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  • Models, Biological  (85)
  • Nature Publishing Group (NPG)  (85)
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    Nature Publishing Group (NPG)
    Publication Date: 2015-02-13
    Description: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P 〈 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338562/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338562/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shungin, Dmitry -- Winkler, Thomas W -- Croteau-Chonka, Damien C -- Ferreira, Teresa -- Locke, Adam E -- Magi, Reedik -- Strawbridge, Rona J -- Pers, Tune H -- Fischer, Krista -- Justice, Anne E -- Workalemahu, Tsegaselassie -- Wu, Joseph M W -- Buchkovich, Martin L -- Heard-Costa, Nancy L -- Roman, Tamara S -- Drong, Alexander W -- Song, Ci -- Gustafsson, Stefan -- Day, Felix R -- Esko, Tonu -- Fall, Tove -- Kutalik, Zoltan -- Luan, Jian'an -- Randall, Joshua C -- Scherag, Andre -- Vedantam, Sailaja -- Wood, Andrew R -- Chen, Jin -- Fehrmann, Rudolf -- Karjalainen, Juha -- Kahali, Bratati -- Liu, Ching-Ti -- Schmidt, Ellen M -- Absher, Devin -- Amin, Najaf -- Anderson, Denise -- Beekman, Marian -- Bragg-Gresham, Jennifer L -- Buyske, Steven -- Demirkan, Ayse -- Ehret, Georg B -- Feitosa, Mary F -- Goel, Anuj -- Jackson, Anne U -- Johnson, Toby -- Kleber, Marcus E -- Kristiansson, Kati -- Mangino, Massimo -- Mateo Leach, Irene -- Medina-Gomez, Carolina -- Palmer, Cameron D -- Pasko, Dorota -- Pechlivanis, Sonali -- Peters, Marjolein J -- Prokopenko, Inga -- Stancakova, Alena -- Ju Sung, Yun -- Tanaka, Toshiko -- Teumer, Alexander -- Van Vliet-Ostaptchouk, Jana V -- Yengo, Loic -- Zhang, Weihua -- Albrecht, Eva -- Arnlov, Johan -- Arscott, Gillian M -- Bandinelli, Stefania -- Barrett, Amy -- Bellis, Claire -- Bennett, Amanda J -- Berne, Christian -- Bluher, Matthias -- Bohringer, Stefan -- Bonnet, Fabrice -- Bottcher, Yvonne -- Bruinenberg, Marcel -- Carba, Delia B -- Caspersen, Ida H -- Clarke, Robert -- Daw, E Warwick -- Deelen, Joris -- Deelman, Ewa -- Delgado, Graciela -- Doney, Alex S F -- Eklund, Niina -- Erdos, Michael R -- Estrada, Karol -- Eury, Elodie -- Friedrich, Nele -- Garcia, Melissa E -- Giedraitis, Vilmantas -- Gigante, Bruna -- Go, Alan S -- Golay, Alain -- Grallert, Harald -- Grammer, Tanja B -- Grassler, Jurgen -- Grewal, Jagvir -- Groves, Christopher J -- Haller, Toomas -- Hallmans, Goran -- Hartman, Catharina A -- Hassinen, Maija -- Hayward, Caroline -- Heikkila, Kauko -- Herzig, Karl-Heinz -- Helmer, Quinta -- Hillege, Hans L -- Holmen, Oddgeir -- Hunt, Steven C -- Isaacs, Aaron -- Ittermann, Till -- James, Alan L -- Johansson, Ingegerd -- Juliusdottir, Thorhildur -- Kalafati, Ioanna-Panagiota -- Kinnunen, Leena -- Koenig, Wolfgang -- Kooner, Ishminder K -- Kratzer, Wolfgang -- Lamina, Claudia -- Leander, Karin -- Lee, Nanette R -- Lichtner, Peter -- Lind, Lars -- Lindstrom, Jaana -- Lobbens, Stephane -- Lorentzon, Mattias -- Mach, Francois -- Magnusson, Patrik K E -- Mahajan, Anubha -- McArdle, Wendy L -- Menni, Cristina -- Merger, Sigrun -- Mihailov, Evelin -- Milani, Lili -- Mills, Rebecca -- Moayyeri, Alireza -- Monda, Keri L -- Mooijaart, Simon P -- Muhleisen, Thomas W -- Mulas, Antonella -- Muller, Gabriele -- Muller-Nurasyid, Martina -- Nagaraja, Ramaiah -- Nalls, Michael A -- Narisu, Narisu -- Glorioso, Nicola -- Nolte, Ilja M -- Olden, Matthias -- Rayner, Nigel W -- Renstrom, Frida -- Ried, Janina S -- Robertson, Neil R -- Rose, Lynda M -- Sanna, Serena -- Scharnagl, Hubert -- Scholtens, Salome -- Sennblad, Bengt -- Seufferlein, Thomas -- Sitlani, Colleen M -- Vernon Smith, Albert -- Stirrups, Kathleen -- Stringham, Heather M -- Sundstrom, Johan -- Swertz, Morris A -- Swift, Amy J -- Syvanen, Ann-Christine -- Tayo, Bamidele O -- Thorand, Barbara -- Thorleifsson, Gudmar -- Tomaschitz, Andreas -- Troffa, Chiara -- van Oort, Floor V A -- Verweij, Niek -- Vonk, Judith M -- Waite, Lindsay L -- Wennauer, Roman -- Wilsgaard, Tom -- Wojczynski, Mary K -- Wong, Andrew -- Zhang, Qunyuan -- Hua Zhao, Jing -- Brennan, Eoin P -- Choi, Murim -- Eriksson, Per -- Folkersen, Lasse -- Franco-Cereceda, Anders -- Gharavi, Ali G -- Hedman, Asa K -- Hivert, Marie-France -- Huang, Jinyan -- Kanoni, Stavroula -- Karpe, Fredrik -- Keildson, Sarah -- Kiryluk, Krzysztof -- Liang, Liming -- Lifton, Richard P -- Ma, Baoshan -- McKnight, Amy J -- McPherson, Ruth -- Metspalu, Andres -- Min, Josine L -- Moffatt, Miriam F -- Montgomery, Grant W -- Murabito, Joanne M -- Nicholson, George -- Nyholt, Dale R -- Olsson, Christian -- Perry, John R B -- Reinmaa, Eva -- Salem, Rany M -- Sandholm, Niina -- Schadt, Eric E -- Scott, Robert A -- Stolk, Lisette -- Vallejo, Edgar E -- Westra, Harm-Jan -- Zondervan, Krina T -- ADIPOGen Consortium -- CARDIOGRAMplusC4D Consortium -- CKDGen Consortium -- GEFOS Consortium -- GENIE Consortium -- GLGC -- ICBP -- International Endogene Consortium -- LifeLines Cohort Study -- MAGIC Investigators -- MuTHER Consortium -- PAGE Consortium -- ReproGen Consortium -- Amouyel, Philippe -- Arveiler, Dominique -- Bakker, Stephan J L -- Beilby, John -- Bergman, Richard N -- Blangero, John -- Brown, Morris J -- Burnier, Michel -- Campbell, Harry -- Chakravarti, Aravinda -- Chines, Peter S -- Claudi-Boehm, Simone -- Collins, Francis S -- Crawford, Dana C -- Danesh, John -- de Faire, Ulf -- de Geus, Eco J C -- Dorr, Marcus -- Erbel, Raimund -- Eriksson, Johan G -- Farrall, Martin -- Ferrannini, Ele -- Ferrieres, Jean -- Forouhi, Nita G -- Forrester, Terrence -- Franco, Oscar H -- Gansevoort, Ron T -- Gieger, Christian -- Gudnason, Vilmundur -- Haiman, Christopher A -- Harris, Tamara B -- Hattersley, Andrew T -- Heliovaara, Markku -- Hicks, Andrew A -- Hingorani, Aroon D -- Hoffmann, Wolfgang -- Hofman, Albert -- Homuth, Georg -- Humphries, Steve E -- Hypponen, Elina -- Illig, Thomas -- Jarvelin, Marjo-Riitta -- Johansen, Berit -- Jousilahti, Pekka -- Jula, Antti M -- Kaprio, Jaakko -- Kee, Frank -- Keinanen-Kiukaanniemi, Sirkka M -- Kooner, Jaspal S -- Kooperberg, Charles -- Kovacs, Peter -- Kraja, Aldi T -- Kumari, Meena -- Kuulasmaa, Kari -- Kuusisto, Johanna -- Lakka, Timo A -- Langenberg, Claudia -- Le Marchand, Loic -- Lehtimaki, Terho -- Lyssenko, Valeriya -- Mannisto, Satu -- Marette, Andre -- Matise, Tara C -- McKenzie, Colin A -- McKnight, Barbara -- Musk, Arthur W -- Mohlenkamp, Stefan -- Morris, Andrew D -- Nelis, Mari -- Ohlsson, Claes -- Oldehinkel, Albertine J -- Ong, Ken K -- Palmer, Lyle J -- Penninx, Brenda W -- Peters, Annette -- Pramstaller, Peter P -- Raitakari, Olli T -- Rankinen, Tuomo -- Rao, D C -- Rice, Treva K -- Ridker, Paul M -- Ritchie, Marylyn D -- Rudan, Igor -- Salomaa, Veikko -- Samani, Nilesh J -- Saramies, Jouko -- Sarzynski, Mark A -- Schwarz, Peter E H -- Shuldiner, Alan R -- Staessen, Jan A -- Steinthorsdottir, Valgerdur -- Stolk, Ronald P -- Strauch, Konstantin -- Tonjes, Anke -- Tremblay, Angelo -- Tremoli, Elena -- Vohl, Marie-Claude -- Volker, Uwe -- Vollenweider, Peter -- Wilson, James F -- Witteman, Jacqueline C -- Adair, Linda S -- Bochud, Murielle -- Boehm, Bernhard O -- Bornstein, Stefan R -- Bouchard, Claude -- Cauchi, Stephane -- Caulfield, Mark J -- Chambers, John C -- Chasman, Daniel I -- Cooper, Richard S -- Dedoussis, George -- Ferrucci, Luigi -- Froguel, Philippe -- Grabe, Hans-Jorgen -- Hamsten, Anders -- Hui, Jennie -- Hveem, Kristian -- Jockel, Karl-Heinz -- Kivimaki, Mika -- Kuh, Diana -- Laakso, Markku -- Liu, Yongmei -- Marz, Winfried -- Munroe, Patricia B -- Njolstad, Inger -- Oostra, Ben A -- Palmer, Colin N A -- Pedersen, Nancy L -- Perola, Markus -- Perusse, Louis -- Peters, Ulrike -- Power, Chris -- Quertermous, Thomas -- Rauramaa, Rainer -- Rivadeneira, Fernando -- Saaristo, Timo E -- Saleheen, Danish -- Sinisalo, Juha -- Slagboom, P Eline -- Snieder, Harold -- Spector, Tim D -- Thorsteinsdottir, Unnur -- Stumvoll, Michael -- Tuomilehto, Jaakko -- Uitterlinden, Andre G -- Uusitupa, Matti -- van der Harst, Pim -- Veronesi, Giovanni -- Walker, Mark -- Wareham, Nicholas J -- Watkins, Hugh -- Wichmann, H-Erich -- Abecasis, Goncalo R -- Assimes, Themistocles L -- Berndt, Sonja I -- Boehnke, Michael -- Borecki, Ingrid B -- Deloukas, Panos -- Franke, Lude -- Frayling, Timothy M -- Groop, Leif C -- Hunter, David J -- Kaplan, Robert C -- O'Connell, Jeffrey R -- Qi, Lu -- Schlessinger, David -- Strachan, David P -- Stefansson, Kari -- van Duijn, Cornelia M -- Willer, Cristen J -- Visscher, Peter M -- Yang, Jian -- Hirschhorn, Joel N -- Zillikens, M Carola -- McCarthy, Mark I -- Speliotes, Elizabeth K -- North, Kari E -- Fox, Caroline S -- Barroso, Ines -- Franks, Paul W -- Ingelsson, Erik -- Heid, Iris M -- Loos, Ruth J F -- Cupples, L Adrienne -- Morris, Andrew P -- Lindgren, Cecilia M -- Mohlke, Karen L -- 084766/Wellcome Trust/United Kingdom -- 085235/Wellcome Trust/United Kingdom -- 097117/Wellcome Trust/United Kingdom -- 098381/Wellcome Trust/United Kingdom -- 098498/Wellcome Trust/United Kingdom -- 12/0004470/Diabetes UK/United Kingdom -- 14136/Cancer Research UK/United Kingdom -- CZB/4/710/Chief Scientist Office/United Kingdom -- G0601261/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- K01 HL116770/HL/NHLBI NIH HHS/ -- K23 DK080145/DK/NIDDK NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_UP_A620_1014/Medical Research Council/United Kingdom -- MC_UU_12011/1/Medical Research Council/United Kingdom -- MC_UU_12015/1/Medical Research Council/United Kingdom -- MC_UU_12015/2/Medical Research Council/United Kingdom -- MC_UU_12015/5/Medical Research Council/United Kingdom -- MR/K011480/1/Medical Research Council/United Kingdom -- MR/K013351/1/Medical Research Council/United Kingdom -- P20 MD006899/MD/NIMHD NIH HHS/ -- P30 DK020541/DK/NIDDK NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 GM103341/GM/NIGMS NIH HHS/ -- P60 DK020541/DK/NIDDK NIH HHS/ -- R00 HL094535/HL/NHLBI NIH HHS/ -- R01 AG041517/AG/NIA NIH HHS/ -- R01 DK062370/DK/NIDDK NIH HHS/ -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK075787/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 DK089256/DK/NIDDK NIH HHS/ -- R01 DK093757/DK/NIDDK NIH HHS/ -- R01 HL109946/HL/NHLBI NIH HHS/ -- R01 HL117626/HL/NHLBI NIH HHS/ -- R21 DA027040/DA/NIDA NIH HHS/ -- T32 GM007092/GM/NIGMS NIH HHS/ -- T32 GM067553/GM/NIGMS NIH HHS/ -- T32 HL007055/HL/NHLBI NIH HHS/ -- T32 HL069768/HL/NHLBI NIH HHS/ -- U01 AG049505/AG/NIA NIH HHS/ -- U01 DK062370/DK/NIDDK NIH HHS/ -- U01 HG007416/HG/NHGRI NIH HHS/ -- U01 HG007419/HG/NHGRI NIH HHS/ -- UM1 CA182910/CA/NCI NIH HHS/ -- Z01 HG000024-14/Intramural NIH HHS/ -- England -- Nature. 2015 Feb 12;518(7538):187-96. doi: 10.1038/nature14132.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Public Health and Clinical Medicine, Unit of Medicine, Umea University, 901 87 Umea, Sweden. [2] Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, 205 02 Malmo, Sweden. [3] Department of Odontology, Umea University, 901 85 Umea, Sweden. ; Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany. ; 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. [4] Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby 2800, Denmark. ; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; 1] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham Massachusetts 01702, USA. [2] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; 1] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [3] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [3] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [4] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1010, Switzerland. [2] Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. [3] Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. ; 1] Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, Essen, 45147 Germany. [2] Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena 07743, Germany. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. ; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. ; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA. ; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. ; Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia 6008, Australia. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; 1] Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. [2] Kidney Epidemiology and Cost Center, University of Michigan, Ann Arbor, Michigan 48109, USA. ; 1] Department of Statistics &Biostatistics, Rutgers University, Piscataway, New Jersey 08854, USA. [2] Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Department of Human Genetics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. ; 1] Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. [2] Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva 1211, Switzerland. ; Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Division of Cardiovacular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK. ; 1] Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. [2] Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. [3] University Institute for Social and Preventative Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne 1005, Switzerland. ; 1] Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany. [2] Department of Internal Medicine II, Ulm University Medical Centre, D-89081 Ulm, Germany. ; National Institute for Health and Welfare, FI-00271 Helsinki, Finland. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [3] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, Essen, 45147 Germany. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [3] Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. ; University of Eastern Finland, FI-70210 Kuopio, Finland. ; Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21225, USA. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. ; Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands. ; 1] CNRS UMR 8199, F-59019 Lille, France. [2] European Genomic Institute for Diabetes, F-59000 Lille, France. [3] Universite de Lille 2, F-59000 Lille, France. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. [3] School of Health and Social Studies, Dalarna University, SE-791 88 Falun, Sweden. ; PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. ; Geriatric Unit, Azienda Sanitaria Firenze (ASF), 50125 Florence, Italy. ; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; 1] Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78227, USA. [2] Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4001, Australia. ; Department of Medical Sciences, Endocrinology, Diabetes and Metabolism, Uppsala University, Uppsala 75185, Sweden. ; 1] Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, D-04103 Leipzig, Germany. [2] Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Inserm UMR991, Department of Endocrinology, University of Rennes, F-35000 Rennes, France. ; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, D-04103 Leipzig, Germany. ; LifeLines Cohort Study, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City 6000, Philippines. ; Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway. ; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. ; Information Sciences Institute, University of Southern California, Marina del Rey, California 90292, USA. ; Department of Public Health and Clinical Medicine, Unit of Medicine, Umea University, 901 87 Umea, Sweden. ; Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. ; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [3] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, Maryland 20892, USA. ; Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala 75185, Sweden. ; Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm 17177, Sweden. ; Kaiser Permanente, Division of Research, Oakland, California 94612, USA. ; Service of Therapeutic Education for Diabetes, Obesity and Chronic Diseases, Geneva University Hospital, Geneva CH-1211, Switzerland. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [3] German Center for Diabetes Research (DZD), D-85764 Neuherberg, Germany. ; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. ; Department of Public Health and Clinical Medicine, Unit of Nutritional Research, Umea University, Umea 90187, Sweden. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands. ; Kuopio Research Institute of Exercise Medicine, FI-70100 Kuopio, Finland. ; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK. ; Hjelt Institute Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland. ; 1] Institute of Biomedicine, University of Oulu, FI-90014 Oulu, Finland. [2] Medical Research Center Oulu and Oulu University Hospital, FI-90014 Oulu, Finland. [3] Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [3] Faculty of Psychology and Education, VU University Amsterdam, 1081BT Amsterdam, The Netherlands. ; 1] Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. [2] Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim 7489, Norway. ; Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84108, USA. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. ; Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] Department of Pulmonary Physiology and Sleep Medicine, Nedlands, Western Australia 6009, Australia. [2] School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia. ; Department of Odontology, Umea University, 901 85 Umea, Sweden. ; Department of Dietetics-Nutrition, Harokopio University, 17671 Athens, Greece. ; Department of Internal Medicine II, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Department of Internal Medicine I, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria. ; Institute of Human Genetics, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 45, Sweden. ; Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva 1211, Switzerland. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden. ; School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK. ; Division of Endocrinology, Diabetes and Metabolism, Ulm University Medical Centre, D-89081 Ulm, Germany. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia. ; 1] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. [2] Farr Institute of Health Informatics Research, University College London, London NW1 2DA, UK. ; 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. [2] The Center for Observational Research, Amgen, Inc., Thousand Oaks, California 91320, USA. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; 1] Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany. [2] Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. ; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cagliari, Sardinia 09042, Italy. ; Center for Evidence-based Healthcare, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. [3] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. [4] Deutsches Forschungszentrum fur Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany. ; Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA. ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Hypertension and Related Diseases Centre - AOU, University of Sassari Medical School, Sassari 07100, Italy. ; Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [3] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, 205 02 Malmo, Sweden. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. ; 1] Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden. [2] Science for Life Laboratory, Karolinska Institutet, Stockholm 171 65, Sweden. ; Department of Medicine, University of Washington, Seattle, Washington 98101, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland. [2] University of Iceland, Reykjavik 101, Iceland. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala 75144, Sweden. ; Department of Public Health Sciences, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 61053, USA. ; 1] German Center for Diabetes Research (DZD), D-85764 Neuherberg, Germany. [2] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; deCODE Genetics, Amgen Inc., Reykjavik 101, Iceland. ; Department of Cardiology, Medical University of Graz, Graz 8036, Austria. ; Department of Child and Adolescent Psychiatry, Psychology, Erasmus MC University Medical Centre, 3000 CB Rotterdam, The Netherlands. ; Department of Clinical Chemistry, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037 Tromso, Norway. ; MRC Unit for Lifelong Health and Ageing at University College London, London WC1B 5JU, UK. ; Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland. ; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea. ; Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 17176, Sweden. ; Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [3] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; 1] Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, Massachusetts 02215, USA. [2] Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; 1] State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; 1] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [2] NIHR Oxford Biomedical Research Centre, OUH Trust, Oxford OX3 7LE, UK. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Harvard School of Public Health, Department of Biostatistics, Harvard University, Boston, Massachusetts 02115, USA. ; Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, New Haven, Connecticut 06520, USA. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning 116026, China. ; Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, County Down BT9 7AB, UK. ; University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada. ; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. ; QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. ; 1] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham Massachusetts 01702, USA. [2] Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; 1] Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK. [2] MRC Harwell, Harwell Science and Innovation Campus, Harwell OX11 0QG, UK. ; 1] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. [2] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. [3] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biomedical Engineering and Computational Science, Aalto University School of Science, FI-00076 Helsinki, Finland. [2] Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, FI-00290 Helsinki, Finland. [3] Folkhalsan Institute of Genetics, Folkhalsan Research Center, FI-00290 Helsinki, Finland. ; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10580, USA. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; Computer Science Department, Tecnologico de Monterrey, Atizapan de Zaragoza, 52926, Mexico. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Nuffield Department of Obstetrics &Gynaecology, University of Oxford, Oxford OX3 7BN, UK. ; Institut Pasteur de Lille; INSERM, U744; Universite de Lille 2; F-59000 Lille, France. ; Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France. ; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. ; 1] PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. [2] Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia 6009, Australia. ; Cedars-Sinai Diabetes and Obesity Research Institute, Los Angeles, California 90048, USA. ; Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78227, USA. ; Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. ; Service of Nephrology, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne 1005, Switzerland. ; Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. ; Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA. [2] Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA. ; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; 1] Biological Psychology, VU University Amsterdam, 1081BT Amsterdam, The Netherlands. [2] Institute for Research in Extramural Medicine, Institute for Health and Care Research, VU University, 1081BT Amsterdam, The Netherlands. ; 1] Department of Internal Medicine B, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Clinic of Cardiology, West-German Heart Centre, University Hospital Essen, 45122 Essen, Germany. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Department of General Practice and Primary Health Care, University of Helsinki, FI-00290 Helsinki, Finland. [3] Unit of General Practice, Helsinki University Central Hospital, Helsinki FI-00290, Finland. ; 1] Department of Internal Medicine, University of Pisa, Pisa 56100, Italy. [2] National Research Council Institute of Clinical Physiology, University of Pisa, Pisa 56124, Italy. ; Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, 31400 Toulouse, France. ; UWI Solutions for Developing Countries, The University of the West Indies, Mona, Kingston 7, Jamaica. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA. ; Institute of Biomedical &Clinical Science, University of Exeter, Barrack Road, Exeter EX2 5DW, UK. ; Center for Biomedicine, European Academy Bozen, Bolzano (EURAC), Bolzano 39100, Italy (affiliated Institute of the University of Lubeck, D-23562 Lubeck, Germany). ; Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK. ; 1] Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Centre for Cardiovascular Genetics, Institute Cardiovascular Sciences, University College London, London WC1E 6JJ, UK. ; 1] Sansom Institute for Health Research, University of South Australia, Adelaide 5000, South Australia, Australia. [2] School of Population Health, University of South Australia, Adelaide 5000, South Australia, Australia. [3] South Australian Health and Medical Research Institute, Adelaide 5000, South Australia, Australia. [4] Population, Policy, and Practice, University College London Institute of Child Health, London WC1N 1EH, UK. ; 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Hannover Unified Biobank, Hannover Medical School, Hannover, D-30625 Hannover, Germany. ; 1] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. [2] Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland. [3] National Institute for Health and Welfare, FI-90101 Oulu, Finland. [4] MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [5] Unit of Primary Care, Oulu University Hospital, FI-90220 Oulu, Finland. [6] Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. [3] Hjelt Institute Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland. ; UK Clinical Research Collaboration Centre of Excellence for Public Health (NI), Queens University of Belfast, Belfast BT7 1NN, Northern Ireland, UK. ; 1] Institute of Health Sciences, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland. [2] Unit of Primary Health Care/General Practice, Oulu University Hospital, FI-90220 Oulu, Finland. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. [3] Imperial College Healthcare NHS Trust, London W12 0HS, UK. ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; 1] Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. [2] Department of Biological and Social Epidemiology, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK. ; Department of Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] Kuopio Research Institute of Exercise Medicine, FI-70100 Kuopio, Finland. [2] Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, FI-70211 Kuopio, Finland. [3] Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. ; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA. ; Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine University of Tampere, FI-33520 Tampere, Finland. ; 1] Steno Diabetes Center A/S, Gentofte DK-2820, Denmark. [2] Lund University Diabetes Centre and Department of Clinical Science, Diabetes &Endocrinology Unit, Lund University, Malmo 221 00, Sweden. ; 1] Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Faculty of Medicine, Laval University, Quebec QC G1V 0A6, Canada. [2] Institute of Nutrition and Functional Foods, Laval University, Quebec QC G1V 0A6, Canada. ; Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA. ; Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA. ; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] MRC Unit for Lifelong Health and Ageing at University College London, London WC1B 5JU, UK. ; 1] Epidemiology and Obstetrics &Gynaecology, University of Toronto, Toronto, Ontario M5G 1E2, Canada. [2] Genetic Epidemiology &Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada. ; 1] Institute for Research in Extramural Medicine, Institute for Health and Care Research, VU University, 1081BT Amsterdam, The Netherlands. [2] Department of Psychiatry, Neuroscience Campus, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands. ; 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Deutsches Forschungszentrum fur Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany. [3] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; 1] Center for Biomedicine, European Academy Bozen, Bolzano (EURAC), Bolzano 39100, Italy (affiliated Institute of the University of Lubeck, D-23562 Lubeck, Germany). [2] Department of Neurology, General Central Hospital, Bolzano 39100, Italy. ; 1] Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, FI-20521 Turku, Finland. [2] Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FI-20521 Turku, Finland. ; Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. ; 1] Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [3] Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Systems Genomics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. [2] Croatian Centre for Global Health, Faculty of Medicine, University of Split, 21000 Split, Croatia. ; 1] Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK. [2] National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK. ; South Carelia Central Hospital, 53130 Lappeenranta, Finland. ; 1] Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. [2] Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), 01307 Dresden, Germany. ; 1] Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [3] Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland 21201, USA. ; 1] Department of Epidemiology, Maastricht University, 6229 HA Maastricht, The Netherlands. [2] Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, B-3000 Leuven, Belgium. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. ; Department of Kinesiology, Laval University, Quebec, QC G1V 0A6, Canada. ; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano &Centro Cardiologico Monzino, Instituto di Ricovero e Cura a Carattere Scientifico, Milan 20133, Italy. ; 1] Institute of Nutrition and Functional Foods, Laval University, Quebec QC G1V 0A6, Canada. [2] Department of Food Science and Nutrition, Laval University, Quebec, QC G1V 0A6, Canada. ; 1] Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Department of Internal Medicine, University Hospital (CHUV) and University of Lausanne, 1011, Switzerland. ; Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; 1] Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1010 Lausanne, Switzerland. [2] Ministry of Health, Victoria, Republic of Seychelles. ; 1] Lee Kong Chian School of Medicine, Imperial College London and Nanyang Technological University, Singapore, 637553 Singapore, Singapore. [2] Department of Internal Medicine I, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. [3] Imperial College Healthcare NHS Trust, London W12 0HS, UK. ; 1] Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. [2] CNRS UMR 8199, F-59019 Lille, France. [3] European Genomic Institute for Diabetes, F-59000 Lille, France. [4] Universite de Lille 2, F-59000 Lille, France. ; 1] Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, D-17475 Greifswald, Germany. [2] German Center for Neurodegenerative Diseases (DZNE), Rostock, Greifswald, D-17475 Greifswald, Germany. ; 1] PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. [2] Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia 6009, Australia. [3] School of Population Health, The University of Western Australia, Nedlands, Western Australia 6009, Australia. ; Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. ; Center for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA. ; 1] Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany. [2] Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. [3] Synlab Academy, Synlab Services GmbH, 68163 Mannheim, Germany. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. [3] Department of Clinical Genetics, Erasmus MC University Medical Center, 3000 CA Rotterdam, The Netherlands. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [3] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. ; 1] Institute of Nutrition and Functional Foods, Laval University, Quebec QC G1V 0A6, Canada. [2] Department of Kinesiology, Laval University, Quebec, QC G1V 0A6, Canada. ; Population, Policy, and Practice, University College London Institute of Child Health, London WC1N 1EH, UK. ; Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA. ; 1] Kuopio Research Institute of Exercise Medicine, FI-70100 Kuopio, Finland. [2] Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] Finnish Diabetes Association, Kirjoniementie 15, FI-33680 Tampere, Finland. [2] Pirkanmaa Hospital District, FI-33521 Tampere, Finland. ; 1] Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. [2] Center for Non-Communicable Diseases, Karatchi, Pakistan. [3] Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA. ; Helsinki University Central Hospital Heart and Lung Center, Department of Medicine, Helsinki University Central Hospital, FI-00290 Helsinki, Finland. ; 1] deCODE Genetics, Amgen Inc., Reykjavik 101, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Instituto de Investigacion Sanitaria del Hospital Universario LaPaz (IdiPAZ), 28046 Madrid, Spain. [3] Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia. [4] Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria. ; 1] Department of Public Health and Clinical Nutrition, University of Eastern Finland, FI-70211 Kuopio, Finland. [2] Research Unit, Kuopio University Hospital, FI-70210 Kuopio, Finland. ; 1] Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. [2] Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. [3] Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands-Netherlands Heart Institute, 3501 DG Utrecht, The Netherlands. ; EPIMED Research Center, Department of Clinical and Experimental Medicine, University of Insubria, Varese I-21100, Italy. ; Institute of Cellular Medicine, Newcastle University, Newcastle NE1 7RU, UK. ; 1] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universitat, D-85764 Munich, Germany. [2] Klinikum Grosshadern, D-81377 Munich, Germany. [3] Institute of Epidemiology I, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. [3] Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, 21589 Jeddah, Saudi Arabia. ; 1] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. [2] Lund University Diabetes Centre and Department of Clinical Science, Diabetes &Endocrinology Unit, Lund University, Malmo 221 00, Sweden. ; 1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [3] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; Albert Einstein College of Medicine, Department of Epidemiology and Population Health, Belfer 1306, New York 10461, USA. ; 1] Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Division of Population Health Sciences &Education, St George's, University of London, London SW17 0RE, UK. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [3] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [4] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. ; 1] Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. [2] Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. [3] Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; 1] Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia. [2] The University of Queensland Diamantina Institute, The Translation Research Institute, Brisbane 4012, Australia. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [3] Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford OX3 7LJ, UK. ; 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham Massachusetts 01702, USA. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK. [3] NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK. ; 1] Department of Public Health and Clinical Medicine, Unit of Medicine, Umea University, 901 87 Umea, Sweden. [2] Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, 205 02 Malmo, Sweden. ; 1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany. [2] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. [3] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. [4] The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; 1] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. [2] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham Massachusetts 01702, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [3] Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25673412" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/metabolism ; Adipogenesis/genetics ; Adipose Tissue/*metabolism ; Age Factors ; *Body Fat Distribution ; Body Mass Index ; Continental Population Groups/genetics ; Epigenesis, Genetic ; Europe/ethnology ; Female ; Genome, Human/genetics ; *Genome-Wide Association Study ; Humans ; Insulin/*metabolism ; Insulin Resistance/genetics ; Male ; Models, Biological ; Neovascularization, Physiologic/genetics ; Obesity/genetics ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/*genetics ; Sex Characteristics ; Transcription, Genetic/genetics ; Waist-Hip Ratio
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  • 2
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2015-04-04
    Description: Human activities, especially conversion and degradation of habitats, are causing global biodiversity declines. How local ecological assemblages are responding is less clear--a concern given their importance for many ecosystem functions and services. We analysed a terrestrial assemblage database of unprecedented geographic and taxonomic coverage to quantify local biodiversity responses to land use and related changes. Here we show that in the worst-affected habitats, these pressures reduce within-sample species richness by an average of 76.5%, total abundance by 39.5% and rarefaction-based richness by 40.3%. We estimate that, globally, these pressures have already slightly reduced average within-sample richness (by 13.6%), total abundance (10.7%) and rarefaction-based richness (8.1%), with changes showing marked spatial variation. Rapid further losses are predicted under a business-as-usual land-use scenario; within-sample richness is projected to fall by a further 3.4% globally by 2100, with losses concentrated in biodiverse but economically poor countries. Strong mitigation can deliver much more positive biodiversity changes (up to a 1.9% average increase) that are less strongly related to countries' socioeconomic status.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newbold, Tim -- Hudson, Lawrence N -- Hill, Samantha L L -- Contu, Sara -- Lysenko, Igor -- Senior, Rebecca A -- Borger, Luca -- Bennett, Dominic J -- Choimes, Argyrios -- Collen, Ben -- Day, Julie -- De Palma, Adriana -- Diaz, Sandra -- Echeverria-Londono, Susy -- Edgar, Melanie J -- Feldman, Anat -- Garon, Morgan -- Harrison, Michelle L K -- Alhusseini, Tamera -- Ingram, Daniel J -- Itescu, Yuval -- Kattge, Jens -- Kemp, Victoria -- Kirkpatrick, Lucinda -- Kleyer, Michael -- Correia, David Laginha Pinto -- Martin, Callum D -- Meiri, Shai -- Novosolov, Maria -- Pan, Yuan -- Phillips, Helen R P -- Purves, Drew W -- Robinson, Alexandra -- Simpson, Jake -- Tuck, Sean L -- Weiher, Evan -- White, Hannah J -- Ewers, Robert M -- Mace, Georgina M -- Scharlemann, Jorn P W -- Purvis, Andy -- BB/F017324/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Apr 2;520(7545):45-50. doi: 10.1038/nature14324.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] United Nations Environment Programme World Conservation Monitoring Centre, 219 Huntingdon Road, Cambridge CB3 0DL, UK. [2] Computational Science Laboratory, Microsoft Research Cambridge, 21 Station Road, Cambridge CB1 2FB, UK. ; Department of Life Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK. ; 1] United Nations Environment Programme World Conservation Monitoring Centre, 219 Huntingdon Road, Cambridge CB3 0DL, UK. [2] Department of Life Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK. ; Department of Life Sciences, Imperial College London, Silwood Park, London SL5 7PY, UK. ; United Nations Environment Programme World Conservation Monitoring Centre, 219 Huntingdon Road, Cambridge CB3 0DL, UK. ; Department of Biosciences, College of Science, Swansea University, Singleton Park, Swansea SA2 8PP, UK. ; 1] Department of Life Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK. [2] Department of Life Sciences, Imperial College London, Silwood Park, London SL5 7PY, UK. ; Department of Genetics, Evolution and Environment, Centre for Biodiversity and Environment Research, University College London, Gower Street, London WC1E 6BT, UK. ; Instituto Multidisciplinario de Biologia Vegetal (CONICET-UNC) and FCEFyN, Universidad Nacional de Cordoba, Casilla de Correo 495, 5000 Cordoba, Argentina. ; Deptartment of Zoology, Faculty of Life Sciences, Tel-Aviv University, 6997801 Tel Aviv, Israel. ; 1] Max Planck Institute for Biogeochemistry, Hans Knoll Strasse 10, 07743 Jena, Germany. [2] German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Deutscher Platz 5e, 04103 Leipzig, Germany. ; Landscape Ecology Group, Institute of Biology and Environmental Sciences, University of Oldenburg, D-26111 Oldenburg, Germany. ; Computational Science Laboratory, Microsoft Research Cambridge, 21 Station Road, Cambridge CB1 2FB, UK. ; Department of Plant Sciences, University of Oxford, Oxford OX1 3RB, UK. ; Biology Department, University of Wisconsin-Eau Claire, Eau Claire, Wisconsin 54701, USA. ; 1] United Nations Environment Programme World Conservation Monitoring Centre, 219 Huntingdon Road, Cambridge CB3 0DL, UK. [2] School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25832402" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Conservation of Natural Resources/trends ; Ecology/trends ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Human Activities ; Models, Biological ; Population Dynamics ; Species Specificity
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  • 3
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2013-07-05
    Description: We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087036/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087036/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galagan, James E -- Minch, Kyle -- Peterson, Matthew -- Lyubetskaya, Anna -- Azizi, Elham -- Sweet, Linsday -- Gomes, Antonio -- Rustad, Tige -- Dolganov, Gregory -- Glotova, Irina -- Abeel, Thomas -- Mahwinney, Chris -- Kennedy, Adam D -- Allard, Rene -- Brabant, William -- Krueger, Andrew -- Jaini, Suma -- Honda, Brent -- Yu, Wen-Han -- Hickey, Mark J -- Zucker, Jeremy -- Garay, Christopher -- Weiner, Brian -- Sisk, Peter -- Stolte, Christian -- Winkler, Jessica K -- Van de Peer, Yves -- Iazzetti, Paul -- Camacho, Diogo -- Dreyfuss, Jonathan -- Liu, Yang -- Dorhoi, Anca -- Mollenkopf, Hans-Joachim -- Drogaris, Paul -- Lamontagne, Julie -- Zhou, Yiyong -- Piquenot, Julie -- Park, Sang Tae -- Raman, Sahadevan -- Kaufmann, Stefan H E -- Mohney, Robert P -- Chelsky, Daniel -- Moody, D Branch -- Sherman, David R -- Schoolnik, Gary K -- HHSN272200800059C/AI/NIAID NIH HHS/ -- HHSN272200800059C/PHS HHS/ -- R01 AI 071155/AI/NIAID NIH HHS/ -- R01 AI071155/AI/NIAID NIH HHS/ -- U19 AI 076217/AI/NIAID NIH HHS/ -- U19 AI076217/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):178-83. doi: 10.1038/nature12337. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA. jgalag@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823726" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Anoxia/*genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; Binding Sites ; Chromatin Immunoprecipitation ; Gene Expression Profiling ; *Gene Regulatory Networks/genetics ; Genomics ; Lipid Metabolism/genetics ; Metabolic Networks and Pathways/*genetics ; Models, Biological ; Mycobacterium tuberculosis/drug effects/*genetics/*metabolism/physiology ; Oxygen/pharmacology ; Proteolysis ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; Sequence Analysis, DNA ; Transcription Factors/genetics/metabolism ; Tuberculosis/metabolism/microbiology
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  • 4
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    Nature Publishing Group (NPG)
    Publication Date: 2011-12-23
    Description: Restriction factors, such as the retroviral complementary DNA deaminase APOBEC3G, are cellular proteins that dominantly block virus replication. The AIDS virus, human immunodeficiency virus type 1 (HIV-1), produces the accessory factor Vif, which counteracts the host's antiviral defence by hijacking a ubiquitin ligase complex, containing CUL5, ELOC, ELOB and a RING-box protein, and targeting APOBEC3G for degradation. Here we reveal, using an affinity tag/purification mass spectrometry approach, that Vif additionally recruits the transcription cofactor CBF-beta to this ubiquitin ligase complex. CBF-beta, which normally functions in concert with RUNX DNA binding proteins, allows the reconstitution of a recombinant six-protein assembly that elicits specific polyubiquitination activity with APOBEC3G, but not the related deaminase APOBEC3A. Using RNA knockdown and genetic complementation studies, we also demonstrate that CBF-beta is required for Vif-mediated degradation of APOBEC3G and therefore for preserving HIV-1 infectivity. Finally, simian immunodeficiency virus (SIV) Vif also binds to and requires CBF-beta to degrade rhesus macaque APOBEC3G, indicating functional conservation. Methods of disrupting the CBF-beta-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310910/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jager, Stefanie -- Kim, Dong Young -- Hultquist, Judd F -- Shindo, Keisuke -- LaRue, Rebecca S -- Kwon, Eunju -- Li, Ming -- Anderson, Brett D -- Yen, Linda -- Stanley, David -- Mahon, Cathal -- Kane, Joshua -- Franks-Skiba, Kathy -- Cimermancic, Peter -- Burlingame, Alma -- Sali, Andrej -- Craik, Charles S -- Harris, Reuben S -- Gross, John D -- Krogan, Nevan J -- P01 AI090935/AI/NIAID NIH HHS/ -- P01 GM091743/GM/NIGMS NIH HHS/ -- P41 GM103481/GM/NIGMS NIH HHS/ -- P41RR001614/RR/NCRR NIH HHS/ -- P50 GM081879/GM/NIGMS NIH HHS/ -- P50 GM082250/GM/NIGMS NIH HHS/ -- P50 GM082250-05/GM/NIGMS NIH HHS/ -- P50GM081879/GM/NIGMS NIH HHS/ -- R01 AI064046/AI/NIAID NIH HHS/ -- T32 AI083196/AI/NIAID NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- England -- Nature. 2011 Dec 21;481(7381):371-5. doi: 10.1038/nature10693.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22190037" target="_blank"〉PubMed〈/a〉
    Keywords: Affinity Labels ; Animals ; Core Binding Factor beta Subunit/*metabolism ; Cullin Proteins/metabolism ; Cytidine Deaminase/*metabolism ; Gene Knockdown Techniques ; Gene Products, vif/*metabolism ; Genetic Complementation Test ; HEK293 Cells ; HIV Infections/*metabolism/*virology ; HIV-1/*physiology ; Host-Pathogen Interactions ; Humans ; Jurkat Cells ; Macaca mulatta/metabolism/virology ; Mass Spectrometry ; Models, Biological ; Protein Binding ; Proteolysis ; Simian Immunodeficiency Virus/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; Ubiquitination ; Virus Replication ; vif Gene Products, Human Immunodeficiency Virus/*metabolism
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  • 5
    Publication Date: 2013-11-29
    Description: Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940870/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNamara, Case W -- Lee, Marcus C S -- Lim, Chek Shik -- Lim, Siau Hoi -- Roland, Jason -- Nagle, Advait -- Simon, Oliver -- Yeung, Bryan K S -- Chatterjee, Arnab K -- McCormack, Susan L -- Manary, Micah J -- Zeeman, Anne-Marie -- Dechering, Koen J -- Kumar, T R Santha -- Henrich, Philipp P -- Gagaring, Kerstin -- Ibanez, Maureen -- Kato, Nobutaka -- Kuhen, Kelli L -- Fischli, Christoph -- Rottmann, Matthias -- Plouffe, David M -- Bursulaya, Badry -- Meister, Stephan -- Rameh, Lucia -- Trappe, Joerg -- Haasen, Dorothea -- Timmerman, Martijn -- Sauerwein, Robert W -- Suwanarusk, Rossarin -- Russell, Bruce -- Renia, Laurent -- Nosten, Francois -- Tully, David C -- Kocken, Clemens H M -- Glynne, Richard J -- Bodenreider, Christophe -- Fidock, David A -- Diagana, Thierry T -- Winzeler, Elizabeth A -- 078285/Wellcome Trust/United Kingdom -- 089275/Wellcome Trust/United Kingdom -- 090534/Wellcome Trust/United Kingdom -- 096157/Wellcome Trust/United Kingdom -- R01 AI079709/AI/NIAID NIH HHS/ -- R01 AI085584/AI/NIAID NIH HHS/ -- R01 AI090141/AI/NIAID NIH HHS/ -- R01 AI103058/AI/NIAID NIH HHS/ -- R01079709/PHS HHS/ -- R01085584/PHS HHS/ -- R01AI090141/AI/NIAID NIH HHS/ -- WT078285/Wellcome Trust/United Kingdom -- WT096157/Wellcome Trust/United Kingdom -- England -- Nature. 2013 Dec 12;504(7479):248-53. doi: 10.1038/nature12782. Epub 2013 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2]. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2]. ; Novartis Institutes for Tropical Disease, 138670 Singapore. ; Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA. ; Department of Parasitology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands. ; TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands. ; Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA. ; Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland. ; 1] Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland [2] University of Basel, CH-4003 Basel, Switzerland. ; Department of Medicine, School of Medicine, Boston University, Boston, Massachusetts 02118, USA. ; Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. ; 1] TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands [2] Department of Medical Microbiology, Radboud University, Nijmegen Medical CentrePO Box 9101, 6500 HB Nijmegen, The Netherlands. ; Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore. ; 1] Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore [2] Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 117545 Singapore. ; 1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK [2] Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2] Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA. ; 1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2] Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24284631" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Phosphatidylinositol 4-Kinase/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cytokinesis/drug effects ; Drug Resistance/drug effects/genetics ; Fatty Acids/metabolism ; Female ; Hepatocytes/parasitology ; Humans ; Imidazoles/metabolism/pharmacology ; Life Cycle Stages/drug effects ; Macaca mulatta ; Malaria/*drug therapy/*parasitology ; Male ; Models, Biological ; Models, Molecular ; Phosphatidylinositol Phosphates/metabolism ; Plasmodium/classification/*drug effects/*enzymology/growth & development ; Pyrazoles/metabolism/pharmacology ; Quinoxalines/metabolism/pharmacology ; Reproducibility of Results ; Schizonts/cytology/drug effects ; rab GTP-Binding Proteins/genetics/metabolism
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  • 6
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2015-12-25
    Description: Phenotypic traits and their associated trade-offs have been shown to have globally consistent effects on individual plant physiological functions, but how these effects scale up to influence competition, a key driver of community assembly in terrestrial vegetation, has remained unclear. Here we use growth data from more than 3 million trees in over 140,000 plots across the world to show how three key functional traits--wood density, specific leaf area and maximum height--consistently influence competitive interactions. Fast maximum growth of a species was correlated negatively with its wood density in all biomes, and positively with its specific leaf area in most biomes. Low wood density was also correlated with a low ability to tolerate competition and a low competitive effect on neighbours, while high specific leaf area was correlated with a low competitive effect. Thus, traits generate trade-offs between performance with competition versus performance without competition, a fundamental ingredient in the classical hypothesis that the coexistence of plant species is enabled via differentiation in their successional strategies. Competition within species was stronger than between species, but an increase in trait dissimilarity between species had little influence in weakening competition. No benefit of dissimilarity was detected for specific leaf area or wood density, and only a weak benefit for maximum height. Our trait-based approach to modelling competition makes generalization possible across the forest ecosystems of the world and their highly diverse species composition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kunstler, Georges -- Falster, Daniel -- Coomes, David A -- Hui, Francis -- Kooyman, Robert M -- Laughlin, Daniel C -- Poorter, Lourens -- Vanderwel, Mark -- Vieilledent, Ghislain -- Wright, S Joseph -- Aiba, Masahiro -- Baraloto, Christopher -- Caspersen, John -- Cornelissen, J Hans C -- Gourlet-Fleury, Sylvie -- Hanewinkel, Marc -- Herault, Bruno -- Kattge, Jens -- Kurokawa, Hiroko -- Onoda, Yusuke -- Penuelas, Josep -- Poorter, Hendrik -- Uriarte, Maria -- Richardson, Sarah -- Ruiz-Benito, Paloma -- Sun, I-Fang -- Stahl, Goran -- Swenson, Nathan G -- Thompson, Jill -- Westerlund, Bertil -- Wirth, Christian -- Zavala, Miguel A -- Zeng, Hongcheng -- Zimmerman, Jess K -- Zimmermann, Niklaus E -- Westoby, Mark -- England -- Nature. 2016 Jan 14;529(7585):204-7. doi: 10.1038/nature16476. Epub 2015 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Irstea, UR EMGR, 2 rue de la Papeterie BP-76, F-38402, St-Martin-d'Heres, France. ; Univ. Grenoble Alpes, F-38402 Grenoble, France. ; Department of Biological Sciences, Macquarie University, New South Wales 2109, Australia. ; Forest Ecology and Conservation Group, Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, UK. ; Mathematical Sciences Institute, The Australian National University, Canberra 0200, Australia. ; National Herbarium of New South Wales, Royal Botanic Gardens and Domain Trust, Sydney 2000, New South Wales, Australia. ; Environmental Research Institute, School of Science, University of Waikato, Hamilton 3240, New Zealand. ; Forest Ecology and Forest Management Group, Wageningen University, 6708 PB Wageningen, The Netherlands. ; Department of Biology, University of Regina, 3737 Wascana Pkwy, Regina SK S4S 0A2, Canada. ; Cirad, UPR BSEF, F-34398 Montpellier, France. ; Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama. ; Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan. ; INRA, UMR Ecologie des Forets de Guyane, BP 709, 97387 Kourou Cedex, France. ; International Center for Tropical Botany, Department of Biological Sciences, Florida International University, Miami, Florida 33199, USA. ; Faculty of Forestry, University of Toronto, 33 Willcocks Street, Toronto, Ontario M5S 3B3, Canada. ; Swiss Federal Research Institute WSL, Landscape Dynamics Unit, CH-8903 Birmensdorf, Switzerland. ; Systems Ecology, Department of Ecological Science, Vrije Universiteit, Amsterdam 1081 HV, The Netherlands. ; Swiss Federal Research Institute WSL, Forest Resources and Management Unit, CH-8903 Birmensdorf, Switzerland. ; University of Freiburg, Chair of Forestry Economics and Planning, D-79106 Freiburg, Germany. ; Cirad, UMR Ecologie des Forets de Guyane, Campus Agronomique, BP 701, 97387 Kourou, France. ; Max Planck Institute for Biogeochemistry, Hans Knoll Str. 10, 07745 Jena, Germany. ; German Centre for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig, Deutscher Platz 5e 04103 Leipzig, Germany. ; Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502 Japan. ; CSIC, Global Ecology Unit CREAF-CSIC-UAB, Cerdanyola del Valles 08193, Catalonia, Spain. ; CREAF, Cerdanyola del Valles, 08193 Barcelona, Catalonia, Spain. ; Plant Sciences (IBG-2), Forschungszentrum Julich GmbH, D-52425 Julich, Germany. ; Department of Ecology, Evolution and Environmental Biology, Columbia University, New York, New York 10027, USA. ; Landcare Research, PO Box 40, Lincoln 7640, New Zealand. ; Biological and Environmental Sciences, School of Natural Sciences, University of Stirling, Stirling FK9 4LA, UK. ; Forest Ecology and Restoration Group, Department of Life Sciences, Science Building, University of Alcala, Campus Universitario, 28805 Alcala de Henares (Madrid), Spain. ; Department of Natural Resources and Environmental Studies, National Dong Hwa University, Hualien 97401, Taiwan. ; Department of Forest Resource Management, Swedish University of Agricultural Sciences (SLU), Skogsmarksgrand, 901 83 Umea, Sweden. ; Department of Biology, University of Maryland, College Park, Maryland 20742, USA. ; Centre for Ecology and Hydrology, Bush Estate, Penicuik, Midlothian EH26 0QB, UK. ; Department of Environmental Sciences, University of Puerto Rico, Rio Piedras Campus PO Box 70377 San Juan, Puerto Rico 00936-8377, USA. ; Institute for Systematic, Botany and Functional Biodiversity, University of Leipzig, Johannisallee 21 04103 Leipzig, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26700807" target="_blank"〉PubMed〈/a〉
    Keywords: Forests ; Internationality ; Models, Biological ; *Phenotype ; Plant Leaves/physiology ; Trees/*anatomy & histology/growth & development/*physiology ; Wood/analysis
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    Electronic ISSN: 1476-4687
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  • 7
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-18
    Description: Animals are grouped into ~35 'phyla' based upon the notion of distinct body plans. Morphological and molecular analyses have revealed that a stage in the middle of development--known as the phylotypic period--is conserved among species within some phyla. Although these analyses provide evidence for their existence, phyla have also been criticized as lacking an objective definition, and consequently based on arbitrary groupings of animals. Here we compare the developmental transcriptomes of ten species, each annotated to a different phylum, with a wide range of life histories and embryonic forms. We find that in all ten species, development comprises the coupling of early and late phases of conserved gene expression. These phases are linked by a divergent 'mid-developmental transition' that uses species-specific suites of signalling pathways and transcription factors. This mid-developmental transition overlaps with the phylotypic period that has been defined previously for three of the ten phyla, suggesting that transcriptional circuits and signalling mechanisms active during this transition are crucial for defining the phyletic body plan and that the mid-developmental transition may be used to define phylotypic periods in other phyla. Placing these observations alongside the reported conservation of mid-development within phyla, we propose that a phylum may be defined as a collection of species whose gene expression at the mid-developmental transition is both highly conserved among them, yet divergent relative to other species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817236/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817236/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levin, Michal -- Anavy, Leon -- Cole, Alison G -- Winter, Eitan -- Mostov, Natalia -- Khair, Sally -- Senderovich, Naftalie -- Kovalev, Ekaterina -- Silver, David H -- Feder, Martin -- Fernandez-Valverde, Selene L -- Nakanishi, Nagayasu -- Simmons, David -- Simakov, Oleg -- Larsson, Tomas -- Liu, Shang-Yun -- Jerafi-Vider, Ayelet -- Yaniv, Karina -- Ryan, Joseph F -- Martindale, Mark Q -- Rink, Jochen C -- Arendt, Detlev -- Degnan, Sandie M -- Degnan, Bernard M -- Hashimshony, Tamar -- Yanai, Itai -- 310927/European Research Council/International -- R01 GM093116/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Mar 31;531(7596):637-41. doi: 10.1038/nature16994. Epub 2016 Feb 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Technion - Israel Institute of Technion, Haifa 32000, Israel. ; School of Biological Sciences, University of Queensland, Brisbane, Queensland, Australia. ; Whitney Laboratory for Marine Bioscience, University of Florida, 9505 N Ocean Shore Blvd, St Augustine, Florida 32080-8610 USA. ; Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. ; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. ; Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26886793" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Body Patterning/genetics ; Conserved Sequence/genetics ; *Embryonic Development/genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Genes, Developmental/genetics ; Models, Biological ; Phenotype ; *Phylogeny ; Species Specificity ; Transcriptome/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Nature Publishing Group (NPG)
    Publication Date: 2011-02-04
    Description: Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression. Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFbeta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Zhihu -- Wu, Chang-Jiun -- Chu, Gerald C -- Xiao, Yonghong -- Ho, Dennis -- Zhang, Jingfang -- Perry, Samuel R -- Labrot, Emma S -- Wu, Xiaoqiu -- Lis, Rosina -- Hoshida, Yujin -- Hiller, David -- Hu, Baoli -- Jiang, Shan -- Zheng, Hongwu -- Stegh, Alexander H -- Scott, Kenneth L -- Signoretti, Sabina -- Bardeesy, Nabeel -- Wang, Y Alan -- Hill, David E -- Golub, Todd R -- Stampfer, Meir J -- Wong, Wing H -- Loda, Massimo -- Mucci, Lorelei -- Chin, Lynda -- DePinho, Ronald A -- P50 CA090381/CA/NCI NIH HHS/ -- P50 CA090381-08/CA/NCI NIH HHS/ -- P50 CA90381/CA/NCI NIH HHS/ -- R01 5R01CA136578/CA/NCI NIH HHS/ -- R01 CA131945/CA/NCI NIH HHS/ -- R01CA131945/CA/NCI NIH HHS/ -- R01CA141298/CA/NCI NIH HHS/ -- U01-CA84313/CA/NCI NIH HHS/ -- England -- Nature. 2011 Feb 10;470(7333):269-73. doi: 10.1038/nature09677. Epub 2011 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21289624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Proliferation ; Cyclin D1/genetics/metabolism ; *Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor/physiology ; Humans ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Mice ; Mice, Transgenic ; Models, Biological ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/*pathology ; Osteopontin/genetics/metabolism ; PTEN Phosphohydrolase/deficiency/genetics ; Penetrance ; Prognosis ; Prostate/metabolism ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/diagnosis/genetics/*pathology ; Smad4 Protein/deficiency/genetics/*metabolism ; Transforming Growth Factor beta
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Nature Publishing Group (NPG)
    Publication Date: 2011-04-29
    Description: Site-specific recognition of DNA in eukaryotic organisms depends on the arrangement of nucleosomes in chromatin. In the yeast Saccharomyces cerevisiae, ISW1a and related chromatin remodelling factors are implicated in establishing the nucleosome repeat during replication and altering nucleosome position to affect gene activity. Here we have solved the crystal structures of S. cerevisiae ISW1a lacking its ATPase domain both alone and with DNA bound at resolutions of 3.25 A and 3.60 A, respectively, and we have visualized two different nucleosome-containing remodelling complexes using cryo-electron microscopy. The composite X-ray and electron microscopy structures combined with site-directed photocrosslinking analyses of these complexes suggest that ISW1a uses a dinucleosome substrate for chromatin remodelling. Results from a remodelling assay corroborate the dinucleosome model. We show how a chromatin remodelling factor could set the spacing between two adjacent nucleosomes acting as a 'protein ruler'.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamada, Kazuhiro -- Frouws, Timothy D -- Angst, Brigitte -- Fitzgerald, Daniel J -- DeLuca, Carl -- Schimmele, Kyoko -- Sargent, David F -- Richmond, Timothy J -- England -- Nature. 2011 Apr 28;472(7344):448-53. doi: 10.1038/nature09947.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ETH Zurich, Institute of Molecular Biology and Biophysics, Schafmattstr. 20, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21525927" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*chemistry/*metabolism ; Animals ; *Chromatin Assembly and Disassembly ; Cryoelectron Microscopy ; Crystallography, X-Ray ; DNA/chemistry/genetics/metabolism ; DNA-Binding Proteins/*chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Nucleosomes/chemistry/genetics/*metabolism ; Protein Conformation ; Saccharomyces cerevisiae/*chemistry/genetics ; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism ; Xenopus laevis
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    Nature Publishing Group (NPG)
    Publication Date: 2014-02-07
    Description: The seasonality of sunlight and rainfall regulates net primary production in tropical forests. Previous studies have suggested that light is more limiting than water for tropical forest productivity, consistent with greening of Amazon forests during the dry season in satellite data. We evaluated four potential mechanisms for the seasonal green-up phenomenon, including increases in leaf area or leaf reflectance, using a sophisticated radiative transfer model and independent satellite observations from lidar and optical sensors. Here we show that the apparent green up of Amazon forests in optical remote sensing data resulted from seasonal changes in near-infrared reflectance, an artefact of variations in sun-sensor geometry. Correcting this bidirectional reflectance effect eliminated seasonal changes in surface reflectance, consistent with independent lidar observations and model simulations with unchanging canopy properties. The stability of Amazon forest structure and reflectance over seasonal timescales challenges the paradigm of light-limited net primary production in Amazon forests and enhanced forest growth during drought conditions. Correcting optical remote sensing data for artefacts of sun-sensor geometry is essential to isolate the response of global vegetation to seasonal and interannual climate variability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morton, Douglas C -- Nagol, Jyoteshwar -- Carabajal, Claudia C -- Rosette, Jacqueline -- Palace, Michael -- Cook, Bruce D -- Vermote, Eric F -- Harding, David J -- North, Peter R J -- England -- Nature. 2014 Feb 13;506(7487):221-4. doi: 10.1038/nature13006. Epub 2014 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA. ; 1] University of Maryland, College Park, Department of Geographical Sciences, College Park, Maryland 20742, USA [2] Global Land Cover Facility, College Park, Maryland 20740, USA. ; 1] NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA [2] Sigma Space Corporation, Lantham, Maryland 20706, USA. ; 1] NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA [2] University of Maryland, College Park, Department of Geographical Sciences, College Park, Maryland 20742, USA [3] Swansea University, Department of Geography, Singleton Park, Swansea SA2 8PP, UK. ; Earth System Research Center, University of New Hampshire, Durham, New Hampshire 03824, USA. ; Swansea University, Department of Geography, Singleton Park, Swansea SA2 8PP, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499816" target="_blank"〉PubMed〈/a〉
    Keywords: Artifacts ; Brazil ; Color ; *Droughts ; Ecosystem ; Fresh Water/analysis ; Models, Biological ; Photosynthesis ; Pigmentation/*physiology ; Plant Leaves/anatomy & histology/growth & development/*physiology ; Rain ; Satellite Imagery ; *Seasons ; *Sunlight ; Trees/anatomy & histology/growth & development/*physiology ; *Tropical Climate
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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