster City, CA 94404 USA.
C3 University of Hawaii System; University of Illinois System; University of Illinois Urbana-Champaign; Nankai University; Nankai University; University System of Maryland; University of Maryland College Park; University of Hawaii System; University System of Georgia; University of Georgia; University of California System; University of California Berkeley; University of Hawaii System; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Indiana University System; Indiana University Bloomington; United States Department of Agriculture (USDA); Texas A&M University System; Texas A&M University College Station; J. Craig Venter Institute; University of Illinois System; University of Illinois Urbana-Champaign; University of Tennessee System; University of Tennessee Health Science Center; University of Hawaii System; Leeward Community College; WiCell Research Institute; Michigan State University; University of Wisconsin System; University of Wisconsin Madison; Duke University; University of California System; University of California Davis; University System of Maryland; University of Maryland College Park; 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; Thermo Fisher Scientific; Applied Biosystems
RP Alam, M (corresponding author), Univ Hawaii, Dept Microbiol, Honolulu, HI 96822 USA.
EM wanglei@nankai.edu.cn; alam@hawaii.edu
FU NIGMS NIH HHS [R01 GM083873] Funding Source: Medline; NLM NIH HHS [R01 LM006845] Funding Source: Medline
NR 51
TC 792
Z9 1003
U1 1
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 24
PY 2008
VL 452
IS 7190
BP 991
EP U7
DI 10.1038/nature06856
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291PF
UT WOS:000255208600039
PM 18432245
DA 2026-03-09
ER

PT J
AU Yamasaki, M
   Li, W
   Johnson, DJD
   Huntington, JA
AF Yamasaki, Masayuki
   Li, Wei
   Johnson, Daniel J. D.
   Huntington, James A.
TI Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization
SO NATURE
LA English
DT Article
ID plasminogen-activator inhibitor-1; alpha(1)-antitrypsin; mechanism; denaturation; deficiency; peptides; dementia; pathway; region; model
AB Repeating intermolecular protein association by means of beta-sheet expansion is the mechanism underlying a multitude of diseases including Alzheimer's, Huntington's and Parkinson's and the prion encephalopathies(1). A family of proteins, known as the serpins, also forms large stable multimers by ordered beta-sheet linkages leading to intracellular accretion and disease(2). These 'serpinopathies' include early- onset dementia caused by mutations in neuroserpin, liver cirrhosis and emphysema caused by mutations in alpha(1)- antitrypsin (alpha(1)AT), and thrombosis caused by mutations in antithrombin(3). Serpin structure and function are quite well understood, and the family has therefore become a model system for understanding the beta-sheet expansion disorders collectively known as the conformational diseases(4). To develop strategies to prevent and reverse these disorders, it is necessary to determine the structural basis of the intermolecular linkage and of the pathogenic monomeric state. Here we report the crystallographic structure of a stable serpin dimer which reveals a domain swap of more than 50 residues, including two long antiparallel beta-strands inserting in the centre of the principal b-sheet of the neighbouring monomer. This structure explains the extreme stability of serpin polymers, the molecular basis of their rapid propagation, and provides critical new insights into the structural changes which initiate irreversible beta-sheet expansion.
C1 [Yamasaki, Masayuki; Li, Wei; Johnson, Daniel J. D.; Huntington, James A.] Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
C3 University of Cambridge
RP Huntington, JA (corresponding author), Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Wellcome Trust MRC Bldg,Hills Rd, Cambridge CB2 0XY, England.
EM jah52@cam.ac.uk
FU National Institutes of Health (USA); Uehara Memorial Foundation Japan
NR 39
TC 209
Z9 224
U1 0
U2 48
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1255
EP U65
DI 10.1038/nature07394
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100048
PM 18923394
DA 2026-03-09
ER

PT J
AU Downs, JP
   Daeschler, EB
   Jenkins, FA
   Shubin, NH
AF Downs, Jason P.
   Daeschler, Edward B.
   Jenkins, Farish A., Jr.
   Shubin, Neil H.
TI The cranial endoskeleton of Tiktaalik roseae
SO NATURE
LA English
DT Article
ID earliest-known tetrapod; early evolution; devonian fish; braincase; stapes; australia; origin; ear
AB Among themorphological changes that occurred during the 'fish- to- tetrapod' transition was a marked reorganization of the cranial endoskeleton. Details of this transition, including the sequence of character acquisition, have not been evident from the fossil record. Here we describe the braincase, palatoquadrate and branchial skeleton of Tiktaalik roseae, the Late Devonian sarcopterygian fish most closely related to tetrapods. Although retaining a primitive configuration in many respects, the cranial endoskeleton of T. roseae shares derived features with tetrapods such as a large basal articulation and a flat, horizontally oriented entopterygoid. Other features in T. roseae, like the short, straight hyomandibula, show morphology intermediate between the condition observed in more primitive fish and that observed in tetrapods. The combination of characters in T. roseae helps to resolve the relative timing of modifications in the cranial endoskeleton. The sequence of modifications suggests changes in head mobility and intracranial kinesis that have ramifications for the origin of vertebrate terrestriality.
C1 [Downs, Jason P.; Daeschler, Edward B.] Acad Nat Sci Philadelphia, Philadelphia, PA 19103 USA.
   [Jenkins, Farish A., Jr.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Jenkins, Farish A., Jr.] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA.
   [Shubin, Neil H.] Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA.
   [Shubin, Neil H.] Field Museum Nat Hist, Chicago, IL 60605 USA.
C3 Drexel University; Harvard University; Harvard University; University of Chicago; Field Museum of Natural History (Chicago)
RP Downs, JP (corresponding author), Acad Nat Sci Philadelphia, 1900 Benjamin Franklin Pkwy, Philadelphia, PA 19103 USA.
EM downs@ansp.org; nshubin@uchicago.edu
FU Polar Continental Shelf Project; Canadian Museum of Nature; Academy of Natural Sciences of Philadelphia; Putnam Expeditionary Fund (Harvard University); University of Chicago; National Science Foundation; National Geographic Society Committee for Research and Exploration
NR 31
TC 52
Z9 62
U1 3
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 925
EP 929
DI 10.1038/nature07189
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300041
PM 18923515
DA 2026-03-09
ER

PT J
AU Irifune, T
   Higo, Y
   Inoue, T
   Kono, Y
   Ohfuji, H
   Funakoshi, K
AF Irifune, T.
   Higo, Y.
   Inoue, T.
   Kono, Y.
   Ohfuji, H.
   Funakoshi, K.
TI Sound velocities of majorite garnet and the composition of the mantle transition region
SO NATURE
LA English
DT Article
ID seismic discontinuity; spinel transitions; high-temperatures; wave velocity; high-pressure; gpa; ringwoodite; elasticity; phase; constraints
AB The composition of the mantle transition region, characterized by anomalous seismic- wave velocity and density changes at depths of similar to 400 to 700 km, has remained controversial. Some have proposed that the mantle transition region has an olivine- rich 'pyrolite' composition(1,2), whereas others have inferred that it is characterized by pyroxene- and garnet- rich compositions ('piclogite'), because the sound velocities in pyrolite estimated from laboratory data are substantially higher than those seismologically observed(3-5). Although the velocities of the olivine polymorphs at these pressures ( wadsleyite and ringwoodite) have been well documented, those of majorite ( another significant high- pressure phase in the mantle transition region) with realistic mantle compositions have never been measured. Here we use combined in situ X- ray and ultrasonic measurements under the pressure and temperature conditions of the mantle transition region to show that majorite in a pyrolite composition has sound velocities substantially lower than those of earlier estimates, owing to strong nonlinear decreases at high temperature, particularly for shear- wave velocity. We found that pyrolite yields seismic velocities more consistent with typical seismological models than those of piclogite in the upper to middle parts of the region, except for the potentially larger velocity jumps in pyrolite relative to those observed at a depth of 410 km. In contrast, both of these compositions lead to significantly low shear- wave velocities in the lower part of the region, suggesting possible subadiabatic temperatures or the existence of a layer of harzburgite- rich material supplied by the subducted slabs stagnant at these depths.
C1 [Irifune, T.; Higo, Y.; Inoue, T.; Kono, Y.; Ohfuji, H.] Ehime Univ, Geodynam Res Ctr, Matsuyama, Ehime 7908577, Japan.
   [Higo, Y.; Funakoshi, K.] Japan Synchrotron Res Inst, Hyogo 6795198, Japan.
C3 Ehime University; Japan Synchrotron Radiation Research Institute
RP Irifune, T (corresponding author), Ehime Univ, Geodynam Res Ctr, Matsuyama, Ehime 7908577, Japan.
EM irifune@dpc.ehime-u.ac.jp
FU Grants-in-Aid for Scientific Research [20244086] Funding Source: KAKEN
NR 29
TC 136
Z9 163
U1 2
U2 71
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 814
EP 817
DI 10.1038/nature06551
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400039
PM 18273016
DA 2026-03-09
ER

PT J
AU Knollmann, BC
   Roden, DM
AF Knollmann, Bjorn C.
   Roden, Dan M.
TI A genetic framework for improving arrhythmia therapy
SO NATURE
LA English
DT Article
ID cardiac ryanodine receptor; left-ventricular dysfunction; polyunsaturated fatty-acids; long-qt syndrome; recent myocardial-infarction; calmodulin kinase-ii; reticulum ca2+ leak; atrial-fibrillation; drug-therapy; sudden-death
AB Abnormalities in heart rhythm continue to cause high rates of illness and death. Better treatment could be provided by solving two main challenges: the early identification of patients who are at risk, and the characterization of molecular pathways that culminate in arrhythmias. By analysing mechanisms that increase susceptibility to arrhythmia in individuals with genetic syndromes, it might be possible to improve current therapies and to develop new ways to treat and prevent common arrhythmias.
C1 [Knollmann, Bjorn C.; Roden, Dan M.] Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA.
C3 Vanderbilt University
RP Roden, DM (corresponding author), Vanderbilt Univ, Sch Med, 1285 Med Res Bldg 4, Nashville, TN 37232 USA.
EM dan.roden@vanderbilt.edu
NR 100
TC 60
Z9 80
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 929
EP 936
DI 10.1038/nature06799
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100033
PM 18288182
DA 2026-03-09
ER

PT J
AU Rader, DJ
   Daugherty, A
AF Rader, Daniel J.
   Daugherty, Alan
TI Translating molecular discoveries into new therapies for atherosclerosis
SO NATURE
LA English
DT Article
ID coronary-artery-disease; apoe-deficient mice; randomized controlled-trial; high-density-lipoproteins; smooth-muscle-cells; transport in-vivo; cardiovascular-disease; myocardial-infarction; apolipoprotein-e; plaque rupture
AB Atherosclerosis is characterized by the thickening of the arterial wall and is the primary cause of coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. Clinical trials have confirmed that certain lipoproteins and the renin-angiotensin-aldosterone system are important in the pathogenesis of atherosclerotic cardiovascular disease, and that interventions targeted towards these are beneficial. Furthermore, efforts to understand how risk factors such as high blood pressure, dysregulated blood lipids and diabetes contribute to atherosclerotic disease, as well as to understand the molecular pathogenesis of atherosclerotic plaques, are leading to new targets for therapy.
C1 [Rader, Daniel J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
   [Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
   [Daugherty, Alan] Univ Kentucky, Cardiovasc Res Ctr, Lexington, KY 40536 USA.
   [Daugherty, Alan] Univ Kentucky, Gill Heart Inst, Lexington, KY 40536 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Kentucky; University of Kentucky
RP Rader, DJ (corresponding author), Univ Penn, Sch Med, Cardiovasc Inst, 654 BRBII-III,421 Curie Blvd, Philadelphia, PA 19104 USA.
EM rader@mail.med.upenn.edu
NR 100
TC 406
Z9 503
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 FEB 21
PY 2008
VL 451
IS 7181
BP 904
EP 913
DI 10.1038/nature06796
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100030
PM 18288179
DA 2026-03-09
ER

PT J
AU White, MA
   Eykelenboom, JK
   Lopez-Vernaza, MA
   Wilson, E
   Leach, DRF
AF White, Martin A.
   Eykelenboom, John K.
   Lopez-Vernaza, Manuel A.
   Wilson, Emily
   Leach, David R. F.
TI Non-random segregation of sister chromosomes in Escherichia coli
SO NATURE
LA English
DT Article
ID separate cell halves; immortal strand hypothesis; bacterial chromosome; dna-polymerase; stem-cells; replication; organization; region; arms; mreb
AB It has long been known that the 59 to 39 polarity of DNA synthesis results in both a leading and lagging strand at all replication forks(1). Until now, however, there has been no evidence that leading or lagging strands are spatially organized in any way within a cell. Here we show that chromosome segregation in Escherichia coli is not random but is driven in a manner that results in the leading and lagging strands being addressed to particular cellular destinations. These destinations are consistent with the known patterns of chromosome segregation(2,3). Our work demonstrates a new level of organization relating to the replication and segregation of the E. coli chromosome.
C1 [White, Martin A.; Eykelenboom, John K.; Lopez-Vernaza, Manuel A.; Wilson, Emily; Leach, David R. F.] Univ Edinburgh, Sch Biol Sci, Inst Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
C3 University of Edinburgh
RP Leach, DRF (corresponding author), Univ Edinburgh, Sch Biol Sci, Inst Cell Biol, Kings Bldg, Edinburgh EH9 3JR, Midlothian, Scotland.
EM D.Leach@ed.ac.uk
FU Medical Research Council; MRC [G0401313] Funding Source: UKRI; Medical Research Council [G0401313] Funding Source: researchfish
NR 30
TC 61
Z9 66
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1248
EP 1250
DI 10.1038/nature07282
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100046
PM 18972020
DA 2026-03-09
ER

PT J
AU Tolstoy, M
   Waldhauser, F
   Bohnenstiehl, DR
   Weekly, RT
   Kim, WY
AF Tolstoy, M.
   Waldhauser, F.
   Bohnenstiehl, D. R.
   Weekly, R. T.
   Kim, W. -Y.
TI Seismic identification of along-axis hydrothermal flow on the East Pacific Rise
SO NATURE
LA English
DT Article
ID ridge spreading centers; midocean ridge; sea-floor; oceanic-crust; magma chamber; heat-flow; 9-degrees-n; california; beneath; fluids
AB Hydrothermal circulation at the axis of mid- ocean ridges affects the chemistry of the lithosphere and overlying ocean, supports chemosynthetic biological communities and is responsible for significant heat transfer from the lithosphere to the ocean(1-3). It is commonly thought that flow in these systems is oriented across the ridge axis, with recharge occurring along off- axis faults(4-6), but the structure and scale of hydrothermal systems are usually inferred from thermal and geochemical models constrained by the geophysical setting(7-9), rather than direct observations. The presence of microearthquakes may shed light on hydrothermal pathways by revealing zones of thermal cracking where cold sea water extracts heat from hot crustal rocks, as well as regions where magmatic and tectonic stresses create fractures that increase porosity and permeability. Here we show that hypocentres beneath a well- studied hydrothermal vent field on the East Pacific Rise cluster in a vertical pipe- like zone near a small axial discontinuity, and in a band that lies directly above the axial magma chamber. The location of the shallow pipe- like cluster relative to the distribution and temperature of hydrothermal vents along this section of the ridge suggests that hydrothermal recharge may be concentrated there as a consequence of the permeability generated by tectonic fracturing. Furthermore, we interpret the band of seismicity above the magma chamber as a zone of hydrothermal cracking, which suggests that hydrothermal circulation may be strongly aligned along the ridge axis. We conclude that models that suggest that hydrothermal cells are oriented across- axis, with diffuse off- axis recharge zones, may not apply to the fast- spreading East Pacific Rise.
C1 [Tolstoy, M.; Waldhauser, F.; Bohnenstiehl, D. R.; Weekly, R. T.; Kim, W. -Y.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
C3 Columbia University
RP Tolstoy, M (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, 61 Route 9W, Palisades, NY 10964 USA.
EM tolstoy@ldeo.columbia.edu
NR 34
TC 126
Z9 145
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 181
EP U7
DI 10.1038/nature06424
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400040
PM 18185585
DA 2026-03-09
ER

PT J
AU Sims, DW
   Southall, EJ
   Humphries, NE
   Hays, GC
   Bradshaw, CJA
   Pitchford, JW
   James, A
   Ahmed, MZ
   Brierley, AS
   Hindell, MA
   Morritt, D
   Musyl, MK
   Righton, D
   Shepard, ELC
   Wearmouth, VJ
   Wilson, RP
   Witt, MJ
   Metcalfe, JD
AF Sims, David W.
   Southall, Emily J.
   Humphries, Nicolas E.
   Hays, Graeme C.
   Bradshaw, Corey J. A.
   Pitchford, Jonathan W.
   James, Alex
   Ahmed, Mohammed Z.
   Brierley, Andrew S.
   Hindell, Mark A.
   Morritt, David
   Musyl, Michael K.
   Righton, David
   Shepard, Emily L. C.
   Wearmouth, Victoria J.
   Wilson, Rory P.
   Witt, Matthew J.
   Metcalfe, Julian D.
TI Scaling laws of marine predator search behaviour
SO NATURE
LA English
DT Article
ID patterns; zooplankton; movements; success
AB Many free- ranging predators have to make foraging decisions with little, if any, knowledge of present resource distribution and availability(1). The optimal search strategy they should use to maximize encounter rates with prey in heterogeneous natural environments remains a largely unresolved issue in ecology(1-3). Levy walks(4) are specialized random walks giving rise to fractal movement trajectories that may represent an optimal solution for searching complex landscapes(5). However, the adaptive significance of this putative strategy in response to natural prey distributions remains untested(6,7). Here we analyse over a million movement displacements recorded from animal- attached electronic tags to show that diverse marine predators - sharks, bony fishes, sea turtles and penguins - exhibit Levy- walk- like behaviour close to a theoretical optimum(2). Prey density distributions also display Levy- like fractal patterns, suggesting response movements by predators to prey distributions. Simulations show that predators have higher encounter rates when adopting Levy- type foraging in natural- like prey fields compared with purely random landscapes. This is consistent with the hypothesis that observed search patterns are adapted to observed statistical patterns of the landscape. This may explain why Levy- like behaviour seems to be widespread among diverse organisms(3), from microbes(8) to humans(9), as a `rule' that evolved in response to patchy resource distributions.
C1 [Sims, David W.; Southall, Emily J.; Humphries, Nicolas E.; Wearmouth, Victoria J.] Marine Biol Assoc United Kingdom Lab, Plymouth PL1 2PB, Devon, England.
   [Sims, David W.] Univ Plymouth, Marine Biol & Ecol Res Ctr, Sch Biol Sci, Plymouth PL4 8AA, Devon, England.
   [Ahmed, Mohammed Z.] Univ Plymouth, Sch Comp Commun & Elect, Plymouth PL4 8AA, Devon, England.
   [Hays, Graeme C.; Shepard, Emily L. C.; Wilson, Rory P.] Univ Coll Swansea, Dept Biol Sci, Inst Environm Sustainabil, Swansea SA2 8PP, W Glam, Wales.
   [Bradshaw, Corey J. A.] Charles Darwin Univ, Sch Environm Res, Darwin, NT 0909, Australia.
   [Pitchford, Jonathan W.; James, Alex] Univ York, Dept Biol, York YO10 5YW, N Yorkshire, England.
   [Pitchford, Jonathan W.; James, Alex] Univ York, York Ctr Complex Syst Anal, York YO10 5YW, N Yorkshire, England.
   [James, Alex] Univ Canterbury, Dept Math & Stat, Christchurch 1, New Zealand.
   [Brierley, Andrew S.] Univ St Andrews, Gatty Marine Lab, Sch Biol, St Andrews KY16 8LB, Fife, Scotland.
   [Hindell, Mark A.] Univ Tasmania, Sch Zool, Hobart, Tas 7001, Australia.
   [Morritt, David] Univ London Royal Holloway & Bedford New Coll, Sch Biol Sci, Egham TW20 0EX, Surrey, England.
   [Musyl, Michael K.] Univ Hawaii Manoa, Joint Inst Marine & Atmospher Res, Pelag Fisheries Res Programme, Kewalo Res Facil,NOAA Fisheries, Honolulu, HI 96814 USA.
   [Righton, David; Metcalfe, Julian D.] Ctr Environm Fisheries & Aquaculture Sci, Lowestoft Lab, Lowestoft NR33 0HT, Suffolk, England.
   [Witt, Matthew J.] Univ Exeter, Ctr Ecol & Conservat, Cornwall TR10 9EZ, England.
C3 Marine Biological Association United Kingdom; University of Plymouth; University of Plymouth; Swansea University; Charles Darwin University; University of York - UK; University of York - UK; University of Canterbury; University of St Andrews; University of Tasmania; University of London; Royal Holloway University London; University of Hawaii System; University of Hawaii Manoa; National Oceanic Atmospheric Admin (NOAA) - USA; Centre for Environment Fisheries & Aquaculture Science; University of Exeter
RP Sims, DW (corresponding author), Marine Biol Assoc United Kingdom Lab, Citadel Hill, Plymouth PL1 2PB, Devon, England.
EM dws@mba.ac.uk
FU Natural Environment Research Council [NER/A/S/2001/01053, NER/A/S/2003/00302, mba010004, NER/G/S/2001/00012, NER/A/S/2001/01251] Funding Source: researchfish; NERC [mba010004] Funding Source: UKRI
NR 31
TC 804
Z9 883
U1 5
U2 408
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1098
EP U5
DI 10.1038/nature06518
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600040
PM 18305542
DA 2026-03-09
ER

PT J
AU Christianson, AD
   Goremychkin, EA
   Osborn, R
   Rosenkranz, S
   Lumsden, MD
   Malliakas, CD
   Todorov, IS
   Claus, H
   Chung, DY
   Kanatzidis, MG
   Bewley, RI
   Guidi, T
AF Christianson, A. D.
   Goremychkin, E. A.
   Osborn, R.
   Rosenkranz, S.
   Lumsden, M. D.
   Malliakas, C. D.
   Todorov, I. S.
   Claus, H.
   Chung, D. Y.
   Kanatzidis, M. G.
   Bewley, R. I.
   Guidi, T.
TI Unconventional superconductivity in Ba0.6K0.4Fe2As2 from inelastic neutron scattering
SO NATURE
LA English
DT Article
ID magnetic excitations; lao1-xfxfeas
AB A new family of superconductors containing layers of iron arsenide(1-3) has attracted considerable interest because of their high transition temperatures (T-c), some of which are > 50 K, and because of similarities with the high-T-c copper oxide superconductors. In both the iron arsenides and the copper oxides, superconductivity arises when an antiferromagnetically ordered phase has been suppressed by chemical doping(4). A universal feature of the copper oxide superconductors is the existence of a resonant magnetic excitation, localized in both energy and wavevector, within the superconducting phase(5-9). This resonance, which has also been observed in several heavy- fermion superconductors(10-12), is predicted to occur when the sign of the superconducting energy gap takes opposite values on different parts of the Fermi surface(13), an unusual gap symmetry which implies that the electron pairing interaction is repulsive at short range(14). Angle- resolved photoelectron spectroscopy shows no evidence of gap anisotropy in the iron arsenides, but such measurements are insensitive to the phase of the gap on separate parts of the Fermi surface(15). Here we report inelastic neutron scattering observations of a magnetic resonance below T-c in Ba0.6K0.4Fe2As2, a phase- sensitive measurement demonstrating that the superconducting energy gap has unconventional symmetry in the iron arsenide superconductors.
C1 [Goremychkin, E. A.; Osborn, R.; Rosenkranz, S.; Malliakas, C. D.; Todorov, I. S.; Claus, H.; Chung, D. Y.; Kanatzidis, M. G.] Argonne Natl Lab, Div Mat Sci, Argonne, IL 60439 USA.
   [Christianson, A. D.; Lumsden, M. D.] Oak Ridge Natl Lab, Neutron Scattering Sci Div, Oak Ridge, TN 37831 USA.
   [Goremychkin, E. A.; Bewley, R. I.; Guidi, T.] Rutherford Appleton Lab, ISIS Pulsed Neutron & Muon Facil, Didcot OX11 0QX, Oxon, England.
   [Malliakas, C. D.; Kanatzidis, M. G.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
C3 United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Oak Ridge National Laboratory; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; Northwestern University
RP Osborn, R (corresponding author), Argonne Natl Lab, Div Mat Sci, 9700 S Cass Ave, Argonne, IL 60439 USA.
EM rosborn@anl.gov
FU Division of Materials Sciences; Engineering Division; Scientific User Facilities Division of the Office of Basic Energy Sciences; US Department of Energy Office of Science.
NR 25
TC 546
Z9 599
U1 1
U2 109
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 930
EP 932
DI 10.1038/nature07625
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300040
PM 19092931
DA 2026-03-09
ER

PT J
AU Sumbre, G
   Muto, A
   Baier, H
   Poo, MM
AF Sumbre, German
   Muto, Akira
   Baier, Herwig
   Poo, Mu-ming
TI Entrained rhythmic activities of neuronal ensembles as perceptual memory of time interval
SO NATURE
LA English
DT Article
ID event-related potentials; in-vivo; prefrontal cortex; larval zebrafish; optic tectum; psychophysics; networks; protein; macaque; retina
AB The ability to process temporal information is fundamental to sensory perception, cognitive processing and motor behaviour of all living organisms, from amoebae to humans(1-4). Neural circuit mechanisms based on neuronal and synaptic properties have been shown to process temporal information over the range of tens of microseconds to hundreds of milliseconds(5-7). How neural circuits process temporal information in the range of seconds to minutes is much less understood. Studies of working memory in monkeys and rats have shown that neurons in the prefrontal cortex(8-10), the parietal cortex(9,11) and the thalamus(12) exhibit ramping activities that linearly correlate with the lapse of time until the end of a specific time interval of several seconds that the animal is trained to memorize. Many organisms can also memorize the time interval of rhythmic sensory stimuli in the timescale of seconds and can coordinate motor behaviour accordingly, for example, by keeping the rhythm after exposure to the beat of music. Here we report a form of rhythmic activity among specific neuronal ensembles in the zebrafish optic tectum, which retains the memory of the time interval ( in the order of seconds) of repetitive sensory stimuli for a duration of up to similar to 20 s. After repetitive visual conditioning stimulation ( CS) of zebrafish larvae, we observed rhythmic post-CS activities among specific tectal neuronal ensembles, with a regular interval that closely matched the CS. Visuomotor behaviour of the zebrafish larvae also showed regular post- CS repetitions at the entrained time interval that correlated with rhythmic neuronal ensemble activities in the tectum. Thus, rhythmic activities among specific neuronal ensembles may act as an adjustable 'metronome' for time intervals in the order of seconds, and serve as a mechanism for the short- term perceptual memory of rhythmic sensory experience.
C1 [Sumbre, German; Poo, Mu-ming] Univ Calif Berkeley, Helen Wills Neurosci Inst, Dept Mol & Cell Biol, Div Neurobiol, Berkeley, CA 94720 USA.
   [Muto, Akira; Baier, Herwig] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California San Francisco
RP Poo, MM (corresponding author), Univ Calif Berkeley, Helen Wills Neurosci Inst, Dept Mol & Cell Biol, Div Neurobiol, Berkeley, CA 94720 USA.
EM mpoo@berkeley.edu
FU US National Institutes of Health
NR 38
TC 112
Z9 124
U1 0
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 6
PY 2008
VL 456
IS 7218
BP 102
EP U6
DI 10.1038/nature07351
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000049
PM 18923391
DA 2026-03-09
ER

PT J
AU Seale, P
   Bjork, B
   Yang, WL
   Kajimura, S
   Chin, S
   Kuang, SH
   Scimè, A
   Devarakonda, S
   Conroe, HM
   Erdjument-Bromage, H
   Tempst, P
   Rudnicki, MA
   Beier, DR
   Spiegelman, BM
AF Seale, Patrick
   Bjork, Bryan
   Yang, Wenli
   Kajimura, Shingo
   Chin, Sherry
   Kuang, Shihuan
   Scime, Anthony
   Devarakonda, Srikripa
   Conroe, Heather M.
   Erdjument-Bromage, Hediye
   Tempst, Paul
   Rudnicki, Michael A.
   Beier, David R.
   Spiegelman, Bruce M.
TI PRDM16 controls a brown fat/skeletal muscle switch
SO NATURE
LA English
DT Article
ID adipose-tissue; ppar-gamma; adipocyte differentiation; white fat; uncoupling protein; skeletal-muscle; gene-expression; satellite cells; adult humans; stem-cells
AB Brown fat can increase energy expenditure and protect against obesity through a specialized program of uncoupled respiration. Here we show by in vivo fate mapping that brown, but not white, fat cells arise from precursors that express Myf5, a gene previously thought to be expressed only in the myogenic lineage. We also demonstrate that the transcriptional regulator PRDM16 ( PRD1- BF1- RIZ1 homologous domain containing 16) controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation. Conversely, ectopic expression of PRDM16 in myoblasts induces their differentiation into brown fat cells. PRDM16 stimulates brown adipogenesis by binding to PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and activating its transcriptional function. Finally, Prdm16-deficient brown fat displays an abnormal morphology, reduced thermogenic gene expression and elevated expression of muscle-specific genes. Taken together, these data indicate that PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis.
C1 [Seale, Patrick; Yang, Wenli; Kajimura, Shingo; Chin, Sherry; Devarakonda, Srikripa; Conroe, Heather M.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Seale, Patrick; Yang, Wenli; Kajimura, Shingo; Chin, Sherry; Devarakonda, Srikripa; Conroe, Heather M.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Bjork, Bryan; Beier, David R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Kuang, Shihuan; Scime, Anthony; Rudnicki, Michael A.] Ottawa Hlth Res Inst, Program Mol Med, Sprott Ctr Stem Cell Res, Ottawa, ON K1H 8L6, Canada.
   [Erdjument-Bromage, Hediye; Tempst, Paul] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Ottawa; Ottawa Hospital Research Institute; Memorial Sloan Kettering Cancer Center
RP Spiegelman, BM (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu
FU American Heart Association; Japan Society for the Promotion of Science; Susan Komen Breast Cancer Foundation; Picower Foundation; National Institutes of Health; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR044031] Funding Source: NIH RePORTER
NR 44
TC 1874
Z9 2315
U1 4
U2 288
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 21
PY 2008
VL 454
IS 7207
BP 961
EP U27
DI 10.1038/nature07182
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000031
PM 18719582
DA 2026-03-09
ER

PT J
AU Dick, IE
   Tadross, MR
   Liang, HY
   Tay, LH
   Yang, WJ
   Yue, DT
AF Dick, Ivy E.
   Tadross, Michael R.
   Liang, Haoya
   Tay, Lai Hock
   Yang, Wanjun
   Yue, David T.
TI A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels
SO NATURE
LA English
DT Article
ID gated calcium-channel; ca2+-dependent inactivation; beta-subunit; facilitation; mechanisms; expression; reveals; gamma; fret
AB Ca2+/ calmodulin- dependent regulation of voltage- gated Ca(V)1 - 2 Ca2+ channels shows extraordinary modes of spatial Ca2+ decoding and channel modulation(1-6), vital for many biological functions(6-9). A single calmodulin ( CaM) molecule associates constitutively with the channel's carboxy- terminal tail(3,10-13), and Ca2+ binding to the C- terminal and N- terminal lobes of CaM can each induce distinct channel regulations(2,14). As expected from close channel proximity, the C- lobe responds to the roughly 100-mu M Ca2+ pulses driven by the associated channel(15,16), a behaviour defined as 'local Ca2+ selectivity'. Conversely, all previous observations have indicated that the N- lobe somehow senses the far weaker signals from distant Ca2+ sources(2,3,17,18). This 'global Ca2+ selectivity' satisfies a general signalling requirement, enabling a resident molecule to remotely sense cellular Ca2+ activity, which would otherwise be overshadowed by Ca2+ entry through the host channel(5,6). Here we show that the spatial Ca2+ selectivity of N- lobe CaM regulation is not invariably global but can be switched by a novel Ca2+/CaM- binding site within the amino terminus of channels ( NSCaTE, for N- terminal spatial Ca2+ transforming element). Native Ca(V)2.2 channels lack this element and show N- lobe regulation with a global selectivity. On the introduction of NSCaTE into these channels, spatial Ca2+ selectivity transforms from a global to local profile. Given this effect, we examined Ca(V)1.2/ Ca(V)1.3 channels, which naturally contain NSCaTE, and found that their N- lobe selectivity is indeed local. Disruption of this element produces a global selectivity, confirming the native function of NSCaTE. Thus, differences in spatial selectivity between advanced Ca(V)1 and Ca(V)2 channel isoforms are explained by the presence or absence of NSCaTE. Beyond functional effects, the position of NSCaTE on the channel's amino terminus indicates that CaM can bridge the amino terminus and carboxy terminus of channels. Finally, the modularity of NSCaTE offers practical means for understanding the basis of global Ca2+ selectivity(19).
C1 [Dick, Ivy E.; Tadross, Michael R.; Liang, Haoya; Tay, Lai Hock; Yang, Wanjun; Yue, David T.] Johns Hopkins Univ, Sch Med, Calcium Signals Lab, Dept Biomed Engn, Baltimore, MD 21205 USA.
   [Dick, Ivy E.; Tadross, Michael R.; Liang, Haoya; Tay, Lai Hock; Yang, Wanjun; Yue, David T.] Johns Hopkins Univ, Sch Med, Calcium Signals Lab, Dept Neurosci, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Yue, DT (corresponding author), Johns Hopkins Univ, Sch Med, Calcium Signals Lab, Dept Biomed Engn, Ross Bldg,Room 713,720 Rutland Ave, Baltimore, MD 21205 USA.
EM dyue@bme.jhu.edu
FU National Institute on Deafness and Other Communication Disorders [T32DC000023] Funding Source: NIH RePORTER; NHLBI NIH HHS [R37 HL076795] Funding Source: Medline; NIDCD NIH HHS [P30 DC005211, T32 DC000023] Funding Source: Medline; NIMH NIH HHS [R01 MH065531] Funding Source: Medline
NR 38
TC 208
Z9 241
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2008
VL 451
IS 7180
BP 830
EP U9
DI 10.1038/nature06529
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400043
PM 18235447
DA 2026-03-09
ER

PT J
AU Stymiest, JL
   Bagutski, V
   French, RM
   Aggarwal, VK
AF Stymiest, Jake L.
   Bagutski, Viktor
   French, Rosalind M.
   Aggarwal, Varinder K.
TI Enantiodivergent conversion of chiral secondary alcohols into tertiary alcohols
SO NATURE
LA English
DT Article
ID asymmetric transfer hydrogenation; electrophilic substitution; carbonyl-compounds; boronic esters; ketones; additions; reagents; catalyst; construction; thalidomide
AB From receptors in the nose to supramolecular biopolymers, nature shows a remarkable degree of specificity in the recognition of chiral molecules, resulting in the mirror image arrangements of the two forms eliciting quite different biological responses(1,2). It is thus critically important that during a chemical synthesis of chiral molecules only one of the two three- dimensional arrangements is created. Although certain classes of chiral molecules ( for example secondary alcohols(3,4)) are now easy to make selectively in the single mirror image form, one class - those containing quaternary stereogenic centres ( a carbon atom with four different non- hydrogen substituents) - remains a great challenge(5-8). Here we present a general solution to this problem which takes easily obtainable secondary alcohols in their single mirror image form and in a two- step sequence converts them into tertiary alcohols ( quaternary stereogenic centres). The overall process involves removing the hydrogen atom ( attached to carbon) of the secondary alcohol and effectively replacing it with an alkyl, alkenyl or aryl group. Furthermore, starting from a single mirror image form of the secondary alcohol, either mirror image form of the tertiary alcohol can be made with high levels of stereo control. Thus, a broad range of tertiary alcohols can now be easily made by this method with very high levels of selectivity. We expect that this methodology could find widespread application, as the intermediate tertiary boronic esters can potentially be converted into a range of functional groups with retention of configuration.
C1 [Stymiest, Jake L.; Bagutski, Viktor; French, Rosalind M.; Aggarwal, Varinder K.] Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England.
C3 University of Bristol
RP Aggarwal, VK (corresponding author), Univ Bristol, Sch Chem, Cantocks Close, Bristol BS8 1TS, Avon, England.
EM v.aggarwal@bristol.ac.uk
FU EPSRC; Merck; Royal Society for a Wolfson Research Merit Award; Senior Research Fellowship
NR 30
TC 346
Z9 394
U1 3
U2 109
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 778
EP U61
DI 10.1038/nature07592
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900046
PM 19079057
DA 2026-03-09
ER

PT J
AU Schenk, P
   Matsuyama, I
   Nimmo, F
AF Schenk, Paul
   Matsuyama, Isamu
   Nimmo, Francis
TI True polar wander on Europa from global-scale small-circle depressions
SO NATURE
LA English
DT Article
ID ice shell; reorientation; convergence; tectonics; planets; surface
AB The tectonic patterns and stress history of Europa are exceedingly complex(1) and many large-scale features remain unexplained. True polar wander, involving reorientation of Europa's floating outer ice shell about the tidal axis with Jupiter, has been proposed(2) as a possible explanation for some of the features. This mechanism is possible if the icy shell is latitudinally variable in thickness and decoupled from the rocky interior. It would impose high stress levels on the shell, leading to predictable fracture patterns(3). No satisfactory match to global-scale features has hitherto been found for polar wander stress patterns(3). Here we describe broad arcuate troughs and depressions on Europa that do not fit other proposed stress mechanisms in their current position. Using imaging from three spacecraft, we have mapped two global-scale organized concentric antipodal sets of arcuate troughs up to hundreds of kilometres long and 300 m to similar to 1.5 km deep. An excellent match to these features is found with stresses caused by an episode of 806 true polar wander. These depressions also appear to be geographically related to other large-scale bright and dark lineaments(4,5), suggesting that many of Europa's tectonic patterns may also be related to true polar wander.
C1 [Schenk, Paul] Lunar & Planetary Inst, Houston, TX 77058 USA.
   [Matsuyama, Isamu] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
   [Nimmo, Francis] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
C3 Carnegie Institution for Science; University of California System; University of California Santa Cruz
RP Schenk, P (corresponding author), Lunar & Planetary Inst, 3303 NASA Rd 1, Houston, TX 77058 USA.
EM schenk@lpi.usra.edu
NR 29
TC 57
Z9 76
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 15
PY 2008
VL 453
IS 7193
BP 368
EP 371
DI 10.1038/nature06911
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400046
PM 18480819
DA 2026-03-09
ER

PT J
AU Gubbels, SP
   Woessner, DW
   Mitchell, JC
   Ricci, AJ
   Brigande, JV
AF Gubbels, Samuel P.
   Woessner, David W.
   Mitchell, John C.
   Ricci, Anthony J.
   Brigande, John V.
TI Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer
SO NATURE
LA English
DT Article
ID inner-ear development; hearing-loss; myosin viia; math1; mouse; therapy; mechanotransduction; replacement; expression; generation
AB Sensory hair cells in the mammalian cochlea convert mechanical stimuli into electrical impulses that subserve audition(1,2). Loss of hair cells and their innervating neurons is the most frequent cause of hearing impairment(3). Atonal homologue 1 ( encoded by Atoh1, also known as Math1) is a basic helix - loop - helix transcription factor required for hair- cell development(4-6), and its misexpression in vitro(7,8) and in vivo(9,10) generates hair- cell- like cells. Atoh1- based gene therapy to ameliorate auditory(10) and vestibular(11) dysfunction has been proposed. However, the biophysical properties of putative hair cells induced by Atoh1 misexpression have not been characterized. Here we show that in utero gene transfer of Atoh1 produces functional supernumerary hair cells in the mouse cochlea. The induced hair cells display stereociliary bundles, attract neuronal processes and express the ribbon synapse marker carboxyterminal binding protein 2 ( refs 12,13). Moreover, the hair cells are capable of mechanoelectrical transduction(1,2) and show basolateral conductances with age- appropriate specializations. Our results demonstrate that manipulation of cell fate by transcription factor misexpression produces functional sensory cells in the postnatal mammalian cochlea. We expect that our in utero gene transfer paradigm will enable the design and validation of gene therapies to ameliorate hearing loss in mouse models of human deafness(14,15).
C1 [Gubbels, Samuel P.; Woessner, David W.; Brigande, John V.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Dept Otolaryngol, Portland, OR 97239 USA.
   [Mitchell, John C.] Oregon Hlth & Sci Univ, Dept Restorat Dent, Div Biomat & Biomech, Sch Dent, Portland, OR 97239 USA.
   [Ricci, Anthony J.] Stanford Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Stanford University
RP Brigande, JV (corresponding author), Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Dept Otolaryngol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM brigande@ohsu.edu
FU National Institute on Deafness and Other Communication Disorders; McKnight Endowment Fund for Neuroscience; American Otological Society; National Institute on Deafness and Other Communication Disorders [R01DC003896] Funding Source: NIH RePORTER
NR 30
TC 213
Z9 278
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 537
EP U47
DI 10.1038/nature07265
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600047
PM 18754012
DA 2026-03-09
ER

PT J
AU Vahisalu, T
   Kollist, H
   Wang, YF
   Nishimura, N
   Chan, WY
   Valerio, G
   Lamminmäki, A
   Brosché, M
   Moldau, H
   Desikan, R
   Schroeder, JI
   Kangasjärvi, J
AF Vahisalu, Triin
   Kollist, Hannes
   Wang, Yong-Fei
   Nishimura, Noriyuki
   Chan, Wai-Yin
   Valerio, Gabriel
   Lamminmaki, Airi
   Brosche, Mikael
   Moldau, Heino
   Desikan, Radhika
   Schroeder, Julian I.
   Kangasjarvi, Jaakko
TI SLAC1 is required for plant guard cell S-type anion channel function in stomatal signalling
SO NATURE
LA English
DT Article
ID abscisic-acid; plasma-membrane; ion channels; arabidopsis-thaliana; escherichia-coli; vicia-faba; closure; ozone; mutant; transduction
AB Stomatal pores, formed by two surrounding guard cells in the epidermis of plant leaves, allow influx of atmospheric carbon dioxide in exchange for transpirational water loss. Stomata also restrict the entry of ozone - an important air pollutant that has an increasingly negative impact on crop yields, and thus global carbon fixation(1) and climate change(2). The aperture of stomatal pores is regulated by the transport of osmotically active ions and metabolites across guard cell membranes(3,4). Despite the vital role of guard cells in controlling plant water loss(3,4), ozone sensitivity(1,2) and CO2 supply(2,5-7), the genes encoding some of the main regulators of stomatal movements remain unknown. It has been proposed that guard cell anion channels function as important regulators of stomatal closure and are essential in mediating stomatal responses to physiological and stress stimuli(3,4,8). However, the genes encoding membrane proteins that mediate guard cell anion efflux have not yet been identified. Here we report the mapping and characterization of an ozone- sensitive Arabidopsis thaliana mutant, slac1. We show that SLAC1 ( SLOW ANION CHANNEL- ASSOCIATED 1) is preferentially expressed in guard cells and encodes a distant homologue of fungal and bacterial dicarboxylate/ malic acid transport proteins. The plasma membrane protein SLAC1 is essential for stomatal closure in response to CO2, abscisic acid, ozone, light/ dark transitions, humidity change, calcium ions, hydrogen peroxide and nitric oxide. Mutations in SLAC1 impair slow ( S- type) anion channel currents that are activated by cytosolic Ca2(+) and abscisic acid, but do not affect rapid ( R- type) anion channel currents or Ca2+ channel function. A low homology of SLAC1 to bacterial and fungal organic acid transport proteins, and the permeability of S- type anion channels to malate(9) suggest a vital role for SLAC1 in the function of S- type anion channels.
C1 [Vahisalu, Triin; Kollist, Hannes; Lamminmaki, Airi; Brosche, Mikael; Kangasjarvi, Jaakko] Univ Helsinki, Dept Biol & Environm Sci, FI-00014 Helsinki, Finland.
   [Vahisalu, Triin] Univ Tartu, Dept Bot, Inst Ecol & Earth Sci, EE-51005 Tartu, Estonia.
   [Kollist, Hannes; Moldau, Heino] Univ Tartu, Inst Technol, EE-50411 Tartu, Estonia.
   [Wang, Yong-Fei; Nishimura, Noriyuki; Chan, Wai-Yin; Valerio, Gabriel; Schroeder, Julian I.] Univ Calif San Diego, Div Biol Sci, Cell & Dev Biol Sect, La Jolla, CA 92093 USA.
   [Desikan, Radhika] Univ W England, Ctr Res Plant Sci, Bristol BS16 1QY, Avon, England.
C3 University of Helsinki; University of Tartu; Tartu University Institute of Ecology & Earth Sciences; University of Tartu; University of California System; University of California San Diego; University of West England
RP Kangasjärvi, J (corresponding author), Univ Helsinki, Dept Biol & Environm Sci, FI-00014 Helsinki, Finland.
EM jaakko.kangasjarvi@helsinki.fi
FU National Institute of Environmental Health Sciences [P42ES010337] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM060396] Funding Source: NIH RePORTER; NIEHS NIH HHS [P42 ES010337] Funding Source: Medline; NIGMS NIH HHS [R01 GM060396] Funding Source: Medline
NR 43
TC 683
Z9 765
U1 6
U2 281
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 487
EP U15
DI 10.1038/nature06608
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300035
PM 18305484
DA 2026-03-09
ER

PT J
AU Xu, YP
   Ramu, Y
   Lu, Z
AF Xu, Yanping
   Ramu, Yajamana
   Lu, Zhe
TI Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K+ channels
SO NATURE
LA English
DT Article
ID potassium channels; gating charge; sodium-channels; lymphocyte-t; activation; sequence; currents; toxin; sphingomyelin; tarantula
AB A fundamental question about the gating mechanism of voltage-activated K+ ( Kv) channels is how five positively charged voltage-sensing residues(1,2) in the fourth transmembrane segment are energetically stabilized, because they operate in a low- dielectric cell membrane. The simplest solution would be to pair them with negative charges(3). However, too few negatively charged channel residues are positioned for such a role(4,5). Recent studies suggest that some of the channel's positively charged residues are exposed to cell membrane phospholipids and interact with their head groups(5-9). A key question nevertheless remains: is the phosphohead of membrane lipids necessary for the proper function of the voltage sensor itself? Here we show that a given type of Kv channel may interact with several species of phospholipid and that enzymatic removal of their phospho-head creates an insuperable energy barrier for the positively charged voltage sensor to move through the initial gating step( s), thus immobilizing it, and also raises the energy barrier for the downstream step( s).
C1 [Xu, Yanping; Ramu, Yajamana; Lu, Zhe] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania
RP Lu, Z (corresponding author), Univ Penn, Dept Physiol, 3700 Hamilton Walk, Philadelphia, PA 19104 USA.
EM zhelu@mail.med.upenn.edu
FU NIGMS NIH HHS [R01 GM055560] Funding Source: Medline; National Institute of General Medical Sciences [R01GM055560] Funding Source: NIH RePORTER
NR 31
TC 158
Z9 177
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 FEB 14
PY 2008
VL 451
IS 7180
BP 826
EP U8
DI 10.1038/nature06618
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 263BA
UT WOS:000253191400042
PM 18273018
DA 2026-03-09
ER

PT J
AU Premenko-Lanier, M
   Moseley, NB
   Pruett, ST
   Romagnoli, PA
   Altman, JD
AF Premenko-Lanier, Mary
   Moseley, Nelson B.
   Pruett, Sarah T.
   Romagnoli, Pablo A.
   Altman, John D.
TI RETRACTED: Transient FTY720 treatment promotes immune-mediated clearance of a chronic viral infection (Retracted article. See vol. 464, pg. 942, 2010)
SO NATURE
LA English
DT Article; Retracted Publication
ID sphingosine 1-phosphate receptors; t-cell responses; lymphocyte egress; virus-infection; persistence; immunomodulator; specificity; impairment; exhaustion; mice
AB For a wide variety of microbial pathogens, the outcome of the infection is indeterminate. In some individuals the microbe is cleared, but in others it establishes a chronic infection, and the factors that tip this balance are often unknown. In a widely used model of chronic viral infection, C57BL/6 mice clear the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), but the clone 13 strain persists(1,2). Here we show that the Armstrong strain induces a profound lymphopenia at days 1-3 after infection, but the clone 13 strain does not. If we transiently augment lymphopenia by treating the clone-13-infected mice with the drug FTY720 at days 0-2 after infection, the mice successfully clear the infection by day 30. Clearance does not occur when CD4 T cells are absent at the time of treatment, indicating that the drug is not exerting direct antiviral effects. Notably, FTY720 treatment of an already established persistent infection also leads to viral clearance. In both models, FTY720 treatment preserves or augments LCMV-specific CD4 and CD8 T-cell responses, a result that is counter-intuitive because FTY720 is generally regarded as a new immunosuppressive agent(3). Because FTY720 targets host pathways that are completely evolutionarily conserved, our results may be translatable into new immunotherapies for the treatment of chronic microbial infections in humans.
C1 [Premenko-Lanier, Mary; Moseley, Nelson B.; Romagnoli, Pablo A.; Altman, John D.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
   [Premenko-Lanier, Mary; Moseley, Nelson B.; Romagnoli, Pablo A.; Altman, John D.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30329 USA.
   [Premenko-Lanier, Mary; Moseley, Nelson B.; Romagnoli, Pablo A.; Altman, John D.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Premenko-Lanier, Mary; Moseley, Nelson B.; Romagnoli, Pablo A.; Altman, John D.] Emory Univ, Sch Med, Atlanta, GA 30329 USA.
   [Pruett, Sarah T.] Yerkes Natl Primate Res Ctr, Div Psychobiol, Atlanta, GA 30329 USA.
C3 Emory University; Emory University; Emory University; Emory University
RP Altman, JD (corresponding author), Emory Univ, Emory Vaccine Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA.
EM mflanie@emory.edu; jaltman@rmy.emory.edu
FU NIAID NIH HHS [5F32AI062002, AI042373] Funding Source: Medline
NR 25
TC 23
Z9 34
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 AUG 14
PY 2008
VL 454
IS 7206
BP 894
EP U52
DI 10.1038/nature07199
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600038
PM 18704087
DA 2026-03-09
ER

PT J
AU Andrews-Hanna, JC
   Zuber, MT
   Banerdt, WB
AF Andrews-Hanna, Jeffrey C.
   Zuber, Maria T.
   Banerdt, W. Bruce
TI The Borealis basin and the origin of the martian crustal dichotomy
SO NATURE
LA English
DT Article
ID internal structure; mantle convection; giant impacts; mars; evolution; topography
AB The most prominent feature on the surface of Mars is the near-hemispheric dichotomy between the southern highlands and northern lowlands. The root of this dichotomy is a change in crustal thickness along an apparently irregular boundary, which can be traced around the planet, except where it is presumably buried beneath the Tharsis volcanic rise(1,2). The isostatic compensation of these distinct provinces(2,3) and the ancient population of impact craters buried beneath the young lowlands surface(4) suggest that the dichotomy is one of the most ancient features on the planet(3). However, the origin of this dichotomy has remained uncertain, with little evidence to distinguish between the suggested causes: a giant impact(5,6) or mantle convection/ overturn(7-9). Here we use the gravity(10) and topography(11) of Mars to constrain the location of the dichotomy boundary beneath Tharsis, taking advantage of the different modes of compensation for Tharsis and the dichotomy to separate their effects. We find that the dichotomy boundary along its entire path around the planet is accurately fitted by an ellipse measuring approximately 10,600 by 8,500 km, centred at 67 degrees N, 208 degrees E. We suggest that the elliptical nature of the crustal dichotomy is most simply explained by a giant impact, representing the largest such structure thus far identified in the Solar System.
C1 [Andrews-Hanna, Jeffrey C.; Zuber, Maria T.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Banerdt, W. Bruce] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 Massachusetts Institute of Technology (MIT); California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL)
RP Andrews-Hanna, JC (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM jhanna@mit.edu
NR 34
TC 249
Z9 291
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 26
PY 2008
VL 453
IS 7199
BP 1212
EP U27
DI 10.1038/nature07011
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 318FA
UT WOS:000257075800036
PM 18580944
DA 2026-03-09
ER

PT J
AU Ogden, SK
   Fei, DL
   Schilling, NS
   Ahmed, YF
   Hwa, J
   Robbins, DJ
AF Ogden, Stacey K.
   Fei, Dennis Liang
   Schilling, Neal S.
   Ahmed, Yashi F.
   Hwa, John
   Robbins, David J.
TI G protein Gαi functions immediately downstream of Smoothened in Hedgehog signalling
SO NATURE
LA English
DT Article
ID heterotrimeric g-proteins; cubitus interruptus; drosophila; expression; kinesin; complex; transduction; repressor; activator; receptor
AB The hedgehog (Hh) signalling pathway has an evolutionarily conserved role in patterning fields of cells during metazoan development, and is inappropriately activated in cancer(1,2). Hh pathway activity is absolutely dependent on signalling by the seven-transmembrane protein smoothened (Smo), which is regulated by the Hh receptor patched (Ptc). Smo signals to an intracellular multi- protein complex containing the Kinesin related protein Costal2 ( Cos2), the protein kinase Fused ( Fu) and the transcription factor Cubitus interruptus (Ci)(3). In the absence of Hh, this complex regulates the cleavage of full-length Ci to a truncated repressor protein, Ci(75), in a process that is dependent on the proteasome and priming phosphorylations by Protein kinase A (PKA)(4). Binding of Hh to Ptc blocks Ptc-mediated Smo inhibition, allowing Smo to signal to the intracellular components to attenuate Ci cleavage. Because of its homology with the Frizzled family of G-protein-coupled receptors ( GPCR) 5, a likely candidate for an immediate Smo effector would be a heterotrimeric G protein. However, the role that G proteins may have in Hh signal transduction is unclear and quite controversial(6-10), which has led to widespread speculation that Smo signals through a variety of novel G-protein-independent mechanisms. Here we present in vitro and in vivo evidence in Drosophila that Smo activates a G protein to modulate intracellular cyclic AMP levels in response to Hh. Our results demonstrate that Smo functions as a canonical GPCR, which signals through G alpha(i) to regulate Hh pathway activation.
C1 [Ogden, Stacey K.; Fei, Dennis Liang; Schilling, Neal S.; Hwa, John; Robbins, David J.] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA.
   [Ahmed, Yashi F.] Dartmouth Med Sch, Dept Genet, Hanover, NH 03755 USA.
   [Hwa, John] Dartmouth Med Sch, Dept Med Cardiol, Hanover, NH 03755 USA.
   [Ahmed, Yashi F.; Robbins, David J.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA.
C3 Dartmouth College; Dartmouth College; Dartmouth College; Dartmouth Cancer Center; Dartmouth College
RP Robbins, DJ (corresponding author), Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA.
EM david.j.robbins@dartmouth.edu
FU National Institutes of Health [CA82628, HL074190]
NR 37
TC 169
Z9 218
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 18
PY 2008
VL 456
IS 7224
BP 967
EP U76
DI 10.1038/nature07459
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300049
PM 18987629
DA 2026-03-09
ER

PT J
AU Losonczy, A
   Makara, JK
   Magee, JC
AF Losonczy, Attila
   Makara, Judit K.
   Magee, Jeffrey C.
TI Compartmentalized dendritic plasticity and input feature storage in neurons
SO NATURE
LA English
DT Article
ID ca1 pyramidal neurons; action-potentials; excitability; hippocampus; patterns; spikes; memory; cells; kv4.2; rat
AB Although information storage in the central nervous system is thought to be primarily mediated by various forms of synaptic plasticity, other mechanisms, such as modifications in membrane excitability, are available. Local dendritic spikes are nonlinear voltage events that are initiated within dendritic branches by spatially clustered and temporally synchronous synaptic input. That local spikes selectively respond only to appropriately correlated input allows them to function as input feature detectors and potentially as powerful information storage mechanisms. However, it is currently unknown whether any effective form of local dendritic spike plasticity exists. Here we show that the coupling between local dendritic spikes and the soma of rat hippocampal CA1 pyramidal neurons can be modified in a branch- specific manner through an N- methyl- D- aspartate receptor ( NMDAR)- dependent regulation of dendritic Kv4.2 potassium channels. These data suggest that compartmentalized changes in branch excitability could store multiple complex features of synaptic input, such as their spatio- temporal correlation. We propose that this 'branch strength potentiation' represents a previously unknown form of information storage that is distinct from that produced by changes in synaptic efficacy both at the mechanistic level and in the type of information stored.
C1 [Losonczy, Attila; Makara, Judit K.; Magee, Jeffrey C.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 Howard Hughes Medical Institute
RP Losonczy, A (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
EM losonczya@janelia.hhmi.org; makaraj@janelia.hhmi.org
NR 30
TC 470
Z9 569
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 27
PY 2008
VL 452
IS 7186
BP 436
EP U3
DI 10.1038/nature06725
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 279FU
UT WOS:000254341300024
PM 18368112
DA 2026-03-09
ER

PT J
AU Zhou, Q
   Brown, J
   Kanarek, A
   Rajagopal, J
   Melton, DA
AF Zhou, Qiao
   Brown, Juliana
   Kanarek, Andrew
   Rajagopal, Jayaraj
   Melton, Douglas A.
TI In vivo reprogramming of adult pancreatic exocrine cells to β-cells
SO NATURE
LA English
DT Article
ID to-mesenchymal transition; insulin-secreting cells; stem-cells; b-cells; differentiation; fibroblasts; transdifferentiation; genes; liver; generation
AB One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re- expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 ( also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
C1 [Zhou, Qiao; Kanarek, Andrew; Rajagopal, Jayaraj; Melton, Douglas A.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Brown, Juliana] Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol,Harvard Stem Cell Inst, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School
RP Melton, DA (corresponding author), Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, 7 Divin Ave, Cambridge, MA 02138 USA.
EM dmelton@harvard.edu
FU Damon-Runyon Cancer Research Foundation Postdoctoral Fellowship; Pathway to Independence (PI) Award; National Institute of Health; Harvard Stem Cell Institute; NIH
NR 41
TC 1617
Z9 2056
U1 0
U2 244
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 627
EP U30
DI 10.1038/nature07314
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700038
PM 18754011
DA 2026-03-09
ER

PT J
AU Bousquet, E
   Dawber, M
   Stucki, N
   Lichtensteiger, C
   Hermet, P
   Gariglio, S
   Triscone, JM
   Ghosez, P
AF Bousquet, Eric
   Dawber, Matthew
   Stucki, Nicolas
   Lichtensteiger, Celine
   Hermet, Patrick
   Gariglio, Stefano
   Triscone, Jean-Marc
   Ghosez, Philippe
TI Improper ferroelectricity in perovskite oxide artificial superlattices
SO NATURE
LA English
DT Article
ID thin-films; polarization enhancement; 1st-principles; batio3; srtio3
AB Ferroelectric thin films and superlattices are currently the subject of intensive research(1,2) because of the interest they raise for technological applications and also because their properties are of fundamental scientific importance(3-5). Ferroelectric superlattices(6) allow the tuning of the ferroelectric properties while maintaining perfect crystal structure and a coherent strain, even throughout relatively thick samples. This tuning is achieved in practice by adjusting both the strain(7-10), to enhance the polarization, and the composition, to interpolate between the properties of the combined compounds(11-15). Here we show that superlattices with very short periods possess a new form of interface coupling, based on rotational distortions, which gives rise to 'improper' ferroelectricity. These observations suggest an approach, based on interface engineering, to produce artificial materials with unique properties. By considering ferroelectric/paraelectric PbTiO3/SrTiO3 multilayers, we first show from first principles that the groundstate of the system is not purely ferroelectric but also primarily involves antiferrodistortive rotations of the oxygen atoms in a way compatible with improper ferroelectricity. We then demonstrate experimentally that, in contrast to pure PbTiO3 and SrTiO3 compounds, the multilayer system indeed behaves like a prototypical improper ferroelectric and exhibits a very large dielectric constant of epsilon(r)approximate to 600, which is also fairly temperature-independent. This behaviour, of practical interest for technological applications(16), is distinct from that of normal ferroelectrics, for which the dielectric constant is typically large but strongly evolves around the phase transition temperature and also differs from that of previously known improper ferroelectrics that exhibit a temperature-independent but small dielectric constant only.
C1 [Bousquet, Eric; Hermet, Patrick; Ghosez, Philippe] Univ Liege, B-4000 Sart Tilman Par Liege, Belgium.
   [Dawber, Matthew; Stucki, Nicolas; Lichtensteiger, Celine; Gariglio, Stefano; Triscone, Jean-Marc] Univ Geneva, DPMC, CH-1211 Geneva 4, Switzerland.
C3 University of Liege; University of Geneva
RP Ghosez, P (corresponding author), Univ Liege, Allee 6 Aout 17 B5, B-4000 Sart Tilman Par Liege, Belgium.
EM matthew.dawber@stonybrook.edu; philippe.ghosez@ulg.ac.be
NR 35
TC 842
Z9 961
U1 7
U2 684
PU 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 10
PY 2008
VL 452
IS 7188
BP 732
EP U4
DI 10.1038/nature06817
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500041
PM 18401406
DA 2026-03-09
ER

PT J
AU Zhang, CL
   Zou, YH
   He, WM
   Gage, FH
   Evans, RM
AF Zhang, Chun-Li
   Zou, Yuhua
   He, Weimin
   Gage, Fred H.
   Evans, Ronald M.
TI A role for adult TLX-positive neural stem cells in learning and behaviour
SO NATURE
LA English
DT Article
ID nuclear receptor tlx; enhanced synaptic plasticity; generated granule cells; hippocampal neurogenesis; dentate gyrus; tailless gene; mice; memory; mouse; proliferation
AB Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress(1). Although newly generated neurons are able to migrate and preferentially incorporate into the neural network(2-5), how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions(6). The adult neural stem cell pool is composed of orphan nuclear receptor TLX- positive cells(7). Here, using genetic approaches in mice, we demonstrate that TLX ( also called NR2E1) regulates adult neural stem cell proliferation in a cell- autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.
C1 [Zhang, Chun-Li; Evans, Ronald M.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Zhang, Chun-Li; Zou, Yuhua; He, Weimin; Evans, Ronald M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
   [Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
C3 Howard Hughes Medical Institute; Salk Institute; Salk Institute; Salk Institute
RP Evans, RM (corresponding author), Salk Inst Biol Studies, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM gage@salk.edu; evans@salk.edu
NR 31
TC 431
Z9 510
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 1004
EP U7
DI 10.1038/nature06562
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100051
PM 18235445
DA 2026-03-09
ER

PT J
AU Deana, A
   Celesnik, H
   Belasco, JG
AF Deana, Atilio
   Celesnik, Helena
   Belasco, Joel G.
TI The bacterial enzyme RppH triggers messenger RNA degradation by 5' pyrophosphate removal
SO NATURE
LA English
DT Article
ID escherichia-coli k1; nudix hydrolase; ribosomal protein-s20; ribonuclease-e; stem-loop; in-vivo; gene; cleavage; stabilization; ability
AB The long- standing assumption that messenger RNA ( mRNA) degradation in Escherichia coli begins with endonucleolytic cleavage has been challenged by the recent discovery that RNA decay can be triggered by a prior non- nucleolytic event that marks transcripts for rapid turnover: the rate- determining conversion of the 5' terminus from a triphosphate to a monophosphate(1). This modification creates better substrates for the endonuclease RNase E, whose cleavage activity at internal sites is greatly enhanced when the RNA 5' end is monophosphorylated(2,3). Moreover, it suggests an explanation for the influence of 5' termini on the endonucleolytic cleavage of primary transcripts, which are triphosphorylated(4-) (8). However, no enzyme capable of removing pyrophosphate from RNA 5' ends has been identified in any bacterial species. Here we show that the E. coli protein RppH ( formerly NudH/Y gdP) is the RNA pyrophosphohydrolase that initiates mRNA decay by this 5'- end- dependent pathway. In vitro, RppH efficiently removes pyrophosphate from the 5' end of triphosphorylated RNA, irrespective of the identity of the 5'- terminal nucleotide. In vivo, it accelerates the degradation of hundreds of E. coli transcripts by converting their triphosphorylated 5' ends to a more labile mono-phosphorylated state that can stimulate subsequent ribonuclease cleavage. That the action of the pyrophosphohydrolase is impeded when the 5' end is structurally sequestered by a stem- loop helps to explain the stabilizing influence of 5'- terminal base pairing on mRNA lifetimes. Together, these findings suggest a possible basis for the effect of RppH and its orthologues on the invasiveness of bacterial pathogens. Interestingly, this master regulator of 5'- end-dependent mRNA degradation in E. coli not only catalyses a process functionally reminiscent of eukaryotic mRNA decapping but also bears an evolutionary relationship to the eukaryotic decapping enzyme Dcp2.
C1 [Deana, Atilio; Celesnik, Helena; Belasco, Joel G.] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Deana, Atilio; Celesnik, Helena; Belasco, Joel G.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
C3 New York University; New York University
RP Belasco, JG (corresponding author), NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA.
EM belasco@saturn.med.nyu.edu
FU National Institute of General Medical Sciences [R01GM035769] Funding Source: NIH RePORTER; NIGMS NIH HHS [R01 GM035769] Funding Source: Medline
NR 31
TC 345
Z9 406
U1 0
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 355
EP U14
DI 10.1038/nature06475
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100054
PM 18202662
DA 2026-03-09
ER

PT J
AU Firestein, R
   Bass, AJ
   Kim, SY
   Dunn, IF
   Silver, SJ
   Guney, I
   Freed, E
   Ligon, AH
   Vena, N
   Ogino, S
   Chheda, MG
   Tamayo, P
   Finn, S
   Shrestha, Y
   Boehm, JS
   Jain, S
   Bojarski, E
   Mermel, C
   Barretina, J
   Chan, JA
   Baselga, J
   Tabernero, J
   Root, DE
   Fuchs, CS
   Loda, M
   Shivdasani, RA
   Meyerson, M
   Hahn, WC
AF Firestein, Ron
   Bass, Adam J.
   Kim, So Young
   Dunn, Ian F.
   Silver, Serena J.
   Guney, Isil
   Freed, Ellen
   Ligon, Azra H.
   Vena, Natalie
   Ogino, Shuji
   Chheda, Milan G.
   Tamayo, Pablo
   Finn, Stephen
   Shrestha, Yashaswi
   Boehm, Jesse S.
   Jain, Supriya
   Bojarski, Emeric
   Mermel, Craig
   Barretina, Jordi
   Chan, Jennifer A.
   Baselga, Jose
   Tabernero, Josep
   Root, David E.
   Fuchs, Charles S.
   Loda, Massimo
   Shivdasani, Ramesh A.
   Meyerson, Matthew
   Hahn, William C.
TI CDK8 is a colorectal cancer oncogene that regulates β-catenin activity
SO NATURE
LA English
DT Article
ID gene-expression; c-myc; activation; apc; identification; mutations; pathway; complex; cells; melanoma
AB Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival(1,2). Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation(3). To identify genes that both modulate beta-catenin activity and are essential for colon cancer cell proliferation, we conducted two loss-of-function screens in human colon cancer cells and compared genes identified in these screens with an analysis of copy number alterations in colon cancer specimens. One of these genes, CDK8, which encodes a member of the mediator complex(4), is located at 13q12.13, a region of recurrent copy number gain in a substantial fraction of colon cancers. Here we show that the suppression of CDK8 expression inhibits proliferation in colon cancer cells characterized by high levels of CDK8 and beta-catenin hyperactivity. CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets. Together these observations suggest that therapeutic interventions targeting CDK8 may confer a clinical benefit in beta-catenin-driven malignancies.
C1 [Firestein, Ron; Bass, Adam J.; Kim, So Young; Dunn, Ian F.; Guney, Isil; Freed, Ellen; Vena, Natalie; Ogino, Shuji; Chheda, Milan G.; Shrestha, Yashaswi; Jain, Supriya; Bojarski, Emeric; Mermel, Craig; Barretina, Jordi; Fuchs, Charles S.; Loda, Massimo; Shivdasani, Ramesh A.; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Firestein, Ron; Ligon, Azra H.; Ogino, Shuji; Finn, Stephen; Chan, Jennifer A.; Loda, Massimo; Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Bass, Adam J.; Kim, So Young; Shivdasani, Ramesh A.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
   [Firestein, Ron; Bass, Adam J.; Kim, So Young; Dunn, Ian F.; Guney, Isil; Freed, Ellen; Ligon, Azra H.; Vena, Natalie; Ogino, Shuji; Chheda, Milan G.; Finn, Stephen; Shrestha, Yashaswi; Jain, Supriya; Bojarski, Emeric; Mermel, Craig; Barretina, Jordi; Chan, Jennifer A.; Fuchs, Charles S.; Loda, Massimo; Shivdasani, Ramesh A.; Meyerson, Matthew; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Chheda, Milan G.] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA.
   [Firestein, Ron; Bass, Adam J.; Kim, So Young; Dunn, Ian F.; Guney, Isil; Shrestha, Yashaswi; Mermel, Craig; Barretina, Jordi; Root, David E.; Fuchs, Charles S.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Firestein, Ron; Bass, Adam J.; Kim, So Young; Dunn, Ian F.; Silver, Serena J.; Guney, Isil; Chheda, Milan G.; Tamayo, Pablo; Shrestha, Yashaswi; Boehm, Jesse S.; Mermel, Craig; Barretina, Jordi; Chan, Jennifer A.; Root, David E.; Meyerson, Matthew; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Baselga, Jose; Tabernero, Josep] Hosp Gen Valle Hebron, Dept Med Oncol, Barcelona 08035, Spain.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Hospital Universitari Vall d'Hebron
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 NCI/NIH [R33CA128625]; NIH [T32]; GI SPORE Career Development [P50CA127003]; Harvard-MIT Clinical Investigator Training Program Fellowship; Department of Defense Prostate Cancer Postdoctoral Fellowships; Warren-Whitman- Richardson, Hagerty Foundation Research Fellowships; K12 award; National Cancer Institute [P50CA127003, T32CA009172] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 30
TC 581
Z9 722
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 25
PY 2008
VL 455
IS 7212
BP 547
EP U60
DI 10.1038/nature07179
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600049
PM 18794900
DA 2026-03-09
ER

PT J
AU de la Cruz, C
   Huang, Q
   Lynn, JW
   Li, JY
   Ratcliff, W
   Zarestky, JL
   Mook, HA
   Chen, GF
   Luo, JL
   Wang, NL
   Dai, PC
AF de la Cruz, Clarina
   Huang, Q.
   Lynn, J. W.
   Li, Jiying
   Ratcliff, W., II
   Zarestky, J. L.
   Mook, H. A.
   Chen, G. F.
   Luo, J. L.
   Wang, N. L.
   Dai, Pengcheng
TI Magnetic order close to superconductivity in the iron-based layered LaO1-xFxFeAs systems
SO NATURE
LA English
DT Article
AB Following the discovery of long- range antiferromagnetic order in the parent compounds of high- transition- temperature ( high- T(c)) copper oxides(1,2), there have been efforts to understand the role of magnetism in the superconductivity that occurs when mobile 'electrons' or 'holes' are doped into the antiferromagnetic parent compounds. Superconductivity in the newly discovered rare- earth iron- based oxide systems ROFeAs ( R, rare- earth metal) also arises from either electron(3-7) or hole(8) doping of their non- superconducting parent compounds. The parent material LaOFeAs is metallic but shows anomalies near 150 K in both resistivity and d. c. magnetic susceptibility(3). Although optical conductivity and theoretical calculations suggest that LaOFeAs exhibits a spin- density- wave ( SDW) instability that is suppressed by doping with electrons to induce superconductivity(9), there has been no direct evidence of SDW order. Here we report neutron- scattering experiments that demonstrate that LaOFeAs undergoes an abrupt structural distortion below 155 K, changing the symmetry from tetragonal ( space group P4/ nmm) to monoclinic ( space group P112/ n) at low temperatures, and then, at similar to 137 K, develops long- range SDW- type antiferromagnetic order with a small moment but simple magnetic structure(9). Doping the system with fluorine suppresses both the magnetic order and the structural distortion in favour of superconductivity. Therefore, like high- T(c) copper oxides, the superconducting regime in these iron- based materials occurs in close proximity to a long- range- ordered antiferromagnetic ground state.
C1 [de la Cruz, Clarina; Dai, Pengcheng] Univ Tennessee, Dept Phys & Astron, Knoxville, TN 37996 USA.
   [de la Cruz, Clarina; Mook, H. A.; Dai, Pengcheng] Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA.
   [Huang, Q.; Lynn, J. W.; Li, Jiying; Ratcliff, W., II] Natl Inst Stand & Technol, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA.
   [Li, Jiying] Univ Maryland, Dept Mat Sci & Engn, College Pk, MD 20742 USA.
   [Zarestky, J. L.] Iowa State Univ, Ames Lab, Ames, IA 50011 USA.
   [Zarestky, J. L.] Iowa State Univ, Dept Phys & Astron, Ames, IA 50011 USA.
   [Chen, G. F.; Luo, J. L.; Wang, N. L.] Chinese Acad Sci, Beijing Natl Lab Condensed Matter Phys, Inst Phys, Beijing 100080, Peoples R China.
C3 University of Tennessee System; University of Tennessee Knoxville; United States Department of Energy (DOE); Oak Ridge National Laboratory; National Institute of Standards & Technology (NIST) - USA; University System of Maryland; University of Maryland College Park; United States Department of Energy (DOE); Ames National Laboratory; Iowa State University; Iowa State University; Chinese Academy of Sciences; Institute of Physics, CAS
RP Dai, PC (corresponding author), Univ Tennessee, Dept Phys & Astron, Knoxville, TN 37996 USA.
EM daip@ornl.gov
NR 17
TC 1708
Z9 1808
U1 6
U2 578
PU 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 12
PY 2008
VL 453
IS 7197
BP 899
EP 902
DI 10.1038/nature07057
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000038
PM 18509333
DA 2026-03-09
ER

PT J
AU Vonk, FJ
   Admiraal, JF
   Jackson, K
   Reshef, R
   de Bakker, MAG
   Vanderschoot, K
   van den Berge, I
   van Atten, M
   Burgerhout, E
   Beck, A
   Mirtschin, PJ
   Kochva, E
   Witte, F
   Fry, BG
   Woods, AE
   Richardson, MK
AF Vonk, Freek J.
   Admiraal, Jeroen F.
   Jackson, Kate
   Reshef, Ram
   de Bakker, Merijn A. G.
   Vanderschoot, Kim
   van den Berge, Iris
   van Atten, Marit
   Burgerhout, Erik
   Beck, Andrew
   Mirtschin, Peter J.
   Kochva, Elazar
   Witte, Frans
   Fry, Bryan G.
   Woods, Anthony E.
   Richardson, Michael K.
TI Evolutionary origin and development of snake fangs
SO NATURE
LA English
DT Article
ID embryonic-development; python-sebae; venom; apparatus; dentition; gland
AB Many advanced snakes use fangs - specialized teeth associated with a venom gland(1,2) - to introduce venom into prey or attacker. Various front- and rear- fanged groups are recognized, according to whether their fangs are positioned anterior ( for example cobras and vipers) or posterior ( for example grass snakes) in the upper jaw(3-5). A fundamental controversy in snake evolution is whether or not front and rear fangs share the same evolutionary and developmental origin(3-9). Resolving this controversy could identify a major evolutionary transition underlying the massive radiation of advanced snakes, and the associated developmental events. Here we examine this issue by visualizing the tooth- forming epithelium in the upper jaw of 96 snake embryos, covering eight species. We use the sonic hedgehog gene as a marker(10-13), and three- dimensionally reconstruct the development in 41 of the embryos. We show that front fangs develop from the posterior end of the upper jaw, and are strikingly similar in morphogenesis to rear fangs. This is consistent with their being homologous. In front- fanged snakes, the anterior part of the upper jaw lacks sonic hedgehog expression, and ontogenetic allometry displaces the fang from its posterior developmental origin to its adult front position - consistent with an ancestral posterior position of the front fang. In rear- fanged snakes, the fangs develop from an independent posterior dental lamina and retain their posterior position. In light of our findings, we put forward a new model for the evolution of snake fangs: a posterior subregion of the tooth- forming epithelium became developmentally uncoupled from the remaining dentition, which allowed the posterior teeth to evolve independently and in close association with the venom gland, becoming highly modified in different lineages. This developmental event could have facilitated the massive radiation of advanced snakes in the Cenozoic era, resulting in the spectacular diversity of snakes seen today(6,14,15).
C1 [Vonk, Freek J.; Admiraal, Jeroen F.; de Bakker, Merijn A. G.; Vanderschoot, Kim; van den Berge, Iris; van Atten, Marit; Burgerhout, Erik; Witte, Frans; Richardson, Michael K.] Leiden Univ, Inst Biol, NL-2300 RA Leiden, Netherlands.
   [Jackson, Kate] Whitman Coll, Dept Biol, Walla Walla, WA 99362 USA.
   [Reshef, Ram] Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel.
   [Beck, Andrew; Mirtschin, Peter J.; Woods, Anthony E.] Univ S Australia, Sansom Inst, Sch Pharm & Med Sci, Adelaide, SA 5001, Australia.
   [Mirtschin, Peter J.] Venom Supplies Pty Ltd, Tanunda, SA 5352, Australia.
   [Kochva, Elazar] Tel Aviv Univ, Dept Zool, IL-69978 Tel Aviv, Israel.
   [Fry, Bryan G.] Univ Melbourne, Dept Biochem & Mol Biol, Inst Bio21, Parkville, Vic 3010, Australia.
C3 Leiden University; Leiden University - Excl LUMC; Whitman College; Technion Israel Institute of Technology; Adelaide University; University of South Australia; Tel Aviv University; University of Melbourne
RP Richardson, MK (corresponding author), Leiden Univ, Inst Biol, Kaiserstr 63,POB 9516, NL-2300 RA Leiden, Netherlands.
EM m.k.richardson@biology.leidenuniv.nl
NR 30
TC 141
Z9 162
U1 0
U2 139
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 630
EP 633
DI 10.1038/nature07178
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500045
PM 18668106
DA 2026-03-09
ER

PT J
AU Estève, J
   Gross, C
   Weller, A
   Giovanazzi, S
   Oberthaler, MK
AF Esteve, J.
   Gross, C.
   Weller, A.
   Giovanazzi, S.
   Oberthaler, M. K.
TI Squeezing and entanglement in a Bose-Einstein condensate
SO NATURE
LA English
DT Article
ID states
AB Entanglement, a key feature of quantum mechanics, is a resource that allows the improvement of precision measurements beyond the conventional bound attainable by classical means(1). This results in the standard quantum limit, which is reached in today's best available sensors of various quantities such as time(2) and position(3,4). Many of these sensors are interferometers in which the standard quantum limit can be overcome by using quantum-entangled states (in particular spin squeezed states(5,6)) at the two input ports. Bose-Einstein condensates of ultracold atoms are considered good candidates to provide such states involving a large number of particles. Here we demonstrate spin squeezed states suitable for atomic interferometry by splitting a condensate into a few parts using a lattice potential. Site-resolved detection of the atoms allows the measurement of the atom number difference and relative phase, which are conjugate variables. The observed fluctuations imply entanglement between the particles(7-9), a resource that would allow a precision gain of 3.8 dB over the standard quantum limit for interferometric measurements.
C1 [Esteve, J.; Gross, C.; Weller, A.; Giovanazzi, S.; Oberthaler, M. K.] Heidelberg Univ, Kirchhoff Inst Phys, D-69120 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Oberthaler, MK (corresponding author), Heidelberg Univ, Kirchhoff Inst Phys, Neuenheimer Feld 227, D-69120 Heidelberg, Germany.
EM entanglement@matterwave.de
FU DFG; GIF; EC (MIDAS STREP); EC Marie-Curie program; Landesgraduiertenforderung Baden-Wurttemberg
NR 28
TC 667
Z9 720
U1 4
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1216
EP 1219
DI 10.1038/nature07332
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100038
PM 18830245
DA 2026-03-09
ER

PT J
AU Wolfe, AM
   Jorgenson, RA
   Robishaw, T
   Heiles, C
   Prochaska, JX
AF Wolfe, Arthur M.
   Jorgenson, Regina A.
   Robishaw, Timothy
   Heiles, Carl
   Prochaska, Jason X.
TI An 84-μG magnetic field in a galaxy at redshift z=0.692
SO NATURE
LA English
DT Article
ID ly-alpha systems; absorption-line; star-formation; 3c 286; absorbers; origin
AB The magnetic field pervading our Galaxy is a crucial constituent of the interstellar medium: it mediates the dynamics of interstellar clouds, the energy density of cosmic rays, and the formation of stars(1). The field associated with ionized interstellar gas has been determined through observations of pulsars in our Galaxy. Radiofrequency measurements of pulse dispersion and the rotation of the plane of linear polarization, that is, Faraday rotation, yield an average value for the magnetic field of B approximate to 3 mu G (ref. 2). The possible detection of Faraday rotation of linearly polarized photons emitted by high-redshift quasars(3) suggests similar magnetic fields are present in foreground galaxies with redshifts z > 1. As Faraday rotation alone, however, determines neither the magnitude nor the redshift of the magnetic field, the strength of galactic magnetic fields at redshifts z. 0 remains uncertain. Here we report a measurement of a magnetic field of B approximate to 84 mu G in a galaxy at z = 0.692, using the same Zeeman- splitting technique that revealed an average value of B = 6 mu G in the neutral interstellar gas of our Galaxy(4). This is unexpected, as the leading theory of magnetic field generation, the mean- field dynamo model, predicts large- scale magnetic fields to be weaker in the past rather than stronger(5).
C1 [Wolfe, Arthur M.; Jorgenson, Regina A.] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [Wolfe, Arthur M.; Jorgenson, Regina A.] Univ Calif San Diego, Ctr Astrophys & Space Sci, La Jolla, CA 92093 USA.
   [Robishaw, Timothy; Heiles, Carl] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Prochaska, Jason X.] UCO Lick Observ, San Jose, CA USA.
   [Prochaska, Jason X.] Univ Calif Santa Cruz, Santa Cruz, CA 95464 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California Berkeley; University of California System; University of California Santa Cruz
RP Wolfe, AM (corresponding author), Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
EM awolfe@ucsd.edu
FU US National Science Foundation
NR 25
TC 58
Z9 58
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 638
EP 640
DI 10.1038/nature07264
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700040
PM 18833273
DA 2026-03-09
ER

PT J
AU Grimson, A
   Srivastava, M
   Fahey, B
   Woodcroft, BJ
   Chiang, HR
   King, N
   Degnan, BM
   Rokhsar, DS
   Bartel, DP
AF Grimson, Andrew
   Srivastava, Mansi
   Fahey, Bryony
   Woodcroft, Ben J.
   Chiang, H. Rosaria
   King, Nicole
   Degnan, Bernard M.
   Rokhsar, Daniel S.
   Bartel, David P.
TI Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals
SO NATURE
LA English
DT Article
ID expression; genome; mechanism; expansion; reveals; biogenesis; complex; sirnas
AB In bilaterian animals, such as humans, flies and worms, hundreds of microRNAs ( miRNAs), some conserved throughout bilaterian evolution, collectively regulate a substantial fraction of the transcriptome. In addition to miRNAs, other bilaterian small RNAs, known as Piwi- interacting RNAs (piRNAs), protect the genome from transposons. Here we identify small RNAs from animal phyla that diverged before the emergence of the Bilateria. The cnidarian Nematostella vectensis ( starlet sea anemone), a close relative to the Bilateria, possesses an extensive repertoire of miRNA genes, two classes of piRNAs and a complement of proteins specific to small- RNA biology comparable to that of humans. The poriferan Amphimedon queenslandica ( sponge), one of the simplest animals and a distant relative of the Bilateria, also possesses miRNAs, both classes of piRNAs and a full complement of the small- RNA machinery. Animal miRNA evolution seems to have been relatively dynamic, with precursor sizes and mature miRNA sequences differing greatly between poriferans, cnidarians and bilaterians. Nonetheless, miRNAs and piRNAs have been available as classes of riboregulators to shape gene expression throughout the evolution and radiation of animal phyla.
C1 [Grimson, Andrew; Chiang, H. Rosaria; Bartel, David P.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Grimson, Andrew; Chiang, H. Rosaria; Bartel, David P.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA.
   [Fahey, Bryony; Woodcroft, Ben J.; Degnan, Bernard M.] Univ Queensland, Sch Integrat Biol, Brisbane, Qld 4072, Australia.
   [Srivastava, Mansi; King, Nicole; Rokhsar, Daniel S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Srivastava, Mansi; King, Nicole; Rokhsar, Daniel S.] Univ Calif Berkeley, Ctr Integrat Genom, Berkeley, CA 94720 USA.
   [Rokhsar, Daniel S.] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; University of Queensland; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI
RP Bartel, DP (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM dbartel@wi.mit.edu
FU NIH postdoctoral fellowship; NIH; Center for Integrative Genomics; Gordon and Betty Moore Foundation; Australian Research Council
NR 35
TC 557
Z9 719
U1 1
U2 90
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1193
EP U15
DI 10.1038/nature07415
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100034
PM 18830242
DA 2026-03-09
ER

PT J
AU Martick, M
   Horan, LH
   Noller, HF
   Scott, WG
AF Martick, Monika
   Horan, Lucas H.
   Noller, Harry F.
   Scott, William G.
TI A discontinuous hammerhead ribozyme embedded in a mammalian messenger RNA
SO NATURE
LA English
DT Article
ID gene-expression; cleavage; lectin; family; transcripts; alignment; sequence; genome; decay
AB Structured RNAs embedded in the untranslated regions (UTRs) of messenger RNAs can regulate gene expression. In bacteria, control of a metabolite gene is mediated by the self-cleaving activity of a ribozyme embedded in its 59 UTR1. This discovery has raised the question of whether gene-regulating ribozymes also exist in eukaryotic mRNAs. Here we show that highly active hammerhead ribozymes(2,3) are present in the 3 ' UTRs of rodent C-type lectin type II (Clec2) genes(4-7). Using a hammerhead RNA motif search with relaxed delimitation of the non-conserved regions, we detected ribozyme sequences in which the invariant regions, in contrast to the previously identified continuous hammerheads(8-10), occur as two fragments separated by hundreds of nucleotides. Notably, a fragment pair can assemble to form an active hammerhead ribozyme structure between the translation termination and the polyadenylation signals within the 3 ' UTR. We demonstrate that this hammerhead structure can self-cleave both in vitro and in vivo, and is able to reduce protein expression in mouse cells. These results indicate that an unrecognized mechanism of post-transcriptional gene regulation involving association of discontinuous ribozyme sequences within an mRNA may be modulating the expression of several CLEC2 proteins that function in bone remodelling and the immune response of several mammals.
C1 [Martick, Monika; Horan, Lucas H.; Noller, Harry F.; Scott, William G.] Univ Calif Santa Cruz, Ctr Mol Biol RNA, Santa Cruz, CA 95064 USA.
C3 University of California System; University of California Santa Cruz
RP Martick, M (corresponding author), Univ Calif Santa Cruz, Ctr Mol Biol RNA, Santa Cruz, CA 95064 USA.
EM mmartick@yahoo.com
FU NIAID NIH HHS [R01 AI043393] Funding Source: Medline; NIGMS NIH HHS [R01 GM087721] Funding Source: Medline; PHS HHS [R01043393] Funding Source: Medline
NR 29
TC 131
Z9 169
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 14
PY 2008
VL 454
IS 7206
BP 899
EP U57
DI 10.1038/nature07117
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 336XH
UT WOS:000258398600039
PM 18615019
DA 2026-03-09
ER

PT J
AU Lüthi, D
   Le Floch, M
   Bereiter, B
   Blunier, T
   Barnola, JM
   Siegenthaler, U
   Raynaud, D
   Jouzel, J
   Fischer, H
   Kawamura, K
   Stocker, TF
AF Luethi, Dieter
   Le Floch, Martine
   Bereiter, Bernhard
   Blunier, Thomas
   Barnola, Jean-Marc
   Siegenthaler, Urs
   Raynaud, Dominique
   Jouzel, Jean
   Fischer, Hubertus
   Kawamura, Kenji
   Stocker, Thomas F.
TI High-resolution carbon dioxide concentration record 650,000-800,000 years before present
SO NATURE
LA English
DT Article
ID past 800,000 years; 8 glacial cycles; c ice core; atmospheric co2; climate variability; bipolar seesaw; antarctica; model; circulation; greenland
AB Changes in past atmospheric carbon dioxide concentrations can be determined by measuring the composition of air trapped in ice cores from Antarctica. So far, the Antarctic Vostok and EPICA Dome C ice cores have provided a composite record of atmospheric carbon dioxide levels over the past 650,000 years(1-4). Here we present results of the lowest 200m of the Dome C ice core, extending the record of atmospheric carbon dioxide concentration by two complete glacial cycles to 800,000 yr before present. From previously published data(1-8) and the present work, we find that atmospheric carbon dioxide is strongly correlated with Antarctic temperature throughout eight glacial cycles but with significantly lower concentrations between 650,000 and 750,000 yr before present. Carbon dioxide levels are below 180 parts per million by volume ( p. p. m. v.) for a period of 3,000 yr during Marine Isotope Stage 16, possibly reflecting more pronounced oceanic carbon storage. We report the lowest carbon dioxide concentration measured in an ice core, which extends the pre-industrial range of carbon dioxide concentrations during the late Quaternary by about 10 p. p. m. v. to 172-300 p. p. m. v.
C1 [Luethi, Dieter; Bereiter, Bernhard; Blunier, Thomas; Siegenthaler, Urs; Kawamura, Kenji; Stocker, Thomas F.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
   [Luethi, Dieter; Bereiter, Bernhard; Blunier, Thomas; Siegenthaler, Urs; Kawamura, Kenji; Stocker, Thomas F.] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Le Floch, Martine; Barnola, Jean-Marc; Raynaud, Dominique] Univ Grenoble 1, CNRS, Lab Glaciol & Geophys Environm, F-38402 St Martin Dheres, France.
   [Jouzel, Jean] Univ Versailles St Quentin, Inst Pierre Simon Laplace, Lab Sci Climat & Environm, CEA CNRS,CE Saclay, F-91191 Gif Sur Yvette, France.
   [Fischer, Hubertus] Alfred Wegener Inst Polar & Marine Res, D-27568 Bremerhaven, Germany.
C3 University of Bern; University of Bern; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Universite Paris Saclay; CEA; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research
RP Lüthi, D (corresponding author), Univ Bern, Inst Phys, Sidlerstr 5, CH-3012 Bern, Switzerland.
EM luethi@climate.unibe.ch
NR 26
TC 1638
Z9 2105
U1 37
U2 785
PU NATURE PUBLISHING 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 15
PY 2008
VL 453
IS 7193
BP 379
EP 382
DI 10.1038/nature06949
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400049
PM 18480821
DA 2026-03-09
ER

PT J
AU Hong, ST
   Bang, S
   Hyun, S
   Kang, JK
   Jeong, K
   Paik, D
   Chung, JK
   Kim, J
AF Hong, Sung-Tae
   Bang, Sunhoe
   Hyun, Seogang
   Kang, Jongkyun
   Jeong, Kyunghwa
   Paik, Donggi
   Chung, Jongkyeong
   Kim, Jaeseob
TI cAMP signalling in mushroom bodies modulates temperature preference behaviour in Drosophila
SO NATURE
LA English
DT Article
ID toxin light-chain; short-term-memory; olfactory memory; expression; neurons; genetics; systems; genes
AB Homoiotherms, for example mammals, regulate their body temperature with physiological responses such as a change of metabolic rate and sweating. In contrast, the body temperature of poikilotherms, for example Drosophila, is the result of heat exchange with the surrounding environment as a result of the large ratio of surface area to volume of their bodies(1,2). Accordingly, these animals must instinctively move to places with an environmental temperature as close as possible to their genetically determined desired temperature. The temperature that Drosophila instinctively prefers has a function equivalent to the 'set point' temperature in mammals. Although various temperature-gated TRP channels have been discovered(3,4), molecular and cellular components in Drosophila brain responsible for determining the desired temperature remain unknown. We identified these components by performing a large-scale genetic screen of temperature preference behaviour (TPB) in Drosophila(5,6). In parallel, we mapped areas of the Drosophila brain controlling TPB by targeted inactivation of neurons with tetanus toxin(7) and a potassium channel (Kir2.1)(8) driven with various brain-specific GAL4s. Here we show that mushroom bodies (MBs) and the cyclic AMP-cAMP-dependent protein kinase A (cAMP-PKA) pathway are essential for controlling TPB. Furthermore, targeted expression of cAMP-PKA pathway components in only the MB was sufficient to rescue abnormal TPB of the corresponding mutants. Preferred temperatures were affected by the level of cAMP and PKA activity in the MBs in various PKA pathway mutants.
C1 [Hong, Sung-Tae; Bang, Sunhoe; Hyun, Seogang; Kang, Jongkyun; Jeong, Kyunghwa; Paik, Donggi; Chung, Jongkyeong; Kim, Jaeseob] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea.
C3 Korea Advanced Institute of Science & Technology (KAIST)
RP Kim, J (corresponding author), Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea.
EM kjaeseob@kaist.ac.kr
NR 27
TC 61
Z9 76
U1 2
U2 18
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 771
EP U97
DI 10.1038/nature07090
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000046
PM 18594510
DA 2026-03-09
ER

PT J
AU Gallagher, FA
   Kettunen, MI
   Day, SE
   Hu, DE
   Ardenkjær-Larsen, JH
   in't Zandt, R
   Jensen, PR
   Karlsson, M
   Golman, K
   Lerche, MH
   Brindle, KM
AF Gallagher, Ferdia A.
   Kettunen, Mikko I.
   Day, Sam E.
   Hu, De-En
   Ardenkjær-Larsen, Jan Henrik
   in't Zandt, Rene
   Jensen, Pernille R.
   Karlsson, Magnus
   Golman, Klaes
   Lerche, Mathilde H.
   Brindle, Kevin M.
TI Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate
SO NATURE
LA English
DT Article
ID extracellular ph; contrast agent; tumor ph; c-13; nmr; spectroscopy; invivo; brain; mrs
AB As alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment(1). Dynamic nuclear polarization is an emerging technique for substantially increasing the sensitivity of magnetic resonance imaging experiments(2,3). Here we show that tissue pH can be imaged in vivo from the ratio of the signal intensities of hyperpolarized bicarbonate ((HCO3-)-C-13) and (CO2)-C-13 following intravenous injection of hyperpolarized (HCO3-)-C-13. The technique was demonstrated in a mouse tumour model, which showed that the average tumour interstitial pH was significantly lower than the surrounding tissue. Given that bicarbonate is an endogenous molecule that can be infused in relatively high concentrations into patients(4), we propose that this technique could be used clinically to image pathological processes that are associated with alterations in tissue pH, such as cancer, ischaemia and inflammation.
C1 [Gallagher, Ferdia A.; Kettunen, Mikko I.; Day, Sam E.; Hu, De-En; Brindle, Kevin M.] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Gallagher, Ferdia A.; Kettunen, Mikko I.; Day, Sam E.; Hu, De-En; Brindle, Kevin M.] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England.
   [Gallagher, Ferdia A.] Univ Cambridge, Addenbrookes Hosp, Dept Radiol, Cambridge CB2 2QQ, England.
   [Ardenkjær-Larsen, Jan Henrik] GE Healthcare, Grove Ctr GC 18, Amersham HP7 9LL, England.
   [in't Zandt, Rene; Jensen, Pernille R.; Karlsson, Magnus; Golman, Klaes; Lerche, Mathilde H.] Imagnia AB, SE-20041 Malmo, Sweden.
C3 CRUK Cambridge Institute; Cancer Research UK; University of Cambridge; University of Cambridge; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; General Electric; GE Healthcare
RP Brindle, KM (corresponding author), Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England.
EM kmb@mole.bio.cam.ac.uk
FU Cancer Research UK [C197/A3514] Funding Source: Medline
NR 30
TC 726
Z9 851
U1 0
U2 235
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 12
PY 2008
VL 453
IS 7197
BP 940
EP U73
DI 10.1038/nature07017
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000048
PM 18509335
DA 2026-03-09
ER

PT J
AU Serganov, A
   Huang, LL
   Patel, DJ
AF Serganov, Alexander
   Huang, Lili
   Patel, Dinshaw J.
TI Structural insights into amino acid binding and gene control by a lysine riboswitch
SO NATURE
LA English
DT Article
ID crystal-structure; s-adenosylmethionine; rna; expression; refinement; biosynthesis; recognition; bacteria; analogs; domain
AB In bacteria, the intracellular concentration of several amino acids is controlled by riboswitches(1-4). One of the important regulatory circuits involves lysine- specific riboswitches, which direct the biosynthesis and transport of lysine and precursors common for lysine and other amino acids(1-3). To understand the molecular basis of amino acid recognition by riboswitches, here we present the crystal structure of the 174- nucleotide sensing domain of the Thermotoga maritima lysine riboswitch in the lysine- bound (1.9 angstrom (angstrom)) and free (3.1 angstrom) states. The riboswitch features an unusual and intricate architecture, involving three-helical and two- helical bundles connected by a compact five- helical junction and stabilized by various long- range tertiary interactions. Lysine interacts with the junctional core of the riboswitch and is specifically recognized through shape- complementarity within the elongated binding pocket and through several direct and K(+)-mediated hydrogen bonds to its charged ends. Our structural and biochemical studies indicate preformation of the riboswitch scaffold and identify conformational changes associated with the formation of a stable lysine- bound state, which prevents alternative folding of the riboswitch and facilitates formation of downstream regulatory elements. We have also determined several structures of the riboswitch bound to different lysine analogues(5), including antibiotics, in an effort to understand the ligand-binding capabilities of the lysine riboswitch and understand the nature of antibiotic resistance. Our results provide insights into a mechanism of lysine- riboswitch- dependent gene control at the molecular level, thereby contributing to continuing efforts at exploration of the pharmaceutical and biotechnological potential of riboswitches.
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 US Department of Energy; National Institutes of Health
NR 32
TC 208
Z9 279
U1 0
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1263
EP U76
DI 10.1038/nature07326
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100050
PM 18784651
DA 2026-03-09
ER

PT J
AU Niu, FL
   Silver, PG
   Daley, TM
   Cheng, X
   Majer, EL
AF Niu, Fenglin
   Silver, Paul G.
   Daley, Thomas M.
   Cheng, Xin
   Majer, Ernest L.
TI Preseismic velocity changes observed from active source monitoring at the Parkfield SAFOD drill site
SO NATURE
LA English
DT Article
ID san-andreas fault; compressional waves; seismic velocity; echo signals; travel-time; rocks; stress; california; cracks
AB Measuring stress changes within seismically active fault zones has been a long- sought goal of seismology. One approach is to exploit the stress dependence of seismic wave velocity, and we have investigated this in an active source cross- well experiment at the San Andreas Fault Observatory at Depth ( SAFOD) drill site. Here we show that stress changes are indeed measurable using this technique. Over a two- month period, we observed an excellent anti-correlation between changes in the time required for a shear wave to travel through the rock along a fixed pathway ( a few microseconds) and variations in barometric pressure. We also observed two large excursions in the travel- time data that are coincident with two earthquakes that are among those predicted to produce the largest coseismic stress changes at SAFOD. The two excursions started approximately 10 and 2 hours before the events, respectively, suggesting that they may be related to pre- rupture stress induced changes in crack properties, as observed in early laboratory studies(1,2).
C1 [Niu, Fenglin; Cheng, Xin] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Silver, Paul G.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
   [Daley, Thomas M.; Majer, Ernest L.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Earth Sci, Berkeley, CA 94720 USA.
C3 Rice University; Carnegie Institution for Science; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Niu, FL (corresponding author), Rice Univ, Dept Earth Sci, MS-126,6100 Main St, Houston, TX 77005 USA.
EM niu@rice.edu
NR 20
TC 238
Z9 320
U1 5
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 10
PY 2008
VL 454
IS 7201
BP 204
EP U44
DI 10.1038/nature07111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 323RU
UT WOS:000257466900041
PM 18615082
DA 2026-03-09
ER

PT J
AU Anderson, CNK
   Hsieh, CH
   Sandin, SA
   Hewitt, R
   Hollowed, A
   Beddington, J
   May, RM
   Sugihara, G
AF Anderson, Christian N. K.
   Hsieh, Chih-Hao
   Sandin, Stuart A.
   Hewitt, Roger
   Hollowed, Anne
   Beddington, John
   May, Robert M.
   Sugihara, George
TI Why fishing magnifies fluctuations in fish abundance
SO NATURE
LA English
DT Article
ID cod gadus-morhua; natural-populations; age structure; life-history; fishery; size; sustainability; variability; ecology; biomass
AB It is now clear that fished populations can fluctuate more than unharvested stocks. However, it is not clear why. Here we distinguish among three major competing mechanisms for this phenomenon, by using the 50- year California Cooperative Oceanic Fisheries Investigations ( CalCOFI) larval fish record. First, variable fishing pressure directly increases variability in exploited populations. Second, commercial fishing can decrease the average body size and age of a stock, causing the truncated population to track environmental fluctuations directly. Third, age- truncated or juvenescent populations have increasingly unstable population dynamics because of changing demographic parameters such as intrinsic growth rates. We find no evidence for the first hypothesis, limited evidence for the second and strong evidence for the third. Therefore, in California Current fisheries, increased temporal variability in the population does not arise from variable exploitation, nor does it reflect direct environmental tracking. More fundamentally, it arises from increased instability in dynamics. This finding has implications for resource management as an empirical example of how selective harvesting can alter the basic dynamics of exploited populations, and lead to unstable booms and busts that can precede systematic declines in stock levels.
C1 [Anderson, Christian N. K.; Hsieh, Chih-Hao; Sandin, Stuart A.; Sugihara, George] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Hsieh, Chih-Hao] Kyoto Univ, Ctr Ecol Res, Otsu, Shiga 5202113, Japan.
   [Hsieh, Chih-Hao] Natl Taiwan Univ, Inst Oceanog, Taipei 10617, Taiwan.
   [Hsieh, Chih-Hao] Natl Taiwan Ocean Univ, Inst Marine Environm Chem & Ecol, Chilung 20224, Taiwan.
   [Hewitt, Roger] Natl Marine Fisheries Serv, SW Fisheries Sci Ctr, La Jolla, CA 92037 USA.
   [Hollowed, Anne] NOAA, Natl Marine Fisheries Serv, Alaska Fisheries Sci Ctr, Seattle, WA 98115 USA.
   [Beddington, John] Univ London Imperial Coll Sci Technol & Med, Div Biol, Fac Nat Sci, London SW7 2AZ, England.
   [May, Robert M.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; Kyoto University; National Taiwan University; National Taiwan Ocean University; National Oceanic Atmospheric Admin (NOAA) - USA; National Oceanic Atmospheric Admin (NOAA) - USA; Imperial College London; University of Oxford
RP Sugihara, G (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
EM gsugihara@ucsd.edu
NR 50
TC 580
Z9 677
U1 5
U2 290
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 17
PY 2008
VL 452
IS 7189
BP 835
EP 839
DI 10.1038/nature06851
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288ZY
UT WOS:000255026000040
PM 18421346
DA 2026-03-09
ER

PT J
AU Brandl, K
   Plitas, G
   Mihu, CN
   Ubeda, C
   Jia, T
   Fleisher, M
   Schnabl, B
   DeMatteo, RP
   Pamer, EG
AF Brandl, Katharina
   Plitas, George
   Mihu, Coralia N.
   Ubeda, Carles
   Jia, Ting
   Fleisher, Martin
   Schnabl, Bernd
   DeMatteo, Ronald P.
   Pamer, Eric G.
TI Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits
SO NATURE
LA English
DT Article
ID toll-like receptor-4; intestinal colonization; bactericidal lectin; mice; gut; lipopolysaccharide; translocation; recognition; infections; therapy
AB Infection with antibiotic- resistant bacteria, such as vancomycin-resistant Enterococcus ( VRE), is a dangerous and costly complication of broad- spectrum antibiotic therapy(1,2). How antibiotic-mediated elimination of commensal bacteria promotes infection by antibiotic- resistant bacteria is a fertile area for speculation with few defined mechanisms. Here we demonstrate that antibiotic treatment of mice notably downregulates intestinal expression of RegIII gamma ( also known as Reg3g), a secreted C- type lectin that kills Gram- positive bacteria, including VRE. Downregulation of RegIII gamma markedly decreases in vivo killing of VRE in the intestine of antibiotic- treated mice. Stimulation of intestinal Toll- like receptor 4 by oral administration of lipopolysaccharide re-induces RegIII gamma, thereby boosting innate immune resistance of antibiotic-treated mice against VRE. Compromised mucosal innate immune defence, as induced by broad- spectrum antibiotic therapy, can be corrected by selectively stimulating mucosal epithelial Toll- like receptors, providing a potential therapeutic approach to reduce colonization and infection by antibiotic- resistant microbes.
C1 [Brandl, Katharina; Mihu, Coralia N.; Ubeda, Carles; Jia, Ting; Pamer, Eric G.] Mem Sloan Kettering Canc Ctr, Infect Dis Serv, Dept Med, Program Immunol,Sloan Kettering Inst, New York, NY 10021 USA.
   [Plitas, George; DeMatteo, Ronald P.] Mem Sloan Kettering Canc Ctr, Hepatobiliary Serv, New York, NY 10021 USA.
   [Fleisher, Martin; Pamer, Eric G.] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10021 USA.
   [Schnabl, Bernd] Columbia Univ, Dept Med, New York, NY 10032 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Columbia University
RP Pamer, EG (corresponding author), Mem Sloan Kettering Canc Ctr, Infect Dis Serv, Dept Med, Program Immunol,Sloan Kettering Inst, 1275 York Ave, New York, NY 10021 USA.
EM pamere@mskcc.org
FU Alexander von Humboldt Foundation; NIH [AI39031, AI42135]
NR 28
TC 538
Z9 663
U1 0
U2 102
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 804
EP U8
DI 10.1038/nature07250
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900048
PM 18724361
DA 2026-03-09
ER

PT J
AU Kim, S
   Jin, JH
   Kim, YJ
   Park, IY
   Kim, Y
   Kim, SW
AF Kim, Seungchul
   Jin, Jonghan
   Kim, Young-Jin
   Park, In-Yong
   Kim, Yunseok
   Kim, Seung-Woo
TI High-harmonic generation by resonant plasmon field enhancement
SO NATURE
LA English
DT Article
ID near-field; pulse laser; x-rays; tips
AB High- harmonic generation by focusing a femtosecond laser onto a gas is a well- known method of producing coherent extreme-ultraviolet ( EUV) light(1-3). This nonlinear conversion process requires high pulse intensities, greater than 10(13) W cm(-2), which are not directly attainable using only the output power of a femtosecond oscillator. Chirped- pulse amplification enables the pulse intensity to exceed this threshold by incorporating several regenerative and/ or multi- pass amplifier cavities in tandem(4,5). Intracavity pulse amplification ( designed not to reduce the pulse repetition rate) also requires a long cavity(6,7). Here we demonstrate a method of high- harmonic generation that requires no extra cavities. This is achieved by exploiting the local field enhancement induced by resonant plasmons within a metallic nanostructure consisting of bow- tie- shaped gold elements on a sapphire substrate. In our experiment, the output beam emitted from a modest femtosecond oscillator ( 100- kW peak power, 1.3- nJ pulse energy and 10- fs pulse duration) is directly focused onto the nanostructure with a pulse intensity of only 10(11) W cm(-2). The enhancement factor exceeds 20 dB, which is sufficient to produce EUV wavelengths down to 47 nm by injection with an argon gas jet. The method could form the basis for constructing laptop- sized EUV light sources for advanced lithography and high- resolution imaging applications.
C1 [Kim, Seungchul; Jin, Jonghan; Kim, Young-Jin; Park, In-Yong; Kim, Yunseok; Kim, Seung-Woo] Korea Adv Inst Sci & Technol, Billionth Uncertainty Precis Engn Grp, Taejon 305701, South Korea.
C3 Korea Advanced Institute of Science & Technology (KAIST)
RP Kim, SW (corresponding author), Korea Adv Inst Sci & Technol, Billionth Uncertainty Precis Engn Grp, Daedeok Sci Town, Taejon 305701, South Korea.
EM swk@kaist.ac.kr
NR 26
TC 1248
Z9 1408
U1 11
U2 695
PU NATURE PUBLISHING 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 5
PY 2008
VL 453
IS 7196
BP 757
EP 760
DI 10.1038/nature07012
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300037
PM 18528390
DA 2026-03-09
ER

PT J
AU Mekhail, K
   Seebacher, J
   Gygi, SP
   Moazed, D
AF Mekhail, Karim
   Seebacher, Jan
   Gygi, Steven P.
   Moazed, Danesh
TI Role for perinuclear chromosome tethering in maintenance of genome stability
SO NATURE
LA English
DT Article
ID ribosomal-rna genes; saccharomyces-cerevisiae; rent complex; yeast rdna; protein; dna; recombination; replication; sir2; transcription
AB Repetitive DNA sequences, which constitute half the genome in some organisms, often undergo homologous recombination. This can instigate genomic instability resulting from a gain or loss of DNA(1). Assembly of DNA into silent chromatin is generally thought to serve as a mechanism ensuring repeat stability by limiting access to the recombination machinery(2). Consistent with this notion is the observation, in the budding yeast Saccharomyces cerevisiae, that stability of the highly repetitive ribosomal DNA( rDNA) sequences requires a Sir2- containing chromatin silencing complex that also inhibits transcription from foreign promoters and transposons inserted within the repeats by a process called rDNA silencing(2-5). Here we describe a protein network that stabilizes rDNA repeats of budding yeast by means of interactions between rDNA- associated silencing proteins and two proteins of the inner nuclear membrane (INM). Deletion of either the INM or silencing proteins reduces perinuclear rDNA positioning, disrupts the nucleolus nucleoplasm boundary, induces the formation of recombination foci, and destabilizes the repeats. In addition, artificial targeting of rDNA repeats to the INM suppresses the instability observed in cells lacking an rDNA- associated silencing protein that is typically required for peripheral tethering of the repeats. Moreover, in contrast to Sir2 and its associated nucleolar factors, the INM proteins are not required for rDNA silencing, indicating that Sir2-dependent silencing is not sufficient to inhibit recombination within the rDNA locus. These findings demonstrate a role for INM proteins in the perinuclear localization of chromosomes and show that tethering to the nuclear periphery is required for the stability of rDNA repeats. The INM proteins studied here are conserved and have been implicated in chromosome organization in metazoans(6,7). Our results therefore reveal an ancient mechanism in which interactions between INM proteins and chromosomal proteins ensure genome stability.
C1 [Mekhail, Karim; Moazed, Danesh] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Mekhail, Karim; Seebacher, Jan; Gygi, Steven P.; Moazed, Danesh] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP Moazed, D (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM danesh@hms.harvard.edu
FU National Institutes of Health; Howard Hughes Medical Institute; Canadian Institutes of Health Research Institute of Aging
NR 36
TC 201
Z9 242
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 DEC 4
PY 2008
VL 456
IS 7222
BP 667
EP U98
DI 10.1038/nature07460
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000047
PM 18997772
DA 2026-03-09
ER

PT J
AU Meyer-Luehmann, M
   Spires-Jones, TL
   Prada, C
   Garcia-Alloza, M
   de Calignon, A
   Rozkalne, A
   Koenigsknecht-Talboo, J
   Holtzman, DM
   Bacskai, BJ
   Hyman, BT
AF Meyer-Luehmann, Melanie
   Spires-Jones, Tara L.
   Prada, Claudia
   Garcia-Alloza, Monica
   de Calignon, Alix
   Rozkalne, Anete
   Koenigsknecht-Talboo, Jessica
   Holtzman, David M.
   Bacskai, Brian J.
   Hyman, Bradley T.
TI Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer's disease
SO NATURE
LA English
DT Article
ID transgenic mice; multiphoton microscopy; precursor protein; in-vivo; microglia; abnormality; neurotoxicity; disruption; deficits; memory
AB Senile plaques accumulate over the course of decades in the brains of patients with Alzheimer's disease. A fundamental tenet of the amyloid hypothesis of Alzheimer's disease is that the deposition of amyloid-beta precedes and induces the neuronal abnormalities that underlie dementia(1). This idea has been challenged, however, by the suggestion that alterations in axonal trafficking and morphological abnormalities precede and lead to senile plaques(2). The role of microglia in accelerating or retarding these processes has been uncertain. To investigate the temporal relation between plaque formation and the changes in local neuritic architecture, we used longitudinal in vivo multiphoton microscopy to sequentially image young APPswe/ PS1d9xYFP ( B6C3-YFP) transgenic mice(3). Here we show that plaques form extraordinarily quickly, over 24 h. Within 1-2 days of a new plaque's appearance, microglia are activated and recruited to the site. Progressive neuritic changes ensue, leading to increasingly dysmorphic neurites over the next days to weeks. These data establish plaques as a critical mediator of neuritic pathology.
C1 [Meyer-Luehmann, Melanie; Spires-Jones, Tara L.; Prada, Claudia; Garcia-Alloza, Monica; de Calignon, Alix; Rozkalne, Anete; Bacskai, Brian J.; Hyman, Bradley T.] Harvard Univ, Massgen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Alzheimers Dis Res Lab,Dept Neurol,Sch Med, Charlestown, MA 02129 USA.
   [Koenigsknecht-Talboo, Jessica; Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Washington University (WUSTL)
RP Hyman, BT (corresponding author), Harvard Univ, Massgen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Alzheimers Dis Res Lab,Dept Neurol,Sch Med, Charlestown, MA 02129 USA.
EM bhyman@partners.org
FU NIA NIH HHS [P50 AG005134, R01 AG008487, P30 AG062421] Funding Source: Medline; NIDDK NIH HHS [P30 DK056341] Funding Source: Medline; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056341] Funding Source: NIH RePORTER
NR 27
TC 874
Z9 1043
U1 2
U2 132
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2008
VL 451
IS 7179
BP 720
EP U5
DI 10.1038/nature06616
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 259HD
UT WOS:000252929500042
PM 18256671
DA 2026-03-09
ER

PT J
AU Tian, DC
   Wang, Q
   Zhang, PF
   Araki, H
   Yang, SH
   Kreitman, M
   Nagylaki, T
   Hudson, R
   Bergelson, J
   Chen, JQ
AF Tian, Dacheng
   Wang, Qiang
   Zhang, Pengfei
   Araki, Hitoshi
   Yang, Sihai
   Kreitman, Martin
   Nagylaki, Thomas
   Hudson, Richard
   Bergelson, Joy
   Chen, Jian-Qun
TI Single-nucleotide mutation rate increases close to insertions/deletions in eukaryotes
SO NATURE
LA English
DT Article
ID human genome; hot-spot; sequence; recombination; substitution; evolution; gene; dna; polymorphism; specificity
AB Mutation hotspots are commonly observed in genomic sequences and certain human disease loci(1-7), but general mechanisms for their formation remain elusive(7-11). Here we investigate the distribution of single- nucleotide changes around insertions/ deletions ( indels) in six independent genome comparisons, including primates, rodents, fruitfly, rice and yeast. In each of these genomic comparisons, nucleotide divergence ( D) is substantially elevated surrounding indels and decreases monotonically to near-background levels over several hundred bases. D is significantly correlated with both size and abundance of nearby indels. In comparisons of closely related species, derived nucleotide substitutions surrounding indels occur in significantly greater numbers in the lineage containing the indel than in the one containing the ancestral ( non- indel) allele; the same holds within species for single- nucleotide mutations surrounding polymorphic indels. We propose that heterozygosity for an indel is mutagenic to surrounding sequences, and use yeast genome- wide polymorphism data to estimate the increase in mutation rate. The consistency of these patterns within and between species suggests that indel- associated substitution is a general mutational mechanism.
C1 [Tian, Dacheng; Wang, Qiang; Zhang, Pengfei; Araki, Hitoshi; Yang, Sihai; Bergelson, Joy; Chen, Jian-Qun] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Dept Biol, Nanjing 210093, Peoples R China.
   [Araki, Hitoshi] EAWAG Ctr Ecol Evolut & Biogeochem, Dept Fish Ecol & Evolut, CH-6047 Kastanienbaum, Switzerland.
   [Kreitman, Martin; Nagylaki, Thomas; Hudson, Richard; Bergelson, Joy] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
C3 Nanjing University; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); University of Chicago
RP Tian, DC (corresponding author), Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Dept Biol, Nanjing 210093, Peoples R China.
EM dtian@nju.edu.cn; chenjq@nju.edu.cn
FU NSFC [30470924, 30470122, 30570987]; NBRPC [2005CCA02100]; 111 Project
NR 28
TC 220
Z9 248
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 105
EP U70
DI 10.1038/nature07175
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200046
PM 18641631
DA 2026-03-09
ER

PT J
AU Setty, SRG
   Tenza, D
   Sviderskaya, EV
   Bennett, DC
   Raposo, G
   Marks, MS
AF Setty, Subba Rao Gangi
   Tenza, Daniele
   Sviderskaya, Elena V.
   Bennett, Dorothy C.
   Raposo, Graca
   Marks, Michael S.
TI Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes
SO NATURE
LA English
DT Article
ID lysosome-related organelles; hermansky-pudlak-syndrome; protein; localization; disease; trafficking; bloc-1; gene; premelanosm; melanogenesis
AB Copper is a cofactor for many cellular enzymes and transporters(1). It can be loaded onto secreted and endomembrane cuproproteins by translocation from the cytosol into membrane- bound organelles by ATP7A or ATP7B transporters, the genes for which are mutated in the copper imbalance syndromes Menkes disease and Wilson disease, respectively(2). Endomembrane cuproproteins are thought to incorporate copper stably on transit through the trans-Golgi network, in which ATP7A accumulates(3) by dynamic cycling through early endocytic compartments(4). Here we show that the pigment- cell- specific cuproenzyme tyrosinase acquires copper only transiently and inefficiently within the trans- Golgi network of mouse melanocytes. To catalyse melanin synthesis, tyrosinase is subsequently reloaded with copper within specialized organelles called melanosomes. Copper is supplied to melanosomes by ATP7A, a cohort of which localizes to melanosomes in a biogenesis of lysosome- related organelles complex-1 ( BLOC-1)- dependent manner. These results indicate that cell- type- specific localization of a metal transporter is required to sustain metallation of an endomembrane cuproenzyme, providing a mechanism for exquisite spatial control of metalloenzyme activity. Moreover, because BLOC- 1 subunits are mutated in subtypes of the genetic disease Hermansky - Pudlak syndrome, these results also show that defects in copper transporter localization contribute to hypopigmentation, and hence perhaps other systemic defects, in Hermansky Pudlak syndrome.
C1 [Setty, Subba Rao Gangi; Marks, Michael S.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Tenza, Daniele; Raposo, Graca] Ctr Rech, Inst Curie, F-75248 Paris, France.
   [Tenza, Daniele; Raposo, Graca] CNRS, UMR 144, F-75248 Paris, France.
   [Sviderskaya, Elena V.; Bennett, Dorothy C.] Univ London St Georges Hosp, Ctr Mol & Metab Signalling, Div Basic Med Sci, London SW17 0RE, England.
C3 University of Pennsylvania; UNICANCER; Universite PSL; Institut Curie; Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Sorbonne Universite; City St Georges, University of London
RP Marks, MS (corresponding author), Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM marksm@mail.med.upenn.edu
FU National Institute of Health [R01 EY015625, R21 GM078474]; CNRS; Institut Curie and Fondation pour la Recherche Medicale; Wellcome Trust program [064583]; American Heart Association [0625437U]; National Eye Institute [R01EY015625] Funding Source: NIH RePORTER; American Heart Association (AHA) [0625437U] Funding Source: American Heart Association (AHA)
NR 33
TC 216
Z9 252
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1142
EP U75
DI 10.1038/nature07163
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600043
PM 18650808
DA 2026-03-09
ER

PT J
AU Yu, RC
   Pesce, CG
   Colman-Lerner, A
   Lok, L
   Pincus, D
   Serra, E
   Holl, M
   Benjamin, K
   Gordon, A
   Brent, R
AF Yu, Richard C.
   Pesce, C. Gustavo
   Colman-Lerner, Alejandro
   Lok, Larry
   Pincus, David
   Serra, Eduard
   Holl, Mark
   Benjamin, Kirsten
   Gordon, Andrew
   Brent, Roger
TI Negative feedback that improves information transmission in yeast signalling
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; invasive growth; mating pathway; protein-kinase; ste5 scaffold; gene networks; pheromone; receptor; binding; transduction
AB Haploid Saccharomyces cerevisiae yeast cells use a prototypic cell signalling system to transmit information about the extracellular concentration of mating pheromone secreted by potential mating partners. The ability of cells to respond distinguishably to different pheromone concentrations depends on how much information about pheromone concentration the system can transmit. Here we show that the mitogen- activated protein kinase Fus3 mediates fast- acting negative feedback that adjusts the dose response of the downstream system response to match the dose response of receptor- ligand binding. This ` dose - response alignment', defined by a linear relationship between receptor occupancy and downstream response, can improve the fidelity of information transmission by making downstream responses corresponding to different receptor occupancies more distinguishable and reducing amplification of stochastic noise during signal transmission. We also show that one target of the feedback is a previously uncharacterized signal- promoting function of the regulator of G- protein signalling protein Sst2. Our work suggests that negative feedback is a general mechanism used in signalling systems to align dose responses and thereby increase the fidelity of information transmission.
C1 [Yu, Richard C.; Pesce, C. Gustavo; Colman-Lerner, Alejandro; Lok, Larry; Pincus, David; Serra, Eduard; Benjamin, Kirsten; Gordon, Andrew; Brent, Roger] Inst Mol Sci, Berkeley, CA 94704 USA.
   [Holl, Mark] Univ Washington, Microscale Life Sci Ctr, Seattle, WA 98195 USA.
C3 The Molecular Sciences Institute; University of Washington; University of Washington Seattle
RP Yu, RC (corresponding author), Inst Mol Sci, 2168 Shattuck Ave, Berkeley, CA 94704 USA.
EM ryu@molsci.org; brent@molsci.org
FU Alpha Project at the Center for Quantitative Genome Function; NIH Center of Excellence in Genomic Science [P50 HG02370]; National Human Genome Research Institute
NR 47
TC 177
Z9 215
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 11
PY 2008
VL 456
IS 7223
BP 755
EP 761
DI 10.1038/nature07513
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900041
PM 19079053
DA 2026-03-09
ER

PT J
AU Raghavan, S
   Manzanillo, P
   Chan, K
   Dovey, C
   Cox, JS
AF Raghavan, Sridharan
   Manzanillo, Paolo
   Chan, Kaman
   Dovey, Cole
   Cox, Jeffery S.
TI Secreted transcription factor controls Mycobacterium tuberculosis virulence
SO NATURE
LA English
DT Article
ID bacillus-calmette-guerin; pseudomonas-aeruginosa; esat-6 secretion; gene-expression; system; infection; antigen; protein; macrophages; vaccination
AB Bacterial pathogens trigger specialized virulence factor secretion systems on encountering host cells. The ESX-1 protein secretion system of Mycobacterium tuberculosis - the causative agent of the human disease tuberculosis - delivers bacterial proteins into host cells during infection and is critical for virulence, but how it is regulated is unknown. Here we show that EspR (also known as Rv3849) is a key regulator of ESX-1 that is required for secretion and virulence in mice. EspR activates transcription of an operon that includes three ESX-1 components, Rv3616c-Rv3614c, whose expression in turn promotes secretion of ESX-1 substrates. EspR directly binds to and activates the Rv3616c-Rv3614c promoter and, unexpectedly, is itself secreted from the bacterial cell by the ESX-1 system that it regulates. Efflux of the DNA-binding regulator results in reduced Rv3616c-Rv3614c transcription, and thus reduced ESX-1 secretion. Our results reveal a direct negative feedback loop that regulates the activity of a secretion system essential for virulence. As the virulence factors secreted by the ESX-1 system are highly antigenic, fine control of secretion may be critical to successful infection.
C1 [Raghavan, Sridharan; Manzanillo, Paolo; Chan, Kaman; Dovey, Cole; Cox, Jeffery S.] Univ Calif San Francisco, Dept Microbiol & Immunol, Program Microbial Pathogenesis & Host Def, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco
RP Cox, JS (corresponding author), Univ Calif San Francisco, Dept Microbiol & Immunol, Program Microbial Pathogenesis & Host Def, 600 16th St,Campus Box 2200, San Francisco, CA 94143 USA.
EM Jeffery.Cox@ucsf.edu
FU National Institute of Allergy and Infectious Diseases [P01AI063302] Funding Source: NIH RePORTER; NIAID NIH HHS [R01 AI051667, P01 AI063302, AI63302, AI51667] Funding Source: Medline
NR 40
TC 164
Z9 226
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 717
EP U49
DI 10.1038/nature07219
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000035
PM 18685700
DA 2026-03-09
ER

PT J
AU Hurtado, A
   Holmes, KA
   Geistlinger, TR
   Hutcheson, IR
   Nicholson, RI
   Brown, M
   Jiang, J
   Howat, WJ
   Ali, S
   Carroll, JS
AF Hurtado, Antoni
   Holmes, Kelly A.
   Geistlinger, Timothy R.
   Hutcheson, Iain R.
   Nicholson, Robert I.
   Brown, Myles
   Jiang, Jie
   Howat, William J.
   Ali, Simak
   Carroll, Jason S.
TI Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen
SO NATURE
LA English
DT Article
ID breast-cancer cells; mcf-7 cells; resistance; coactivator; expression; activation; aib1; transcription; survival; therapy
AB Crosstalk between the oestrogen receptor (ER) and ERBB2/HER-2 pathways has long been implicated in breast cancer aetiology and drug eresponse(1), yet no direct connection at a transcriptional level has been shown. Here we show that oestrogen-ER and tamoxifen ER complexes directly repress ERBB2 transcription by means of a cis- regulatory element within the ERBB2 gene in human cell lines. We implicate the paired box 2 gene product ( PAX2), in a previously unrecognized role, as a crucial mediator of ER repression of ERBB2 by the anti- cancer drug tamoxifen. Weshow that PAX2 and the ER co-activator AIB-1/SRC-3 compete for binding and regulation of ERBB2 transcription, the outcome of which determines tamoxifen response in breast cancer cells. The repression of ERBB2 by ER-PAX2 links these two breast cancer subtypes and suggests that aggressive ERBB2- positive tumours can originate from ER- positive luminal tumours by circumventing this repressive mechanism. These data provide mechanistic insight into the molecular basis of endocrine resistance in breast cancer.
C1 [Hurtado, Antoni; Holmes, Kelly A.; Howat, William J.; Carroll, Jason S.] Cambridge Res Inst, Canc Res UK, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Geistlinger, Timothy R.; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Geistlinger, Timothy R.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Hutcheson, Iain R.; Nicholson, Robert I.] Cardiff Univ, Tenovus Ctr Canc Res, Welsh Sch Pharm, Cardiff CF10 3XF, Wales.
   [Jiang, Jie; Ali, Simak] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London W12 0NN, England.
C3 University of Cambridge; CRUK Cambridge Institute; Cancer Research UK; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Cardiff University; Imperial College London
RP Carroll, JS (corresponding author), Cambridge Res Inst, Canc Res UK, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England.
EM jason.carroll@cancer.org.uk
FU National Institute of Diabetes and Digestive and Kidney Disease [R01DK074967]; National Cancer Institute [P01CA8011105]; DF/HCC Breast Cancer SPORE; University of Cambridge; Cancer Research UK; Hutchison Whampoa Limited
NR 30
TC 262
Z9 313
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 4
PY 2008
VL 456
IS 7222
BP 663
EP U93
DI 10.1038/nature07483
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 378QW
UT WOS:000261340000046
PM 19005469
DA 2026-03-09
ER

PT J
AU Kim, HJ
   Oh, SA
   Brownfield, L
   Hong, SH
   Ryu, H
   Hwang, I
   Twell, D
   Nam, HG
AF Kim, Hyo Jung
   Oh, Sung Aeong
   Brownfield, Lynette
   Hong, Sung Hyun
   Ryu, Hojin
   Hwang, Ildoo
   Twell, David
   Nam, Hong Gil
TI Control of plant germline proliferation by SCFFBL17 degradation of cell cycle inhibitors
SO NATURE
LA English
DT Article
ID f-box proteins; functional-analysis; arabidopsis; expression; signal; gene; insights; mutants; complex; tobacco
AB Flowering plants possess a unique reproductive strategy, involving double fertilization by twin sperm cells(1). Unlike animal germ lines, the male germ cell lineage in plants only forms after meiosis and involves asymmetric division of haploid microspores, to produce a large, non- germline vegetative cell and a germ cell that undergoes one further division to produce the twin sperm cells(2). Although this switch in cell cycle control is critical for sperm cell production and delivery, the underlying molecular mechanisms are unknown. Here we identify a novel F- box protein of Arabidopsis thaliana, designated FBL17 ( F- box- like 17), that enables this switch by targeting the degradation of cyclin- dependent kinase A; 1 inhibitors specifically in male germ cells. We show that FBL17 is transiently expressed in the male germ line after asymmetric division and forms an SKP1 -Cullin1 - F- box protein ( SCF) E3 ubiquitin ligase complex (SCFFBL17) that targets the cyclin- dependent kinase inhibitors KRP6 and KRP7 for proteasome- dependent degradation. Accordingly, the loss of FBL17 function leads to the stabilization of KRP6 and inhibition of germ cell cycle progression. Our results identify SCFFBL17 as an essential male germ cell proliferation complex that promotes twin sperm cell production and double fertilization in flowering plants.
C1 [Oh, Sung Aeong; Brownfield, Lynette; Twell, David] Univ Leicester, Dept Biol, Leicester LE1 7RH, Leics, England.
   [Kim, Hyo Jung; Hong, Sung Hyun; Ryu, Hojin; Hwang, Ildoo; Nam, Hong Gil] Pohang Univ Sci & Technol, Div Mol Life Sci, Pohang 790784, South Korea.
   [Nam, Hong Gil] Pohang Univ Sci & Technol, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, South Korea.
C3 University of Leicester; Pohang University of Science & Technology (POSTECH); Pohang University of Science & Technology (POSTECH)
RP Twell, D (corresponding author), Univ Leicester, Dept Biol, Univ Rd, Leicester LE1 7RH, Leics, England.
EM twe@le.ac.uk; nam@postech.ac.kr
FU MOST ( KOSEF) through the National Core Research Center for Systems Bio-Dynamics; Crop Functional Genomics Research Program; Biotechnology and Biological Sciences Research Council; BK21 research fellowship for Life Science, Kyungpook National University; KRF grant; MOHERD; BBSRC [BB/E001017/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/E001017/1, BB/C004205/1] Funding Source: researchfish
NR 36
TC 179
Z9 203
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 23
PY 2008
VL 455
IS 7216
BP 1134
EP U14
DI 10.1038/nature07289
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600050
PM 18948957
DA 2026-03-09
ER

PT J
AU Herry, C
   Ciocchi, S
   Senn, V
   Demmou, L
   Müller, C
   Lüthi, A
AF Herry, Cyril
   Ciocchi, Stephane
   Senn, Verena
   Demmou, Lynda
   Mueller, Christian
   Luethi, Andreas
TI Switching on and off fear by distinct neuronal circuits
SO NATURE
LA English
DT Article
ID hippocampal inactivation disrupts; medial prefrontal cortex; lateral amygdala neurons; basolateral amygdala; extinction; memory; responses; context; acquisition; modulation
AB Switching between exploratory and defensive behaviour is fundamental to survival of many animals, but how this transition is achieved by specific neuronal circuits is not known. Here, using the converse behavioural states of fear extinction and its context- dependent renewal as a model in mice, we show that bi- directional transitions between states of high and low fear are triggered by a rapid switch in the balance of activity between two distinct populations of basal amygdala neurons. These two populations are integrated into discrete neuronal circuits differentially connected with the hippocampus and the medial prefrontal cortex. Targeted and reversible neuronal inactivation of the basal amygdala prevents behavioural changes without affecting memory or expression of behaviour. Our findings indicate that switching between distinct behavioural states can be triggered by selective activation of specific neuronal circuits integrating sensory and contextual information. These observations provide a new framework for understanding context- dependent changes of fear behaviour.
C1 [Herry, Cyril; Ciocchi, Stephane; Senn, Verena; Demmou, Lynda; Mueller, Christian; Luethi, Andreas] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research
RP Lüthi, A (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM cyril.herry@fmi.ch; andreas.luthi@fmi.ch
NR 50
TC 763
Z9 966
U1 0
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 600
EP U28
DI 10.1038/nature07166
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500038
PM 18615015
DA 2026-03-09
ER

PT J
AU Wang, YJ
   Cheng, H
   Edwards, RL
   Kong, XG
   Shao, XH
   Chen, ST
   Wu, JY
   Jiang, XY
   Wang, XF
   An, ZS
AF Wang, Yongjin
   Cheng, Hai
   Edwards, R. Lawrence
   Kong, Xinggong
   Shao, Xiaohua
   Chen, Shitao
   Wu, Jiangyin
   Jiang, Xiouyang
   Wang, Xianfeng
   An, Zhisheng
TI Millennial- and orbital-scale changes in the East Asian monsoon over the past 224,000 years
SO NATURE
LA English
DT Article
ID hulu cave; climate; record; holocene; variability; insolation; cycle
AB High- resolution speleothem records from China have provided insights into the factors that control the strength of the East Asian monsoon(1-4). Our understanding of these factors remains incomplete, however, owing to gaps in the record of monsoon history over the past two interglacial - glacial cycles. In particular, missing sections have hampered our ability to test ideas about orbital- scale controls on the monsoon(5-7), the causes of millennial- scale events(8,9) and relationships between changes in the monsoon and climate in other regions. Here we present an absolute- dated oxygen isotope record from Sanbao cave, central China, that completes a Chinese-cave-based record of the strength of the East Asian monsoon that covers the past 224,000 years. The record is dominated by 23,000-year- long cycles that are synchronous within dating errors with summer insolation at 65 degrees N ( ref. 10), supporting the idea that tropical/ subtropical monsoons respond dominantly and directly to changes in Northern Hemisphere summer insolation on orbital timescales(5). The cycles are punctuated by millennial- scale strong-summer-monsoon events ( Chinese interstadials(1)), and the new record allows us to identify the complete series of these events over the past two interglacial - glacial cycles. Their duration decreases and their frequency increases during glacial build- up in both the last and penultimate glacial periods, indicating that ice sheet size affects their character and pacing. The ages of the events are exceptionally well constrained and may thus serve as benchmarks for correlating and calibrating climate records.
C1 [Wang, Yongjin; Cheng, Hai; Kong, Xinggong; Shao, Xiaohua; Chen, Shitao; Wu, Jiangyin; Jiang, Xiouyang] Nanjing Normal Univ, Coll Geog Sci, Jiangsu 210097, Peoples R China.
   [Cheng, Hai; Edwards, R. Lawrence; Wang, Xianfeng] Univ Minnesota, Dept Geol & Geophys, Minneapolis, MN 55455 USA.
   [An, Zhisheng] Chinese Acad Sci, State Key Lab Loess & Quaternary Geol, Inst Earth Environm, Xian 710054, Peoples R China.
C3 Nanjing Normal University; University of Minnesota System; University of Minnesota Twin Cities; Chinese Academy of Sciences; Institute of Earth Environment, CAS
RP Wang, YJ (corresponding author), Nanjing Normal Univ, Coll Geog Sci, Jiangsu 210097, Peoples R China.
EM yjwang@njnu.edu.cn; cheng021@umn.edu; edwar001@umn.edu
NR 29
TC 1647
Z9 2066
U1 24
U2 689
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1090
EP 1093
DI 10.1038/nature06692
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600038
PM 18305541
DA 2026-03-09
ER

PT J
AU Sallee, NA
   Rivera, GM
   Dueber, JE
   Vasilescu, D
   Mullins, RD
   Mayer, BJ
   Lim, WA
AF Sallee, Nathan A.
   Rivera, Gonzalo M.
   Dueber, John E.
   Vasilescu, Dan
   Mullins, R. Dyche
   Mayer, Bruce J.
   Lim, Wendell A.
TI The pathogen protein EspFU hijacks actin polymerization using mimicry and multivalency
SO NATURE
LA English
DT Article
ID aldrich-syndrome protein; arp2/3 complex; n-wasp; wasp/scar proteins; activation; effector; nucleation; nck; cytoskeleton; mechanisms
AB Enterohaemorrhagic Escherichia coli attaches to the intestine through actin pedestals that are formed when the bacterium injects its protein EspFU ( also known as TccP) into host cells(1). EspFU potently activates the host WASP ( Wiskott - Aldrich syndrome protein) family of actin- nucleating factors, which are normally activated by the GTPase CDC42, among other signalling molecules. Apart from its amino- terminal type III secretion signal, EspFU consists of five- and- a- half 47- amino- acid repeats. Here we show that a 17- residue motif within this EspFU repeat is sufficient for interaction with N- WASP ( also known as WASL). Unlike most pathogen proteins that interface with the cytoskeletal machinery, this motif does not mimic natural upstream activators: instead of mimicking an activated state of CDC42, EspFU mimics an auto-nhibitory element found within N- WASP. Thus, EspFU activates N- WASP by competitively disrupting the autoinhibited state. By mimicking an internal regulatory element and not the natural activator, EspFU selectively activates only a precise subset of CDC42- activated processes. Although one repeat is able to stimulate actin polymerization, we show that multiple- repeat fragments have notably increased potency. The activities of these EspFU fragments correlate with their ability to coordinate activation of at least two N- WASP proteins. Thus, this pathogen has used a simple autoinhibitory fragment as a component to build a highly effective actin polymerization machine.
C1 [Sallee, Nathan A.; Dueber, John E.; Mullins, R. Dyche; Lim, Wendell A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Sallee, Nathan A.; Dueber, John E.; Mullins, R. Dyche; Lim, Wendell A.] Univ Calif San Francisco, Cell Propuls Lab, NIH Nanomed Dev Ctr, San Francisco, CA 94158 USA.
   [Sallee, Nathan A.] Univ Calif San Francisco, Grad Program Chem & Chem Biol, San Francisco, CA 94158 USA.
   [Rivera, Gonzalo M.; Vasilescu, Dan; Mayer, Bruce J.] Univ Connecticut, Ctr Hlth, Raymond & Beverly Sackler Lab Genet & Mol Med, Dept Genet & Dev Biol, Farmington, CT 06030 USA.
   [Rivera, Gonzalo M.; Vasilescu, Dan; Mayer, Bruce J.] Univ Connecticut, Ctr Hlth, CCAM, Farmington, CT 06030 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 Connecticut; University of Connecticut
RP Lim, WA (corresponding author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, 600 16th St, San Francisco, CA 94158 USA.
EM lim@cmp.ucsf.edu
FU NIH; NIGMS; Nanomedicine Development Centers; NIH Roadmap; NSF; Packard Foundation; American Heart Association
NR 35
TC 95
Z9 114
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 21
PY 2008
VL 454
IS 7207
BP 1005
EP U49
DI 10.1038/nature07170
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000041
PM 18650806
DA 2026-03-09
ER

PT J
AU Umbach, JL
   Kramer, MF
   Jurak, I
   Karnowski, HW
   Coen, DM
   Cullen, BR
AF Umbach, Jennifer Lin
   Kramer, Martha F.
   Jurak, Igor
   Karnowski, Heather W.
   Coen, Donald M.
   Cullen, Bryan R.
TI MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs
SO NATURE
LA English
DT Article
ID herpes-simplex-virus; reading-frame-p; type-1 latency; neuronal survival; gene-expression; sensory neurons; transcript; reactivation; cells; icp0
AB Herpesviruses are characterized by their ability to maintain lifelong latent infections in their animal hosts. However, the mechanisms that allow establishment and maintenance of the latent state remain poorly understood. Herpes simplex virus 1 (HSV-1) establishes latency in neurons of sensory ganglia, where the only abundant viral gene product is a non-coding RNA, the latency associated transcript (LAT)(1,2). Here we show that LAT functions as a primary microRNA (miRNA) precursor that encodes four distinct miRNAs in HSV-1 infected cells. One of these miRNAs, miR-H2-3p, is transcribed in an antisense orientation to ICP0-a viral immediate-early transcriptional activator that is important for productive HSV-1 replication and thought to have a role in reactivation from latency(3). We show that miR-H2-3p is able to reduce ICP0 protein expression, but does not significantly affect ICP0 messenger RNA levels. We also identified a fifth HSV-1 miRNA in latently infected trigeminal ganglia, miR-H6, which derives from a previously unknown transcript distinct from LAT. miR-H6 shows extended seed complementarity to the mRNA encoding a second HSV-1 transcription factor, ICP4, and inhibits expression of ICP4, which is required for expression of most HSV-1 genes during productive infection(4). These results may explain the reported ability of LAT to promote latency(5-9). Thus, HSV-1 expresses at least two primary miRNA precursors in latently infected neurons that may facilitate the establishment and maintenance of viral latency by post-transcriptionally regulating viral gene expression.
C1 [Umbach, Jennifer Lin; Karnowski, Heather W.; Cullen, Bryan R.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
   [Umbach, Jennifer Lin; Karnowski, Heather W.; Cullen, Bryan R.] Duke Univ, Med Ctr, Ctr Virol, Durham, NC 27710 USA.
   [Kramer, Martha F.; Jurak, Igor; Coen, Donald M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 Duke University; Duke University; Harvard University; Harvard Medical School
RP Cullen, BR (corresponding author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM culle002@mc.duke.edu
FU National Cancer Institute [T32CA009111] Funding Source: NIH RePORTER; NCI NIH HHS [T32 CA009111] Funding Source: Medline; NIAID NIH HHS [R01 AI067968] Funding Source: Medline
NR 37
TC 543
Z9 719
U1 2
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 780
EP U108
DI 10.1038/nature07103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000048
PM 18596690
DA 2026-03-09
ER

PT J
AU Pesu, M
   Watford, WT
   Wei, L
   Xu, LL
   Fuss, I
   Strober, W
   Andersson, J
   Shevach, EM
   Quezado, M
   Bouladoux, N
   Roebroek, A
   Belkaid, Y
   Creemers, J
   O'Shea, JJ
AF Pesu, Marko
   Watford, Wendy T.
   Wei, Lai
   Xu, Lili
   Fuss, Ivan
   Strober, Warren
   Andersson, John
   Shevach, Ethan M.
   Quezado, Martha
   Bouladoux, Nicolas
   Roebroek, Anton
   Belkaid, Yasmine
   Creemers, John
   O'Shea, John J.
TI T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance
SO NATURE
LA English
DT Article
ID activation; beta; growth; mice; conversion; induction; colitis; master; foxp3
AB Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins(1). It is induced in activated T cells and is reported to process a variety of substrates including the anti- inflammatory cytokine transforming growth factor (TGF)-beta 1 ( refs 2 - 4), but the non- redundant functions of furin versus other proprotein convertases in T cells are unclear. Here we show that conditional deletion of furin in T cells allowed for normal T- cell development but impaired the function of regulatory and effector T cells, which produced less TGF-beta 1. Furin-deficient T regulatory (T-reg) cells were less protective in a T- cell transfer colitis model and failed to induce Foxp3 in normal T cells. Additionally, furin- deficient effector cells were inherently over-active and were resistant to suppressive activity of wild- type T-reg cells. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its non- redundant, essential function in regulating TGF-beta 1 production. Targeting furin has emerged as a strategy in malignant and infectious disease(5,6). Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.
C1 [Pesu, Marko; Watford, Wendy T.; Wei, Lai; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
   [Xu, Lili; Fuss, Ivan; Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
   [Andersson, John; Shevach, Ethan M.] NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Bouladoux, Nicolas; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   [Roebroek, Anton; Creemers, John] Katholieke Univ Leuven, Biochem Neuroendocrinol Lab, B-3000 Louvain, Belgium.
   [Roebroek, Anton; Creemers, John] VIB, B-3000 Louvain, Belgium.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); KU Leuven; Flanders Institute for Biotechnology (VIB)
RP Pesu, M (corresponding author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM pesum@mail.nih.gov
FU Intramural Research Program of NIAMS; Academy of Finland; Finnish Medical Foundation; Maud Kuistila Memorial Foundation; Fonds voor Wetenschappelijk Onderzoek Vlaanderen; Geconcerteerde Onderzoeksactie van de Vlaamse Gemeenschap; National Institute of Allergy and Infectious Diseases [ZIAAI000959, ZIAAI000354] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIAAR041159] Funding Source: NIH RePORTER
NR 25
TC 179
Z9 213
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 11
PY 2008
VL 455
IS 7210
BP 246
EP U73
DI 10.1038/nature07210
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800052
PM 18701887
DA 2026-03-09
ER

PT J
AU Thorgeirsson, TE
   Geller, F
   Sulem, P
   Rafnar, T
   Wiste, A
   Magnusson, KP
   Manolescu, A
   Thorleifsson, G
   Stefansson, H
   Ingason, A
   Stacey, SN
   Bergthorsson, JT
   Thorlacius, S
   Gudmundsson, J
   Jonsson, T
   Jakobsdottir, M
   Saemundsdottir, J
   Olafsdottir, O
   Gudmundsson, LJ
   Bjornsdottir, G
   Kristjansson, K
   Skuladottir, H
   Isaksson, HJ
   Gudbjartsson, T
   Jones, GT
   Mueller, T
   Gottsäter, A
   Flex, A
   Aben, KKH
   de Vegt, F
   Mulders, PFA
   Isla, D
   Vidal, MJ
   Asin, L
   Saez, B
   Murillo, L
   Blondal, T
   Kolbeinsson, H
   Stefansson, JG
   Hansdottir, I
   Runarsdottir, V
   Pola, R
   Lindblad, B
   van Rij, AM
   Dieplinger, B
   Haltmayer, M
   Mayordomo, JI
   Kiemeney, LA
   Matthiasson, SE
   Oskarsson, H
   Tyrfingsson, T
   Gudbjartsson, DF
   Gulcher, JR
   Jonsson, S
   Thorsteinsdottir, U
   Kong, A
   Stefansson, K
AF Thorgeirsson, Thorgeir E.
   Geller, Frank
   Sulem, Patrick
   Rafnar, Thorunn
   Wiste, Anna
   Magnusson, Kristinn P.
   Manolescu, Andrei
   Thorleifsson, Gudmar
   Stefansson, Hreinn
   Ingason, Andres
   Stacey, Simon N.
   Bergthorsson, Jon T.
   Thorlacius, Steinunn
   Gudmundsson, Julius
   Jonsson, Thorlakur
   Jakobsdottir, Margret
   Saemundsdottir, Jona
   Olafsdottir, Olof
   Gudmundsson, Larus J.
   Bjornsdottir, Gyda
   Kristjansson, Kristleifur
   Skuladottir, Halla
   Isaksson, Helgi J.
   Gudbjartsson, Tomas
   Jones, Gregory T.
   Mueller, Thomas
   Gottsater, Anders
   Flex, Andrea
   Aben, Katja K. H.
   de Vegt, Femmie
   Mulders, Peter F. A.
   Isla, Dolores
   Vidal, Maria J.
   Asin, Laura
   Saez, Berta
   Murillo, Laura
   Blondal, Thorsteinn
   Kolbeinsson, Halldor
   Stefansson, Jon G.
   Hansdottir, Ingunn
   Runarsdottir, Valgerdur
   Pola, Roberto
   Lindblad, Bengt
   van Rij, Andre M.
   Dieplinger, Benjamin
   Haltmayer, Meinhard
   Mayordomo, Jose I.
   Kiemeney, Lambertus A.
   Matthiasson, Stefan E.
   Oskarsson, Hogni
   Tyrfingsson, Thorarinn
   Gudbjartsson, Daniel F.
   Gulcher, Jeffrey R.
   Jonsson, Steinn
   Thorsteinsdottir, Unnur
   Kong, Augustine
   Stefansson, Kari
TI A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
SO NATURE
LA English
DT Article
ID genetic influence; lower-extremity; fagerstrom test; risk-factors; smoking; carcinoma; smokers; statistics; addiction; ischemia
AB Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.
C1 [Thorgeirsson, Thorgeir E.; Geller, Frank; Sulem, Patrick; Rafnar, Thorunn; Wiste, Anna; Magnusson, Kristinn P.; Manolescu, Andrei; Thorleifsson, Gudmar; Stefansson, Hreinn; Ingason, Andres; Stacey, Simon N.; Bergthorsson, Jon T.; Thorlacius, Steinunn; Gudmundsson, Julius; Jonsson, Thorlakur; Jakobsdottir, Margret; Saemundsdottir, Jona; Olafsdottir, Olof; Gudmundsson, Larus J.; Bjornsdottir, Gyda; Kristjansson, Kristleifur; Gudbjartsson, Daniel F.; Gulcher, Jeffrey R.; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland.
   [Wiste, Anna] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
   [Skuladottir, Halla] Landspital Univ Hosp, Dept Med Oncol, IS-101 Reykjavik, Iceland.
   [Isaksson, Helgi J.] Landspital Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland.
   [Gudbjartsson, Tomas] Landspital Univ Hosp, Dept Cardiothorac Surg, IS-101 Reykjavik, Iceland.
   [Kolbeinsson, Halldor; Stefansson, Jon G.] Landspital Univ Hosp, Dept Gen Adult Psychiat, IS-101 Reykjavik, Iceland.
   [Jonsson, Steinn] Landspital Univ Hosp, Dept Med, IS-101 Reykjavik, Iceland.
   [Jones, Gregory T.; van Rij, Andre M.] Univ Otago, Dept Surg, Dunedin Sch Med, Dunedin 9054, New Zealand.
   [Mueller, Thomas; Dieplinger, Benjamin; Haltmayer, Meinhard] Konventhosp Barmherzige Brueder, Dept Lab Med, A-4020 Linz, Austria.
   [Gottsater, Anders; Lindblad, Bengt] Malmo Univ Hosp, MAS, Ctr Vasc Dis, S-20502 Malmo, Sweden.
   [Flex, Andrea; Pola, Roberto] Univ Cattolica Sacro Cuore, Sch Med, Lab Vasc Biol & Genet, A Gemelli Univ Hosp, I-00168 Rome, Italy.
   [Aben, Katja K. H.; de Vegt, Femmie; Kiemeney, Lambertus A.] Radboud Univ Nijmegen Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands.
   [Aben, Katja K. H.; Kiemeney, Lambertus A.] Comprehens Canc Ctr E, NL-6501 BG Nijmegen, Netherlands.
   [Mulders, Peter F. A.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen Med Ctr, Dept Urol, NL-6525 GA Nijmegen, Netherlands.
   [Isla, Dolores; Vidal, Maria J.; Mayordomo, Jose I.] Univ Hosp, Div Med Oncol, Zaragoza 5009, Spain.
   [Asin, Laura; Mayordomo, Jose I.] Nanotechnol Inst Aragon, Zaragoza 5009, Spain.
   [Saez, Berta; Mayordomo, Jose I.] Hlth Sci Inst, Zaragoza 5009, Spain.
   [Murillo, Laura] Hosp Reina Sofia, Div Med Oncol, Tudela 31500, Spain.
   [Blondal, Thorsteinn] Primary Hlth Care Ctr, Dept Lung Dis, IS-101 Reykjavik, Iceland.
   [Hansdottir, Ingunn; Runarsdottir, Valgerdur; Tyrfingsson, Thorarinn] Vogur SAA Addict Treatment Ctr, IS-112 Reykjavik, Iceland.
   [Pola, Roberto] IRCCS, OASI Inst Res & Care, I-94018 Troina, EN, Italy.
   [Matthiasson, Stefan E.; Stefansson, Kari] Univ Iceland, Sch Med, IS-101 Reykjavik, Iceland.
   [Oskarsson, Hogni] Therapeia, IS-101 Reykjavik, Iceland.
C3 Decode Genetics; Emory University; Landspitali National University Hospital; Landspitali National University Hospital; Landspitali National University Hospital; Landspitali National University Hospital; Landspitali National University Hospital; University of Otago; Konventhospital Der Barmherzigen Bruder; Lund University; Skane University Hospital; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; Radboud University Nijmegen; Radboud University Nijmegen; Miguel Servet University Hospital; Servicio Navarro de Salud - Osasunbidea; IRCCS - Oasi Research Institute; University of Iceland
RP Thorgeirsson, TE (corresponding author), deCODE Genet, IS-101 Reykjavik, Iceland.
EM thorgeir@decode.is; kari.stefansson@decode.is
FU NIDA NIH HHS [R01 DA017932] Funding Source: Medline
NR 39
TC 1201
Z9 1345
U1 2
U2 163
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 638
EP U9
DI 10.1038/nature06846
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200047
PM 18385739
DA 2026-03-09
ER

PT J
AU Yin, P
   Choi, HMT
   Calvert, CR
   Pierce, NA
AF Yin, Peng
   Choi, Harry M. T.
   Calvert, Colby R.
   Pierce, Niles A.
TI Programming biomolecular self-assembly pathways
SO NATURE
LA English
DT Article
ID dna; design; hybridization; devices; enzyme; track; fuel
AB In nature, self- assembling and disassembling complexes of proteins and nucleic acids bound to a variety of ligands perform intricate and diverse dynamic functions. In contrast, attempts to rationally encode structure and function into synthetic amino acid and nucleic acid sequences have largely focused on engineering molecules that self- assemble into prescribed target structures, rather than on engineering transient system dynamics(1,2). To design systems that perform dynamic functions without human intervention, it is necessary to encode within the biopolymer sequences the reaction pathways by which self- assembly occurs. Nucleic acids show promise as a design medium for engineering dynamic functions, including catalytic hybridization(3-6), triggered self- assembly(7) and molecular computation(8,9). Here, we program diverse molecular self- assembly and disassembly pathways using a 'reaction graph' abstraction to specify complementarity relationships between modular domains in a versatile DNA hairpin motif. Molecular programs are executed for a variety of dynamic functions: catalytic formation of branched junctions, autocatalytic duplex formation by a cross- catalytic circuit, nucleated dendritic growth of a binary molecular 'tree', and autonomous locomotion of a bipedal walker.
C1 [Yin, Peng; Choi, Harry M. T.; Calvert, Colby R.; Pierce, Niles A.] CALTECH, Dept Bioengn, Pasadena, CA 91125 USA.
   [Yin, Peng] CALTECH, Dept Comp Sci, Pasadena, CA 91125 USA.
   [Pierce, Niles A.] CALTECH, Dept Appl & Computat Math, Pasadena, CA 91125 USA.
C3 California Institute of Technology; California Institute of Technology; California Institute of Technology
RP Pierce, NA (corresponding author), CALTECH, Dept Bioengn, Pasadena, CA 91125 USA.
EM niles@caltech.edu
FU Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [0832824] Funding Source: National Science Foundation
NR 32
TC 1383
Z9 1617
U1 24
U2 1247
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 17
PY 2008
VL 451
IS 7176
BP 318
EP U4
DI 10.1038/nature06451
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100046
PM 18202654
DA 2026-03-09
ER

PT J
AU Luyssaert, S
   Schulze, ED
   Börner, A
   Knohl, A
   Hessenmöller, D
   Law, BE
   Ciais, P
   Grace, J
AF Luyssaert, Sebastiaan
   Schulze, E. -Detlef
   Boerner, Annett
   Knohl, Alexander
   Hessenmoeller, Dominik
   Law, Beverly E.
   Ciais, Philippe
   Grace, John
TI Old-growth forests as global carbon sinks
SO NATURE
LA English
DT Article
ID net primary production; storage; boreal; temperate; exchange; dioxide; decline; biomass; fluxes; pine
AB Old- growth forests remove carbon dioxide from the atmosphere(1,2) at rates that vary with climate and nitrogen deposition(3). The sequestered carbon dioxide is stored in live woody tissues and slowly decomposing organic matter in litter and soil(4). Old- growth forests therefore serve as a global carbon dioxide sink, but they are not protected by international treaties, because it is generally thought that ageing forests cease to accumulate carbon(5,6). Here we report a search of literature and databases for forest carbon- flux estimates. We find that in forests between 15 and 800 years of age, net ecosystem productivity ( the net carbon balance of the forest including soils) is usually positive. Our results demonstrate that old- growth forests can continue to accumulate carbon, contrary to the long-standing view that they are carbon neutral. Over 30 per cent of the global forest area is unmanaged primary forest, and this area contains the remaining old- growth forests(7). Half of the primary forests (6 x 10(8) hectares) are located in the boreal and temperate regions of the Northern Hemisphere. On the basis of our analysis, these forests alone sequester about 1.3 +/- 0.5 gigatonnes of carbon per year. Thus, our findings suggest that 15 per cent of the global forest area, which is currently not considered when offsetting increasing atmospheric carbon dioxide concentrations, provides at least 10 per cent of the global net ecosystem productivity(8). Old- growth forests accumulate carbon for centuries and contain large quantities of it. We expect, however, that much of this carbon, even soil carbon(9), will move back to the atmosphere if these forests are disturbed.
C1 [Luyssaert, Sebastiaan] Univ Antwerp, Dept Biol, B-2610 Antwerp, Belgium.
   [Luyssaert, Sebastiaan; Law, Beverly E.] Oregon State Univ, Coll Forestry, Corvallis, OR 97331 USA.
   [Schulze, E. -Detlef; Boerner, Annett; Hessenmoeller, Dominik] Max Planck Inst Biogeochem, D-07701 Jena, Germany.
   [Knohl, Alexander] ETH, Inst Plant Sci, CH-8092 Zurich, Switzerland.
   [Ciais, Philippe] CEA CNRS UVSQ, IPSL LSCE, Lab Sci Climat & Environm, F-91191 Gif Sur Yvette, France.
   [Grace, John] Univ Edinburgh, Sch Geosci, Edinburgh EH9 3JN, Midlothian, Scotland.
C3 University of Antwerp; Oregon State University; Max Planck Society; Swiss Federal Institutes of Technology Domain; ETH Zurich; Universite Paris Saclay; CEA; University of Edinburgh
RP Luyssaert, S (corresponding author), Univ Antwerp, Dept Biol, B-2610 Antwerp, Belgium.
EM sebastiaan.luyssaert@ua.ac.be
FU CoE ECO UA-Methusalem and the Research Foundation - Flanders (FWO-Vlaanderen); European Union with a Marie Curie fellowship; North American Carbon Program project ORCA; US Department of Energy, Terrestrial Carbon Program [DE-FG02-04ER63917]; DFG-Exploratories.; CarboEuropeIP [GOCE-CT-2003-505572]; Ameriflux; NERC [earth010003] Funding Source: UKRI; Natural Environment Research Council [earth010003] Funding Source: researchfish
NR 29
TC 1373
Z9 1658
U1 37
U2 1106
PU NATURE PUBLISHING 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 11
PY 2008
VL 455
IS 7210
BP 213
EP 215
DI 10.1038/nature07276
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800044
PM 18784722
DA 2026-03-09
ER

PT J
AU Bertaina, S
   Gambarelli, S
   Mitra, T
   Tsukerblat, B
   Müller, A
   Barbara, B
AF Bertaina, S.
   Gambarelli, S.
   Mitra, T.
   Tsukerblat, B.
   Mueller, A.
   Barbara, B.
TI Quantum oscillations in a molecular magnet
SO NATURE
LA English
DT Article
ID weak ferromagnetism; magnetization; v-15; cluster; relaxation; qubits; phase
AB The term 'molecular magnet' generally refers to a molecular entity containing several magnetic ions whose coupled spins generate a collective spin, S ( ref. 1). Such complex multi- spin systems provide attractive targets for the study of quantum effects at the mesoscopic scale. In these molecules, the large energy barriers between collective spin states can be crossed by thermal activation or quantum tunnelling, depending on the temperature or an applied magnetic field(2-4). There is the hope that these mesoscopic spin states can be harnessed for the realization of quantum bits 'qubits', the basic building blocks of a quantum computer - based on molecular magnets(5-8). But strong decoherence(9) must be overcome if the envisaged applications are to become practical. Here we report the observation and analysis of Rabi oscillations ( quantum oscillations resulting from the coherent absorption and emission of photons driven by an electromagnetic wave(10)) of a molecular magnet in a hybrid system, in which discrete and well-separated magnetic V-15(IV) clusters are embedded in a self- organized non- magnetic environment. Each cluster contains 15 antiferromagnetically coupled S = 1/ 2 spins, leading to an S = 1/ 2 collective ground state(11-13). When this system is placed into a resonant cavity, the microwave field induces oscillatory transitions between the ground and excited collective spin states, indicative of long-lived quantum coherence. The present observation of quantum oscillations suggests that low- dimension self- organized qubit networks having coherence times of the order of 100 mu s ( at liquid helium temperatures) are a realistic prospect.
C1 [Bertaina, S.; Barbara, B.] CNRS, Inst Neel, F-38042 Grenoble 9, France.
   [Gambarelli, S.; Barbara, B.] CEA Grenoble, INAC, UMR CEA UJF E3, Lab Chim Inorgan & Biol, F-38054 Grenoble 9, France.
   [Mitra, T.; Mueller, A.] Univ Bielefeld, Fak Chem, D-33501 Bielefeld, Germany.
   [Tsukerblat, B.] Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel.
C3 Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); University of Bielefeld; Ben-Gurion University of the Negev
RP Barbara, B (corresponding author), CNRS, Inst Neel, 25 Ave Martyrs,BP166, F-38042 Grenoble 9, France.
EM a.mueller@uni-bielefeld.de; bernard.barbara@grenoble.cnrs.fr
NR 30
TC 330
Z9 354
U1 1
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 8
PY 2008
VL 453
IS 7192
BP 203
EP U5
DI 10.1038/nature06962
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400035
PM 18464738
DA 2026-03-09
ER

PT J
AU Smith, N
AF Smith, Nathan
TI A blast wave from the 1843 eruption of η Carinae
SO NATURE
LA English
DT Article
ID homunculus-nebula; population-iii; high-velocity; massive star; outer shell; spectroscopy; discovery; emission; analog; shape
AB Very massive stars shed much of their mass in violent precursor eruptions(1) as luminous blue variables(2) ( LBVs) before reaching their most likely end as supernovae, but the cause of LBV eruptions is unknown. The nineteenth- century eruption of eta Carinae, the prototype of these events(3), ejected about 12 solar masses at speeds of 650 km s(-1), with a kinetic energy of almost 10(50) erg ( ref. 4). Some faster material with speeds up to 1,000 2,000 km s(-1) had previously been reported(5-8) but its full distribution was unknown. Here I report observations of much faster material with speeds up to 3,500-6,000 km s(-1), reaching farther from the star than the fastest material in previous reports(5). This fast material roughly doubles the kinetic energy of the nineteenth-century event and suggests that it released a blast wave now propagating ahead of the massive ejecta. As a result, eta Carinae's outer shell now mimics a low- energy supernova remnant. The eruption has usually been discussed in terms of an extreme wind driven by the star's luminosity(2,3,9,10), but the fast material reported here indicates that it may have been powered by a deep- seated explosion rivalling a supernova, perhaps triggered by the pulsational pair instability(11). This may alter interpretations of similar events seen in other galaxies.
C1 [Smith, Nathan] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Smith, N (corresponding author), Univ Calif Berkeley, Dept Astron, 601 Campbell Hall, Berkeley, CA 94720 USA.
EM nathans@astro.berkeley.edu
NR 29
TC 86
Z9 92
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 11
PY 2008
VL 455
IS 7210
BP 201
EP 203
DI 10.1038/nature07269
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800041
PM 18784719
DA 2026-03-09
ER

PT J
AU Biver, S
   Belge, H
   Bourgeois, S
   Van Vooren, P
   Nowik, M
   Scohy, S
   Houillier, P
   Szpirer, J
   Szpirer, C
   Wagner, CA
   Devuyst, O
   Marini, AM
AF Biver, Sophie
   Belge, Hendrica
   Bourgeois, Soline
   Van Vooren, Pascale
   Nowik, Marta
   Scohy, Sophie
   Houillier, Pascal
   Szpirer, Josiane
   Szpirer, Claude
   Wagner, Carsten A.
   Devuyst, Olivier
   Marini, Anna Maria
TI A role for Rhesus factor Rhcg in renal ammonium excretion and male fertility
SO NATURE
LA English
DT Article
ID tubular-acidosis; rhag protein; transport; glycoprotein; kidney; rhbg; expression; mechanisms; mouse; identification
AB The kidney has an important role in the regulation of acid - base homeostasis. Renal ammonium production and excretion are essential for net acid excretion under basal conditions and during metabolic acidosis. Ammonium is secreted into the urine by the collecting duct, a distal nephron segment where ammonium transport is believed to occur by non- ionic NH3 diffusion coupled to H+ secretion. Here we show that this process is largely dependent on the Rhesus factor Rhcg. Mice lacking Rhcg have abnormal urinary acidification due to impaired ammonium excretion on acid loading - a feature of distal renal tubular acidosis. In vitro microperfused collecting ducts of Rhcg(-/-) acid- loaded mice show reduced apical permeability to NH3 and impaired transepithelial NH3 transport. Furthermore, Rhcg is localized in epididymal epithelial cells and is required for normal fertility and epididymal fluid pH. We anticipate a critical role for Rhcg in ammonium handling and pH homeostasis both in the kidney and the male reproductive tract.
C1 [Biver, Sophie; Van Vooren, Pascale; Scohy, Sophie; Szpirer, Josiane; Szpirer, Claude; Marini, Anna Maria] Univ Libre Bruxelles, Inst Biol & Med Mol, Labs Biol Dev & Physiol Mol Cellule, B-6041 Gosselies, Belgium.
   [Belge, Hendrica; Devuyst, Olivier] Catholic Univ Louvain, Div Nephrol, B-1200 Brussels, Belgium.
   [Bourgeois, Soline; Nowik, Marta; Wagner, Carsten A.] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland.
   [Bourgeois, Soline; Nowik, Marta; Wagner, Carsten A.] Univ Zurich, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland.
   [Bourgeois, Soline; Houillier, Pascal] INSERM, UMS 872, F-75006 Paris, France.
   [Bourgeois, Soline; Houillier, Pascal] Univ Paris 06, F-75006 Paris, France.
   [Bourgeois, Soline; Houillier, Pascal] Univ Paris 05, F-75006 Paris, France.
C3 Universite Libre de Bruxelles; Universite Catholique Louvain; University of Zurich; University of Zurich; Zurich Center Integrative Human Physiology (ZIHP); Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Universite Paris Cite
RP Marini, AM (corresponding author), Univ Libre Bruxelles, Inst Biol & Med Mol, Labs Biol Dev & Physiol Mol Cellule, Rue Prof Jeener & Brachet 12, B-6041 Gosselies, Belgium.
EM ammarini@dbm.ulb.ac.be
FU Belgian agencies FNRS; FRSM [3.4.546.04. F, 3.4.635.05. F, 3.4592.06. F]; Fonds Brachet-recherche; Fonds Van Buuren; Fondation Alphonse Jean Forton; Concerted Research Action [05/10-328]; Inter-university Attraction Pole [IUAP P6/05]; Swiss National Science Foundation [31-109677]; INSERM; EuReGene; EUNEFRON [GA#201590]; European Community [FP6, FP7]; FRIA fellowship
NR 40
TC 147
Z9 154
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 NOV 20
PY 2008
VL 456
IS 7220
BP 339
EP 343
DI 10.1038/nature07518
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JM
UT WOS:000261039600033
PM 19020613
DA 2026-03-09
ER

PT J
AU McNamara, JM
   Barta, Z
   Fromhage, L
   Houston, AI
AF McNamara, John M.
   Barta, Zoltan
   Fromhage, Lutz
   Houston, Alasdair I.
TI The coevolution of choosiness and cooperation
SO NATURE
LA English
DT Article
ID prisoners-dilemma; evolution; divorce; reciprocity; conflict; altruism; behavior; models; parent
AB Explaining the rise and maintenance of cooperation is central to our understanding of biological systems(1,2) and human societies(3,4). When an individual's cooperativeness is used by other individuals as a choice criterion, there can be competition to be more generous than others, a situation called competitive altruism(5). The evolution of cooperation between non- relatives can then be driven by a positive feedback between increasing levels of cooperativeness and choosiness(6). Here we use evolutionary simulations to show that, in a situation where individuals have the opportunity to engage in repeated pairwise interactions, the equilibrium degree of cooperativeness depends critically on the amount of behavioural variation that is being maintained in the population by processes such as mutation. Because our model does not invoke complex mechanisms such as negotiation behaviour, it can be applied to a wide range of species. The results suggest an important role of lifespan in the evolution of cooperation.
C1 [Fromhage, Lutz; Houston, Alasdair I.] Univ Bristol, Sch Biol Sci, Bristol BS8 1UG, Avon, England.
   [McNamara, John M.] Univ Bristol, Dept Math, Bristol BS8 1TW, Avon, England.
   [Barta, Zoltan] Univ Debrecen, Dept Evolutionary Zool, H-4010 Debrecen, Hungary.
C3 University of Bristol; University of Bristol; University of Debrecen
RP Fromhage, L (corresponding author), Univ Bristol, Sch Biol Sci, Woodland Rd, Bristol BS8 1UG, Avon, England.
EM lutzfromhage@web.de
NR 30
TC 177
Z9 194
U1 1
U2 69
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2008
VL 451
IS 7175
BP 189
EP 192
DI 10.1038/nature06455
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 249GA
UT WOS:000252214400042
PM 18185587
DA 2026-03-09
ER

PT J
AU Yang, YD
   Cho, HW
   Koo, JY
   Tak, MH
   Cho, YY
   Shim, WS
   Park, SP
   Lee, J
   Lee, B
   Kim, BM
   Raouf, R
   Shin, YK
   Oh, U
AF Yang, Young Duk
   Cho, Hawon
   Koo, Jae Yeon
   Tak, Min Ho
   Cho, Yeongyo
   Shim, Won-Sik
   Park, Seung Pyo
   Lee, Jesun
   Lee, Byeongjun
   Kim, Byung-Moon
   Raouf, Ramin
   Shin, Young Ki
   Oh, Uhtaek
TI TMEM16A confers receptor-activated calcium-dependent chloride conductance
SO NATURE
LA English
DT Article
ID ca2+-activated cl-channels; rat submandibular-gland; parotid acinar-cells; cystic-fibrosis; protein-kinase; transcriptome analysis; endothelial-cells; airway epithelia; smooth-muscle; membrane
AB Calcium (Ca2+)-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A(TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca2+-activated chloride channel that is activated by intracellular Ca2+ and Ca2+- mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca2+- activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca2+-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca2+-activated chloride channel that mediates receptor- activated chloride currents in diverse physiological processes.
C1 [Yang, Young Duk; Cho, Hawon; Koo, Jae Yeon; Tak, Min Ho; Cho, Yeongyo; Shim, Won-Sik; Park, Seung Pyo; Lee, Jesun; Lee, Byeongjun; Kim, Byung-Moon; Shin, Young Ki; Oh, Uhtaek] Seoul Natl Univ, Sensory Res Ctr, CRI, Coll Pharm, Seoul 151742, South Korea.
   [Raouf, Ramin] UCL, Mol Nocicept Grp, London WC1E 6BT, England.
C3 Seoul National University (SNU); University of London; University College London
RP Oh, U (corresponding author), Seoul Natl Univ, Sensory Res Ctr, CRI, Coll Pharm, Seoul 151742, South Korea.
EM utoh@snu.ac.kr
FU Acceleration Research of MOEST/KOSEF of Korea; Brain Korea 21 Project; Wellcome Trust Foundation, UK
NR 42
TC 1102
Z9 1284
U1 3
U2 126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1210
EP U36
DI 10.1038/nature07313
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100037
PM 18724360
DA 2026-03-09
ER

PT J
AU Bernet, ML
   Miniati, F
   Lilly, SJ
   Kronberg, PP
   Dessauges-Zavadsky, M
AF Bernet, Martin L.
   Miniati, Francesco
   Lilly, Simon J.
   Kronberg, Philipp P.
   Dessauges-Zavadsky, Miroslava
TI Strong magnetic fields in normal galaxies at high redshift
SO NATURE
LA English
DT Article
ID rotation measure distribution; faraday-rotation; absorption-lines; alpha systems; telescope
AB The origin and growth of magnetic fields in galaxies is still something of an enigma(1). It is generally assumed that seed fields are amplified over time through the dynamo effect(2-5), but there are few constraints on the timescale. It was recently demonstrated that field strengths as traced by rotation measures of distant ( and hence ancient) quasars are comparable to those seen today(6), but it was unclear whether the high fields were in the unusual environments of the quasars themselves or distributed along the lines of sight. Here we report high- resolution spectra that demonstrate that the quasars with strong Mg II absorption lines are unambiguously associated with larger rotation measures. Because Mg II absorption occurs in the haloes of normal galaxies(7-11) along the sightlines to the quasars, this association requires that organized fields of surprisingly high strengths are associated with normal galaxies when the Universe was only about one- third of its present age.
C1 [Bernet, Martin L.; Miniati, Francesco; Lilly, Simon J.] ETH, Dept Phys, CH-8093 Zurich, Switzerland.
   [Kronberg, Philipp P.] Los Alamos Natl Lab, IGPP, Los Alamos, NM 87545 USA.
   [Kronberg, Philipp P.] Univ Toronto, Dept Phys, Toronto, ON M5S 1A7, Canada.
   [Dessauges-Zavadsky, Miroslava] Univ Geneva, Observ Geneva, CH-1290 Sauverny, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; United States Department of Energy (DOE); Los Alamos National Laboratory; University of Toronto; University of Geneva
RP Miniati, F (corresponding author), ETH, Dept Phys, Wolfgang Pauli Str 16, CH-8093 Zurich, Switzerland.
EM fm@phys.ethz.ch
NR 27
TC 281
Z9 291
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 17
PY 2008
VL 454
IS 7202
BP 302
EP 304
DI 10.1038/nature07105
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 326ND
UT WOS:000257665300031
PM 18633410
DA 2026-03-09
ER

PT J
AU Ackermann, M
   Stecher, B
   Freed, NE
   Songhet, P
   Hardt, WD
   Doebeli, M
AF Ackermann, Martin
   Stecher, Baerbel
   Freed, Nikki E.
   Songhet, Pascal
   Hardt, Wolf-Dietrich
   Doebeli, Michael
TI Self-destructive cooperation mediated by phenotypic noise
SO NATURE
LA English
DT Article
ID gene-expression; in-vivo; evolution; infection
AB In many biological examples of cooperation, individuals that cooperate cannot benefit from the resulting public good. This is especially clear in cases of self- destructive cooperation, where individuals die when helping others. If self- destructive cooperation is genetically encoded, these genes can only be maintained if they are expressed by just a fraction of their carriers, whereas the other fraction benefits from the public good. One mechanism that can mediate this differentiation into two phenotypically different sub- populations is phenotypic noise(1,2). Here we show that noisy expression of self- destructive cooperation can evolve if individuals that have a higher probability for self- destruction have, on average, access to larger public goods. This situation, which we refer to as assortment, can arise if the environment is spatially structured. These results provide a new perspective on the significance of phenotypic noise in bacterial pathogenesis: it might promote the formation of cooperative sub- populations that die while preparing the ground for a successful infection. We show experimentally that this model captures essential features of Salmonella typhimurium pathogenesis. We conclude that noisily expressed self- destructive cooperative actions can evolve under conditions of assortment, that self- destructive cooperation is a plausible biological function of phenotypic noise, and that self- destructive cooperation mediated by phenotypic noise could be important in bacterial pathogenesis.
C1 [Ackermann, Martin; Freed, Nikki E.] ETH, Inst Integrat Biol, CH-8092 Zurich, Switzerland.
   [Stecher, Baerbel; Songhet, Pascal; Hardt, Wolf-Dietrich] ETH, Inst Microbiol, CH-8092 Zurich, Switzerland.
   [Doebeli, Michael] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
   [Doebeli, Michael] Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z4, Canada.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of British Columbia; University of British Columbia
RP Ackermann, M (corresponding author), ETH, Inst Integrat Biol, CH-8092 Zurich, Switzerland.
EM martin.ackermann@env.ethz.ch; hardt@micro.biol.ethz.ch; doebeli@zoology.ubc.ca
FU Roche Research Foundation; Novartis Foundation; NSERC ( Canada); UBS foundation; ETH research foundation [TH-10 06-1]; Swiss National Science Foundation [310000-113623/1]; European Union [SavinMucoPath number 032296]
NR 29
TC 327
Z9 385
U1 1
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 AUG 21
PY 2008
VL 454
IS 7207
BP 987
EP 990
DI 10.1038/nature07067
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339QB
UT WOS:000258591000037
PM 18719588
DA 2026-03-09
ER

PT J
AU Rohr, JR
   Schotthoefer, AM
   Raffel, TR
   Carrick, HJ
   Halstead, N
   Hoverman, JT
   Johnson, CM
   Johnson, LB
   Lieske, C
   Piwoni, MD
   Schoff, PK
   Beasley, VR
AF Rohr, Jason R.
   Schotthoefer, Anna M.
   Raffel, Thomas R.
   Carrick, Hunter J.
   Halstead, Neal
   Hoverman, Jason T.
   Johnson, Catherine M.
   Johnson, Lucinda B.
   Lieske, Camilla
   Piwoni, Marvin D.
   Schoff, Patrick K.
   Beasley, Val R.
TI Agrochemicals increase trematode infections in a declining amphibian species
SO NATURE
LA English
DT Article
ID frogs rana-pipiens; limb development; atrazine; exposure; survival; survivorship; deformity; herbicide; disease; stage
AB Global amphibian declines have often been attributed to disease(1,2), but ignorance of the relative importance and mode of action of potential drivers of infection has made it difficult to develop effective remediation. In a field study, here we show that the widely used herbicide, atrazine, was the best predictor ( out of more than 240 plausible candidates) of the abundance of larval trematodes ( parasitic flatworms) in the declining northern leopard frog Rana pipiens. The effects of atrazine were consistent across trematode taxa. The combination of atrazine and phosphate - principal agrochemicals in global corn and sorghum production - accounted for 74% of the variation in the abundance of these often debilitating larval trematodes ( atrazine alone accounted for 51%). Analysis of field data supported a causal mechanism whereby both agrochemicals increase exposure and susceptibility to larval trematodes by augmenting snail intermediate hosts and suppressing amphibian immunity. A mesocosm experiment demonstrated that, relative to control tanks, atrazine tanks had immunosuppressed tadpoles, had significantly more attached algae and snails, and had tadpoles with elevated trematode loads, further supporting a causal relationship between atrazine and elevated trematode infections in amphibians. These results raise concerns about the role of atrazine and phosphate in amphibian declines, and illustrate the value of quantifying the relative importance of several possible drivers of disease risk while determining the mechanisms by which they facilitate disease emergence.
C1 [Rohr, Jason R.; Raffel, Thomas R.; Halstead, Neal] Univ S Florida, Dept Biol, Tampa, FL 33620 USA.
   [Rohr, Jason R.; Raffel, Thomas R.] Penn State Univ, Penn State Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
   [Schotthoefer, Anna M.; Lieske, Camilla; Beasley, Val R.] Univ Illinois, Coll Vet Med, Urbana, IL 61802 USA.
   [Carrick, Hunter J.] Penn State Univ, Sch Forest Resources, University Pk, PA 16802 USA.
   [Hoverman, Jason T.] Univ Tennessee, Dept Forest Wildlife & Fisheries, Knoxville, TN 37996 USA.
   [Johnson, Catherine M.; Johnson, Lucinda B.; Schoff, Patrick K.] Univ Minnesota, Nat Resources Res Inst, Duluth, MN 55811 USA.
   [Piwoni, Marvin D.] Illinois Waste Management & Res Ctr, Champaign, IL 61820 USA.
C3 State University System of Florida; University of South Florida; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Illinois System; University of Illinois Urbana-Champaign; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Tennessee System; University of Tennessee Knoxville; University of Minnesota System; University of Minnesota Duluth
RP Rohr, JR (corresponding author), Univ S Florida, Dept Biol, Tampa, FL 33620 USA.
EM jasonrohr@gmail.com
FU National Science Foundation [DEB-0809487]; US Department of Agriculture [NRI 2008-00622, NRI 2008-01785]; US Environmental Protection Agency STAR [R825867, R833835]; Direct For Biological Sciences; Division Of Environmental Biology [0809487] Funding Source: National Science Foundation; EPA [150194, R833835] Funding Source: Federal RePORTER
NR 30
TC 363
Z9 443
U1 3
U2 211
PU 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 30
PY 2008
VL 455
IS 7217
BP 1235
EP U50
DI 10.1038/nature07281
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100043
PM 18972018
DA 2026-03-09
ER

PT J
AU Stouffer, AL
   Acharya, R
   Salom, D
   Levine, AS
   Di Costanzo, L
   Soto, CS
   Tereshko, V
   Nanda, V
   Stayrook, S
   DeGrado, WF
AF Stouffer, Amanda L.
   Acharya, Rudresh
   Salom, David
   Levine, Anna S.
   Di Costanzo, Luigi
   Soto, Cinque S.
   Tereshko, Valentina
   Nanda, Vikas
   Stayrook, Steven
   DeGrado, William F.
TI Structural basis for the function and inhibition of an influenza virus proton channel
SO NATURE
LA English
DT Article
ID m-2 ion-channel; a virus; adamantane resistance; transmembrane domain; membrane-proteins; m2; mechanism; model; helix; state
AB The M2 protein from influenza A virus is a pH- activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti- influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% ( ref. 1). Here we describe the crystal structure of the transmembrane- spanning region of the homotetrameric protein in the presence and absence of the channel- blocking drug amantadine. pH- dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating(2). The drug- binding site is lined by residues that are mutated in amantadine- resistant viruses(3,4). Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2- channel blockers.
C1 [Stouffer, Amanda L.; Acharya, Rudresh; Salom, David; Levine, Anna S.; Soto, Cinque S.; Nanda, Vikas; Stayrook, Steven; DeGrado, William F.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
   [Stouffer, Amanda L.; Di Costanzo, Luigi; DeGrado, William F.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
   [Tereshko, Valentina] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Chicago
RP DeGrado, WF (corresponding author), Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
EM wdegrado@mail.med.upenn.edu
FU National Institute of General Medical Sciences [R01GM088204] Funding Source: NIH RePORTER; NIAID NIH HHS [U01 AI074571] Funding Source: Medline; NIGMS NIH HHS [R01 GM088204, R01 GM054616, R37 GM054616, R01 GM056423, T32 GM008275] Funding Source: Medline
NR 42
TC 522
Z9 629
U1 1
U2 128
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 596
EP U13
DI 10.1038/nature06528
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900047
PM 18235504
DA 2026-03-09
ER

PT J
AU Thompson, JD
   Zwickl, BM
   Jayich, AM
   Marquardt, F
   Girvin, SM
   Harris, JGE
AF Thompson, J. D.
   Zwickl, B. M.
   Jayich, A. M.
   Marquardt, Florian
   Girvin, S. M.
   Harris, J. G. E.
TI Strong dispersive coupling of a high-finesse cavity to a micromechanical membrane
SO NATURE
LA English
DT Article
ID radiation; photon; noise; band
AB Macroscopic mechanical objects and electromagnetic degrees of freedom can couple to each other through radiation pressure. Optomechanical systems in which this coupling is sufficiently strong are predicted to show quantum effects and are a topic of considerable interest. Devices in this regime would offer new types of control over the quantum state of both light and matter(1-4), and would provide a new arena in which to explore the boundary between quantum and classical physics(5-7). Experiments so far have achieved sufficient optomechanical coupling to laser- cool mechanical devices(8-12), but have not yet reached the quantum regime. The outstanding technical challenge in this field is integrating sensitive micromechanical elements ( which must be small, light and flexible) into high- finesse cavities ( which are typically rigid and massive) without compromising the mechanical or optical properties of either. A second, and more fundamental, challenge is to read out the mechanical element's energy eigenstate. Displacement measurements ( no matter how sensitive) cannot determine an oscillator's energy eigenstate(13), and measurements coupling to quantities other than displacement(14-16) have been difficult to realize in practice. Here we present an optomechanical system that has the potential to resolve both of these challenges. We demonstrate a cavity which is detuned by the motion of a 50-nm- thick dielectric membrane placed between two macroscopic, rigid, high- finesse mirrors. This approach segregates optical and mechanical functionality to physically distinct structures and avoids compromising either. It also allows for direct measurement of the square of the membrane's displacement, and thus in principle the membrane's energy eigenstate. We estimate that it should be practical to use this scheme to observe quantum jumps of a mechanical system, an important goal in the field of quantum measurement.
C1 [Thompson, J. D.; Zwickl, B. M.; Jayich, A. M.; Girvin, S. M.; Harris, J. G. E.] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
   [Marquardt, Florian] Univ Munich, Dept Phys, Ctr Nanosci, D-80333 Munich, Germany.
   [Marquardt, Florian] Univ Munich, Arnold Sommerfeld Ctr Theoret Phys, D-80333 Munich, Germany.
   [Girvin, S. M.; Harris, J. G. E.] Yale Univ, Dept Appl Phys, New Haven, CT 06520 USA.
C3 Yale University; University of Munich; University of Munich; Yale University
RP Harris, JGE (corresponding author), Yale Univ, Dept Phys, 217 Prospect St, New Haven, CT 06520 USA.
EM jack.harris@yale.edu
NR 30
TC 1196
Z9 1342
U1 6
U2 238
PU NATURE PUBLISHING 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 6
PY 2008
VL 452
IS 7183
BP 72
EP U5
DI 10.1038/nature06715
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 269SZ
UT WOS:000253671900048
PM 18322530
DA 2026-03-09
ER

PT J
AU Kanamori, H
AF Kanamori, Hiroo
TI Earthquake physics and real-time seismology
SO NATURE
LA English
DT Article
ID slip
AB The past few decades have witnessed significant progress in our understanding of the physics and complexity of earthquakes. This has implications for hazard mitigation.
C1 CALTECH, Seismol Lab, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Kanamori, H (corresponding author), CALTECH, Seismol Lab, Pasadena, CA 91125 USA.
EM hiroo@gps.caltech.edu
NR 15
TC 23
Z9 30
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 JAN 17
PY 2008
VL 451
IS 7176
BP 271
EP 273
DI 10.1038/nature06585
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 252FJ
UT WOS:000252432100032
PM 18202640
DA 2026-03-09
ER

PT J
AU Yang, XY
   Ongusaha, PP
   Miles, PD
   Havstad, JC
   Zhang, FX
   So, WV
   Kudlow, JE
   Michell, RH
   Olefsky, JM
   Field, SJ
   Evans, RM
AF Yang, Xiaoyong
   Ongusaha, Pat P.
   Miles, Philip D.
   Havstad, Joyce C.
   Zhang, Fengxue
   So, W. Venus
   Kudlow, Jeffrey E.
   Michell, Robert H.
   Olefsky, Jerrold M.
   Field, Seth J.
   Evans, Ronald M.
TI Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance
SO NATURE
LA English
DT Article
ID n-acetylglucosamine; nucleocytoplasmic glycosylation; cytosolic proteins; activation; muscle; nuclear; glucose; identification; glcnacylation; phosphatases
AB Glucose flux through the hexosamine biosynthetic pathway leads to the post-translational modification of cytoplasmic and nuclear proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc). This tandem system serves as a nutrient sensor to couple systemic metabolic status to cellular regulation of signal transduction, transcription, and protein degradation. Here we show that O-GlcNAc transferase (OGT) harbours a previously unrecognized type of phosphoinositide-binding domain. After induction with insulin, phosphatidylinositol 3,4,5-trisphosphate recruits OGT from the nucleus to the plasma membrane, where the enzyme catalyses dynamic modification of the insulin signalling pathway by O-GlcNAc. This results in the alteration in phosphorylation of key signalling molecules and the attenuation of insulin signal transduction. Hepatic overexpression of OGT impairs the expression of insulin-responsive genes and causes insulin resistance and dyslipidaemia. These findings identify a molecular mechanism by which nutritional cues regulate insulin signalling through O-GlcNAc, and underscore the contribution of this modification to the aetiology of insulin resistance and type 2 diabetes.
C1 [Yang, Xiaoyong; Havstad, Joyce C.; Evans, Ronald M.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Yang, Xiaoyong; Havstad, Joyce C.; Evans, Ronald M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
   [Ongusaha, Pat P.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
   [Ongusaha, Pat P.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   [Miles, Philip D.; Olefsky, Jerrold M.; Field, Seth J.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Zhang, Fengxue; Kudlow, Jeffrey E.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
   [So, W. Venus] Hoffmann La Roche Inc, Roche Grp Res Informat, Nutley, NJ 07110 USA.
   [Michell, Robert H.] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England.
C3 Salk Institute; Howard Hughes Medical Institute; Salk Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; University of California System; University of California San Diego; University of Alabama System; University of Alabama Birmingham; Roche Holding; Roche Holding USA; University of Birmingham
RP Evans, RM (corresponding author), Salk Inst Biol Studies, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM evans@salk.edu
FU National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline
NR 50
TC 490
Z9 598
U1 1
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2008
VL 451
IS 7181
BP 964
EP U1
DI 10.1038/nature06668
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264TK
UT WOS:000253313100042
PM 18288188
DA 2026-03-09
ER

PT J
AU Yu, XK
   Jin, L
   Zhou, ZH
AF Yu, Xuekui
   Jin, Lei
   Zhou, Z. Hong
TI 3.88 Å structure of cytoplasmic polyhedrosis virus by cryo-electron microscopy
SO NATURE
LA English
DT Article
ID protein-rna interactions; electron cryomicroscopy; spherical virus; fourier synthesis; atomic-structure; reovirus core; genome; visualization; cypovirus; reveals
AB Cytoplasmic polyhedrosis virus (CPV) is unique within the Reoviridae family in having a turreted single-layer capsid contained within polyhedrin inclusion bodies, yet being fully capable of cell entry and endogenous RNA transcription(1-4). Biochemical data have shown that the amino-terminal 79 residues of the CPV turret protein (TP) is sufficient to bring CPV or engineered proteins into the polyhedrin matrix for micro-encapsulation(5,6). Here we report the three-dimensional structure of CPV at 3.88 angstrom resolution using single-particle cryo-electron microscopy. Our map clearly shows the turns and deep grooves of alpha-helices, the strand separation in beta-sheets, and densities for loops and many bulky side chains; thus permitting atomic model-building effort from cryoelectron microscopy maps. We observed a helix-to-beta-hairpin conformational change between the two conformational states of the capsid shell protein in the region directly interacting with genomic RNA. We have also discovered a messenger RNA release hole coupled with the mRNA capping machinery unique to CPV. Furthermore, we have identified the polyhedrin-binding domain, a structure that has potential in nanobiotechnology applications.
C1 [Yu, Xuekui; Jin, Lei; Zhou, Z. Hong] Univ Texas Houston, Sch Med, Dept Pathol & Lab Med, Houston, TX 77030 USA.
   [Yu, Xuekui; Jin, Lei; Zhou, Z. Hong] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
   [Yu, Xuekui; Jin, Lei; Zhou, Z. Hong] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA.
C3 University of Texas System; University of Texas Health Science Center Houston; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Zhou, ZH (corresponding author), Univ Texas Houston, Sch Med, Dept Pathol & Lab Med, Houston, TX 77030 USA.
EM Hong.Zhou@UCLA.edu
FU National Institute of General Medical Sciences [R01GM071940] Funding Source: NIH RePORTER; NCRR NIH HHS [P41 RR002250] Funding Source: Medline; NIAID NIH HHS [R01 AI069015] Funding Source: Medline; NIGMS NIH HHS [R01 GM071940] Funding Source: Medline
NR 37
TC 238
Z9 299
U1 2
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 MAY 15
PY 2008
VL 453
IS 7193
BP 415
EP U73
DI 10.1038/nature06893
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400057
PM 18449192
DA 2026-03-09
ER

PT J
AU Cook, EH
   Scherer, SW
AF Cook, Edwin H., Jr.
   Scherer, Stephen W.
TI Copy-number variations associated with neuropsychiatric conditions
SO NATURE
LA English
DT Article
ID comparative genomic hybridization; familial parkinsons-disease; autism spectrum disorders; structural variation; mental-retardation; chromosomal rearrangements; microdeletion syndrome; tourette-syndrome; gene; duplication
AB Neuropsychiatric conditions such as autism and schizophrenia have long been attributed to genetic alterations, but identifying the genes responsible has proved challenging. Microarray experiments have now revealed abundant copy- number variation - a type of variation in which stretches of DNA are duplicated, deleted and sometimes rearranged - in the human population. Genes affected by copy- number variation are good candidates for research into disease susceptibility. The complexity of neuropsychiatric genetics, however, dictates that assessment of the biomedical relevance of copy- number variants and the genes that they affect needs to be considered in an integrated context.
C1 [Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto Med Discovery Tower MaRS Discovery Dist, Toronto, ON M5G 1L7, Canada.
   [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Cook, Edwin H., Jr.] Univ Illinois, Inst Juvenile Res, Dept Psychiat, Chicago, IL 60608 USA.
C3 University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
RP Scherer, SW (corresponding author), Hosp Sick Children, Ctr Appl Genom, Toronto Med Discovery Tower MaRS Discovery Dist, 14th Floor,101 Coll St, Toronto, ON M5G 1L7, Canada.
EM steve@genet.sickkids.on.ca
FU The Centre for Applied Genomics; Genome Canada-Ontario Genomics Institute; Canadian Institutes for Health Research; Canadian Institute for Advanced Research; McLaughlin Centre for Molecular Medicine; Canadian Foundation for Innovation; Ontario Ministry of Research Innovation; National Institutes of Health [HD055751]; Children's Brain Research Foundation; Jean Young and Walden W. Shaw Foundation; Autism Speaks; SickKids Foundation
NR 52
TC 484
Z9 660
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 OCT 16
PY 2008
VL 455
IS 7215
BP 919
EP 923
DI 10.1038/nature07458
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300040
PM 18923514
DA 2026-03-09
ER

PT J
AU de Godoy, LMF
   Olsen, JV
   Cox, J
   Nielsen, ML
   Hubner, NC
   Fröhlich, F
   Walther, TC
   Mann, M
AF de Godoy, Lyris M. F.
   Olsen, Jesper V.
   Cox, Juergen
   Nielsen, Michael L.
   Hubner, Nina C.
   Froehlich, Florian
   Walther, Tobias C.
   Mann, Matthias
TI Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; sequence databases; global analysis; identification; expression; silac; proteins; genomics; pathway; gels
AB Mass spectrometry is a powerful technology for the analysis of large numbers of endogenous proteins(1,2). However, the analytical challenges associated with comprehensive identification and relative quantification of cellular proteomes have so far appeared to be insurmountable(3). Here, using advances in computational proteomics, instrument performance and sample preparation strategies, we compare protein levels of essentially all endogenous proteins in haploid yeast cells to their diploid counterparts. Our analysis spans more than four orders of magnitude in protein abundance with no discrimination against membrane or low level regulatory proteins. Stable- isotope labelling by amino acids in cell culture (SILAC) quantification(4,5) was very accurate across the proteome, as demonstrated by one- to- one ratios of most yeast proteins. Key members of the pheromone pathway were specific to haploid yeast but others were unaltered, suggesting an efficient control mechanism of the mating response. Several retrotransposon- associated proteins were specific to haploid yeast. Gene ontology analysis pinpointed a significant change for cell wall components in agreement with geometrical considerations: diploid cells have twice the volume but not twice the surface area of haploid cells. Transcriptome levels agreed poorly with proteome changes overall. However, after filtering out low confidence microarray measurements, messenger RNA changes and SILAC ratios correlated very well for pheromone pathway components. Systems- wide, precise quantification directly at the protein level opens up new perspectives in post- genomics and systems biology.
C1 [de Godoy, Lyris M. F.; Olsen, Jesper V.; Cox, Juergen; Nielsen, Michael L.; Hubner, Nina C.; Froehlich, Florian; Walther, Tobias C.; Mann, Matthias] Max Planck Inst Biochem, D-82152 Martinsried, Germany.
C3 Max Planck Society
RP Walther, TC (corresponding author), Max Planck Inst Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
EM twalther@biochem.mpg.de; mmann@biochem.mpg.de
FU Human Frontier Science Program; European Molecular Biology Organization (EMBO); Novo Nordisk Foundation Center for Protein Research [PI Jesper Velgaard Olsen] Funding Source: researchfish
NR 28
TC 748
Z9 874
U1 2
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 30
PY 2008
VL 455
IS 7217
BP 1251
EP U60
DI 10.1038/nature07341
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 366DZ
UT WOS:000260462100047
PM 18820680
DA 2026-03-09
ER

PT J
AU Hashimoto, H
   Horton, JR
   Zhang, X
   Bostick, M
   Jacobsen, SE
   Cheng, XD
AF Hashimoto, Hideharu
   Horton, John R.
   Zhang, Xing
   Bostick, Magnolia
   Jacobsen, Steven E.
   Cheng, Xiaodong
TI The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix
SO NATURE
LA English
DT Article
ID adenine methyltransferase; substrate-recognition; binding domain; methylated dna; target base; protein; cells; np95; establishment; maintenance
AB Maintenance methylation of hemimethylated CpG dinucleotides at DNA replication forks is the key to faithful mitotic inheritance of genomic methylation patterns. UHRF1 ( ubiquitin- like, containing PHD and RING finger domains 1) is required for maintenance methylation by interacting with DNA nucleotide methyltransferase 1 ( DNMT1), the maintenance methyltransferase, and with hemi-methylated CpG, the substrate for DNMT1 ( refs 1 and 2). Here we present the crystal structure of the SET and RING- associated ( SRA) domain of mouse UHRF1 in complex with DNA containing a hemimethylated CpGsite. The DNA is contacted in both the major and minor grooves by two loops that penetrate into the middle of the DNA helix. The 5- methylcytosine has flipped completely out of the DNA helix and is positioned in a binding pocket with planar stacking contacts, Watson - Crick polar hydrogen bonds and van der Waals interactions specific for 5- methylcytosine. Hence, UHRF1 contains a previously unknown DNA- binding module and is the first example of a non- enzymatic, sequence- specific DNA- binding protein domain to use the base flipping mechanism to interact with DNA.
C1 [Hashimoto, Hideharu; Horton, John R.; Zhang, Xing; Cheng, Xiaodong] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA.
   [Bostick, Magnolia; Jacobsen, Steven E.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Jacobsen, Steven E.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
C3 Emory University; University of California System; University of California Los Angeles; Howard Hughes Medical Institute; University of California System; University of California Los Angeles
RP Cheng, XD (corresponding author), Emory Univ, Sch Med, Dept Biochem, 1510 Clifton Rd, Atlanta, GA 30322 USA.
EM xcheng@emory.edu
FU National Institutes of Health [GM049245, GM060398]; NIH-NSRA Fellowship [CA1263022]; Howard Hughes Medical Institute; Georgia Research Alliance Eminent Scholar
NR 36
TC 351
Z9 409
U1 1
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 826
EP U14
DI 10.1038/nature07280
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900053
PM 18772888
DA 2026-03-09
ER

PT J
AU Hanikenne, M
   Talke, IN
   Haydon, MJ
   Lanz, C
   Nolte, A
   Motte, P
   Kroymann, J
   Weigel, D
   Krämer, U
AF Hanikenne, Marc
   Talke, Ina N.
   Haydon, Michael J.
   Lanz, Christa
   Nolte, Andrea
   Motte, Patrick
   Kroymann, Juergen
   Weigel, Detlef
   Kraemer, Ute
TI Evolution of metal hyperaccumulation required cis-regulatory changes and triplication of HMA4
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; zinc tolerance; genetic-basis; copy number; homeostasis; plant; transporter; expression; selection; cadmium
AB Little is known about the types of mutations underlying the evolution of species-specific traits. The metal hyperaccumulator Arabidopsis halleri has the rare ability to colonize heavy-metal-polluted soils, and, as an extremophile sister species of Arabidopsis thaliana, it is a powerful model for research on adaptation(1-3). A. halleri naturally accumulates and tolerates leaf concentrations as high as 2.2% zinc and 0.28% cadmium in dry biomass(4). On the basis of transcriptomics studies, metal hyperaccumulation in A. halleri has been associated with more than 30 candidate genes that are expressed at higher levels in A. halleri than in A. thaliana(4-6). Some of these genes have been genetically mapped to broad chromosomal segments of between 4 and 24 cM co-segregating with Zn and Cd hypertolerance(7-9). However, the in planta loss-of-function approaches required to demonstrate the contribution of a given candidate gene to metal hyperaccumulation or hypertolerance have not been pursued to date. Using RNA interference to downregulate HMA4 (HEAVY METAL ATPASE 4) expression, we show here that Zn hyperaccumulation and full hypertolerance to Cd and Zn in A. halleri depend on the metal pump HMA4. Contrary to a postulated global trans regulatory factor governing high expression of numerous metal hyperaccumulation genes, we demonstrate that enhanced expression of HMA4 in A. halleri is attributable to a combination of modified cis-regulatory sequences and copy number expansion, in comparison to A. thaliana. Transfer of an A. halleri HMA4 gene to A. thaliana recapitulates Zn partitioning into xylem vessels and the constitutive transcriptional upregulation of Zn deficiency response genes characteristic of Zn hyperaccumulators. Our results demonstrate the importance of cis-regulatory mutations and gene copy number expansion in the evolution of a complex naturally selected extreme trait(10). The elucidation of a natural strategy for metal hyperaccumulation enables the rational design of technologies for the clean-up of metal-contaminated soils and for bio-fortification.
C1 [Hanikenne, Marc; Talke, Ina N.; Haydon, Michael J.; Nolte, Andrea; Kraemer, Ute] Max Planck Inst Mol Plant Physiol, D-14476 Potsdam, Germany.
   [Lanz, Christa; Weigel, Detlef] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany.
   [Motte, Patrick] Univ Liege, Dept Life Sci, B-4000 Liege, Belgium.
   [Motte, Patrick] Univ Liege, Ctr Assistance Technol Microscopy, Dept Chem, B-4000 Liege, Belgium.
   [Kroymann, Juergen] Max Planck Inst Chem Ecol, D-07745 Jena, Germany.
C3 Max Planck Society; Max Planck Society; University of Liege; University of Liege; Max Planck Society
RP Krämer, U (corresponding author), Heidelberg Univ, BIOQUANT Ctr, Heidelberg Inst Plant Sci, D-69120 Heidelberg, Germany.
EM ute.kraemer@bioquant.uni-heidelberg.de
NR 38
TC 632
Z9 704
U1 3
U2 367
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 15
PY 2008
VL 453
IS 7193
BP 391
EP U44
DI 10.1038/nature06877
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400052
PM 18425111
DA 2026-03-09
ER

PT J
AU Clauset, A
   Moore, C
   Newman, MEJ
AF Clauset, Aaron
   Moore, Cristopher
   Newman, M. E. J.
TI Hierarchical structure and the prediction of missing links in networks
SO NATURE
LA English
DT Article
ID food-web structure; metabolic networks; complex networks; community structure; social networks; organization; modularity
AB Networks have in recent years emerged as an invaluable tool for describing and quantifying complex systems in many branches of science(1-3). Recent studies suggest that networks often exhibit hierarchical organization, in which vertices divide into groups that further subdivide into groups of groups, and so forth over multiple scales. In many cases the groups are found to correspond to known functional units, such as ecological niches in food webs, modules in biochemical networks ( protein interaction networks, metabolic networks or genetic regulatory networks) or communities in social networks(4-7). Here we present a general technique for inferring hierarchical structure from network data and show that the existence of hierarchy can simultaneously explain and quantitatively reproduce many commonly observed topological properties of networks, such as right- skewed degree distributions, high clustering coefficients and short path lengths. We further show that knowledge of hierarchical structure can be used to predict missing connections in partly known networks with high accuracy, and for more general network structures than competing techniques(8). Taken together, our results suggest that hierarchy is a central organizing principle of complex networks, capable of offering insight into many network phenomena.
C1 [Clauset, Aaron; Moore, Cristopher] Univ New Mexico, Dept Comp Sci, Albuquerque, NM 87131 USA.
   [Moore, Cristopher] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA.
   [Clauset, Aaron; Moore, Cristopher; Newman, M. E. J.] Santa Fe Inst, Santa Fe, NM 87501 USA.
   [Newman, M. E. J.] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA.
   [Newman, M. E. J.] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
C3 University of New Mexico; University of New Mexico; The Santa Fe Institute; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Clauset, A (corresponding author), Univ New Mexico, Dept Comp Sci, Albuquerque, NM 87131 USA.
EM aaronc@santafe.edu
NR 30
TC 1505
Z9 1851
U1 5
U2 438
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 1
PY 2008
VL 453
IS 7191
BP 98
EP 101
DI 10.1038/nature06830
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800046
PM 18451861
DA 2026-03-09
ER

PT J
AU Milner, JD
   Brenchley, JM
   Laurence, A
   Freeman, AF
   Hill, BJ
   Elias, KM
   Kanno, Y
   Spalding, C
   Elloumi, HZ
   Paulson, ML
   Davis, J
   Hsu, A
   Asher, AI
   O'Shea, J
   Holland, SM
   Paul, WE
   Douek, DC
AF Milner, Joshua D.
   Brenchley, Jason M.
   Laurence, Arian
   Freeman, Alexandra F.
   Hill, Brenna J.
   Elias, Kevin M.
   Kanno, Yuka
   Spalding, Christine
   Elloumi, Houda Z.
   Paulson, Michelle L.
   Davis, Joie
   Hsu, Amy
   Asher, Ava I.
   O'Shea, John
   Holland, Steven M.
   Paul, William E.
   Douek, Daniel C.
TI Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome
SO NATURE
LA English
DT Article
ID helper t-cells; neutrophil recruitment; host-defense; il-21; generation; stat3; activation; expression; cytokine; interleukin-17
AB The autosomal dominant hyper-IgE syndrome (HIES, 'Job's syndrome') is characterized by recurrent and often severe pulmonary infections, pneumatoceles, eczema, staphylococcal abscesses, mucocutaneous candidiasis, and abnormalities of bone and connective tissue(1,2). Mutations presumed to underlie HIES have recently been identified in stat3, the gene encoding STAT3 (signal transducer and activator of transcription 3) (refs 3, 4). Although impaired production of interferon-gamma and tumour-necrosis factor by T cells(5), diminished memory T-cell populations, decreased delayed-type-hypersensitivity responses and decreased in vitro lymphoproliferation in response to specific antigens(6) have variably been described, specific immunological abnormalities that can explain the unique susceptibility to particular infections seen in HIES have not yet been defined. Here we show that interleukin (IL)-17 production by T cells is absent in HIES individuals. We observed that ex vivo T cells from subjects with HIES failed to produce IL-17, but not IL-2, tumour-necrosis factor or interferon-gamma, on mitogenic stimulation with staphylococcal enterotoxin B or on antigenic stimulation with Candida albicans or streptokinase. Purified naive T cells were unable to differentiate into IL-17-producing (T(H)17) T helper cells in vitro and had lower expression of retinoid-related orphan receptor (ROR)-gamma t, which is consistent with a crucial role for STAT3 signalling in the generation of T(H)17 cells(7-14). T(H)17 cells have emerged as an important subset of helper T cells(15) that are believed to be critical in the clearance of fungal(16) and extracellular bacterial(17) infections. Thus, our data suggest that the inability to produce T(H)17 cells is a mechanism underlying the susceptibility to the recurrent infections commonly seen in HIES.
C1 [Brenchley, Jason M.; Hill, Brenna J.; Asher, Ava I.; Douek, Daniel C.] NIAMSD, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Milner, Joshua D.; Paul, William E.] NIAMSD, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Laurence, Arian; Elias, Kevin M.; Kanno, Yuka; O'Shea, John] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
   [Freeman, Alexandra F.; Spalding, Christine; Elloumi, Houda Z.; Paulson, Michelle L.; Davis, Joie; Hsu, Amy; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Elias, Kevin M.] Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Vanderbilt University
RP Douek, DC (corresponding author), NIAMSD, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM ddouek@nih.gov
FU National Institute of Allergy and Infectious Diseases [ZIAAI000646] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIAAR041159] Funding Source: NIH RePORTER; Intramural NIH HHS [Z99 AI999999] Funding Source: Medline
NR 30
TC 939
Z9 1058
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 10
PY 2008
VL 452
IS 7188
BP 773
EP U11
DI 10.1038/nature06764
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 285QY
UT WOS:000254792500050
PM 18337720
DA 2026-03-09
ER

PT J
AU Gillis, AJ
   Schuller, AP
   Skordalakes, E
AF Gillis, Andrew J.
   Schuller, Anthony P.
   Skordalakes, Emmanuel
TI Structure of the Tribolium castaneum telomerase catalytic subunit TERT
SO NATURE
LA English
DT Article
ID template boundary definition; hiv-1 reverse-transcriptase; rna-binding domain; functional multimerization; cellular senescence; secondary-structure; crystal-structure; in-vivo; yeast; polymerase
AB A common hallmark of human cancers is the overexpression of telomerase, a ribonucleoprotein complex that is responsible for maintaining the length and integrity of chromosome ends. Telomere length deregulation and telomerase activation is an early, and perhaps necessary, step in cancer cell evolution. Here we present the high- resolution structure of the Tribolium castaneum catalytic subunit of telomerase, TERT. The protein consists of three highly conserved domains, organized into a ring- like structure that shares common features with retroviral reverse transcriptases, viral RNA polymerases and B- family DNA polymerases. Domain organization places motifs implicated in substrate binding and catalysis in the interior of the ring, which can accommodate seven to eight bases of double- stranded nucleic acid. Modelling of an RNA - DNA heteroduplex in the interior of this ring demonstrates a perfect fit between the protein and the nucleic acid substrate, and positions the 39- end of the DNA primer at the active site of the enzyme, providing evidence for the formation of an active telomerase elongation complex.
C1 [Gillis, Andrew J.; Schuller, Anthony P.; Skordalakes, Emmanuel] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA.
C3 The Wistar Institute
RP Skordalakes, E (corresponding author), Wistar Inst Anat & Biol, Gene Express & Regulat Program, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM skorda@wistar.org
FU Pennsylvania Department of Health; The Ellison Medical Foundation
NR 56
TC 237
Z9 311
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 OCT 2
PY 2008
VL 455
IS 7213
BP 633
EP U36
DI 10.1038/nature07283
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700039
PM 18758444
DA 2026-03-09
ER

PT J
AU Randau, L
   Schröder, I
   Söll, D
AF Randau, Lennart
   Schroder, Imke
   Soll, Dieter
TI Life without RNase P
SO NATURE
LA English
DT Article
ID nanoarchaeum-equitans; ribonuclease-p; genes; evolution; protein; genome; enzyme; sequences; promoter; subunit
AB The universality of ribonuclease P ( RNase P), the ribonucleoprotein essential for transfer RNA ( tRNA) 5' maturation(1,2), is challenged in the archaeon Nanoarchaeum equitans. Neither extensive computational analysis of the genome nor biochemical tests in cell extracts revealed the existence of this enzyme. Here we show that the conserved placement of its tRNA gene promoters allows the synthesis of leaderless tRNAs, whose presence was verified by the observation of 5' triphosphorylated mature tRNA species. Initiation of tRNA gene transcription requires a purine, which coincides with the finding that tRNAs with a cytosine in position 1 display unusually extended 5' termini with an extra purine residue. These tRNAs were shown to be substrates for their cognate aminoacyl- tRNA synthetases. These findings demonstrate how nature can cope with the loss of the universal and supposedly ancient RNase P through genomic rearrangement at tRNA genes under the pressure of genome condensation.
C1 [Randau, Lennart; Soll, Dieter] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Soll, Dieter] Yale Univ, Dept Chem, New Haven, CT 06520 USA.
   [Schroder, Imke] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA.
C3 Yale University; Yale University; University of California System; University of California Los Angeles
RP Söll, D (corresponding author), Yale Univ, Dept Mol Biophys & Biochem, POB 6666, New Haven, CT 06520 USA.
EM dieter.soll@yale.edu
FU NIGMS NIH HHS [R01 GM022854] Funding Source: Medline
NR 32
TC 91
Z9 120
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 1
PY 2008
VL 453
IS 7191
BP 120
EP +
DI 10.1038/nature06833
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800051
PM 18451863
DA 2026-03-09
ER

PT J
AU Tsukazaki, T
   Mori, H
   Fukai, S
   Ishitani, R
   Mori, T
   Dohmae, N
   Perederina, A
   Sugita, Y
   Vassylyev, DG
   Ito, K
   Nureki, O
AF Tsukazaki, Tomoya
   Mori, Hiroyuki
   Fukai, Shuya
   Ishitani, Ryuichiro
   Mori, Takaharu
   Dohmae, Naoshi
   Perederina, Anna
   Sugita, Yuji
   Vassylyev, Dmitry G.
   Ito, Koreaki
   Nureki, Osamu
TI Conformational transition of Sec machinery inferred from bacterial SecYE structures
SO NATURE
LA English
DT Article
ID translocation atpase seca; protein-translocation; preprotein translocation; membrane; channel; complex; components; parallel; domain; phase
AB Over 30% of proteins are secreted across or integrated into membranes. Their newly synthesized forms contain either cleavable signal sequences or non- cleavable membrane anchor sequences, which direct them to the evolutionarily conserved Sec translocon (SecYEG in prokaryotes and Sec61, comprising alpha-, gamma- and beta-subunits, in eukaryotes). The translocon then functions as a protein-conducting channel(1). These processes of protein localization occur either at or after translation. In bacteria, the SecA ATPase(2,3) drives post- translational translocation. The only high- resolution structure of a translocon available so far is that for SecYE beta from the archaeon Methanococcus jannaschii(4), which lacks SecA. Here we present the 3.2- A-resolution crystal structure of the SecYE translocon from a SecA- containing organism, Thermus thermophilus. The structure, solved as a complex with an anti- SecY Fab fragment, revealed a 'pre-open' state of SecYE, in which several transmembrane helices are shifted, as compared to the previous SecYEb structure(4), to create a hydrophobic crack open to the cytoplasm. Fab and SecA bind to a common site at the tip of the cytoplasmic domain of SecY. Molecular dynamics and disulphide mapping analyses suggest that the pre- open state might represent a SecYE conformational transition that is inducible by SecA binding. Moreover, we identified a SecA - SecYE interface that comprises SecA residues originally buried inside the protein, indicating that both the channel and the motor components of the Sec machinery undergo cooperative conformational changes on formation of the functional complex.
C1 [Tsukazaki, Tomoya; Fukai, Shuya; Nureki, Osamu] Tokyo Inst Technol, Dept Biol Informat, Grad Sch Biosci & Biotechnol, Midori Ku, Kanagawa 2268501, Japan.
   [Mori, Hiroyuki; Ito, Koreaki] Kyoto Univ, Inst Virus Res, Kyoto 6068507, Japan.
   [Ishitani, Ryuichiro; Nureki, Osamu] Univ Tokyo, Div Struct Biol, Dept Basic Med Sci, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan.
   [Dohmae, Naoshi] RIKEN, Biomol Characterizat Team, Wako, Saitama 3510198, Japan.
   [Dohmae, Naoshi] RIKEN, CREST JST, Wako, Saitama 3510198, Japan.
   [Perederina, Anna; Vassylyev, Dmitry G.] Univ Alabama Birmingham, Sch Med, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
   [Perederina, Anna; Vassylyev, Dmitry G.] Univ Alabama Birmingham, Sch Dent, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
C3 Institute of Science Tokyo; Tokyo Institute of Technology; Kyoto University; University of Tokyo; RIKEN; RIKEN; Japan Science & Technology Agency (JST); University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham
RP Nureki, O (corresponding author), Tokyo Inst Technol, Dept Biol Informat, Grad Sch Biosci & Biotechnol, Midori Ku, 4259 Nagatsuta Cho, Kanagawa 2268501, Japan.
EM Koreaki.Ito@ky5.ecs.kyoto-u.ac.jp; nureki@ims.u-tokyo.ac.jp
FU SORST program; CREST; BIRD; Global COE Program (Center of Education and Research for Advanced Genome-Based Medicine); National Project on Protein Structural and Functional Analyses; NIH; MEXT; Mitsubishi Foundation; Grants-in-Aid for Scientific Research [20247020] Funding Source: KAKEN
NR 43
TC 182
Z9 216
U1 0
U2 23
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 988
EP U72
DI 10.1038/nature07421
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300055
PM 18923527
DA 2026-03-09
ER

PT J
AU Ammon, CJ
   Kanamori, H
   Lay, T
AF Ammon, Charles J.
   Kanamori, Hiroo
   Lay, Thorne
TI A great earthquake doublet and seismic stress transfer cycle in the central Kuril islands
SO NATURE
LA English
DT Article
ID coupled subduction zones; outer rise earthquakes; solomon-islands; mantle; trench; plate; model
AB Temporal variations of the frictional resistance on subduction-zone plate boundary faults associated with the stick - slip cycle of large interplate earthquakes are thought to modulate the stress regime and earthquake activity within the subducting oceanic plate(1-3). Here we report on two great earthquakes that occurred near the Kuril islands, which shed light on this process and demonstrate the enhanced seismic hazard accompanying triggered faulting. On 15 November 2006, an event of moment magnitude 8.3 ruptured the shallow- dipping plate boundary along which the Pacific plate descends beneath the central Kuril arc. The thrust ruptured a seismic gap that previously had uncertain seismogenic potential(4,5), although the earlier occurrence of outer- rise compressional events had suggested the presence of frictional resistance(1,2). Within minutes of this large underthrusting event, intraplate extensional earthquakes commenced in the outer rise region seaward of the Kuril trench, and on 13 January 2007, an event of moment magnitude 8.1 ruptured a normal fault extending through the upper portion of the Pacific plate, producing one of the largest recorded shallow extensional earthquakes. This energetic earthquake sequence demonstrates the stress transfer process within the subducting lithosphere, and the distinct rupture characteristics of these great earthquakes illuminate differences in seismogenic properties and seismic hazard of such interplate and intraplate faults.
C1 [Lay, Thorne] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Ammon, Charles J.] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Kanamori, Hiroo] CALTECH, Seismol Lab, Pasadena, CA 91125 USA.
C3 University of California System; University of California Santa Cruz; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; California Institute of Technology
RP Lay, T (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
EM thorne@pmc.ucsc.edu
NR 30
TC 161
Z9 186
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 561
EP U4
DI 10.1038/nature06521
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900039
PM 18235499
DA 2026-03-09
ER

PT J
AU Kaganovich, D
   Kopito, R
   Frydman, J
AF Kaganovich, Daniel
   Kopito, Ron
   Frydman, Judith
TI Misfolded proteins partition between two distinct quality control compartments
SO NATURE
LA English
DT Article
ID tumor-suppressor complex; saccharomyces-cerevisiae; endoplasmic-reticulum; fluorescent protein; in-vivo; polyglutamine expansion; molecular chaperones; alpha-synuclein; yeast; degradation
AB The accumulation of misfolded proteins in intracellular amyloid inclusions, typical of many neurodegenerative disorders including Huntington's and prion disease, is thought to occur after failure of the cellular protein quality control mechanisms. Here we examine the formation of misfolded protein inclusions in the eukaryotic cytosol of yeast and mammalian cell culture models. We identify two intracellular compartments for the sequestration of misfolded cytosolic proteins. Partition of quality control substrates to either compartment seems to depend on their ubiquitination status and aggregation state. Soluble ubiquitinated misfolded proteins accumulate in a juxtanuclear compartment where proteasomes are concentrated. In contrast, terminally aggregated proteins are sequestered in a perivacuolar inclusion. Notably, disease- associated Huntingtin and prion proteins are preferentially directed to the perivacuolar compartment. Enhancing ubiquitination of a prion protein suffices to promote its delivery to the juxtanuclear inclusion. Our findings provide a framework for understanding the preferential accumulation of amyloidogenic proteins in inclusions linked to human disease.
C1 [Kaganovich, Daniel; Kopito, Ron; Frydman, Judith] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Kaganovich, Daniel; Kopito, Ron; Frydman, Judith] Stanford Univ, BioX Program, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Frydman, J (corresponding author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
EM jfrydman@stanford.edu
FU NIH; National Institute of General Medical Sciences [R01GM056433] Funding Source: NIH RePORTER
NR 56
TC 758
Z9 907
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 AUG 28
PY 2008
VL 454
IS 7208
BP 1088
EP U36
DI 10.1038/nature07195
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600031
PM 18756251
DA 2026-03-09
ER

PT J
AU Domingues, CM
   Church, JA
   White, NJ
   Gleckler, PJ
   Wijffels, SE
   Barker, PM
   Dunn, JR
AF Domingues, Catia M.
   Church, John A.
   White, Neil J.
   Gleckler, Peter J.
   Wijffels, Susan E.
   Barker, Paul M.
   Dunn, Jeff R.
TI Improved estimates of upper-ocean warming and multi-decadal sea-level rise
SO NATURE
LA English
DT Article
ID temperature; pressure; impact
AB Changes in the climate system's energy budget are predominantly revealed in ocean temperatures(1,2) and the associated thermal expansion contribution to sea-level rise(2). Climate models, however, do not reproduce the large decadal variability in globally averaged ocean heat content inferred from the sparse observational database(3,4), even when volcanic and other variable climate forcings are included. The sum of the observed contributions has also not adequately explained the overall multi-decadal rise(2). Here we report improved estimates of near-global ocean heat content and thermal expansion for the upper 300 m and 700 m of the ocean for 1950-2003, using statistical techniques that allow for sparse data coverage(5-7) and applying recent corrections(8) to reduce systematic biases in the most common ocean temperature observations(9). Our ocean warming and thermal expansion trends for 1961-2003 are about 50 per cent larger than earlier estimates but about 40 per cent smaller for 1993-2003, which is consistent with the recognition that previously estimated rates for the 1990s had a positive bias as a result of instrumental errors(8-10). On average, the decadal variability of the climate models with volcanic forcing now agrees approximately with the observations, but the modelled multi-decadal trends are smaller than observed. We add our observational estimate of upper-ocean thermal expansion to other contributions to sea-level rise and find that the sum of contributions from 1961 to 2003 is about 1.5 +/- 0.4 mm yr(-1), in good agreement with our updated estimate of near-global mean sea-level rise (using techniques established in earlier studies(6,7)) of 1.6 +/- 0.2 mm yr(-1).
C1 [Domingues, Catia M.; Church, John A.; White, Neil J.; Wijffels, Susan E.; Barker, Paul M.; Dunn, Jeff R.] CSIRO Marine & Atmospher Res, Ctr Australian Weather & Climate Res, Hobart, Tas 7001, Australia.
   [Church, John A.; White, Neil J.] Antarctic Climate & Ecosyst Cooperat Res Ctr, Hobart, Tas 7001, Australia.
   [Gleckler, Peter J.] Lawrence Livermore Natl Lab, Program Climate Model Diag & Intercomparison, Livermore, CA 94550 USA.
C3 Commonwealth Scientific & Industrial Research Organisation (CSIRO); Antarctic Climate & Ecosystems Cooperative Research Centre (ACE CRC); United States Department of Energy (DOE); Lawrence Livermore National Laboratory
RP Domingues, CM (corresponding author), CSIRO Marine & Atmospher Res, Ctr Australian Weather & Climate Res, GPO Box 1538, Hobart, Tas 7001, Australia.
EM catia.domingues@csiro.au
NR 33
TC 568
Z9 644
U1 2
U2 269
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2008
VL 453
IS 7198
BP 1090
EP U6
DI 10.1038/nature07080
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900054
PM 18563162
DA 2026-03-09
ER

PT J
AU Huertas, P
   Cortés-Ledesma, F
   Sartori, AA
   Aguilera, A
   Jackson, SP
AF Huertas, Pablo
   Cortes-Ledesma, Felipe
   Sartori, Alessandro A.
   Aguilera, Andres
   Jackson, Stephen P.
TI CDK targets Sae2 to control DNA-end resection and homologous recombination
SO NATURE
LA English
DT Article
ID double-strand breaks; saccharomyces-cerevisiae; cell-cycle; repair pathways; damage response; kinase-activity; protein-kinase; mre11 complex; human ctip; gene
AB DNA double- strand breaks ( DSBs) are repaired by two principal mechanisms: non- homologous end- joining ( NHEJ) and homologous recombination ( HR)(1). HR is the most accurate DSB repair mechanism but is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as a repair template(2-5). By contrast, NHEJ operates throughout the cell cycle but assumes most importance in G1 ( refs 4, 6). The choice between repair pathways is governed by cyclindependent protein kinases (CDKs)(2,3,5,7), with a major site of control being at the level of DSB resection, an event that is necessary for HR but not NHEJ, and which takes place most effectively in S and G2 ( refs 2, 5). Here we establish that cell- cycle control of DSB resection in Saccharomyces cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non- phosphorylatable residue causes phenotypes comparable to those of a sae2 Delta null mutant, including hypersensitivity to camptothecin, defective sporulation, reduced hairpin- induced recombination, severely impaired DNA- end processing and faulty assembly and disassembly of HR factors. Furthermore, a Sae2 mutation that mimics constitutive Ser 267 phosphorylation complements these phenotypes and overcomes the necessity of CDK activity for DSB resection. The Sae2 mutations also cause cell- cycle- stage specific hypersensitivity to DNA damage and affect the balance between HR and NHEJ. These findings therefore provide amechanistic basis for cell- cycle control of DSB repair and highlight the importance of regulating DSB resection.
C1 [Huertas, Pablo; Sartori, Alessandro A.; Jackson, Stephen P.] Univ Cambridge, Wellcome Trust & Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England.
   [Huertas, Pablo; Sartori, Alessandro A.; Jackson, Stephen P.] Univ Cambridge, Dept Zool, Cambridge CB2 1QN, England.
   [Cortes-Ledesma, Felipe; Aguilera, Andres] Univ Seville, CSIC, Ctr Andaluz Biol Mol & Med Regenerat, CABIMER, Seville 41092, Spain.
C3 University of Cambridge; University of Cambridge; Consejo Superior de Investigaciones Cientificas (CSIC); Universidad Pablo de Olavide; University of Sevilla; CSIC - Centro Andaluz de Biologia Molecular y Medicina Regenerativa (CABIMER)
RP Jackson, SP (corresponding author), Univ Cambridge, Wellcome Trust & Canc Res UK Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
EM s.jackson@gurdon.cam.ac.uk
FU Long- Term EMBO Fellowship; Swiss National Foundation Grant; Cancer Research UK; European Community [LSHG-CT-2005-512113)]; Spanish Ministry of Science and Education [BFU2006-05, CDS2007-0015260]; Junta de Andalucia [CVI624]
NR 31
TC 382
Z9 501
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 689
EP U86
DI 10.1038/nature07215
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700052
PM 18716619
DA 2026-03-09
ER

PT J
AU Biastoch, A
   Böning, CW
   Lutjeharms, JRE
AF Biastoch, A.
   Boening, C. W.
   Lutjeharms, J. R. E.
TI Agulhas leakage dynamics affects decadal variability in Atlantic overturning circulation
SO NATURE
LA English
DT Article
ID north-atlantic; exchange; rings
AB Predicting the evolution of climate over decadal timescales requires a quantitative understanding of the dynamics that govern the meridional overturning circulation (MOC)(1). Comprehensive ocean measurement programmes aiming to monitor MOC variations have been established in the subtropical North Atlantic(2,3) ( RAPID, at latitude 26.56 degrees N, and MOVE, at latitude 16 degrees N) and show strong variability on intraseasonal to interannual timescales. Observational evidence of longer- term changes in MOC transport remains scarce, owing to infrequent sampling of transoceanic sections over past decades(4,5). Inferences based on long- term sea surface temperature records, however, supported by model simulations, suggest a variability with an amplitude of +/- 1.5-3 Sv ( 1 Sv = 10(6) m(3) s(-1)) on decadal timescales in the subtropics(6). Such variability has been attributed to variations of deep water formation in the sub- arctic Atlantic, particularly the renewal rate of Labrador Sea Water(7). Here we present results from a model simulation that suggest an additional influence on decadal MOC variability having a Southern Hemisphere origin: dynamic signals originating in the Agulhas leakage region at the southern tip of Africa. These contribute a MOC signal in the tropical and subtropical North Atlantic that is of the same order of magnitude as the northern source. A complete rationalization of observed MOC changes therefore also requires consideration of signals arriving from the south.
C1 [Biastoch, A.; Boening, C. W.] Leibniz Inst Marine Sci, 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 Marine Sci, Dusternbrooker Weg 20, D-24105 Kiel, Germany.
EM abiastoch@ifm-geomar.de
FU Alexander von Humboldt-Stiftung
NR 30
TC 237
Z9 250
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 489
EP 492
DI 10.1038/nature07426
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500035
PM 19037313
DA 2026-03-09
ER

PT J
AU Goncharov, AF
   Haugen, BD
   Struzhkin, VV
   Beck, P
   Jacobsen, SD
AF Goncharov, Alexander F.
   Haugen, Benjamin D.
   Struzhkin, Viktor V.
   Beck, Pierre
   Jacobsen, Steven D.
TI Radiative conductivity in the Earth's lower mantle
SO NATURE
LA English
DT Article
ID optical-absorption spectra; thermal-conductivity; electronic-structure; heat-transport; iron; perovskite; olivine; transitions; viscosity; (mg
AB Iron in crustal and mantle minerals adopts several possible oxidation states: this has implications for biogeochemical processes(1), oxygenation of the atmosphere(2) and the oxidation state of the mantle(3,4). In the deep Earth, iron in silicate perovskite, (Mg0.9Fe0.1)SiO3, and ferropericlase, (Mg0.85Fe0.15)O, influences the thermal conductivity of the lower mantle and therefore heat flux from the core. Little is known, however, about the effect of iron oxidation states on transport properties. Here we show that the radiative component of thermal conductivity in the dominant silicate perovskite material of Earth's lower mantle is controlled by the amount of ferric iron, Fe3+. We obtained the optical absorption spectra of silicate perovskite and ferropericlase at pressures up to 133 GPa, corresponding to pressures at the core - mantle boundary. Absorption spectra of ferropericlase up to 800 K and 60 GPa exhibit minimal temperature dependence. The results on silicate perovskite show that optical absorption in the visible and near- infrared spectral range is dominated by O-Fe3+ charge transfer and Fe3+-Fe2+ intervalence transitions, whereas a contribution from the Fe2+ crystal- field transitions is substantially smaller. The estimated pressure- dependent radiative conductivity, k(rad), from these data is 2-5 times lower than previously inferred from model extrapolations, with implications for the evolution of the mantle, such as generation and stability of thermo- chemical plumes in the lower mantle.
C1 [Goncharov, Alexander F.; Haugen, Benjamin D.; Struzhkin, Viktor V.; Beck, Pierre] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Haugen, Benjamin D.] Univ Colorado, Dept Geol Sci, Boulder, CO 80309 USA.
   [Jacobsen, Steven D.] Northwestern Univ, Dept Earth & Planetary Sci, Evanston, IL 60208 USA.
C3 Carnegie Institution for Science; University of Colorado System; University of Colorado Boulder; Northwestern University
RP Goncharov, AF (corresponding author), Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA.
EM goncharov@gl.ciw.edu
FU NSF/EAR; DOE/BES; DOE/NNSA (CDAC); W. M. Keck Foundation; NSF Research Experience for Undergraduates (REU) Program at the Carnegie Institution of Washington; Balzan Foundation
NR 30
TC 82
Z9 96
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 NOV 13
PY 2008
VL 456
IS 7219
BP 231
EP 234
DI 10.1038/nature07412
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300038
PM 19005553
DA 2026-03-09
ER

PT J
AU Disney, MJ
   Romano, JD
   Garcia-Appadoo, DA
   West, AA
   Dalcanton, JJ
   Cortese, L
AF Disney, M. J.
   Romano, J. D.
   Garcia-Appadoo, D. A.
   West, A. A.
   Dalcanton, J. J.
   Cortese, L.
TI Galaxies appear simpler than expected
SO NATURE
LA English
DT Article
ID integral property; hipass catalog; density
AB Galaxies are complex systems the evolution of which apparently results from the interplay of dynamics, star formation, chemical enrichment and feedback from supernova explosions and super-massive black holes(1). The hierarchical theory of galaxy formation holds that galaxies are assembled from smaller pieces, through numerous mergers of cold dark matter(2-4). The properties of an individual galaxy should be controlled by six independent parameters including mass, angular momentum, baryon fraction, age and size, as well as by the accidents of its recent haphazard merger history. Here we report that a sample of galaxies that were first detected through their neutral hydrogen radio- frequency emission, and are thus free from optical selection effects(5), shows five independent correlations among six independent observables, despite having a wide range of properties. This implies that the structure of these galaxies must be controlled by a single parameter, although we cannot identify this parameter from our data set. Such a degree of organization appears to be at odds with hierarchical galaxy formation, a central tenet of the cold dark matter model in cosmology(6).
C1 [Disney, M. J.; Romano, J. D.; Garcia-Appadoo, D. A.; Cortese, L.] Cardiff Univ, Sch Phys & Astron, Cardiff CF24 3AA, Wales.
   [Romano, J. D.] Univ Texas Brownsville, Dept Phys & Astron, Brownsville, TX 78520 USA.
   [Garcia-Appadoo, D. A.] European So Observ, Santiago 19, Chile.
   [West, A. A.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [West, A. A.; Dalcanton, J. J.] Univ Washington, Dept Astron, Seattle, WA 98195 USA.
C3 Cardiff University; University of Texas System; University of Texas Rio Grande Valley; European Southern Observatory; University of California System; University of California Berkeley; University of Washington; University of Washington Seattle
RP Disney, MJ (corresponding author), Cardiff Univ, Sch Phys & Astron, 5 Parade, Cardiff CF24 3AA, Wales.
EM mjd@astro.cf.ac.uk
NR 29
TC 95
Z9 106
U1 0
U2 4
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1082
EP 1084
DI 10.1038/nature07366
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600038
PM 18948949
DA 2026-03-09
ER

PT J
AU Schreiner, PR
   Reisenauer, HP
   Pickard, FC
   Simmonett, AC
   Allen, WD
   Mátyus, E
   Császár, AG
AF Schreiner, Peter R.
   Reisenauer, Hans Peter
   Pickard, Frank C.
   Simmonett, Andrew C.
   Allen, Wesley D.
   Matyus, Edit
   Csaszar, Attila G.
TI Capture of hydroxymethylene and its fast disappearance through tunnelling
SO NATURE
LA English
DT Article
ID molecular vibrational anharmonicity; higher-derivative methods; potential-energy surface; metal-carbene complexes; gaussian-basis sets; solid rare-gases; ab-initio limit; hydroxycarbene intermediate; polyatomic-molecules; rotation interaction
AB Singlet carbenes exhibit a divalent carbon atom whose valence shell contains only six electrons, four involved in bonding to two other atoms and the remaining two forming a non- bonding electron pair. These features render singlet carbenes so reactive that they were long considered too short- lived for isolation and direct characterization. This view changed when it was found that attaching the divalent carbon atom to substituents that are bulky and/ or able to donate electrons produces carbenes that can be isolated and stored(1). N- heterocyclic carbenes are such compounds now in wide use, for example as ligands in metathesis catalysis(2). In contrast, oxygen- donor- substituted carbenes are inherently less stable and have been less studied. The pre- eminent case is hydroxymethylene, H-C-OH; although it is the key intermediate in the high- energy chemistry of its tautomer formaldehyde(3-7), has been implicated since 1921 in the photocatalytic formation of carbohydrates(8), and is the parent of alkoxycarbenes that lie at the heart of transition- metal carbene chemistry, all attempts to observe this species or other alkoxycarbenes have failed(9). However, theoretical considerations indicate that hydroxymethylene should be isolatable(10). Here we report the synthesis of hydroxymethylene and its capture by matrix isolation. We unexpectedly find that H -C-OH rearranges to formaldehyde with a half- life of only 2 h at 11 K by pure hydrogen tunnelling through a large energy barrier in excess of 30 kcal mol(-1).
C1 [Schreiner, Peter R.; Reisenauer, Hans Peter] Univ Giessen, Inst Organ Chem, D-35392 Giessen, Germany.
   [Pickard, Frank C.; Simmonett, Andrew C.; Allen, Wesley D.] Univ Georgia, Ctr Computat Chem, Athens, GA 30602 USA.
   [Pickard, Frank C.; Simmonett, Andrew C.; Allen, Wesley D.] Univ Georgia, Dept Chem, Athens, GA 30602 USA.
   [Matyus, Edit; Csaszar, Attila G.] Eotvos Lorand Univ, Lab Mol Spect, Inst Chem, H-1518 Budapest, Hungary.
C3 Justus Liebig University Giessen; University System of Georgia; University of Georgia; University System of Georgia; University of Georgia; Eotvos Lorand University; Hungarian Academy of Sciences; Chemical Research Center - HAS
RP Schreiner, PR (corresponding author), Univ Giessen, Inst Organ Chem, Heinrich Buff Ring 58, D-35392 Giessen, Germany.
EM prs@org.chemie.uni-giessen.de; wdallen@uga.edu
NR 57
TC 252
Z9 280
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 JUN 12
PY 2008
VL 453
IS 7197
BP 906
EP U42
DI 10.1038/nature07010
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 311WV
UT WOS:000256632000040
PM 18548067
DA 2026-03-09
ER

PT J
AU Holmes, E
   Loo, RL
   Stamler, J
   Bictash, M
   Yap, IKS
   Chan, Q
   Ebbels, T
   De Iorio, M
   Brown, IJ
   Veselkov, KA
   Daviglus, ML
   Kesteloot, H
   Ueshima, H
   Zhao, LC
   Nicholson, JK
   Elliott, P
AF Holmes, Elaine
   Loo, Ruey Leng
   Stamler, Jeremiah
   Bictash, Magda
   Yap, Ivan K. S.
   Chan, Queenie
   Ebbels, Tim
   De Iorio, Maria
   Brown, Ian J.
   Veselkov, Kirill A.
   Daviglus, Martha L.
   Kesteloot, Hugo
   Ueshima, Hirotsugu
   Zhao, Liancheng
   Nicholson, Jeremy K.
   Elliott, Paul
TI Human metabolic phenotype diversity and its association with diet and blood pressure
SO NATURE
LA English
DT Article
ID complex biological mixtures; h-1-nmr; spectroscopy
AB Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic(1-3). We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on H-1 NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide(4)). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study(5), involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure(6). Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities(2,7), are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.
C1 [Holmes, Elaine; Loo, Ruey Leng; Bictash, Magda; Yap, Ivan K. S.; Ebbels, Tim; Veselkov, Kirill A.; Nicholson, Jeremy K.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Surg Oncol Reprod Biol & Anaesthet SORA, London SW7 2AZ, England.
   [Loo, Ruey Leng; Bictash, Magda; Yap, Ivan K. S.; Chan, Queenie; De Iorio, Maria; Brown, Ian J.; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England.
   [Stamler, Jeremiah; Daviglus, Martha L.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
   [Kesteloot, Hugo] Akad Ziekenhuis St Rafael, Dept Publ Hlth, Div Epidemiol, B-3000 Louvain, Belgium.
   [Ueshima, Hirotsugu] Shiga Univ Med Sci, Dept Hlth Sci, Shiga 5202192, Japan.
   [Zhao, Liancheng] Chinese Acad Med Sci, Dept Epidemiol, Fu Wai Hosp, Beijing 100037, Peoples R China.
   [Zhao, Liancheng] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China.
C3 Imperial College London; Imperial College London; Northwestern University; Feinberg School of Medicine; KU Leuven; Shiga University of Medical Science; Chinese Academy of Medical Sciences - Peking Union Medical College; Fu Wai Hospital - CAMS; Chinese Academy of Medical Sciences - Peking Union Medical College
RP Nicholson, JK (corresponding author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Surg Oncol Reprod Biol & Anaesthet SORA, S Kensington Campus, London SW7 2AZ, England.
EM j.nicholson@imperial.ac.uk; p.elliott@imperial.ac.uk
FU NHLBI NIH HHS [R01 HL050490, R01 HL084228, R01 HL50490] Funding Source: Medline
NR 30
TC 859
Z9 954
U1 3
U2 307
PU NATURE PUBLISHING 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 15
PY 2008
VL 453
IS 7193
BP 396
EP U50
DI 10.1038/nature06882
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301AI
UT WOS:000255868400053
PM 18425110
DA 2026-03-09
ER

PT J
AU de Smit, E
   Swart, I
   Creemer, JF
   Hoveling, GH
   Gilles, MK
   Tyliszczak, T
   Kooyman, PJ
   Zandbergen, HW
   Morin, C
   Weckhuysen, BM
   de Groot, FMF
AF de Smit, Emiel
   Swart, Ingmar
   Creemer, J. Fredrik
   Hoveling, Gerard H.
   Gilles, Mary K.
   Tyliszczak, Tolek
   Kooyman, Patricia J.
   Zandbergen, Henny W.
   Morin, Cynthia
   Weckhuysen, Bert M.
   de Groot, Frank M. F.
TI Nanoscale chemical imaging of a working catalyst by scanning transmission X-ray microscopy
SO NATURE
LA English
DT Article
ID fischer-tropsch synthesis; advanced light-source; electron-microscopy; reduction behavior; zeolite crystals; tem-eels; absorption; silica; oxygen; microspectroscopy
AB The modern chemical industryuses heterogeneous catalysts in almost every production process(1). They commonly consist of nanometre- size active components ( typically metals or metal oxides) dispersed on a high- surface- area solid support, with performance depending on the catalysts' nanometre- size features and on interactions involving the active components, the support and the reactant and product molecules. To gain insight into the mechanisms of heterogeneous catalysts, which could guide the design of improved or novel catalysts, it is thus necessary to have a detailed characterization of the physicochemical composition of heterogeneous catalysts in their working state at the nanometre scale(1,2). Scanning probe microscopy methods have been used to study inorganic catalyst phases at subnanometre resolution(3-6), but detailed chemical information of the materials in their working state is often difficult to obtain(5-7). By contrast, optical microspectroscopic approaches offer much flexibility for in situ chemical characterization; however, this comes at the expense of limited spatial resolution(8-11). A recent development promising high spatial resolution and chemical characterization capabilities is scanning transmission X- ray microscopy(4,12,13), which has been used in a proof- of- principle study to characterize a solid catalyst(14). Here we show that when adapting a nanoreactor specially designed for high-resolution electron microscopy(7), scanning transmission X- ray microscopy can be used at atmospheric pressure and up to 350 degrees C to monitor in situ phase changes in a complex iron- based Fisher-Tropsch catalyst and the nature and location of carbon species produced. We expect that our system, which is capable of operating up to 500 degrees C, will open new opportunities for nanometre- resolution imaging of a range of important chemical processes taking place on solids in gaseous or liquid environments.
C1 [de Smit, Emiel; Swart, Ingmar; Morin, Cynthia; Weckhuysen, Bert M.; de Groot, Frank M. F.] Univ Utrecht, Debye Inst, NL-3584 CA Utrecht, Netherlands.
   [Creemer, J. Fredrik] Delft Univ Technol, DIMES ECTM, NL-2600 GB Delft, Netherlands.
   [Hoveling, Gerard H.] Delft Univ Technol, NL-2600 GA Delft, Netherlands.
   [Gilles, Mary K.; Tyliszczak, Tolek] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Kooyman, Patricia J.] Delft Univ Technol, DelftChemTech, NL-2628 BL Delft, Netherlands.
   [Kooyman, Patricia J.] Delft Univ Technol, Natl Ctr High Resolut Elect Microscopy, NL-2628 BL Delft, Netherlands.
   [Zandbergen, Henny W.] Delft Univ Technol, Kavli Inst Nanosci, Natl Ctr High Resolut Elect Microscopy, NL-2600 GA Delft, Netherlands.
C3 Utrecht University; Delft University of Technology; Delft University of Technology; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Delft University of Technology; Delft University of Technology; Delft University of Technology
RP de Groot, FMF (corresponding author), Univ Utrecht, Debye Inst, Sorbonnelaan 16, NL-3584 CA Utrecht, Netherlands.
EM b.m.weckhuysen@uu.nl; f.m.f.degroot@uu.nl
FU Dutch National Science Foundation; VICI; Netherlands Research School Combination on Catalysis; Shell Global Solutions; Office of Science; Office of Basic Energy Sciences; US Department of Energy
NR 30
TC 343
Z9 372
U1 6
U2 459
PU 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 13
PY 2008
VL 456
IS 7219
BP 222
EP U39
DI 10.1038/nature07516
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300036
PM 19005551
DA 2026-03-09
ER

PT J
AU Wiens, DA
   Anandakrishnan, S
   Winberry, JP
   King, MA
AF Wiens, Douglas A.
   Anandakrishnan, Sridhar
   Winberry, J. Paul
   King, Matt A.
TI Simultaneous teleseismic and geodetic observations of the stick-slip motion of an Antarctic ice stream
SO NATURE
LA English
DT Article
ID free oscillations; glacial earthquakes; waves; mouth; model
AB Long- period seismic sources associated with glacier motion have been recently discovered(1,2), and an increase in ice flow over the past decade has been suggested on the basis of secular changes in such measurements(3). Their significance, however, remains uncertain, as a relationship to ice flow has not been confirmed by direct observation. Here we combine long- period surface- wave observations with simultaneous Global Positioning System measurements of ice displacement to study the tidally modulated stick - slip motion of the Whillans Ice Stream in West Antarctica(4,5). The seismic origin time corresponds to slip nucleation at a region of the bed of the Whillans Ice Stream that is likely stronger than in surrounding regions and, thus, acts like an 'asperity' in traditional fault models. In addition to the initial pulse, two seismic arrivals occurring 10 - 23 minutes later represent stopping phases as the slip terminates at the ice stream edge and the grounding line. Seismic amplitude and average rupture velocity are correlated with tidal amplitude for the different slip events during the spring- to- neap tidal cycle. Although the total seismic moment calculated from ice rigidity, slip displacement, and rupture area is equivalent to an earthquake of moment magnitude seven ( M-w 7), seismic amplitudes are modest ( M-s 3.6 - 4.2), owing to the source duration of 20 - 30 minutes. Seismic radiation from ice movement is proportional to the derivative of the moment rate function at periods of 25 - 100 seconds and very long- period radiation is not detected, owing to the source geometry. Long- period seismic waves are thus useful for detecting and studying sudden ice movements but are insensitive to the total amount of slip.
C1 [Wiens, Douglas A.] Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
   [Anandakrishnan, Sridhar; Winberry, J. Paul] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [King, Matt A.] Univ Newcastle, Sch Civil Engn & Geosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
C3 Washington University (WUSTL); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Newcastle University - UK
RP Wiens, DA (corresponding author), Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
EM doug@wustl.edu
FU Natural Environment Research Council [NE/C002121/1] Funding Source: researchfish; NERC [NE/C002121/1] Funding Source: UKRI
NR 34
TC 126
Z9 156
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2008
VL 453
IS 7196
BP 770
EP U3
DI 10.1038/nature06990
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 308UK
UT WOS:000256415300041
PM 18528392
DA 2026-03-09
ER

PT J
AU Jördens, R
   Strohmaier, N
   Günther, K
   Moritz, H
   Esslinger, T
AF Joerdens, Robert
   Strohmaier, Niels
   Guenther, Kenneth
   Moritz, Henning
   Esslinger, Tilman
TI A Mott insulator of fermionic atoms in an optical lattice
SO NATURE
LA English
DT Article
ID gas
AB Strong interactions between electrons in a solid material can lead to surprising properties. A prime example is the Mott insulator, in which suppression of conductivity occurs as a result of interactions rather than a filled Bloch band(1). Proximity to the Mott insulating phase in fermionic systems is the origin of many intriguing phenomena in condensed matter physics(2), most notably high- temperature superconductivity(3). The Hubbard model(4), which encompasses the essential physics of the Mott insulator, also applies to quantum gases trapped in an optical lattice(5,6). It is therefore now possible to access this regime with tools developed in atomic physics. However, an atomic Mott insulator has so far been realized only with a gas of bosons(7), which lack the rich and peculiar nature of fermions. Here we report the formation of a Mott insulator of a repulsively interacting two- component Fermi gas in an optical lattice. It is identified by three features: a drastic suppression of doubly occupied lattice sites, a strong reduction of the compressibility inferred from the response of double occupancy to an increase in atom number, and the appearance of a gapped mode in the excitation spectrum. Direct control of the interaction strength allows us to compare the Mott insulating regime and the non- interacting regime without changing tunnel- coupling or confinement. Our results pave the way for further studies of the Mott insulator, including spin- ordering and ultimately the question of d- wave superfluidity(6,8).
C1 [Joerdens, Robert; Strohmaier, Niels; Guenther, Kenneth; Moritz, Henning; Esslinger, Tilman] ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
   [Guenther, Kenneth] Ecole Normale Super, Lab Kastler Brossel, F-75005 Paris, France.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite
RP Moritz, H (corresponding author), ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
EM moritz@phys.ethz.ch
FU Swiss National Science Foundation (SNF); EU projects Optical Lattices and Quantum Information (OLAQUI); Scalable Quantum Computing with Light and Atoms ( SCALA); Quantum Science and Technology (QSIT) project of ETH Zurich
NR 28
TC 874
Z9 976
U1 1
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 11
PY 2008
VL 455
IS 7210
BP 204
EP U34
DI 10.1038/nature07244
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 346SZ
UT WOS:000259090800042
PM 18784720
DA 2026-03-09
ER

PT J
AU Verheyden, JM
   Sun, X
AF Verheyden, Jamie M.
   Sun, Xin
TI An Fgf/Gremlin inhibitory feedback loop triggers termination of limb bud outgrowth
SO NATURE
LA English
DT Article
ID conditional knockout mice; apical ectodermal ridge; programmed cell-death; fgf; gremlin; antagonism; expression; size; inactivation; generation
AB During organ formation and regeneration a proper balance between promoting and restricting growth is critical to achieve stereotypical size. Limb bud outgrowth is driven by signals in a positive feedback loop involving fibroblast growth factor ( Fgf) genes, sonic hedgehog ( Shh) and Gremlin1 ( Grem1)(1). Precise termination of these signals is essential to restrict limb bud size(2-4). The current model predicts a sequence of signal termination consistent with that in chick limb buds(4). Our finding that the sequence in mouse limb buds is different led us to explore alternative mechanisms. Here we show, by analysing compound mouse mutants defective in genes comprising the positive loop, genetic evidence that FGF signalling can repress Grem1 expression, revealing a novel Fgf/Grem1 inhibitory loop. This repression occurs both in mouse and chick limb buds, and is dependent on high FGF activity. These data support a mechanism where the positive Fgf/ Shh loop drives outgrowth and an increase in FGF signalling, which triggers the Fgf/ Grem1 inhibitory loop. The inhibitory loop then operates to terminate outgrowth signals in the order observed in either mouse or chick limb buds. Our study unveils the concept of a self- promoting and self- terminating circuit that may be used to attain proper tissue size in a broad spectrum of developmental and regenerative settings.
C1 [Verheyden, Jamie M.; Sun, Xin] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison
RP Sun, X (corresponding author), Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
EM xsun@wisc.edu
FU NICHD NIH HHS [R01 HD045522] Funding Source: Medline; NIGMS NIH HHS [T32 GM007133, 5T32GM07133] Funding Source: Medline; National Institute of General Medical Sciences [T32GM007133] Funding Source: NIH RePORTER
NR 32
TC 147
Z9 177
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 638
EP U45
DI 10.1038/nature07085
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500047
PM 18594511
DA 2026-03-09
ER

PT J
AU Ahart, M
   Somayazulu, M
   Cohen, RE
   Ganesh, P
   Dera, P
   Mao, HK
   Hemley, RJ
   Ren, Y
   Liermann, P
   Wu, ZG
AF Ahart, Muhtar
   Somayazulu, Maddury
   Cohen, R. E.
   Ganesh, P.
   Dera, Przemyslaw
   Mao, Ho-Kwang
   Hemley, Russell J.
   Ren, Yang
   Liermann, Peter
   Wu, Zhigang
TI Origin of morphotropic phase boundaries in ferroelectrics
SO NATURE
LA English
DT Article
ID raman; pbtio3
AB A piezoelectric material is one that generates a voltage in response to a mechanical strain ( and vice versa). The most useful piezoelectric materials display a transition region in their composition phase diagrams, known as a morphotropic phase boundary(1,2), where the crystal structure changes abruptly and the electromechanical properties are maximal. As a result, modern piezoelectric materials for technological applications are usually complex, engineered, solid solutions, which complicates their manufacture as well as introducing complexity in the study of the microscopic origins of their properties. Here we show that even a pure compound, in this case lead titanate, can display a morphotropic phase boundary under pressure. The results are consistent with first-principles theoretical predictions(3), but show a richer phase diagram than anticipated; moreover, the predicted electromechanical coupling at the transition is larger than any known. Our results show that the high electromechanical coupling in solid solutions with lead titanate is due to tuning of the high- pressure morphotropic phase boundary in pure lead titanate to ambient pressure. We also find that complex microstructures or compositions are not necessary to obtain strong piezoelectricity. This opens the door to the possible discovery of high- performance, pure-compound electromechanical materials, which could greatly decrease costs and expand the utility of piezoelectric materials.
C1 [Ahart, Muhtar; Somayazulu, Maddury; Cohen, R. E.; Ganesh, P.; Dera, Przemyslaw; Mao, Ho-Kwang; Hemley, Russell J.] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Ren, Yang] Argonne Natl Lab, Xray Sci Div, Argonne, IL 60439 USA.
   [Liermann, Peter] Carnegie Inst Sci, Adv Photon Source, HPCAT, Argonne, IL 60439 USA.
   [Wu, Zhigang] Univ Calif Berkeley, BNNI, Berkeley, CA 94720 USA.
C3 Carnegie Institution for Science; United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Argonne National Laboratory; Carnegie Institution for Science; University of California System; University of California Berkeley
RP Cohen, RE (corresponding author), Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA.
EM rcohen@ciw.edu
FU Division Of Materials Research; Direct For Mathematical & Physical Scien [0805056] Funding Source: National Science Foundation
NR 28
TC 841
Z9 905
U1 12
U2 605
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 545
EP U2
DI 10.1038/nature06459
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900035
PM 18235495
DA 2026-03-09
ER

PT J
AU Worobey, M
   Gemmel, M
   Teuwen, DE
   Haselkorn, T
   Kunstman, K
   Bunce, M
   Muyembe, JJ
   Kabongo, JMM
   Kalengayi, RM
   Van Marck, E
   Gilbert, MTP
   Wolinsky, SM
AF Worobey, Michael
   Gemmel, Marlea
   Teuwen, Dirk E.
   Haselkorn, Tamara
   Kunstman, Kevin
   Bunce, Michael
   Muyembe, Jean-Jacques
   Kabongo, Jean-Marie M.
   Kalengayi, Raphael M.
   Van Marck, Eric
   Gilbert, M. Thomas P.
   Wolinsky, Steven M.
TI Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960
SO NATURE
LA English
DT Article
ID human-immunodeficiency-virus; origin; inference; type-1; reservoirs; ancestor; subtypes
AB Human immunodeficiency virus type 1 ( HIV- 1) sequences that pre- date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution(1,2). A viral sequence from 1959 ( ZR59) is the oldest known HIV- 1 infection(1). Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976. Here we report the amplification and characterization of viral sequences from a Bouin's- fixed paraffin- embedded lymph node biopsy specimen obtained in 1960 from an adult female in Leopoldville, Belgian Congo ( now Kinshasa, Democratic Republic of the Congo ( DRC)), and we use them to conduct the first comparative evolutionary genetic study of early pre- AIDS epidemic HIV- 1 group M viruses. Phylogenetic analyses position this viral sequence ( DRC60) closest to the ancestral node of subtype A ( excluding A2). Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most recent common ancestor of the M group to near the beginning of the twentieth century. The sizeable genetic distance between DRC60 and ZR59 directly demonstrates that diversification of HIV- 1 in west- central Africa occurred long before the recognized AIDS pandemic. The recovery of viral gene sequences from decades- old paraffin- embedded tissues opens the door to a detailed palaeovirological investigation of the evolutionary history of HIV- 1 that is not accessible by other methods.
C1 [Worobey, Michael; Gemmel, Marlea; Haselkorn, Tamara; Gilbert, M. Thomas P.] Univ Arizona, Tucson, AZ 85721 USA.
   [Teuwen, Dirk E.] Sanofi Pasteur, F-69367 Lyon 07, France.
   [Teuwen, Dirk E.] UCB SA Pharma, BE-1420 Braine Lalleud, Belgium.
   [Kunstman, Kevin; Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Bunce, Michael] Murdoch Univ, Sch Biol Sci & Biotechnol, Ancient DNA Lab, Perth, WA 6150, Australia.
   [Muyembe, Jean-Jacques; Kabongo, Jean-Marie M.; Kalengayi, Raphael M.] Univ Kinshasa, Dept Anat & Pathol, Kinshasa, DEM REP CONGO.
   [Muyembe, Jean-Jacques] Natl Lab Publ Hlth, Natl Inst Biomed Res, Kinshasa, DEM REP CONGO.
   [Van Marck, Eric] Univ Antwerp, Univ Hosp, Dept Pathol, B-2610 Antwerp, Belgium.
C3 University of Arizona; UCB Pharma SA; Northwestern University; Feinberg School of Medicine; Murdoch University; Universite de Kinshasa; Institute Nacional de Recherche Biomedical; University of Antwerp
RP Worobey, M (corresponding author), Univ Arizona, Tucson, AZ 85721 USA.
EM worobey@email.arizona.edu
FU NIH/NIAID; David and Lucile Packard Foundation
NR 27
TC 393
Z9 619
U1 0
U2 138
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 661
EP U57
DI 10.1038/nature07390
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700046
PM 18833279
DA 2026-03-09
ER

PT J
AU Zabow, G
   Dodd, S
   Moreland, J
   Koretsky, A
AF Zabow, Gary
   Dodd, Stephen
   Moreland, John
   Koretsky, Alan
TI Micro-engineered local field control for high-sensitivity multispectral MRI
SO NATURE
LA English
DT Article
ID iron-oxide; cells; particles; safety; agents
AB In recent years, biotechnology and biomedical research have benefited from the introduction of a variety of specialized nanoparticles whose well-defined, optically distinguishable signatures enable simultaneous tracking of numerous biological indicators. Unfortunately, equivalent multiplexing capabilities are largely absent in the field of magnetic resonance imaging (MRI). Comparable magnetic-resonance labels have generally been limited to relatively simple chemically synthesized superparamagnetic microparticles that are, to a large extent, indistinguishable from one another. Here we show how it is instead possible to use a top-down microfabrication approach to effectively encode distinguishable spectral signatures into the geometry of magnetic microstructures. Although based on different physical principles from those of optically probed nanoparticles, these geometrically defined magnetic microstructures permit a multiplexing functionality in the magnetic resonance radio-frequency spectrum that is in many ways analogous to that permitted by quantum dots in the optical spectrum. Additionally, in situ modification of particle geometries may facilitate radio-frequency probing of various local physiological variables.
C1 [Zabow, Gary; Dodd, Stephen; Koretsky, Alan] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
   [Zabow, Gary; Moreland, John] NIST, Electromagnet Div, Boulder, CO 80305 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); National Institute of Standards & Technology (NIST) - USA
RP Zabow, G (corresponding author), Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
EM zabow@boulder.nist.gov
FU National Institute of Neurological Disorders and Stroke [ZIANS003047] Funding Source: NIH RePORTER; Intramural NIH HHS [Z01 NS003047] Funding Source: Medline
NR 32
TC 104
Z9 125
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 JUN 19
PY 2008
VL 453
IS 7198
BP 1058
EP U2
DI 10.1038/nature07048
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 314WM
UT WOS:000256839900048
PM 18563157
DA 2026-03-09
ER

PT J
AU Davis, S
   Trapman, P
   Leirs, H
   Begon, M
   Heesterbeek, JAP
AF Davis, S.
   Trapman, P.
   Leirs, H.
   Begon, M.
   Heesterbeek, J. A. P.
TI The abundance threshold for plague as a critical percolation phenomenon
SO NATURE
LA English
DT Article
ID wildlife disease; epidemic; networks; models; populations; parameters; infection; serengeti; kazakstan; invasion
AB Percolation theory is most commonly associated with the slow flow of liquid through a porous medium, with applications to the physical sciences(1). Epidemiological applications have been anticipated for disease systems where the host is a plant or volume of soil(2,3), and hence is fixed in space. However, no natural examples have been reported. The central question of interest in percolation theory(4), the possibility of an infinite connected cluster, corresponds in infectious disease to a positive probability of an epidemic. Archived records of plague ( infection with Yersinia pestis) in populations of great gerbils ( Rhombomys opimus) in Kazakhstan have been used to show that epizootics only occur when more than about 0.33 of the burrow systems built by the host are occupied by family groups(5). The underlying mechanism for this abundance threshold is unknown. Here we present evidence that it is a percolation threshold, which arises from the difference in scale between the movements that transport infectious fleas between family groups and the vast size of contiguous landscapes colonized by gerbils. Conventional theory predicts that abundance thresholds for the spread of infectious disease arise when transmission between hosts is density dependent such that the basic reproduction number ( R(0)) increases with abundance, attaining 1 at the threshold. Percolation thresholds, however, are separate, spatially explicit thresholds that indicate long- range connectivity in a system and do not coincide with R(0) = 1. Abundance thresholds are the theoretical basis for attempts to manage infectious disease by reducing the abundance of susceptibles, including vaccination and the culling of wildlife(6-8). This first natural example of a percolation threshold in a disease system invites a re- appraisal of other invasion thresholds, such as those for epidemic viral infections in African lions ( Panthera leo), and of other disease systems such as bovine tuberculosis ( caused by Mycobacterium bovis) in badgers ( Meles meles).
C1 [Davis, S.; Heesterbeek, J. A. P.] Univ Utrecht, Fac Vet Med, NL-3584 CL Utrecht, Netherlands.
   [Trapman, P.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands.
   [Leirs, H.] Univ Antwerp, Dept Biol, B-2020 Antwerp, Belgium.
   [Leirs, H.] Univ Aarhus, Danish Pest Infestat Lab, Fac Agr Sci, Dept Integrated Pest Management, DK-2800 Lyngby, Denmark.
   [Begon, M.] Univ Liverpool, Host Parasite Biol Res Grp, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England.
C3 Utrecht University; Utrecht University; Utrecht University Medical Center; University of Antwerp; Aarhus University; University of Liverpool
RP Davis, S (corresponding author), Univ Utrecht, Fac Vet Med, Yalelaan 7, NL-3584 CL Utrecht, Netherlands.
EM S.A.Davis@uu.nl
FU NERC [NE/E007899/1] Funding Source: UKRI; Natural Environment Research Council [NE/E007899/1] Funding Source: researchfish
NR 27
TC 149
Z9 168
U1 1
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 634
EP 637
DI 10.1038/nature07053
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500046
PM 18668107
DA 2026-03-09
ER

PT J
AU McLellan, JS
   Zheng, XY
   Hauk, G
   Ghirlando, R
   Beachy, PA
   Leahy, DJ
AF McLellan, Jason S.
   Zheng, Xiaoyan
   Hauk, Glenn
   Ghirlando, Rodolfo
   Beachy, Philip A.
   Leahy, Daniel J.
TI The mode of Hedgehog binding to Ihog homologues is not conserved across different phyla
SO NATURE
LA English
DT Article
ID sonic hedgehog; candidate gene; proteins; cdo; gas1; ultracentrifugation; expression; mutations; pathway; complex
AB Hedgehog ( Hh) proteins specify tissue pattern in metazoan embryos by forming gradients that emanate from discrete sites of expression and elicit concentration- dependent cellular differentiation or proliferation responses(1,2). Cellular responses to Hh and the movement of Hh through tissues are both precisely regulated, and abnormal Hh signalling has been implicated in human birth defects and cancer(3-7). Hh signalling is mediated by its amino- terminal domain ( HhN), which is dually lipidated and secreted as part of a multivalent lipoprotein particle(8-10). Reception of the HhN signal is modulated by several cell- surface proteins on responding cells, including Patched ( Ptc), Smoothened ( Smo), Ihog ( known as CDO or CDON in mammals) and the vertebrate- specific proteins Hip ( also known as Hhip) and Gas1 ( ref. 11). Drosophila Ihog and its vertebrate homologues CDO and BOC contain multiple immunoglobulin and fibronectin type III ( FNIII) repeats, and the first FNIII repeat of Ihog binds Drosophila HhN in a heparin-dependent manner(12,13). Surprisingly, pull- down experiments suggest that a mammalian Sonic hedgehog N- terminal domain ( ShhN) binds a non- orthologous FNIII repeat of CDO12,14. Here we report biochemical, biophysical and X- ray structural studies of a complex between ShhN and the third FNIII repeat of CDO. We show that the ShhN - CDO interaction is completely unlike the HhN - Ihog interaction and requires calcium, which binds at a previously undetected site on ShhN. This site is conserved in nearly all Hh proteins and is a hotspot for mediating interactions between ShhN and CDO, Ptc, Hip and Gas1. Mutations in vertebrate Hh proteins causing holoprosencephaly and brachydactyly type A1 map to this calcium-binding site and disrupt interactions with these partners.
C1 [McLellan, Jason S.; Hauk, Glenn; Leahy, Daniel J.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
   [Zheng, Xiaoyan; Beachy, Philip A.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
   [Beachy, Philip A.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Ghirlando, Rodolfo] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
C3 Johns Hopkins University; Stanford University; Stanford University; Howard Hughes Medical Institute; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Leahy, DJ (corresponding author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
EM dleahy@jhmi.edu
FU Intramural Research Program of the NIH; National Institute of Diabetes and Digestive and Kidney Diseases; National Science Foundation Graduate Research Fellowship; Damon Runyon Cancer Research Foundation [DRG-1915-06];  [R01 HD055545]
NR 38
TC 128
Z9 162
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 OCT 16
PY 2008
VL 455
IS 7215
BP 979
EP U62
DI 10.1038/nature07358
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300053
PM 18794898
DA 2026-03-09
ER

PT J
AU Hoernle, K
   Abt, DL
   Fischer, KM
   Nichols, H
   Hauff, F
   Abers, GA
   van den Bogaard, P
   Heydolph, K
   Alvarado, G
   Protti, M
   Strauch, W
AF Hoernle, Kaj
   Abt, David L.
   Fischer, Karen M.
   Nichols, Holly
   Hauff, Folkmar
   Abers, Geoffrey A.
   van den Bogaard, Paul
   Heydolph, Ken
   Alvarado, Guillermo
   Protti, Marino
   Strauch, Wilfried
TI Arc-parallel flow in the mantle wedge beneath Costa Rica and Nicaragua
SO NATURE
LA English
DT Article
ID seismic anisotropy; elastic-constants; history; asthenosphere; olivine; volcano; ma
AB Resolving flow geometry in the mantle wedge is central to understanding the thermal and chemical structure of subduction zones, subducting plate dehydration, and melting that leads to arc volcanism, which can threaten large populations and alter climate through gas and particle emission. Here we show that isotope geochemistry and seismic velocity anisotropy provide strong evidence for trench- parallel flow in the mantle wedge beneath Costa Rica and Nicaragua. This finding contradicts classical models, which predict trench- normal flow owing to the overlying wedge mantle being dragged downwards by the subducting plate. The isotopic signature of central Costa Rican volcanic rocks is not consistent with its derivation from the mantle wedge(1-3) or eroded fore- arc complexes(4) but instead from seamounts of the Galapagos hotspot track on the subducting Cocos plate. This isotopic signature decreases continuously from central Costa Rica to northwestern Nicaragua. As the age of the isotopic signature beneath Costa Rica can be constrained and its transport distance is known, minimum northwestward flow rates can be estimated ( 63 - 190 mm yr(-1)) and are comparable to the magnitude of subducting Cocos plate motion (similar to 85 mm yr(-1)). Trench- parallel flow needs to be taken into account in models evaluating thermal and chemical structure and melt generation in subduction zones.
C1 [Hoernle, Kaj; Nichols, Holly; van den Bogaard, Paul; Heydolph, Ken] Univ Kiel, SFB 574, D-24148 Kiel, Germany.
   [Hoernle, Kaj; Hauff, Folkmar; van den Bogaard, Paul] Univ Kiel, Leibniz Inst Marine Sci, IFM GEOMAR, D-24148 Kiel, Germany.
   [Abt, David L.; Fischer, Karen M.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Abers, Geoffrey A.] Boston Univ, Dept Earth Sci, Boston, MA 02215 USA.
   [Alvarado, Guillermo] ICE, OSIVAM, Heredia 1000, Costa Rica.
   [Protti, Marino] Univ Nacl, Observ Vulcanol & Sismol Costa Rica, Heredia 3000, Costa Rica.
   [Strauch, Wilfried] Inst Nicaraguense Estud Terr, Managua, Nicaragua.
C3 University of Kiel; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; University of Kiel; Brown University; Boston University; Universidad Nacional Costa Rica
RP Hoernle, K (corresponding author), Univ Kiel, SFB 574, Wischhofstr 1-3, D-24148 Kiel, Germany.
EM khoernle@ifm-geomar.de
NR 37
TC 205
Z9 243
U1 2
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2008
VL 451
IS 7182
BP 1094
EP U4
DI 10.1038/nature06550
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266RB
UT WOS:000253453600039
PM 18223639
DA 2026-03-09
ER

PT J
AU Cadwell, K
   Liu, JY
   Brown, SL
   Miyoshi, H
   Loh, J
   Lennerz, JK
   Kishi, C
   Kc, W
   Carrero, JA
   Hunt, S
   Stone, CD
   Brunt, EM
   Xavier, RJ
   Sleckman, BP
   Li, E
   Mizushima, N
   Stappenbeck, TS
   Virgin, HW
AF Cadwell, Ken
   Liu, John Y.
   Brown, Sarah L.
   Miyoshi, Hiroyuki
   Loh, Joy
   Lennerz, Jochen K.
   Kishi, Chieko
   Kc, Wumesh
   Carrero, Javier A.
   Hunt, Steven
   Stone, Christian D.
   Brunt, Elizabeth M.
   Xavier, Ramnik J.
   Sleckman, Barry P.
   Li, Ellen
   Mizushima, Noboru
   Stappenbeck, Thaddeus S.
   Virgin, Herbert W.
TI A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells
SO NATURE
LA English
DT Article
ID genome-wide association; mesenteric adipose-tissue; susceptibility loci; crohn-disease; protein; pathogenesis; expression; membrane; complex
AB Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci(1). One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 ( ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment(3). ATG16L1- andATG5- deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1- deficient Paneth cells including increased expression of genes involved in peroxisome proliferator- activated receptor ( PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy- protein- deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.
C1 [Cadwell, Ken; Liu, John Y.; Brown, Sarah L.; Miyoshi, Hiroyuki; Loh, Joy; Lennerz, Jochen K.; Kc, Wumesh; Carrero, Javier A.; Brunt, Elizabeth M.; Sleckman, Barry P.; Stappenbeck, Thaddeus S.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Hunt, Steven] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
   [Stone, Christian D.; Li, Ellen] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Virgin, Herbert W.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Kishi, Chieko; Mizushima, Noboru] Tokyo Med & Dent Univ, Grad Sch, Dept Physiol & Cell Biol, Tokyo 1138519, Japan.
   [Kishi, Chieko; Mizushima, Noboru] Tokyo Med & Dent Univ, Fac Med, Dept Physiol & Cell Biol, Tokyo 1138519, Japan.
   [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Virgin, HW (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
EM stappenb@wustl.edu; virgin@wustl.edu
FU Broad Foundation; NIH [T32 AR07279, R01 AI062832, AI062773, DK43351]; Lallage Feazel Wall Fellowship [DRG-1972-08]; Damon Runyon Cancer Research Foundation; Pew Foundation; Washington University Digestive Diseases Research Core Center [P30 DK52574]; Barnes Jewish Foundation; Johnson and Johnson Translational Seed Award; Crohn's Colitis Foundation of America; Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Toray Science Foundation;  [U54 AI057160 Project 6]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32AR007279] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK040561, P30DK043351, P30DK052574] Funding Source: NIH RePORTER
NR 29
TC 1258
Z9 1429
U1 3
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 NOV 13
PY 2008
VL 456
IS 7219
BP 259
EP U62
DI 10.1038/nature07416
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 374JJ
UT WOS:000261039300044
PM 18849966
DA 2026-03-09
ER

PT J
AU Chiba, D
   Sawicki, M
   Nishitani, Y
   Nakatani, Y
   Matsukura, F
   Ohno, H
AF Chiba, D.
   Sawicki, M.
   Nishitani, Y.
   Nakatani, Y.
   Matsukura, F.
   Ohno, H.
TI Magnetization vector manipulation by electric fields
SO NATURE
LA English
DT Article
ID ferromagnetic semiconductor; memory device; (ga,mn)as; anisotropy
AB Conventional semiconductor devices use electric fields to control conductivity, a scalar quantity, for information processing. In magnetic materials, the direction of magnetization, a vector quantity, is of fundamental importance. In magnetic data storage, magnetization is manipulated with a current-generated magnetic field (Oersted-Ampere field), and spin current(1,2) is being studied for use in non- volatile magnetic memories(3,4). To make control of magnetization fully compatible with semiconductor devices, it is highly desirable to control magnetization using electric fields. Conventionally, this is achieved by means of magnetostriction produced by mechanically generated strain through the use of piezoelectricity(5-8). Multiferroics(9,10) have been widely studied in an alternative approach where ferroelectricity is combined with ferromagnetism. Magnetic- field control of electric polarization has been reported in these multiferroics using the magnetoelectric effect, but the inverse effect - direct electrical control of magnetization - has not so far been observed(11). Here we show that the manipulation of magnetization can be achieved solely by electric fields in a ferromagnetic semiconductor, (Ga,Mn)As. The magnetic anisotropy, which determines the magnetization direction, depends on the charge carrier (hole) concentration in (Ga,Mn) As. By applying an electric field using a metal - insulator - semiconductor structure(12-14), the hole concentration and, thereby, the magnetic anisotropy can be controlled, allowing manipulation of the magnetization direction.
C1 [Chiba, D.; Sawicki, M.; Nishitani, Y.; Matsukura, F.; Ohno, H.] Tohoku Univ, Aoba Ku, Lab Nanoelect & Spintron, Res Inst Elect Commun, Sendai, Miyagi 9808577, Japan.
   [Chiba, D.; Matsukura, F.; Ohno, H.] Japan Sci & Technol Agcy, Chiyoda Ku, Semicond Spintron Project, Tokyo 1020075, Japan.
   [Sawicki, M.] Polish Acad Sci, Inst Phys, PL-02668 Warsaw, Poland.
   [Nakatani, Y.] Univ Electrocommun, Tokyo 1828585, Japan.
C3 Tohoku University; Japan Science & Technology Agency (JST); Polish Academy of Sciences; Institute of Physics - Polish Academy of Sciences; University of Electro-Communications - Japan
RP Ohno, H (corresponding author), Tohoku Univ, Aoba Ku, Lab Nanoelect & Spintron, Res Inst Elect Commun, Katahira 2-1-1, Sendai, Miyagi 9808577, Japan.
EM ohno@riec.tohoku.ac.jp
FU MEXT/JSPS; GCOE Program at Tohoku University; Research and Development for Next-Generation Information Technology Program (MEXT); Research Fellowship from JSPS
NR 30
TC 603
Z9 650
U1 1
U2 332
PU NATURE PUBLISHING 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 25
PY 2008
VL 455
IS 7212
BP 515
EP 518
DI 10.1038/nature07318
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 351TU
UT WOS:000259449600042
PM 18818654
DA 2026-03-09
ER

PT J
AU Shimada, A
   Ueguchi-Tanaka, M
   Nakatsu, T
   Nakajima, M
   Naoe, Y
   Ohmiya, H
   Kato, H
   Matsuoka, M
AF Shimada, Asako
   Ueguchi-Tanaka, Miyako
   Nakatsu, Toru
   Nakajima, Masatoshi
   Naoe, Youichi
   Ohmiya, Hiroko
   Kato, Hiroaki
   Matsuoka, Makoto
TI Structural basis for gibberellin recognition by its receptor GID1
SO NATURE
LA English
DT Article
ID protein; mechanism
AB Gibberellins ( GAs) are phytohormones essential for many developmental processes in plants(1). A nuclear GA receptor, GIBBERELLIN INSENSITIVEDWARF1 ( GID1), has a primary structure similar to that of the hormone- sensitive lipases (HSLs)(2,3). Here we analyse the crystal structure of Oryza sativa GID1 (OsGID1) bound with GA(4) and GA(3) at 1.9 angstrom resolution. The overall structure of both complexes shows an alpha/beta-hydrolase fold similar to that of HSLs except for an amino- terminal lid. The GA- binding pocket corresponds to the substrate- binding site of HSLs. On the basis of the OsGID1 structure, we mutagenized important residues for GA binding and examined their binding activities. Almost all of them showed very little or no activity, confirming that the residues revealed by structural analysis are important for GA binding. The replacement of Ile 133 with Leu or Val - residues corresponding to those of the lycophyte Selaginella moellendorffii GID1s - caused an increase in the binding affinity for GA(34), a 2 beta-hydroxylated GA(4). These observations indicate that GID1 originated from HSL and was further modified to have higher affinity and more strict selectivity for bioactive GAs by adapting the amino acids involved in GA binding in the course of plant evolution.
C1 [Nakatsu, Toru; Naoe, Youichi; Kato, Hiroaki] Kyoto Univ, Dept Biol Struct, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan.
   [Shimada, Asako; Ueguchi-Tanaka, Miyako; Ohmiya, Hiroko; Matsuoka, Makoto] Nagoya Univ, Biosci & Biotechnol Ctr, Nagoya, Aichi 4648601, Japan.
   [Nakatsu, Toru; Kato, Hiroaki] RIKEN, Harima Inst SPring 8, Mikazuki, Hyogo 6795148, Japan.
   [Nakajima, Masatoshi] Univ Tokyo, Dept Appl Biol Chem, Bunkyo Ku, Tokyo 1138657, Japan.
C3 Kyoto University; Nagoya University; RIKEN; University of Tokyo
RP Kato, H (corresponding author), Kyoto Univ, Dept Biol Struct, Grad Sch Pharmaceut Sci, Sakyo Ku, 46-29 Yoshida Shimoadachi Cho, Kyoto 6068501, Japan.
EM katohiro@pharm.kyoto-u.ac.jp; makoto@nuagr1.agr.nagoya-u.ac.jp
FU Target Protein Research Program; Scientific Research; Special Coordination Funds for Promoting Science and Technology; Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research [20108016] Funding Source: KAKEN
NR 19
TC 294
Z9 347
U1 3
U2 106
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2008
VL 456
IS 7221
BP 520
EP U44
DI 10.1038/nature07546
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 376FW
UT WOS:000261170500042
PM 19037316
DA 2026-03-09
ER

PT J
AU Gordon, GRJ
   Choi, HB
   Rungta, RL
   Ellis-Davies, GCR
   MacVicar, BA
AF Gordon, Grant R. J.
   Choi, Hyun B.
   Rungta, Ravi L.
   Ellis-Davies, Graham C. R.
   MacVicar, Brian A.
TI Brain metabolism dictates the polarity of astrocyte control over arterioles
SO NATURE
LA English
DT Article
ID cerebral-blood-flow; prostaglandin transporter pgt; rat hippocampal slices; activated human brain; neuronal-activity; oxidative-metabolism; in-vivo; extracellular lactate; sensory stimulation; cortical astrocytes
AB Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter- mediated uptake from the extracellular space of prostaglandin E(2), leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte- mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation.
C1 [Gordon, Grant R. J.; Choi, Hyun B.; Rungta, Ravi L.; MacVicar, Brian A.] Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC T2N 2B5, Canada.
   [Ellis-Davies, Graham C. R.] Drexel Univ, Coll Med, Dept Physiol & Pharmacol, Philadelphia, PA 19102 USA.
C3 University of British Columbia; Drexel University
RP MacVicar, BA (corresponding author), Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC T2N 2B5, Canada.
EM bmacvicar@brain.ubc.ca
FU Canadian Institutes of Health Research; Alberta Heritage Foundation for Medical Research; Natural Science and Engineering Council of Canada; Wilms Foundation; Heart and Stroke Foundation of Canada
NR 49
TC 595
Z9 699
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 11
PY 2008
VL 456
IS 7223
BP 745
EP U45
DI 10.1038/nature07525
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 381TX
UT WOS:000261559900039
PM 18971930
DA 2026-03-09
ER

PT J
AU Yuan, ZS
   Chen, YA
   Zhao, B
   Chen, S
   Schmiedmayer, J
   Pan, JW
AF Yuan, Zhen-Sheng
   Chen, Yu-Ao
   Zhao, Bo
   Chen, Shuai
   Schmiedmayer, Joerg
   Pan, Jian-Wei
TI Experimental demonstration of a BDCZ quantum repeater node
SO NATURE
LA English
DT Article
ID atomic ensembles; entanglement; communication; distance
AB Quantum communication is a method that offers efficient and secure ways for the exchange of information in a network. Large- scale quantum communication(1-4) ( of the order of 100 km) has been achieved; however, serious problems occur beyond this distance scale, mainly due to inevitable photon loss in the transmission channel. Quantum communication eventually fails(5) when the probability of a dark count in the photon detectors becomes comparable to the probability that a photon is correctly detected. To overcome this problem, Briegel, Dur, Cirac and Zoller ( BDCZ) introduced the concept of quantum repeaters(6), combining entanglement swapping(7) and quantum memory to efficiently extend the achievable distances. Although entanglement swapping has been experimentally demonstrated(8), the implementation of BDCZ quantum repeaters has proved challenging owing to the difficulty of integrating a quantum memory. Here we realize entanglement swapping with storage and retrieval of light, a building block of the BDCZ quantum repeater. We follow a scheme(9,10) that incorporates the strategy of BDCZ with atomic quantum memories(11). Two atomic ensembles, each originally entangled with a single emitted photon, are projected into an entangled state by performing a joint Bell state measurement on the two single photons after they have passed through a 300- m fibre- based communication channel. The entanglement is stored in the atomic ensembles and later verified by converting the atomic excitations into photons. Our method is intrinsically phase insensitive and establishes the essential element needed to realize quantum repeaters with stationary atomic qubits as quantum memories and flying photonic qubits as quantum messengers.
C1 [Yuan, Zhen-Sheng; Chen, Yu-Ao; Zhao, Bo; Chen, Shuai; Pan, Jian-Wei] Univ Heidelberg, Inst Phys, D-69120 Heidelberg, Germany.
   [Yuan, Zhen-Sheng; Chen, Yu-Ao; Pan, Jian-Wei] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Anhua 230026, Peoples R China.
   [Yuan, Zhen-Sheng; Chen, Yu-Ao; Pan, Jian-Wei] Univ Sci & Technol China, Dept Modern Phys, Anhua 230026, Peoples R China.
   [Schmiedmayer, Joerg] Vienna Univ Technol, Atominst Osterreichischen Univ, A-1020 Vienna, Austria.
C3 Ruprecht Karls University Heidelberg; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Technische Universitat Wien
RP Chen, YA (corresponding author), Univ Heidelberg, Inst Phys, Philosophenweg 12, D-69120 Heidelberg, Germany.
EM yuao@physi.uni-heidelberg.de; jian-wei.pan@physi.uni-heidelberg.de
FU Deutsche Forschungsgemeinschaft, the Alexander von Humboldt Foundation; Marie Curie Excellence Grant; ERC Grant; National Fundamental Research Program [2006CB921900]; CAS; NNSFC; Austrian Science Fund (FWF) [Z 118] Funding Source: researchfish
NR 27
TC 395
Z9 444
U1 0
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1098
EP 1101
DI 10.1038/nature07241
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600033
PM 18756253
DA 2026-03-09
ER

PT J
AU Lu, PJ
   Zaccarelli, E
   Ciulla, F
   Schofield, AB
   Sciortino, F
   Weitz, DA
AF Lu, Peter J.
   Zaccarelli, Emanuela
   Ciulla, Fabio
   Schofield, Andrew B.
   Sciortino, Francesco
   Weitz, David A.
TI Gelation of particles with short-range attraction
SO NATURE
LA English
DT Article
ID phase-behavior; aggregation; dependence; dynamics; diagram
AB Nanoscale or colloidal particles are important in many realms of science and technology. They can dramatically change the properties of materials, imparting solid-like behaviour to a wide variety of complex fluids(1,2). This behaviour arises when particles aggregate to form mesoscopic clusters and networks. The essential component leading to aggregation is an interparticle attraction, which can be generated by many physical and chemical mechanisms. In the limit of irreversible aggregation, infinitely strong interparticle bonds lead to diffusion-limited cluster aggregation(3) (DLCA). This is understood as a purely kinetic phenomenon that can form solid-like gels at arbitrarily low particle volume fraction(4,5). Far more important technologically are systems with weaker attractions, where gel formation requires higher volume fractions. Numerous scenarios for gelation have been proposed, including DLCA(6), kinetic or dynamic arrest(4,7-10), phase separation(5,6,11-16), percolation(4,12,17,18) and jamming(8). No consensus has emerged and, despite its ubiquity and significance, gelation is far from understood-even the location of the gelation phase boundary is not agreed on(5). Here we report experiments showing that gelation of spherical particles with isotropic, short-range attractions is initiated by spinodal decomposition; this thermodynamic instability triggers the formation of density fluctuations, leading to spanning clusters that dynamically arrest to create a gel. This simple picture of gelation does not depend on microscopic system-specific details, and should thus apply broadly to any particle system with short- range attractions. Our results suggest that gelation-often considered a purely kinetic phenomenon(4,8-10)-is in fact a direct consequence of equilibrium liquid gas phase separation(5,13-15). Without exception, we observe gelation in all of our samples predicted by theory and simulation to phaseseparate; this suggests that it is phase separation, not percolation(12), that corresponds to gelation in models for attractive spheres.
C1 [Lu, Peter J.; Weitz, David A.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Lu, Peter J.; Weitz, David A.] Harvard Univ, SEAS, Cambridge, MA 02138 USA.
   [Zaccarelli, Emanuela; Ciulla, Fabio; Sciortino, Francesco] Univ Roma La Sapienza, Dipartimento Fis, I-00185 Rome, Italy.
   [Zaccarelli, Emanuela; Sciortino, Francesco] Univ Roma La Sapienza, CNR INFM SOFT, I-00185 Rome, Italy.
   [Schofield, Andrew B.] Univ Edinburgh, Sch Phys, Edinburgh EH9 3JZ, Midlothian, Scotland.
C3 Harvard University; Harvard University; Sapienza University Rome; Sapienza University Rome; Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale per la Fisica della Materia (INFM-CNR); University of Edinburgh
RP Lu, PJ (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM plu@fas.harvard.edu
FU Engineering and Physical Sciences Research Council [EP/E030173/1] Funding Source: researchfish; EPSRC [EP/E030173/1] Funding Source: UKRI
NR 36
TC 858
Z9 980
U1 4
U2 534
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 499
EP U4
DI 10.1038/nature06931
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700037
PM 18497820
DA 2026-03-09
ER

PT J
AU Mullighan, CG
   Miller, CB
   Radtke, I
   Phillips, LA
   Dalton, J
   Ma, J
   White, D
   Hughes, TP
   Le Beau, MM
   Pui, CH
   Relling, MV
   Shurtleff, SA
   Downing, JR
AF Mullighan, Charles G.
   Miller, Christopher B.
   Radtke, Ina
   Phillips, Letha A.
   Dalton, James
   Ma, Jing
   White, Deborah
   Hughes, Timothy P.
   Le Beau, Michelle M.
   Pui, Ching-Hon
   Relling, Mary V.
   Shurtleff, Sheila A.
   Downing, James R.
TI BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros
SO NATURE
LA English
DT Article
ID chronic myeloid-leukemia; gene encodes; expression; isoforms; proteins; family; disease; genome; cells; model
AB The Philadelphia chromosome, a chromosomal abnormality that encodes BCR - ABL1, is the defining lesion of chronic myelogenous leukaemia ( CML) and a subset of acute lymphoblastic leukaemia (ALL)(1-3). To define oncogenic lesions that cooperate with BCR ABL1 to induce ALL, we performed a genome- wide analysis of diagnostic leukaemia samples from 304 individuals with ALL, including 43 BCR - ABL1 B- progenitor ALLs and 23 CML cases. IKZF1 ( encoding the transcription factor Ikaros) was deleted in 83.7% of BCR - ABL1 ALL, but not in chronic- phase CML. Deletion of IKZF1 was also identified as an acquired lesion at the time of transformation of CML to ALL ( lymphoid blast crisis). The IKZF1 deletions resulted in haploin sufficiency, expression of a dominant- negative Ikaros isoform, or the complete loss of Ikaros expression. Sequencing of IKZF1 deletion breakpoints suggested that aberrant RAG- mediated recombination is responsible for the deletions. These findings suggest that genetic lesions resulting in the loss of Ikaros function are an important event in the development of BCR - ABL1 ALL.
C1 [Mullighan, Charles G.; Miller, Christopher B.; Radtke, Ina; Phillips, Letha A.; Dalton, James; Shurtleff, Sheila A.; Downing, James R.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Relling, Mary V.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
   [Ma, Jing] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
   [White, Deborah; Hughes, Timothy P.] Inst Med & Vet Sci, Div Haematol, Adelaide, SA 5000, Australia.
   [Le Beau, Michelle M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; University of Tennessee System; University of Tennessee Health Science Center; St Jude Children's Research Hospital; St Jude Children's Research Hospital; SA Pathology; University of Chicago
RP Downing, JR (corresponding author), St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM james.downing@stjude.org
NR 32
TC 846
Z9 973
U1 1
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 MAY 1
PY 2008
VL 453
IS 7191
BP 110
EP +
DI 10.1038/nature06866
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294ID
UT WOS:000255398800049
PM 18408710
DA 2026-03-09
ER

PT J
AU Yamagata, M
   Sanes, JR
AF Yamagata, Masahito
   Sanes, Joshua R.
TI Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina
SO NATURE
LA English
DT Article
ID cell-adhesion molecule; homophilic intercellular-adhesion; choline-acetyltransferase; mammalian retina; drosophila dscam; axon guidance; diversity; system; transposition; segregation
AB Synaptic circuits in the retina transform visual input gathered by photoreceptors into messages that retinal ganglion cells ( RGCs) send to the brain. Processes of retinal interneurons ( amacrine and bipolar cells) form synapses on dendrites of RGCs in the inner plexiform layer ( IPL). The IPL is divided into at least 10 parallel sublaminae; subsets of interneurons and RGCs arborize and form synapses in just one or a few of them(1-3). These lamina- specific circuits determine the visual features to which RGC subtypes respond(3-5). Here we show that four closely related immunoglobulin superfamily ( IgSF) adhesion molecules - Dscam ( Down's syndrome cell adhesion molecule), DscamL ( refs 6 - 9), Sidekick- 1 and Sidekick- 2 ( ref. 10) - are expressed in chick by non- overlapping subsets of interneurons and RGCs that form synapses in distinct IPL sublaminae. Moreover, each protein is concentrated within the appropriate sublaminae and each mediates homophilic adhesion. Loss- and gain- of- function studies in vivo indicate that these IgSF members participate in determining the IPL sublaminae in which synaptic partners arborize and connect. Thus, vertebrate Dscams, like Drosophila Dscams(11-19), play roles in neural connectivity. Together, our results on Dscams and Sidekicks suggest the existence of an IgSF code for laminar specificity in retina and, by implication, in other parts of the central nervous system.
C1 [Yamagata, Masahito; Sanes, Joshua R.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Yamagata, Masahito; Sanes, Joshua R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University
RP Sanes, JR (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM sanesj@mcb.harvard.edu
NR 33
TC 317
Z9 435
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 24
PY 2008
VL 451
IS 7177
BP 465
EP U6
DI 10.1038/nature06469
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100045
PM 18216854
DA 2026-03-09
ER

PT J
AU MacMillan, DWC
AF MacMillan, David W. C.
TI The advent and development of organocatalysis
SO NATURE
LA English
DT Article
ID enantioselective synthesis; asymmetric epoxidation; organic catalysis; strategy
AB The use of small organic molecules as catalysts has been known for more than a century. But only in the past decade has organocatalysis become a thriving area of general concepts and widely applicable asymmetric reactions. Here I present my opinion on why the field of organocatalysis has blossomed so dramatically over the past decade.
C1 [MacMillan, David W. C.] Princeton Univ, Merck Ctr Catalysis, Frick Lab 116, Princeton, NJ 08540 USA.
C3 Princeton University
RP MacMillan, DWC (corresponding author), Princeton Univ, Merck Ctr Catalysis, Frick Lab 116, Princeton, NJ 08540 USA.
FU National Institute of General Medical Sciences [R01 GM078201-01-01]
NR 30
TC 2207
Z9 2462
U1 24
U2 991
PU NATURE PUBLISHING 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 18
PY 2008
VL 455
IS 7211
BP 304
EP 308
DI 10.1038/nature07367
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200030
PM 18800128
DA 2026-03-09
ER

PT J
AU Holden, LG
   Prochnow, C
   Chang, YP
   Bransteitter, R
   Chelico, L
   Sen, U
   Stevens, RC
   Goodman, MF
   Chen, XJS
AF Holden, Lauren G.
   Prochnow, Courtney
   Chang, Y. Paul
   Bransteitter, Ronda
   Chelico, Linda
   Sen, Udayaditya
   Stevens, Raymond C.
   Goodman, Myron F.
   Chen, Xiaojiang S.
TI Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications
SO NATURE
LA English
DT Article
ID dna deaminase domain; restriction; model
AB The APOBEC family members are involved in diverse biological functions. APOBEC3G restricts the replication of human immunodeficiency virus (HIV), hepatitis B virus and retroelements by cytidine deamination on single- stranded DNA or by RNA binding(1-4). Here we report the high- resolution crystal structure of the carboxy- terminal deaminase domain of APOBEC3G (APOBEC3G-CD2) purified from Escherichia coli. The APOBEC3G-CD2 structure has a five- stranded beta- sheet core that is common to all known deaminase structures and closely resembles the structure of another APOBEC protein, APOBEC2 ( ref. 5). A comparison of APOBEC3G-CD2 with other deaminase structures shows a structural conservation of the active- site loops that are directly involved in substrate binding. In the X- ray structure, these APOBEC3G active- site loops form a continuous 'substrate groove' around the active centre. The orientation of this putative substrate groove differs markedly ( by 90 degrees) from the groove predicted by the NMR structure(6). We have introduced mutations around the groove, and have identified residues involved in substrate specificity, single- stranded DNA binding and deaminase activity. These results provide a basis for understanding the underlying mechanisms of substrate specificity for the APOBEC family.
C1 [Holden, Lauren G.; Prochnow, Courtney; Chang, Y. Paul; Bransteitter, Ronda; Chelico, Linda; Sen, Udayaditya; Goodman, Myron F.; Chen, Xiaojiang S.] Univ So Calif, Los Angeles, CA 90089 USA.
   [Stevens, Raymond C.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
C3 University of Southern California; Scripps Research Institute
RP Chen, XJS (corresponding author), Univ So Calif, Los Angeles, CA 90089 USA.
EM xiaojiang.chen@usc.edu
FU CBM; National Institutes of Health
NR 15
TC 189
Z9 271
U1 0
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 NOV 6
PY 2008
VL 456
IS 7218
BP 121
EP U13
DI 10.1038/nature07357
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 369DH
UT WOS:000260674000053
PM 18849968
DA 2026-03-09
ER

PT J
AU Schnell, JR
   Chou, JJ
AF Schnell, Jason R.
   Chou, James J.
TI Structure and mechanism of the M2 proton channel of influenza A virus
SO NATURE
LA English
DT Article
ID ion-channel; membrane-protein; amantadine; localization; couplings; alignment; sequence; reveals; forms; drug
AB The integral membrane protein M2 of influenza virus forms pH-gated proton channels in the viral lipid envelope(1). The low pH of an endosome activates the M2 channel before haemagglutinin-mediated fusion. Conductance of protons acidifies the viral interior and thereby facilitates dissociation of the matrix protein from the viral nucleoproteins - a required process for unpacking of the viral genome(2). In addition to its role in release of viral nucleoproteins, M2 in the trans- Golgi network ( TGN) membrane prevents premature conformational rearrangement of newly synthesized haemagglutinin during transport to the cell surface by equilibrating the pH of the TGN with that of the host cell cytoplasm(3). Inhibiting the proton conductance of M2 using the anti- viral drug amantadine or rimantadine inhibits viral replication(4-7). Here we present the structure of the tetrameric M2 channel in complex with rimantadine, determined by NMR. In the closed state, four tightly packed transmembrane helices define a narrow channel, in which a 'tryptophan gate' is locked by intermolecular interactions with aspartic acid. A carboxy- terminal, amphipathic helix oriented nearly perpendicular to the transmembrane helix forms an inward- facing base. Lowering the pH destabilizes the transmembrane helical packing and unlocks the gate, admitting water to conduct protons, whereas the C- terminal base remains intact, preventing dissociation of the tetramer. Rimantadine binds at four equivalent sites near the gate on the lipid- facing side of the channel and stabilizes the closed conformation of the pore. Drug-resistance mutations are predicted to counter the effect of drug binding by either increasing the hydrophilicity of the pore or weakening helix - helix packing, thus facilitating channel opening.
C1 [Schnell, Jason R.; Chou, James J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Chou, JJ (corresponding author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM james_chou@hms.harvard.edu
FU NIAID NIH HHS [R01 AI067438] Funding Source: Medline
NR 39
TC 938
Z9 1103
U1 3
U2 304
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2008
VL 451
IS 7178
BP 591
EP U12
DI 10.1038/nature06531
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 256OQ
UT WOS:000252739900046
PM 18235503
DA 2026-03-09
ER

PT J
AU Li, ZY
   Young, NP
   Di Vece, M
   Palomba, S
   Palmer, RE
   Bleloch, AL
   Curley, BC
   Johnston, RL
   Jiang, J
   Yuan, J
AF Li, Z. Y.
   Young, N. P.
   Di Vece, M.
   Palomba, S.
   Palmer, R. E.
   Bleloch, A. L.
   Curley, B. C.
   Johnston, R. L.
   Jiang, J.
   Yuan, J.
TI Three-dimensional atomic-scale structure of size-selected gold nanoclusters
SO NATURE
LA English
DT Article
ID oxidation; surfaces; cluster
AB An unambiguous determination of the three-dimensional structure of nanoparticles is challenging(1). Electron tomography requires a series of images taken for many different specimen orientations(2). This approach is ideal for stable and stationary structures(3). But ultrasmall nanoparticles are intrinsically structurally unstable and may interact with the incident electron beam(4-6), constraining the electron beam density that can be used and the duration of the observation. Here we use aberration-corrected scanning transmission electron microscopy(7), coupled with simple imaging simulation, to determine with atomic resolution the size, three- dimensional shape, orientation and atomic arrangement of size- selected gold nanoclusters that are preformed in the gas phase and soft- landed on an amorphous carbon substrate. The structures of gold nanoclusters containing 309 +/- 6 atoms can be identified with either Ino- decahedral, cuboctahedral or icosahedral geometries. Comparison with theoretical modelling of the system suggests that the structures are consistent with energetic considerations. The discovery that nanoscale gold particles function as active and selective catalysts for a variety of important chemical reactions has provoked much research interest in recent years(8-12). We believe that the detailed structure information we provide will help to unravel the role of these nanoclusters in size- and structure-specific catalytic reactions(11,12). We note that the technique will be of use in investigations of other supported ultrasmall metal cluster systems.
C1 [Li, Z. Y.; Young, N. P.; Di Vece, M.; Palomba, S.; Palmer, R. E.] Univ Birmingham, Sch Phys & Astron, Nanoscale Phys Res Lab, Birmingham B15 2TT, W Midlands, England.
   [Curley, B. C.; Johnston, R. L.] Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands, England.
   [Bleloch, A. L.] SERC, Daresbury Lab, UK SuperSTEM Lab, Daresbury WA4 4AD, England.
   [Jiang, J.; Yuan, J.] Tsinghua Univ, Beijing Electron Microscopy Ctr, Beijing 100084, Peoples R China.
   [Jiang, J.; Yuan, J.] Tsinghua Univ, Adv Mat Lab, Beijing 100084, Peoples R China.
   [Jiang, J.; Yuan, J.] Tsinghua Univ, Dept Mat Sci & Engn, Beijing 100084, Peoples R China.
C3 University of Birmingham; University of Birmingham; STFC Daresbury Laboratory; Tsinghua University; Tsinghua University; Tsinghua University
RP Li, ZY (corresponding author), Univ Birmingham, Sch Phys & Astron, Nanoscale Phys Res Lab, Birmingham B15 2TT, W Midlands, England.
EM ziyouli@nprl.ph.bham.ac.uk
FU EPSRC [EP/D049245/1, EP/E005918/1, EP/D056241/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/D056241/1, EP/E005918/1, EP/D049245/1] Funding Source: researchfish
NR 27
TC 377
Z9 400
U1 0
U2 342
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2008
VL 451
IS 7174
BP 46
EP U2
DI 10.1038/nature06470
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247KZ
UT WOS:000252079300029
PM 18066049
DA 2026-03-09
ER

PT J
AU Schreiner, P
   Chen, X
   Husnjak, K
   Randles, L
   Zhang, NX
   Elsasser, S
   Finley, D
   Dikic, I
   Walters, KJ
   Groll, M
AF Schreiner, Patrick
   Chen, Xiang
   Husnjak, Koraljka
   Randles, Leah
   Zhang, Naixia
   Elsasser, Suzanne
   Finley, Daniel
   Dikic, Ivan
   Walters, Kylie J.
   Groll, Michael
TI Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction
SO NATURE
LA English
DT Article
ID deubiquitinating enzyme; structural basis; multiubiquitin chain; protein interactome; eap45-glue domain; recognition; degradation; complex; binding; subunit
AB Targeted protein degradation is largely performed by the ubiquitin-proteasome pathway, in which substrate proteins are marked by covalently attached ubiquitin chains that mediate recognition by the proteasome. It is currently unclear how the proteasome recognizes its substrates, as the only established ubiquitin receptor intrinsic to the proteasome is Rpn10/S5a (ref. 1), which is not essential for ubiquitin- mediated protein degradation in budding yeast(2). In the accompanying manuscript we report that Rpn13 (refs 3-7), a component of the nine-subunit proteasome base, functions as a ubiquitin receptor(8), complementing its known role in docking de-ubiquitinating enzyme Uch37/UCHL5 (refs 4-6) to the proteasome. Here we merge crystallography and NMRdata to describe the ubiquitin-binding mechanism of Rpn13. We determine the structure of Rpn13 alone and complexed with ubiquitin. The co-complex reveals a novel ubiquitin-binding mode in which loops rather than secondary structural elements are used to capture ubiquitin. Further support for the role of Rpn13 as a proteasomal ubiquitin receptor is demonstrated by its ability to bind ubiquitin and proteasome subunit Rpn2/S1 simultaneously. Finally, we provide a model structure of Rpn13 complexed to diubiquitin, which provides insights into how Rpn13 as a ubiquitin receptor is coupled to substrate deubiquitination by Uch37.
C1 [Schreiner, Patrick; Groll, Michael] Tech Univ Munich, Ctr Integrated Prot Sci, Dept Chem, Lehrstuhl Biochem, D-85747 Garching, Germany.
   [Chen, Xiang; Randles, Leah; Zhang, Naixia; Walters, Kylie J.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
   [Husnjak, Koraljka; Dikic, Ivan] Univ Frankfurt, Inst Biochem 2, D-60590 Frankfurt, Germany.
   [Husnjak, Koraljka; Dikic, Ivan] Mediterranean Inst Life Sci, Tumor Biol Program, Split 21000, Croatia.
   [Elsasser, Suzanne; Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Dikic, Ivan] Univ Split, Sch Med, Dept Immunol, Split 21000, Croatia.
   [Groll, Michael] Charite Univ Med Berlin CCM, Inst Biochem, D-10117 Berlin, Germany.
C3 Technical University of Munich; University of Minnesota System; University of Minnesota Twin Cities; Goethe University Frankfurt; University of Split; Harvard University; Harvard Medical School; University of Split; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
RP Groll, M (corresponding author), Tech Univ Munich, Ctr Integrated Prot Sci, Dept Chem, Lehrstuhl Biochem, Lichtenbergstr 4, D-85747 Garching, Germany.
EM ivan.dikic@biochem2.de; walte048@umn.edu; michael.groll@ch.tum.de
FU NCI NIH HHS [R01 CA097004, CA097004] Funding Source: Medline; NIGMS NIH HHS [GM008700, T32 GM008700, R01 GM043601, R37 GM043601, GM43601] Funding Source: Medline
NR 28
TC 273
Z9 361
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 22
PY 2008
VL 453
IS 7194
BP 548
EP 552
DI 10.1038/nature06924
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303EL
UT WOS:000256023700048
PM 18497827
DA 2026-03-09
ER

PT J
AU La Scola, B
   Desnues, C
   Pagnier, I
   Robert, C
   Barrassi, L
   Fournous, G
   Merchat, M
   Suzan-Monti, M
   Forterre, P
   Koonin, E
   Raoult, D
AF La Scola, Bernard
   Desnues, Christelle
   Pagnier, Isabelle
   Robert, Catherine
   Barrassi, Lina
   Fournous, Ghislain
   Merchat, Michele
   Suzan-Monti, Marie
   Forterre, Patrick
   Koonin, Eugene
   Raoult, Didier
TI The virophage as a unique parasite of the giant mimivirus
SO NATURE
LA English
DT Article
ID multiple sequence alignment; ocean sampling expedition; bacterial; virus
AB Viruses are obligate parasites of Eukarya, Archaea and Bacteria. Acanthamoeba polyphaga mimivirus ( APMV) is the largest known virus; it grows only in amoeba and is visible under the optical microscope. Mimivirus possesses a 1,185- kilobase double- stranded linear chromosome whose coding capacity is greater than that of numerous bacteria and archaea(1-3). Here we describe an icosahedral small virus, Sputnik, 50 nm in size, found associated with a new strain of APMV. Sputnik cannot multiply in Acanthamoeba castellanii but grows rapidly, after an eclipse phase, in the giant virus factory found in amoebae co- infected with APMV(4). Sputnik growth is deleterious to APMV and results in the production of abortive forms and abnormal capsid assembly of the host virus. The Sputnik genome is an 18.343- kilobase circular double- stranded DNA and contains genes that are linked to viruses infecting each of the three domains of life Eukarya, Archaea and Bacteria. Of the 21 predicted protein- coding genes, eight encode proteins with detectable homologues, including three proteins apparently derived from APMV, a homologue of an archaeal virus integrase, a predicted primase helicase, a packaging ATPase with homologues in bacteriophages and eukaryotic viruses, a distant homologue of bacterial insertion sequence transposase DNA- binding subunit, and a Zn- ribbon protein. The closest homologues of the last four of these proteins were detected in the Global Ocean Survey environmental data set(5), suggesting that Sputnik represents a currently unknown family of viruses. Considering its functional analogy with bacteriophages, we classify this virus as a virophage. The virophage could be a vehicle mediating lateral gene transfer between giant viruses.
C1 [La Scola, Bernard; Desnues, Christelle; Pagnier, Isabelle; Robert, Catherine; Barrassi, Lina; Fournous, Ghislain; Suzan-Monti, Marie; Raoult, Didier] Univ Mediterranee, URMITE, Ctr Natl Rech Sci, Fac Med,UMR IRD 6236, F-13385 Marseille 5, France.
   [Merchat, Michele] Climespace, F-75012 Paris, France.
   [Forterre, Patrick] Univ Paris 11, Ctr Orsay, Inst Microbiol & Genet, F-91405 Orsay, France.
   [Forterre, Patrick] Inst Pasteur, Dept Microbiol, F-75724 Paris 15, France.
   [Koonin, Eugene] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
C3 Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Engie; Universite Paris Saclay; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM)
RP Raoult, D (corresponding author), Univ Mediterranee, URMITE, Ctr Natl Rech Sci, Fac Med,UMR IRD 6236, 27 Blvd Jean Moulin, F-13385 Marseille 5, France.
EM didier.raoult@gmail.com
FU Centre National de la Recherche Scientifique; CIFFRE fellowship; Intramural Research Program of the National Institutes of Health; National Library of Medicine; Institut Universitaire de France
NR 27
TC 428
Z9 514
U1 1
U2 179
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 4
PY 2008
VL 455
IS 7209
BP 100
EP U65
DI 10.1038/nature07218
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343XS
UT WOS:000258890200045
PM 18690211
DA 2026-03-09
ER

PT J
AU Krishnan, V
   Nestler, EJ
AF Krishnan, Vaishnav
   Nestler, Eric J.
TI The molecular neurobiology of depression
SO NATURE
LA English
DT Article
ID adult hippocampal neurogenesis; neurotrophic factor val66met; deep brain-stimulation; major depression; mood disorders; psychiatric-disorders; essential mediator; nucleus-accumbens; rat hippocampus; knockout mice
C1 [Krishnan, Vaishnav; Nestler, Eric J.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
   [Krishnan, Vaishnav; Nestler, Eric J.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
   [Nestler, Eric J.] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY 10029 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Icahn School of Medicine at Mount Sinai
RP Nestler, EJ (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
EM eric.nestler@mssm.edu
FU National Institute of Mental Health; National Institute of Mental Health [R01MH051399] Funding Source: NIH RePORTER
NR 99
TC 2265
Z9 2721
U1 7
U2 752
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 894
EP 902
DI 10.1038/nature07455
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300037
PM 18923511
DA 2026-03-09
ER

PT J
AU Malcolmson, SJ
   Meek, SJ
   Sattely, ES
   Schrock, RR
   Hoveyda, AH
AF Malcolmson, Steven J.
   Meek, Simon J.
   Sattely, Elizabeth S.
   Schrock, Richard R.
   Hoveyda, Amir H.
TI Highly efficient molybdenum-based catalysts for enantioselective alkene metathesis
SO NATURE
LA English
DT Article
ID ring-closing metathesis; imido alkylidene complexes; olefin-metathesis; metal-complexes; tungsten; amines; ethers; ligand
AB Discovery of efficient catalysts is one of the most compelling objectives of modern chemistry. Chiral catalysts are in particularly high demand, as they facilitate synthesis of enantiomerically enriched small molecules that are critical to developments in medicine, biology and materials science(1). Especially noteworthy are catalysts that promote - with otherwise inaccessible efficiency and selectivity levels - reactions demonstrated to be of great utility in chemical synthesis. Here we report a class of chiral catalysts that initiate alkene metathesis(1) with very high efficiency and enantioselectivity. Such attributes arise from structural fluxionality of the chiral catalysts and the central role that enhanced electronic factors have in the catalytic cycle. The new catalysts have a stereogenic metal centre and carry only monodentate ligands; the molybdenum- based complexes are prepared stereoselectively by a ligand exchange process involving an enantiomerically pure aryloxide, a class of ligands scarcely used in enantioselective catalysis(2,3). We demonstrate the application of the new catalysts in an enantioselective synthesis of the Aspidosperma alkaloid, quebrachamine, through an alkene metathesis reaction that cannot be promoted by any of the previously reported chiral catalysts.
C1 [Malcolmson, Steven J.; Meek, Simon J.; Sattely, Elizabeth S.; Hoveyda, Amir H.] Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
   [Schrock, Richard R.] MIT, Dept Chem, Cambridge, MA 02139 USA.
C3 Boston College; Massachusetts Institute of Technology (MIT)
RP Hoveyda, AH (corresponding author), Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
EM amir.hoveyda@bc.edu
FU US National Institutes of Health; Institute of General Medical Sciences [GM-59426]; US National Science Foundation [DBI-0619576]
NR 29
TC 231
Z9 276
U1 2
U2 139
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2008
VL 456
IS 7224
BP 933
EP 937
DI 10.1038/nature07594
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 384TY
UT WOS:000261768300041
PM 19011612
DA 2026-03-09
ER

PT J
AU Halberda, J
   Mazzocco, MMM
   Feigenson, L
AF Halberda, Justin
   Mazzocco, Michele M. M.
   Feigenson, Lisa
TI Individual differences in non-verbal number acuity correlate with maths achievement
SO NATURE
LA English
DT Article
ID children; skills; representations
AB Human mathematical competence emerges from two representational systems. Competence in some domains of mathematics, such as calculus, relies on symbolic representations that are unique to humans who have undergone explicit teaching(1,2). More basic numerical intuitions are supported by an evolutionarily ancient approximate number system that is shared by adults(3-6), infants(7) and non- human animals(8-13) - these groups can all represent the approximate number of items in visual or auditory arrays without verbally counting, and use this capacity to guide everyday behaviour such as foraging. Despite the widespread nature of the approximate number system both across species and across development, it is not known whether some individuals have a more precise non- verbal 'number sense' than others. Furthermore, the extent to which this system interfaces with the formal, symbolic maths abilities that humans acquire by explicit instruction remains unknown. Here we show that there are large individual differences in the non- verbal approximation abilities of 14- year- old children, and that these individual differences in the present correlate with children's past scores on standardized maths achievement tests, extending all the way back to kindergarten. Moreover, this correlation remains significant when controlling for individual differences in other cognitive and performance factors. Our results show that individual differences in achievement in school mathematics are related to individual differences in the acuity of an evolutionarily ancient, unlearned approximate number sense. Further research will determine whether early differences in number sense acuity affect later maths learning, whether maths education enhances number sense acuity, and the extent to which tertiary factors can affect both.
C1 [Halberda, Justin; Mazzocco, Michele M. M.; Feigenson, Lisa] Johns Hopkins Univ, Baltimore, MD 21218 USA.
   [Mazzocco, Michele M. M.] Kennedy Krieger Inst, Baltimore, MD 21211 USA.
C3 Johns Hopkins University; Kennedy Krieger Institute
RP Halberda, J (corresponding author), Johns Hopkins Univ, Ames Hall,3400 N Charles St, Baltimore, MD 21218 USA.
EM halberda@jhu.edu
FU National Institutes of Health [RO1 HD 034061]
NR 27
TC 1104
Z9 1289
U1 6
U2 293
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 665
EP U62
DI 10.1038/nature07246
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700047
PM 18776888
DA 2026-03-09
ER

PT J
AU Soroceanu, L
   Akhavan, A
   Cobbs, CS
AF Soroceanu, Liliana
   Akhavan, Armin
   Cobbs, Charles S.
TI Platelet-derived growth factor-α receptor activation is required for human cytomegalovirus infection
SO NATURE
LA English
DT Article
ID nf-kappa-b; glycoprotein-b; soluble form; neutralizing antibody; signal-transduction; cellular receptor; viral replication; permissive cells; up-regulation; entry
AB Human cytomegalovirus ( HCMV) is a ubiquitous human herpesvirus that can cause life- threatening disease in the fetus and the immunocompromised host(1). Upon attachment to the cell, the virus induces robust inflammatory, interferon- and growth- factor-like signalling(2-9). The mechanisms facilitating viral entry and gene expression are not clearly understood(4). Here we show that platelet- derived growth factor-alpha receptor (PDGFR-alpha) is specifically phosphorylated by both laboratory and clinical isolates of HCMV in various human cell types, resulting in activation of the phosphoinositide-3-kinase (PI(3)K) signalling pathway. Upon stimulation by HCMV, tyrosine- phosphorylated PDGFR-alpha associated with the p85 regulatory subunit of PI( 3) K and induced protein kinase B ( also known as Akt) phosphorylation, similar to the genuine ligand, PDGF-AA. Cells in which PDGFR-alpha was genetically deleted(10) or functionally blocked were non- permissive to HCMV entry, viral gene expression or infectious virus production. Re- introducing human PDGFRA gene into knockout cells restored susceptibility to viral entry and essential viral gene expression. Blockade of receptor function with a humanized PDGFR-alpha blocking antibody (IMC-3G3)(11) or targeted inhibition of its kinase activity with a small molecule (Gleevec)(12) completely inhibited HCMV viral internalization and gene expression in human epithelial, endothelial and fibroblast cells. Viral entry in cells harbouring endogenous PDGFR-alpha was competitively inhibited by pretreatment with PDGF-AA. We further demonstrate that HCMV glycoprotein B directly interacts with PDGFR-alpha, resulting in receptor tyrosine phosphorylation, and that glycoprotein B neutralizing antibodies(13) inhibit HCMV- induced PDGFR-alpha phosphorylation. Taken together, these data indicate that PDGFR-alpha is a critical receptor required for HCMV infection, and thus a target for novel anti- viral therapies.
C1 [Soroceanu, Liliana; Akhavan, Armin; Cobbs, Charles S.] Calif Pacific Med Ctr, Res Inst, Dept Neurosci, San Francisco, CA 94107 USA.
   [Cobbs, Charles S.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
C3 California Pacific Medical Center; California Pacific Medical Center Research Institute; University of California System; University of California San Francisco
RP Cobbs, CS (corresponding author), Calif Pacific Med Ctr, Res Inst, Dept Neurosci, Suite 220,475 Brannan St, San Francisco, CA 94107 USA.
EM charles.cobbs@gmail.com
FU California Pacific Medical Center Research Institute; Arthur Flaming Foundation
NR 36
TC 251
Z9 338
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 18
PY 2008
VL 455
IS 7211
BP 391
EP U43
DI 10.1038/nature07209
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 349EX
UT WOS:000259265200045
PM 18701889
DA 2026-03-09
ER

PT J
AU Fouchet, T
   Guerlet, S
   Strobel, DF
   Simon-Miller, AA
   Bézard, B
   Flasar, FM
AF Fouchet, T.
   Guerlet, S.
   Strobel, D. F.
   Simon-Miller, A. A.
   Bezard, B.
   Flasar, F. M.
TI An equatorial oscillation in Saturn's middle atmosphere
SO NATURE
LA English
DT Article
ID quasi-biennial oscillation; jupiters stratosphere; model; temperatures; troposphere; planets; system; winds; time
AB The middle atmospheres of planets are driven by a combination of radiative heating and cooling, mean meridional motions, and vertically propagating waves ( which originate in the deep troposphere). It is very difficult to model these effects and, therefore, observations are essential to advancing our understanding of atmospheres. The equatorial stratospheres of Earth and Jupiter oscillate quasi- periodically on timescales of about two and four years, respectively, driven by wave- induced momentum transport(1-5). On Venus and Titan, waves originating from surface atmosphere interaction and inertial instability are thought to drive the atmosphere to rotate more rapidly than the surface ( superrotation). However, the relevant wave modes have not yet been precisely identified. Here we report infrared observations showing that Saturn has an equatorial oscillation like those found on Earth and Jupiter, as well as a mid- latitude subsidence that may be associated with the equatorial motion. The latitudinal extent of Saturn's oscillation shows that it obeys the same basic physics as do those on Earth and Jupiter. Future highly resolved observations of the temperature profile together with modelling of these three different atmospheres will allow us determine the wave mode, the wavelength and the wave amplitude that lead to middle atmosphere oscillation.
C1 [Fouchet, T.; Guerlet, S.; Bezard, B.] Univ Paris 06, Observ Paris, CNRS, LESIA, F-92195 Meudon, France.
   [Strobel, D. F.] Johns Hopkins Univ, Dept Earth & Planetary Sci, Baltimore, MD 21218 USA.
   [Strobel, D. F.] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Simon-Miller, A. A.; Flasar, F. M.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
C3 Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Johns Hopkins University; Johns Hopkins University; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Fouchet, T (corresponding author), Univ Paris 06, Observ Paris, CNRS, LESIA, F-92195 Meudon, France.
EM thierry.fouchet@obspm.fr
NR 23
TC 90
Z9 93
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 MAY 8
PY 2008
VL 453
IS 7192
BP 200
EP 202
DI 10.1038/nature06912
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BP
UT WOS:000255592400034
PM 18464737
DA 2026-03-09
ER

PT J
AU Obayashi, E
   Yoshida, H
   Kawai, F
   Shibayama, N
   Kawaguchi, A
   Nagata, K
   Tame, JRH
   Park, SY
AF Obayashi, Eiji
   Yoshida, Hisashi
   Kawai, Fumihiro
   Shibayama, Naoya
   Kawaguchi, Atsushi
   Nagata, Kyosuke
   Tame, Jeremy R. H.
   Park, Sam-Yong
TI The structural basis for an essential subunit interaction in influenza virus RNA polymerase
SO NATURE
LA English
DT Article
ID amino-acid mutation; a virus; pa subunit; cap-binding; protein; replication; complex; design; transcription; inhibitors
AB Influenza A virus is a major human and animal pathogen with the potential to cause catastrophic loss of life. The virus reproduces rapidly, mutates frequently and occasionally crosses species barriers. The recent emergence in Asia of avian influenza related to highly pathogenic forms of the human virus has highlighted the urgent need for new effective treatments(1). Here we demonstrate the importance to viral replication of a subunit interface in the viral RNA polymerase, thereby providing a new set of potential drug binding sites entirely independent of surface antigen type. No current medication targets this heterotrimeric polymerase complex. All three subunits, PB1, PB2 and PA, are required for both transcription and replication(2-4). PB1 carries the polymerase active site, PB2 includes the capped- RNA recognition domain, and PA is involved in assembly of the functional complex(5-7), but so far very little structural information has been reported for any of them(8-11). We describe the crystal structure of a large fragment of one subunit ( PA) of influenza A RNA polymerase bound to a fragment of another subunit ( PB1). The carboxy- terminal domain of PA forms a novel fold, and forms a deep, highly hydrophobic groove into which the amino- terminal residues of PB1 can fit by forming a 3(10) helix.
C1 [Obayashi, Eiji; Yoshida, Hisashi; Kawai, Fumihiro; Tame, Jeremy R. H.; Park, Sam-Yong] Yokohama City Univ, Prot Design Lab, Yokohama, Kanagawa 2300045, Japan.
   [Shibayama, Naoya] Jichi Med Univ, Dept Physiol, Div Biophys, Shimotsuke, Tochigi 3290498, Japan.
   [Kawaguchi, Atsushi; Nagata, Kyosuke] Univ Tsukuba, Dept Infect Biol, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan.
   [Kawaguchi, Atsushi; Nagata, Kyosuke] Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 3058575, Japan.
C3 Yokohama City University; Jichi Medical University; University of Tsukuba; University of Tsukuba
RP Park, SY (corresponding author), Yokohama City Univ, Prot Design Lab, 1-7-29 Suehiro, Yokohama, Kanagawa 2300045, Japan.
EM park@tsurumi.yokohama-cu.ac.jp
FU ISS applied research partnership program
NR 42
TC 237
Z9 278
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 28
PY 2008
VL 454
IS 7208
BP 1127
EP U57
DI 10.1038/nature07225
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341MW
UT WOS:000258719600040
PM 18660801
DA 2026-03-09
ER

PT J
AU Mikhael, J
   Roth, J
   Helden, L
   Bechinger, C
AF Mikhael, Jules
   Roth, Johannes
   Helden, Laurent
   Bechinger, Clemens
TI Archimedean-like tiling on decagonal quasicrystalline surfaces
SO NATURE
LA English
DT Article
ID phase; fields
AB Monolayers on crystalline surfaces often form complex structures with physical and chemical properties that differ strongly from those of their bulk phases(1). Such hetero-epitactic overlayers are currently used in nanotechnology and understanding their growth mechanism is important for the development of new materials and devices. In comparison with crystals, quasicrystalline surfaces exhibit much larger structural and chemical complexity leading, for example, to unusual frictional(2), catalytical(3) or optical properties(4,5). Deposition of thin films on such substrates can lead to structures that may have typical quasicrystalline properties. Recent experiments have indeed showed 5-fold symmetries in the diffraction pattern of metallic layers adsorbed on quasicrystals(6,7). Here we report a real-space investigation of the phase behaviour of a colloidal monolayer interacting with a quasicrystalline decagonal substrate created by interfering five laser beams. We find a pseudomorphic phase that shows both crystalline and quasicrystalline structural properties. It can be described by an archimedean-like tiling(8,9) consisting of alternating rows of square and triangular tiles. The calculated diffraction pattern of this phase is in agreement with recent observations of copper adsorbed on icosahedral Al(70)Pd(21)Mn(9) surfaces(10). In addition to establishing a link between archimedean tilings and quasicrystals, our experiments allow us to investigate in real space how single-element monolayers can form commensurate structures on quasicrystalline surfaces.
C1 [Mikhael, Jules; Helden, Laurent; Bechinger, Clemens] Univ Stuttgart, Inst Phys 2, D-70569 Stuttgart, Germany.
   [Roth, Johannes] Univ Stuttgart, Inst Theoret & Angew Phys, D-70569 Stuttgart, Germany.
   [Bechinger, Clemens] Max Planck Inst Met Res, D-70569 Stuttgart, Germany.
C3 University of Stuttgart; University of Stuttgart; Max Planck Society
RP Bechinger, C (corresponding author), Univ Stuttgart, Inst Phys 2, Pfaffenwaldring 57, D-70569 Stuttgart, Germany.
EM c.bechinger@physik.uni-stuttgart.de
NR 29
TC 201
Z9 223
U1 1
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 24
PY 2008
VL 454
IS 7203
BP 501
EP 504
DI 10.1038/nature07074
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 329IC
UT WOS:000257860300047
PM 18650921
DA 2026-03-09
ER

PT J
AU Vandermeer, J
   Perfecto, I
   Philpott, SM
AF Vandermeer, John
   Perfecto, Ivette
   Philpott, Stacy M.
TI Clusters of ant colonies and robust criticality in a tropical agroecosystem
SO NATURE
LA English
DT Article
ID self-organization; pattern; scale; mutualism; prey
AB Although sometimes difficult to measure at large scales, spatial pattern is important in natural biological spaces as a determinant of key ecological properties such as species diversity, stability, resiliency and others(1-6). Here we demonstrate, at a large spatial scale, that a common species of tropical arboreal ant forms clusters of nests through a combination of local satellite colony formation and density- dependent control by natural enemies, mainly a parasitic fly. Cluster sizes fall off as a power law consistent with a so-called robust critical state(7). This endogenous cluster formation at a critical state is a unique example of an insect population forming a non- random pattern at a large spatial scale. Furthermore, because the species is a keystone of a larger network that contributes to the ecosystem function of pest control, this is an example of how spatial dynamics at a large scale can affect ecosystem service at a local level.
C1 [Vandermeer, John] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
   [Vandermeer, John; Perfecto, Ivette] Univ Michigan, Sch Nat Resources & Environm, Ann Arbor, MI 48109 USA.
   [Philpott, Stacy M.] Univ Toledo, Dept Environm Sci, Toledo, OH 43606 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University System of Ohio; University of Toledo
RP Vandermeer, J (corresponding author), Univ Michigan, Dept Ecol & Evolutionary Biol, Kraus Nat Sci Bldg, Ann Arbor, MI 48109 USA.
EM jvander@umich.edu
NR 20
TC 102
Z9 116
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 24
PY 2008
VL 451
IS 7177
BP 457
EP U3
DI 10.1038/nature06477
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 253YS
UT WOS:000252554100043
PM 18216853
DA 2026-03-09
ER

