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  • *Ecosystem  (1,597)
  • Signal Transduction  (1,508)
  • Cells, Cultured  (1,353)
  • American Association for the Advancement of Science (AAAS)  (4,312)
  • Nature Publishing Group
  • American Association of Petroleum Geologists (AAPG)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-03-25
    Description: Author: L. Bryan Ray
    Keywords: Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-09-03
    Description: Author: L. Bryan Ray
    Keywords: Signal Transduction
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-20
    Description: Author: L. Bryan Ray
    Keywords: Signal Transduction
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    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-29
    Description: Author: L. Bryan Ray
    Keywords: Signal Transduction
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2016-02-26
    Description: Voltage-gated CaV1.2 channels (L-type calcium channel alpha1C subunits) are critical mediators of transcription-dependent neural plasticity. Whether these channels signal via the influx of calcium ion (Ca(2+)), voltage-dependent conformational change (VDeltaC), or a combination of the two has thus far been equivocal. We fused CaV1.2 to a ligand-gated Ca(2+)-permeable channel, enabling independent control of localized Ca(2+) and VDeltaC signals. This revealed an unexpected dual requirement: Ca(2+) must first mobilize actin-bound Ca(2+)/calmodulin-dependent protein kinase II, freeing it for subsequent VDeltaC-mediated accumulation. Neither signal alone sufficed to activate transcription. Signal order was crucial: Efficiency peaked when Ca(2+) preceded VDeltaC by 10 to 20 seconds. CaV1.2 VDeltaC synergistically augmented signaling by N-methyl-d-aspartate receptors. Furthermore, VDeltaC mistuning correlated with autistic symptoms in Timothy syndrome. Thus, nonionic VDeltaC signaling is vital to the function of CaV1.2 in synaptic and neuropsychiatric processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Boxing -- Tadross, Michael R -- Tsien, Richard W -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):863-7. doi: 10.1126/science.aad3647.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience and Physiology and New York University Neuroscience Institute, New York, NY 10016, USA. ; Department of Molecular and Cellular Physiology, Beckman Center, School of Medicine, Stanford University, Stanford, CA 94305, USA. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. tadrossm@janelia.hhmi.org. ; Department of Neuroscience and Physiology and New York University Neuroscience Institute, New York, NY 10016, USA. Department of Molecular and Cellular Physiology, Beckman Center, School of Medicine, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912895" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/genetics/metabolism ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/chemistry/*metabolism ; *Calcium Signaling ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein/metabolism ; *Gene Expression Regulation ; HEK293 Cells ; Hippocampus/cytology ; Humans ; Long QT Syndrome/genetics/metabolism ; Neuronal Plasticity/*genetics ; Neurons/drug effects/*metabolism ; Nimodipine/pharmacology ; Protein Conformation/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism ; Syndactyly/genetics/metabolism
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  • 6
    Publication Date: 2016-01-23
    Description: Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soucie, Erinn L -- Weng, Ziming -- Geirsdottir, Laufey -- Molawi, Kaaweh -- Maurizio, Julien -- Fenouil, Romain -- Mossadegh-Keller, Noushine -- Gimenez, Gregory -- VanHille, Laurent -- Beniazza, Meryam -- Favret, Jeremy -- Berruyer, Carole -- Perrin, Pierre -- Hacohen, Nir -- Andrau, J-C -- Ferrier, Pierre -- Dubreuil, Patrice -- Sidow, Arend -- Sieweke, Michael H -- P01AG036695/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):aad5510. doi: 10.1126/science.aad5510. Epub 2016 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Centre de Recherche en Cancerologie de Marseille, INSERM (U1068), CNRS (U7258), Universite Aix-Marseille (UM105), Marseille, France. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu. ; Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA. ; Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. ; Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft, 10 Robert-Rossle-Strasse, 13125 Berlin, Germany. ; Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA. ; Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Institut de Genetique Moleculaire de Montpellier, CNRS UMR 5535, 1919 Route de Mende, 34293 Montpellier, France. ; Centre de Recherche en Cancerologie de Marseille, INSERM (U1068), CNRS (U7258), Universite Aix-Marseille (UM105), Marseille, France. ; Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA. Department of Genetics, Stanford University, Stanford, CA 94305, USA. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu. ; Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft, 10 Robert-Rossle-Strasse, 13125 Berlin, Germany. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797145" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/*genetics ; Cell Lineage/*genetics ; Cell Proliferation ; Cells, Cultured ; Down-Regulation ; Embryonic Stem Cells/*cytology ; Enhancer Elements, Genetic/*physiology ; *Gene Expression Regulation ; Gene Regulatory Networks ; Macrophages/*cytology ; MafB Transcription Factor/metabolism ; Mice ; Proto-Oncogene Proteins c-maf/metabolism ; Single-Cell Analysis ; Transcriptional Activation
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  • 7
    Publication Date: 2016-04-09
    Description: Activation of various cell surface receptors triggers the reorganization of downstream signaling molecules into micrometer- or submicrometer-sized clusters. However, the functional consequences of such clustering have been unclear. We biochemically reconstituted a 12-component signaling pathway on model membranes, beginning with T cell receptor (TCR) activation and ending with actin assembly. When TCR phosphorylation was triggered, downstream signaling proteins spontaneously separated into liquid-like clusters that promoted signaling outputs both in vitro and in human Jurkat T cells. Reconstituted clusters were enriched in kinases but excluded phosphatases and enhanced actin filament assembly by recruiting and organizing actin regulators. These results demonstrate that protein phase separation can create a distinct physical and biochemical compartment that facilitates signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, Xiaolei -- Ditlev, Jonathon A -- Hui, Enfu -- Xing, Wenmin -- Banjade, Sudeep -- Okrut, Julia -- King, David S -- Taunton, Jack -- Rosen, Michael K -- Vale, Ronald D -- 5-F32-DK101188/DK/NIDDK NIH HHS/ -- F32 DK101188/DK/NIDDK NIH HHS/ -- R01 GM056322/GM/NIGMS NIH HHS/ -- R01-GM56322/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):595-9. doi: 10.1126/science.aad9964. Epub 2016 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. ; Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; HHMI Mass Spectrometry Laboratory and Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA. ; Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ron.vale@ucsf.edu michael.rosen@utsouthwestern.edu. ; Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. ron.vale@ucsf.edu michael.rosen@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27056844" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Adaptor Proteins, Signal Transducing/*metabolism ; Fluorescence Recovery After Photobleaching ; Humans ; Jurkat Cells ; Membrane Proteins/*metabolism ; Mitogen-Activated Protein Kinase Kinases ; Phosphorylation ; Polymerization ; Receptors, Antigen, T-Cell/*agonists ; Signal Transduction ; T-Lymphocytes/*metabolism
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  • 8
    Publication Date: 2016-03-19
    Description: Systemic inflammation, which results from the massive release of proinflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are not fully understood. We observed that prostaglandin E2 (PGE2), through its receptor EP4, is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treatment with EP4 agonists. Mechanistically, we demonstrate that PGE2-EP4 signaling acts directly on type 3 innate lymphoid cells (ILCs), promoting their homeostasis and driving them to produce interleukin-22 (IL-22). Disruption of the ILC-IL-22 axis impairs PGE2-mediated inhibition of systemic inflammation. Hence, the ILC-IL-22 axis is essential in protecting against gut barrier dysfunction, enabling PGE2-EP4 signaling to impede systemic inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841390/" 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/PMC4841390/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duffin, Rodger -- O'Connor, Richard A -- Crittenden, Siobhan -- Forster, Thorsten -- Yu, Cunjing -- Zheng, Xiaozhong -- Smyth, Danielle -- Robb, Calum T -- Rossi, Fiona -- Skouras, Christos -- Tang, Shaohui -- Richards, James -- Pellicoro, Antonella -- Weller, Richard B -- Breyer, Richard M -- Mole, Damian J -- Iredale, John P -- Anderton, Stephen M -- Narumiya, Shuh -- Maizels, Rick M -- Ghazal, Peter -- Howie, Sarah E -- Rossi, Adriano G -- Yao, Chengcan -- 106122/Wellcome Trust/United Kingdom -- BB/K091121/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- DK37097/DK/NIDDK NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1333-8. doi: 10.1126/science.aad9903.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK. ; Division of Pathway Medicine, Edinburgh Infectious Diseases, The University of Edinburgh, Edinburgh EH16 4SB, UK. ; Institute for Immunology and Infection Research, The University of Edinburgh, Edinburgh EH9 3JT, UK. ; MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, UK. ; Department of Gastroenterology, First Affiliated Hospital of Jinan University, Guangzhou 510630, China. ; Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN 37212, USA. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. ; Center for Innovation in Immunoregulative Technology and Therapeutics (AK Project), Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan. ; Division of Pathway Medicine, Edinburgh Infectious Diseases, The University of Edinburgh, Edinburgh EH16 4SB, UK. Centre for Synthetic and Systems Biology (SynthSys), The University of Edinburgh, Edinburgh EH9 3JD, UK. ; Medical Research Council (MRC) Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK. chengcan.yao@ed.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Infections/genetics/immunology ; Dinoprostone/*immunology ; Gene Expression ; Humans ; Immunity, Innate ; Inflammation/drug therapy/*immunology/microbiology ; Interleukins/*immunology ; Intestines/*immunology/microbiology ; Lymphocytes/*immunology ; Mice ; Receptors, Prostaglandin E, EP4 Subtype/antagonists & ; inhibitors/genetics/*immunology ; Signal Transduction
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  • 9
    Publication Date: 2016-01-23
    Description: Oligodendrocytes myelinate axons in the central nervous system and develop from oligodendrocyte precursor cells (OPCs) that must first migrate extensively during brain and spinal cord development. We show that OPCs require the vasculature as a physical substrate for migration. We observed that OPCs of the embryonic mouse brain and spinal cord, as well as the human cortex, emerge from progenitor domains and associate with the abluminal endothelial surface of nearby blood vessels. Migrating OPCs crawl along and jump between vessels. OPC migration in vivo was disrupted in mice with defective vascular architecture but was normal in mice lacking pericytes. Thus, physical interactions with the vascular endothelium are required for OPC migration. We identify Wnt-Cxcr4 (chemokine receptor 4) signaling in regulation of OPC-endothelial interactions and propose that this signaling coordinates OPC migration with differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsai, Hui-Hsin -- Niu, Jianqin -- Munji, Roeben -- Davalos, Dimitrios -- Chang, Junlei -- Zhang, Haijing -- Tien, An-Chi -- Kuo, Calvin J -- Chan, Jonah R -- Daneman, Richard -- Fancy, Stephen P J -- 1P01 NS083513/NS/NINDS NIH HHS/ -- 1R01NS064517/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):379-84. doi: 10.1126/science.aad3839.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, University of California at San Francisco (UCSF), San Francisco, CA 94158, USA. ; Departments of Pharmacology and Neuroscience, University of California at San Diego (UCSD), San Diego, CA 92093, USA. ; Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. ; Division of Hematology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. ; Division of Hematology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. Department of Urology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. Howard Hughes Medical Institute (HHMI), Chevy Chase, MD 20815, USA. Duke University School of Medicine, Durham, NC 27710, USA. ; Department of Neurology, UCSF, San Francisco, CA 94158, USA. ; Department of Pediatrics, University of California at San Francisco (UCSF), San Francisco, CA 94158, USA. Department of Neurology, UCSF, San Francisco, CA 94158, USA. Division of Neonatology, UCSF, San Francisco, CA 94158, USA. Newborn Brain Research Institute, UCSF, San Francisco, CA 94158, USA. stephen.fancy@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26798014" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Vessels/cytology/embryology ; *Cell Movement ; Cerebral Cortex/blood supply/*embryology ; Endothelium, Vascular/cytology ; Humans ; Mice ; Neural Stem Cells/cytology/*physiology ; *Neurogenesis ; Oligodendroglia/cytology/*physiology ; *Organogenesis ; Pericytes/cytology/physiology ; Receptors, CXCR4/metabolism ; Signal Transduction ; Spinal Cord/blood supply/cytology/*embryology ; Wnt Proteins/metabolism
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  • 10
    Publication Date: 2016-02-26
    Description: Astrocytes are specialized and heterogeneous cells that contribute to central nervous system function and homeostasis. However, the mechanisms that create and maintain differences among astrocytes and allow them to fulfill particular physiological roles remain poorly defined. We reveal that neurons actively determine the features of astrocytes in the healthy adult brain and define a role for neuron-derived sonic hedgehog (Shh) in regulating the molecular and functional profile of astrocytes. Thus, the molecular and physiological program of astrocytes is not hardwired during development but, rather, depends on cues from neurons that drive and sustain their specialized properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farmer, W Todd -- Abrahamsson, Therese -- Chierzi, Sabrina -- Lui, Christopher -- Zaelzer, Cristian -- Jones, Emma V -- Bally, Blandine Ponroy -- Chen, Gary G -- Theroux, Jean-Francois -- Peng, Jimmy -- Bourque, Charles W -- Charron, Frederic -- Ernst, Carl -- Sjostrom, P Jesper -- Murai, Keith K -- FDN 143337/Canadian Institutes of Health Research/Canada -- MOP 111152/Canadian Institutes of Health Research/Canada -- MOP 123390/Canadian Institutes of Health Research/Canada -- MOP 126137/Canadian Institutes of Health Research/Canada -- NIA 288936/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):849-54. doi: 10.1126/science.aab3103.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada. ; Department of Psychiatry, McGill University, Montreal, Quebec, Canada. McGill Group for Suicide Studies, Douglas Hospital, Montreal, Quebec, Canada. ; Molecular Biology of Neural Development, Institut de Recherches Cliniques de Montreal, Department of Medicine, University of Montreal, Montreal, Quebec, Canada. Department of Biology, McGill University, Montreal, Quebec, Canada. ; Department of Psychiatry, McGill University, Montreal, Quebec, Canada. McGill Group for Suicide Studies, Douglas Hospital, Montreal, Quebec, Canada. Department of Human Genetics, McGill University, Montreal, Quebec, Canada. Douglas Hospital Research Institute, Verdun, Quebec, Canada. ; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada. keith.murai@mcgill.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912893" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/*metabolism ; Cerebellar Cortex/*cytology ; Female ; Gene Deletion ; Hedgehog Proteins/genetics/*metabolism ; Male ; Mice ; Mice, Mutant Strains ; Neurons/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Signal Transduction
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  • 11
    Publication Date: 2016-02-26
    Description: Purine biosynthetic enzymes organize into dynamic cellular bodies called purinosomes. Little is known about the spatiotemporal control of these structures. Using super-resolution microscopy, we demonstrated that purinosomes colocalized with mitochondria, and these results were supported by isolation of purinosome enzymes with mitochondria. Moreover, the number of purinosome-containing cells responded to dysregulation of mitochondrial function and metabolism. To explore the role of intracellular signaling, we performed a kinome screen using a label-free assay and found that mechanistic target of rapamycin (mTOR) influenced purinosome assembly. mTOR inhibition reduced purinosome-mitochondria colocalization and suppressed purinosome formation stimulated by mitochondria dysregulation. Collectively, our data suggest an mTOR-mediated link between purinosomes and mitochondria, and a general means by which mTOR regulates nucleotide metabolism by spatiotemporal control over protein association.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉French, Jarrod B -- Jones, Sara A -- Deng, Huayun -- Pedley, Anthony M -- Kim, Doory -- Chan, Chung Yu -- Hu, Haibei -- Pugh, Raymond J -- Zhao, Hong -- Zhang, Youxin -- Huang, Tony Jun -- Fang, Ye -- Zhuang, Xiaowei -- Benkovic, Stephen J -- 1R33EB019785-01/EB/NIBIB NIH HHS/ -- GM024129/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):733-7. doi: 10.1126/science.aac6054.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Cell Biology, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. ; Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, NY 14831, USA. ; Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA. ; Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802, USA. ; Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, NY 14831, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA. Department of Physics, Harvard University, Cambridge, MA 02138, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu. ; Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912862" target="_blank"〉PubMed〈/a〉
    Keywords: HeLa Cells ; Humans ; Microscopy ; Mitochondria/*metabolism/ultrastructure ; Purines/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism
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  • 12
    Publication Date: 2016-02-26
    Description: Bruns and Taylor argue that our finding of widespread distribution among Glomeromycota "virtual taxa" is undermined by the species definition applied. Although identifying appropriate species concepts and accessing taxonomically informative traits are challenges for microorganism biogeography, the virtual taxa represent a pragmatic classification that corresponds approximately to the species rank of classical Glomeromycota taxonomy, yet is applicable to environmental DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Opik, Maarja -- Davison, John -- Moora, Mari -- Partel, Meelis -- Zobel, Martin -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):826. doi: 10.1126/science.aad5495.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Botany, University of Tartu, 40 Lai Street, 51005 Tartu, Estonia. maarja.opik@ut.ee. ; Department of Botany, University of Tartu, 40 Lai Street, 51005 Tartu, Estonia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912890" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; Humans ; *Mycorrhizae ; Plant Roots/*microbiology ; *Symbiosis
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  • 13
    Publication Date: 2016-01-23
    Description: The plant root cap, surrounding the very tip of the growing root, perceives and transmits environmental signals to the inner root tissues. In Arabidopsis thaliana, auxin released by the root cap contributes to the regular spacing of lateral organs along the primary root axis. Here, we show that the periodicity of lateral organ induction is driven by recurrent programmed cell death at the most distal edge of the root cap. We suggest that synchronous bursts of cell death in lateral root cap cells release pulses of auxin to surrounding root tissues, establishing the pattern for lateral root formation. The dynamics of root cap turnover may therefore coordinate primary root growth with root branching in order to optimize the uptake of water and nutrients from the soil.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xuan, Wei -- Band, Leah R -- Kumpf, Robert P -- Van Damme, Daniel -- Parizot, Boris -- De Rop, Gieljan -- Opdenacker, Davy -- Moller, Barbara K -- Skorzinski, Noemi -- Njo, Maria F -- De Rybel, Bert -- Audenaert, Dominique -- Nowack, Moritz K -- Vanneste, Steffen -- Beeckman, Tom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):384-7. doi: 10.1126/science.aad2776.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Systems Biology, Vlaams Instituut voor Biotechnologie (VIB), Technologiepark 927, 9052 Ghent, Belgium. Department of Plant Biotechnology and Bioinformatics, Gent University, Technologiepark 927, 9052 Ghent, Belgium. State Key Laboratory of Crop Genetics and Germplasm Enhancement and MOA Key Laboratory of Plant Nutrition and Fertilization in Lower-Middle Reaches of the Yangtze River, Nanjing Agricultural University, Weigang No. 1, Nanjing 210095, PR China. ; Centre for Plant Integrative Biology, University of Nottingham, Nottingham LE12 5RD, UK. ; Department of Plant Systems Biology, Vlaams Instituut voor Biotechnologie (VIB), Technologiepark 927, 9052 Ghent, Belgium. Department of Plant Biotechnology and Bioinformatics, Gent University, Technologiepark 927, 9052 Ghent, Belgium. ; Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tubingen, Germany. ; Department of Plant Systems Biology, Vlaams Instituut voor Biotechnologie (VIB), Technologiepark 927, 9052 Ghent, Belgium. Department of Plant Biotechnology and Bioinformatics, Gent University, Technologiepark 927, 9052 Ghent, Belgium. Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703HA Wageningen, Netherlands. ; Department of Plant Systems Biology, Vlaams Instituut voor Biotechnologie (VIB), Technologiepark 927, 9052 Ghent, Belgium. Department of Plant Biotechnology and Bioinformatics, Gent University, Technologiepark 927, 9052 Ghent, Belgium. tobee@psb.vib-ugent.be.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26798015" target="_blank"〉PubMed〈/a〉
    Keywords: *Apoptosis ; Arabidopsis/cytology/*growth & development/metabolism ; Indoleacetic Acids/*metabolism ; Plant Epidermis/cytology/growth & development/metabolism ; Plant Root Cap/cytology/*growth & development/metabolism ; Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism ; Signal Transduction ; Soil ; Water/metabolism
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  • 14
    Publication Date: 2016-02-06
    Description: The intestinal epithelium forms an essential barrier between a host and its microbiota. Protozoa and helminths are members of the gut microbiota of mammals, including humans, yet the many ways that gut epithelial cells orchestrate responses to these eukaryotes remain unclear. Here we show that tuft cells, which are taste-chemosensory epithelial cells, accumulate during parasite colonization and infection. Disruption of chemosensory signaling through the loss of TRMP5 abrogates the expansion of tuft cells, goblet cells, eosinophils, and type 2 innate lymphoid cells during parasite colonization. Tuft cells are the primary source of the parasite-induced cytokine interleukin-25, which indirectly induces tuft cell expansion by promoting interleukin-13 production by innate lymphoid cells. Our results identify intestinal tuft cells as critical sentinels in the gut epithelium that promote type 2 immunity in response to intestinal parasites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howitt, Michael R -- Lavoie, Sydney -- Michaud, Monia -- Blum, Arthur M -- Tran, Sara V -- Weinstock, Joel V -- Gallini, Carey Ann -- Redding, Kevin -- Margolskee, Robert F -- Osborne, Lisa C -- Artis, David -- Garrett, Wendy S -- F31DK105653/DK/NIDDK NIH HHS/ -- F32DK098826/DK/NIDDK NIH HHS/ -- R01 CA154426/CA/NCI NIH HHS/ -- R01 GM099531/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1329-33. doi: 10.1126/science.aaf1648. Epub 2016 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA. ; Division of Gastroenterology, Tufts Medical Center, Boston, MA 02111, USA. ; Monell Chemical Senses Center, Philadelphia, PA 19104, USA. ; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, Cornell University, New York, NY 10021, USA. ; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. wgarrett@hsph.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26847546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemoreceptor Cells/*immunology ; Eosinophils/immunology ; Goblet Cells/immunology ; Helminthiasis/immunology/parasitology ; Helminths/immunology ; Immunity, Mucosal ; Interleukin-13/immunology ; Interleukin-17/immunology ; Intestinal Diseases, Parasitic/*immunology/parasitology ; Intestinal Mucosa/*immunology/*parasitology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Microbiota/*immunology ; Protein-Serine-Threonine Kinases/immunology ; Protozoan Infections/immunology/parasitology ; Signal Transduction ; TRPM Cation Channels/*immunology ; Taste ; Transducin/genetics/immunology ; Tritrichomonas/immunology
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  • 15
    Publication Date: 2016-02-06
    Description: SH3 and multiple ankyrin repeat domains 3 (SHANK3) haploinsufficiency is causative for the neurological features of Phelan-McDermid syndrome (PMDS), including a high risk of autism spectrum disorder (ASD). We used unbiased, quantitative proteomics to identify changes in the phosphoproteome of Shank3-deficient neurons. Down-regulation of protein kinase B (PKB/Akt)-mammalian target of rapamycin complex 1 (mTORC1) signaling resulted from enhanced phosphorylation and activation of serine/threonine protein phosphatase 2A (PP2A) regulatory subunit, B56beta, due to increased steady-state levels of its kinase, Cdc2-like kinase 2 (CLK2). Pharmacological and genetic activation of Akt or inhibition of CLK2 relieved synaptic deficits in Shank3-deficient and PMDS patient-derived neurons. CLK2 inhibition also restored normal sociability in a Shank3-deficient mouse model. Our study thereby provides a novel mechanistic and potentially therapeutic understanding of deregulated signaling downstream of Shank3 deficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bidinosti, Michael -- Botta, Paolo -- Kruttner, Sebastian -- Proenca, Catia C -- Stoehr, Natacha -- Bernhard, Mario -- Fruh, Isabelle -- Mueller, Matthias -- Bonenfant, Debora -- Voshol, Hans -- Carbone, Walter -- Neal, Sarah J -- McTighe, Stephanie M -- Roma, Guglielmo -- Dolmetsch, Ricardo E -- Porter, Jeffrey A -- Caroni, Pico -- Bouwmeester, Tewis -- Luthi, Andreas -- Galimberti, Ivan -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1199-203. doi: 10.1126/science.aad5487. Epub 2016 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Friedrich Miescher Institute, Basel, Switzerland. ; Analytical Sciences and Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Neuroscience, Novartis Institutes for Biomedical Research, Cambridge, USA. ; Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ivan.galimberti@novartis.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26847545" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Autism Spectrum Disorder/*drug therapy/enzymology/genetics ; Chromosome Deletion ; Chromosome Disorders/genetics ; Chromosomes, Human, Pair 22/genetics ; Disease Models, Animal ; Down-Regulation ; Gene Knockdown Techniques ; Humans ; Insulin-Like Growth Factor I/metabolism ; Mice ; Molecular Sequence Data ; Multiprotein Complexes/metabolism ; Nerve Tissue Proteins/*genetics ; Neurons/enzymology ; Phosphorylation ; Protein Phosphatase 2/metabolism ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Proteomics ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; Rats ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-29
    Description: Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Hypoxia is a potent microenvironmental factor promoting metastatic progression. Clinically, hypoxia and the expression of the hypoxia-inducible transcription factors HIF-1 and HIF-2 are associated with increased distant metastasis and poor survival in a variety of tumor types. Moreover, HIF signaling in malignant cells influences multiple steps within the metastatic cascade. Here we review research focused on elucidating the mechanisms by which the hypoxic tumor microenvironment promotes metastatic progression. These studies have identified potential biomarkers and therapeutic targets regulated by hypoxia that could be incorporated into strategies aimed at preventing and treating metastatic disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rankin, Erinn B -- Giaccia, Amato J -- CA-197713/CA/NCI NIH HHS/ -- CA-198291/CA/NCI NIH HHS/ -- CA-67166/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):175-80. doi: 10.1126/science.aaf4405. Epub 2016 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305-5152, USA. Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA 94305-5152, USA. ; Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305-5152, USA. giaccia@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27124451" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Biomarkers, Tumor/analysis/metabolism ; Cell Hypoxia ; Cell Movement ; Disease Progression ; Drug Resistance, Neoplasm ; Epithelial-Mesenchymal Transition ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis/*pathology/*therapy ; Radiation Tolerance ; Signal Transduction ; *Tumor Microenvironment
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  • 17
    Publication Date: 2016-02-26
    Description: Davison et al. (Reports, 28 August 2015, p. 970) claim that virtual taxa of Glomeromycota show little endemism and that endemism that exists is similar to the levels seen in plant families. We show that this is likely due to the conservative species definition rather than to any ecological pattern.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bruns, Thomas D -- Taylor, John W -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):826. doi: 10.1126/science.aad4228.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant and Microbial Biology, 111 Koshland Hall, Berkeley, CA 94720-3102, USA. pogon@berkeley.edu. ; Department of Plant and Microbial Biology, 111 Koshland Hall, Berkeley, CA 94720-3102, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912889" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; Humans ; *Mycorrhizae ; Plant Roots/*microbiology ; *Symbiosis
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  • 18
    Publication Date: 2016-03-12
    Description: The oncogene MDMX is overexpressed in many cancers, leading to suppression of the tumor suppressor p53. Inhibitors of the oncogene product MDMX therefore might help reactivate p53 and enhance the efficacy of DNA-damaging drugs. However, we currently lack a quantitative understanding of how MDMX inhibition affects the p53 signaling pathway and cell sensitivity to DNA damage. Live cell imaging showed that MDMX depletion triggered two distinct phases of p53 accumulation in single cells: an initial postmitotic pulse, followed by low-amplitude oscillations. The response to DNA damage was sharply different in these two phases; in the first phase, MDMX depletion was synergistic with DNA damage in causing cell death, whereas in the second phase, depletion of MDMX inhibited cell death. Thus a quantitative understanding of signal dynamics and cellular states is important for designing an optimal schedule of dual-drug administration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Sheng-Hong -- Forrester, William -- Lahav, Galit -- F32GM105205/GM/NIGMS NIH HHS/ -- GM083303/GM/NIGMS NIH HHS/ -- R01 GM083303/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1204-8. doi: 10.1126/science.aac5610. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, MA, USA. ; Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Cambridge, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965628" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/*administration & dosage ; Apoptosis ; *DNA Damage ; Gene Knockdown Techniques ; Humans ; MCF-7 Cells ; Molecular Imaging ; Neoplasms/*drug therapy ; Proto-Oncogene Proteins c-mdm2/*antagonists & inhibitors/genetics ; RNA, Small Interfering/genetics ; Signal Transduction ; Time Factors ; Tumor Suppressor Protein p53/*metabolism
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  • 19
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-08-16
    Description: Author: L. Bryan Ray
    Keywords: Signal Transduction
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  • 20
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-10-14
    Description: Authors: Caroline Ash, L. Bryan Ray
    Keywords: Signal Transduction
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  • 21
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-10-14
    Description: Reversible protein phosphorylation plays a fundamental role in signal transduction networks. Phosphorylation alters protein function by regulating enzymatic activity, stability, cellular localization, or binding partners. Over three-quarters of human proteins may be phosphorylated, with many targeted at multiple sites. Such multisite phosphorylation substantially increases the scope for modulating protein function—a protein with n phosphorylation sites has the potential to exist in 2n distinct phosphorylation states, each of which could, in theory, display modified functionality. Proteins can be substrates for several protein kinases, thereby integrating distinct signals to provide a coherent biological response. However, they can also be phosphorylated at multiple sites by a single protein kinase to promote a specific functional output that can be reversed by dephosphorylation by protein phosphatases. On page 233 of this issue, Mylona et al. (1) reveal an unexpected role for multisite phosphorylation, whereby a protein kinase progressively phosphorylates sites on a transcription factor to promote and then subsequently limit its activity independently of dephosphorylation. Authors: Alan J. Whitmarsh, Roger J. Davis
    Keywords: Signal Transduction
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  • 22
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dantzer, Ben -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):822-3. doi: 10.1126/science.aaa6480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology and Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA. dantzer@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700499" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Competitive Behavior ; *Ecosystem ; Female ; Male ; *Maternal Behavior ; Songbirds/*physiology
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  • 23
    Publication Date: 2015-04-11
    Description: Protein phosphorylation regulates virtually all biological processes. Although protein kinases are popular drug targets, targeting protein phosphatases remains a challenge. Here, we describe Sephin1 (selective inhibitor of a holophosphatase), a small molecule that safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively bound and inhibited the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis. Thus, regulatory subunits of phosphatases are drug targets, a property exploited here to safely prevent two protein misfolding diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490275/" 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/PMC4490275/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Indrajit -- Krzyzosiak, Agnieszka -- Schneider, Kim -- Wrabetz, Lawrence -- D'Antonio, Maurizio -- Barry, Nicholas -- Sigurdardottir, Anna -- Bertolotti, Anne -- 309516/European Research Council/International -- MC_U105185860/Medical Research Council/United Kingdom -- R01-NS55256/NS/NINDS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Apr 10;348(6231):239-42. doi: 10.1126/science.aaa4484.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. ; Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy. ; Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. aberto@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25859045" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; Cells, Cultured ; Charcot-Marie-Tooth Disease/drug therapy/metabolism/pathology ; Disease Models, Animal ; Endoplasmic Reticulum Stress/drug effects ; Enzyme Inhibitors/metabolism/pharmacokinetics/*pharmacology/toxicity ; Guanabenz/*analogs & derivatives/chemical ; synthesis/metabolism/pharmacology/toxicity ; HeLa Cells ; Humans ; Mice ; Mice, Transgenic ; Molecular Targeted Therapy ; Phosphorylation ; Protein Folding ; Protein Phosphatase 1/*antagonists & inhibitors ; Proteostasis Deficiencies/*drug therapy/*prevention & control ; Signal Transduction
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1454. doi: 10.1126/science.350.6267.1454.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680170" target="_blank"〉PubMed〈/a〉
    Keywords: Contract Services/*economics ; Ecology/*economics ; *Ecosystem ; United States
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  • 25
    Publication Date: 2015-09-01
    Description: The global biogeography of microorganisms remains largely unknown, in contrast to the well-studied diversity patterns of macroorganisms. We used arbuscular mycorrhizal (AM) fungus DNA from 1014 plant-root samples collected worldwide to determine the global distribution of these plant symbionts. We found that AM fungal communities reflected local environmental conditions and the spatial distance between sites. However, despite AM fungi apparently possessing limited dispersal ability, we found 93% of taxa on multiple continents and 34% on all six continents surveyed. This contrasts with the high spatial turnover of other fungal taxa and with the endemism displayed by plants at the global scale. We suggest that the biogeography of AM fungi is driven by unexpectedly efficient dispersal, probably via both abiotic and biotic vectors, including humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davison, J -- Moora, M -- Opik, M -- Adholeya, A -- Ainsaar, L -- Ba, A -- Burla, S -- Diedhiou, A G -- Hiiesalu, I -- Jairus, T -- Johnson, N C -- Kane, A -- Koorem, K -- Kochar, M -- Ndiaye, C -- Partel, M -- Reier, U -- Saks, U -- Singh, R -- Vasar, M -- Zobel, M -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):970-3. doi: 10.1126/science.aab1161.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. ; Centre for Mycorrhizal Research, The Energy and Resources Institute (TERI), India Habitat Centre, Lodhi Road, New Delhi 110 003, India. ; Laboratoire des Symbioses Tropicales et Mediterraneennes, Unite Mixte de Recherche 113, Laboratoire de Biologie et Physiologie Vegetales, Faculte des Sciences Exactes et Naturelles, Universite des Antilles, BP 592, 97159, Pointe-a-Pitre, Guadeloupe (French West Indies). ; Laboratoire Commun de Microbiologie de l'Institut de Recherche pour le Developpement-Institut Senegalais de Recherches Agricoles-Universite Cheikh Anta Diop (UCAD), Departement de Biologie Vegetale, UCAD, BP 5005 Dakar, Senegal. ; Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. Institute of Botany, Czech Academy of Sciences, Dukelska 135, 379 01 Trebon, Czech Republic. ; School of Earth Sciences and Environmental Sustainability, Northern Arizona University, Flagstaff, AZ 86011-5694, USA. ; Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. Netherlands Institute of Ecology, Droevendaalsesteeg 10, 6708 PB Wageningen, Netherlands. ; TERI-Deakin Nano Biotechnology Centre, Biotechnology and Management of Bioresources Division, TERI, India Habitat Centre, Lodhi Road, New Delhi 110 003, India.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315436" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; DNA, Fungal/analysis ; *Ecosystem ; Environment ; Humans ; *Mycorrhizae/genetics/isolation & purification/physiology ; Phylogeny ; Phylogeography ; Plant Roots/*microbiology ; *Symbiosis ; Water ; Wind
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  • 26
    Publication Date: 2015-08-22
    Description: Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras-dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687752/" 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/PMC4687752/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Yong -- Wong, Ching-On -- Cho, Kwang-jin -- van der Hoeven, Dharini -- Liang, Hong -- Thakur, Dhananiay P -- Luo, Jialie -- Babic, Milos -- Zinsmaier, Konrad E -- Zhu, Michael X -- Hu, Hongzhen -- Venkatachalam, Kartik -- Hancock, John F -- R01 NS081301/NS/NINDS NIH HHS/ -- R01NS081301/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):873-6. doi: 10.1126/science.aaa5619.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. ; Department of Diagnostic and Biomedical Sciences, Dental School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA. ; Department of Neuroscience, University of Arizona, Tucson, AZ 85721, USA. ; Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Program in Cell and Regulatory Biology, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. ; Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Program in Cell and Regulatory Biology, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. john.f.hancock@uth.tmc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293964" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Membrane/metabolism/*physiology ; Cricetinae ; Drosophila melanogaster ; Fibroblasts ; *Membrane Potentials ; Mice ; Neurons ; Phosphatidylinositol 4,5-Diphosphate/*metabolism ; Phosphatidylserines/*metabolism ; Signal Transduction ; ras Proteins/*metabolism
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  • 27
    Publication Date: 2015-02-07
    Description: Self-organized spatial vegetation patterning is widespread and has been described using models of scale-dependent feedback between plants and water on homogeneous substrates. As rainfall decreases, these models yield a characteristic sequence of patterns with increasingly sparse vegetation, followed by sudden collapse to desert. Thus, the final, spot-like pattern may provide early warning for such catastrophic shifts. In many arid ecosystems, however, termite nests impart substrate heterogeneity by altering soil properties, thereby enhancing plant growth. We show that termite-induced heterogeneity interacts with scale-dependent feedbacks to produce vegetation patterns at different spatial grains. Although the coarse-grained patterning resembles that created by scale-dependent feedback alone, it does not indicate imminent desertification. Rather, mound-field landscapes are more robust to aridity, suggesting that termites may help stabilize ecosystems under global change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonachela, Juan A -- Pringle, Robert M -- Sheffer, Efrat -- Coverdale, Tyler C -- Guyton, Jennifer A -- Caylor, Kelly K -- Levin, Simon A -- Tarnita, Corina E -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):651-5. doi: 10.1126/science.1261487.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. Mpala Research Centre, Post Office Box 555, Nanyuki, Kenya. ; Mpala Research Centre, Post Office Box 555, Nanyuki, Kenya. Department of Civil and Environmental Engineering, Princeton University, Princeton, NJ 08544, USA. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. Mpala Research Centre, Post Office Box 555, Nanyuki, Kenya. ctarnita@princeton.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657247" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Climate Change ; Conservation of Natural Resources ; *Desert Climate ; *Ecosystem ; Feedback ; Isoptera/*physiology ; Models, Biological ; *Plant Development ; *Rain ; Soil ; *Water
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  • 28
    Publication Date: 2015-03-06
    Description: Sedimentary basins in eastern Africa preserve a record of continental rifting and contain important fossil assemblages for interpreting hominin evolution. However, the record of hominin evolution between 3 and 2.5 million years ago (Ma) is poorly documented in surface outcrops, particularly in Afar, Ethiopia. Here we present the discovery of a 2.84- to 2.58-million-year-old fossil and hominin-bearing sediments in the Ledi-Geraru research area of Afar, Ethiopia, that have produced the earliest record of the genus Homo. Vertebrate fossils record a faunal turnover indicative of more open and probably arid habitats than those reconstructed earlier in this region, which is in broad agreement with hypotheses addressing the role of environmental forcing in hominin evolution at this time. Geological analyses constrain depositional and structural models of Afar and date the LD 350-1 Homo mandible to 2.80 to 2.75 Ma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DiMaggio, Erin N -- Campisano, Christopher J -- Rowan, John -- Dupont-Nivet, Guillaume -- Deino, Alan L -- Bibi, Faysal -- Lewis, Margaret E -- Souron, Antoine -- Garello, Dominique -- Werdelin, Lars -- Reed, Kaye E -- Arrowsmith, J Ramon -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1355-9. doi: 10.1126/science.aaa1415. Epub 2015 Mar 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geosciences, Pennsylvania State University, University Park, PA 16802, USA. dimaggio@psu.edu kreed@asu.edu. ; Institute of Human Origins, School of Human Evolution and Social Change, Arizona State University, Tempe, AZ 85287, USA. ; CNRS Geosciences Rennes, Campus de Beaulieu, 35042 Rennes, France. ; Berkeley Geochronology Center, 2455 Ridge Road, Berkeley, CA 94709, USA. ; Museum fur Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Invalidenstrasse 43, 10115 Berlin, Germany. ; Biology Program, Stockton University, 101 Vera King Farris Drive, Galloway, NJ 08205, USA. ; Human Evolution Research Center, University of California, Berkeley, 3101 Valley Life Sciences Building, Berkeley, CA, 94720-3160, USA. ; School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287, USA. ; Swedish Museum of Natural History, Department of Palaeobiology, Box 50007, SE-10405 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25739409" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Ecosystem ; Ethiopia ; Fossils ; *Geologic Sediments ; *Hominidae
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  • 29
    Publication Date: 2015-06-20
    Description: The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform "identification of direct RNA interacting proteins" (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors-including cohesins, condensins, topoisomerases, RNA helicases, chromatin remodelers, and modifiers-that synergistically repress Xi transcription. Inhibiting two or three interactors destabilizes silencing. Although Xist attracts some interactors, it repels architectural factors. Xist evicts cohesins from the Xi and directs an Xi-specific chromosome conformation. Upon deleting Xist, the Xi acquires the cohesin-binding and chromosomal architecture of the active X. Our study unveils many layers of Xi repression and demonstrates a central role for RNA in the topological organization of mammalian chromosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Minajigi, Anand -- Froberg, John E -- Wei, Chunyao -- Sunwoo, Hongjae -- Kesner, Barry -- Colognori, David -- Lessing, Derek -- Payer, Bernhard -- Boukhali, Myriam -- Haas, Wilhelm -- Lee, Jeannie T -- R01-DA-38695/DA/NIDA NIH HHS/ -- R03-MH97478/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 17;349(6245). pii: aab2276. doi: 10.1126/science.aab2276. Epub 2015 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA. ; Massachusetts General Hospital Cancer Center, Charlestown, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA, USA. ; Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA. lee@molbio.mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089354" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Animals ; Cell Cycle Proteins/*metabolism ; Cells, Cultured ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA-Binding Proteins/metabolism ; Embryonic Stem Cells/metabolism ; Fibroblasts/metabolism ; Gene Knockdown Techniques ; Gene Silencing ; Mice ; Multiprotein Complexes/metabolism ; Nucleic Acid Conformation ; Proteomics ; RNA Helicases/metabolism ; RNA, Long Noncoding/*metabolism ; X Chromosome/chemistry/genetics/*metabolism ; *X Chromosome Inactivation
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  • 30
    Publication Date: 2015-09-19
    Description: Prostate cancer is initially responsive to androgen deprivation, but the effectiveness of androgen receptor (AR) inhibitors in recurrent disease is variable. Biopsy of bone metastases is challenging; hence, sampling circulating tumor cells (CTCs) may reveal drug-resistance mechanisms. We established single-cell RNA-sequencing (RNA-Seq) profiles of 77 intact CTCs isolated from 13 patients (mean six CTCs per patient), by using microfluidic enrichment. Single CTCs from each individual display considerable heterogeneity, including expression of AR gene mutations and splicing variants. Retrospective analysis of CTCs from patients progressing under treatment with an AR inhibitor, compared with untreated cases, indicates activation of noncanonical Wnt signaling (P = 0.0064). Ectopic expression of Wnt5a in prostate cancer cells attenuates the antiproliferative effect of AR inhibition, whereas its suppression in drug-resistant cells restores partial sensitivity, a correlation also evident in an established mouse model. Thus, single-cell analysis of prostate CTCs reveals heterogeneity in signaling pathways that could contribute to treatment failure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miyamoto, David T -- Zheng, Yu -- Wittner, Ben S -- Lee, Richard J -- Zhu, Huili -- Broderick, Katherine T -- Desai, Rushil -- Fox, Douglas B -- Brannigan, Brian W -- Trautwein, Julie -- Arora, Kshitij S -- Desai, Niyati -- Dahl, Douglas M -- Sequist, Lecia V -- Smith, Matthew R -- Kapur, Ravi -- Wu, Chin-Lee -- Shioda, Toshi -- Ramaswamy, Sridhar -- Ting, David T -- Toner, Mehmet -- Maheswaran, Shyamala -- Haber, Daniel A -- 2R01CA129933/CA/NCI NIH HHS/ -- EB008047/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1351-6. doi: 10.1126/science.aab0917.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Urology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Center for Bioengineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. haber@helix.mgh.harvard.edu smaheswaran@mgh.harvard.edu. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. haber@helix.mgh.harvard.edu smaheswaran@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383955" target="_blank"〉PubMed〈/a〉
    Keywords: Androgen Antagonists/pharmacology/*therapeutic use ; Animals ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; Humans ; Male ; Mice ; Neoplastic Cells, Circulating/drug effects/*metabolism ; Phenylthiohydantoin/*analogs & derivatives/pharmacology/therapeutic use ; Prostate/drug effects/metabolism/pathology ; Prostatic Neoplasms/*drug therapy/*pathology ; Proto-Oncogene Proteins/genetics/metabolism ; RNA Splicing ; Receptors, Androgen/*genetics ; Sequence Analysis, RNA/methods ; Signal Transduction ; Single-Cell Analysis/methods ; Transcriptome ; Wnt Proteins/genetics/*metabolism ; Xenograft Model Antitumor Assays
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  • 31
    Publication Date: 2015-06-20
    Description: G protein-coupled receptors (GPCRs) relay diverse extracellular signals into cells by catalyzing nucleotide release from heterotrimeric G proteins, but the mechanism underlying this quintessential molecular signaling event has remained unclear. Here we use atomic-level simulations to elucidate the nucleotide-release mechanism. We find that the G protein alpha subunit Ras and helical domains-previously observed to separate widely upon receptor binding to expose the nucleotide-binding site-separate spontaneously and frequently even in the absence of a receptor. Domain separation is necessary but not sufficient for rapid nucleotide release. Rather, receptors catalyze nucleotide release by favoring an internal structural rearrangement of the Ras domain that weakens its nucleotide affinity. We use double electron-electron resonance spectroscopy and protein engineering to confirm predictions of our computationally determined mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dror, Ron O -- Mildorf, Thomas J -- Hilger, Daniel -- Manglik, Aashish -- Borhani, David W -- Arlow, Daniel H -- Philippsen, Ansgar -- Villanueva, Nicolas -- Yang, Zhongyu -- Lerch, Michael T -- Hubbell, Wayne L -- Kobilka, Brian K -- Sunahara, Roger K -- Shaw, David E -- P30EY00331/EY/NEI NIH HHS/ -- R01EY05216/EY/NEI NIH HHS/ -- R01GM083118/GM/NIGMS NIH HHS/ -- T32 GM008294/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 19;348(6241):1361-5. doi: 10.1126/science.aaa5264.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉D. E. Shaw Research, New York, NY 10036, USA. ron.dror@deshawresearch.com david.shaw@deshawresearch.com. ; D. E. Shaw Research, New York, NY 10036, USA. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. ; Jules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA. ; D. E. Shaw Research, New York, NY 10036, USA. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. ron.dror@deshawresearch.com david.shaw@deshawresearch.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089515" target="_blank"〉PubMed〈/a〉
    Keywords: GTP-Binding Protein alpha Subunits, Gi-Go/*chemistry ; GTP-Binding Protein alpha Subunits, Gs/*chemistry ; Guanine Nucleotide Exchange Factors/*chemistry ; Humans ; Models, Chemical ; Molecular Dynamics Simulation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/*chemistry ; Signal Transduction
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  • 32
    Publication Date: 2015-02-24
    Description: An important question in ecology is how mechanistic processes occurring among individuals drive large-scale patterns of community formation and change. Here we show that in two species of bluebirds, cycles of replacement of one by the other emerge as an indirect consequence of maternal influence on offspring behavior in response to local resource availability. Sampling across broad temporal and spatial scales, we found that western bluebirds, the more competitive species, bias the birth order of offspring by sex in a way that influences offspring aggression and dispersal, setting the stage for rapid increases in population density that ultimately result in the replacement of their sister species. Our results provide insight into how predictable community dynamics can occur despite the contingency of local behavioral interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duckworth, Renee A -- Belloni, Virginia -- Anderson, Samantha R -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):875-7. doi: 10.1126/science.1260154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. rad3@email.arizona.edu. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700519" target="_blank"〉PubMed〈/a〉
    Keywords: Androgens/analysis ; Animals ; *Biological Evolution ; Clutch Size ; *Competitive Behavior ; *Ecosystem ; Egg Yolk/chemistry ; Female ; Fires ; Male ; *Maternal Behavior ; Population Density ; Songbirds/*physiology ; United States
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  • 33
    Publication Date: 2015-08-22
    Description: Elucidating the signaling mechanism of strigolactones has been the key to controlling the devastating problem caused by the parasitic plant Striga hermonthica. To overcome the genetic intractability that has previously interfered with identification of the strigolactone receptor, we developed a fluorescence turn-on probe, Yoshimulactone Green (YLG), which activates strigolactone signaling and illuminates signal perception by the strigolactone receptors. Here we describe how strigolactones bind to and act via ShHTLs, the diverged family of alpha/beta hydrolase-fold proteins in Striga. Live imaging using YLGs revealed that a dynamic wavelike propagation of strigolactone perception wakes up Striga seeds. We conclude that ShHTLs function as the strigolactone receptors mediating seed germination in Striga. Our findings enable access to strigolactone receptors and observation of the regulatory dynamics for strigolactone signal transduction in Striga.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsuchiya, Yuichiro -- Yoshimura, Masahiko -- Sato, Yoshikatsu -- Kuwata, Keiko -- Toh, Shigeo -- Holbrook-Smith, Duncan -- Zhang, Hua -- McCourt, Peter -- Itami, Kenichiro -- Kinoshita, Toshinori -- Hagihara, Shinya -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):864-8. doi: 10.1126/science.aab3831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Department of Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto, Ontario M5S 3B2, Canada. yuichiro@itbm.nagoya-u.ac.jp hagi@itbm.nagoya-u.ac.jp. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Department of Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto, Ontario M5S 3B2, Canada. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Japan Science and Technology Agency-Exploratory Research for Advanced Technology, Itami Molecular Nanocarbon Project, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. yuichiro@itbm.nagoya-u.ac.jp hagi@itbm.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293962" target="_blank"〉PubMed〈/a〉
    Keywords: Fluoresceins/chemistry/metabolism ; Fluorescence ; Fluorescent Dyes/chemistry/metabolism ; *Germination ; Hydrolases/metabolism ; Hydrolysis ; Lactones/*metabolism ; Molecular Imaging/methods ; Molecular Sequence Data ; Plant Growth Regulators/*metabolism ; Plant Proteins/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Seeds/*growth & development/metabolism ; Signal Transduction ; Striga/*growth & development/metabolism
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  • 34
    Publication Date: 2015-01-17
    Description: Vegetation structure is a key determinant of ecosystems and ecosystem function, but paleoecological techniques to quantify it are lacking. We present a method for reconstructing leaf area index (LAI) based on light-dependent morphology of leaf epidermal cells and phytoliths derived from them. Using this proxy, we reconstruct LAI for the Cenozoic (49 million to 11 million years ago) of middle-latitude Patagonia. Our record shows that dense forests opened up by the late Eocene; open forests and shrubland habitats then fluctuated, with a brief middle-Miocene regreening period. Furthermore, endemic herbivorous mammals show accelerated tooth crown height evolution during open, yet relatively grass-free, shrubland habitat intervals. Our Patagonian LAI record provides a high-resolution, sensitive tool with which to dissect terrestrial ecosystem response to changing Southern Ocean conditions during the Cenozoic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dunn, Regan E -- Stromberg, Caroline A E -- Madden, Richard H -- Kohn, Matthew J -- Carlini, Alfredo A -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):258-61. doi: 10.1126/science.1260947.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Burke Museum of Natural History and Culture, University of Washington, Seattle, WA 98195, USA. dunnr@u.washington.edu. ; Department of Biology and Burke Museum of Natural History and Culture, University of Washington, Seattle, WA 98195, USA. ; Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA. ; Department of Geosciences, Boise State University, Boise, ID 83725, USA. ; Paleontologia de Vertebrados, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), La Plata, Argentina.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25593182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Cell Shape ; Cell Size ; *Climate Change ; Costa Rica ; *Ecosystem ; *Forests ; Fossils ; Grassland ; Mammals/anatomy & histology ; Plant Epidermis/cytology ; *Plant Leaves/anatomy & histology ; *Plants ; South America ; Time ; Tooth Crown/anatomy & histology
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  • 35
    Publication Date: 2015-01-31
    Description: The mechanistic basis of eukaryotic circadian oscillators in model systems as diverse as Neurospora, Drosophila, and mammalian cells is thought to be a transcription-and-translation-based negative feedback loop, wherein progressive and controlled phosphorylation of one or more negative elements ultimately elicits their own proteasome-mediated degradation, thereby releasing negative feedback and determining circadian period length. The Neurospora crassa circadian negative element FREQUENCY (FRQ) exemplifies such proteins; it is progressively phosphorylated at more than 100 sites, and strains bearing alleles of frq with anomalous phosphorylation display abnormal stability of FRQ that is well correlated with altered periods or apparent arrhythmicity. Unexpectedly, we unveiled normal circadian oscillations that reflect the allelic state of frq but that persist in the absence of typical degradation of FRQ. This manifest uncoupling of negative element turnover from circadian period length determination is not consistent with the consensus eukaryotic circadian model.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432837/" 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/PMC4432837/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larrondo, Luis F -- Olivares-Yanez, Consuelo -- Baker, Christopher L -- Loros, Jennifer J -- Dunlap, Jay C -- P01 GM68087/GM/NIGMS NIH HHS/ -- R01 GM034985/GM/NIGMS NIH HHS/ -- R01 GM083336/GM/NIGMS NIH HHS/ -- R01 GM34985/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):1257277. doi: 10.1126/science.1257277.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. jay.c.dunlap@dartmouth.edu llarrondo@bio.puc.cl. ; Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. ; Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. ; Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. ; Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. jay.c.dunlap@dartmouth.edu llarrondo@bio.puc.cl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635104" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/analogs & derivatives/pharmacology ; Alleles ; *Circadian Clocks ; *Circadian Rhythm ; Feedback, Physiological ; Fungal Proteins/biosynthesis/*genetics/*metabolism ; Half-Life ; Neurospora crassa/*physiology ; Phosphorylation ; Proteasome Endopeptidase Complex/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Stability ; Proteolysis ; Signal Transduction
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 36
    Publication Date: 2015-05-23
    Description: Viruses influence ecosystems by modulating microbial population size, diversity, metabolic outputs, and gene flow. Here, we use quantitative double-stranded DNA (dsDNA) viral-fraction metagenomes (viromes) and whole viral community morphological data sets from 43 Tara Oceans expedition samples to assess viral community patterns and structure in the upper ocean. Protein cluster cataloging defined pelagic upper-ocean viral community pan and core gene sets and suggested that this sequence space is well-sampled. Analyses of viral protein clusters, populations, and morphology revealed biogeographic patterns whereby viral communities were passively transported on oceanic currents and locally structured by environmental conditions that affect host community structure. Together, these investigations establish a global ocean dsDNA viromic data set with analyses supporting the seed-bank hypothesis to explain how oceanic viral communities maintain high local diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brum, Jennifer R -- Ignacio-Espinoza, J Cesar -- Roux, Simon -- Doulcier, Guilhem -- Acinas, Silvia G -- Alberti, Adriana -- Chaffron, Samuel -- Cruaud, Corinne -- de Vargas, Colomban -- Gasol, Josep M -- Gorsky, Gabriel -- Gregory, Ann C -- Guidi, Lionel -- Hingamp, Pascal -- Iudicone, Daniele -- Not, Fabrice -- Ogata, Hiroyuki -- Pesant, Stephane -- Poulos, Bonnie T -- Schwenck, Sarah M -- Speich, Sabrina -- Dimier, Celine -- Kandels-Lewis, Stefanie -- Picheral, Marc -- Searson, Sarah -- Tara Oceans Coordinators -- Bork, Peer -- Bowler, Chris -- Sunagawa, Shinichi -- Wincker, Patrick -- Karsenti, Eric -- Sullivan, Matthew B -- New York, N.Y. -- Science. 2015 May 22;348(6237):1261498. doi: 10.1126/science.1261498.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. ; Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Environmental and Evolutionary Genomics Section, Institut de Biologie de l'Ecole Normale Superieure (IBENS), CNRS, UMR8197, INSERM U1024, 75230 Paris, France. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta 37-49, Barcelona, E08003, Spain. ; Genoscope, Commissariat a l'Energie Atomique (CEA)-Institut de Genomique, 2 rue Gaston Cremieux, 91057 Evry, France. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie, Universite Paris 06, and UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; CNRS, UMR 7093, Laboratoire d'oceanographie de Villefranche (LOV), Observatoire Oceanologique, 06230 Villefranche-sur-mer, France. Sorbonne Universites, Uiversite Pierre et Marie Curie, Universite Paris 06, UMR 7093, Laboratoire d'oceanographie de Villefranche (LOV), Observatoire Oceanologique, 06230 Villefranche-sur-mer, France. ; Soil, Water, and Environmental Science, University of Arizona, Tucson, AZ 85721, USA. ; Aix Marseille Universite, CNRS IGS UMR 7256, 13288 Marseille, France. ; Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy. ; Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0001, Japan. ; PANGAEA, Data Publisher for Earth and Environmental Science, University of Bremen, 28359 Bremen, Germany. MARUM, Center for Marine Environmental Sciences, University of Bremen, 28359 Bremen, Germany. ; Laboratoire de Physique des Oceans, Institut Universitaire Europeen de la Mer, Universite de Bretagne Occidentale (UBO-IUEM), Place Copernic, 29820 Plouzane, France. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie, Universite Paris 06, and UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Institut de Biologie de l'Ecole Normale Superieure (IBENS), and INSERM U1024, and CNRS UMR 8197, Paris, 75005, France. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Directors' Research, European Molecular Biology Laboratory Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Max-Delbruck-Centre for Molecular Medicine, 13092 Berlin, Germany. ; Institut de Biologie de l'Ecole Normale Superieure (IBENS), and INSERM U1024, and CNRS UMR 8197, Paris, 75005, France. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Genoscope, Commissariat a l'Energie Atomique (CEA)-Institut de Genomique, 2 rue Gaston Cremieux, 91057 Evry, France. CNRS, UMR 8030, CP5706, 91057 Evry, France. Universite d'Evry, UMR 8030, CP5706, 91057 Evry, France. ; Institut de Biologie de l'Ecole Normale Superieure (IBENS), and INSERM U1024, and CNRS UMR 8197, Paris, 75005, France. Directors' Research, European Molecular Biology Laboratory Meyerhofstrasse 1, 69117 Heidelberg, Germany. mbsulli@gmail.com karsenti@embl.de. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA. Soil, Water, and Environmental Science, University of Arizona, Tucson, AZ 85721, USA. mbsulli@gmail.com karsenti@embl.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999515" target="_blank"〉PubMed〈/a〉
    Keywords: Biodiversity ; DNA, Viral/genetics ; Ecological and Environmental Processes ; *Ecosystem ; Metagenome/genetics ; Microbiota/genetics ; Oceans and Seas ; Plankton/*classification/genetics ; Seawater/*virology ; Viral Proteins/genetics ; Viruses/*classification/genetics
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  • 37
    Publication Date: 2015-02-28
    Description: Ebola virus causes sporadic outbreaks of lethal hemorrhagic fever in humans, but there is no currently approved therapy. Cells take up Ebola virus by macropinocytosis, followed by trafficking through endosomal vesicles. However, few factors controlling endosomal virus movement are known. Here we find that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small-molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule that we tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. Therefore, TPC proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550587/" 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/PMC4550587/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakurai, Yasuteru -- Kolokoltsov, Andrey A -- Chen, Cheng-Chang -- Tidwell, Michael W -- Bauta, William E -- Klugbauer, Norbert -- Grimm, Christian -- Wahl-Schott, Christian -- Biel, Martin -- Davey, Robert A -- R01 AI063513/AI/NIAID NIH HHS/ -- R01AI063513/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):995-8. doi: 10.1126/science.1258758.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Texas Biomedical Research Institute, San Antonio, TX, USA. ; The University of Texas Medical Branch, Galveston, TX, USA. ; Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universitat Munchen, Munich, Germany. ; Southwest Research Institute, San Antonio, TX, USA. ; Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-Universitat Freiburg, Freiburg, Germany. ; Texas Biomedical Research Institute, San Antonio, TX, USA. rdavey@txbiomed.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25722412" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/*pharmacology/therapeutic use ; BALB 3T3 Cells ; Benzylisoquinolines/pharmacology/therapeutic use ; Calcium Channel Blockers/*pharmacology/therapeutic use ; Calcium Channels/genetics/*physiology ; Ebolavirus/drug effects/*physiology ; Female ; Gene Knockout Techniques ; HeLa Cells ; Hemorrhagic Fever, Ebola/drug therapy/*therapy/virology ; Humans ; Macrophages/drug effects/virology ; Mice ; *Molecular Targeted Therapy ; NADP/analogs & derivatives/metabolism ; RNA Interference ; Signal Transduction ; Verapamil/pharmacology/therapeutic use ; Virus Internalization/*drug effects
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  • 38
    Publication Date: 2015-05-09
    Description: Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, which precludes genetic manipulation in the cell in which the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell-based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465434/" 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/PMC4465434/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Egan, Elizabeth S -- Jiang, Rays H Y -- Moechtar, Mischka A -- Barteneva, Natasha S -- Weekes, Michael P -- Nobre, Luis V -- Gygi, Steven P -- Paulo, Joao A -- Frantzreb, Charles -- Tani, Yoshihiko -- Takahashi, Junko -- Watanabe, Seishi -- Goldberg, Jonathan -- Paul, Aditya S -- Brugnara, Carlo -- Root, David E -- Wiegand, Roger C -- Doench, John G -- Duraisingh, Manoj T -- 100140/Wellcome Trust/United Kingdom -- 1K08AI103034-01A1/AI/NIAID NIH HHS/ -- K01 DK098285/DK/NIDDK NIH HHS/ -- K01DK098285/DK/NIDDK NIH HHS/ -- K08 AI103034/AI/NIAID NIH HHS/ -- K12-HD000850/HD/NICHD NIH HHS/ -- R01AI091787/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 May 8;348(6235):711-4. doi: 10.1126/science.aaa3526.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA. ; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Department of Global Health and Center for Drug Discovery and Innovation, University of South Florida, Tampa, FL, USA. ; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. ; Department of Pediatrics, Harvard Medical School and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. ; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. ; Department of Cell Biology, Harvard Medical School, Boston, MA, USA. ; Japanese Red Cross Kinki Block Blood Center, Osaka, Japan. ; Japanese Red Cross Kyushu Block Blood Center, Fukuoka, Japan. ; Department of Laboratory Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. ; The Broad Institute of Harvard and Massachussetts Insititute of Technology, Cambridge, MA, USAA. ; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. The Broad Institute of Harvard and Massachussetts Insititute of Technology, Cambridge, MA, USAA. mduraisi@hsph.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25954012" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD44/genetics ; Antigens, CD55/*genetics ; Cell Differentiation/genetics ; Cells, Cultured ; Erythrocytes/cytology/metabolism/*parasitology ; Genetic Testing ; Hematopoietic Stem Cells/cytology ; Host-Parasite Interactions/*genetics ; Humans ; Malaria, Falciparum/*genetics/*parasitology ; Plasmodium falciparum/*pathogenicity ; RNA, Small Interfering/genetics
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  • 39
    Publication Date: 2015-09-01
    Description: Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell-derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and beta-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618316/" 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/PMC4618316/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hinson, John T -- Chopra, Anant -- Nafissi, Navid -- Polacheck, William J -- Benson, Craig C -- Swist, Sandra -- Gorham, Joshua -- Yang, Luhan -- Schafer, Sebastian -- Sheng, Calvin C -- Haghighi, Alireza -- Homsy, Jason -- Hubner, Norbert -- Church, George -- Cook, Stuart A -- Linke, Wolfgang A -- Chen, Christopher S -- Seidman, J G -- Seidman, Christine E -- EB017103/EB/NIBIB NIH HHS/ -- HG005550/HG/NHGRI NIH HHS/ -- HL007374/HL/NHLBI NIH HHS/ -- HL115553/HL/NHLBI NIH HHS/ -- HL125807/HL/NHLBI NIH HHS/ -- K08 HL125807/HL/NHLBI NIH HHS/ -- T32 HL007208/HL/NHLBI NIH HHS/ -- Department of Health/United Kingdom -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):982-6. doi: 10.1126/science.aaa5458.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. jthinson@partners.org cseidman@genetics.med.harvard.edu. ; Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA. The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA. ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ; Department of Cardiovascular Physiology, Ruhr University Bochum, MA 3/56 D-44780, Bochum, Germany. ; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Cardiovascular and Metabolic Sciences, Max Delbruck Center for Molecular Medicine, Berlin, Germany. ; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. ; Cardiovascular and Metabolic Sciences, Max Delbruck Center for Molecular Medicine, Berlin, Germany. DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany. ; National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease at Royal Brompton and Harefield National Health Service (NHS) Foundation Trust, Imperial College London, London, UK. National Heart Centre and Duke-National University, Singapore, Singapore. ; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. jthinson@partners.org cseidman@genetics.med.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315439" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-Agonists/pharmacology ; Cardiomyopathy, Dilated/*genetics/pathology/*physiopathology ; Cells, Cultured ; Connectin/chemistry/*genetics/*physiology ; Heart Rate ; Humans ; Induced Pluripotent Stem Cells/*physiology ; Isoproterenol/pharmacology ; Mutant Proteins/chemistry/physiology ; *Mutation, Missense ; Myocardial Contraction ; Myocytes, Cardiac/*physiology ; RNA/genetics/metabolism ; Sarcomeres/*physiology/ultrastructure ; Sequence Analysis, RNA ; Signal Transduction ; Stress, Physiological
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  • 40
    Publication Date: 2015-06-13
    Description: Cell division progresses to anaphase only after all chromosomes are connected to spindle microtubules through kinetochores and the spindle assembly checkpoint (SAC) is satisfied. We show that the amino-terminal localization module of the SAC protein kinase MPS1 (monopolar spindle 1) directly interacts with the HEC1 (highly expressed in cancer 1) calponin homology domain in the NDC80 (nuclear division cycle 80) kinetochore complex in vitro, in a phosphorylation-dependent manner. Microtubule polymers disrupted this interaction. In cells, MPS1 binding to kinetochores or to ectopic NDC80 complexes was prevented by end-on microtubule attachment, independent of known kinetochore protein-removal mechanisms. Competition for kinetochore binding between SAC proteins and microtubules provides a direct and perhaps evolutionarily conserved way to detect a properly organized spindle ready for cell division.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hiruma, Yoshitaka -- Sacristan, Carlos -- Pachis, Spyridon T -- Adamopoulos, Athanassios -- Kuijt, Timo -- Ubbink, Marcellus -- von Castelmur, Eleonore -- Perrakis, Anastassis -- Kops, Geert J P L -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1264-7. doi: 10.1126/science.aaa4055. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. ; Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. ; Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. ; Leiden Institute of Chemistry, Leiden University, Post Office Box 9502, 2300 RA Leiden, Netherlands. ; Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. g.j.p.l.kops@umcutrecht.nl a.perrakis@nki.nl. ; Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. g.j.p.l.kops@umcutrecht.nl a.perrakis@nki.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068855" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; Binding, Competitive ; Calcium-Binding Proteins/genetics/metabolism ; *Cell Cycle Checkpoints ; Cell Cycle Proteins/*metabolism ; HeLa Cells ; Humans ; Kinetochores/*metabolism ; Microfilament Proteins/genetics/metabolism ; Microtubules/*metabolism ; Nuclear Proteins/chemistry/*metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/*metabolism ; Protein-Tyrosine Kinases/*metabolism ; Signal Transduction ; Spindle Apparatus/*metabolism
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  • 41
    Publication Date: 2015-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naeem, S -- Ingram, J C -- Varga, A -- Agardy, T -- Barten, P -- Bennett, G -- Bloomgarden, E -- Bremer, L L -- Burkill, P -- Cattau, M -- Ching, C -- Colby, M -- Cook, D C -- Costanza, R -- DeClerck, F -- Freund, C -- Gartner, T -- Goldman-Benner, R -- Gunderson, J -- Jarrett, D -- Kinzig, A P -- Kiss, A -- Koontz, A -- Kumar, P -- Lasky, J R -- Masozera, M -- Meyers, D -- Milano, F -- Naughton-Treves, L -- Nichols, E -- Olander, L -- Olmsted, P -- Perge, E -- Perrings, C -- Polasky, S -- Potent, J -- Prager, C -- Quetier, F -- Redford, K -- Saterson, K -- Thoumi, G -- Vargas, M T -- Vickerman, S -- Weisser, W -- Wilkie, D -- Wunder, S -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1206-7. doi: 10.1126/science.aaa1403. Epub 2015 Mar 12.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766222" target="_blank"〉PubMed〈/a〉
    Keywords: *Conservation of Natural Resources/economics ; *Ecosystem ; *Environment ; Guidelines as Topic ; Policy
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hochberg, Yael V -- Fehder, Daniel C -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1202-3. doi: 10.1126/science.aab3351.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rice University, Houston, TX 77251, USA. Massachusetts Institute of Technology, Cambridge, MA 02139, USA. National Bureau of Economic Research, Cambridge, MA 02138, USA. hochberg@rice.edu. ; Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068829" target="_blank"〉PubMed〈/a〉
    Keywords: *Ecosystem ; *Entrepreneurship ; Software
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  • 43
    Publication Date: 2015-10-03
    Description: Body-size constancy and symmetry are signs of developmental stability. Yet, it is unclear exactly how developing animals buffer size variation. Drosophila insulin-like peptide Dilp8 is responsive to growth perturbations and controls homeostatic mechanisms that coordinately adjust growth and maturation to maintain size within the normal range. Here we show that Lgr3 is a Dilp8 receptor. Through the use of functional and adenosine 3',5'-monophosphate assays, we defined a pair of Lgr3 neurons that mediate homeostatic regulation. These neurons have extensive axonal arborizations, and genetic and green fluorescent protein reconstitution across synaptic partners show that these neurons connect with the insulin-producing cells and prothoracicotropic hormone-producing neurons to attenuate growth and maturation. This previously unrecognized circuit suggests how growth and maturation rate are matched and co-regulated according to Dilp8 signals to stabilize organismal size.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vallejo, Diana M -- Juarez-Carreno, Sergio -- Bolivar, Jorge -- Morante, Javier -- Dominguez, Maria -- OD010949-10/OD/NIH HHS/ -- P40OD018537/OD/NIH HHS/ -- R01-GM084947/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):aac6767. doi: 10.1126/science.aac6767. Epub 2015 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas and Universidad Miguel Hernandez, Campus de Sant Joan, Apartado 18, 03550 Sant Joan, Alicante, Spain. ; Departamento de Biomedicina, Biotecnologia y Salud Publica, Facultad de Ciencias, Universidad de Cadiz, Poligono Rio San Pedro s/n, 11510 Puerto Real, Spain. ; Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas and Universidad Miguel Hernandez, Campus de Sant Joan, Apartado 18, 03550 Sant Joan, Alicante, Spain. m.dominguez@umh.es j.morante@umh.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26429885" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Monophosphate/metabolism ; Animals ; Body Size ; Brain/cytology/*growth & development/metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*growth & development/metabolism ; Homeostasis ; Insect Hormones/genetics/metabolism ; Insulin/*metabolism ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; Nerve Net/cytology/metabolism ; Neurons/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Receptors, Peptide/genetics/*metabolism ; Signal Transduction ; Synapses/metabolism
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  • 44
    Publication Date: 2015-11-21
    Description: Stabilization of the hypoxia-inducible factor 1 (HIF-1) increases life span and health span in nematodes through an unknown mechanism. We report that neuronal stabilization of HIF-1 mediates these effects in Caenorhabditis elegans through a cell nonautonomous signal to the intestine, which results in activation of the xenobiotic detoxification enzyme flavin-containing monooxygenase-2 (FMO-2). This prolongevity signal requires the serotonin biosynthetic enzyme TPH-1 in neurons and the serotonin receptor SER-7 in the intestine. Intestinal FMO-2 is also activated by dietary restriction (DR) and is necessary for DR-mediated life-span extension, which suggests that this enzyme represents a point of convergence for two distinct longevity pathways. FMOs are conserved in eukaryotes and induced by multiple life span-extending interventions in mice, which suggests that these enzymes may play a critical role in promoting health and longevity across phyla.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leiser, Scott F -- Miller, Hillary -- Rossner, Ryan -- Fletcher, Marissa -- Leonard, Alison -- Primitivo, Melissa -- Rintala, Nicholas -- Ramos, Fresnida J -- Miller, Dana L -- Kaeberlein, Matt -- P30AG013280/AG/NIA NIH HHS/ -- R00AGA0033050/PHS HHS/ -- R01AG038518/AG/NIA NIH HHS/ -- T32AG000057/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Dec 11;350(6266):1375-8. doi: 10.1126/science.aac9257. Epub 2015 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Washington, Seattle, WA 98195, USA. ; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. ; Department of Pathology, University of Washington, Seattle, WA 98195, USA. kaeber@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586189" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Caenorhabditis elegans/genetics/metabolism/*physiology ; Caenorhabditis elegans Proteins/chemistry/genetics/metabolism/*physiology ; Diet ; Intestines/*enzymology ; Longevity/genetics/*physiology ; Mice ; Neurons/*metabolism ; Oxygenases/genetics/*physiology ; Protein Stability ; RNA Interference ; Receptors, Serotonin/metabolism ; Signal Transduction ; Transcription Factors/chemistry/*metabolism ; Tryptophan Hydroxylase/metabolism
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  • 45
    Publication Date: 2015-06-06
    Description: Aneuploidy in human eggs is the leading cause of pregnancy loss and several genetic disorders such as Down syndrome. Most aneuploidy results from chromosome segregation errors during the meiotic divisions of an oocyte, the egg's progenitor cell. The basis for particularly error-prone chromosome segregation in human oocytes is not known. We analyzed meiosis in more than 100 live human oocytes and identified an error-prone chromosome-mediated spindle assembly mechanism as a major contributor to chromosome segregation defects. Human oocytes assembled a meiotic spindle independently of either centrosomes or other microtubule organizing centers. Instead, spindle assembly was mediated by chromosomes and the small guanosine triphosphatase Ran in a process requiring ~16 hours. This unusually long spindle assembly period was marked by intrinsic spindle instability and abnormal kinetochore-microtubule attachments, which favor chromosome segregation errors and provide a possible explanation for high rates of aneuploidy in human eggs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477045/" 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/PMC4477045/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holubcova, Zuzana -- Blayney, Martyn -- Elder, Kay -- Schuh, Melina -- MC_U105192711/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1143-7. doi: 10.1126/science.aaa9529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK. ; Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. mschuh@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26045437" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; *Aneuploidy ; Animals ; Cells, Cultured ; *Chromosome Segregation ; Female ; Green Fluorescent Proteins/genetics/metabolism ; Humans ; Kinetochores/metabolism ; *Meiosis ; Mice ; Microtubule-Associated Proteins/genetics/metabolism ; Microtubule-Organizing Center/metabolism ; Oocytes/*pathology ; Spindle Apparatus/*metabolism ; ran GTP-Binding Protein/metabolism
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  • 46
    Publication Date: 2015-09-05
    Description: Growing up on a dairy farm protects children from allergy, hay fever, and asthma. A mechanism linking exposure to this endotoxin (bacterial lipopolysaccharide)-rich environment with protection has remained elusive. Here we show that chronic exposure to low-dose endotoxin or farm dust protects mice from developing house dust mite (HDM)-induced asthma. Endotoxin reduced epithelial cell cytokines that activate dendritic cells (DCs), thus suppressing type 2 immunity to HDMs. Loss of the ubiquitin-modifying enzyme A20 in lung epithelium abolished the protective effect. A single-nucleotide polymorphism in the gene encoding A20 was associated with allergy and asthma risk in children growing up on farms. Thus, the farming environment protects from allergy by modifying the communication between barrier epithelial cells and DCs through A20 induction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schuijs, Martijn J -- Willart, Monique A -- Vergote, Karl -- Gras, Delphine -- Deswarte, Kim -- Ege, Markus J -- Madeira, Filipe Branco -- Beyaert, Rudi -- van Loo, Geert -- Bracher, Franz -- von Mutius, Erika -- Chanez, Pascal -- Lambrecht, Bart N -- Hammad, Hamida -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1106-10. doi: 10.1126/science.aac6623.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium. ; Department of Respiratory Medicine, Assistance Publique Hopitaux de Marseille, UMR INSERM U1067 CNRS 7333, Aix Marseille University, Marseille, France. ; Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universitat, Munich, Germany. ; Unit of Molecular Signal Transduction, VIB Inflammation Research Center, Ghent, Belgium. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. ; Center for Drug Research, Department of Pharmacy, Ludwig Maximilians University, Butenandtstrasse 5-13, D-81377 Munich, Germany. ; Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium. Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, Netherlands. hamida.hammad@ugent.be bart.lambrecht@ugent.be. ; Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium. hamida.hammad@ugent.be bart.lambrecht@ugent.be.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26339029" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Asthma/immunology/prevention & control ; Cells, Cultured ; Child ; DNA-Binding Proteins/*biosynthesis ; Dairying ; Dendritic Cells/immunology ; Dust/*immunology ; Female ; Humans ; Hygiene Hypothesis ; Hypersensitivity/enzymology/immunology/*prevention & control ; Inhalation Exposure ; Intracellular Signaling Peptides and Proteins/*biosynthesis ; Lipopolysaccharides/*immunology ; Lung/*enzymology/immunology ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins/*biosynthesis ; Pyroglyphidae/*immunology ; Respiratory Mucosa/*enzymology/immunology
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  • 47
    Publication Date: 2015-01-03
    Description: Lysosomes are crucial cellular organelles for human health that function in digestion and recycling of extracellular and intracellular macromolecules. We describe a signaling role for lysosomes that affects aging. In the worm Caenorhabditis elegans, the lysosomal acid lipase LIPL-4 triggered nuclear translocalization of a lysosomal lipid chaperone LBP-8, which promoted longevity by activating the nuclear hormone receptors NHR-49 and NHR-80. We used high-throughput metabolomic analysis to identify several lipids in which abundance was increased in worms constitutively overexpressing LIPL-4. Among them, oleoylethanolamide directly bound to LBP-8 and NHR-80 proteins, activated transcription of target genes of NHR-49 and NHR-80, and promoted longevity in C. elegans. These findings reveal a lysosome-to-nucleus signaling pathway that promotes longevity and suggest a function of lysosomes as signaling organelles in metazoans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425353/" 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/PMC4425353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Folick, Andrew -- Oakley, Holly D -- Yu, Yong -- Armstrong, Eric H -- Kumari, Manju -- Sanor, Lucas -- Moore, David D -- Ortlund, Eric A -- Zechner, Rudolf -- Wang, Meng C -- F30 AG046043/AG/NIA NIH HHS/ -- F30AG046043/AG/NIA NIH HHS/ -- R00 AG034988/AG/NIA NIH HHS/ -- R00AG034988/AG/NIA NIH HHS/ -- R01 AG045183/AG/NIA NIH HHS/ -- R01 DK095750/DK/NIDDK NIH HHS/ -- R01AG045183/AG/NIA NIH HHS/ -- R01DK095750/DK/NIDDK NIH HHS/ -- T32 GM008602/GM/NIGMS NIH HHS/ -- T32GM008602/GM/NIGMS NIH HHS/ -- T32HD055200/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):83-6. doi: 10.1126/science.1258857.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. ; Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. ; Department of Biochemistry, Discovery and Developmental Therapeutics, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA. ; Institute of Molecular Biosciences, University of Graz, Graz, A-8010, Austria. ; Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. ; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. ; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. wmeng@bcm.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554789" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Nucleus/metabolism ; Lipase/metabolism ; Lipid Metabolism ; Longevity/genetics/*physiology ; Lysosomes/*metabolism ; Molecular Chaperones/genetics/*metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Signal Transduction
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  • 48
    Publication Date: 2015-09-01
    Description: A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types-an "activator" strain and a "repressor" strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597888/" 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/PMC4597888/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Ye -- Kim, Jae Kyoung -- Hirning, Andrew J -- Josic, Kresimir -- Bennett, Matthew R -- R01 GM104974/GM/NIGMS NIH HHS/ -- R01GM104974/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):986-9. doi: 10.1126/science.aaa3794.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biosciences, Rice University, Houston, TX 77005, USA. ; Department of Mathematical Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea. Mathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210, USA. ; Department of Mathematics, University of Houston, Houston, TX 77204, USA. Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA. ; Department of Biosciences, Rice University, Houston, TX 77005, USA. Institute of Biosciences and Bioengineering, Rice University, Houston, TX 77005, USA. matthew.bennett@rice.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315440" target="_blank"〉PubMed〈/a〉
    Keywords: 4-Butyrolactone/analogs & derivatives/metabolism ; Escherichia coli/*genetics/*physiology ; Escherichia coli Proteins/genetics/metabolism ; Feedback, Physiological ; *Gene Expression Regulation, Bacterial ; *Gene Regulatory Networks ; Genetic Engineering ; Lab-On-A-Chip Devices ; Microbial Consortia/*genetics/*physiology ; Microbial Interactions ; Models, Biological ; Promoter Regions, Genetic ; Quorum Sensing ; Signal Transduction ; Synthetic Biology ; Transcription, Genetic
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  • 49
    Publication Date: 2015-08-08
    Description: Cytoplasmic aggregation of TDP-43, accompanied by its nuclear clearance, is a key common pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). However, a limited understanding of this RNA-binding protein (RBP) impedes the clarification of pathogenic mechanisms underlying TDP-43 proteinopathy. In contrast to RBPs that regulate splicing of conserved exons, we found that TDP-43 repressed the splicing of nonconserved cryptic exons, maintaining intron integrity. When TDP-43 was depleted from mouse embryonic stem cells, these cryptic exons were spliced into messenger RNAs, often disrupting their translation and promoting nonsense-mediated decay. Moreover, enforced repression of cryptic exons prevented cell death in TDP-43-deficient cells. Furthermore, repression of cryptic exons was impaired in ALS-FTD cases, suggesting that this splicing defect could potentially underlie TDP-43 proteinopathy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ling, Jonathan P -- Pletnikova, Olga -- Troncoso, Juan C -- Wong, Philip C -- P50AG05146/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):650-5. doi: 10.1126/science.aab0983.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. wong@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250685" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/*genetics ; Animals ; Base Sequence ; Cells, Cultured ; Cysteine Endopeptidases/genetics ; DNA-Binding Proteins/genetics/*physiology ; Embryonic Stem Cells ; Exons/*genetics ; Frontotemporal Dementia/*genetics ; Gene Knockout Techniques ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Protein Isoforms/genetics ; *RNA Splicing ; RNA Stability ; RNA, Messenger/metabolism ; Sequence Analysis, DNA
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  • 50
    Publication Date: 2015-01-09
    Description: The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine with a high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295826/" 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/PMC4295826/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Shuyu -- Tsun, Zhi-Yang -- Wolfson, Rachel L -- Shen, Kuang -- Wyant, Gregory A -- Plovanich, Molly E -- Yuan, Elizabeth D -- Jones, Tony D -- Chantranupong, Lynne -- Comb, William -- Wang, Tim -- Bar-Peled, Liron -- Zoncu, Roberto -- Straub, Christoph -- Kim, Choah -- Park, Jiwon -- Sabatini, Bernardo L -- Sabatini, David M -- AI47389/AI/NIAID NIH HHS/ -- F30 CA180754/CA/NCI NIH HHS/ -- F31 AG044064/AG/NIA NIH HHS/ -- F31 CA180271/CA/NCI NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R37 AI047389/AI/NIAID NIH HHS/ -- T32 GM007287/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):188-94. doi: 10.1126/science.1257132. Epub 2015 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Harvard Medical School, 260 Longwood Avenue, Boston, MA 02115, USA. ; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. ; Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. sabatini@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25567906" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Transport Systems/chemistry/genetics/*metabolism ; Arginine/deficiency/*metabolism ; HEK293 Cells ; Humans ; Lysosomes/*enzymology ; Molecular Sequence Data ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes/*metabolism ; Protein Structure, Tertiary ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism
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  • 51
    Publication Date: 2015-02-01
    Description: During virus infection, the adaptor proteins MAVS and STING transduce signals from the cytosolic nucleic acid sensors RIG-I and cGAS, respectively, to induce type I interferons (IFNs) and other antiviral molecules. Here we show that MAVS and STING harbor two conserved serine and threonine clusters that are phosphorylated by the kinases IKK and/or TBK1 in response to stimulation. Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. We further show that TRIF, an adaptor protein in Toll-like receptor signaling, activates IRF3 through a similar phosphorylation-dependent mechanism. These results reveal that phosphorylation of innate adaptor proteins is an essential and conserved mechanism that selectively recruits IRF3 to activate the type I IFN pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Siqi -- Cai, Xin -- Wu, Jiaxi -- Cong, Qian -- Chen, Xiang -- Li, Tuo -- Du, Fenghe -- Ren, Junyao -- Wu, You-Tong -- Grishin, Nick V -- Chen, Zhijian J -- AI-93967/AI/NIAID NIH HHS/ -- GM-094575/GM/NIGMS NIH HHS/ -- GM-63692/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):aaa2630. doi: 10.1126/science.aaa2630. Epub 2015 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. ; Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. ; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. Howard Hughes Medical Institute (HHMI), University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. ; Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. Howard Hughes Medical Institute (HHMI), University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. ; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. Howard Hughes Medical Institute (HHMI), University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. zhijian.chen@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25636800" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/chemistry/*metabolism ; Adaptor Proteins, Vesicular Transport/chemistry/*metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Humans ; I-kappa B Kinase/metabolism ; Interferon Regulatory Factor-3/chemistry/*metabolism ; Interferon-alpha/biosynthesis ; Interferon-beta/biosynthesis ; Membrane Proteins/chemistry/*metabolism ; Mice ; Molecular Sequence Data ; Phosphorylation ; Protein Binding ; Protein Multimerization ; Protein-Serine-Threonine Kinases/metabolism ; Recombinant Proteins/metabolism ; Sendai virus/physiology ; Serine/metabolism ; Signal Transduction ; Ubiquitination ; Vesiculovirus/physiology
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  • 52
    Publication Date: 2015-07-18
    Description: Secretion of the cytokine interleukin-1beta (IL-1beta) by macrophages, a major driver of pathogenesis in atherosclerosis, requires two steps: Priming signals promote transcription of immature IL-1beta, and then endogenous "danger" signals activate innate immune signaling complexes called inflammasomes to process IL-1beta for secretion. Although cholesterol crystals are known to act as danger signals in atherosclerosis, what primes IL-1beta transcription remains elusive. Using a murine model of atherosclerosis, we found that cholesterol crystals acted both as priming and danger signals for IL-1beta production. Cholesterol crystals triggered neutrophils to release neutrophil extracellular traps (NETs). NETs primed macrophages for cytokine release, activating T helper 17 (TH17) cells that amplify immune cell recruitment in atherosclerotic plaques. Therefore, danger signals may drive sterile inflammation, such as that seen in atherosclerosis, through their interactions with neutrophils.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warnatsch, Annika -- Ioannou, Marianna -- Wang, Qian -- Papayannopoulos, Venizelos -- MC_UP_1202/13/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):316-20. doi: 10.1126/science.aaa8064. Epub 2015 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UK. ; Mill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UK. veni.p@crick.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26185250" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apolipoproteins E/genetics ; Atherosclerosis/*immunology ; Cells, Cultured ; Cholesterol/chemistry/immunology ; Disease Models, Animal ; Extracellular Traps/*immunology ; Humans ; Inflammasomes/immunology ; Inflammation/immunology ; Interleukin-1beta/*biosynthesis/genetics ; Macrophages/*immunology ; Mice ; Mice, Mutant Strains ; Neutrophils/*immunology ; Signal Transduction ; Th17 Cells/immunology ; Transcription, Genetic
    Print ISSN: 0036-8075
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  • 53
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garber, Ken -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):129. doi: 10.1126/science.349.6244.129.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160924" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Oxidoreductases/chemistry/metabolism ; Collagen/metabolism ; Copper/*metabolism ; Humans ; Melanoma/drug therapy/pathology ; Neoplasms/*drug therapy/pathology ; Proto-Oncogene Proteins B-raf/*antagonists & inhibitors/genetics ; Signal Transduction ; Skin Diseases/drug therapy/pathology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 54
    Publication Date: 2015-03-15
    Description: Rgs2, a regulator of G proteins, lowers blood pressure by decreasing signaling through Galphaq. Human patients expressing Met-Leu-Rgs2 (ML-Rgs2) or Met-Arg-Rgs2 (MR-Rgs2) are hypertensive relative to people expressing wild-type Met-Gln-Rgs2 (MQ-Rgs2). We found that wild-type MQ-Rgs2 and its mutant, MR-Rgs2, were destroyed by the Ac/N-end rule pathway, which recognizes N(alpha)-terminally acetylated (Nt-acetylated) proteins. The shortest-lived mutant, ML-Rgs2, was targeted by both the Ac/N-end rule and Arg/N-end rule pathways. The latter pathway recognizes unacetylated N-terminal residues. Thus, the Nt-acetylated Ac-MX-Rgs2 (X = Arg, Gln, Leu) proteins are specific substrates of the mammalian Ac/N-end rule pathway. Furthermore, the Ac/N-degron of Ac-MQ-Rgs2 was conditional, and Teb4, an endoplasmic reticulum (ER) membrane-embedded ubiquitin ligase, was able to regulate G protein signaling by targeting Ac-MX-Rgs2 proteins for degradation through their N(alpha)-terminal acetyl group.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748709/" 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/PMC4748709/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Sang-Eun -- Kim, Jeong-Mok -- Seok, Ok-Hee -- Cho, Hanna -- Wadas, Brandon -- Kim, Seon-Young -- Varshavsky, Alexander -- Hwang, Cheol-Sang -- DK039520/DK/NIDDK NIH HHS/ -- GM031530/GM/NIGMS NIH HHS/ -- R01 DK039520/DK/NIDDK NIH HHS/ -- R01 GM031530/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1249-52. doi: 10.1126/science.aaa3844.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, South Korea. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. ; Medical Genomics Research Center, KRIBB, Daejeon, South Korea. Department of Functional Genomics, University of Science and Technology, Daejeon, South Korea. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. cshwang@postech.ac.kr avarsh@caltech.edu. ; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, South Korea. cshwang@postech.ac.kr avarsh@caltech.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766235" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; GTP-Binding Protein alpha Subunits, Gq-G11/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Membrane Proteins/genetics/metabolism ; Mutant Proteins/chemistry/metabolism ; Protein Processing, Post-Translational ; Protein Stability ; Proteolysis ; RGS Proteins/chemistry/genetics/*metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Signal Transduction ; Ubiquitin-Protein Ligases/genetics/metabolism ; Ubiquitination
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  • 55
    Publication Date: 2015-07-04
    Description: The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems-and the goods and services they provide-for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend. A reduced emissions scenario-consistent with the Copenhagen Accord's goal of a global temperature increase of less than 2 degrees C-is much more favorable to the ocean but still substantially alters important marine ecosystems and associated goods and services. The management options to address ocean impacts narrow as the ocean warms and acidifies. Consequently, any new climate regime that fails to minimize ocean impacts would be incomplete and inadequate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gattuso, J-P -- Magnan, A -- Bille, R -- Cheung, W W L -- Howes, E L -- Joos, F -- Allemand, D -- Bopp, L -- Cooley, S R -- Eakin, C M -- Hoegh-Guldberg, O -- Kelly, R P -- Portner, H-O -- Rogers, A D -- Baxter, J M -- Laffoley, D -- Osborn, D -- Rankovic, A -- Rochette, J -- Sumaila, U R -- Treyer, S -- Turley, C -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):aac4722. doi: 10.1126/science.aac4722.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire d'Oceanographie de Villefranche, CNRS-Institut National des Sciences de l'Univers, F-06230 Villefranche-sur-mer, France. Sorbonne Universites, Universite Pierre et Marie Curie, Univ Paris 06, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. gattuso@obs-vlfr.fr. ; Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. ; Secretariat of the Pacific Community, B.P. D5, 98848 Noumea Cedex, New Caledonia. ; Nippon Foundation-UBC Nereus Program, University of British Columbia (UBC), Vancouver, BC V6T 1Z4, Canada. ; Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research, Am Handelshafen 12, D-27570, Bremenrhaven, Germany. ; Climate and Environmental Physics, Physics Institute and Oeschger Centre for Climate Change Research, University of Bern, Sidlerstrasse 5, CH-3012 Bern, Switzerland. ; Centre Scientifique de Monaco, 8 Quai Antoine Ier, MC-98000 Monaco, Principality of Monaco. Institut Pierre Simon Laplace/Laboratoire des Science du Climat et de l'Environnement, UMR8212, CNRS-Commissariat a l'Energie Atomique et aux Energies Alternatives-Universite de Versailles Saint-Quentin-en-Yvelines, Gif sur Yvette, France. ; Ocean Conservancy, 1300 19th Street NW, 8th Floor, Washington, DC 20036, USA. ; Coral Reef Watch, National Oceanic and Atmospheric Administration, College Park, MD 20740, USA. ; Global Change Institute and Australian Research Council Centre for Excellence in Coral Reef Studies, University of Queensland, Building 20, St Lucia, 4072 Queensland, Australia. ; School of Marine and Environmental Affairs, University of Washington, 3707 Brooklyn Avenue NE, Seattle, WA 98105, USA. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Scottish Natural Heritage, 231 Corstorphine Road, Edinburgh EH12 7AT, Scotland. ; IUCN, Rue Mauverney 28, CH-1196 Gland, Switzerland. ; Environment Laboratories, International Atomic Energy Agency, 4a Quai Antoine 1er, MC-98000 Monaco, Principality of Monaco. ; Program on Science, Technology, and Society, John F. Kennedy School of Government, Harvard University, 79 John F. Kennedy Street, Cambridge, MA 02138, USA. ; Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. Fisheries Economics Research Unit, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. ; Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3DH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138982" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquaculture ; *Aquatic Organisms ; *Carbon Dioxide ; *Ecosystem ; *Global Warming ; *Greenhouse Effect ; Health ; Humans ; Oceans and Seas ; Risk ; Travel
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  • 56
    Publication Date: 2015-04-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allred, Brady W -- Smith, W Kolby -- Twidwell, Dirac -- Haggerty, Julia H -- Running, Steven W -- Naugle, David E -- Fuhlendorf, Samuel D -- New York, N.Y. -- Science. 2015 Apr 24;348(6233):401-2. doi: 10.1126/science.aaa4785. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉College of Forestry and Conservation, University of Montana, Missoula, MT 59812, USA. brady.allred@umontana.edu. ; College of Forestry and Conservation, University of Montana, Missoula, MT 59812, USA. Institute on the Environment, University of Minnesota, St. Paul, MN 55108, USA. ; Department of Agronomy and Horticulture, University of Nebraska-Lincoln, Lincoln, NE 68583, USA. ; Department of Earth Sciences, Montana State University, Bozeman, MT 59717, USA. ; College of Forestry and Conservation, University of Montana, Missoula, MT 59812, USA. ; Department of Natural Resource Ecology and Management, Oklahoma State University, Stillwater, OK 74078, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908812" target="_blank"〉PubMed〈/a〉
    Keywords: Canada ; *Crops, Agricultural ; *Ecosystem ; *Extraction and Processing Industry ; *Oil and Gas Fields ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 57
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1452. doi: 10.1126/science.350.6267.1452.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680168" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; *Extinction, Biological ; *Human Activities ; Humans ; Paleontology ; Plants
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  • 58
    Publication Date: 2015-02-24
    Description: Navigation depends on multiple neural systems that encode the moment-to-moment changes in an animal's direction and location in space. These include head direction (HD) cells representing the orientation of the head and grid cells that fire at multiple locations, forming a repeating hexagonal grid pattern. Computational models hypothesize that generation of the grid cell signal relies upon HD information that ascends to the hippocampal network via the anterior thalamic nuclei (ATN). We inactivated or lesioned the ATN and subsequently recorded single units in the entorhinal cortex and parasubiculum. ATN manipulation significantly disrupted grid and HD cell characteristics while sparing theta rhythmicity in these regions. These results indicate that the HD signal via the ATN is necessary for the generation and function of grid cell activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476794/" 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/PMC4476794/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winter, Shawn S -- Clark, Benjamin J -- Taube, Jeffrey S -- NS053907/NS/NINDS NIH HHS/ -- R01 MH048924/MH/NIMH NIH HHS/ -- R01 NS053907/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):870-4. doi: 10.1126/science.1259591. Epub 2015 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychological and Brain Sciences, Center for Cognitive Neuroscience, Dartmouth College, Hanover, NH 03755, USA. ; Department of Psychological and Brain Sciences, Center for Cognitive Neuroscience, Dartmouth College, Hanover, NH 03755, USA. jeffrey.taube@dartmouth.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700518" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anterior Thalamic Nuclei/drug effects/*physiology ; Entorhinal Cortex/cytology/*physiology ; Female ; Head ; Hippocampus/cytology/physiology ; Lidocaine/pharmacology ; Nerve Net/cytology/drug effects/*physiology ; Neurons/*physiology ; Orientation/*physiology ; Rats ; Rats, Inbred LEC ; Signal Transduction ; Spatial Navigation/*physiology ; Theta Rhythm
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  • 59
    Publication Date: 2015-11-14
    Description: In healthy individuals, the intestinal microbiota cannot access the liver, spleen, or other peripheral tissues. Some pathogenic bacteria can reach these sites, however, and can induce a systemic immune response. How such compartmentalization is achieved is unknown. We identify a gut-vascular barrier (GVB) in mice and humans that controls the translocation of antigens into the blood stream and prohibits entry of the microbiota. Salmonella typhimurium can penetrate the GVB in a manner dependent on its pathogenicity island (Spi) 2-encoded type III secretion system and on decreased beta-catenin-dependent signaling in gut endothelial cells. The GVB is modified in celiac disease patients with elevated serum transaminases, which indicates that GVB dismantling may be responsible for liver damage in these patients. Understanding the GVB may provide new insights into the regulation of the gut-liver axis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spadoni, Ilaria -- Zagato, Elena -- Bertocchi, Alice -- Paolinelli, Roberta -- Hot, Edina -- Di Sabatino, Antonio -- Caprioli, Flavio -- Bottiglieri, Luca -- Oldani, Amanda -- Viale, Giuseppe -- Penna, Giuseppe -- Dejana, Elisabetta -- Rescigno, Maria -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):830-4. doi: 10.1126/science.aad0135.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. ; The Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology (IFOM), Milan, Italy. ; First Department of Medicine, St. Matteo Hospital, University of Pavia, Pavia, Italy. ; Unita Operativa Gastroenterologia ed Endoscopia, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico di Milano, and Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universita degli Studi di Milano, Milan, Italy. ; Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy. ; The Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology (IFOM), Milan, Italy. Department of Biosciences, Universita degli Studi di Milano, Italy. Department of Genetics, Immunology and Pathology, Uppsala University, Uppsala, Sweden. ; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. Department of Biosciences, Universita degli Studi di Milano, Italy. maria.rescigno@ieo.eu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26564856" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Bacterial/blood/immunology ; Capillary Permeability/*immunology ; Celiac Disease/blood/immunology/microbiology ; Genomic Islands/genetics/immunology ; Humans ; Ileum/blood supply/immunology/microbiology ; Intestinal Mucosa/immunology/microbiology ; Intestines/blood supply/*immunology/*microbiology ; Liver/immunology ; Mice ; Mice, Inbred C57BL ; Microbiota/*immunology ; Salmonella Infections/*immunology ; Salmonella typhimurium/genetics/*immunology/pathogenicity ; Signal Transduction ; Spleen/immunology ; Transaminases/blood ; Type III Secretion Systems/genetics/immunology ; Wnt Signaling Pathway ; beta Catenin/metabolism
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  • 60
    Publication Date: 2015-01-24
    Description: The 26S proteasome is a key player in eukaryotic protein quality control and in the regulation of numerous cellular processes. Here, we describe quantitative in situ structural studies of this highly dynamic molecular machine in intact hippocampal neurons. We used electron cryotomography with the Volta phase plate, which allowed high fidelity and nanometer precision localization of 26S proteasomes. We undertook a molecular census of single- and double-capped proteasomes and assessed the conformational states of individual complexes. Under the conditions of the experiment-that is, in the absence of proteotoxic stress-only 20% of the 26S proteasomes were engaged in substrate processing. The remainder was in the substrate-accepting ground state. These findings suggest that in the absence of stress, the capacity of the proteasome system is not fully used.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Asano, Shoh -- Fukuda, Yoshiyuki -- Beck, Florian -- Aufderheide, Antje -- Forster, Friedrich -- Danev, Radostin -- Baumeister, Wolfgang -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):439-42. doi: 10.1126/science.1261197.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany. ; Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany. baumeist@biochem.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25613890" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Hippocampus/*cytology/enzymology ; Neurons/*enzymology/*ultrastructure ; Proteasome Endopeptidase Complex/*chemistry ; Protein Conformation ; Rats ; Stress, Physiological
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  • 61
    Publication Date: 2015-09-26
    Description: Cellular senescence is a terminal stress-activated program controlled by the p53 and p16(INK4a) tumor suppressor proteins. A striking feature of senescence is the senescence-associated secretory phenotype (SASP), a pro-inflammatory response linked to tumor promotion and aging. We have identified the transcription factor GATA4 as a senescence and SASP regulator. GATA4 is stabilized in cells undergoing senescence and is required for the SASP. Normally, GATA4 is degraded by p62-mediated selective autophagy, but this regulation is suppressed during senescence, thereby stabilizing GATA4. GATA4 in turn activates the transcription factor NF-kappaB to initiate the SASP and facilitate senescence. GATA4 activation depends on the DNA damage response regulators ATM and ATR, but not on p53 or p16(INK4a). GATA4 accumulates in multiple tissues, including the aging brain, and could contribute to aging and its associated inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Chanhee -- Xu, Qikai -- Martin, Timothy D -- Li, Mamie Z -- Demaria, Marco -- Aron, Liviu -- Lu, Tao -- Yankner, Bruce A -- Campisi, Judith -- Elledge, Stephen J -- AG009909/AG/NIA NIH HHS/ -- AG017242/AG/NIA NIH HHS/ -- AG046174/AG/NIA NIH HHS/ -- DP1 OD006849/OD/NIH HHS/ -- DP1OD006849/OD/NIH HHS/ -- GM44664/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Sep 25;349(6255):aaa5612. doi: 10.1126/science.aaa5612.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA. ; Buck Institute for Research on Aging, Novato, CA 94945, USA. ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA. selledge@genetics.med.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26404840" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*genetics/metabolism ; Animals ; Ataxia Telangiectasia Mutated Proteins/metabolism ; Autophagy/*genetics ; Brain/metabolism ; Cell Aging/*genetics ; Cell Cycle/genetics ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16 ; *DNA Damage ; Fibroblasts ; GATA4 Transcription Factor/genetics/*metabolism ; Gene Expression Profiling ; Humans ; Inflammation/*genetics ; Interleukin-1alpha/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; MicroRNAs/genetics/metabolism ; NF-kappa B/metabolism ; Phenotype ; Promoter Regions, Genetic ; Tumor Necrosis Factor Receptor-Associated Peptides and ; Proteins/genetics/metabolism ; Tumor Suppressor Protein p53/metabolism
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jeremiah Y -- New York, N.Y. -- Science. 2015 Oct 2;350(6256):47. doi: 10.1126/science.aad3003.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Solomon H. Snyder Department of Neuroscience, Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. jeremiah.cohen@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26430113" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*physiology ; Dopamine/*metabolism ; Dopaminergic Neurons/*metabolism ; Electric Stimulation ; Humans ; Mice ; Neurophysiology/trends ; *Reward ; Serotonin/*metabolism ; Signal Transduction ; Time Factors ; Ventral Tegmental Area/*cytology
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  • 63
    Publication Date: 2015-02-24
    Description: Pancreatic beta cells lower insulin release in response to nutrient depletion. The question of whether starved beta cells induce macroautophagy, a predominant mechanism maintaining energy homeostasis, remains poorly explored. We found that, in contrast to many mammalian cells, macroautophagy in pancreatic beta cells was suppressed upon starvation. Instead, starved beta cells induced lysosomal degradation of nascent secretory insulin granules, which was controlled by protein kinase D (PKD), a key player in secretory granule biogenesis. Starvation-induced nascent granule degradation triggered lysosomal recruitment and activation of mechanistic target of rapamycin that suppressed macroautophagy. Switching from macroautophagy to insulin granule degradation was important to keep insulin secretion low upon fasting. Thus, beta cells use a PKD-dependent mechanism to adapt to nutrient availability and couple autophagy flux to secretory function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goginashvili, Alexander -- Zhang, Zhirong -- Erbs, Eric -- Spiegelhalter, Coralie -- Kessler, Pascal -- Mihlan, Michael -- Pasquier, Adrien -- Krupina, Ksenia -- Schieber, Nicole -- Cinque, Laura -- Morvan, Joelle -- Sumara, Izabela -- Schwab, Yannick -- Settembre, Carmine -- Ricci, Romeo -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):878-82. doi: 10.1126/science.aaa2628.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM, CNRS, Universite de Strasbourg, 67404 Illkirch, France. ; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany. ; Dulbecco Telethon Institute and Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy. ; Dulbecco Telethon Institute and Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy. Medical Genetics, Department of Medical and Translational Science Unit, Federico II University, Via Pansini 5, 80131 Naples, Italy. ; Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM, CNRS, Universite de Strasbourg, 67404 Illkirch, France. Nouvel Hopital Civil, Laboratoire de Biochimie et de Biologie Moleculaire, Universite de Strasbourg, 67091 Strasbourg, France. romeo.ricci@igbmc.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700520" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Autophagy ; Cells, Cultured ; Fasting ; Humans ; Insulin/*secretion ; Insulin-Secreting Cells/*physiology/secretion/ultrastructure ; Mice ; Mice, Mutant Strains ; Mice, Transgenic ; Mitogen-Activated Protein Kinase 13/genetics ; Protein Kinase C/physiology ; Secretory Vesicles/*physiology/secretion
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  • 64
    Publication Date: 2015-08-15
    Description: Astrocytes are important regulatory elements in brain function. They respond to neurotransmitters and release gliotransmitters that modulate synaptic transmission. However, the cell- and synapse-specificity of the functional relationship between astrocytes and neurons in certain brain circuits remains unknown. In the dorsal striatum, which mainly comprises two intermingled subtypes (striatonigral and striatopallidal) of medium spiny neurons (MSNs) and synapses belonging to two neural circuits (the direct and indirect pathways of the basal ganglia), subpopulations of astrocytes selectively responded to specific MSN subtype activity. These subpopulations of astrocytes released glutamate that selectively activated N-methyl-d-aspartate receptors in homotypic, but not heterotypic, MSNs. Likewise, astrocyte subpopulations selectively regulated homotypic synapses through metabotropic glutamate receptor activation. Therefore, bidirectional astrocyte-neuron signaling selectively occurs between specific subpopulations of astrocytes, neurons, and synapses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martin, R -- Bajo-Graneras, R -- Moratalla, R -- Perea, G -- Araque, A -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):730-4. doi: 10.1126/science.aaa7945.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto Cajal, Consejo Superior de Investigaciones Cientificas, 28002 Madrid, Spain. ; Instituto Cajal, Consejo Superior de Investigaciones Cientificas, 28002 Madrid, Spain. Centro de Investigacion Biomedica en Red Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain. ; Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. araque@umn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26273054" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/*physiology ; Basal Ganglia/cytology/*physiology ; Cell Communication ; Glutamates/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Net/physiology ; Neurons/*physiology ; Receptors, Metabotropic Glutamate/agonists/metabolism ; Receptors, N-Methyl-D-Aspartate/agonists/metabolism ; Signal Transduction ; Synapses/*physiology ; *Synaptic Transmission
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  • 65
    Publication Date: 2015-02-24
    Description: Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts that are typically created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. We found that in melanocytes, CPDs are generated for 〉3 hours after exposure to UVA, a major component of the radiation in sunlight and in tanning beds. These "dark CPDs" constitute the majority of CPDs and include the cytosine-containing CPDs that initiate UV-signature C--〉T mutations. Dark CPDs arise when UV-induced reactive oxygen and nitrogen species combine to excite an electron in fragments of the pigment melanin. This creates a quantum triplet state that has the energy of a UV photon but induces CPDs by energy transfer to DNA in a radiation-independent manner. Melanin may thus be carcinogenic as well as protective against cancer. These findings also validate the long-standing suggestion that chemically generated excited electronic states are relevant to mammalian biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432913/" 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/PMC4432913/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Premi, Sanjay -- Wallisch, Silvia -- Mano, Camila M -- Weiner, Adam B -- Bacchiocchi, Antonella -- Wakamatsu, Kazumasa -- Bechara, Etelvino J H -- Halaban, Ruth -- Douki, Thierry -- Brash, Douglas E -- 2 P50 CA121974/CA/NCI NIH HHS/ -- P30 DK034989/DK/NIDDK NIH HHS/ -- P30 DK34989/DK/NIDDK NIH HHS/ -- P50 CA121974/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):842-7. doi: 10.1126/science.1256022.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. ; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo 05513-970 SP, Brazil. ; Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA. ; Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192, Japan. ; Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo 05513-970 SP, Brazil. Departamento de Ciencias Exatas e da Terra, Universidade Federal de Sao Paulo, Diadema, Sao Paulo 09972-270 SP, Brazil. ; Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA. Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA. ; INAC/LCIB UMR-E3 CEA-UJF/Commissariat a l'Energie Atomique (CEA), 38054 Grenoble Cedex 9, France. ; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA. douglas.brash@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700512" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cytosine/metabolism ; DNA/chemistry/genetics/*radiation effects ; DNA Damage/*genetics ; Energy Transfer ; Humans ; Melanins/chemistry/*metabolism ; Melanocytes/metabolism/*radiation effects ; Melanoma/*genetics ; Mice ; Mice, Inbred C57BL ; Mutagenesis ; Mutation ; Neoplasms, Radiation-Induced/*genetics ; Photons ; Pyrimidine Dimers/*metabolism ; Receptor, Melanocortin, Type 1/genetics ; Skin Neoplasms/*genetics ; Sunlight/adverse effects ; Thymine/metabolism ; Ultraviolet Rays
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  • 66
    Publication Date: 2015-01-17
    Description: Marine defaunation, or human-caused animal loss in the oceans, emerged forcefully only hundreds of years ago, whereas terrestrial defaunation has been occurring far longer. Though humans have caused few global marine extinctions, we have profoundly affected marine wildlife, altering the functioning and provisioning of services in every ocean. Current ocean trends, coupled with terrestrial defaunation lessons, suggest that marine defaunation rates will rapidly intensify as human use of the oceans industrializes. Though protected areas are a powerful tool to harness ocean productivity, especially when designed with future climate in mind, additional management strategies will be required. Overall, habitat degradation is likely to intensify as a major driver of marine wildlife loss. Proactive intervention can avert a marine defaunation disaster of the magnitude observed on land.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCauley, Douglas J -- Pinsky, Malin L -- Palumbi, Stephen R -- Estes, James A -- Joyce, Francis H -- Warner, Robert R -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):1255641. doi: 10.1126/science.1255641.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, CA 93106, USA. douglas.mccauley@lifesci.ucsb.edu. ; Department of Ecology, Evolution, and Natural Resources, Institute of Marine and Coastal Sciences, Rutgers University, New Brunswick, NJ 08901, USA. ; Department of Biology, Stanford University, Hopkins Marine Station, Pacific Grove, CA 93950, USA. ; Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, CA 95060, USA. ; Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, CA 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25593191" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Wild ; *Aquatic Organisms ; Biodiversity ; Climate Change ; *Ecosystem ; *Endangered Species ; *Extinction, Biological ; Human Activities ; Humans ; Oceans and Seas ; Population Dynamics ; *Seawater
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  • 67
    Publication Date: 2015-09-26
    Description: Dying cells initiate adaptive immunity by providing both antigens and inflammatory stimuli for dendritic cells, which in turn activate CD8(+) T cells through a process called antigen cross-priming. To define how different forms of programmed cell death influence immunity, we established models of necroptosis and apoptosis, in which dying cells are generated by receptor-interacting protein kinase-3 and caspase-8 dimerization, respectively. We found that the release of inflammatory mediators, such as damage-associated molecular patterns, by dying cells was not sufficient for CD8(+) T cell cross-priming. Instead, robust cross-priming required receptor-interacting protein kinase-1 (RIPK1) signaling and nuclear factor kappaB (NF-kappaB)-induced transcription within dying cells. Decoupling NF-kappaB signaling from necroptosis or inflammatory apoptosis reduced priming efficiency and tumor immunity. Our results reveal that coordinated inflammatory and cell death signaling pathways within dying cells orchestrate adaptive immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651449/" 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/PMC4651449/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yatim, Nader -- Jusforgues-Saklani, Helene -- Orozco, Susana -- Schulz, Oliver -- Barreira da Silva, Rosa -- Reis e Sousa, Caetano -- Green, Douglas R -- Oberst, Andrew -- Albert, Matthew L -- 5R01AI108685-02/AI/NIAID NIH HHS/ -- AI44848/AI/NIAID NIH HHS/ -- R01 AI108685/AI/NIAID NIH HHS/ -- R01AI108685/AI/NIAID NIH HHS/ -- R21 CA185681/CA/NCI NIH HHS/ -- R21CA185681/CA/NCI NIH HHS/ -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):328-34. doi: 10.1126/science.aad0395. Epub 2015 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France. Institut National de la Sante et de la Recherche Medicale, U818, 25 Rue du Docteur Roux, 75015 Paris, France. Frontieres du Vivant Doctoral School, Ecole Doctorale 474, Universite Paris Diderot-Paris 7, Sorbonne Paris Cite, 8-10 Rue Charles V, 75004 Paris, France. ; Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France. Institut National de la Sante et de la Recherche Medicale, U818, 25 Rue du Docteur Roux, 75015 Paris, France. ; Department of Immunology, University of Washington, Campus Box 358059, 750 Republican Street, Seattle, WA 98109, USA. ; Immunobiology Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. ; Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26405229" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Caspase 8/metabolism ; Cell Survival ; Cross-Priming ; Dendritic Cells/immunology ; Mice ; Mice, Inbred C57BL ; NF-kappa B/*metabolism ; NIH 3T3 Cells ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/*metabolism ; Signal Transduction
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  • 68
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, Richard -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1046-7. doi: 10.1126/science.349.6252.1046.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26339010" target="_blank"〉PubMed〈/a〉
    Keywords: Acinonyx ; Animals ; *Droughts ; *Ecosystem ; *Environmental Restoration and Remediation ; Extinction, Biological ; Iran ; *Lakes
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  • 69
    Publication Date: 2015-08-01
    Description: The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1alpha (DD1alpha), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1alpha appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1alpha-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1alpha thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoon, Kyoung Wan -- Byun, Sanguine -- Kwon, Eunjeong -- Hwang, So-Young -- Chu, Kiki -- Hiraki, Masatsugu -- Jo, Seung-Hee -- Weins, Astrid -- Hakroush, Samy -- Cebulla, Angelika -- Sykes, David B -- Greka, Anna -- Mundel, Peter -- Fisher, David E -- Mandinova, Anna -- Lee, Sam W -- CA142805/CA/NCI NIH HHS/ -- CA149477/CA/NCI NIH HHS/ -- CA80058/CA/NCI NIH HHS/ -- DK062472/DK/NIDDK NIH HHS/ -- DK091218/DK/NIDDK NIH HHS/ -- DK093378/DK/NIDDK NIH HHS/ -- DK57683/DK/NIDDK NIH HHS/ -- S10RR027673/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 31;349(6247):1261669. doi: 10.1126/science.1261669.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. ; Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. ; Center for Regenerative Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ; Department of Medicine, Glom-NExT Center for Glomerular Kidney Disease and Novel Experimental Therapeutics, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. swlee@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26228159" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis/genetics/*immunology ; Autoimmune Diseases/genetics/immunology ; Cell Line, Tumor ; Female ; Humans ; Inflammation/genetics/immunology ; Macrophages/immunology ; Male ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Phagocytosis/*immunology ; Phosphatidylserines/*metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/*metabolism
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  • 70
    Publication Date: 2015-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Groner, Maya -- Breyta, Rachel -- Dobson, Andy -- Friedman, Carolyn S -- Froelich, Brett -- Garren, Melissa -- Gulland, Frances -- Maynard, Jeffrey -- Weil, Ernesto -- Wyllie-Echeverria, Sandy -- Harvell, Drew -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1210. doi: 10.1126/science.347.6227.1210-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Veterinary and Epidemiological Research, Department of Health Management, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3, Canada. mgroner@upei.ca. ; School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195, USA. ; Department of Ecology and Evolutionary Biology, Princeton, NJ 08544, USA. ; Department of Marine Science, University of North Carolina, Chapel Hill, NC 27599, USA. ; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; The Marine Mammal Center, Sausalito, CA 94965, USA. ; Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY 14853, USA. ; Department of Marine Sciences, University of Puerto Rico, Mayaguez, Mayaguez, PR 00680, USA. ; Friday Harbor Laboratories, University of Washington, Friday Harbor, WA 98250, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766223" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms/*microbiology ; *Ecosystem ; Oceans and Seas ; *Plant Diseases ; *Seawater
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kintisch, Eli -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):578-81. doi: 10.1126/science.349.6248.578.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250666" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arctic Regions ; *Ecosystem ; Fishes ; *Global Warming ; *Ice Cover ; Oceans and Seas ; Plankton ; Species Specificity
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  • 72
    Publication Date: 2015-11-21
    Description: Drosophila intestinal stem cells (ISCs) generate enterocytes (ECs) and enteroendocrine (ee) cells. Previous work suggests that different levels of the Notch ligand Delta (Dl) in ISCs unidirectionally activate Notch in daughters to control multipotency. However, the mechanisms driving different outcomes remain unknown. We found that during ee cell formation, the ee cell marker Prospero localizes to the basal side of dividing ISCs. After asymmetric division, the ee daughter cell acts as a source of Dl that induces low Notch activity in the ISC to maintain identity. Alternatively, ISCs expressing Dl induce high Notch activity in daughter cells to promote EC formation. Our data reveal a conserved role for Notch in Drosophila and mammalian ISC maintenance and suggest that bidirectional Notch signaling may regulate multipotency in other systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Zheng -- Ohlstein, Benjamin -- New York, N.Y. -- Science. 2015 Nov 20;350(6263). pii: aab0988. doi: 10.1126/science.aab0988.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA. ; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA. bo2160@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586765" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Division ; Cell Polarity ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/cytology/*growth & development/metabolism ; Enterocytes/*cytology ; Enteroendocrine Cells/*cytology ; Multipotent Stem Cells/*cytology/metabolism ; Nuclear Proteins/*metabolism ; Phosphoproteins/*metabolism ; Receptors, Notch/*metabolism ; Signal Transduction ; Transcription Factors/*metabolism
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rau, Greg H -- Greene, Charles H -- New York, N.Y. -- Science. 2015 Sep 25;349(6255):1459. doi: 10.1126/science.349.6255.1459-b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Marine Sciences, University of California, Santa Cruz, CA 95064, USA. ghrau@sbcglobal.net. ; Ocean Resources and Ecosystems Program, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26404817" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Aquatic Organisms ; *Carbon Dioxide ; *Ecosystem ; *Global Warming ; *Greenhouse Effect ; Humans
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  • 74
    Publication Date: 2015-11-07
    Description: In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34(+) cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er, and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead, only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult "two-tier" hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Notta, Faiyaz -- Zandi, Sasan -- Takayama, Naoya -- Dobson, Stephanie -- Gan, Olga I -- Wilson, Gavin -- Kaufmann, Kerstin B -- McLeod, Jessica -- Laurenti, Elisa -- Dunant, Cyrille F -- McPherson, John D -- Stein, Lincoln D -- Dror, Yigal -- Dick, John E -- Canadian Institutes of Health Research/Canada -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2016 Jan 8;351(6269):aab2116. doi: 10.1126/science.aab2116. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. ; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. Ontario Institute for Cancer Research, Toronto, Ontario, Canada. ; Wellcome Trust, Medical Research Council Cambridge Stem Cell Institute, Department of Haematology, University of Cambridge, Cambridge, UK. ; Ecole Polytechnique Federale de Lausanne, LMC, Station 12, Lausanne, CH-1015, Switzerland. ; Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Ontario Institute for Cancer Research, Toronto, Ontario, Canada. ; The Hospital for Sick Children Research Institute, University of Toronto, Ontario, Canada. ; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. jdick@uhnres.utoronto.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541609" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Antigens, CD34/analysis ; Cell Lineage/genetics/*physiology ; Cell Separation ; Cells, Cultured ; Erythroid Cells/*cytology ; Fetal Blood/cytology ; Gene Expression Profiling ; Hematopoiesis/genetics/*physiology ; Humans ; Liver/cytology/embryology ; Megakaryocyte Progenitor Cells/*cytology ; Megakaryocytes/*cytology ; Multipotent Stem Cells/cytology ; Myeloid Cells/*cytology ; Transcription, Genetic
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  • 75
    Publication Date: 2015-10-10
    Description: Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate the Rags, including GATOR1, aGTPase-activating protein; GATOR2, a positive regulator of unknown function; and Sestrin2, a GATOR2-interacting protein that inhibits mTORC1 signaling. We find that leucine, but not arginine, disrupts the Sestrin2-GATOR2 interaction by binding to Sestrin2 with a dissociation constant of 20 micromolar, which is the leucine concentration that half-maximally activates mTORC1. The leucine-binding capacity of Sestrin2 is required for leucine to activate mTORC1 in cells. These results indicate that Sestrin2 is a leucine sensor for the mTORC1 pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698017/" 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/PMC4698017/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolfson, Rachel L -- Chantranupong, Lynne -- Saxton, Robert A -- Shen, Kuang -- Scaria, Sonia M -- Cantor, Jason R -- Sabatini, David M -- AI47389/AI/NIAID NIH HHS/ -- F30 CA189333/CA/NCI NIH HHS/ -- F31 CA180271/CA/NCI NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R37 AI047389/AI/NIAID NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):43-8. doi: 10.1126/science.aab2674. Epub 2015 Oct 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. sabatini@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26449471" target="_blank"〉PubMed〈/a〉
    Keywords: GTPase-Activating Proteins/*metabolism ; HEK293 Cells ; Humans ; Leucine/*metabolism ; Metabolic Networks and Pathways ; Multiprotein Complexes/*metabolism ; Nuclear Proteins/chemistry/genetics/*metabolism ; Protein Binding ; Proteins/chemistry/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism
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  • 76
    Publication Date: 2014-05-17
    Description: A switchlike response in nuclear factor-kappaB (NF-kappaB) activity implies the existence of a threshold in the NF-kappaB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-kappaB (IkappaB) kinase-beta (IKKbeta) module is a switch mechanism for NF-kappaB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKbeta to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKbeta target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-kappaB in single cells, suggesting that phosphorylation of this residue accounts for the feedback.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinohara, Hisaaki -- Behar, Marcelo -- Inoue, Kentaro -- Hiroshima, Michio -- Yasuda, Tomoharu -- Nagashima, Takeshi -- Kimura, Shuhei -- Sanjo, Hideki -- Maeda, Shiori -- Yumoto, Noriko -- Ki, Sewon -- Akira, Shizuo -- Sako, Yasushi -- Hoffmann, Alexander -- Kurosaki, Tomohiro -- Okada-Hatakeyama, Mariko -- 5R01CA141722/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 May 16;344(6185):760-4. doi: 10.1126/science.1250020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ; Laboratory for Cell Signaling Dynamics, RIKEN Quantitative Biology Center (QBiC), 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan. Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Graduate School of Engineering, Tottori University 4-101, Koyama-minami, Tottori 680-8552, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ; Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism ; CARD Signaling Adaptor Proteins/genetics/*metabolism ; Cell Line ; Chickens ; Feedback, Physiological ; Guanylate Cyclase/genetics/*metabolism ; I-kappa B Kinase/*metabolism ; MAP Kinase Kinase Kinases/genetics/*metabolism ; Mice ; Mice, Knockout ; Mutation ; NF-kappa B/*agonists ; Phosphorylation ; Receptors, Antigen, B-Cell/genetics/*metabolism ; Serine/genetics/metabolism ; Signal Transduction
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-07-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woodroffe, Rosie -- Hedges, Simon -- Durant, Sarah -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):389-90. doi: 10.1126/science.345.6195.389-b. Epub 2014 Jul 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Zoology, Zoological Society of London, London, NW1 4RY, UK. rosie.woodroffe@ioz.ac.uk. ; Wildlife Conservation Society, Bronx, NY 10460, USA. ; Institute of Zoology, Zoological Society of London, London, NW1 4RY, UK. Wildlife Conservation Society, Bronx, NY 10460, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061195" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Wild ; *Biodiversity ; *Conservation of Natural Resources ; *Ecosystem ; Humans
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  • 78
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1470-1. doi: 10.1126/science.344.6191.1470.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970076" target="_blank"〉PubMed〈/a〉
    Keywords: Biodiversity ; *Ecosystem ; Geologic Sediments/*microbiology ; *Natural Gas ; Oil and Gas Fields/*microbiology
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  • 79
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woodroffe, Rosie -- Hedges, Simon -- Durant, Sarah M -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):46-8. doi: 10.1126/science.1246251.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Zoology, Regent's Park, London NW1 4RY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700847" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Wild ; *Biodiversity ; *Conservation of Natural Resources ; *Ecosystem ; Humans
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  • 80
    Publication Date: 2014-02-08
    Description: Neuronal intracellular chloride concentration [Cl(-)](i) is an important determinant of gamma-aminobutyric acid type A (GABA(A)) receptor (GABA(A)R)-mediated inhibition and cytoplasmic volume regulation. Equilibrative cation-chloride cotransporters (CCCs) move Cl(-) across the membrane, but accumulating evidence suggests factors other than the bulk concentrations of transported ions determine [Cl(-)](i). Measurement of [Cl(-)](i) in murine brain slice preparations expressing the transgenic fluorophore Clomeleon demonstrated that cytoplasmic impermeant anions ([A](i)) and polyanionic extracellular matrix glycoproteins ([A](o)) constrain the local [Cl(-)]. CCC inhibition had modest effects on [Cl(-)](i) and neuronal volume, but substantial changes were produced by alterations of the balance between [A](i) and [A](o). Therefore, CCCs are important elements of Cl(-) homeostasis, but local impermeant anions determine the homeostatic set point for [Cl(-)], and hence, neuronal volume and the polarity of local GABA(A)R signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220679/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220679/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glykys, J -- Dzhala, V -- Egawa, K -- Balena, T -- Saponjian, Y -- Kuchibhotla, K V -- Bacskai, B J -- Kahle, K T -- Zeuthen, T -- Staley, K J -- NS 40109-06/NS/NINDS NIH HHS/ -- R01 EB000768/EB/NIBIB NIH HHS/ -- R01 NS040109/NS/NINDS NIH HHS/ -- R01 NS074772/NS/NINDS NIH HHS/ -- R25 NS065743/NS/NINDS NIH HHS/ -- S10 RR025645/RR/NCRR NIH HHS/ -- U41 RR019703/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):670-5. doi: 10.1126/science.1245423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*metabolism ; Cell Membrane Permeability ; Cell Polarity ; Chloride Channels/*metabolism ; Chlorides/*metabolism ; Cytoplasm/metabolism ; Extracellular Matrix Proteins/metabolism ; Glycoproteins/metabolism ; Mice ; Mice, Transgenic ; Neurons/*metabolism ; Receptors, GABA-A/*metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Signal Transduction
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  • 81
    Publication Date: 2014-06-28
    Description: Reef-building in metazoans represents an important ecological innovation whereby individuals collectively enhance feeding efficiency and gain protection from competitors and predation. The appearance of metazoan reefs in the fossil record therefore indicates an adaptive response to complex ecological pressures. In the Nama Group, Namibia, we found evidence of reef-building by the earliest known skeletal metazoan, the globally distributed Cloudina, ~548 million years ago. These Cloudina reefs formed open frameworks without a microbial component but with mutual attachment and cementation between individuals. Orientated growth implies a passive suspension-feeding habit into nutrient-rich currents. The characteristics of Cloudina support the view that metazoan reef-building was promoted by the rise of substrate competitors and predators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penny, A M -- Wood, R -- Curtis, A -- Bowyer, F -- Tostevin, R -- Hoffman, K-H -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1504-6. doi: 10.1126/science.1253393.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of GeoSciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JW, UK. a.m.penny@ed.ac.uk. ; School of GeoSciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JW, UK. ; Department of Earth Sciences, University College London, Gower Street, London WC1E 6BT, UK. ; Geological Survey of Namibia, Private Bag 13297, Windhoek, Namibia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970084" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbonates ; *Ecosystem ; *Fossils ; Invertebrates/anatomy & histology/*growth & development/physiology ; Namibia ; Predatory Behavior
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  • 82
    Publication Date: 2014-04-05
    Description: Development of vertebrate embryos involves tightly regulated molecular and cellular processes that progressively instruct proliferating embryonic cells about their identity and behavior. Whereas numerous gene activities have been found to be essential during early embryogenesis, little is known about the minimal conditions and factors that would be sufficient to instruct pluripotent cells to organize the embryo. Here, we show that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Peng-Fei -- Houssin, Nathalie -- Ferri-Lagneau, Karine F -- Thisse, Bernard -- Thisse, Christine -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):87-9. doi: 10.1126/science.1248252.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700857" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastula/*physiology ; Body Patterning ; Bone Morphogenetic Proteins/genetics/*physiology ; Embryo, Nonmammalian/*physiology ; *Embryonic Development ; Gastrula/physiology ; Gastrulation ; Gene Expression Regulation, Developmental ; Morphogenesis ; Nodal Protein/genetics/*physiology ; RNA, Messenger/genetics ; Signal Transduction ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*physiology
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  • 83
    Publication Date: 2014-09-23
    Description: Reported trends in the mean and variability of coastal upwelling in eastern boundary currents have raised concerns about the future of these highly productive and biodiverse marine ecosystems. However, the instrumental records on which these estimates are based are insufficiently long to determine whether such trends exceed preindustrial limits. In the California Current, a 576-year reconstruction of climate variables associated with winter upwelling indicates that variability increased over the latter 20th century to levels equaled only twice during the past 600 years. This modern trend in variance may be unique, because it appears to be driven by an unprecedented succession of extreme, downwelling-favorable, winter climate conditions that profoundly reduce productivity for marine predators of commercial and conservation interest.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Black, Bryan A -- Sydeman, William J -- Frank, David C -- Griffin, Daniel -- Stahle, David W -- Garcia-Reyes, Marisol -- Rykaczewski, Ryan R -- Bograd, Steven J -- Peterson, William T -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1498-502. doi: 10.1126/science.1253209.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX 78373, USA. bryan.black@utexas.edu. ; Farallon Institute for Advanced Ecosystem Research, 101 H Street, Suite Q, Petaluma, CA 94952, USA. ; Swiss Federal Research Institute WSL, Zurcherstrasse 111, CH-8903 Birmensdorf, Switzerland and Oeschger Centre for Climate Change Research, University of Bern, Zahringerstrasse 25, CH-3012 Bern, Switzerland. ; Department of Geology and Geophysics, Woods Hole Oceanographic Institution, 266 Woods Hole Road, Woods Hole, MA 02543, USA. ; Department of Geosciences, University of Arkansas, 216 Ozark Hall, Fayetteville, AR 72701, USA. ; Department of Biological Sciences and Marine Science Program, University of South Carolina, 701 Sumter Street, Columbia, SC 29208, USA. ; Environmental Research Division, Southwest Fisheries Science Center, National Oceanic and Atmospheric Administration (NOAA), 1352 Lighthouse Avenue, Pacific Grove, CA 93950, USA. ; Northwest Fisheries Science Center, Hatfield Marine Science Center, NOAA, 2030 Southeast Marine Science Drive, Newport, OR 97365, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237100" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Aquatic Organisms ; Biodiversity ; Climate Change ; *Ecosystem ; Food Chain ; *Oceans and Seas ; Seasons
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  • 84
    Publication Date: 2014-08-30
    Description: Cells use actomyosin contractility to move through three-dimensional (3D) extracellular matrices. Contractility affects the type of protrusions cells use to migrate in 3D, but the mechanisms are unclear. In this work, we found that contractility generated high-pressure lobopodial protrusions in human cells migrating in a 3D matrix. In these cells, the nucleus physically divided the cytoplasm into forward and rear compartments. Actomyosin contractility with the nucleoskeleton-intermediate filament linker protein nesprin-3 pulled the nucleus forward and pressurized the front of the cell. Reducing expression of nesprin-3 decreased and equalized the intracellular pressure. Thus, the nucleus can act as a piston that physically compartmentalizes the cytoplasm and increases the hydrostatic pressure between the nucleus and the leading edge of the cell to drive lamellipodia-independent 3D cell migration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petrie, Ryan J -- Koo, Hyun -- Yamada, Kenneth M -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1062-5. doi: 10.1126/science.1256965.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA. petrier@mail.nih.gov kyamada@mail.nih.gov. ; Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA. Center for Oral Biology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. Biofilm Research Labs, Levy Center for Oral Health, Department of Orthodontics, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104-6030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170155" target="_blank"〉PubMed〈/a〉
    Keywords: Actomyosin/physiology ; Cell Movement/*physiology ; Cell Nucleus/*physiology ; Cells, Cultured ; Cytoplasm/physiology ; Extracellular Matrix/*physiology/ultrastructure ; Fibroblasts/*physiology ; Humans ; Hydrostatic Pressure ; Microfilament Proteins ; Pseudopodia/*physiology ; Vimentin/metabolism
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  • 85
    Publication Date: 2014-12-06
    Description: Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils' bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280847/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280847/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sreeramkumar, Vinatha -- Adrover, Jose M -- Ballesteros, Ivan -- Cuartero, Maria Isabel -- Rossaint, Jan -- Bilbao, Izaskun -- Nacher, Maria -- Pitaval, Christophe -- Radovanovic, Irena -- Fukui, Yoshinori -- McEver, Rodger P -- Filippi, Marie-Dominique -- Lizasoain, Ignacio -- Ruiz-Cabello, Jesus -- Zarbock, Alexander -- Moro, Maria A -- Hidalgo, Andres -- HL03463/HL/NHLBI NIH HHS/ -- HL085607/HL/NHLBI NIH HHS/ -- HL090676/HL/NHLBI NIH HHS/ -- P01 HL085607/HL/NHLBI NIH HHS/ -- R01 HL034363/HL/NHLBI NIH HHS/ -- R01 HL090676/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1234-8. doi: 10.1126/science.1256478. Epub 2014 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. ; Unidad de Investigacion Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain. ; Department of Anesthesiology and Critical Care Medicine, University of Munster and Max Planck Institute Munster, Munster, Germany. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Australia. ; Division of Immunogenetics, Department of Immunobiology and Neuroscience, Kyushu University, Japan. ; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. ; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany. ahidalgo@cnic.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477463" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Circulation ; Blood Platelets/*immunology ; Cell Movement ; Cell Polarity ; Endothelium, Vascular/immunology ; Inflammation/blood/*immunology ; Male ; Membrane Glycoproteins ; Mice ; Mice, Inbred C57BL ; Neutrophils/*immunology ; *Platelet Activation ; Signal Transduction ; Thrombosis/*immunology ; Venules/immunology
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  • 86
    Publication Date: 2014-07-06
    Description: In 1990, Andrew Bakun proposed that increasing greenhouse gas concentrations would force intensification of upwelling-favorable winds in eastern boundary current systems that contribute substantial services to society. Because there is considerable disagreement about whether contemporary wind trends support Bakun's hypothesis, we performed a meta-analysis of the literature on upwelling-favorable wind intensification. The preponderance of published analyses suggests that winds have intensified in the California, Benguela, and Humboldt upwelling systems and weakened in the Iberian system over time scales ranging up to 60 years; wind change is equivocal in the Canary system. Stronger intensification signals are observed at higher latitudes, consistent with the warming pattern associated with climate change. Overall, reported changes in coastal winds, although subtle and spatially variable, support Bakun's hypothesis of upwelling intensification in eastern boundary current systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sydeman, W J -- Garcia-Reyes, M -- Schoeman, D S -- Rykaczewski, R R -- Thompson, S A -- Black, B A -- Bograd, S J -- New York, N.Y. -- Science. 2014 Jul 4;345(6192):77-80. doi: 10.1126/science.1251635.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. wsydeman@comcast.net. ; Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. ; Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Locked Bag 4, Maroochydore DC, Queensland 4558, Australia. ; Department of Biological Sciences and Marine Science Program, University of South Carolina, 701 Sumter Street, Columbia, SC 29208, USA. ; Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. Climate Impacts Group, University of Washington, Box 355674, Seattle, WA 98195, USA. ; Marine Science Institute, University of Texas, 750 Channel View Drive, Port Aransas, TX 78373, USA. ; Environmental Research Division, National Oceanic and Atmospheric Administration (NOAA) Southwest Fisheries Science Center, 1352 Lighthouse Avenue, Pacific Grove, CA 93950-2097, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24994651" target="_blank"〉PubMed〈/a〉
    Keywords: California ; *Climate Change ; *Ecosystem ; Greenhouse Effect ; *Wind
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  • 87
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gramling, Carolyn -- New York, N.Y. -- Science. 2014 May 2;344(6183):463. doi: 10.1126/science.344.6183.463.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786058" target="_blank"〉PubMed〈/a〉
    Keywords: *Aquatic Organisms ; Copper ; *Ecosystem ; Gold ; Mining/*economics ; Papua New Guinea ; *Seawater
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  • 88
    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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  • 89
    Publication Date: 2014-09-06
    Description: Pathogens traverse multiple barriers during infection, including cell membranes. We found that during this transition, pathogens carried covalently attached complement C3 into the cell, triggering immediate signaling and effector responses. Sensing of C3 in the cytosol activated mitochondrial antiviral signaling (MAVS)-dependent signaling cascades and induced proinflammatory cytokine secretion. C3 also flagged viruses for rapid proteasomal degradation, preventing their replication. This system could detect both viral and bacterial pathogens but was antagonized by enteroviruses, such as rhinovirus and poliovirus, which cleave C3 using their 3C protease. The antiviral rupintrivir inhibited 3C protease and prevented C3 cleavage, rendering enteroviruses susceptible to intracellular complement sensing. Thus, complement C3 allows cells to detect and disable pathogens that have invaded the cytosol.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172439/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172439/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tam, Jerry C H -- Bidgood, Susanna R -- McEwan, William A -- James, Leo C -- 281627/European Research Council/International -- MC_U105181010/Medical Research Council/United Kingdom -- U105181010/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1256070. doi: 10.1126/science.1256070. Epub 2014 Sep 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. lcj@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190799" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/*immunology ; Adenovirus Infections, Human/*immunology ; Animals ; Antibodies, Viral/immunology ; Complement C3/*immunology ; Cytokines/biosynthesis/genetics ; Dogs ; HEK293 Cells ; Host-Pathogen Interactions/*immunology ; Humans ; *Immunity, Innate ; Interferon Regulatory Factors/metabolism ; NF-kappa B/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ribonucleoproteins/genetics/metabolism ; Signal Transduction ; Transcription Factor AP-1/metabolism
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  • 90
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bar-Peled, Liron -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1191-2. doi: 10.1126/science.aaa1808.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Scripps Research Institute, La Jolla, CA 92122, USA. lironbp@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477447" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/*metabolism ; Animals ; *Body Size ; *Cell Enlargement ; *Cell Proliferation ; GTP-Binding Protein Regulators/*metabolism ; Lysosomes/*metabolism ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes/metabolism ; Protein Transport ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
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  • 91
    Publication Date: 2014-11-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferreira, J -- Aragao, L E O C -- Barlow, J -- Barreto, P -- Berenguer, E -- Bustamante, M -- Gardner, T A -- Lees, A C -- Lima, A -- Louzada, J -- Pardini, R -- Parry, L -- Peres, C A -- Pompeu, P S -- Tabarelli, M -- Zuanon, J -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):706-7. doi: 10.1126/science.1260194.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉See the supplementary materials for author af liations. joice.ferreira@embrapa.br. ; See the supplementary materials for author af liations.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25378611" target="_blank"〉PubMed〈/a〉
    Keywords: Biodiversity ; Brazil ; Conservation of Natural Resources/*trends ; *Ecosystem ; Federal Government ; *Mining ; Risk
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  • 92
    Publication Date: 2014-08-30
    Description: Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing derepression of PRC2 target genes and developmental perturbations. Similarly, an H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various Drosophila tissues. The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M-containing nucleosomes, and its misregulation in Drosophila results in changes of H3K9 methylation levels and heterochromatic silencing defects. We have established histone lysine-to-methionine mutants as robust in vivo tools for inhibiting methylation pathways that also function as biochemical reagents for capturing site-specific histone-modifying enzymes, thus providing molecular insight into chromatin signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508193/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herz, Hans-Martin -- Morgan, Marc -- Gao, Xin -- Jackson, Jessica -- Rickels, Ryan -- Swanson, Selene K -- Florens, Laurence -- Washburn, Michael P -- Eissenberg, Joel C -- Shilatifard, Ali -- CA R01CA089455/CA/NCI NIH HHS/ -- R01 CA089455/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1065-70. doi: 10.1126/science.1255104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ; Saint Louis University School of Medicine, Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis, MO, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ash@northwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170156" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Chromatin/*metabolism ; Disease Models, Animal ; Drosophila Proteins/genetics ; Drosophila melanogaster ; Gene Silencing ; Glioma/genetics/metabolism ; Heterochromatin/metabolism ; Histone-Lysine N-Methyltransferase/genetics ; Histones/*genetics/metabolism ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Lysine/*genetics ; Methionine/*genetics ; Methylation ; Mutation ; Signal Transduction
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  • 93
    Publication Date: 2014-07-26
    Description: In theoretical ecology, traditional studies based on dynamical stability and numerical simulations have not found a unified answer to the effect of network architecture on community persistence. Here, we introduce a mathematical framework based on the concept of structural stability to explain such a disparity of results. We investigated the range of conditions necessary for the stable coexistence of all species in mutualistic systems. We show that the apparently contradictory conclusions reached by previous studies arise as a consequence of overseeing either the necessary conditions for persistence or its dependence on model parameterization. We show that observed network architectures maximize the range of conditions for species coexistence. We discuss the applicability of structural stability to study other types of interspecific interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rohr, Rudolf P -- Saavedra, Serguei -- Bascompte, Jordi -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):1253497. doi: 10.1126/science.1253497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. Unit of Ecology and Evolution, Department of Biology, University of Fribourg, Chemin du Musee 10, CH-1700 Fribourg, Switzerland. ; Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. ; Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. bascompte@ebd.csic.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061214" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Computer Simulation ; *Ecosystem ; *Models, Biological ; Plants ; *Symbiosis
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  • 94
    Publication Date: 2014-03-01
    Description: Understanding the spatial organization of gene expression with single-nucleotide resolution requires localizing the sequences of expressed RNA transcripts within a cell in situ. Here, we describe fluorescent in situ RNA sequencing (FISSEQ), in which stably cross-linked complementary DNA (cDNA) amplicons are sequenced within a biological sample. Using 30-base reads from 8102 genes in situ, we examined RNA expression and localization in human primary fibroblasts with a simulated wound-healing assay. FISSEQ is compatible with tissue sections and whole-mount embryos and reduces the limitations of optical resolution and noisy signals on single-molecule detection. Our platform enables massively parallel detection of genetic elements, including gene transcripts and molecular barcodes, and can be used to investigate cellular phenotype, gene regulation, and environment in situ.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140943/" 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/PMC4140943/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Je Hyuk -- Daugharthy, Evan R -- Scheiman, Jonathan -- Kalhor, Reza -- Yang, Joyce L -- Ferrante, Thomas C -- Terry, Richard -- Jeanty, Sauveur S F -- Li, Chao -- Amamoto, Ryoji -- Peters, Derek T -- Turczyk, Brian M -- Marblestone, Adam H -- Inverso, Samuel A -- Bernard, Amy -- Mali, Prashant -- Rios, Xavier -- Aach, John -- Church, George M -- GM080177/GM/NIGMS NIH HHS/ -- MH098977/MH/NIMH NIH HHS/ -- P50 HG005550/HG/NHGRI NIH HHS/ -- RC2 HL102815/HL/NHLBI NIH HHS/ -- RC2HL102815/HL/NHLBI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32 GM080177/GM/NIGMS NIH HHS/ -- U01 MH098977/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1360-3. doi: 10.1126/science.1250212. Epub 2014 Feb 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wyss Institute, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24578530" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line ; Cells, Cultured ; DNA, Complementary ; Fluorescence ; Gene Expression Profiling/*methods ; Humans ; Induced Pluripotent Stem Cells ; RNA, Messenger/genetics/metabolism ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis ; Transcription Initiation Site ; *Transcriptome ; Wound Healing
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  • 95
    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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
    Publication Date: 2014-01-05
    Description: Decapentaplegic (Dpp), a Drosophila morphogen signaling protein, transfers directly at synapses made at sites of contact between cells that produce Dpp and cytonemes that extend from recipient cells. The Dpp that cytonemes receive moves together with activated receptors toward the recipient cell body in motile puncta. Genetic loss-of-function conditions for diaphanous, shibire, neuroglian, and capricious perturbed cytonemes by reducing their number or only the synapses they make with cells they target, and reduced cytoneme-mediated transport of Dpp and Dpp signaling. These experiments provide direct evidence that cells use cytonemes to exchange signaling proteins, that cytoneme-based exchange is essential for signaling and normal development, and that morphogen distribution and signaling can be contact-dependent, requiring cytoneme synapses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336149/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336149/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roy, Sougata -- Huang, Hai -- Liu, Songmei -- Kornberg, Thomas B -- GM030637/GM/NIGMS NIH HHS/ -- K99HL114867/HL/NHLBI NIH HHS/ -- R01 GM030637/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):1244624. doi: 10.1126/science.1244624. Epub 2014 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385607" target="_blank"〉PubMed〈/a〉
    Keywords: Air Sacs/cytology/metabolism ; Animals ; Carrier Proteins/genetics/metabolism ; Cell Adhesion Molecules, Neuronal/genetics/metabolism ; *Cell Communication ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*cytology/*metabolism ; Dynamins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; Protein Transport ; Pseudopodia/*metabolism ; Signal Transduction ; Trachea/cytology/metabolism
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2014-01-25
    Description: The physical manifestation of learning and memory formation in the brain can be expressed by strengthening or weakening of synaptic connections through morphological changes. Local actin remodeling underlies some forms of plasticity and may be facilitated by local beta-actin synthesis, but dynamic information is lacking. In this work, we use single-molecule in situ hybridization to demonstrate that dendritic beta-actin messenger RNA (mRNA) and ribosomes are in a masked, neuron-specific form. Chemically induced long-term potentiation prompts transient mRNA unmasking, which depends on factors active during synaptic activity. Ribosomes and single beta-actin mRNA motility increase after stimulation, indicative of release from complexes. Hence, the single-molecule assays we developed allow for the quantification of activity-induced unmasking and availability for active translation. Further, our work demonstrates that beta-actin mRNA and ribosomes are in a masked state that is alleviated by stimulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121734/" 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/PMC4121734/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buxbaum, Adina R -- Wu, Bin -- Singer, Robert H -- GM84364/GM/NIGMS NIH HHS/ -- NS083085-19/NS/NINDS NIH HHS/ -- R01 NS083085/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):419-22. doi: 10.1126/science.1242939.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458642" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*biosynthesis/genetics ; Animals ; Cells, Cultured ; Dendrites/metabolism ; In Situ Hybridization, Fluorescence/methods ; Long-Term Potentiation/drug effects/*physiology ; Memory/physiology ; Mice ; Mice, Transgenic ; Neuronal Plasticity/drug effects/physiology ; Neurons/*metabolism ; *Protein Biosynthesis ; RNA, Messenger/analysis/*biosynthesis ; RNA, Ribosomal/metabolism ; Ribosomes/*metabolism ; Synapses/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cardinale, Bradley -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1098. doi: 10.1126/science.344.6188.1098-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Natural Resources and Environment, University of Michigan, Ann Arbor, MI 48103, USA. bradcard@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904146" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; *Birds ; *Ecosystem ; *Fishes ; *Invertebrates ; *Mammals ; *Plants
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2014-03-15
    Description: Motor neurons, which relay neural commands to drive skeletal muscle movements, encompass types ranging from "slow" to "fast," whose biophysical properties govern the timing, gradation, and amplitude of muscle force. Here we identify the noncanonical Notch ligand Delta-like homolog 1 (Dlk1) as a determinant of motor neuron functional diversification. Dlk1, expressed by ~30% of motor neurons, is necessary and sufficient to promote a fast biophysical signature in the mouse and chick. Dlk1 suppresses Notch signaling and activates expression of the K(+) channel subunit Kcng4 to modulate delayed-rectifier currents. Dlk1 inactivation comprehensively shifts motor neurons toward slow biophysical and transcriptome signatures, while abolishing peak force outputs. Our findings provide insights into the development of motor neuron functional diversity and its contribution to the execution of movements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Daniel -- Cherukuri, Pitchaiah -- Henningfeld, Kristine -- Poh, Chor Hoon -- Wittler, Lars -- Grote, Phillip -- Schluter, Oliver -- Schmidt, Jennifer -- Laborda, Jorge -- Bauer, Steven R -- Brownstone, Robert M -- Marquardt, Till -- R01 HD042013/HD/NICHD NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1264-6. doi: 10.1126/science.1246448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Neurobiology Laboratory, European Neuroscience Institute (ENI-G), Grisebachstrasse 5, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626931" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation ; Intercellular Signaling Peptides and Proteins/genetics/*physiology ; Mice ; Mice, Knockout ; Motor Neurons/*metabolism ; Movement ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/innervation/*physiology ; Potassium Channels, Voltage-Gated/genetics ; Receptors, Notch/*physiology ; Signal Transduction ; Transcriptome
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2014-02-01
    Description: Ecologists have long sought to understand the factors controlling the structure of savanna vegetation. Using data from 2154 sites in savannas across Africa, Australia, and South America, we found that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal area. However, among continents, the magnitude of these effects varied substantially, so that a single model cannot adequately represent savanna woody biomass across these regions. Historical and environmental differences drive the regional variation in the functional relationships between woody vegetation, fire, and climate. These same differences will determine the regional responses of vegetation to future climates, with implications for global carbon stocks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lehmann, Caroline E R -- Anderson, T Michael -- Sankaran, Mahesh -- Higgins, Steven I -- Archibald, Sally -- Hoffmann, William A -- Hanan, Niall P -- Williams, Richard J -- Fensham, Roderick J -- Felfili, Jeanine -- Hutley, Lindsay B -- Ratnam, Jayashree -- San Jose, Jose -- Montes, Ruben -- Franklin, Don -- Russell-Smith, Jeremy -- Ryan, Casey M -- Durigan, Giselda -- Hiernaux, Pierre -- Haidar, Ricardo -- Bowman, David M J S -- Bond, William J -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):548-52. doi: 10.1126/science.1247355.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Macquarie University, New South Wales 2109, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482480" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Australia ; *Climate ; *Ecosystem ; *Fires ; Humidity ; Models, Biological ; South America ; *Trees
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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