ALBERT

Description: Article Extending matter-wave interferometry to nanoscale objects requires beam splitters that can cope with their internal complexity. Here, the authors demonstrate that the absorption of individual photons allows the center-of-mass coherence of large molecules to be maintained. Nature Communications doi: 10.1038/ncomms8336 Authors: J. P. Cotter, S. Eibenberger, L. Mairhofer, X. Cheng, P. Asenbaum, M. Arndt, K. Walter, S. Nimmrichter, K. Hornberger

Description: The analysis of the spatiotemporal variability of wind power remains limited during the planning stage of an offshore wind farm. This study provides a framework to investigate how offshore wind power varies along the Central California Coast over diurnal and seasonal time scales, which is critical for reliability and functionality of the grid system. We find that offshore wind power in this region peaks during evening hours across all seasons and maximizes in spring and summer. The timing of peak offshore wind power production better aligns with that of peak demand across California than solar and land-based wind power production, highlighting its potential to fill the supply gap when demand is high and power production from other renewable energy sources is low. We further assess the value of offshore wind power using demand-based and wholesale market metrics. Both metrics indicate high potential value of offshore wind power over most areas in this region. Finally, we show that...

Description: Erratum Nature Communications doi: 10.1038/ncomms10121 Authors: J. P. Cotter, S. Eibenberger, L. Mairhofer, X. Cheng, P. Asenbaum, M. Arndt, K. Walter, S. Nimmrichter, K. Hornberger

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〉

Description: Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617611/" 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/PMC4617611/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sudmant, Peter H -- Rausch, Tobias -- Gardner, Eugene J -- Handsaker, Robert E -- Abyzov, Alexej -- Huddleston, John -- Zhang, Yan -- Ye, Kai -- Jun, Goo -- Hsi-Yang Fritz, Markus -- Konkel, Miriam K -- Malhotra, Ankit -- Stutz, Adrian M -- Shi, Xinghua -- Paolo Casale, Francesco -- Chen, Jieming -- Hormozdiari, Fereydoun -- Dayama, Gargi -- Chen, Ken -- Malig, Maika -- Chaisson, Mark J P -- Walter, Klaudia -- Meiers, Sascha -- Kashin, Seva -- Garrison, Erik -- Auton, Adam -- Lam, Hugo Y K -- Jasmine Mu, Xinmeng -- Alkan, Can -- Antaki, Danny -- Bae, Taejeong -- Cerveira, Eliza -- Chines, Peter -- Chong, Zechen -- Clarke, Laura -- Dal, Elif -- Ding, Li -- Emery, Sarah -- Fan, Xian -- Gujral, Madhusudan -- Kahveci, Fatma -- Kidd, Jeffrey M -- Kong, Yu -- Lameijer, Eric-Wubbo -- McCarthy, Shane -- Flicek, Paul -- Gibbs, Richard A -- Marth, Gabor -- Mason, Christopher E -- Menelaou, Androniki -- Muzny, Donna M -- Nelson, Bradley J -- Noor, Amina -- Parrish, Nicholas F -- Pendleton, Matthew -- Quitadamo, Andrew -- Raeder, Benjamin -- Schadt, Eric E -- Romanovitch, Mallory -- Schlattl, Andreas -- Sebra, Robert -- Shabalin, Andrey A -- Untergasser, Andreas -- Walker, Jerilyn A -- Wang, Min -- Yu, Fuli -- Zhang, Chengsheng -- Zhang, Jing -- Zheng-Bradley, Xiangqun -- Zhou, Wanding -- Zichner, Thomas -- Sebat, Jonathan -- Batzer, Mark A -- McCarroll, Steven A -- 1000 Genomes Project Consortium -- Mills, Ryan E -- Gerstein, Mark B -- Bashir, Ali -- Stegle, Oliver -- Devine, Scott E -- Lee, Charles -- Eichler, Evan E -- Korbel, Jan O -- P01HG007497/HG/NHGRI NIH HHS/ -- R01 CA166661/CA/NCI NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- R01 HG002898/HG/NHGRI NIH HHS/ -- R01CA166661/CA/NCI NIH HHS/ -- R01GM59290/GM/NIGMS NIH HHS/ -- R01HG002898/HG/NHGRI NIH HHS/ -- R01HG007068/HG/NHGRI NIH HHS/ -- RR029676-01/RR/NCRR NIH HHS/ -- RR19895/RR/NCRR NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- U41 HG007497/HG/NHGRI NIH HHS/ -- U41HG007497/HG/NHGRI NIH HHS/ -- WT085532/Z/08/Z/Wellcome Trust/United Kingdom -- WT104947/Z/14/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Oct 1;526(7571):75-81. doi: 10.1038/nature15394.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, 3720 15th Avenue NE, Seattle, Washington 98195-5065, USA. ; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Institute for Genome Sciences, University of Maryland School of Medicine, 801 W Baltimore Street, Baltimore, Maryland 21201, USA. ; Department of Genetics, Harvard Medical School, Boston, 25 Shattuck Street, Boston, Massachusetts 02115, USA. ; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. ; Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA. ; Program in Computational Biology and Bioinformatics, Yale University, BASS 432 &437, 266 Whitney Avenue, New Haven, Connecticut 06520, USA. ; Department of Molecular Biophysics and Biochemistry, School of Medicine, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA. ; The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Department of Genetics, Washington University in St Louis, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA. ; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, 1200 Pressler St., Houston, Texas 77030, USA. ; Department of Biological Sciences, Louisiana State University, 202 Life Sciences Building, Baton Rouge, Louisiana 70803, USA. ; The Jackson Laboratory for Genomic Medicine, 10 Discovery 263 Farmington Avenue, Farmington, Connecticut 06030, USA. ; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, North Carolina 28223, USA. ; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, Connecticut 06520, USA. ; Department of Computational Medicine &Bioinformatics, University of Michigan, 500 S. State Street, Ann Arbor, Michigan 48109, USA. ; The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. ; Department of Biology, Boston College, 355 Higgins Hall, 140 Commonwealth Avenue, Chestnut Hill, Massachusetts 02467, USA. ; Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, New York 10461, USA. ; Bina Technologies, Roche Sequencing, 555 Twin Dolphin Drive, Redwood City, California 94065, USA. ; Cancer Program, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; Department of Computer Engineering, Bilkent University, 06800 Ankara, Turkey. ; University of California San Diego (UCSD), 9500 Gilman Drive, La Jolla, California 92093, USA. ; National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 USA. ; Department of Medicine, Washington University in St Louis, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Siteman Cancer Center, 660 South Euclid Avenue, St Louis, Missouri 63110, USA. ; Department of Human Genetics, University of Michigan, 1241 Catherine Street, Ann Arbor, Michigan 48109, USA. ; Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RA, The Netherlands. ; Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA. ; The Department of Physiology and Biophysics and the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, 1305 York Avenue, Weill Cornell Medical College, New York, New York 10065, USA. ; The Feil Family Brain and Mind Research Institute, 413 East 69th St, Weill Cornell Medical College, New York, New York 10065, USA. ; University of Oxford, 1 South Parks Road, Oxford OX3 9DS, UK. ; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands. ; Department of Genetics and Genomic Sciences, Icahn School of Medicine, New York School of Natural Sciences, 1428 Madison Avenue, New York, New York 10029, USA. ; Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. ; Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, 1112 East Clay Street, McGuire Hall, Richmond, Virginia 23298-0581, USA. ; Zentrum fur Molekulare Biologie, University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. ; Department of Computer Science, Yale University, 51 Prospect Street, New Haven, Connecticut 06511, USA. ; Department of Graduate Studies - Life Sciences, Ewha Womans University, Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, South Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26432246" target="_blank"〉PubMed〈/a〉

Description: The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7x) or exomes (high read depth, 80x) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773891/" 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/PMC4773891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉UK10K Consortium -- Walter, Klaudia -- Min, Josine L -- Huang, Jie -- Crooks, Lucy -- Memari, Yasin -- McCarthy, Shane -- Perry, John R B -- Xu, ChangJiang -- Futema, Marta -- Lawson, Daniel -- Iotchkova, Valentina -- Schiffels, Stephan -- Hendricks, Audrey E -- Danecek, Petr -- Li, Rui -- Floyd, James -- Wain, Louise V -- Barroso, Ines -- Humphries, Steve E -- Hurles, Matthew E -- Zeggini, Eleftheria -- Barrett, Jeffrey C -- Plagnol, Vincent -- Richards, J Brent -- Greenwood, Celia M T -- Timpson, Nicholas J -- Durbin, Richard -- Soranzo, Nicole -- 091551/Wellcome Trust/United Kingdom -- 095515/Wellcome Trust/United Kingdom -- 095564/Wellcome Trust/United Kingdom -- 098498/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- 104036/Wellcome Trust/United Kingdom -- CZD/16/6/4/Chief Scientist Office/United Kingdom -- MC_UU_12013/3/Medical Research Council/United Kingdom -- RG/10/13/28570/British Heart Foundation/United Kingdom -- WT091310/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Oct 1;526(7571):82-90. doi: 10.1038/nature14962. Epub 2015 Sep 14.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26367797" target="_blank"〉PubMed〈/a〉

Description: Single molecule FISH (smFISH) allows studying transcription and RNA localization by imaging individual mRNAs in single cells. We present smiFISH (single molecule inexpensive FISH), an easy to use and flexible RNA visualization and quantification approach that uses unlabelled primary probes and a fluorescently labelled secondary detector oligonucleotide. The gene-specific probes are unlabelled and can therefore be synthesized at low cost, thus allowing to use more probes per mRNA resulting in a substantial increase in detection efficiency. smiFISH is also flexible since differently labelled secondary detector probes can be used with the same primary probes. We demonstrate that this flexibility allows multicolor labelling without the need to synthesize new probe sets. We further demonstrate that the use of a specific acrydite detector oligonucleotide allows smiFISH to be combined with expansion microscopy, enabling the resolution of transcripts in 3D below the diffraction limit on a standard microscope. Lastly, we provide improved, fully automated software tools from probe-design to quantitative analysis of smFISH images. In short, we provide a complete workflow to obtain automatically counts of individual RNA molecules in single cells.

Description: The oceanic response to high-frequency local diurnal wind forcing is examined in a small coastal embayment located along an understudied stretch of the central California coast. We show that local diurnal wind forcing is the dominant control on nearshore temperature variability and circulation patterns. A complex empirical orthogonal function (CEOF) analysis of velocities in San Luis Obispo Bay reveals that the first mode CEOF amplitude time series, which accounts for 47.9% of the variance, is significantly coherent with the local wind signal at the diurnal frequency and aligns with periods of weak and strong wind forcing. The diurnal evolution of the hydrographic structure and circulation in the bay is examined using both individual events and composite-day averages. During the late afternoon, the local wind strengthens and results in a sheared flow with near-surface warm waters directed out of the bay and a compensating flow of colder waters into the bay over the bottom portion of the water column. This cold water intrusion into the bay causes isotherms to shoal towards the surface and delivers subthermocline waters to shallow reaches of the bay, representing a mechanism for small-scale upwelling. When the local winds relax, the warm water mass advects back into the bay in the form of a buoyant plume front. Local diurnal winds are expected to play an important role in nearshore dynamics and local upwelling in other small coastal embayments with important implications for various biological and ecological processes. This article is protected by copyright. All rights reserved.

Description: The transcriptional programs that regulate CD8 T-cell differentiation and function in the context of viral infections or tumor immune surveillance have been extensively studied; yet how long noncoding RNAs (lncRNAs) and the loci that transcribe them contribute to the regulation of CD8 T cells during viral infections remains largely unexplored. Here, we report that transcription of the lncRNA Morrbid is specifically induced by T-cell receptor (TCR) and type I IFN stimulation during the early stages of acute and chronic lymphocytic choriomeningitis virus (LCMV) infection. In response to type I IFN, the Morrbid RNA and its locus control CD8 T cell expansion, survival, and effector function by regulating the expression of the proapoptotic factor, Bcl2l11, and by modulating the strength of the PI3K–AKT signaling pathway. Thus, our results demonstrate that inflammatory cue-responsive lncRNA loci represent fundamental mechanisms by which CD8 T cells are regulated in response to pathogens and potentially cancer.

Description: Oceanographic features, such as eddies and fronts, enhance and concentrate productivity, generating high-quality patches that dispersive marine larvae may encounter in the plankton. Although broad-scale movement of larvae associated with these features can be captured in biophysical models, direct evidence of processes influencing survival within them, and subsequent effects on...