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  • 1
    Publication Date: 2016-02-26
    Description: Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, Peter -- Chang, David K -- Nones, Katia -- Johns, Amber L -- Patch, Ann-Marie -- Gingras, Marie-Claude -- Miller, David K -- Christ, Angelika N -- Bruxner, Tim J C -- Quinn, Michael C -- Nourse, Craig -- Murtaugh, L Charles -- Harliwong, Ivon -- Idrisoglu, Senel -- Manning, Suzanne -- Nourbakhsh, Ehsan -- Wani, Shivangi -- Fink, Lynn -- Holmes, Oliver -- Chin, Venessa -- Anderson, Matthew J -- Kazakoff, Stephen -- Leonard, Conrad -- Newell, Felicity -- Waddell, Nick -- Wood, Scott -- Xu, Qinying -- Wilson, Peter J -- Cloonan, Nicole -- Kassahn, Karin S -- Taylor, Darrin -- Quek, Kelly -- Robertson, Alan -- Pantano, Lorena -- Mincarelli, Laura -- Sanchez, Luis N -- Evers, Lisa -- Wu, Jianmin -- Pinese, Mark -- Cowley, Mark J -- Jones, Marc D -- Colvin, Emily K -- Nagrial, Adnan M -- Humphrey, Emily S -- Chantrill, Lorraine A -- Mawson, Amanda -- Humphris, Jeremy -- Chou, Angela -- Pajic, Marina -- Scarlett, Christopher J -- Pinho, Andreia V -- Giry-Laterriere, Marc -- Rooman, Ilse -- Samra, Jaswinder S -- Kench, James G -- Lovell, Jessica A -- Merrett, Neil D -- Toon, Christopher W -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Moran-Jones, Kim -- Jamieson, Nigel B -- Graham, Janet S -- Duthie, Fraser -- Oien, Karin -- Hair, Jane -- Grutzmann, Robert -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Corbo, Vincenzo -- Bassi, Claudio -- Rusev, Borislav -- Capelli, Paola -- Salvia, Roberto -- Tortora, Giampaolo -- Mukhopadhyay, Debabrata -- Petersen, Gloria M -- Australian Pancreatic Cancer Genome Initiative -- Munzy, Donna M -- Fisher, William E -- Karim, Saadia A -- Eshleman, James R -- Hruban, Ralph H -- Pilarsky, Christian -- Morton, Jennifer P -- Sansom, Owen J -- Scarpa, Aldo -- Musgrove, Elizabeth A -- Bailey, Ulla-Maja Hagbo -- Hofmann, Oliver -- Sutherland, Robert L -- Wheeler, David A -- Gill, Anthony J -- Gibbs, Richard A -- Pearson, John V -- Waddell, Nicola -- Biankin, Andrew V -- Grimmond, Sean M -- 103721/Z/14/Z/Wellcome Trust/United Kingdom -- A12481/Cancer Research UK/United Kingdom -- A18076/Cancer Research UK/United Kingdom -- C29717/A17263/Cancer Research UK/United Kingdom -- England -- Nature. 2016 Mar 3;531(7592):47-52. doi: 10.1038/nature16965. Epub 2016 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. ; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia. ; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia. ; QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. ; Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. ; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA. ; Genetic and Molecular Pathology, SA Pathology, Adelaide, South Australia 5000, Australia. ; School of Biological Sciences, The University of Adelaide, Adelaide, South Australia 5000, Australia. ; Harvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA. ; Macarthur Cancer Therapy Centre, Campbelltown Hospital, New South Wales 2560, Australia. ; Department of Pathology. SydPath, St Vincent's Hospital, Sydney, NSW 2010, Australia. ; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2052, Australia. ; School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. ; Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia. ; University of Sydney, Sydney, New South Wales 2006, Australia. ; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown New South Wales 2050, Australia. ; School of Medicine, University of Western Sydney, Penrith, New South Wales 2175, Australia. ; Fiona Stanley Hospital, Robin Warren Drive, Murdoch, Western Australia 6150, Australia. ; Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. ; Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. ; School of Surgery M507, University of Western Australia, 35 Stirling Hwy, Nedlands 6009, Australia and St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia. ; Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK. ; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. ; Department of Medical Oncology, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. ; Department of Pathology, Southern General Hospital, Greater Glasgow &Clyde NHS, Glasgow G51 4TF, UK. ; GGC Bio-repository, Pathology Department, Southern General Hospital, 1345 Govan Road, Glasgow G51 4TY, UK. ; Department of Surgery, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. ; Departments of Pathology and Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston Texas 77030, USA. ; The David M. Rubenstein Pancreatic Cancer Research Center and Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona, Verona 37134, Italy. ; Department of Pathology and Diagnostics, University of Verona, Verona 37134, Italy. ; Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. ; Department of Medical Oncology, Comprehensive Cancer Centre, University and Hospital Trust of Verona, Verona 37134, Italy. ; Mayo Clinic, Rochester, Minnesota 55905, USA. ; Elkins Pancreas Center, Baylor College of Medicine, One Baylor Plaza, MS226, Houston, Texas 77030-3411, USA. ; Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK. ; Institute for Cancer Science, University of Glasgow, Glasgow G12 8QQ, UK. ; University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26909576" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Carcinoma, Pancreatic ; Ductal/classification/genetics/immunology/metabolism/pathology ; Cell Line, Tumor ; DNA Methylation ; DNA-Binding Proteins/genetics ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genes, Neoplasm/*genetics ; Genome, Human/*genetics ; *Genomics ; Hepatocyte Nuclear Factor 3-beta/genetics ; Hepatocyte Nuclear Factor 3-gamma/genetics ; Histone Demethylases/genetics ; Homeodomain Proteins/genetics ; Humans ; Mice ; Mutation/*genetics ; Nuclear Proteins/genetics ; Pancreatic Neoplasms/*classification/*genetics/immunology/metabolism/pathology ; Prognosis ; Receptors, Cytoplasmic and Nuclear/genetics ; Survival Analysis ; Trans-Activators/genetics ; Transcription Factors/genetics ; Transcription, Genetic ; Transcriptome ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Proteins/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-09-15
    Description: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF 〈/= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755714/" 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/PMC4755714/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Hou-Feng -- Forgetta, Vincenzo -- Hsu, Yi-Hsiang -- Estrada, Karol -- Rosello-Diez, Alberto -- Leo, Paul J -- Dahia, Chitra L -- Park-Min, Kyung Hyun -- Tobias, Jonathan H -- Kooperberg, Charles -- Kleinman, Aaron -- Styrkarsdottir, Unnur -- Liu, Ching-Ti -- Uggla, Charlotta -- Evans, Daniel S -- Nielson, Carrie M -- Walter, Klaudia -- Pettersson-Kymmer, Ulrika -- McCarthy, Shane -- Eriksson, Joel -- Kwan, Tony -- Jhamai, Mila -- Trajanoska, Katerina -- Memari, Yasin -- Min, Josine -- Huang, Jie -- Danecek, Petr -- Wilmot, Beth -- Li, Rui -- Chou, Wen-Chi -- Mokry, Lauren E -- Moayyeri, Alireza -- Claussnitzer, Melina -- Cheng, Chia-Ho -- Cheung, Warren -- Medina-Gomez, Carolina -- Ge, Bing -- Chen, Shu-Huang -- Choi, Kwangbom -- Oei, Ling -- Fraser, James -- Kraaij, Robert -- Hibbs, Matthew A -- Gregson, Celia L -- Paquette, Denis -- Hofman, Albert -- Wibom, Carl -- Tranah, Gregory J -- Marshall, Mhairi -- Gardiner, Brooke B -- Cremin, Katie -- Auer, Paul -- Hsu, Li -- Ring, Sue -- Tung, Joyce Y -- Thorleifsson, Gudmar -- Enneman, Anke W -- van Schoor, Natasja M -- de Groot, Lisette C P G M -- van der Velde, Nathalie -- Melin, Beatrice -- Kemp, John P -- Christiansen, Claus -- Sayers, Adrian -- Zhou, Yanhua -- Calderari, Sophie -- van Rooij, Jeroen -- Carlson, Chris -- Peters, Ulrike -- Berlivet, Soizik -- Dostie, Josee -- Uitterlinden, Andre G -- Williams, Stephen R -- Farber, Charles -- Grinberg, Daniel -- LaCroix, Andrea Z -- Haessler, Jeff -- Chasman, Daniel I -- Giulianini, Franco -- Rose, Lynda M -- Ridker, Paul M -- Eisman, John A -- Nguyen, Tuan V -- Center, Jacqueline R -- Nogues, Xavier -- Garcia-Giralt, Natalia -- Launer, Lenore L -- Gudnason, Vilmunder -- Mellstrom, Dan -- Vandenput, Liesbeth -- Amin, Najaf -- van Duijn, Cornelia M -- Karlsson, Magnus K -- Ljunggren, Osten -- Svensson, Olle -- Hallmans, Goran -- Rousseau, Francois -- Giroux, Sylvie -- Bussiere, Johanne -- Arp, Pascal P -- Koromani, Fjorda -- Prince, Richard L -- Lewis, Joshua R -- Langdahl, Bente L -- Hermann, A Pernille -- Jensen, Jens-Erik B -- Kaptoge, Stephen -- Khaw, Kay-Tee -- Reeve, Jonathan -- Formosa, Melissa M -- Xuereb-Anastasi, Angela -- Akesson, Kristina -- McGuigan, Fiona E -- Garg, Gaurav -- Olmos, Jose M -- Zarrabeitia, Maria T -- Riancho, Jose A -- Ralston, Stuart H -- Alonso, Nerea -- Jiang, Xi -- Goltzman, David -- Pastinen, Tomi -- Grundberg, Elin -- Gauguier, Dominique -- Orwoll, Eric S -- Karasik, David -- Davey-Smith, George -- AOGC Consortium -- Smith, Albert V -- Siggeirsdottir, Kristin -- Harris, Tamara B -- Zillikens, M Carola -- van Meurs, Joyce B J -- Thorsteinsdottir, Unnur -- Maurano, Matthew T -- Timpson, Nicholas J -- Soranzo, Nicole -- Durbin, Richard -- Wilson, Scott G -- Ntzani, Evangelia E -- Brown, Matthew A -- Stefansson, Kari -- Hinds, David A -- Spector, Tim -- Cupples, L Adrienne -- Ohlsson, Claes -- Greenwood, Celia M T -- UK10K Consortium -- Jackson, Rebecca D -- Rowe, David W -- Loomis, Cynthia A -- Evans, David M -- Ackert-Bicknell, Cheryl L -- Joyner, Alexandra L -- Duncan, Emma L -- Kiel, Douglas P -- Rivadeneira, Fernando -- Richards, J Brent -- G1000143/Medical Research Council/United Kingdom -- K01 AR062655/AR/NIAMS NIH HHS/ -- MC_UU_12013/3/Medical Research Council/United Kingdom -- R01 AG005394/AG/NIA NIH HHS/ -- R01 AG005407/AG/NIA NIH HHS/ -- R01 AG027574/AG/NIA NIH HHS/ -- R01 AG027576/AG/NIA NIH HHS/ -- R01 AR035582/AR/NIAMS NIH HHS/ -- R01 AR035583/AR/NIAMS NIH HHS/ -- RC2 AR058973/AR/NIAMS NIH HHS/ -- U01 AG018197/AG/NIA NIH HHS/ -- U01 AG042140/AG/NIA NIH HHS/ -- U01 AG042143/AG/NIA NIH HHS/ -- U01 AR045580/AR/NIAMS NIH HHS/ -- U01 AR045583/AR/NIAMS NIH HHS/ -- U01 AR045614/AR/NIAMS NIH HHS/ -- U01 AR045632/AR/NIAMS NIH HHS/ -- U01 AR045647/AR/NIAMS NIH HHS/ -- U01 AR045654/AR/NIAMS NIH HHS/ -- U01 AR066160/AR/NIAMS NIH HHS/ -- England -- Nature. 2015 Oct 1;526(7571):112-7. doi: 10.1038/nature14878. Epub 2015 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal H3A 1A2, Canada. ; Department of Medicine, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal H3T 1E2, Canada. ; Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts 02131, USA. ; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Broad Institute of MIT and Harvard, Boston, Massachusetts 02115, USA. ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3015GE, The Netherlands. ; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Developmental Biology Program, Sloan Kettering Institute, New York, New York 10065, USA. ; The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane 4102, Australia. ; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York 10065, USA. ; Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, New York 10021, USA. ; Rheumatology Divison, Hospital for Special Surgery New York, New York 10021, USA. ; School of Clinical Science, University of Bristol, Bristol BS10 5NB, UK. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; Department of Research, 23andMe, Mountain View, California 94041, USA. ; Department of Population Genomics, deCODE Genetics, Reykjavik IS-101, Iceland. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden. ; California Pacific Medical Center Research Institute, San Francisco, California 94158, USA. ; Department of Public Health and Preventive Medicine, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Bone &Mineral Unit, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK. ; Departments of Pharmacology and Clinical Neurosciences, Umea University, Umea S-901 87, Sweden. ; Department of Public Health and Clinical Medicine, Umea University, Umea SE-901 87, Sweden. ; Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden. ; McGill University and Genome Quebec Innovation Centre, Montreal H3A 0G1, Canada. ; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015GE, The Netherlands. ; Oregon Clinical and Translational Research Institute, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Department of Medical and Clinical Informatics, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Farr Institute of Health Informatics Research, University College London, London NW1 2DA, UK. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. ; Department of Human Genetics, McGill University, Montreal H3A 1B1, Canada. ; Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden 2300RC, The Netherlands. ; Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA. ; Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal H3G 1Y6, Canada. ; Department of Computer Science, Trinity University, San Antonio, Texas 78212, USA. ; Musculoskeletal Research Unit, University of Bristol, Bristol BS10 5NB, UK. ; Department of Radiation Sciences, Umea University, Umea S-901 87, Sweden. ; School of Public Health, University of Wisconsin, Milwaukee, Wisconsin 53726, USA. ; School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK. ; Department of Statistics, deCODE Genetics, Reykjavik IS-101, Iceland. ; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam 1007 MB, The Netherlands. ; Department of Human Nutrition, Wageningen University, Wageningen 6700 EV, The Netherlands. ; Department of Internal Medicine, Section Geriatrics, Academic Medical Center, Amsterdam 1105, The Netherlands. ; Nordic Bioscience, Herlev 2730, Denmark. ; Cordeliers Research Centre, INSERM UMRS 1138, Paris 75006, France. ; Institute of Cardiometabolism and Nutrition, University Pierre &Marie Curie, Paris 75013, France. ; Departments of Medicine (Cardiovascular Medicine), Centre for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22908, USA. ; Department of Genetics, University of Barcelona, Barcelona 08028, Spain. ; U-720, Centre for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona 28029, Spain. ; Department of Human Molecular Genetics, The Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona 08028, Spain. ; Women's Health Center of Excellence Family Medicine and Public Health, University of California - San Diego, San Diego, California 92093, USA. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; Osteoporosis &Bone Biology Program, Garvan Institute of Medical Research, Sydney 2010, Australia. ; School of Medicine Sydney, University of Notre Dame Australia, Sydney 6959, Australia. ; St. Vincent's Hospital &Clinical School, NSW University, Sydney 2010, Australia. ; Musculoskeletal Research Group, Institut Hospital del Mar d'Investigacions Mediques, Barcelona 08003, Spain. ; Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III, 28029, Spain. ; Department of Internal Medicine, Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona 08193, Spain. ; Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Icelandic Heart Association, Kopavogur IS-201, Iceland. ; Faculty of Medicine, University of Iceland, Reykjavik IS-101, Iceland. ; Genetic epidemiology unit, Department of Epidemiology, Erasmus MC, Rotterdam 3000CA, The Netherlands. ; Department of Orthopaedics, Skane University Hospital Malmo 205 02, Sweden. ; Department of Medical Sciences, University of Uppsala, Uppsala 751 85, Sweden. ; Department of Surgical and Perioperative Sciences, Umea Unviersity, Umea 901 85, Sweden. ; Department of Molecular Biology, Medical Biochemistry and Pathology, Universite Laval, Quebec City G1V 0A6, Canada. ; Axe Sante des Populations et Pratiques Optimales en Sante, Centre de recherche du CHU de Quebec, Quebec City G1V 4G2, Canada. ; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands 6009, Australia. ; Department of Medicine, University of Western Australia, Perth 6009, Australia. ; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C 8000, Denmark. ; Department of Endocrinology, Odense University Hospital, Odense C 5000, Denmark. ; Department of Endocrinology, Hvidovre University Hospital, Hvidovre 2650, Denmark. ; Clinical Gerontology Unit, University of Cambridge, Cambridge CB2 2QQ, UK. ; Medicine and Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; Institute of Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford OX3 7LD, UK. ; Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida MSD 2080, Malta. ; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmo, Lund University, 205 02, Sweden. ; Department of Medicine and Psychiatry, University of Cantabria, Santander 39011, Spain. ; Department of Internal Medicine, Hospital U.M. Valdecilla- IDIVAL, Santander 39008, Spain. ; Department of Legal Medicine, University of Cantabria, Santander 39011, Spain. ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. ; Department of Medicine and Physiology, McGill University, Montreal H4A 3J1, Canada. ; Department of Medicine, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 13010, Israel. ; Laboratory of Epidemiology, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia. ; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece. ; Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, Rhode Island 02903, USA. ; deCODE Genetics, Reykjavik IS-101, Iceland. ; Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal H3A 1A2, Canada. ; Department of Oncology, Gerald Bronfman Centre, McGill University, Montreal H2W 1S6, Canada. ; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio 43210, USA. ; The Ronald O. Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA. ; Department of Diabetes and Endocrinology, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26367794" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Density/*genetics ; Bone and Bones/metabolism ; Disease Models, Animal ; Europe/ethnology ; European Continental Ancestry Group/genetics ; Exome/genetics ; Female ; Fractures, Bone/*genetics ; Gene Frequency/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Genome, Human/*genetics ; Genomics ; Genotype ; Homeodomain Proteins/*genetics ; Humans ; Mice ; Sequence Analysis, DNA ; Wnt Proteins/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-03-13
    Description: Stochastic processes in cells are associated with fluctuations in mRNA, protein production and degradation, noisy partition of cellular components at division, and other cell processes. Variability within a clonal population of cells originates from such stochastic processes, which may be amplified or reduced by deterministic factors. Cell-to-cell variability, such as that seen in the heterogeneous response of bacteria to antibiotics, or of cancer cells to treatment, is understood as the inevitable consequence of stochasticity. Variability in cell-cycle duration was observed long ago; however, its sources are still unknown. A central question is whether the variance of the observed distribution originates from stochastic processes, or whether it arises mostly from a deterministic process that only appears to be random. A surprising feature of cell-cycle-duration inheritance is that it seems to be lost within one generation but to be still present in the next generation, generating poor correlation between mother and daughter cells but high correlation between cousin cells. This observation suggests the existence of underlying deterministic factors that determine the main part of cell-to-cell variability. We developed an experimental system that precisely measures the cell-cycle duration of thousands of mammalian cells along several generations and a mathematical framework that allows discrimination between stochastic and deterministic processes in lineages of cells. We show that the inter- and intra-generation correlations reveal complex inheritance of the cell-cycle duration. Finally, we build a deterministic nonlinear toy model for cell-cycle inheritance that reproduces the main features of our data. Our approach constitutes a general method to identify deterministic variability in lineages of cells or organisms, which may help to predict and, eventually, reduce cell-to-cell heterogeneity in various systems, such as cancer cells under treatment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandler, Oded -- Mizrahi, Sivan Pearl -- Weiss, Noga -- Agam, Oded -- Simon, Itamar -- Balaban, Nathalie Q -- England -- Nature. 2015 Mar 26;519(7544):468-71. doi: 10.1038/nature14318. Epub 2015 Mar 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel. ; 1] Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel [2] Racah Institute of Physics, Edmond J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel. ; Racah Institute of Physics, Edmond J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25762143" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Cell Cycle/drug effects/*genetics ; Cell Division/drug effects/genetics ; Cell Line ; *Cell Lineage ; Mammals ; Models, Biological ; Stochastic Processes ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-11-13
    Description: The pressures on honeybee (Apis mellifera) populations, resulting from threats by modern pesticides, parasites, predators and diseases, have raised awareness of the economic importance and critical role this insect plays in agricultural societies across the globe. However, the association of humans with A. mellifera predates post-industrial-revolution agriculture, as evidenced by the widespread presence of ancient Egyptian bee iconography dating to the Old Kingdom (approximately 2400 BC). There are also indications of Stone Age people harvesting bee products; for example, honey hunting is interpreted from rock art in a prehistoric Holocene context and a beeswax find in a pre-agriculturalist site. However, when and where the regular association of A. mellifera with agriculturalists emerged is unknown. One of the major products of A. mellifera is beeswax, which is composed of a complex suite of lipids including n-alkanes, n-alkanoic acids and fatty acyl wax esters. The composition is highly constant as it is determined genetically through the insect's biochemistry. Thus, the chemical 'fingerprint' of beeswax provides a reliable basis for detecting this commodity in organic residues preserved at archaeological sites, which we now use to trace the exploitation by humans of A. mellifera temporally and spatially. Here we present secure identifications of beeswax in lipid residues preserved in pottery vessels of Neolithic Old World farmers. The geographical range of bee product exploitation is traced in Neolithic Europe, the Near East and North Africa, providing the palaeoecological range of honeybees during prehistory. Temporally, we demonstrate that bee products were exploited continuously, and probably extensively in some regions, at least from the seventh millennium cal BC, likely fulfilling a variety of technological and cultural functions. The close association of A. mellifera with Neolithic farming communities dates to the early onset of agriculture and may provide evidence for the beginnings of a domestication process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roffet-Salque, Melanie -- Regert, Martine -- Evershed, Richard P -- Outram, Alan K -- Cramp, Lucy J E -- Decavallas, Orestes -- Dunne, Julie -- Gerbault, Pascale -- Mileto, Simona -- Mirabaud, Sigrid -- Paakkonen, Mirva -- Smyth, Jessica -- Soberl, Lucija -- Whelton, Helen L -- Alday-Ruiz, Alfonso -- Asplund, Henrik -- Bartkowiak, Marta -- Bayer-Niemeier, Eva -- Belhouchet, Lotfi -- Bernardini, Federico -- Budja, Mihael -- Cooney, Gabriel -- Cubas, Miriam -- Danaher, Ed M -- Diniz, Mariana -- Domboroczki, Laszlo -- Fabbri, Cristina -- Gonzalez-Urquijo, Jesus E -- Guilaine, Jean -- Hachi, Slimane -- Hartwell, Barrie N -- Hofmann, Daniela -- Hohle, Isabel -- Ibanez, Juan J -- Karul, Necmi -- Kherbouche, Farid -- Kiely, Jacinta -- Kotsakis, Kostas -- Lueth, Friedrich -- Mallory, James P -- Manen, Claire -- Marciniak, Arkadiusz -- Maurice-Chabard, Brigitte -- Mc Gonigle, Martin A -- Mulazzani, Simone -- Ozdogan, Mehmet -- Peric, Olga S -- Peric, Slavisa R -- Petrasch, Jorg -- Petrequin, Anne-Marie -- Petrequin, Pierre -- Poensgen, Ulrike -- Pollard, C Joshua -- Poplin, Francois -- Radi, Giovanna -- Stadler, Peter -- Stauble, Harald -- Tasic, Nenad -- Urem-Kotsou, Dushka -- Vukovic, Jasna B -- Walsh, Fintan -- Whittle, Alasdair -- Wolfram, Sabine -- Zapata-Pena, Lydia -- Zoughlami, Jamel -- Wellcome Trust/United Kingdom -- England -- Nature. 2015 Nov 12;527(7577):226-30. doi: 10.1038/nature15757.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Organic Geochemistry Unit, School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK. ; CEPAM - Cultures et Environnements. Prehistoire, Antiquite, Moyen Age, UMR 7264, Universite Nice Sophia Antipolis - CNRS, 06300 Nice, France. ; Department of Archaeology, University of Exeter, Laver Building, North Park Road, Exeter, Devon EX4 4QE, UK. ; Department of Archaeology and Anthropology, University of Bristol, 43 Woodland Road, Bristol BS8 1UU, UK. ; Universite Bordeaux Montaigne, 33607 Pessac, France. ; Laboratoire du Centre de Recherche et de Restauration des Musees de France (C2RMF), UMR 171, Palais du Louvre, Porte des Lions, 14 Quai Francois Mitterrand, 75001 Paris, France. ; Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK. ; Department of Anthropology, University College London, London WC1H 0BW, UK. ; Institut fur Prahistorische Archaologie, Freie Universitat Berlin, Altensteinstr. 15, Berlin 14195, Germany. ; Department of Archaeology, University of Turku, 20014 Turun Yliopisto, Finland. ; University of Ljubljana, Faculty of Arts, Department of Archaeology, Askerceva 2, box 580, 1000 Ljubljana, Slovenia. ; Department of Geography, Prehistory and Archaeology. University of Basque Country (EHU-UPV), Francisco Tomas y Valiente s/n, 01006 Vitoria-Gasteiz, Spain. ; Institute of Prehistory, Adam Mickiewicz University, Umultowska 89d, 61-614 Poznan, Poland. ; Museum Quintana - Archaologie in Kunzing, Partnermuseum der Archaologischen Staatssammlung Munchen, Osterhofener Str. 2, 94550 Kunzing, Germany. ; Musee Archeologique de Sousse, Rue Marshall Tito, 4000 Sousse, Tunisia. ; Centro Fermi, Museo Storico della Fisica e Centro di Studi e Ricerche Enrico Fermi, 00184 Rome, Italy. ; Multidisciplinary Laboratory, The Abdus Salam International Centre for Theoretical Physics, 34151 Trieste, Italy. ; UCD School of Archaeology, University College Dublin, Dublin 4, Ireland. ; International Institute for Prehistoric Research of Cantabria, University of Cantabria, Avd de los Castros s/n, 39005 Santander, Spain. ; Department of Archaeology, University College Galway, Galway, Ireland. ; UNIARQ-Departamento de Historia, Faculdade de Letras de Lisboa, Universidade de Lisboa, 1600-214 Lisboa, Portugal. ; Istvan Dobo Castle Museum, Var ut 1, 3300 Eger, Hungary. ; Dipartimento Civilta e Forme del Sapere, Universita di Pisa, Via Galvani 1, 56126 Pisa, Italy. ; CNRS - UMR 5608 - TRACES, Maison de la recherche, Universite Toulouse Jean Jaures, 5 Allee Antonio Machado, 31058 Toulouse cedex 9, France. ; CNRPAH, Centre National de Recherche Prehistorique, Anthropologique et Historique, Algiers, Algeria. ; School of Geography, Archaeology and Palaeoecology, Queen's University Belfast, Belfast BT7 1NN, UK. ; Universitat Hamburg, Archaologisches Institut, Edmund-Siemers-Allee 1, Flugel West, 20146 Hamburg, Germany. ; a.r.t.e.s. Graduate School for the Humanities Cologne, Graduiertenschule der Philosophischen Fakultat, Aachener Str. 217, 50931 Cologne, Germany. ; IMF-CSIC, Egipciacas 15, 08001 Barcelona, Spain. ; Istanbul University, Faculty of Letters, Department of Prehistory, 34434 Laleli Istanbul, Turkey. ; Eachtra Archaeological Projects, Lickybeg, Clashmore, County Waterford, Ireland. ; School of History and Archaeology, Faculty of Philosophy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. ; German Archaeological Institute, Podbielskiallee 69-71, 14 195 Berlin, Germany. ; Musee Rolin, 3 rue des Bancs, 71400 Autun, France. ; John Cronin &Associates, 28 Upper Main Street, Buncrana, County Donegal, Ireland. ; Aix-Marseille Universite, CNRS, Ministere de la Culture et de la Communication, UMR 7269 LAMPEA, LabexMed, 13284 Marseille, France. ; Dipartimento di Biologia Ambientale, Universita degli Studi di Roma La Sapienza, Rome 00185, Italy. ; Institute of Archaeology Belgrade, Kneza Mihaila 35/4 11000 Belgrade, Serbia. ; Eberhard-Karls-Universitat Tubingen, Institut fur Ur- und Fruhgeschichte und Archaologie des Mittelalters - Abt. Jungere Urgeschichte und Fruhgeschichte - Schloss Hohentubingen, 72070 Tubingen, Germany. ; Maison des Sciences de l'Homme et de l'Environnement C.N. Ledoux, CNRS &Universite de Franche-Comte, 32 rue Megevand, 25030 Besancon Cedex, France. ; Kampfenstr. 20, 78315 Radolfzell, Germany. ; Department of Archaeology, Faculty of Humanities, University of Southampton, Avenue Campus, Highfield, Southampton SO17 1BF, UK. ; Museum National d'Histoire Naturelle, 55 rue de Buffon, 75005 Paris, France. ; Department of Pre- and Protohistory, University of Vienna, 1190 Vienna, Austria. ; Landesamt fur Archaeologie, Zur Wetterwarte 7, 01109 Dresden, Germany. ; Department of Archaeology, Faculty of Philosophy, Belgrade University, 18-20 Cika Ljubina Street, 11000 Belgrade, Serbia. ; Department of History and Ethnology, Democritus University of Thrace, Komotini, Greece. ; Irish Archaeological Consultancy, Unit G1, Network Enterprise Park, Kilcoole, County Wicklow, Ireland. ; Department of Archaeology and Conservation, Cardiff University, John Percival Building, Colum Drive, Cardiff CF10 3EU, UK. ; State Museum of Archaeology Chemnitz, Stefan-Heym-Platz 1, 09111 Chemnitz, Germany. ; Institut National du Patrimoine de Tunis - Musee archeologique de Carthage, Carthage, Tunisia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26560301" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Northern ; Animals ; Archaeology ; Beekeeping/*history ; *Bees ; Ceramics/chemistry/history ; Europe ; Farmers/history ; Geographic Mapping ; History, Ancient ; Lipids/analysis/chemistry ; Middle East ; Spatio-Temporal Analysis ; Waxes/*analysis/chemistry/*history
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-01-30
    Description: A key event in human evolution is the expansion of modern humans of African origin across Eurasia between 60 and 40 thousand years (kyr) before present (bp), replacing all other forms of hominins. Owing to the scarcity of human fossils from this period, these ancestors of all present-day non-African modern populations remain largely enigmatic. Here we describe a partial calvaria, recently discovered at Manot Cave (Western Galilee, Israel) and dated to 54.7 +/- 5.5 kyr bp (arithmetic mean +/- 2 standard deviations) by uranium-thorium dating, that sheds light on this crucial event. The overall shape and discrete morphological features of the Manot 1 calvaria demonstrate that this partial skull is unequivocally modern. It is similar in shape to recent African skulls as well as to European skulls from the Upper Palaeolithic period, but different from most other early anatomically modern humans in the Levant. This suggests that the Manot people could be closely related to the first modern humans who later successfully colonized Europe. Thus, the anatomical features used to support the 'assimilation model' in Europe might not have been inherited from European Neanderthals, but rather from earlier Levantine populations. Moreover, at present, Manot 1 is the only modern human specimen to provide evidence that during the Middle to Upper Palaeolithic interface, both modern humans and Neanderthals contemporaneously inhabited the southern Levant, close in time to the likely interbreeding event with Neanderthals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hershkovitz, Israel -- Marder, Ofer -- Ayalon, Avner -- Bar-Matthews, Miryam -- Yasur, Gal -- Boaretto, Elisabetta -- Caracuta, Valentina -- Alex, Bridget -- Frumkin, Amos -- Goder-Goldberger, Mae -- Gunz, Philipp -- Holloway, Ralph L -- Latimer, Bruce -- Lavi, Ron -- Matthews, Alan -- Slon, Viviane -- Mayer, Daniella Bar-Yosef -- Berna, Francesco -- Bar-Oz, Guy -- Yeshurun, Reuven -- May, Hila -- Hans, Mark G -- Weber, Gerhard W -- Barzilai, Omry -- England -- Nature. 2015 Apr 9;520(7546):216-9. doi: 10.1038/nature14134. Epub 2015 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] The Dan David Laboratory for the Search and Study of Modern Humans, Sackler Faculty of Medicine, Tel Aviv University, PO Box 39040, Tel Aviv 6997801, Israel [2] The Steinhardt Museum of Natural History and National Research Center, Tel Aviv University, PO Box 39040, Tel Aviv 6997801, Israel. ; Archaeology Division, Ben-Gurion University of the Negev, PO Box 653, Beer-Sheva 8410501, Israel. ; Geological Survey of Israel, 30 Malkhe Israel Street, Jerusalem 95501, Israel. ; Max Planck Society-Weizmann Institute Center for Integrative Archaeology and Anthropology, D-REAMS Radiocarbon Laboratory, Weizmann Institute of Science, Rehovot 76100, Israel. ; 1] Max Planck Society-Weizmann Institute Center for Integrative Archaeology and Anthropology, D-REAMS Radiocarbon Laboratory, Weizmann Institute of Science, Rehovot 76100, Israel [2] Department of Anthropology and Human Evolutionary Biology, Harvard University, 11 Divinity Avenue, Cambridge, Massachusetts 02138, USA. ; Department of Geography, The Hebrew University of Jerusalem, Jerusalem 91905, Israel. ; Institute of Archaeology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel. ; Department of Human Evolution, Max-Planck-Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103, Leipzig, Germany. ; Department of Anthropology, Columbia University, New York 10027, USA. ; 1] Department of Anatomy, Case Western Reserve University, Cleveland, Ohio 44106, USA [2] Department of Orthodontics, Case Western Reserve University School of Dental Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA. ; 8 Dan Street, Modi'in 7173161, Israel. ; Institute of Earth Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel. ; The Dan David Laboratory for the Search and Study of Modern Humans, Sackler Faculty of Medicine, Tel Aviv University, PO Box 39040, Tel Aviv 6997801, Israel. ; The Steinhardt Museum of Natural History and National Research Center, Tel Aviv University, PO Box 39040, Tel Aviv 6997801, Israel. ; Department of Archaeology, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada. ; Zinman Institute of Archaeology, University of Haifa, Haifa 3498838, Israel. ; 1] The Steinhardt Museum of Natural History and National Research Center, Tel Aviv University, PO Box 39040, Tel Aviv 6997801, Israel [2] Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, PO Box 39040, Tel Aviv 6997801, Israel. ; Department of Orthodontics, Case Western Reserve University School of Dental Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA. ; 1] Department of Anthropology, University of Vienna, Althanstrasse 12-14, A-1090 Vienna, Austria [2] The Core Facility for Micro-Computed Tomography, University of Vienna, Althanstrasse 12-14, A-1090, Vienna, Austria. ; Israel Antiquities Authority, PO Box 586, Jerusalem 91004, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25629628" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/ethnology ; Animals ; *Caves ; Europe/ethnology ; *Fossils ; Humans ; Israel ; Neanderthals/anatomy & histology/physiology ; *Phylogeny ; Skull/*anatomy & histology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2015-09-15
    Description: Bromodomain and extra terminal protein (BET) inhibitors are first-in-class targeted therapies that deliver a new therapeutic opportunity by directly targeting bromodomain proteins that bind acetylated chromatin marks. Early clinical trials have shown promise, especially in acute myeloid leukaemia, and therefore the evaluation of resistance mechanisms is crucial to optimize the clinical efficacy of these drugs. Here we use primary mouse haematopoietic stem and progenitor cells immortalized with the fusion protein MLL-AF9 to generate several single-cell clones that demonstrate resistance, in vitro and in vivo, to the prototypical BET inhibitor, I-BET. Resistance to I-BET confers cross-resistance to chemically distinct BET inhibitors such as JQ1, as well as resistance to genetic knockdown of BET proteins. Resistance is not mediated through increased drug efflux or metabolism, but is shown to emerge from leukaemia stem cells both ex vivo and in vivo. Chromatin-bound BRD4 is globally reduced in resistant cells, whereas the expression of key target genes such as Myc remains unaltered, highlighting the existence of alternative mechanisms to regulate transcription. We demonstrate that resistance to BET inhibitors, in human and mouse leukaemia cells, is in part a consequence of increased Wnt/beta-catenin signalling, and negative regulation of this pathway results in restoration of sensitivity to I-BET in vitro and in vivo. Together, these findings provide new insights into the biology of acute myeloid leukaemia, highlight potential therapeutic limitations of BET inhibitors, and identify strategies that may enhance the clinical utility of these unique targeted therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fong, Chun Yew -- Gilan, Omer -- Lam, Enid Y N -- Rubin, Alan F -- Ftouni, Sarah -- Tyler, Dean -- Stanley, Kym -- Sinha, Devbarna -- Yeh, Paul -- Morison, Jessica -- Giotopoulos, George -- Lugo, Dave -- Jeffrey, Philip -- Lee, Stanley Chun-Wei -- Carpenter, Christopher -- Gregory, Richard -- Ramsay, Robert G -- Lane, Steven W -- Abdel-Wahab, Omar -- Kouzarides, Tony -- Johnstone, Ricky W -- Dawson, Sarah-Jane -- Huntly, Brian J P -- Prinjha, Rab K -- Papenfuss, Anthony T -- Dawson, Mark A -- England -- Nature. 2015 Sep 24;525(7570):538-42. doi: 10.1038/nature14888. Epub 2015 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, East Melbourne, Victoria 3002, Australia. ; Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. ; Bioinformatics Division, The Walter &Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. ; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia. ; Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust-MRC Stem Cell Institute, Cambridge CB2 0XY, UK. ; Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK. ; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Cancer Epigenetics DPU, Oncology R&D, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA. ; QIMR Berghofer Medical Research Institute, University of Queensland, Brisbane, Queensland 4029, Australia. ; Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26367796" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Azepines/pharmacology ; Benzodiazepines/*pharmacology ; Cell Line, Tumor ; Cells, Cultured ; Chromatin/metabolism ; Clone Cells/drug effects/metabolism/pathology ; Drug Resistance, Neoplasm/*drug effects/genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, myc/genetics ; Hematopoietic Stem Cells/cytology/drug effects/metabolism ; Humans ; Leukemia, Myeloid, Acute/*drug therapy/genetics/*metabolism/pathology ; Mice ; Molecular Targeted Therapy ; Neoplastic Stem Cells/*drug effects/metabolism/*pathology ; Nuclear Proteins/*antagonists & inhibitors/metabolism ; Transcription Factors/*antagonists & inhibitors/metabolism ; Transcription, Genetic/drug effects ; Triazoles/pharmacology ; Wnt Signaling Pathway/drug effects ; beta Catenin/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2015-05-23
    Description: Marine plankton support global biological and geochemical processes. Surveys of their biodiversity have hitherto been geographically restricted and have not accounted for the full range of plankton size. We assessed eukaryotic diversity from 334 size-fractionated photic-zone plankton communities collected across tropical and temperate oceans during the circumglobal Tara Oceans expedition. We analyzed 18S ribosomal DNA sequences across the intermediate plankton-size spectrum from the smallest unicellular eukaryotes (protists, 〉0.8 micrometers) to small animals of a few millimeters. Eukaryotic ribosomal diversity saturated at ~150,000 operational taxonomic units, about one-third of which could not be assigned to known eukaryotic groups. Diversity emerged at all taxonomic levels, both within the groups comprising the ~11,200 cataloged morphospecies of eukaryotic plankton and among twice as many other deep-branching lineages of unappreciated importance in plankton ecology studies. Most eukaryotic plankton biodiversity belonged to heterotrophic protistan groups, particularly those known to be parasites or symbiotic hosts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Vargas, Colomban -- Audic, Stephane -- Henry, Nicolas -- Decelle, Johan -- Mahe, Frederic -- Logares, Ramiro -- Lara, Enrique -- Berney, Cedric -- Le Bescot, Noan -- Probert, Ian -- Carmichael, Margaux -- Poulain, Julie -- Romac, Sarah -- Colin, Sebastien -- Aury, Jean-Marc -- Bittner, Lucie -- Chaffron, Samuel -- Dunthorn, Micah -- Engelen, Stefan -- Flegontova, Olga -- Guidi, Lionel -- Horak, Ales -- Jaillon, Olivier -- Lima-Mendez, Gipsi -- Lukes, Julius -- Malviya, Shruti -- Morard, Raphael -- Mulot, Matthieu -- Scalco, Eleonora -- Siano, Raffaele -- Vincent, Flora -- Zingone, Adriana -- Dimier, Celine -- Picheral, Marc -- Searson, Sarah -- Kandels-Lewis, Stefanie -- Tara Oceans Coordinators -- Acinas, Silvia G -- Bork, Peer -- Bowler, Chris -- Gorsky, Gabriel -- Grimsley, Nigel -- Hingamp, Pascal -- Iudicone, Daniele -- Not, Fabrice -- Ogata, Hiroyuki -- Pesant, Stephane -- Raes, Jeroen -- Sieracki, Michael E -- Speich, Sabrina -- Stemmann, Lars -- Sunagawa, Shinichi -- Weissenbach, Jean -- Wincker, Patrick -- Karsenti, Eric -- New York, N.Y. -- Science. 2015 May 22;348(6237):1261605. doi: 10.1126/science.1261605.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie (UPMC) Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. vargas@sb-roscoff.fr pwincker@genoscope.cns.fr karsenti@embl.de. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie (UPMC) Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; Department of Ecology, University of Kaiserslautern, Erwin-Schroedinger Street, 67663 Kaiserslautern, Germany. CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie (UPMC) Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; Department of Marine Biology and Oceanography, Institute of Marine Science (ICM)-Consejo Superior de Investigaciones Cientificas (CSIC), Passeig Maritim de la Barceloneta 37-49, Barcelona E08003, Spain. ; Laboratory of Soil Biology, University of Neuchatel, Rue Emile-Argand 11, 2000 Neuchatel, Switzerland. ; CNRS, FR2424, Roscoff Culture Collection, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, UPMC Paris 06, FR 2424, Roscoff Culture Collection, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie (UPMC) Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris, F-75005 France. ; Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA), Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91000 Evry, France. ; CNRS FR3631, Institut de Biologie Paris-Seine, F-75005, Paris, France. Sorbonne Universites, UPMC Paris 06, Institut de Biologie Paris-Seine, F-75005, Paris, France. Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris, F-75005 France. CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie (UPMC) Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; Department of Ecology, University of Kaiserslautern, Erwin-Schroedinger Street, 67663 Kaiserslautern, Germany. ; Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Branisovska 31, 37005 Ceske Budejovice, Czech Republic. Faculty of Science, University of South Bohemia, Branisovska 31, 37005 Ceske Budejovice, Czech Republic. ; CNRS, UMR 7093, Laboratoire d'Oceanographie de Villefranche-sur-Mer (LOV), Observatoire Oceanologique, F-06230, Villefranche-sur-Mer, France. Sorbonne Universites, UPMC Paris 06, UMR 7093, LOV, Observatoire Oceanologique, F-06230, Villefranche-sur-Mer, France. ; Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA), Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91000 Evry, France. CNRS, UMR 8030, CP5706, Evry, France. Universite d'Evry, UMR 8030, CP5706, Evry, France. ; Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Branisovska 31, 37005 Ceske Budejovice, Czech Republic. Faculty of Science, University of South Bohemia, Branisovska 31, 37005 Ceske Budejovice, Czech Republic. Canadian Institute for Advanced Research, 180 Dundas Street West, Suite 1400, Toronto, Ontario M5G 1Z8, Canada. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris, F-75005 France. ; MARUM, Center for Marine Environmental Sciences, University of Bremen, 28359 Bremen, Germany. CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie (UPMC) Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy. ; Ifremer, Centre de Brest, DYNECO/Pelagos CS 10070, 29280 Plouzane, France. ; Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris, F-75005 France. ; Structural and Computational Biology, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany. Directors' Research, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Structural and Computational Biology, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany. Max-Delbruck-Centre for Molecular Medicine, 13092 Berlin, Germany. ; CNRS UMR 7232, Biologie Integrative des Organismes Marins (BIOM), Avenue du Fontaule, 66650 Banyuls-sur-Mer, France. Sorbonne Universites Paris 06, Observatoire Oceanologique de Banyuls (OOB) UPMC, Avenue du Fontaule, 66650 Banyuls-sur-Mer, France. ; Aix Marseille Universite, CNRS IGS UMR 7256, 13288 Marseille, France. ; Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan. ; PANGAEA, Data Publisher for Earth and Environmental Science, University of Bremen, Bremen, Germany. MARUM, Center for Marine Environmental Sciences, University of Bremen, 28359 Bremen, Germany. ; Bigelow Laboratory for Ocean Sciences, East Boothbay, ME 04544, USA. National Science Foundation, Arlington, VA 22230, USA. ; Department of Geosciences, Laboratoire de Meteorologie Dynamique (LMD), Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris Cedex 05, France. Laboratoire de Physique des Oceans, Universite de Bretagne Occidentale (UBO)-Institut Universitaire Europeen de la Mer (IUEM), Place Copernic, 29820 Plouzane, France. ; Structural and Computational Biology, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA), Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91000 Evry, France. CNRS, UMR 8030, CP5706, Evry, France. Universite d'Evry, UMR 8030, CP5706, Evry, France. vargas@sb-roscoff.fr pwincker@genoscope.cns.fr karsenti@embl.de. ; Directors' Research, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris, F-75005 France. vargas@sb-roscoff.fr pwincker@genoscope.cns.fr karsenti@embl.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999516" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; DNA Barcoding, Taxonomic ; DNA, Ribosomal/genetics ; Eukaryota/*classification/genetics ; Oceans and Seas ; Phylogeny ; Plankton/*classification/genetics ; Ribosomes/genetics ; Sequence Analysis, DNA ; Sunlight
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  • 8
    Publication Date: 2015-08-01
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692367/" 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/PMC4692367/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akbari, Omar S -- Bellen, Hugo J -- Bier, Ethan -- Bullock, Simon L -- Burt, Austin -- Church, George M -- Cook, Kevin R -- Duchek, Peter -- Edwards, Owain R -- Esvelt, Kevin M -- Gantz, Valentino M -- Golic, Kent G -- Gratz, Scott J -- Harrison, Melissa M -- Hayes, Keith R -- James, Anthony A -- Kaufman, Thomas C -- Knoblich, Juergen -- Malik, Harmit S -- Matthews, Kathy A -- O'Connor-Giles, Kate M -- Parks, Annette L -- Perrimon, Norbert -- Port, Fillip -- Russell, Steven -- Ueda, Ryu -- Wildonger, Jill -- R01 AI070654/AI/NIAID NIH HHS/ -- R01 AI110713/AI/NIAID NIH HHS/ -- T32 GM007133/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):927-9. doi: 10.1126/science.aac7932. Epub 2015 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Entomology, Univ. of California, Riverside, CA 92507, USA. Center for Disease Vector Research, Institute for Integrative Genome Biology, Univ. of California, Riverside, CA 92507, USA. ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. ; Section of Cell and Developmental Biology, Univ. of California, San Diego, La Jolla, CA 92095, USA. kevin.esvelt@wyss.harvard.edu ebier@ucsd.edu. ; Division of Cell Biology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berks SL5 7PY, UK. ; Wyss Institute for Biologically Inspired Engineering, Harvard Medical School, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Bloomington Drosophila Stock Center, Department of Biology, Indiana Univ., Bloomington, IN 47405, USA. ; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria. ; CSIRO Centre for Environment and Life Sciences, Underwood Avenue, Floreat, WA 6014, Australia. ; Wyss Institute for Biologically Inspired Engineering, Harvard Medical School, Boston, MA 02115, USA. kevin.esvelt@wyss.harvard.edu ebier@ucsd.edu. ; Section of Cell and Developmental Biology, Univ. of California, San Diego, La Jolla, CA 92095, USA. ; Department of Biology, Univ. of Utah, Salt Lake City, UT 84112, USA. ; Laboratory of Genetics, Univ. of Wisconsin-Madison, Madison, WI 53706, USA. ; Department of Biomolecular Chemistry, Univ. of Wisconsin-Madison, Madison, WI 53706, USA. ; CSIRO Biosecurity Flagship, General Post Of ce Box 1538, Hobart, Tasmania, 7001, Australia. ; Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, Univ. of California at Irvine, Irvine, CA 92697, USA. ; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; Laboratory of Genetics, Univ. of Wisconsin-Madison, Madison, WI 53706, USA. Laboratory of Cell and Molecular Biology, Univ. of Wisconsin-Madison, Madison, WI 53706, USA. ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. ; Department of Genetics, Univ. of Cambridge, Cambridge, Cambridgeshire CB2 3EH, UK. ; Department of Genetics, Graduate Univ. for Advanced Studies, Mishima, Shizuoka 411-8540, Japan. NIG-Fly Stock Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan. ; Department of Biochemistry, Univ. of Wisconsin-Madison, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26229113" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; *Containment of Biohazards ; Endonucleases/metabolism ; *Genetic Engineering ; *Genetic Research ; Genome ; *Organisms, Genetically Modified ; *Safety
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  • 9
    Publication Date: 2015-07-04
    Description: The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems-and the goods and services they provide-for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend. A reduced emissions scenario-consistent with the Copenhagen Accord's goal of a global temperature increase of less than 2 degrees C-is much more favorable to the ocean but still substantially alters important marine ecosystems and associated goods and services. The management options to address ocean impacts narrow as the ocean warms and acidifies. Consequently, any new climate regime that fails to minimize ocean impacts would be incomplete and inadequate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gattuso, J-P -- Magnan, A -- Bille, R -- Cheung, W W L -- Howes, E L -- Joos, F -- Allemand, D -- Bopp, L -- Cooley, S R -- Eakin, C M -- Hoegh-Guldberg, O -- Kelly, R P -- Portner, H-O -- Rogers, A D -- Baxter, J M -- Laffoley, D -- Osborn, D -- Rankovic, A -- Rochette, J -- Sumaila, U R -- Treyer, S -- Turley, C -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):aac4722. doi: 10.1126/science.aac4722.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire d'Oceanographie de Villefranche, CNRS-Institut National des Sciences de l'Univers, F-06230 Villefranche-sur-mer, France. Sorbonne Universites, Universite Pierre et Marie Curie, Univ Paris 06, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. gattuso@obs-vlfr.fr. ; Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. ; Secretariat of the Pacific Community, B.P. D5, 98848 Noumea Cedex, New Caledonia. ; Nippon Foundation-UBC Nereus Program, University of British Columbia (UBC), Vancouver, BC V6T 1Z4, Canada. ; Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research, Am Handelshafen 12, D-27570, Bremenrhaven, Germany. ; Climate and Environmental Physics, Physics Institute and Oeschger Centre for Climate Change Research, University of Bern, Sidlerstrasse 5, CH-3012 Bern, Switzerland. ; Centre Scientifique de Monaco, 8 Quai Antoine Ier, MC-98000 Monaco, Principality of Monaco. Institut Pierre Simon Laplace/Laboratoire des Science du Climat et de l'Environnement, UMR8212, CNRS-Commissariat a l'Energie Atomique et aux Energies Alternatives-Universite de Versailles Saint-Quentin-en-Yvelines, Gif sur Yvette, France. ; Ocean Conservancy, 1300 19th Street NW, 8th Floor, Washington, DC 20036, USA. ; Coral Reef Watch, National Oceanic and Atmospheric Administration, College Park, MD 20740, USA. ; Global Change Institute and Australian Research Council Centre for Excellence in Coral Reef Studies, University of Queensland, Building 20, St Lucia, 4072 Queensland, Australia. ; School of Marine and Environmental Affairs, University of Washington, 3707 Brooklyn Avenue NE, Seattle, WA 98105, USA. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Scottish Natural Heritage, 231 Corstorphine Road, Edinburgh EH12 7AT, Scotland. ; IUCN, Rue Mauverney 28, CH-1196 Gland, Switzerland. ; Environment Laboratories, International Atomic Energy Agency, 4a Quai Antoine 1er, MC-98000 Monaco, Principality of Monaco. ; Program on Science, Technology, and Society, John F. Kennedy School of Government, Harvard University, 79 John F. Kennedy Street, Cambridge, MA 02138, USA. ; Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. Fisheries Economics Research Unit, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. ; Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3DH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138982" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquaculture ; *Aquatic Organisms ; *Carbon Dioxide ; *Ecosystem ; *Global Warming ; *Greenhouse Effect ; Health ; Humans ; Oceans and Seas ; Risk ; Travel
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  • 10
    Publication Date: 2015-02-14
    Description: Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681433/" 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/PMC4681433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arner, Erik -- Daub, Carsten O -- Vitting-Seerup, Kristoffer -- Andersson, Robin -- Lilje, Berit -- Drablos, Finn -- Lennartsson, Andreas -- Ronnerblad, Michelle -- Hrydziuszko, Olga -- Vitezic, Morana -- Freeman, Tom C -- Alhendi, Ahmad M N -- Arner, Peter -- Axton, Richard -- Baillie, J Kenneth -- Beckhouse, Anthony -- Bodega, Beatrice -- Briggs, James -- Brombacher, Frank -- Davis, Margaret -- Detmar, Michael -- Ehrlund, Anna -- Endoh, Mitsuhiro -- Eslami, Afsaneh -- Fagiolini, Michela -- Fairbairn, Lynsey -- Faulkner, Geoffrey J -- Ferrai, Carmelo -- Fisher, Malcolm E -- Forrester, Lesley -- Goldowitz, Daniel -- Guler, Reto -- Ha, Thomas -- Hara, Mitsuko -- Herlyn, Meenhard -- Ikawa, Tomokatsu -- Kai, Chieko -- Kawamoto, Hiroshi -- Khachigian, Levon M -- Klinken, S Peter -- Kojima, Soichi -- Koseki, Haruhiko -- Klein, Sarah -- Mejhert, Niklas -- Miyaguchi, Ken -- Mizuno, Yosuke -- Morimoto, Mitsuru -- Morris, Kelly J -- Mummery, Christine -- Nakachi, Yutaka -- Ogishima, Soichi -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry -- Passier, Robert -- Patrikakis, Margaret -- Pombo, Ana -- Qin, Xian-Yang -- Roy, Sugata -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schwegmann, Anita -- Sugiyama, Daisuke -- Swoboda, Rolf -- Tanaka, Hiroshi -- Tomoiu, Andru -- Winteringham, Louise N -- Wolvetang, Ernst -- Yanagi-Mizuochi, Chiyo -- Yoneda, Misako -- Zabierowski, Susan -- Zhang, Peter -- Abugessaisa, Imad -- Bertin, Nicolas -- Diehl, Alexander D -- Fukuda, Shiro -- Furuno, Masaaki -- Harshbarger, Jayson -- Hasegawa, Akira -- Hori, Fumi -- Ishikawa-Kato, Sachi -- Ishizu, Yuri -- Itoh, Masayoshi -- Kawashima, Tsugumi -- Kojima, Miki -- Kondo, Naoto -- Lizio, Marina -- Meehan, Terrence F -- Mungall, Christopher J -- Murata, Mitsuyoshi -- Nishiyori-Sueki, Hiromi -- Sahin, Serkan -- Nagao-Sato, Sayaka -- Severin, Jessica -- de Hoon, Michiel J L -- Kawai, Jun -- Kasukawa, Takeya -- Lassmann, Timo -- Suzuki, Harukazu -- Kawaji, Hideya -- Summers, Kim M -- Wells, Christine -- FANTOM Consortium -- Hume, David A -- Forrest, Alistair R R -- Sandelin, Albin -- Carninci, Piero -- Hayashizaki, Yoshihide -- P30 CA010815/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):1010-4. doi: 10.1126/science.1259418. Epub 2015 Feb 12.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678556" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cattle ; Cell Differentiation/*genetics ; Dogs ; *Enhancer Elements, Genetic ; *Gene Expression Regulation, Developmental ; Mice ; RNA, Messenger/genetics/metabolism ; Rats ; Stem Cells/*cytology/metabolism ; Transcription Factors/*metabolism ; *Transcription, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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