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  • 151. Englund, Camilla
    et al.
    Loren, Christina
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Grabbe, Caroline
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Varshney, Gaurav
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Deleuil, Fabiene
    Hallberg, Bengt
    Palmer, Ruth
    Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 425, no 6957, p. 512-516Article in journal (Refereed)
  • 152. Erb, Karl-Heinz
    et al.
    Kastner, Thomas
    Plutzar, Christoph
    Bais, Anna Liza S.
    Carvalhais, Nuno
    Fetzel, Tamara
    Gingrich, Simone
    Haberl, Helmut
    Lauk, Christian
    Iedertscheider, Maria N.
    Pongratz, Julia
    Thurner, Martin
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Luyssaert, Sebastiaan
    Unexpectedly large impact of forest management and grazing on global vegetation biomass2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 553, no 7686, p. 73-76Article in journal (Refereed)
    Abstract [en]

    Carbon stocks in vegetation have a key role in the climate system(1-4). However, the magnitude, patterns and uncertainties of carbon stocks and the effect of land use on the stocks remain poorly quantified. Here we show, using state-of-the-art datasets, that vegetation currently stores around 450 petagrams of carbon. In the hypothetical absence of land use, potential vegetation would store around 916 petagrams of carbon, under current climate conditions. This difference highlights the massive effect of land use on biomass stocks. Deforestation and other land-cover changes are responsible for 53-58% of the difference between current and potential biomass stocks. Land management effects (the biomass stock changes induced by land use within the same land cover) contribute 42-47%, but have been underestimated in the literature. Therefore, avoiding deforestation is necessary but not sufficient for mitigation of climate change. Our results imply that trade-offs exist between conserving carbon stocks on managed land and raising the contribution of biomass to raw material and energy supply for the mitigation of climate change. Efforts to raise biomass stocks are currently verifiable only in temperate forests, where their potential is limited. By contrast, large uncertainties hinder verification in the tropical forest, where the largest potential is located, pointing to challenges for the upcoming stocktaking exercises under the Paris agreement.

  • 153.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mitochondria in the second act2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 531, no 7592, p. 39-40Article in journal (Other academic)
    Abstract [en]

    A large phylogenomics study reveals that the symbiotic event that led to the emergence of organelles known as mitochondria may have occurred later in the evolution of complex cells than was thought.

  • 154.
    Evans, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Sports doping vastly underestimated2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 519, no 7541, p. 33-33Article in journal (Refereed)
  • 155. Figueres, Christiana
    et al.
    Schellnhuber, Hans Joachim
    Whiteman, Gail
    Rockström, Johan
    Stockholm University, Faculty of Science, Stockholm Resilience Centre.
    Hobley, Anthony
    Rahmstorf, Stefan
    Three years to safeguard our climate2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 546, no 7660, p. 593-595Article in journal (Other academic)
  • 156.
    Flanagan, J Randall
    et al.
    Queen's University, Kingston, Ontario K7L 3N6.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Action plans used in action observation2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, ISSN 1476-4687, Vol. 424, no 6950, p. 769-771Article in journal (Refereed)
    Abstract [en]

    How do we understand the actions of others? According to the direct matching hypothesis, action understanding results from a mechanism that maps an observed action onto motor representations of that action. Although supported by neurophysiological and brain-imaging studies, direct evidence for this hypothesis is sparse. In visually guided actions, task-specific proactive eye movements are crucial for planning and control. Because the eyes are free to move when observing such actions, the direct matching hypothesis predicts that subjects should produce eye movements similar to those produced when they perform the tasks. If an observer analyses action through purely visual means, however, eye movements will be linked reactively to the observed action. Here we show that when subjects observe a block stacking task, the coordination between their gaze and the actor's hand is predictive, rather than reactive, and is highly similar to the gaze-hand coordination when they perform the task themselves. These results indicate that during action observation subjects implement eye motor programs directed by motor representations of manual actions and thus provide strong evidence for the direct matching hypothesis.

  • 157. Foley, Jonathan A.
    et al.
    Ramankutty, Navin
    Brauman, Kate A.
    Cassidy, Emily S.
    Gerber, James S.
    Johnston, Matt
    Mueller, Nathaniel D.
    O'Connell, Christine
    Ray, Deepak K.
    West, Paul C.
    Balzer, Christian
    Bennett, Elena M.
    Carpenter, Stephen R.
    Hill, Jason
    Monfreda, Chad
    Polasky, Stephen
    Rockström, Johan
    Stockholm University, Stockholm Resilience Centre, Stockholm Environment Institute.
    Sheehan, John
    Siebert, Stefan
    Tilman, David
    Zaks, David P. M.
    Solutions for a cultivated planet2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 478, no 7369, p. 337-342Article in journal (Refereed)
    Abstract [en]

    Increasing population and consumption are placing unprecedented demands on agriculture and natural resources. Today, approximately a billion people are chronically malnourished while our agricultural systems are concurrently degrading land, water, biodiversity and climate on a global scale. To meet the world's future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture's environmental footprint must shrink dramatically. Here we analyse solutions to this dilemma, showing that tremendous progress could be made by halting agricultural expansion, closing 'yield gaps' on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste. Together, these strategies could double food production while greatly reducing the environmental impacts of agriculture.

  • 158.
    Fonfara, Ines
    et al.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Helmholtz Centre for Infection Research, Department of Regulation in Infection Biology, Braunschweig 38124, Germany; 3Max Planck Institute for Infection Biology, Department of Regulation in Infection Biology, Berlin 10117, Germany.
    Richter, Hagen
    Bratovic, Majda
    Le Rhun, Anaïs
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Helmholtz Centre for Infection Research, Department of Regulation in Infection Biology, Braunschweig 38124, Germany; 3Max Planck Institute for Infection Biology, Department of Regulation in Infection Biology, Berlin 10117, Germany.
    Charpentier, Emmanuelle
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Helmholtz Centre for Infection Research, Department of Regulation in Infection Biology, Braunschweig 38124, Germany; 3Max Planck Institute for Infection Biology, Department of Regulation in Infection Biology, Berlin 10117, Germany.
    The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 532, no 7600, p. 517-520Article in journal (Refereed)
    Abstract [en]

    CRISPR-Cas systems that provide defence against mobile genetic elements in bacteria and archaea have evolved a variety of mechanisms to target and cleave RNA or DNA(1). The well-studied types I, II and III utilize a set of distinct CRISPR-associated ( Cas) proteins for production of mature CRISPR RNAs (crRNAs) and interference with invading nucleic acids. In types I and III, Cas6 or Cas5d cleaves precursor crRNA (pre-crRNA)(2-5) and the mature crRNAs then guide a complex of Cas proteins ( Cascade-Cas3, type I; Csm or Cmr, type III) to target and cleave invading DNA or RNA(6-12). In type II systems, RNase III cleaves pre-crRNA base-paired with trans-activating crRNA (tracrRNA) in the presence of Cas9 (refs 13, 14). The mature tracrRNA-crRNA duplex then guides Cas9 to cleave target DNA15. Here, we demonstrate a novel mechanism in CRISPR-Cas immunity. We show that type V-A Cpf1 from Francisella novicida is a dual-nuclease that is specific to crRNA biogenesis and target DNA interference. Cpf1 cleaves pre-crRNA upstream of a hairpin structure formed within the CRISPR repeats and thereby generates intermediate crRNAs that are processed further, leading to mature crRNAs. After recognition of a 5'-YTN- 3' protospacer adjacent motif on the non-target DNA strand and subsequent probing for an eight-nucleotide seed sequence, Cpf1, guided by the single mature repeat-spacer crRNA, introduces double-stranded breaks in the target DNA to generate a 5' overhang(16). The RNase and DNase activities of Cpf1 require sequence- and structure-specific binding to the hairpin of crRNA repeats. Cpf1 uses distinct active domains for both nuclease reactions and cleaves nucleic acids in the presence of magnesium or calcium. This study uncovers a new family of enzymes with specific dual endoribonuclease and endonuclease activities, and demonstrates that type V- A constitutes the most minimalistic of the CRISPR- Cas systems so far described.

  • 159.
    Frank, Franziska
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Real-world results2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 557, no 7703, p. 130-130Article in journal (Other academic)
  • 160.
    Fransson, Thord
    et al.
    Naturhistoriska Riksmuseet.
    Jakobsson, Sven
    Stockholm University, Faculty of Science, Department of Zoology.
    Johansson, Patrik
    Sveriges geologiska undersökningar.
    Kullberg, Cecilia
    Stockholm University, Faculty of Science, Department of Zoology.
    Lind, Johan
    Stockholm University, Faculty of Science, Department of Zoology.
    Valllin, Adrian
    Stockholm University, Faculty of Science, Department of Zoology.
    Magnetic cues trigger extensive refuelling2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 414, p. 35-36Article in journal (Refereed)
  • 161. Fray, Nicolas
    et al.
    Bardyn, Anaïs
    Cottin, Hervé
    Altwegg, Kathrin
    Baklouti, Donia
    Briois, Christelle
    Colangeli, Luigi
    Engrand, Cécile
    Fischer, Henning
    Glasmachers, Albrecht
    Grün, Eberhard
    Haerendel, Gerhard
    Henkel, Hartmut
    Höfner, Herwig
    Hornung, Klaus
    Jessberger, Elmar K.
    Koch, Andreas
    Krüger, Harald
    Langevin, Yves
    Lehto, Harry
    Lehto, Kirsi
    Le Roy, Léna
    Merouane, Sihane
    Modica, Paola
    Orthous-Daunay, François-Régis
    Paquette, John
    Raulin, François
    Rynö, Jouni
    Schulz, Rita
    Silén, Johan
    Siljeström, Sandra
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Steiger, Wolfgang
    Stenzel, Oliver
    Stephan, Thomas
    Thirkell, Laurent
    Thomas, Roger
    Torkar, Klaus
    Varmuza, Kurt
    Wanczek, Karl-Peter
    Zaprudin, Boris
    Kissel, Jochen
    Hilchenbach, Martin
    High-molecular-weight organic matter in the particles of comet 67P/Churyumov–Gerasimenko2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 538, no 7623, p. 72-74Article in journal (Refereed)
    Abstract [en]

    The presence of solid carbonaceous matter in cometary dust was established by the detection of elements such as carbon, hydrogen, oxygen and nitrogen in particles from comet 1P/Halley1, 2. Such matter is generally thought to have originated in the interstellar medium3, but it might have formed in the solar nebula—the cloud of gas and dust that was left over after the Sun formed4. This solid carbonaceous material cannot be observed from Earth, so it has eluded unambiguous characterization5. Many gaseous organic molecules, however, have been observed6, 7, 8, 9; they come mostly from the sublimation of ices at the surface or in the subsurface of cometary nuclei8. These ices could have been formed from material inherited from the interstellar medium that suffered little processing in the solar nebula10. Here we report the in situ detection of solid organic matter in the dust particles emitted by comet 67P/Churyumov–Gerasimenko; the carbon in this organic material is bound in very large macromolecular compounds, analogous to the insoluble organic matter found in the carbonaceous chondrite meteorites11, 12. The organic matter in meteorites might have formed in the interstellar medium and/or the solar nebula, but was almost certainly modified in the meteorites’ parent bodies11. We conclude that the observed cometary carbonaceous solid matter could have the same origin as the meteoritic insoluble organic matter, but suffered less modification before and/or after being incorporated into the comet.

  • 162.
    Fuchsberger, Christian
    et al.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.;Univ Lubeck, European Acad Bolzano Bozen EURAC, Ctr Biomed, Bolzano, Italy..
    Flannick, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Agarwala, Vineeta
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA..
    Gaulton, Kyle J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Ma, Clement
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Fontanillas, Pierre
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Moutsianas, Loukas
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    McCarthy, Davis J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Rivas, Manuel A.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Perry, John R. B.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England.;Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Blackwell, Thomas W.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Robertson, Neil R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Rayner, N. William
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Cingolani, Pablo
    McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.;McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Tajes, Juan Fernandez
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Human Genet Ctr, Houston, TX 77030 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Chines, Peter S.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Hartl, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Chen, Han
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Huyghe, Jeroen R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    van de Bunt, Martijn
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Pearson, Richard D.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Kumar, Ashish
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Basel, Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol, Basel, Switzerland..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Gamazon, Eric R.
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Lee, Jaehoon
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Chen, Yuhui
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Below, Jennifer E.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Chen, Peng
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Huang, Jinyan
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Go, Min Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Stitzel, Michael L.
    Jackson Lab Genom Med, Farmington, CT USA..
    Pasko, Dorota
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Parker, Stephen C. J.
    Univ Michigan, Dept Computat Med, Ann Arbor, MI USA.;Univ Michigan, Dept Bioinformat & Human Genet, Ann Arbor, MI USA..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden..
    Green, Todd
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Beer, Nicola L.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Day-Williams, Aaron G.
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Fingerlin, Tasha
    Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA..
    Horikoshi, Momoko
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hu, Cheng
    Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Huh, Iksoo
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Ikram, Mohammad Kamran
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Kim, Yongkang
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Kwon, Min-Seok
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Lee, Juyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Lee, Selyeong
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Lin, Keng-Han
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Maxwell, Taylor J.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Nagai, Yoshihiko
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada..
    Wang, Xu
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Welch, Ryan P.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Yoon, Joon
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Zhang, Weihua
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA..
    Voight, Benjamin F.
    Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Jenkinson, Christopher P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.;South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Manning, Alisa
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Balkau, Beverley
    INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France..
    Stancakova, Alena
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland..
    Abboud, Hanna E.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India..
    Gottesman, Omri
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Scott, James
    Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Carey, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Grant, George
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Smith, Joshua D.
    Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA..
    Neale, Benjamin M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA..
    Purcell, Shaun
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Psychiat, New York, NY 10029 USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Lee, Heung Man
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Kwak, Soo-Heon
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea..
    Zhao, Wei
    Univ Penn, Dept Med, Philadelphia, PA 19104 USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Lam, Vincent K. L.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Park, Kyong Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea.;Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea.;Seoul Natl Univ, Coll Med, Seoul, South Korea..
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    So, Wing Yee
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Tam, Claudia H. T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Afzal, Uzma
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Aguilar, David
    Baylor Coll Med, Div Cardiovasc, Houston, TX 77030 USA..
    Arya, Rector
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Aung, Tin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Chan, Edmund
    Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Navarro, Carmen
    IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.;Univ Murcia, CIBERESP, Murcia, Spain.;Univ Murcia, Sch Med, Unit Prevent Med & Publ Hlth, E-30001 Murcia, Spain..
    Cheng, Ching-Yu
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Florence, Italy..
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Curran, Joanne E.
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Rybin, Denis
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Farook, Vidya S.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Fowler, Sharon P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Freedman, Barry I.
    Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA..
    Griswold, Michael
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Hale, Daniel Esten
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Hicks, Pamela J.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Khor, Chiea-Chuen
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    Kumar, Satish
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Lehne, Benjamin
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Thuillier, Dorothee
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Lim, Wei Yen
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Liu, Jianjun
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Loh, Marie
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland.;ASTAR, TLGM, Singapore, Singapore..
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Puppala, Sobha
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Scott, William R.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Yengo, Loic
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Taylor, Herman A., Jr.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Thameem, Farook
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Wilson, Gregory, Sr.
    Jackson State Univ, Coll Publ Serv, Jackson, MS USA..
    Wong, Tien Yin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Njolstad, Pal Rasmus
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Dept Pediat, Bergen, Norway..
    Levy, Jonathan C.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Schwarzmayr, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Surdulescu, Gabriela L.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Herder, Christian
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Wieland, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark.;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark..
    Christensen, Cramer
    Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Minerva Fdn, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland..
    Doney, Alex S. F.
    Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA..
    Farmer, Andrew J.
    Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England..
    Hakaste, Liisa
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland..
    Hodgkiss, Dylan
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Kravic, Jasmina
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Lyssenko, Valeriya
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Hollensted, Mette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Jorgensen, Torben
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, Copenhagen, Denmark.;Aalborg Univ, Med, Aalborg, Denmark..
    Ladenvall, Claes
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland..
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Rathmann, Wolfgang
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lauritzen, Torsten
    Aarhus Univ, Sect Gen Practice, Dept Publ Hlth, Aarhus, Denmark..
    Narisu, Narisu
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Melander, Olle
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc, Malmo, Sweden..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden..
    Qi, Lu
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Qi, Qibin
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA..
    Roden, Michael
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Swift, Amy
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Rosengren, Anders H.
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Stirrups, Kathleen
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Blancher, Christine
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Carneiro, Mauricio O.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Maguire, Jared
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Poplin, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Shakir, Khalid
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Fennell, Timothy
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    DePristo, Mark
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    de Angelis, Martin Hrabe
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany.;Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, Freising Weihenstephan, Germany..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jun, Goo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Nilsson, Peter
    Lund Univ, Dept Clin Sci, Med, Malmo, Sweden..
    Murphy, Jacquelyn
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Onofrio, Robert
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark..
    Meisinger, Christa
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Hu, Frank B.
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Peters, Annette
    Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Huth, Cornelia
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    O'Rahilly, Stephen P.
    Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England..
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Autonomous Univ Madrid, Univ Hosp LaPaz, Inst Invest Sanitaria Hosp Univ LaPaz IdiPAZ, Madrid, Spain.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Watanabe, Richard M.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dabet & Obes Res Inst, Los Angeles, CA USA..
    Syvanen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergman, Richard N.
    Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA..
    Bharadwaj, Dwaipayan
    CSIR IGIB, Funct Genom Unit, New Delhi, India..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea..
    Chandak, Giriraj R.
    CSIR Ctr Cellular & Mol Biol, Hyderabad, Telangana, India..
    Chan, Juliana C. N.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    Chia, Kee Seng
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Daly, Mark J.
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Ebrahim, Shah B.
    Ctr Chron Dis Control, New Delhi, India..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Jablonski, Kathleen A.
    George Washington Univ, Biostat Ctr, Rockville, MD USA..
    Lehman, Donna M.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Jia, Weiping
    Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Ma, Ronald C. W.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    Pollin, Toni I.
    Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Sandhu, Manjinder
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Tandon, Nikhil
    All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India..
    Froguel, Philippe
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England..
    Teo, Yik Ying
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Inst Life Sci, Singapore, Singapore.;Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany..
    DeFronzo, Ralph A.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Glaser, Benjamin
    Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Banks, Eric
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Gieger, Christian
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    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. Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Im, Hae Kyung
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Illig, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, NH, Germany.;Hannover Med Sch, Inst Human Genet, Hannover, NH, Germany..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Buck, Gemma
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Trakalo, Joseph
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Buck, David
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Prokopenko, Inga
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farjoun, Yossi
    Broad Inst, Data Sci & Data Engn, Cambridge, MA USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Gloyn, Anna L.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Tuomi, Tiinamaija
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.;Univ Helsinki, FIMM, Helsinki, Finland..
    Kooner, Jaspal Singh
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Lee, Jong-Young
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Park, Taesung
    Seoul Natl Univ, Dept Stat, Seoul, South Korea.;Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Donnelly, Peter
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Hattersley, Andrew T.
    Univ Exeter, Sch Med, Exeter, Devon, England..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Collins, Francis S.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Atzmon, Gil
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA.;Univ Haifa, Dept Nat Sci, Haifa, Israel..
    Chambers, John C.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Laakso, Markku
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Strom, Tim M.
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Bell, Graeme I.
    Univ Chicago, Dept Med Genet, Chicago, IL 60637 USA.;Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA..
    Blangero, John
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Duggirala, Ravindranath
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Tai, E. Shyong
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.;Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, Singapore..
    McVean, Gilean
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Hanis, Craig L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Seielstad, Mark
    Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.;Blood Syst Res Inst, San Francisco, CA USA..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Meigs, James B.
    Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Cox, Nancy J.
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Sladek, Rob
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada..
    Lander, Eric S.
    Broad Inst MIT & Harvard, Cambridge, MA USA..
    Gabriel, Stacey
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Meitinger, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Groop, Leif
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.;Univ Helsinki, FIMM, Helsinki, Finland..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Florez, Jose C.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA..
    Scott, Laura J.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Kang, Hyun Min
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Altshuler, David
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.;MIT, Dept Biol, Cambridge, MA USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    The genetic architecture of type 2 diabetes2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 536, no 7614, p. 41-47Article in journal (Refereed)
    Abstract [en]

    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

  • 163. Fuchsberger, Christian
    et al.
    Flannick, Jason
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    Mahajan, Anubha
    Agarwala, Vineeta
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    Ma, Clement
    Fontanillas, Pierre
    Moutsianas, Loukas
    McCarthy, Davis J.
    Rivas, Manuel A.
    Perry, John R. B.
    Sim, Xueling
    Blackwell, Thomas W.
    Robertson, Neil R.
    Rayner, N. William
    Cingolani, Pablo
    Locke, Adam E.
    Tajes, Juan Fernandez
    Highland, Heather M.
    Dupuis, Josee
    Chines, Peter S.
    Lindgren, Cecilia M.
    Hartl, Christopher
    Jackson, Anne U.
    Chen, Han
    Huyghe, Jeroen R.
    van de Bunt, Martijn
    Pearson, Richard D.
    Kumar, Ashish
    Mueller-Nurasyid, Martina
    Grarup, Niels
    Stringham, Heather M.
    Gamazon, Eric R.
    Lee, Jaehoon
    Chen, Yuhui
    Scott, Robert A.
    Below, Jennifer E.
    Chen, Peng
    Huang, Jinyan
    Go, Min Jin
    Stitzel, Michael L.
    Pasko, Dorota
    Parker, Stephen C. J.
    Varga, Tibor V.
    Green, Todd
    Beer, Nicola L.
    Day-Williams, Aaron G.
    Ferreira, Teresa
    Fingerlin, Tasha
    Horikoshi, Momoko
    Hu, Cheng
    Huh, Iksoo
    Ikram, Mohammad Kamran
    Kim, Bong-Jo
    Kim, Yongkang
    Kim, Young Jin
    Kwon, Min-Seok
    Lee, Juyoung
    Lee, Selyeong
    Lin, Keng-Han
    Maxwell, Taylor J.
    Nagai, Yoshihiko
    Wang, Xu
    Welch, Ryan P.
    Yoon, Joon
    Zhang, Weihua
    Barzilai, Nir
    Voight, Benjamin F.
    Han, Bok-Ghee
    Jenkinson, Christopher P.
    Kuulasmaa, Teemu
    Kuusisto, Johanna
    Manning, Alisa
    Ng, Maggie C. Y.
    Palmer, Nicholette D.
    Balkau, Beverley
    Stancakova, Alena
    Abboud, Hanna E.
    Boeing, Heiner
    Giedraitis, Vilmantas
    Prabhakaran, Dorairaj
    Gottesman, Omri
    Scott, James
    Carey, Jason
    Kwan, Phoenix
    Grant, George
    Smith, Joshua D.
    Neale, Benjamin M.
    Purcell, Shaun
    Butterworth, Adam S.
    Howson, Joanna M. M.
    Lee, Heung Man
    Lu, Yingchang
    Kwak, Soo-Heon
    Zhao, Wei
    Danesh, John
    Lam, Vincent K. L.
    Park, Kyong Soo
    Saleheen, Danish
    So, Wing Yee
    Tam, Claudia H. T.
    Afzal, Uzma
    Aguilar, David
    Arya, Rector
    Aung, Tin
    Chan, Edmund
    Navarro, Carmen
    Cheng, Ching-Yu
    Palli, Domenico
    Correa, Adolfo
    Curran, Joanne E.
    Rybin, Denis
    Farook, Vidya S.
    Fowler, Sharon P.
    Freedman, Barry I.
    Griswold, Michael
    Hale, Daniel Esten
    Hicks, Pamela J.
    Khor, Chiea-Chuen
    Kumar, Satish
    Lehne, Benjamin
    Thuillier, Dorothee
    Lim, Wei Yen
    Liu, Jianjun
    van der Schouw, Yvonne T.
    Loh, Marie
    Musani, Solomon K.
    Puppala, Sobha
    Scott, William R.
    Yengo, Loic
    Tan, Sian-Tsung
    Taylor, Herman A., Jr.
    Thameem, Farook
    Wilson, Gregory, Sr.
    Wong, Tien Yin
    Njolstad, Pal Rasmus
    Levy, Jonathan C.
    Mangino, Massimo
    Bonnycastle, Lori L.
    Schwarzmayr, Thomas
    Fadista, Joao
    Surdulescu, Gabriela L.
    Herder, Christian
    Groves, Christopher J.
    Wieland, Thomas
    Bork-Jensen, Jette
    Brandslund, Ivan
    Christensen, Cramer
    Koistinen, Heikki A.
    Doney, Alex S. F.
    Kinnunen, Leena
    Esko, Tonu
    Farmer, Andrew J.
    Hakaste, Liisa
    Hodgkiss, Dylan
    Kravic, Jasmina
    Lyssenko, Valeriya
    Hollensted, Mette
    Jorgensen, Marit E.
    Jorgensen, Torben
    Ladenvall, Claes
    Justesen, Johanne Marie
    Karajamaki, Annemari
    Kriebel, Jennifer
    Rathmann, Wolfgang
    Lannfelt, Lars
    Lauritzen, Torsten
    Narisu, Narisu
    Linneberg, Allan
    Melander, Olle
    Milani, Lili
    Neville, Matt
    Orho-Melander, Marju
    Qi, Lu
    Qi, Qibin
    Roden, Michael
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Swift, Amy
    Rosengren, Anders H.
    Stirrups, Kathleen
    Wood, Andrew R.
    Mihailov, Evelin
    Blancher, Christine
    Carneiro, Mauricio O.
    Maguire, Jared
    Poplin, Ryan
    Shakir, Khalid
    Fennell, Timothy
    DePristo, Mark
    de Angelis, Martin Hrabe
    Deloukas, Panos
    Gjesing, Anette P.
    Jun, Goo
    Nilsson, Peter
    Murphy, Jacquelyn
    Onofrio, Robert
    Thorand, Barbara
    Hansen, Torben
    Meisinger, Christa
    Hu, Frank B.
    Isomaa, Bo
    Karpe, Fredrik
    Liang, Liming
    Peters, Annette
    Huth, Cornelia
    O'Rahilly, Stephen P.
    Palmer, Colin N. A.
    Pedersen, Oluf
    Rauramaa, Rainer
    Tuomilehto, Jaakko
    Salomaa, Veikko
    Watanabe, Richard M.
    Syvanen, Ann-Christine
    Bergman, Richard N.
    Bharadwaj, Dwaipayan
    Bottinger, Erwin P.
    Cho, Yoon Shin
    Chandak, Giriraj R.
    Chan, Juliana C. N.
    Chia, Kee Seng
    Daly, Mark J.
    Ebrahim, Shah B.
    Langenberg, Claudia
    Elliott, Paul
    Jablonski, Kathleen A.
    Lehman, Donna M.
    Jia, Weiping
    Ma, Ronald C. W.
    Pollin, Toni I.
    Sandhu, Manjinder
    Tandon, Nikhil
    Froguel, Philippe
    Barroso, Ines
    Teo, Yik Ying
    Zeggini, Eleftheria
    Loos, Ruth J. F.
    Small, Kerrin S.
    Ried, Janina S.
    DeFronzo, Ralph A.
    Grallert, Harald
    Glaser, Benjamin
    Metspalu, Andres
    Wareham, Nicholas J.
    Walker, Mark
    Banks, Eric
    Gieger, Christian
    Ingelsson, Erik
    Im, Hae Kyung
    Illig, Thomas
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
    Buck, Gemma
    Trakalo, Joseph
    Buck, David
    Prokopenko, Inga
    Magi, Reedik
    Lind, Lars
    Farjoun, Yossi
    Owen, Katharine R.
    Gloyn, Anna L.
    Strauch, Konstantin
    Tuomi, Tiinamaija
    Kooner, Jaspal Singh
    Lee, Jong-Young
    Park, Taesung
    Donnelly, Peter
    Morris, Andrew D.
    Hattersley, Andrew T.
    Bowden, Donald W.
    Collins, Francis S.
    Atzmon, Gil
    Chambers, John C.
    Spector, Timothy D.
    Laakso, Markku
    Strom, Tim M.
    Bell, Graeme I.
    Blangero, John
    Duggirala, Ravindranath
    Tai, E. Shyong
    McVean, Gilean
    Hanis, Craig L.
    Wilson, James G.
    Seielstad, Mark
    Frayling, Timothy M.
    Meigs, James B.
    Cox, Nancy J.
    Sladek, Rob
    Lander, Eric S.
    Gabriel, Stacey
    Burtt, Noel P.
    Mohlke, Karen L.
    Meitinger, Thomas
    Groop, Leif
    Abecasis, Goncalo
    Florez, Jose C.
    Scott, Laura J.
    Morris, Andrew P.
    Kang, Hyun Min
    Boehnke, Michael
    Altshuler, David
    McCarthy, Mark I.
    The genetic architecture of type 2 diabetes2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 536, no 7614, p. 41-47Article in journal (Refereed)
    Abstract [en]

    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

  • 164.
    Fälthammar, Carl-Gunne
    et al.
    KTH, Superseded Departments, Alfvén Laboratory. KTH, School of Electrical Engineering (EES), Space and Plasma Physics.
    Akasofu, S.I.
    Alfvén, Hannes
    KTH, Superseded Departments, Alfvén Laboratory. KTH, School of Electrical Engineering (EES), Space and Plasma Physics.
    Significance of magnetospheric research for progress in astrophysics1978In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 275, p. 185-188Article in journal (Refereed)
  • 165.
    Fölling, Simon
    et al.
    Institut für Physik, Johannes Gutenberg-Universität, 55099 Mainz, Germany.
    Trotzky, Stefan
    Institut für Physik, Johannes Gutenberg-Universität, 55099 Mainz, Germany.
    Cheinet, Patrick
    Institut für Physik, Johannes Gutenberg-Universität, 55099 Mainz, Germany.
    Feld, Michael
    Institut für Physik, Johannes Gutenberg-Universität, 55099 Mainz, Germany.
    Saers, Robert
    Umeå University, Faculty of Science and Technology, Physics.
    Widera, Artur
    Institut für Physik, Johannes Gutenberg-Universität, 55099 Mainz, Germany, Institut für Angewandte Physik, Universität Bonn, 53115 Bonn, Germany.
    Müller, Torben
    Institut für Physik, Johannes Gutenberg-Universität, 55099 Mainz, Germany, Institute of Quantum Electronics, ETH Zürich, 8093 Zürich, Switzerland.
    Bloch, Immanuel
    Institut für Physik, Johannes Gutenberg-Universität, 55099 Mainz, Germany.
    Direct observation of second-order atom tunnelling2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 448, no 7157, p. 1029-1032Article in journal (Refereed)
  • 166. Gad, Helge
    et al.
    Koolmeister, Tobias
    Jemth, Ann-Sofie
    Eshtad, Saeed
    Jacques, Sylvain A.
    Strom, Cecilia E.
    Svensson, Linda M.
    Schultz, Niklas
    Lundback, Thomas
    Einarsdottir, Berglind Osk
    Saleh, Aljona
    Gokturk, Camilla
    Baranczewski, Pawel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Svensson, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Berntsson, Ronnie P. -A.
    Gustafsson, Robert
    Stromberg, Kia
    Sanjiv, Kumar
    Jacques-Cordonnier, Marie-Caroline
    Desroses, Matthieu
    Gustavsson, Anna-Lena
    Olofsson, Roger
    Johansson, Fredrik
    Homan, Evert J.
    Loseva, Olga
    Brautigam, Lars
    Johansson, Lars
    Hoglund, Andreas
    Hagenkort, Anna
    Pham, Therese
    Altun, Mikael
    Gaugaz, Fabienne Z.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Vikingsson, Svante
    Evers, Bastiaan
    Henriksson, Martin
    Vallin, Karl S. A.
    Wallner, Olov A.
    Hammarstrom, Lars G. J.
    Wiita, Elisee
    Almlof, Ingrid
    Kalderen, Christina
    Axelsson, Hanna
    Djureinovic, Tatjana
    Puigvert, Jordi Carreras
    Haggblad, Maria
    Jeppsson, Fredrik
    Martens, Ulf
    Lundin, Cecilia
    Lundgren, Bo
    Granelli, Ingrid
    Jensen, Annika Jenmalm
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nilsson, Jonas A.
    Stenmark, Pal
    Scobie, Martin
    Berglund, Ulrika Warpman
    Helleday, Thomas
    MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 508, no 7495, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

  • 167.
    Gad, Helge
    et al.
    Karolinska Institute, Sweden .
    Koolmeister, Tobias
    Karolinska Institute, Sweden .
    Jemth, Ann-Sofie
    Karolinska Institute, Sweden .
    Eshtad, Saeed
    Karolinska Institute, Sweden .
    Jacques, Sylvain A.
    Karolinska Institute, Sweden .
    Ström, Cecilia E.
    Karolinska Institute, Sweden .
    Svensson, Linda M.
    Stockholm University, Sweden .
    Schultz, Niklas
    Karolinska Institute, Sweden .
    Lundbäck, Thomas
    Karolinska Institute, Sweden .
    Osk Einarsdottir, Berglind
    University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden .
    Saleh, Aljona
    Stockholm University, Sweden .
    Göktürk, Camilla
    Karolinska Institute, Sweden .
    Baranczewski, Pawel
    Karolinska Institute, Sweden Uppsala University, Sweden .
    Svensson, Richard
    Karolinska Institute, Sweden; Uppsala University, Sweden .
    Berntsson, Ronnie P. -A.
    Stockholm University, Sweden .
    Gustafsson, Robert
    Stockholm University, Sweden .
    Strömberg, Kia
    Karolinska Institute, Sweden .
    Sanjiv, Kumar
    Karolinska Institute, Sweden .
    Jacques-Cordonnier, Marie-Caroline
    Karolinska Institute, Sweden .
    Desroses, Matthieu
    Karolinska Institute, Sweden .
    Gustavsson, Anna-Lena
    Karolinska Institute, Sweden .
    Olofsson, Roger
    University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden .
    Johansson, Fredrik
    Stockholm University, Sweden .
    Homan, Evert J.
    Karolinska Institute, Sweden .
    Loseva, Olga
    Karolinska Institute, Sweden .
    Bräutigam, Lars
    Karolinska Institute, Sweden .
    Johansson, Lars
    Karolinska Institute, Sweden .
    Höglund, Andreas
    Karolinska Institute, Sweden .
    Hagenkort, Anna
    Karolinska Institute, Sweden .
    Pham, Therese
    Karolinska Institute, Sweden .
    Altun, Mikael
    Karolinska Institute, Sweden .
    Gaugaz, Fabienne Z.
    Karolinska Institute, Sweden; Uppsala University, Sweden .
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Evers, Bastiaan
    Karolinska Institute, Sweden .
    Henriksson, Martin
    Karolinska Institute, Sweden .
    Vallin, Karl S. A.
    Karolinska Institute, Sweden .
    Wallner, Olov A.
    Karolinska Institute, Sweden .
    Hammarström, Lars G. J.
    Karolinska Institute, Sweden .
    Wiita, Elisee
    Karolinska Institute, Sweden .
    Almlöf, Ingrid
    Karolinska Institute, Sweden .
    Kalderén, Christina
    Karolinska Institute, Sweden .
    Axelsson, Hanna
    Karolinska Institute, Sweden .
    Djureinovic, Tatjana
    Stockholm University, Sweden .
    Carreras Puigvert, Jordi
    Karolinska Institute, Sweden .
    Häggblad, Maria
    Stockholm University, Sweden .
    Jeppsson, Fredrik
    Karolinska Institute, Sweden .
    Martens, Ulf
    Stockholm University, Sweden .
    Lundin, Cecilia
    Karolinska Institute, Sweden .
    Lundgren, Bo
    Stockholm University, Sweden .
    Granelli, Ingrid
    Stockholm University, Sweden .
    Jenmalm Jensen, Annika
    Karolinska Institute, Sweden .
    Artursson, Per
    Karolinska Institute, Sweden; Uppsala University, Sweden .
    Nilsson, Jonas A.
    University of Gothenburg, Sweden, Sahlgrens University Hospital, Sweden .
    Stenmark, Pål
    Stockholm University, Sweden .
    Scobie, Martin
    Karolinska Institute, Sweden .
    Warpman Berglund, Ulrika
    Karolinska Institute, Sweden .
    Helleday, Thomas
    Karolinska Institute, Sweden .
    MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 508, no 7495, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

  • 168. Gad, Helge
    et al.
    Svensson, Linda M.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Saleh, Aljona
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Berntsson, Ronnie P.-A.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Gustafsson, Robert
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Johansson, Fredrik
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Djureinovic, Tatjana
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Häggblad, Maria
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Martens, Ulf
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Lundgren, Bo
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Granelli, Ingrid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Stenmark, Pål
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Helleday, Thomas
    MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 508, no 7495, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

  • 169. Gall, Christa
    et al.
    Hjorth, Jens
    Watson, Darach
    Dwek, Eli
    Maund, Justyn R.
    Fox, Ori
    Leloudas, Giorgos
    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.
    Malesani, Daniele
    Day-Jones, Avril C.
    Rapid formation of large dust grains in the luminous supernova 2010j12014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 511, no 7509, p. 326-+Article in journal (Refereed)
    Abstract [en]

    The origin of dust in galaxies is still a mystery(1-4). The majority of the refractory elements are produced in supernova explosions, but it is unclear how and where dust grains condense and grow, and how they avoid destruction in the harsh environments of star-forming galaxies. The recent detection of 0.1 to 0.5 solar masses of dust in nearby supernova remnants(5-7) suggests in situ dust formation, while other observations reveal very little dust in supernovae in the first few years after explosion(1,8,10). Observations of the spectral evolution of the bright SN 2010j1 have been interpreted as pre-existing dust(11), dust formationlz(12,13) or no dust at all(14). Here we report the rapid (40 to 240 days) formation of dust in its dense circumstellar medium. The wavelength-dependent extinction of this dust reveals the presence of very large (exceeding one micrometre) grains, which resist destruction(15). At later times (500 to 900 days), the near-infrared thermal emission shows an accelerated growth in dust mass, marking the transition of the dust source from the circumstellar medium to the ejecta. This provides the link between the early and late dust mass evolution in supernovae with dense circumstellar media.

  • 170. Gal-Yam, Avishay
    et al.
    Arcavi, I.
    Ofek, E. O.
    Ben-Ami, S.
    Cenko, S. B.
    Kasliwal, M. M.
    Cao, Y.
    Yaron, O.
    Tal, D.
    Silverman, J. M.
    Horesh, A.
    De Cia, A.
    Taddia, Francesco
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Sollerman, Jesper
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Perley, D.
    Vreeswijk, P. M.
    Kulkarni, S. R.
    Nugent, P. E.
    Filippenko, A. V.
    Wheeler, J. C.
    A Wolf-Rayet-like progenitor of SN 2013cu from spectral observations of a stellar wind2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 509, no 7501, p. 471-+Article in journal (Refereed)
    Abstract [en]

    The explosive fate of massive Wolf-Rayet stars(1) (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections(4). Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 1012 centimetres, as expected for some WRSs(5). The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions(6).

  • 171. Garrouste, Romain
    et al.
    Clement, Gael
    Nel, Patricia
    Engel, Michael S.
    Grandcolas, Philippe
    D'Haese, Cyrille A.
    Lagebro, Linda
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Denayer, Julien
    Gueriau, Pierre
    Lafaite, Patrick
    Olive, Sebastien
    Prestianni, Cyrille
    Nel, Andre
    Is Strudiella a Devonian insect?: Reply2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 494, no 7437, p. E4-E5Article in journal (Refereed)
  • 172. Garrouste, Romain
    et al.
    Clement, Gael
    Nel, Patricia
    Engel, Michael S.
    Grandcolas, Philippe
    D'Haese, Cyrille
    Lagebro, Linda
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Denayer, Julien
    Gueriau, Pierre
    Lafaite, Patrick
    Olive, Sebastien
    Prestianni, Cyrille
    Nel, Andre
    A complete insect from the Late Devonian period2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 488, no 7409, p. 82-85Article in journal (Refereed)
    Abstract [en]

    After terrestrialization, the diversification of arthropods and vertebrates is thought to have occurred in two distinct phases(1), the first between the Silurian and the Frasnian stages (Late Devonian period) (425-385 million years (Myr) ago), and the second characterized by the emergence of numerous new major taxa, during the Late Carboniferous period (after 345 Myr ago). These two diversification periods bracket the depauperate vertebrate Romer's gap (360-345 Myr ago) and arthropod gap (385-325 Myr ago)(1), which could be due to preservational artefact(2,3). Although a recent molecular dating has given an age of 390 Myr for the Holometabola(4), the record of hexapods during the Early-Middle Devonian (411.5-391 Myr ago, Pragian to Givetian stages) is exceptionally sparse and based on fragmentary remains, which hinders the timing of this diversification. Indeed, although Devonian Archaeognatha are problematic(5,6), the Pragian of Scotland has given some Collembola and the incomplete insect Rhyniognatha, with its diagnostic dicondylic, metapterygotan mandibles(5,7). The oldest, definitively winged insects are from the Serpukhovian stage (latest Early Carboniferous period)(8). Here we report the first complete Late Devonian insect, which was probably a terrestrial species. Its 'orthopteroid' mandibles are of an omnivorous type, clearly not modified for a solely carnivorous diet. This discovery narrows the 45-Myr gap in the fossil record of Hexapoda, and demonstrates [GRAPHICS] further a first Devonian phase of diversification for the Hexapoda, as in vertebrates, and suggests that the Pterygota diversified before and during Romer's gap.

  • 173. George, Julie
    et al.
    Lim, Jing Shan
    Jang, Se Jin
    Cun, Yupeng
    Ozretic, Luka
    Kong, Gu
    Leenders, Frauke
    Lu, Xin
    Fernandez-Cuesta, Lynnette
    Bosco, Graziella
    Mueller, Christian
    Dahmen, Ilona
    Jahchan, Nadine S.
    Park, Kwon-Sik
    Yang, Dian
    Karnezis, Anthony N.
    Vaka, Dedeepya
    Torres, Angela
    Wang, Maia Segura
    Korbel, Jan O.
    Menon, Roopika
    Chun, Sung-Min
    Kim, Deokhoon
    Wilkerson, Matt
    Hayes, Neil
    Engelmann, David
    Puetzer, Brigitte
    Bos, Marc
    Michels, Sebastian
    Vlasic, Ignacija
    Seidel, Danila
    Pinther, Berit
    Schaub, Philipp
    Becker, Christian
    Altmueller, Janine
    Yokota, Jun
    Kohno, Takashi
    Iwakawa, Reika
    Tsuta, Koji
    Noguchi, Masayuki
    Muley, Thomas
    Hoffmann, Hans
    Schnabel, Philipp A.
    Petersen, Iver
    Chen, Yuan
    Soltermann, Alex
    Tischler, Verena
    Choi, Chang-min
    Kim, Yong-Hee
    Massion, Pierre P.
    Zou, Yong
    Jovanovic, Dragana
    Kontic, Milica
    Wright, Gavin M.
    Russell, Prudence A.
    Solomon, Benjamin
    Koch, Ina
    Lindner, Michael
    Muscarella, Lucia A.
    la Torre, Annamaria
    Field, John K.
    Jakopovic, Marko
    Knezevic, Jelena
    Castanos-Velez, Esmeralda
    Roz, Luca
    Pastorino, Ugo
    Brustugun, Odd-Terje
    Lund-Iversen, Marius
    Thunnissen, Erik
    Koehler, Jens
    Schuler, Martin
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Sanchez-Cespedes, Montserrat
    Salvesen, Helga B.
    Achter, Viktor
    Lang, Ulrich
    Bogus, Magdalena
    Schneider, Peter M.
    Zander, Thomas
    Ansen, Sascha
    Hallek, Michael
    Wolf, Juergen
    Vingron, Martin
    Yatabe, Yasushi
    Travis, William D.
    Nuernberg, Peter
    Reinhardt, Christian
    Perner, Sven
    Heukamp, Lukas
    Buettner, Reinhard
    Haas, Stefan A.
    Brambilla, Elisabeth
    Peifer, Martin
    Sage, Julien
    Thomas, Roman K.
    Comprehensive genomic profiles of small cell lung cancer2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, no 7563, p. 47-U73Article in journal (Refereed)
    Abstract [en]

    We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

  • 174.
    Gomez-Consarnau, Laura
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Gonzalez, J M
    Coll-Llado, Montserrat
    Gourdon, Pontus
    Pascher, Torbjörn
    Neutze, Richard
    Pedros-Alio, C
    Pinhassi, Jarone
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Light stimulates growth of proteorhodopsin-containing marine Flavobacteria2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 445, p. 210-213Article in journal (Refereed)
  • 175. Groenen, M. A.
    et al.
    Archibald, A. L.
    Uenishi, H.
    Tuggle, C. K.
    Takeuchi, Y.
    Rothschild, M. F.
    Rogel-Gaillard, C.
    Park, C.
    Milan, D.
    Megens, H. J.
    Li, S.
    Larkin, D. M.
    Kim, H.
    Frantz, L. A.
    Caccamo, M.
    Ahn, H.
    Aken, B. L.
    Anselmo, A.
    Anthon, C.
    Auvil, L.
    Badaoui, B.
    Beattie, C. W.
    Bendixen, C.
    Berman, D.
    Blecha, F.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Bolund, L.
    Bosse, M.
    Botti, S.
    Bujie, Z.
    Byström, M.
    Capitanu, B.
    Carvalho-Silva, D.
    Chardon, P.
    Chen, C.
    Cheng, R.
    Choi, S. H.
    Chow, W.
    Clark, R. C.
    Clee, C.
    Crooijmans, R. P.
    Dawson, H. D.
    Dehais, P.
    De Sapio, F.
    Dibbits, B.
    Drou, N.
    Du, Z. Q.
    Eversole, K.
    Fadista, J.
    Fairley, S.
    Faraut, T.
    Faulkner, G. J.
    Fowler, K. E.
    Fredholm, M.
    Fritz, E.
    Gilbert, J. G.
    Giuffra, E.
    Gorodkin, J.
    Griffin, D. K.
    Harrow, J. L.
    Hayward, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Howe, K.
    Hu, Z. L.
    Humphray, S. J.
    Hunt, T.
    Hornshoj, H.
    Jeon, J. T.
    Jern, Patric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jones, M.
    Jurka, J.
    Kanamori, H.
    Kapetanovic, R.
    Kim, J.
    Kim, J. H.
    Kim, K. W.
    Kim, T. H.
    Larson, G.
    Lee, K.
    Lee, K. T.
    Leggett, R.
    Lewin, H. A.
    Li, Y.
    Liu, W.
    Loveland, J. E.
    Lu, Y.
    Lunney, J. K.
    Ma, J.
    Madsen, O.
    Mann, K.
    Matthews, L.
    McLaren, S.
    Morozumi, T.
    Murtaugh, M. P.
    Narayan, J.
    Nguyen, D. T.
    Ni, P.
    Oh, S. J.
    Onteru, S.
    Panitz, F.
    Park, E. W.
    Park, H. S.
    Pascal, G.
    Paudel, Y.
    Perez-Enciso, M.
    Ramirez-Gonzalez, R.
    Reecy, J. M.
    Rodriguez-Zas, S.
    Rohrer, G. A.
    Rund, L.
    Sang, Y.
    Schachtschneider, K.
    Schraiber, J. G.
    Schwartz, J.
    Scobie, L.
    Scott, C.
    Searle, S.
    Servin, B.
    Southey, B. R.
    Sperber, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Stadler, P.
    Sweedler, J. V.
    Tafer, H.
    Thomsen, B.
    Wali, R.
    Wang, J.
    White, S.
    Xu, X.
    Yerle, M.
    Zhang, G.
    Zhang, J.
    Zhao, S.
    Rogers, J.
    Churcher, C.
    Schook, L. B.
    Analyses of pig genomes provide insight into porcine demography and evolution2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 491, no 7424, p. 393-398Article in journal (Refereed)
    Abstract [en]

    For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

  • 176. Guan, Y.
    et al.
    Webby, R.
    Capua, I.
    Waldenström, Jonas
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    H5N1: How to track a flu virus2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 483, no 7391, p. 535-536Article in journal (Refereed)
  • 177.
    Gudasz, Cristian
    et al.
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Bastviken, David
    Linköping University, The Tema Institute, Department of Water and Environmental Studies. Linköping University, Faculty of Arts and Sciences.
    Steger, Kristin
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Premke, Katrin
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Sobek, Sebastian
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Tranvik, Lars J.
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Temperature-controlled organic carbon mineralization in lake sediments2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7305, p. 478-481Article in journal (Other academic)
    Abstract [en]

    Peatlands, soils and the ocean floor are well-recognized as sites of organic carbon accumulation and represent important global carbon sinks. Although the annual burial of organic carbon in lakes and reservoirs exceeds that of ocean sediments, these inland waters are components of the global carbon cycle that receive only limited attention. Of the organic carbon that is being deposited onto the sediments, a certain proportion will be mineralized and the remainder will be buried over geological timescales. Here we assess the relationship between sediment organic carbon mineralization and temperature in a cross-system survey of boreal lakes in Sweden, and with input from a compilation of published data from a wide range of lakes that differ with respect to climate, productivity and organic carbon source. We find that the mineralization of organic carbon in lake sediments exhibits a strongly positive relationship with temperature, which suggests that warmer water temperatures lead to more mineralization and less organic carbon burial. Assuming that future organic carbon delivery to the lake sediments will be similar to that under present-day conditions, we estimate that temperature increases following the latest scenarios presented by the Intergovernmental Panel on Climate Change could result in a 4-27 per cent (0.9-6.4 Tg C yr(-1)) decrease in annual organic carbon burial in boreal lakes.

  • 178.
    Gudasz, Cristian
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Bastviken, David
    Steger, Kristin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Premke, Katrin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Sobek, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Tranvik, Lars J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Temperature-controlled organic carbon mineralization in lake sediments2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7305, p. 478-481Article in journal (Refereed)
    Abstract [en]

    Peatlands, soils and the ocean floor are well-recognized as sites of organic carbonaccumulation andrepresentimportant global carbon sinks(1,2). Although the annual burial of organic carbon in lakes and reservoirs exceeds that of ocean sediments(3), these inland waters are components of the global carbon cycle that receive only limited attention(4-6). Of the organic carbon that is being deposited onto the sediments, a certain proportion will be mineralized and the remainder will be buried over geological timescales. Here we assess the relationship between sediment organic carbon mineralization and temperature in a cross-system survey of boreal lakes in Sweden, and with input froma compilation of published data from awide range of lakes that differ with respect to climate, productivity and organic carbon source. We find that the mineralization of organic carbon in lake sediments exhibits a strongly positive relationship with temperature, which suggests that warmer water temperatures lead to more mineralization and less organic carbon burial. Assuming that future organic carbon delivery to the lake sediments will be similar to that under present-day conditions, we estimate that temperature increases following the latest scenarios presented by the Intergovernmental Panel on Climate Change(7) could result in a 4-27 per cent (0.9-6.4 Tg Cyr(-1)) decrease in annual organic carbon burial in boreal lakes.

  • 179.
    Gudasz, Cristian
    et al.
    Limnology, Department of Ecology and Evolution, Uppsala University, Norbyvägen 18D, SE-752 36 Uppsala, Sweden.
    Bastviken, David
    Steger, Kristin
    Premke, Katrin
    Sobek, Sebastian
    Tranvik, Lars J
    Temperature-controlled organic carbon mineralization in lake sediments2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7305, p. 478-481Article in journal (Refereed)
    Abstract [en]

    Peatlands, soils and the ocean floor are well-recognized as sites of organic carbon accumulation and represent important global carbon sinks. Although the annual burial of organic carbon in lakes and reservoirs exceeds that of ocean sediments, these inland waters are components of the global carbon cycle that receive only limited attention. Of the organic carbon that is being deposited onto the sediments, a certain proportion will be mineralized and the remainder will be buried over geological timescales. Here we assess the relationship between sediment organic carbon mineralization and temperature in a cross-system survey of boreal lakes in Sweden, and with input from a compilation of published data from a wide range of lakes that differ with respect to climate, productivity and organic carbon source. We find that the mineralization of organic carbon in lake sediments exhibits a strongly positive relationship with temperature, which suggests that warmer water temperatures lead to more mineralization and less organic carbon burial. Assuming that future organic carbon delivery to the lake sediments will be similar to that under present-day conditions, we estimate that temperature increases following the latest scenarios presented by the Intergovernmental Panel on Climate Change could result in a 4-27 per cent (0.9-6.4 Tg C yr(-1)) decrease in annual organic carbon burial in boreal lakes.

  • 180.
    Guo, Peng
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Shin, Jiho
    Greenaway, Alex G.
    Min, Jung Gi
    Su, Jie
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Choi, Hyun June
    Liu, Leifeng
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Cox, Paul A.
    Hong, Suk Bong
    Wright, Paul A.
    Zou, Xiaodong
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    A zeolite family with expanding structural complexity and embedded isoreticular structures2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, p. 74-78Article in journal (Refereed)
    Abstract [en]

    The prediction and synthesis of new crystal structures enable the targeted preparation of materials with desired properties. Among porous solids, this has been achieved for metal-organic frameworks(1-3), but not for the more widely applicable zeolites(4,5), where new materials are usually discovered using exploratory synthesis. Although millions of hypothetical zeolite structures have been proposed(6,7), not enough is known about their synthesis mechanism to allow any given structure to be prepared. Here we present an approach that combines structure solution with structure prediction, and inspires the targeted synthesis of new super-complex zeolites. We used electron diffraction to identify a family of related structures and to discover the structural 'coding' within them. This allowed us to determine the complex, and previously unknown, structure of zeolite ZSM-25 (ref. 8), which has the largest unit-cell volume of all known zeolites (91,554 cubic angstroms) and demonstrates selective CO2 adsorption. By extending our method, we were able to predict other members of a family of increasingly complex, but structurally related, zeolites and to synthesize two more-complex zeolites in the family, PST-20 and PST-25, with much larger cell volumes (166,988 and 275,178 cubic angstroms, respectively) and similar selective adsorption properties. Members of this family have the same symmetry, but an expanding unit cell, and are related by hitherto unrecognized structural principles; we call these family members embedded isoreticular zeolite structures.

  • 181. Gupta, Kallol
    et al.
    Donlan, Joseph A. C.
    Hopper, Jonathan T. S.
    Uzdavinys, Povilas
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Landreh, Michael
    Struwe, Weston B.
    Drew, David
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Baldwin, Andrew J.
    Stansfeld, Phillip J.
    Robinson, Carol V.
    The role of interfacial lipids in stabilizing membrane protein oligomers2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 541, no 7637, p. 421-424Article in journal (Refereed)
    Abstract [en]

    Oligomerization of membrane proteins in response to lipid binding has a critical role in many cell-signalling pathways(1) but is often difficult to define(2) or predict(3). Here we report the development of a mass spectrometry platform to determine simultaneously the presence of interfacial lipids and oligomeric stability and to uncover how lipids act as key regulators of membrane-protein association. Evaluation of oligomeric strength for a dataset of 125 alpha-helical oligomeric membrane proteins reveals an absence of interfacial lipids in the mass spectra of 12 membrane proteins with high oligomeric stability. For the bacterial homologue of the eukaryotic biogenic transporters (LeuT(4), one of the proteins with the lowest oligomeric stability), we found a precise cohort of lipids within the dimer interface. Delipidation, mutation of lipid-binding sites or expression in cardiolipin-deficient Escherichia coli abrogated dimer formation. Molecular dynamics simulation revealed that cardiolipin acts as a bidentate ligand, bridging across subunits. Subsequently, we show that for the Vibrio splendidus sugar transporter SemiSWEET(5), another protein with low oligomeric stability, cardiolipin shifts the equilibrium from monomer to functional dimer. We hypothesized that lipids are essential for dimerization of the Na+/H+ antiporter NhaA from E. coli, which has the lowest oligomeric strength, but not for the substantially more stable homologous Thermus thermophilus protein NapA. We found that lipid binding is obligatory for dimerization of NhaA, whereas NapA has adapted to form an interface that is stable without lipids. Overall, by correlating interfacial strength with the presence of interfacial lipids, we provide a rationale for understanding the role of lipids in both transient and stable interactions within a range of a-helical membrane proteins, including G-protein-coupled receptors.

  • 182.
    Gustafsson, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Astronomy and Space Physics.
    Sanctions against scientists threaten progress2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 461, no 7265, p. 723-723Article in journal (Refereed)
  • 183.
    Gustafsson, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Astronomy and Space Physics.
    Scientists should promote co-operation, not boycott2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 447, no 7147, p. 908-908Article in journal (Refereed)
  • 184. Haak, Wolfgang
    et al.
    Lazaridis, Iosif
    Patterson, Nick
    Rohland, Nadin
    Mallick, Swapan
    Llamas, Bastien
    Brandt, Guido
    Nordenfelt, Susanne
    Harney, Eadaoin
    Stewardson, Kristin
    Fu, Qiaomei
    Mittnik, Alissa
    Banffy, Eszter
    Economou, Christos
    Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies, Archaeological Research Laboratory.
    Francken, Michael
    Friederich, Susanne
    Pena, Rafael Garrido
    Hallgren, Fredrik
    Khartanovich, Valery
    Khokhlov, Aleksandr
    Kunst, Michael
    Kuznetsov, Pavel
    Meller, Harald
    Mochalov, Oleg
    Moiseyev, Vayacheslav
    Nicklisch, Nicole
    Pichler, Sandra L.
    Risch, Roberto
    Rojo Guerra, Manuel A.
    Roth, Christina
    Szecsenyi-Nagy, Anna
    Wahl, Joachim
    Meyer, Matthias
    Krause, Johannes
    Brown, Dorcas
    Anthony, David
    Cooper, Alan
    Alt, Kurt Werner
    Reich, David
    Massive migration from the steppe was a source for Indo-European languages in Europe2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 522, no 7555, p. 207-+Article in journal (Refereed)
    Abstract [en]

    We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies(1-8) and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, similar to 8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a similar to 24,000-year-old Siberian(6). By similar to 6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact similar to 4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced similar to 75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least similar to 3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin(9) of at least some of the Indo-European languages of Europe.

  • 185. Haas, Brian J.
    et al.
    Kamoun, Sophien
    Zody, Michael C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Jiang, Rays H. Y.
    Handsaker, Robert E.
    Cano, Liliana M.
    Grabherr, Manfred
    Kodira, Chinnappa D.
    Raffaele, Sylvain
    Torto-Alalibo, Trudy
    Bozkurt, Tolga O.
    Ah-Fong, Audrey M. V.
    Alvarado, Lucia
    Anderson, Vicky L.
    Armstrong, Miles R.
    Avrova, Anna
    Baxter, Laura
    Beynon, Jim
    Boevink, Petra C.
    Bollmann, Stephanie R.
    Bos, Jorunn I. B.
    Bulone, Vincent
    Cai, Guohong
    Cakir, Cahid
    Carrington, James C.
    Chawner, Megan
    Conti, Lucio
    Costanzo, Stefano
    Ewan, Richard
    Fahlgren, Noah
    Fischbach, Michael A.
    Fugelstad, Johanna
    Gilroy, Eleanor M.
    Gnerre, Sante
    Green, Pamela J.
    Grenville-Briggs, Laura J.
    Griffith, John
    Gruenwald, Niklaus J.
    Horn, Karolyn
    Horner, Neil R.
    Hu, Chia-Hui
    Huitema, Edgar
    Jeong, Dong-Hoon
    Jones, Alexandra M. E.
    Jones, Jonathan D. G.
    Jones, Richard W.
    Karlsson, Elinor K.
    Kunjeti, Sridhara G.
    Lamour, Kurt
    Liu, Zhenyu
    Ma, LiJun
    MacLean, Daniel
    Chibucos, Marcus C.
    McDonald, Hayes
    McWalters, Jessica
    Meijer, Harold J. G.
    Morgan, William
    Morris, Paul F.
    Munro, Carol A.
    O'Neill, Keith
    Ospina-Giraldo, Manuel
    Pinzon, Andres
    Pritchard, Leighton
    Ramsahoye, Bernard
    Ren, Qinghu
    Restrepo, Silvia
    Roy, Sourav
    Sadanandom, Ari
    Savidor, Alon
    Schornack, Sebastian
    Schwartz, David C.
    Schumann, Ulrike D.
    Schwessinger, Ben
    Seyer, Lauren
    Sharpe, Ted
    Silvar, Cristina
    Song, Jing
    Studholme, David J.
    Sykes, Sean
    Thines, Marco
    van de Vondervoort, Peter J. I.
    Phuntumart, Vipaporn
    Wawra, Stephan
    Weide, Rob
    Win, Joe
    Young, Carolyn
    Zhou, Shiguo
    Fry, William
    Meyers, Blake C.
    van West, Pieter
    Ristaino, Jean
    Govers, Francine
    Birch, Paul R. J.
    Whisson, Stephen C.
    Judelson, Howard S.
    Nusbaum, Chad
    Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 461, no 7262, p. 393-398Article in journal (Refereed)
    Abstract [en]

    Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

  • 186. Haas, Brian J.
    et al.
    Kamoun, Sophien
    Zody, Michael C.
    Jiang, Rays H. Y.
    Handsaker, Robert E.
    Cano, Liliana M.
    Grabherr, Manfred
    Kodira, Chinnappa D.
    Raffaele, Sylvain
    Torto-Alalibo, Trudy
    Bozkurt, Tolga O.
    Bulone, Vincent
    KTH, School of Biotechnology (BIO), Glycoscience.
    Fugelstad, Johanna
    KTH, School of Biotechnology (BIO), Glycoscience.
    Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 461, no 7262, p. 393-398Article in journal (Refereed)
    Abstract [en]

    Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

  • 187. Hagberg, Carolina E.
    et al.
    Falkevall, Annelie
    Wang, Xun
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Huusko, Jenni
    Nilsson, Ingrid
    van Meeteren, Laurens A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Samen, Erik
    Lu, Li
    Vanwildemeersch, Maarten
    Klar, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Genove, Guillem
    Pietras, Kristian
    Stone-Elander, Sharon
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ylä-Herttuala, Seppo
    Lindahl, Per
    Eriksson, Ulf
    Vascular endothelial growth factor B controls endothelial fatty acid uptake2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7290, p. 917-921Article in journal (Refereed)
    Abstract [en]

    The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology. However, the detailed role of VEGF-B in blood vessel function has remained unclear. Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood. Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb(-/-) mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.

  • 188. Handa, I. Tanya
    et al.
    Aerts, Rien
    Berendse, Frank
    Berg, Matty P.
    Bruder, Andreas
    Butenschoen, Olaf
    Chauvet, Eric
    Gessner, Mark O.
    Jabiol, Jeremy
    Makkonen, Marika
    McKie, Brendan G.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Malmqvist, Bjoern
    Peeters, Edwin T. H. M.
    Scheu, Stefan
    Schmid, Bernhard
    van Ruijven, Jasper
    Vos, Veronique C. A.
    Haettenschwiler, Stephan
    Consequences of biodiversity loss for litter decomposition across biomes2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 509, no 7499, p. 218-221Article in journal (Refereed)
    Abstract [en]

    The decomposition of dead organic matter is a major determinant of carbon and nutrient cycling in ecosystems, and of carbon fluxes between the biosphere and the atmosphere(1-3). Decomposition is driven by a vast diversity of organisms that are structured in complex food webs(2,4). Identifying the mechanisms underlying the effects of biodiversity on decomposition is critical(4-6) given the rapid loss of species worldwide and the effects of this loss on human well-being(7-9). Yet despite comprehensive syntheses of studies on how biodiversity affects litter decomposition(4-6,10), key questions remain, including when, where and how biodiversity has a role and whether general patterns and mechanisms occur across ecosystems and different functional types of organism(4,9-12). Here, in field experiments across five terrestrial and aquatic locations, ranging from the subarctic to the tropics, we show that reducing the functional diversity of decomposer organisms and plant litter types slowed the cycling of litter carbon and nitrogen. Moreover, we found evidence of nitrogen transfer from the litter of nitrogen-fixing plants to that of rapidly decomposing plants, but not between other plant functional types, highlighting that specific interactions in litter mixtures control carbon and nitrogen cycling during decomposition. The emergence of this general mechanism and the coherence of patterns across contrasting terrestrial and aquatic ecosystems suggest that biodiversity loss has consistent consequences for litter decomposition and the cycling of major elements on broad spatial scales.

  • 189.
    Hansson, Mats G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Biobanks: Validate gene findings before telling donors2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 484, no 7395, p. 455-455Article in journal (Refereed)
  • 190.
    Hashimoto, Takuya
    et al.
    Osaka Sangyo Univ, Dept Environm Sci & Technol, Fac Design Technol, Osaka, Japan;Natl Astron Observ Japan, Tokyo, Japan.
    Laporte, Nicolas
    UCL, Dept Phys & Astron, London, England;Univ Toulouse, CNRS, IRAP, UPS,CNES, Toulouse, France.
    Mawatari, Ken
    Osaka Sangyo Univ, Dept Environm Sci & Technol, Fac Design Technol, Osaka, Japan.
    Ellis, Richard S.
    UCL, Dept Phys & Astron, London, England.
    Inoue, Akio K.
    Osaka Sangyo Univ, Dept Environm Sci & Technol, Fac Design Technol, Osaka, Japan.
    Zackrisson, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Observational Astronomy.
    Roberts-Borsani, Guido
    UCL, Dept Phys & Astron, London, England.
    Zheng, Wei
    Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
    Tamura, Yoichi
    Nagoya Univ, Grad Sch Sci, Div Particle & Astrophys Sci, Nagoya, Aichi, Japan.
    Bauer, Franz E.
    Pontificia Univ Catolica Chile, Fac Fis, Inst Astrofis, Santiago, Chile;Pontificia Univ Catolica Chile, Fac Fis, Ctr Astroingn, Santiago, Chile;Space Sci Inst, Boulder, CO USA.
    Fletcher, Thomas
    UCL, Dept Phys & Astron, London, England.
    Harikane, Yuichi
    Univ Tokyo, Inst Cosm Ray Res, Chiba, Japan;Univ Tokyo, Grad Sch Sci, Dept Phys, Tokyo, Japan.
    Hatsukade, Bunyo
    Univ Tokyo, Inst Astron, Tokyo, Japan.
    Hayatsu, Natsuki H.
    Univ Tokyo, Grad Sch Sci, Dept Phys, Tokyo, Japan;European Southern Observ, Garching, Germany.
    Matsuda, Yuichi
    Natl Astron Observ Japan, Tokyo, Japan;Grad Univ Adv Studies SOKENDAI, Sch Phys Sci, Dept Astron Sci, Tokyo, Japan.
    Matsuo, Hiroshi
    Natl Astron Observ Japan, Tokyo, Japan;Grad Univ Adv Studies SOKENDAI, Sch Phys Sci, Dept Astron Sci, Tokyo, Japan.
    Okamoto, Takashi
    Hokakido Univ, Dept Cosmosci, Grad Sch Sci, Sapporo, Hokkaido, Japan.
    Ouchi, Masami
    Univ Tokyo, Inst Cosm Ray Res, Chiba, Japan;Univ Tokyo, Kavli Inst Phys & Math Universe WPI, Todai Inst Adv Study, Chiba, Japan.
    Pello, Roser
    Univ Toulouse, CNRS, IRAP, UPS,CNES, Toulouse, France.
    Rydberg, Claes-Erik
    Heidelberg Univ, Zentrum Astron, Inst Theoret Astrophys, Heidelberg, Germany.
    Shimizu, Ikkoh
    Osaka Univ, Dept Earth & Space Sci, Theoret Astrophys, Osaka, Japan.
    Taniguchi, Yoshiaki
    Open Univ Japan, Chiba, Japan.
    Umehata, Hideki
    Open Univ Japan, Chiba, Japan;Inst Phys & Chem Res RIKEN, Saitama, Japan.
    Yoshida, Naoki
    Univ Tokyo, Grad Sch Sci, Dept Phys, Tokyo, Japan;Univ Tokyo, Kavli Inst Phys & Math Universe WPI, Todai Inst Adv Study, Chiba, Japan.
    The onset of star formation 250 million years after the Big Bang2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 557, no 7705, p. 392-395Article in journal (Refereed)
    Abstract [en]

    A fundamental quest of modern astronomy is to locate the earliest galaxies and study how they influenced the intergalactic medium a few hundred million years after the Big Bang(1-3). The abundance of star-forming galaxies is known to decline(4,5) from redshifts of about 6 to 10, but a key question is the extent of star formation at even earlier times, corresponding to the period when the first galaxies might have emerged. Here we report spectroscopic observations of MACS1149-JD1(6), a gravitationally lensed galaxy observed when the Universe was less than four per cent of its present age. We detect an emission line of doubly ionized oxygen at a redshift of 9.1096 +/- 0.0006, with an uncertainty of one standard deviation. This precisely determined redshift indicates that the red rest-frame optical colour arises from a dominant stellar component that formed about 250 million years after the Big Bang, corresponding to a redshift of about 15. Our results indicate that it may be possible to detect such early episodes of star formation in similar galaxies with future telescopes.

  • 191. Hayes, Matthew
    et al.
    Östlin, Göran
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Schaerer, Daniel
    Miguel Mas-Hesse, J.
    Leitherer, Claus
    Atek, Hakim
    Kunth, Daniel
    Verhamme, Anne
    de Barros, Stephane
    Melinder, Jens
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Escape of about five per cent of Lyman-alpha photons from high-redshift star-forming galaxies2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7288, p. 562-565Article in journal (Refereed)
    Abstract [en]

    The Lyman-alpha (Ly alpha) emission line is the primary observational signature of star-forming galaxies at the highest redshifts(1), and has enabled the compilation of large samples of galaxies with which to study cosmic evolution(2-5). The resonant nature of the line, however, means that Ly alpha photons scatter in the neutral interstellar medium of their host galaxies, and their sensitivity to absorption by interstellar dust may therefore be greatly enhanced. This implies that the Ly alpha luminosity may be significantly reduced, or even completely suppressed. Hitherto, no unbiased empirical test of the escaping fraction (f(esc)) of Ly alpha photons has been performed at high redshifts. Here we report that the average f(esc) from star-forming galaxies at redshift z=2.2 is just 5 per cent by performing a blind narrowband survey in Ly alpha and H alpha. This implies that numerous conclusions based on Ly alpha-selected samples will require upwards revision by an order of magnitude and we provide a benchmark for this revision. We demonstrate that almost 90 per cent of star-forming galaxies emit insufficient Ly alpha to be detected by standard selection criteria(2-5). Both samples show an anti-correlation of f(esc) with dust content, and we show that Ly alpha- and H alpha-selection recovers populations that differ substantially in dust content and f(esc).

  • 192.
    Heinzel, T.
    et al.
    University of California, San Diego, USA.
    Lavinsky, R. M.
    University of California, San Diego, USA.
    Mullen, T. M.
    University of California, San Diego, USA.
    Söderström, Mats
    University of California, San Diego, USA.
    Laherty, C. D.
    Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
    Torchia, J.
    University of California, San Diego, USA.
    Yang, W. M.
    University of South Florida, Tampa, USA.
    Brard, G.
    University of California, San Diego, USA.
    Ngo, S. D.
    University of California, San Diego, USA.
    Davie, J. R.
    University of Manitoba, Winnipeg, Canada.
    Seto, E.
    University of South Florida, Tampa, USA.
    Eisenman, R. N.
    Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
    Rose, D. W.
    University of California, San Diego, USA.
    Glass, C. K.
    University of California, San Diego, USA.
    Rosenfeld, M. G.
    University of California, San Diego, USA.
    A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression1997In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 387, no 6628, p. 43-48Article in journal (Refereed)
    Abstract [en]

    Transcriptional repression by nuclear receptors has been correlated to binding of the putative co-repressor, N-CoR. A complex has been identified that contains N-CoR, the Mad presumptive co-repressor mSin3, and the histone deacetylase mRPD3, and which is required for both nuclear receptor- and Mad-dependent repression, but not for repression by transcription factors of the ets-domain family. These data predict that the ligand-induced switch of heterodimeric nuclear receptors from repressor to activator functions involves the exchange of complexes containing histone deacetylases with those that have histone acetylase activity.

  • 193.
    Hessa, Tara
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kim, Hyun
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Bihlmaier, Karl
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lundin, Carolina
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Boekel, Jorrit
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Andersson, Helena
    Nilsson, IngMarie
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    White, Stephen
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Recognition of transmembrane helices by the endoplasmic reticulum translocon2005In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 433, no 7024, p. 377-381Article in journal (Refereed)
    Abstract [en]

    Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein - lipid interactions are critical during translocon-mediated membrane insertion.

  • 194.
    Hessa, Tara
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Meindl-Beinker, Nadja M.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Bernsel, Andreas
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kim, Hyun
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Sato, Yoko
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lerch-Bader, Mirjam
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Nilsson, IngMarie
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    White, Stephen H.
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Molecular code for transmembrane-helix recognition by the Sec61 translocon2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 450, no 7172, p. 1026-1030Article in journal (Refereed)
    Abstract [en]

    Transmembrane alpha-helices in integral membrane proteins are recognized co-translationally and inserted into the membrane of the endoplasmic reticulum by the Sec61 translocon. A full quantitative description of this phenomenon, linking amino acid sequence to membrane insertion efficiency, is still lacking. Here, using in vitro translation of a model protein in the presence of dog pancreas rough microsomes to analyse a large number of systematically designed hydrophobic segments, we present a quantitative analysis of the position- dependent contribution of all 20 amino acids to membrane insertion efficiency, as well as of the effects of transmembrane segment length and flanking amino acids. The emerging picture of translocon- mediated transmembrane helix assembly is simple, with the critical sequence characteristics mirroring the physical properties of the lipid bilayer.

  • 195. Hibar, Derrek P.
    et al.
    Stein, Jason L.
    Renteria, Miguel E.
    Arias-Vasquez, Alejandro
    Desrivieres, Sylvane
    Jahanshad, Neda
    Toro, Roberto
    Wittfeld, Katharina
    Abramovic, Lucija
    Andersson, Micael
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Aribisala, Benjamin S.
    Armstrong, Nicola J.
    Bernard, Manon
    Bohlken, Marc M.
    Boks, Marco P.
    Bralten, Janita
    Brown, Andrew A.
    Chakravarty, M. Mallar
    Chen, Qiang
    Ching, Christopher R. K.
    Cuellar-Partida, Gabriel
    den Braber, Anouk
    Giddaluru, Sudheer
    Goldman, Aaron L.
    Grimm, Oliver
    Guadalupe, Tulio
    Hass, Johanna
    Woldehawariat, Girma
    Holmes, Avram J.
    Hoogman, Martine
    Janowitz, Deborah
    Jia, Tianye
    Kim, Sungeun
    Klein, Marieke
    Kraemer, Bernd
    Lee, Phil H.
    Loohuis, Loes M. Olde
    Luciano, Michelle
    Macare, Christine
    Mather, Karen A.
    Mattheisen, Manuel
    Milaneschi, Yuri
    Nho, Kwangsik
    Papmeyer, Martina
    Ramasamy, Adaikalavan
    Risacher, Shannon L.
    Roiz-Santianez, Roberto
    Rose, Emma J.
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Saemann, Philipp G.
    Schmaal, Lianne
    Schork, Andrew J.
    Shin, Jean
    Strike, Lachlan T.
    Teumer, Alexander
    van Donkelaar, Marjolein M. J.
    van Eijk, Kristel R.
    Walters, Raymond K.
    Westlye, Lars T.
    Whelan, Christopher D.
    Winkler, Anderson M.
    Zwiers, Marcel P.
    Alhusaini, Saud
    Athanasiu, Lavinia
    Ehrlich, Stefan
    Hakobjan, Marina M. H.
    Hartberg, Cecilie B.
    Haukvik, Unn K.
    Heister, Angelien J. G. A. M.
    Hoehn, David
    Kasperaviciute, Dalia
    Liewald, David C. M.
    Lopez, Lorna M.
    Makkinje, Remco R. R.
    Matarin, Mar
    Naber, Marlies A. M.
    McKay, D. Reese
    Needham, Margaret
    Nugent, Allison C.
    Puetz, Benno
    Royle, Natalie A.
    Shen, Li
    Sprooten, Emma
    Trabzuni, Daniah
    van der Marel, Saskia S. L.
    van Hulzen, Kimm J. E.
    Walton, Esther
    Wolf, Christiane
    Almasy, Laura
    Ames, David
    Arepalli, Sampath
    Assareh, Amelia A.
    Bastin, Mark E.
    Brodaty, Henry
    Bulayeva, Kazima B.
    Carless, Melanie A.
    Cichon, Sven
    Corvin, Aiden
    Curran, Joanne E.
    Czisch, Michael
    de Zubicaray, Greig I.
    Dillman, Allissa
    Duggirala, Ravi
    Dyer, Thomas D.
    Erk, Susanne
    Fedko, Iryna O.
    Ferrucci, Luigi
    Foroud, Tatiana M.
    Fox, Peter T.
    Fukunaga, Masaki
    Gibbs, J. Raphael
    Goering, Harald H. H.
    Green, Robert C.
    Guelfi, Sebastian
    Hansell, Narelle K.
    Hartman, Catharina A.
    Hegenscheid, Katrin
    Heinz, Andreas
    Hernandez, Dena G.
    Heslenfeld, Dirk J.
    Hoekstra, Pieter J.
    Holsboer, Florian
    Homuth, Georg
    Hottenga, Jouke-Jan
    Ikeda, Masashi
    Jack, Clifford R., Jr.
    Jenkinson, Mark
    Johnson, Robert
    Kanai, Ryota
    Keil, Maria
    Kent, Jack W., Jr.
    Kochunov, Peter
    Kwok, John B.
    Lawrie, Stephen M.
    Liu, Xinmin
    Longo, Dan L.
    McMahon, Katie L.
    Meisenzah, Eva
    Melle, Ingrid
    Mahnke, Sebastian
    Montgomery, Grant W.
    Mostert, Jeanette C.
    Muehleisen, Thomas W.
    Nalls, Michael A.
    Nichols, Thomas E.
    Nilsson, Lars G.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Noethen, Markus M.
    Ohi, Kazutaka
    Olvera, Rene L.
    Perez-Iglesias, Rocio
    Pike, G. Bruce
    Potkin, Steven G.
    Reinvang, Ivar
    Reppermund, Simone
    Rietschel, Marcella
    Romanczuk-Seiferth, Nina
    Rosen, Glenn D.
    Rujescu, Dan
    Schnell, Knut
    Schofield, Peter R.
    Smith, Colin
    Steen, Vidar M.
    Sussmann, Jessika E.
    Thalamuthu, Anbupalam
    Toga, Arthur W.
    Traynor, Bryan J.
    Troncoso, Juan
    Turner, Jessica A.
    Valdes Hernandez, Maria C.
    van't Ent, Dennis
    van der Brug, Marcel
    van der Wee, Nic J. A.
    van Tol, Marie-Jose
    Veltman, Dick J.
    Wassink, Thomas H.
    Westman, Eric
    Zielke, Ronald H.
    Zonderman, Alan B.
    Ashbrook, David G.
    Hager, Reinmar
    Lu, Lu
    McMahon, Francis J.
    Morris, Derek W.
    Williams, Robert W.
    Brunner, Han G.
    Buckner, Randy L.
    Buitelaar, Jan K.
    Cahn, Wiepke
    Calhoun, Vince D.
    Cavalleri, Gianpiero L.
    Crespo-Facorro, Benedicto
    Dale, Anders M.
    Davies, Gareth E.
    Delanty, Norman
    Depondt, Chantal
    Djurovic, Srdjan
    Drevets, Wayne C.
    Espeseth, Thomas
    Gollub, Randy L.
    Ho, Beng-Choon
    Hoffman, Wolfgang
    Hosten, Norbert
    Kahn, Rene S.
    Le Hellard, Stephanie
    Meyer-Lindenberg, Andreas
    Mueller-Myhsok, Bertram
    Nauck, Matthias
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Pandolfo, Massimo
    Penninx, Brenda W. J. H.
    Roffman, Joshua L.
    Sisodiya, Sanjay M.
    Smoller, Jordan W.
    van Bokhoven, Hans
    van Haren, Neeltje E. M.
    Voelzke, Henry
    Walter, Henrik
    Weiner, Michael W.
    Wen, Wei
    White, Tonya
    Agartz, Ingrid
    Andreassen, Ole A.
    Blangero, John
    Boomsma, Dorret I.
    Brouwer, Rachel M.
    Cannon, Dara M.
    Cookson, Mark R.
    de Geus, Eco J. C.
    Deary, Ian J.
    Donohoe, Gary
    Fernandez, Guillen
    Fisher, Simon E.
    Francks, Clyde
    Glahn, David C.
    Grabe, Hans J.
    Gruber, Oliver
    Hardy, John
    Hashimoto, Ryota
    Pol, Hilleke E. Hulshoff
    Joensson, Erik G.
    Kloszewska, Iwona
    Lovestone, Simon
    Mattay, Venkata S.
    Mecocci, Patrizia
    McDonald, Colm
    McIntosh, Andrew M.
    Ophoff, Roel A.
    Paus, Tomas
    Pausova, Zdenka
    Ryten, Mina
    Sachdev, Perminder S.
    Saykin, Andrew J.
    Simmons, Andy
    Singleton, Andrew
    Soininen, Hilkka
    Wardlaw, Joanna M.
    Weale, Michael E.
    Weinberger, Daniel R.
    Adams, Hieab H. H.
    Launer, Lenore J.
    Seiler, Stephan
    Schmidt, Reinhold
    Chauhan, Ganesh
    Satizabal, Claudia L.
    Becker, James T.
    Yanek, Lisa
    van der Lee, Sven J.
    Ebling, Maritza
    Fischl, Bruce
    Longstreth, W. T., Jr.
    Greve, Douglas
    Schmidt, Helena
    Nyquist, Paul
    Vinke, Louis N.
    van Duijn, Cornelia M.
    Xue, Luting
    Mazoyer, Bernard
    Bis, Joshua C.
    Gudnason, Vilmundur
    Seshadri, Sudha
    Ikram, M. Arfan
    Martin, Nicholas G.
    Wright, Margaret J.
    Schumann, Gunter
    Franke, Barbara
    Thompson, Paul M., Jr.
    Medland, Sarah E.
    Common genetic variants influence human subcortical brain structures2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 520, no 7546, p. 224-U216Article in journal (Refereed)
    Abstract [en]

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

  • 196.
    Hieronymus, C.F.
    et al.
    Danish Lithosphere Centre.
    Bercovici, D.
    University of Hawaii.
    Discrete alternating hotspot islands formed by interaction of magma transport and lithospheric flexure1999In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 397, no 6720, p. 604-607Article in journal (Refereed)
    Abstract [en]

    The large-scale geometry and age progression of many hotspot island chains, such as the Hawaiian-Emperor chain, are well explained by the steady movement of tectonic plates over stationary hotspots. But on a smaller scale, hotspot tracks are composed of discrete volcanic islands whose spacing correlates with lithospheric thickness(1). Moreover, the volcanic shields themselves are often not positioned along single lines, but in more complicated patterns, such as the dual line known as the Kea and Loa trends of the Hawaiian islands(2,3). Here we make use of the hypothesis that. island spacing is controlled by lithospheric flexure(1) to develop a simple nonlinear model coupling magma flow, which feeds volcanic growth, to the flexure caused by volcanic loads on the underlying plate. For a steady source of melt underneath a moving lithospheric plate, magma is found to reach the surface and build a chain of separate volcanic edifices with realistic spacing. If a volcano is introduced away from the axis of the chain, as might occur following a change in the direction of plate motion, the model perpetuates the asymmetry for long distances and times, thereby producing an alternating: series of edifices similar to that observed in the Kea and Loa trends of the Hawaiian island chain.

  • 197.
    Hill, Russell
    et al.
    Karolinska Institutet.
    Århem, Peter
    Karolinska Institutet.
    Lindahl, B. I. B.
    Stockholm University, Faculty of Humanities, Department of Philosophy.
    Origin of Life1994In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 371, p. 646-Article in journal (Other academic)
  • 198. Hillier, Ladeana W
    et al.
    Miller, Webb
    Birney, Ewan
    Warren, Wesley
    Hardison, Ross C
    Ponting, Chris P
    Bork, Peer
    Burt, David W
    Groenen, Martien A M
    Delany, Mary E
    Dodgson, Jerry B
    Chinwalla, Asif T
    Cliften, Paul F
    Clifton, Sandra W
    Delehaunty, Kimberly D
    Fronick, Catrina
    Fulton, Robert S
    Graves, Tina A
    Kremitzki, Colin
    Layman, Dan
    Magrini, Vincent
    McPherson, John D
    Miner, Tracie L
    Minx, Patrick
    Nash, William E
    Nhan, Michael N
    Nelson, Joanne O
    Oddy, Lachlan G
    Pohl, Craig S
    Randall-Maher, Jennifer
    Smith, Scott M
    Wallis, John W
    Yang, Shiaw-Pyng
    Romanov, Michael N
    Rondelli, Catherine M
    Paton, Bob
    Smith, Jacqueline
    Morrice, David
    Daniels, Laura
    Tempest, Helen G
    Robertson, Lindsay
    Masabanda, Julio S
    Griffin, Darren K
    Vignal, Alain
    Fillon, Valerie
    Jacobbson, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kerje, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Crooijmans, Richard P M
    Aerts, Jan
    van der Poel, Jan J
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Caldwell, Randolph B
    Hubbard, Simon J
    Grafham, Darren V
    Kierzek, Andrzej M
    McLaren, Stuart R
    Overton, Ian M
    Arakawa, Hiroshi
    Beattie, Kevin J
    Bezzubov, Yuri
    Boardman, Paul E
    Bonfield, James K
    Croning, Michael D R
    Davies, Robert M
    Francis, Matthew D
    Humphray, Sean J
    Scott, Carol E
    Taylor, Ruth G
    Tickle, Cheryll
    Brown, William R A
    Rogers, Jane
    Buerstedde, Jean-Marie
    Wilson, Stuart A
    Stubbs, Lisa
    Ovcharenko, Ivan
    Gordon, Laurie
    Lucas, Susan
    Miller, Marcia M
    Inoko, Hidetoshi
    Shiina, Takashi
    Kaufman, Jim
    Salomonsen, Jan
    Skjoedt, Karsten
    Wong, Gane Ka-Shu
    Wang, Jun
    Liu, Bin
    Wang, Jian
    Yu, Jun
    Yang, Huanming
    Nefedov, Mikhail
    Koriabine, Maxim
    Dejong, Pieter J
    Goodstadt, Leo
    Webber, Caleb
    Dickens, Nicholas J
    Letunic, Ivica
    Suyama, Mikita
    Torrents, David
    von Mering, Christian
    Zdobnov, Evgeny M
    Makova, Kateryna
    Nekrutenko, Anton
    Elnitski, Laura
    Eswara, Pallavi
    King, David C
    Yang, Shan
    Tyekucheva, Svitlana
    Radakrishnan, Anusha
    Harris, Robert S
    Chiaromonte, Francesca
    Taylor, James
    He, Jianbin
    Rijnkels, Monique
    Griffiths-Jones, Sam
    Ureta-Vidal, Abel
    Hoffman, Michael M
    Severin, Jessica
    Searle, Stephen M J
    Law, Andy S
    Speed, David
    Waddington, Dave
    Cheng, Ze
    Tuzun, Eray
    Eichler, Evan
    Bao, Zhirong
    Flicek, Paul
    Shteynberg, David D
    Brent, Michael R
    Bye, Jacqueline M
    Huckle, Elizabeth J
    Chatterji, Sourav
    Dewey, Colin
    Pachter, Lior
    Kouranov, Andrei
    Mourelatos, Zissimos
    Hatzigeorgiou, Artemis G
    Paterson, Andrew H
    Ivarie, Robert
    Brandström, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Axelsson, Erik
    Backström, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Berlin, Sofia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Webster, Matthew T
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Pourquie, Olivier
    Reymond, Alexandre
    Ucla, Catherine
    Antonarakis, Stylianos E
    Long, Manyuan
    Emerson, J J
    Betrán, Esther
    Dupanloup, Isabelle
    Kaessmann, Henrik
    Hinrichs, Angie S
    Bejerano, Gill
    Furey, Terrence S
    Harte, Rachel A
    Raney, Brian
    Siepel, Adam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kent, W James
    Haussler, David
    Eyras, Eduardo
    Castelo, Robert
    Abril, Josep F
    Castellano, Sergi
    Camara, Francisco
    Parra, Genis
    Guigo, Roderic
    Bourque, Guillaume
    Tesler, Glenn
    Pevzner, Pavel A
    Smit, Arian
    Fulton, Lucinda A
    Mardis, Elaine R
    Wilson, Richard K
    Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution2004In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 432, no 7018, p. 695-716Article in journal (Refereed)
    Abstract [en]

    We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.

  • 199. Hilton, Robert G.
    et al.
    Galy, Valier
    Gaillardet, Jerome
    Dellinger, Mathieu
    Bryant, Charlotte
    O'Regan, Matt
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Groecke, Darren R.
    Coxall, Helen
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Bouchez, Julien
    Calmels, Damien
    Erosion of organic carbon in the Arctic as a geological carbon dioxide sink2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, no 7563, p. 84-U162Article in journal (Refereed)
    Abstract [en]

    Soils of the northern high latitudes store carbon over millennial timescales (thousands of years) and contain approximately double the carbon stock of the atmosphere(1-3). Warming and associated permafrost thaw can expose soil organic carbon and result in mineralization and carbon dioxide (CO2) release(4-6). However, some of this soil organic carbon may be eroded and transferred to rivers(7-9). If it escapes degradation during river transport and is buried in marine sediments, then it can contribute to a longer-term (more than ten thousand years), geological CO2 sink(8-10). Despite this recognition, the erosional flux and fate of particulate organic carbon (POC) in large rivers at high latitudes remains poorly constrained. Here, we quantify the source of POC in the Mackenzie River, the main sediment supplier to the Arctic Ocean(11,12), and assess its flux and fate. We combine measurements of radiocarbon, stable carbon isotopes and element ratios to correct for rock-derived POC10,13,14. Our samples reveal that the eroded biospheric POC has resided in the basin for millennia, with a mean radiocarbon age of 5,800 +/- 800 years, much older than the POC in large tropical rivers(13,14). From the measured biospheric POC content and variability in annual sediment yield(15), we calculate a biospheric POC flux of 2.2(-0.9)(+1.3) teragrams of carbon per year from the Mackenzie River, which is three times the CO2 drawdown by silicate weathering in this basin(16). Offshore, we find evidence for efficient terrestrial organic carbon burial over the Holocene period, suggesting that erosion of organic carbon-rich, high-latitude soils may result in an important geological CO2 sink.

  • 200. Hinke, C. B.
    et al.
    Boehmer, M.
    Boutachkov, P.
    Faestermann, T.
    Geissel, H.
    Gerl, J.
    Gernhaeuser, R.
    Gorska, M.
    Gottardo, A.
    Grawe, H.
    Grebosz, J. L.
    Kruecken, R.
    Kurz, N.
    Liu, Z.
    Maier, L.
    Nowacki, F.
    Pietri, S.
    Podolyak, Zs
    Sieja, K.
    Steiger, K.
    Straub, K.
    Weick, H.
    Wollersheim, H. -J
    Woods, P. J.
    Al-Dahan, N.
    Alkhomashi, N.
    Atac, A.
    Blazhev, A.
    Braun, N. F.
    Celikovic, I. T.
    Davinson, T.
    Dillmann, I.
    Domingo-Pardo, C.
    Doornenbal, P. C.
    de France, G.
    Farrelly, G. F.
    Farinon, F.
    Goel, N.
    Habermann, T. C.
    Hoischen, R.
    Janik, R.
    Karny, M.
    Kaskas, A.
    Kojouharov, I. M.
    Kroell, Th
    Litvinov, Y.
    Myalski, S.
    Nebel, F.
    Nishimura, S.
    Nociforo, C.
    Nyberg, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Parikh, A. R.
    Prochazka, A.
    Regan, P. H.
    Rigollet, C.
    Schaffner, H.
    Scheidenberger, C.
    Schwertel, S.
    Soederstroem, P. -A
    Steer, S. J.
    Stolz, A.
    Strmen, P.
    Superallowed Gamow-Teller decay of the doubly magic nucleus 100Sn2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 486, no 7403, p. 341-345Article in journal (Refereed)
    Abstract [en]

    The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During beta(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of Sn-100, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the beta-decay of Sn-100, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear beta-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, In-100, are well reproduced by modern, large-scale shell model calculations.

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