ALBERT

Beschreibung: Influenza A virus, being responsible for seasonal epidemics and reoccurring pandemics, represents a worldwide threat to public health. High mutation rates facilitate the generation of viral escape mutants, rendering vaccines and drugs directed against virus-encoded targets potentially ineffective. In contrast, targeting host cell determinants temporarily dispensable for the host but crucial for virus replication could prevent viral escape. Here we report the discovery of 287 human host cell genes influencing influenza A virus replication in a genome-wide RNA interference (RNAi) screen. Using an independent assay we confirmed 168 hits (59%) inhibiting either the endemic H1N1 (119 hits) or the current pandemic swine-origin (121 hits) influenza A virus strains, with an overlap of 60%. Notably, a subset of these common hits was also essential for replication of a highly pathogenic avian H5N1 strain. In-depth analyses of several factors provided insights into their infection stage relevance. Notably, SON DNA binding protein (SON) was found to be important for normal trafficking of influenza virions to late endosomes early in infection. We also show that a small molecule inhibitor of CDC-like kinase 1 (CLK1) reduces influenza virus replication by more than two orders of magnitude, an effect connected with impaired splicing of the viral M2 messenger RNA. Furthermore, influenza-virus-infected p27(-/-) (cyclin-dependent kinase inhibitor 1B; Cdkn1b) mice accumulated significantly lower viral titres in the lung, providing in vivo evidence for the importance of this gene. Thus, our results highlight the potency of genome-wide RNAi screening for the dissection of virus-host interactions and the identification of drug targets for a broad range of influenza viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlas, Alexander -- Machuy, Nikolaus -- Shin, Yujin -- Pleissner, Klaus-Peter -- Artarini, Anita -- Heuer, Dagmar -- Becker, Daniel -- Khalil, Hany -- Ogilvie, Lesley A -- Hess, Simone -- Maurer, Andre P -- Muller, Elke -- Wolff, Thorsten -- Rudel, Thomas -- Meyer, Thomas F -- England -- Nature. 2010 Feb 11;463(7282):818-22. doi: 10.1038/nature08760. Epub 2010 Jan 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Department, Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20081832" target="_blank"〉PubMed〈/a〉

Beschreibung: RANK ligand (RANKL), a TNF-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor RANK. Mammary glands of RANK- and RANKL-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of mammary epithelium. It has been shown that RANKL is responsible for the major proliferative response of mouse mammary epithelium to progesterone during mammary lactational morphogenesis, and in mouse models, manipulated to induce activation of the RANK/RANKL pathway in the absence of strict hormonal control, inappropriate mammary proliferation is observed. However, there is no evidence so far of a functional contribution of RANKL to tumorigenesis. Here we show that RANK and RANKL are expressed within normal, pre-malignant and neoplastic mammary epithelium, and using complementary gain-of-function (mouse mammary tumour virus (MMTV)-RANK transgenic mice) and loss-of function (pharmacological inhibition of RANKL) approaches, define a direct contribution of this pathway in mammary tumorigenesis. Accelerated pre-neoplasias and increased mammary tumour formation were observed in MMTV-RANK transgenic mice after multiparity or treatment with carcinogen and hormone (progesterone). Reciprocally, selective pharmacological inhibition of RANKL attenuated mammary tumour development not only in hormone- and carcinogen-treated MMTV-RANK and wild-type mice, but also in the MMTV-neu transgenic spontaneous tumour model. The reduction in tumorigenesis upon RANKL inhibition was preceded by a reduction in pre-neoplasias as well as rapid and sustained reductions in hormone- and carcinogen-induced mammary epithelial proliferation and cyclin D1 levels. Collectively, our results indicate that RANKL inhibition is acting directly on hormone-induced mammary epithelium at early stages in tumorigenesis, and the permissive contribution of progesterone to increased mammary cancer incidence is due to RANKL-dependent proliferative changes in the mammary epithelium. The current study highlights a potential role for RANKL inhibition in the management of proliferative breast disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzalez-Suarez, Eva -- Jacob, Allison P -- Jones, Jon -- Miller, Robert -- Roudier-Meyer, Martine P -- Erwert, Ryan -- Pinkas, Jan -- Branstetter, Dan -- Dougall, William C -- England -- Nature. 2010 Nov 4;468(7320):103-7. doi: 10.1038/nature09495. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Hematology/Oncology Research, Amgen Inc, Seattle, Washington 98119, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881963" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175758/" 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/PMC3175758/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Sean -- Meyer, Tobias -- R01 GM030179/GM/NIGMS NIH HHS/ -- R01 GM030179-24A1/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Sep 16;467(7313):283. doi: 10.1038/467283a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844529" target="_blank"〉PubMed〈/a〉

Beschreibung: Functional and structural brain imaging has identified neural and neurotransmitter systems involved in schizophrenia and their link to cognitive and behavioural disturbances such as psychosis. Mapping such abnormalities in patients, however, cannot fully capture the strong neurodevelopmental component of schizophrenia that pre-dates manifest illness. A recent strategy to address this issue has been to focus on mechanisms of disease risk. Imaging genetics techniques have made it possible to define neural systems that mediate heritable risk linked to candidate and genome-wide-supported common variants, and mechanisms for environmental risk and gene-environment interactions are emerging. Characterizing the neural risk architecture of schizophrenia provides a translational research strategy for future treatments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer-Lindenberg, Andreas -- England -- Nature. 2010 Nov 11;468(7321):194-202. doi: 10.1038/nature09569.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, J5, 68159 Mannheim, Germany. a.meyer-lindenberg@zi-mannheim.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068827" target="_blank"〉PubMed〈/a〉

Beschreibung: Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Green, Richard E -- Krause, Johannes -- Briggs, Adrian W -- Maricic, Tomislav -- Stenzel, Udo -- Kircher, Martin -- Patterson, Nick -- Li, Heng -- Zhai, Weiwei -- Fritz, Markus Hsi-Yang -- Hansen, Nancy F -- Durand, Eric Y -- Malaspinas, Anna-Sapfo -- Jensen, Jeffrey D -- Marques-Bonet, Tomas -- Alkan, Can -- Prufer, Kay -- Meyer, Matthias -- Burbano, Hernan A -- Good, Jeffrey M -- Schultz, Rigo -- Aximu-Petri, Ayinuer -- Butthof, Anne -- Hober, Barbara -- Hoffner, Barbara -- Siegemund, Madlen -- Weihmann, Antje -- Nusbaum, Chad -- Lander, Eric S -- Russ, Carsten -- Novod, Nathaniel -- Affourtit, Jason -- Egholm, Michael -- Verna, Christine -- Rudan, Pavao -- Brajkovic, Dejana -- Kucan, Zeljko -- Gusic, Ivan -- Doronichev, Vladimir B -- Golovanova, Liubov V -- Lalueza-Fox, Carles -- de la Rasilla, Marco -- Fortea, Javier -- Rosas, Antonio -- Schmitz, Ralf W -- Johnson, Philip L F -- Eichler, Evan E -- Falush, Daniel -- Birney, Ewan -- Mullikin, James C -- Slatkin, Montgomery -- Nielsen, Rasmus -- Kelso, Janet -- Lachmann, Michael -- Reich, David -- Paabo, Svante -- GM40282/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 May 7;328(5979):710-22. doi: 10.1126/science.1188021.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolutionary Genetics, Max-Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany. green@eva.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448178" target="_blank"〉PubMed〈/a〉

Beschreibung: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified 〉300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" 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/PMC3235490/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International HIV Controllers Study -- Pereyra, Florencia -- Jia, Xiaoming -- McLaren, Paul J -- Telenti, Amalio -- de Bakker, Paul I W -- Walker, Bruce D -- Ripke, Stephan -- Brumme, Chanson J -- Pulit, Sara L -- Carrington, Mary -- Kadie, Carl M -- Carlson, Jonathan M -- Heckerman, David -- Graham, Robert R -- Plenge, Robert M -- Deeks, Steven G -- Gianniny, Lauren -- Crawford, Gabriel -- Sullivan, Jordan -- Gonzalez, Elena -- Davies, Leela -- Camargo, Amy -- Moore, Jamie M -- Beattie, Nicole -- Gupta, Supriya -- Crenshaw, Andrew -- Burtt, Noel P -- Guiducci, Candace -- Gupta, Namrata -- Gao, Xiaojiang -- Qi, Ying -- Yuki, Yuko -- Piechocka-Trocha, Alicja -- Cutrell, Emily -- Rosenberg, Rachel -- Moss, Kristin L -- Lemay, Paul -- O'Leary, Jessica -- Schaefer, Todd -- Verma, Pranshu -- Toth, Ildiko -- Block, Brian -- Baker, Brett -- Rothchild, Alissa -- Lian, Jeffrey -- Proudfoot, Jacqueline -- Alvino, Donna Marie L -- Vine, Seanna -- Addo, Marylyn M -- Allen, Todd M -- Altfeld, Marcus -- Henn, Matthew R -- Le Gall, Sylvie -- Streeck, Hendrik -- Haas, David W -- Kuritzkes, Daniel R -- Robbins, Gregory K -- Shafer, Robert W -- Gulick, Roy M -- Shikuma, Cecilia M -- Haubrich, Richard -- Riddler, Sharon -- Sax, Paul E -- Daar, Eric S -- Ribaudo, Heather J -- Agan, Brian -- Agarwal, Shanu -- Ahern, Richard L -- Allen, Brady L -- Altidor, Sherly -- Altschuler, Eric L -- Ambardar, Sujata -- Anastos, Kathryn -- Anderson, Ben -- Anderson, Val -- Andrady, Ushan -- Antoniskis, Diana -- Bangsberg, David -- Barbaro, Daniel -- Barrie, William -- Bartczak, J -- Barton, Simon -- Basden, Patricia -- Basgoz, Nesli -- Bazner, Suzane -- Bellos, Nicholaos C -- Benson, Anne M -- Berger, Judith -- Bernard, Nicole F -- Bernard, Annette M -- Birch, Christopher -- Bodner, Stanley J -- Bolan, Robert K -- Boudreaux, Emilie T -- Bradley, Meg -- Braun, James F -- Brndjar, Jon E -- Brown, Stephen J -- Brown, Katherine -- Brown, Sheldon T -- Burack, Jedidiah -- Bush, Larry M -- Cafaro, Virginia -- Campbell, Omobolaji -- Campbell, John -- Carlson, Robert H -- Carmichael, J Kevin -- Casey, Kathleen K -- Cavacuiti, Chris -- Celestin, Gregory -- Chambers, Steven T -- Chez, Nancy -- Chirch, Lisa M -- Cimoch, Paul J -- Cohen, Daniel -- Cohn, Lillian E -- Conway, Brian -- Cooper, David A -- Cornelson, Brian -- Cox, David T -- Cristofano, Michael V -- Cuchural, George Jr -- Czartoski, Julie L -- Dahman, Joseph M -- Daly, Jennifer S -- Davis, Benjamin T -- Davis, Kristine -- Davod, Sheila M -- DeJesus, Edwin -- Dietz, Craig A -- Dunham, Eleanor -- Dunn, Michael E -- Ellerin, Todd B -- Eron, Joseph J -- Fangman, John J W -- Farel, Claire E -- Ferlazzo, Helen -- Fidler, Sarah -- Fleenor-Ford, Anita -- Frankel, Renee -- Freedberg, Kenneth A -- French, Neel K -- Fuchs, Jonathan D -- Fuller, Jon D -- Gaberman, Jonna -- Gallant, Joel E -- Gandhi, Rajesh T -- Garcia, Efrain -- Garmon, Donald -- Gathe, Joseph C Jr -- Gaultier, Cyril R -- Gebre, Wondwoosen -- Gilman, Frank D -- Gilson, Ian -- Goepfert, Paul A -- Gottlieb, Michael S -- Goulston, Claudia -- Groger, Richard K -- Gurley, T Douglas -- Haber, Stuart -- Hardwicke, Robin -- Hardy, W David -- Harrigan, P Richard -- Hawkins, Trevor N -- Heath, Sonya -- Hecht, Frederick M -- Henry, W Keith -- Hladek, Melissa -- Hoffman, Robert P -- Horton, James M -- Hsu, Ricky K -- Huhn, Gregory D -- Hunt, Peter -- Hupert, Mark J -- Illeman, Mark L -- Jaeger, Hans -- Jellinger, Robert M -- John, Mina -- Johnson, Jennifer A -- Johnson, Kristin L -- Johnson, Heather -- Johnson, Kay -- Joly, Jennifer -- Jordan, Wilbert C -- Kauffman, Carol A -- Khanlou, Homayoon -- Killian, Robert K -- Kim, Arthur Y -- Kim, David D -- Kinder, Clifford A -- Kirchner, Jeffrey T -- Kogelman, Laura -- Kojic, Erna Milunka -- Korthuis, P Todd -- Kurisu, Wayne -- Kwon, Douglas S -- LaMar, Melissa -- Lampiris, Harry -- Lanzafame, Massimiliano -- Lederman, Michael M -- Lee, David M -- Lee, Jean M L -- Lee, Marah J -- Lee, Edward T Y -- Lemoine, Janice -- Levy, Jay A -- Llibre, Josep M -- Liguori, Michael A -- Little, Susan J -- Liu, Anne Y -- Lopez, Alvaro J -- Loutfy, Mono R -- Loy, Dawn -- Mohammed, Debbie Y -- Man, Alan -- Mansour, Michael K -- Marconi, Vincent C -- Markowitz, Martin -- Marques, Rui -- Martin, Jeffrey N -- Martin, Harold L Jr -- Mayer, Kenneth Hugh -- McElrath, M Juliana -- McGhee, Theresa A -- McGovern, Barbara H -- McGowan, Katherine -- McIntyre, Dawn -- Mcleod, Gavin X -- Menezes, Prema -- Mesa, Greg -- Metroka, Craig E -- Meyer-Olson, Dirk -- Miller, Andy O -- Montgomery, Kate -- Mounzer, Karam C -- Nagami, Ellen H -- Nagin, Iris -- Nahass, Ronald G -- Nelson, Margret O -- Nielsen, Craig -- Norene, David L -- O'Connor, David H -- Ojikutu, Bisola O -- Okulicz, Jason -- Oladehin, Olakunle O -- Oldfield, Edward C 3rd -- Olender, Susan A -- Ostrowski, Mario -- Owen, William F Jr -- Pae, Eunice -- Parsonnet, Jeffrey -- Pavlatos, Andrew M -- Perlmutter, Aaron M -- Pierce, Michael N -- Pincus, Jonathan M -- Pisani, Leandro -- Price, Lawrence Jay -- Proia, Laurie -- Prokesch, Richard C -- Pujet, Heather Calderon -- Ramgopal, Moti -- Rathod, Almas -- Rausch, Michael -- Ravishankar, J -- Rhame, Frank S -- Richards, Constance Shamuyarira -- Richman, Douglas D -- Rodes, Berta -- Rodriguez, Milagros -- Rose, Richard C 3rd -- Rosenberg, Eric S -- Rosenthal, Daniel -- Ross, Polly E -- Rubin, David S -- Rumbaugh, Elease -- Saenz, Luis -- Salvaggio, Michelle R -- Sanchez, William C -- Sanjana, Veeraf M -- Santiago, Steven -- Schmidt, Wolfgang -- Schuitemaker, Hanneke -- Sestak, Philip M -- Shalit, Peter -- Shay, William -- Shirvani, Vivian N -- Silebi, Vanessa I -- Sizemore, James M Jr -- Skolnik, Paul R -- Sokol-Anderson, Marcia -- Sosman, James M -- Stabile, Paul -- Stapleton, Jack T -- Starrett, Sheree -- Stein, Francine -- Stellbrink, Hans-Jurgen -- Sterman, F Lisa -- Stone, Valerie E -- Stone, David R -- Tambussi, Giuseppe -- Taplitz, Randy A -- Tedaldi, Ellen M -- Theisen, William -- Torres, Richard -- Tosiello, Lorraine -- Tremblay, Cecile -- Tribble, Marc A -- Trinh, Phuong D -- Tsao, Alice -- Ueda, Peggy -- Vaccaro, Anthony -- Valadas, Emilia -- Vanig, Thanes J -- Vecino, Isabel -- Vega, Vilma M -- Veikley, Wenoah -- Wade, Barbara H -- Walworth, Charles -- Wanidworanun, Chingchai -- Ward, Douglas J -- Warner, Daniel A -- Weber, Robert D -- Webster, Duncan -- Weis, Steve -- Wheeler, David A -- White, David J -- Wilkins, Ed -- Winston, Alan -- Wlodaver, Clifford G -- van't Wout, Angelique -- Wright, David P -- Yang, Otto O -- Yurdin, David L -- Zabukovic, Brandon W -- Zachary, Kimon C -- Zeeman, Beth -- Zhao, Meng -- AI030914/AI/NIAID NIH HHS/ -- AI068636/AI/NIAID NIH HHS/ -- AI069415/AI/NIAID NIH HHS/ -- AI069419/AI/NIAID NIH HHS/ -- AI069423/AI/NIAID NIH HHS/ -- AI069424/AI/NIAID NIH HHS/ -- AI069428/AI/NIAID NIH HHS/ -- AI069432/AI/NIAID NIH HHS/ -- AI069434/AI/NIAID NIH HHS/ -- AI069450/AI/NIAID NIH HHS/ -- AI069452/AI/NIAID NIH HHS/ -- AI069465/AI/NIAID NIH HHS/ -- AI069471/AI/NIAID NIH HHS/ -- AI069472/AI/NIAID NIH HHS/ -- AI069474/AI/NIAID NIH HHS/ -- AI069477/AI/NIAID NIH HHS/ -- AI069484/AI/NIAID NIH HHS/ -- AI069495/AI/NIAID NIH HHS/ -- AI069501/AI/NIAID NIH HHS/ -- AI069502/AI/NIAID NIH HHS/ -- AI069511/AI/NIAID NIH HHS/ -- AI069513/AI/NIAID NIH HHS/ -- AI069532/AI/NIAID NIH HHS/ -- AI069556/AI/NIAID NIH HHS/ -- AI077505/AI/NIAID NIH HHS/ -- AI087145/AI/NIAID NIH HHS/ -- AI25859/AI/NIAID NIH HHS/ -- 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NIH HHS/ -- UM1 AI068634/AI/NIAID NIH HHS/ -- UM1 AI068634-06/AI/NIAID NIH HHS/ -- UM1 AI068634-07/AI/NIAID NIH HHS/ -- UM1 AI068636-06/AI/NIAID NIH HHS/ -- UM1 AI068636-07/AI/NIAID NIH HHS/ -- UM1 AI069477/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1551-7. doi: 10.1126/science.1195271. Epub 2010 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051598" target="_blank"〉PubMed〈/a〉

Beschreibung: It is now possible to perform whole-genome shotgun sequencing as well as capture of specific genomic regions for extinct organisms. However, targeted resequencing of large parts of nuclear genomes has yet to be demonstrated for ancient DNA. Here we show that hybridization capture on microarrays can successfully recover more than a megabase of target regions from Neandertal DNA even in the presence of approximately 99.8% microbial DNA. Using this approach, we have sequenced approximately 14,000 protein-coding positions inferred to have changed on the human lineage since the last common ancestor shared with chimpanzees. By generating the sequence of one Neandertal and 50 present-day humans at these positions, we have identified 88 amino acid substitutions that have become fixed in humans since our divergence from the Neandertals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140021/" 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/PMC3140021/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burbano, Hernan A -- Hodges, Emily -- Green, Richard E -- Briggs, Adrian W -- Krause, Johannes -- Meyer, Matthias -- Good, Jeffrey M -- Maricic, Tomislav -- Johnson, Philip L F -- Xuan, Zhenyu -- Rooks, Michelle -- Bhattacharjee, Arindam -- Brizuela, Leonardo -- Albert, Frank W -- de la Rasilla, Marco -- Fortea, Javier -- Rosas, Antonio -- Lachmann, Michael -- Hannon, Gregory J -- Paabo, Svante -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- P01 CA013106-39/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 May 7;328(5979):723-5. doi: 10.1126/science.1188046.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448179" target="_blank"〉PubMed〈/a〉

Beschreibung: We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30x) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617501/" 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/PMC3617501/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, Matthias -- Kircher, Martin -- Gansauge, Marie-Theres -- Li, Heng -- Racimo, Fernando -- Mallick, Swapan -- Schraiber, Joshua G -- Jay, Flora -- Prufer, Kay -- de Filippo, Cesare -- Sudmant, Peter H -- Alkan, Can -- Fu, Qiaomei -- Do, Ron -- Rohland, Nadin -- Tandon, Arti -- Siebauer, Michael -- Green, Richard E -- Bryc, Katarzyna -- Briggs, Adrian W -- Stenzel, Udo -- Dabney, Jesse -- Shendure, Jay -- Kitzman, Jacob -- Hammer, Michael F -- Shunkov, Michael V -- Derevianko, Anatoli P -- Patterson, Nick -- Andres, Aida M -- Eichler, Evan E -- Slatkin, Montgomery -- Reich, David -- Kelso, Janet -- Paabo, Svante -- GM100233/GM/NIGMS NIH HHS/ -- R01 GM040282/GM/NIGMS NIH HHS/ -- R01 GM100233/GM/NIGMS NIH HHS/ -- R01-GM40282/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Oct 12;338(6104):222-6. doi: 10.1126/science.1224344. Epub 2012 Aug 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany. mmeyer@eva.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22936568" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lynch, Sharonann -- Ford, Nathan -- van Cutsem, Gilles -- Bygrave, Helen -- Janssens, Bart -- Decroo, Tom -- Andrieux-Meyer, Isabelle -- Roberts, Teri -- Balkan, Suna -- Casas, Esther -- Ferreyra, Cecilia -- Bemelmans, Marielle -- Cohn, Jen -- Kahn, Patricia -- Goemaere, Eric -- New York, N.Y. -- Science. 2012 Jul 20;337(6092):298-300. doi: 10.1126/science.1225702. Epub 2012 Jul 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medecins Sans Frontieres Access Campaign, New York, NY 10001, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22798404" target="_blank"〉PubMed〈/a〉

Beschreibung: Prenatal infection and exposure to traumatizing experiences during peripuberty have each been associated with increased risk for neuropsychiatric disorders. Evidence is lacking for the cumulative impact of such prenatal and postnatal environmental challenges on brain functions and vulnerability to psychiatric disease. Here, we show in a translational mouse model that combined exposure to prenatal immune challenge and peripubertal stress induces synergistic pathological effects on adult behavioral functions and neurochemistry. We further demonstrate that the prenatal insult markedly increases the vulnerability of the pubescent offspring to brain immune changes in response to stress. Our findings reveal interactions between two adverse environmental factors that have individually been associated with neuropsychiatric disease and support theories that mental illnesses with delayed onsets involve multiple environmental hits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giovanoli, Sandra -- Engler, Harald -- Engler, Andrea -- Richetto, Juliet -- Voget, Mareike -- Willi, Roman -- Winter, Christine -- Riva, Marco A -- Mortensen, Preben B -- Feldon, Joram -- Schedlowski, Manfred -- Meyer, Urs -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1095-9. doi: 10.1126/science.1228261.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physiology and Behavior Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, 8603 Schwerzenbach, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23449593" target="_blank"〉PubMed〈/a〉