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  • Articles  (279)
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  • Articles  (279)
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  • 1
    Publication Date: 2012-06-16
    Description: Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Won, Hyejung -- Lee, Hye-Ryeon -- Gee, Heon Yung -- Mah, Won -- Kim, Jae-Ick -- Lee, Jiseok -- Ha, Seungmin -- Chung, Changuk -- Jung, Eun Suk -- Cho, Yi Sul -- Park, Sae-Geun -- Lee, Jung-Soo -- Lee, Kyungmin -- Kim, Daesoo -- Bae, Yong Chul -- Kaang, Bong-Kiun -- Lee, Min Goo -- Kim, Eunjoon -- England -- Nature. 2012 Jun 13;486(7402):261-5. doi: 10.1038/nature11208.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22699620" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Antimetabolites/pharmacology ; *Autistic Disorder/genetics/metabolism ; Behavior, Animal/*drug effects/physiology ; Benzamides/*pharmacology ; Cycloserine/*pharmacology ; Disease Models, Animal ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/*genetics ; Pyrazoles/*pharmacology ; Receptors, N-Methyl-D-Aspartate/*agonists/*metabolism
    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: 2016-01-19
    Description: Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Seung-Kyun -- Murphy, Rory K J -- Hwang, Suk-Won -- Lee, Seung Min -- Harburg, Daniel V -- Krueger, Neil A -- Shin, Jiho -- Gamble, Paul -- Cheng, Huanyu -- Yu, Sooyoun -- Liu, Zhuangjian -- McCall, Jordan G -- Stephen, Manu -- Ying, Hanze -- Kim, Jeonghyun -- Park, Gayoung -- Webb, R Chad -- Lee, Chi Hwan -- Chung, Sangjin -- Wie, Dae Seung -- Gujar, Amit D -- Vemulapalli, Bharat -- Kim, Albert H -- Lee, Kyung-Mi -- Cheng, Jianjun -- Huang, Younggang -- Lee, Sang Hoon -- Braun, Paul V -- Ray, Wilson Z -- Rogers, John A -- F31MH101956/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Feb 4;530(7588):71-6. doi: 10.1038/nature16492. Epub 2016 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; Department of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 136-701, Republic of Korea. ; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; Department of Engineering Science and Mechanics, Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; Institute of High Performance Computing, Singapore 138632, Singapore. ; Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Biomicrosystem Technology, Korea University, Seoul 136-701, South Korea. ; Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-713, South Korea. ; Weldon School of Biomedical Engineering, School of Mechanical Engineering, The Center for Implantable Devices, Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907, USA. ; School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907, USA. ; Department of Mechanical Engineering, Civil and Environmental Engineering, Materials Science and Engineering, and Skin Disease Research Center, Northwestern University, Evanston, Illinois 60208, USA. ; Department of Biomedical Engineering, College of Health Science, Korea University, Seoul 136-703, South Korea. ; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26779949" target="_blank"〉PubMed〈/a〉
    Keywords: *Absorbable Implants/adverse effects ; Administration, Cutaneous ; Animals ; Body Temperature ; Brain/*metabolism/surgery ; Electronics/*instrumentation ; Equipment Design ; Hydrolysis ; Male ; Monitoring, Physiologic/adverse effects/*instrumentation ; Organ Specificity ; Pressure ; *Prostheses and Implants/adverse effects ; Rats ; Rats, Inbred Lew ; *Silicon ; Telemetry/instrumentation ; Wireless Technology/instrumentation
    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: 2011-09-13
    Description: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (〉/=140 mm Hg systolic blood pressure or 〉/=90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340926/" 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/PMC3340926/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Consortium for Blood Pressure Genome-Wide Association Studies -- Ehret, Georg B -- Munroe, Patricia B -- Rice, Kenneth M -- Bochud, Murielle -- Johnson, Andrew D -- Chasman, Daniel I -- Smith, Albert V -- Tobin, Martin D -- Verwoert, Germaine C -- Hwang, Shih-Jen -- Pihur, Vasyl -- Vollenweider, Peter -- O'Reilly, Paul F -- Amin, Najaf -- Bragg-Gresham, Jennifer L -- Teumer, Alexander -- Glazer, Nicole L -- Launer, Lenore -- Zhao, Jing Hua -- Aulchenko, Yurii -- Heath, Simon -- Sober, Siim -- Parsa, Afshin -- Luan, Jian'an -- Arora, Pankaj -- Dehghan, Abbas -- Zhang, Feng -- Lucas, Gavin -- Hicks, Andrew A -- Jackson, Anne U -- Peden, John F -- Tanaka, Toshiko -- Wild, Sarah H -- Rudan, Igor -- Igl, Wilmar -- Milaneschi, Yuri -- Parker, Alex N -- Fava, Cristiano -- Chambers, John C -- Fox, Ervin R -- Kumari, Meena -- Go, Min Jin -- van der Harst, Pim -- Kao, Wen Hong Linda -- Sjogren, Marketa -- Vinay, D G -- Alexander, Myriam -- Tabara, Yasuharu -- Shaw-Hawkins, Sue -- Whincup, Peter H -- Liu, Yongmei -- Shi, Gang -- Kuusisto, Johanna -- Tayo, Bamidele -- Seielstad, Mark -- Sim, Xueling -- Nguyen, Khanh-Dung Hoang -- Lehtimaki, Terho -- Matullo, Giuseppe -- Wu, Ying -- Gaunt, Tom R -- Onland-Moret, N Charlotte -- Cooper, Matthew N -- Platou, Carl G P -- Org, Elin -- Hardy, Rebecca -- Dahgam, Santosh -- Palmen, Jutta -- Vitart, Veronique -- Braund, Peter S -- Kuznetsova, Tatiana -- Uiterwaal, Cuno S P M -- Adeyemo, Adebowale -- Palmas, Walter -- Campbell, Harry -- Ludwig, Barbara -- Tomaszewski, Maciej -- Tzoulaki, Ioanna -- Palmer, Nicholette D -- CARDIoGRAM consortium -- CKDGen Consortium -- KidneyGen Consortium -- EchoGen consortium -- CHARGE-HF consortium -- Aspelund, Thor -- Garcia, Melissa -- Chang, Yen-Pei C -- O'Connell, Jeffrey R -- Steinle, Nanette I -- Grobbee, Diederick E -- Arking, Dan E -- Kardia, Sharon L -- Morrison, Alanna C -- Hernandez, Dena -- Najjar, Samer -- McArdle, Wendy L -- Hadley, David -- Brown, Morris J -- Connell, John M -- Hingorani, Aroon D -- Day, Ian N M -- Lawlor, Debbie A -- Beilby, John P -- Lawrence, Robert W -- Clarke, Robert -- Hopewell, Jemma C -- Ongen, Halit -- Dreisbach, Albert W -- Li, Yali -- Young, J Hunter -- Bis, Joshua C -- Kahonen, Mika -- Viikari, Jorma -- Adair, Linda S -- Lee, Nanette R -- Chen, Ming-Huei -- Olden, Matthias -- Pattaro, Cristian -- Bolton, Judith A Hoffman -- Kottgen, Anna -- Bergmann, Sven -- Mooser, Vincent -- Chaturvedi, Nish -- Frayling, Timothy M -- Islam, Muhammad -- Jafar, Tazeen H -- Erdmann, Jeanette -- Kulkarni, Smita R -- Bornstein, Stefan R -- Grassler, Jurgen -- Groop, Leif -- Voight, Benjamin F -- Kettunen, Johannes -- Howard, Philip -- Taylor, Andrew -- Guarrera, Simonetta -- Ricceri, Fulvio -- Emilsson, Valur -- Plump, Andrew -- Barroso, Ines -- Khaw, Kay-Tee -- Weder, Alan B -- Hunt, Steven C -- Sun, Yan V -- Bergman, Richard N -- Collins, Francis S -- Bonnycastle, Lori L -- Scott, Laura J -- Stringham, Heather M -- Peltonen, Leena -- Perola, Markus -- Vartiainen, Erkki -- Brand, Stefan-Martin -- Staessen, Jan A -- Wang, Thomas J -- Burton, Paul R -- Soler Artigas, Maria -- Dong, Yanbin -- Snieder, Harold -- Wang, Xiaoling -- Zhu, Haidong -- Lohman, Kurt K -- Rudock, Megan E -- Heckbert, Susan R -- Smith, Nicholas L -- Wiggins, Kerri L -- Doumatey, Ayo -- Shriner, Daniel -- Veldre, Gudrun -- Viigimaa, Margus -- Kinra, Sanjay -- Prabhakaran, Dorairaj -- Tripathy, Vikal -- Langefeld, Carl D -- Rosengren, Annika -- Thelle, Dag S -- Corsi, Anna Maria -- Singleton, Andrew -- Forrester, Terrence -- Hilton, Gina -- McKenzie, Colin A -- Salako, Tunde -- Iwai, Naoharu -- Kita, Yoshikuni -- Ogihara, Toshio -- Ohkubo, Takayoshi -- Okamura, Tomonori -- Ueshima, Hirotsugu -- Umemura, Satoshi -- Eyheramendy, Susana -- Meitinger, Thomas -- Wichmann, H-Erich -- Cho, Yoon Shin -- Kim, Hyung-Lae -- Lee, Jong-Young -- Scott, James -- Sehmi, Joban S -- Zhang, Weihua -- Hedblad, Bo -- Nilsson, Peter -- Smith, George Davey -- Wong, Andrew -- Narisu, Narisu -- Stancakova, Alena -- Raffel, Leslie J -- Yao, Jie -- Kathiresan, Sekar -- O'Donnell, Christopher J -- Schwartz, Stephen M -- Ikram, M Arfan -- Longstreth, W T Jr -- Mosley, Thomas H -- Seshadri, Sudha -- Shrine, Nick R G -- Wain, Louise V -- Morken, Mario A -- Swift, Amy J -- Laitinen, Jaana -- Prokopenko, Inga -- Zitting, Paavo -- Cooper, Jackie A -- Humphries, Steve E -- Danesh, John -- Rasheed, Asif -- Goel, Anuj -- Hamsten, Anders -- Watkins, Hugh -- Bakker, Stephan J L -- van Gilst, Wiek H -- Janipalli, Charles S -- Mani, K Radha -- Yajnik, Chittaranjan S -- Hofman, Albert -- Mattace-Raso, Francesco U S -- Oostra, Ben A -- Demirkan, Ayse -- Isaacs, Aaron -- Rivadeneira, Fernando -- Lakatta, Edward G -- Orru, Marco -- Scuteri, Angelo -- Ala-Korpela, Mika -- Kangas, Antti J -- Lyytikainen, Leo-Pekka -- Soininen, Pasi -- Tukiainen, Taru -- Wurtz, Peter -- Ong, Rick Twee-Hee -- Dorr, Marcus -- Kroemer, Heyo K -- Volker, Uwe -- Volzke, Henry -- Galan, Pilar -- Hercberg, Serge -- Lathrop, Mark -- Zelenika, Diana -- Deloukas, Panos -- Mangino, Massimo -- Spector, Tim D -- Zhai, Guangju -- Meschia, James F -- Nalls, Michael A -- Sharma, Pankaj -- Terzic, Janos -- Kumar, M V Kranthi -- Denniff, Matthew -- Zukowska-Szczechowska, Ewa -- Wagenknecht, Lynne E -- Fowkes, F Gerald R -- Charchar, Fadi J -- Schwarz, Peter E H -- Hayward, Caroline -- Guo, Xiuqing -- Rotimi, Charles -- Bots, Michiel L -- Brand, Eva -- Samani, Nilesh J -- Polasek, Ozren -- Talmud, Philippa J -- Nyberg, Fredrik -- Kuh, Diana -- Laan, Maris -- Hveem, Kristian -- Palmer, Lyle J -- van der Schouw, Yvonne T -- Casas, Juan P -- Mohlke, Karen L -- Vineis, Paolo -- Raitakari, Olli -- Ganesh, Santhi K -- Wong, Tien Y -- Tai, E Shyong -- Cooper, Richard S -- Laakso, Markku -- Rao, Dabeeru C -- Harris, Tamara B -- Morris, Richard W -- Dominiczak, Anna F -- Kivimaki, Mika -- Marmot, Michael G -- Miki, Tetsuro -- Saleheen, Danish -- Chandak, Giriraj R -- Coresh, Josef -- Navis, Gerjan -- Salomaa, Veikko -- Han, Bok-Ghee -- Zhu, Xiaofeng -- Kooner, Jaspal S -- Melander, Olle -- Ridker, Paul M -- Bandinelli, Stefania -- Gyllensten, Ulf B -- Wright, Alan F -- Wilson, James F -- Ferrucci, Luigi -- Farrall, Martin -- Tuomilehto, Jaakko -- Pramstaller, Peter P -- Elosua, Roberto -- Soranzo, Nicole -- Sijbrands, Eric J G -- Altshuler, David -- Loos, Ruth J F -- Shuldiner, Alan R -- Gieger, Christian -- Meneton, Pierre -- Uitterlinden, Andre G -- Wareham, Nicholas J -- Gudnason, Vilmundur -- Rotter, Jerome I -- Rettig, Rainer -- Uda, Manuela -- Strachan, David P -- Witteman, Jacqueline C M -- Hartikainen, Anna-Liisa -- Beckmann, Jacques S -- Boerwinkle, Eric -- Vasan, Ramachandran S -- Boehnke, Michael -- Larson, Martin G -- Jarvelin, Marjo-Riitta -- Psaty, Bruce M -- Abecasis, Goncalo R -- Chakravarti, Aravinda -- Elliott, Paul -- van Duijn, Cornelia M -- Newton-Cheh, Christopher -- Levy, Daniel -- Caulfield, Mark J -- Johnson, Toby -- 068545/Z/02/Wellcome Trust/United Kingdom -- 070191/Z/03/Z/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 080747/Z/06/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 1R01AG032098-01A/AG/NIA NIH HHS/ -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 263 MD 821336/MD/NIMHD NIH HHS/ -- 263 MD 9164/MD/NIMHD NIH HHS/ -- 263-MA-410953/PHS HHS/ -- 2M01RR010284/RR/NCRR NIH HHS/ -- 33014/PHS HHS/ -- 55005617/Howard Hughes Medical Institute/ -- 5R01HL086694-03/HL/NHLBI NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01HL08770002/HL/NHLBI NIH HHS/ -- 5R01MH63706:02/MH/NIMH NIH HHS/ -- 5U01CA086308/CA/NCI NIH HHS/ -- AG13196/AG/NIA NIH HHS/ -- CH/03/001/British Heart Foundation/United Kingdom -- CZB/4/276/Chief Scientist Office/United Kingdom -- CZB/4/710/Chief Scientist Office/United Kingdom -- DK062370/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK072193/DK/NIDDK NIH HHS/ -- DK075787/DK/NIDDK NIH HHS/ -- DK078150/DK/NIDDK NIH HHS/ -- DK56350/DK/NIDDK NIH HHS/ -- ES10126/ES/NIEHS NIH HHS/ -- FS05/125/British Heart Foundation/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- G0100222/Medical Research Council/United Kingdom -- G0400874/Medical Research Council/United Kingdom -- G0401527/Medical Research Council/United Kingdom -- G0500539/Medical Research Council/United Kingdom -- G0501942/British Heart Foundation/United Kingdom -- G0501942/Medical Research Council/United Kingdom -- G0600331/Medical Research Council/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G0902037/Medical Research Council/United Kingdom -- G0902313/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- G19/35/Medical Research Council/United Kingdom -- G20234/Biotechnology and Biological Sciences Research Council/United Kingdom -- G8802774/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- G9521010D/Medical Research Council/United Kingdom -- HG003054/HG/NHGRI NIH HHS/ -- HG005581/HG/NHGRI NIH HHS/ -- HHSN268200625226C/PHS HHS/ -- HHSN268200782096/PHS HHS/ -- HHSN268200782096C/PHS HHS/ -- HL 54512/HL/NHLBI NIH HHS/ -- HL-87660/HL/NHLBI NIH HHS/ -- HL043851/HL/NHLBI NIH HHS/ -- HL080025/HL/NHLBI NIH HHS/ -- HL084729/HL/NHLBI NIH HHS/ -- HL085144/HL/NHLBI NIH HHS/ -- HL086718/HL/NHLBI NIH HHS/ -- HL087647/HL/NHLBI NIH HHS/ -- HL098283/HL/NHLBI NIH HHS/ -- HL36310/HL/NHLBI NIH HHS/ -- HL45508/HL/NHLBI NIH HHS/ -- HL53353/HL/NHLBI NIH HHS/ -- HL54512/HL/NHLBI NIH HHS/ -- HS06516/HS/AHRQ HHS/ -- K12RR023250/RR/NCRR NIH HHS/ -- M01 RR16500/RR/NCRR NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- MC_U123092720/Medical Research Council/United Kingdom -- MC_U123092723/Medical Research Council/United Kingdom -- MC_U127561128/Medical Research Council/United Kingdom -- MC_U137686857/Medical Research Council/United Kingdom -- MC_UP_A100_1003/Medical Research Council/United Kingdom -- MOP-82810/Canadian Institutes of Health Research/Canada -- MOP172605/Canadian Institutes of Health Research/Canada -- MOP77682/Canadian Institutes of Health Research/Canada -- N01 HC-15103/HC/NHLBI NIH HHS/ -- N01 HC-55222/HC/NHLBI NIH HHS/ -- N01 HC-95159/HC/NHLBI NIH HHS/ -- N01 HC-95169/HC/NHLBI NIH HHS/ -- N01-AG-1-2109/AG/NIA NIH HHS/ -- N01-AG-12100/AG/NIA NIH HHS/ -- N01-HC-25195/HC/NHLBI NIH HHS/ -- N01-HC-35129/HC/NHLBI NIH HHS/ -- N01-HC-45133/HC/NHLBI NIH HHS/ -- N01-HC-55015/HC/NHLBI NIH HHS/ -- N01-HC-55016/HC/NHLBI NIH HHS/ -- N01-HC-55018/HC/NHLBI NIH HHS/ -- N01-HC-55019/HC/NHLBI NIH HHS/ -- N01-HC-55020/HC/NHLBI NIH HHS/ -- N01-HC-55021/HC/NHLBI NIH HHS/ -- N01-HC-55022/HC/NHLBI NIH HHS/ -- N01-HC-75150/HC/NHLBI NIH HHS/ -- N01-HC-85079/HC/NHLBI NIH HHS/ -- N01-HC-85080/HC/NHLBI NIH HHS/ -- N01-HC-85081/HC/NHLBI NIH HHS/ -- N01-HC-85082/HC/NHLBI NIH HHS/ -- N01-HC-85083/HC/NHLBI NIH HHS/ -- N01-HC-85084/HC/NHLBI NIH HHS/ -- N01-HC-85085/HC/NHLBI NIH HHS/ -- N01-HC-85086/HC/NHLBI NIH HHS/ -- N01-HC-95160/HC/NHLBI NIH HHS/ -- N01-HC-95161/HC/NHLBI NIH HHS/ -- N01-HC-95162/HC/NHLBI NIH HHS/ -- N01-HC-95163/HC/NHLBI NIH HHS/ -- N01-HC-95164/HC/NHLBI NIH HHS/ -- N01-HC-95165/HC/NHLBI NIH HHS/ -- N01-HC-95166/HC/NHLBI NIH HHS/ -- N01-HC-95167/HC/NHLBI NIH HHS/ -- N01-HC-95168/HC/NHLBI NIH HHS/ -- N01-HD-1-3107/HD/NICHD NIH HHS/ -- N01AG6210/AG/NIA NIH HHS/ -- N01AG62101/AG/NIA NIH HHS/ -- N01AG62103/AG/NIA NIH HHS/ -- N02-HL-6-4278/HL/NHLBI NIH HHS/ -- P01CA055075/CA/NCI NIH HHS/ -- P01CA087969/CA/NCI NIH HHS/ -- P30 ES010126/ES/NIEHS NIH HHS/ -- P30ES007033/ES/NIEHS NIH HHS/ -- PG/02/128/British Heart Foundation/United Kingdom -- PG97012/British Heart Foundation/United Kingdom -- PG97027/British Heart Foundation/United Kingdom -- R01 AG017644-09S1/AG/NIA NIH HHS/ -- R01 AG18728/AG/NIA NIH HHS/ -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 HL073410/HL/NHLBI NIH HHS/ -- R01 HL085251/HL/NHLBI NIH HHS/ -- R01 HL086694/HL/NHLBI NIH HHS/ -- R01 HL086694-03/HL/NHLBI NIH HHS/ -- R01 HL086694-04A1/HL/NHLBI NIH HHS/ -- R01 HL086694-05/HL/NHLBI NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087652/HL/NHLBI NIH HHS/ -- R01 HL088119/HL/NHLBI NIH HHS/ -- R01 NS39987/NS/NINDS NIH HHS/ -- R01 NS42733/NS/NINDS NIH HHS/ -- R01DK058845/DK/NIDDK NIH HHS/ -- R01DK066574/DK/NIDDK NIH HHS/ -- R01HL056931/HL/NHLBI NIH HHS/ -- R01HL060894/HL/NHLBI NIH HHS/ -- R01HL060919/HL/NHLBI NIH HHS/ -- R01HL06094/HL/NHLBI NIH HHS/ -- R01HL061019/HL/NHLBI NIH HHS/ -- R01HL071051/HL/NHLBI NIH HHS/ -- R01HL071205/HL/NHLBI NIH HHS/ -- R01HL071250/HL/NHLBI NIH HHS/ -- R01HL071251/HL/NHLBI NIH HHS/ -- R01HL071252/HL/NHLBI NIH HHS/ -- R01HL071258/HL/NHLBI NIH HHS/ -- R01HL071259/HL/NHLBI NIH HHS/ -- R01HL086694/HL/NHLBI NIH HHS/ -- R01HL087641/HL/NHLBI NIH HHS/ -- R01HL089650-02/HL/NHLBI NIH HHS/ -- R01HL59367/HL/NHLBI NIH HHS/ -- R03 TW007165/TW/FIC NIH HHS/ -- R37HL051021/HL/NHLBI NIH HHS/ -- RG/07/005/23633/British Heart Foundation/United Kingdom -- RG/07/008/23674/British Heart Foundation/United Kingdom -- RG/08/008/25291/British Heart Foundation/United Kingdom -- RG/08/013/25942/British Heart Foundation/United Kingdom -- RG/08/014/24067/British Heart Foundation/United Kingdom -- RG/98002/British Heart Foundation/United Kingdom -- RG08/01/British Heart Foundation/United Kingdom -- RR-024156/RR/NCRR NIH HHS/ -- RR20649/RR/NCRR NIH HHS/ -- S06GM008016-320107/GM/NIGMS NIH HHS/ -- S06GM008016-380111/GM/NIGMS NIH HHS/ -- SP/04/002/British Heart Foundation/United Kingdom -- SP/08/005/25115/British Heart Foundation/United Kingdom -- TW008288/TW/FIC NIH HHS/ -- TW05596/TW/FIC NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 GM074518-04/GM/NIGMS NIH HHS/ -- U01 HL054466/HL/NHLBI NIH HHS/ -- U01 HL054466-11/HL/NHLBI NIH HHS/ -- U01 HL054471/HL/NHLBI NIH HHS/ -- U01 HL054473/HL/NHLBI NIH HHS/ -- U01 HL054527/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 NS069208/NS/NINDS NIH HHS/ -- U01 NS069208-01/NS/NINDS NIH HHS/ -- U01DE018903/DE/NIDCR NIH HHS/ -- U01DE01899/DE/NIDCR NIH HHS/ -- U01HG004399/HG/NHGRI NIH HHS/ -- U01HG004402/HG/NHGRI NIH HHS/ -- U01HG004415/HG/NHGRI NIH HHS/ -- U01HG004422/HG/NHGRI NIH HHS/ -- U01HG004423/HG/NHGRI NIH HHS/ -- U01HG004436/HG/NHGRI NIH HHS/ -- U01HG004438/HG/NHGRI NIH HHS/ -- U01HG004446/HG/NHGRI NIH HHS/ -- U01HG004726/HG/NHGRI NIH HHS/ -- U01HG004728/HG/NHGRI NIH HHS/ -- U01HG004729/HG/NHGRI NIH HHS/ -- U01HG004735/HG/NHGRI NIH HHS/ -- U01HG004738/HG/NHGRI NIH HHS/ -- U10 HL054512/HL/NHLBI NIH HHS/ -- U10HL054512/HL/NHLBI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1RR025005/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Sep 11;478(7367):103-9. doi: 10.1038/nature10405.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21909115" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/ethnology ; Asia/ethnology ; Blood Pressure/*genetics/physiology ; Cardiovascular Diseases/*genetics ; Coronary Artery Disease/genetics ; Europe/ethnology ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Humans ; Hypertension/genetics ; Kidney Diseases/genetics ; Polymorphism, Single Nucleotide/*genetics ; Stroke/genetics
    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: 2011-05-27
    Description: Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150801/" 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/PMC3150801/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jae Man -- Lee, Yoon Kwang -- Mamrosh, Jennifer L -- Busby, Scott A -- Griffin, Patrick R -- Pathak, Manish C -- Ortlund, Eric A -- Moore, David D -- DK-079638/DK/NIDDK NIH HHS/ -- R01 CA134873/CA/NCI NIH HHS/ -- R01 DK068804/DK/NIDDK NIH HHS/ -- R01 DK083572/DK/NIDDK NIH HHS/ -- R01 DK083572-02/DK/NIDDK NIH HHS/ -- T32 DK007696/DK/NIDDK NIH HHS/ -- U54 MH084512/MH/NIMH NIH HHS/ -- England -- Nature. 2011 May 25;474(7352):506-10. doi: 10.1038/nature10111.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21614002" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bile Acids and Salts/biosynthesis/metabolism/pharmacology ; Blood Glucose/metabolism ; Cell Line ; Disease Models, Animal ; Fatty Liver/drug therapy/enzymology ; HeLa Cells ; Homeostasis/drug effects ; Humans ; Hypoglycemic Agents/pharmacology ; Insulin Resistance/physiology ; Ligands ; Lipogenesis/drug effects ; Liver/drug effects/enzymology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phosphatidylcholines/*metabolism/pharmacology ; Protein Binding ; Receptors, Cytoplasmic and Nuclear/agonists/deficiency/genetics/*metabolism ; Signal Transduction/drug effects ; Triglycerides/metabolism
    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: 2015-01-22
    Description: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393366/" 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/PMC4393366/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hibar, Derrek P -- Stein, Jason L -- Renteria, Miguel E -- Arias-Vasquez, Alejandro -- Desrivieres, Sylvane -- Jahanshad, Neda -- Toro, Roberto -- Wittfeld, Katharina -- Abramovic, Lucija -- Andersson, Micael -- Aribisala, Benjamin S -- Armstrong, Nicola J -- Bernard, Manon -- Bohlken, Marc M -- Boks, Marco P -- Bralten, Janita -- Brown, Andrew A -- Chakravarty, M Mallar -- Chen, Qiang -- Ching, Christopher R K -- Cuellar-Partida, Gabriel -- den Braber, Anouk -- Giddaluru, Sudheer -- Goldman, Aaron L -- Grimm, Oliver -- Guadalupe, Tulio -- Hass, Johanna -- Woldehawariat, Girma -- Holmes, Avram J -- Hoogman, Martine -- Janowitz, Deborah -- Jia, Tianye -- Kim, Sungeun -- Klein, Marieke -- Kraemer, Bernd -- Lee, Phil H -- Olde Loohuis, Loes M -- Luciano, Michelle -- Macare, Christine -- Mather, Karen A -- Mattheisen, Manuel -- Milaneschi, Yuri -- Nho, Kwangsik -- Papmeyer, Martina -- Ramasamy, Adaikalavan -- Risacher, Shannon L -- Roiz-Santianez, Roberto -- Rose, Emma J -- Salami, Alireza -- Samann, Philipp G -- Schmaal, Lianne -- Schork, Andrew J -- Shin, Jean -- Strike, Lachlan T -- Teumer, Alexander -- van Donkelaar, Marjolein M J -- van Eijk, Kristel R -- Walters, Raymond K -- Westlye, Lars T -- Whelan, Christopher D -- Winkler, Anderson M -- Zwiers, Marcel P -- Alhusaini, Saud -- Athanasiu, Lavinia -- Ehrlich, Stefan -- Hakobjan, Marina M H -- Hartberg, Cecilie B -- Haukvik, Unn K -- Heister, Angelien J G A M -- Hoehn, David -- Kasperaviciute, Dalia -- Liewald, David C M -- Lopez, Lorna M -- Makkinje, Remco R R -- Matarin, Mar -- Naber, Marlies A M -- McKay, D Reese -- Needham, Margaret -- Nugent, Allison C -- Putz, Benno -- Royle, Natalie A -- Shen, Li -- Sprooten, Emma -- Trabzuni, Daniah -- van der Marel, Saskia S L -- van Hulzen, Kimm J E -- Walton, Esther -- Wolf, Christiane -- Almasy, Laura -- Ames, David -- Arepalli, Sampath -- Assareh, Amelia A -- Bastin, Mark E -- Brodaty, Henry -- Bulayeva, Kazima B -- Carless, Melanie A -- Cichon, Sven -- Corvin, Aiden -- Curran, Joanne E -- Czisch, Michael -- de Zubicaray, Greig I -- Dillman, Allissa -- Duggirala, Ravi -- Dyer, Thomas D -- Erk, Susanne -- Fedko, Iryna O -- Ferrucci, Luigi -- Foroud, Tatiana M -- Fox, Peter T -- Fukunaga, Masaki -- Gibbs, J Raphael -- Goring, Harald H H -- Green, Robert C -- Guelfi, Sebastian -- Hansell, Narelle K -- Hartman, Catharina A -- Hegenscheid, Katrin -- Heinz, Andreas -- Hernandez, Dena G -- Heslenfeld, Dirk J -- Hoekstra, Pieter J -- Holsboer, Florian -- Homuth, Georg -- Hottenga, Jouke-Jan -- Ikeda, Masashi -- Jack, Clifford R Jr -- Jenkinson, Mark -- Johnson, Robert -- Kanai, Ryota -- Keil, Maria -- Kent, Jack W Jr -- Kochunov, Peter -- Kwok, John B -- Lawrie, Stephen M -- Liu, Xinmin -- Longo, Dan L -- McMahon, Katie L -- Meisenzahl, Eva -- Melle, Ingrid -- Mohnke, Sebastian -- Montgomery, Grant W -- Mostert, Jeanette C -- Muhleisen, Thomas W -- Nalls, Michael A -- Nichols, Thomas E -- Nilsson, Lars G -- Nothen, Markus M -- Ohi, Kazutaka -- Olvera, Rene L -- Perez-Iglesias, Rocio -- Pike, G Bruce -- Potkin, Steven G -- Reinvang, Ivar -- Reppermund, Simone -- Rietschel, Marcella -- Romanczuk-Seiferth, Nina -- Rosen, Glenn D -- Rujescu, Dan -- Schnell, Knut -- Schofield, Peter R -- Smith, Colin -- Steen, Vidar M -- Sussmann, Jessika E -- Thalamuthu, Anbupalam -- Toga, Arthur W -- Traynor, Bryan J -- Troncoso, Juan -- Turner, Jessica A -- Valdes Hernandez, Maria C -- van 't Ent, Dennis -- van der Brug, Marcel -- van der Wee, Nic J A -- van Tol, Marie-Jose -- Veltman, Dick J -- Wassink, Thomas H -- Westman, Eric -- Zielke, Ronald H -- Zonderman, Alan B -- Ashbrook, David G -- Hager, Reinmar -- Lu, Lu -- McMahon, Francis J -- Morris, Derek W -- Williams, Robert W -- Brunner, Han G -- Buckner, Randy L -- Buitelaar, Jan K -- Cahn, Wiepke -- Calhoun, Vince D -- Cavalleri, Gianpiero L -- Crespo-Facorro, Benedicto -- Dale, Anders M -- Davies, Gareth E -- Delanty, Norman -- Depondt, Chantal -- Djurovic, Srdjan -- Drevets, Wayne C -- Espeseth, Thomas -- Gollub, Randy L -- Ho, Beng-Choon -- Hoffmann, Wolfgang -- Hosten, Norbert -- Kahn, Rene S -- Le Hellard, Stephanie -- Meyer-Lindenberg, Andreas -- Muller-Myhsok, Bertram -- Nauck, Matthias -- Nyberg, Lars -- Pandolfo, Massimo -- Penninx, Brenda W J H -- Roffman, Joshua L -- Sisodiya, Sanjay M -- Smoller, Jordan W -- van Bokhoven, Hans -- van Haren, Neeltje E M -- Volzke, Henry -- Walter, Henrik -- Weiner, Michael W -- Wen, Wei -- White, Tonya -- Agartz, Ingrid -- Andreassen, Ole A -- Blangero, John -- Boomsma, Dorret I -- Brouwer, Rachel M -- Cannon, Dara M -- Cookson, Mark R -- de Geus, Eco J C -- Deary, Ian J -- Donohoe, Gary -- Fernandez, Guillen -- Fisher, Simon E -- Francks, Clyde -- Glahn, David C -- Grabe, Hans J -- Gruber, Oliver -- Hardy, John -- Hashimoto, Ryota -- Hulshoff Pol, Hilleke E -- Jonsson, Erik G -- Kloszewska, Iwona -- Lovestone, Simon -- Mattay, Venkata S -- Mecocci, Patrizia -- McDonald, Colm -- McIntosh, Andrew M -- Ophoff, Roel A -- Paus, Tomas -- Pausova, Zdenka -- Ryten, Mina -- Sachdev, Perminder S -- Saykin, Andrew J -- Simmons, Andy -- Singleton, Andrew -- Soininen, Hilkka -- Wardlaw, Joanna M -- Weale, Michael E -- Weinberger, Daniel R -- Adams, Hieab H H -- Launer, Lenore J -- Seiler, Stephan -- Schmidt, Reinhold -- Chauhan, Ganesh -- Satizabal, Claudia L -- Becker, James T -- Yanek, Lisa -- van der Lee, Sven J -- Ebling, Maritza -- Fischl, Bruce -- Longstreth, W T Jr -- Greve, Douglas -- Schmidt, Helena -- Nyquist, Paul -- Vinke, Louis N -- van Duijn, Cornelia M -- Xue, Luting -- Mazoyer, Bernard -- Bis, Joshua C -- Gudnason, Vilmundur -- Seshadri, Sudha -- Ikram, M Arfan -- Alzheimer's Disease Neuroimaging Initiative -- CHARGE Consortium -- EPIGEN -- IMAGEN -- SYS -- Martin, Nicholas G -- Wright, Margaret J -- Schumann, Gunter -- Franke, Barbara -- Thompson, Paul M -- Medland, Sarah E -- 100309/Wellcome Trust/United Kingdom -- 104036/Wellcome Trust/United Kingdom -- BB/F019394/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G0701120/Medical Research Council/United Kingdom -- G1001245/Medical Research Council/United Kingdom -- K99 LM011384/LM/NLM NIH HHS/ -- K99 MH101367/MH/NIMH NIH HHS/ -- MR/K026992/1/Medical Research Council/United Kingdom -- P41 EB015922/EB/NIBIB NIH HHS/ -- P50 AG005133/AG/NIA NIH HHS/ -- P50 AG005134/AG/NIA NIH HHS/ -- P50 AG005146/AG/NIA NIH HHS/ -- R00 LM011384/LM/NLM NIH HHS/ -- R01 AG040060/AG/NIA NIH HHS/ -- R01 EB015611/EB/NIBIB NIH HHS/ -- RF1 AG041915/AG/NIA NIH HHS/ -- U01 AG049505/AG/NIA NIH HHS/ -- U24 AG021886/AG/NIA NIH HHS/ -- U54 EB020403/EB/NIBIB NIH HHS/ -- UL1 TR001108/TR/NCATS NIH HHS/ -- UL1 TR001120/TR/NCATS NIH HHS/ -- England -- Nature. 2015 Apr 9;520(7546):224-9. doi: 10.1038/nature14101. Epub 2015 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. ; 1] Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. [2] Neurogenetics Program, Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095, USA. ; QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [4] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. ; 1] Laboratory of Human Genetics and Cognitive Functions, Institut Pasteur, Paris 75015, France. [2] Centre Nationale de Recherche Scientifique (CNRS) Unite de Recherche Associee (URA) 2182 Genes, Synapses and Cognition, Institut Pasteur, Paris 75015, France. [3] Universite Paris Diderot, Sorbonne Paris Cite, Paris 75015, France. ; 1] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany. [2] Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. ; Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. ; Umea Centre for Functional Brain Imaging (UFBI), Umea University, Umea 901 87, Sweden. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Department of Computer Science, Lagos State University, Lagos, Nigeria. [3] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. [2] School of Mathematics and Statistics, University of Sydney, Sydney 2006, Australia. ; The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway. ; 1] Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal H4H 1R3, Canada. [2] Department of Psychiatry and Biomedical Engineering, McGill University, Montreal H3A 2B4, Canada. ; Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. ; 1] Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. [2] Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California 90095, USA. ; Biological Psychology, Neuroscience Campus Amsterdam &EMGO Institute for Health and Care Research, VU University &VU Medical Center, Amsterdam 1081 BT, The Netherlands. ; 1] NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. [2] Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway. ; Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim 68159, Germany. ; 1] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands. [2] International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands. ; Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden 01307 Germany. ; Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. ; 1] Department of Psychology, Yale University, New Haven, Connecticut 06511, USA. [2] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [3] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts 02141, USA. [4] Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA. ; Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. ; 1] Department of Biomedicine, Aarhus University, Aarhus DK-8000, Denmark. [2] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen DK-8000, Denmark. [3] Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus DK-8000, Denmark. ; Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands. ; Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. ; 1] Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. [2] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] Department of Psychiatry, University Hospital Marques de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander 39008, Spain. [2] Cibersam (Centro Investigacion Biomedica en Red Salud Mental), Madrid 28029, Spain. ; 1] Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. [2] Center for Translational Research on Adversity, Neurodevelopment and Substance Abuse (C-TRANS), Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21045, USA. ; 1] Umea Centre for Functional Brain Imaging (UFBI), Umea University, Umea 901 87, Sweden. [2] Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden. ; Max Planck Institute of Psychiatry, Munich 80804, Germany. ; 1] Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA. [2] Department of Cognitive Sciences, University of California, San Diego, California 92161, USA. ; 1] QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. [2] School of Psychology, University of Queensland, Brisbane 4072, Australia. [3] Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia. ; Institute for Community Medicine, University Medicine Greifswald, Greifswald D-17475, Germany. ; 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Medical and Population Genetics Program, Broad Institute of Harvard and MIT, Boston, Massachusetts 02142, USA. ; 1] NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway. [2] Department of Psychology, University of Oslo, Oslo 0373, Norway. ; 1] The Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford OX3 9DU, UK. [2] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. ; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada. ; 1] Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden 01307 Germany. [2] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway. ; NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. ; 1] UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK. [2] Department of Medicine, Imperial College London, London W12 0NN, UK. ; Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK. ; 1] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. [2] Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA. ; Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [3] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; 1] Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. [2] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. [3] Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. ; 1] Texas Biomedical Research Institute, San Antonio, Texas 78245, USA. [2] University of Texas Health Science Center, San Antonio, Texas 78229, USA. ; 1] National Ageing Research Institute, Royal Melbourne Hospital, Melbourne 3052, Australia. [2] Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia. ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. [3] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [4] Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia. ; Texas Biomedical Research Institute, San Antonio, Texas 78245, USA. ; 1] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel 4055, Switzerland. [2] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [3] Institute of Neuroscience and Medicine (INM-1), Research Centre Julich, Julich, D-52425, Germany. [4] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; School of Psychology, University of Queensland, Brisbane 4072, Australia. ; Department of Psychiatry and Psychotherapy, Charite Universitatsmedizin Berlin, CCM, Berlin 10117, Germany. ; Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA. ; 1] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] University of Texas Health Science Center, San Antonio, Texas 78229, USA. [2] South Texas Veterans Health Care System, San Antonio, Texas 78229, USA. ; Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia. ; 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands. ; Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; Departments of Cognitive and Clinical Neuropsychology, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17489, Germany. ; Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. ; Radiology, Mayo Clinic, Rochester, Minnesota 55905, USA. ; FMRIB Centre, University of Oxford, Oxford OX3 9DU, UK. ; NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA. ; 1] School of Psychology, University of Sussex, Brighton BN1 9QH, UK. [2] Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK. ; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA. ; 1] Neuroscience Research Australia, Sydney 2031, Australia. [2] School of Medical Sciences, UNSW, Sydney 2052, Australia. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA. ; Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. ; Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia. ; Department of Psychiatry, Ludwig-Maximilians-Universitat, Munich 80336, Germany. ; 1] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [2] Institute of Neuroscience and Medicine (INM-1), Research Centre Julich, Julich, D-52425, Germany. [3] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; 1] FMRIB Centre, University of Oxford, Oxford OX3 9DU, UK. [2] Department of Statistics &WMG, University of Warwick, Coventry CV4 7AL, UK. ; 1] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [2] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] Cibersam (Centro Investigacion Biomedica en Red Salud Mental), Madrid 28029, Spain. [2] Institute of Psychiatry, King's College London, London SE5 8AF, UK. ; 1] Department of Neurology, University of Calgary, Calgary T2N 2T9, Canada. [2] Department of Clinical Neuroscience, University of Calgary, Calgary T2N 2T9, Canada. ; Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA. ; Department of Psychology, University of Oslo, Oslo 0373, Norway. ; 1] Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of General Psychiatry, Heidelberg University Hospital, Heidelberg 69115, Germany. ; Department of Neuropathology, MRC Sudden Death Brain Bank Project, University of Edinburgh, Edinburgh EH8 9AG, UK. ; Laboratory of Neuro Imaging, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. ; Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21287, USA. ; Psychology Department and Neuroscience Institute, Georgia State University, Atlanta, Georgia 30302, USA. ; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Genentech, South San Francisco, California 94080, USA. ; Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands. ; Neuroimaging Centre, University of Groningen, University Medical Center Groningen, Groningen 9713 AW, The Netherlands. ; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. ; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden. ; Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA. ; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. ; 1] Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [2] Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [3] Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China. ; 1] Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. [2] Cognitive Genetics and Therapy Group, School of Psychology &Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland. ; 1] Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [2] Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [3] Department of Clinical Genetics, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Department of Psychology, Center for Brain Science, Harvard University, Boston, Massachusetts 02138, USA. ; 1] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [3] Karakter Child and Adolescent Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. ; 1] The Mind Research Network &LBERI, Albuquerque, New Mexico 87106, USA. [2] Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA. ; 1] Center for Translational Imaging and Personalized Medicine, University of California, San Diego, California 92093, USA. [2] Departments of Neurosciences, Radiology, Psychiatry, and Cognitive Science, University of California, San Diego, California 92093, USA. ; Avera Institute for Human Genetics, Sioux Falls, South Dakota, 57108, USA. ; 1] Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland. [2] Neurology Division, Beaumont Hospital, Dublin 9, Ireland. ; Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Janssen Research &Development, Johnson &Johnson, Titusville, New Jersey 08560, USA. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [3] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA. ; 1] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany. [2] Institute for Community Medicine, University Medicine Greifswald, Greifswald D-17475, Germany. ; 1] Max Planck Institute of Psychiatry, Munich 80804, Germany. [2] Munich Cluster for Systems Neurology (SyNergy), Munich 81377, Germany. [3] University of Liverpool, Institute of Translational Medicine, Liverpool L69 3BX, UK. ; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. ; UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts 02141, USA. [4] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, California 94121, USA. ; 1] Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands. [2] Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway. [3] Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE-171 76, Sweden. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. ; 1] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; 1] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [2] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands. ; 1] Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. [2] Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund 18435, Germany. ; 1] Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany. [2] Max Planck Institute of Psychiatry, Munich 80804, Germany. ; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE-171 76, Sweden. ; Medical University of Lodz, Lodz 90-419, Poland. ; 1] Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK. [2] NIHR Dementia Biomedical Research Unit, King's College London, London SE5 8AF, UK. ; 1] Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia 06156, Italy. ; Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. ; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [2] Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. ; 1] Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. [2] Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA. ; 1] Rotman Research Institute, University of Toronto, Toronto M6A 2E1, Canada. [2] Departments of Psychology and Psychiatry, University of Toronto, Toronto M5T 1R8, Canada. ; 1] The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada. [2] Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto M5S 3E2, Canada. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. ; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. [2] Neuropsychiatric Institute, Prince of Wales Hospital, Sydney 2031, Australia. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [3] Department of Psychiatry and Psychotherapy, Charite Universitatsmedizin Berlin, CCM, Berlin 10117, Germany. ; 1] Department of Neuroimaging, Institute of Psychiatry, King's College London, London SE5 8AF, UK. [2] Biomedical Research Centre for Mental Health, King's College London, London SE5 8AF, UK. [3] Biomedical Research Unit for Dementia, King's College London, London SE5 8AF, UK. ; 1] Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio FI-70211, Finland. [2] Neurocentre Neurology, Kuopio University Hospital, Kuopio FI-70211, Finland. ; Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. ; 1] Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. [2] Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. [2] Department of Epidemiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland 20892, USA. ; Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria. ; INSERM U897, University of Bordeaux, Bordeaux 33076, France. ; 1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [2] Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; 1] Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. [2] Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. [3] Department of Psychology, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. ; General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Epidemiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; 1] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [2] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. ; 1] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [2] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. [3] Computer Science and AI Lab, Massachusetts Institute of Technology, Boston, Massachusetts 02141, USA. ; Department of Neurology University of Washington, Seattle, Washington 98195, USA. ; Institute of Molecular Biology and Biochemistry, Medical University Graz, 8010 Graz, Austria. ; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Groupe d'Imagerie Neurofonctionnelle, UMR5296 CNRS, CEA and University of Bordeaux, Bordeaux 33076, France. ; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA. ; Icelandic Heart Association, University of Iceland, Faculty of Medicine, Reykjavik 101, Iceland. ; 1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [2] Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. ; 1] QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. [2] School of Psychology, University of Queensland, Brisbane 4072, Australia. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25607358" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/genetics ; Apoptosis/genetics ; Brain/*anatomy & histology ; Caudate Nucleus/anatomy & histology ; Child ; Female ; Gene Expression Regulation, Developmental/genetics ; Genetic Loci/genetics ; Genetic Variation/*genetics ; *Genome-Wide Association Study ; Hippocampus/anatomy & histology ; Humans ; Magnetic Resonance Imaging ; Male ; Membrane Proteins/genetics ; Middle Aged ; Organ Size/genetics ; Putamen/anatomy & histology ; Sex Characteristics ; Skull/anatomy & histology ; Young Adult
    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: 2014-05-03
    Description: To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4(+) T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raj, Towfique -- Rothamel, Katie -- Mostafavi, Sara -- Ye, Chun -- Lee, Mark N -- Replogle, Joseph M -- Feng, Ting -- Lee, Michelle -- Asinovski, Natasha -- Frohlich, Irene -- Imboywa, Selina -- Von Korff, Alina -- Okada, Yukinori -- Patsopoulos, Nikolaos A -- Davis, Scott -- McCabe, Cristin -- Paik, Hyun-il -- Srivastava, Gyan P -- Raychaudhuri, Soumya -- Hafler, David A -- Koller, Daphne -- Regev, Aviv -- Hacohen, Nir -- Mathis, Diane -- Benoist, Christophe -- Stranger, Barbara E -- De Jager, Philip L -- F32 AG043267/AG/NIA NIH HHS/ -- RC2 GM093080/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 2;344(6183):519-23. doi: 10.1126/science.1249547.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786080" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity/genetics ; Alleles ; Alzheimer Disease/ethnology/genetics ; Autoimmune Diseases/ethnology/*genetics ; Autoimmunity/*genetics ; CD4-Positive T-Lymphocytes/*immunology ; Ethnic Groups/genetics ; Genetic Predisposition to Disease/ethnology/*genetics ; Genome-Wide Association Study ; Humans ; Immunity, Innate/genetics ; Monocytes/*immunology ; Multiple Sclerosis/ethnology/genetics ; Neurodegenerative Diseases/ethnology/*genetics ; Parkinson Disease/ethnology/genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Rheumatic Fever/ethnology/genetics ; Transcriptome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2012-08-17
    Description: Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 (ENO1) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2. Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712624/" 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/PMC3712624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Florian L -- Colla, Simona -- Aquilanti, Elisa -- Manzo, Veronica E -- Genovese, Giannicola -- Lee, Jaclyn -- Eisenson, Daniel -- Narurkar, Rujuta -- Deng, Pingna -- Nezi, Luigi -- Lee, Michelle A -- Hu, Baoli -- Hu, Jian -- Sahin, Ergun -- Ong, Derrick -- Fletcher-Sananikone, Eliot -- Ho, Dennis -- Kwong, Lawrence -- Brennan, Cameron -- Wang, Y Alan -- Chin, Lynda -- DePinho, Ronald A -- 3 P01 CA095616-08S1/CA/NCI NIH HHS/ -- 57006984/Howard Hughes Medical Institute/ -- P01 CA095616/CA/NCI NIH HHS/ -- P01CA95616/CA/NCI NIH HHS/ -- T32-CA009361/CA/NCI NIH HHS/ -- England -- Nature. 2012 Aug 16;488(7411):337-42. doi: 10.1038/nature11331.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895339" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers, Tumor/deficiency/genetics ; Brain Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Chromosomes, Human, Pair 1/genetics ; DNA-Binding Proteins/deficiency/genetics ; Enzyme Inhibitors ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genes, Essential/*genetics ; Genes, Tumor Suppressor ; Glioblastoma/*drug therapy/*genetics/pathology ; Homozygote ; Humans ; Hydroxamic Acids/pharmacology/therapeutic use ; Mice ; Molecular Targeted Therapy/*methods ; Neoplasm Transplantation ; Phosphonoacetic Acid/analogs & derivatives/pharmacology/therapeutic use ; Phosphopyruvate Hydratase/antagonists & inhibitors/deficiency/genetics/metabolism ; RNA, Small Interfering/genetics ; Sequence Deletion/*genetics ; Tumor Suppressor Proteins/deficiency/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2012-09-08
    Description: DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify approximately 2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect approximately 580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721348/" 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/PMC3721348/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thurman, Robert E -- Rynes, Eric -- Humbert, Richard -- Vierstra, Jeff -- Maurano, Matthew T -- Haugen, Eric -- Sheffield, Nathan C -- Stergachis, Andrew B -- Wang, Hao -- Vernot, Benjamin -- Garg, Kavita -- John, Sam -- Sandstrom, Richard -- Bates, Daniel -- Boatman, Lisa -- Canfield, Theresa K -- Diegel, Morgan -- Dunn, Douglas -- Ebersol, Abigail K -- Frum, Tristan -- Giste, Erika -- Johnson, Audra K -- Johnson, Ericka M -- Kutyavin, Tanya -- Lajoie, Bryan -- Lee, Bum-Kyu -- Lee, Kristen -- London, Darin -- Lotakis, Dimitra -- Neph, Shane -- Neri, Fidencio -- Nguyen, Eric D -- Qu, Hongzhu -- Reynolds, Alex P -- Roach, Vaughn -- Safi, Alexias -- Sanchez, Minerva E -- Sanyal, Amartya -- Shafer, Anthony -- Simon, Jeremy M -- Song, Lingyun -- Vong, Shinny -- Weaver, Molly -- Yan, Yongqi -- Zhang, Zhancheng -- Zhang, Zhuzhu -- Lenhard, Boris -- Tewari, Muneesh -- Dorschner, Michael O -- Hansen, R Scott -- Navas, Patrick A -- Stamatoyannopoulos, George -- Iyer, Vishwanath R -- Lieb, Jason D -- Sunyaev, Shamil R -- Akey, Joshua M -- Sabo, Peter J -- Kaul, Rajinder -- Furey, Terrence S -- Dekker, Job -- Crawford, Gregory E -- Stamatoyannopoulos, John A -- F30 DK095678/DK/NIDDK NIH HHS/ -- GM076036/GM/NIGMS NIH HHS/ -- HG004563/HG/NHGRI NIH HHS/ -- HG004592/HG/NHGRI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- MC_UP_1102/1/Medical Research Council/United Kingdom -- P30 CA016086/CA/NCI NIH HHS/ -- R01 GM076036/GM/NIGMS NIH HHS/ -- R01 HG003143/HG/NHGRI NIH HHS/ -- R01 MH084676/MH/NIMH NIH HHS/ -- R01MH084676/MH/NIMH NIH HHS/ -- U54 HG004563/HG/NHGRI NIH HHS/ -- U54 HG004592/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Sep 6;489(7414):75-82. doi: 10.1038/nature11232.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22955617" target="_blank"〉PubMed〈/a〉
    Keywords: Chromatin/*genetics/*metabolism ; DNA/*genetics ; DNA Footprinting ; DNA Methylation ; DNA-Binding Proteins/metabolism ; Deoxyribonuclease I/metabolism ; *Encyclopedias as Topic ; Evolution, Molecular ; Genome, Human/*genetics ; Genomics ; Humans ; *Molecular Sequence Annotation ; Mutation Rate ; Promoter Regions, Genetic/genetics ; Regulatory Sequences, Nucleic Acid/*genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-04-04
    Description: The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105188/" 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/PMC4105188/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Jeremy A -- Ding, Song-Lin -- Sunkin, Susan M -- Smith, Kimberly A -- Ng, Lydia -- Szafer, Aaron -- Ebbert, Amanda -- Riley, Zackery L -- Royall, Joshua J -- Aiona, Kaylynn -- Arnold, James M -- Bennet, Crissa -- Bertagnolli, Darren -- Brouner, Krissy -- Butler, Stephanie -- Caldejon, Shiella -- Carey, Anita -- Cuhaciyan, Christine -- Dalley, Rachel A -- Dee, Nick -- Dolbeare, Tim A -- Facer, Benjamin A C -- Feng, David -- Fliss, Tim P -- Gee, Garrett -- Goldy, Jeff -- Gourley, Lindsey -- Gregor, Benjamin W -- Gu, Guangyu -- Howard, Robert E -- Jochim, Jayson M -- Kuan, Chihchau L -- Lau, Christopher -- Lee, Chang-Kyu -- Lee, Felix -- Lemon, Tracy A -- Lesnar, Phil -- McMurray, Bergen -- Mastan, Naveed -- Mosqueda, Nerick -- Naluai-Cecchini, Theresa -- Ngo, Nhan-Kiet -- Nyhus, Julie -- Oldre, Aaron -- Olson, Eric -- Parente, Jody -- Parker, Patrick D -- Parry, Sheana E -- Stevens, Allison -- Pletikos, Mihovil -- Reding, Melissa -- Roll, Kate -- Sandman, David -- Sarreal, Melaine -- Shapouri, Sheila -- Shapovalova, Nadiya V -- Shen, Elaine H -- Sjoquist, Nathan -- Slaughterbeck, Clifford R -- Smith, Michael -- Sodt, Andy J -- Williams, Derric -- Zollei, Lilla -- Fischl, Bruce -- Gerstein, Mark B -- Geschwind, Daniel H -- Glass, Ian A -- Hawrylycz, Michael J -- Hevner, Robert F -- Huang, Hao -- Jones, Allan R -- Knowles, James A -- Levitt, Pat -- Phillips, John W -- Sestan, Nenad -- Wohnoutka, Paul -- Dang, Chinh -- Bernard, Amy -- Hohmann, John G -- Lein, Ed S -- 5R24HD0008836/HD/NICHD NIH HHS/ -- R00 HD061485/HD/NICHD NIH HHS/ -- R01 MH092535/MH/NIMH NIH HHS/ -- R24 HD000836/HD/NICHD NIH HHS/ -- RC2 MH089921/MH/NIMH NIH HHS/ -- RC2MH089921/MH/NIMH NIH HHS/ -- England -- Nature. 2014 Apr 10;508(7495):199-206. doi: 10.1038/nature13185. Epub 2014 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Allen Institute for Brain Science, Seattle, Washington 98103, USA [2]. ; Allen Institute for Brain Science, Seattle, Washington 98103, USA. ; Division of Genetic Medicine, Department of Pediatrics, University of Washington, 1959 North East Pacific Street, Box 356320, Seattle, Washington 98195, USA. ; 1] Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Computer Science and AI Lab, MIT, Cambridge, Massachusetts 02139, USA. ; Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA. ; Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. ; 1] Program in Computational Biology and Bioinformatics, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA [2] Department of Computer Science, Yale University, New Haven, Connecticut 06520, USA. ; Program in Neurogenetics, Department of Neurology and Semel Institute David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA. ; 1] Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, USA [2] Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington 98105, USA. ; Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas 75390, USA. ; Zilkha Neurogenetic Institute, and Department of Psychiatry, University of Southern California, Los Angeles, California 90033, USA. ; 1] Department of Pediatrics, Children's Hospital, Los Angeles, California 90027, USA [2] Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695229" target="_blank"〉PubMed〈/a〉
    Keywords: Anatomy, Artistic ; Animals ; Atlases as Topic ; Brain/embryology/*metabolism ; Conserved Sequence/genetics ; Fetus/cytology/embryology/*metabolism ; Gene Expression Regulation, Developmental/*genetics ; Gene Regulatory Networks/genetics ; Humans ; Mice ; Neocortex/embryology/metabolism ; Species Specificity ; *Transcriptome
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2014-10-23
    Description: The holotype of Deinocheirus mirificus was collected by the 1965 Polish-Mongolian Palaeontological Expedition at Altan Uul III in the southern Gobi of Mongolia. Because the holotype consists mostly of giant forelimbs (2.4 m in length) with scapulocoracoids, for almost 50 years Deinocheirus has remained one of the most mysterious dinosaurs. The mosaic of ornithomimosaur and non-ornithomimosaur characters in the holotype has made it difficult to resolve the phylogenetic status of Deinocheirus. Here we describe two new specimens of Deinocheirus that were discovered in the Nemegt Formation of Altan Uul IV in 2006 and Bugiin Tsav in 2009. The Bugiin Tsav specimen (MPC-D 100/127) includes a left forelimb clearly identifiable as Deinocheirus and is 6% longer than the holotype. The Altan Uul IV specimen (MPC-D 100/128) is approximately 74% the size of MPC-D 100/127. Cladistic analysis indicates that Deinocheirus is the largest member of the Ornithomimosauria; however, it has many unique skeletal features unknown in other ornithomimosaurs, indicating that Deinocheirus was a heavily built, non-cursorial animal with an elongate snout, a deep jaw, tall neural spines, a pygostyle, a U-shaped furcula, an expanded pelvis for strong muscle attachments, a relatively short hind limb and broad-tipped pedal unguals. Ecomorphological features in the skull, more than a thousand gastroliths, and stomach contents (fish remains) suggest that Deinocheirus was a megaomnivore that lived in mesic environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Yuong-Nam -- Barsbold, Rinchen -- Currie, Philip J -- Kobayashi, Yoshitsugu -- Lee, Hang-Jae -- Godefroit, Pascal -- Escuillie, Francois -- Chinzorig, Tsogtbaatar -- England -- Nature. 2014 Nov 13;515(7526):257-60. doi: 10.1038/nature13874. Epub 2014 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geological Museum, Korea Institute of Geoscience and Mineral Resources, Daejeon 305-350, South Korea. ; Paleontological Center, Mongolian Academy of Sciences, Ulaanbaatar 210-351, Mongolia. ; Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada. ; Hokkaido University Museum, Hokkaido University, Sapporo 060-0810, Japan. ; Earth and History of Life, Royal Belgian Institute of Natural Sciences, Rue Vautier 29, 1000 Bruxelles, Belgium. ; Eldonia, 9 Avenue des Portes Occitanes, 3800 Gannat, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25337880" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Size ; Dinosaurs/*anatomy & histology/*classification ; *Fossils ; Mongolia ; Phylogeny ; Skeleton ; Skull/anatomy & histology ; Spine/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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