Change search
Refine search result
3456789 251 - 300 of 453
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 251.
    Makarova, Tatiana L
    et al.
    Umeå University, Faculty of Science and Technology, Physics.
    Sundqvist, Bertil
    Umeå University, Faculty of Science and Technology, Physics.
    Höhne, Roland
    Esquinazi, Pablo
    Kopelevich, Yakov
    Scharff, Peter
    Davydov, Valerii A.
    Kashevarova, Ludmila S.
    Rakhmaninova, Aleksandra V.
    Magnetic Carbon2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 413, no 6857, 716-718 p.Article in journal (Refereed)
    Abstract [en]

    Paper retracted.

  • 252. Malavelle, Florent F.
    et al.
    Haywood, Jim M.
    Ones, Andy J.
    Gettelman, Andrew
    Larisse, Lieven C.
    Bauduin, Sophie
    Allan, Richard P.
    Karset, Inger Helene H.
    Kristjansson, Jon Egill
    Oreopoulos, Lazaros
    Ho, Nayeong C.
    Lee, Dongmin
    Bellouin, Nicolas
    Boucher, Olivier
    Grosvenor, Daniel P.
    Arslaw, Ken S. C.
    Dhomse, Sandip
    Mann, Graham W.
    Schmidt, Anja
    Coe, Hugh
    Hartley, Margaret E.
    Dalvi, Mohit
    Hill, Adrian A.
    Johnson, Ben T.
    Johnson, Colin E.
    Knight, Jeff R.
    O'Connor, Fiona M.
    Partridge, Daniel G.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. University of Oxford, UK.
    Stier, Philip
    Myhre, Gunnar
    Platnick, Steven
    Stephens, Graeme L.
    Takahashi, Hanii
    Thordarson, Thorvaldur
    Strong constraints on aerosol-cloud interactions from volcanic eruptions2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 546, no 7659, 485-491 p.Article in journal (Refereed)
    Abstract [en]

    Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response.

  • 253.
    Marcaide, J. M.
    et al.
    Departamento de Astronomía, Universitat de València, Valencia, Spain & Harvard-Smithsonian Ctr. Astrophys., Cambridge, United States .
    Alberdi, A.
    Inst. de Astrofis. de Andalucia, Spain.
    Ros, E.
    Departamento de Astronomía, Universitat de València, Valencia, Spain.
    Diamond, P.
    National Radio Astronomy Observatory, Socorro, United States.
    Schmidt, B.
    Harvard-Smithsonian Ctr. Astrophys., Cambridge, United States.
    Shapiro, I.I.
    Harvard-Smithsonian Ctr. Astrophys., Cambridge, United States.
    Bååth, L.B.
    Onsala Space Observatory, Onsala, Sweden.
    Davis, R. J.
    Nuffield Radio Astron. Laboratories, Macclesfield, Cheshire, United Kingdom.
    Debruyn, A. G.
    Netherlands Found. Res. in Astron., Dwingeloo, Netherlands.
    Elosegui, P.
    Harvard-Smithsonian Ctr. Astrophys., Cambridge, United States.
    Guirado, J. C.
    Inst. de Astrofis. de Andalucia, CSIC, Granada, Spain.
    Jones, D. L.
    Jet Propulsion Laboratory, California Institute of Technology, Pasadena, United States.
    Krichbaum, T. P.
    Max-Planck-Inst. F. Radioastronomie, Bonn, Germany.
    Mantovani, F.
    Istituto di Radioastronomia, CNR, Bologna, Italy.
    Preston, R. A.
    Jet Propulsion Laboratory, California Institute of Technology, Pasadena, United States.
    Ratner, M. I.
    Harvard-Smithsonian Ctr. Astrophys., Cambridge, United States.
    Rius, A.
    Inst. de Astronomia y Geodesia, Fac. de Ciencias Matemáticas, Madrid, Spain.
    Rogers, A. E. E.
    MIT-Haystack Observatory, Westford, United States.
    Schilizzi, R. T.
    Joint Institute for VLBI in Europe, Dwingaloo, Netherlands.
    Trigilio, C.
    Istituto di Radioastronomia, CNR, Noto, Italy.
    Whitney, A. R.
    MIT-Haystack Observatory, Westford, United States.
    Witzel, A.
    Max-Planck-Inst. F. Radioastronomie, Bonn, Germany.
    Zensus, A.
    National Radio Astronomy Observatory, Socorro, United States.
    Discovery of shell-like radio-structure in SN1993J1995In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 373, no 6509, 44-45 p.Article in journal (Refereed)
    Abstract [en]

    SUPERNOVA explosions are poorly understood, partly because of difficulties in modelling them theoretically(1), and partly because there have been no supernovae observed in our Galaxy since the invention of the telescope. But the recent discovery(2) of supernova SN1993J in the nearby galaxy M81 offers an opportunity to investigate the evolution of the remnant, and its interaction with the surrounding interstellar medium, at high resolution. Here we present radio observations of SN1993J, made using very-long-baseline interferometry, which show the development of a shell structure. This 8-month-old radio shell is the youngest ever discovered in a supernova. The data suggest that the supernova explosion and the expanding shell of the remnant have nearly spherical symmetry, with small deviations where some parts of the shell are brighter than others. If these deviations arise because of variations in the density of the shell, this may reconcile earlier reports of symmetric radio emission(3) with the observed optical asymmetry(4,5), as the density variations could easily cause the latter. We infer that the radio emission is generated at the interface(6-9), where the surrounding gas is shocked by the ejecta.

  • 254.
    Marcuse, Reinhard
    SIK – Svenska institutet för konserveringsforskning.
    Antioxidative effect of amino-acids1960In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 186, no 4728, 886-887 p.Article in journal (Refereed)
    Abstract [en]

    AMINO-ACIDS are often mentioned as synergisbic antioxidants. Their mechanism of enhancing the effect, of primary antioxidants can be explained in different ways: by chelation of pro-oxidative metal traces1 and by regeneration of oxidized primary antioxidants2-4. It has also been shown that amino-acids may play the part of synergistic antioxidants as natural constituents of food material5. On the other hand, there is a lack of systematic survey on a more general basis of this effect of amino-acids. Certain results have been published, which, however, refer to special conditions6,7. No data are available on the effect of amino-acids in absence of other anti-oxidative substances. © 1960 Nature Publishing Group.

  • 255.
    Marklund, Göran T.
    et al.
    KTH, Superseded Departments, Alfvén Laboratory.
    Ivchenko, Nickolay V.
    KTH, Superseded Departments, Alfvén Laboratory.
    Karlsson, Tomas
    KTH, Superseded Departments, Alfvén Laboratory.
    Fazakerley, A.
    Dunlop, M.
    Lindqvist, Per-Arne
    KTH, Superseded Departments, Alfvén Laboratory.
    Buchert, S.
    Owen, C.
    Taylor, M.
    Vaivalds, A.
    Carter, P.
    Andre, M.
    Balogh, A.
    Temporal evolution of the electric field accelerating electrons away from the auroral ionosphere2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 414, no 6865, 724-727 p.Article in journal (Refereed)
    Abstract [en]

    The bright night-time aurorae that are visible to the unaided eye are caused by electrons accelerated towards Earth by an upward-pointing electric field(1-3). On adjacent geomagnetic field lines the reverse process occurs: a downward-pointing electric field accelerates electrons away from Earth(4-11). Such magnetic-field-aligned electric fields in the collisionless plasma above the auroral ionosphere have been predicted(12), but how they could be maintained is still a matter for debate(13). The spatial and temporal behaviour of the electric fields-a knowledge of which is crucial to an understanding of their nature-cannot be resolved uniquely by single satellite measurements. Here we report on the first observations by a formation of identically instrumented satellites crossing a beam of upward-accelerated electrons. The structure of the electric potential accelerating the beam grew in magnitude and width for about 200 s, accompanied by a widening of the downward-current sheet, with the total current remaining constant. The 200-s timescale suggests that the evacuation of the electrons from the ionosphere contributes to the formation of the downward-pointing magnetic-field-aligned electric fields. This evolution implies a growing load in the downward leg of the current circuit, which may affect the visible discrete aurorae.

  • 256.
    Marouli, Eirini
    et al.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Graff, Mariaelisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Medina-Gomez, Carolina
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Lo, Ken Sin
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Kjaer, Troels R.
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    Fine, Rebecca S.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Lu, Yingchang
    Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.;Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Univ Texas Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Rueger, Sina
    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Lamparter, David
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Univ Cambridge, Dept Hematol, Cambridge CB2 0PT, England..
    Turcot, Valerie
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Young, Kristin L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany..
    Esko, Tonu
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63108 USA..
    Masca, Nicholas G. D.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA..
    Mudgal, Poorva
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA..
    Rivas, Manuel A.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Nuffield Dept Clin Med, Oxford OX3 7BN, England..
    Vedantam, Sailaja
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Aben, Katja K.
    Netherland Comprehens Canc Org, NL-3501 DB Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Adair, Linda S.
    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA..
    Alam, Dewan S.
    Ctr Control Chron Dis, Dhaka 1212, Bangladesh..
    Albrecht, Eva
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Allin, Kristine H.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA..
    Amouyel, Philippe
    INSERM, U1167, F-59019 Lille, France.;Inst Pasteur, U1167, F-59019 Lille, France.;Univ Lille, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, F-59019 Lille, France..
    Appel, Emil V.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Arveiler, Dominique
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, F-67085 Strasbourg, France.;Univ Hosp Strasbourg, Dept Publ Hlth, F-67081 Strasbourg, France..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.;ICIN Netherland Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England..
    Auer, Paul L.
    Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA..
    Balkau, Beverley
    INSERM, Ctr Rech Epidemiol & Sante Populat CESP, U1018, Villejuif, France..
    Banas, Bernhard
    Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany..
    Bang, Lia E.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, DK-2100 Copenhagen, Denmark..
    Benn, Marianne
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Bergmann, Sven
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Blueher, Matthias
    Univ Leipzig, Dept Med, D-04103 Leipzig, Germany..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, D-14558 Nuthetal, Germany..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27157 USA..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, DK-7100 Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, DK-5000 Odense, Denmark..
    Breen, Gerome
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.;NIHR Biomed Res Ctr Mental Hlth Maudsley, London SE5 8AF, England..
    Brilliant, Murray H.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Broer, Linda
    Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Burt, Amber A.
    Univ Washington, Dept Med, Seattle, WA 98195 USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England..
    Carey, David J.
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA..
    Caulfield, Mark J.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Chambers, John C.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England..
    Chasman, Daniel I.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA..
    Chen, Yii-Der Ida
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    Christensen, Cramer
    Lillebaelt Hosp, Dept Med, DK-7100 Vejle, Denmark..
    Chu, Audrey Y.
    Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;NHLBI, Framingham Heart Study, Framingham, MA 01702 USA..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
    Collins, Francis S.
    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Corley, Janie
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Galbany, Jordi Corominas
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands..
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld, Australia..
    Cuellar-Partida, Gabriel
    Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia.;QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.;Univ Cambridge, Dept Med, Cambridge Escellence, British Heart Fdn, Cambridge CB2 0QQ, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, NL-3584 CX Utrecht, Netherlands..
    de Borst, Gert J.
    Univ Med Ctr Utrecht, Dept Vasc Surg, Div Surg Specialties, NL-3584 CX Utrecht, Netherlands..
    de Denus, Simon
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    de Groot, Mark C. H.
    Univ Med Ctr Utrecht, Div Lab & Pharm, Dept Clin Chem & Haematol, NL-3508 GA Utrecht, Netherlands.;Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
    den Hollander, Anneke I.
    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
    Dennis, Joe G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, London WC1E 6JF, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Du, Mengmeng
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA..
    Dunning, Alison M.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Easton, Douglas F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Ebeling, Tapani
    Oulu Univ Hosp, Dept Med, Oulu 90029, Finland.;Univ Oulu, Res Unit Internal Med, FI-90014 Oulu, Finland..
    Edwards, Todd L.
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA..
    Ellinor, Patrick T.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Evangelou, Evangelos
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Feng, Shuang
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Ferrannini, Ele
    CNR Inst Clin Physiol, Pisa, Italy.;Univ Pisa, Dept Clin & Expt Med, Pisa, Italy..
    Ferrario, Marco M.
    Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, I-21100 Varese, Italy..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, F-31059 Toulouse, France..
    Florez, Jose C.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA..
    Ford, Ian
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Med Unit, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Frikke-Schmidt, Ruth
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Gan, Wei
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Gandin, Ilaria
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy..
    Gasparini, Paolo
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Giri, Ayush
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA..
    Girotto, Giorgia
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Gordon, Scott D.
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Gordon-Larsen, Penny
    Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA..
    Gorski, Mathias
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany.;Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Gudnason, Vilmundur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;Icelandic Heart Assoc, IS-201 Kopavogur, Iceland..
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Hansen, Torben
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Harris, Kathleen Mullan
    Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Sociol, Chapel Hill, NC 27514 USA..
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Hattersley, Andrew T.
    Univ Exeter, Univ Exeter Med Sch, Exeter EX2 5DW, Devon, England..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    He, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC 27708 USA.;Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland..
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Heikkila, Kauko
    Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Helgeland, Oyvind
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway..
    Hernesniemi, Jussi
    Tampere Univ Hosp, Dept Cardiol, Ctr Heart, FI-33521 Tampere, Finland.;Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Hewitt, Alex W.
    Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA 6009, Australia.;Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas 7000, Australia..
    Hocking, Lynne J.
    Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh EH4 2XU, Midlothian, Scotland.;Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen AB25 2ZD, Scotland..
    Hollensted, Mette
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7600 Trondheim, Norway..
    Hovingh, G. Kees
    AMC, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    Hoyng, Carel B.
    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
    Huang, Paul L.
    Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway..
    Ikram, M. Arfan
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Neurol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Radiol, NL-3015 GE Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.;Res Unit Skelleftea, SE-93141 Skelleftea, Sweden..
    Jarvik, Gail P.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Univ Washington, Dept Genom Sci, Seattle, WA 98195 USA..
    Jensen, Gorm B.
    Frederiksberg Univ Hosp, Copenhagen City Heart Study, DK-2000 Frederiksberg, Denmark..
    Jhun, Min A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Jia, Yucheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Jiang, Xuejuan
    Univ Calif Los Angeles, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.;Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA..
    Johansson, Stefan
    Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway..
    Jorgensen, Marit E.
    Univ Southern Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark.;Steno Diabet Ctr, DK-2820 Gentofte, Denmark..
    Jorgensen, Torben
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Aalborg Hosp, DK-9000 Aalborg, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark..
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Jukema, J. Wouter
    Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, NL-2333 Utrecht, Netherlands..
    Kahali, Bratati
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA..
    Kahn, Rene S.
    Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands..
    Kahonen, Mika
    Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland..
    Kamstrup, Pia R.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Kaprio, Jaakko
    Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland.;Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Karaleftheri, Maria
    Echinos Med Ctr, Echinos, Greece..
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Res, Belfast BT12 6BJ, Antrim, North Ireland..
    Keeman, Renske
    Netherlands Canc Inst, Antoni van Leewenhoek Hosp, NL-1066 CX Amsterdam, Netherlands..
    Kiemeney, Lambertus A.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Kitajima, Hidetoshi
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Kluivers, Kirsten B.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Kocher, Thomas
    Univ Med Greifswald, Dept Restorat Dent Periodontol & Endodontol, D-17475 Greifswald, Germany..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland..
    Kontto, Jukka
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Kooner, Jaspal S.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England.;Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London W12 0NN, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany..
    Kriebel, Jennifer
    German Ctr Diabet Res, D-85764 Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany..
    Kuivaniemi, Helena
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Dept Psychiat, ZA-7505 Tygerberg, Western Cape, South Africa.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, ZA-7505 Tygerberg, Western Cape, South Africa..
    Kury, Sebastien
    CHU Nantes, Serv Genet Med, F-44093 Nantes, France..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    La Bianca, Martina
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland.;Univ Eastern Finland, Inst Biomed & Physiol, Kuopio 70210, Finland..
    Lange, Ethan M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Langefeld, Carl D.
    Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27157 USA..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Larson, Eric B.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Seattle, WA 98101 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA..
    Lee, I-Te
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung 407, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.;Chung Shan Med Univ, Sch Med, Taichung 402, Taiwan..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Lewis, Cora E.
    Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35205 USA..
    Li, Huaixing
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Li, Jin
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Palo Alto, CA 94305 USA..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA..
    Lin, Li-An
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Lin, Xu
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Linneberg, Allan
    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.;Rigshosp, Dept Expt Med, DK-2200 Copenhagen, Denmark..
    Liu, Yeheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA..
    Lophatananon, Artitaya
    Warsaw Acad Med & Hosp, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Lubitz, Steven A.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Mackey, David A.
    Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA 6009, Australia..
    Madden, Pamela A. F.
    Washington Univ, Dept Psychiat, St Louis, MO 63110 USA..
    Manning, Alisa K.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Marenne, Gaelle
    Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Mazul, Angela L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Meidtner, Karina
    German Ctr Diabet Res, D-85764 Munich, Germany.;German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, D-14558 Nuthetal, Germany..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Mitchell, Paul
    Univ Sydney, Ctr Vis Res, Westmead Millennium Inst Med Res, Sydney, NSW 2022, Australia.;Univ Sydney, Dept Ophthalmol, Sydney, NSW 2022, Australia..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 RC Leiden, Netherlands..
    Morgan, Anna
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy..
    Morris, Andrew D.
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Univ Munich, Dept Med 1, D-81377 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany..
    Munroe, Patricia B.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Nauck, Matthias
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.;Univ Med Greifswald, Inst Clin Chem, D-17475 Greifswald, Germany.;Univ Med Greifswald, Lab Med, D-17475 Greifswald, Germany..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Nikus, Kjell
    Univ Tampere, Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.;Univ Tampere, Sch Med, Tampere 33521, Finland..
    Njolstad, Pal R.
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway..
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Ntalla, Ioanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    O'Connel, Jeffrey R.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA..
    Oksa, Heikki
    Tampere Univ Hosp, Dept Med, Tampere 33521, Finland..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA..
    Ophoff, Roel A.
    Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Packard, Chris J.
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Med Res Inst, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee DD1 9SY, Scotland..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, NL-3584 CX Utrecht, Netherlands..
    Patel, Aniruddh P.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Peissig, Peggy L.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Peloso, Gina M.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Pennell, Craig E.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia..
    Perola, Markus
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, FI-00014 Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, FI-00014 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Perry, James A.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Person, Thomas N.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Pirie, Ailith
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Polasek, Ozren
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Split, Sch Med, Split 21000, Croatia..
    Posthuma, Danielle
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogenom & Cognit Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Neurosci Campus Amsterdam, NL-1081 HV Amsterdam, Netherlands..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland..
    Reilly, Dermot F.
    MRL Merck & Co Inc, Genet & Pharmacogenom, Boston, MA 02115 USA..
    Reiner, Alex P.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Renstrom, Frida
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Umea Univ, Dept Biobank Res, SE-90187 Umea, Sweden..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA..
    Rioux, John D.
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Robertson, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England..
    Robino, Antonietta
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.;Umea Univ, Unit Family Med, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden..
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Ruth, Katherine S.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Saleheen, Danish
    Ctr Noncommunicable Dis, Karachi, Pakistan.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Sandow, Kevin
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Sapkota, Yadav
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Sattar, Naveed
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Schmidt, Marjanka K.
    Netherlands Canc Inst, Antoni van Leewenhoek Hosp, NL-1066 CX Amsterdam, Netherlands..
    Schreiner, Pamela J.
    Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
    Schulze, Matthias B.
    German Ctr Diabet Res, D-85764 Munich, Germany.;German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, D-14558 Nuthetal, Germany..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Segura-Lepe, Marcelo P.
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Shah, Svati
    Duke Univ, Durham, NC 27703 USA..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Sivapalaratnam, Suthesh
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England.;AMC, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Smith, Albert Vernon
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;Icelandic Heart Assoc, IS-201 Kopavogur, Iceland..
    Smith, Jennifer A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Southam, Lorraine
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Speliotes, Elizabeth K.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Steinthorsdottir, Valgerdur
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Stumvoll, Michael
    Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany.;Univ Leipzig, Dept Med, D-04103 Leipzig, Germany..
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    't Hart, Leen M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands.;Leiden Univ, Med Ctr, Dept Mol & Cell Biol, NL-2333 ZC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2333 ZC Leiden, Netherlands..
    Tansey, Katherine E.
    Cardiff Univ, Coll Biomed & Life Sci, Cardiff CF14 4EP, S Glam, Wales.;Univ Bristol, Dept Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Tardif, Jean-Claude
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Taylor, Kent D.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Teumer, Alexander
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.;Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thompson, Deborah J.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Thorsteinsdottir, Unnur
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Thuesen, Betina H.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark..
    Toenjes, Anke
    Univ Leipzig, Dept Womens & Child Hlth, Ctr Pediat Res, D-04103 Leipzig, Germany..
    Tromp, Gerard
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Human Genet & Mol Biol, ZA-7505 Tygerberg, Western Cape, South Africa..
    Trompet, Stella
    Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2333 Leiden, Netherlands..
    Tsafantakis, Emmanouil
    Anogia Med Ctr, Anogia, Greece..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria.;Dasman Diabet Inst, Dasman 15462, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah 21589, Saudi Arabia..
    Tybjaerg-Hansen, Anne
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark..
    Tyrer, Jonathan P.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Uher, Rudolf
    Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 4R2, Canada..
    Uitterlinden, Andre G.
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Ulivi, Sheila
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    van der Laan, Sander W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, NL-3584 CX Utrecht, Netherlands..
    Van Der Leij, Andries R.
    Univ Amsterdam, Dept Brain & Cognit, NL-1018 WS Amsterdam, Netherlands..
    van Duijn, Cornelia M.
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands..
    Varbo, Anette
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Varga, Tibor V.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Varma, Rohit
    Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA..
    Vermeulen, Sita H.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Vestergaard, Henrik
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    Vogt, Thomas F.
    MRL Merck Co Inc, Cardiometab Dis, Kenilworth, NJ 07033 USA..
    Vozzi, Diego
    Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England..
    Wang, Feijie
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Wang, Carol A.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia..
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Wang, Yiqin
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Warren, Helen R.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Wessel, Jennifer
    Indiana Univ, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Dept Epidemiol & Med, Indianapolis, IN 46202 USA.;Indiana Univ, Sch Med, Indianapolis, IN 46202 USA..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Witte, Daniel R.
    Danish Diabet Acad, DK-5000 Odense, Denmark.;Aarhus Univ, Dept Publ Hlth, DK-8000 Aarhus, Denmark..
    Woods, Michael O.
    Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF A1B 3V6, Canada..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Yao, Jie
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Yao, Pang
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA.;GlaxoSmithKlein, King Of Prussia, PA 19406 USA..
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Zhan, Xiaowei
    Univ Texas Southwestern Med Ctr Dallas, Quantitat Biomed Res Ctr, Ctr Genet Host Def, Dept Clin Sci, Dallas, TX 75390 USA..
    Zhang, Weihua
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Zhao, Wei
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Zheng, He
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Zhou, Wei
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Rotter, Jerome I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Kathiresan, Sekar
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Willer, Cristen J.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Stefansson, Kari
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Liu, Dajiang J.
    Penn State Univ, Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA 17033 USA..
    North, Kari E.
    Dept Epidemiol, Chapel Hill, NC 27514 USA.;Carolina Ctr Genome Sci, Chapel Hill, NC 27514 USA..
    Heard-Costa, Nancy L.
    NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA..
    Pers, Tune H.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, DK-2200 Copenhagen, Denmark..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7BN, England..
    Oxvig, Claus
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    Kutalik, Zoltan
    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Rivadeneira, Fernando
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10069 USA..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Hirschhorn, Joel N.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Harvard Med Sch, Dept Pediat & Genet, Boston, MA 02115 USA..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia..
    Lettre, Guillaume
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Rare and low-frequency coding variants alter human adult height2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 542, no 7640, 186-190 p.Article in journal (Refereed)
    Abstract [en]

    Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

  • 257. Marouli, Eirini
    et al.
    Graff, Mariaelisa
    Medina-Gomez, Carolina
    Lo, Ken Sin
    Wood, Andrew R.
    Kjaer, Troels R.
    Fine, Rebecca S.
    Lu, Yingchang
    Schurmann, Claudia
    Highland, Heather M.
    Rueger, Sina
    Thorleifsson, Gudmar
    Justice, Anne E.
    Lamparter, David
    Stirrups, Kathleen E.
    Turcot, Valerie
    Young, Kristin L.
    Winkler, Thomas W.
    Esko, Tonu
    Karaderi, Tugce
    Locke, Adam E.
    Masca, Nicholas G. D.
    Ng, Maggie C. Y.
    Mudgal, Poorva
    Rivas, Manuel A.
    Vedantam, Sailaja
    Mahajan, Anubha
    Guo, Xiuqing
    Abecasis, Goncalo
    Aben, Katja K.
    Adair, Linda S.
    Alam, Dewan S.
    Albrecht, Eva
    Allin, Kristine H.
    Allison, Matthew
    Amouyel, Philippe
    Appel, Emil V.
    Arveiler, Dominique
    Asselbergs, Folkert W.
    Auer, Paul L.
    Balkau, Beverley
    Banas, Bernhard
    Bang, Lia E.
    Benn, Marianne
    Bergmann, Sven
    Bielak, Lawrence F.
    Blueher, Matthias
    Boeing, Heiner
    Boerwinkle, Eric
    Boeger, Carsten A.
    Bonnycastle, Lori L.
    Bork-Jensen, Jette
    Bots, Michiel L.
    Bottinger, Erwin P.
    Bowden, Donald W.
    Brandslund, Ivan
    Breen, Gerome
    Brilliant, Murray H.
    Broer, Linda
    Burt, Amber A.
    Butterworth, Adam S.
    Carey, David J.
    Caulfield, Mark J.
    Chambers, John C.
    Chasman, Daniel I.
    Chen, Yii-Der Ida
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audrey Y.
    Cocca, Massimiliano
    Collins, Francis S.
    Cook, James P.
    Corley, Janie
    Galbany, Jordi Corominas
    Cox, Amanda J.
    Cuellar-Partida, Gabriel
    Danesh, John
    Davies, Gail
    de Bakker, Paul I. W.
    de Borst, Gert J.
    de Denus, Simon
    de Groot, Mark C. H.
    de Mutsert, Renee
    Deary, Ian J.
    Dedoussis, George
    Demerath, Ellen W.
    den Hollander, Anneke I.
    Dennis, Joe G.
    Di Angelantonio, Emanuele
    Drenos, Fotios
    Du, Mengmeng
    Dunning, Alison M.
    Easton, Douglas F.
    Ebeling, Tapani
    Edwards, Todd L.
    Ellinor, Patrick T.
    Elliott, Paul
    Evangelou, Evangelos
    Farmaki, Aliki-Eleni
    Faul, Jessica D.
    Feitosa, Mary F.
    Feng, Shuang
    Ferrannini, Ele
    Ferrario, Marco M.
    Ferrieres, Jean
    Florez, Jose C.
    Ford, Ian
    Fornage, Myriam
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Frikke-Schmidt, Ruth
    Galesloot, Tessel E.
    Gan, Wei
    Gandin, Ilaria
    Gasparini, Paolo
    Giedraitis, Vilmantas
    Giri, Ayush
    Girotto, Giorgia
    Gordon, Scott D.
    Gordon-Larsen, Penny
    Gorski, Mathias
    Grarup, Niels
    Grove, Megan L.
    Gudnason, Vilmundur
    Gustafsson, Stefan
    Hansen, Torben
    Harris, Kathleen Mullan
    Harris, Tamara B.
    Hattersley, Andrew T.
    Hayward, Caroline
    He, Liang
    Heid, Iris M.
    Heikkila, Kauko
    Helgeland, Oyvind
    Hernesniemi, Jussi
    Hewitt, Alex W.
    Hocking, Lynne J.
    Hollensted, Mette
    Holmen, Oddgeir L.
    Hovingh, G. Kees
    Howson, Joanna M. M.
    Hoyng, Carel B.
    Huang, Paul L.
    Hveem, Kristian
    Ikram, M. Arfan
    Ingelsson, Erik
    Jackson, Anne U.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Jarvik, Gail P.
    Jensen, Gorm B.
    Jhun, Min A.
    Jia, Yucheng
    Jiang, Xuejuan
    Johansson, Stefan
    Jorgensen, Marit E.
    Jorgensen, Torben
    Jousilahti, Pekka
    Jukema, J. Wouter
    Kahali, Bratati
    Kahn, Rene S.
    Kahonen, Mika
    Kamstrup, Pia R.
    Kanoni, Stavroula
    Kaprio, Jaakko
    Karaleftheri, Maria
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kee, Frank
    Keeman, Renske
    Kiemeney, Lambertus A.
    Kitajima, Hidetoshi
    Kluivers, Kirsten B.
    Kocher, Thomas
    Komulainen, Pirjo
    Kontto, Jukka
    Kooner, Jaspal S.
    Kooperberg, Charles
    Kovacs, Peter
    Kriebel, Jennifer
    Kuivaniemi, Helena
    Kury, Sebastien
    Kuusisto, Johanna
    La Bianca, Martina
    Laakso, Markku
    Lakka, Timo A.
    Lange, Ethan M.
    Lange, Leslie A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Larson, Eric B.
    Lee, I-Te
    Lehtimaki, Terho
    Lewis, Cora E.
    Li, Huaixing
    Li, Jin
    Li-Gao, Ruifang
    Lin, Honghuang
    Lin, Li-An
    Lin, Xu
    Lind, Lars
    Lindstrom, Jaana
    Linneberg, Allan
    Liu, Yeheng
    Liu, Yongmei
    Lophatananon, Artitaya
    Luan, Jian'an
    Lubitz, Steven A.
    Lyytikainen, Leo-Pekka
    Mackey, David A.
    Madden, Pamela A. F.
    Manning, Alisa K.
    Mannisto, Satu
    Marenne, Gaelle
    Marten, Jonathan
    Martin, Nicholas G.
    Mazul, Angela L.
    Meidtner, Karina
    Metspalu, Andres
    Mitchell, Paul
    Mohlke, Karen L.
    Mook-Kanamori, Dennis O.
    Morgan, Anna
    Morris, Andrew D.
    Morris, Andrew P.
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Nalls, Mike A.
    Nauck, Matthias
    Nelson, Christopher P.
    Neville, Matt
    Nielsen, Sune F.
    Nikus, Kjell
    Njolstad, Pal R.
    Nordestgaard, Borge G.
    Ntalla, Ioanna
    O'Connel, Jeffrey R.
    Oksa, Heikki
    Loohuis, Loes M. Olde
    Ophoff, Roel A.
    Owen, Katharine R.
    Packard, Chris J.
    Padmanabhan, Sandosh
    Palmer, Colin N. A.
    Pasterkamp, Gerard
    Patel, Aniruddh P.
    Pattie, Alison
    Pedersen, Oluf
    Peissig, Peggy L.
    Peloso, Gina M.
    Pennell, Craig E.
    Perola, Markus
    Perry, James A.
    Perry, John R. B.
    Person, Thomas N.
    Pirie, Ailith
    Polasek, Ozren
    Posthuma, Danielle
    Raitakari, Olli T.
    Rasheed, Asif
    Rauramaa, Rainer
    Reilly, Dermot F.
    Reiner, Alex P.
    Renstrom, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Ridker, Paul M.
    Rioux, John D.
    Robertson, Neil
    Robino, Antonietta
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Rudan, Igor
    Ruth, Katherine S.
    Saleheen, Danish
    Salomaa, Veikko
    Samani, Nilesh J.
    Sandow, Kevin
    Sapkota, Yadav
    Sattar, Naveed
    Schmidt, Marjanka K.
    Schreiner, Pamela J.
    Schulze, Matthias B.
    Scott, Robert A.
    Segura-Lepe, Marcelo P.
    Shah, Svati
    Sim, Xueling
    Sivapalaratnam, Suthesh
    Small, Kerrin S.
    Smith, Albert Vernon
    Smith, Jennifer A.
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Starr, John M.
    Steinthorsdottir, Valgerdur
    Stringham, Heather M.
    Stumvoll, Michael
    Surendran, Praveen
    t Hart, Leen M.
    Tansey, Katherine E.
    Tardif, Jean-Claude
    Taylor, Kent D.
    Teumer, Alexander
    Thompson, Deborah J.
    Thorsteinsdottir, Unnur
    Thuesen, Betina H.
    Toenjes, Anke
    Tromp, Gerard
    Trompet, Stella
    Tsafantakis, Emmanouil
    Tuomilehto, Jaakko
    Tybjaerg-Hansen, Anne
    Tyrer, Jonathan P.
    Uher, Rudolf
    Uitterlinden, Andre G.
    Ulivi, Sheila
    van der Laan, Sander W.
    Van Der Leij, Andries R.
    van Duijn, Cornelia M.
    van Schoor, Natasja M.
    van Setten, Jessica
    Varbo, Anette
    Varga, Tibor V.
    Varma, Rohit
    Edwards, Digna R. Velez
    Vermeulen, Sita H.
    Vestergaard, Henrik
    Vitart, Veronique
    Vogt, Thomas F.
    Vozzi, Diego
    Walker, Mark
    Wang, Feijie
    Wang, Carol A.
    Wang, Shuai
    Wang, Yiqin
    Wareham, Nicholas J.
    Warren, Helen R.
    Wessel, Jennifer
    Willems, Sara M.
    Wilson, James G.
    Witte, Daniel R.
    Woods, Michael O.
    Wu, Ying
    Yaghootkar, Hanieh
    Yao, Jie
    Yao, Pang
    Yerges-Armstrong, Laura M.
    Young, Robin
    Zeggini, Eleftheria
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Jing Hua
    Zhao, Wei
    Zheng, He
    Zhou, Wei
    Rotter, Jerome I.
    Boehnke, Michael
    Kathiresan, Sekar
    McCarthy, Mark I.
    Willer, Cristen J.
    Stefansson, Kari
    Borecki, Ingrid B.
    Liu, Dajiang J.
    North, Kari E.
    Heard-Costa, Nancy L.
    Pers, Tune H.
    Lindgren, Cecilia M.
    Oxvig, Claus
    Kutalik, Zoltan
    Rivadeneira, Fernando
    Loos, Ruth J. F.
    Frayling, Timothy M.
    Hirschhorn, Joel N.
    Deloukas, Panos
    Lettre, Guillaume
    Rare and low-frequency coding variants alter human adult height2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 542, no 7640, 186-190 p.Article in journal (Refereed)
    Abstract [en]

    Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

  • 258. Marteyn, Benoit
    et al.
    West, Nicholas P.
    Browning, Douglas F.
    Cole, Jeffery A.
    Shaw, Jonathan G.
    Palm, Fredrik
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Mounier, Joelle
    Prevost, Marie-Christine
    Sansonetti, Philippe
    Tang, Christoph M.
    Modulation of Shigella virulence in response to available oxygen in vivo2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 465, no 7296, 355-358 p.Article in journal (Refereed)
    Abstract [en]

    Bacteria coordinate expression of virulence determinants in response to localized microenvironments in their hosts. Here we show that Shigella flexneri, which causes dysentery, encounters varying oxygen concentrations in the gastrointestinal tract, which govern activity of its type three secretion system (T3SS). The T3SS is essential for cell invasion and virulence(1). In anaerobic environments (for example, the gastrointestinal tract lumen), Shigella is primed for invasion and expresses extended T3SS needles while reducing Ipa (invasion plasmid antigen) effector secretion. This is mediated by FNR (fumarate and nitrate reduction), a regulator of anaerobic metabolism that represses transcription of spa32 and spa33, virulence genes that regulate secretion through the T3SS. We demonstrate there is a zone of relative oxygenation adjacent to the gastrointestinal tract mucosa, caused by diffusion from the capillary network at the tips of villi. This would reverse the anaerobic block of Ipa secretion, allowing T3SS activation at its precise site of action, enhancing invasion and virulence.

  • 259. Marteyn, Benoit
    et al.
    West, Nicholas P.
    Browning, Douglas F.
    Cole, Jeffery A.
    Shaw, Jonathan G.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Mounier, Joelle
    Prevost, Marie-Christine
    Sansonetti, Philippe
    Tang, Christoph M.
    Modulation of Shigella virulence in response to available oxygen in vivo2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 465, no 7296, 355-358 p.Article in journal (Refereed)
    Abstract [en]

    Bacteria coordinate expression of virulence determinants in response to localized microenvironments in their hosts. Here we show that Shigella flexneri, which causes dysentery, encounters varying oxygen concentrations in the gastrointestinal tract, which govern activity of its type three secretion system (T3SS). The T3SS is essential for cell invasion and virulence(1). In anaerobic environments (for example, the gastrointestinal tract lumen), Shigella is primed for invasion and expresses extended T3SS needles while reducing Ipa (invasion plasmid antigen) effector secretion. This is mediated by FNR (fumarate and nitrate reduction), a regulator of anaerobic metabolism that represses transcription of spa32 and spa33, virulence genes that regulate secretion through the T3SS. We demonstrate there is a zone of relative oxygenation adjacent to the gastrointestinal tract mucosa, caused by diffusion from the capillary network at the tips of villi. This would reverse the anaerobic block of Ipa secretion, allowing T3SS activation at its precise site of action, enhancing invasion and virulence.

  • 260.
    Martinez Molina, Daniel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Niegowski, Damian
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 448, no 7153, 613-616 p.Article in journal (Refereed)
    Abstract [en]

    Cysteinyl leukotrienes are key mediators in inflammation and have an important role in acute and chronic inflammatory diseases of the cardiovascular and respiratory systems, in particular bronchial asthma. In the biosynthesis of cysteinyl leukotrienes, conversion of arachidonic acid forms the unstable epoxide leukotriene A4 (LTA4). This intermediate is conjugated with glutathione (GSH) to produce leukotriene C4 (LTC4) in a reaction catalysed by LTC4 synthase: this reaction is the key step in cysteinyl leukotriene formation. Here we present the crystal structure of the human LTC4 synthase in its apo and GSH-complexed forms to 2.00 and 2.15 A resolution, respectively. The structure reveals a homotrimer, where each monomer is composed of four transmembrane segments. The structure of the enzyme in complex with substrate reveals that the active site enforces a horseshoe-shaped conformation on GSH, and effectively positions the thiol group for activation by a nearby arginine at the membrane-enzyme interface. In addition, the structure provides a model for how the omega-end of the lipophilic co-substrate is pinned at one end of a hydrophobic cleft, providing a molecular 'ruler' to align the reactive epoxide at the thiol of glutathione. This provides new structural insights into the mechanism of LTC4 formation, and also suggests that the observed binding and activation of GSH might be common for a family of homologous proteins important for inflammatory and detoxification responses.

  • 261.
    Massironi, Matteo
    et al.
    Univ Padua, Dipartimento Geosci, I-35131 Padua, Italy.;Univ Padua, Ctr Ateneo Studi & Attivita Spaziali Giuseppe Col, I-35131 Padua, Italy..
    Simioni, Emanuele
    CNR INFN UOS Padova LUXOR, I-35131 Padua, Italy..
    Marzari, Francesco
    Univ Padua, Dept Phys & Astron, I-35122 Padua, Italy..
    Cremonese, Gabriele
    Osserv Astron Padova, INAF, I-35122 Padua, Italy..
    Giacomini, Lorenza
    Univ Padua, Dipartimento Geosci, I-35131 Padua, Italy..
    Pajola, Maurizio
    Univ Padua, Ctr Ateneo Studi & Attivita Spaziali Giuseppe Col, I-35131 Padua, Italy..
    Jorda, Laurent
    Aix Marseille Univ, CNRS, UMR 7326, LAM, F-13388 Marseille, France..
    Naletto, Giampiero
    Univ Padua, Ctr Ateneo Studi & Attivita Spaziali Giuseppe Col, I-35131 Padua, Italy.;CNR INFN UOS Padova LUXOR, I-35131 Padua, Italy.;Univ Padua, Dept Informat Engn, I-35131 Padua, Italy..
    Lowry, Stephen
    Univ Kent, Sch Phys Sci, Canterbury CT2 7NZ, Kent, England..
    El-Maarry, Mohamed Ramy
    Univ Bern, Inst Phys, CH-3012 Bern, Switzerland..
    Preusker, Frank
    Deutsch Zentrum Luft & Raumfahrt DLR, Inst Planetenforsch, D-12489 Berlin, Germany..
    Scholten, Frank
    Deutsch Zentrum Luft & Raumfahrt DLR, Inst Planetenforsch, D-12489 Berlin, Germany..
    Sierks, Holger
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Barbieri, Cesare
    Univ Padua, Dept Phys & Astron, I-35122 Padua, Italy..
    Lamy, Philippe
    Aix Marseille Univ, CNRS, UMR 7326, LAM, F-13388 Marseille, France..
    Rodrigo, Rafael
    CSIC INTA, Ctr Astrobiol, Madrid 28850, Spain.;Int Space Sci Inst, CH-3012 Bern, Switzerland..
    Koschny, Detlef
    European Space Res & Technol Ctr ESA, Sci Support Off, NL-2201 AZ Noordwijk, Netherlands..
    Rickman, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy. PAS Space Res Ctr, PL-00716 Warsaw, Poland..
    Keller, Horst Uwe
    Tech Univ Carolo Wilhelmina Braunschweig, Inst Geophys & Extraterr Phys IGEP, D-38106 Braunschweig, Germany..
    A'Hearn, Michael F.
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany.;Univ Maryland, Dept Astron, College Pk, MD 20742 USA.;Akad Wissensch Gottingen, D-37077 Gottingen, Germany..
    Agarwal, Jessica
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Auger, Anne-Therese
    Aix Marseille Univ, CNRS, UMR 7326, LAM, F-13388 Marseille, France..
    Barucci, M. Antonella
    Univ Paris Diderot, Univ Paris 06, CNRS, LESIA,Observ Paris, F-92195 Meudon, France..
    Bertaux, Jean-Loup
    CNRS UVSQ IPSL, LATMOS, F-78280 Guyancourt, France..
    Bertini, Ivano
    Univ Padua, Ctr Ateneo Studi & Attivita Spaziali Giuseppe Col, I-35131 Padua, Italy..
    Besse, Sebastien
    European Space Res & Technol Ctr ESA, Sci Support Off, NL-2201 AZ Noordwijk, Netherlands..
    Bodewits, Dennis
    Univ Maryland, Dept Astron, College Pk, MD 20742 USA..
    Capanna, Claire
    Aix Marseille Univ, CNRS, UMR 7326, LAM, F-13388 Marseille, France..
    Da Deppo, Vania
    CNR INFN UOS Padova LUXOR, I-35131 Padua, Italy..
    Davidsson, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Debei, Stefano
    Univ Padua, Dept Ind Engn, I-35131 Padua, Italy..
    De Cecco, Mario Lino
    Univ Trent, I-38100 Trento, Italy..
    Ferri, Francesca
    Univ Padua, Ctr Ateneo Studi & Attivita Spaziali Giuseppe Col, I-35131 Padua, Italy..
    Fornasier, Sonia
    Univ Paris Diderot, Univ Paris 06, CNRS, LESIA,Observ Paris, F-92195 Meudon, France..
    Fulle, Marco
    Osserv Astron Trieste, INAF, I-34014 Trieste, Italy..
    Gaskell, Robert
    Planetary Sci Inst, Tucson, AZ 85719 USA..
    Groussin, Olivier
    Aix Marseille Univ, CNRS, UMR 7326, LAM, F-13388 Marseille, France..
    Gutierrez, Pedro J.
    CSIC, Inst Astrofis Andalucia, E-18008 Granada, Spain..
    Guettler, Carsten
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Hviid, Stubbe F.
    Deutsch Zentrum Luft & Raumfahrt DLR, Inst Planetenforsch, D-12489 Berlin, Germany.;Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Ip, Wing-Huen
    Natl Cent Univ, Grad Inst Astron, Chungli 32054, Taiwan..
    Knollenberg, Joerg
    Deutsch Zentrum Luft & Raumfahrt DLR, Inst Planetenforsch, D-12489 Berlin, Germany..
    Kovacs, Gabor
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Kramm, Rainer
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Kuehrt, Ekkehard
    Deutsch Zentrum Luft & Raumfahrt DLR, Inst Planetenforsch, D-12489 Berlin, Germany..
    Kueppers, Michael
    European Space Astron Ctr ESA, Operat Dept, Madrid 28691, Spain..
    La Forgia, Fiorangela
    Univ Padua, Dept Phys & Astron, I-35122 Padua, Italy..
    Lara, Luisa M.
    CSIC, Inst Astrofis Andalucia, E-18008 Granada, Spain..
    Lazzarin, Monica
    Univ Padua, Dept Phys & Astron, I-35122 Padua, Italy..
    Lin, Zhong-Yi
    Natl Cent Univ, Grad Inst Astron, Chungli 32054, Taiwan..
    Lopez Moreno, Jose J.
    CSIC, Inst Astrofis Andalucia, E-18008 Granada, Spain..
    Magrin, Sara
    Univ Padua, Dept Phys & Astron, I-35122 Padua, Italy..
    Michalik, Harald
    TU Braunschweig, Inst Datentech & Kommunikat, D-38106 Braunschweig, Germany..
    Mottola, Stefano
    Deutsch Zentrum Luft & Raumfahrt DLR, Inst Planetenforsch, D-12489 Berlin, Germany..
    Oklay, Nilda
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Pommerol, Antoine
    Univ Bern, Inst Phys, CH-3012 Bern, Switzerland..
    Thomas, Nicolas
    Univ Bern, Inst Phys, CH-3012 Bern, Switzerland..
    Tubiana, Cecilia
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Vincent, Jean-Baptiste
    Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany..
    Two independent and primitive envelopes of the bilobate nucleus of comet 67P2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, no 7573, 402-405 p.Article in journal (Refereed)
    Abstract [en]

    The factors shaping cometary nuclei are still largely unknown, but could be the result of concurrent effects of evolutionary(1,2) and primordial processes(3,4). The peculiar bilobed shape of comet 67P/Churyumov-Gerasimenko may be the result of the fusion of two objects that were once separate or the result of a localized excavation by outgassing at the interface between the two lobes(5). Here we report that the comet's major lobe is enveloped by a nearly continuous set of strata, up to 650 metres thick, which are independent of an analogous stratified envelope on the minor lobe. Gravity vectors computed for the two lobes separately are closer to perpendicular to the strata than those calculated for the entire nucleus and adjacent to the neck separating the two lobes. Therefore comet 67P/Churyumov-Gerasimenko is an accreted body of two distinct objects with 'onion-like' stratification, which formed before they merged. We conclude that gentle, low-velocity collisions occurred between two fully formed kilometre-sized cometesimals in the early stages of the Solar System. The notable structural similarities between the two lobes of comet 67P/Churyumov-Gerasimenko indicate that the early-forming cometesimals experienced similar primordial stratified accretion, even though they formed independently.

  • 262. Mayor, Jordan R.
    et al.
    Sanders, Nathan J.
    Classen, Aimee T.
    Bardgett, Richard D.
    Clement, Jean-Christophe
    Fajardo, Alex
    Lavorel, Sandra
    Sundqvist, Maja K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Center for Macroecology, Evolution and Climate, The Natural History Museum of Denmark, University of Copenhagen DK-2100, Copenhagen Ø, Denmark.
    Bahn, Michael
    Chisholm, Chelsea
    Cieraad, Ellen
    Gedalof, Ze'ev
    Grigulis, Karl
    Kudo, Gaku
    Oberski, Daniel L.
    Wardle, David A.
    Elevation alters ecosystem properties across temperate treelines globally2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 542, no 7639, 91-95 p.Article in journal (Refereed)
    Abstract [en]

    Temperature is a primary driver of the distribution of biodiversity as well as of ecosystem boundaries(1,2). Declining temperature with increasing elevation in montane systems has long been recognized as a major factor shaping plant community biodiversity, metabolic processes, and ecosystem dynamics(3,4). Elevational gradients, as thermoclines, also enable prediction of long-term ecological responses to climate warming(5-7). One of the most striking manifestations of increasing elevation is the abrupt transitions from forest to treeless alpine tundra(8). However, whether there are globally consistent above-and belowground responses to these transitions remains an open question(4). To disentangle the direct and indirect effects of temperature on ecosystem properties, here we evaluate replicate treeline ecotones in seven temperate regions of the world. We find that declining temperatures with increasing elevation did not affect tree leaf nutrient concentrations, but did reduce ground-layer community-weighted plant nitrogen, leading to the strong stoichiometric convergence of ground-layer plant community nitrogen to phosphorus ratios across all regions. Further, elevation-driven changes in plant nutrients were associated with changes in soil organic matter content and quality (carbon to nitrogen ratios) and microbial properties. Combined, our identification of direct and indirect temperature controls over plant communities and soil properties in seven contrasting regions suggests that future warming may disrupt the functional properties of montane ecosystems, particularly where plant community reorganization outpaces treeline advance.

  • 263. McCalley, Carmody K.
    et al.
    Woodcroft, Ben J.
    Hodgkins, Suzanne B.
    Wehr, Richard A.
    Kim, Eun-Hae
    Mondav, Rhiannon
    Crill, Patrick M.
    Chanton, Jeffrey P.
    Rich, Virginia I.
    Tyson, Gene W.
    Saleska, Scott R.
    Methane dynamics regulated by microbial community response to permafrost thaw2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 514, no 7523, 478-481 p.Article in journal (Refereed)
    Abstract [en]

    Permafrost contains about 50% of the global soil carbon1. It is thought that the thawing of permafrost can lead to a loss of soil carbon in the form of methane and carbon dioxide emissions2, 3. The magnitude of the resulting positive climate feedback of such greenhouse gas emissions is still unknown3 and may to a large extent depend on the poorly understood role of microbial community composition in regulating the metabolic processes that drive such ecosystem-scale greenhouse gas fluxes. Here we show that changes in vegetation and increasing methane emissions with permafrost thaw are associated with a switch from hydrogenotrophic to partly acetoclastic methanogenesis, resulting in a large shift in the δ13C signature (10–15‰) of emitted methane. We used a natural landscape gradient of permafrost thaw in northern Sweden4, 5 as a model to investigate the role of microbial communities in regulating methane cycling, and to test whether a knowledge of community dynamics could improve predictions of carbon emissions under loss of permafrost. Abundance of the methanogen Candidatus ‘Methanoflorens stordalenmirensis6 is a key predictor of the shifts in methane isotopes, which in turn predicts the proportions of carbon emitted as methane and as carbon dioxide, an important factor for simulating the climate feedback associated with permafrost thaw in global models3, 7. By showing that the abundance of key microbial lineages can be used to predict atmospherically relevant patterns in methane isotopes and the proportion of carbon metabolized to methane during permafrost thaw, we establish a basis for scaling changing microbial communities to ecosystem isotope dynamics. Our findings indicate that microbial ecology may be important in ecosystem-scale responses to global change.

  • 264. McCalley, Carmody K.
    et al.
    Woodcroft, Ben J.
    Hodgkins, Suzanne B.
    Wehr, Richard A.
    Kim, Eun-Hae
    Mondav, Rhiannon
    Crill, Patrick M.
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Chanton, Jeffrey P.
    Rich, Virginia I.
    Tyson, Gene W.
    Saleska, Scott R.
    Methane dynamics regulated by microbial community response to permafrost thaw2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 514, no 7523, 478-+ p.Article in journal (Refereed)
    Abstract [en]

    Permafrost contains about 50% of the global soil carbon(1). It is thought that the thawing of permafrost can lead to a loss of soil carbon in the form of methane and carbon dioxide emissions(2,3). The magnitude of the resulting positive climate feedback of such greenhouse gas emissions is still unknown(3) and may to a large extent depend on the poorly understood role of microbial community composition in regulating the metabolic processes that drive such ecosystem-scale greenhouse gas fluxes. Here we show that changes in vegetation and increasing methane emissions with permafrost thaw are associated with a switch from hydrogenotrophic to partly acetoclastic methanogenesis, resulting in a large shift in the delta C-13 signature (1015 parts per thousand) of emitted methane. We used a natural landscape gradient of permafrost thaw in northern Sweden(4,5) as a model to investigate the role of microbial communities in regulating methane cycling, and to test whether a knowledge of community dynamics could improve predictions of carbon emissions under loss of permafrost. Abundance of the methanogen Candidatus Methanoflorens stordalenmirensis(6) is a key predictor of the shifts in methane isotopes, which in turn predicts the proportions of carbon emitted as methane and as carbon dioxide, an important factor for simulating the climate feedback associated with permafrost thaw in global models(3,7). By showing that the abundance of key microbial lineages can be used to predict atmospherically relevant patterns in methane isotopes and the proportion of carbon metabolized to methane during permafrost thaw, we establish a basis for scaling changing microbial communities to ecosystem isotope dynamics. Our findings indicate that microbial ecology may be important in ecosystem-scale responses to global change.

  • 265.
    McCalley, Carmody
    et al.
    Department of Ecology and Evolutionary Biology, University of Arizona.
    Woodcroft, Ben
    Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland.
    Hodgkins, Suzanne
    Department of Earth, Ocean and Atmospheric Science, Florida State University.
    Wehr, Richard
    Department of Ecology and Evolutionary Biology, University of Arizona.
    Kim, Eun-Hae
    Department of Soil, Water and Environmental Science, University of Arizona,.
    Mondav, Rhiannon
    Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland.
    Crill, Patrick
    Department of Geological Sciences, Stockholm University.
    Chanton, Jeffrey
    epartment of Earth, Ocean and Atmospheric Science, Florida State University.
    Rich, Virginia
    Department of Soil, Water and Environmental Science, University of Arizona.
    Tyson, Gene
    Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland.
    Saleska, Scott
    Department of Ecology and Evolutionary Biology, University of Arizona.
    Methane dynamics regulated by microbial community response to permafrost thaw2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 514, no 7523, 478-481 p.Article in journal (Refereed)
    Abstract [en]

    Permafrost contains about 50% of the global soil carbon1. It is thought that the thawing of permafrost can lead to a loss of soil carbon in the form of methane and carbon dioxide emissions2, 3. The magnitude of the resulting positive climate feedback of such greenhouse gas emissions is still unknown3 and may to a large extent depend on the poorly understood role of microbial community composition in regulating the metabolic processes that drive such ecosystem-scale greenhouse gas fluxes. Here we show that changes in vegetation and increasing methane emissions with permafrost thaw are associated with a switch from hydrogenotrophic to partly acetoclastic methanogenesis, resulting in a large shift in the δ13C signature (10–15‰) of emitted methane. We used a natural landscape gradient of permafrost thaw in northern Sweden4, 5 as a model to investigate the role of microbial communities in regulating methane cycling, and to test whether a knowledge of community dynamics could improve predictions of carbon emissions under loss of permafrost. Abundance of the methanogen Candidatus ‘Methanoflorens stordalenmirensis6 is a key predictor of the shifts in methane isotopes, which in turn predicts the proportions of carbon emitted as methane and as carbon dioxide, an important factor for simulating the climate feedback associated with permafrost thaw in global models3, 7. By showing that the abundance of key microbial lineages can be used to predict atmospherically relevant patterns in methane isotopes and the proportion of carbon metabolized to methane during permafrost thaw, we establish a basis for scaling changing microbial communities to ecosystem isotope dynamics. Our findings indicate that microbial ecology may be important in ecosystem-scale responses to global change.

  • 266. McElreath, Richard
    et al.
    Luttbeg, barney
    Fogarty, Sean P
    Brodin, Tomas
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Sih, Andrew
    Evolution of animal personalities2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 450, E5- p.Article in journal (Refereed)
  • 267. Mendenhall, Chase D.
    et al.
    Karp, Daniel S.
    Meyer, Christoph F. J.
    Hadly, Elizabeth A.
    Daily, Gretchen C.
    Stockholm University, Faculty of Science, Stockholm Resilience Centre. Royal Swedish Academy of Sciences, Sweden; Stanford University, USA.
    Predicting biodiversity change and averting collapse in agricultural landscapes2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 509, no 7499, 213-217 p.Article in journal (Refereed)
    Abstract [en]

    The equilibrium theory of island biogeography(1) is the basis for estimating extinction rates(2) and a pillar of conservation science(3,4). The default strategy for conserving biodiversity is the designation of nature reserves, treated as islands in an inhospitable sea of human activity(5). Despite the profound influence of islands on conservation theory and practice(3,4), their mainland analogues, forest fragments in human-dominated landscapes, consistently defy expected biodiversity patterns based on island biogeography theory(6-13). Countryside biogeography is an alternative framework, which recognizes that the fate of the world's wildlife will be decided largely by the hospitality of agricultural or countryside ecosystems(12,14-17). Here we directly test these biogeographic theories by comparing a Neotropical countryside ecosystem with a nearby island ecosystem, and show that each supports similar bat biodiversity in fundamentally different ways. The island ecosystem conforms to island biogeographic predictions of bat species loss, in which the water matrix is not habitat. In contrast, the countryside ecosystem has high species richness and evenness across forest reserves and smaller forest fragments. Relative to forest reserves and fragments, deforested countryside habitat supports a less species-rich, yet equally even, bat assemblage. Moreover, the bat assemblage associated with deforested habitat is compositionally novel because of predictable changes in abundances by many species using human-made habitat. Finally, we perform a global meta-analysis of bat biogeographic studies, spanning more than 700 species. It generalizes our findings, showing that separate biogeographic theories for countryside and island ecosystems are necessary. A theory of countryside biogeography is essential to conservation strategy in the agricultural ecosystems that comprise roughly half of the global land surface and are likely to increase even further(14).

  • 268. Merckx, Vincent S. F. T.
    et al.
    Hendriks, Kasper P.
    Beentjes, Kevin K.
    Mennes, Constantijn B.
    Becking, Leontine E.
    Peijnenburg, Katja T. C. A.
    Afendy, Aqilah
    Arumugam, Nivaarani
    de Boer, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Biun, Alim
    Buang, Matsain M.
    Chen, Ping-Ping
    Chung, Arthur Y. C.
    Dow, Rory
    Feijen, Frida A. A.
    Feijen, Hans
    Soest, Cobi Feijen-van
    Geml, Jozsef
    Geurts, Rene
    Gravendeel, Barbara
    Hovenkamp, Peter
    Imbun, Paul
    Ipor, Isa
    Janssens, Steven B.
    Jocque, Merlijn
    Kappes, Heike
    Khoo, Eyen
    Koomen, Peter
    Lens, Frederic
    Majapun, Richard J.
    Morgado, Luis N.
    Neupane, Suman
    Nieser, Nico
    Pereira, Joan T.
    Rahman, Homathevi
    Sabran, Suzana
    Sawang, Anati
    Schwallier, Rachel M.
    Shim, Phyau-Soon
    Smit, Harry
    Sol, Nicolien
    Spait, Maipul
    Stech, Michael
    Stokvis, Frank
    Sugau, John B.
    Suleiman, Monica
    Sumail, Sukaibin
    Thomas, Daniel C.
    van Tol, Jan
    Tuh, Fred Y. Y.
    Yahya, Bakhtiar E.
    Nais, Jamili
    Repin, Rimi
    Lakim, Maklarin
    Schilthuizen, Menno
    Evolution of endemismon a young tropical mountain2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, no 7565, 347-+ p.Article in journal (Refereed)
    Abstract [en]

    Tropical mountains are hot spots of biodiversity and endemism(1-3), but the evolutionary origins of their unique biotas are poorly understood(4). In varying degrees, local and regional extinction, long-distance colonization, and local recruitment may all contribute to the exceptional character of these communities(5). Also, it is debated whether mountain endemics mostly originate from local lowland taxa, or from lineages that reach the mountain by long-range dispersal from cool localities elsewhere(6). Here we investigate the evolutionary routes to endemism by sampling an entire tropical mountain biota on the 4,095-metre-high Mount Kinabalu in Sabah, East Malaysia. We discover that most of its unique biodiversity is younger than the mountain itself (6 million years), and comprises a mix of immigrant pre-adapted lineages and descendants from local lowland ancestors, although substantial shifts from lower to higher vegetation zones in this latter group were rare. These insights could improve forecasts of the likelihood of extinction and 'evolutionary rescue'(7) in montane biodiversity hot spots under climate change scenarios.

  • 269. Middleton, Matthew J.
    et al.
    Miller-Jones, James C. A.
    Markoff, Sera
    Fender, Rob
    Henze, Martin
    Hurley-Walker, Natasha
    Scaife, Anna M. M.
    Roberts, Timothy P.
    Walton, Dominic
    Carpenter, John
    Macquart, Jean-Pierre
    Bower, Geoffrey C.
    Gurwell, Mark
    Pietsch, Wolfgang
    Haberl, Frank
    Harris, Jonathan
    Daniel, Michael
    Miah, Junayd
    Done, Chris
    Morgan, John S.
    Dickinson, Hugh
    Stockholm University, Faculty of Science, Department of Physics. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Charles, Phil
    Burwitz, Vadim
    Della Valle, Massimo
    Freyberg, Michael
    Greiner, Jochen
    Hernanz, Margarita
    Hartmann, Dieter H.
    Hatzidimitriou, Despina
    Riffeser, Arno
    Sala, Gloria
    Seitz, Stella
    Reig, Pablo
    Rau, Arne
    Orio, Marina
    Titterington, David
    Grainge, Keith
    Bright radio emission from an ultraluminous stellar-mass microquasar in M 312013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 493, no 7431, 187-190 p.Article in journal (Refereed)
    Abstract [en]

    A subset of ultraluminous X-ray sources (those with luminosities of less than 10(40) erg s(-1); ref. 1) are thought to be powered by the accretion of gas onto black holes with masses of similar to 5-20M(circle dot), probably by means of an accretion disk(2,3). The X-ray and radio emission are coupled in such Galactic sources; the radio emission originates in a relativistic jet thought to be launched from the innermost regions near the black hole(4,5), with the most powerful emission occurring when the rate of infalling matter approaches a theoretical maximum (the Eddington limit). Only four such maximal sources are known in the Milky Way(6), and the absorption of soft X-rays in the interstellar medium hinders the determination of the causal sequence of events that leads to the ejection of the jet. Here we report radio and X-ray observations of a bright new X-ray source in the nearby galaxy M 31, whose peak luminosity exceeded 10(39) erg s(-1). The radio luminosity is extremely high and shows variability on a timescale of tens of minutes, arguing that the source is highly compact and powered by accretion close to the Eddington limit onto a black hole of stellar mass. Continued radio and X-ray monitoring of such sources should reveal the causal relationship between the accretion flow and the powerful jet emission.

  • 270.
    Mikkelsen, Tarjei
    et al.
    Broad Institute.
    Hillier, LaDeana
    Washington University School of Medicine, Genome Sequencing Center.
    Eichler, Evan
    University of Washington, Department of Genome Sciences.
    Zody, Michael
    Broad Institute.
    Jaffe, David
    Broad Institute.
    Yang, Shiaw-Pyng
    Washington University School of Medicine, Genome Sequencing Center.
    Enard, Wolfgang
    Max Planck Institute of Evolutionary Anthropology.
    Hellmann, Ines
    Max Planck Institute of Evolutionary Anthropology.
    Lindblad-Toh, Kerstin
    Broad Institute.
    Altheide, Tasha
    University of California, San Diego.
    Archidiacono, Nicoletta
    University of Bari, Department of Genetics and Microbiology.
    Bork, Peer
    EMBL.
    Butler, Jonathan
    Broad Institute.
    Chang, Jean
    Broad Institute.
    Cheng, Ze
    University of Washington, Department of Genome Sciences.
    Chinwalla, Asif
    Washington University School of Medicine, Genome Sequencing Center.
    de Jong, Pieter
    Children's Hospital Oakland Research Institute.
    Delehaunty, Kimberley
    Washington University School of Medicine, Genome Sequencing Center.
    Fronick, Catrina
    Washington University School of Medicine, Genome Sequencing Center.
    Fulton, Lucinda
    Washington University School of Medicine, Genome Sequencing Center.
    Gilad, Yoav
    Yale University School of Medicine, Department of Genetics.
    Glusman, Gustavo
    Institute for Systems Biology.
    Gnerre, Sante
    Broad Institute.
    Graves, Tina
    Washington University School of Medicine, Genome Sequencing Center.
    Hayakawa, Toshiyuki
    University of California, San Diego.
    Hayden, Karen
    Case Western Reserve University, Department of Genetics.
    Huang, Xiaoqiu
    Iowa State University, Department of Computer Science.
    Ji, Hongkai
    Harvard University, Department of Statistics.
    Kent, W.
    University of California, Santa Cruz, Center for Biomolecular Science and Engineering.
    King, Mary-Claire
    University of Washington, Department of Genome Sciences.
    Kulbokas, Edward
    Broad Institute.
    Lee, Ming
    University of Washington, Department of Genome Sciences.
    Liu, Ge
    Case Western Reserve University, Department of Genetics.
    Lopez-Otin, Carlos
    Universidad de Oviedo, Instituto Universitario de Oncologia del Principado de Asturias, Departamento de Bioquimica y Biologia Molecular.
    Makova, Kateryna
    The Pennsylvania State University, Center for Comparative Genomics and Bioinformatics and Department of Biology.
    Man, Orna
    Weizmann Institute of Science, Department of Structural Biology.
    Mardis, Elaine
    Washington University School of Medicine, Genome Sequencing Center.
    Mauceli, Evan
    Broad Institute.
    Miner, Tracie
    Washington University School of Medicine, Genome Sequencing Center.
    Nash, illiam
    Washington University School of Medicine, Genome Sequencing Center.
    Nelson, Joanne
    Washington University School of Medicine, Genome Sequencing Center.
    Pääbo, Svante
    Max Planck Institute of Evolutionary Anthropology.
    Patterson, Nick
    Broad Institute.
    Pohl, Craig
    Washington University School of Medicine, Genome Sequencing Center.
    Pollard, Katherine
    University of California, Santa Cruz, Center for Biomolecular Science and Engineering.
    Prüfer, Kay
    Max Planck Institute for Evolutionary Anthropology.
    Puente, Xose
    Universidad de Oviedo, Instituto Universitario de Oncologia del Principado de Asturias, Departamento de Bioquimica y Biologia Molecular.
    Reich, David
    Broad Institute.
    Rocchi, Mariano
    University of Bari, Department of Genetics and Microbiology.
    Rosenbloom, Kate
    University of California, Santa Cruz, Center for Biomolecular Science and Engineering.
    Ruvolo, Maryellen
    Harvard University, Department of Anthropology and of Organismic and Evolutionary Biology.
    Richter, Daniel
    Broad Institute.
    Schaffner, Stephen
    Broad Institute.
    Smit, Arian
    Institute for Systems Biology.
    Smith, Scott
    Washington University School of Medicine, Genome Sequencing Center.
    Suyama, Mikita
    EMBL.
    Taylor, James
    The Pennsylvania State University, Center for Comparative Genomics and Bioinformatics and Department of Biology.
    Torrents, David
    EMBL.
    Tuzun, Eray
    University of Washington, Department of Genome Sciences.
    Varki, Ajit
    University of California, San Diego.
    Velasco, Gloria
    Universidad de Oviedo, Instituto Universitario de Oncologia del Principado de Asturias, Departamento de Bioquimica y Biologia Molecular.
    Ventura, Mario
    University of Bari, Department of Genetics and Microbiology.
    Wallis, John
    Washington University School of Medicine, Genome Sequencing Center.
    Wendl, Michael
    Washington University School of Medicine, Genome Sequencing Center.
    Wilson, Richard
    Washington University School of Medicine, Genome Sequencing Center.
    Lander, Eric
    Broad Institute.
    Waterston, Robert
    University of Washington, Department of Genome Sciences.
    Initial sequence of the chimpanzee genome and comparison with the human genome2005In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 437, no 7055, 69-87 p.Article in journal (Refereed)
    Abstract [en]

    Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences that have accumulated since the human and chimpanzee species diverged from our common ancestor, constituting approximately thirty-five million single-nucleotide changes, five million insertion/deletion events, and various chromosomal rearrangements. We use this catalogue to explore the magnitude and regional variation of mutational forces shaping these two genomes, and the strength of positive and negative selection acting on their genes. In particular, we find that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles. We also use the chimpanzee genome as an outgroup to investigate human population genetics and identify signatures of selective sweeps in recent human evolution.

  • 271. Mikkelsen, Tarjei S
    et al.
    Wakefield, Matthew J
    Aken, Bronwen
    Amemiya, Chris T
    Chang, Jean L
    Duke, Shannon
    Garber, Manuel
    Gentles, Andrew J
    Goodstadt, Leo
    Heger, Andreas
    Jurka, Jerzy
    Kamal, Michael
    Mauceli, Evan
    Searle, Stephen M J
    Sharpe, Ted
    Baker, Michelle L
    Batzer, Mark A
    Benos, Panayiotis V
    Belov, Katherine
    Clamp, Michele
    Cook, April
    Cuff, James
    Das, Radhika
    Davidow, Lance
    Deakin, Janine E
    Fazzari, Melissa J
    Glass, Jacob L
    Grabherr, Manfred
    Greally, John M
    Gu, Wanjun
    Hore, Timothy A
    Huttley, Gavin A
    Kleber, Michael
    Jirtle, Randy L
    Koina, Edda
    Lee, Jeannie T
    Mahony, Shaun
    Marra, Marco A
    Miller, Robert D
    Nicholls, Robert D
    Oda, Mayumi
    Papenfuss, Anthony T
    Parra, Zuly E
    Pollock, David D
    Ray, David A
    Schein, Jacqueline E
    Speed, Terence P
    Thompson, Katherine
    VandeBerg, John L
    Wade, Claire M
    Walker, Jerilyn A
    Waters, Paul D
    Webber, Caleb
    Weidman, Jennifer R
    Xie, Xiaohui
    Zody, Michael C
    Graves, Jennifer A Marshall
    Ponting, Chris P
    Breen, Matthew
    Samollow, Paul B
    Lander, Eric S
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 447, no 7141, 167-177 p.Article in journal (Refereed)
    Abstract [en]

    We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.

  • 272. Miller, Webb
    et al.
    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
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lander, Eric S
    Knight, James R
    Irzyk, Gerard P
    Fredrikson, Karin M
    Harkins, Timothy T
    Sheridan, Sharon
    Pringle, Tom
    Schuster, Stephan C
    Sequencing the nuclear genome of the extinct woolly mammoth.2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 456, no 7220, 387-390 p.Article in journal (Refereed)
    Abstract [en]

    In 1994, two independent groups extracted DNA from several Pleistocene epoch mammoths and noted differences among individual specimens. Subsequently, DNA sequences have been published for a number of extinct species. However, such ancient DNA is often fragmented and damaged, 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 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.

  • 273. Miniati, Francesco
    et al.
    Beresnyak, Andrey
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Self-similar energetics in large clusters of galaxies2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 523, no 7558, 59-+ p.Article in journal (Refereed)
    Abstract [en]

    Massive galaxy clusters are filled with a hot, turbulent and magnetized intra-cluster medium. Still forming under the action of gravitational instability, they grow in mass by accretion of supersonic flows. These flows partially dissipate into heat through a complex network of large-scale shocks(1), while residual transonic (near-sonic) flows create giant turbulent eddies and cascades(2,3). Turbulence heats the intra-cluster medium(4) and also amplifies magnetic energy by way of dynamo action(5-8). However, the pattern regulating the transformation of gravitational energy into kinetic, thermal, turbulent and magnetic energies remains unknown. Here we report that the energy components of the intra-cluster medium are ordered according to a permanent hierarchy, in which the ratio of thermal to turbulent to magnetic energy densities remains virtually unaltered throughout the cluster's history, despite evolution of each individual component and the drive towards equipartition of the turbulent dynamo. This result revolves around the approximately constant efficiency of turbulence generation from the gravitational energy that is freed during mass accretion, revealed by our computational model of cosmological structure formation(3,9). The permanent character of this hierarchy reflects yet another type of self-similarity in cosmology(10-13), while its structure, consistent with current data(14-18), encodes information about the efficiency of turbulent heating and dynamo action.

  • 274. Miniati, Francesco
    et al.
    Beresnyak, Andrey
    Stockholm University, Nordic Institute for Theoretical Physics (Nordita).
    Self-similar energetics in large clusters of galaxies2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 523, no 7558, 59-+ p.Article in journal (Refereed)
    Abstract [en]

    Massive galaxy clusters are filled with a hot, turbulent and magnetized intra-cluster medium. Still forming under the action of gravitational instability, they grow in mass by accretion of supersonic flows. These flows partially dissipate into heat through a complex network of large-scale shocks(1), while residual transonic (near-sonic) flows create giant turbulent eddies and cascades(2,3). Turbulence heats the intra-cluster medium(4) and also amplifies magnetic energy by way of dynamo action(5-8). However, the pattern regulating the transformation of gravitational energy into kinetic, thermal, turbulent and magnetic energies remains unknown. Here we report that the energy components of the intra-cluster medium are ordered according to a permanent hierarchy, in which the ratio of thermal to turbulent to magnetic energy densities remains virtually unaltered throughout the cluster's history, despite evolution of each individual component and the drive towards equipartition of the turbulent dynamo. This result revolves around the approximately constant efficiency of turbulence generation from the gravitational energy that is freed during mass accretion, revealed by our computational model of cosmological structure formation(3,9). The permanent character of this hierarchy reflects yet another type of self-similarity in cosmology(10-13), while its structure, consistent with current data(14-18), encodes information about the efficiency of turbulent heating and dynamo action.

  • 275.
    Moor, Kathrin
    et al.
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland.;Univ Zurich, Ctr Dent Med, Zurich, Switzerland..
    Diard, Mederic
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Sellin, Mikael E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Felmy, Boas
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Wotzka, Sandra Y.
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Toska, Albulena
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Bakkeren, Erik
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Arnoldini, Markus
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Bansept, Florence
    CNRS UPMC, Lab Jean Perrin, UMR 8237, F-75005 Paris, France..
    Dal Co, Alma
    ETH, Dept Environm Syst Sci, Zurich, Switzerland.;Swiss Fed Inst Aquat Sci & Technol, Eawag, Dept Environm Microbiol, Dubendorf, Switzerland..
    Voller, Tom
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Minola, Andrea
    Humabs BioMed SA, CH-6500 Bellinzona, Switzerland..
    Fernandez-Rodriguez, Blanca
    Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland..
    Agatic, Gloria
    Humabs BioMed SA, CH-6500 Bellinzona, Switzerland..
    Barbieri, Sonia
    Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland..
    Piccoli, Luca
    Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland..
    Casiraghi, Costanza
    Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland.;Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy..
    Corti, Davide
    Humabs BioMed SA, CH-6500 Bellinzona, Switzerland..
    Lanzavecchia, Antonio
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland.;Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland..
    Regoes, Roland R.
    ETH, Inst Integrat Biol, CH-8092 Zurich, Switzerland..
    Loverdo, Claude
    CNRS UPMC, Lab Jean Perrin, UMR 8237, F-75005 Paris, France..
    Stocker, Roman
    ETH, Dept Civil Environm & Geomat Engn, Inst Environm Engn, CH-8093 Zurich, Switzerland..
    Brumley, Douglas R.
    ETH, Dept Civil Environm & Geomat Engn, Inst Environm Engn, CH-8093 Zurich, Switzerland.;Univ Melbourne, Sch Math & Stat, Parkville, Vic 3010, Australia..
    Hardt, Wolf-Dietrich
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    Slack, Emma
    ETH, Inst Microbiol, CH-8093 Zurich, Switzerland..
    High-avidity IgA protects the intestine by enchaining growing bacteria2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 544, no 7651, 498-+ p.Article in journal (Refereed)
    Abstract [en]

    Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by directly neutralizing virulence factors or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues ('immune exclusion')(1-3). IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (>= 10(8) non-motile bacteria per gram). In typical infections, much lower densities(4,5) (10(0)-10(7) colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo. Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.

  • 276.
    Moore, R.L.
    et al.
    Owens Valley Radio Observatory, California Institute of Technology, Pasadena, USA.
    Readhead, A.C.S.
    Owens Valley Radio Observatory, California Institute of Technology, Pasadena, USA.
    Bååth, L.B.
    Onsala Space Observatory, Chalmers University of Technology, Gothenburg, Sweden.
    Superluminal Acceleration in 3C3451983In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 306, no 5938, 44-46 p.Article in journal (Refereed)
    Abstract [en]

    The superluminal quasar 3C345 has a curved, one-sided jet-like radio structure1,2. Ejected material has been observed travelling at apparent speeds of 13–17c (ref. 3). We report here new observations at 22 GHz which show that the most recently ejected component4 is not moving radially away from the compact radio core, but along a trajectory which could be interpreted as either a curved path originating in the compact core, or a straight line, in which case the origin of ejection is not coincident with the compact radio core. The observations provide evidence of acceleration of this component. © 1983 Nature Publishing Group.

  • 277. Moran, Kathryn
    et al.
    Backman, Jan
    Brinkhuis, Henk
    Clemens, Steven C.
    Cronin, Thomas
    Dickens, Gerald R.
    Eynaud, Frederique
    Gattacceca, Jerome
    Jakobsson, Martin
    Jordan, Richard W.
    Kaminski, Michael
    King, John
    Koc, Nalan
    Krylov, Alexey
    Martinez, Nahysa
    Matthiessen, Jens
    McInroy, David
    Moore, Theodore C.
    Onodera, Jonaotaro
    O’Regan, Matthew
    Palike, Heiko
    Rea, Brice
    Rio, Domenico
    Sakamoto, Tatsuhiko
    Smith, David C.
    Stein, Ruediger
    St John, Kristen
    Suto, Itsuki
    Suzuki, Noritoshi
    Takahashi, Kozo
    Watanabe, Mahito
    Yamamoto, Masanobu
    Farrell, John
    Frank, Martin
    Kubik, Peter
    Jokat, Wilfried
    Kristoffersen, Yngve
    The Cenozoic palaeoenvironment of the Arctic Ocean2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 441, no 7093, 601-605 p.Article in journal (Refereed)
    Abstract [en]

    The history of the Arctic Ocean during the Cenozoic era ( 0 - 65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm ‘greenhouse’ world, during the late Palaeocene and early Eocene epochs, to a colder ‘icehouse’ world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent similar to 14 Myr, we find sedimentation rates of 1 - 2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (similar to 3.2 Myr ago) and East Antarctic ice (similar to 14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (similar to 45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at,49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (similar to 55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.

  • 278. Naveira Garabato, Alberto C.
    et al.
    Forryan, Alexander
    Dutrieux, Pierre
    Brannigan, Liam
    Stockholm University, Faculty of Science, Department of Meteorology .
    Biddle, Louise C.
    Heywood, Karen J.
    Jenkins, Adrian
    Firing, Yvonne L.
    Kimura, Satoshi
    Vigorous lateral export of the meltwater outflow from beneath an Antarctic ice shelf2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 542, no 7640, 219-222 p.Article in journal (Refereed)
    Abstract [en]

    The instability and accelerated melting of the Antarctic Ice Sheet are among the foremost elements of contemporary global climate change la. The increased freshwater output from Antarctica is important in determining sea level rise(1,3), the fate of Antarctic sea ice and its effect on the Earth's albedo(4,5), ongoing changes in global deep-ocean ventilation(3,6), and the evolution of Southern Ocean ecosystems and carbon cycling(7,8). A key uncertainty in assessing and predicting the impacts of Antarctic Ice Sheet melting concerns the vertical distribution of the exported meltwater. This is usually represented by climate-scale models(3-5,9) as a near-surface freshwater input to the ocean, yet measurements around Antarctica reveal the meltwater to be concentrated at deeper levels(10-14). Here we use observations of the turbulent properties of the meltwater outflows from beneath a rapidly melting Antarctic ice shelf to identify the mechanism responsible for the depth of the meltwater. We show that the initial ascent of the meltwater outflow from the ice shelf cavity triggers a centrifugal overturning instability that grows by extracting kinetic energy from the lateral shear of the background oceanic flow. The instability promotes vigorous lateral export, rapid dilution by turbulent mixing, and finally settling of meltwater at depth. We use an idealized ocean circulation model to show that this mechanism is relevant to a broad spectrum of Antarctic ice shelves. Our findings demonstrate that the mechanism producing meltwater at depth is a dynamically robust feature of Antarctic melting that should be incorporated into climate-scale models.

  • 279. Negre, Nicolas
    et al.
    Brown, Christopher D.
    Ma, Lijia
    Bristow, Christopher Aaron
    Miller, Steven W.
    Wagner, Ulrich
    Kheradpour, Pouya
    Eaton, Matthew L.
    Loriaux, Paul
    Sealfon, Rachel
    Li, Zirong
    Ishii, Haruhiko
    Spokony, Rebecca F.
    Chen, Jia
    Hwang, Lindsay
    Cheng, Chao
    Auburn, Richard P.
    Davis, Melissa B.
    Domanus, Marc
    Shah, Parantu K.
    Morrison, Carolyn A.
    Zieba, Jennifer
    Suchy, Sarah
    Senderowicz, Lionel
    Victorsen, Alec
    Bild, Nicholas A.
    Grundstad, A. Jason
    Hanley, David
    MacAlpine, David M.
    Mannervik, Mattias
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Developmental Biology.
    Venken, Koen
    Bellen, Hugo
    White, Robert
    Gerstein, Mark
    Russell, Steven
    Grossman, Robert L.
    Ren, Bing
    Posakony, James W.
    Kellis, Manolis
    White, Kevin P.
    A cis-regulatory map of the Drosophila genome2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 471, no 7339, 527-531 p.Article in journal (Refereed)
    Abstract [en]

    Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide(1,2) has successfully identified specific subtypes of regulatory elements(3). In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements(4), chromatin states(5), transcription factor binding sites(6-9), RNA polymerase II regulation(8) and insulator elements(10); however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships.

  • 280.
    Nesbitt, Sterling J.
    et al.
    Virginia Tech, Dept Geosci, Blacksburg, VA 24061 USA..
    Butler, Richard J.
    Univ Birmingham, Sch Geog Earth & Environm Sci, Birmingham B15 2TT, W Midlands, England..
    Ezcurra, Martin D.
    Univ Birmingham, Sch Geog Earth & Environm Sci, Birmingham B15 2TT, W Midlands, England.;Museo Argentino Ciencias Nat Bernardino Rivadavia, CONICET, Secc Paleontol Vertebrados, Buenos Aires, DF, Argentina..
    Barrett, Paul M.
    Nat Hist Museum, Dept Earth Sci, Cromwell Rd, London SW7 5BD, England..
    Stocker, Michelle R.
    Virginia Tech, Dept Geosci, Blacksburg, VA 24061 USA..
    Angielczyk, Kenneth D.
    Field Museum Nat Hist, Integrat Res Ctr, 1400 South Lake Shore Dr, Chicago, IL 60605 USA..
    Smith, Roger M. H.
    Univ Witwatersrand, Evolutionary Studies Inst, PO Wits 2050, Johannesburg, South Africa.;Iziko South African Museum, POB 61, Cape Town, South Africa..
    Sidor, Christian A.
    Univ Washington, Burke Museum, Seattle, WA 98195 USA.;Univ Washington, Dept Biol, Seattle, WA 98195 USA..
    Niedzwiedzki, Grzegorz
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Sennikov, Andrey G.
    Russian Acad Sci, Borissiak Paleontol Inst, Profsoyuznaya 123, Moscow 117997, Russia.;Kazan Fed Univ, Kremlyovskaya Ul 18, Kazan 420008, Russia..
    Charig, Alan J.
    Nat Hist Museum, Dept Earth Sci, Cromwell Rd, London SW7 5BD, England..
    The earliest bird-line archosaurs and the assembly of the dinosaur body plan2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 544, no 7651, 484-+ p.Article in journal (Refereed)
    Abstract [en]

    The relationship between dinosaurs and other reptiles is well established(1-4), but the sequence of acquisition of dinosaurian features has been obscured by the scarcity of fossils with transitional morphologies. The closest extinct relatives of dinosaurs either have highly derived morphologies(5-7) or are known from poorly preserved(8,9) or incomplete material(10,11). Here we describe one of the stratigraphically lowest and phylogenetically earliest members of the avian stem lineage (Avemetatarsalia), Teleocrater rhadinus gen. et sp. nov., from the Middle Triassic epoch. The anatomy of T. rhadinus provides key information that unites several enigmatic taxa from across Pangaea into a previously unrecognized clade, Aphanosauria. This clade is the sister taxon of Ornithodira (pterosaurs and birds) and shortens the ghost lineage inferred at the base of Avemetatarsalia. We demonstrate that several anatomical features long thought to characterize Dinosauria and dinosauriforms evolved much earlier, soon after the bird-crocodylian split, and that the earliest avemetatarsalians retained the crocodylian-like ankle morphology and hindlimb proportions of stem archosaurs and early pseudosuchians. Early avemetatarsalians were substantially more species-rich, widely geographically distributed and morphologically diverse than previously recognized. Moreover, several early dinosauromorphs that were previously used as models to understand dinosaur origins may represent specialized forms rather than the ancestral avemetatarsalian morphology.

  • 281. Nicholl, M.
    et al.
    Smartt, S. J.
    Jerkstrand, A.
    Inserra, C.
    McCrum, M.
    Kotak, R.
    Fraser, M.
    Wright, D.
    Chen, T-W
    Smith, K.
    Young, D. R.
    Sim, S. A.
    Valenti, S.
    Howell, D. A.
    Bresolin, F.
    Kudritzki, R. P.
    Tonry, J. L.
    Huber, M. E.
    Rest, A.
    Pastorello, A.
    Tomasella, L.
    Cappellaro, E.
    Benetti, S.
    Mattila, S.
    Kankare, E.
    Kangas, T.
    Leloudas, Georgios
    Stockholm University, Faculty of Science, Department of Physics. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC). University of Copenhagen, Denmark.
    Sollerman, Jesper
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Taddia, Francesco
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Berger, E.
    Chornock, R.
    Narayan, G.
    Stubbs, C. W.
    Foley, R. J.
    Lunnan, R.
    Söderberg, A.
    Sanders, N.
    Milisavljevic, D.
    Margutti, R.
    Kirshner, R. P.
    Elias-Rosa, N.
    Morales-Garoffolo, A.
    Taubenberger, S.
    Botticella, M. T.
    Gezari, S.
    Urata, Y.
    Rodney, S.
    Riess, A. G.
    Scolnic, D.
    Wood-Vasey, W. M.
    Burgett, W. S.
    Chambers, K.
    Flewelling, H. A.
    Magnier, E. A.
    Kaiser, N.
    Metcalfe, N.
    Morgan, J.
    Price, P. A.
    Sweeney, W.
    Waters, C.
    Slowly fading super-luminous supernovae that are not pair-instability explosions2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 502, no 7471, 346-+ p.Article in journal (Refereed)
    Abstract [en]

    Super-luminous supernovae(1-4) that radiate more than 1044 ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae(5,6). Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of Ni-56 are synthesized; this isotope decays to Fe-56 via Co-56, powering bright light curves(7,8). Such massive progenitors are expected to have formed from metal-poor gas in the early Universe(9). Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova(1,10). Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae(2,11,12), which are not powered by radio-activity. Modelling our observations with 10-16 solar masses of magnetar-energized(13,14) ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 x 10(-6) times that of the core-collapse rate.

  • 282. Niedzwiedzki, Grzegorz
    et al.
    Szrek, Piotr
    Narkiewicz, Katarzyna
    Narkiewicz, Marek
    Ahlberg, Per Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolution and Developmental Biology.
    Tetrapod trackways from the early Middle Devonian period of Poland2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 463, no 7277, 43-48 p.Article in journal (Refereed)
    Abstract [en]

    The fossil record of the earliest tetrapods (vertebrates with limbs rather than paired fins) consists of body fossils and trackways. The earliest body fossils of tetrapods date to the Late Devonian period (late Frasnian stage) and are preceded by transitional elpistostegids such as Panderichthys and Tiktaalik that still have paired fins. Claims of tetrapod trackways predating these body fossils have remained controversial with regard to both age and the identity of the track makers. Here we present well-preserved and securely dated tetrapod tracks from Polish marine tidal flat sediments of early Middle Devonian (Eifelian stage) age that are approximately 18 million years older than the earliest tetrapod body fossils and 10 million years earlier than the oldest elpistostegids. They force a radical reassessment of the timing, ecology and environmental setting of the fish-tetrapod transition, as well as the completeness of the body fossil record.

  • 283.
    Niegowski, Damian
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Martinez, Daniel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Wetterholm, Anders
    Kohl, Andreas
    McCarthy, Andrew
    Ohlson, Eva
    Hammarberg, Tove
    Häggström, Jesper
    Nordlund, Pär
    Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 448, no 7153, 613-616 p.Article in journal (Refereed)
    Abstract [en]

    Cysteinyl leukotrienes are key mediators in inflammation and have an important role in acute and chronic inflammatory diseases of the cardiovascular and respiratory systems, in particular bronchial asthma. In the biosynthesis of cysteinyl leukotrienes, conversion of arachidonic acid forms the unstable epoxide leukotriene A4 (LTA4). This intermediate is conjugated with glutathione (GSH) to produce leukotriene C4 (LTC4) in a reaction catalysed by LTC4 synthase1: this  eaction is the key step in cysteinyl leukotriene formation. Here we present the rystal structure of the human LTC4 synthase in its apo and GSH-complexed forms to 2.00 and 2.15 A ̊resolution, respectively. The structure reveals a homotrimer,  here each monomer is composed of four transmembrane segments. The structure of the enzyme in complex with substrate reveals that the active site enforces a  orseshoe-shaped conformation on GSH, and effectively positions the thiol group or activation by a nearby arginine at the membrane–enzyme interface. In addition, the structure provides a model for how the v-end of the lipophilic co-substrate is pinned at one end of a hydrophobic cleft, providing a molecular ‘ruler’ to align the  eactive epoxide at the thiol of glutathione. This provides new structural insights nto the mechanism of LTC4 formation, and also suggests that the observed inding and activation of GSH might be common for a family of homologous proteins mportant for inflammatory and detoxification responses.

  • 284.
    Nielsen, Rasmus
    et al.
    Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.;Univ Calif Berkeley, Dept Stat, Berkeley, CA USA.;Univ Copenhagen, Ctr GeoGenet, Nat Hist Museum Denmark, DK-1350 Copenhagen K, Denmark..
    Akey, Joshua M.
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA..
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Pritchard, Jonathan K.
    Stanford Univ, Dept Genet, Stanford, CA 94305 USA.;Stanford Univ, Dept Biol, Stanford, CA 94305 USA.;Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA..
    Tishkoff, Sarah
    Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.;Univ Penn, Dept Biol, Philadelphia, PA 19104 USA..
    Willerslev, Eske
    Univ Copenhagen, Ctr GeoGenet, Nat Hist Museum Denmark, DK-1350 Copenhagen K, Denmark.;Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Tracing the peopling of the world through genomics2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 541, no 7637, 302-310 p.Article, review/survey (Refereed)
    Abstract [en]

    Advances in the sequencing and the analysis of the genomes of both modern and ancient peoples have facilitated a number of breakthroughs in our understanding of human evolutionary history. These include the discovery of interbreeding between anatomically modern humans and extinct hominins; the development of an increasingly detailed description of the complex dispersal of modern humans out of Africa and their population expansion worldwide; and the characterization of many of the genetic adaptions of humans to local environmental conditions. Our interpretation of the evolutionary history and adaptation of humans is being transformed by analyses of these new genomic data.

  • 285.
    Nilsson, Christer
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Flood warnings: [review of "The future of large dams" by T. Scudder]2005In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 435, no 7045, 1031-1031 p.Article, book review (Other academic)
  • 286.
    Nilsson, Måns
    et al.
    KTH, School of Architecture and the Built Environment (ABE), Sustainable development, Environmental science and Engineering.
    Griggs, D.
    Visbeck, M.
    Erratum: Create a global microbiome effort (Nature (2015) 526 631-634))2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 534, no 7607Article in journal (Refereed)
  • 287.
    Nilsson, Måns
    et al.
    KTH, School of Architecture and the Built Environment (ABE), Sustainable development, Environmental science and Engineering, Environmental Strategies Research (fms). Stockholm Environment Institute, Sweden.
    Griggs, Dave
    Visbeck, Martin
    Map the interactions between Sustainable Development Goals2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 534, no 7607, 320-322 p.Article in journal (Refereed)
  • 288. Nomura, Norimichi
    et al.
    Verdon, Gregory
    Kang, Hae Joo
    Shimamura, Tatsuro
    Nomura, Yayoi
    Sonoda, Yo
    Hussien, Saba Abdul
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Qureshi, Aziz Abdul
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Coincon, Mathieu
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Sato, Yumi
    Abe, Hitomi
    Nakada-Nakura, Yoshiko
    Hino, Tomoya
    Arakawa, Takatoshi
    Kusano-Arai, Osamu
    Iwanari, Hiroko
    Murata, Takeshi
    Kobayashi, Takuya
    Hamakubo, Takao
    Kasahara, Michihiro
    Iwata, So
    Drew, David
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Imperial College London, UK.
    Structure and mechanism of the mammalian fructose transporter GLUT52015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, no 7573, 397-+ p.Article in journal (Refereed)
    Abstract [en]

    The altered activity of the fructose transporter GLUT5, an isoform of the facilitated-diffusion glucose transporter family, has been linked to disorders such as type 2 diabetes and obesity. GLUT5 is also overexpressed in certain tumour cells, and inhibitors are potential drugs for these conditions. Here we describe the crystal structures of GLUT5 from Rattus norvegicus and Bos taurus in open outward-and open inward-facing conformations, respectively. GLUT5 has a major facilitator superfamily fold like other homologous monosaccharide transporters. On the basis of a comparison of the inward-facing structures of GLUT5 and human GLUT1, a ubiquitous glucose transporter, we show that a single point mutation is enough to switch the substrate-binding preference of GLUT5 from fructose to glucose. A comparison of the substrate-free structures of GLUT5 with occluded substrate-bound structures of Escherichia coli XylE suggests that, in addition to global rocker-switch-like re-orientation of the bundles, local asymmetric rearrangements of carboxy-terminal transmembrane bundle helices TM7 and TM10 underlie a 'gated-pore' transport mechanism in such monosaccharide transporters.

  • 289.
    Nordquist, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dabbling in science journalism2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 439, no 7077, 760-760 p.Article, book review (Other (popular science, discussion, etc.))
  • 290. Novak, R
    et al.
    Henriques, B
    Charpentier, E
    Normark, S
    Tuomanen, E
    Emergence of vancomycin tolerance in Streptococcus pneumoniae.1999In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 399, no 6736, 590-593 p.Article in journal (Refereed)
    Abstract [en]

    Streptococcus pneumoniae, the pneumococcus, is the most common cause of sepsis and meningitis. Multiple-antibiotic-resistant strains are widespread, and vancomycin is the antibiotic of last resort. Emergence of vancomycin resistance in this community-acquired bacterium would be catastrophic. Antibiotic tolerance, the ability of bacteria to survive but not grow in the presence of antibiotics, is a precursor phenotype to resistance. Here we show that loss of function of the VncS histidine kinase of a two-component sensor-regulator system in S. pneumoniae produced tolerance to vancomycin and other classes of antibiotic. Bacterial two-component systems monitor environmental parameters through a sensor histidine-kinase/phosphatase, which phosphorylates/dephosphorylates a response regulator that in turn mediates changes in gene expression. These results indicate that signal transduction is critical for the bactericidal activity of antibiotics. Experimental meningitis caused by the vncS mutant failed to respond to vancomycin. Clinical isolates tolerant to vancomycin were identified and DNA sequencing revealed nucleotide alterations in vncS. We conclude that broad antibiotic tolerance of S. pneumoniae has emerged in the community by a molecular mechanism that eliminates sensitivity to the current cornerstone of therapy, vancomycin.

  • 291. Nystedt, Bjorn
    et al.
    Street, Nathaniel R.
    Wetterbom, Anna
    Zuccolo, Andrea
    Lin, Yao-Cheng
    Scofield, Douglas G.
    Vezzi, Francesco
    Delhomme, Nicolas
    Giacomello, Stefania
    Alexeyenko, Andrey
    Vicedomini, Riccardo
    Sahlin, Kristoffer
    Sherwood, Ellen
    Elfstrand, Malin
    Gramzow, Lydia
    Holmberg, Kristina
    Hallman, Jimmie
    Keech, Olivier
    Klasson, Lisa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Koriabine, Maxim
    Kucukoglu, Melis
    Kaller, Max
    Luthman, Johannes
    Lysholm, Fredrik
    Niittyla, Totte
    Olson, Ake
    Rilakovic, Nemanja
    Ritland, Carol
    Rossello, Josep A.
    Sena, Juliana
    Svensson, Thomas
    Talavera-Lopez, Carlos
    Theissen, Guenter
    Tuominen, Hannele
    Vanneste, Kevin
    Wu, Zhi-Qiang
    Zhang, Bo
    Zerbe, Philipp
    Arvestad, Lars
    Bhalerao, Rishikesh
    Bohlmann, Joerg
    Bousquet, Jean
    Gil, Rosario Garcia
    Hvidsten, Torgeir R.
    de Jong, Pieter
    MacKay, John
    Morgante, Michele
    Ritland, Kermit
    Sundberg, Bjorn
    Thompson, Stacey Lee
    Van de Peer, Yves
    Andersson, Bjorn
    Nilsson, Ove
    Ingvarsson, Par K.
    Lundeberg, Joakim
    Jansson, Stefan
    The Norway spruce genome sequence and conifer genome evolution2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 497, no 7451, 579-584 p.Article in journal (Refereed)
    Abstract [en]

    Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

  • 292. Nystedt, Bjorn
    et al.
    Street, Nathaniel Robert
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Wetterbom, Anna
    Zuccolo, Andrea
    Lin, Yao-Cheng
    Scofield, Douglas G.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Vezzi, Francesco
    Delhomme, Nicolas
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Giacomello, Stefania
    Alexeyenko, Andrey
    Vicedomini, Riccardo
    Sahlin, Kristoffer
    Sherwood, Ellen
    Elfstrand, Malin
    Gramzow, Lydia
    Holmberg, Kristina
    Hallman, Jimmie
    Keech, Olivier
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Klasson, Lisa
    Koriabine, Maxim
    Kucukoglu, Melis
    Kaller, Max
    Luthman, Johannes
    Lysholm, Fredrik
    Niittyla, Totte
    Olson, Ake
    Rilakovic, Nemanja
    Ritland, Carol
    Rossello, Josep A.
    Sena, Juliana
    Svensson, Thomas
    Talavera-Lopez, Carlos
    Theissen, Guenter
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Vanneste, Kevin
    Wu, Zhi-Qiang
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Zhang, Bo
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Zerbe, Philipp
    Arvestad, Lars
    Bhalerao, Rishikesh
    Bohlmann, Joerg
    Bousquet, Jean
    Gil, Rosario Garcia
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    de Jong, Pieter
    MacKay, John
    Morgante, Michele
    Ritland, Kermit
    Sundberg, Bjorn
    Thompson, Stacey Lee
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Van de Peer, Yves
    Andersson, Bjorn
    Nilsson, Ove
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lundeberg, Joakim
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    The Norway spruce genome sequence and conifer genome evolution2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 497, no 7451, 579-584 p.Article in journal (Refereed)
    Abstract [en]

    Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

  • 293.
    Nystedt, Björn
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Sherwood, Ellen
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Zerbe, Philipp
    Arvestad, Lars
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA).
    Jansson, Stefan
    The Norway spruce genome sequence and conifer genome evolution2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 497, no 7451, 579-584 p.Article in journal (Refereed)
    Abstract [en]

    Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

  • 294.
    Nystedt, Björn
    et al.
    Stockholm University.
    Vezzi, Francesco
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Alekseenko, Andrey
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sahlin, Kristoffer
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hällman, Jimmie
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Käller, Max
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Rilakovic, Nemanja
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Arvestad, Lars
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    et, al,
    The Norway spruce genome sequence and conifer genome evolution2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 497, no 7451, 579-584 p.Article in journal (Refereed)
    Abstract [en]

    Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

  • 295. Näsholm, Torgny
    et al.
    Ekblad, Alf
    Örebro University, Department of Natural Sciences.
    Nordin, Annika
    Giesler, Reiner
    Högberg, Mona
    Högberg, Peter
    Boreal forest plants take up organic nitrogen1998In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 392, no 6679, 914-916 p.Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Plant growth in the boreal forest, the largest terrestrial biome, is generally limited by the availability of nitrogen. The presumed cause of this limitation is slow mineralization of soil organic nitrogen1,2. Here we demonstrate, to our knowledge for the first time, the uptake of organic nitrogen in the field by the trees Pinus sylvestris and Picea abies, the dwarf shrub Vaccinium myrtillus and the grass Deschampsia flexuosa. These results show that these plants, irrespective of their different types of root–fungal associations (mycorrhiza), bypass nitrogen mineralization. A trace of the amino acid glycine, labelled with the stable isotopes 13C and 15N, was injected into the organic (mor) layer of an old successional boreal coniferous forest. Ratios of 13C:15N in the roots showed that at least 91, 64 and 42% of the nitrogen from the absorbed glycine was taken up in intact glycine by the dwarf shrub, the grass and the trees, respectively. Rates of glycine uptake were similar to those of 15N-ammonium. Our data indicate that organic nitrogen is important for these different plants, even when they are competing with each other and with non-symbiotic microorganisms. This has major implications for our understanding of the effects of nitrogen deposition, global warming and intensified forestry.

  • 296.
    O’Carroll, Conor
    et al.
    European Research Area Steering Group on Human Resources and Mobility, Newry.
    Scholz, Beate
    Scholz Consulting, Bonn, Germany.
    Nogueira, Maria Manuela
    European Science Foundation, Strasbourg, France.
    Avellis, Gianna
    InnovaPuglia, Valenzano, Italy, m-WiSET Working Group of the Marie Curie Fellows Association, Brussels.
    Marin, Laura
    Swedish Research Council, Stockholm, Sweden.
    Dan, Maria Bostenaru
    Ion Mincu University of Architecture and Urbanism, Bucharest, Romania.
    Chmielowski, Riia
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Geosciences and Environmental Engineering.
    Trapani, Antonella di
    European Research Council Executive Agency, Brussels.
    Theodoridou, Magdalini
    University of Cyprus, Nicosia.
    Careers: Virtual mobility can drive equality2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 511, no 292, 292- p.Article in journal (Refereed)
    Abstract [en]

    At a EuroScience Open Forum meeting last month, scientists, policy-makers and the public discussed ‘virtual mobility’. Could it replace the conventional geographical mobility of earlycareer researchers between labs? (See also R. Garwood Nature 510, 313; 2014.) The group concluded that virtual mobility would work, but should be combined with short-term visits to other labs to allow face-to-face contact, which in our view is crucial for building trust and for working across cultures. However, more than half of scientists questioned in a European Commission survey (www.more-2.eu) considered that virtual mobility would make short-term visits unnecessary. Meeting participants agreed that virtual mobility would provide equal access to and for researchers with physical disabilities, would help those on parental leave to maintain contact with their national and international networks, and would enable researchers in poorer regions to access wellresourced labs and to collaborate internationally. We maintain that virtual mobility should be considered on the same footing as mobility between disciplines, sectors and geographical regions, and that it should be seen as a driver of equal opportunities. Peer review and evaluation structures need to acknowledge these new mobility concepts.

  • 297.
    Ohlsson, Tommy
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Particle Physics.
    Another collider is not the way forward2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 494, no 7435, 35-35 p.Article in journal (Other academic)
  • 298.
    Ohlsson, Tommy
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Particle Physics.
    Don't let furore over neutrinos blur results2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 485, no 7398, 309-309 p.Article in journal (Refereed)
  • 299.
    Ohlsson, Tommy
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Particle Physics.
    International Linear Collider: Another collider is not the way forward2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 494, no 7435Article in journal (Refereed)
  • 300.
    Ohlsson, Tommy
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Particle Physics.
    Preprint servers: Follow arXiv's lead2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 489, no 7416, 367- p.Article in journal (Refereed)
3456789 251 - 300 of 453
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf