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  • Amino Acid Sequence  (2,082)
  • Rats  (1,105)
  • Transfection  (791)
  • American Association for the Advancement of Science (AAAS)  (3,462)
  • American Association of Petroleum Geologists (AAPG)
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  • 2000-2004  (776)
  • 1995-1999  (1,125)
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  • 1
    Publication Date: 2014-04-12
    Description: Plant embryogenesis initiates with the establishment of an apical-basal axis; however, the molecular mechanisms accompanying this early event remain unclear. Here, we show that a small cysteine-rich peptide family is required for formation of the zygotic basal cell lineage and proembryo patterning in Arabidopsis. EMBRYO SURROUNDING FACTOR 1 (ESF1) peptides accumulate before fertilization in central cell gametes and thereafter in embryo-surrounding endosperm cells. Biochemical and structural analyses revealed cleavage of ESF1 propeptides to form biologically active mature peptides. Further, these peptides act in a non-cell-autonomous manner and synergistically with the receptor-like kinase SHORT SUSPENSOR to promote suspensor elongation through the YODA mitogen-activated protein kinase pathway. Our findings demonstrate that the second female gamete and its sexually derived endosperm regulate early embryonic patterning in flowering plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Costa, Liliana M -- Marshall, Eleanor -- Tesfaye, Mesfin -- Silverstein, Kevin A T -- Mori, Masashi -- Umetsu, Yoshitaka -- Otterbach, Sophie L -- Papareddy, Ranjith -- Dickinson, Hugh G -- Boutiller, Kim -- VandenBosch, Kathryn A -- Ohki, Shinya -- Gutierrez-Marcos, Jose F -- BB/F008082/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/L003023/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/L003023/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):168-72. doi: 10.1126/science.1243005.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Sciences, University of Oxford, South Parks Road, OX1 3RB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24723605" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/*embryology/genetics ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; *Body Patterning ; Endosperm/embryology/genetics ; Flowers/*embryology/genetics ; Gene Duplication ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Gene Knockout Techniques ; Interleukin-1 Receptor-Associated Kinases/metabolism ; MAP Kinase Kinase Kinases/metabolism ; Molecular Sequence Data ; Peptides/chemistry/genetics/metabolism ; Seeds/*embryology/genetics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-05-31
    Description: Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilhelm, Benjamin G -- Mandad, Sunit -- Truckenbrodt, Sven -- Krohnert, Katharina -- Schafer, Christina -- Rammner, Burkhard -- Koo, Seong Joo -- Classen, Gala A -- Krauss, Michael -- Haucke, Volker -- Urlaub, Henning -- Rizzoli, Silvio O -- New York, N.Y. -- Science. 2014 May 30;344(6187):1023-8. doi: 10.1126/science.1252884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Neurosciences, 37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Molecular Biology, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. ; Leibniz Institut fur Molekulare Pharmakologie, Department of Molecular Pharmacology and Cell Biology, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. Bioanalytics, Department of Clinical Chemistry, University Medical Center Gottingen, 37075 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. srizzol@gwdg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876496" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*metabolism/ultrastructure ; Exocytosis ; Imaging, Three-Dimensional ; Immunoblotting/methods ; Mass Spectrometry/methods ; Microscopy, Electron/methods ; Models, Neurological ; Presynaptic Terminals/chemistry/*metabolism/ultrastructure ; Protein Transport ; Rats ; Rats, Wistar ; Synaptic Vesicles/chemistry/*metabolism ; Synaptosomes/chemistry/*metabolism/ultrastructure ; Vesicular Transport Proteins/analysis/*metabolism
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  • 3
    Publication Date: 2014-03-29
    Description: The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl(-)-binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wietek, Jonas -- Wiegert, J Simon -- Adeishvili, Nona -- Schneider, Franziska -- Watanabe, Hiroshi -- Tsunoda, Satoshi P -- Vogt, Arend -- Elstner, Marcus -- Oertner, Thomas G -- Hegemann, Peter -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):409-12. doi: 10.1126/science.1249375. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biology, Experimental Biophysics, Humboldt Universitat zu Berlin, D-10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674867" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Binding Sites ; CA1 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Ion Channel Gating ; Light ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Patch-Clamp Techniques ; Protein Conformation ; Protein Engineering ; Pyramidal Cells/metabolism ; Rats ; Recombinant Fusion Proteins/chemistry ; Rhodopsin/*chemistry/genetics/*metabolism ; Transfection
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-09-23
    Description: Ribonucleotide reductase (RNR) supplies the balanced pools of deoxynucleotide triphosphates (dNTPs) necessary for DNA replication and maintenance of genomic integrity. RNR is subject to allosteric regulatory mechanisms in all eukaryotes, as well as to control by small protein inhibitors Sml1p and Spd1p in budding and fission yeast, respectively. Here, we show that the metazoan protein IRBIT forms a deoxyadenosine triphosphate (dATP)-dependent complex with RNR, which stabilizes dATP in the activity site of RNR and thus inhibits the enzyme. Formation of the RNR-IRBIT complex is regulated through phosphorylation of IRBIT, and ablation of IRBIT expression in HeLa cells causes imbalanced dNTP pools and altered cell cycle progression. We demonstrate a mechanism for RNR regulation in higher eukaryotes that acts by enhancing allosteric RNR inhibition by dATP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arnaoutov, Alexei -- Dasso, Mary -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1512-5. doi: 10.1126/science.1251550.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. arnaouta@mail.nih.gov. ; Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237103" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Sequence ; Catalytic Domain ; Deoxyadenine Nucleotides/*metabolism ; HeLa Cells ; Humans ; Immunoprecipitation ; Lectins, C-Type/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Molecular Sequence Data ; Phosphorylation ; Ribonucleotide Reductases/*antagonists & inhibitors/metabolism
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  • 5
    Publication Date: 2014-04-26
    Description: Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodopsins (originally cation-conducting) converted into chloride-conducting anion channels. These tools enable fast optical inhibition of action potentials and can be engineered to display step-function kinetics for stable inhibition, outlasting light pulses and for orders-of-magnitude-greater light sensitivity of inhibited cells. The resulting family of proteins defines an approach to more physiological, efficient, and sensitive optogenetic inhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096039/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096039/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berndt, Andre -- Lee, Soo Yeun -- Ramakrishnan, Charu -- Deisseroth, Karl -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):420-4. doi: 10.1126/science.1252367.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763591" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Amino Acid Sequence ; Animals ; CA1 Region, Hippocampal/cytology ; CA3 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Light ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Neurons/*physiology ; Optogenetics ; Patch-Clamp Techniques ; Protein Engineering ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/chemistry/metabolism ; Rhodopsin/*chemistry/genetics/*metabolism
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  • 6
    Publication Date: 2014-03-08
    Description: The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991565/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Huixian -- Wang, Chong -- Gregory, Karen J -- Han, Gye Won -- Cho, Hyekyung P -- Xia, Yan -- Niswender, Colleen M -- Katritch, Vsevolod -- Meiler, Jens -- Cherezov, Vadim -- Conn, P Jeffrey -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DK097376/DK/NIDDK NIH HHS/ -- R01 GM080403/GM/NIGMS NIH HHS/ -- R01 GM099842/GM/NIGMS NIH HHS/ -- R01 MH062646/MH/NIMH NIH HHS/ -- R01 MH090192/MH/NIMH NIH HHS/ -- R01 NS031373/NS/NINDS NIH HHS/ -- R21 NS078262/NS/NINDS NIH HHS/ -- R37 NS031373/NS/NINDS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):58-64. doi: 10.1126/science.1249489. Epub 2014 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24603153" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Allosteric Site ; Amino Acid Sequence ; Benzamides/*chemistry/*metabolism ; Binding Sites ; Cholesterol ; Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Metabotropic Glutamate/*chemistry/*metabolism ; Structure-Activity Relationship ; Thiazoles/*chemistry/*metabolism
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  • 7
    Publication Date: 2014-03-22
    Description: The development of cells specialized for water conduction or support is a striking innovation of plants that has enabled them to colonize land. The NAC transcription factors regulate the differentiation of these cells in vascular plants. However, the path by which plants with these cells have evolved from their nonvascular ancestors is unclear. We investigated genes of the moss Physcomitrella patens that encode NAC proteins. Loss-of-function mutants formed abnormal water-conducting and supporting cells, as well as malformed sporophyte cells, and overexpression induced ectopic differentiation of water-conducting-like cells. Our results show conservation of transcriptional regulation and cellular function between moss and Arabidopsis thaliana water-conducting cells. The conserved genetic basis suggests roles for NAC proteins in the adaptation of plants to land.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Bo -- Ohtani, Misato -- Yamaguchi, Masatoshi -- Toyooka, Kiminori -- Wakazaki, Mayumi -- Sato, Mayuko -- Kubo, Minoru -- Nakano, Yoshimi -- Sano, Ryosuke -- Hiwatashi, Yuji -- Murata, Takashi -- Kurata, Tetsuya -- Yoneda, Arata -- Kato, Ko -- Hasebe, Mitsuyasu -- Demura, Taku -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1505-8. doi: 10.1126/science.1248417. Epub 2014 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24652936" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Amino Acid Sequence ; Arabidopsis/genetics/*physiology ; Bryopsida/genetics/*physiology ; *Gene Expression Regulation, Plant ; Genetic Loci ; Genome, Plant ; Molecular Sequence Data ; Plant Proteins/genetics/*physiology ; Plant Stems/growth & development ; Trans-Activators/genetics/*physiology ; Transcription, Genetic ; Water/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):239. doi: 10.1126/science.343.6168.239.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436399" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ants/*microbiology/physiology ; Brain/metabolism/microbiology ; Fat Body/virology ; Female ; Gryllidae/physiology/*virology ; Guanidines/analysis/metabolism ; *Host-Pathogen Interactions ; Hypocreales/*physiology ; Insect Viruses/*physiology ; Lizards/virology ; Male ; Rats ; Sexual Behavior, Animal/*physiology ; Sphingosine/analysis/metabolism ; Virus Replication
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-08-26
    Description: Sensory systems define an animal's capacity for perception and can evolve to promote survival in new environmental niches. We have uncovered a noncanonical mechanism for sweet taste perception that evolved in hummingbirds since their divergence from insectivorous swifts, their closest relatives. We observed the widespread absence in birds of an essential subunit (T1R2) of the only known vertebrate sweet receptor, raising questions about how specialized nectar feeders such as hummingbirds sense sugars. Receptor expression studies revealed that the ancestral umami receptor (the T1R1-T1R3 heterodimer) was repurposed in hummingbirds to function as a carbohydrate receptor. Furthermore, the molecular recognition properties of T1R1-T1R3 guided taste behavior in captive and wild hummingbirds. We propose that changing taste receptor function enabled hummingbirds to perceive and use nectar, facilitating the massive radiation of hummingbird species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302410/" 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/PMC4302410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldwin, Maude W -- Toda, Yasuka -- Nakagita, Tomoya -- O'Connell, Mary J -- Klasing, Kirk C -- Misaka, Takumi -- Edwards, Scott V -- Liberles, Stephen D -- R01 DC013289/DC/NIDCD NIH HHS/ -- R01DC013289/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):929-33. doi: 10.1126/science.1255097.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, and Museum of Comparative Zoology, Cambridge, MA 02138, USA. maudebaldwin@gmail.com stephen_liberles@hms.harvard.edu. ; Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. ; Bioinformatics and Molecular Evolution Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. ; Department of Animal Science, University of California, Davis, Davis, CA 95616, USA. ; Department of Organismic and Evolutionary Biology, Harvard University, and Museum of Comparative Zoology, Cambridge, MA 02138, USA. ; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. maudebaldwin@gmail.com stephen_liberles@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25146290" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Mice ; Molecular Sequence Data ; Plant Nectar ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/chemistry/classification/*genetics ; Taste/*physiology ; Taste Perception/genetics/*physiology
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  • 10
    Publication Date: 2014-04-26
    Description: The hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Here, we report the 11-angstrom-resolution cryogenic electron microscopy (cryo-EM) structures of 30-nanometer chromatin fibers reconstituted in the presence of linker histone H1 and with different nucleosome repeat lengths. The structures show a histone H1-dependent left-handed twist of the repeating tetranucleosomal structural units, within which the four nucleosomes zigzag back and forth with a straight linker DNA. The asymmetric binding and the location of histone H1 in chromatin play a role in the formation of the 30-nanometer fiber. Our results provide mechanistic insights into how nucleosomes compact into higher-order chromatin fibers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Feng -- Chen, Ping -- Sun, Dapeng -- Wang, Mingzhu -- Dong, Liping -- Liang, Dan -- Xu, Rui-Ming -- Zhu, Ping -- Li, Guohong -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):376-80. doi: 10.1126/science.1251413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763583" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Chromatin/chemistry/metabolism/*ultrastructure ; Cryoelectron Microscopy ; DNA/chemistry/*ultrastructure ; Histones/*chemistry/metabolism ; Imaging, Three-Dimensional ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Nucleosomes/*ultrastructure ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; Xenopus Proteins/chemistry ; Xenopus laevis
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  • 11
    Publication Date: 2014-10-18
    Description: Nitrogen (N) is a critical nutrient for plants but is often distributed unevenly in the soil. Plants therefore have evolved a systemic mechanism by which N starvation on one side of the root system leads to a compensatory and increased nitrate uptake on the other side. Here, we study the molecular systems that support perception of N and the long-distance signaling needed to alter root development. Rootlets starved of N secrete small peptides that are translocated to the shoot and received by two leucine-rich repeat receptor kinases (LRR-RKs). Arabidopsis plants deficient in this pathway show growth retardation accompanied with N-deficiency symptoms. Thus, signaling from the root to the shoot helps the plant adapt to fluctuations in local N availability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabata, Ryo -- Sumida, Kumiko -- Yoshii, Tomoaki -- Ohyama, Kentaro -- Shinohara, Hidefumi -- Matsubayashi, Yoshikatsu -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):343-6. doi: 10.1126/science.1257800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. ; Department of Applied Molecular Biosciences, Graduate School of Bio-Agricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. matsu@bio.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324386" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Molecular Sequence Data ; Nitrogen/*metabolism ; Peptides/*metabolism ; Plant Roots/genetics/*growth & development/metabolism ; Plant Shoots/genetics/*growth & development/metabolism ; Receptors, Peptide/genetics/*metabolism ; Signal Transduction
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  • 12
    Publication Date: 2014-07-26
    Description: Proteins that cap the ends of the actin filament are essential regulators of cytoskeleton dynamics. Whereas several proteins cap the rapidly growing barbed end, tropomodulin (Tmod) is the only protein known to cap the slowly growing pointed end. The lack of structural information severely limits our understanding of Tmod's capping mechanism. We describe crystal structures of actin complexes with the unstructured amino-terminal and the leucine-rich repeat carboxy-terminal domains of Tmod. The structures and biochemical analysis of structure-inspired mutants showed that one Tmod molecule interacts with three actin subunits at the pointed end, while also contacting two tropomyosin molecules on each side of the filament. We found that Tmod achieves high-affinity binding through several discrete low-affinity interactions, which suggests a mechanism for controlled subunit exchange at the pointed end.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367809/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rao, Jampani Nageswara -- Madasu, Yadaiah -- Dominguez, Roberto -- GM-0080/GM/NIGMS NIH HHS/ -- R01 GM073791/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):463-7. doi: 10.1126/science.1256159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. droberto@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061212" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*chemistry ; Actins/*chemistry ; Amino Acid Sequence ; Animals ; Crystallography, X-Ray ; Humans ; Molecular Sequence Data ; Mutation ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rabbits ; Tropomodulin/*chemistry/genetics
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  • 13
    Publication Date: 2014-05-24
    Description: Cushing's syndrome is caused by excess cortisol production from the adrenocortical gland. In corticotropin-independent Cushing's syndrome, the excess cortisol production is primarily attributed to an adrenocortical adenoma, in which the underlying molecular pathogenesis has been poorly understood. We report a hotspot mutation (L206R) in PRKACA, which encodes the catalytic subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), in more than 50% of cases with adrenocortical adenomas associated with corticotropin-independent Cushing's syndrome. The L206R PRKACA mutant abolished its binding to the regulatory subunit of PKA (PRKAR1A) that inhibits catalytic activity of PRKACA, leading to constitutive, cAMP-independent PKA activation. These results highlight the major role of cAMP-independent activation of cAMP/PKA signaling by somatic mutations in corticotropin-independent Cushing's syndrome, providing insights into the diagnosis and therapeutics of this syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sato, Yusuke -- Maekawa, Shigekatsu -- Ishii, Ryohei -- Sanada, Masashi -- Morikawa, Teppei -- Shiraishi, Yuichi -- Yoshida, Kenichi -- Nagata, Yasunobu -- Sato-Otsubo, Aiko -- Yoshizato, Tetsuichi -- Suzuki, Hiromichi -- Shiozawa, Yusuke -- Kataoka, Keisuke -- Kon, Ayana -- Aoki, Kosuke -- Chiba, Kenichi -- Tanaka, Hiroko -- Kume, Haruki -- Miyano, Satoru -- Fukayama, Masashi -- Nureki, Osamu -- Homma, Yukio -- Ogawa, Seishi -- New York, N.Y. -- Science. 2014 May 23;344(6186):917-20. doi: 10.1126/science.1252328.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan. ; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. sogawa-tky@umin.ac.jp homma-uro@umin.ac.jp. ; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. sogawa-tky@umin.ac.jp homma-uro@umin.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855271" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenal Cortex Neoplasms/*genetics ; Adrenocortical Adenoma/*genetics ; Adrenocorticotropic Hormone/metabolism ; Animals ; Catalytic Domain/genetics ; Cushing Syndrome/*genetics/metabolism ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/*genetics/metabolism ; DNA Mutational Analysis ; GTP-Binding Protein alpha Subunits/genetics ; HEK293 Cells ; Humans ; Mice ; Mutation ; NIH 3T3 Cells ; PC12 Cells ; Rats
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  • 14
    Publication Date: 2014-01-18
    Description: Transcription factors (TFs) are key players in evolution. Changes affecting their function can yield novel life forms but may also have deleterious effects. Consequently, gene duplication events that release one gene copy from selective pressure are thought to be the common mechanism by which TFs acquire new activities. Here, we show that LEAFY, a major regulator of flower development and cell division in land plants, underwent changes to its DNA binding specificity, even though plant genomes generally contain a single copy of the LEAFY gene. We examined how these changes occurred at the structural level and identify an intermediate LEAFY form in hornworts that appears to adopt all different specificities. This promiscuous intermediate could have smoothed the evolutionary transitions, thereby allowing LEAFY to evolve new binding specificities while remaining a single-copy gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sayou, Camille -- Monniaux, Marie -- Nanao, Max H -- Moyroud, Edwige -- Brockington, Samuel F -- Thevenon, Emmanuel -- Chahtane, Hicham -- Warthmann, Norman -- Melkonian, Michael -- Zhang, Yong -- Wong, Gane Ka-Shu -- Weigel, Detlef -- Parcy, Francois -- Dumas, Renaud -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):645-8. doi: 10.1126/science.1248229. Epub 2014 Jan 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, Laboratoire de Physiologie Cellulaire et Vegetale (LPCV), UMR 5168, 38054 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436181" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis Proteins/chemistry/classification/genetics ; DNA, Plant/*chemistry ; DNA-Binding Proteins/*chemistry/classification/*genetics ; Electrophoretic Mobility Shift Assay ; *Evolution, Molecular ; Gene Dosage ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Proteins/*chemistry/classification/*genetics ; Protein Binding/genetics ; Protein Structure, Tertiary ; Species Specificity ; Transcription Factors/chemistry/classification/genetics
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  • 15
    Publication Date: 2014-02-08
    Description: We report that the oxytocin-mediated neuroprotective gamma-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naive mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tyzio, Roman -- Nardou, Romain -- Ferrari, Diana C -- Tsintsadze, Timur -- Shahrokhi, Amene -- Eftekhari, Sanaz -- Khalilov, Ilgam -- Tsintsadze, Vera -- Brouchoud, Corinne -- Chazal, Genevieve -- Lemonnier, Eric -- Lozovaya, Natalia -- Burnashev, Nail -- Ben-Ari, Yehezkel -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):675-9. doi: 10.1126/science.1247190.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503856" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*chemically induced/*genetics/metabolism ; Behavior, Animal ; Bumetanide/administration & dosage ; Chlorides/metabolism ; *Cytoprotection ; Disease Models, Animal ; Female ; Fragile X Mental Retardation Protein/genetics ; Maternal-Fetal Exchange ; Mice ; Oxytocin/*metabolism ; Parturition ; Pregnancy ; Rats ; Valproic Acid/pharmacology ; gamma-Aminobutyric Acid/*metabolism
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  • 16
    Publication Date: 2014-05-03
    Description: We demonstrate a technique for mapping brain activity that combines molecular specificity and spatial coverage using a neurotransmitter sensor detectable by magnetic resonance imaging (MRI). This molecular functional MRI (fMRI) method yielded time-resolved volumetric measurements of dopamine release evoked by reward-related lateral hypothalamic brain stimulation of rats injected with the neurotransmitter sensor. Peak dopamine concentrations and release rates were observed in the anterior nucleus accumbens core. Substantial dopamine transients were also present in more caudal areas. Dopamine-release amplitudes correlated with the rostrocaudal stimulation coordinate, suggesting participation of hypothalamic circuitry in modulating dopamine responses. This work provides a foundation for development and application of quantitative molecular fMRI techniques targeted toward numerous components of neural physiology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Taekwan -- Cai, Lili X -- Lelyveld, Victor S -- Hai, Aviad -- Jasanoff, Alan -- DP2-OD002114/OD/NIH HHS/ -- R01-DA02899/DA/NIDA NIH HHS/ -- R01-NS076462/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 May 2;344(6183):533-5. doi: 10.1126/science.1249380.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786083" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/*chemistry/genetics ; Brain Mapping/*methods ; Contrast Media/*chemistry ; Cytochrome P-450 Enzyme System/*chemistry/genetics ; Dopamine/*metabolism ; Dopaminergic Neurons ; Magnetic Resonance Imaging/*methods ; Male ; Molecular Imaging/*methods ; NADPH-Ferrihemoprotein Reductase/*chemistry/genetics ; Nucleus Accumbens/*metabolism ; Rats ; Rats, Sprague-Dawley
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  • 17
    Publication Date: 2014-07-12
    Description: Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naive recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289910/" 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/PMC4289910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carlson, Jonathan M -- Schaefer, Malinda -- Monaco, Daniela C -- Batorsky, Rebecca -- Claiborne, Daniel T -- Prince, Jessica -- Deymier, Martin J -- Ende, Zachary S -- Klatt, Nichole R -- DeZiel, Charles E -- Lin, Tien-Ho -- Peng, Jian -- Seese, Aaron M -- Shapiro, Roger -- Frater, John -- Ndung'u, Thumbi -- Tang, Jianming -- Goepfert, Paul -- Gilmour, Jill -- Price, Matt A -- Kilembe, William -- Heckerman, David -- Goulder, Philip J R -- Allen, Todd M -- Allen, Susan -- Hunter, Eric -- 2P51RR000165-51/RR/NCRR NIH HHS/ -- G108/626/Medical Research Council/United Kingdom -- OD P51OD11132/OD/NIH HHS/ -- P01-AI074415/AI/NIAID NIH HHS/ -- P30 AI050409/AI/NIAID NIH HHS/ -- P51 OD010425/OD/NIH HHS/ -- P51 OD011132/OD/NIH HHS/ -- P51RR165/RR/NCRR NIH HHS/ -- R01 AI064060/AI/NIAID NIH HHS/ -- R01 AI64060/AI/NIAID NIH HHS/ -- R37 AI051231/AI/NIAID NIH HHS/ -- R37 AI51231/AI/NIAID NIH HHS/ -- T32 AI007387/AI/NIAID NIH HHS/ -- T32-AI007387/AI/NIAID NIH HHS/ -- U01 AI 66454/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):1254031. doi: 10.1126/science.1254031. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microsoft Research, Redmond, WA 98052, USA. carlson@microsoft.com ehunte4@emory.edu. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. ; Microsoft Research, Redmond, WA 98052, USA. ; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 7BN, UK. National Institute of Health Research, Oxford Biomedical Research Centre, Oxford OX3 7LE, UK. Oxford Martin School, University of Oxford, Oxford OX1 3BD, UK. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa. Max Planck Institute for Infection Biology, D-10117 Berlin, Germany. ; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. ; International AIDS Vaccine Initiative, London SW10 9NH, UK. Imperial College of Science Technology and Medicine, London SW10 9NH, UK. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94105, USA. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. ; Microsoft Research, Los Angeles, CA 98117, USA. ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Microsoft Research, Los Angeles, CA 98117, USA. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. carlson@microsoft.com ehunte4@emory.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013080" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Consensus Sequence ; DNA Mutational Analysis ; Disease Transmission, Infectious/statistics & numerical data ; Female ; HIV Infections/*transmission ; HIV-1/*genetics ; *Heterosexuality ; High-Throughput Nucleotide Sequencing ; Human Immunodeficiency Virus Proteins/genetics ; Humans ; Male ; Models, Statistical ; Molecular Sequence Data ; Point Mutation ; Risk Factors ; *Selection, Genetic ; Viral Load
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  • 18
    Publication Date: 2014-04-05
    Description: Damage to the central nervous system caused by traumatic injury or neurological disorders can lead to permanent loss of voluntary motor function and muscle paralysis. Here, we describe an approach that circumvents central motor circuit pathology to restore specific skeletal muscle function. We generated murine embryonic stem cell-derived motor neurons that express the light-sensitive ion channel channelrhodopsin-2, which we then engrafted into partially denervated branches of the sciatic nerve of adult mice. These engrafted motor neurons not only reinnervated lower hind-limb muscles but also enabled their function to be restored in a controllable manner using optogenetic stimulation. This synthesis of regenerative medicine and optogenetics may be a successful strategy to restore muscle function after traumatic injury or disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bryson, J Barney -- Machado, Carolina Barcellos -- Crossley, Martin -- Stevenson, Danielle -- Bros-Facer, Virginie -- Burrone, Juan -- Greensmith, Linda -- Lieberam, Ivo -- 095589/Wellcome Trust/United Kingdom -- G0900585/Medical Research Council/United Kingdom -- G1001234/Biotechnology and Biological Sciences Research Council/United Kingdom -- MR/K000608/1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):94-7. doi: 10.1126/science.1248523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Cell Line ; Electric Stimulation ; Embryonic Stem Cells/cytology/physiology ; Female ; Hindlimb ; Isometric Contraction ; *Light ; Mice ; Mice, Inbred C57BL ; Motor Neurons/cytology/*physiology/*transplantation ; Muscle Denervation ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/*innervation/*physiology ; Nerve Regeneration ; *Optogenetics ; Rhodopsin/genetics/metabolism ; Sciatic Nerve/physiology ; Transfection ; Transgenes
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  • 19
    Publication Date: 2014-05-17
    Description: Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family of versatile cell recognition molecules, as retrograde signals for elimination of redundant climbing fiber to Purkinje cell synapses in developing mouse cerebellum. Knockdown of Sema3A, a secreted semaphorin, in Purkinje cells or its receptor in climbing fibers accelerated synapse elimination during postnatal day 8 (P8) to P18. Conversely, knockdown of Sema7A, a membrane-anchored semaphorin, in Purkinje cells or either of its two receptors in climbing fibers impaired synapse elimination after P15. The effect of Sema7A involves signaling by metabotropic glutamate receptor 1, a canonical pathway for climbing fiber synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of synapse elimination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uesaka, Naofumi -- Uchigashima, Motokazu -- Mikuni, Takayasu -- Nakazawa, Takanobu -- Nakao, Harumi -- Hirai, Hirokazu -- Aiba, Atsu -- Watanabe, Masahiko -- Kano, Masanobu -- New York, N.Y. -- Science. 2014 May 30;344(6187):1020-3. doi: 10.1126/science.1252514. Epub 2014 May 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. ; Laboratory of Animal Resources, Center for Disease Biology and Integrated Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ; Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. ; Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. mkano-tky@m.u-tokyo.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24831527" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/genetics/*metabolism ; Brain/*growth & development/metabolism ; Gene Knockdown Techniques ; Mice ; Mice, Inbred C57BL ; Purkinje Cells/metabolism/*physiology ; RNA Interference ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/genetics/metabolism ; Semaphorin-3A/genetics/*metabolism ; Semaphorins/genetics/*metabolism ; Signal Transduction ; Synapses/genetics/*physiology
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):149. doi: 10.1126/science.346.6206.149-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Geographic Information Systems ; Hippocampus/*cytology ; Humans ; Neurons/*physiology ; *Neurosciences ; *Nobel Prize ; Rats ; Spatial Behavior/*physiology
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  • 21
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cappellini, Enrico -- Collins, Matthew J -- Gilbert, M Thomas P -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1320-2. doi: 10.1126/science.1249274.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653025" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Databases, Protein ; Fossils ; Humans ; *Mass Spectrometry/instrumentation/methods ; Mummies ; Proteins/*chemistry/isolation & purification ; Proteolysis ; Proteomics
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  • 22
    Publication Date: 2014-11-22
    Description: Chromosome segregation depends on sister chromatid cohesion mediated by cohesin. The cohesin subunits Smc1, Smc3, and Scc1 form tripartite rings that are thought to open at distinct sites to allow entry and exit of DNA. However, direct evidence for the existence of open forms of cohesin is lacking. We found that cohesin's proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. Mutation of this interface abolished cohesin's ability to stably associate with chromatin and to mediate cohesion. Electron microscopy revealed that weakening of the Smc3-Scc1 interface resulted in opening of cohesin rings, as did proteolytic cleavage of Scc1. These open forms may resemble intermediate states of cohesin normally generated by the release factor Wapl and the protease separase, respectively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huis in 't Veld, Pim J -- Herzog, Franz -- Ladurner, Rene -- Davidson, Iain F -- Piric, Sabina -- Kreidl, Emanuel -- Bhaskara, Venugopal -- Aebersold, Ruedi -- Peters, Jan-Michael -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):968-72. doi: 10.1126/science.1256904.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria. ; Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland. Department of Biochemistry, Gene Center, Ludwig-Maximilian University, 81377 Munich, Germany. ; Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland. ; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria. peters@imp.ac.at.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25414306" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Carrier Proteins/genetics/metabolism ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Chondroitin Sulfate Proteoglycans/chemistry/genetics/*metabolism ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/chemistry/genetics/*metabolism ; *Chromosome Segregation ; DNA/*metabolism ; DNA Replication ; Humans ; Mass Spectrometry ; Microscopy, Electron ; Molecular Sequence Data ; Nuclear Proteins/chemistry/genetics/*metabolism ; Phosphoproteins/chemistry/genetics/*metabolism ; Protein Multimerization ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/genetics/metabolism ; Separase/metabolism
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  • 23
    Publication Date: 2014-05-31
    Description: Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4Kbeta (PI4KIIIbeta) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIbeta interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIbeta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIbeta to combat malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046302/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046302/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, John E -- Inglis, Alison J -- Perisic, Olga -- Masson, Glenn R -- McLaughlin, Stephen H -- Rutaganira, Florentine -- Shokat, Kevan M -- Williams, Roger L -- MC_U105184308/Medical Research Council/United Kingdom -- PG/11/109/29247/British Heart Foundation/United Kingdom -- PG11/109/29247/British Heart Foundation/United Kingdom -- R01AI099245/AI/NIAID NIH HHS/ -- T32 GM064337/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. jeburke@uvic.ca rlw@mrc-lmb.cam.ac.uk. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876499" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antimalarials/chemistry/pharmacology ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Drug Design ; Humans ; I-kappa B Kinase/*chemistry ; Molecular Sequence Data ; Mutation ; Phosphotransferases (Alcohol Group Acceptor)/*chemistry/genetics ; Plasmodium/drug effects/growth & development ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; rab GTP-Binding Proteins/*chemistry
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  • 24
    Publication Date: 2014-01-05
    Description: Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Delta(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vallee, Monique -- Vitiello, Sergio -- Bellocchio, Luigi -- Hebert-Chatelain, Etienne -- Monlezun, Stephanie -- Martin-Garcia, Elena -- Kasanetz, Fernando -- Baillie, Gemma L -- Panin, Francesca -- Cathala, Adeline -- Roullot-Lacarriere, Valerie -- Fabre, Sandy -- Hurst, Dow P -- Lynch, Diane L -- Shore, Derek M -- Deroche-Gamonet, Veronique -- Spampinato, Umberto -- Revest, Jean-Michel -- Maldonado, Rafael -- Reggio, Patricia H -- Ross, Ruth A -- Marsicano, Giovanni -- Piazza, Pier Vincenzo -- 260515/European Research Council/International -- DA-003934/DA/NIDA NIH HHS/ -- DA-03672/DA/NIDA NIH HHS/ -- DA-09789/DA/NIDA NIH HHS/ -- K05 DA021358/DA/NIDA NIH HHS/ -- R01 DA003934/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):94-8. doi: 10.1126/science.1243985.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U862, F-33000 Bordeaux, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385629" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*drug effects/metabolism ; Cannabinoid Receptor Antagonists/administration & dosage ; Cannabis/*toxicity ; Dronabinol/*toxicity ; Male ; Marijuana Abuse/drug therapy ; Mice ; Mice, Inbred C57BL ; Pregnenolone/*administration & dosage/*metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptor, Cannabinoid, CB1/*agonists/*antagonists & inhibitors
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  • 25
    Publication Date: 2014-01-11
    Description: It has been assumed that most, if not all, signals regulating early development have been identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence and overproduction of Toddler reduce the movement of mesendodermal cells during zebrafish gastrulation. Local and ubiquitous production of Toddler promote cell movement, suggesting that Toddler is neither an attractant nor a repellent but acts globally as a motogen. Toddler drives internalization of G protein-coupled APJ/Apelin receptors, and activation of APJ/Apelin signaling rescues toddler mutants. These results indicate that Toddler is an activator of APJ/Apelin receptor signaling, promotes gastrulation movements, and might be the first in a series of uncharacterized developmental signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107353/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pauli, Andrea -- Norris, Megan L -- Valen, Eivind -- Chew, Guo-Liang -- Gagnon, James A -- Zimmerman, Steven -- Mitchell, Andrew -- Ma, Jiao -- Dubrulle, Julien -- Reyon, Deepak -- Tsai, Shengdar Q -- Joung, J Keith -- Saghatelian, Alan -- Schier, Alexander F -- K99 HD076935/HD/NICHD NIH HHS/ -- R01 GM056211/GM/NIGMS NIH HHS/ -- R01 GM102491/GM/NIGMS NIH HHS/ -- R01 HG005111/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):1248636. doi: 10.1126/science.1248636. Epub 2014 Jan 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24407481" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Cell Movement ; Chemokine CXCL12/metabolism ; Frameshift Mutation ; Gastrulation/genetics/*physiology ; Molecular Sequence Data ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Signal Transduction ; Zebrafish/*embryology/genetics/metabolism ; Zebrafish Proteins/genetics/*metabolism
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  • 26
    Publication Date: 2014-10-18
    Description: Small molecules are useful tools for probing the biological function and therapeutic potential of individual proteins, but achieving selectivity is challenging when the target protein shares structural domains with other proteins. The Bromo and Extra-Terminal (BET) proteins have attracted interest because of their roles in transcriptional regulation, epigenetics, and cancer. The BET bromodomains (protein interaction modules that bind acetyl-lysine) have been targeted by potent small-molecule inhibitors, but these inhibitors lack selectivity for individual family members. We developed an ethyl derivative of an existing small-molecule inhibitor, I-BET/JQ1, and showed that it binds leucine/alanine mutant bromodomains with nanomolar affinity and achieves up to 540-fold selectivity relative to wild-type bromodomains. Cell culture studies showed that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. Expansion of this approach could help identify the individual roles of single BET proteins in human physiology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458378/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458378/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baud, Matthias G J -- Lin-Shiao, Enrique -- Cardote, Teresa -- Tallant, Cynthia -- Pschibul, Annica -- Chan, Kwok-Ho -- Zengerle, Michael -- Garcia, Jordi R -- Kwan, Terence T-L -- Ferguson, Fleur M -- Ciulli, Alessio -- 097945/Z/11/Z/Wellcome Trust/United Kingdom -- 100476/Z/12/Z/Wellcome Trust/United Kingdom -- BB/G023123/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J001201/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):638-41. doi: 10.1126/science.1249830. Epub 2014 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. a.ciulli@dundee.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25323695" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Azepines/chemistry/pharmacology ; Cell Line, Tumor ; Chromatin/chemistry ; Crystallography, X-Ray ; Humans ; Leucine/genetics ; Models, Molecular ; Molecular Probes/*chemistry ; Mutation ; Nuclear Proteins/antagonists & inhibitors/*chemistry/genetics ; Protein Engineering/*methods ; Protein Structure, Tertiary ; Transcription Factors/antagonists & inhibitors/*chemistry/genetics ; Triazoles/chemistry/pharmacology
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimm, David -- New York, N.Y. -- Science. 2014 May 2;344(6183):461. doi: 10.1126/science.344.6183.461.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786056" target="_blank"〉PubMed〈/a〉
    Keywords: Analgesia ; Animals ; Anti-Inflammatory Agents/administration & dosage ; Biomedical Research/*standards ; Female ; Humans ; Male ; Mice ; *Odors ; Pain/*physiopathology/prevention & control ; Pain Measurement ; Pain Threshold ; Rats ; Sex Factors ; *Smell
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):361-3. doi: 10.1126/science.343.6169.361.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458620" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemically-Induced Disorders/*genetics ; DNA Methylation/drug effects ; *Epigenesis, Genetic ; Epigenomics/economics/trends ; Evolution, Molecular ; Female ; Humans ; Male ; Rats ; Reproduction/drug effects/genetics ; Sexual Behavior, Animal/drug effects ; Spermatozoa/*abnormalities/*drug effects
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-31
    Description: N-Methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors, which mediate most excitatory synaptic transmission in mammalian brains. Calcium permeation triggered by activation of NMDA receptors is the pivotal event for initiation of neuronal plasticity. Here, we show the crystal structure of the intact heterotetrameric GluN1-GluN2B NMDA receptor ion channel at 4 angstroms. The NMDA receptors are arranged as a dimer of GluN1-GluN2B heterodimers with the twofold symmetry axis running through the entire molecule composed of an amino terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD). The ATD and LBD are much more highly packed in the NMDA receptors than non-NMDA receptors, which may explain why ATD regulates ion channel activity in NMDA receptors but not in non-NMDA receptors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113085/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113085/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karakas, Erkan -- Furukawa, Hiro -- MH085926/MH/NIMH NIH HHS/ -- R01 GM105730/GM/NIGMS NIH HHS/ -- R01 MH085926/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):992-7. doi: 10.1126/science.1251915.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, W. M. Keck Structural Biology Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. ; Cold Spring Harbor Laboratory, W. M. Keck Structural Biology Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. furukawa@cshl.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876489" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Calcium/chemistry/metabolism ; Crystallography, X-Ray ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Receptors, N-Methyl-D-Aspartate/*chemistry/metabolism
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  • 30
    Publication Date: 2014-11-22
    Description: Through their association with a kleisin subunit (Scc1), cohesin's Smc1 and Smc3 subunits are thought to form tripartite rings that mediate sister chromatid cohesion. Unlike the structure of Smc1/Smc3 and Smc1/Scc1 interfaces, that of Smc3/Scc1 is not known. Disconnection of this interface is thought to release cohesin from chromosomes in a process regulated by acetylation. We show here that the N-terminal domain of yeast Scc1 contains two alpha helices, forming a four-helix bundle with the coiled coil emerging from Smc3's adenosine triphosphatase head. Mutations affecting this interaction compromise cohesin's association with chromosomes. The interface is far from Smc3 residues, whose acetylation prevents cohesin's dissociation from chromosomes. Cohesin complexes holding chromatids together in vivo do indeed have the configuration of hetero-trimeric rings, and sister DNAs are entrapped within these.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300515/" 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/PMC4300515/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gligoris, Thomas G -- Scheinost, Johanna C -- Burmann, Frank -- Petela, Naomi -- Chan, Kok-Lung -- Uluocak, Pelin -- Beckouet, Frederic -- Gruber, Stephan -- Nasmyth, Kim -- Lowe, Jan -- 091859/Z/10/Z/Wellcome Trust/United Kingdom -- 095514/Wellcome Trust/United Kingdom -- 095514/Z/11/Z/Wellcome Trust/United Kingdom -- C573/A 12386/Cancer Research UK/United Kingdom -- C573/A11625/Medical Research Council/United Kingdom -- MC_U105184326/Medical Research Council/United Kingdom -- U10518432/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):963-7. doi: 10.1126/science.1256917.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. ; Max-Planck-Institut fur Biochemie, 82152, Martinsried, Germany. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Medical Research Council (MRC) Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Dunn School of Pathology, University of Oxford, Oxford OX1 3RF, UK. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. kim.nasmyth@bioch.ox.ac.uk jyl@mrc-lmb.cam.ac.uk. ; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK. kim.nasmyth@bioch.ox.ac.uk jyl@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25414305" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/chemistry ; Amino Acid Sequence ; Cell Cycle Proteins/*chemistry/genetics ; Chromosomal Proteins, Non-Histone/*chemistry/genetics ; Conserved Sequence ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; DNA/chemistry ; Mutation ; Protein Multimerization ; Protein Structure, Tertiary ; Saccharomyces cerevisiae Proteins/*chemistry/genetics
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1194-7. doi: 10.1126/science.343.6176.1194.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626911" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria ; Beetles ; Cough/microbiology ; Humans ; Plant Leaves ; Rats ; Skin ; Sneezing ; Surface Tension ; Viruses ; Water/*chemistry ; *Wettability
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  • 32
    Publication Date: 2014-12-20
    Description: Evolution and design of protein complexes are almost always viewed through the lens of amino acid mutations at protein interfaces. We showed previously that residues not involved in the physical interaction between proteins make important contributions to oligomerization by acting indirectly or allosterically. In this work, we sought to investigate the mechanism by which allosteric mutations act, using the example of the PyrR family of pyrimidine operon attenuators. In this family, a perfectly sequence-conserved helix that forms a tetrameric interface is exposed as solvent-accessible surface in dimeric orthologs. This means that mutations must be acting from a distance to destabilize the interface. We identified 11 key mutations controlling oligomeric state, all distant from the interfaces and outside ligand-binding pockets. Finally, we show that the key mutations introduce conformational changes equivalent to the conformational shift between the free versus nucleotide-bound conformations of the proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337988/" 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/PMC4337988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perica, Tina -- Kondo, Yasushi -- Tiwari, Sandhya P -- McLaughlin, Stephen H -- Kemplen, Katherine R -- Zhang, Xiuwei -- Steward, Annette -- Reuter, Nathalie -- Clarke, Jane -- Teichmann, Sarah A -- 095195/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1254346. doi: 10.1126/science.1254346.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Department of Molecular Biology, University of Bergen University of Bergen, P.O. Box 7803, N-5020 Bergen, Norway. Computational Biology Unit, Department of Informatics, University of Bergen, P.O. Box 7803, N-5020 Bergen, Norway. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. saraht@ebi.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525255" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/*genetics ; Amino Acid Sequence ; Bacillus subtilis/metabolism ; Bacterial Proteins/*chemistry/genetics ; Conserved Sequence ; *Evolution, Molecular ; Ligands ; Mutation ; Pentosyltransferases/*chemistry/genetics ; Protein Binding/genetics ; Protein Conformation ; *Protein Engineering ; Protein Multimerization/*genetics ; Repressor Proteins/*chemistry/genetics
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  • 33
    Publication Date: 2014-07-19
    Description: Cytoplasmic dynein is a molecular motor that transports a large variety of cargoes (e.g., organelles, messenger RNAs, and viruses) along microtubules over long intracellular distances. The dynactin protein complex is important for dynein activity in vivo, but its precise role has been unclear. Here, we found that purified mammalian dynein did not move processively on microtubules in vitro. However, when dynein formed a complex with dynactin and one of four different cargo-specific adapter proteins, the motor became ultraprocessive, moving for distances similar to those of native cargoes in living cells. Thus, we propose that dynein is largely inactive in the cytoplasm and that a variety of adapter proteins activate processive motility by linking dynactin to dynein only when the motor is bound to its proper cargo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224444/" 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/PMC4224444/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKenney, Richard J -- Huynh, Walter -- Tanenbaum, Marvin E -- Bhabha, Gira -- Vale, Ronald D -- F32GM096484/GM/NIGMS NIH HHS/ -- R01 GM097312/GM/NIGMS NIH HHS/ -- R01GM097312/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):337-41. doi: 10.1126/science.1254198. Epub 2014 Jun 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. ; Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. vale@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035494" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; Cytoplasmic Dyneins/chemistry/*metabolism ; Humans ; Mice ; Microtubule-Associated Proteins/*metabolism ; Microtubules/chemistry/*metabolism ; Motion ; Protein Transport ; Rats
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  • 34
    Publication Date: 2014-04-20
    Description: Tight junctions are cell-cell adhesion structures in epithelial cell sheets that surround organ compartments in multicellular organisms and regulate the permeation of ions through the intercellular space. Claudins are the major constituents of tight junctions and form strands that mediate cell adhesion and function as paracellular barriers. We report the structure of mammalian claudin-15 at a resolution of 2.4 angstroms. The structure reveals a characteristic beta-sheet fold comprising two extracellular segments, which is anchored to a transmembrane four-helix bundle by a consensus motif. Our analyses suggest potential paracellular pathways with distinctive charges on the extracellular surface, providing insight into the molecular basis of ion homeostasis across tight junctions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Hiroshi -- Nishizawa, Tomohiro -- Tani, Kazutoshi -- Yamazaki, Yuji -- Tamura, Atsushi -- Ishitani, Ryuichiro -- Dohmae, Naoshi -- Tsukita, Sachiko -- Nureki, Osamu -- Fujiyoshi, Yoshinori -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):304-7. doi: 10.1126/science.1248571.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744376" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Claudins/*chemistry ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Static Electricity ; Tight Junctions/*chemistry/physiology
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  • 35
    Publication Date: 2014-08-16
    Description: Natural interconversions between distinct somatic cell types have been reported in species as diverse as jellyfish and mice. The efficiency and reproducibility of some reprogramming events represent unexploited avenues in which to probe mechanisms that ensure robust cell conversion. We report that a conserved H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex cooperate to ensure invariant transdifferentiation (Td) of postmitotic Caenorhabditis elegans hindgut cells into motor neurons. At single-cell resolution, robust conversion requires stepwise histone-modifying activities, functionally partitioned into discrete phases of Td through nuclear degradation of JMJD-3.1 and phase-specific interactions with transcription factors that have conserved roles in cell plasticity and terminal fate selection. Our results draw parallels between epigenetic mechanisms underlying robust Td in nature and efficient cell reprogramming in vitro.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zuryn, Steven -- Ahier, Arnaud -- Portoso, Manuela -- White, Esther Redhouse -- Morin, Marie-Charlotte -- Margueron, Raphael -- Jarriault, Sophie -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):826-9. doi: 10.1126/science.1255885.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Development and Stem Cells, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Universite de Strasbourg, 67404 Illkirch CU Strasbourg, France. ; Institut Curie, INSERM U934, CNRS UMR3215, 26, Rue d'Ulm, 75005 Paris, France. ; Department of Development and Stem Cells, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Universite de Strasbourg, 67404 Illkirch CU Strasbourg, France. sophie@igbmc.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124442" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/*cytology/genetics ; Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism ; Cell Dedifferentiation ; Cell Nucleus/metabolism/ultrastructure ; *Cell Transdifferentiation ; Digestive System/cytology ; Histone Demethylases/chemistry/genetics/*metabolism ; Histone-Lysine N-Methyltransferase/genetics/*metabolism ; Histones/*metabolism ; Lysine/metabolism ; Methylation ; Models, Biological ; Molecular Sequence Data ; Motor Neurons/*cytology ; Transcription Factors/metabolism
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  • 36
    Publication Date: 2014-12-17
    Description: Iron sequestration provides an innate defense, termed nutritional immunity, leading pathogens to scavenge iron from hosts. Although the molecular basis of this battle for iron is established, its potential as a force for evolution at host-pathogen interfaces is unknown. We show that the iron transport protein transferrin is engaged in ancient and ongoing evolutionary conflicts with TbpA, a transferrin surface receptor from bacteria. Single substitutions in transferrin at rapidly evolving sites reverse TbpA binding, providing a mechanism to counteract bacterial iron piracy among great apes. Furthermore, the C2 transferrin polymorphism in humans evades TbpA variants from Haemophilus influenzae, revealing a functional basis for standing genetic variation. These findings identify a central role for nutritional immunity in the persistent evolutionary conflicts between primates and bacterial pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455941/" 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/PMC4455941/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barber, Matthew F -- Elde, Nels C -- 1F32GM108288/GM/NIGMS NIH HHS/ -- GM090042/GM/NIGMS NIH HHS/ -- R00 GM090042/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1362-6. doi: 10.1126/science.1259329.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. ; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. nelde@genetics.utah.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504720" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Evolution, Molecular ; Haemophilus influenzae/*metabolism ; Haplorhini/*genetics/immunology/*metabolism ; Humans ; Immunity, Innate ; Models, Molecular ; Molecular Sequence Data ; Neisseria/*metabolism ; Neisseria gonorrhoeae/metabolism ; Neisseria meningitidis/metabolism ; Phylogeny ; Polymorphism, Genetic ; Protein Binding ; Selection, Genetic ; Transferrin/chemistry/*genetics/*metabolism ; Transferrin-Binding Protein A/chemistry/*genetics/*metabolism
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  • 37
    Publication Date: 2014-08-12
    Description: Ionotropic glutamate receptors (iGluRs) mediate most excitatory neurotransmission in the central nervous system and function by opening their ion channel in response to binding of agonist glutamate. Here, we report a structure of a homotetrameric rat GluA2 receptor in complex with partial agonist (S)-5-nitrowillardiine. Comparison of this structure with the closed-state structure in complex with competitive antagonist ZK 200775 suggests conformational changes that occur during iGluR gating. Guided by the structures, we engineered disulfide cross-links to probe domain interactions that are important for iGluR gating events. The combination of structural information, kinetic modeling, and biochemical and electrophysiological experiments provides insight into the mechanism of iGluR gating.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383034/" 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/PMC4383034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yelshanskaya, Maria V -- Li, Minfen -- Sobolevsky, Alexander I -- NS083660/NS/NINDS NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- P41 GM111244/GM/NIGMS NIH HHS/ -- R01 NS083660/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1070-4. doi: 10.1126/science.1256508. Epub 2014 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, NY 10032, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, NY 10032, USA. as4005@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25103407" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; Cysteine/chemistry ; Glutamic Acid/pharmacology ; HEK293 Cells ; Humans ; *Ion Channel Gating ; Models, Chemical ; Organophosphonates/chemistry/pharmacology ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Pyrimidinones/*pharmacology ; Quinoxalines/chemistry/pharmacology ; Rats ; Receptors, AMPA/*agonists/*chemistry/genetics
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  • 38
    Publication Date: 2014-01-25
    Description: Little is known about how microcircuits are organized in layer 2 of the medial entorhinal cortex. We visualized principal cell microcircuits and determined cellular theta-rhythmicity in freely moving rats. Non-dentate-projecting, calbindin-positive pyramidal cells bundled dendrites together and formed patches arranged in a hexagonal grid aligned to layer 1 axons, parasubiculum, and cholinergic inputs. Calbindin-negative, dentate-gyrus-projecting stellate cells were distributed across layer 2 but avoided centers of calbindin-positive patches. Cholinergic drive sustained theta-rhythmicity, which was twofold stronger in pyramidal than in stellate neurons. Theta-rhythmicity was cell-type-specific but not distributed as expected from cell-intrinsic properties. Layer 2 divides into a weakly theta-locked stellate cell lattice and spatiotemporally highly organized pyramidal grid. It needs to be assessed how these two distinct principal cell networks contribute to grid cell activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ray, Saikat -- Naumann, Robert -- Burgalossi, Andrea -- Tang, Qiusong -- Schmidt, Helene -- Brecht, Michael -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):891-6. doi: 10.1126/science.1243028. Epub 2014 Jan 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bernstein Center for Computational Neuroscience, Humboldt University of Berlin, Philippstrasse 13 Haus 6, 10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24457213" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/metabolism ; Animals ; Calbindins/analysis/metabolism ; Dendrites/physiology ; Dentate Gyrus/physiology ; Entorhinal Cortex/*cytology/metabolism/physiology ; Female ; Male ; *Nerve Net ; Pyramidal Cells/metabolism/*physiology/*ultrastructure ; Rats ; Rats, Wistar ; Staining and Labeling ; *Theta Rhythm
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  • 39
    Publication Date: 2014-06-21
    Description: Primate lentiviruses exhibit narrow host tropism, reducing the occurrence of zoonoses but also impairing the development of optimal animal models of AIDS. To delineate the factors limiting cross-species HIV-1 transmission, we passaged a modified HIV-1 in pigtailed macaques that were transiently depleted of CD8(+) cells during acute infection. During adaptation over four passages in macaques, HIV-1 acquired the ability to antagonize the macaque restriction factor tetherin, replicated at progressively higher levels, and ultimately caused marked CD4(+) T cell depletion and AIDS-defining conditions. Transient treatment with an antibody to CD8 during acute HIV-1 infection caused rapid progression to AIDS, whereas untreated animals exhibited an elite controller phenotype. Thus, an adapted HIV-1 can cause AIDS in macaques, and stark differences in outcome can be determined by immunological perturbations during early infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266393/" 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/PMC4266393/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hatziioannou, Theodora -- Del Prete, Gregory Q -- Keele, Brandon F -- Estes, Jacob D -- McNatt, Matthew W -- Bitzegeio, Julia -- Raymond, Alice -- Rodriguez, Anthony -- Schmidt, Fabian -- Mac Trubey, C -- Smedley, Jeremy -- Piatak, Michael Jr -- KewalRamani, Vineet N -- Lifson, Jeffrey D -- Bieniasz, Paul D -- HHSN261200800001E/PHS HHS/ -- R01 AI050111/AI/NIAID NIH HHS/ -- R01 AI078788/AI/NIAID NIH HHS/ -- R01AI078788/AI/NIAID NIH HHS/ -- R01AI50111/AI/NIAID NIH HHS/ -- R37 AI064003/AI/NIAID NIH HHS/ -- R37AI64003/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jun 20;344(6190):1401-5. doi: 10.1126/science.1250761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA. ; Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. ; Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. ; Laboratory Animal Sciences Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA. ; HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org. ; Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. Howard Hughes Medical Institute, 455 First Avenue, New York, NY 10016, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24948736" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/immunology/transmission/*virology ; Amino Acid Sequence ; Animals ; Antigens, CD8/immunology ; CD4-Positive T-Lymphocytes/immunology ; *Disease Models, Animal ; HIV-1/genetics/*physiology ; Host-Pathogen Interactions/*immunology ; Human Immunodeficiency Virus Proteins/chemistry/genetics/metabolism ; Lymphocyte Depletion ; Macaca nemestrina/immunology/*virology ; Molecular Sequence Data ; Protein Structure, Tertiary ; Viral Regulatory and Accessory Proteins/chemistry/genetics/metabolism ; Virus Replication
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  • 40
    Publication Date: 2014-08-16
    Description: The rules governing the formation of spatial maps in the hippocampus have not been determined. We investigated the large-scale structure of place field activity by recording hippocampal neurons in rats exploring a previously unencountered 48-meter-long track. Single-cell and population activities were well described by a two-parameter stochastic model. Individual neurons had their own characteristic propensity for forming fields randomly along the track, with some cells expressing many fields and many exhibiting few or none. Because of the particular distribution of propensities across cells, the number of neurons with fields scaled logarithmically with track length over a wide, ethological range. These features constrain hippocampal memory mechanisms, may allow efficient encoding of environments and experiences of vastly different extents and durations, and could reflect general principles of population coding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rich, P Dylan -- Liaw, Hua-Peng -- Lee, Albert K -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):814-7. doi: 10.1126/science.1255635. Epub 2014 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK. richp@janelia.hhmi.org leea@janelia.hhmi.org. ; Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. ; Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. richp@janelia.hhmi.org leea@janelia.hhmi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124440" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Brain Mapping ; CA1 Region, Hippocampal/cytology/*physiology ; Electrodes, Implanted ; Exploratory Behavior ; Male ; Maze Learning ; Memory/physiology ; Orientation ; Poisson Distribution ; Pyramidal Cells/*physiology ; Rats ; Rats, Long-Evans ; *Space Perception
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  • 41
    Publication Date: 2014-03-22
    Description: Under resting conditions, Pink1 knockout cells and cells derived from patients with PINK1 mutations display a loss of mitochondrial complex I reductive activity, causing a decrease in the mitochondrial membrane potential. Analyzing the phosphoproteome of complex I in liver and brain from Pink1(-/-) mice, we found specific loss of phosphorylation of serine-250 in complex I subunit NdufA10. Phosphorylation of serine-250 was needed for ubiquinone reduction by complex I. Phosphomimetic NdufA10 reversed Pink1 deficits in mouse knockout cells and rescued mitochondrial depolarization and synaptic transmission defects in pink(B9)-null mutant Drosophila. Complex I deficits and adenosine triphosphate synthesis were also rescued in cells derived from PINK1 patients. Thus, this evolutionary conserved pathway may contribute to the pathogenic cascade that eventually leads to Parkinson's disease in patients with PINK1 mutations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morais, Vanessa A -- Haddad, Dominik -- Craessaerts, Katleen -- De Bock, Pieter-Jan -- Swerts, Jef -- Vilain, Sven -- Aerts, Liesbeth -- Overbergh, Lut -- Grunewald, Anne -- Seibler, Philip -- Klein, Christine -- Gevaert, Kris -- Verstreken, Patrik -- De Strooper, Bart -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):203-7. doi: 10.1126/science.1249161. Epub 2014 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉VIB Center for the Biology of Disease, 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24652937" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Brain/enzymology ; Drosophila Proteins/*metabolism ; Electron Transport Complex I/*metabolism ; Humans ; Liver/enzymology ; Membrane Potential, Mitochondrial/genetics ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; NADH Dehydrogenase/*metabolism ; Parkinson Disease/*enzymology/*genetics ; Phosphorylation/genetics ; Protein Kinases/*genetics ; Proteome ; Serine/chemistry/metabolism
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  • 42
    Publication Date: 2014-05-17
    Description: Signaling from JAK (Janus kinase) protein kinases to STAT (signal transducers and activators of transcription) transcription factors is key to many aspects of biology and medicine, yet the mechanism by which cytokine receptors initiate signaling is enigmatic. We present a complete mechanistic model for activation of receptor-bound JAK2, based on an archetypal cytokine receptor, the growth hormone receptor. For this, we used fluorescence resonance energy transfer to monitor positioning of the JAK2 binding motif in the receptor dimer, substitution of the receptor extracellular domains with Jun zippers to control the position of its transmembrane (TM) helices, atomistic modeling of TM helix movements, and docking of the crystal structures of the JAK2 kinase and its inhibitory pseudokinase domain with an opposing kinase-pseudokinase domain pair. Activation of the receptor dimer induced a separation of its JAK2 binding motifs, driven by a ligand-induced transition from a parallel TM helix pair to a left-handed crossover arrangement. This separation leads to removal of the pseudokinase domain from the kinase domain of the partner JAK2 and pairing of the two kinase domains, facilitating trans-activation. This model may well generalize to other class I cytokine receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brooks, Andrew J -- Dai, Wei -- O'Mara, Megan L -- Abankwa, Daniel -- Chhabra, Yash -- Pelekanos, Rebecca A -- Gardon, Olivier -- Tunny, Kathryn A -- Blucher, Kristopher M -- Morton, Craig J -- Parker, Michael W -- Sierecki, Emma -- Gambin, Yann -- Gomez, Guillermo A -- Alexandrov, Kirill -- Wilson, Ian A -- Doxastakis, Manolis -- Mark, Alan E -- Waters, Michael J -- New York, N.Y. -- Science. 2014 May 16;344(6185):1249783. doi: 10.1126/science.1249783.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. m.waters@uq.edu.au a.brooks@uq.edu.au. ; Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77004, USA. ; The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Queensland 4072, Australia. ; The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. ; Biota Structural Biology Laboratory and Australian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. ; Biota Structural Biology Laboratory and Australian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. Department of Biochemistry and Molecular Biology and Bio21 Institute, University of Melbourne, Parkville, Victoria 3052, Australia. ; Scripps Research Institute, La Jolla, CA 92037, USA. ; The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Queensland 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833397" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Cysteine/chemistry ; Enzyme Activation ; HEK293 Cells ; Humans ; Janus Kinase 2/antagonists & inhibitors/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Somatotropin/chemistry/genetics/*metabolism
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  • 43
    Publication Date: 2014-02-18
    Description: In this work, we investigate morphological differences between Arabidopsis thaliana, which has simple leaves, and its relative Cardamine hirsuta, which has dissected leaves comprising distinct leaflets. With the use of genetics, interspecific gene transfers, and time-lapse imaging, we show that leaflet development requires the REDUCED COMPLEXITY (RCO) homeodomain protein. RCO functions specifically in leaves, where it sculpts developing leaflets by repressing growth at their flanks. RCO evolved in the Brassicaceae family through gene duplication and was lost in A. thaliana, contributing to leaf simplification in this species. Species-specific RCO action with respect to its paralog results from its distinct gene expression pattern in the leaf base. Thus, regulatory evolution coupled with gene duplication and loss generated leaf shape diversity by modifying local growth patterns during organogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vlad, Daniela -- Kierzkowski, Daniel -- Rast, Madlen I -- Vuolo, Francesco -- Dello Ioio, Raffaele -- Galinha, Carla -- Gan, Xiangchao -- Hajheidari, Mohsen -- Hay, Angela -- Smith, Richard S -- Huijser, Peter -- Bailey, C Donovan -- Tsiantis, Miltos -- BB/H006974/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/H011455/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):780-3. doi: 10.1126/science.1248384.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531971" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/anatomy & histology/genetics ; Brassicaceae/*anatomy & histology/*genetics ; Chromosome Mapping ; *Evolution, Molecular ; Gene Duplication ; *Gene Expression Regulation, Plant ; *Genes, Homeobox ; Genetic Complementation Test ; Molecular Sequence Data ; Plant Leaves/*anatomy & histology/*genetics
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  • 44
    Publication Date: 2014-05-03
    Description: Regulation of cell volume is critical for many cellular and organismal functions, yet the molecular identity of a key player, the volume-regulated anion channel VRAC, has remained unknown. A genome-wide small interfering RNA screen in mammalian cells identified LRRC8A as a VRAC component. LRRC8A formed heteromers with other LRRC8 multispan membrane proteins. Genomic disruption of LRRC8A ablated VRAC currents. Cells with disruption of all five LRRC8 genes required LRRC8A cotransfection with other LRRC8 isoforms to reconstitute VRAC currents. The isoform combination determined VRAC inactivation kinetics. Taurine flux and regulatory volume decrease also depended on LRRC8 proteins. Our work shows that VRAC defines a class of anion channels, suggests that VRAC is identical to the volume-sensitive organic osmolyte/anion channel VSOAC, and explains the heterogeneity of native VRAC currents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Voss, Felizia K -- Ullrich, Florian -- Munch, Jonas -- Lazarow, Katina -- Lutter, Darius -- Mah, Nancy -- Andrade-Navarro, Miguel A -- von Kries, Jens P -- Stauber, Tobias -- Jentsch, Thomas J -- New York, N.Y. -- Science. 2014 May 9;344(6184):634-8. doi: 10.1126/science.1252826. Epub 2014 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz-Institut fur Molekulare Pharmakologie (FMP), Berlin.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24790029" target="_blank"〉PubMed〈/a〉
    Keywords: Agammaglobulinemia/genetics ; *Cell Size ; Chloride Channels/*metabolism ; Gene Knockout Techniques ; Genome-Wide Association Study ; HCT116 Cells ; HEK293 Cells ; Humans ; Membrane Proteins/genetics/*metabolism ; Mutation ; Protein Multimerization ; RNA Interference ; RNA, Small Interfering/genetics ; Taurine/metabolism ; Transfection
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  • 45
    Publication Date: 2014-02-08
    Description: The distance between Ca(2+) channels and release sensors determines the speed and efficacy of synaptic transmission. Tight "nanodomain" channel-sensor coupling initiates transmitter release at synapses in the mature brain, whereas loose "microdomain" coupling appears restricted to early developmental stages. To probe the coupling configuration at a plastic synapse in the mature central nervous system, we performed paired recordings between mossy fiber terminals and CA3 pyramidal neurons in rat hippocampus. Millimolar concentrations of both the fast Ca(2+) chelator BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] and the slow chelator EGTA efficiently suppressed transmitter release, indicating loose coupling between Ca(2+) channels and release sensors. Loose coupling enabled the control of initial release probability by fast endogenous Ca(2+) buffers and the generation of facilitation by buffer saturation. Thus, loose coupling provides the molecular framework for presynaptic plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vyleta, Nicholas P -- Jonas, Peter -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):665-70. doi: 10.1126/science.1244811.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IST Austria (Institute of Science and Technology Austria), Am Campus 1, A-3400 Klosterneuburg, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503854" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CA3 Region, Hippocampal/metabolism/physiology ; Calcium Channels/*metabolism ; Chelating Agents/pharmacology ; Egtazic Acid/analogs & derivatives/pharmacology ; Hippocampus/drug effects/metabolism/*physiology ; Mossy Fibers, Hippocampal/drug effects/metabolism/physiology ; Neuronal Plasticity/drug effects/*physiology ; Rats ; Synapses/drug effects/metabolism/*physiology ; Synaptic Transmission/drug effects/*physiology
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  • 46
    Publication Date: 2014-03-15
    Description: Histone variants have been proposed to act as determinants for posttranslational modifications with widespread regulatory functions. We identify a histone-modifying enzyme that selectively methylates the replication-dependent histone H3 variant H3.1. The crystal structure of the SET domain of the histone H3 lysine-27 (H3K27) methyltransferase ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) in complex with a H3.1 peptide shows that ATXR5 contains a bipartite catalytic domain that specifically "reads" alanine-31 of H3.1. Variation at position 31 between H3.1 and replication-independent H3.3 is conserved in plants and animals, and threonine-31 in H3.3 is responsible for inhibiting the activity of ATXR5 and its paralog, ATXR6. Our results suggest a simple model for the mitotic inheritance of the heterochromatic mark H3K27me1 and the protection of H3.3-enriched genes against heterochromatization during DNA replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049228/" 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/PMC4049228/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacob, Yannick -- Bergamin, Elisa -- Donoghue, Mark T A -- Mongeon, Vanessa -- LeBlanc, Chantal -- Voigt, Philipp -- Underwood, Charles J -- Brunzelle, Joseph S -- Michaels, Scott D -- Reinberg, Danny -- Couture, Jean-Francois -- Martienssen, Robert A -- BMA-355900/Canadian Institutes of Health Research/Canada -- GM064844/GM/NIGMS NIH HHS/ -- GM067014/GM/NIGMS NIH HHS/ -- GM075060/GM/NIGMS NIH HHS/ -- R01 GM067014/GM/NIGMS NIH HHS/ -- R01 GM075060/GM/NIGMS NIH HHS/ -- R37 GM037120/GM/NIGMS NIH HHS/ -- R37GM037120/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1249-53. doi: 10.1126/science.1248357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626927" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/*chemistry/metabolism ; Catalytic Domain ; Conserved Sequence ; Crystallography, X-Ray ; DNA Replication ; Epigenesis, Genetic ; Gene Expression Regulation, Plant ; Heterochromatin/*metabolism ; Histones/*metabolism ; Methylation ; Methyltransferases/*chemistry/metabolism ; Mitosis ; Molecular Sequence Data ; *Protein Processing, Post-Translational ; Threonine/metabolism
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  • 47
    Publication Date: 2014-06-28
    Description: Lassa virus spreads from a rodent to humans and can lead to lethal hemorrhagic fever. Despite its broad tropism, chicken cells were reported 30 years ago to resist infection. We found that Lassa virus readily engaged its cell-surface receptor alpha-dystroglycan in avian cells, but virus entry in susceptible species involved a pH-dependent switch to an intracellular receptor, the lysosome-resident protein LAMP1. Iterative haploid screens revealed that the sialyltransferase ST3GAL4 was required for the interaction of the virus glycoprotein with LAMP1. A single glycosylated residue in LAMP1, present in susceptible species but absent in birds, was essential for interaction with the Lassa virus envelope protein and subsequent infection. The resistance of Lamp1-deficient mice to Lassa virus highlights the relevance of this receptor switch in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239993/" 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/PMC4239993/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jae, Lucas T -- Raaben, Matthijs -- Herbert, Andrew S -- Kuehne, Ana I -- Wirchnianski, Ariel S -- Soh, Timothy K -- Stubbs, Sarah H -- Janssen, Hans -- Damme, Markus -- Saftig, Paul -- Whelan, Sean P -- Dye, John M -- Brummelkamp, Thijn R -- AI081842/AI/NIAID NIH HHS/ -- AI109740/AI/NIAID NIH HHS/ -- R01 AI081842/AI/NIAID NIH HHS/ -- T32 AI007245/AI/NIAID NIH HHS/ -- U19 AI109740/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1506-10. doi: 10.1126/science.1252480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. ; Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. ; U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA. ; Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. ; Biochemisches Institut, Christian Albrechts-Universitat Kiel, 24118 Kiel, Germany. ; Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu. ; U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu. ; Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Cancer Genomics Center (CGC.nl), Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970085" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/metabolism/virology ; Cells, Cultured ; Chickens ; Dystroglycans/genetics/metabolism ; Glycosylation ; Humans ; Hydrogen-Ion Concentration ; Lassa Fever/virology ; Lassa virus/*physiology ; Lysosomal-Associated Membrane Protein 1/chemistry/*metabolism ; Lysosomes/metabolism/virology ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Protein Binding ; Receptors, Virus/*metabolism ; Sialyltransferases/metabolism ; Viral Envelope Proteins/*metabolism ; *Virus Internalization
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  • 48
    Publication Date: 2014-03-22
    Description: The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of five transmembrane alpha helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism for the stimulation of cholesterol transport into mitochondria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaremko, Lukasz -- Jaremko, Mariusz -- Giller, Karin -- Becker, Stefan -- Zweckstetter, Markus -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Biophysikalische Chemie, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653034" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Biological Transport ; Cholesterol/metabolism ; Hydrophobic and Hydrophilic Interactions ; Isoquinolines/*chemistry/metabolism ; Ligands ; Mice ; Micelles ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, GABA/*chemistry/metabolism ; Recombinant Proteins/chemistry/metabolism
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  • 49
    Publication Date: 2014-06-14
    Description: The brain exhibits limited capacity for spontaneous restoration of lost motor functions after stroke. Rehabilitation is the prevailing clinical approach to augment functional recovery, but the scientific basis is poorly understood. Here, we show nearly full recovery of skilled forelimb functions in rats with large strokes when a growth-promoting immunotherapy against a neurite growth-inhibitory protein was applied to boost the sprouting of new fibers, before stabilizing the newly formed circuits by intensive training. In contrast, early high-intensity training during the growth phase destroyed the effect and led to aberrant fiber patterns. Pharmacogenetic experiments identified a subset of corticospinal fibers originating in the intact half of the forebrain, side-switching in the spinal cord to newly innervate the impaired limb and restore skilled motor function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wahl, A S -- Omlor, W -- Rubio, J C -- Chen, J L -- Zheng, H -- Schroter, A -- Gullo, M -- Weinmann, O -- Kobayashi, K -- Helmchen, F -- Ommer, B -- Schwab, M E -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1250-5. doi: 10.1126/science.1253050.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. Brain Research Institute, University of Zurich, Zurich, Switzerland. schwab@hifo.uzh.ch wahl@hifo.uzh.ch. ; Brain Research Institute, University of Zurich, Zurich, Switzerland. ; Computer Vision Group, Heidelberg Collaboratory for Image Processing and Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Heidelberg, Germany. ; Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland. ; Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. Brain Research Institute, University of Zurich, Zurich, Switzerland. ; National Institute for Physiological Sciences, National Institute of Natural Sciences Myodaiji, Okazaki, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24926013" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Immunotherapy/methods ; Motor Cortex/*physiopathology ; Myelin Proteins/*antagonists & inhibitors ; Physical Conditioning, Animal ; Prosencephalon/physiopathology ; Pyramidal Tracts/*injuries/*physiology ; Rats ; Rats, Long-Evans ; *Recovery of Function ; Stroke/*rehabilitation
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  • 50
    Publication Date: 2014-08-12
    Description: AMPA-sensitive glutamate receptors are crucial to the structural and dynamic properties of the brain, to the development and function of the central nervous system, and to the treatment of neurological conditions from depression to cognitive impairment. However, the molecular principles underlying AMPA receptor activation have remained elusive. We determined multiple x-ray crystal structures of the GluA2 AMPA receptor in complex with a Conus striatus cone snail toxin, a positive allosteric modulator, and orthosteric agonists, at 3.8 to 4.1 angstrom resolution. We show how the toxin acts like a straightjacket on the ligand-binding domain (LBD) "gating ring," restraining the domains via both intra- and interdimer cross-links such that agonist-induced closure of the LBD "clamshells" is transduced into an irislike expansion of the gating ring. By structural analysis of activation-enhancing mutants, we show how the expansion of the LBD gating ring results in pulling forces on the M3 helices that, in turn, are coupled to ion channel gating.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263349/" 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/PMC4263349/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lei -- Durr, Katharina L -- Gouaux, Eric -- F32 MH100331/MH/NIMH NIH HHS/ -- F32MH100331/MH/NIMH NIH HHS/ -- R01 NS038631/NS/NINDS NIH HHS/ -- R37 NS038631/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1021-6. doi: 10.1126/science.1258409. Epub 2014 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. ; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Howard Hughes Medical Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. gouauxe@ohsu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25103405" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conotoxins/*chemistry ; Conus Snail ; Crystallography, X-Ray ; *Ion Channel Gating ; Ligands ; Mutation ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Receptors, AMPA/*agonists/*chemistry/genetics
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  • 51
    Publication Date: 2014-05-09
    Description: Although neuronal spikes can be readily detected from extracellular recordings, synaptic and subthreshold activity remains undifferentiated within the local field potential (LFP). In the hippocampus, neurons discharge selectively when the rat is at certain locations, while LFPs at single anatomical sites exhibit no such place-tuning. Nonetheless, because the representation of position is sparse and distributed, we hypothesized that spatial information can be recovered from multiple-site LFP recordings. Using high-density sampling of LFP and computational methods, we show that the spatiotemporal structure of the theta rhythm can encode position as robustly as neuronal spiking populations. Because our approach exploits the rhythmicity and sparse structure of neural activity, features found in many brain regions, it is useful as a general tool for discovering distributed LFP codes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agarwal, Gautam -- Stevenson, Ian H -- Berenyi, Antal -- Mizuseki, Kenji -- Buzsaki, Gyorgy -- Sommer, Friedrich T -- 1F32MH093048/MH/NIMH NIH HHS/ -- 337075/European Research Council/International -- MH-54671/MH/NIMH NIH HHS/ -- NS-034994/NS/NINDS NIH HHS/ -- NS074015/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 May 9;344(6184):626-30. doi: 10.1126/science.1250444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Redwood Center for Theoretical Neuroscience, University of California, Berkeley, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24812401" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Hippocampus/cytology/*physiology ; Maze Learning ; Neurons/physiology ; Periodicity ; Rats ; Running ; Spatio-Temporal Analysis ; Synaptic Potentials/*physiology ; Theta Rhythm
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  • 52
    Publication Date: 2014-06-07
    Description: Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157056/" 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/PMC4157056/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Yu -- Xie, Min -- Chen, Wenbin -- Talbot, Richard -- Maddox, Jillian F -- Faraut, Thomas -- Wu, Chunhua -- Muzny, Donna M -- Li, Yuxiang -- Zhang, Wenguang -- Stanton, Jo-Ann -- Brauning, Rudiger -- Barris, Wesley C -- Hourlier, Thibaut -- Aken, Bronwen L -- Searle, Stephen M J -- Adelson, David L -- Bian, Chao -- Cam, Graham R -- Chen, Yulin -- Cheng, Shifeng -- DeSilva, Udaya -- Dixen, Karen -- Dong, Yang -- Fan, Guangyi -- Franklin, Ian R -- Fu, Shaoyin -- Fuentes-Utrilla, Pablo -- Guan, Rui -- Highland, Margaret A -- Holder, Michael E -- Huang, Guodong -- Ingham, Aaron B -- Jhangiani, Shalini N -- Kalra, Divya -- Kovar, Christie L -- Lee, Sandra L -- Liu, Weiqing -- Liu, Xin -- Lu, Changxin -- Lv, Tian -- Mathew, Tittu -- McWilliam, Sean -- Menzies, Moira -- Pan, Shengkai -- Robelin, David -- Servin, Bertrand -- Townley, David -- Wang, Wenliang -- Wei, Bin -- White, Stephen N -- Yang, Xinhua -- Ye, Chen -- Yue, Yaojing -- Zeng, Peng -- Zhou, Qing -- Hansen, Jacob B -- Kristiansen, Karsten -- Gibbs, Richard A -- Flicek, Paul -- Warkup, Christopher C -- Jones, Huw E -- Oddy, V Hutton -- Nicholas, Frank W -- McEwan, John C -- Kijas, James W -- Wang, Jun -- Worley, Kim C -- Archibald, Alan L -- Cockett, Noelle -- Xu, Xun -- Wang, Wen -- Dalrymple, Brian P -- 095908/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- BB/1025360/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025328/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025360/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025506/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- U54 HG003273/HG/NHGRI NIH HHS/ -- WT095908/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1168-73. doi: 10.1126/science.1252806.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. ; BGI-Shenzhen, Shenzhen 518083, China. ; Ediburgh Genomics, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. ; Utah State University, Logan, UT 84322-4815, USA. ; Institut National de la Recherche Agronomique, Laboratoire de Genetique Cellulaire, UMR 444, Castanet-Tolosan F-31326, France. ; Utah State University, Logan, UT 84322-1435, USA. ; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Inner Mongolia Agricultural University, Hohhot 010018, China. Institute of ATCG, Nei Mongol Bio-Information, Hohhot, China. ; Department of Anatomy, University of Otago, Dunedin 9054, New Zealand. ; AgResearch, Invermay Agricultural Centre, Mosgiel 9053, New Zealand. ; Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. ; Department of Biology, University of Copenhagen, DK-2100 Copenhagen O, Denmark. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. ; Inner Mongolia Agricultural University, Hohhot 010018, China. ; U.S. Department of Agriculture Agricultural Research Service Animal Disease Research Unit, Pullman, WA 99164, USA. Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA. ; BGI-Shenzhen, Shenzhen 518083, China. Maize Research Institute, Sichuan Agricultural University, Chengdu 611130, China. ; Lanzhou Institute of Husbandry and Pharmaceutical Science, Lanzhou, 730050, China. ; Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark. ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; Biosciences Knowledge Transfer Network, The Roslin Institute, Easter Bush, Midlothian, EH25 9RG, UK. ; School of Environmental and Rural Science, University of New England, Armidale, NSW 2351, Australia. ; Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia. ; BGI-Shenzhen, Shenzhen 518083, China. Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Macau University of Science and Technology, Macau 999078, China. ; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; Utah State University, Logan, UT 84322-1435, USA. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; BGI-Shenzhen, Shenzhen 518083, China. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904168" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Fatty Acids, Volatile/metabolism/physiology ; Gene Expression Regulation ; Genome ; Keratins, Hair-Specific/genetics ; Lipid Metabolism/genetics/*physiology ; Molecular Sequence Data ; Phylogeny ; Rumen/metabolism/*physiology ; Sheep, Domestic/classification/*genetics/*metabolism ; Transcriptome ; Wool/growth & development
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  • 53
    Publication Date: 2014-02-08
    Description: Type II CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems use an RNA-guided DNA endonuclease, Cas9, to generate double-strand breaks in invasive DNA during an adaptive bacterial immune response. Cas9 has been harnessed as a powerful tool for genome editing and gene regulation in many eukaryotic organisms. We report 2.6 and 2.2 angstrom resolution crystal structures of two major Cas9 enzyme subtypes, revealing the structural core shared by all Cas9 family members. The architectures of Cas9 enzymes define nucleic acid binding clefts, and single-particle electron microscopy reconstructions show that the two structural lobes harboring these clefts undergo guide RNA-induced reorientation to form a central channel where DNA substrates are bound. The observation that extensive structural rearrangements occur before target DNA duplex binding implicates guide RNA loading as a key step in Cas9 activation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184034/" 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/PMC4184034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jinek, Martin -- Jiang, Fuguo -- Taylor, David W -- Sternberg, Samuel H -- Kaya, Emine -- Ma, Enbo -- Anders, Carolin -- Hauer, Michael -- Zhou, Kaihong -- Lin, Steven -- Kaplan, Matias -- Iavarone, Anthony T -- Charpentier, Emmanuelle -- Nogales, Eva -- Doudna, Jennifer A -- T32 GM066698/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1247997. doi: 10.1126/science.1247997. Epub 2014 Feb 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24505130" target="_blank"〉PubMed〈/a〉
    Keywords: Actinomyces/*enzymology ; Amino Acid Sequence ; Bacterial Proteins/*chemistry ; Caspase 9/*chemistry ; Crystallography, X-Ray ; DNA Cleavage ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/*chemistry ; Streptococcus pyogenes/*enzymology
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  • 54
    Publication Date: 2014-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Servick, Kelly -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1161-2. doi: 10.1126/science.346.6214.1161.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477435" target="_blank"〉PubMed〈/a〉
    Keywords: Analgesics, Non-Narcotic/adverse effects ; Anesthesia/*adverse effects ; Anesthetics, Dissociative/adverse effects ; Animals ; Apoptosis/drug effects ; Brain/*drug effects/*growth & development ; Caenorhabditis elegans ; Child ; Child, Preschool ; Dexmedetomidine/adverse effects ; Humans ; Infant ; Ketamine/adverse effects ; Models, Animal ; Neurons/*drug effects ; Rats ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; United States ; United States Food and Drug Administration
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  • 55
    Publication Date: 2014-09-23
    Description: The lateral habenula (LHb), a key regulator of monoaminergic brain regions, is activated by negatively valenced events. Its hyperactivity is associated with depression. Although enhanced excitatory input to the LHb has been linked to depression, little is known about inhibitory transmission. We discovered that gamma-aminobutyric acid (GABA) is co-released with its functional opponent, glutamate, from long-range basal ganglia inputs (which signal negative events) to limit LHb activity in rodents. At this synapse, the balance of GABA/glutamate signaling is shifted toward reduced GABA in a model of depression and increased GABA by antidepressant treatment. GABA and glutamate co-release therefore controls LHb activity, and regulation of this form of transmission may be important for determining the effect of negative life events on mood and behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305433/" 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/PMC4305433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shabel, Steven J -- Proulx, Christophe D -- Piriz, Joaquin -- Malinow, Roberto -- NS047101/NS/NINDS NIH HHS/ -- R01 MH091119/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1494-8. doi: 10.1126/science.1250469. Epub 2014 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA, USA. sshabel@gmail.com. ; Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA, USA. ; Grupo de Neurociencia de Sistemas, Instituto de Fisiologia y Biofisica Houssay (CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237099" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antidepressive Agents/*pharmacology ; Depression/*metabolism ; Entopeduncular Nucleus/drug effects/metabolism ; Glutamate Decarboxylase/metabolism ; Glutamic Acid/*metabolism ; Habenula/*drug effects/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Rhodopsin/genetics ; Synaptic Transmission/drug effects/*physiology ; Vesicular Glutamate Transport Protein 2/metabolism ; gamma-Aminobutyric Acid/*metabolism
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  • 56
    Publication Date: 2014-12-06
    Description: Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naive T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becattini, Simone -- Latorre, Daniela -- Mele, Federico -- Foglierini, Mathilde -- De Gregorio, Corinne -- Cassotta, Antonino -- Fernandez, Blanca -- Kelderman, Sander -- Schumacher, Ton N -- Corti, Davide -- Lanzavecchia, Antonio -- Sallusto, Federica -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):400-6. doi: 10.1126/science.1260668. Epub 2014 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. Institute of Microbiology, ETH Zurich, Zurich, Switzerland. ; Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. ; Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. ; Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. federica.sallusto@irb.usi.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477212" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; CD4-Positive T-Lymphocytes/*immunology ; Candida albicans/*immunology ; Cells, Cultured ; Clone Cells ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions/*immunology ; Humans ; *Immunologic Memory ; Lymphocyte Activation ; Molecular Sequence Data ; Mycobacterium tuberculosis/*immunology ; Receptors, Antigen, T-Cell/genetics ; T-Lymphocyte Subsets/*immunology ; Th1 Cells/immunology ; Th17 Cells/immunology ; Th2 Cells/immunology ; Vaccines/*immunology
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  • 57
    Publication Date: 2014-12-17
    Description: The emergence of artemisinin resistance in Southeast Asia imperils efforts to reduce the global malaria burden. We genetically modified the Plasmodium falciparum K13 locus using zinc-finger nucleases and measured ring-stage survival rates after drug exposure in vitro; these rates correlate with parasite clearance half-lives in artemisinin-treated patients. With isolates from Cambodia, where resistance first emerged, survival rates decreased from 13 to 49% to 0.3 to 2.4% after the removal of K13 mutations. Conversely, survival rates in wild-type parasites increased from 〈/=0.6% to 2 to 29% after the insertion of K13 mutations. These mutations conferred elevated resistance to recent Cambodian isolates compared with that of reference lines, suggesting a contemporary contribution of additional genetic factors. Our data provide a conclusive rationale for worldwide K13-propeller sequencing to identify and eliminate artemisinin-resistant parasites.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349400/" 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/PMC4349400/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Straimer, Judith -- Gnadig, Nina F -- Witkowski, Benoit -- Amaratunga, Chanaki -- Duru, Valentine -- Ramadani, Arba Pramundita -- Dacheux, Melanie -- Khim, Nimol -- Zhang, Lei -- Lam, Stephen -- Gregory, Philip D -- Urnov, Fyodor D -- Mercereau-Puijalon, Odile -- Benoit-Vical, Francoise -- Fairhurst, Rick M -- Menard, Didier -- Fidock, David A -- R01 AI109023/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):428-31. doi: 10.1126/science.1260867. Epub 2014 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA. ; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie de Coordination UPR8241, Toulouse, France. Universite de Toulouse, UPS, Institut National Polytechnique de Toulouse, Toulouse, France. ; Sangamo BioSciences, Richmond, CA, USA. ; Institut Pasteur, Parasite Molecular Immunology Unit, Paris, France. ; Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA. Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. df2260@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25502314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antimalarials/*pharmacology ; Artemisinins/*pharmacology ; Cambodia ; Drug Resistance/*genetics ; Genetic Loci ; Humans ; Malaria, Falciparum/drug therapy/parasitology ; Molecular Sequence Data ; Mutation ; Plasmodium falciparum/*drug effects/*genetics ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry/*genetics
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  • 58
    Publication Date: 2013-11-23
    Description: Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally derived second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference knockdown and biochemical complementation assays, and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for 〉99% of schistosomiasis cases worldwide.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136436/" 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/PMC4136436/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Valentim, Claudia L L -- Cioli, Donato -- Chevalier, Frederic D -- Cao, Xiaohang -- Taylor, Alexander B -- Holloway, Stephen P -- Pica-Mattoccia, Livia -- Guidi, Alessandra -- Basso, Annalisa -- Tsai, Isheng J -- Berriman, Matthew -- Carvalho-Queiroz, Claudia -- Almeida, Marcio -- Aguilar, Hector -- Frantz, Doug E -- Hart, P John -- LoVerde, Philip T -- Anderson, Timothy J C -- 098051/Wellcome Trust/United Kingdom -- 5R21-AI072704/AI/NIAID NIH HHS/ -- 5R21-AI096277/AI/NIAID NIH HHS/ -- C06 RR013556/RR/NCRR NIH HHS/ -- HHSN272201000005I/PHS HHS/ -- R01 AI097576/AI/NIAID NIH HHS/ -- R01-AI097576/AI/NIAID NIH HHS/ -- R21 AI072704/AI/NIAID NIH HHS/ -- R21 AI096277/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1385-9. doi: 10.1126/science.1243106. Epub 2013 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Biochemistry and Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24263136" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Drug Resistance/*genetics ; Gene Knockdown Techniques ; Genetic Linkage ; Helminth Proteins/*genetics ; Humans ; Molecular Sequence Data ; Mutation ; Oxamniquine/*pharmacology ; Phylogeny ; Protein Conformation ; Quantitative Trait Loci ; RNA Interference ; Schistosoma mansoni/*drug effects/*genetics ; Schistosomicides/*pharmacology ; Sulfotransferases/chemistry/classification/*genetics
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  • 59
    Publication Date: 2013-06-08
    Description: Evolutionarily young genes that serve essential functions represent a paradox; they must perform a function that either was not required until after their birth or was redundant with another gene. How young genes rapidly acquire essential function is largely unknown. We traced the evolutionary steps by which the Drosophila gene Umbrea acquired an essential role in chromosome segregation in D. melanogaster since the gene's origin less than 15 million years ago. Umbrea neofunctionalization occurred via loss of an ancestral heterochromatin-localizing domain, followed by alterations that rewired its protein interaction network and led to species-specific centromere localization. Our evolutionary cell biology approach provides temporal and mechanistic detail about how young genes gain essential function. Such innovations may constantly alter the repertoire of centromeric proteins in eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119826/" 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/PMC4119826/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ross, Benjamin D -- Rosin, Leah -- Thomae, Andreas W -- Hiatt, Mary Alice -- Vermaak, Danielle -- de la Cruz, Aida Flor A -- Imhof, Axel -- Mellone, Barbara G -- Malik, Harmit S -- R01 GM074108/GM/NIGMS NIH HHS/ -- R01GM074108/GM/NIGMS NIH HHS/ -- T32HG000035/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1211-4. doi: 10.1126/science.1234393.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744945" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Centromere/genetics/*physiology ; Chromosomal Proteins, Non-Histone/*genetics ; Drosophila/*genetics ; Drosophila Proteins/*genetics ; *Evolution, Molecular ; Gene Duplication ; Genes, Insect/*physiology ; Molecular Sequence Data
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  • 60
    Publication Date: 2013-08-31
    Description: Invasion of microbial DNA into the cytoplasm of animal cells triggers a cascade of host immune reactions that help clear the infection; however, self DNA in the cytoplasm can cause autoimmune diseases. Biochemical approaches led to the identification of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses. Here, we show that cells from cGAS-deficient (cGas(-/-)) mice, including fibroblasts, macrophages, and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection. cGas(-/-) mice were more susceptible to lethal infection with herpes simplex virus 1 (HSV1) than wild-type mice. We also show that cGAMP is an adjuvant that boosts antigen-specific T cell activation and antibody production in mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863637/" 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/PMC3863637/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Xiao-Dong -- Wu, Jiaxi -- Gao, Daxing -- Wang, Hua -- Sun, Lijun -- Chen, Zhijian J -- 5T32AI070116/AI/NIAID NIH HHS/ -- AI-093967/AI/NIAID NIH HHS/ -- R01 AI093967/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1390-4. doi: 10.1126/science.1244040. Epub 2013 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23989956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/biosynthesis ; DNA, Viral/genetics/immunology ; Dendritic Cells/immunology ; Fibroblasts/immunology ; Herpes Simplex/*immunology ; *Herpesvirus 1, Human ; Interferon Regulatory Factor-3/genetics ; Interferon-beta/*biosynthesis/genetics ; Lymphocyte Activation ; Macrophages/immunology ; Mice ; Mice, Knockout ; Nucleotidyltransferases/genetics/*immunology ; Signal Transduction ; T-Lymphocytes/immunology ; Transfection
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  • 61
    Publication Date: 2013-07-28
    Description: The essential bacterial protein FtsZ is a guanosine triphosphatase that self-assembles into a structure at the division site termed the "Z ring". During cytokinesis, the Z ring exerts a constrictive force on the membrane by using the chemical energy of guanosine triphosphate hydrolysis. However, the structural basis of this constriction remains unresolved. Here, we present the crystal structure of a guanosine diphosphate-bound Mycobacterium tuberculosis FtsZ protofilament, which exhibits a curved conformational state. The structure reveals a longitudinal interface that is important for function. The protofilament curvature highlights a hydrolysis-dependent conformational switch at the T3 loop that leads to longitudinal bending between subunits, which could generate sufficient force to drive cytokinesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816583/" 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/PMC3816583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ying -- Hsin, Jen -- Zhao, Lingyun -- Cheng, Yiwen -- Shang, Weina -- Huang, Kerwyn Casey -- Wang, Hong-Wei -- Ye, Sheng -- 1F32GM100677-01A1/GM/NIGMS NIH HHS/ -- DP2 OD006466/OD/NIH HHS/ -- DP2OD006466/OD/NIH HHS/ -- F32 GM100677/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):392-5. doi: 10.1126/science.1239248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Institute, Zhejiang University, Hangzhou, 310058 Zhejiang, P.R. China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23888039" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Cell Membrane/physiology ; Crystallography, X-Ray ; *Cytokinesis ; Cytoskeletal Proteins/*chemistry/genetics/*metabolism ; Escherichia coli/chemistry ; Guanosine Diphosphate/chemistry/metabolism ; Guanosine Triphosphate/metabolism ; Hydrolysis ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Mycobacterium tuberculosis/*chemistry/physiology ; Point Mutation ; Protein Conformation ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Staphylococcus aureus/chemistry
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  • 62
    Publication Date: 2013-10-26
    Description: Painful venoms are used to deter predators. Pain itself, however, can signal damage and thus serves an important adaptive function. Evolution to reduce general pain responses, although valuable for preying on venomous species, is rare, likely because it comes with the risk of reduced response to tissue damage. Bark scorpions capitalize on the protective pain pathway of predators by inflicting intensely painful stings. However, grasshopper mice regularly attack and consume bark scorpions, grooming only briefly when stung. Bark scorpion venom induces pain in many mammals (house mice, rats, humans) by activating the voltage-gated Na(+) channel Nav1.7, but has no effect on Nav1.8. Grasshopper mice Nav1.8 has amino acid variants that bind bark scorpion toxins and inhibit Na(+) currents, blocking action potential propagation and inducing analgesia. Thus, grasshopper mice have solved the predator-pain problem by using a toxin bound to a nontarget channel to block transmission of the pain signals the venom itself is initiating.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172297/" 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/PMC4172297/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rowe, Ashlee H -- Xiao, Yucheng -- Rowe, Matthew P -- Cummins, Theodore R -- Zakon, Harold H -- NS 053422/NS/NINDS NIH HHS/ -- R01 NS053422/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 25;342(6157):441-6. doi: 10.1126/science.1236451.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Neurobiology, The University of Texas at Austin, Austin, TX 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24159039" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects/physiology ; Amino Acid Sequence ; Animals ; Arvicolinae/*metabolism ; *Food Chain ; Formaldehyde/pharmacology ; Mice ; Molecular Sequence Data ; NAV1.7 Voltage-Gated Sodium Channel/chemistry/genetics/*metabolism ; NAV1.8 Voltage-Gated Sodium Channel/chemistry/genetics/*metabolism ; Pain/chemically induced/*metabolism ; *Predatory Behavior ; Protein Structure, Tertiary ; Scorpion Venoms
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  • 63
    Publication Date: 2013-03-23
    Description: Glycosylated alpha-dystroglycan (alpha-DG) serves as cellular entry receptor for multiple pathogens, and defects in its glycosylation cause hereditary Walker-Warburg syndrome (WWS). At least eight proteins are critical to glycosylate alpha-DG, but many genes mutated in WWS remain unknown. To identify modifiers of alpha-DG, we performed a haploid screen for Lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated alpha-DG to enter cells. In complementary screens, we profiled cells for absence of alpha-DG carbohydrate chains or biochemically related glycans. This revealed virus host factors and a suite of glycosylation units, including all known Walker-Warburg genes and five additional factors critical for the modification of alpha-DG. Our findings accentuate the complexity of this posttranslational feature and point out genes defective in dystroglycanopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919138/" 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/PMC3919138/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jae, Lucas T -- Raaben, Matthijs -- Riemersma, Moniek -- van Beusekom, Ellen -- Blomen, Vincent A -- Velds, Arno -- Kerkhoven, Ron M -- Carette, Jan E -- Topaloglu, Haluk -- Meinecke, Peter -- Wessels, Marja W -- Lefeber, Dirk J -- Whelan, Sean P -- van Bokhoven, Hans -- Brummelkamp, Thijn R -- AI057159/AI/NIAID NIH HHS/ -- AI081842/AI/NIAID NIH HHS/ -- R01 AI081842/AI/NIAID NIH HHS/ -- U54 AI057159/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 26;340(6131):479-83. doi: 10.1126/science.1233675. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23519211" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Dystroglycans/*metabolism ; Female ; Glycosylation ; Haploidy ; Host-Pathogen Interactions/*genetics ; Humans ; Infant ; Lassa Fever/*genetics/virology ; Lassa virus/*physiology ; Male ; Membrane Proteins/*genetics ; Molecular Sequence Data ; Mutation ; Pedigree ; Proteome/*metabolism ; *Virus Internalization ; Walker-Warburg Syndrome/*genetics
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  • 64
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2013 Dec 20;342(6165):1440-1. doi: 10.1126/science.342.6165.1440-b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357292" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/administration & dosage ; Fusobacterium/physiology ; Gastrointestinal Tract/*microbiology ; *Health ; Humans ; Infant ; Infant Formula/chemistry ; Kidney/metabolism ; Kidney Calculi/chemically induced/etiology ; Klebsiella/drug effects/metabolism ; Malnutrition/microbiology ; Neoplasms/microbiology ; Rats ; Triazines/metabolism/toxicity
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  • 65
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2013 Dec 20;342(6165):1434-5. doi: 10.1126/science.342.6165.1434-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357285" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; DNA/genetics ; Genetic Diseases, Inborn/*surgery ; Genetic Therapy/*methods ; Humans ; Mice ; Microsurgery/*methods ; *RNA Editing ; RNA, Guide/genetics/metabolism ; Rats
    Print ISSN: 0036-8075
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  • 66
    Publication Date: 2013-07-03
    Description: Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is a devastating disease that can cause severe yield losses. A previously uncharacterized Pgt race, designated Ug99, has overcome most of the widely used resistance genes and is threatening major wheat production areas. Here, we demonstrate that the Sr35 gene from Triticum monococcum is a coiled-coil, nucleotide-binding, leucine-rich repeat gene that confers near immunity to Ug99 and related races. This gene is absent in the A-genome diploid donor and in polyploid wheat but is effective when transferred from T. monococcum to polyploid wheat. The cloning of Sr35 opens the door to the use of biotechnological approaches to control this devastating disease and to analyses of the molecular interactions that define the wheat-rust pathosystem.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748951/" 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/PMC4748951/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saintenac, Cyrille -- Zhang, Wenjun -- Salcedo, Andres -- Rouse, Matthew N -- Trick, Harold N -- Akhunov, Eduard -- Dubcovsky, Jorge -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 16;341(6147):783-6. doi: 10.1126/science.1239022. Epub 2013 Jun 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology, Kansas State University, Manhattan, KS 66506, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23811222" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Amino Acid Sequence ; *Basidiomycota/pathogenicity ; Cloning, Molecular ; Disease Resistance/genetics ; *Genes, Plant ; Haplotypes ; Molecular Sequence Annotation ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Diseases/genetics/*immunology/microbiology ; Plant Proteins/chemistry/genetics ; Plant Stems/microbiology ; Plants, Genetically Modified ; Polymorphism, Single Nucleotide ; Polyploidy ; Sequence Analysis, DNA ; Triticum/*genetics/immunology/microbiology
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  • 67
    Publication Date: 2013-04-06
    Description: A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784322/" 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/PMC3784322/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Apps, Richard -- Qi, Ying -- Carlson, Jonathan M -- Chen, Haoyan -- Gao, Xiaojiang -- Thomas, Rasmi -- Yuki, Yuko -- Del Prete, Greg Q -- Goulder, Philip -- Brumme, Zabrina L -- Brumme, Chanson J -- John, Mina -- Mallal, Simon -- Nelson, George -- Bosch, Ronald -- Heckerman, David -- Stein, Judy L -- Soderberg, Kelly A -- Moody, M Anthony -- Denny, Thomas N -- Zeng, Xue -- Fang, Jingyuan -- Moffett, Ashley -- Lifson, Jeffrey D -- Goedert, James J -- Buchbinder, Susan -- Kirk, Gregory D -- Fellay, Jacques -- McLaren, Paul -- Deeks, Steven G -- Pereyra, Florencia -- Walker, Bruce -- Michael, Nelson L -- Weintrob, Amy -- Wolinsky, Steven -- Liao, Wilson -- Carrington, Mary -- 5-M01-RR-00722/RR/NCRR NIH HHS/ -- HHSN261200800001E/CA/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- K08 AR057763/AR/NIAMS NIH HHS/ -- K08AR057763/AR/NIAMS NIH HHS/ -- K24 AI069994/AI/NIAID NIH HHS/ -- K24AI069994/AI/NIAID NIH HHS/ -- N02-CP-55504/CP/NCI NIH HHS/ -- P30 AI027763/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-24/AI/NIAID NIH HHS/ -- P30 MH62246/MH/NIMH NIH HHS/ -- PG/09/077/27964/British Heart Foundation/United Kingdom -- R01 AI046995/AI/NIAID NIH HHS/ -- R01 AI060460/AI/NIAID NIH HHS/ -- R01 AI087145/AI/NIAID NIH HHS/ -- R01 AR065174/AR/NIAMS NIH HHS/ -- R01-AI046995/AI/NIAID NIH HHS/ -- R01-AI060460/AI/NIAID NIH HHS/ -- R01-DA-04334/DA/NIDA NIH HHS/ -- R01-DA-12568/DA/NIDA NIH HHS/ -- R01-DA04334/DA/NIDA NIH HHS/ -- R01-DA12568/DA/NIDA NIH HHS/ -- R24 AI067039/AI/NIAID NIH HHS/ -- U01-AI-067854/AI/NIAID NIH HHS/ -- U01-AI-35039/AI/NIAID NIH HHS/ -- U01-AI-35040/AI/NIAID NIH HHS/ -- U01-AI-35041/AI/NIAID NIH HHS/ -- U01-AI-35042/AI/NIAID NIH HHS/ -- U01-AI-35043/AI/NIAID NIH HHS/ -- U01-AI-37613/AI/NIAID NIH HHS/ -- U01-AI-37984/AI/NIAID NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):87-91. doi: 10.1126/science.1232685.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer and Inflammation Program, Laboratory of Experimental Immunology, Science Applications International Corporation-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23559252" target="_blank"〉PubMed〈/a〉
    Keywords: African Americans/genetics ; Alleles ; Amino Acid Sequence ; Anti-Retroviral Agents/therapeutic use ; Crohn Disease/genetics/immunology ; *Gene Expression Regulation ; HIV/genetics/*immunology ; HIV Infections/drug therapy/*genetics/*immunology ; HLA-C Antigens/*genetics ; Humans ; Immunodominant Epitopes/genetics ; Molecular Sequence Data ; Mutation ; Peptide Fragments/immunology ; Polymorphism, Single Nucleotide ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Load/genetics
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  • 68
    Publication Date: 2013-02-02
    Description: The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778192/" 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/PMC3778192/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shapiro, Michael D -- Kronenberg, Zev -- Li, Cai -- Domyan, Eric T -- Pan, Hailin -- Campbell, Michael -- Tan, Hao -- Huff, Chad D -- Hu, Haofu -- Vickrey, Anna I -- Nielsen, Sandra C A -- Stringham, Sydney A -- Hu, Hao -- Willerslev, Eske -- Gilbert, M Thomas P -- Yandell, Mark -- Zhang, Guojie -- Wang, Jun -- GO RC2HG005619/HG/NHGRI NIH HHS/ -- R01 GM104390/GM/NIGMS NIH HHS/ -- R01 HG004694/HG/NHGRI NIH HHS/ -- R01HG004694/HG/NHGRI NIH HHS/ -- R44 HG006579/HG/NHGRI NIH HHS/ -- RC2 HG005619/HG/NHGRI NIH HHS/ -- T32 GM007464/GM/NIGMS NIH HHS/ -- T32 HD007491/HD/NICHD NIH HHS/ -- T32GM007464/GM/NIGMS NIH HHS/ -- T32HD07491/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1063-7. doi: 10.1126/science.1230422. Epub 2013 Jan 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. mike.shapiro@utah.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23371554" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Domestic/anatomy & histology/classification/genetics ; Animals, Wild/anatomy & histology/classification/genetics ; Breeding ; Columbidae/anatomy & histology/*classification/*genetics ; *Evolution, Molecular ; Feathers/anatomy & histology ; *Genetic Variation ; Genome ; Head/*anatomy & histology ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable ; Receptor, EphB2/genetics ; Sequence Analysis, DNA
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  • 69
    Publication Date: 2013-04-27
    Description: Senescent and damaged mitochondria undergo selective mitophagic elimination through mechanisms requiring two Parkinson's disease factors, the mitochondrial kinase PINK1 (PTEN-induced putative kinase protein 1; PTEN is phosphatase and tensin homolog) and the cytosolic ubiquitin ligase Parkin. The nature of the PINK-Parkin interaction and the identity of key factors directing Parkin to damaged mitochondria are unknown. We show that the mitochondrial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged mitochondria. Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. Ablation of Mfn2 in mouse cardiac myocytes prevented depolarization-induced translocation of Parkin to the mitochondria and suppressed mitophagy. Accumulation of morphologically and functionally abnormal mitochondria induced respiratory dysfunction in Mfn2-deficient mouse embryonic fibroblasts and cardiomyocytes and in Parkin-deficient Drosophila heart tubes, causing dilated cardiomyopathy. Thus, Mfn2 functions as a mitochondrial receptor for Parkin and is required for quality control of cardiac mitochondria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774525/" 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/PMC3774525/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Yun -- Dorn, Gerald W 2nd -- R01 HL059888/HL/NHLBI NIH HHS/ -- R21 HL107276/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 26;340(6131):471-5. doi: 10.1126/science.1231031.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23620051" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Autophagy ; Cardiomyopathies/enzymology ; Drosophila melanogaster ; Fibroblasts/ultrastructure ; GTP Phosphohydrolases/genetics/*metabolism ; HEK293 Cells ; Humans ; Mice ; Mice, Mutant Strains ; Mitochondria/enzymology ; Mitochondria, Heart/*enzymology ; Molecular Sequence Data ; Myocytes, Cardiac/*enzymology/ultrastructure ; Phosphorylation ; Protein Kinases/*metabolism ; Ubiquitin-Protein Ligases/*metabolism ; Ubiquitination
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  • 70
    Publication Date: 2013-10-05
    Description: Most models of gene duplication assume that the ancestral functions of the preduplication gene are independent and can therefore be neatly partitioned between descendant paralogs. However, many gene products, such as transcriptional regulators, are components within cooperative assemblies; here, we show that a natural consequence of duplication and divergence of such proteins can be competitive interference between the paralogs. Our example is based on the duplication of the essential MADS-box transcriptional regulator Mcm1, which is found in all fungi and regulates a large set of genes. We show that a set of historical amino acid sequence substitutions minimized paralog interference in contemporary species and, in doing so, increased the molecular complexity of this gene regulatory network. We propose that paralog interference is a common constraint on gene duplicate evolution, and its resolution, which can generate additional regulatory complexity, is needed to stabilize duplicated genes in the genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911913/" 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/PMC3911913/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, Christopher R -- Hanson-Smith, Victor -- Johnson, Alexander D -- F32 GM108299/GM/NIGMS NIH HHS/ -- R01 GM037049/GM/NIGMS NIH HHS/ -- R01 GM057049/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 4;342(6154):104-8. doi: 10.1126/science.1240810.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbiology, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24092741" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arginine/genetics ; Candida albicans/genetics ; *Evolution, Molecular ; *Gene Duplication ; *Gene Regulatory Networks ; Kluyveromyces/genetics ; Minichromosome Maintenance 1 Protein/*genetics ; Molecular Sequence Data ; Saccharomyces cerevisiae/genetics ; Sequence Deletion ; *Transcription, Genetic
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  • 71
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-11-23
    Description: In many mammalian tissues, mature differentiated cells are replaced by self-renewing stem cells, either continuously during homeostasis or in response to challenge and injury. For example, hematopoietic stem cells generate all mature blood cells, including monocytes, which have long been thought to be the major source of tissue macrophages. Recently, however, major macrophage populations were found to be derived from embryonic progenitors and to renew independently of hematopoietic stem cells. This process may not require progenitors, as mature macrophages can proliferate in response to specific stimuli indefinitely and without transformation or loss of functional differentiation. These findings suggest that macrophages are mature differentiated cells that may have a self-renewal potential similar to that of stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sieweke, Michael H -- Allen, Judith E -- MR/J001929/1/Medical Research Council/United Kingdom -- MR/K01207X1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):1242974. doi: 10.1126/science.1242974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Universite, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24264994" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Proliferation ; Cytokines/metabolism ; Embryonic Stem Cells/cytology ; Humans ; Macrophages/*cytology ; Mice ; Monocytes/cytology ; Rats ; Signal Transduction ; Stem Cells/*cytology
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  • 72
    Publication Date: 2013-03-23
    Description: Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/" 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/PMC3644373/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Chong -- Jiang, Yi -- Ma, Jinming -- Wu, Huixian -- Wacker, Daniel -- Katritch, Vsevolod -- Han, Gye Won -- Liu, Wei -- Huang, Xi-Ping -- Vardy, Eyal -- McCorvy, John D -- Gao, Xiang -- Zhou, X Edward -- Melcher, Karsten -- Zhang, Chenghai -- Bai, Fang -- Yang, Huaiyu -- Yang, Linlin -- Jiang, Hualiang -- Roth, Bryan L -- Cherezov, Vadim -- Stevens, Raymond C -- Xu, H Eric -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DA027170/DA/NIDA NIH HHS/ -- R01 DA27170/DA/NIDA NIH HHS/ -- R01 DK071662/DK/NIDDK NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH61887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH82441/MH/NIMH NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 May 3;340(6132):610-4. doi: 10.1126/science.1232807. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23519210" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Dihydroergotamine/chemistry/*metabolism ; Ergotamine/chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Lysergic Acid Diethylamide/chemistry/metabolism ; Models, Molecular ; Molecular Docking Simulation ; Molecular Sequence Data ; Mutagenesis ; Norfenfluramine/chemistry/metabolism ; Pindolol/analogs & derivatives/chemistry/metabolism ; Propranolol/chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Receptor, Serotonin, 5-HT1B/*chemistry/genetics/*metabolism ; Serotonin 5-HT1 Receptor Agonists/*chemistry/*metabolism ; Tryptamines/chemistry/metabolism
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  • 73
    Publication Date: 2013-08-24
    Description: Small open reading frames (smORFs) are short DNA sequences that are able to encode small peptides of less than 100 amino acids. Study of these elements has been neglected despite thousands existing in our genomes. We and others previously showed that peptides as short as 11 amino acids are translated and provide essential functions during insect development. Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of species from flies to humans, in which they have been implicated in cardiac pathologies. Such conservation suggests that the mechanisms for heart regulation are ancient and that smORFs may be a fundamental genome component that should be studied systematically.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Magny, Emile G -- Pueyo, Jose Ignacio -- Pearl, Frances M G -- Cespedes, Miguel Angel -- Niven, Jeremy E -- Bishop, Sarah A -- Couso, Juan Pablo -- 087516/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Sep 6;341(6150):1116-20. doi: 10.1126/science.1238802. Epub 2013 Aug 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23970561" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/*metabolism ; Conserved Sequence ; Drosophila Proteins/chemistry/genetics/metabolism/*physiology ; Drosophila melanogaster ; Evolution, Molecular ; Ion Transport ; Molecular Sequence Data ; Muscle Proteins/chemistry/genetics/*physiology ; Muscle, Skeletal/*metabolism ; *Myocardial Contraction ; Myocardium/*metabolism ; Open Reading Frames ; Peptides/chemistry/genetics/*physiology ; Protein Structure, Secondary ; Transaldolase/genetics/metabolism
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  • 74
    Publication Date: 2013-06-01
    Description: Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763809/" 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/PMC3763809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kato, Hidenori -- Jiang, Jiansheng -- Zhou, Bing-Rui -- Rozendaal, Marieke -- Feng, Hanqiao -- Ghirlando, Rodolfo -- Xiao, T Sam -- Straight, Aaron F -- Bai, Yawen -- R01 GM074728/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- ZIA AI000960-07/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 31;340(6136):1110-3. doi: 10.1126/science.1235532.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723239" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Autoantigens/metabolism ; Binding Sites ; Centromere/*metabolism ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; Conserved Sequence ; Drosophila ; Histones/*metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Molecular Sequence Data ; Nucleosomes/*metabolism ; Protein Structure, Secondary
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  • 75
    Publication Date: 2013-12-18
    Description: Erythropoietin is a signaling glycoprotein that controls the fundamental process of erythropoiesis, orchestrating the production and maintenance of red blood cells. As administrated clinically, erythropoietin has a polypeptide backbone with complex dishomogeneity in its carbohydrate domains. Here we describe the total synthesis of homogeneous erythropoietin with consensus carbohydrate domains incorporated at all of the native glycosylation sites. The oligosaccharide sectors were built by total synthesis and attached stereospecifically to peptidyl fragments of the wild-type primary sequence, themselves obtained by solid-phase peptide synthesis. The glycopeptidyl constructs were joined by chemical ligation, followed by metal-free dethiylation, and subsequently folded. This homogeneous erythropoietin glycosylated at the three wild-type aspartates with N-linked high-mannose sialic acid-containing oligosaccharides and O-linked glycophorin exhibits Procrit-level in vivo activity in mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080428/" 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/PMC4080428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Ping -- Dong, Suwei -- Shieh, Jae-Hung -- Peguero, Elizabeth -- Hendrickson, Ronald -- Moore, Malcolm A S -- Danishefsky, Samuel J -- HL025848/HL/NHLBI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 GM109760/GM/NIGMS NIH HHS/ -- R01 HL025848/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1357-60. doi: 10.1126/science.1245095.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24337294" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Aspartic Acid/chemistry ; Cells, Cultured ; Consensus Sequence ; Dose-Response Relationship, Drug ; Erythrocyte Count ; Erythropoietin/*administration & dosage/*chemical synthesis/chemistry ; Glycophorin/chemistry ; Glycosylation ; Injections, Subcutaneous ; Mannose/chemistry ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; N-Acetylneuraminic Acid/chemistry ; Oligosaccharides/chemistry ; Reticulocytes/drug effects
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  • 76
    Publication Date: 2013-01-26
    Description: The human genome contains ~50 genes that were derived from transposable elements or transposons, and many are now integral components of cellular gene expression programs. The human THAP9 gene is related to the Drosophila P-element transposase. Here, we show that human THAP9 can mobilize Drosophila P-elements in both Drosophila and human cells. Chimeric proteins formed between the Drosophila P-element transposase N-terminal THAP DNA binding domain and the C-terminal regions of human THAP9 can also mobilize Drosophila P elements. Our results indicate that human THAP9 is an active DNA transposase that, although "domesticated," still retains the catalytic activity to mobilize P transposable elements across species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779457/" 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/PMC3779457/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Majumdar, Sharmistha -- Singh, Anita -- Rio, Donald C -- R01 GM048862/GM/NIGMS NIH HHS/ -- R01 GM094890/GM/NIGMS NIH HHS/ -- R01 GM097352/GM/NIGMS NIH HHS/ -- R01 GM104385/GM/NIGMS NIH HHS/ -- R01GM094890/GM/NIGMS NIH HHS/ -- R01GM104385/GM/NIGMS NIH HHS/ -- R01GM48862/GM/NIGMS NIH HHS/ -- R01GM61987/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):446-8. doi: 10.1126/science.1231789.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349291" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; *DNA Transposable Elements ; Drosophila/genetics ; Genome, Human ; HEK293 Cells ; Humans ; Molecular Sequence Data ; Recombinant Fusion Proteins/metabolism ; Sequence Analysis, DNA ; Transfection ; Transposases/chemistry/*genetics/*metabolism
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  • 77
    Publication Date: 2013-07-03
    Description: Wheat stem rust, caused by the fungus Puccinia graminis f. sp. tritici, afflicts bread wheat (Triticum aestivum). New virulent races collectively referred to as "Ug99" have emerged, which threaten global wheat production. The wheat gene Sr33, introgressed from the wild relative Aegilops tauschii into bread wheat, confers resistance to diverse stem rust races, including the Ug99 race group. We cloned Sr33, which encodes a coiled-coil, nucleotide-binding, leucine-rich repeat protein. Sr33 is orthologous to the barley (Hordeum vulgare) Mla mildew resistance genes that confer resistance to Blumeria graminis f. sp. hordei. The wheat Sr33 gene functions independently of RAR1, SGT1, and HSP90 chaperones. Haplotype analysis from diverse collections of Ae. tauschii placed the origin of Sr33 resistance near the southern coast of the Caspian Sea.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Periyannan, Sambasivam -- Moore, John -- Ayliffe, Michael -- Bansal, Urmil -- Wang, Xiaojing -- Huang, Li -- Deal, Karin -- Luo, Mingcheng -- Kong, Xiuying -- Bariana, Harbans -- Mago, Rohit -- McIntosh, Robert -- Dodds, Peter -- Dvorak, Jan -- Lagudah, Evans -- New York, N.Y. -- Science. 2013 Aug 16;341(6147):786-8. doi: 10.1126/science.1239028. Epub 2013 Jun 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Commonwealth Scientific and Industrial Research Organization (CSIRO) Plant Industry, Canberra, ACT 2601, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23811228" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Basidiomycota/pathogenicity ; Cloning, Molecular ; Disease Resistance/genetics ; *Genes, Plant ; Haplotypes ; Hordeum/genetics ; Hybridization, Genetic ; Molecular Chaperones/genetics/metabolism ; Molecular Sequence Data ; Mutation ; Plant Diseases/genetics/*immunology/microbiology ; Plant Proteins/chemistry/genetics/metabolism ; Plant Stems/microbiology ; Plants, Genetically Modified ; Poaceae/*genetics ; Synteny ; Triticum/*genetics/*microbiology
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  • 78
    Publication Date: 2013-03-23
    Description: Kinesin-mediated cargo transport is required for many cellular functions and plays a key role in pathological processes. Structural information on how kinesins recognize their cargoes is required for a molecular understanding of this fundamental and ubiquitous process. Here, we present the crystal structure of the tetratricopeptide repeat domain of kinesin light chain 2 in complex with a cargo peptide harboring a "tryptophan-acidic" motif derived from SKIP (SifA-kinesin interacting protein), a critical host determinant in Salmonella pathogenesis and a regulator of lysosomal positioning. Structural data together with biophysical, biochemical, and cellular assays allow us to propose a framework for intracellular transport based on the binding by kinesin-1 of W-acidic cargo motifs through a combination of electrostatic interactions and sequence-specific elements, providing direct molecular evidence of the mechanisms for kinesin-1:cargo recognition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693442/" 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/PMC3693442/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pernigo, Stefano -- Lamprecht, Anneri -- Steiner, Roberto A -- Dodding, Mark P -- 097316/Wellcome Trust/United Kingdom -- British Heart Foundation/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Apr 19;340(6130):356-9. doi: 10.1126/science.1234264. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23519214" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Bacterial Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Glycoproteins/*chemistry/metabolism ; HeLa Cells ; Humans ; Mice ; Microtubule-Associated Proteins/*chemistry/genetics/metabolism ; Molecular Sequence Data ; Mutation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Tryptophan/chemistry/genetics/metabolism
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  • 79
    Publication Date: 2013-12-07
    Description: The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu(226), a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike alpha2-6-linked receptors and strong preference for a subset of avian-like alpha2-3-linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954636/" 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/PMC3954636/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Rui -- de Vries, Robert P -- Zhu, Xueyong -- Nycholat, Corwin M -- McBride, Ryan -- Yu, Wenli -- Paulson, James C -- Wilson, Ian A -- GM62116/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R56 AI099275/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1230-5. doi: 10.1126/science.1243761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24311689" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Birds ; Carbohydrate Conformation ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*metabolism ; Humans ; Influenza A Virus, H7N9 Subtype/*metabolism/*pathogenicity ; Influenza in Birds/transmission/virology ; Influenza, Human/transmission/virology ; Ligands ; Microarray Analysis ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Polysaccharides/chemistry/*metabolism ; Receptors, Virus/chemistry/*metabolism ; Recombinant Proteins/chemistry/metabolism
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  • 80
    Publication Date: 2013-06-08
    Description: Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730555/" 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/PMC4730555/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, Christian H -- Healey, Eleanor -- van Erp, Susan -- Bishop, Benjamin -- Tang, Chenxiang -- Gilbert, Robert J C -- Aricescu, A Radu -- Pasterkamp, R Jeroen -- Siebold, Christian -- 082301/Wellcome Trust/United Kingdom -- 083111/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 097301/Wellcome Trust/United Kingdom -- A14414/Cancer Research UK/United Kingdom -- G0700232/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Jul 5;341(6141):77-80. doi: 10.1126/science.1232322. Epub 2013 Jun 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. christian@strubi.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744777" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biophysical Phenomena ; Cell Adhesion Molecules, Neuronal/*chemistry/genetics ; Conserved Sequence ; Crystallography, X-Ray ; Humans ; Membrane Proteins/*chemistry ; Mutation ; Oligopeptides/chemistry ; Protein Structure, Tertiary ; Signal Transduction
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  • 81
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-11-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bendor, Daniel -- 1-K99-DC012321-01/DC/NIDCD NIH HHS/ -- 5R01MH061976/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 1;342(6158):574. doi: 10.1126/science.1245966.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University College London, 26 Bedford Way, London WC1H 0AP, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24179215" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cues ; Hippocampus/*physiology ; Humans ; Memory/*physiology/*radiation effects ; Microelectrodes ; Rats ; Sleep Stages/*physiology
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  • 82
    Publication Date: 2013-06-08
    Description: Phosphatase and tensin homolog on chromosome ten (PTEN) is a tumor suppressor and an antagonist of the phosphoinositide-3 kinase (PI3K) pathway. We identified a 576-amino acid translational variant of PTEN, termed PTEN-Long, that arises from an alternative translation start site 519 base pairs upstream of the ATG initiation sequence, adding 173 N-terminal amino acids to the normal PTEN open reading frame. PTEN-Long is a membrane-permeable lipid phosphatase that is secreted from cells and can enter other cells. As an exogenous agent, PTEN-Long antagonized PI3K signaling and induced tumor cell death in vitro and in vivo. By providing a means to restore a functional tumor-suppressor protein to tumor cells, PTEN-Long may have therapeutic uses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935617/" 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/PMC3935617/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hopkins, Benjamin D -- Fine, Barry -- Steinbach, Nicole -- Dendy, Meaghan -- Rapp, Zachary -- Shaw, Jacquelyn -- Pappas, Kyrie -- Yu, Jennifer S -- Hodakoski, Cindy -- Mense, Sarah -- Klein, Joshua -- Pegno, Sarah -- Sulis, Maria-Luisa -- Goldstein, Hannah -- Amendolara, Benjamin -- Lei, Liang -- Maurer, Matthew -- Bruce, Jeffrey -- Canoll, Peter -- Hibshoosh, Hanina -- Parsons, Ramon -- 2T32 CA09503/CA/NCI NIH HHS/ -- CA082783/CA/NCI NIH HHS/ -- CA097403/CA/NCI NIH HHS/ -- P01 CA097403/CA/NCI NIH HHS/ -- R01 CA082783/CA/NCI NIH HHS/ -- R01 CA155117/CA/NCI NIH HHS/ -- R01 NS066955/NS/NINDS NIH HHS/ -- R01 NS073610/NS/NINDS NIH HHS/ -- R01NS066955/NS/NINDS NIH HHS/ -- T32 CA009503/CA/NCI NIH HHS/ -- T32 GM008224/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):399-402. doi: 10.1126/science.1234907. Epub 2013 Jun 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744781" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line, Tumor ; *Cell Survival ; Embryonic Stem Cells ; Glioblastoma/drug therapy/metabolism/pathology ; HEK293 Cells ; Humans ; Mice ; Mice, Nude ; Molecular Sequence Data ; Mutation ; PTEN Phosphohydrolase/*chemistry/genetics/*metabolism/pharmacology ; Peptide Chain Initiation, Translational ; Phosphatidylinositol 3-Kinase/*metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Messenger/genetics/metabolism ; *Signal Transduction/drug effects ; Xenograft Model Antitumor Assays
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  • 83
    Publication Date: 2013-06-01
    Description: Successive contrast effects, in which behavior is dependent on whether conditions are currently better or worse than they were before, are a striking illustration of the fact that animals evaluate the world in relative terms. Existing explanations for these effects are based on descriptive models of psychological and physiological processes, but little attention has been paid to the factors promoting their evolution. Using a simple and general optimality model, we show that contrast effects can result from an adaptive response to uncertainty in a changing, unpredictable world. A wide range of patterns of environmental change will select for sensitivity to past conditions, generating positive and negative contrast effects. Our analysis reveals the importance of incorporating uncertainty and environmental stochasticity into models of adaptive behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNamara, John M -- Fawcett, Tim W -- Houston, Alasdair I -- New York, N.Y. -- Science. 2013 May 31;340(6136):1084-6. doi: 10.1126/science.1230599.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Mathematics, University of Bristol, University Walk, Bristol, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723234" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; *Adaptation, Psychological ; Animals ; Cognition ; *Models, Psychological ; Rats ; *Uncertainty
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  • 84
    Publication Date: 2013-05-04
    Description: The hippocampal cognitive map is thought to be driven by distal visual cues and self-motion cues. However, other sensory cues also influence place cells. Hence, we measured rat hippocampal activity in virtual reality (VR), where only distal visual and nonvestibular self-motion cues provided spatial information, and in the real world (RW). In VR, place cells showed robust spatial selectivity; however, only 20% were track active, compared with 45% in the RW. This indicates that distal visual and nonvestibular self-motion cues are sufficient to provide selectivity, but vestibular and other sensory cues present in RW are necessary to fully activate the place-cell population. In addition, bidirectional cells preferentially encoded distance along the track in VR, while encoding absolute position in RW. Taken together, these results suggest the differential contributions of these sensory cues in shaping the hippocampal population code. Theta frequency was reduced, and its speed dependence was abolished in VR, but phase precession was unaffected, constraining mechanisms governing both hippocampal theta oscillations and temporal coding. These results reveal cooperative and competitive interactions between sensory cues for control over hippocampal spatiotemporal selectivity and theta rhythm.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049564/" 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/PMC4049564/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ravassard, Pascal -- Kees, Ashley -- Willers, Bernard -- Ho, David -- Aharoni, Daniel -- Cushman, Jesse -- Aghajan, Zahra M -- Mehta, Mayank R -- 5R01MH092925-02/MH/NIMH NIH HHS/ -- R01 MH092925/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 14;340(6138):1342-6. doi: 10.1126/science.1232655. Epub 2013 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉W. M. Keck Center for Neurophysics, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641063" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Mapping ; Cues ; Hippocampus/*physiology ; Male ; Rats ; Rats, Inbred LEC ; *Space Perception ; *Spatial Behavior ; Theta Rhythm ; *Time Perception ; User-Computer Interface
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  • 85
    Publication Date: 2013-05-04
    Description: Superoxide and other reactive oxygen species (ROS) originate from several natural sources and profoundly influence numerous elemental cycles, including carbon and trace metals. In the deep ocean, the permanent absence of light precludes currently known ROS sources, yet ROS production mysteriously occurs. Here, we show that taxonomically and ecologically diverse heterotrophic bacteria from aquatic and terrestrial environments are a vast, unrecognized, and light-independent source of superoxide, and perhaps other ROS derived from superoxide. Superoxide production by a model bacterium within the ubiquitous Roseobacter clade involves an extracellular oxidoreductase that is stimulated by the reduced form of nicotinamide adenine dinucleotide (NADH), suggesting a surprising homology with eukaryotic organisms. The consequences of ROS cycling in immense aphotic zones representing key sites of nutrient regeneration and carbon export must now be considered, including potential control of carbon remineralization and metal bioavailability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diaz, Julia M -- Hansel, Colleen M -- Voelker, Bettina M -- Mendes, Chantal M -- Andeer, Peter F -- Zhang, Tong -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1223-6. doi: 10.1126/science.1237331. Epub 2013 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641059" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Carbon Cycle ; *Heterotrophic Processes ; Mercury/*metabolism ; Molecular Sequence Data ; NAD/metabolism ; Oxidoreductases/metabolism ; Phylogeny ; Roseobacter/classification/*metabolism ; Superoxides/*metabolism
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  • 86
    Publication Date: 2013-03-23
    Description: Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanji, Hiromi -- Ohto, Umeharu -- Shibata, Takuma -- Miyake, Kensuke -- Shimizu, Toshiyuki -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520111" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Imidazoles/chemistry/*metabolism ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Quinolines/chemistry/*metabolism ; Signal Transduction ; Thiazoles/chemistry/*metabolism ; Toll-Like Receptor 8/*agonists/*chemistry/metabolism
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  • 87
    Publication Date: 2013-05-11
    Description: Differences in biomolecular sequence and function underlie dramatic ranges of appearance and behavior among species. We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. Metazoans have a higher proportion of heteromeric bZIP interactions and more network complexity than the single-cell species. The metazoan bZIP interactomes have broadly similar structures, but there has been extensive rewiring of connections compared to the last common ancestor, and each species network is highly distinct. Many metazoan bZIP orthologs and paralogs have strikingly different interaction specificities, and some differences arise from minor sequence changes. Our data show that a shifting landscape of biochemical functions related to signaling and gene expression contributes to species diversity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115154/" 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/PMC4115154/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reinke, Aaron W -- Baek, Jiyeon -- Ashenberg, Orr -- Keating, Amy E -- GM067681/GM/NIGMS NIH HHS/ -- R01 GM067681/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 May 10;340(6133):730-4. doi: 10.1126/science.1233465.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts Institute of Technology, Department of Biology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661758" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Basic-Leucine Zipper Transcription Factors/chemistry/genetics/*metabolism ; Conserved Sequence ; *Evolution, Molecular ; Humans ; *Metabolic Networks and Pathways ; Molecular Sequence Data ; Protein Multimerization
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  • 88
    Publication Date: 2013-03-09
    Description: A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1alpha and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu(230), located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799917/" 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/PMC3799917/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hubbard, Basil P -- Gomes, Ana P -- Dai, Han -- Li, Jun -- Case, April W -- Considine, Thomas -- Riera, Thomas V -- Lee, Jessica E -- E, Sook Yen -- Lamming, Dudley W -- Pentelute, Bradley L -- Schuman, Eli R -- Stevens, Linda A -- Ling, Alvin J Y -- Armour, Sean M -- Michan, Shaday -- Zhao, Huizhen -- Jiang, Yong -- Sweitzer, Sharon M -- Blum, Charles A -- Disch, Jeremy S -- Ng, Pui Yee -- Howitz, Konrad T -- Rolo, Anabela P -- Hamuro, Yoshitomo -- Moss, Joel -- Perni, Robert B -- Ellis, James L -- Vlasuk, George P -- Sinclair, David A -- P01 AG027916/AG/NIA NIH HHS/ -- R01 AG019719/AG/NIA NIH HHS/ -- R01 AG028730/AG/NIA NIH HHS/ -- R37 AG028730/AG/NIA NIH HHS/ -- ZIA HL000659-20/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 8;339(6124):1216-9. doi: 10.1126/science.1231097.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23471411" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Motifs ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Cells, Cultured ; Enzyme Activation ; Forkhead Transcription Factors/chemistry/genetics ; Glutamic Acid/chemistry/genetics ; Heterocyclic Compounds with 4 or More Rings/chemistry/pharmacology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Mice ; Molecular Sequence Data ; Myoblasts/drug effects/enzymology ; Protein Structure, Tertiary ; Sirtuin 1/*chemistry/genetics/*metabolism ; Stilbenes/chemistry/*pharmacology ; Substrate Specificity
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  • 89
    Publication Date: 2013-03-30
    Description: Posttranslational lipidation provides critical modulation of the functions of some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X is any residue). Isoprenylation is followed by cleavage of the AAX amino acid residues and, in some cases, by additional proteolytic cuts. We determined the crystal structure of the CAAX protease Ste24p, a zinc metalloprotease catalyzing two proteolytic steps in the maturation of yeast mating pheromone a-factor. The Ste24p core structure is a ring of seven transmembrane helices enclosing a voluminous cavity containing the active site and substrate-binding groove. The cavity is accessible to the external milieu by means of gaps between splayed transmembrane helices. We hypothesize that cleavage proceeds by means of a processive mechanism of substrate insertion, translocation, and ejection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136949/" 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/PMC4136949/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pryor, Edward E Jr -- Horanyi, Peter S -- Clark, Kathleen M -- Fedoriw, Nadia -- Connelly, Sara M -- Koszelak-Rosenblum, Mary -- Zhu, Guangyu -- Malkowski, Michael G -- Wiener, Michael C -- Dumont, Mark E -- P30 CA044579/CA/NCI NIH HHS/ -- U54 GM094611/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1600-4. doi: 10.1126/science.1232048.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Membrane Protein Structural Biology Consortium, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539602" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Cell Membrane/*enzymology ; Crystallography, X-Ray ; Membrane Proteins/*chemistry ; Metalloendopeptidases/*chemistry ; Molecular Sequence Data ; Protein Structure, Secondary ; Saccharomyces cerevisiae Proteins/*chemistry ; Substrate Specificity
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  • 90
    Publication Date: 2013-04-20
    Description: Both bats and rats exhibit grid cells in medial entorhinal cortex that fire as they visit a regular array of spatial locations. In rats, grid-cell firing field properties correlate with theta-frequency rhythmicity of spiking and membrane-potential resonance; however, bat grid cells do not exhibit theta rhythmic spiking, generating controversy over the role of theta rhythm. To test whether this discrepancy reflects differences in rhythmicity at a cellular level, we performed whole-cell patch recordings from entorhinal neurons in both species to record theta-frequency resonance. Bat neurons showed no theta-frequency resonance, suggesting grid-cell coding via different mechanisms in bats and rats or lack of theta rhythmic contributions to grid-cell firing in either species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heys, James G -- MacLeod, Katrina M -- Moss, Cynthia F -- Hasselmo, Michael E -- New York, N.Y. -- Science. 2013 Apr 19;340(6130):363-7. doi: 10.1126/science.1233831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Program for Neuroscience, Center for Memory and Brain, Boston University, 2 Cummington Street, Boston, MA 02215, USA. jimheys@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23599495" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chiroptera ; Entorhinal Cortex/cytology/*physiology ; Female ; Male ; Membrane Potentials ; Models, Neurological ; Neurons/cytology/*physiology ; Patch-Clamp Techniques ; Rats ; Rats, Long-Evans ; *Theta Rhythm
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  • 91
    Publication Date: 2013-03-30
    Description: Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases of lamin processing (laminopathies), such as the premature aging disease progeria and metabolic disorders. ZMPSTE24 processes prelamin A, a component of the nuclear lamina intermediate filaments, by cleaving it at two sites. Failure of this processing results in accumulation of farnesylated, membrane-associated prelamin A. The 3.4 angstrom crystal structure of human ZMPSTE24 has a seven transmembrane alpha-helical barrel structure, surrounding a large, water-filled, intramembrane chamber, capped by a zinc metalloprotease domain with the catalytic site facing into the chamber. The 3.8 angstrom structure of a complex with a CSIM tetrapeptide showed that the mode of binding of the substrate resembles that of an insect metalloprotease inhibitor in thermolysin. Laminopathy-associated mutations predicted to reduce ZMPSTE24 activity map to the zinc metalloprotease peptide-binding site and to the bottom of the chamber.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quigley, Andrew -- Dong, Yin Yao -- Pike, Ashley C W -- Dong, Liang -- Shrestha, Leela -- Berridge, Georgina -- Stansfeld, Phillip J -- Sansom, Mark S P -- Edwards, Aled M -- Bountra, Chas -- von Delft, Frank -- Bullock, Alex N -- Burgess-Brown, Nicola A -- Carpenter, Elisabeth P -- 092809/Wellcome Trust/United Kingdom -- Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1604-7. doi: 10.1126/science.1231513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539603" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Lamin Type A ; Membrane Proteins/*chemistry/genetics ; Metabolism, Inborn Errors/genetics/*metabolism ; Metalloendopeptidases/*chemistry/genetics ; Molecular Sequence Data ; Nuclear Proteins/chemistry/genetics/*metabolism ; Progeria/genetics/metabolism ; Protein Conformation ; Protein Precursors/chemistry/genetics/*metabolism ; Substrate Specificity ; Thermolysin/chemistry
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  • 92
    Publication Date: 2013-04-06
    Description: We used a combined optogenetic-electrophysiological strategy to determine the functional identity of entorhinal cells with output to the place-cell population in the hippocampus. Channelrhodopsin-2 (ChR2) was expressed selectively in the hippocampus-targeting subset of entorhinal projection neurons by infusing retrogradely transportable ChR2-coding recombinant adeno-associated virus in the hippocampus. Virally transduced ChR2-expressing cells were identified in medial entorhinal cortex as cells that fired at fixed minimal latencies in response to local flashes of light. A large number of responsive cells were grid cells, but short-latency firing was also induced in border cells and head-direction cells, as well as cells with irregular or nonspatial firing correlates, which suggests that place fields may be generated by convergence of signals from a broad spectrum of entorhinal functional cell types.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Sheng-Jia -- Ye, Jing -- Miao, Chenglin -- Tsao, Albert -- Cerniauskas, Ignas -- Ledergerber, Debora -- Moser, May-Britt -- Moser, Edvard I -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):1232627. doi: 10.1126/science.1232627.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres gate 9, Norwegian Brain Centre, 7491 Trondheim, Norway. sheng-jia.zhang@ntnu.no〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23559255" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; CA1 Region, Hippocampal/cytology/physiology ; *Cell Communication ; Dependovirus ; Entorhinal Cortex/cytology/*physiology ; Gene Targeting ; Hippocampus/cytology/*physiology ; Neurons/*physiology ; Photic Stimulation ; Rats ; Rhodopsin/biosynthesis/genetics ; Transduction, Genetic
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  • 93
    Publication Date: 2013-08-03
    Description: The posttranslational modification of proteins and their regulation by metabolites represent conserved mechanisms in biology. At the confluence of these two processes, we report that the primary glycolytic intermediate 1,3-bisphosphoglycerate (1,3-BPG) reacts with select lysine residues in proteins to form 3-phosphoglyceryl-lysine (pgK). This reaction, which does not require enzyme catalysis, but rather exploits the electrophilicity of 1,3-BPG, was found by proteomic profiling to be enriched on diverse classes of proteins and prominently in or around the active sites of glycolytic enzymes. pgK modifications inhibit glycolytic enzymes and, in cells exposed to high glucose, accumulate on these enzymes to create a potential feedback mechanism that contributes to the buildup and redirection of glycolytic intermediates to alternate biosynthetic pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005992/" 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/PMC4005992/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moellering, Raymond E -- Cravatt, Benjamin F -- CA087660/CA/NCI NIH HHS/ -- R37 CA087660/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):549-53. doi: 10.1126/science.1238327.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA. rmoeller@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23908237" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Biomarkers, Tumor/chemistry/metabolism ; Catalysis ; Cell Line ; DNA-Binding Proteins/chemistry/metabolism ; Diphosphoglyceric Acids/*metabolism ; Glucose/metabolism ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/chemistry/metabolism ; Glycerophosphates/*metabolism ; *Glycolysis ; Humans ; Lysine/*analogs & derivatives/*metabolism ; Mice ; Molecular Sequence Data ; Phosphopyruvate Hydratase/chemistry/metabolism ; *Protein Processing, Post-Translational ; Proteins/chemistry/*metabolism ; Tumor Suppressor Proteins/chemistry/metabolism
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  • 94
    Publication Date: 2013-05-04
    Description: In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type alpha-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies showed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ying -- Zhang, Qianyi -- Kong, Huihui -- Jiang, Yongping -- Gao, Yuwei -- Deng, Guohua -- Shi, Jianzhong -- Tian, Guobin -- Liu, Liling -- Liu, Jinxiong -- Guan, Yuntao -- Bu, Zhigao -- Chen, Hualan -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1459-63. doi: 10.1126/science.1229455. Epub 2013 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641061" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Brain/virology ; Cell Line ; Ferrets ; Genes, Viral ; Guinea Pigs ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics ; Humans ; Influenza A Virus, H1N1 Subtype/*genetics/pathogenicity ; Influenza A Virus, H5N1 Subtype/*genetics/pathogenicity ; Influenza, Human/transmission/virology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Mutation ; Orthomyxoviridae Infections/*transmission/*virology ; Reassortant Viruses/*genetics/*pathogenicity ; Receptors, Cell Surface/metabolism ; Receptors, Virus/metabolism ; Respiratory System/*virology ; Reverse Genetics ; Ribonucleoproteins/metabolism ; Viral Proteins/genetics/metabolism ; Virus Replication
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  • 95
    Publication Date: 2013-08-03
    Description: Robust transmission of information despite the presence of variation is a fundamental problem in cellular functions. However, the capability and characteristics of information transmission in signaling pathways remain poorly understood. We describe robustness and compensation of information transmission of signaling pathways at the cell population level. We calculated the mutual information transmitted through signaling pathways for the growth factor-mediated gene expression. Growth factors appeared to carry only information sufficient for a binary decision. Information transmission was generally more robust than average signal intensity despite pharmacological perturbations, and compensation of information transmission occurred. Information transmission to the biological output of neurite extension appeared robust. Cells may use information entropy as information so that messages can be robustly transmitted despite variation in molecular activities among individual cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uda, Shinsuke -- Saito, Takeshi H -- Kudo, Takamasa -- Kokaji, Toshiya -- Tsuchiya, Takaho -- Kubota, Hiroyuki -- Komori, Yasunori -- Ozaki, Yu-ichi -- Kuroda, Shinya -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):558-61. doi: 10.1126/science.1234511.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Bunkyo-ku, Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23908238" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cyclic AMP Response Element-Binding Protein/metabolism ; Early Growth Response Protein 1/metabolism ; Gene Expression/drug effects ; *Information Theory ; Intercellular Signaling Peptides and Proteins/pharmacology ; PC12 Cells ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; *Signal Transduction
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  • 96
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-04-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Mitch -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):27. doi: 10.1126/science.340.6128.27.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23559233" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Guanylate Kinase/*chemistry/*genetics ; Humans ; Neoplasms/enzymology ; Neurons/*enzymology ; Protein Structure, Secondary ; *Pseudogenes
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  • 97
    Publication Date: 2013-01-05
    Description: The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination of protein substrates. We used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography. We extended the selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes and found that ubiquitin variants can also enhance enzyme activity. Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815447/" 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/PMC3815447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ernst, Andreas -- Avvakumov, George -- Tong, Jiefei -- Fan, Yihui -- Zhao, Yanling -- Alberts, Philipp -- Persaud, Avinash -- Walker, John R -- Neculai, Ana-Mirela -- Neculai, Dante -- Vorobyov, Andrew -- Garg, Pankaj -- Beatty, Linda -- Chan, Pak-Kei -- Juang, Yu-Chi -- Landry, Marie-Claude -- Yeh, Christina -- Zeqiraj, Elton -- Karamboulas, Konstantina -- Allali-Hassani, Abdellah -- Vedadi, Masoud -- Tyers, Mike -- Moffat, Jason -- Sicheri, Frank -- Pelletier, Laurence -- Durocher, Daniel -- Raught, Brian -- Rotin, Daniela -- Yang, Jianhua -- Moran, Michael F -- Dhe-Paganon, Sirano -- Sidhu, Sachdev S -- 092076/Wellcome Trust/United Kingdom -- 092381/Wellcome Trust/United Kingdom -- 1R01NS072420-01/Canadian Institutes of Health Research/Canada -- MOP-102536/Canadian Institutes of Health Research/Canada -- MOP-111149/Canadian Institutes of Health Research/Canada -- MOP-13494/Canadian Institutes of Health Research/Canada -- MOP-57795/Canadian Institutes of Health Research/Canada -- R01 NS072420/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):590-5. doi: 10.1126/science.1230161. Epub 2013 Jan 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23287719" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Combinatorial Chemistry Techniques ; Conserved Sequence ; Drug Design ; Endopeptidases/chemistry/*metabolism ; HEK293 Cells ; Humans ; Molecular Sequence Data ; Protease Inhibitors/chemistry/*isolation & purification/pharmacology ; Protein Conformation ; Protein Structure, Secondary ; Small Molecule Libraries ; Ubiquitin/chemistry/genetics/*metabolism ; Ubiquitin Thiolesterase/chemistry/*metabolism ; Ubiquitin-Conjugating Enzymes/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; Ubiquitination/*drug effects
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  • 98
    Publication Date: 2013-08-31
    Description: The lateral habenula (LHb) has recently emerged as a key brain region in the pathophysiology of depression. However, the molecular mechanism by which LHb becomes hyperactive in depression remains unknown. Through a quantitative proteomic screen, we found that expression of the beta form of calcium/calmodulin-dependent protein kinase type II (betaCaMKappaIotaIota) was significantly up-regulated in the LHb of animal models of depression and down-regulated by antidepressants. Increasing beta-, but not alpha-, CaMKII in the LHb strongly enhanced the synaptic efficacy and spike output of LHb neurons and was sufficient to produce profound depressive symptoms, including anhedonia and behavioral despair. Down-regulation of betaCaMKII levels, blocking its activity or its target molecule the glutamate receptor GluR1 reversed the depressive symptoms. These results identify betaCaMKII as a powerful regulator of LHb neuron function and a key molecular determinant of depression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932364/" 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/PMC3932364/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Kun -- Zhou, Tao -- Liao, Lujian -- Yang, Zhongfei -- Wong, Catherine -- Henn, Fritz -- Malinow, Roberto -- Yates, John R 3rd -- Hu, Hailan -- P41 GM103533/GM/NIGMS NIH HHS/ -- R01 MH067880/MH/NIMH NIH HHS/ -- R01 MH091119/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1016-20. doi: 10.1126/science.1240729.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P R China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990563" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antidepressive Agents/pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & ; inhibitors/*biosynthesis/genetics ; Depressive Disorder, Major/*enzymology/genetics/psychology ; Disease Models, Animal ; Gene Knockdown Techniques ; Habenula/drug effects/*enzymology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects/enzymology ; Promoter Regions, Genetic ; Proteomics ; Rats ; Rats, Sprague-Dawley
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  • 99
    Publication Date: 2013-03-30
    Description: Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689846/" 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/PMC3689846/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jardine, Joseph -- Julien, Jean-Philippe -- Menis, Sergey -- Ota, Takayuki -- Kalyuzhniy, Oleksandr -- McGuire, Andrew -- Sok, Devin -- Huang, Po-Ssu -- MacPherson, Skye -- Jones, Meaghan -- Nieusma, Travis -- Mathison, John -- Baker, David -- Ward, Andrew B -- Burton, Dennis R -- Stamatatos, Leonidas -- Nemazee, David -- Wilson, Ian A -- Schief, William R -- 5T32AI007606-10/AI/NIAID NIH HHS/ -- AI081625/AI/NIAID NIH HHS/ -- AI33292/AI/NIAID NIH HHS/ -- AI84817/AI/NIAID NIH HHS/ -- P01 AI094419/AI/NIAID NIH HHS/ -- P30 AI027767-24/AI/NIAID NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R01 AI033292/AI/NIAID NIH HHS/ -- R01 AI073148/AI/NIAID NIH HHS/ -- R01 AI081625/AI/NIAID NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- R37 AI033292/AI/NIAID NIH HHS/ -- T32 CA080416/CA/NCI NIH HHS/ -- T32CA080416/CA/NCI NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 May 10;340(6133):711-6. doi: 10.1126/science.1234150. Epub 2013 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539181" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/genetics/*immunology ; Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/immunology ; Antigens, CD4/immunology ; B-Lymphocytes/immunology ; Crystallography, X-Ray ; DNA Mutational Analysis ; Germ Cells/*immunology ; HIV Envelope Protein gp120/chemistry/genetics/*immunology ; HIV Infections/*prevention & control ; HIV-1/*immunology ; Humans ; Macaca ; Mice ; Models, Animal ; Molecular Sequence Data ; Nanoparticles ; Protein Engineering ; Protein Structure, Tertiary ; Receptors, Antigen, B-Cell/*immunology
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  • 100
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-07-03
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749839/" 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/PMC3749839/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nedergaard, Maiken -- R01 MH099578/MH/NIMH NIH HHS/ -- R01 NS075177/NS/NINDS NIH HHS/ -- R01 NS078167/NS/NINDS NIH HHS/ -- R01 NS078304/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1529-30. doi: 10.1126/science.1240514.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY 14642, USA. nedergaard@urmc.rochester.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812703" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquaporin 4/*metabolism ; Brain/*physiopathology ; Cerebrospinal Fluid/metabolism ; Extracellular Fluid/metabolism ; Humans ; Lymphatic Vessels/*metabolism ; Mice ; Neurodegenerative Diseases/cerebrospinal fluid/*physiopathology/*therapy ; Neuroglia/*metabolism ; Neurons/metabolism ; Rats
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