ALBERT

Beschreibung: A switchlike response in nuclear factor-kappaB (NF-kappaB) activity implies the existence of a threshold in the NF-kappaB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-kappaB (IkappaB) kinase-beta (IKKbeta) module is a switch mechanism for NF-kappaB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKbeta to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKbeta target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-kappaB in single cells, suggesting that phosphorylation of this residue accounts for the feedback.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinohara, Hisaaki -- Behar, Marcelo -- Inoue, Kentaro -- Hiroshima, Michio -- Yasuda, Tomoharu -- Nagashima, Takeshi -- Kimura, Shuhei -- Sanjo, Hideki -- Maeda, Shiori -- Yumoto, Noriko -- Ki, Sewon -- Akira, Shizuo -- Sako, Yasushi -- Hoffmann, Alexander -- Kurosaki, Tomohiro -- Okada-Hatakeyama, Mariko -- 5R01CA141722/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 May 16;344(6185):760-4. doi: 10.1126/science.1250020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ; Laboratory for Cell Signaling Dynamics, RIKEN Quantitative Biology Center (QBiC), 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan. Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Graduate School of Engineering, Tottori University 4-101, Koyama-minami, Tottori 680-8552, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ; Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833394" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):405-6. doi: 10.1126/science.346.6208.405.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342776" target="_blank"〉PubMed〈/a〉

Beschreibung: Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilhelm, Benjamin G -- Mandad, Sunit -- Truckenbrodt, Sven -- Krohnert, Katharina -- Schafer, Christina -- Rammner, Burkhard -- Koo, Seong Joo -- Classen, Gala A -- Krauss, Michael -- Haucke, Volker -- Urlaub, Henning -- Rizzoli, Silvio O -- New York, N.Y. -- Science. 2014 May 30;344(6187):1023-8. doi: 10.1126/science.1252884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Neurosciences, 37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Molecular Biology, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. ; Leibniz Institut fur Molekulare Pharmakologie, Department of Molecular Pharmacology and Cell Biology, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. Bioanalytics, Department of Clinical Chemistry, University Medical Center Gottingen, 37075 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. srizzol@gwdg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876496" target="_blank"〉PubMed〈/a〉

Beschreibung: The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl(-)-binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wietek, Jonas -- Wiegert, J Simon -- Adeishvili, Nona -- Schneider, Franziska -- Watanabe, Hiroshi -- Tsunoda, Satoshi P -- Vogt, Arend -- Elstner, Marcus -- Oertner, Thomas G -- Hegemann, Peter -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):409-12. doi: 10.1126/science.1249375. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biology, Experimental Biophysics, Humboldt Universitat zu Berlin, D-10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674867" target="_blank"〉PubMed〈/a〉

Beschreibung: Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Benyue -- Chassaing, Benoit -- Shi, Zhenda -- Uchiyama, Robin -- Zhang, Zhan -- Denning, Timothy L -- Crawford, Sue E -- Pruijssers, Andrea J -- Iskarpatyoti, Jason A -- Estes, Mary K -- Dermody, Terence S -- Ouyang, Wenjun -- Williams, Ifor R -- Vijay-Kumar, Matam -- Gewirtz, Andrew T -- AI038296/AI/NIAID NIH HHS/ -- AI080656/AI/NIAID NIH HHS/ -- AI107943/AI/NIAID NIH HHS/ -- DK061417/DK/NIDDK NIH HHS/ -- DK064730/DK/NIDDK NIH HHS/ -- DK56338/DK/NIDDK NIH HHS/ -- R01 AI038296/AI/NIAID NIH HHS/ -- R37 AI038296/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):861-5. doi: 10.1126/science.1256999.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. ; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. ; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA. ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA. Departments of Pediatrics, Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA. ; Department of Immunology, Genentech, South San Francisco, CA, USA. ; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. ; Department of Nutritional Sciences and Medicine, Pennsylvania State University, University Park, PA 16802, USA. ; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. agewirtz@gsu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395539" target="_blank"〉PubMed〈/a〉

Beschreibung: In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000x coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431643/" 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/PMC4431643/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gire, Stephen K -- Goba, Augustine -- Andersen, Kristian G -- Sealfon, Rachel S G -- Park, Daniel J -- Kanneh, Lansana -- Jalloh, Simbirie -- Momoh, Mambu -- Fullah, Mohamed -- Dudas, Gytis -- Wohl, Shirlee -- Moses, Lina M -- Yozwiak, Nathan L -- Winnicki, Sarah -- Matranga, Christian B -- Malboeuf, Christine M -- Qu, James -- Gladden, Adrianne D -- Schaffner, Stephen F -- Yang, Xiao -- Jiang, Pan-Pan -- Nekoui, Mahan -- Colubri, Andres -- Coomber, Moinya Ruth -- Fonnie, Mbalu -- Moigboi, Alex -- Gbakie, Michael -- Kamara, Fatima K -- Tucker, Veronica -- Konuwa, Edwin -- Saffa, Sidiki -- Sellu, Josephine -- Jalloh, Abdul Azziz -- Kovoma, Alice -- Koninga, James -- Mustapha, Ibrahim -- Kargbo, Kandeh -- Foday, Momoh -- Yillah, Mohamed -- Kanneh, Franklyn -- Robert, Willie -- Massally, James L B -- Chapman, Sinead B -- Bochicchio, James -- Murphy, Cheryl -- Nusbaum, Chad -- Young, Sarah -- Birren, Bruce W -- Grant, Donald S -- Scheiffelin, John S -- Lander, Eric S -- Happi, Christian -- Gevao, Sahr M -- Gnirke, Andreas -- Rambaut, Andrew -- Garry, Robert F -- Khan, S Humarr -- Sabeti, Pardis C -- 095831/Wellcome Trust/United Kingdom -- 1DP2OD006514-01/OD/NIH HHS/ -- 1U01HG007480-01/HG/NHGRI NIH HHS/ -- 260864/European Research Council/International -- DP2 OD006514/OD/NIH HHS/ -- GM080177/GM/NIGMS NIH HHS/ -- HHSN272200900049C/AI/NIAID NIH HHS/ -- HHSN272200900049C/PHS HHS/ -- T32 GM080177/GM/NIGMS NIH HHS/ -- U01 HG007480/HG/NHGRI NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U19 AI115589/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1369-72. doi: 10.1126/science.1259657. Epub 2014 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Kenema Government Hospital, Kenema, Sierra Leone. andersen@broadinstitute.org augstgoba@yahoo.com psabeti@oeb.harvard.edu. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. andersen@broadinstitute.org augstgoba@yahoo.com psabeti@oeb.harvard.edu. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Kenema Government Hospital, Kenema, Sierra Leone. ; Kenema Government Hospital, Kenema, Sierra Leone. Eastern Polytechnic College, Kenema, Sierra Leone. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Tulane University Medical Center, New Orleans, LA 70112, USA. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Redeemer's University, Ogun State, Nigeria. ; University of Sierra Leone, Freetown, Sierra Leone. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214632" target="_blank"〉PubMed〈/a〉

Beschreibung: Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390078/" 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/PMC4390078/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Guojie -- Li, Cai -- Li, Qiye -- Li, Bo -- Larkin, Denis M -- Lee, Chul -- Storz, Jay F -- Antunes, Agostinho -- Greenwold, Matthew J -- Meredith, Robert W -- Odeen, Anders -- Cui, Jie -- Zhou, Qi -- Xu, Luohao -- Pan, Hailin -- Wang, Zongji -- Jin, Lijun -- Zhang, Pei -- Hu, Haofu -- Yang, Wei -- Hu, Jiang -- Xiao, Jin -- Yang, Zhikai -- Liu, Yang -- Xie, Qiaolin -- Yu, Hao -- Lian, Jinmin -- Wen, Ping -- Zhang, Fang -- Li, Hui -- Zeng, Yongli -- Xiong, Zijun -- Liu, Shiping -- Zhou, Long -- Huang, Zhiyong -- An, Na -- Wang, Jie -- Zheng, Qiumei -- Xiong, Yingqi -- Wang, Guangbiao -- Wang, Bo -- Wang, Jingjing -- Fan, Yu -- da Fonseca, Rute R -- Alfaro-Nunez, Alonzo -- Schubert, Mikkel -- Orlando, Ludovic -- Mourier, Tobias -- Howard, Jason T -- Ganapathy, Ganeshkumar -- Pfenning, Andreas -- Whitney, Osceola -- Rivas, Miriam V -- Hara, Erina -- Smith, Julia -- Farre, Marta -- Narayan, Jitendra -- Slavov, Gancho -- Romanov, Michael N -- Borges, Rui -- Machado, Joao Paulo -- Khan, Imran -- Springer, Mark S -- Gatesy, John -- Hoffmann, Federico G -- Opazo, Juan C -- Hastad, Olle -- Sawyer, Roger H -- Kim, Heebal -- Kim, Kyu-Won -- Kim, Hyeon Jeong -- Cho, Seoae -- Li, Ning -- Huang, Yinhua -- Bruford, Michael W -- Zhan, Xiangjiang -- Dixon, Andrew -- Bertelsen, Mads F -- Derryberry, Elizabeth -- Warren, Wesley -- Wilson, Richard K -- Li, Shengbin -- Ray, David A -- Green, Richard E -- O'Brien, Stephen J -- Griffin, Darren -- Johnson, Warren E -- Haussler, David -- Ryder, Oliver A -- Willerslev, Eske -- Graves, Gary R -- Alstrom, Per -- Fjeldsa, Jon -- Mindell, David P -- Edwards, Scott V -- Braun, Edward L -- Rahbek, Carsten -- Burt, David W -- Houde, Peter -- Zhang, Yong -- Yang, Huanming -- Wang, Jian -- Avian Genome Consortium -- Jarvis, Erich D -- Gilbert, M Thomas P -- Wang, Jun -- DP1 OD000448/OD/NIH HHS/ -- DP1OD000448/OD/NIH HHS/ -- R01 HL087216/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1311-20. doi: 10.1126/science.1251385. Epub 2014 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. Centre for Social Evolution, Department of Biology, Universitetsparken 15, University of Copenhagen, DK-2100 Copenhagen, Denmark. zhanggj@genomics.cn jarvis@neuro.duke.edu mtpgilbert@gmail.com wangj@genomics.cn. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. ; Royal Veterinary College, University of London, London, UK. ; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Republic of Korea. Cho and Kim Genomics, Seoul National University Research Park, Seoul 151-919, Republic of Korea. ; School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA. ; Centro de Investigacion en Ciencias del Mar y Limnologia (CIMAR)/Centro Interdisciplinar de Investigacao Marinha e Ambiental (CIIMAR), Universidade do Porto, Rua dos Bragas, 177, 4050-123 Porto, Portugal. Departamento de Biologia, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal. ; Department of Biological Sciences, University of South Carolina, Columbia, SC, USA. ; Department of Biology and Molecular Biology, Montclair State University, Montclair, NJ 07043, USA. ; Department of Animal Ecology, Uppsala University, Norbyvagen 18D, S-752 36 Uppsala, Sweden. ; Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857, Singapore. ; Department of Integrative Biology University of California, Berkeley, CA 94720, USA. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. College of Life Sciences, Wuhan University, Wuhan 430072, China. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. BGI Education Center,University of Chinese Academy of Sciences,Shenzhen, 518083, China. ; Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. ; Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, UK. ; School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK. ; Centro de Investigacion en Ciencias del Mar y Limnologia (CIMAR)/Centro Interdisciplinar de Investigacao Marinha e Ambiental (CIIMAR), Universidade do Porto, Rua dos Bragas, 177, 4050-123 Porto, Portugal. Instituto de Ciencias Biomedicas Abel Salazar (ICBAS), Universidade do Porto, Portugal. ; Department of Biology, University of California Riverside, Riverside, CA 92521, USA. ; Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA. Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA. ; Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile. ; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Post Office Box 7011, S-750 07, Uppsala, Sweden. ; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Republic of Korea. Cho and Kim Genomics, Seoul National University Research Park, Seoul 151-919, Republic of Korea. Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea. ; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Republic of Korea. ; Cho and Kim Genomics, Seoul National University Research Park, Seoul 151-919, Republic of Korea. ; State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, China. ; State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, China. College of Animal Science and Technology, China Agricultural University, Beijing 100094, China. ; Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK. ; Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK. Key Lab of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 China. ; International Wildlife Consultants, Carmarthen SA33 5YL, Wales, UK. ; Centre for Zoo and Wild Animal Health, Copenhagen Zoo, Roskildevej 38, DK-2000 Frederiksberg, Denmark. ; Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, LA, USA. Museum of Natural Science, Louisiana State University, Baton Rouge, LA 70803, USA. ; The Genome Institute at Washington University, St. Louis, MO 63108, USA. ; College of Medicine and Forensics, Xi'an Jiaotong University, Xi'an, 710061, China. ; Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA. ; Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA. ; Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia. Nova Southeastern University Oceanographic Center 8000 N Ocean Drive, Dania, FL 33004, USA. ; Smithsonian Conservation Biology Institute, National Zoological Park, 1500 Remount Road, Front Royal, VA 22630, USA. ; Genetics Division, San Diego Zoo Institute for Conservation Research, 15600 San Pasqual Valley Road, Escondido, CA 92027, USA. ; Department of Vertebrate Zoology, MRC-116, National Museum of Natural History, Smithsonian Institution, Post Office Box 37012, Washington, DC 20013-7012, USA. Center for Macroecology, Evolution and Climate, the Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. ; Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China. Swedish Species Information Centre, Swedish University of Agricultural Sciences, Box 7007, SE-750 07 Uppsala, Sweden. ; Center for Macroecology, Evolution and Climate, the Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. ; Department of Biochemistry & Biophysics, University of California, San Francisco, CA 94158, USA. ; Department of Organismic and Evolutionary Biology and Museum of Comparative Zoology, Harvard University, 26 Oxford Street, Cambridge, MA 02138, USA. ; Department of Biology and Genetics Institute, University of Florida, Gainesville, FL 32611, USA. ; Center for Macroecology, Evolution and Climate, the Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. Imperial College London, Grand Challenges in Ecosystems and the Environment Initiative, Silwood Park Campus, Ascot, Berkshire SL5 7PY, UK. ; Division of Genetics and Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, The Roslin Institute Building, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK. ; Department of Biology, New Mexico State University, Box 30001 MSC 3AF, Las Cruces, NM 88003, USA. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. Macau University of Science and Technology, Avenida Wai long, Taipa, Macau 999078, China. ; Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. zhanggj@genomics.cn jarvis@neuro.duke.edu mtpgilbert@gmail.com wangj@genomics.cn. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Trace and Environmental DNA Laboratory, Department of Environment and Agriculture, Curtin University, Perth, Western Australia, 6102, Australia. zhanggj@genomics.cn jarvis@neuro.duke.edu mtpgilbert@gmail.com wangj@genomics.cn. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. Macau University of Science and Technology, Avenida Wai long, Taipa, Macau 999078, China. Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Department of Medicine, University of Hong Kong, Hong Kong. zhanggj@genomics.cn jarvis@neuro.duke.edu mtpgilbert@gmail.com wangj@genomics.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504712" target="_blank"〉PubMed〈/a〉

Beschreibung: Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354858/" 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/PMC4354858/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jianjun -- Fujimoto, Junya -- Zhang, Jianhua -- Wedge, David C -- Song, Xingzhi -- Zhang, Jiexin -- Seth, Sahil -- Chow, Chi-Wan -- Cao, Yu -- Gumbs, Curtis -- Gold, Kathryn A -- Kalhor, Neda -- Little, Latasha -- Mahadeshwar, Harshad -- Moran, Cesar -- Protopopov, Alexei -- Sun, Huandong -- Tang, Jiabin -- Wu, Xifeng -- Ye, Yuanqing -- William, William N -- Lee, J Jack -- Heymach, John V -- Hong, Waun Ki -- Swisher, Stephen -- Wistuba, Ignacio I -- Futreal, P Andrew -- CA016672/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P50 CA070907/CA/NCI NIH HHS/ -- P50CA70907/CA/NCI NIH HHS/ -- T32 CA-009666/CA/NCI NIH HHS/ -- T32 CA009666/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):256-9. doi: 10.1126/science.1256930.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Applied Cancer Science Institute, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Honorary Faculty, Wellcome Trust Sanger Institute, Hinxton, UK CB10 1SA. afutreal@mdanderson.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301631" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woodroffe, Rosie -- Hedges, Simon -- Durant, Sarah -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):389-90. doi: 10.1126/science.345.6195.389-b. Epub 2014 Jul 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Zoology, Zoological Society of London, London, NW1 4RY, UK. rosie.woodroffe@ioz.ac.uk. ; Wildlife Conservation Society, Bronx, NY 10460, USA. ; Institute of Zoology, Zoological Society of London, London, NW1 4RY, UK. Wildlife Conservation Society, Bronx, NY 10460, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061195" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1470-1. doi: 10.1126/science.344.6191.1470.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970076" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woodroffe, Rosie -- Hedges, Simon -- Durant, Sarah M -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):46-8. doi: 10.1126/science.1246251.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Zoology, Regent's Park, London NW1 4RY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700847" target="_blank"〉PubMed〈/a〉

Beschreibung: Neuronal intracellular chloride concentration [Cl(-)](i) is an important determinant of gamma-aminobutyric acid type A (GABA(A)) receptor (GABA(A)R)-mediated inhibition and cytoplasmic volume regulation. Equilibrative cation-chloride cotransporters (CCCs) move Cl(-) across the membrane, but accumulating evidence suggests factors other than the bulk concentrations of transported ions determine [Cl(-)](i). Measurement of [Cl(-)](i) in murine brain slice preparations expressing the transgenic fluorophore Clomeleon demonstrated that cytoplasmic impermeant anions ([A](i)) and polyanionic extracellular matrix glycoproteins ([A](o)) constrain the local [Cl(-)]. CCC inhibition had modest effects on [Cl(-)](i) and neuronal volume, but substantial changes were produced by alterations of the balance between [A](i) and [A](o). Therefore, CCCs are important elements of Cl(-) homeostasis, but local impermeant anions determine the homeostatic set point for [Cl(-)], and hence, neuronal volume and the polarity of local GABA(A)R signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220679/" 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/PMC4220679/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glykys, J -- Dzhala, V -- Egawa, K -- Balena, T -- Saponjian, Y -- Kuchibhotla, K V -- Bacskai, B J -- Kahle, K T -- Zeuthen, T -- Staley, K J -- NS 40109-06/NS/NINDS NIH HHS/ -- R01 EB000768/EB/NIBIB NIH HHS/ -- R01 NS040109/NS/NINDS NIH HHS/ -- R01 NS074772/NS/NINDS NIH HHS/ -- R25 NS065743/NS/NINDS NIH HHS/ -- S10 RR025645/RR/NCRR NIH HHS/ -- U41 RR019703/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):670-5. doi: 10.1126/science.1245423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503855" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kean, Sam -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1457-9. doi: 10.1126/science.343.6178.1457.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24675950" target="_blank"〉PubMed〈/a〉

Beschreibung: Lingham-Soliar questions our interpretation of integumentary structures in the Middle-Late Jurassic ornithischian dinosaur Kulindadromeus as feather-like appendages and alternatively proposes that the compound structures observed around the humerus and femur of Kulindadromeus are support fibers associated with badly degraded scales. We consider this hypothesis highly unlikely because of the taphonomy and morphology of the preserved structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Godefroit, Pascal -- Sinitsa, Sofia M -- Dhouailly, Danielle -- Bolotsky, Yuri L -- Sizov, Alexander V -- McNamara, Maria E -- Benton, Michael J -- Spagna, Paul -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):434. doi: 10.1126/science.1260146.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Directorate, Earth and History of Life, Royal Belgian Institute of Natural Sciences, Rue Vautier 29, B-1000 Brussels, Belgium. pascal.godefroit@naturalsciences.be. ; Institute of Natural Resources, Ecology, and Cryology, 26 Butin Street, 672 014 Chita, Russia. ; UJF-CNRS FRE 3405, AGIM, Universite Joseph Fourier, Site Sante, 38 706 La Tronche, France. ; Institute of Geology and Nature Management, FEB RAS, 1 Relochny Street 675 000, Blagoveschensk, Russia. ; Institute of the Earth Crust, SB RAS, 128 Lermontov Street, 664 033 Irkutsk, Russia. ; School of Biological, Earth, and Environmental Science, University College Cork, Cork, Ireland. School of Earth Sciences, University of Bristol, Bristol BS8 1RJ, UK. ; School of Earth Sciences, University of Bristol, Bristol BS8 1RJ, UK. ; Directorate, Earth and History of Life, Royal Belgian Institute of Natural Sciences, Rue Vautier 29, B-1000 Brussels, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342796" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martin, William F -- Sousa, Filipa L -- Lane, Nick -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1092-3. doi: 10.1126/science.1251653.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Evolution, Heinrich-Heine-Universitat, Universitatsstrasse 1, 40225 Dusseldorf, Germany. bill@hhu.de. ; Institute of Molecular Evolution, Heinrich-Heine-Universitat, Universitatsstrasse 1, 40225 Dusseldorf, Germany. ; Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904143" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koschowitz, Marie-Claire -- Fischer, Christian -- Sander, Martin -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):416-8. doi: 10.1126/science.1258957.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Paleontology, Steinmann Institute for Geology, Mineralogy and Paleontology, University of Bonn, Nussallee 8, 53115 Bonn, Germany. Institute for Zoology and Anthropology, Department of Morphology, Systematics and Evolutionary Biology with Zoological Museum, Georg-August-Universitat Gottingen, Berliner Strasse 28, 37073 Goettingen, Germany. m.koschowitz@uni-bonn.de. ; Institute for Zoology and Anthropology, Department of Morphology, Systematics and Evolutionary Biology with Zoological Museum, Georg-August-Universitat Gottingen, Berliner Strasse 28, 37073 Goettingen, Germany. ; Division of Paleontology, Steinmann Institute for Geology, Mineralogy and Paleontology, University of Bonn, Nussallee 8, 53115 Bonn, Germany. Natural History Museum of Los Angeles County, 900 Exposition Boulevard, Los Angeles, CA 90007, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342783" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pringle, Heather -- New York, N.Y. -- Science. 2014 Feb 28;343(6174):961-3. doi: 10.1126/science.343.6174.961.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24578560" target="_blank"〉PubMed〈/a〉

Beschreibung: Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodopsins (originally cation-conducting) converted into chloride-conducting anion channels. These tools enable fast optical inhibition of action potentials and can be engineered to display step-function kinetics for stable inhibition, outlasting light pulses and for orders-of-magnitude-greater light sensitivity of inhibited cells. The resulting family of proteins defines an approach to more physiological, efficient, and sensitive optogenetic inhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096039/" 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/PMC4096039/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berndt, Andre -- Lee, Soo Yeun -- Ramakrishnan, Charu -- Deisseroth, Karl -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):420-4. doi: 10.1126/science.1252367.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763591" target="_blank"〉PubMed〈/a〉

Beschreibung: The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991565/" 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/PMC3991565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Huixian -- Wang, Chong -- Gregory, Karen J -- Han, Gye Won -- Cho, Hyekyung P -- Xia, Yan -- Niswender, Colleen M -- Katritch, Vsevolod -- Meiler, Jens -- Cherezov, Vadim -- Conn, P Jeffrey -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DK097376/DK/NIDDK NIH HHS/ -- R01 GM080403/GM/NIGMS NIH HHS/ -- R01 GM099842/GM/NIGMS NIH HHS/ -- R01 MH062646/MH/NIMH NIH HHS/ -- R01 MH090192/MH/NIMH NIH HHS/ -- R01 NS031373/NS/NINDS NIH HHS/ -- R21 NS078262/NS/NINDS NIH HHS/ -- R37 NS031373/NS/NINDS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):58-64. doi: 10.1126/science.1249489. Epub 2014 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24603153" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharjee, Yudhijit -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1306-9. doi: 10.1126/science.343.6177.1306.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653017" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kennett, Douglas J -- Asmerom, Yemane -- Kemp, Brian M -- Polyak, Victor -- Bolnick, Deborah A -- Malhi, Ripan S -- Culleton, Brendan J -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):390. doi: 10.1126/science.345.6195.390-a. Epub 2014 Jul 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anthropology and Institutes of Energy and the Environment, Pennsylvania State University, University Park, PA 16802, USA. djk23@psu.edu. ; Department of Earth and Planetary Sciences, University of New Mexico, Albuquerque, NM 87131-0001, USA. ; Department of Anthropology and School of Biological Sciences, Washington State University, Pullman, WA 99164, USA. ; Department of Anthropology and Population Research Center, University of Texas at Austin, Austin, TX 78712, USA. ; Institute of Genomic Biology, University of Illinois, Urbana-Champaign, IL 61801, USA. ; Department of Anthropology and Institutes of Energy and the Environment, Pennsylvania State University, University Park, PA 16802, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061196" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):239. doi: 10.1126/science.343.6168.239.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436399" target="_blank"〉PubMed〈/a〉

Beschreibung: The hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Here, we report the 11-angstrom-resolution cryogenic electron microscopy (cryo-EM) structures of 30-nanometer chromatin fibers reconstituted in the presence of linker histone H1 and with different nucleosome repeat lengths. The structures show a histone H1-dependent left-handed twist of the repeating tetranucleosomal structural units, within which the four nucleosomes zigzag back and forth with a straight linker DNA. The asymmetric binding and the location of histone H1 in chromatin play a role in the formation of the 30-nanometer fiber. Our results provide mechanistic insights into how nucleosomes compact into higher-order chromatin fibers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Feng -- Chen, Ping -- Sun, Dapeng -- Wang, Mingzhu -- Dong, Liping -- Liang, Dan -- Xu, Rui-Ming -- Zhu, Ping -- Li, Guohong -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):376-80. doi: 10.1126/science.1251413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763583" target="_blank"〉PubMed〈/a〉

Beschreibung: Reef-building in metazoans represents an important ecological innovation whereby individuals collectively enhance feeding efficiency and gain protection from competitors and predation. The appearance of metazoan reefs in the fossil record therefore indicates an adaptive response to complex ecological pressures. In the Nama Group, Namibia, we found evidence of reef-building by the earliest known skeletal metazoan, the globally distributed Cloudina, ~548 million years ago. These Cloudina reefs formed open frameworks without a microbial component but with mutual attachment and cementation between individuals. Orientated growth implies a passive suspension-feeding habit into nutrient-rich currents. The characteristics of Cloudina support the view that metazoan reef-building was promoted by the rise of substrate competitors and predators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penny, A M -- Wood, R -- Curtis, A -- Bowyer, F -- Tostevin, R -- Hoffman, K-H -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1504-6. doi: 10.1126/science.1253393.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of GeoSciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JW, UK. a.m.penny@ed.ac.uk. ; School of GeoSciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JW, UK. ; Department of Earth Sciences, University College London, Gower Street, London WC1E 6BT, UK. ; Geological Survey of Namibia, Private Bag 13297, Windhoek, Namibia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970084" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayr, Gerald -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1466. doi: 10.1126/science.346.6216.1466-b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Senckenberg Research Institute and Natural History Museum Frankfurt, Ornithological Section, D-60325 Frankfurt am Main, Germany. gerald.mayr@senckenberg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525236" target="_blank"〉PubMed〈/a〉

Beschreibung: Development of vertebrate embryos involves tightly regulated molecular and cellular processes that progressively instruct proliferating embryonic cells about their identity and behavior. Whereas numerous gene activities have been found to be essential during early embryogenesis, little is known about the minimal conditions and factors that would be sufficient to instruct pluripotent cells to organize the embryo. Here, we show that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Peng-Fei -- Houssin, Nathalie -- Ferri-Lagneau, Karine F -- Thisse, Bernard -- Thisse, Christine -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):87-9. doi: 10.1126/science.1248252.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700857" target="_blank"〉PubMed〈/a〉

Beschreibung: Reported trends in the mean and variability of coastal upwelling in eastern boundary currents have raised concerns about the future of these highly productive and biodiverse marine ecosystems. However, the instrumental records on which these estimates are based are insufficiently long to determine whether such trends exceed preindustrial limits. In the California Current, a 576-year reconstruction of climate variables associated with winter upwelling indicates that variability increased over the latter 20th century to levels equaled only twice during the past 600 years. This modern trend in variance may be unique, because it appears to be driven by an unprecedented succession of extreme, downwelling-favorable, winter climate conditions that profoundly reduce productivity for marine predators of commercial and conservation interest.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Black, Bryan A -- Sydeman, William J -- Frank, David C -- Griffin, Daniel -- Stahle, David W -- Garcia-Reyes, Marisol -- Rykaczewski, Ryan R -- Bograd, Steven J -- Peterson, William T -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1498-502. doi: 10.1126/science.1253209.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX 78373, USA. bryan.black@utexas.edu. ; Farallon Institute for Advanced Ecosystem Research, 101 H Street, Suite Q, Petaluma, CA 94952, USA. ; Swiss Federal Research Institute WSL, Zurcherstrasse 111, CH-8903 Birmensdorf, Switzerland and Oeschger Centre for Climate Change Research, University of Bern, Zahringerstrasse 25, CH-3012 Bern, Switzerland. ; Department of Geology and Geophysics, Woods Hole Oceanographic Institution, 266 Woods Hole Road, Woods Hole, MA 02543, USA. ; Department of Geosciences, University of Arkansas, 216 Ozark Hall, Fayetteville, AR 72701, USA. ; Department of Biological Sciences and Marine Science Program, University of South Carolina, 701 Sumter Street, Columbia, SC 29208, USA. ; Environmental Research Division, Southwest Fisheries Science Center, National Oceanic and Atmospheric Administration (NOAA), 1352 Lighthouse Avenue, Pacific Grove, CA 93950, USA. ; Northwest Fisheries Science Center, Hatfield Marine Science Center, NOAA, 2030 Southeast Marine Science Drive, Newport, OR 97365, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237100" target="_blank"〉PubMed〈/a〉

Beschreibung: Decisions take time if information gradually accumulates to a response threshold, but the neural mechanisms of integration and thresholding are unknown. We characterized a decision process in Drosophila that bears the behavioral signature of evidence accumulation. As stimulus contrast in trained odor discriminations decreased, reaction times increased and perceptual accuracy declined, in quantitative agreement with a drift-diffusion model. FoxP mutants took longer than wild-type flies to form decisions of similar or reduced accuracy, especially in difficult, low-contrast tasks. RNA interference with FoxP expression in alphabeta core Kenyon cells, or the overexpression of a potassium conductance in these neurons, recapitulated the FoxP mutant phenotype. A mushroom body subdomain whose development or function require the transcription factor FoxP thus supports the progression of a decision toward commitment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206523/" 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/PMC4206523/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DasGupta, Shamik -- Ferreira, Clara Howcroft -- Miesenbock, Gero -- 090309/Wellcome Trust/United Kingdom -- G0700888/Medical Research Council/United Kingdom -- G0701225/Medical Research Council/United Kingdom -- R01 DA030601/DA/NIDA NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 May 23;344(6186):901-4. doi: 10.1126/science.1252114.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, OX1 3SR, UK. ; Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, OX1 3SR, UK. gero.miesenboeck@cncb.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855268" target="_blank"〉PubMed〈/a〉

Beschreibung: Sex-specific chromosomes, like the W of most female birds and the Y of male mammals, usually have lost most genes owing to a lack of recombination. We analyze newly available genomes of 17 bird species representing the avian phylogenetic range, and find that more than half of them do not have as fully degenerated W chromosomes as that of chicken. We show that avian sex chromosomes harbor tremendous diversity among species in their composition of pseudoautosomal regions and degree of Z/W differentiation. Punctuated events of shared or lineage-specific recombination suppression have produced a gradient of "evolutionary strata" along the Z chromosome, which initiates from the putative avian sex-determining gene DMRT1 and ends at the pseudoautosomal region. W-linked genes are subject to ongoing functional decay after recombination was suppressed, and the tempo of degeneration slows down in older strata. Overall, we unveil a complex history of avian sex chromosome evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Qi -- Zhang, Jilin -- Bachtrog, Doris -- An, Na -- Huang, Quanfei -- Jarvis, Erich D -- Gilbert, M Thomas P -- Zhang, Guojie -- GM076007/GM/NIGMS NIH HHS/ -- GM093182/GM/NIGMS NIH HHS/ -- R01 GM076007/GM/NIGMS NIH HHS/ -- R01 GM093182/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1246338. doi: 10.1126/science.1246338. Epub 2014 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Biology, University of California, Berkeley, CA94720, USA. zhouqi@berkeley.edu zhanggj@genomics.org.cn. ; China National Genebank, BGI-Shenzhen, Shenzhen, 518083. China. ; Department of Integrative Biology, University of California, Berkeley, CA94720, USA. ; Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Trace and Environmental DNA laboratory, Department of Environment and Agriculture, Curtin University, Perth, Western Australia 6102, Australia. ; China National Genebank, BGI-Shenzhen, Shenzhen, 518083. China. Centre for Social Evolution, Department of Biology, Universitetsparken 15, University of Copenhagen, DK-2100 Copenhagen, Denmark. zhouqi@berkeley.edu zhanggj@genomics.org.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504727" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coley, Phyllis D -- Kursar, Thomas A -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):35-6. doi: 10.1126/science.1248110.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Utah, Salt Lake City, UT 84112, USA, and Smithsonian Tropical Research Institute, Panama City, Panama.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385624" target="_blank"〉PubMed〈/a〉

Beschreibung: Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils' bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280847/" 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/PMC4280847/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sreeramkumar, Vinatha -- Adrover, Jose M -- Ballesteros, Ivan -- Cuartero, Maria Isabel -- Rossaint, Jan -- Bilbao, Izaskun -- Nacher, Maria -- Pitaval, Christophe -- Radovanovic, Irena -- Fukui, Yoshinori -- McEver, Rodger P -- Filippi, Marie-Dominique -- Lizasoain, Ignacio -- Ruiz-Cabello, Jesus -- Zarbock, Alexander -- Moro, Maria A -- Hidalgo, Andres -- HL03463/HL/NHLBI NIH HHS/ -- HL085607/HL/NHLBI NIH HHS/ -- HL090676/HL/NHLBI NIH HHS/ -- P01 HL085607/HL/NHLBI NIH HHS/ -- R01 HL034363/HL/NHLBI NIH HHS/ -- R01 HL090676/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1234-8. doi: 10.1126/science.1256478. Epub 2014 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. ; Unidad de Investigacion Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain. ; Department of Anesthesiology and Critical Care Medicine, University of Munster and Max Planck Institute Munster, Munster, Germany. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Australia. ; Division of Immunogenetics, Department of Immunobiology and Neuroscience, Kyushu University, Japan. ; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. ; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany. ahidalgo@cnic.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477463" target="_blank"〉PubMed〈/a〉

Beschreibung: In 1990, Andrew Bakun proposed that increasing greenhouse gas concentrations would force intensification of upwelling-favorable winds in eastern boundary current systems that contribute substantial services to society. Because there is considerable disagreement about whether contemporary wind trends support Bakun's hypothesis, we performed a meta-analysis of the literature on upwelling-favorable wind intensification. The preponderance of published analyses suggests that winds have intensified in the California, Benguela, and Humboldt upwelling systems and weakened in the Iberian system over time scales ranging up to 60 years; wind change is equivocal in the Canary system. Stronger intensification signals are observed at higher latitudes, consistent with the warming pattern associated with climate change. Overall, reported changes in coastal winds, although subtle and spatially variable, support Bakun's hypothesis of upwelling intensification in eastern boundary current systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sydeman, W J -- Garcia-Reyes, M -- Schoeman, D S -- Rykaczewski, R R -- Thompson, S A -- Black, B A -- Bograd, S J -- New York, N.Y. -- Science. 2014 Jul 4;345(6192):77-80. doi: 10.1126/science.1251635.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. wsydeman@comcast.net. ; Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. ; Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Locked Bag 4, Maroochydore DC, Queensland 4558, Australia. ; Department of Biological Sciences and Marine Science Program, University of South Carolina, 701 Sumter Street, Columbia, SC 29208, USA. ; Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. Climate Impacts Group, University of Washington, Box 355674, Seattle, WA 98195, USA. ; Marine Science Institute, University of Texas, 750 Channel View Drive, Port Aransas, TX 78373, USA. ; Environmental Research Division, National Oceanic and Atmospheric Administration (NOAA) Southwest Fisheries Science Center, 1352 Lighthouse Avenue, Pacific Grove, CA 93950-2097, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24994651" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gramling, Carolyn -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):537. doi: 10.1126/science.346.6209.537.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359946" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gramling, Carolyn -- New York, N.Y. -- Science. 2014 May 2;344(6183):463. doi: 10.1126/science.344.6183.463.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786058" target="_blank"〉PubMed〈/a〉

Beschreibung: Nitrogen (N) is a critical nutrient for plants but is often distributed unevenly in the soil. Plants therefore have evolved a systemic mechanism by which N starvation on one side of the root system leads to a compensatory and increased nitrate uptake on the other side. Here, we study the molecular systems that support perception of N and the long-distance signaling needed to alter root development. Rootlets starved of N secrete small peptides that are translocated to the shoot and received by two leucine-rich repeat receptor kinases (LRR-RKs). Arabidopsis plants deficient in this pathway show growth retardation accompanied with N-deficiency symptoms. Thus, signaling from the root to the shoot helps the plant adapt to fluctuations in local N availability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabata, Ryo -- Sumida, Kumiko -- Yoshii, Tomoaki -- Ohyama, Kentaro -- Shinohara, Hidefumi -- Matsubayashi, Yoshikatsu -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):343-6. doi: 10.1126/science.1257800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. ; Department of Applied Molecular Biosciences, Graduate School of Bio-Agricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. matsu@bio.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324386" target="_blank"〉PubMed〈/a〉

Beschreibung: Proteins that cap the ends of the actin filament are essential regulators of cytoskeleton dynamics. Whereas several proteins cap the rapidly growing barbed end, tropomodulin (Tmod) is the only protein known to cap the slowly growing pointed end. The lack of structural information severely limits our understanding of Tmod's capping mechanism. We describe crystal structures of actin complexes with the unstructured amino-terminal and the leucine-rich repeat carboxy-terminal domains of Tmod. The structures and biochemical analysis of structure-inspired mutants showed that one Tmod molecule interacts with three actin subunits at the pointed end, while also contacting two tropomyosin molecules on each side of the filament. We found that Tmod achieves high-affinity binding through several discrete low-affinity interactions, which suggests a mechanism for controlled subunit exchange at the pointed end.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367809/" 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/PMC4367809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rao, Jampani Nageswara -- Madasu, Yadaiah -- Dominguez, Roberto -- GM-0080/GM/NIGMS NIH HHS/ -- R01 GM073791/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):463-7. doi: 10.1126/science.1256159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. droberto@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061212" target="_blank"〉PubMed〈/a〉

Beschreibung: Pathogens traverse multiple barriers during infection, including cell membranes. We found that during this transition, pathogens carried covalently attached complement C3 into the cell, triggering immediate signaling and effector responses. Sensing of C3 in the cytosol activated mitochondrial antiviral signaling (MAVS)-dependent signaling cascades and induced proinflammatory cytokine secretion. C3 also flagged viruses for rapid proteasomal degradation, preventing their replication. This system could detect both viral and bacterial pathogens but was antagonized by enteroviruses, such as rhinovirus and poliovirus, which cleave C3 using their 3C protease. The antiviral rupintrivir inhibited 3C protease and prevented C3 cleavage, rendering enteroviruses susceptible to intracellular complement sensing. Thus, complement C3 allows cells to detect and disable pathogens that have invaded the cytosol.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172439/" 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/PMC4172439/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tam, Jerry C H -- Bidgood, Susanna R -- McEwan, William A -- James, Leo C -- 281627/European Research Council/International -- MC_U105181010/Medical Research Council/United Kingdom -- U105181010/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1256070. doi: 10.1126/science.1256070. Epub 2014 Sep 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. lcj@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190799" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2014 May 2;344(6183):457-8. doi: 10.1126/science.344.6183.457.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786052" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bar-Peled, Liron -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1191-2. doi: 10.1126/science.aaa1808.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Scripps Research Institute, La Jolla, CA 92122, USA. lironbp@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477447" target="_blank"〉PubMed〈/a〉

Beschreibung: Cushing's syndrome is caused by excess cortisol production from the adrenocortical gland. In corticotropin-independent Cushing's syndrome, the excess cortisol production is primarily attributed to an adrenocortical adenoma, in which the underlying molecular pathogenesis has been poorly understood. We report a hotspot mutation (L206R) in PRKACA, which encodes the catalytic subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), in more than 50% of cases with adrenocortical adenomas associated with corticotropin-independent Cushing's syndrome. The L206R PRKACA mutant abolished its binding to the regulatory subunit of PKA (PRKAR1A) that inhibits catalytic activity of PRKACA, leading to constitutive, cAMP-independent PKA activation. These results highlight the major role of cAMP-independent activation of cAMP/PKA signaling by somatic mutations in corticotropin-independent Cushing's syndrome, providing insights into the diagnosis and therapeutics of this syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sato, Yusuke -- Maekawa, Shigekatsu -- Ishii, Ryohei -- Sanada, Masashi -- Morikawa, Teppei -- Shiraishi, Yuichi -- Yoshida, Kenichi -- Nagata, Yasunobu -- Sato-Otsubo, Aiko -- Yoshizato, Tetsuichi -- Suzuki, Hiromichi -- Shiozawa, Yusuke -- Kataoka, Keisuke -- Kon, Ayana -- Aoki, Kosuke -- Chiba, Kenichi -- Tanaka, Hiroko -- Kume, Haruki -- Miyano, Satoru -- Fukayama, Masashi -- Nureki, Osamu -- Homma, Yukio -- Ogawa, Seishi -- New York, N.Y. -- Science. 2014 May 23;344(6186):917-20. doi: 10.1126/science.1252328.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan. ; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. sogawa-tky@umin.ac.jp homma-uro@umin.ac.jp. ; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. sogawa-tky@umin.ac.jp homma-uro@umin.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855271" target="_blank"〉PubMed〈/a〉

Beschreibung: Transcription factors (TFs) are key players in evolution. Changes affecting their function can yield novel life forms but may also have deleterious effects. Consequently, gene duplication events that release one gene copy from selective pressure are thought to be the common mechanism by which TFs acquire new activities. Here, we show that LEAFY, a major regulator of flower development and cell division in land plants, underwent changes to its DNA binding specificity, even though plant genomes generally contain a single copy of the LEAFY gene. We examined how these changes occurred at the structural level and identify an intermediate LEAFY form in hornworts that appears to adopt all different specificities. This promiscuous intermediate could have smoothed the evolutionary transitions, thereby allowing LEAFY to evolve new binding specificities while remaining a single-copy gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sayou, Camille -- Monniaux, Marie -- Nanao, Max H -- Moyroud, Edwige -- Brockington, Samuel F -- Thevenon, Emmanuel -- Chahtane, Hicham -- Warthmann, Norman -- Melkonian, Michael -- Zhang, Yong -- Wong, Gane Ka-Shu -- Weigel, Detlef -- Parcy, Francois -- Dumas, Renaud -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):645-8. doi: 10.1126/science.1248229. Epub 2014 Jan 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, Laboratoire de Physiologie Cellulaire et Vegetale (LPCV), UMR 5168, 38054 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436181" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferreira, J -- Aragao, L E O C -- Barlow, J -- Barreto, P -- Berenguer, E -- Bustamante, M -- Gardner, T A -- Lees, A C -- Lima, A -- Louzada, J -- Pardini, R -- Parry, L -- Peres, C A -- Pompeu, P S -- Tabarelli, M -- Zuanon, J -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):706-7. doi: 10.1126/science.1260194.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉See the supplementary materials for author af liations. joice.ferreira@embrapa.br. ; See the supplementary materials for author af liations.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25378611" target="_blank"〉PubMed〈/a〉

Beschreibung: Godefroit et al. (Reports, 25 July 2014, p. 451) reported scales and feathers, including "basal plates," in an ornithischian dinosaur. Their arguments against the filaments being collagen fibers are not supported because of a fundamental misinterpretation of such structures and underestimation of their size. The parsimonious explanation is that the filaments are support fibers in association with badly degraded scales and that they do not represent early feather stages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lingham-Soliar, Theagarten -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):434. doi: 10.1126/science.1259983.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nelson Mandela Metropolitan University, Port Elizabeth, South Africa.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342795" target="_blank"〉PubMed〈/a〉

Beschreibung: Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing derepression of PRC2 target genes and developmental perturbations. Similarly, an H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various Drosophila tissues. The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M-containing nucleosomes, and its misregulation in Drosophila results in changes of H3K9 methylation levels and heterochromatic silencing defects. We have established histone lysine-to-methionine mutants as robust in vivo tools for inhibiting methylation pathways that also function as biochemical reagents for capturing site-specific histone-modifying enzymes, thus providing molecular insight into chromatin signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508193/" 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/PMC4508193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herz, Hans-Martin -- Morgan, Marc -- Gao, Xin -- Jackson, Jessica -- Rickels, Ryan -- Swanson, Selene K -- Florens, Laurence -- Washburn, Michael P -- Eissenberg, Joel C -- Shilatifard, Ali -- CA R01CA089455/CA/NCI NIH HHS/ -- R01 CA089455/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1065-70. doi: 10.1126/science.1255104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ; Saint Louis University School of Medicine, Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis, MO, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ash@northwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170156" target="_blank"〉PubMed〈/a〉

Beschreibung: The prevention of fertilization through self-pollination (or pollination by a close relative) in the Brassicaceae plant family is determined by the genotype of the plant at the self-incompatibility locus (S locus). The many alleles at this locus exhibit a dominance hierarchy that determines which of the two allelic specificities of a heterozygous genotype is expressed at the phenotypic level. Here, we uncover the evolution of how at least 17 small RNA (sRNA)-producing loci and their multiple target sites collectively control the dominance hierarchy among alleles within the gene controlling the pollen S-locus phenotype in a self-incompatible Arabidopsis species. Selection has created a dynamic repertoire of sRNA-target interactions by jointly acting on sRNA genes and their target sites, which has resulted in a complex system of regulation among alleles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Durand, Eleonore -- Meheust, Raphael -- Soucaze, Marion -- Goubet, Pauline M -- Gallina, Sophie -- Poux, Celine -- Fobis-Loisy, Isabelle -- Guillon, Eline -- Gaude, Thierry -- Sarazin, Alexis -- Figeac, Martin -- Prat, Elisa -- Marande, William -- Berges, Helene -- Vekemans, Xavier -- Billiard, Sylvain -- Castric, Vincent -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1200-5. doi: 10.1126/science.1259442.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire Genetique et Evolution des Populations Vegetales, CNRS UMR 8198, Universite Lille 1, F-59655 Villeneuve d'Ascq cedex, France. ; Reproduction et Developpement des Plantes, Institut Federatif de Recherche 128, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Universite Claude Bernard Lyon I, Ecole Normale Superieure de Lyon, F-69364 Lyon, Cedex 07, France. ; Department of Biology, Swiss Federal Institute of Technology Zurich, CH-8093 Zurich, Switzerland. ; UDSL Universite Lille 2 Droit et Sante, and Plate-forme de genomique fonctionnelle et structurale IFR-114, F-59000 Lille, France. ; Centre National des Ressources Genomiques Vegetales, INRA UPR 1258, Castanet-Tolosan, France. ; Laboratoire Genetique et Evolution des Populations Vegetales, CNRS UMR 8198, Universite Lille 1, F-59655 Villeneuve d'Ascq cedex, France. vincent.castric@univ-lille1.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477454" target="_blank"〉PubMed〈/a〉

Beschreibung: In theoretical ecology, traditional studies based on dynamical stability and numerical simulations have not found a unified answer to the effect of network architecture on community persistence. Here, we introduce a mathematical framework based on the concept of structural stability to explain such a disparity of results. We investigated the range of conditions necessary for the stable coexistence of all species in mutualistic systems. We show that the apparently contradictory conclusions reached by previous studies arise as a consequence of overseeing either the necessary conditions for persistence or its dependence on model parameterization. We show that observed network architectures maximize the range of conditions for species coexistence. We discuss the applicability of structural stability to study other types of interspecific interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rohr, Rudolf P -- Saavedra, Serguei -- Bascompte, Jordi -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):1253497. doi: 10.1126/science.1253497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. Unit of Ecology and Evolution, Department of Biology, University of Fribourg, Chemin du Musee 10, CH-1700 Fribourg, Switzerland. ; Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. ; Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. bascompte@ebd.csic.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061214" target="_blank"〉PubMed〈/a〉

Beschreibung: We report that the oxytocin-mediated neuroprotective gamma-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naive mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tyzio, Roman -- Nardou, Romain -- Ferrari, Diana C -- Tsintsadze, Timur -- Shahrokhi, Amene -- Eftekhari, Sanaz -- Khalilov, Ilgam -- Tsintsadze, Vera -- Brouchoud, Corinne -- Chazal, Genevieve -- Lemonnier, Eric -- Lozovaya, Natalia -- Burnashev, Nail -- Ben-Ari, Yehezkel -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):675-9. doi: 10.1126/science.1247190.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503856" target="_blank"〉PubMed〈/a〉

Beschreibung: We demonstrate a technique for mapping brain activity that combines molecular specificity and spatial coverage using a neurotransmitter sensor detectable by magnetic resonance imaging (MRI). This molecular functional MRI (fMRI) method yielded time-resolved volumetric measurements of dopamine release evoked by reward-related lateral hypothalamic brain stimulation of rats injected with the neurotransmitter sensor. Peak dopamine concentrations and release rates were observed in the anterior nucleus accumbens core. Substantial dopamine transients were also present in more caudal areas. Dopamine-release amplitudes correlated with the rostrocaudal stimulation coordinate, suggesting participation of hypothalamic circuitry in modulating dopamine responses. This work provides a foundation for development and application of quantitative molecular fMRI techniques targeted toward numerous components of neural physiology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Taekwan -- Cai, Lili X -- Lelyveld, Victor S -- Hai, Aviad -- Jasanoff, Alan -- DP2-OD002114/OD/NIH HHS/ -- R01-DA02899/DA/NIDA NIH HHS/ -- R01-NS076462/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 May 2;344(6183):533-5. doi: 10.1126/science.1249380.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786083" target="_blank"〉PubMed〈/a〉

Beschreibung: A major evolutionary transition to eusociality with reproductive division of labor between queens and workers has arisen independently at least 10 times in the ants, bees, and wasps. Pheromones produced by queens are thought to play a key role in regulating this complex social system, but their evolutionary history remains unknown. Here, we identify the first sterility-inducing queen pheromones in a wasp, bumblebee, and desert ant and synthesize existing data on compounds that characterize female fecundity in 64 species of social insects. Our results show that queen pheromones are strikingly conserved across at least three independent origins of eusociality, with wasps, ants, and some bees all appearing to use nonvolatile, saturated hydrocarbons to advertise fecundity and/or suppress worker reproduction. These results suggest that queen pheromones evolved from conserved signals of solitary ancestors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Oystaeyen, Annette -- Oliveira, Ricardo Caliari -- Holman, Luke -- van Zweden, Jelle S -- Romero, Carmen -- Oi, Cintia A -- d'Ettorre, Patrizia -- Khalesi, Mohammadreza -- Billen, Johan -- Wackers, Felix -- Millar, Jocelyn G -- Wenseleers, Tom -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):287-90. doi: 10.1126/science.1244899.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Socioecology and Social Evolution, Zoological Institute, University of Leuven, Naamsestraat 59-Box 2466, 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436417" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Libby, Eric -- Ratcliff, William C -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):426-7. doi: 10.1126/science.1262053.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Santa Fe Institute, Santa Fe, NM 87501, USA. elibby@santafe.edu. ; School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342789" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117199/" 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/PMC4117199/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosenberg, Susan M -- Queitsch, Christine -- DP1 CA174424/CA/NCI NIH HHS/ -- DP1-CA174424/CA/NCI NIH HHS/ -- DP2 OD008371/OD/NIH HHS/ -- DP2-OD008371/OD/NIH HHS/ -- R01 CA085777/CA/NCI NIH HHS/ -- R01 GM053158/GM/NIGMS NIH HHS/ -- R01-CA85777/CA/NCI NIH HHS/ -- R01-GM53158/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1088-9. doi: 10.1126/science.1247472.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Molecular and Human Genetics, Biochemistry and Molecular Biology, Molecular Virology and Microbiology, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604189" target="_blank"〉PubMed〈/a〉

Beschreibung: Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family of versatile cell recognition molecules, as retrograde signals for elimination of redundant climbing fiber to Purkinje cell synapses in developing mouse cerebellum. Knockdown of Sema3A, a secreted semaphorin, in Purkinje cells or its receptor in climbing fibers accelerated synapse elimination during postnatal day 8 (P8) to P18. Conversely, knockdown of Sema7A, a membrane-anchored semaphorin, in Purkinje cells or either of its two receptors in climbing fibers impaired synapse elimination after P15. The effect of Sema7A involves signaling by metabotropic glutamate receptor 1, a canonical pathway for climbing fiber synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of synapse elimination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uesaka, Naofumi -- Uchigashima, Motokazu -- Mikuni, Takayasu -- Nakazawa, Takanobu -- Nakao, Harumi -- Hirai, Hirokazu -- Aiba, Atsu -- Watanabe, Masahiko -- Kano, Masanobu -- New York, N.Y. -- Science. 2014 May 30;344(6187):1020-3. doi: 10.1126/science.1252514. Epub 2014 May 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. ; Laboratory of Animal Resources, Center for Disease Biology and Integrated Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ; Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. ; Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. mkano-tky@m.u-tokyo.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24831527" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):149. doi: 10.1126/science.346.6206.149-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301593" target="_blank"〉PubMed〈/a〉

Beschreibung: Despite recent advances, the structures of many proteins cannot be determined by electron cryomicroscopy because the individual proteins move during irradiation. This blurs the images so that they cannot be aligned with each other to calculate a three-dimensional density. Much of this movement stems from instabilities in the carbon substrates used to support frozen samples in the microscope. Here we demonstrate a gold specimen support that nearly eliminates substrate motion during irradiation. This increases the subnanometer image contrast such that alpha helices of individual proteins are resolved. With this improvement, we determine the structure of apoferritin, a smooth octahedral shell of alpha-helical subunits that is particularly difficult to solve by electron microscopy. This advance in substrate design will enable the solution of currently intractable protein structures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296556/" 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/PMC4296556/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russo, Christopher J -- Passmore, Lori A -- 261151/European Research Council/International -- MC_U105192715/Medical Research Council/United Kingdom -- U105192715/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1377-80. doi: 10.1126/science.1259530.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. passmore@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504723" target="_blank"〉PubMed〈/a〉

Beschreibung: Human mitochondrial ribosomes are highly divergent from all other known ribosomes and are specialized to exclusively translate membrane proteins. They are linked with hereditary mitochondrial diseases and are often the unintended targets of various clinically useful antibiotics. Using single-particle cryogenic electron microscopy, we have determined the structure of its large subunit to 3.4 angstrom resolution, revealing 48 proteins, 21 of which are specific to mitochondria. The structure unveils an adaptation of the exit tunnel for hydrophobic nascent peptides, extensive remodeling of the central protuberance, including recruitment of mitochondrial valine transfer RNA (tRNA(Val)) to play an integral structural role, and changes in the tRNA binding sites related to the unusual characteristics of mitochondrial tRNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246062/" 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/PMC4246062/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Alan -- Amunts, Alexey -- Bai, Xiao-chen -- Sugimoto, Yoichiro -- Edwards, Patricia C -- Murshudov, Garib -- Scheres, Sjors H W -- Ramakrishnan, V -- 096570/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- MC_UP_A025_1012/Medical Research Council/United Kingdom -- MC_UP_A025_1013/Medical Research Council/United Kingdom -- WT096570/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):718-22. doi: 10.1126/science.1258026. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ramak@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278503" target="_blank"〉PubMed〈/a〉

Beschreibung: Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4Kbeta (PI4KIIIbeta) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIbeta interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIbeta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIbeta to combat malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046302/" 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/PMC4046302/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, John E -- Inglis, Alison J -- Perisic, Olga -- Masson, Glenn R -- McLaughlin, Stephen H -- Rutaganira, Florentine -- Shokat, Kevan M -- Williams, Roger L -- MC_U105184308/Medical Research Council/United Kingdom -- PG/11/109/29247/British Heart Foundation/United Kingdom -- PG11/109/29247/British Heart Foundation/United Kingdom -- R01AI099245/AI/NIAID NIH HHS/ -- T32 GM064337/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. jeburke@uvic.ca rlw@mrc-lmb.cam.ac.uk. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876499" target="_blank"〉PubMed〈/a〉

Beschreibung: Decapentaplegic (Dpp), a Drosophila morphogen signaling protein, transfers directly at synapses made at sites of contact between cells that produce Dpp and cytonemes that extend from recipient cells. The Dpp that cytonemes receive moves together with activated receptors toward the recipient cell body in motile puncta. Genetic loss-of-function conditions for diaphanous, shibire, neuroglian, and capricious perturbed cytonemes by reducing their number or only the synapses they make with cells they target, and reduced cytoneme-mediated transport of Dpp and Dpp signaling. These experiments provide direct evidence that cells use cytonemes to exchange signaling proteins, that cytoneme-based exchange is essential for signaling and normal development, and that morphogen distribution and signaling can be contact-dependent, requiring cytoneme synapses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336149/" 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/PMC4336149/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roy, Sougata -- Huang, Hai -- Liu, Songmei -- Kornberg, Thomas B -- GM030637/GM/NIGMS NIH HHS/ -- K99HL114867/HL/NHLBI NIH HHS/ -- R01 GM030637/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):1244624. doi: 10.1126/science.1244624. Epub 2014 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385607" target="_blank"〉PubMed〈/a〉

Beschreibung: Recent discoveries have highlighted the dramatic evolutionary transformation of massive, ground-dwelling theropod dinosaurs into light, volant birds. Here, we apply Bayesian approaches (originally developed for inferring geographic spread and rates of molecular evolution in viruses) in a different context: to infer size changes and rates of anatomical innovation (across up to 1549 skeletal characters) in fossils. These approaches identify two drivers underlying the dinosaur-bird transition. The theropod lineage directly ancestral to birds undergoes sustained miniaturization across 50 million years and at least 12 consecutive branches (internodes) and evolves skeletal adaptations four times faster than other dinosaurs. The distinct, prolonged phase of miniaturization along the bird stem would have facilitated the evolution of many novelties associated with small body size, such as reorientation of body mass, increased aerial ability, and paedomorphic skulls with reduced snouts but enlarged eyes and brains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Michael S Y -- Cau, Andrea -- Naish, Darren -- Dyke, Gareth J -- New York, N.Y. -- Science. 2014 Aug 1;345(6196):562-6. doi: 10.1126/science.1252243.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Earth Sciences Section, South Australian Museum, North Terrace, Adelaide 5000, Australia. School of Earth and Environmental Sciences, University of Adelaide 5005, Australia. mike.lee@samuseum.sa.gov.au. ; Museo Geologico e Paleontologico "Giovanni Capellini," Via Zamboni 63, 40126 Bologna, Italy. Dipartimento di Scienze Biologiche, Geologiche e Ambientali, Alma Mater Studiorum Universita di Bologna, 40126 Bologna, Italy. ; Ocean and Earth Science, University of Southampton, Southampton SO14 3ZH, UK. ; Ocean and Earth Science, University of Southampton, Southampton SO14 3ZH, UK. MTA-DE Lendulet Behavioural Ecology Research Group, Department of Evolutionary Zoology and Human Biology, University of Debrecen, 4032 Debrecen, Egyetem ter 1, Hungary.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25082702" target="_blank"〉PubMed〈/a〉

Beschreibung: Parenting behaviors, such as the provisioning of food by parents to offspring, are known to be highly responsive to changes in environment. However, we currently know little about how such flexibility affects the ways in which parenting is adapted and evolves in response to environmental variation. This is because few studies quantify how individuals vary in their response to changing environments, especially social environments created by other individuals with which parents interact. Social environmental factors differ from nonsocial factors, such as food availability, because parents and offspring both contribute and respond to the social environment they experience. This interdependence leads to the coevolution of flexible behaviors involved in parenting, which could, paradoxically, constrain the ability of individuals to rapidly adapt to changes in their nonsocial environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Royle, Nick J -- Russell, Andrew F -- Wilson, Alastair J -- BB/G022976/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):776-81. doi: 10.1126/science.1253294. Epub 2014 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Ecology and Conservation, College of Life and Environmental Sciences, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK. n.j.royle@exeter.ac.uk. ; Centre for Ecology and Conservation, College of Life and Environmental Sciences, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124432" target="_blank"〉PubMed〈/a〉

Beschreibung: Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918581/" 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/PMC3918581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murchison, Elizabeth P -- Wedge, David C -- Alexandrov, Ludmil B -- Fu, Beiyuan -- Martincorena, Inigo -- Ning, Zemin -- Tubio, Jose M C -- Werner, Emma I -- Allen, Jan -- De Nardi, Andrigo Barboza -- Donelan, Edward M -- Marino, Gabriele -- Fassati, Ariberto -- Campbell, Peter J -- Yang, Fengtang -- Burt, Austin -- Weiss, Robin A -- Stratton, Michael R -- 088340/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- G0501446/Medical Research Council/United Kingdom -- G0900950/Medical Research Council/United Kingdom -- G9721629/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):437-40. doi: 10.1126/science.1247167.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458646" target="_blank"〉PubMed〈/a〉

Beschreibung: Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Delta(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/" 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/PMC4057431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vallee, Monique -- Vitiello, Sergio -- Bellocchio, Luigi -- Hebert-Chatelain, Etienne -- Monlezun, Stephanie -- Martin-Garcia, Elena -- Kasanetz, Fernando -- Baillie, Gemma L -- Panin, Francesca -- Cathala, Adeline -- Roullot-Lacarriere, Valerie -- Fabre, Sandy -- Hurst, Dow P -- Lynch, Diane L -- Shore, Derek M -- Deroche-Gamonet, Veronique -- Spampinato, Umberto -- Revest, Jean-Michel -- Maldonado, Rafael -- Reggio, Patricia H -- Ross, Ruth A -- Marsicano, Giovanni -- Piazza, Pier Vincenzo -- 260515/European Research Council/International -- DA-003934/DA/NIDA NIH HHS/ -- DA-03672/DA/NIDA NIH HHS/ -- DA-09789/DA/NIDA NIH HHS/ -- K05 DA021358/DA/NIDA NIH HHS/ -- R01 DA003934/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):94-8. doi: 10.1126/science.1243985.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U862, F-33000 Bordeaux, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385629" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cardinale, Bradley -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1098. doi: 10.1126/science.344.6188.1098-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Natural Resources and Environment, University of Michigan, Ann Arbor, MI 48103, USA. bradcard@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904146" target="_blank"〉PubMed〈/a〉

Beschreibung: Motor neurons, which relay neural commands to drive skeletal muscle movements, encompass types ranging from "slow" to "fast," whose biophysical properties govern the timing, gradation, and amplitude of muscle force. Here we identify the noncanonical Notch ligand Delta-like homolog 1 (Dlk1) as a determinant of motor neuron functional diversification. Dlk1, expressed by ~30% of motor neurons, is necessary and sufficient to promote a fast biophysical signature in the mouse and chick. Dlk1 suppresses Notch signaling and activates expression of the K(+) channel subunit Kcng4 to modulate delayed-rectifier currents. Dlk1 inactivation comprehensively shifts motor neurons toward slow biophysical and transcriptome signatures, while abolishing peak force outputs. Our findings provide insights into the development of motor neuron functional diversity and its contribution to the execution of movements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Daniel -- Cherukuri, Pitchaiah -- Henningfeld, Kristine -- Poh, Chor Hoon -- Wittler, Lars -- Grote, Phillip -- Schluter, Oliver -- Schmidt, Jennifer -- Laborda, Jorge -- Bauer, Steven R -- Brownstone, Robert M -- Marquardt, Till -- R01 HD042013/HD/NICHD NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1264-6. doi: 10.1126/science.1246448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Neurobiology Laboratory, European Neuroscience Institute (ENI-G), Grisebachstrasse 5, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626931" target="_blank"〉PubMed〈/a〉

Beschreibung: Ecologists have long sought to understand the factors controlling the structure of savanna vegetation. Using data from 2154 sites in savannas across Africa, Australia, and South America, we found that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal area. However, among continents, the magnitude of these effects varied substantially, so that a single model cannot adequately represent savanna woody biomass across these regions. Historical and environmental differences drive the regional variation in the functional relationships between woody vegetation, fire, and climate. These same differences will determine the regional responses of vegetation to future climates, with implications for global carbon stocks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lehmann, Caroline E R -- Anderson, T Michael -- Sankaran, Mahesh -- Higgins, Steven I -- Archibald, Sally -- Hoffmann, William A -- Hanan, Niall P -- Williams, Richard J -- Fensham, Roderick J -- Felfili, Jeanine -- Hutley, Lindsay B -- Ratnam, Jayashree -- San Jose, Jose -- Montes, Ruben -- Franklin, Don -- Russell-Smith, Jeremy -- Ryan, Casey M -- Durigan, Giselda -- Hiernaux, Pierre -- Haidar, Ricardo -- Bowman, David M J S -- Bond, William J -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):548-52. doi: 10.1126/science.1247355.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Macquarie University, New South Wales 2109, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482480" target="_blank"〉PubMed〈/a〉

Beschreibung: Primordial germ cell (PGC) specification occurs either by induction from pluripotent cells (epigenesis) or by a cell-autonomous mechanism mediated by germ plasm (preformation). Among vertebrates, epigenesis is basal, whereas germ plasm has evolved convergently across lineages and is associated with greater speciation. We compared protein-coding sequences of vertebrate species that employ preformation with their sister taxa that use epigenesis and demonstrate that genes evolve more rapidly in species containing germ plasm. Furthermore, differences in rates of evolution appear to cause phylogenetic incongruence in protein-coding sequence comparisons between vertebrate taxa. Our results support the hypothesis that germ plasm liberates constraints on somatic development and that enhanced evolvability drives the evolution of germ plasm.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Evans, Teri -- Wade, Christopher M -- Chapman, Frank A -- Johnson, Andrew D -- Loose, Matthew -- G1100025/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):200-3. doi: 10.1126/science.1249325.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24723612" target="_blank"〉PubMed〈/a〉

Beschreibung: Adrenal Cushing's syndrome is caused by excess production of glucocorticoid from adrenocortical tumors and hyperplasias, which leads to metabolic disorders. We performed whole-exome sequencing of 49 blood-tumor pairs and RNA sequencing of 44 tumors from cortisol-producing adrenocortical adenomas (ACAs), adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasias (AIMAHs), and adrenocortical oncocytomas (ADOs). We identified a hotspot in the PRKACA gene with a L205R mutation in 69.2% (27 out of 39) of ACAs and validated in 65.5% of a total of 87 ACAs. Our data revealed that the activating L205R mutation, which locates in the P+1 loop of the protein kinase A (PKA) catalytic subunit, promoted PKA substrate phosphorylation and target gene expression. Moreover, we discovered the recurrently mutated gene DOT1L in AIMAHs and CLASP2 in ADOs. Collectively, these data highlight potentially functional mutated genes in adrenal Cushing's syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, Yanan -- He, Minghui -- Gao, Zhibo -- Peng, Ying -- Li, Yanli -- Li, Lin -- Zhou, Weiwei -- Li, Xiangchun -- Zhong, Xu -- Lei, Yiming -- Su, Tingwei -- Wang, Hang -- Jiang, Yiran -- Yang, Lin -- Wei, Wei -- Yang, Xu -- Jiang, Xiuli -- Liu, Li -- He, Juan -- Ye, Junna -- Wei, Qing -- Li, Yingrui -- Wang, Weiqing -- Wang, Jun -- Ning, Guang -- New York, N.Y. -- Science. 2014 May 23;344(6186):913-7. doi: 10.1126/science.1249480. Epub 2014 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. ; BGI-Shanghai, BGI-Shenzhen, Shenzhen, China. ; Department of Pathology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. ; Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. guangning@medmail.com.cn wangj@genomics.org.cn wqingw@hotmail.com. ; BGI-Shanghai, BGI-Shenzhen, Shenzhen, China. Department of Biology, University of Copenhagen, Copenhagen, Denmark. King Abdulaziz University, Jeddah, Saudi Arabia. Macau University of Science and Technology, Macau, China. Department of Medicine, University of Hong Kong, Hong Kong. guangning@medmail.com.cn wangj@genomics.org.cn wqingw@hotmail.com. ; Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), and Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China. guangning@medmail.com.cn wangj@genomics.org.cn wqingw@hotmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700472" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patek, S N -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1448-9. doi: 10.1126/science.1256617.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Duke University, Durham, NC 27708, USA. snp2@duke.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237086" target="_blank"〉PubMed〈/a〉

Beschreibung: It has been assumed that most, if not all, signals regulating early development have been identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence and overproduction of Toddler reduce the movement of mesendodermal cells during zebrafish gastrulation. Local and ubiquitous production of Toddler promote cell movement, suggesting that Toddler is neither an attractant nor a repellent but acts globally as a motogen. Toddler drives internalization of G protein-coupled APJ/Apelin receptors, and activation of APJ/Apelin signaling rescues toddler mutants. These results indicate that Toddler is an activator of APJ/Apelin receptor signaling, promotes gastrulation movements, and might be the first in a series of uncharacterized developmental signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107353/" 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/PMC4107353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pauli, Andrea -- Norris, Megan L -- Valen, Eivind -- Chew, Guo-Liang -- Gagnon, James A -- Zimmerman, Steven -- Mitchell, Andrew -- Ma, Jiao -- Dubrulle, Julien -- Reyon, Deepak -- Tsai, Shengdar Q -- Joung, J Keith -- Saghatelian, Alan -- Schier, Alexander F -- K99 HD076935/HD/NICHD NIH HHS/ -- R01 GM056211/GM/NIGMS NIH HHS/ -- R01 GM102491/GM/NIGMS NIH HHS/ -- R01 HG005111/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):1248636. doi: 10.1126/science.1248636. Epub 2014 Jan 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24407481" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pawar, Samraat -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):383. doi: 10.1126/science.1256466.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berkshire SL5 7PY, U K. s.pawar@imperial.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061191" target="_blank"〉PubMed〈/a〉

Beschreibung: Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATalpha allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033833/" 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/PMC4033833/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Annaluru, Narayana -- Muller, Heloise -- Mitchell, Leslie A -- Ramalingam, Sivaprakash -- Stracquadanio, Giovanni -- Richardson, Sarah M -- Dymond, Jessica S -- Kuang, Zheng -- Scheifele, Lisa Z -- Cooper, Eric M -- Cai, Yizhi -- Zeller, Karen -- Agmon, Neta -- Han, Jeffrey S -- Hadjithomas, Michalis -- Tullman, Jennifer -- Caravelli, Katrina -- Cirelli, Kimberly -- Guo, Zheyuan -- London, Viktoriya -- Yeluru, Apurva -- Murugan, Sindurathy -- Kandavelou, Karthikeyan -- Agier, Nicolas -- Fischer, Gilles -- Yang, Kun -- Martin, J Andrew -- Bilgel, Murat -- Bohutski, Pavlo -- Boulier, Kristin M -- Capaldo, Brian J -- Chang, Joy -- Charoen, Kristie -- Choi, Woo Jin -- Deng, Peter -- DiCarlo, James E -- Doong, Judy -- Dunn, Jessilyn -- Feinberg, Jason I -- Fernandez, Christopher -- Floria, Charlotte E -- Gladowski, David -- Hadidi, Pasha -- Ishizuka, Isabel -- Jabbari, Javaneh -- Lau, Calvin Y L -- Lee, Pablo A -- Li, Sean -- Lin, Denise -- Linder, Matthias E -- Ling, Jonathan -- Liu, Jaime -- Liu, Jonathan -- London, Mariya -- Ma, Henry -- Mao, Jessica -- McDade, Jessica E -- McMillan, Alexandra -- Moore, Aaron M -- Oh, Won Chan -- Ouyang, Yu -- Patel, Ruchi -- Paul, Marina -- Paulsen, Laura C -- Qiu, Judy -- Rhee, Alex -- Rubashkin, Matthew G -- Soh, Ina Y -- Sotuyo, Nathaniel E -- Srinivas, Venkatesh -- Suarez, Allison -- Wong, Andy -- Wong, Remus -- Xie, Wei Rose -- Xu, Yijie -- Yu, Allen T -- Koszul, Romain -- Bader, Joel S -- Boeke, Jef D -- Chandrasegaran, Srinivasan -- 092076/Wellcome Trust/United Kingdom -- GM077291/GM/NIGMS NIH HHS/ -- R01 GM077291/GM/NIGMS NIH HHS/ -- R01 GM090192/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):55-8. doi: 10.1126/science.1249252. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Health Sciences, Johns Hopkins University (JHU) School of Public Health, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674868" target="_blank"〉PubMed〈/a〉

Beschreibung: Integration of evidence over the past decade has revised understandings about the major adaptations underlying the origin and early evolution of the genus Homo. Many features associated with Homo sapiens, including our large linear bodies, elongated hind limbs, large energy-expensive brains, reduced sexual dimorphism, increased carnivory, and unique life history traits, were once thought to have evolved near the origin of the genus in response to heightened aridity and open habitats in Africa. However, recent analyses of fossil, archaeological, and environmental data indicate that such traits did not arise as a single package. Instead, some arose substantially earlier and some later than previously thought. From ~2.5 to 1.5 million years ago, three lineages of early Homo evolved in a context of habitat instability and fragmentation on seasonal, intergenerational, and evolutionary time scales. These contexts gave a selective advantage to traits, such as dietary flexibility and larger body size, that facilitated survival in shifting environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anton, Susan C -- Potts, Richard -- Aiello, Leslie C -- New York, N.Y. -- Science. 2014 Jul 4;345(6192):1236828. doi: 10.1126/science.1236828.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Study of Human Origins, Department of Anthropology, New York University, Rufus D. Smith Hall, 25 Waverly Place, New York, NY 10003, USA. E-mail: susan.anton@nyu.edu. ; Human Origins Program, National Museum of Natural History, Smithsonian Institution, Post Office Box 37012, Washington, DC 20013-7012, USA. E-mail: pottsr@si.edu. ; Wenner-Gren Foundation, 470 Park Avenue South, 8th Floor, New York, NY 10016, USA. E-mail: laiello@wennergren.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24994657" target="_blank"〉PubMed〈/a〉

Beschreibung: Robustness, the maintenance of a character in the presence of genetic change, can help preserve adaptive traits but also may hinder evolvability, the ability to bring forth novel adaptations. We used genotype networks to analyze the binding site repertoires of 193 transcription factors from mice and yeast, providing empirical evidence that robustness and evolvability need not be conflicting properties. Network vertices represent binding sites where two sites are connected if they differ in a single nucleotide. We show that the binding sites of larger genotype networks are not only more robust, but the sequences adjacent to such networks can also bind more transcription factors, thus demonstrating that robustness can facilitate evolvability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Payne, Joshua L -- Wagner, Andreas -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):875-7. doi: 10.1126/science.1249046.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Zurich, Institute of Evolutionary Biology and Environmental Studies, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24558158" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 May 16;344(6185):687-9. doi: 10.1126/science.344.6185.687.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833372" target="_blank"〉PubMed〈/a〉

Beschreibung: Small molecules are useful tools for probing the biological function and therapeutic potential of individual proteins, but achieving selectivity is challenging when the target protein shares structural domains with other proteins. The Bromo and Extra-Terminal (BET) proteins have attracted interest because of their roles in transcriptional regulation, epigenetics, and cancer. The BET bromodomains (protein interaction modules that bind acetyl-lysine) have been targeted by potent small-molecule inhibitors, but these inhibitors lack selectivity for individual family members. We developed an ethyl derivative of an existing small-molecule inhibitor, I-BET/JQ1, and showed that it binds leucine/alanine mutant bromodomains with nanomolar affinity and achieves up to 540-fold selectivity relative to wild-type bromodomains. Cell culture studies showed that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. Expansion of this approach could help identify the individual roles of single BET proteins in human physiology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458378/" 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/PMC4458378/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baud, Matthias G J -- Lin-Shiao, Enrique -- Cardote, Teresa -- Tallant, Cynthia -- Pschibul, Annica -- Chan, Kwok-Ho -- Zengerle, Michael -- Garcia, Jordi R -- Kwan, Terence T-L -- Ferguson, Fleur M -- Ciulli, Alessio -- 097945/Z/11/Z/Wellcome Trust/United Kingdom -- 100476/Z/12/Z/Wellcome Trust/United Kingdom -- BB/G023123/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J001201/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):638-41. doi: 10.1126/science.1249830. Epub 2014 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. a.ciulli@dundee.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25323695" target="_blank"〉PubMed〈/a〉

Beschreibung: The oxygenation of Earth's surface fundamentally altered global biogeochemical cycles and ultimately paved the way for the rise of metazoans at the end of the Proterozoic. However, current estimates for atmospheric oxygen (O2) levels during the billion years leading up to this time vary widely. On the basis of chromium (Cr) isotope data from a suite of Proterozoic sediments from China, Australia, and North America, interpreted in the context of data from similar depositional environments from Phanerozoic time, we find evidence for inhibited oxidation of Cr at Earth's surface in the mid-Proterozoic (1.8 to 0.8 billion years ago). These data suggest that atmospheric O2 levels were at most 0.1% of present atmospheric levels. Direct evidence for such low O2 concentrations in the Proterozoic helps explain the late emergence and diversification of metazoans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Planavsky, Noah J -- Reinhard, Christopher T -- Wang, Xiangli -- Thomson, Danielle -- McGoldrick, Peter -- Rainbird, Robert H -- Johnson, Thomas -- Fischer, Woodward W -- Lyons, Timothy W -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):635-8. doi: 10.1126/science.1258410.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department Geology and Geophysics, Yale University, CT, USA. noah.planavsky@yale.edu chris.reinhard@eas.gatech.edu. ; School of Earth and Atmospheric Sciences, Georgia Institute of Technology, GA, USA. noah.planavsky@yale.edu chris.reinhard@eas.gatech.edu. ; Department Geology and Geophysics, Yale University, CT, USA. Department of Geology, University of Illinois, Champaign, IL, USA. ; Department of Earth Science, Carleton University, Ottawa, ON, Canada. ; Centre for Ore Deposit and Exploration Science, University of Tasmania, TAS, Australia. ; Geological Survey of Canada, Ottawa, ON, Canada. ; Department of Geology, University of Illinois, Champaign, IL, USA. ; Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA, USA. ; Department of Earth Sciences, University of California, Riverside, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359975" target="_blank"〉PubMed〈/a〉

Beschreibung: Animal migrations span the globe, involving immense numbers of individuals from a wide range of taxa. Migrants transport nutrients, energy, and other organisms as they forage and are preyed upon throughout their journeys. These highly predictable, pulsed movements across large spatial scales render migration a potentially powerful yet underappreciated dimension of biodiversity that is intimately embedded within resident communities. We review examples from across the animal kingdom to distill fundamental processes by which migratory animals influence communities and ecosystems, demonstrating that they can uniquely alter energy flow, food-web topology and stability, trophic cascades, and the structure of metacommunities. Given the potential for migration to alter ecological networks worldwide, we suggest an integrative framework through which community dynamics and ecosystem functioning may explicitly consider animal migrations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bauer, S -- Hoye, B J -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):1242552. doi: 10.1126/science.1242552.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bird Migration, Swiss Ornithological Institute, 6204 Sempach, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700862" target="_blank"〉PubMed〈/a〉

Beschreibung: The cloning of the breast cancer susceptibility genes BRCA1 and BRCA2 nearly two decades ago helped set in motion an avalanche of research exploring how genomic information can be optimally applied to identify and clinically care for individuals with a high risk of developing cancer. Genetic testing for mutations in BRCA1, BRCA2, and other breast cancer susceptibility genes has since proved to be a valuable tool for determining eligibility for enhanced screening and prevention strategies, as well as for identifying patients most likely to benefit from a targeted therapy. Here, we discuss the landscape of inherited mutations and sequence variants in BRCA1 and BRCA2, the complexities of determining disease risk when the pathogenicity of sequence variants is uncertain, and current strategies for clinical management of women who carry BRCA1/2 mutations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074902/" 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/PMC4074902/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couch, Fergus J -- Nathanson, Katherine L -- Offit, Kenneth -- 3P30CA008748-47/CA/NCI NIH HHS/ -- CA016520/CA/NCI NIH HHS/ -- CA116167/CA/NCI NIH HHS/ -- CA116201/CA/NCI NIH HHS/ -- CA128978/CA/NCI NIH HHS/ -- CA135509/CA/NCI NIH HHS/ -- P50 CA116201/CA/NCI NIH HHS/ -- R01 CA128978/CA/NCI NIH HHS/ -- R01 CA135509/CA/NCI NIH HHS/ -- U01 CA116167/CA/NCI NIH HHS/ -- U01 CA164947/CA/NCI NIH HHS/ -- U01CA164947/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1466-70. doi: 10.1126/science.1251827.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24675953" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1167-70. doi: 10.1126/science.346.6214.1167.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477439" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimm, David -- New York, N.Y. -- Science. 2014 May 2;344(6183):461. doi: 10.1126/science.344.6183.461.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786056" target="_blank"〉PubMed〈/a〉

Beschreibung: Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six patients with estrogen receptor-positive breast cancer. Three of five CTC lines tested were tumorigenic in mice. Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. Drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture conditions, this strategy may help identify the best therapies for individual cancer patients over the course of their disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358808/" 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/PMC4358808/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Min -- Bardia, Aditya -- Aceto, Nicola -- Bersani, Francesca -- Madden, Marissa W -- Donaldson, Maria C -- Desai, Rushil -- Zhu, Huili -- Comaills, Valentine -- Zheng, Zongli -- Wittner, Ben S -- Stojanov, Petar -- Brachtel, Elena -- Sgroi, Dennis -- Kapur, Ravi -- Shioda, Toshihiro -- Ting, David T -- Ramaswamy, Sridhar -- Getz, Gad -- Iafrate, A John -- Benes, Cyril -- Toner, Mehmet -- Maheswaran, Shyamala -- Haber, Daniel A -- CA129933/CA/NCI NIH HHS/ -- EB008047/EB/NIBIB NIH HHS/ -- P41 EB002503/EB/NIBIB NIH HHS/ -- R01 CA129933/CA/NCI NIH HHS/ -- U01 EB012493/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):216-20. doi: 10.1126/science.1253533.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medical Epidemiology and Biostatistics, Karolinska Insitutet, Stockholm, Sweden. ; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. ; Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. ; Center for Bioengineering in Medicine, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. ; Center for Bioengineering in Medicine, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Harvard Medical School, Charlestown, MA 02129, USA. maheswaran@helix.mgh.harvard.edu haber@helix.mgh.harvard.edu. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA. maheswaran@helix.mgh.harvard.edu haber@helix.mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013076" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):24-7. doi: 10.1126/science.346.6205.24. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278593" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1301. doi: 10.1126/science.343.6177.1301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653015" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):361-3. doi: 10.1126/science.343.6169.361.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458620" target="_blank"〉PubMed〈/a〉

Beschreibung: T cell responses are initiated by antigen and promoted by a range of costimulatory signals. Understanding how T cells integrate alternative signal combinations and make decisions affecting immune response strength or tolerance poses a considerable theoretical challenge. Here, we report that T cell receptor (TCR) and costimulatory signals imprint an early, cell-intrinsic, division fate, whereby cells effectively count through generations before returning automatically to a quiescent state. This autonomous program can be extended by cytokines. Signals from the TCR, costimulatory receptors, and cytokines add together using a linear division calculus, allowing the strength of a T cell response to be predicted from the sum of the underlying signal components. These data resolve a long-standing costimulation paradox and provide a quantitative paradigm for therapeutically manipulating immune response strength.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marchingo, Julia M -- Kan, Andrey -- Sutherland, Robyn M -- Duffy, Ken R -- Wellard, Cameron J -- Belz, Gabrielle T -- Lew, Andrew M -- Dowling, Mark R -- Heinzel, Susanne -- Hodgkin, Philip D -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1123-7. doi: 10.1126/science.1260044.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. ; Hamilton Institute, National University of Ireland, Maynooth, Ireland. ; Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. The Royal Melbourne Hospital, Parkville, VIC, Australia. ; Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. hodgkin@wehi.edu.au.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25430770" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNutt, Marcia -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1289. doi: 10.1126/science.1253412.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marcia McNutt is Editor-in-Chief of Science.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653006" target="_blank"〉PubMed〈/a〉

Beschreibung: The signal recognition particle (SRP) is central to membrane protein targeting; SRP RNA is essential for SRP assembly, elongation arrest, and activation of SRP guanosine triphosphatases. In eukaryotes, SRP function relies on the SRP68-SRP72 heterodimer. We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19. SRP68-RBD is a tetratricopeptide-like module that binds to a RNA three-way junction, bends the RNA, and inserts an alpha-helical arginine-rich motif (ARM) into the major groove. The ARM opens the conserved 5f RNA loop, which in ribosome-bound SRP establishes a contact to ribosomal RNA. Our data provide the structural basis for eukaryote-specific, SRP68-driven RNA remodeling required for protein translocation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grotwinkel, Jan Timo -- Wild, Klemens -- Segnitz, Bernd -- Sinning, Irmgard -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):101-4. doi: 10.1126/science.1249094.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700861" target="_blank"〉PubMed〈/a〉

Beschreibung: Cytoplasmic plant immune receptors recognize specific pathogen effector proteins and initiate effector-triggered immunity. In Arabidopsis, the immune receptors RPS4 and RRS1 are both required to activate defense to three different pathogens. We show that RPS4 and RRS1 physically associate. Crystal structures of the N-terminal Toll-interleukin-1 receptor/resistance (TIR) domains of RPS4 and RRS1, individually and as a heterodimeric complex (respectively at 2.05, 1.75, and 2.65 angstrom resolution), reveal a conserved TIR/TIR interaction interface. We show that TIR domain heterodimerization is required to form a functional RRS1/RPS4 effector recognition complex. The RPS4 TIR domain activates effector-independent defense, which is inhibited by the RRS1 TIR domain through the heterodimerization interface. Thus, RPS4 and RRS1 function as a receptor complex in which the two components play distinct roles in recognition and signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Simon J -- Sohn, Kee Hoon -- Wan, Li -- Bernoux, Maud -- Sarris, Panagiotis F -- Segonzac, Cecile -- Ve, Thomas -- Ma, Yan -- Saucet, Simon B -- Ericsson, Daniel J -- Casey, Lachlan W -- Lonhienne, Thierry -- Winzor, Donald J -- Zhang, Xiaoxiao -- Coerdt, Anne -- Parker, Jane E -- Dodds, Peter N -- Kobe, Bostjan -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):299-303. doi: 10.1126/science.1247357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744375" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- R01 CA154517/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):356-7. doi: 10.1126/science.343.6169.356.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458615" target="_blank"〉PubMed〈/a〉

Beschreibung: N-Methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors, which mediate most excitatory synaptic transmission in mammalian brains. Calcium permeation triggered by activation of NMDA receptors is the pivotal event for initiation of neuronal plasticity. Here, we show the crystal structure of the intact heterotetrameric GluN1-GluN2B NMDA receptor ion channel at 4 angstroms. The NMDA receptors are arranged as a dimer of GluN1-GluN2B heterodimers with the twofold symmetry axis running through the entire molecule composed of an amino terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD). The ATD and LBD are much more highly packed in the NMDA receptors than non-NMDA receptors, which may explain why ATD regulates ion channel activity in NMDA receptors but not in non-NMDA receptors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113085/" 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/PMC4113085/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karakas, Erkan -- Furukawa, Hiro -- MH085926/MH/NIMH NIH HHS/ -- R01 GM105730/GM/NIGMS NIH HHS/ -- R01 MH085926/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):992-7. doi: 10.1126/science.1251915.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, W. M. Keck Structural Biology Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. ; Cold Spring Harbor Laboratory, W. M. Keck Structural Biology Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. furukawa@cshl.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876489" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):532-3. doi: 10.1126/science.346.6209.532.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359943" target="_blank"〉PubMed〈/a〉

Beschreibung: Extensive genomic diversity within coexisting members of a microbial species has been revealed through selected cultured isolates and metagenomic assemblies. Yet, the cell-by-cell genomic composition of wild uncultured populations of co-occurring cells is largely unknown. In this work, we applied large-scale single-cell genomics to study populations of the globally abundant marine cyanobacterium Prochlorococcus. We show that they are composed of hundreds of subpopulations with distinct "genomic backbones," each backbone consisting of a different set of core gene alleles linked to a small distinctive set of flexible genes. These subpopulations are estimated to have diverged at least a few million years ago, suggesting ancient, stable niche partitioning. Such a large set of coexisting subpopulations may be a general feature of free-living bacterial species with huge populations in highly mixed habitats.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kashtan, Nadav -- Roggensack, Sara E -- Rodrigue, Sebastien -- Thompson, Jessie W -- Biller, Steven J -- Coe, Allison -- Ding, Huiming -- Marttinen, Pekka -- Malmstrom, Rex R -- Stocker, Roman -- Follows, Michael J -- Stepanauskas, Ramunas -- Chisholm, Sallie W -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):416-20. doi: 10.1126/science.1248575.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Civil and Environmental Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763590" target="_blank"〉PubMed〈/a〉

Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Aug 8;345(6197):611-3. doi: 10.1126/science.345.6197.611.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25104366" target="_blank"〉PubMed〈/a〉