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  • United States  (1,832)
  • Rats  (565)
  • Models, Molecular  (526)
  • Protein Structure, Secondary
  • American Association for the Advancement of Science (AAAS)  (3,042)
  • 2015-2019  (206)
  • 2005-2009  (1,477)
  • 1995-1999  (1,359)
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  • 1
    Publication Date: 2016-01-20
    Description: Massive open online courses (MOOCs) are often characterized as remedies to educational disparities related to social class. Using data from 68 MOOCs offered by Harvard and MIT between 2012 and 2014, we found that course participants from the United States tended to live in more-affluent and better-educated neighborhoods than the average U.S. resident. Among those who did register for courses, students with greater socioeconomic resources were more likely to earn a certificate. Furthermore, these differences in MOOC access and completion were larger for adolescents and young adults, the traditional ages where people find on-ramps into science, technology, engineering, and mathematics (STEM) coursework and careers. Our findings raise concerns that MOOCs and similar approaches to online learning can exacerbate rather than reduce disparities in educational outcomes related to socioeconomic status.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, John D -- Reich, Justin -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1245-8. doi: 10.1126/science.aab3782. Epub 2015 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard Graduate School of Education, Harvard University, Cambridge, MA 02138, USA. john_hansen@mail.harvard.edu. ; Office of Digital Learning, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785488" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Career Choice ; Certification/*methods ; Education, Distance/*methods ; Engineering/education ; Humans ; Internet ; Learning ; Mathematics/education ; *Online Systems ; Science/education ; *Social Class ; Students ; Technology/education ; United States ; Young Adult
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1188-90. doi: 10.1126/science.350.6265.1188.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785475" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/blood/genetics/*physiology ; Animals ; Biological Clocks/genetics/*physiology ; Biomarkers/blood/metabolism ; DNA/genetics ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Mice ; Rats ; Telomere Homeostasis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2016-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Claiborne, Anne B -- English, Rebecca A -- Kahn, Jeffrey P -- 10002265/PHS HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):668-70. doi: 10.1126/science.aaf3091. Epub 2016 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Medicine, U.S. National Academies of Sciences, Engineering, and Medicine, Washington, DC 20001, USA. aclaiborne@nas.edu. ; Institute of Medicine, U.S. National Academies of Sciences, Engineering, and Medicine, Washington, DC 20001, USA. ; Johns Hopkins Berman Institute of Bioethics, Johns Hopkins University, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842937" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Ethics, Medical ; *Government Regulation ; Humans ; Mitochondrial Diseases/genetics/*prevention & control ; Mitochondrial Replacement Therapy/*ethics/*standards ; *Oocytes ; United States ; United States Food and Drug Administration ; *Zygote
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Servick, Kelly -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):15. doi: 10.1126/science.351.6268.15.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721984" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; California ; Cell Differentiation ; Clinical Trials as Topic ; Drug Industry ; Embryonic Stem Cells/cytology/*transplantation ; Financing, Organized ; Humans ; Photoreceptor Cells/physiology ; Rats ; Regenerative Medicine/*economics/*trends ; Retina/cytology/physiology ; Stem Cell Research/*economics
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):16-9. doi: 10.1126/science.351.6268.16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721985" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*economics ; Communicable Disease Control/*economics ; Financial Management ; Humans ; National Institutes of Health (U.S.) ; United States ; Vaccines/*economics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shanahan, Jesse -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):418. doi: 10.1126/science.351.6271.418.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jesse Shanahan is a master's student in astronomy at Wesleyan University in Middletown, Connecticut. Send your story to SciCareerEditor@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26798017" target="_blank"〉PubMed〈/a〉
    Keywords: Astronomy/*education ; *Career Mobility ; Disabled Persons/*psychology/statistics & numerical data ; Fear ; *Hostility ; Humans ; Male ; United States
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-02-26
    Description: Hundreds of pathways for degradation converge at ubiquitin recognition by a proteasome. Here, we found that the five known proteasomal ubiquitin receptors in yeast are collectively nonessential for ubiquitin recognition and identified a sixth receptor, Rpn1. A site ( T1: ) in the Rpn1 toroid recognized ubiquitin and ubiquitin-like ( UBL: ) domains of substrate shuttling factors. T1 structures with monoubiquitin or lysine 48 diubiquitin show three neighboring outer helices engaging two ubiquitins. T1 contributes a distinct substrate-binding pathway with preference for lysine 48-linked chains. Proximal to T1 within the Rpn1 toroid is a second UBL-binding site ( T2: ) that assists in ubiquitin chain disassembly, by binding the UBL of deubiquitinating enzyme Ubp6. Thus, a two-site recognition domain intrinsic to the proteasome uses distinct ubiquitin-fold ligands to assemble substrates, shuttling factors, and a deubiquitinating enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Yuan -- Chen, Xiang -- Elsasser, Suzanne -- Stocks, Bradley B -- Tian, Geng -- Lee, Byung-Hoon -- Shi, Yanhong -- Zhang, Naixia -- de Poot, Stefanie A H -- Tuebing, Fabian -- Sun, Shuangwu -- Vannoy, Jacob -- Tarasov, Sergey G -- Engen, John R -- Finley, Daniel -- Walters, Kylie J -- New York, N.Y. -- Science. 2016 Feb 19;351(6275). pii: aad9421. doi: 10.1126/science.aad9421.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. ; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China. ; Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Linganore High School, Frederick, MD 21701, USA. ; Biophysics Resource, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. ; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu. ; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912900" target="_blank"〉PubMed〈/a〉
    Keywords: DNA-Binding Proteins/metabolism ; Endopeptidases/metabolism ; Metabolic Networks and Pathways ; Models, Molecular ; Mutation ; Proteasome Endopeptidase Complex/chemistry/genetics/*metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism ; Ubiquitin-Specific Proteases/metabolism ; Ubiquitination
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  • 8
    Publication Date: 2016-02-26
    Description: Voltage-gated CaV1.2 channels (L-type calcium channel alpha1C subunits) are critical mediators of transcription-dependent neural plasticity. Whether these channels signal via the influx of calcium ion (Ca(2+)), voltage-dependent conformational change (VDeltaC), or a combination of the two has thus far been equivocal. We fused CaV1.2 to a ligand-gated Ca(2+)-permeable channel, enabling independent control of localized Ca(2+) and VDeltaC signals. This revealed an unexpected dual requirement: Ca(2+) must first mobilize actin-bound Ca(2+)/calmodulin-dependent protein kinase II, freeing it for subsequent VDeltaC-mediated accumulation. Neither signal alone sufficed to activate transcription. Signal order was crucial: Efficiency peaked when Ca(2+) preceded VDeltaC by 10 to 20 seconds. CaV1.2 VDeltaC synergistically augmented signaling by N-methyl-d-aspartate receptors. Furthermore, VDeltaC mistuning correlated with autistic symptoms in Timothy syndrome. Thus, nonionic VDeltaC signaling is vital to the function of CaV1.2 in synaptic and neuropsychiatric processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Boxing -- Tadross, Michael R -- Tsien, Richard W -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):863-7. doi: 10.1126/science.aad3647.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience and Physiology and New York University Neuroscience Institute, New York, NY 10016, USA. ; Department of Molecular and Cellular Physiology, Beckman Center, School of Medicine, Stanford University, Stanford, CA 94305, USA. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. tadrossm@janelia.hhmi.org. ; Department of Neuroscience and Physiology and New York University Neuroscience Institute, New York, NY 10016, USA. Department of Molecular and Cellular Physiology, Beckman Center, School of Medicine, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912895" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/genetics/metabolism ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/chemistry/*metabolism ; *Calcium Signaling ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein/metabolism ; *Gene Expression Regulation ; HEK293 Cells ; Hippocampus/cytology ; Humans ; Long QT Syndrome/genetics/metabolism ; Neuronal Plasticity/*genetics ; Neurons/drug effects/*metabolism ; Nimodipine/pharmacology ; Protein Conformation/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism ; Syndactyly/genetics/metabolism
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  • 9
    Publication Date: 2016-04-02
    Description: Global climate change is a major threat to biodiversity. Large-scale analyses have generally focused on the impacts of climate change on the geographic ranges of species and on phenology, the timing of ecological phenomena. We used long-term monitoring of the abundance of breeding birds across Europe and the United States to produce, for both regions, composite population indices for two groups of species: those for which climate suitability has been either improving or declining since 1980. The ratio of these composite indices, the climate impact indicator (CII), reflects the divergent fates of species favored or disadvantaged by climate change. The trend in CII is positive and similar in the two regions. On both continents, interspecific and spatial variation in population abundance trends are well predicted by climate suitability trends.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, Philip A -- Mason, Lucy R -- Green, Rhys E -- Gregory, Richard D -- Sauer, John R -- Alison, Jamie -- Aunins, Ainars -- Brotons, Lluis -- Butchart, Stuart H M -- Campedelli, Tommaso -- Chodkiewicz, Tomasz -- Chylarecki, Przemyslaw -- Crowe, Olivia -- Elts, Jaanus -- Escandell, Virginia -- Foppen, Ruud P B -- Heldbjerg, Henning -- Herrando, Sergi -- Husby, Magne -- Jiguet, Frederic -- Lehikoinen, Aleksi -- Lindstrom, Ake -- Noble, David G -- Paquet, Jean-Yves -- Reif, Jiri -- Sattler, Thomas -- Szep, Tibor -- Teufelbauer, Norbert -- Trautmann, Sven -- van Strien, Arco J -- van Turnhout, Chris A M -- Vorisek, Petr -- Willis, Stephen G -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):84-7. doi: 10.1126/science.aac4858.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Conservation Ecology Group, School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK. ; Royal Society for the Protection of Birds, Centre for Conservation Science, The Lodge, Sandy, Bedfordshire SG19 2DL, UK. ; Royal Society for the Protection of Birds, Centre for Conservation Science, The Lodge, Sandy, Bedfordshire SG19 2DL, UK. Conservation Science Group, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. ; United States Geological Survey, Patuxent Wildlife Research Center, 12100 Beech Forest Road, Laurel, MD 20708, USA. ; Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 3BX, UK. ; Faculty of Biology, University of Latvia, Jelgavas iela 1, Riga, LV-1004, Latvia. ; Center for Mediterranean Forest Research, Centre Tecnologic Forestal de Catalunya, InForest JRU, Solsona 25280, Spain. REAF, Cerdanyola del Valles 08193, Catalonia, Spain. CSIC, Cerdanyola del Valles 08193, Catalonia, Spain. ; Conservation Science Group, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. BirdLife International, The David Attenborough Building, Pembroke Street, Cambridge CB2 3QZ, UK. ; MITO2000 National Committee; c/o Dream Italia, Via Garibaldi 3, 52015, Pratovecchio-Stia, Arezzo, Italy. ; Ogolnopolskie Towarzystwo Ochrony Ptakow, Odrowaza 24,05-270 Marki, Poland. ; Museum and Institute of Zoology, Polish Academy of Sciences, Wilcza 64, 00-679 Warszawa, Poland. ; BirdWatch Ireland, Unit 20 Block D Bullford Business Campus, Kilcoole, County Wicklow, Ireland. ; Institute of Ecology and Earth Sciences, University of Tartu, Vanemuise Street 46, 51014 Tartu, Estonia. Estonian Ornithological Society, Veski 4, 51005 Tartu, Estonia. ; Sociedad Espanola de Ornitologia/BirdLife Melquiades Biencinto, 34, 28053 Madrid. Spain. ; European Bird Census Council, Post Office Box 6521, 6503 GA Nijmegen, Netherlands. Sovon Dutch Centre for Field Ornithology, Post Office Box 6521, 6503 GA Nijmegen, Netherlands. Department of Animal Ecology and Ecophysiology, Institute for Water and Wetland Research, Radboud University, Post Office Box 9010, 6500 GL Nijmegen, Netherlands. ; Dansk Ornitologisk Forening-BirdLife Denmark and University of Aarhus, Vesterbrogade 140, 1620 Kobenhavn V, Denmark. ; European Bird Census Council-Catalan Ornithological Institute, Natural History Museum of Barcelona, Placa Leonardo da Vinci 4-5, 08019 Barcelona, Catalonia, Spain. ; Section for Science, Nord University, 7600 Levanger, Norway. ; UMR7204 Sorbonne Universites-MNHN-CNRS-UPMC, CESCO, CRBPO, CP 135, 43 Rue Buffon, 75005 Paris, France. ; The Helsinki Lab of Ornithology, Finnish Museum of Natural History, Post Office Box 17, 00014 University of Helsinki, Finland. ; Biodiversity Unit, Department of Biology, Lund University, Ecology Building, S-223 62 Lund, Sweden. ; The British Trust for Ornithology, The Nunnery, Thetford, Norfolk IP24 2PU, UK. ; Natagora, Departement Etudes, Rue Nanon 98, B-5000 Namur, Belgium. ; Institute for Environmental Studies, Faculty of Science, Charles University in Prague, Czech Republic. Department of Zoology and Laboratory of Ornithology, Faculty of Science, Palacky University Olomouc, 17 Listopadu 50, 771 43 Olomouc, Czech Republic. ; Swiss Ornithological Institute, Seerose 1, 6204 Sempach, Switzerland. ; Institute of Environmental Sciences, University of Nyiregyhaza, Sostoi ut 31/b, 4400 Nyiregyhaza, Hungary. ; BirdLife Austria, Museumsplatz 1/10/8, A-1070 Vienna, Austria. ; Dachverband Deutscher Avifaunisten e.V. (Federation of German Avifaunists), An den Speichern 6, D-48157 Munster, Germany. ; Statistics Netherlands, Post Office Box 24500, 2490 HA The Hague, Netherlands. ; Sovon Dutch Centre for Field Ornithology, Post Office Box 6521, 6503 GA Nijmegen, Netherlands. Department of Animal Ecology and Ecophysiology, Institute for Water and Wetland Research, Radboud University, Post Office Box 9010, 6500 GL Nijmegen, Netherlands. ; Department of Zoology and Laboratory of Ornithology, Faculty of Science, Palacky University Olomouc, 17 Listopadu 50, 771 43 Olomouc, Czech Republic. Pan-European Common Bird Monitoring Scheme, Czech Society for Ornithology, Na Belidle 252/34, CZ-15000 Prague 5, Czech Republic.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034371" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration ; Animals ; Biodiversity ; *Birds ; Breeding ; *Climate Change ; Ecological Parameter Monitoring ; Europe ; Population Dynamics ; United States
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, Richard -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1138-40. doi: 10.1126/science.351.6278.1138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965605" target="_blank"〉PubMed〈/a〉
    Keywords: Computer Simulation ; *Explosions ; *Forensic Sciences ; Humans ; *Nuclear Weapons ; United States
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNutt, Marcia -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):641. doi: 10.1126/science.aaf4014. Epub 2016 Feb 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marcia McNutt Editor-in-Chief Science Journals.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912832" target="_blank"〉PubMed〈/a〉
    Keywords: Corrosion ; Federal Government ; Humans ; Michigan ; *Public Health ; Safety/*economics ; Trust ; United States ; United States Environmental Protection Agency ; Water Supply/*economics
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  • 12
    Publication Date: 2016-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fahlgren, Noah -- Bart, Rebecca -- Herrera-Estrella, Luis -- Rellan-Alvarez, Ruben -- Chitwood, Daniel H -- Dinneny, Jose R -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):824. doi: 10.1126/science.351.6275.824-a. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donald Danforth Plant Science Center, St. Louis, MO 63132, USA. ; Nacional de Genomica para la Biodiversidad, Irapuato, 36821, Mexico. ; Donald Danforth Plant Science Center, St. Louis, MO 63132, USA. jdinneny@carnegiescience.edu dchitwood@danforthcenter.org. ; Carnegie Institution for Science, Stanford, CA 94305, USA. jdinneny@carnegiescience.edu dchitwood@danforthcenter.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912883" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Food, Genetically Modified/*adverse effects ; Genetic Engineering/*utilization ; Health ; Humans ; Plants, Genetically Modified/*adverse effects/genetics ; United States ; Zea mays/genetics
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  • 13
    Publication Date: 2016-01-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2016 Jan 8;351(6269):115. doi: 10.1126/science.351.6269.115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26744390" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; Financing, Organized/*statistics & numerical data ; Humans ; Research Personnel ; Research Support as Topic/*statistics & numerical data ; *Sexism ; United States ; *Women, Working
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):10-1. doi: 10.1126/science.351.6268.10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉With reporting from Science's news staff.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721980" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; Budgets ; Humans ; National Institutes of Health (U.S.)/*economics ; *Research Support as Topic ; United States ; United States National Aeronautics and Space Administration/economics
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):277-8. doi: 10.1126/science.352.6283.277.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081045" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Brain ; *Datasets as Topic ; European Union ; Humans ; International Cooperation ; Neurosciences/*trends ; United States
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  • 16
    Publication Date: 2016-01-02
    Description: Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772156/" 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/PMC4772156/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferenczi, Emily A -- Zalocusky, Kelly A -- Liston, Conor -- Grosenick, Logan -- Warden, Melissa R -- Amatya, Debha -- Katovich, Kiefer -- Mehta, Hershel -- Patenaude, Brian -- Ramakrishnan, Charu -- Kalanithi, Paul -- Etkin, Amit -- Knutson, Brian -- Glover, Gary H -- Deisseroth, Karl -- 1F31MH105151_01/MH/NIMH NIH HHS/ -- P41 EB015891/EB/NIBIB NIH HHS/ -- R00 MH097822/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):aac9698. doi: 10.1126/science.aac9698.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Neurosciences Program, Stanford University, Stanford, CA 94305, USA. ; Brain Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA. ; Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA. ; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. ; Department of Psychology, Stanford University, Stanford, CA 94305, USA. ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA. ; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA. ; Department of Radiology, Stanford University, Stanford, CA, 94305, USA. ; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA. deissero@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26722001" target="_blank"〉PubMed〈/a〉
    Keywords: Anhedonia/*physiology ; Animals ; Brain Mapping ; Corpus Striatum/cytology/drug effects/*physiology ; Depressive Disorder/physiopathology ; Dopamine/pharmacology ; Dopaminergic Neurons/drug effects/*physiology ; Female ; Magnetic Resonance Imaging ; Male ; Mesencephalon/cytology/drug effects/physiology ; *Motivation ; Nerve Net/physiology ; Oxygen/blood ; Prefrontal Cortex/cytology/drug effects/*physiology ; Rats ; Rats, Inbred LEC ; Rats, Sprague-Dawley ; *Reward ; Schizophrenia/physiopathology
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  • 17
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Varmus, Harold -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):123. doi: 10.1126/science.aaf7301.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harold Varmus is the Lewis Thomas University Professor at the Meyer Cancer Center, Weill Cornell Medicine, New York, NY; Senior Associate Member of the New York Genome Center, New York, NY; and former director of the U.S. National Cancer Institute. varmus@med.cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27124426" target="_blank"〉PubMed〈/a〉
    Keywords: Federal Government ; Humans ; Information Dissemination ; *Leadership ; Medical Oncology/economics/*trends ; Neoplasms/diagnosis/drug therapy/prevention & control ; United States
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  • 18
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fu, He -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):486. doi: 10.1126/science.352.6284.486.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉He Fu is a Ph.D. candidate in the Department of Microbiology at the University of Illinois, Urbana-Champaign. For more on life and careers, visit sciencecareers.org. Send your story to SciCareerEditor@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102487" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; China ; *International Educational Exchange ; Microbiology/*education ; United States
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  • 19
    Publication Date: 2016-03-19
    Description: Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme alpha/beta hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Melissa R -- Mannowetz, Nadja -- Iavarone, Anthony T -- Safavi, Rojin -- Gracheva, Elena O -- Smith, James F -- Hill, Rose Z -- Bautista, Diana M -- Kirichok, Yuriy -- Lishko, Polina V -- 1S10OD020062-01/OD/NIH HHS/ -- R01 AR059385/AR/NIAMS NIH HHS/ -- R01AR059385/AR/NIAMS NIH HHS/ -- R01GM111802/GM/NIGMS NIH HHS/ -- R01HD068914/HD/NICHD NIH HHS/ -- R21HD081403/HD/NICHD NIH HHS/ -- S10RR025622/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):555-9. doi: 10.1126/science.aad6887. Epub 2016 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; QB3/Chemistry Mass Spectrometry Facility, University of California, Berkeley, CA 94720, USA. ; Department of Cellular and Molecular Physiology; Department of Neuroscience, Program in Cellular Neuroscience, Neurodegeneration, and Repair (CNNR), Yale School of Medicine, Yale University, New Haven, CT 06536, USA. ; Department of Urology, University of California, San Francisco, CA 94143, USA. ; Department of Physiology, University of California, San Francisco, CA 94158, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. lishko@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989199" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Arachidonic Acids/*deficiency ; Calcium/metabolism ; Calcium Channels/metabolism ; Calcium Signaling ; Cell Membrane/metabolism ; Endocannabinoids/*deficiency ; Fertilization ; Glycerides/*deficiency ; Humans ; Hydrolases/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Progesterone/*metabolism/pharmacology ; Rats ; Rats, Wistar ; Receptors, Progesterone/genetics/*metabolism ; Sperm Motility/drug effects/*physiology ; Spermatozoa/drug effects/metabolism/*physiology ; Young Adult
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: Secreted and integral membrane proteins compose up to one-third of the biological proteome. These proteins contain hydrophobic signals that direct their translocation across or insertion into the lipid bilayer by the Sec61 protein-conducting channel. The molecular basis of how hydrophobic signals within a nascent polypeptide trigger channel opening is not understood. Here, we used cryo-electron microscopy to determine the structure of an active Sec61 channel that has been opened by a signal sequence. The signal supplants helix 2 of Sec61alpha, which triggers a rotation that opens the central pore both axially across the membrane and laterally toward the lipid bilayer. Comparisons with structures of Sec61 in other states suggest a pathway for how hydrophobic signals engage the channel to gain access to the lipid bilayer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700591/" 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/PMC4700591/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Voorhees, Rebecca M -- Hegde, Ramanujan S -- MC_UP_A022_1007/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):88-91. doi: 10.1126/science.aad4992.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Medical Research Council, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; MRC Laboratory of Molecular Biology, Medical Research Council, Francis Crick Avenue, Cambridge CB2 0QH, UK. rhegde@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721998" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Dogs ; Hydrophobic and Hydrophilic Interactions ; Lipid Bilayers/chemistry ; Membrane Proteins/*chemistry ; Protein Sorting Signals ; Protein Structure, Secondary ; Ribosomes/chemistry
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  • 21
    Publication Date: 2016-02-26
    Description: Monoubiquitinated histone H2B plays multiple roles in transcription activation. H2B is deubiquitinated by the Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator, which contains a four-protein subcomplex known as the deubiquitinating (DUB) module. The crystal structure of the Ubp8/Sgf11/Sus1/Sgf73 DUB module bound to a ubiquitinated nucleosome reveals that the DUB module primarily contacts H2A/H2B, with an arginine cluster on the Sgf11 zinc finger domain docking on the conserved H2A/H2B acidic patch. The Ubp8 catalytic domain mediates additional contacts with H2B, as well as with the conjugated ubiquitin. We find that the DUB module deubiquitinates H2B both in the context of the nucleosome and in H2A/H2B dimers complexed with the histone chaperone, FACT, suggesting that SAGA could target H2B at multiple stages of nucleosome disassembly and reassembly during transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morgan, Michael T -- Haj-Yahya, Mahmood -- Ringel, Alison E -- Bandi, Prasanthi -- Brik, Ashraf -- Wolberger, Cynthia -- GM-095822/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):725-8. doi: 10.1126/science.aac5681.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ; Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel. ; Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 3200008, Israel. ; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. cwolberg@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912860" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalytic Domain ; Crystallography, X-Ray ; Endopeptidases/*chemistry ; Histone Acetyltransferases/*chemistry ; Histones/*chemistry ; Nuclear Proteins/*chemistry ; Nucleosomes/enzymology ; Protein Multimerization ; Protein Structure, Secondary ; RNA-Binding Proteins/*chemistry ; Saccharomyces cerevisiae Proteins/*chemistry ; Trans-Activators/*chemistry ; Transcription Factors/*chemistry ; Transcriptional Activation ; Ubiquitin/chemistry ; *Ubiquitination ; Xenopus laevis ; Zinc Fingers
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  • 22
    Publication Date: 2016-03-26
    Description: Cell assembly sequences during learning are "replayed" during hippocampal ripples and contribute to the consolidation of episodic memories. However, neuronal sequences may also reflect preexisting dynamics. We report that sequences of place-cell firing in a novel environment are formed from a combination of the contributions of a rigid, predominantly fast-firing subset of pyramidal neurons with low spatial specificity and limited change across sleep-experience-sleep and a slow-firing plastic subset. Slow-firing cells, rather than fast-firing cells, gained high place specificity during exploration, elevated their association with ripples, and showed increased bursting and temporal coactivation during postexperience sleep. Thus, slow- and fast-firing neurons, although forming a continuous distribution, have different coding and plastic properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grosmark, Andres D -- Buzsaki, Gyorgy -- MH102840/MH/NIMH NIH HHS/ -- MH54671/MH/NIMH NIH HHS/ -- NS075015/NS/NINDS NIH HHS/ -- R01 MH107396/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1440-3. doi: 10.1126/science.aad1935.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Columbia University Medical Center, New York, NY 10019, USA. The Neuroscience Institute, School of Medicine, New York University, New York, NY 10016, USA. ; The Neuroscience Institute, School of Medicine, New York University, New York, NY 10016, USA. Center for Neural Science, New York University, New York, NY 10016, USA. gyorgy.buzsaki@nyumc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013730" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Hippocampus/cytology/*physiopathology ; Learning/*physiology ; Male ; Maze Learning ; Neuronal Plasticity ; Pyramidal Cells/*physiology ; Rats ; Rats, Inbred LEC ; Sleep/physiology
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  • 23
    Publication Date: 2016-02-26
    Description: The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution of 7 angstroms using single-particle cryo-electron microscopy (cryo-EM). We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein cross-linking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the ubiquitin C-terminal hydrolase-like protein Sad1 likely tethers the helicase Brr2 to its preactivation position. Comparison of our model with cryo-EM three-dimensional structures of the Saccharomyces cerevisiae tri-snRNP and Schizosaccharomyces pombe spliceosome indicates that Brr2 undergoes a marked conformational change during spliceosome activation, and that the scaffolding protein Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agafonov, Dmitry E -- Kastner, Berthold -- Dybkov, Olexandr -- Hofele, Romina V -- Liu, Wen-Ti -- Urlaub, Henning -- Luhrmann, Reinhard -- Stark, Holger -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1416-20. doi: 10.1126/science.aad2085. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Gottingen, D-37075 Gottingen, Germany. ; Department of 3D Electron Cryomicroscopy, Georg-August Universitat Gottingen, D-37077 Gottingen, Germany. Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Gottingen, D-37075 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de. ; Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de. ; Department of 3D Electron Cryomicroscopy, Georg-August Universitat Gottingen, D-37077 Gottingen, Germany. Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912367" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Crystallography, X-Ray ; DEAD-box RNA Helicases/chemistry ; Enzyme Activation ; HeLa Cells ; Humans ; Models, Molecular ; Peptide Elongation Factors/chemistry ; Protein Conformation ; RNA Helicases/chemistry ; RNA-Binding Proteins/chemistry ; Ribonucleoprotein, U4-U6 Small Nuclear/*chemistry ; Ribonucleoprotein, U5 Small Nuclear/*chemistry ; Ribonucleoproteins, Small Nuclear/chemistry ; Saccharomyces cerevisiae Proteins/chemistry ; Schizosaccharomyces/metabolism ; Ubiquitin Thiolesterase/chemistry
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alberts, Bruce -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):207. doi: 10.1126/science.aaf2001.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bruce Alberts is the Chancellor's Leadership Chair in Biochemistry and Biophysics for Science and Education at the University of California, San Francisco, CA, and emeritus editor-in-chief of Science. Bruce.Alberts@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816352" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; *Faculty ; Humans ; Leadership ; Policy Making ; *Power (Psychology) ; Schools/*manpower/trends ; Teaching/*manpower/methods/trends ; United States
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  • 25
    Publication Date: 2016-03-19
    Description: Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Decreased expression of C9orf72 is seen in expansion carriers, suggesting that loss of function may play a role in disease. We found that two independent mouse lines lacking the C9orf72 ortholog (3110043O21Rik) in all tissues developed normally and aged without motor neuron disease. Instead, C9orf72 null mice developed progressive splenomegaly and lymphadenopathy with accumulation of engorged macrophage-like cells. C9orf72 expression was highest in myeloid cells, and the loss of C9orf72 led to lysosomal accumulation and altered immune responses in macrophages and microglia, with age-related neuroinflammation similar to C9orf72 ALS but not sporadic ALS human patient tissue. Thus, C9orf72 is required for the normal function of myeloid cells, and altered microglial function may contribute to neurodegeneration in C9orf72 expansion carriers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Rourke, J G -- Bogdanik, L -- Yanez, A -- Lall, D -- Wolf, A J -- Muhammad, A K M G -- Ho, R -- Carmona, S -- Vit, J P -- Zarrow, J -- Kim, K J -- Bell, S -- Harms, M B -- Miller, T M -- Dangler, C A -- Underhill, D M -- Goodridge, H S -- Lutz, C M -- Baloh, R H -- GM085796/GM/NIGMS NIH HHS/ -- NS069669/NS/NINDS NIH HHS/ -- NS078398/NS/NINDS NIH HHS/ -- NS087351/NS/NINDS NIH HHS/ -- UL1TR000124/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1324-9. doi: 10.1126/science.aaf1064.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. ; The Jackson Laboratory, Bar Harbor, ME, USA. ; Division of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. ; Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. ; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. Department of Neurology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989253" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/immunology ; Amyotrophic Lateral Sclerosis/genetics/*immunology ; Animals ; Frontotemporal Dementia/genetics/*immunology ; Gene Knockdown Techniques ; Guanine Nucleotide Exchange Factors/genetics/*physiology ; Heterozygote ; Humans ; Lymphatic Diseases/genetics/immunology ; Macrophages/*immunology ; Mice ; Mice, Knockout ; Microglia/*immunology ; Myeloid Cells/*immunology ; Proteins/genetics/*physiology ; Rats ; Splenomegaly/genetics/immunology
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  • 26
    Publication Date: 2016-01-23
    Description: Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8alphabeta(+) T cells, at ~4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8(+) T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769032/" 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/PMC4769032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Scott G -- Wu, Helen L -- Burwitz, Benjamin J -- Hughes, Colette M -- Hammond, Katherine B -- Ventura, Abigail B -- Reed, Jason S -- Gilbride, Roxanne M -- Ainslie, Emily -- Morrow, David W -- Ford, Julia C -- Selseth, Andrea N -- Pathak, Reesab -- Malouli, Daniel -- Legasse, Alfred W -- Axthelm, Michael K -- Nelson, Jay A -- Gillespie, Geraldine M -- Walters, Lucy C -- Brackenridge, Simon -- Sharpe, Hannah R -- Lopez, Cesar A -- Fruh, Klaus -- Korber, Bette T -- McMichael, Andrew J -- Gnanakaran, S -- Sacha, Jonah B -- Picker, Louis J -- HHSN272201100013C/AI/NIAID NIH HHS/ -- HHSN272201100013C/PHS HHS/ -- P01 AI094417/AI/NIAID NIH HHS/ -- P01-AI094417/AI/NIAID NIH HHS/ -- P50-GM065794/GM/NIGMS NIH HHS/ -- P51 OD011092/OD/NIH HHS/ -- P51-OD011092/OD/NIH HHS/ -- R01 AI059457/AI/NIAID NIH HHS/ -- R01 AI095113/AI/NIAID NIH HHS/ -- R01 AI117802/AI/NIAID NIH HHS/ -- R01 DE021291/DE/NIDCR NIH HHS/ -- R01-AI059457/AI/NIAID NIH HHS/ -- R01-AI095113/AI/NIAID NIH HHS/ -- R01-AI117802/AI/NIAID NIH HHS/ -- R01-DE021291/DE/NIDCR NIH HHS/ -- R37 AI054292/AI/NIAID NIH HHS/ -- R37-AI054292/AI/NIAID NIH HHS/ -- U24 OD010850/OD/NIH HHS/ -- U24-OD010850/OD/NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- UM1-AI100645-01/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):714-20. doi: 10.1126/science.aac9475. Epub 2016 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA. ; Nuffield Department of Medicine, University of Oxford, Oxford OX37FZ, UK. ; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. ; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. The New Mexico Consortium, Los Alamos, NM 87545, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797147" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; Antigenic Variation ; CD8-Positive T-Lymphocytes/*immunology ; Cytomegalovirus/genetics/*immunology ; Epitopes, T-Lymphocyte/chemistry/*immunology ; Genetic Vectors/genetics/immunology ; Histocompatibility Antigens Class I/chemistry/*immunology ; Host-Pathogen Interactions/immunology ; Immune Evasion ; Killer Cells, Natural/immunology ; Macaca mulatta ; Protein Structure, Secondary ; Simian Immunodeficiency Virus/*immunology ; Vaccination
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  • 27
    Publication Date: 2016-01-09
    Description: beta-Barrel outer membrane proteins (OMPs) are found in the outer membranes of Gram-negative bacteria and are essential for nutrient import, signaling, and adhesion. A 200-kilodalton five-component complex called the beta-barrel assembly machinery (BAM) complex has been implicated in the biogenesis of OMPs. We report the structure of the BAM complex from Escherichia coli, revealing that binding of BamCDE modulates the conformation of BamA, the central component, which may serve to regulate the BAM complex. The periplasmic domain of BamA was in a closed state that prevents access to the barrel lumen, which indicates substrate OMPs may not be threaded through the barrel during biogenesis. Further, conformational shifts in the barrel domain lead to opening of the exit pore and rearrangement at the lateral gate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bakelar, Jeremy -- Buchanan, Susan K -- Noinaj, Nicholas -- 1K22AI113078-01/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 8;351(6269):180-6. doi: 10.1126/science.aad3460.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Markey Center for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA. ; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ; Markey Center for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA. nnoinaj@purdue.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26744406" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Outer Membrane Proteins/*chemistry ; Crystallography, X-Ray ; Escherichia coli/*metabolism ; Escherichia coli Proteins/*chemistry ; Multiprotein Complexes/*chemistry ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):394-5. doi: 10.1126/science.352.6284.394. Epub 2016 Apr 21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102455" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Evolution, Molecular ; Foundations ; Genes ; Genetic Research/*economics ; Great Britain ; Humans ; *Research Support as Topic ; *Selection, Genetic ; Sweden ; United States
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  • 29
    Publication Date: 2016-03-12
    Description: AMPA-type glutamate receptors (AMPARs), which are central mediators of rapid neurotransmission and synaptic plasticity, predominantly exist as heteromers of the subunits GluA1 to GluA4. Here we report the first AMPAR heteromer structures, which deviate substantially from existing GluA2 homomer structures. Crystal structures of the GluA2/3 and GluA2/4 N-terminal domains reveal a novel compact conformation with an alternating arrangement of the four subunits around a central axis. This organization is confirmed by cysteine cross-linking in full-length receptors, and it permitted us to determine the structure of an intact GluA2/3 receptor by cryogenic electron microscopy. Two models in the ligand-free state, at resolutions of 8.25 and 10.3 angstroms, exhibit substantial vertical compression and close associations between domain layers, reminiscent of N-methyl-D-aspartate receptors. Model 1 resembles a resting state and model 2 a desensitized state, thus providing snapshots of gating transitions in the nominal absence of ligand. Our data reveal organizational features of heteromeric AMPARs and provide a framework to decipher AMPAR architecture and signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852135/" 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/PMC4852135/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herguedas, Beatriz -- Garcia-Nafria, Javier -- Cais, Ondrej -- Fernandez-Leiro, Rafael -- Krieger, James -- Ho, Hinze -- Greger, Ingo H -- MC_U105174197/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):aad3873. doi: 10.1126/science.aad3873. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurobiology Division, Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, UK. ; Structural Studies Division, MRC Laboratory of Molecular Biology, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26966189" target="_blank"〉PubMed〈/a〉
    Keywords: Brain/metabolism ; Cryoelectron Microscopy ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; Ligands ; Models, Molecular ; *Protein Multimerization ; Protein Structure, Tertiary ; Receptors, AMPA/*chemistry/ultrastructure
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  • 30
    Publication Date: 2016-01-30
    Description: p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild-type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 and 2.4 angstroms, respectively. We also report cryo-EM structures (at resolutions of ~3.3, 3.2, and 3.3 angstroms, respectively) for three distinct, coexisting functional states of p97 with occupancies of zero, one, or two molecules of adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) per protomer. A large corkscrew-like change in molecular architecture, coupled with upward displacement of the N-terminal domain, is observed only when ATPgammaS is bound to both the D1 and D2 domains of the protomer. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small-molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between the D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Banerjee, Soojay -- Bartesaghi, Alberto -- Merk, Alan -- Rao, Prashant -- Bulfer, Stacie L -- Yan, Yongzhao -- Green, Neal -- Mroczkowski, Barbara -- Neitz, R Jeffrey -- Wipf, Peter -- Falconieri, Veronica -- Deshaies, Raymond J -- Milne, Jacqueline L S -- Huryn, Donna -- Arkin, Michelle -- Subramaniam, Sriram -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):871-5. doi: 10.1126/science.aad7974. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA. ; Small Molecule Discovery Center, Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143, USA. ; University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, PA 15260, USA. ; Leidos Biomedical Research Inc., Frederick, MD 21702, USA. ; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. ; Division of Biology and Biological Engineering and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91107, USA. ; Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA. ss1@nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26822609" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/chemistry ; Adenosine Triphosphatases/*antagonists & inhibitors/*chemistry ; Adenosine Triphosphate/analogs & derivatives/chemistry ; Allosteric Regulation ; Binding Sites ; Cryoelectron Microscopy ; Enzyme Inhibitors ; Humans ; Models, Molecular ; Nuclear Proteins/*antagonists & inhibitors/*chemistry ; Protein Structure, Tertiary
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  • 31
    Publication Date: 2016-02-06
    Description: SH3 and multiple ankyrin repeat domains 3 (SHANK3) haploinsufficiency is causative for the neurological features of Phelan-McDermid syndrome (PMDS), including a high risk of autism spectrum disorder (ASD). We used unbiased, quantitative proteomics to identify changes in the phosphoproteome of Shank3-deficient neurons. Down-regulation of protein kinase B (PKB/Akt)-mammalian target of rapamycin complex 1 (mTORC1) signaling resulted from enhanced phosphorylation and activation of serine/threonine protein phosphatase 2A (PP2A) regulatory subunit, B56beta, due to increased steady-state levels of its kinase, Cdc2-like kinase 2 (CLK2). Pharmacological and genetic activation of Akt or inhibition of CLK2 relieved synaptic deficits in Shank3-deficient and PMDS patient-derived neurons. CLK2 inhibition also restored normal sociability in a Shank3-deficient mouse model. Our study thereby provides a novel mechanistic and potentially therapeutic understanding of deregulated signaling downstream of Shank3 deficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bidinosti, Michael -- Botta, Paolo -- Kruttner, Sebastian -- Proenca, Catia C -- Stoehr, Natacha -- Bernhard, Mario -- Fruh, Isabelle -- Mueller, Matthias -- Bonenfant, Debora -- Voshol, Hans -- Carbone, Walter -- Neal, Sarah J -- McTighe, Stephanie M -- Roma, Guglielmo -- Dolmetsch, Ricardo E -- Porter, Jeffrey A -- Caroni, Pico -- Bouwmeester, Tewis -- Luthi, Andreas -- Galimberti, Ivan -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1199-203. doi: 10.1126/science.aad5487. Epub 2016 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Friedrich Miescher Institute, Basel, Switzerland. ; Analytical Sciences and Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Neuroscience, Novartis Institutes for Biomedical Research, Cambridge, USA. ; Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ivan.galimberti@novartis.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26847545" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Autism Spectrum Disorder/*drug therapy/enzymology/genetics ; Chromosome Deletion ; Chromosome Disorders/genetics ; Chromosomes, Human, Pair 22/genetics ; Disease Models, Animal ; Down-Regulation ; Gene Knockdown Techniques ; Humans ; Insulin-Like Growth Factor I/metabolism ; Mice ; Molecular Sequence Data ; Multiprotein Complexes/metabolism ; Nerve Tissue Proteins/*genetics ; Neurons/enzymology ; Phosphorylation ; Protein Phosphatase 2/metabolism ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Proteomics ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; Rats ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blum, Arlene -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1117. doi: 10.1126/science.aaf5468. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Arlene Blum is founder and executive director of the Green Science Policy Institute, Berkeley, CA. arlene@GreenSciencePolicy.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965592" target="_blank"〉PubMed〈/a〉
    Keywords: Consumer Product Safety/*legislation & jurisprudence ; Health ; Household Products/*toxicity ; Humans ; Manufactured Materials/*toxicity ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):14. doi: 10.1126/science.351.6268.14.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721983" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Databases, Genetic/*economics ; Financial Support ; Human Genome Project/*economics ; Humans ; Models, Animal ; National Human Genome Research Institute (U.S.)/*economics ; United States
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richmond, Geraldine -- New York, N.Y. -- Science. 2016 Jan 29;351(6272):427. doi: 10.1126/science.aaf2869. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geraldine Richmond is president of AAAS and Presidential Chair in Science and professor in the Department of Chemistry and Biochemistry at the University of Oregon, Eugene, OR. richmond@oregon.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26823402" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Asia ; *Food Supply ; Humans ; *Internationality ; United States ; *Water Supply
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):20. doi: 10.1126/science.352.6281.20.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034352" target="_blank"〉PubMed〈/a〉
    Keywords: Awards and Prizes ; Biomedical Research/*economics ; *Financing, Government ; National Institute of General Medical Sciences (U.S.) ; United States
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  • 36
    Publication Date: 2016-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):325-6. doi: 10.1126/science.351.6271.325.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797992" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*organization & administration ; Federal Government ; Humans ; Neoplasms/*therapy ; Policy ; United States
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  • 37
    Publication Date: 2016-04-23
    Description: The microtubule (MT) cytoskeleton can transmit mechanical signals and resist compression in contracting cardiomyocytes. How MTs perform these roles remains unclear because of difficulties in observing MTs during the rapid contractile cycle. Here, we used high spatial and temporal resolution imaging to characterize MT behavior in beating mouse myocytes. MTs deformed under contractile load into sinusoidal buckles, a behavior dependent on posttranslational "detyrosination" of alpha-tubulin. Detyrosinated MTs associated with desmin at force-generating sarcomeres. When detyrosination was reduced, MTs uncoupled from sarcomeres and buckled less during contraction, which allowed sarcomeres to shorten and stretch with less resistance. Conversely, increased detyrosination promoted MT buckling, stiffened the myocyte, and correlated with impaired function in cardiomyopathy. Thus, detyrosinated MTs represent tunable, compression-resistant elements that may impair cardiac function in disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robison, Patrick -- Caporizzo, Matthew A -- Ahmadzadeh, Hossein -- Bogush, Alexey I -- Chen, Christina Yingxian -- Margulies, Kenneth B -- Shenoy, Vivek B -- Prosser, Benjamin L -- HL089847/HL/NHLBI NIH HHS/ -- HL105993/HL/NHLBI NIH HHS/ -- R00-HL114879/HL/NHLBI NIH HHS/ -- R01EB017753/EB/NIBIB NIH HHS/ -- T32AR053461-09/AR/NIAMS NIH HHS/ -- T32HL007954/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):aaf0659. doi: 10.1126/science.aaf0659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. ; Department of Materials Science and Engineering, University of Pennsylvania School of Engineering and Applied Science, Philadelphia, PA 19104, USA. ; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. ; Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. bpros@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102488" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Desmin/metabolism ; Elasticity ; Heart Failure/metabolism/physiopathology ; Humans ; Male ; Mice ; Microtubules/*metabolism ; Models, Biological ; *Myocardial Contraction ; Myocytes, Cardiac/metabolism/*physiology ; Peptide Synthases/genetics/metabolism ; *Protein Processing, Post-Translational ; RNA, Small Interfering/genetics ; Rats ; Rats, Sprague-Dawley ; Sarcomeres/metabolism ; Tubulin/*metabolism ; Tyrosine/*metabolism
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roman, Joe -- Kraska, James -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1258-60. doi: 10.1126/science.aad4247.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gund Institute for Ecological Economics, University of Vermont, Burlington, VT 05405, USA. jroman@uvm.edu. ; Stockton Center for the Study of International Law, U.S. Naval War College, Newport, RI 02841, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989232" target="_blank"〉PubMed〈/a〉
    Keywords: *Bays ; *Conservation of Natural Resources ; Cuba ; Diplomacy ; United States
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  • 39
    Publication Date: 2016-04-30
    Description: The cytochrome bd oxidases are terminal oxidases that are present in bacteria and archaea. They reduce molecular oxygen (dioxygen) to water, avoiding the production of reactive oxygen species. In addition to their contribution to the proton motive force, they mediate viability under oxygen-related stress conditions and confer tolerance to nitric oxide, thus contributing to the virulence of pathogenic bacteria. Here we present the atomic structure of the bd oxidase from Geobacillus thermodenitrificans, revealing a pseudosymmetrical subunit fold. The arrangement and order of the heme cofactors support the conclusions from spectroscopic measurements that the cleavage of the dioxygen bond may be mechanistically similar to that in the heme-copper-containing oxidases, even though the structures are completely different.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Safarian, Schara -- Rajendran, Chitra -- Muller, Hannelore -- Preu, Julia -- Langer, Julian D -- Ovchinnikov, Sergey -- Hirose, Taichiro -- Kusumoto, Tomoichirou -- Sakamoto, Junshi -- Michel, Hartmut -- R01GM092802/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):583-6. doi: 10.1126/science.aaf2477.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, D-60438 Frankfurt/Main, Germany. ; Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, D-60438 Frankfurt/Main, Germany. Present address: Faculty of Biology and Preclinical Medicine, University of Regensburg, Universitatsstrasse 31, D-93051 Regensburg, Germany. ; Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, D-60438 Frankfurt/Main, Germany. Present address: Department of Molecular Membrane Biology, Max Planck Institute for Brain Research, Max-von-Laue-Strasse 4, D-60438 Frankfurt/Main, Germany. ; Department of Biochemistry, University of Washington, Seattle, WA, USA. ; Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Kawazu 680-4, Iizuka, Fukuoka-ken 820-8502, Japan. ; Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, D-60438 Frankfurt/Main, Germany. hartmut.michel@biophys.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126043" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/ultrastructure ; Cytochrome d Group/*chemistry/ultrastructure ; Cytochromes b/*chemistry/ultrastructure ; Electron Transport Complex IV/*chemistry/ultrastructure ; Geobacillus/*enzymology ; Oxygen/*chemistry ; Protein Folding ; Protein Structure, Secondary
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  • 40
    Publication Date: 2016-03-12
    Description: Type IVa pili are filamentous cell surface structures observed in many bacteria. They pull cells forward by extending, adhering to surfaces, and then retracting. We used cryo-electron tomography of intact Myxococcus xanthus cells to visualize type IVa pili and the protein machine that assembles and retracts them (the type IVa pilus machine, or T4PM) in situ, in both the piliated and nonpiliated states, at a resolution of 3 to 4 nanometers. We found that T4PM comprises an outer membrane pore, four interconnected ring structures in the periplasm and cytoplasm, a cytoplasmic disc and dome, and a periplasmic stem. By systematically imaging mutants lacking defined T4PM proteins or with individual proteins fused to tags, we mapped the locations of all 10 T4PM core components and the minor pilins, thereby providing insights into pilus assembly, structure, and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Yi-Wei -- Rettberg, Lee A -- Treuner-Lange, Anke -- Iwasa, Janet -- Sogaard-Andersen, Lotte -- Jensen, Grant J -- R01 GM094800B/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):aad2001. doi: 10.1126/science.aad2001. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Institute of Technology, Pasadena, CA 91125, USA. Howard Hughes Medical Institute, Pasadena, CA 91125, USA. ; Howard Hughes Medical Institute, Pasadena, CA 91125, USA. ; Max Planck Institute for Terrestrial Microbiology, 35043 Marburg, Germany. ; University of Utah, Salt Lake City, UT 84112, USA. ; California Institute of Technology, Pasadena, CA 91125, USA. Howard Hughes Medical Institute, Pasadena, CA 91125, USA. jensen@caltech.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965631" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Adhesion ; Cryoelectron Microscopy ; Fimbriae, Bacterial/genetics/*ultrastructure ; Microscopy, Electron, Transmission ; Models, Molecular ; Mutation ; Myxococcus xanthus/genetics/physiology/*ultrastructure
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  • 41
    Publication Date: 2016-04-16
    Description: Nuclear pore complexes (NPCs) are 110-megadalton assemblies that mediate nucleocytoplasmic transport. NPCs are built from multiple copies of ~30 different nucleoporins, and understanding how these nucleoporins assemble into the NPC scaffold imposes a formidable challenge. Recently, it has been shown how the Y complex, a prominent NPC module, forms the outer rings of the nuclear pore. However, the organization of the inner ring has remained unknown until now. We used molecular modeling combined with cross-linking mass spectrometry and cryo-electron tomography to obtain a composite structure of the inner ring. This architectural map explains the vast majority of the electron density of the scaffold. We conclude that despite obvious differences in morphology and composition, the higher-order structure of the inner and outer rings is unexpectedly similar.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kosinski, Jan -- Mosalaganti, Shyamal -- von Appen, Alexander -- Teimer, Roman -- DiGuilio, Amanda L -- Wan, William -- Bui, Khanh Huy -- Hagen, Wim J H -- Briggs, John A G -- Glavy, Joseph S -- Hurt, Ed -- Beck, Martin -- 1R21AG047433-01/AG/NIA NIH HHS/ -- R21 AG047433/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):363-5. doi: 10.1126/science.aaf0643.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. ; Biochemistry Center of Heidelberg University, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany. ; Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, 507 River Street, Hoboken, NJ 07030, USA. ; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. ; Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081072" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Cryoelectron Microscopy ; Electron Microscope Tomography ; HeLa Cells ; Humans ; Mass Spectrometry ; Models, Molecular ; Nuclear Matrix/metabolism/ultrastructure ; Nuclear Pore/*metabolism/*ultrastructure ; Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kloor, Keith -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):699. doi: 10.1126/science.347.6223.699.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678635" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; Agriculture/*legislation & jurisprudence ; Biotechnology/*legislation & jurisprudence ; Commerce ; Food Labeling/*legislation & jurisprudence ; Food, Genetically Modified/*adverse effects ; Humans ; Research Personnel ; United States ; Universities
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, Rachel -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):269. doi: 10.1126/science.348.6232.269.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883332" target="_blank"〉PubMed〈/a〉
    Keywords: Engineering/*education/manpower ; Faculty/*statistics & numerical data ; Female ; Humans ; Male ; Mathematics/*education/manpower ; Science/*education/manpower ; Sex Factors ; Technology/*education/manpower ; United States ; Women, Working/*statistics & numerical data
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hackett, Perry -- Carroll, Dana -- P01 HD032652/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1324. doi: 10.1126/science.347.6228.1324.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Cell Biology, and Development, Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. hacke004@umn.edu. ; Department of Biochemistry, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792322" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*legislation & jurisprudence ; Animals ; *Government Regulation ; *Organisms, Genetically Modified ; United States
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-11-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dajani, Rana -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1043. doi: 10.1126/science.350.6264.1043-b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan. rdajani@hu.edu.jo.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612944" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Art ; Equipment Reuse ; Fibroblasts ; Gloves, Protective ; Jordan ; Laboratories ; Mice ; Recycling/*methods ; United States
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  • 46
    Publication Date: 2015-03-07
    Description: Human higher cognition is attributed to the evolutionary expansion and elaboration of the human cerebral cortex. However, the genetic mechanisms contributing to these developmental changes are poorly understood. We used comparative epigenetic profiling of human, rhesus macaque, and mouse corticogenesis to identify promoters and enhancers that have gained activity in humans. These gains are significantly enriched in modules of coexpressed genes in the cortex that function in neuronal proliferation, migration, and cortical-map organization. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting that they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes during corticogenesis, providing insight into human cortical evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426903/" 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/PMC4426903/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reilly, Steven K -- Yin, Jun -- Ayoub, Albert E -- Emera, Deena -- Leng, Jing -- Cotney, Justin -- Sarro, Richard -- Rakic, Pasko -- Noonan, James P -- 099175/Z/12/Z/Wellcome Trust/United Kingdom -- DA023999/DA/NIDA NIH HHS/ -- F32 GM106628/GM/NIGMS NIH HHS/ -- GM094780/GM/NIGMS NIH HHS/ -- NS014841/NS/NINDS NIH HHS/ -- P30 CA016359/CA/NCI NIH HHS/ -- R01 DA023999/DA/NIDA NIH HHS/ -- R01 GM094780/GM/NIGMS NIH HHS/ -- T32 GM007223/GM/NIGMS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1155-9. doi: 10.1126/science.1260943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. ; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. james.noonan@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745175" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/*growth & development ; Enhancer Elements, Genetic/*genetics ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Humans ; Macaca mulatta ; Mice ; Organogenesis/*genetics ; Promoter Regions, Genetic/*genetics ; Rats
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  • 47
    Publication Date: 2015-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Merrigan, Kathleen -- Griffin, Timothy -- Wilde, Parke -- Robien, Kimberly -- Goldberg, Jeanne -- Dietz, William -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):165-6. doi: 10.1126/science.aab2031. Epub 2015 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Trachtenberg School of Public Policy and Public Administration, the George Washington University, Washington, DC 20052, USA. kmerrigan@gwu.edu. ; Friedman School of Nutrition Science and Policy, Tufts University, Medford, MA 02155, USA. ; Milken Institute School of Public Health, the George Washington University, Washington, DC 20052, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26429883" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Diet/*standards ; Food Assistance ; Food Technology/*standards ; Humans ; *Nutrition Policy ; United States
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  • 48
    Publication Date: 2015-07-15
    Description: Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited. Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with TM3 and TM4 contributing to homotrimerization. The six TMs enclose a V-shaped cavity that can accommodate a diacylglycerol molecule. A homology-based structural model of human Insig-2, together with biochemical characterizations, suggest that the central cavity of Insig-2 accommodates 25-hydroxycholesterol, whereas TM3 and TM4 engage in Scap binding. These analyses provide an important framework for further functional and mechanistic understanding of Insig proteins and the sterol regulatory element-binding protein pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704858/" 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/PMC4704858/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, Ruobing -- Zhou, Xinhui -- He, Yuan -- Ke, Meng -- Wu, Jianping -- Liu, Xiaohui -- Yan, Chuangye -- Wu, Yixuan -- Gong, Xin -- Lei, Xiaoguang -- Yan, S Frank -- Radhakrishnan, Arun -- Yan, Nieng -- HL-20948/HL/NHLBI NIH HHS/ -- P01 HL020948/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):187-91. doi: 10.1126/science.aab1091.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. Center for Structural Biology, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China. ; National Institute of Biological Sciences, Beijing 102206, China. ; Molecular Design and Chemical Biology, Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Shanghai, Shanghai 201203, China. ; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160948" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry ; Crystallography, X-Ray ; Diglycerides/chemistry ; Humans ; Hydroxycholesterols/chemistry/*metabolism ; Intracellular Signaling Peptides and Proteins/*chemistry ; Membrane Proteins/*chemistry ; Mycobacterium/*metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Sterol Regulatory Element Binding Proteins/*chemistry
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kohane, Isaac S -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):37-8. doi: 10.1126/science.aab1328. Epub 2015 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. isaac_kohane@harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138968" target="_blank"〉PubMed〈/a〉
    Keywords: *Evidence-Based Medicine ; Genomics/trends ; *Health Policy ; Humans ; Medical Record Linkage ; Reproducibility of Results ; United States
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1454. doi: 10.1126/science.350.6267.1454.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680170" target="_blank"〉PubMed〈/a〉
    Keywords: Contract Services/*economics ; Ecology/*economics ; *Ecosystem ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kollipara, Puneet -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1403-4. doi: 10.1126/science.347.6229.1403-b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814561" target="_blank"〉PubMed〈/a〉
    Keywords: Agrochemicals ; Chemical Industry/*legislation & jurisprudence ; Conservation of Natural Resources/*legislation & jurisprudence ; Ecotoxicology/*legislation & jurisprudence ; Toxicity Tests ; United States ; United States Environmental Protection Agency
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):896. doi: 10.1126/science.350.6263.896.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586739" target="_blank"〉PubMed〈/a〉
    Keywords: *African Americans ; Biomedical Research/economics ; Biotechnology/*economics/*manpower ; Financial Support ; Government Programs ; Humans ; Laboratory Personnel/*economics ; National Institutes of Health (U.S.)/*economics ; Small Business/economics/trends ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Sep 25;349(6255):1436-41. doi: 10.1126/science.349.6255.1436. Epub 2015 Sep 24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26404807" target="_blank"〉PubMed〈/a〉
    Keywords: Data Collection ; Environmental Monitoring/*methods/standards ; Foundations ; United States
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  • 54
    Publication Date: 2015-01-03
    Description: Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complicated membrane protein complexes. The enzyme contributes substantially to oxidative energy conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. We report the x-ray structure of mitochondrial complex I at a resolution of 3.6 to 3.9 angstroms, describing in detail the central subunits that execute the bioenergetic function. A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the "deactive" form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site, providing support for a two-state stabilization-change mechanism of proton pumping.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zickermann, Volker -- Wirth, Christophe -- Nasiri, Hamid -- Siegmund, Karin -- Schwalbe, Harald -- Hunte, Carola -- Brandt, Ulrich -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):44-9. doi: 10.1126/science.1259859.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe-University, 60438 Frankfurt am Main, Germany. Cluster of Excellence Frankfurt "Macromolecular Complexes," Goethe-University, 60438 Frankfurt am Main, Germany. zickermann@med.uni-frankfurt.de carola.hunte@biochemie.uni-freiburg.de ulrich.brandt@radboudumc.nl. ; Institute for Biochemistry and Molecular Biology, ZBMZ, BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. ; Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK. Institute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance, 60438 Frankfurt am Main, Germany. ; Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe-University, 60438 Frankfurt am Main, Germany. ; Cluster of Excellence Frankfurt "Macromolecular Complexes," Goethe-University, 60438 Frankfurt am Main, Germany. Institute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance, 60438 Frankfurt am Main, Germany. ; Institute for Biochemistry and Molecular Biology, ZBMZ, BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. zickermann@med.uni-frankfurt.de carola.hunte@biochemie.uni-freiburg.de ulrich.brandt@radboudumc.nl. ; Cluster of Excellence Frankfurt "Macromolecular Complexes," Goethe-University, 60438 Frankfurt am Main, Germany. Nijmegen Center for Mitochondrial Disorders, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. zickermann@med.uni-frankfurt.de carola.hunte@biochemie.uni-freiburg.de ulrich.brandt@radboudumc.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554780" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; Electron Transport Complex I/*chemistry/ultrastructure ; Mitochondria/*enzymology ; Mitochondrial Membranes/*enzymology ; Protein Structure, Secondary ; Protons ; Ubiquinone/chemistry ; Yarrowia/enzymology
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):574. doi: 10.1126/science.349.6248.574.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250664" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Ecology/*economics ; Ecosystem ; Foundations ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):225. doi: 10.1126/science.349.6245.225. Epub 2015 Jul 16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26185225" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; Budgets ; National Institutes of Health (U.S.)/*economics ; Salaries and Fringe Benefits/*trends ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):16. doi: 10.1126/science.349.6243.16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138958" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Age Factors ; Animal Experimentation ; Animals ; *Attitude ; Data Collection ; Female ; Global Warming ; Humans ; Nuclear Energy ; Politics ; *Public Opinion ; *Research ; Sex Factors ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 May 29;348(6238):956. doi: 10.1126/science.348.6238.956.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26023115" target="_blank"〉PubMed〈/a〉
    Keywords: Behavioral Sciences/*economics ; Climate Change/*economics ; Federal Government ; Financing, Government/*legislation & jurisprudence ; Foundations ; Social Sciences/*economics ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Apr 24;348(6233):384. doi: 10.1126/science.348.6233.384.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908803" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/*trends ; Financing, Government ; *National Institutes of Health (U.S.) ; *Peer Review, Research ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krupic, Julija -- New York, N.Y. -- Science. 2015 Oct 2;350(6256):47. doi: 10.1126/science.aad3002.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK. j.krupic@ucl.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26430112" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; Brain/*physiology/*ultrastructure ; *Distance Perception ; Fourier Analysis ; Humans ; Metric System ; Neurons/*physiology/*ultrastructure ; Rats ; Spatial Navigation/*physiology
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1054. doi: 10.1126/science.347.6226.1054.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745139" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; Biology/*education ; Curriculum ; *Faculty ; Knowledge ; *Professional Competence ; *Religion and Science ; Role ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeMarco, Emily -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):915-7. doi: 10.1126/science.349.6251.915.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315416" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Astacoidea/classification/genetics/physiology ; Coal Mining ; Ecosystem ; *Endangered Species/legislation & jurisprudence ; Environmental Pollution ; Genetic Speciation ; United States ; West Virginia
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeMarco, Emily -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):570-1. doi: 10.1126/science.349.6248.570.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250661" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Migration ; Animals ; Breeding ; *Butterflies ; *Conservation of Natural Resources ; Female ; Mexico ; Plant Nectar ; Population ; Seasons ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):602-5. doi: 10.1126/science.347.6222.602.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657228" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Career Mobility ; *Faculty ; Fellowships and Scholarships/*economics ; *Government Programs ; Mathematics/*education ; Science/*education ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):599-601. doi: 10.1126/science.347.6222.599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657226" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; *Financing, Government ; Research/*economics ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):466-7. doi: 10.1126/science.347.6221.466.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635067" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets/*legislation & jurisprudence ; Federal Government ; Financing, Government ; National Institutes of Health (U.S.)/*economics/legislation & jurisprudence ; *Politics ; Public Policy ; Research Support as Topic/legislation & jurisprudence ; United States ; United States Government Agencies/*economics/legislation & jurisprudence ; United States National Aeronautics and Space ; Administration/*economics/legislation & jurisprudence
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):221-2. doi: 10.1126/science.349.6245.221. Epub 2015 Jul 16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26185221" target="_blank"〉PubMed〈/a〉
    Keywords: Federal Government ; Humans ; Leadership ; Psychology/*ethics ; *Public Policy ; Security Measures/*ethics ; Social Change ; Societies, Scientific/ethics ; Torture/*ethics ; United States
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  • 68
    Publication Date: 2015-07-04
    Description: Lactic acid racemization is involved in lactate metabolism and cell wall assembly of many microorganisms. Lactate racemase (Lar) requires nickel, but the nickel-binding site and the role of three accessory proteins required for its activation remain enigmatic. We combined mass spectrometry and x-ray crystallography to show that Lar from Lactobacillus plantarum possesses an organometallic nickel-containing prosthetic group. A nicotinic acid mononucleotide derivative is tethered to Lys(184) and forms a tridentate pincer complex that coordinates nickel through one metal-carbon and two metal-sulfur bonds, with His(200) as another ligand. Although similar complexes have been previously synthesized, there was no prior evidence for the existence of pincer cofactors in enzymes. The wide distribution of the accessory proteins without Lar suggests that it may play a role in other enzymes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Desguin, Benoit -- Zhang, Tuo -- Soumillion, Patrice -- Hols, Pascal -- Hu, Jian -- Hausinger, Robert P -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):66-9. doi: 10.1126/science.aab2272.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. ; Institute of Life Sciences, Universite Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA. hujian1@msu.edu hausinge@msu.edu. ; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. hujian1@msu.edu hausinge@msu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138974" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics ; Binding Sites ; Carbon/chemistry ; Catalysis ; Crystallography, X-Ray ; Histidine/chemistry ; Holoenzymes/chemistry ; Lactic Acid/*biosynthesis/chemistry ; Lactobacillus plantarum/*enzymology/genetics ; Ligands ; Lysine/chemistry ; Metalloproteins/*chemistry/genetics ; Niacin/*chemistry ; Nickel/*chemistry ; Nicotinamide Mononucleotide/analogs & derivatives/chemistry ; Protein Processing, Post-Translational ; Protein Structure, Secondary ; Racemases and Epimerases/*chemistry/genetics ; Spectrometry, Mass, Electrospray Ionization ; Sulfur
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):263-4. doi: 10.1126/science.350.6258.263.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472886" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/*ultrastructure ; *Computer Simulation ; Investments ; *Models, Neurological ; Neurons/*ultrastructure ; Neurosciences/*economics ; Rats
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):495-7. doi: 10.1126/science.347.6221.495.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635082" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Computer Security ; Financing, Government ; Humans ; *Mathematics ; *Privacy ; Research Support as Topic ; *Security Measures ; Societies ; Trust ; United States ; *United States Department of Defense/economics/ethics ; Universities
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Aubrey -- Birnbaum, Linda -- New York, N.Y. -- Science. 2015 May 15;348(6236):766-7. doi: 10.1126/science.348.6236.766-c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. miller.aubrey@nih.gov. ; National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977543" target="_blank"〉PubMed〈/a〉
    Keywords: Disaster Planning/*methods ; Humans ; National Institute of Environmental Health Sciences (U.S.) ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hand, Eric -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):813-4. doi: 10.1126/science.347.6224.813.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700494" target="_blank"〉PubMed〈/a〉
    Keywords: *Exobiology ; *Ice Cover ; *Minor Planets ; United States ; United States National Aeronautics and Space Administration
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  • 73
    Publication Date: 2015-05-23
    Description: Extremophiles, microorganisms thriving in extreme environmental conditions, must have proteins and nucleic acids that are stable at extremes of temperature and pH. The nonenveloped, rod-shaped virus SIRV2 (Sulfolobus islandicus rod-shaped virus 2) infects the hyperthermophilic acidophile Sulfolobus islandicus, which lives at 80 degrees C and pH 3. We have used cryo-electron microscopy to generate a three-dimensional reconstruction of the SIRV2 virion at ~4 angstrom resolution, which revealed a previously unknown form of virion organization. Although almost half of the capsid protein is unstructured in solution, this unstructured region folds in the virion into a single extended alpha helix that wraps around the DNA. The DNA is entirely in the A-form, which suggests a common mechanism with bacterial spores for protecting DNA in the most adverse environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DiMaio, Frank -- Yu, Xiong -- Rensen, Elena -- Krupovic, Mart -- Prangishvili, David -- Egelman, Edward H -- GM035269/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 22;348(6237):914-7. doi: 10.1126/science.aaa4181.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. ; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. ; Institut Pasteur, Department of Microbiology, 25 rue du Dr. Roux, Paris 75015, France. ; Institut Pasteur, Department of Microbiology, 25 rue du Dr. Roux, Paris 75015, France. egelman@virginia.edu david.prangishvili@pasteur.fr. ; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. egelman@virginia.edu david.prangishvili@pasteur.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999507" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cryoelectron Microscopy ; DNA, A-Form/*metabolism ; Molecular Sequence Data ; Protein Multimerization ; Protein Structure, Secondary ; Rudiviridae/*metabolism/ultrastructure ; Spores, Bacterial/genetics/virology ; Sulfolobus/*genetics/*virology ; Virion/*ultrastructure
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  • 74
    Publication Date: 2015-10-10
    Description: Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toh, Shigeo -- Holbrook-Smith, Duncan -- Stogios, Peter J -- Onopriyenko, Olena -- Lumba, Shelley -- Tsuchiya, Yuichiro -- Savchenko, Alexei -- McCourt, Peter -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):203-7. doi: 10.1126/science.aac9476.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto M5S 3B2, Canada. ; Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, 200 College Street, Toronto M5S 3E5, Canada. Center for Structural Genomics of Infectious Diseases, contracted by National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, 200 College Street, Toronto M5S 3E5, Canada. ; Institute of Transformative Bio-Molecules, Nagoya University, Japan, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan. ; Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto M5S 3B2, Canada. peter.mccourt@utoronto.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26450211" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/metabolism ; Catalytic Domain ; Germination/drug effects ; Heterocyclic Compounds, 3-Ring/*metabolism/pharmacology ; Lactones/*metabolism/pharmacology ; Molecular Sequence Data ; Phylogeny ; Plant Growth Regulators/*metabolism/pharmacology ; Plant Proteins/*chemistry/classification/genetics ; Protein Structure, Secondary ; Receptors, Cell Surface/*chemistry/classification/genetics ; Seeds/genetics/growth & development/metabolism ; Striga/genetics/growth & development/*metabolism ; Structure-Activity Relationship
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Topik, Christopher -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1263. doi: 10.1126/science.aad4202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Christopher Topik is the director of Restoring America's Forests at The Nature Conservancy North America Region, Arlington, VA. ctopik@tnc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383924" target="_blank"〉PubMed〈/a〉
    Keywords: Disasters/*economics ; Federal Government ; Financial Management/legislation & jurisprudence ; Fires/*economics ; United States
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  • 76
    Publication Date: 2015-03-15
    Description: TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Yin Yao -- Pike, Ashley C W -- Mackenzie, Alexandra -- McClenaghan, Conor -- Aryal, Prafulla -- Dong, Liang -- Quigley, Andrew -- Grieben, Mariana -- Goubin, Solenne -- Mukhopadhyay, Shubhashish -- Ruda, Gian Filippo -- Clausen, Michael V -- Cao, Lishuang -- Brennan, Paul E -- Burgess-Brown, Nicola A -- Sansom, Mark S P -- Tucker, Stephen J -- Carpenter, Elisabeth P -- 084655/Wellcome Trust/United Kingdom -- 092809/Z/10/Z/Wellcome Trust/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1256-9. doi: 10.1126/science.1261512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Pfizer Neusentis, Granta Park, Cambridge CB21 6GS, UK. ; OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766236" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arachidonic Acid/pharmacology ; Binding Sites ; Crystallography, X-Ray ; Fluoxetine/analogs & derivatives/chemistry/metabolism/pharmacology ; Humans ; *Ion Channel Gating ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Potassium/metabolism ; Potassium Channels, Tandem Pore Domain/antagonists & ; inhibitors/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 77
    Publication Date: 2015-10-10
    Description: Phosphatidylinositol 3-kinase Vps34 complexes regulate intracellular membrane trafficking in endocytic sorting, cytokinesis, and autophagy. We present the 4.4 angstrom crystal structure of the 385-kilodalton endosomal complex II (PIK3C3-CII), consisting of Vps34, Vps15 (p150), Vps30/Atg6 (Beclin 1), and Vps38 (UVRAG). The subunits form a Y-shaped complex, centered on the Vps34 C2 domain. Vps34 and Vps15 intertwine in one arm, where the Vps15 kinase domain engages the Vps34 activation loop to regulate its activity. Vps30 and Vps38 form the other arm that brackets the Vps15/Vps34 heterodimer, suggesting a path for complex assembly. We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to reveal conformational changes accompanying membrane binding and identify a Vps30 loop that is critical for the ability of complex II to phosphorylate giant liposomes on which complex I is inactive.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601532/" 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/PMC4601532/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rostislavleva, Ksenia -- Soler, Nicolas -- Ohashi, Yohei -- Zhang, Lufei -- Pardon, Els -- Burke, John E -- Masson, Glenn R -- Johnson, Chris -- Steyaert, Jan -- Ktistakis, Nicholas T -- Williams, Roger L -- BB/K019155/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_U105184308/Medical Research Council/United Kingdom -- PG11/109/29247/British Heart Foundation/United Kingdom -- U105184308/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):aac7365. doi: 10.1126/science.aac7365.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Structural Biology Research Center, VIB, B-1050 Brussels, Belgium. Structural Biology Brussels, Vrije Universiteit Brussel, B-1050 Brussels, Belgium. ; The Babraham Institute, Cambridge, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. rlw@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26450213" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/chemistry/*enzymology ; Class III Phosphatidylinositol 3-Kinases/chemistry/*ultrastructure ; Crystallography, X-Ray ; Endosomes/chemistry/*enzymology ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/enzymology ; Vacuolar Sorting Protein VPS15/chemistry/ultrastructure
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  • 78
    Publication Date: 2015-06-20
    Description: G protein-coupled receptors (GPCRs) relay diverse extracellular signals into cells by catalyzing nucleotide release from heterotrimeric G proteins, but the mechanism underlying this quintessential molecular signaling event has remained unclear. Here we use atomic-level simulations to elucidate the nucleotide-release mechanism. We find that the G protein alpha subunit Ras and helical domains-previously observed to separate widely upon receptor binding to expose the nucleotide-binding site-separate spontaneously and frequently even in the absence of a receptor. Domain separation is necessary but not sufficient for rapid nucleotide release. Rather, receptors catalyze nucleotide release by favoring an internal structural rearrangement of the Ras domain that weakens its nucleotide affinity. We use double electron-electron resonance spectroscopy and protein engineering to confirm predictions of our computationally determined mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dror, Ron O -- Mildorf, Thomas J -- Hilger, Daniel -- Manglik, Aashish -- Borhani, David W -- Arlow, Daniel H -- Philippsen, Ansgar -- Villanueva, Nicolas -- Yang, Zhongyu -- Lerch, Michael T -- Hubbell, Wayne L -- Kobilka, Brian K -- Sunahara, Roger K -- Shaw, David E -- P30EY00331/EY/NEI NIH HHS/ -- R01EY05216/EY/NEI NIH HHS/ -- R01GM083118/GM/NIGMS NIH HHS/ -- T32 GM008294/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 19;348(6241):1361-5. doi: 10.1126/science.aaa5264.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉D. E. Shaw Research, New York, NY 10036, USA. ron.dror@deshawresearch.com david.shaw@deshawresearch.com. ; D. E. Shaw Research, New York, NY 10036, USA. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. ; Jules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA. ; D. E. Shaw Research, New York, NY 10036, USA. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. ron.dror@deshawresearch.com david.shaw@deshawresearch.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089515" target="_blank"〉PubMed〈/a〉
    Keywords: GTP-Binding Protein alpha Subunits, Gi-Go/*chemistry ; GTP-Binding Protein alpha Subunits, Gs/*chemistry ; Guanine Nucleotide Exchange Factors/*chemistry ; Humans ; Models, Chemical ; Molecular Dynamics Simulation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/*chemistry ; Signal Transduction
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  • 79
    Publication Date: 2015-02-24
    Description: An important question in ecology is how mechanistic processes occurring among individuals drive large-scale patterns of community formation and change. Here we show that in two species of bluebirds, cycles of replacement of one by the other emerge as an indirect consequence of maternal influence on offspring behavior in response to local resource availability. Sampling across broad temporal and spatial scales, we found that western bluebirds, the more competitive species, bias the birth order of offspring by sex in a way that influences offspring aggression and dispersal, setting the stage for rapid increases in population density that ultimately result in the replacement of their sister species. Our results provide insight into how predictable community dynamics can occur despite the contingency of local behavioral interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duckworth, Renee A -- Belloni, Virginia -- Anderson, Samantha R -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):875-7. doi: 10.1126/science.1260154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. rad3@email.arizona.edu. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700519" target="_blank"〉PubMed〈/a〉
    Keywords: Androgens/analysis ; Animals ; *Biological Evolution ; Clutch Size ; *Competitive Behavior ; *Ecosystem ; Egg Yolk/chemistry ; Female ; Fires ; Male ; *Maternal Behavior ; Population Density ; Songbirds/*physiology ; United States
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  • 80
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-31
    Description: Massive data collection by businesses and governments calls into question traditional methods for protecting privacy, underpinned by two core principles: (i) notice, that there should be no data collection system whose existence is secret, and (ii) consent, that data collected for one purpose not be used for another without user permission. But notice, designated as a fundamental privacy principle in a different era, makes little sense in situations where collection consists of lots and lots of small amounts of information, whereas consent is no longer realistic, given the complexity and number of decisions that must be made. Thus, efforts to protect privacy by controlling use of data are gaining more attention. I discuss relevant technology, policy, and law, as well as some examples that can illuminate the way.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Landau, Susan -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):504-6. doi: 10.1126/science.aaa4961.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Worcester Polytechnic Institute, Worcester, MA 01609, USA. susan.landau@privacyink.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635089" target="_blank"〉PubMed〈/a〉
    Keywords: *Computer Security ; *Data Collection/legislation & jurisprudence ; Genetic Privacy/legislation & jurisprudence ; Humans ; *Information Dissemination/legislation & jurisprudence ; *Informed Consent ; *Internet/legislation & jurisprudence ; *Privacy/legislation & jurisprudence ; Security Measures ; United States
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  • 81
    Publication Date: 2015-03-15
    Description: After central nervous system (CNS) injury, inhibitory factors in the lesion scar and poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration of a blood-brain barrier-permeable microtubule-stabilizing drug, epothilone B (epoB), decreased scarring after rodent spinal cord injury (SCI) by abrogating polarization and directed migration of scar-forming fibroblasts. Conversely, epothilone B reactivated neuronal polarization by inducing concerted microtubule polymerization into the axon tip, which propelled axon growth through an inhibitory environment. Together, these drug-elicited effects promoted axon regeneration and improved motor function after SCI. With recent clinical approval, epothilones hold promise for clinical use after CNS injury.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445125/" 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/PMC4445125/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruschel, Jorg -- Hellal, Farida -- Flynn, Kevin C -- Dupraz, Sebastian -- Elliott, David A -- Tedeschi, Andrea -- Bates, Margaret -- Sliwinski, Christopher -- Brook, Gary -- Dobrindt, Kristina -- Peitz, Michael -- Brustle, Oliver -- Norenberg, Michael D -- Blesch, Armin -- Weidner, Norbert -- Bunge, Mary Bartlett -- Bixby, John L -- Bradke, Frank -- R01 HD057632/HD/NICHD NIH HHS/ -- R01 NS059866/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):347-52. doi: 10.1126/science.aaa2958. Epub 2015 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. ; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 Northwest 14th Terrace, Miami, FL33136, USA. ; Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstr. 200A, 69118 Heidelberg, Germany. ; Institute for Neuropathology, RWTH Aachen University, Steinbergweg 20, 52074, Aachen, Germany. Julich-Aachen Research Alliance-Translational Brain Medicine. ; Institute of Reconstructive Neurobiology, Life&Brain Center, University of Bonn and Hertie Foundation, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. ; Departments of Pathology, Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA. ; Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. frank.bradke@dzne.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25765066" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*drug effects/physiology ; Cell Movement/drug effects ; Cell Polarity/drug effects ; Cicatrix/pathology/*prevention & control ; Epothilones/*administration & dosage ; Fibroblasts/drug effects/pathology ; Humans ; Meninges/drug effects/pathology ; Motor Activity/drug effects ; Nerve Regeneration/*drug effects ; Neurons/drug effects/pathology ; Rats ; Spinal Cord Injuries/*drug therapy/pathology/physiopathology ; Tubulin Modulators/*administration & dosage
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  • 82
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breitling, Rainer -- Takano, Eriko -- Gardner, Timothy S -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):107. doi: 10.1126/science.aaa5253.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rainer Breitling is a Professor of Systems Biology at the University of Manchester, Manchester, UK, and an external expert to the European Commission Scientific Committees. rainer.breitling@manchester.ac.uk. ; Eriko Takano is a Professor of Synthetic Biology and Co-Director of the Manchester Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), University of Manchester, Manchester, UK, and an external expert to the European Commission Scientific Committees. eriko.takano@manchester.ac.uk. ; Timothy S. Gardner is Chief Executive Officer of Riffyn, Inc., in Oakland, CA, USA, and an external expert to the European Commission Scientific Committees. tg@riffyn.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25573995" target="_blank"〉PubMed〈/a〉
    Keywords: Europe ; European Union ; Risk Assessment/methods/standards ; Synthetic Biology/*trends ; United States
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  • 83
    Publication Date: 2015-03-31
    Description: During intracellular membrane trafficking, N-ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment protein (alpha-SNAP) disassemble the soluble NSF attachment protein receptor (SNARE) complex for recycling of the SNARE proteins. The molecular mechanism by which NSF disassembles the SNARE complex is largely unknown. Using single-molecule fluorescence spectroscopy and magnetic tweezers, we found that NSF disassembled a single SNARE complex in only one round of adenosine triphosphate (ATP) turnover. Upon ATP cleavage, the NSF hexamer developed internal tension with dissociation of phosphate ions. After latent time measuring tens of seconds, NSF released the built-up tension in a burst within 20 milliseconds, resulting in disassembly followed by immediate release of the SNARE proteins. Thus, NSF appears to use a "spring-loaded" mechanism to couple ATP hydrolysis and unfolding of substrate proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441202/" 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/PMC4441202/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ryu, Je-Kyung -- Min, Duyoung -- Rah, Sang-Hyun -- Kim, Soo Jin -- Park, Yongsoo -- Kim, Haesoo -- Hyeon, Changbong -- Kim, Ho Min -- Jahn, Reinhard -- Yoon, Tae-Young -- 3P01GM072694-05S1/GM/NIGMS NIH HHS/ -- P01 GM072694/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1485-9. doi: 10.1126/science.aaa5267.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Creative Research Initiative Center for Single-Molecule Systems Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea. Department of Physics, KAIST, Daejeon 305-701, South Korea. ; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, South Korea. ; Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Korea Institute for Advanced Study, Seoul 130-722, South Korea. ; Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. rjahn@gwdg.de tyyoon@kaist.ac.kr. ; National Creative Research Initiative Center for Single-Molecule Systems Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea. Department of Physics, KAIST, Daejeon 305-701, South Korea. rjahn@gwdg.de tyyoon@kaist.ac.kr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814585" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism ; Animals ; Cattle ; Cricetinae ; Fluorescence Resonance Energy Transfer ; Hydrolysis ; N-Ethylmaleimide-Sensitive Proteins/*metabolism ; Rats ; SNARE Proteins/*metabolism ; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins/*metabolism ; Spectrometry, Fluorescence
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morell, Virginia -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1302-7. doi: 10.1126/science.347.6228.1302.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792312" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Conservation of Natural Resources ; Female ; *Food Chain ; Humans ; Male ; *Predatory Behavior ; Puma ; Ruminants ; United States ; Ursidae ; Wolves
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  • 85
    Publication Date: 2015-08-01
    Description: The actin cross-linking domain (ACD) is an actin-specific toxin produced by several pathogens, including life-threatening spp. of Vibrio cholerae, Vibrio vulnificus, and Aeromonas hydrophila. Actin cross-linking by ACD is thought to lead to slow cytoskeleton failure owing to a gradual sequestration of actin in the form of nonfunctional oligomers. Here, we found that ACD converted cytoplasmic actin into highly toxic oligomers that potently "poisoned" the ability of major actin assembly proteins, formins, to sustain actin polymerization. Thus, ACD can target the most abundant cellular protein by using actin oligomers as secondary toxins to efficiently subvert cellular functions of actin while functioning at very low doses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648357/" 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/PMC4648357/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heisler, David B -- Kudryashova, Elena -- Grinevich, Dmitry O -- Suarez, Cristian -- Winkelman, Jonathan D -- Birukov, Konstantin G -- Kotha, Sainath R -- Parinandi, Narasimham L -- Vavylonis, Dimitrios -- Kovar, David R -- Kudryashov, Dmitri S -- R01 GM079265/GM/NIGMS NIH HHS/ -- R01 GM098430/GM/NIGMS NIH HHS/ -- R01 GM114666/GM/NIGMS NIH HHS/ -- R01 HL076259/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 31;349(6247):535-9. doi: 10.1126/science.aab4090.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. kudryashov.1@osu.edu kudryashova.1@osu.edu. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. ; Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA. ; Section of Pulmonary and Critical Care and Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. ; Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA. ; Department of Physics, Lehigh University, Bethlehem, PA 18015, USA. ; Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA. Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. kudryashov.1@osu.edu kudryashova.1@osu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26228148" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Animals ; Antigens, Bacterial/*chemistry/genetics/*toxicity ; Bacterial Toxins/*chemistry/genetics/*toxicity ; Cell Line ; Fetal Proteins/*antagonists & inhibitors ; Intestinal Mucosa/drug effects/metabolism ; Microfilament Proteins/*antagonists & inhibitors ; Nuclear Proteins/*antagonists & inhibitors ; Polymerization/drug effects ; Protein Structure, Tertiary ; Rats
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  • 86
    Publication Date: 2015-02-14
    Description: The C-terminal region of Clostridium perfringens enterotoxin (C-CPE) can bind to specific claudins, resulting in the disintegration of tight junctions (TJs) and an increase in the paracellular permeability across epithelial cell sheets. Here we present the structure of mammalian claudin-19 in complex with C-CPE at 3.7 A resolution. The structure shows that C-CPE forms extensive hydrophobic and hydrophilic interactions with the two extracellular segments of claudin-19. The claudin-19/C-CPE complex shows no density of a short extracellular helix that is critical for claudins to assemble into TJ strands. The helix displacement may thus underlie C-CPE-mediated disassembly of TJs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saitoh, Yasunori -- Suzuki, Hiroshi -- Tani, Kazutoshi -- Nishikawa, Kouki -- Irie, Katsumasa -- Ogura, Yuki -- Tamura, Atsushi -- Tsukita, Sachiko -- Fujiyoshi, Yoshinori -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):775-8. doi: 10.1126/science.1261833.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. ; Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan. yoshi@cespi.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678664" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Claudins/*chemistry ; Enterotoxins/*chemistry ; Hydrophobic and Hydrophilic Interactions ; Mice ; Protein Structure, Secondary ; Tight Junctions/chemistry/*ultrastructure
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  • 87
    Publication Date: 2015-07-04
    Description: Larger brains tend to have more folded cortices, but what makes the cortex fold has remained unknown. We show that the degree of cortical folding scales uniformly across lissencephalic and gyrencephalic species, across individuals, and within individual cortices as a function of the product of cortical surface area and the square root of cortical thickness. This relation is derived from the minimization of the effective free energy associated with cortical shape according to a simple physical model, based on known mechanisms of axonal elongation. This model also explains the scaling of the folding index of crumpled paper balls. We discuss the implications of this finding for the evolutionary and developmental origin of folding, including the newfound continuum between lissencephaly and gyrencephaly, and for pathologies such as human lissencephaly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mota, Bruno -- Herculano-Houzel, Suzana -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):74-7. doi: 10.1126/science.aaa9101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. ; Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Instituto Nacional de Neurociencia Translacional, INCT/MCT, Sao Paulo, Brazil. suzanahh@gmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Count ; *Cerebral Cortex/cytology/embryology/pathology ; Humans ; Lissencephaly/*pathology ; Mice ; Models, Neurological ; Neurons/*cytology/pathology ; Rats ; Species Specificity
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 88
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1186-7. doi: 10.1126/science.348.6240.1186.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068818" target="_blank"〉PubMed〈/a〉
    Keywords: Brain/*physiology ; Clinical Trials as Topic/*ethics ; Humans ; Implantable Neurostimulators/*ethics ; Male ; Middle Aged ; National Institutes of Health (U.S.) ; Neurosciences/*ethics ; United States ; United States Food and Drug Administration
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Apr 24;348(6233):378-9. doi: 10.1126/science.348.6233.378.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908798" target="_blank"〉PubMed〈/a〉
    Keywords: Brain Injury, Chronic/*diagnosis/pathology ; Football/*injuries ; Humans ; Los Angeles ; Neuroimaging/*methods ; United States ; United States Food and Drug Administration ; Universities ; tau Proteins/analysis
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  • 90
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandrian, Michelle Gabriele -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):346. doi: 10.1126/science.347.6219.346.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Michelle Gabriele Sandrian is now an assistant professor of ophthalmology and bioengineering at the University of Pittsburgh in Pennsylvania. For more on life and careers, visit www.sciencecareers.org. Send your story to SciCareerEditor@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25593190" target="_blank"〉PubMed〈/a〉
    Keywords: Education, Graduate ; Europe ; Female ; Humans ; Infant ; *Infant Care ; Male ; *Parental Leave ; United States ; *Women, Working
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):707. doi: 10.1126/science.347.6223.707.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678641" target="_blank"〉PubMed〈/a〉
    Keywords: *Droughts ; *Global Warming ; Models, Theoretical ; United States
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  • 92
    Publication Date: 2015-03-07
    Description: Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state-like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor's inactive state.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445376/" 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/PMC4445376/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burg, John S -- Ingram, Jessica R -- Venkatakrishnan, A J -- Jude, Kevin M -- Dukkipati, Abhiram -- Feinberg, Evan N -- Angelini, Alessandro -- Waghray, Deepa -- Dror, Ron O -- Ploegh, Hidde L -- Garcia, K Christopher -- DP1 GM106409/GM/NIGMS NIH HHS/ -- R01 GM097015/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1113-7. doi: 10.1126/science.aaa5026.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Computer Science, Stanford University, Stanford, CA 94305, USA. Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA. ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. kcgarcia@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745166" target="_blank"〉PubMed〈/a〉
    Keywords: CCR5 Receptor Antagonists/chemistry ; Chemokine CX3CL1/*chemistry ; Crystallography, X-Ray ; Cyclohexanes/chemistry ; Humans ; Ligands ; Piperidines/chemistry ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, CXCR4/antagonists & inhibitors ; Receptors, Chemokine/agonists/*chemistry ; Triazoles/chemistry ; Viral Proteins/agonists/*chemistry
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  • 93
    Publication Date: 2015-03-31
    Description: Dynactin is an essential cofactor for the microtubule motor cytoplasmic dynein-1. We report the structure of the 23-subunit dynactin complex by cryo-electron microscopy to 4.0 angstroms. Our reconstruction reveals how dynactin is built around a filament containing eight copies of the actin-related protein Arp1 and one of beta-actin. The filament is capped at each end by distinct protein complexes, and its length is defined by elongated peptides that emerge from the alpha-helical shoulder domain. A further 8.2 angstrom structure of the complex between dynein, dynactin, and the motility-inducing cargo adaptor Bicaudal-D2 shows how the translational symmetry of the dynein tail matches that of the dynactin filament. The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413427/" 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/PMC4413427/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Urnavicius, Linas -- Zhang, Kai -- Diamant, Aristides G -- Motz, Carina -- Schlager, Max A -- Yu, Minmin -- Patel, Nisha A -- Robinson, Carol V -- Carter, Andrew P -- 100387/Wellcome Trust/United Kingdom -- MC_UP_A025_1011/Medical Research Council/United Kingdom -- WT100387/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1441-6. doi: 10.1126/science.aaa4080. Epub 2015 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK. ; Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK. cartera@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814576" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/chemistry ; Animals ; Cryoelectron Microscopy ; Dyneins/*chemistry ; Humans ; Mice ; Microtubule-Associated Proteins/*chemistry ; Multiprotein Complexes/*chemistry ; Protein Interaction Mapping ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Swine
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buzsaki, Gyorgy -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):612-3. doi: 10.1126/science.aaa6505.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉New York University Neuroscience Institute, New York University Langone Center, New York, NY 10016, USA. gyorgy.buzsaki@nyumc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657232" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Mapping ; Hippocampus/*physiology ; Maze Learning ; Pyramidal Cells/*physiology ; Rats ; Sensation/*physiology ; Space Perception/*physiology
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  • 95
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erwin, Douglas H -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):517. doi: 10.1126/science.aad6065.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Paleobiology, National Museum of Natural History, Smithsonian Institution, Washington, DC 20013-7012, USA. erwind@si.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516272" target="_blank"〉PubMed〈/a〉
    Keywords: Developmental Biology/*history ; *Evolution, Molecular ; *Gene Regulatory Networks ; History, 20th Century ; History, 21st Century ; United States
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  • 96
    Publication Date: 2015-02-28
    Description: Polycomb and Trithorax group proteins encode the epigenetic memory of cellular positional identity by establishing inheritable domains of repressive and active chromatin within the Hox clusters. Here we demonstrate that the CCCTC-binding factor (CTCF) functions to insulate these adjacent yet antagonistic chromatin domains during embryonic stem cell differentiation into cervical motor neurons. Deletion of CTCF binding sites within the Hox clusters results in the expansion of active chromatin into the repressive domain. CTCF functions as an insulator by organizing Hox clusters into spatially disjoint domains. Ablation of CTCF binding disrupts topological boundaries such that caudal Hox genes leave the repressed domain and become subject to transcriptional activation. Hence, CTCF is required to insulate facultative heterochromatin from impinging euchromatin to produce discrete positional identities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428148/" 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/PMC4428148/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narendra, Varun -- Rocha, Pedro P -- An, Disi -- Raviram, Ramya -- Skok, Jane A -- Mazzoni, Esteban O -- Reinberg, Danny -- GM-64844/GM/NIGMS NIH HHS/ -- GM086852/GM/NIGMS NIH HHS/ -- GM112192/GM/NIGMS NIH HHS/ -- P30 CA016087/CA/NCI NIH HHS/ -- R01 GM086852/GM/NIGMS NIH HHS/ -- R01 GM112192/GM/NIGMS NIH HHS/ -- R01 HD079682/HD/NICHD NIH HHS/ -- R01HD079682/HD/NICHD NIH HHS/ -- R37-37120/PHS HHS/ -- T32 GM007238/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):1017-21. doi: 10.1126/science.1262088.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. ; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. ; Department of Biology, New York University, New York, NY 10003, USA. ; Department of Biology, New York University, New York, NY 10003, USA. danny.reinberg@nyumc.org eom204@nyu.edu. ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. danny.reinberg@nyumc.org eom204@nyu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25722416" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/*genetics ; Chromatin/chemistry/genetics/*metabolism ; Dogs ; Embryonic Stem Cells/*cytology ; *Gene Expression Regulation ; *Genes, Homeobox ; Humans ; Mice ; Motor Neurons/*cytology ; Multigene Family ; Neck ; Protein Structure, Tertiary ; Rats ; Repressor Proteins/chemistry/genetics/*metabolism
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holt, Rush D -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):807. doi: 10.1126/science.aaa9126. Epub 2015 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rush D. Holt is Chief Executive Officer of AAAS and Executive Publisher of Science.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700491" target="_blank"〉PubMed〈/a〉
    Keywords: Science/*trends ; Societies ; United States
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  • 98
    Publication Date: 2015-11-28
    Description: Protein domains can fold into stable tertiary structures while they are synthesized on the ribosome. We used a high-performance, reconstituted in vitro translation system to investigate the folding of a small five-helix protein domain-the N-terminal domain of Escherichia coli N5-glutamine methyltransferase HemK-in real time. Our observations show that cotranslational folding of the protein, which folds autonomously and rapidly in solution, proceeds through a compact, non-native conformation that forms within the peptide tunnel of the ribosome. The compact state rearranges into a native-like structure immediately after the full domain sequence has emerged from the ribosome. Both folding transitions are rate-limited by translation, allowing for quasi-equilibrium sampling of the conformational space restricted by the ribosome. Cotranslational folding may be typical of small, intrinsically rapidly folding protein domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holtkamp, Wolf -- Kokic, Goran -- Jager, Marcus -- Mittelstaet, Joerg -- Komar, Anton A -- Rodnina, Marina V -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1104-7. doi: 10.1126/science.aad0344.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Center for Gene Regulation in Health and Disease and Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA. ; Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. rodnina@mpibpc.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612953" target="_blank"〉PubMed〈/a〉
    Keywords: Escherichia coli Proteins/biosynthesis/chemistry ; Fluorescence Resonance Energy Transfer/*methods ; Peptides/chemistry ; *Protein Biosynthesis ; *Protein Folding ; Protein Methyltransferases/biosynthesis/chemistry ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proteolysis ; Ribosomes/chemistry/*metabolism ; Time Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉LeRoy, Carri J -- New York, N.Y. -- Science. 2015 May 1;348(6234):511. doi: 10.1126/science.348.6234.511-b. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sustainability in Prisons Project, The Evergreen State College, Olympia, WA 98505, USA. LeRoyC@evergreen.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931545" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Prisoners/*education ; Prisons/*education ; Science/*education ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leshner, Alan I -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):587. doi: 10.1126/science.aaa8081.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Alan I. Leshner is the Chief Executive Officer of AAAS and Executive Publisher of Science.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657219" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Mobility ; Financial Support ; Publishing ; Science/*economics/*trends ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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