ALBERT

Description: A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) approximately 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for approximately 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751588/" 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/PMC3751588/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rietveld, Cornelius A -- Medland, Sarah E -- Derringer, Jaime -- Yang, Jian -- Esko, Tonu -- Martin, Nicolas W -- Westra, Harm-Jan -- Shakhbazov, Konstantin -- Abdellaoui, Abdel -- Agrawal, Arpana -- Albrecht, Eva -- Alizadeh, Behrooz Z -- Amin, Najaf -- Barnard, John -- Baumeister, Sebastian E -- Benke, Kelly S -- Bielak, Lawrence F -- Boatman, Jeffrey A -- Boyle, Patricia A -- Davies, Gail -- de Leeuw, Christiaan -- Eklund, Niina -- Evans, Daniel S -- Ferhmann, Rudolf -- Fischer, Krista -- Gieger, Christian -- Gjessing, Hakon K -- Hagg, Sara -- Harris, Jennifer R -- Hayward, Caroline -- Holzapfel, Christina -- Ibrahim-Verbaas, Carla A -- Ingelsson, Erik -- Jacobsson, Bo -- Joshi, Peter K -- Jugessur, Astanand -- Kaakinen, Marika -- Kanoni, Stavroula -- Karjalainen, Juha -- Kolcic, Ivana -- Kristiansson, Kati -- Kutalik, Zoltan -- Lahti, Jari -- Lee, Sang H -- Lin, Peng -- Lind, Penelope A -- Liu, Yongmei -- Lohman, Kurt -- Loitfelder, Marisa -- McMahon, George -- Vidal, Pedro Marques -- Meirelles, Osorio -- Milani, Lili -- Myhre, Ronny -- Nuotio, Marja-Liisa -- Oldmeadow, Christopher J -- Petrovic, Katja E -- Peyrot, Wouter J -- Polasek, Ozren -- Quaye, Lydia -- Reinmaa, Eva -- Rice, John P -- Rizzi, Thais S -- Schmidt, Helena -- Schmidt, Reinhold -- Smith, Albert V -- Smith, Jennifer A -- Tanaka, Toshiko -- Terracciano, Antonio -- van der Loos, Matthijs J H M -- Vitart, Veronique -- Volzke, Henry -- Wellmann, Jurgen -- Yu, Lei -- Zhao, Wei -- Allik, Juri -- Attia, John R -- Bandinelli, Stefania -- Bastardot, Francois -- Beauchamp, Jonathan -- Bennett, David A -- Berger, Klaus -- Bierut, Laura J -- Boomsma, Dorret I -- Bultmann, Ute -- Campbell, Harry -- Chabris, Christopher F -- Cherkas, Lynn -- Chung, Mina K -- Cucca, Francesco -- de Andrade, Mariza -- De Jager, Philip L -- De Neve, Jan-Emmanuel -- Deary, Ian J -- Dedoussis, George V -- Deloukas, Panos -- Dimitriou, Maria -- Eiriksdottir, Guethny -- Elderson, Martin F -- Eriksson, Johan G -- Evans, David M -- Faul, Jessica D -- Ferrucci, Luigi -- Garcia, Melissa E -- Gronberg, Henrik -- Guethnason, Vilmundur -- Hall, Per -- Harris, Juliette M -- Harris, Tamara B -- Hastie, Nicholas D -- Heath, Andrew C -- Hernandez, Dena G -- Hoffmann, Wolfgang -- Hofman, Adriaan -- Holle, Rolf -- Holliday, Elizabeth G -- Hottenga, Jouke-Jan -- Iacono, William G -- Illig, Thomas -- Jarvelin, Marjo-Riitta -- Kahonen, Mika -- Kaprio, Jaakko -- Kirkpatrick, Robert M -- Kowgier, Matthew -- Latvala, Antti -- Launer, Lenore J -- Lawlor, Debbie A -- Lehtimaki, Terho -- Li, Jingmei -- Lichtenstein, Paul -- Lichtner, Peter -- Liewald, David C -- Madden, Pamela A -- Magnusson, Patrik K E -- Makinen, Tomi E -- Masala, Marco -- McGue, Matt -- Metspalu, Andres -- Mielck, Andreas -- Miller, Michael B -- Montgomery, Grant W -- Mukherjee, Sutapa -- Nyholt, Dale R -- Oostra, Ben A -- Palmer, Lyle J -- Palotie, Aarno -- Penninx, Brenda W J H -- Perola, Markus -- Peyser, Patricia A -- Preisig, Martin -- Raikkonen, Katri -- Raitakari, Olli T -- Realo, Anu -- Ring, Susan M -- Ripatti, Samuli -- Rivadeneira, Fernando -- Rudan, Igor -- Rustichini, Aldo -- Salomaa, Veikko -- Sarin, Antti-Pekka -- Schlessinger, David -- Scott, Rodney J -- Snieder, Harold -- St Pourcain, Beate -- Starr, John M -- Sul, Jae Hoon -- Surakka, Ida -- Svento, Rauli -- Teumer, Alexander -- LifeLines Cohort Study -- Tiemeier, Henning -- van Rooij, Frank J A -- Van Wagoner, David R -- Vartiainen, Erkki -- Viikari, Jorma -- Vollenweider, Peter -- Vonk, Judith M -- Waeber, Gerard -- Weir, David R -- Wichmann, H-Erich -- Widen, Elisabeth -- Willemsen, Gonneke -- Wilson, James F -- Wright, Alan F -- Conley, Dalton -- Davey-Smith, George -- Franke, Lude -- Groenen, Patrick J F -- Hofman, Albert -- Johannesson, Magnus -- Kardia, Sharon L R -- Krueger, Robert F -- Laibson, David -- Martin, Nicholas G -- Meyer, Michelle N -- Posthuma, Danielle -- Thurik, A Roy -- Timpson, Nicholas J -- Uitterlinden, Andre G -- van Duijn, Cornelia M -- Visscher, Peter M -- Benjamin, Daniel J -- Cesarini, David -- Koellinger, Philipp D -- AA09367/AA/NIAAA NIH HHS/ -- AA11886/AA/NIAAA NIH HHS/ -- BB/F019394/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- CZB/4/710/Chief Scientist Office/United Kingdom -- DA024417/DA/NIDA NIH HHS/ -- DA029377/DA/NIDA NIH HHS/ -- DA05147/DA/NIDA NIH HHS/ -- DA13240/DA/NIDA NIH HHS/ -- ETM/55/Chief Scientist Office/United Kingdom -- F31 DA029377/DA/NIDA NIH HHS/ -- G0600705/Medical Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G9815508/Medical Research Council/United Kingdom -- K05 AA017688/AA/NIAAA NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_UU_12013/1/Medical Research Council/United Kingdom -- MC_UU_12013/3/Medical Research Council/United Kingdom -- MC_UU_12013/5/Medical Research Council/United Kingdom -- MH016880/MH/NIMH NIH HHS/ -- MH066140/MH/NIMH NIH HHS/ -- MR/K026992/1/Medical Research Council/United Kingdom -- P01 AG005842/AG/NIA NIH HHS/ -- P01 CA089392/CA/NCI NIH HHS/ -- P01 GM099568/GM/NIGMS NIH HHS/ -- P01-AG005842/AG/NIA NIH HHS/ -- P01-AG005842-20S2/AG/NIA NIH HHS/ -- P30 AG012810/AG/NIA NIH HHS/ -- P30-AG012810/AG/NIA NIH HHS/ -- R01 AA009367/AA/NIAAA NIH HHS/ -- R01 AA011886/AA/NIAAA NIH HHS/ -- R01 DA013240/DA/NIDA NIH HHS/ -- R01 HL090620/HL/NHLBI NIH HHS/ -- R01 HL105756/HL/NHLBI NIH HHS/ -- R01 HL111314/HL/NHLBI NIH HHS/ -- R01 MH066140/MH/NIMH NIH HHS/ -- R37 DA005147/DA/NIDA NIH HHS/ -- T32 AG000186/AG/NIA NIH HHS/ -- T32 MH016880/MH/NIMH NIH HHS/ -- T32-AG000186-23/AG/NIA NIH HHS/ -- U01 AG009740/AG/NIA NIH HHS/ -- U01 DA024417/DA/NIDA NIH HHS/ -- Z01 AG001050-01/Intramural NIH HHS/ -- ZIA AG000196-03/Intramural NIH HHS/ -- ZIA AG000196-04/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1467-71. doi: 10.1126/science.1235488. Epub 2013 May 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23722424" target="_blank"〉PubMed〈/a〉

Description: Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a blind injection where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M25M and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.

Description: Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927/" 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/PMC3703927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howe, Kerstin -- Clark, Matthew D -- Torroja, Carlos F -- Torrance, James -- Berthelot, Camille -- Muffato, Matthieu -- Collins, John E -- Humphray, Sean -- McLaren, Karen -- Matthews, Lucy -- McLaren, Stuart -- Sealy, Ian -- Caccamo, Mario -- Churcher, Carol -- Scott, Carol -- Barrett, Jeffrey C -- Koch, Romke -- Rauch, Gerd-Jorg -- White, Simon -- Chow, William -- Kilian, Britt -- Quintais, Leonor T -- Guerra-Assuncao, Jose A -- Zhou, Yi -- Gu, Yong -- Yen, Jennifer -- Vogel, Jan-Hinnerk -- Eyre, Tina -- Redmond, Seth -- Banerjee, Ruby -- Chi, Jianxiang -- Fu, Beiyuan -- Langley, Elizabeth -- Maguire, Sean F -- Laird, Gavin K -- Lloyd, David -- Kenyon, Emma -- Donaldson, Sarah -- Sehra, Harminder -- Almeida-King, Jeff -- Loveland, Jane -- Trevanion, Stephen -- Jones, Matt -- Quail, Mike -- Willey, Dave -- Hunt, Adrienne -- Burton, John -- Sims, Sarah -- McLay, Kirsten -- Plumb, Bob -- Davis, Joy -- Clee, Chris -- Oliver, Karen -- Clark, Richard -- Riddle, Clare -- Elliot, David -- Threadgold, Glen -- Harden, Glenn -- Ware, Darren -- Begum, Sharmin -- Mortimore, Beverley -- Kerry, Giselle -- Heath, Paul -- Phillimore, Benjamin -- Tracey, Alan -- Corby, Nicole -- Dunn, Matthew -- Johnson, Christopher -- Wood, Jonathan -- Clark, Susan -- Pelan, Sarah -- Griffiths, Guy -- Smith, Michelle -- Glithero, Rebecca -- Howden, Philip -- Barker, Nicholas -- Lloyd, Christine -- Stevens, Christopher -- Harley, Joanna -- Holt, Karen -- Panagiotidis, Georgios -- Lovell, Jamieson -- Beasley, Helen -- Henderson, Carl -- Gordon, Daria -- Auger, Katherine -- Wright, Deborah -- Collins, Joanna -- Raisen, Claire -- Dyer, Lauren -- Leung, Kenric -- Robertson, Lauren -- Ambridge, Kirsty -- Leongamornlert, Daniel -- McGuire, Sarah -- Gilderthorp, Ruth -- Griffiths, Coline -- Manthravadi, Deepa -- Nichol, Sarah -- Barker, Gary -- Whitehead, Siobhan -- Kay, Michael -- Brown, Jacqueline -- Murnane, Clare -- Gray, Emma -- Humphries, Matthew -- Sycamore, Neil -- Barker, Darren -- Saunders, David -- Wallis, Justene -- Babbage, Anne -- Hammond, Sian -- Mashreghi-Mohammadi, Maryam -- Barr, Lucy -- Martin, Sancha -- Wray, Paul -- Ellington, Andrew -- Matthews, Nicholas -- Ellwood, Matthew -- Woodmansey, Rebecca -- Clark, Graham -- Cooper, James D -- Tromans, Anthony -- Grafham, Darren -- Skuce, Carl -- Pandian, Richard -- Andrews, Robert -- Harrison, Elliot -- Kimberley, Andrew -- Garnett, Jane -- Fosker, Nigel -- Hall, Rebekah -- Garner, Patrick -- Kelly, Daniel -- Bird, Christine -- Palmer, Sophie -- Gehring, Ines -- Berger, Andrea -- Dooley, Christopher M -- Ersan-Urun, Zubeyde -- Eser, Cigdem -- Geiger, Horst -- Geisler, Maria -- Karotki, Lena -- Kirn, Anette -- Konantz, Judith -- Konantz, Martina -- Oberlander, Martina -- Rudolph-Geiger, Silke -- Teucke, Mathias -- Lanz, Christa -- Raddatz, Gunter -- Osoegawa, Kazutoyo -- Zhu, Baoli -- Rapp, Amanda -- Widaa, Sara -- Langford, Cordelia -- Yang, Fengtang -- Schuster, Stephan C -- Carter, Nigel P -- Harrow, Jennifer -- Ning, Zemin -- Herrero, Javier -- Searle, Steve M J -- Enright, Anton -- Geisler, Robert -- Plasterk, Ronald H A -- Lee, Charles -- Westerfield, Monte -- de Jong, Pieter J -- Zon, Leonard I -- Postlethwait, John H -- Nusslein-Volhard, Christiane -- Hubbard, Tim J P -- Roest Crollius, Hugues -- Rogers, Jane -- Stemple, Derek L -- 095908/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- 1 R01 DK55377-01A1/DK/NIDDK NIH HHS/ -- P01 HD022486/HD/NICHD NIH HHS/ -- P01 HD22486/HD/NICHD NIH HHS/ -- R01 GM085318/GM/NIGMS NIH HHS/ -- R01 OD011116/OD/NIH HHS/ -- R01 RR010715/RR/NCRR NIH HHS/ -- R01 RR020833/RR/NCRR NIH HHS/ -- England -- Nature. 2013 Apr 25;496(7446):498-503. doi: 10.1038/nature12111. Epub 2013 Apr 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23594743" target="_blank"〉PubMed〈/a〉

Description: Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-beta precursor protein (APP) and extracellular Abeta42 and Abeta40 (the 42- and 40-residue isoforms of the amyloid-beta peptide), and knockdown of PLD3 leads to a significant increase in extracellular Abeta42 and Abeta40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050701/" 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/PMC4050701/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cruchaga, Carlos -- Karch, Celeste M -- Jin, Sheng Chih -- Benitez, Bruno A -- Cai, Yefei -- Guerreiro, Rita -- Harari, Oscar -- Norton, Joanne -- Budde, John -- Bertelsen, Sarah -- Jeng, Amanda T -- Cooper, Breanna -- Skorupa, Tara -- Carrell, David -- Levitch, Denise -- Hsu, Simon -- Choi, Jiyoon -- Ryten, Mina -- UK Brain Expression Consortium -- Hardy, John -- Trabzuni, Daniah -- Weale, Michael E -- Ramasamy, Adaikalavan -- Smith, Colin -- Sassi, Celeste -- Bras, Jose -- Gibbs, J Raphael -- Hernandez, Dena G -- Lupton, Michelle K -- Powell, John -- Forabosco, Paola -- Ridge, Perry G -- Corcoran, Christopher D -- Tschanz, Joann T -- Norton, Maria C -- Munger, Ronald G -- Schmutz, Cameron -- Leary, Maegan -- Demirci, F Yesim -- Bamne, Mikhil N -- Wang, Xingbin -- Lopez, Oscar L -- Ganguli, Mary -- Medway, Christopher -- Turton, James -- Lord, Jenny -- Braae, Anne -- Barber, Imelda -- Brown, Kristelle -- Alzheimer's Research UK Consortium -- Passmore, Peter -- Craig, David -- Johnston, Janet -- McGuinness, Bernadette -- Todd, Stephen -- Heun, Reinhard -- Kolsch, Heike -- Kehoe, Patrick G -- Hooper, Nigel M -- Vardy, Emma R L C -- Mann, David M -- Pickering-Brown, Stuart -- Kalsheker, Noor -- Lowe, James -- Morgan, Kevin -- David Smith, A -- Wilcock, Gordon -- Warden, Donald -- Holmes, Clive -- Pastor, Pau -- Lorenzo-Betancor, Oswaldo -- Brkanac, Zoran -- Scott, Erick -- Topol, Eric -- Rogaeva, Ekaterina -- Singleton, Andrew B -- Kamboh, M Ilyas -- St George-Hyslop, Peter -- Cairns, Nigel -- Morris, John C -- Kauwe, John S K -- Goate, Alison M -- 081864/Wellcome Trust/United Kingdom -- 089698/Wellcome Trust/United Kingdom -- 089703/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- 1R01AG041797/AG/NIA NIH HHS/ -- 5U24AG026395/AG/NIA NIH HHS/ -- AG005133/AG/NIA NIH HHS/ -- AG023652/AG/NIA NIH HHS/ -- AG030653/AG/NIA NIH HHS/ -- AG041718/AG/NIA NIH HHS/ -- AG07562/AG/NIA NIH HHS/ -- G0802189/Medical Research Council/United Kingdom -- G0802462/Medical Research Council/United Kingdom -- G0901254/Medical Research Council/United Kingdom -- G1100695/Medical Research Council/United Kingdom -- K01 AG046374/AG/NIA NIH HHS/ -- MC_G1000734/Medical Research Council/United Kingdom -- NIH P50 AG05681/AG/NIA NIH HHS/ -- NIH R01039700/PHS HHS/ -- P01 AG003991/AG/NIA NIH HHS/ -- P01 AG026276/AG/NIA NIH HHS/ -- P01 AG03991/AG/NIA NIH HHS/ -- P30 NS069329/NS/NINDS NIH HHS/ -- P30-NS069329/NS/NINDS NIH HHS/ -- P50 AG005133/AG/NIA NIH HHS/ -- P50 AG005681/AG/NIA NIH HHS/ -- R01 AG011380/AG/NIA NIH HHS/ -- R01 AG030653/AG/NIA NIH HHS/ -- R01 AG035083/AG/NIA NIH HHS/ -- R01 AG039700/AG/NIA NIH HHS/ -- R01 AG041718/AG/NIA NIH HHS/ -- R01 AG041797/AG/NIA NIH HHS/ -- R01 AG042611/AG/NIA NIH HHS/ -- R01 AG044546/AG/NIA NIH HHS/ -- R01-AG035083/AG/NIA NIH HHS/ -- R01-AG042611/AG/NIA NIH HHS/ -- R01-AG044546/AG/NIA NIH HHS/ -- R01-AG11380/AG/NIA NIH HHS/ -- R01-AG18712/AG/NIA NIH HHS/ -- R01-AG21136/AG/NIA NIH HHS/ -- R01AG21136/AG/NIA NIH HHS/ -- R25 DA027995/DA/NIDA NIH HHS/ -- U24 AG021886/AG/NIA NIH HHS/ -- U24 AG026395/AG/NIA NIH HHS/ -- U24AG21886/AG/NIA NIH HHS/ -- WT089698/Wellcome Trust/United Kingdom -- ZIA AG000950-11/Intramural NIH HHS/ -- ZO1 AG000950-10/AG/NIA NIH HHS/ -- ZO1AG000950-11/AG/NIA NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2014 Jan 23;505(7484):550-4. doi: 10.1038/nature12825. Epub 2013 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University 425 South Euclid Avenue, St. Louis, Missouri 63110, USA. ; 1] Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [3]. ; 1] Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2]. ; Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA. ; 1] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK [2] Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35 Room 1A1014, 35 Lincoln Drive, Bethesda, Maryland 20892, USA. ; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. ; Department of Medical and Molecular Genetics, King's College London, 16 De Crespigny Park, London SE5 8AF UK. ; MRC Sudden Death Brain Bank Project, University of Edinburgh, South Bridge, Edinburgh EH8 9YL UK. ; 1] Institute of Psychiatry, King's College London, 16 De Crespigny Park, London SE5 8AF, UK [2] Neuroimaging Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia. ; Institute of Psychiatry, King's College London, 16 De Crespigny Park, London SE5 8AF, UK. ; Istituto di Genetica delle Popolazioni - CNR, Trav. La Crucca, 3 - Reg. Baldinca - 07100 Li Punti, Sassari, Italy. ; Department of Biology, Brigham Young University, Provo, Utah 84602, USA. ; 1] Department of Mathematics and Statistics, Utah State University, Logan, Utah 84322, USA [2] Center for Epidemiologic Studies, Utah State University, Logan, Utah 84322, USA. ; 1] Center for Epidemiologic Studies, Utah State University, Logan, Utah 84322, USA [2] Department of Psychology, Utah State University, Logan, Utah 84322, USA. ; 1] Center for Epidemiologic Studies, Utah State University, Logan, Utah 84322, USA [2] Department of Psychology, Utah State University, Logan, Utah 84322, USA [3] Department of Family Consumer and Human Development, Utah State University, Logan, Utah 84322, USA. ; 1] Department of Family Consumer and Human Development, Utah State University, Logan, Utah 84322, USA [2] Department of Nutrition, Dietetics, and Food Sciences, Utah State University, Logan, Utah 84322, USA. ; Department of Human Genetics, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA. ; 1] Alzheimer's Disease Research Center, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA [2] Department of Neurology, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA. ; Department of Psychiatry, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA. ; Human Genetics, School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. ; Queen's University Belfast, University Road, Belfast BT7 1NN, UK. ; Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3NE, UK. ; University of Bonn, Regina-Pacis-Weg 3, 53113 Bonn, Germany. ; University of Bristol, Tyndall Avenue, Bristol, City of Bristol BS8 1TH, UK. ; University of Leeds, Woodhouse Lane, Leeds, West Yorkshire LS2 9JT, UK. ; University of Newcastle, Newcastle upon Tyne, Tyne and Wear NE1 7RU, UK. ; University of Manchester, Oxford Road, Manchester, Greater Manchester M13 9PL, UK. ; University of Oxford (OPTIMA), Wellington Square, Oxford OX1 2JD, UK. ; 1] Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Avenida Pio XII, 55. 31008 Pamplona, Navarra, Spain [2] Department of Neurology, Clinica Universidad de Navarra, School of Medicine, University of Navarra Avenida Pio XII, 36. 31008 Pamplona, Spain [3] CIBERNED, Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain. ; Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Avenida Pio XII, 55. 31008 Pamplona, Navarra, Spain. ; University of Washington, 325 Ninth Avenue, Seattle, Washington 98104-2499, USA. ; The Scripps Research Institute, La Jolla, California 3344 North Torrey Pines Court, La Jolla, California 92037, USA. ; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Avenue, Toronto, Ontario M5T 2S8, Canada. ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35 Room 1A1014, 35 Lincoln Drive, Bethesda, Maryland 20892, USA. ; 1] Department of Human Genetics, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA [2] Alzheimer's Disease Research Center, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA [3] Department of Neurology, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA. ; 1] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Avenue, Toronto, Ontario M5T 2S8, Canada [2] Cambridge Institute for Medical Research, and the Department of Clinical Neurosciences, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. ; 1] Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Pathology and Immunology, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA. ; 1] Pathology and Immunology, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Department of Neurology, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [3] Knight ADRC, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA. ; 1] Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [3] Department of Neurology, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [4] Knight ADRC, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [5] Department of Genetics, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24336208" target="_blank"〉PubMed〈/a〉

Description: Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the approximately 4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 x 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 x 10(-10) and P = 7.8 x 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P 〈 10(-8)), as has been reported previously for autism spectrum disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773011/" 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/PMC3773011/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Epi4K Consortium -- Epilepsy Phenome/Genome Project -- Allen, Andrew S -- Berkovic, Samuel F -- Cossette, Patrick -- Delanty, Norman -- Dlugos, Dennis -- Eichler, Evan E -- Epstein, Michael P -- Glauser, Tracy -- Goldstein, David B -- Han, Yujun -- Heinzen, Erin L -- Hitomi, Yuki -- Howell, Katherine B -- Johnson, Michael R -- Kuzniecky, Ruben -- Lowenstein, Daniel H -- Lu, Yi-Fan -- Madou, Maura R Z -- Marson, Anthony G -- Mefford, Heather C -- Esmaeeli Nieh, Sahar -- O'Brien, Terence J -- Ottman, Ruth -- Petrovski, Slave -- Poduri, Annapurna -- Ruzzo, Elizabeth K -- Scheffer, Ingrid E -- Sherr, Elliott H -- Yuskaitis, Christopher J -- Abou-Khalil, Bassel -- Alldredge, Brian K -- Bautista, Jocelyn F -- Boro, Alex -- Cascino, Gregory D -- Consalvo, Damian -- Crumrine, Patricia -- Devinsky, Orrin -- Fiol, Miguel -- Fountain, Nathan B -- French, Jacqueline -- Friedman, Daniel -- Geller, Eric B -- Glynn, Simon -- Haut, Sheryl R -- Hayward, Jean -- Helmers, Sandra L -- Joshi, Sucheta -- Kanner, Andres -- Kirsch, Heidi E -- Knowlton, Robert C -- Kossoff, Eric H -- Kuperman, Rachel -- McGuire, Shannon M -- Motika, Paul V -- Novotny, Edward J -- Paolicchi, Juliann M -- Parent, Jack M -- Park, Kristen -- Shellhaas, Renee A -- Shih, Jerry J -- Singh, Rani -- Sirven, Joseph -- Smith, Michael C -- Sullivan, Joseph -- Lin Thio, Liu -- Venkat, Anu -- Vining, Eileen P G -- Von Allmen, Gretchen K -- Weisenberg, Judith L -- Widdess-Walsh, Peter -- Winawer, Melodie R -- 1RC2NS070342/NS/NINDS NIH HHS/ -- NS053998/NS/NINDS NIH HHS/ -- NS077274/NS/NINDS NIH HHS/ -- NS077276/NS/NINDS NIH HHS/ -- NS077303/NS/NINDS NIH HHS/ -- NS077364/NS/NINDS NIH HHS/ -- R56AI098588/AI/NIAID NIH HHS/ -- U01 NS053998/NS/NINDS NIH HHS/ -- U01 NS077274/NS/NINDS NIH HHS/ -- U01 NS077276/NS/NINDS NIH HHS/ -- U01 NS077303/NS/NINDS NIH HHS/ -- U01 NS077364/NS/NINDS NIH HHS/ -- U01AI067854/AI/NIAID NIH HHS/ -- UL1 TR000005/TR/NCATS NIH HHS/ -- England -- Nature. 2013 Sep 12;501(7466):217-21. doi: 10.1038/nature12439. Epub 2013 Aug 11.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23934111" target="_blank"〉PubMed〈/a〉

Description: We present Interplanetary Network (IPN) data for the gamma-ray bursts in the first Fermi Gamma-Ray BurstMonitor (GBM) catalog. Of the 491 bursts in that catalog, covering 2008 July 12 to 2010 July 11, 427 wereobserved by at least one other instrument in the nine-spacecraft IPN. Of the 427, the localizations of 149 could beimproved by arrival time analysis (or triangulation). For any given burst observed by the GBM and one otherdistant spacecraft, triangulation gives an annulus of possible arrival directions whose half-width varies betweenabout 0. 4 and 32, depending on the intensity, time history, and arrival direction of the burst, as well as the distancebetween the spacecraft. We find that the IPN localizations intersect the 1 GBM error circles in only 52 of thecases, if no systematic uncertainty is assumed for the latter. If a 6 systematic uncertainty is assumed and added inquadrature, the two localization samples agree about 87 of the time, as would be expected. If we then multiply theresulting error radii by a factor of three, the two samples agree in slightly over 98 of the cases, providing a goodestimate of the GBM 3 error radius. The IPN 3 error boxes have areas between about 1 arcmin2 and 110 deg2,and are, on the average, a factor of 180 smaller than the corresponding GBM localizations. We identify two burstsin the IPNGBM sample that did not appear in the GBM catalog. In one case, the GBM triggered on a terrestrialgamma flash, and in the other, its origin was given as uncertain. We also discuss the sensitivity and calibration ofthe IPN.

Description: Down's syndrome is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21. We tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST (the X-inactivation gene). Using genome editing with zinc finger nucleases, we inserted a large, inducible XIST transgene into the DYRK1A locus on chromosome 21, in Down's syndrome pluripotent stem cells. The XIST non-coding RNA coats chromosome 21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a 'chromosome 21 Barr body'. This provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise. Notably, deficits in proliferation and neural rosette formation are rapidly reversed upon silencing one chromosome 21. Successful trisomy silencing in vitro also surmounts the major first step towards potential development of 'chromosome therapy'.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848249/" 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/PMC3848249/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Jun -- Jing, Yuanchun -- Cost, Gregory J -- Chiang, Jen-Chieh -- Kolpa, Heather J -- Cotton, Allison M -- Carone, Dawn M -- Carone, Benjamin R -- Shivak, David A -- Guschin, Dmitry Y -- Pearl, Jocelynn R -- Rebar, Edward J -- Byron, Meg -- Gregory, Philip D -- Brown, Carolyn J -- Urnov, Fyodor D -- Hall, Lisa L -- Lawrence, Jeanne B -- 1F32CA154086/CA/NCI NIH HHS/ -- 2T32HD007439/HD/NICHD NIH HHS/ -- F32 CA154086/CA/NCI NIH HHS/ -- GM053234/GM/NIGMS NIH HHS/ -- GM085548/GM/NIGMS NIH HHS/ -- GM096400 RC4/GM/NIGMS NIH HHS/ -- MOP-13680/Canadian Institutes of Health Research/Canada -- R01 GM053234/GM/NIGMS NIH HHS/ -- R01 GM085548/GM/NIGMS NIH HHS/ -- RC4 GM096400/GM/NIGMS NIH HHS/ -- T32 HD007439/HD/NICHD NIH HHS/ -- England -- Nature. 2013 Aug 15;500(7462):296-300. doi: 10.1038/nature12394. Epub 2013 Jul 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23863942" target="_blank"〉PubMed〈/a〉

Description: In this paper, we present the Fermi All-sky Variability Analysis (FAVA), a tool to systematically study the variability of the gamma-ray sky measured by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope.For each direction on the sky, FAVA compares the number of gamma-rays observed in a given time window to the number of gamma-rays expected for the average emission detected from that direction. This method is used in weekly time intervals to derive a list of 215 flaring gamma-ray sources. We proceed to discuss the 27 sources found at Galactic latitudes smaller than 10 and show that, despite their low latitudes, most of them are likely of extragalactic origin.

Description: Author(s): N. M. Lučić, B. M. Bokić, D. Ž. Grujić, D. V. Pantelić, B. M. Jelenković, A. Piper, D. M. Jović, and D. V. Timotijević We demonstrate both theoretically and experimentally that a finite Airy beam changes its trajectory and shape in optically induced waveguide arrays consisting of different kinds of defects. The propagation dynamics and beam acceleration are controlled with positive and negative defects, and appropri... [Phys. Rev. A 88, 063815] Published Fri Dec 06, 2013

Description: Somatic cells can be inefficiently and stochastically reprogrammed into induced pluripotent stem (iPS) cells by exogenous expression of Oct4 (also called Pou5f1), Sox2, Klf4 and Myc (hereafter referred to as OSKM). The nature of the predominant rate-limiting barrier(s) preventing the majority of cells to successfully and synchronously reprogram remains to be defined. Here we show that depleting Mbd3, a core member of the Mbd3/NuRD (nucleosome remodelling and deacetylation) repressor complex, together with OSKM transduction and reprogramming in naive pluripotency promoting conditions, result in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). Our findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes. Subsequently, the latter interactions, which are largely depleted during early pre-implantation development in vivo, lead to a stochastic and protracted reprogramming trajectory towards pluripotency in vitro. The deterministic reprogramming approach devised here offers a novel platform for the dissection of molecular dynamics leading to establishing pluripotency at unprecedented flexibility and resolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rais, Yoach -- Zviran, Asaf -- Geula, Shay -- Gafni, Ohad -- Chomsky, Elad -- Viukov, Sergey -- Mansour, Abed AlFatah -- Caspi, Inbal -- Krupalnik, Vladislav -- Zerbib, Mirie -- Maza, Itay -- Mor, Nofar -- Baran, Dror -- Weinberger, Leehee -- Jaitin, Diego A -- Lara-Astiaso, David -- Blecher-Gonen, Ronnie -- Shipony, Zohar -- Mukamel, Zohar -- Hagai, Tzachi -- Gilad, Shlomit -- Amann-Zalcenstein, Daniela -- Tanay, Amos -- Amit, Ido -- Novershtern, Noa -- Hanna, Jacob H -- England -- Nature. 2013 Oct 3;502(7469):65-70. doi: 10.1038/nature12587. Epub 2013 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24048479" target="_blank"〉PubMed〈/a〉