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  • Mice, Inbred C57BL  (207)
  • Rats
  • American Association for the Advancement of Science (AAAS)  (333)
  • American Chemical Society (ACS)
  • 2010-2014  (333)
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  • 1
    Publication Date: 2014-09-23
    Description: The neuromuscular junction (NMJ) is the synapse between a motor neuron and skeletal muscle. Defects in NMJ transmission cause muscle weakness, termed myasthenia. The muscle protein Dok-7 is essential for activation of the receptor kinase MuSK, which governs NMJ formation, and DOK7 mutations underlie familial limb-girdle myasthenia (DOK7 myasthenia), a neuromuscular disease characterized by small NMJs. Here, we show in a mouse model of DOK7 myasthenia that therapeutic administration of an adeno-associated virus (AAV) vector encoding the human DOK7 gene resulted in an enlargement of NMJs and substantial increases in muscle strength and life span. When applied to model mice of another neuromuscular disorder, autosomal dominant Emery-Dreifuss muscular dystrophy, DOK7 gene therapy likewise resulted in enlargement of NMJs as well as positive effects on motor activity and life span. These results suggest that therapies aimed at enlarging the NMJ may be useful for a range of neuromuscular disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arimura, Sumimasa -- Okada, Takashi -- Tezuka, Tohru -- Chiyo, Tomoko -- Kasahara, Yuko -- Yoshimura, Toshiro -- Motomura, Masakatsu -- Yoshida, Nobuaki -- Beeson, David -- Takeda, Shin'ichi -- Yamanashi, Yuji -- G0701521/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1505-8. doi: 10.1126/science.1250744.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. ; Department of Occupational Therapy, Nagasaki University School of Health Sciences, Nagasaki, Japan. ; Department of Electrical and Electronics Engineering, Faculty of Engineering, Nagasaki Institute of Applied Science, Nagasaki, Japan. ; Laboratory of Developmental Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. ; Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. yyamanas@ims.u-tokyo.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237101" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dependovirus ; Disease Models, Animal ; Female ; Genetic Therapy/*methods ; Genetic Vectors/administration & dosage ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle Proteins/*genetics ; Muscle, Skeletal/*innervation/physiopathology ; Muscular Dystrophies, Limb-Girdle/genetics/*pathology/*therapy ; Neuromuscular Junction/*pathology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-05-31
    Description: Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilhelm, Benjamin G -- Mandad, Sunit -- Truckenbrodt, Sven -- Krohnert, Katharina -- Schafer, Christina -- Rammner, Burkhard -- Koo, Seong Joo -- Classen, Gala A -- Krauss, Michael -- Haucke, Volker -- Urlaub, Henning -- Rizzoli, Silvio O -- New York, N.Y. -- Science. 2014 May 30;344(6187):1023-8. doi: 10.1126/science.1252884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Neurosciences, 37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Molecular Biology, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. ; Leibniz Institut fur Molekulare Pharmakologie, Department of Molecular Pharmacology and Cell Biology, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. Bioanalytics, Department of Clinical Chemistry, University Medical Center Gottingen, 37075 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. srizzol@gwdg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876496" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*metabolism/ultrastructure ; Exocytosis ; Imaging, Three-Dimensional ; Immunoblotting/methods ; Mass Spectrometry/methods ; Microscopy, Electron/methods ; Models, Neurological ; Presynaptic Terminals/chemistry/*metabolism/ultrastructure ; Protein Transport ; Rats ; Rats, Wistar ; Synaptic Vesicles/chemistry/*metabolism ; Synaptosomes/chemistry/*metabolism/ultrastructure ; Vesicular Transport Proteins/analysis/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-03-29
    Description: The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl(-)-binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wietek, Jonas -- Wiegert, J Simon -- Adeishvili, Nona -- Schneider, Franziska -- Watanabe, Hiroshi -- Tsunoda, Satoshi P -- Vogt, Arend -- Elstner, Marcus -- Oertner, Thomas G -- Hegemann, Peter -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):409-12. doi: 10.1126/science.1249375. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biology, Experimental Biophysics, Humboldt Universitat zu Berlin, D-10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674867" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Binding Sites ; CA1 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Ion Channel Gating ; Light ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Patch-Clamp Techniques ; Protein Conformation ; Protein Engineering ; Pyramidal Cells/metabolism ; Rats ; Recombinant Fusion Proteins/chemistry ; Rhodopsin/*chemistry/genetics/*metabolism ; Transfection
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-01-25
    Description: Episodic memory requires associations of temporally discontiguous events. In the entorhinal-hippocampal network, temporal associations are driven by a direct pathway from layer III of the medial entorhinal cortex (MECIII) to the hippocampal CA1 region. However, the identification of neural circuits that regulate this association has remained unknown. In layer II of entorhinal cortex (ECII), we report clusters of excitatory neurons called island cells, which appear in a curvilinear matrix of bulblike structures, directly project to CA1, and activate interneurons that target the distal dendrites of CA1 pyramidal neurons. Island cells suppress the excitatory MECIII input through the feed-forward inhibition to control the strength and duration of temporal association in trace fear memory. Together, the two EC inputs compose a control circuit for temporal association memory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kitamura, Takashi -- Pignatelli, Michele -- Suh, Junghyup -- Kohara, Keigo -- Yoshiki, Atsushi -- Abe, Kuniya -- Tonegawa, Susumu -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):896-901. doi: 10.1126/science.1244634. Epub 2014 Jan 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24457215" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Association ; CA1 Region, Hippocampal/cytology/*physiology ; Entorhinal Cortex/cytology/*physiology ; GABAergic Neurons/physiology ; Interneurons/physiology ; Membrane Proteins/genetics ; *Memory, Episodic ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Net ; Neurons/*physiology
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  • 5
    Publication Date: 2014-11-15
    Description: Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Benyue -- Chassaing, Benoit -- Shi, Zhenda -- Uchiyama, Robin -- Zhang, Zhan -- Denning, Timothy L -- Crawford, Sue E -- Pruijssers, Andrea J -- Iskarpatyoti, Jason A -- Estes, Mary K -- Dermody, Terence S -- Ouyang, Wenjun -- Williams, Ifor R -- Vijay-Kumar, Matam -- Gewirtz, Andrew T -- AI038296/AI/NIAID NIH HHS/ -- AI080656/AI/NIAID NIH HHS/ -- AI107943/AI/NIAID NIH HHS/ -- DK061417/DK/NIDDK NIH HHS/ -- DK064730/DK/NIDDK NIH HHS/ -- DK56338/DK/NIDDK NIH HHS/ -- R01 AI038296/AI/NIAID NIH HHS/ -- R37 AI038296/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):861-5. doi: 10.1126/science.1256999.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. ; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. ; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA. ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA. Departments of Pediatrics, Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA. ; Department of Immunology, Genentech, South San Francisco, CA, USA. ; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. ; Department of Nutritional Sciences and Medicine, Pennsylvania State University, University Park, PA 16802, USA. ; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. agewirtz@gsu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395539" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diarrhea/immunology/therapy/virology ; Disease Models, Animal ; Feces/virology ; Flagellin/*administration & dosage/immunology ; Homeodomain Proteins/genetics ; *Immunity, Innate ; Interleukin-18/administration & dosage/genetics/*immunology ; Interleukins/administration & dosage/genetics/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mutation ; Rotavirus Infections/immunology/*prevention & control/therapy ; Toll-Like Receptor 5/genetics/*physiology ; Virus Shedding
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  • 6
    Publication Date: 2014-05-07
    Description: Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral "rejuvenating" factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104429/" 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/PMC4104429/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sinha, Manisha -- Jang, Young C -- Oh, Juhyun -- Khong, Danika -- Wu, Elizabeth Y -- Manohar, Rohan -- Miller, Christine -- Regalado, Samuel G -- Loffredo, Francesco S -- Pancoast, James R -- Hirshman, Michael F -- Lebowitz, Jessica -- Shadrach, Jennifer L -- Cerletti, Massimiliano -- Kim, Mi-Jeong -- Serwold, Thomas -- Goodyear, Laurie J -- Rosner, Bernard -- Lee, Richard T -- Wagers, Amy J -- 1DP2 OD004345/OD/NIH HHS/ -- 1R01 AG033053/AG/NIA NIH HHS/ -- 1R01 AG040019/AG/NIA NIH HHS/ -- 5U01 HL100402/HL/NHLBI NIH HHS/ -- DP2 OD004345/OD/NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- R01 AG032977/AG/NIA NIH HHS/ -- R01 AG033053/AG/NIA NIH HHS/ -- R01 AG040019/AG/NIA NIH HHS/ -- R01 AR042238/AR/NIAMS NIH HHS/ -- R01 AR42238/AR/NIAMS NIH HHS/ -- T32 DE007057/DE/NIDCR NIH HHS/ -- U01 HL100402/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 9;344(6184):649-52. doi: 10.1126/science.1251152. Epub 2014 May 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24797481" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Aging/blood/drug effects/*physiology ; Animals ; Bone Morphogenetic Proteins/administration & dosage/blood/*physiology ; Growth Differentiation Factors/administration & dosage/blood/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*blood supply/drug effects/*physiology ; Myoblasts, Skeletal/drug effects/*physiology ; Parabiosis ; *Regeneration ; *Rejuvenation
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  • 7
    Publication Date: 2014-04-26
    Description: Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodopsins (originally cation-conducting) converted into chloride-conducting anion channels. These tools enable fast optical inhibition of action potentials and can be engineered to display step-function kinetics for stable inhibition, outlasting light pulses and for orders-of-magnitude-greater light sensitivity of inhibited cells. The resulting family of proteins defines an approach to more physiological, efficient, and sensitive optogenetic inhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096039/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096039/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berndt, Andre -- Lee, Soo Yeun -- Ramakrishnan, Charu -- Deisseroth, Karl -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):420-4. doi: 10.1126/science.1252367.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763591" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Amino Acid Sequence ; Animals ; CA1 Region, Hippocampal/cytology ; CA3 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Light ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Neurons/*physiology ; Optogenetics ; Patch-Clamp Techniques ; Protein Engineering ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/chemistry/metabolism ; Rhodopsin/*chemistry/genetics/*metabolism
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):239. doi: 10.1126/science.343.6168.239.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436399" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ants/*microbiology/physiology ; Brain/metabolism/microbiology ; Fat Body/virology ; Female ; Gryllidae/physiology/*virology ; Guanidines/analysis/metabolism ; *Host-Pathogen Interactions ; Hypocreales/*physiology ; Insect Viruses/*physiology ; Lizards/virology ; Male ; Rats ; Sexual Behavior, Animal/*physiology ; Sphingosine/analysis/metabolism ; Virus Replication
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  • 9
    Publication Date: 2014-05-31
    Description: Netrins are secreted proteins that regulate axon guidance and neuronal migration. Deleted in colorectal cancer (DCC) is a well-established netrin-1 receptor mediating attractive responses. We provide evidence that its close relative neogenin is also a functional netrin-1 receptor that acts with DCC to mediate guidance in vivo. We determined the structures of a functional netrin-1 region, alone and in complexes with neogenin or DCC. Netrin-1 has a rigid elongated structure containing two receptor-binding sites at opposite ends through which it brings together receptor molecules. The ligand/receptor complexes reveal two distinct architectures: a 2:2 heterotetramer and a continuous ligand/receptor assembly. The differences result from different lengths of the linker connecting receptor domains fibronectin type III domain 4 (FN4) and FN5, which differs among DCC and neogenin splice variants, providing a basis for diverse signaling outcomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369087/" 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/PMC4369087/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Kai -- Wu, Zhuhao -- Renier, Nicolas -- Antipenko, Alexander -- Tzvetkova-Robev, Dorothea -- Xu, Yan -- Minchenko, Maria -- Nardi-Dei, Vincenzo -- Rajashankar, Kanagalaghatta R -- Himanen, Juha -- Tessier-Lavigne, Marc -- Nikolov, Dimitar B -- P41 GM103403/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1275-9. doi: 10.1126/science.1255149. Epub 2014 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ; Laboratory of Brain Development and Repair, Rockefeller University, New York, NY 10065, USA. ; Department of Chemistry and Chemical Biology, Cornell University and Northeastern Collaborative Access Team, Advanced Photon Source, Argonne, IL 60439, USA. ; Laboratory of Brain Development and Repair, Rockefeller University, New York, NY 10065, USA. nikolovd@mskcc.org marctl@mail.rockefeller.edu. ; Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. nikolovd@mskcc.org marctl@mail.rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876346" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Cell Movement ; Fibronectins/chemistry ; Ligands ; Membrane Proteins/*chemistry/genetics/ultrastructure ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Nerve Growth Factors/*chemistry/genetics/ultrastructure ; Neurons/physiology ; Protein Multimerization ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/ultrastructure ; Tumor Suppressor Proteins/*chemistry/genetics/ultrastructure
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  • 10
    Publication Date: 2014-09-13
    Description: Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774895/" 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/PMC4774895/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goto, Yoshiyuki -- Obata, Takashi -- Kunisawa, Jun -- Sato, Shintaro -- Ivanov, Ivaylo I -- Lamichhane, Aayam -- Takeyama, Natsumi -- Kamioka, Mariko -- Sakamoto, Mitsuo -- Matsuki, Takahiro -- Setoyama, Hiromi -- Imaoka, Akemi -- Uematsu, Satoshi -- Akira, Shizuo -- Domino, Steven E -- Kulig, Paulina -- Becher, Burkhard -- Renauld, Jean-Christophe -- Sasakawa, Chihiro -- Umesaki, Yoshinori -- Benno, Yoshimi -- Kiyono, Hiroshi -- 1R01DK098378/DK/NIDDK NIH HHS/ -- R01 DK098378/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1254009. doi: 10.1126/science.1254009. Epub 2014 Aug 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka 567-0085, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. ; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Nippon Institute for Biological Science, Tokyo 198-0024, Japan. ; Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Yakult Central Institute, Tokyo 186-8650, Japan. ; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Department of Mucosal Immunology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. ; Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI 48109-5617, USA. ; Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland. ; Ludwig Institute for Cancer Research and Universite Catholique de Louvain, Brussels B-1200, Belgium. ; Nippon Institute for Biological Science, Tokyo 198-0024, Japan. Division of Bacterial Infection, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan. ; Benno Laboratory, Innovation Center, RIKEN, Wako, Saitama 351-0198, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214634" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Disease Models, Animal ; Fucose/*metabolism ; Fucosyltransferases/genetics/metabolism ; Germ-Free Life ; Glycosylation ; Goblet Cells/enzymology/immunology/microbiology ; Ileum/enzymology/immunology/microbiology ; *Immunity, Innate ; Interleukins/immunology ; Intestinal Mucosa/enzymology/*immunology/microbiology ; Lymphocytes/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Microbiota/*immunology ; Molecular Sequence Data ; Paneth Cells/enzymology/immunology/microbiology ; Salmonella Infections/*immunology/microbiology ; *Salmonella typhimurium
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  • 11
    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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  • 12
    Publication Date: 2014-10-25
    Description: During cell entry, capsids of incoming influenza A viruses (IAVs) must be uncoated before viral ribonucleoproteins (vRNPs) can enter the nucleus for replication. After hemagglutinin-mediated membrane fusion in late endocytic vacuoles, the vRNPs and the matrix proteins dissociate from each other and disperse within the cytosol. Here, we found that for capsid disassembly, IAV takes advantage of the host cell's aggresome formation and disassembly machinery. The capsids mimicked misfolded protein aggregates by carrying unanchored ubiquitin chains that activated a histone deacetylase 6 (HDAC6)-dependent pathway. The ubiquitin-binding domain was essential for recruitment of HDAC6 to viral fusion sites and for efficient uncoating and infection. That other components of the aggresome processing machinery, including dynein, dynactin, and myosin II, were also required suggested that physical forces generated by microtubule- and actin-associated motors are essential for IAV entry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Banerjee, Indranil -- Miyake, Yasuyuki -- Nobs, Samuel Philip -- Schneider, Christoph -- Horvath, Peter -- Kopf, Manfred -- Matthias, Patrick -- Helenius, Ari -- Yamauchi, Yohei -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):473-7. doi: 10.1126/science.1257037.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biochemistry, Eidgenossische Technische Hochschule (ETH) Zurich, Switzerland. ; Epigenetics, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. ; Institute of Molecular Health Sciences, ETH Zurich, Switzerland. ; Synthetic and Systems Biology Unit, Biological Research Center, Szeged, Hungary. ; Epigenetics, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. Faculty of Sciences, University of Basel, Basel, Switzerland. ; Institute of Biochemistry, Eidgenossische Technische Hochschule (ETH) Zurich, Switzerland. ari.helenius@bc.biol.ethz.ch yohei.yamauchi@bc.biol.ethz.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342804" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Capsid/*metabolism ; Cell Line, Tumor ; Cell Nucleus/virology ; Dyneins/metabolism ; Gene Knockout Techniques ; Histone Deacetylases/genetics/*physiology ; Host-Pathogen Interactions ; Humans ; Influenza A virus/*physiology ; Influenza, Human/genetics/metabolism/*virology ; Membrane Fusion/genetics/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubule-Associated Proteins/metabolism ; Microtubules/metabolism ; Myosin Type II/metabolism ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; RNA Interference ; Ribonucleoproteins/metabolism ; Ubiquitin/chemistry/metabolism ; *Virus Internalization ; Virus Replication
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  • 13
    Publication Date: 2014-11-02
    Description: Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice from the Collaborative Cross panel of recombinant inbred mice exhibit distinct disease phenotypes after mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, probably mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241145/" 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/PMC4241145/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rasmussen, Angela L -- Okumura, Atsushi -- Ferris, Martin T -- Green, Richard -- Feldmann, Friederike -- Kelly, Sara M -- Scott, Dana P -- Safronetz, David -- Haddock, Elaine -- LaCasse, Rachel -- Thomas, Matthew J -- Sova, Pavel -- Carter, Victoria S -- Weiss, Jeffrey M -- Miller, Darla R -- Shaw, Ginger D -- Korth, Marcus J -- Heise, Mark T -- Baric, Ralph S -- de Villena, Fernando Pardo-Manuel -- Feldmann, Heinz -- Katze, Michael G -- P51 OD010425/OD/NIH HHS/ -- U19 AI100625/AI/NIAID NIH HHS/ -- U19 AI109761/AI/NIAID NIH HHS/ -- U54 AI081680/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):987-91. doi: 10.1126/science.1259595. Epub 2014 Oct 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Washington, Seattle, WA, USA. ; Department of Microbiology, University of Washington, Seattle, WA, USA. Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA. ; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA. ; Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA. ; Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA. ; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA. Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA. ; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA. ; Department of Microbiology, University of Washington, Seattle, WA, USA. Washington National Primate Research Center, Seattle, WA, USA. honey@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359852" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Blood Coagulation/genetics ; Capillary Permeability/genetics ; *Disease Models, Animal ; Endothelium, Vascular/physiopathology ; *Genetic Predisposition to Disease ; Hemorrhagic Fever, Ebola/blood/*genetics/*immunology ; Host-Pathogen Interactions/*genetics ; Liver/blood supply/metabolism/pathology ; Lymphocyte Activation/immunology ; *Mice ; Mice, Inbred C57BL ; Neovascularization, Physiologic/genetics ; Receptor, TIE-2/*genetics
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  • 14
    Publication Date: 2014-02-01
    Description: Genetic errors in meiosis can lead to birth defects and spontaneous abortions. Checkpoint mechanisms of hitherto unknown nature eliminate oocytes with unrepaired DNA damage, causing recombination-defective mutant mice to be sterile. Here, we report that checkpoint kinase 2 (Chk2 or Chek2), is essential for culling mouse oocytes bearing unrepaired meiotic or induced DNA double-strand breaks (DSBs). Female infertility caused by a meiotic recombination mutation or irradiation was reversed by mutation of Chk2. Both meiotically programmed and induced DSBs trigger CHK2-dependent activation of TRP53 (p53) and TRP63 (p63), effecting oocyte elimination. These data establish CHK2 as essential for DNA damage surveillance in female meiosis and indicate that the oocyte DSB damage response primarily involves a pathway hierarchy in which ataxia telangiectasia and Rad3-related (ATR) signals to CHK2, which then activates p53 and p63.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048839/" 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/PMC4048839/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bolcun-Filas, Ewelina -- Rinaldi, Vera D -- White, Michelle E -- Schimenti, John C -- GM45415/GM/NIGMS NIH HHS/ -- R01 GM045415/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):533-6. doi: 10.1126/science.1247671.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Sciences, Cornell University, Ithaca, NY 14850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482479" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/genetics/metabolism ; Animals ; Cell Cycle Proteins/genetics/metabolism ; Checkpoint Kinase 2/genetics/*physiology ; *DNA Breaks, Double-Stranded ; Female ; HeLa Cells ; Humans ; Infertility, Female/*genetics/pathology ; Meiosis/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Oocytes/*metabolism/pathology ; Phosphoproteins/*metabolism ; Trans-Activators/*metabolism ; Tumor Suppressor Protein p53/*metabolism
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  • 15
    Publication Date: 2014-05-24
    Description: Cushing's syndrome is caused by excess cortisol production from the adrenocortical gland. In corticotropin-independent Cushing's syndrome, the excess cortisol production is primarily attributed to an adrenocortical adenoma, in which the underlying molecular pathogenesis has been poorly understood. We report a hotspot mutation (L206R) in PRKACA, which encodes the catalytic subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), in more than 50% of cases with adrenocortical adenomas associated with corticotropin-independent Cushing's syndrome. The L206R PRKACA mutant abolished its binding to the regulatory subunit of PKA (PRKAR1A) that inhibits catalytic activity of PRKACA, leading to constitutive, cAMP-independent PKA activation. These results highlight the major role of cAMP-independent activation of cAMP/PKA signaling by somatic mutations in corticotropin-independent Cushing's syndrome, providing insights into the diagnosis and therapeutics of this syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sato, Yusuke -- Maekawa, Shigekatsu -- Ishii, Ryohei -- Sanada, Masashi -- Morikawa, Teppei -- Shiraishi, Yuichi -- Yoshida, Kenichi -- Nagata, Yasunobu -- Sato-Otsubo, Aiko -- Yoshizato, Tetsuichi -- Suzuki, Hiromichi -- Shiozawa, Yusuke -- Kataoka, Keisuke -- Kon, Ayana -- Aoki, Kosuke -- Chiba, Kenichi -- Tanaka, Hiroko -- Kume, Haruki -- Miyano, Satoru -- Fukayama, Masashi -- Nureki, Osamu -- Homma, Yukio -- Ogawa, Seishi -- New York, N.Y. -- Science. 2014 May 23;344(6186):917-20. doi: 10.1126/science.1252328.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan. ; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. sogawa-tky@umin.ac.jp homma-uro@umin.ac.jp. ; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. sogawa-tky@umin.ac.jp homma-uro@umin.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855271" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenal Cortex Neoplasms/*genetics ; Adrenocortical Adenoma/*genetics ; Adrenocorticotropic Hormone/metabolism ; Animals ; Catalytic Domain/genetics ; Cushing Syndrome/*genetics/metabolism ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/*genetics/metabolism ; DNA Mutational Analysis ; GTP-Binding Protein alpha Subunits/genetics ; HEK293 Cells ; Humans ; Mice ; Mutation ; NIH 3T3 Cells ; PC12 Cells ; Rats
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  • 16
    Publication Date: 2014-02-08
    Description: We report that the oxytocin-mediated neuroprotective gamma-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naive mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tyzio, Roman -- Nardou, Romain -- Ferrari, Diana C -- Tsintsadze, Timur -- Shahrokhi, Amene -- Eftekhari, Sanaz -- Khalilov, Ilgam -- Tsintsadze, Vera -- Brouchoud, Corinne -- Chazal, Genevieve -- Lemonnier, Eric -- Lozovaya, Natalia -- Burnashev, Nail -- Ben-Ari, Yehezkel -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):675-9. doi: 10.1126/science.1247190.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503856" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*chemically induced/*genetics/metabolism ; Behavior, Animal ; Bumetanide/administration & dosage ; Chlorides/metabolism ; *Cytoprotection ; Disease Models, Animal ; Female ; Fragile X Mental Retardation Protein/genetics ; Maternal-Fetal Exchange ; Mice ; Oxytocin/*metabolism ; Parturition ; Pregnancy ; Rats ; Valproic Acid/pharmacology ; gamma-Aminobutyric Acid/*metabolism
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  • 17
    Publication Date: 2014-05-03
    Description: We demonstrate a technique for mapping brain activity that combines molecular specificity and spatial coverage using a neurotransmitter sensor detectable by magnetic resonance imaging (MRI). This molecular functional MRI (fMRI) method yielded time-resolved volumetric measurements of dopamine release evoked by reward-related lateral hypothalamic brain stimulation of rats injected with the neurotransmitter sensor. Peak dopamine concentrations and release rates were observed in the anterior nucleus accumbens core. Substantial dopamine transients were also present in more caudal areas. Dopamine-release amplitudes correlated with the rostrocaudal stimulation coordinate, suggesting participation of hypothalamic circuitry in modulating dopamine responses. This work provides a foundation for development and application of quantitative molecular fMRI techniques targeted toward numerous components of neural physiology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Taekwan -- Cai, Lili X -- Lelyveld, Victor S -- Hai, Aviad -- Jasanoff, Alan -- DP2-OD002114/OD/NIH HHS/ -- R01-DA02899/DA/NIDA NIH HHS/ -- R01-NS076462/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 May 2;344(6183):533-5. doi: 10.1126/science.1249380.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786083" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/*chemistry/genetics ; Brain Mapping/*methods ; Contrast Media/*chemistry ; Cytochrome P-450 Enzyme System/*chemistry/genetics ; Dopamine/*metabolism ; Dopaminergic Neurons ; Magnetic Resonance Imaging/*methods ; Male ; Molecular Imaging/*methods ; NADPH-Ferrihemoprotein Reductase/*chemistry/genetics ; Nucleus Accumbens/*metabolism ; Rats ; Rats, Sprague-Dawley
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  • 18
    Publication Date: 2014-04-05
    Description: Damage to the central nervous system caused by traumatic injury or neurological disorders can lead to permanent loss of voluntary motor function and muscle paralysis. Here, we describe an approach that circumvents central motor circuit pathology to restore specific skeletal muscle function. We generated murine embryonic stem cell-derived motor neurons that express the light-sensitive ion channel channelrhodopsin-2, which we then engrafted into partially denervated branches of the sciatic nerve of adult mice. These engrafted motor neurons not only reinnervated lower hind-limb muscles but also enabled their function to be restored in a controllable manner using optogenetic stimulation. This synthesis of regenerative medicine and optogenetics may be a successful strategy to restore muscle function after traumatic injury or disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bryson, J Barney -- Machado, Carolina Barcellos -- Crossley, Martin -- Stevenson, Danielle -- Bros-Facer, Virginie -- Burrone, Juan -- Greensmith, Linda -- Lieberam, Ivo -- 095589/Wellcome Trust/United Kingdom -- G0900585/Medical Research Council/United Kingdom -- G1001234/Biotechnology and Biological Sciences Research Council/United Kingdom -- MR/K000608/1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):94-7. doi: 10.1126/science.1248523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Cell Line ; Electric Stimulation ; Embryonic Stem Cells/cytology/physiology ; Female ; Hindlimb ; Isometric Contraction ; *Light ; Mice ; Mice, Inbred C57BL ; Motor Neurons/cytology/*physiology/*transplantation ; Muscle Denervation ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/*innervation/*physiology ; Nerve Regeneration ; *Optogenetics ; Rhodopsin/genetics/metabolism ; Sciatic Nerve/physiology ; Transfection ; Transgenes
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  • 19
    Publication Date: 2014-05-17
    Description: Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family of versatile cell recognition molecules, as retrograde signals for elimination of redundant climbing fiber to Purkinje cell synapses in developing mouse cerebellum. Knockdown of Sema3A, a secreted semaphorin, in Purkinje cells or its receptor in climbing fibers accelerated synapse elimination during postnatal day 8 (P8) to P18. Conversely, knockdown of Sema7A, a membrane-anchored semaphorin, in Purkinje cells or either of its two receptors in climbing fibers impaired synapse elimination after P15. The effect of Sema7A involves signaling by metabotropic glutamate receptor 1, a canonical pathway for climbing fiber synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of synapse elimination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uesaka, Naofumi -- Uchigashima, Motokazu -- Mikuni, Takayasu -- Nakazawa, Takanobu -- Nakao, Harumi -- Hirai, Hirokazu -- Aiba, Atsu -- Watanabe, Masahiko -- Kano, Masanobu -- New York, N.Y. -- Science. 2014 May 30;344(6187):1020-3. doi: 10.1126/science.1252514. Epub 2014 May 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. ; Laboratory of Animal Resources, Center for Disease Biology and Integrated Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ; Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. ; Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. mkano-tky@m.u-tokyo.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24831527" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/genetics/*metabolism ; Brain/*growth & development/metabolism ; Gene Knockdown Techniques ; Mice ; Mice, Inbred C57BL ; Purkinje Cells/metabolism/*physiology ; RNA Interference ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/genetics/metabolism ; Semaphorin-3A/genetics/*metabolism ; Semaphorins/genetics/*metabolism ; Signal Transduction ; Synapses/genetics/*physiology
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):149. doi: 10.1126/science.346.6206.149-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Geographic Information Systems ; Hippocampus/*cytology ; Humans ; Neurons/*physiology ; *Neurosciences ; *Nobel Prize ; Rats ; Spatial Behavior/*physiology
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  • 21
    Publication Date: 2014-01-05
    Description: Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Delta(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vallee, Monique -- Vitiello, Sergio -- Bellocchio, Luigi -- Hebert-Chatelain, Etienne -- Monlezun, Stephanie -- Martin-Garcia, Elena -- Kasanetz, Fernando -- Baillie, Gemma L -- Panin, Francesca -- Cathala, Adeline -- Roullot-Lacarriere, Valerie -- Fabre, Sandy -- Hurst, Dow P -- Lynch, Diane L -- Shore, Derek M -- Deroche-Gamonet, Veronique -- Spampinato, Umberto -- Revest, Jean-Michel -- Maldonado, Rafael -- Reggio, Patricia H -- Ross, Ruth A -- Marsicano, Giovanni -- Piazza, Pier Vincenzo -- 260515/European Research Council/International -- DA-003934/DA/NIDA NIH HHS/ -- DA-03672/DA/NIDA NIH HHS/ -- DA-09789/DA/NIDA NIH HHS/ -- K05 DA021358/DA/NIDA NIH HHS/ -- R01 DA003934/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):94-8. doi: 10.1126/science.1243985.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U862, F-33000 Bordeaux, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385629" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*drug effects/metabolism ; Cannabinoid Receptor Antagonists/administration & dosage ; Cannabis/*toxicity ; Dronabinol/*toxicity ; Male ; Marijuana Abuse/drug therapy ; Mice ; Mice, Inbred C57BL ; Pregnenolone/*administration & dosage/*metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptor, Cannabinoid, CB1/*agonists/*antagonists & inhibitors
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  • 22
    Publication Date: 2014-01-25
    Description: Liver regeneration requires spatially and temporally precisely coordinated proliferation of the two major hepatic cell populations, hepatocytes and liver sinusoidal endothelial cells (LSECs), to reconstitute liver structure and function. The underlying mechanisms of this complex molecular cross-talk remain elusive. Here, we show that the expression of Angiopoietin-2 (Ang2) in LSECs is dynamically regulated after partial hepatectomy. During the early inductive phase of liver regeneration, Ang2 down-regulation leads to reduced LSEC transforming growth factor-beta1 production, enabling hepatocyte proliferation by releasing an angiocrine proliferative brake. During the later angiogenic phase of liver regeneration, recovery of endothelial Ang2 expression enables regenerative angiogenesis by controlling LSEC vascular endothelial growth factor receptor 2 expression. The data establish LSECs as a dynamic rheostat of liver regeneration, spatiotemporally orchestrating hepatocyte and LSEC proliferation through angiocrine- and autocrine-acting Ang2, respectively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Junhao -- Srivastava, Kshitij -- Wieland, Matthias -- Runge, Anja -- Mogler, Carolin -- Besemfelder, Eva -- Terhardt, Dorothee -- Vogel, Marion J -- Cao, Liji -- Korn, Claudia -- Bartels, Susanne -- Thomas, Markus -- Augustin, Hellmut G -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):416-9. doi: 10.1126/science.1244880.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), DKFZ-Center for Molecular Biology Alliance, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458641" target="_blank"〉PubMed〈/a〉
    Keywords: Angiopoietin-2/genetics/*metabolism ; Animals ; *Cell Proliferation ; Endothelium, Vascular/*metabolism ; Hepatectomy ; Hepatocytes/cytology/*physiology ; Liver Regeneration/genetics/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neovascularization, Physiologic/genetics/physiology ; Transforming Growth Factor beta/metabolism
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  • 23
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimm, David -- New York, N.Y. -- Science. 2014 May 2;344(6183):461. doi: 10.1126/science.344.6183.461.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786056" target="_blank"〉PubMed〈/a〉
    Keywords: Analgesia ; Animals ; Anti-Inflammatory Agents/administration & dosage ; Biomedical Research/*standards ; Female ; Humans ; Male ; Mice ; *Odors ; Pain/*physiopathology/prevention & control ; Pain Measurement ; Pain Threshold ; Rats ; Sex Factors ; *Smell
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):361-3. doi: 10.1126/science.343.6169.361.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458620" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemically-Induced Disorders/*genetics ; DNA Methylation/drug effects ; *Epigenesis, Genetic ; Epigenomics/economics/trends ; Evolution, Molecular ; Female ; Humans ; Male ; Rats ; Reproduction/drug effects/genetics ; Sexual Behavior, Animal/drug effects ; Spermatozoa/*abnormalities/*drug effects
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  • 25
    Publication Date: 2014-12-20
    Description: Multivalent molecules with repetitive structures including bacterial capsular polysaccharides and viral capsids elicit antibody responses through B cell receptor (BCR) crosslinking in the absence of T cell help. We report that immunization with these T cell-independent type 2 (TI-2) antigens causes up-regulation of endogenous retrovirus (ERV) RNAs in antigen-specific mouse B cells. These RNAs are detected via a mitochondrial antiviral signaling protein (MAVS)-dependent RNA sensing pathway or reverse-transcribed and detected via the cGAS-cGAMP-STING pathway, triggering a second, sustained wave of signaling that promotes specific immunoglobulin M production. Deficiency of both MAVS and cGAS, or treatment of MAVS-deficient mice with reverse transcriptase inhibitors, dramatically inhibits TI-2 antibody responses. These findings suggest that ERV and two innate sensing pathways that detect them are integral components of the TI-2 B cell signaling apparatus.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391621/" 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/PMC4391621/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zeng, Ming -- Hu, Zeping -- Shi, Xiaolei -- Li, Xiaohong -- Zhan, Xiaoming -- Li, Xiao-Dong -- Wang, Jianhui -- Choi, Jin Huk -- Wang, Kuan-wen -- Purrington, Tiana -- Tang, Miao -- Fina, Maggy -- DeBerardinis, Ralph J -- Moresco, Eva Marie Y -- Pedersen, Gabriel -- McInerney, Gerald M -- Karlsson Hedestam, Gunilla B -- Chen, Zhijian J -- Beutler, Bruce -- P01 AI070167/AI/NIAID NIH HHS/ -- R01 AI093967/AI/NIAID NIH HHS/ -- R01 CA157996/CA/NCI NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1486-92. doi: 10.1126/science.346.6216.1486.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. ; Department of Pediatrics and Children's Medical Center Research Institute, and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. ; Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA. ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels vag 16, SE-171 77 Stockholm, Sweden. ; Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. Bruce.Beutler@UTSouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525240" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/*immunology ; Animals ; Antibody Formation ; Antigens, T-Independent/*immunology ; B-Lymphocytes/*immunology ; Cytosol/immunology ; DNA/immunology ; Endogenous Retroviruses/genetics/*immunology ; Lymphocyte Activation ; Membrane Proteins/immunology ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Nucleotides, Cyclic/immunology ; Nucleotidyltransferases/genetics/*immunology ; RNA, Viral/genetics/*immunology ; Transcription, Genetic
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  • 26
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-31
    Description: N-Methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors, which mediate most excitatory synaptic transmission in mammalian brains. Calcium permeation triggered by activation of NMDA receptors is the pivotal event for initiation of neuronal plasticity. Here, we show the crystal structure of the intact heterotetrameric GluN1-GluN2B NMDA receptor ion channel at 4 angstroms. The NMDA receptors are arranged as a dimer of GluN1-GluN2B heterodimers with the twofold symmetry axis running through the entire molecule composed of an amino terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD). The ATD and LBD are much more highly packed in the NMDA receptors than non-NMDA receptors, which may explain why ATD regulates ion channel activity in NMDA receptors but not in non-NMDA receptors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113085/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113085/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karakas, Erkan -- Furukawa, Hiro -- MH085926/MH/NIMH NIH HHS/ -- R01 GM105730/GM/NIGMS NIH HHS/ -- R01 MH085926/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):992-7. doi: 10.1126/science.1251915.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, W. M. Keck Structural Biology Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. ; Cold Spring Harbor Laboratory, W. M. Keck Structural Biology Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. furukawa@cshl.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876489" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Calcium/chemistry/metabolism ; Crystallography, X-Ray ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Receptors, N-Methyl-D-Aspartate/*chemistry/metabolism
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  • 27
    Publication Date: 2014-05-07
    Description: In the adult central nervous system, the vasculature of the neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline of neurogenesis and cognitive function is associated with reduced blood flow and decreased numbers of neural stem cells. Therefore, restoring the functionality of the niche should counteract some of the negative effects of aging. We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice. Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative and neurovascular diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123747/" 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/PMC4123747/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsimpardi, Lida -- Litterman, Nadia K -- Schein, Pamela A -- Miller, Christine M -- Loffredo, Francesco S -- Wojtkiewicz, Gregory R -- Chen, John W -- Lee, Richard T -- Wagers, Amy J -- Rubin, Lee L -- 1DP2 OD004345/OD/NIH HHS/ -- 1R01 AG033053/AG/NIA NIH HHS/ -- 1R01 AG040019/AG/NIA NIH HHS/ -- 5U01 HL100402/HL/NHLBI NIH HHS/ -- DP2 OD004345/OD/NIH HHS/ -- R01 AG032977/AG/NIA NIH HHS/ -- R01 AG033053/AG/NIA NIH HHS/ -- R01 AG040019/AG/NIA NIH HHS/ -- R01 NS070835/NS/NINDS NIH HHS/ -- R01 NS072167/NS/NINDS NIH HHS/ -- R01NS070835/NS/NINDS NIH HHS/ -- R01NS072167/NS/NINDS NIH HHS/ -- U01 HL100402/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 9;344(6184):630-4. doi: 10.1126/science.1251141. Epub 2014 May 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24797482" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*drug effects ; Animals ; Bone Morphogenetic Proteins/*administration & dosage/blood/physiology ; Brain/blood supply/*drug effects ; Cerebrovascular Circulation/*drug effects ; Cognition/drug effects ; Endothelium, Vascular/cytology/drug effects ; Growth Differentiation Factors/*administration & dosage/blood/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/cytology/*drug effects ; Neurogenesis/*drug effects ; Olfactory Bulb/cytology/drug effects ; Parabiosis ; Recombinant Proteins/administration & dosage ; *Rejuvenation
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  • 28
    Publication Date: 2014-08-12
    Description: Top-down modulation of sensory processing allows the animal to select inputs most relevant to current tasks. We found that the cingulate (Cg) region of the mouse frontal cortex powerfully influences sensory processing in the primary visual cortex (V1) through long-range projections that activate local gamma-aminobutyric acid-ergic (GABAergic) circuits. Optogenetic activation of Cg neurons enhanced V1 neuron responses and improved visual discrimination. Focal activation of Cg axons in V1 caused a response increase at the activation site but a decrease at nearby locations (center-surround modulation). Whereas somatostatin-positive GABAergic interneurons contributed preferentially to surround suppression, vasoactive intestinal peptide-positive interneurons were crucial for center facilitation. Long-range corticocortical projections thus act through local microcircuits to exert spatially specific top-down modulation of sensory processing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Siyu -- Xu, Min -- Kamigaki, Tsukasa -- Hoang Do, Johnny Phong -- Chang, Wei-Cheng -- Jenvay, Sean -- Miyamichi, Kazunari -- Luo, Liqun -- Dan, Yang -- R01 EY018861/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 8;345(6197):660-5. doi: 10.1126/science.1254126.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. ; Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. ; Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. ydan@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25104383" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Discrimination (Psychology) ; GABAergic Neurons/chemistry/*physiology ; Gyrus Cinguli/cytology/*physiology ; Interneurons ; Mice ; Mice, Inbred C57BL ; Neural Inhibition ; Photic Stimulation ; Somatostatin/analysis ; Visual Cortex/cytology/*physiology ; Visual Perception/*physiology
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1194-7. doi: 10.1126/science.343.6176.1194.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626911" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria ; Beetles ; Cough/microbiology ; Humans ; Plant Leaves ; Rats ; Skin ; Sneezing ; Surface Tension ; Viruses ; Water/*chemistry ; *Wettability
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  • 30
    Publication Date: 2014-02-22
    Description: Growth factors (GFs) are critical in tissue repair, but their translation to clinical use has been modest. Physiologically, GF interactions with extracellular matrix (ECM) components facilitate localized and spatially regulated signaling; therefore, we reasoned that the lack of ECM binding in their clinically used forms could underlie the limited translation. We discovered that a domain in placenta growth factor-2 (PlGF-2(123-144)) binds exceptionally strongly and promiscuously to ECM proteins. By fusing this domain to the GFs vascular endothelial growth factor-A, platelet-derived growth factor-BB, and bone morphogenetic protein-2, we generated engineered GF variants with super-affinity to the ECM. These ECM super-affinity GFs induced repair in rodent models of chronic wounds and bone defects that was greatly enhanced as compared to treatment with the wild-type GFs, demonstrating that this approach may be useful in several regenerative medicine applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martino, Mikael M -- Briquez, Priscilla S -- Guc, Esra -- Tortelli, Federico -- Kilarski, Witold W -- Metzger, Stephanie -- Rice, Jeffrey J -- Kuhn, Gisela A -- Muller, Ralph -- Swartz, Melody A -- Hubbell, Jeffrey A -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):885-8. doi: 10.1126/science.1247663.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24558160" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Protein 2/chemistry/genetics/metabolism ; Disease Models, Animal ; Extracellular Matrix/*metabolism ; Extracellular Matrix Proteins/chemistry/metabolism ; Heparitin Sulfate/chemistry/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pregnancy Proteins/chemistry/genetics/metabolism ; Protein Engineering ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-sis/chemistry/genetics/metabolism ; Vascular Endothelial Growth Factor A/chemistry/genetics/metabolism ; *Wound Healing
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  • 31
    Publication Date: 2014-07-19
    Description: Cytoplasmic dynein is a molecular motor that transports a large variety of cargoes (e.g., organelles, messenger RNAs, and viruses) along microtubules over long intracellular distances. The dynactin protein complex is important for dynein activity in vivo, but its precise role has been unclear. Here, we found that purified mammalian dynein did not move processively on microtubules in vitro. However, when dynein formed a complex with dynactin and one of four different cargo-specific adapter proteins, the motor became ultraprocessive, moving for distances similar to those of native cargoes in living cells. Thus, we propose that dynein is largely inactive in the cytoplasm and that a variety of adapter proteins activate processive motility by linking dynactin to dynein only when the motor is bound to its proper cargo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224444/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224444/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKenney, Richard J -- Huynh, Walter -- Tanenbaum, Marvin E -- Bhabha, Gira -- Vale, Ronald D -- F32GM096484/GM/NIGMS NIH HHS/ -- R01 GM097312/GM/NIGMS NIH HHS/ -- R01GM097312/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):337-41. doi: 10.1126/science.1254198. Epub 2014 Jun 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. ; Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. vale@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035494" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; Cytoplasmic Dyneins/chemistry/*metabolism ; Humans ; Mice ; Microtubule-Associated Proteins/*metabolism ; Microtubules/chemistry/*metabolism ; Motion ; Protein Transport ; Rats
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  • 32
    Publication Date: 2014-01-25
    Description: How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A-deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)-producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313730/" 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/PMC4313730/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spencer, S P -- Wilhelm, C -- Yang, Q -- Hall, J A -- Bouladoux, N -- Boyd, A -- Nutman, T B -- Urban, J F Jr -- Wang, J -- Ramalingam, T R -- Bhandoola, A -- Wynn, T A -- Belkaid, Y -- F30 DK094708/DK/NIDDK NIH HHS/ -- Z99 AI999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):432-7. doi: 10.1126/science.1247606.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunity at Barrier Sites Initiative, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458645" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptive Immunity ; Animals ; Citrobacter rodentium/immunology ; Enterobacteriaceae Infections/immunology ; Homeodomain Proteins/genetics ; *Immunity, Innate ; Interleukin-13/biosynthesis ; Lymphocytes/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Micronutrients/*deficiency ; Vitamin A/*immunology ; Vitamin A Deficiency/*immunology
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  • 33
    Publication Date: 2014-01-11
    Description: Expression from both alleles is generally observed in analyses of diploid cell populations, but studies addressing allelic expression patterns genome-wide in single cells are lacking. Here, we present global analyses of allelic expression across individual cells of mouse preimplantation embryos of mixed background (CAST/EiJ x C57BL/6J). We discovered abundant (12 to 24%) monoallelic expression of autosomal genes and that expression of the two alleles occurs independently. The monoallelic expression appeared random and dynamic because there was considerable variation among closely related embryonic cells. Similar patterns of monoallelic expression were observed in mature cells. Our allelic expression analysis also demonstrates the de novo inactivation of the paternal X chromosome. We conclude that independent and stochastic allelic transcription generates abundant random monoallelic expression in the mammalian cell.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Qiaolin -- Ramskold, Daniel -- Reinius, Bjorn -- Sandberg, Rickard -- New York, N.Y. -- Science. 2014 Jan 10;343(6167):193-6. doi: 10.1126/science.1245316.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24408435" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Animals ; Embryonic Development/genetics ; Female ; *Gene Expression Regulation, Developmental ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Messenger, Stored/genetics ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; X Chromosome/genetics ; X Chromosome Inactivation/*genetics
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  • 34
    Publication Date: 2014-08-12
    Description: Ionotropic glutamate receptors (iGluRs) mediate most excitatory neurotransmission in the central nervous system and function by opening their ion channel in response to binding of agonist glutamate. Here, we report a structure of a homotetrameric rat GluA2 receptor in complex with partial agonist (S)-5-nitrowillardiine. Comparison of this structure with the closed-state structure in complex with competitive antagonist ZK 200775 suggests conformational changes that occur during iGluR gating. Guided by the structures, we engineered disulfide cross-links to probe domain interactions that are important for iGluR gating events. The combination of structural information, kinetic modeling, and biochemical and electrophysiological experiments provides insight into the mechanism of iGluR gating.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383034/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yelshanskaya, Maria V -- Li, Minfen -- Sobolevsky, Alexander I -- NS083660/NS/NINDS NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- P41 GM111244/GM/NIGMS NIH HHS/ -- R01 NS083660/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1070-4. doi: 10.1126/science.1256508. Epub 2014 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, NY 10032, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, NY 10032, USA. as4005@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25103407" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; Cysteine/chemistry ; Glutamic Acid/pharmacology ; HEK293 Cells ; Humans ; *Ion Channel Gating ; Models, Chemical ; Organophosphonates/chemistry/pharmacology ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Pyrimidinones/*pharmacology ; Quinoxalines/chemistry/pharmacology ; Rats ; Receptors, AMPA/*agonists/*chemistry/genetics
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  • 35
    Publication Date: 2014-01-25
    Description: Little is known about how microcircuits are organized in layer 2 of the medial entorhinal cortex. We visualized principal cell microcircuits and determined cellular theta-rhythmicity in freely moving rats. Non-dentate-projecting, calbindin-positive pyramidal cells bundled dendrites together and formed patches arranged in a hexagonal grid aligned to layer 1 axons, parasubiculum, and cholinergic inputs. Calbindin-negative, dentate-gyrus-projecting stellate cells were distributed across layer 2 but avoided centers of calbindin-positive patches. Cholinergic drive sustained theta-rhythmicity, which was twofold stronger in pyramidal than in stellate neurons. Theta-rhythmicity was cell-type-specific but not distributed as expected from cell-intrinsic properties. Layer 2 divides into a weakly theta-locked stellate cell lattice and spatiotemporally highly organized pyramidal grid. It needs to be assessed how these two distinct principal cell networks contribute to grid cell activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ray, Saikat -- Naumann, Robert -- Burgalossi, Andrea -- Tang, Qiusong -- Schmidt, Helene -- Brecht, Michael -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):891-6. doi: 10.1126/science.1243028. Epub 2014 Jan 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bernstein Center for Computational Neuroscience, Humboldt University of Berlin, Philippstrasse 13 Haus 6, 10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24457213" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/metabolism ; Animals ; Calbindins/analysis/metabolism ; Dendrites/physiology ; Dentate Gyrus/physiology ; Entorhinal Cortex/*cytology/metabolism/physiology ; Female ; Male ; *Nerve Net ; Pyramidal Cells/metabolism/*physiology/*ultrastructure ; Rats ; Rats, Wistar ; Staining and Labeling ; *Theta Rhythm
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  • 36
    Publication Date: 2014-08-12
    Description: Type I interferon (IFN) protects against viruses, yet it also has a poorly understood suppressive influence on inflammation. Here, we report that activated mouse macrophages lacking the IFN-stimulated gene cholesterol 25-hydroxylase (Ch25h) and that are unable to produce the oxysterol 25-hydroxycholesterol (25-HC) overproduce inflammatory interleukin-1 (IL-1) family cytokines. 25-HC acts by antagonizing sterol response element-binding protein (SREBP) processing to reduce Il1b transcription and to broadly repress IL-1-activating inflammasomes. In accord with these dual actions of 25-HC, Ch25h-deficient mice exhibit increased sensitivity to septic shock, exacerbated experimental autoimmune encephalomyelitis, and a stronger ability to repress bacterial growth. These findings identify an oxysterol, 25-HC, as a critical mediator in the negative-feedback pathway of IFN signaling on IL-1 family cytokine production and inflammasome activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289637/" 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/PMC4289637/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reboldi, Andrea -- Dang, Eric V -- McDonald, Jeffrey G -- Liang, Guosheng -- Russell, David W -- Cyster, Jason G -- 2P01HL20948/HL/NHLBI NIH HHS/ -- AI40098/AI/NIAID NIH HHS/ -- P01 HL020948/HL/NHLBI NIH HHS/ -- R01 AI040098/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 8;345(6197):679-84. doi: 10.1126/science.1254790.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA. ; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Howard Hughes Medical Institute, Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA. jason.cyster@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25104388" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Encephalomyelitis, Autoimmune, Experimental/genetics/immunology ; Feedback, Physiological ; Hydroxycholesterols/*metabolism ; Inflammasomes/genetics/immunology ; Inflammation/*genetics/immunology/microbiology ; Interferon Type I/*immunology ; Interleukin-1/immunology ; Macrophage Activation ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Response Elements/genetics ; Shock, Septic/genetics/immunology ; Steroid Hydroxylases/genetics/*immunology
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  • 37
    Publication Date: 2014-06-28
    Description: Mammals are coinfected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine gamma-herpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-gamma (IFNgamma) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi's sarcoma-associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFNgamma reactivated latent murine gamma-herpesvirus infection in vivo, suggesting a "two-signal" model for viral reactivation. Thus, chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531374/" 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/PMC4531374/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reese, T A -- Wakeman, B S -- Choi, H S -- Hufford, M M -- Huang, S C -- Zhang, X -- Buck, M D -- Jezewski, A -- Kambal, A -- Liu, C Y -- Goel, G -- Murray, P J -- Xavier, R J -- Kaplan, M H -- Renne, R -- Speck, S H -- Artyomov, M N -- Pearce, E J -- Virgin, H W -- AI032573/AI/NIAID NIH HHS/ -- AI084887/AI/NIAID NIH HHS/ -- CA119917/CA/NCI NIH HHS/ -- CA164062/CA/NCI NIH HHS/ -- CA52004/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- R01 AI032573/AI/NIAID NIH HHS/ -- R01 AI084887/AI/NIAID NIH HHS/ -- R01 AI095282/AI/NIAID NIH HHS/ -- R01 CA052004/CA/NCI NIH HHS/ -- R01 CA119917/CA/NCI NIH HHS/ -- R01 CA164062/CA/NCI NIH HHS/ -- U54 AI057160/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 1;345(6196):573-7. doi: 10.1126/science.1254517. Epub 2014 Jun 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Emory University Vaccine Center, Atlanta, GA 30322, USA. ; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. ; Departments of Pediatrics and Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. ; Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ; Departments of Infectious Diseases and Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. virgin@wustl.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24968940" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gammaherpesvirinae/genetics/*physiology ; Gene Expression Regulation, Viral ; Herpesvirus 8, Human/genetics/*physiology ; Humans ; Interferon-gamma/*immunology/pharmacology ; Interleukin-4/*metabolism/pharmacology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Nematospiroides dubius/immunology ; Ovum/immunology ; Promoter Regions, Genetic ; STAT6 Transcription Factor/*metabolism ; Schistosoma mansoni/*immunology ; Schistosomiasis mansoni/*immunology ; Strongylida Infections/immunology ; Virus Activation/drug effects/genetics/*physiology ; Virus Latency/physiology ; Virus Replication/physiology
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  • 38
    Publication Date: 2014-08-16
    Description: The rules governing the formation of spatial maps in the hippocampus have not been determined. We investigated the large-scale structure of place field activity by recording hippocampal neurons in rats exploring a previously unencountered 48-meter-long track. Single-cell and population activities were well described by a two-parameter stochastic model. Individual neurons had their own characteristic propensity for forming fields randomly along the track, with some cells expressing many fields and many exhibiting few or none. Because of the particular distribution of propensities across cells, the number of neurons with fields scaled logarithmically with track length over a wide, ethological range. These features constrain hippocampal memory mechanisms, may allow efficient encoding of environments and experiences of vastly different extents and durations, and could reflect general principles of population coding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rich, P Dylan -- Liaw, Hua-Peng -- Lee, Albert K -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):814-7. doi: 10.1126/science.1255635. Epub 2014 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK. richp@janelia.hhmi.org leea@janelia.hhmi.org. ; Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. ; Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. richp@janelia.hhmi.org leea@janelia.hhmi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124440" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Brain Mapping ; CA1 Region, Hippocampal/cytology/*physiology ; Electrodes, Implanted ; Exploratory Behavior ; Male ; Maze Learning ; Memory/physiology ; Orientation ; Poisson Distribution ; Pyramidal Cells/*physiology ; Rats ; Rats, Long-Evans ; *Space Perception
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  • 39
    Publication Date: 2014-01-11
    Description: Many bacterial pathogens cause persistent infections despite repeated antibiotic exposure. Bacterial persisters are antibiotic-tolerant cells, but little is known about their growth status and the signals and pathways leading to their formation in infected tissues. We used fluorescent single-cell analysis to identify Salmonella persisters during infection. These were part of a nonreplicating population formed immediately after uptake by macrophages and were induced by vacuolar acidification and nutritional deprivation, conditions that also induce Salmonella virulence gene expression. The majority of 14 toxin-antitoxin modules contributed to intracellular persister formation. Some persisters resumed intracellular growth after phagocytosis by naive macrophages. Thus, the vacuolar environment induces phenotypic heterogeneity, leading to either bacterial replication or the formation of nonreplicating persisters that could provide a reservoir for relapsing infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helaine, Sophie -- Cheverton, Angela M -- Watson, Kathryn G -- Faure, Laura M -- Matthews, Sophie A -- Holden, David W -- 095484/Wellcome Trust/United Kingdom -- MR/K027077/1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Jan 10;343(6167):204-8. doi: 10.1126/science.1244705.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24408438" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Antitoxins/genetics ; Bacterial Toxins/genetics ; Cefotaxime/pharmacology ; Gene Deletion ; Gene Expression Regulation, Bacterial ; Lymph Nodes/immunology/microbiology ; Macrophages/*microbiology ; Mesentery/immunology/microbiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Operon/genetics ; Phagocytosis ; Pyrophosphatases/genetics ; Recurrence ; Salmonella Infections/*immunology/*microbiology ; Salmonella typhimurium/drug effects/genetics/*growth & development ; Spleen/immunology/microbiology ; Virulence
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  • 40
    Publication Date: 2014-04-20
    Description: Myelin is a defining feature of the vertebrate nervous system. Variability in the thickness of the myelin envelope is a structural feature affecting the conduction of neuronal signals. Conversely, the distribution of myelinated tracts along the length of axons has been assumed to be uniform. Here, we traced high-throughput electron microscopy reconstructions of single axons of pyramidal neurons in the mouse neocortex and built high-resolution maps of myelination. We find that individual neurons have distinct longitudinal distribution of myelin. Neurons in the superficial layers displayed the most diversified profiles, including a new pattern where myelinated segments are interspersed with long, unmyelinated tracts. Our data indicate that the profile of longitudinal distribution of myelin is an integral feature of neuronal identity and may have evolved as a strategy to modulate long-distance communication in the neocortex.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122120/" 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/PMC4122120/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomassy, Giulio Srubek -- Berger, Daniel R -- Chen, Hsu-Hsin -- Kasthuri, Narayanan -- Hayworth, Kenneth J -- Vercelli, Alessandro -- Seung, H Sebastian -- Lichtman, Jeff W -- Arlotta, Paola -- 1P50MH094271/MH/NIMH NIH HHS/ -- NS062849/NS/NINDS NIH HHS/ -- NS078164/NS/NINDS NIH HHS/ -- P50 MH094271/MH/NIMH NIH HHS/ -- R01 EB016411/EB/NIBIB NIH HHS/ -- R01 NS062849/NS/NINDS NIH HHS/ -- R01 NS078164/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):319-24. doi: 10.1126/science.1249766.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744380" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Image Processing, Computer-Assisted ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron ; Myelin Sheath/*physiology ; Neocortex/*cytology/physiology ; Oligodendroglia/cytology/physiology ; Pyramidal Cells/cytology/*physiology ; Somatosensory Cortex/*cytology/physiology ; Visual Cortex/*cytology/physiology
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  • 41
    Publication Date: 2014-08-30
    Description: The pathogen recognition theory dictates that, upon viral infection, the innate immune system first detects microbial products and then responds by providing instructions to adaptive CD8 T cells. Here, we show in mice that tissue resident memory CD8 T cells (T(RM) cells), non-recirculating cells located at common sites of infection, can achieve near-sterilizing immunity against viral infections by reversing this flow of information. Upon antigen resensitization within the mouse female reproductive mucosae, CD8(+) T(RM) cells secrete cytokines that trigger rapid adaptive and innate immune responses, including local humoral responses, maturation of local dendritic cells, and activation of natural killer cells. This provided near-sterilizing immunity against an antigenically unrelated viral infection. Thus, CD8(+) T(RM) cells rapidly trigger an antiviral state by amplifying receptor-derived signals from previously encountered pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449618/" 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/PMC4449618/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schenkel, Jason M -- Fraser, Kathryn A -- Beura, Lalit K -- Pauken, Kristen E -- Vezys, Vaiva -- Masopust, David -- DP2 OD006467/OD/NIH HHS/ -- DP2-OD-006467/OD/NIH HHS/ -- F30 DK100159/DK/NIDDK NIH HHS/ -- F30DK100159/DK/NIDDK NIH HHS/ -- R01 AI084913/AI/NIAID NIH HHS/ -- R01AI084913/AI/NIAID NIH HHS/ -- T32 AI007313/AI/NIAID NIH HHS/ -- T32AI007313/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):98-101. doi: 10.1126/science.1254536. Epub 2014 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. ; Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. masopust@umn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170049" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity/*immunology ; Animals ; Antigens, Viral/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Female ; Immunity, Humoral/immunology ; Immunity, Innate/*immunology ; *Immunologic Memory ; Interferon-gamma/immunology ; Mice ; Mice, Inbred C57BL ; Mucous Membrane/immunology/virology ; Vascular Cell Adhesion Molecule-1/immunology ; Virus Diseases/*immunology
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  • 42
    Publication Date: 2014-10-25
    Description: Cognitive processes require working memory (WM) that involves a brief period of memory retention known as the delay period. Elevated delay-period activity in the medial prefrontal cortex (mPFC) has been observed, but its functional role in WM tasks remains unclear. We optogenetically suppressed or enhanced activity of pyramidal neurons in mouse mPFC during the delay period. Behavioral performance was impaired during the learning phase but not after the mice were well trained. Delay-period mPFC activity appeared to be more important in memory retention than in inhibitory control, decision-making, or motor selection. Furthermore, endogenous delay-period mPFC activity showed more prominent modulation that correlated with memory retention and behavioral performance. Thus, properly regulated mPFC delay-period activity is critical for information retention during learning of a WM task.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Ding -- Gu, Xiaowei -- Zhu, Jia -- Zhang, Xiaoxing -- Han, Zhe -- Yan, Wenjun -- Cheng, Qi -- Hao, Jiang -- Fan, Hongmei -- Hou, Ruiqing -- Chen, Zhaoqin -- Chen, Yulei -- Li, Chengyu T -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):458-63. doi: 10.1126/science.1256573.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuroscience and Key Laboratory of Primate Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. University of Chinese Academy of Sciences, Beijing 100049, China. ; Institute of Neuroscience and Key Laboratory of Primate Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; Institute of Neuroscience and Key Laboratory of Primate Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. tonylicy@ion.ac.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342800" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/metabolism ; Learning/*physiology ; Luminescent Proteins/genetics/metabolism ; Male ; Memory, Short-Term/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Prefrontal Cortex/cytology/*physiology ; Pyramidal Cells/*physiology ; Reaction Time ; *Retention (Psychology) ; Rhodopsin/genetics/metabolism ; Smell
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  • 43
    Publication Date: 2014-02-01
    Description: Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2'-O methylation of the 5' cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5' cap lacking 2'-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5'-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209899/" 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/PMC4209899/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hyde, Jennifer L -- Gardner, Christina L -- Kimura, Taishi -- White, James P -- Liu, Gai -- Trobaugh, Derek W -- Huang, Cheng -- Tonelli, Marco -- Paessler, Slobodan -- Takeda, Kiyoshi -- Klimstra, William B -- Amarasinghe, Gaya K -- Diamond, Michael S -- AI049820/AI/NIAID NIH HHS/ -- P41GM66326/GM/NIGMS NIH HHS/ -- P41RR02301/RR/NCRR NIH HHS/ -- R01 AI083383/AI/NIAID NIH HHS/ -- R01 AI104972/AI/NIAID NIH HHS/ -- U19 AI083019/AI/NIAID NIH HHS/ -- UL1 TR000071/TR/NCATS NIH HHS/ -- UL1TR000071/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):783-7. doi: 10.1126/science.1248465. Epub 2014 Jan 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482115" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/immunology ; Alphavirus/*pathogenicity/physiology ; Alphavirus Infections/*immunology/virology ; Animals ; Carrier Proteins/antagonists & inhibitors/genetics/immunology ; Host-Pathogen Interactions/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mutation ; Nucleic Acid Conformation ; RNA Caps/*chemistry/*immunology ; RNA, Viral/*chemistry/*immunology ; Virus Replication
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  • 44
    Publication Date: 2014-08-02
    Description: Several symptoms associated with chronic pain, including fatigue and depression, are characterized by reduced motivation to initiate or complete goal-directed tasks. However, it is unknown whether maladaptive modifications in neural circuits that regulate motivation occur during chronic pain. Here, we demonstrate that the decreased motivation elicited in mice by two different models of chronic pain requires a galanin receptor 1-triggered depression of excitatory synaptic transmission in indirect pathway nucleus accumbens medium spiny neurons. These results demonstrate a previously unknown pathological adaption in a key node of motivational neural circuitry that is required for one of the major sequela of chronic pain states and syndromes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219555/" 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/PMC4219555/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwartz, Neil -- Temkin, Paul -- Jurado, Sandra -- Lim, Byung Kook -- Heifets, Boris D -- Polepalli, Jai S -- Malenka, Robert C -- P01 DA008227/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 1;345(6196):535-42. doi: 10.1126/science.1253994.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA. ; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA. Department of Pharmacology, School of Medicine, University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201, USA. ; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA. Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA. malenka@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25082697" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chronic Pain/*physiopathology/*psychology ; Disease Models, Animal ; Gene Knockdown Techniques ; Long-Term Synaptic Depression/drug effects/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; *Motivation ; Nucleus Accumbens/*physiopathology ; Receptor, Galanin, Type 1/antagonists & inhibitors/genetics/*physiology
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  • 45
    Publication Date: 2014-07-26
    Description: In higher eukaryotes, transfer RNAs (tRNAs) with the same anticodon are encoded by multiple nuclear genes, and little is known about how mutations in these genes affect translation and cellular homeostasis. Similarly, the surveillance systems that respond to such defects in higher eukaryotes are not clear. Here, we discover that loss of GTPBP2, a novel binding partner of the ribosome recycling protein Pelota, in mice with a mutation in a tRNA gene that is specifically expressed in the central nervous system causes ribosome stalling and widespread neurodegeneration. Our results not only define GTPBP2 as a ribosome rescue factor but also unmask the disease potential of mutations in nuclear-encoded tRNA genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281038/" 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/PMC4281038/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ishimura, Ryuta -- Nagy, Gabor -- Dotu, Ivan -- Zhou, Huihao -- Yang, Xiang-Lei -- Schimmel, Paul -- Senju, Satoru -- Nishimura, Yasuharu -- Chuang, Jeffrey H -- Ackerman, Susan L -- CA34196/CA/NCI NIH HHS/ -- P30 CA034196/CA/NCI NIH HHS/ -- R01 NS085092/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):455-9. doi: 10.1126/science.1249749.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. ; The Jackson Laboratory for Genomic Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA. ; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan. ; Howard Hughes Medical Institute and The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. susan.ackerman@jax.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061210" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/genetics/*metabolism ; Cell Nucleus/genetics ; Cerebellum/*metabolism/pathology ; GTP-Binding Proteins/genetics/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microfilament Proteins/genetics/*metabolism ; Neurodegenerative Diseases/*genetics ; Point Mutation ; Protein Biosynthesis/*genetics ; RNA Splice Sites/genetics ; RNA, Transfer, Arg/*genetics ; Ribosomes/*metabolism
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  • 46
    Publication Date: 2014-05-09
    Description: Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases, including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an "alternatively activated" phenotype. TAM terminal differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204732/" 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/PMC4204732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Franklin, Ruth A -- Liao, Will -- Sarkar, Abira -- Kim, Myoungjoo V -- Bivona, Michael R -- Liu, Kang -- Pamer, Eric G -- Li, Ming O -- AI101251/AI/NIAID NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 AI101251/AI/NIAID NIH HHS/ -- R37 AI039031/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 May 23;344(6186):921-5. doi: 10.1126/science.1252510. Epub 2014 May 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA. ; New York Genome Center, New York, NY 10022, USA. ; Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. ; Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA. ; Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. lim@mskcc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24812208" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Female ; Inflammation/immunology/pathology ; Macrophages/*immunology ; Mammary Neoplasms, Animal/*immunology/*pathology ; Mice ; Mice, Inbred C57BL ; Monocyte-Macrophage Precursor Cells/immunology ; Receptors, Notch/metabolism ; Signal Transduction ; Vascular Cell Adhesion Molecule-1/metabolism
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  • 47
    Publication Date: 2014-02-08
    Description: The distance between Ca(2+) channels and release sensors determines the speed and efficacy of synaptic transmission. Tight "nanodomain" channel-sensor coupling initiates transmitter release at synapses in the mature brain, whereas loose "microdomain" coupling appears restricted to early developmental stages. To probe the coupling configuration at a plastic synapse in the mature central nervous system, we performed paired recordings between mossy fiber terminals and CA3 pyramidal neurons in rat hippocampus. Millimolar concentrations of both the fast Ca(2+) chelator BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] and the slow chelator EGTA efficiently suppressed transmitter release, indicating loose coupling between Ca(2+) channels and release sensors. Loose coupling enabled the control of initial release probability by fast endogenous Ca(2+) buffers and the generation of facilitation by buffer saturation. Thus, loose coupling provides the molecular framework for presynaptic plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vyleta, Nicholas P -- Jonas, Peter -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):665-70. doi: 10.1126/science.1244811.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IST Austria (Institute of Science and Technology Austria), Am Campus 1, A-3400 Klosterneuburg, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503854" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CA3 Region, Hippocampal/metabolism/physiology ; Calcium Channels/*metabolism ; Chelating Agents/pharmacology ; Egtazic Acid/analogs & derivatives/pharmacology ; Hippocampus/drug effects/metabolism/*physiology ; Mossy Fibers, Hippocampal/drug effects/metabolism/physiology ; Neuronal Plasticity/drug effects/*physiology ; Rats ; Synapses/drug effects/metabolism/*physiology ; Synaptic Transmission/drug effects/*physiology
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  • 48
    Publication Date: 2014-04-20
    Description: Typical therapies try to reverse pathogenic mechanisms. Here, we describe treatment effects achieved by enhancing depression-causing mechanisms in ventral tegmental area (VTA) dopamine (DA) neurons. In a social defeat stress model of depression, depressed (susceptible) mice display hyperactivity of VTA DA neurons, caused by an up-regulated hyperpolarization-activated current (I(h)). Mice resilient to social defeat stress, however, exhibit stable normal firing of these neurons. Unexpectedly, resilient mice had an even larger I(h), which was observed in parallel with increased potassium (K(+)) channel currents. Experimentally further enhancing Ih or optogenetically increasing the hyperactivity of VTA DA neurons in susceptible mice completely reversed depression-related behaviors, an antidepressant effect achieved through resilience-like, projection-specific homeostatic plasticity. These results indicate a potential therapeutic path of promoting natural resilience for depression treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334447/" 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/PMC4334447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedman, Allyson K -- Walsh, Jessica J -- Juarez, Barbara -- Ku, Stacy M -- Chaudhury, Dipesh -- Wang, Jing -- Li, Xianting -- Dietz, David M -- Pan, Nina -- Vialou, Vincent F -- Neve, Rachael L -- Yue, Zhenyu -- Han, Ming-Hu -- F31 MH095425/MH/NIMH NIH HHS/ -- F32 MH096464/MH/NIMH NIH HHS/ -- R01 MH092306/MH/NIMH NIH HHS/ -- R01 NS060123/NS/NINDS NIH HHS/ -- T32 MH 087004/MH/NIMH NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- T32 MH087004/MH/NIMH NIH HHS/ -- T32 MH096678/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):313-9. doi: 10.1126/science.1249240.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744379" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/drug effects ; Depression/*physiopathology ; Dopaminergic Neurons/*physiology ; Electrophysiological Phenomena ; Homeostasis ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Male ; Membrane Potentials/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Optogenetics ; Patch-Clamp Techniques ; Potassium Channels/metabolism ; *Resilience, Psychological ; Social Behavior ; Stress, Psychological/*physiopathology ; Triazines/pharmacology ; Ventral Tegmental Area/*physiology
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  • 49
    Publication Date: 2014-02-18
    Description: In multicellular organisms, biological function emerges when heterogeneous cell types form complex organs. Nevertheless, dissection of tissues into mixtures of cellular subpopulations is currently challenging. We introduce an automated massively parallel single-cell RNA sequencing (RNA-seq) approach for analyzing in vivo transcriptional states in thousands of single cells. Combined with unsupervised classification algorithms, this facilitates ab initio cell-type characterization of splenic tissues. Modeling single-cell transcriptional states in dendritic cells and additional hematopoietic cell types uncovers rich cell-type heterogeneity and gene-modules activity in steady state and after pathogen activation. Cellular diversity is thereby approached through inference of variable and dynamic pathway activity rather than a fixed preprogrammed cell-type hierarchy. These data demonstrate single-cell RNA-seq as an effective tool for comprehensive cellular decomposition of complex tissues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412462/" 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/PMC4412462/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaitin, Diego Adhemar -- Kenigsberg, Ephraim -- Keren-Shaul, Hadas -- Elefant, Naama -- Paul, Franziska -- Zaretsky, Irina -- Mildner, Alexander -- Cohen, Nadav -- Jung, Steffen -- Tanay, Amos -- Amit, Ido -- P50 HG006193/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):776-9. doi: 10.1126/science.1247651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Weizmann Institute, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers ; Dendritic Cells/metabolism ; Female ; Hematopoiesis/genetics ; Mice, Inbred C57BL ; RNA, Messenger/*genetics ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; Spleen/metabolism ; *Transcription, Genetic
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  • 50
    Publication Date: 2014-07-06
    Description: Protein folding by the endoplasmic reticulum (ER) is physiologically critical; its disruption causes ER stress and augments disease. ER stress activates the unfolded protein response (UPR) to restore homeostasis. If stress persists, the UPR induces apoptotic cell death, but the mechanisms remain elusive. Here, we report that unmitigated ER stress promoted apoptosis through cell-autonomous, UPR-controlled activation of death receptor 5 (DR5). ER stressors induced DR5 transcription via the UPR mediator CHOP; however, the UPR sensor IRE1alpha transiently catalyzed DR5 mRNA decay, which allowed time for adaptation. Persistent ER stress built up intracellular DR5 protein, driving ligand-independent DR5 activation and apoptosis engagement via caspase-8. Thus, DR5 integrates opposing UPR signals to couple ER stress and apoptotic cell fate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284148/" 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/PMC4284148/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Min -- Lawrence, David A -- Marsters, Scot -- Acosta-Alvear, Diego -- Kimmig, Philipp -- Mendez, Aaron S -- Paton, Adrienne W -- Paton, James C -- Walter, Peter -- Ashkenazi, Avi -- R01 GM032384/GM/NIGMS NIH HHS/ -- T32 GM064337/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 4;345(6192):98-101. doi: 10.1126/science.1254312.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. ; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA. ; Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia, 5005, Australia. ; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA. peter@walterlab.ucsf.edu aa@gene.com. ; Cancer Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. peter@walterlab.ucsf.edu aa@gene.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24994655" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Caspases ; Endoplasmic Reticulum Stress/genetics/*physiology ; Endoribonucleases/metabolism ; HCT116 Cells ; Humans ; Ligands ; Mice ; Mice, Inbred C57BL ; Protein-Serine-Threonine Kinases/metabolism ; RNA Stability ; RNA, Messenger/metabolism ; Receptors, TNF-Related Apoptosis-Inducing Ligand/agonists/genetics/*physiology ; Transcription Factor CHOP ; *Unfolded Protein Response
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  • 51
    Publication Date: 2014-06-14
    Description: The brain exhibits limited capacity for spontaneous restoration of lost motor functions after stroke. Rehabilitation is the prevailing clinical approach to augment functional recovery, but the scientific basis is poorly understood. Here, we show nearly full recovery of skilled forelimb functions in rats with large strokes when a growth-promoting immunotherapy against a neurite growth-inhibitory protein was applied to boost the sprouting of new fibers, before stabilizing the newly formed circuits by intensive training. In contrast, early high-intensity training during the growth phase destroyed the effect and led to aberrant fiber patterns. Pharmacogenetic experiments identified a subset of corticospinal fibers originating in the intact half of the forebrain, side-switching in the spinal cord to newly innervate the impaired limb and restore skilled motor function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wahl, A S -- Omlor, W -- Rubio, J C -- Chen, J L -- Zheng, H -- Schroter, A -- Gullo, M -- Weinmann, O -- Kobayashi, K -- Helmchen, F -- Ommer, B -- Schwab, M E -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1250-5. doi: 10.1126/science.1253050.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. Brain Research Institute, University of Zurich, Zurich, Switzerland. schwab@hifo.uzh.ch wahl@hifo.uzh.ch. ; Brain Research Institute, University of Zurich, Zurich, Switzerland. ; Computer Vision Group, Heidelberg Collaboratory for Image Processing and Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Heidelberg, Germany. ; Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland. ; Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. Brain Research Institute, University of Zurich, Zurich, Switzerland. ; National Institute for Physiological Sciences, National Institute of Natural Sciences Myodaiji, Okazaki, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24926013" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Immunotherapy/methods ; Motor Cortex/*physiopathology ; Myelin Proteins/*antagonists & inhibitors ; Physical Conditioning, Animal ; Prosencephalon/physiopathology ; Pyramidal Tracts/*injuries/*physiology ; Rats ; Rats, Long-Evans ; *Recovery of Function ; Stroke/*rehabilitation
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  • 52
    Publication Date: 2014-08-12
    Description: AMPA-sensitive glutamate receptors are crucial to the structural and dynamic properties of the brain, to the development and function of the central nervous system, and to the treatment of neurological conditions from depression to cognitive impairment. However, the molecular principles underlying AMPA receptor activation have remained elusive. We determined multiple x-ray crystal structures of the GluA2 AMPA receptor in complex with a Conus striatus cone snail toxin, a positive allosteric modulator, and orthosteric agonists, at 3.8 to 4.1 angstrom resolution. We show how the toxin acts like a straightjacket on the ligand-binding domain (LBD) "gating ring," restraining the domains via both intra- and interdimer cross-links such that agonist-induced closure of the LBD "clamshells" is transduced into an irislike expansion of the gating ring. By structural analysis of activation-enhancing mutants, we show how the expansion of the LBD gating ring results in pulling forces on the M3 helices that, in turn, are coupled to ion channel gating.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263349/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263349/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lei -- Durr, Katharina L -- Gouaux, Eric -- F32 MH100331/MH/NIMH NIH HHS/ -- F32MH100331/MH/NIMH NIH HHS/ -- R01 NS038631/NS/NINDS NIH HHS/ -- R37 NS038631/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1021-6. doi: 10.1126/science.1258409. Epub 2014 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. ; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Howard Hughes Medical Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. gouauxe@ohsu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25103405" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conotoxins/*chemistry ; Conus Snail ; Crystallography, X-Ray ; *Ion Channel Gating ; Ligands ; Mutation ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Receptors, AMPA/*agonists/*chemistry/genetics
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  • 53
    Publication Date: 2014-05-09
    Description: Although neuronal spikes can be readily detected from extracellular recordings, synaptic and subthreshold activity remains undifferentiated within the local field potential (LFP). In the hippocampus, neurons discharge selectively when the rat is at certain locations, while LFPs at single anatomical sites exhibit no such place-tuning. Nonetheless, because the representation of position is sparse and distributed, we hypothesized that spatial information can be recovered from multiple-site LFP recordings. Using high-density sampling of LFP and computational methods, we show that the spatiotemporal structure of the theta rhythm can encode position as robustly as neuronal spiking populations. Because our approach exploits the rhythmicity and sparse structure of neural activity, features found in many brain regions, it is useful as a general tool for discovering distributed LFP codes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agarwal, Gautam -- Stevenson, Ian H -- Berenyi, Antal -- Mizuseki, Kenji -- Buzsaki, Gyorgy -- Sommer, Friedrich T -- 1F32MH093048/MH/NIMH NIH HHS/ -- 337075/European Research Council/International -- MH-54671/MH/NIMH NIH HHS/ -- NS-034994/NS/NINDS NIH HHS/ -- NS074015/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 May 9;344(6184):626-30. doi: 10.1126/science.1250444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Redwood Center for Theoretical Neuroscience, University of California, Berkeley, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24812401" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Hippocampus/cytology/*physiology ; Maze Learning ; Neurons/physiology ; Periodicity ; Rats ; Running ; Spatio-Temporal Analysis ; Synaptic Potentials/*physiology ; Theta Rhythm
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  • 54
    Publication Date: 2014-08-02
    Description: The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immunomodulatory effects, but whether these effects are mediated by direct regulation of host immunity or indirectly through eliciting changes in the microbiota is unknown. We tested this in the context of virus-helminth coinfection. Helminth coinfection resulted in impaired antiviral immunity and was associated with changes in the microbiota and STAT6-dependent helminth-induced alternative activation of macrophages. Notably, helminth-induced impairment of antiviral immunity was evident in germ-free mice, but neutralization of Ym1, a chitinase-like molecule that is associated with alternatively activated macrophages, could partially restore antiviral immunity. These data indicate that helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548887/" 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/PMC4548887/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Osborne, Lisa C -- Monticelli, Laurel A -- Nice, Timothy J -- Sutherland, Tara E -- Siracusa, Mark C -- Hepworth, Matthew R -- Tomov, Vesselin T -- Kobuley, Dmytro -- Tran, Sara V -- Bittinger, Kyle -- Bailey, Aubrey G -- Laughlin, Alice L -- Boucher, Jean-Luc -- Wherry, E John -- Bushman, Frederic D -- Allen, Judith E -- Virgin, Herbert W -- Artis, David -- 095831/Wellcome Trust/United Kingdom -- 2-P30 CA016520/CA/NCI NIH HHS/ -- 5T32A100716334/PHS HHS/ -- AI061570/AI/NIAID NIH HHS/ -- AI074878/AI/NIAID NIH HHS/ -- AI082630/AI/NIAID NIH HHS/ -- AI083022/AI/NIAID NIH HHS/ -- AI087990/AI/NIAID NIH HHS/ -- AI095466/AI/NIAID NIH HHS/ -- AI095608/AI/NIAID NIH HHS/ -- AI097333/AI/NIAID NIH HHS/ -- AI102942/AI/NIAID NIH HHS/ -- AI106697/AI/NIAID NIH HHS/ -- F32 AI085828/AI/NIAID NIH HHS/ -- F32-AI085828/AI/NIAID NIH HHS/ -- HHSN272201300006C/PHS HHS/ -- K08 DK097301/DK/NIDDK NIH HHS/ -- K08-DK097301/DK/NIDDK NIH HHS/ -- MR/J001929/1/Medical Research Council/United Kingdom -- P01 AI106697/AI/NIAID NIH HHS/ -- P30-AI045008/AI/NIAID NIH HHS/ -- P30-DK050306/DK/NIDDK NIH HHS/ -- R01 AI 084887/AI/NIAID NIH HHS/ -- R01 AI061570/AI/NIAID NIH HHS/ -- R01 AI074878/AI/NIAID NIH HHS/ -- R01 AI095466/AI/NIAID NIH HHS/ -- R01 AI097333/AI/NIAID NIH HHS/ -- R01 AI102942/AI/NIAID NIH HHS/ -- R21 AI087990/AI/NIAID NIH HHS/ -- T32-AI007532/AI/NIAID NIH HHS/ -- U01 AI095608/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 1;345(6196):578-82. doi: 10.1126/science.1256942. Epub 2014 Jul 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK. ; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Universite Paris Descartes, Paris, France. ; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. dartis@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25082704" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/immunology ; Caliciviridae Infections/*immunology ; Coinfection/*immunology/microbiology/parasitology ; Gastroenteritis/*immunology/virology ; Germ-Free Life ; *Immunomodulation ; Intestines/immunology/microbiology/virology ; Lectins/*immunology ; Macrophage Activation ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Microbiota/*immunology ; Norovirus/*immunology ; Trichinella/*immunology ; Trichinellosis/*immunology ; beta-N-Acetylhexosaminidases/*immunology
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  • 55
    Publication Date: 2014-09-27
    Description: Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent beta-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1alpha (hypoxia-inducible factor-1alpha) pathway. Inhibition of Akt, mTOR, or HIF-1alpha blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1alpha were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1alpha pathway represents the metabolic basis of trained immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226238/" 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/PMC4226238/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Shih-Chin -- Quintin, Jessica -- Cramer, Robert A -- Shepardson, Kelly M -- Saeed, Sadia -- Kumar, Vinod -- Giamarellos-Bourboulis, Evangelos J -- Martens, Joost H A -- Rao, Nagesha Appukudige -- Aghajanirefah, Ali -- Manjeri, Ganesh R -- Li, Yang -- Ifrim, Daniela C -- Arts, Rob J W -- van der Veer, Brian M J W -- Deen, Peter M T -- Logie, Colin -- O'Neill, Luke A -- Willems, Peter -- van de Veerdonk, Frank L -- van der Meer, Jos W M -- Ng, Aylwin -- Joosten, Leo A B -- Wijmenga, Cisca -- Stunnenberg, Hendrik G -- Xavier, Ramnik J -- Netea, Mihai G -- 1P30GM106394-01/GM/NIGMS NIH HHS/ -- 5P30GM103415-03/GM/NIGMS NIH HHS/ -- DK097485/DK/NIDDK NIH HHS/ -- DK43351/DK/NIDDK NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- P30 GM103415/GM/NIGMS NIH HHS/ -- P30 GM106394/GM/NIGMS NIH HHS/ -- R01 AI081838/AI/NIAID NIH HHS/ -- R01 DK097485/DK/NIDDK NIH HHS/ -- R01AI81838/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 26;345(6204):1250684. doi: 10.1126/science.1250684.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. ; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. ; Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands. ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. ; 4th Department of Internal Medicine, University of Athens Medical School, 12462 Athens, Greece. ; Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands. ; Department of Physiology, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. ; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. ; Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. mihai.netea@radboudumc.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25258083" target="_blank"〉PubMed〈/a〉
    Keywords: Aerobiosis/immunology ; Animals ; Candida albicans/immunology ; Candidiasis/immunology/metabolism ; Disease Models, Animal ; *Epigenesis, Genetic ; Female ; Glucose/metabolism ; Glycolysis/*immunology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Immunity, Innate/*genetics ; Immunologic Memory/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes/*immunology/metabolism ; Sepsis/genetics/immunology/metabolism ; Staphylococcal Infections/immunology/metabolism ; Staphylococcus aureus ; TOR Serine-Threonine Kinases/genetics/*metabolism ; Transcriptome ; beta-Glucans/immunology
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  • 56
    Publication Date: 2014-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Servick, Kelly -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1161-2. doi: 10.1126/science.346.6214.1161.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477435" target="_blank"〉PubMed〈/a〉
    Keywords: Analgesics, Non-Narcotic/adverse effects ; Anesthesia/*adverse effects ; Anesthetics, Dissociative/adverse effects ; Animals ; Apoptosis/drug effects ; Brain/*drug effects/*growth & development ; Caenorhabditis elegans ; Child ; Child, Preschool ; Dexmedetomidine/adverse effects ; Humans ; Infant ; Ketamine/adverse effects ; Models, Animal ; Neurons/*drug effects ; Rats ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; United States ; United States Food and Drug Administration
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  • 57
    Publication Date: 2014-05-09
    Description: Throughout life, new neurons are continuously added to the dentate gyrus. As this continuous addition remodels hippocampal circuits, computational models predict that neurogenesis leads to degradation or forgetting of established memories. Consistent with this, increasing neurogenesis after the formation of a memory was sufficient to induce forgetting in adult mice. By contrast, during infancy, when hippocampal neurogenesis levels are high and freshly generated memories tend to be rapidly forgotten (infantile amnesia), decreasing neurogenesis after memory formation mitigated forgetting. In precocial species, including guinea pigs and degus, most granule cells are generated prenatally. Consistent with reduced levels of postnatal hippocampal neurogenesis, infant guinea pigs and degus did not exhibit forgetting. However, increasing neurogenesis after memory formation induced infantile amnesia in these species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akers, Katherine G -- Martinez-Canabal, Alonso -- Restivo, Leonardo -- Yiu, Adelaide P -- De Cristofaro, Antonietta -- Hsiang, Hwa-Lin Liz -- Wheeler, Anne L -- Guskjolen, Axel -- Niibori, Yosuke -- Shoji, Hirotaka -- Ohira, Koji -- Richards, Blake A -- Miyakawa, Tsuyoshi -- Josselyn, Sheena A -- Frankland, Paul W -- MOP74650/Canadian Institutes of Health Research/Canada -- MOP86762/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 May 9;344(6184):598-602. doi: 10.1126/science.1248903.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24812394" target="_blank"〉PubMed〈/a〉
    Keywords: Amnesia/*pathology/*physiopathology ; Animals ; Dentate Gyrus/cytology ; Female ; Guinea Pigs ; Hippocampus/*cytology ; Male ; *Memory ; Mice ; Mice, Inbred C57BL ; *Neurogenesis ; Neurons/cytology
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  • 58
    Publication Date: 2014-11-02
    Description: Neurotrophins regulate diverse aspects of neuronal development and plasticity, but their precise in vivo functions during neural circuit assembly in the central brain remain unclear. We show that the neurotrophin receptor tropomyosin-related kinase C (TrkC) is required for dendritic growth and branching of mouse cerebellar Purkinje cells. Sparse TrkC knockout reduced dendrite complexity, but global Purkinje cell knockout had no effect. Removal of the TrkC ligand neurotrophin-3 (NT-3) from cerebellar granule cells, which provide major afferent input to developing Purkinje cell dendrites, rescued the dendrite defects caused by sparse TrkC disruption in Purkinje cells. Our data demonstrate that NT-3 from presynaptic neurons (granule cells) is required for TrkC-dependent competitive dendrite morphogenesis in postsynaptic neurons (Purkinje cells)--a previously unknown mechanism of neural circuit development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631524/" 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/PMC4631524/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joo, William -- Hippenmeyer, Simon -- Luo, Liqun -- 5 F31 NS071697/NS/NINDS NIH HHS/ -- F31 NS071697/NS/NINDS NIH HHS/ -- R01 NS050835/NS/NINDS NIH HHS/ -- R01-NS050835/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):626-9. doi: 10.1126/science.1258996.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. Neurosciences Program, Stanford University, Stanford, CA 94305, USA. ; Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. ; Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. Neurosciences Program, Stanford University, Stanford, CA 94305, USA. lluo@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359972" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dendrites/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Net/cytology/*growth & development ; *Neurogenesis ; Neurotrophin 3/*metabolism ; Purkinje Cells/*cytology/metabolism ; Receptor, trkC/genetics/*metabolism ; Signal Transduction ; Synapses/physiology
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  • 59
    Publication Date: 2014-09-23
    Description: The lateral habenula (LHb), a key regulator of monoaminergic brain regions, is activated by negatively valenced events. Its hyperactivity is associated with depression. Although enhanced excitatory input to the LHb has been linked to depression, little is known about inhibitory transmission. We discovered that gamma-aminobutyric acid (GABA) is co-released with its functional opponent, glutamate, from long-range basal ganglia inputs (which signal negative events) to limit LHb activity in rodents. At this synapse, the balance of GABA/glutamate signaling is shifted toward reduced GABA in a model of depression and increased GABA by antidepressant treatment. GABA and glutamate co-release therefore controls LHb activity, and regulation of this form of transmission may be important for determining the effect of negative life events on mood and behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305433/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shabel, Steven J -- Proulx, Christophe D -- Piriz, Joaquin -- Malinow, Roberto -- NS047101/NS/NINDS NIH HHS/ -- R01 MH091119/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1494-8. doi: 10.1126/science.1250469. Epub 2014 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA, USA. sshabel@gmail.com. ; Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA, USA. ; Grupo de Neurociencia de Sistemas, Instituto de Fisiologia y Biofisica Houssay (CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237099" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antidepressive Agents/*pharmacology ; Depression/*metabolism ; Entopeduncular Nucleus/drug effects/metabolism ; Glutamate Decarboxylase/metabolism ; Glutamic Acid/*metabolism ; Habenula/*drug effects/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Rhodopsin/genetics ; Synaptic Transmission/drug effects/*physiology ; Vesicular Glutamate Transport Protein 2/metabolism ; gamma-Aminobutyric Acid/*metabolism
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  • 60
    Publication Date: 2014-10-11
    Description: Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 +/- 210 (mean +/- SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Magnusson, Jens P -- Goritz, Christian -- Tatarishvili, Jemal -- Dias, David O -- Smith, Emma M K -- Lindvall, Olle -- Kokaia, Zaal -- Frisen, Jonas -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):237-41. doi: 10.1126/science.346.6206.237. Epub 2014 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden. ; Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden. ; Division of Translational Cancer Research, Lund University, SE-223 63 Lund, Sweden. ; Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden. jonas.frisen@ki.se.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301628" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/cytology/*physiology ; Corpus Striatum/pathology/physiopathology ; Gene Deletion ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neural Stem Cells/cytology/*physiology ; Neurogenesis/genetics/*physiology ; Neurons/cytology/*physiology ; Receptor, Notch1/genetics/*physiology ; *Signal Transduction ; Stroke/pathology/*physiopathology
    Print ISSN: 0036-8075
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  • 61
    Publication Date: 2014-11-29
    Description: Norovirus gastroenteritis is a major public health burden worldwide. Although fecal shedding is important for transmission of enteric viruses, little is known about the immune factors that restrict persistent enteric infection. We report here that although the cytokines interferon-alpha (IFN-alpha) and IFN-beta prevented the systemic spread of murine norovirus (MNoV), only IFN-lambda controlled persistent enteric infection. Infection-dependent induction of IFN-lambda was governed by the MNoV capsid protein and correlated with diminished enteric persistence. Treatment of established infection with IFN-lambda cured mice in a manner requiring nonhematopoietic cell expression of the IFN-lambda receptor, Ifnlr1, and independent of adaptive immunity. These results suggest the therapeutic potential of IFN-lambda for curing virus infections in the gastrointestinal tract.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398891/" 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/PMC4398891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nice, Timothy J -- Baldridge, Megan T -- McCune, Broc T -- Norman, Jason M -- Lazear, Helen M -- Artyomov, Maxim -- Diamond, Michael S -- Virgin, Herbert W -- 5T32A100716334/PHS HHS/ -- 5T32AI007163/AI/NIAID NIH HHS/ -- 5T32CA009547/CA/NCI NIH HHS/ -- F31 CA177194/CA/NCI NIH HHS/ -- F31CA177194-01/CA/NCI NIH HHS/ -- R01 AI084887/AI/NIAID NIH HHS/ -- T32 AI007163/AI/NIAID NIH HHS/ -- T32 CA009547/CA/NCI NIH HHS/ -- U19 AI083019/AI/NIAID NIH HHS/ -- U19 AI106772/AI/NIAID NIH HHS/ -- U19 AI109725/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):269-73. doi: 10.1126/science.1258100. Epub 2014 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. virgin@wustl.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25431489" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity ; Animals ; Caliciviridae Infections/*drug therapy/*immunology/virology ; Capsid Proteins/immunology/metabolism ; Cells, Cultured ; Cytokines/biosynthesis/*immunology/*therapeutic use ; Feces/virology ; Gastroenteritis/drug therapy/*immunology/virology ; Immunity, Innate ; Interferon-alpha/biosynthesis/immunology ; Interferon-beta/biosynthesis/immunology ; Mice ; Mice, Inbred C57BL ; Norovirus/*immunology/*physiology ; Virus Replication ; Virus Shedding
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  • 62
    Publication Date: 2014-11-29
    Description: The capacity of human norovirus (NoV), which causes 〉90% of global epidemic nonbacterial gastroenteritis, to infect a subset of people persistently may contribute to its spread. How such enteric viruses establish persistent infections is not well understood. We found that antibiotics prevented persistent murine norovirus (MNoV) infection, an effect that was reversed by replenishment of the bacterial microbiota. Antibiotics did not prevent tissue infection or affect systemic viral replication but acted specifically in the intestine. The receptor for the antiviral cytokine interferon-lambda, Ifnlr1, as well as the transcription factors Stat1 and Irf3, were required for antibiotics to prevent viral persistence. Thus, the bacterial microbiome fosters enteric viral persistence in a manner counteracted by specific components of the innate immune system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409937/" 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/PMC4409937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldridge, Megan T -- Nice, Timothy J -- McCune, Broc T -- Yokoyama, Christine C -- Kambal, Amal -- Wheadon, Michael -- Diamond, Michael S -- Ivanova, Yulia -- Artyomov, Maxim -- Virgin, Herbert W -- 1F31CA177194/CA/NCI NIH HHS/ -- 5T32AI007163/AI/NIAID NIH HHS/ -- 5T32CA009547/CA/NCI NIH HHS/ -- F31 CA177194/CA/NCI NIH HHS/ -- R01 AI084887/AI/NIAID NIH HHS/ -- T32 AI007163/AI/NIAID NIH HHS/ -- T32 CA009547/CA/NCI NIH HHS/ -- U19 AI083019/AI/NIAID NIH HHS/ -- U19 AI106772/AI/NIAID NIH HHS/ -- U19 AI109725/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):266-9. doi: 10.1126/science.1258025. Epub 2014 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. virgin@wustl.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25431490" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Caliciviridae Infections/drug therapy/immunology/microbiology/*virology ; Cytokines/*physiology ; Female ; Gastroenteritis/drug therapy/immunology/microbiology/*virology ; Intestines/*microbiology/virology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; *Microbiota/drug effects ; Norovirus/immunology/*physiology ; Receptors, Cytokine/genetics/metabolism ; Signal Transduction ; *Symbiosis ; Viral Load ; Virus Replication ; Virus Shedding
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  • 63
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2013 Dec 20;342(6165):1440-1. doi: 10.1126/science.342.6165.1440-b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357292" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/administration & dosage ; Fusobacterium/physiology ; Gastrointestinal Tract/*microbiology ; *Health ; Humans ; Infant ; Infant Formula/chemistry ; Kidney/metabolism ; Kidney Calculi/chemically induced/etiology ; Klebsiella/drug effects/metabolism ; Malnutrition/microbiology ; Neoplasms/microbiology ; Rats ; Triazines/metabolism/toxicity
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  • 64
    Publication Date: 2013-05-21
    Description: The generation of high-affinity antibodies depends on the ability of B cells to extract antigens from the surfaces of antigen-presenting cells. B cells that express high-affinity B cell receptors (BCRs) acquire more antigen and obtain better T cell help. However, the mechanisms by which B cells extract antigen remain unclear. Using fluid and flexible membrane substrates to mimic antigen-presenting cells, we showed that B cells acquire antigen by dynamic myosin IIa-mediated contractions that pull out and invaginate the presenting membranes. The forces generated by myosin IIa contractions ruptured most individual BCR-antigen bonds and promoted internalization of only high-affinity, multivalent BCR microclusters. Thus, B cell contractility contributes to affinity discrimination by mechanically testing the strength of antigen binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713314/" 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/PMC3713314/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Natkanski, Elizabeth -- Lee, Wing-Yiu -- Mistry, Bhakti -- Casal, Antonio -- Molloy, Justin E -- Tolar, Pavel -- MC_U117570592/Medical Research Council/United Kingdom -- MC_U117597138/Medical Research Council/United Kingdom -- U117570592/Medical Research Council/United Kingdom -- U117597138/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1587-90. doi: 10.1126/science.1237572. Epub 2013 May 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immune Cell Biology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23686338" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antibody Affinity ; *Antigen Presentation ; Antigens/*immunology ; B-Lymphocytes/*immunology ; Cells, Cultured ; Mechanical Processes ; Mice ; Mice, Inbred C57BL ; Microscopy, Atomic Force ; Nonmuscle Myosin Type IIA/*physiology ; Receptors, Antigen, B-Cell/immunology
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  • 65
    Publication Date: 2013-04-27
    Description: Secondary bacterial pneumonia leads to increased morbidity and mortality from influenza virus infections. What causes this increased susceptibility, however, is not well defined. Host defense from infection relies not only on immune resistance mechanisms but also on the ability to tolerate a given level of pathogen burden. Failure of either resistance or tolerance can contribute to disease severity, making it hard to distinguish their relative contribution. We employ a coinfection mouse model of influenza virus and Legionella pneumophila in which we can separate resistance and tolerance. We demonstrate that influenza virus can promote susceptibility to lethal bacterial coinfection, even when bacterial infection is controlled by the immune system. We propose that this failure of host defense is due to impaired ability to tolerate tissue damage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933032/" 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/PMC3933032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jamieson, Amanda M -- Pasman, Lesley -- Yu, Shuang -- Gamradt, Pia -- Homer, Robert J -- Decker, Thomas -- Medzhitov, Ruslan -- AI R01 055502/AI/NIAID NIH HHS/ -- R01 046688/PHS HHS/ -- R01 AI046688/AI/NIAID NIH HHS/ -- R01 AI055502/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1230-4. doi: 10.1126/science.1233632. Epub 2013 Apr 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. amanda_jamieson@brown.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23618765" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspase 1 ; Coinfection/*immunology/pathology ; Disease Models, Animal ; Host-Pathogen Interactions/immunology ; Interleukin-1beta/metabolism ; *Legionella pneumophila ; Legionnaires' Disease/*immunology/pathology ; Lung/microbiology/pathology/virology ; Mice ; Mice, Inbred C57BL ; *Orthomyxoviridae ; Orthomyxoviridae Infections/*immunology/pathology ; Pneumonia, Bacterial/*immunology/pathology ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 3/metabolism ; Toll-Like Receptor 4/metabolism ; Tumor Necrosis Factor-alpha/metabolism
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  • 66
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2013 Dec 20;342(6165):1434-5. doi: 10.1126/science.342.6165.1434-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357285" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; DNA/genetics ; Genetic Diseases, Inborn/*surgery ; Genetic Therapy/*methods ; Humans ; Mice ; Microsurgery/*methods ; *RNA Editing ; RNA, Guide/genetics/metabolism ; Rats
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  • 67
    Publication Date: 2013-07-06
    Description: DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/" 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/PMC3785061/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lister, Ryan -- Mukamel, Eran A -- Nery, Joseph R -- Urich, Mark -- Puddifoot, Clare A -- Johnson, Nicholas D -- Lucero, Jacinta -- Huang, Yun -- Dwork, Andrew J -- Schultz, Matthew D -- Yu, Miao -- Tonti-Filippini, Julian -- Heyn, Holger -- Hu, Shijun -- Wu, Joseph C -- Rao, Anjana -- Esteller, Manel -- He, Chuan -- Haghighi, Fatemeh G -- Sejnowski, Terrence J -- Behrens, M Margarita -- Ecker, Joseph R -- AI44432/AI/NIAID NIH HHS/ -- CA151535/CA/NCI NIH HHS/ -- HD065812/HD/NICHD NIH HHS/ -- HG006827/HG/NHGRI NIH HHS/ -- K99NS080911/NS/NINDS NIH HHS/ -- MH094670/MH/NIMH NIH HHS/ -- R01 AI044432/AI/NIAID NIH HHS/ -- R01 CA151535/CA/NCI NIH HHS/ -- R01 HD065812/HD/NICHD NIH HHS/ -- R01 HG006827/HG/NHGRI NIH HHS/ -- R01 MH094670/MH/NIMH NIH HHS/ -- R01 MH094774/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ryan.lister@uwa.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23828890" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Adult ; Animals ; Base Sequence ; Conserved Sequence ; Cytosine/*analogs & derivatives/metabolism ; *DNA Methylation ; *Epigenesis, Genetic ; Epigenomics ; Frontal Lobe/*growth & development ; *Gene Expression Regulation, Developmental ; Genome-Wide Association Study ; Humans ; Longevity ; Mice ; Mice, Inbred C57BL ; X Chromosome Inactivation/genetics
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  • 68
    Publication Date: 2013-01-26
    Description: Caspases are either apoptotic or inflammatory. Among inflammatory caspases, caspase-1 and -11 trigger pyroptosis, a form of programmed cell death. Whereas both can be detrimental in inflammatory disease, only caspase-1 has an established protective role during infection. Here, we report that caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria. Although Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) aberrantly enter the cytosol. These mutants triggered caspase-11, which enhanced clearance of S. typhimurium sifA in vivo. This response did not require NLRP3, NLRC4, or ASC inflammasome pathways. Burkholderia species that naturally invade the cytosol also triggered caspase-11, which protected mice from lethal challenge with B. thailandensis and B. pseudomallei. Thus, caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697099/" 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/PMC3697099/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aachoui, Youssef -- Leaf, Irina A -- Hagar, Jon A -- Fontana, Mary F -- Campos, Cristine G -- Zak, Daniel E -- Tan, Michael H -- Cotter, Peggy A -- Vance, Russell E -- Aderem, Alan -- Miao, Edward A -- AI057141/AI/NIAID NIH HHS/ -- AI063302/AI/NIAID NIH HHS/ -- AI065359/AI/NIAID NIH HHS/ -- AI075039/AI/NIAID NIH HHS/ -- AI080749/AI/NIAID NIH HHS/ -- AI097518/AI/NIAID NIH HHS/ -- P01 AI063302/AI/NIAID NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- R01 AI075039/AI/NIAID NIH HHS/ -- R01 AI080749/AI/NIAID NIH HHS/ -- R01 AI097518/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 AI057141/AI/NIAID NIH HHS/ -- U54 AI065359/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 22;339(6122):975-8. doi: 10.1126/science.1230751. Epub 2013 Jan 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23348507" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Burkholderia/pathogenicity/physiology ; Burkholderia Infections/enzymology/immunology/metabolism ; Burkholderia pseudomallei/pathogenicity/physiology ; Caspases/*metabolism ; *Cell Death ; Cytosol/*microbiology ; Gram-Negative Bacterial Infections/enzymology/*immunology/microbiology ; Immunity, Innate ; Inflammasomes/metabolism ; Macrophages/immunology/*microbiology ; Mice ; Mice, Inbred C57BL ; Phagosomes/microbiology ; Salmonella Infections, Animal/enzymology/immunology/microbiology ; Salmonella typhimurium/pathogenicity/physiology ; Vacuoles/*microbiology
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  • 69
    Publication Date: 2013-03-02
    Description: Prenatal infection and exposure to traumatizing experiences during peripuberty have each been associated with increased risk for neuropsychiatric disorders. Evidence is lacking for the cumulative impact of such prenatal and postnatal environmental challenges on brain functions and vulnerability to psychiatric disease. Here, we show in a translational mouse model that combined exposure to prenatal immune challenge and peripubertal stress induces synergistic pathological effects on adult behavioral functions and neurochemistry. We further demonstrate that the prenatal insult markedly increases the vulnerability of the pubescent offspring to brain immune changes in response to stress. Our findings reveal interactions between two adverse environmental factors that have individually been associated with neuropsychiatric disease and support theories that mental illnesses with delayed onsets involve multiple environmental hits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giovanoli, Sandra -- Engler, Harald -- Engler, Andrea -- Richetto, Juliet -- Voget, Mareike -- Willi, Roman -- Winter, Christine -- Riva, Marco A -- Mortensen, Preben B -- Feldon, Joram -- Schedlowski, Manfred -- Meyer, Urs -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1095-9. doi: 10.1126/science.1228261.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physiology and Behavior Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, 8603 Schwerzenbach, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23449593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytokines/immunology ; Disease Models, Animal ; Female ; Humans ; Mental Disorders/*immunology ; Mice ; Mice, Inbred C57BL ; Poly I-C/immunology/pharmacology ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology/virology ; Puberty/*immunology ; Stress, Physiological/*immunology
    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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  • 70
    Publication Date: 2013-01-19
    Description: Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weber, Michele -- Hauschild, Robert -- Schwarz, Jan -- Moussion, Christine -- de Vries, Ingrid -- Legler, Daniel F -- Luther, Sanjiv A -- Bollenbach, Tobias -- Sixt, Michael -- New York, N.Y. -- Science. 2013 Jan 18;339(6117):328-32. doi: 10.1126/science.1228456.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IST Austria (Institute of Science and Technology Austria), Klosterneuburg, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23329049" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemokine CCL19/metabolism ; Chemokine CCL21/chemistry/*immunology ; Chemotaxis/*immunology ; Dendritic Cells/*immunology ; Heparitin Sulfate/chemistry ; Immobilized Proteins/chemistry/immunology ; Lymphatic Vessels/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Receptors, CCR7/genetics ; Skin/*immunology
    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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  • 71
    Publication Date: 2013-05-11
    Description: gamma-aminobutyric acid-mediated (GABAergic) inhibition plays a critical role in shaping neuronal activity in the neocortex. Numerous experimental investigations have examined perisomatic inhibitory synapses, which control action potential output from pyramidal neurons. However, most inhibitory synapses in the neocortex are formed onto pyramidal cell dendrites, where theoretical studies suggest they may focally regulate cellular activity. The precision of GABAergic control over dendritic electrical and biochemical signaling is unknown. By using cell type-specific optical stimulation in combination with two-photon calcium (Ca(2+)) imaging, we show that somatostatin-expressing interneurons exert compartmentalized control over postsynaptic Ca(2+) signals within individual dendritic spines. This highly focal inhibitory action is mediated by a subset of GABAergic synapses that directly target spine heads. GABAergic inhibition thus participates in localized control of dendritic electrical and biochemical signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752161/" 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/PMC3752161/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chiu, Chiayu Q -- Lur, Gyorgy -- Morse, Thomas M -- Carnevale, Nicholas T -- Ellis-Davies, Graham C R -- Higley, Michael J -- DC009977/DC/NIDCD NIH HHS/ -- GM053395/GM/NIGMS NIH HHS/ -- K01 MH097961/MH/NIMH NIH HHS/ -- MH099045/MH/NIMH NIH HHS/ -- NS011613/NS/NINDS NIH HHS/ -- NS069720/NS/NINDS NIH HHS/ -- R01 DC009977/DC/NIDCD NIH HHS/ -- R01 GM053395/GM/NIGMS NIH HHS/ -- R01 MH099045/MH/NIMH NIH HHS/ -- R01 NS011613/NS/NINDS NIH HHS/ -- R01 NS069720/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 May 10;340(6133):759-62. doi: 10.1126/science.1234274.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661763" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Computer Simulation ; Dendritic Spines/*physiology ; Female ; Glutamic Acid/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neocortex/*physiology ; *Neural Inhibition ; Photic Stimulation ; Pyramidal Cells/*physiology ; Rhodopsin/metabolism ; Synapses/physiology ; gamma-Aminobutyric Acid/*physiology
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  • 72
    Publication Date: 2013-03-02
    Description: The innate immune system senses pathogens through pattern-recognition receptors (PRRs) that signal to induce effector cytokines, such as type I interferons (IFNs). We characterized IFN-epsilon as a type I IFN because it signaled via the Ifnar1 and Ifnar2 receptors to induce IFN-regulated genes. In contrast to other type I IFNs, IFN-epsilon was not induced by known PRR pathways; instead, IFN-epsilon was constitutively expressed by epithelial cells of the female reproductive tract (FRT) and was hormonally regulated. Ifn-epsilon-deficient mice had increased susceptibility to infection of the FRT by the common sexually transmitted infections (STIs) herpes simplex virus 2 and Chlamydia muridarum. Thus, IFN-epsilon is a potent antipathogen and immunoregulatory cytokine that may be important in combating STIs that represent a major global health and socioeconomic burden.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617553/" 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/PMC3617553/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fung, Ka Yee -- Mangan, Niamh E -- Cumming, Helen -- Horvat, Jay C -- Mayall, Jemma R -- Stifter, Sebastian A -- De Weerd, Nicole -- Roisman, Laila C -- Rossjohn, Jamie -- Robertson, Sarah A -- Schjenken, John E -- Parker, Belinda -- Gargett, Caroline E -- Nguyen, Hong P T -- Carr, Daniel J -- Hansbro, Philip M -- Hertzog, Paul J -- R01 AI053108/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1088-92. doi: 10.1126/science.1233321.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23449591" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Chlamydia Infections/genetics/*immunology ; *Chlamydia muridarum ; Estrogens/administration & dosage/immunology ; Female ; HEK293 Cells ; Herpes Genitalis/genetics/*immunology ; *Herpesvirus 2, Human ; Humans ; Interferons/genetics/*immunology ; Ligands ; Mice ; Mice, Inbred C57BL ; Oligodeoxyribonucleotides/immunology ; Poly I-C/immunology ; Poly dA-dT/immunology ; Toll-Like Receptors/*immunology ; Uterus/immunology ; Vagina/*immunology/microbiology/virology
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  • 73
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-11-23
    Description: In many mammalian tissues, mature differentiated cells are replaced by self-renewing stem cells, either continuously during homeostasis or in response to challenge and injury. For example, hematopoietic stem cells generate all mature blood cells, including monocytes, which have long been thought to be the major source of tissue macrophages. Recently, however, major macrophage populations were found to be derived from embryonic progenitors and to renew independently of hematopoietic stem cells. This process may not require progenitors, as mature macrophages can proliferate in response to specific stimuli indefinitely and without transformation or loss of functional differentiation. These findings suggest that macrophages are mature differentiated cells that may have a self-renewal potential similar to that of stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sieweke, Michael H -- Allen, Judith E -- MR/J001929/1/Medical Research Council/United Kingdom -- MR/K01207X1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):1242974. doi: 10.1126/science.1242974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Universite, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24264994" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Proliferation ; Cytokines/metabolism ; Embryonic Stem Cells/cytology ; Humans ; Macrophages/*cytology ; Mice ; Monocytes/cytology ; Rats ; Signal Transduction ; Stem Cells/*cytology
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  • 74
    Publication Date: 2013-02-01
    Description: Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667500/" 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/PMC3667500/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Michelle I -- Yatsunenko, Tanya -- Manary, Mark J -- Trehan, Indi -- Mkakosya, Rajhab -- Cheng, Jiye -- Kau, Andrew L -- Rich, Stephen S -- Concannon, Patrick -- Mychaleckyj, Josyf C -- Liu, Jie -- Houpt, Eric -- Li, Jia V -- Holmes, Elaine -- Nicholson, Jeremy -- Knights, Dan -- Ursell, Luke K -- Knight, Rob -- Gordon, Jeffrey I -- DK078669/DK/NIDDK NIH HHS/ -- DK30292/DK/NIDDK NIH HHS/ -- F32 DK091044/DK/NIDDK NIH HHS/ -- P01 DK078669/DK/NIDDK NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- R37 DK030292/DK/NIDDK NIH HHS/ -- T32 HD049338/HD/NICHD NIH HHS/ -- T32-HD049338/HD/NICHD NIH HHS/ -- T35 DK074375/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):548-54. doi: 10.1126/science.1229000. Epub 2013 Jan 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23363771" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/metabolism ; Animals ; Arachis ; Carbohydrate Metabolism ; Child, Preschool ; Diseases in Twins/*microbiology ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Infant ; Kwashiorkor/diet therapy/epidemiology/*microbiology ; Longitudinal Studies ; Malawi/epidemiology ; Male ; *Metagenome ; Mice ; Mice, Inbred C57BL
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  • 75
    Publication Date: 2013-12-18
    Description: The central nervous system rapidly learns that particular stimuli predict imminent danger. This learning is thought to involve associations between neutral and harmful stimuli in cortical and limbic brain regions, though associative neuroplasticity in sensory structures is increasingly appreciated. We observed the synaptic output of olfactory sensory neurons (OSNs) in individual mice before and after they learned that a particular odor indicated an impending foot shock. OSNs are the first cells in the olfactory system, physically contacting the odor molecules in the nose and projecting their axons to the brain's olfactory bulb. OSN output evoked by the shock-predictive odor was selectively facilitated after fear conditioning. These results indicate that affective information about a stimulus can be encoded in its very earliest representation in the nervous system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011636/" 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/PMC4011636/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kass, Marley D -- Rosenthal, Michelle C -- Pottackal, Joseph -- McGann, John P -- DC009442/DC/NIDCD NIH HHS/ -- DC013090/DC/NIDCD NIH HHS/ -- MH101293/MH/NIMH NIH HHS/ -- R00 DC009442/DC/NIDCD NIH HHS/ -- R01 DC013090/DC/NIDCD NIH HHS/ -- R01 MH101293/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1389-92. doi: 10.1126/science.1244916.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Behavioral and Systems Neuroscience Section, Department of Psychology, Rutgers, The State University of New Jersey, 152 Frelinghuysen Road, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24337299" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conditioning, Classical/physiology ; Fear/*psychology ; Learning/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity ; *Odors ; Olfactory Receptor Neurons/*physiology ; Smell/*physiology ; Synapses/*physiology
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  • 76
    Publication Date: 2013-12-18
    Description: Erythropoietin is a signaling glycoprotein that controls the fundamental process of erythropoiesis, orchestrating the production and maintenance of red blood cells. As administrated clinically, erythropoietin has a polypeptide backbone with complex dishomogeneity in its carbohydrate domains. Here we describe the total synthesis of homogeneous erythropoietin with consensus carbohydrate domains incorporated at all of the native glycosylation sites. The oligosaccharide sectors were built by total synthesis and attached stereospecifically to peptidyl fragments of the wild-type primary sequence, themselves obtained by solid-phase peptide synthesis. The glycopeptidyl constructs were joined by chemical ligation, followed by metal-free dethiylation, and subsequently folded. This homogeneous erythropoietin glycosylated at the three wild-type aspartates with N-linked high-mannose sialic acid-containing oligosaccharides and O-linked glycophorin exhibits Procrit-level in vivo activity in mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080428/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Ping -- Dong, Suwei -- Shieh, Jae-Hung -- Peguero, Elizabeth -- Hendrickson, Ronald -- Moore, Malcolm A S -- Danishefsky, Samuel J -- HL025848/HL/NHLBI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 GM109760/GM/NIGMS NIH HHS/ -- R01 HL025848/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1357-60. doi: 10.1126/science.1245095.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24337294" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Aspartic Acid/chemistry ; Cells, Cultured ; Consensus Sequence ; Dose-Response Relationship, Drug ; Erythrocyte Count ; Erythropoietin/*administration & dosage/*chemical synthesis/chemistry ; Glycophorin/chemistry ; Glycosylation ; Injections, Subcutaneous ; Mannose/chemistry ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; N-Acetylneuraminic Acid/chemistry ; Oligosaccharides/chemistry ; Reticulocytes/drug effects
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  • 77
    Publication Date: 2013-10-19
    Description: The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of beta-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880190/" 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/PMC3880190/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xie, Lulu -- Kang, Hongyi -- Xu, Qiwu -- Chen, Michael J -- Liao, Yonghong -- Thiyagarajan, Meenakshisundaram -- O'Donnell, John -- Christensen, Daniel J -- Nicholson, Charles -- Iliff, Jeffrey J -- Takano, Takahiro -- Deane, Rashid -- Nedergaard, Maiken -- NS028642/NS/NINDS NIH HHS/ -- NS078167/NS/NINDS NIH HHS/ -- NS078304/NS/NINDS NIH HHS/ -- R01 DE022743/DE/NIDCR NIH HHS/ -- R01 NS075177/NS/NINDS NIH HHS/ -- R01 NS078167/NS/NINDS NIH HHS/ -- R01 NS078304/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 18;342(6156):373-7. doi: 10.1126/science.1241224.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136970" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic Antagonists/administration & dosage ; Amyloid beta-Peptides/*metabolism ; Animals ; Brain/*metabolism/physiology ; Cerebral Cortex/metabolism/physiology ; Cerebrospinal Fluid/metabolism ; Diffusion ; Electroencephalography ; Extracellular Space ; Intracellular Space ; Male ; Mice ; Mice, Inbred C57BL ; Neurodegenerative Diseases/*metabolism ; Quaternary Ammonium Compounds/chemistry ; Receptors, Adrenergic/metabolism ; Sleep/*physiology ; Wakefulness/physiology
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  • 78
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-03-16
    Description: Increased fear memory generalization is associated with posttraumatic stress disorder, but the circuit mechanisms that regulate memory specificity remain unclear. Here, we define a neural circuit-composed of the medial prefrontal cortex, the nucleus reuniens (NR), and the hippocampus-that controls fear memory generalization. Inactivation of prefrontal inputs into the NR or direct silencing of NR projections enhanced fear memory generalization, whereas constitutive activation of NR neurons decreased memory generalization. Direct optogenetic activation of phasic and tonic action-potential firing of NR neurons during memory acquisition enhanced or reduced memory generalization, respectively. We propose that the NR determines the specificity and generalization of memory attributes for a particular context by processing information from the medial prefrontal cortex en route to the hippocampus.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651700/" 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/PMC3651700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Wei -- Sudhof, Thomas C -- K99 MH099153/MH/NIMH NIH HHS/ -- NS077906/NS/NINDS NIH HHS/ -- P50 MH086403/MH/NIMH NIH HHS/ -- R01 NS077906/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Mar 15;339(6125):1290-5. doi: 10.1126/science.1229534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94304-5453, USA. weixu@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23493706" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Mapping ; Dependovirus ; Fear/*physiology ; *Generalization (Psychology) ; Green Fluorescent Proteins/genetics/metabolism ; Hippocampus/physiology ; Male ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Midline Thalamic Nuclei/physiology ; Neural Pathways ; Prefrontal Cortex/*physiology ; Synapses/physiology ; Vesicle-Associated Membrane Protein 2/genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 79
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-11-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bendor, Daniel -- 1-K99-DC012321-01/DC/NIDCD NIH HHS/ -- 5R01MH061976/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 1;342(6158):574. doi: 10.1126/science.1245966.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University College London, 26 Bedford Way, London WC1H 0AP, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24179215" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cues ; Hippocampus/*physiology ; Humans ; Memory/*physiology/*radiation effects ; Microelectrodes ; Rats ; Sleep Stages/*physiology
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  • 80
    Publication Date: 2013-06-01
    Description: Successive contrast effects, in which behavior is dependent on whether conditions are currently better or worse than they were before, are a striking illustration of the fact that animals evaluate the world in relative terms. Existing explanations for these effects are based on descriptive models of psychological and physiological processes, but little attention has been paid to the factors promoting their evolution. Using a simple and general optimality model, we show that contrast effects can result from an adaptive response to uncertainty in a changing, unpredictable world. A wide range of patterns of environmental change will select for sensitivity to past conditions, generating positive and negative contrast effects. Our analysis reveals the importance of incorporating uncertainty and environmental stochasticity into models of adaptive behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNamara, John M -- Fawcett, Tim W -- Houston, Alasdair I -- New York, N.Y. -- Science. 2013 May 31;340(6136):1084-6. doi: 10.1126/science.1230599.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Mathematics, University of Bristol, University Walk, Bristol, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723234" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; *Adaptation, Psychological ; Animals ; Cognition ; *Models, Psychological ; Rats ; *Uncertainty
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  • 81
    Publication Date: 2013-05-04
    Description: The hippocampal cognitive map is thought to be driven by distal visual cues and self-motion cues. However, other sensory cues also influence place cells. Hence, we measured rat hippocampal activity in virtual reality (VR), where only distal visual and nonvestibular self-motion cues provided spatial information, and in the real world (RW). In VR, place cells showed robust spatial selectivity; however, only 20% were track active, compared with 45% in the RW. This indicates that distal visual and nonvestibular self-motion cues are sufficient to provide selectivity, but vestibular and other sensory cues present in RW are necessary to fully activate the place-cell population. In addition, bidirectional cells preferentially encoded distance along the track in VR, while encoding absolute position in RW. Taken together, these results suggest the differential contributions of these sensory cues in shaping the hippocampal population code. Theta frequency was reduced, and its speed dependence was abolished in VR, but phase precession was unaffected, constraining mechanisms governing both hippocampal theta oscillations and temporal coding. These results reveal cooperative and competitive interactions between sensory cues for control over hippocampal spatiotemporal selectivity and theta rhythm.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049564/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049564/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ravassard, Pascal -- Kees, Ashley -- Willers, Bernard -- Ho, David -- Aharoni, Daniel -- Cushman, Jesse -- Aghajan, Zahra M -- Mehta, Mayank R -- 5R01MH092925-02/MH/NIMH NIH HHS/ -- R01 MH092925/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 14;340(6138):1342-6. doi: 10.1126/science.1232655. Epub 2013 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉W. M. Keck Center for Neurophysics, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641063" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Mapping ; Cues ; Hippocampus/*physiology ; Male ; Rats ; Rats, Inbred LEC ; *Space Perception ; *Spatial Behavior ; Theta Rhythm ; *Time Perception ; User-Computer Interface
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  • 82
    Publication Date: 2013-04-13
    Description: During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell-dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640797/" 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/PMC3640797/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teijaro, John R -- Ng, Cherie -- Lee, Andrew M -- Sullivan, Brian M -- Sheehan, Kathleen C F -- Welch, Megan -- Schreiber, Robert D -- de la Torre, Juan Carlos -- Oldstone, Michael B A -- AI007354/AI/NIAID NIH HHS/ -- AI047140/AI/NIAID NIH HHS/ -- AI077719/AI/NIAID NIH HHS/ -- AI09484/AI/NIAID NIH HHS/ -- CA43059/CA/NCI NIH HHS/ -- HL007195/HL/NHLBI NIH HHS/ -- NS041219/NS/NINDS NIH HHS/ -- R01 AI009484/AI/NIAID NIH HHS/ -- R01 AI047140/AI/NIAID NIH HHS/ -- R01 AI077719/AI/NIAID NIH HHS/ -- U54 AI057160/AI/NIAID NIH HHS/ -- U54AI057160/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 12;340(6129):207-11. doi: 10.1126/science.1235214.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23580529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/blood ; Antigens, CD274/metabolism ; Arenaviridae Infections/*immunology/pathology/*virology ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/metabolism ; Dendritic Cells/immunology/virology ; Female ; Immune Tolerance ; Interferon Type I/immunology/*metabolism ; Interleukin-10/metabolism ; Lymphocytes/immunology/virology ; Lymphocytic choriomeningitis virus/*immunology/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Receptor, Interferon alpha-beta/immunology/metabolism ; *Signal Transduction ; Spleen/immunology/pathology ; Viremia
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  • 83
    Publication Date: 2013-11-10
    Description: Circadian clocks regulate numerous physiological processes that vary across the day-night (diurnal) cycle, but if and how the circadian clock regulates the adaptive immune system is mostly unclear. Interleukin-17-producing CD4(+) T helper (T(H)17) cells are proinflammatory immune cells that protect against bacterial and fungal infections at mucosal surfaces. Their lineage specification is regulated by the orphan nuclear receptor RORgammat. We show that the transcription factor NFIL3 suppresses T(H)17 cell development by directly binding and repressing the Rorgammat promoter. NFIL3 links T(H)17 cell development to the circadian clock network through the transcription factor REV-ERBalpha. Accordingly, TH17 lineage specification varies diurnally and is altered in Rev-erbalpha(-/-) mice. Light-cycle disruption elevated intestinal T(H)17 cell frequencies and increased susceptibility to inflammatory disease. Thus, lineage specification of a key immune cell is under direct circadian control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165400/" 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/PMC4165400/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Xiaofei -- Rollins, Darcy -- Ruhn, Kelly A -- Stubblefield, Jeremy J -- Green, Carla B -- Kashiwada, Masaki -- Rothman, Paul B -- Takahashi, Joseph S -- Hooper, Lora V -- R01 DK070855/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):727-30. doi: 10.1126/science.1243884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24202171" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic-Leucine Zipper Transcription Factors/genetics/*metabolism ; CLOCK Proteins/genetics ; Cell Differentiation/*genetics ; Cell Lineage/genetics ; Circadian Clocks/genetics/*immunology ; *Gene Expression Regulation ; Germ-Free Life ; HEK293 Cells ; Humans ; Intestine, Small/immunology/microbiology ; Jurkat Cells ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Nuclear Receptor Subfamily 1, Group D, Member 1/genetics/metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 3/*genetics ; Promoter Regions, Genetic ; Th17 Cells/*cytology
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  • 84
    Publication Date: 2013-08-21
    Description: Proteinases and the innate immune receptor Toll-like receptor 4 (TLR4) are essential for expression of allergic inflammation and diseases such as asthma. A mechanism that links these inflammatory mediators is essential for explaining the fundamental basis of allergic disease but has been elusive. Here, we demonstrate that TLR4 is activated by airway proteinase activity to initiate both allergic airway disease and antifungal immunity. These outcomes were induced by proteinase cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage products that acted as TLR4 ligands on airway epithelial cells and macrophages. Thus, allergic airway inflammation represents an antifungal defensive strategy that is driven by fibrinogen cleavage and TLR4 activation. These findings clarify the molecular basis of allergic disease and suggest new therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898200/" 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/PMC3898200/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millien, Valentine Ongeri -- Lu, Wen -- Shaw, Joanne -- Yuan, Xiaoyi -- Mak, Garbo -- Roberts, Luz -- Song, Li-Zhen -- Knight, J Morgan -- Creighton, Chad J -- Luong, Amber -- Kheradmand, Farrah -- Corry, David B -- AI057696/AI/NIAID NIH HHS/ -- AI070973/AI/NIAID NIH HHS/ -- CA125123/CA/NCI NIH HHS/ -- HL75243/HL/NHLBI NIH HHS/ -- K02 HL075243/HL/NHLBI NIH HHS/ -- R01 AI057696/AI/NIAID NIH HHS/ -- R01 HL095382/HL/NHLBI NIH HHS/ -- R01 HL117181/HL/NHLBI NIH HHS/ -- R25GM56929/GM/NIGMS NIH HHS/ -- T32 GM088129/GM/NIGMS NIH HHS/ -- T32GM088129/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 16;341(6147):792-6. doi: 10.1126/science.1240342.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, TX, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23950537" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aspergillus niger/growth & development/*immunology ; Aspergillus oryzae/enzymology ; Bronchoalveolar Lavage Fluid/cytology ; Epithelial Cells/immunology/metabolism ; Fibrinogen/*metabolism ; Immunity, Innate ; Ligands ; Macrophage Activation ; Macrophages/immunology/metabolism/microbiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Peptide Hydrolases/immunology/*metabolism ; Respiratory Hypersensitivity/*immunology/*metabolism ; Respiratory Mucosa/cytology/immunology/metabolism ; Th2 Cells/immunology ; Toll-Like Receptor 4/genetics/*metabolism
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  • 85
    Publication Date: 2013-12-21
    Description: The inbred mouse C57BL/6J is the reference strain for genome sequence and for most behavioral and physiological phenotypes. However, the International Knockout Mouse Consortium uses an embryonic stem cell line derived from a related C57BL/6N substrain. We found that C57BL/6N has a lower acute and sensitized response to cocaine and methamphetamine. We mapped a single causative locus and identified a nonsynonymous mutation of serine to phenylalanine (S968F) in Cytoplasmic FMRP interacting protein 2 (Cyfip2) as the causative variant. The S968F mutation destabilizes CYFIP2, and deletion of the C57BL/6N mutant allele leads to acute and sensitized cocaine-response phenotypes. We propose that CYFIP2 is a key regulator of cocaine response in mammals and present a framework to use mouse substrains to identify previously unknown genes and alleles regulating behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500108/" 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/PMC4500108/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, Vivek -- Kim, Kyungin -- Joseph, Chryshanthi -- Kourrich, Said -- Yoo, Seung-Hee -- Huang, Hung Chung -- Vitaterna, Martha H -- de Villena, Fernando Pardo-Manuel -- Churchill, Gary -- Bonci, Antonello -- Takahashi, Joseph S -- F32 DA024556/DA/NIDA NIH HHS/ -- F32DA024556/DA/NIDA NIH HHS/ -- U01 MH061915/MH/NIMH NIH HHS/ -- U01MH61915/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Dec 20;342(6165):1508-12. doi: 10.1126/science.1245503.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357318" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Central Nervous System Stimulants/administration & dosage ; Cocaine/*administration & dosage ; Cocaine-Related Disorders/*genetics/*psychology ; *Drug-Seeking Behavior ; Methamphetamine/administration & dosage ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects ; Mutation ; Nerve Tissue Proteins/genetics/*physiology ; Phenylalanine/genetics ; Polymorphism, Single Nucleotide ; Psychomotor Performance/drug effects ; Quantitative Trait Loci ; Serine/genetics
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  • 86
    Publication Date: 2013-04-20
    Description: Both bats and rats exhibit grid cells in medial entorhinal cortex that fire as they visit a regular array of spatial locations. In rats, grid-cell firing field properties correlate with theta-frequency rhythmicity of spiking and membrane-potential resonance; however, bat grid cells do not exhibit theta rhythmic spiking, generating controversy over the role of theta rhythm. To test whether this discrepancy reflects differences in rhythmicity at a cellular level, we performed whole-cell patch recordings from entorhinal neurons in both species to record theta-frequency resonance. Bat neurons showed no theta-frequency resonance, suggesting grid-cell coding via different mechanisms in bats and rats or lack of theta rhythmic contributions to grid-cell firing in either species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heys, James G -- MacLeod, Katrina M -- Moss, Cynthia F -- Hasselmo, Michael E -- New York, N.Y. -- Science. 2013 Apr 19;340(6130):363-7. doi: 10.1126/science.1233831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Program for Neuroscience, Center for Memory and Brain, Boston University, 2 Cummington Street, Boston, MA 02215, USA. jimheys@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23599495" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chiroptera ; Entorhinal Cortex/cytology/*physiology ; Female ; Male ; Membrane Potentials ; Models, Neurological ; Neurons/cytology/*physiology ; Patch-Clamp Techniques ; Rats ; Rats, Long-Evans ; *Theta Rhythm
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  • 87
    Publication Date: 2013-04-06
    Description: We used a combined optogenetic-electrophysiological strategy to determine the functional identity of entorhinal cells with output to the place-cell population in the hippocampus. Channelrhodopsin-2 (ChR2) was expressed selectively in the hippocampus-targeting subset of entorhinal projection neurons by infusing retrogradely transportable ChR2-coding recombinant adeno-associated virus in the hippocampus. Virally transduced ChR2-expressing cells were identified in medial entorhinal cortex as cells that fired at fixed minimal latencies in response to local flashes of light. A large number of responsive cells were grid cells, but short-latency firing was also induced in border cells and head-direction cells, as well as cells with irregular or nonspatial firing correlates, which suggests that place fields may be generated by convergence of signals from a broad spectrum of entorhinal functional cell types.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Sheng-Jia -- Ye, Jing -- Miao, Chenglin -- Tsao, Albert -- Cerniauskas, Ignas -- Ledergerber, Debora -- Moser, May-Britt -- Moser, Edvard I -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):1232627. doi: 10.1126/science.1232627.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres gate 9, Norwegian Brain Centre, 7491 Trondheim, Norway. sheng-jia.zhang@ntnu.no〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23559255" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; CA1 Region, Hippocampal/cytology/physiology ; *Cell Communication ; Dependovirus ; Entorhinal Cortex/cytology/*physiology ; Gene Targeting ; Hippocampus/cytology/*physiology ; Neurons/*physiology ; Photic Stimulation ; Rats ; Rhodopsin/biosynthesis/genetics ; Transduction, Genetic
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  • 88
    Publication Date: 2013-01-12
    Description: An extensive literature shows that astrocytes exhibit metabotropic glutamate receptor 5 (mGluR5)-dependent increases in cytosolic calcium ions (Ca(2+)) in response to glutamatergic transmission and, in turn, modulate neuronal activity by their Ca(2+)-dependent release of gliotransmitters. These findings, based on studies of young rodents, have led to the concept of the tripartite synapse, in which astrocytes actively participate in neurotransmission. Using genomic analysis, immunoelectron microscopy, and two-photon microscopy of astrocytic Ca(2+) signaling in vivo, we found that astrocytic expression of mGluR5 is developmentally regulated and is undetectable after postnatal week 3. In contrast, mGluR3, whose activation inhibits adenylate cyclase but not calcium signaling, was expressed in astrocytes at all developmental stages. Neuroglial signaling in the adult brain may therefore occur in a manner fundamentally distinct from that exhibited during development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569008/" 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/PMC3569008/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Wei -- McConnell, Evan -- Pare, Jean-Francois -- Xu, Qiwu -- Chen, Michael -- Peng, Weiguo -- Lovatt, Ditte -- Han, Xiaoning -- Smith, Yoland -- Nedergaard, Maiken -- NS075177/NS/NINDS NIH HHS/ -- NS078304/NS/NINDS NIH HHS/ -- P51OD011132/OD/NIH HHS/ -- P51RR000165/RR/NCRR NIH HHS/ -- R01 NS075177/NS/NINDS NIH HHS/ -- R01 NS078167/NS/NINDS NIH HHS/ -- R01 NS078304/NS/NINDS NIH HHS/ -- RR00165/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 11;339(6116):197-200. doi: 10.1126/science.1226740.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23307741" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; *Aging ; Animals ; Astrocytes/*metabolism ; Calcium/metabolism ; *Calcium Signaling ; Cerebral Cortex/cytology/*metabolism/ultrastructure ; Female ; Glutamic Acid/*metabolism ; Hippocampus/cytology/metabolism/ultrastructure ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/agonists/*metabolism ; Synaptic Transmission
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  • 89
    Publication Date: 2013-07-28
    Description: Memories can be unreliable. We created a false memory in mice by optogenetically manipulating memory engram-bearing cells in the hippocampus. Dentate gyrus (DG) or CA1 neurons activated by exposure to a particular context were labeled with channelrhodopsin-2. These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context, in which a foot shock was never delivered. The recall of this false memory was context-specific, activated similar downstream regions engaged during natural fear memory recall, and was also capable of driving an active fear response. Our data demonstrate that it is possible to generate an internally represented and behaviorally expressed fear memory via artificial means.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramirez, Steve -- Liu, Xu -- Lin, Pei-Ann -- Suh, Junghyup -- Pignatelli, Michele -- Redondo, Roger L -- Ryan, Tomas J -- Tonegawa, Susumu -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):387-91. doi: 10.1126/science.1239073.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN-Massachusetts Institute of Technology Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology, MIT, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23888038" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/physiology ; Animals ; Association ; CA1 Region, Hippocampal/cytology/*physiology ; *Conditioning (Psychology) ; Dentate Gyrus/cytology/*physiology ; Dependovirus/genetics ; Doxycycline/administration & dosage ; Fear ; Genes, fos ; Light ; Memory/*physiology ; Mental Recall/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons/*physiology ; Optogenetics ; Rhodopsin/genetics/metabolism
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  • 90
    Publication Date: 2013-08-03
    Description: Robust transmission of information despite the presence of variation is a fundamental problem in cellular functions. However, the capability and characteristics of information transmission in signaling pathways remain poorly understood. We describe robustness and compensation of information transmission of signaling pathways at the cell population level. We calculated the mutual information transmitted through signaling pathways for the growth factor-mediated gene expression. Growth factors appeared to carry only information sufficient for a binary decision. Information transmission was generally more robust than average signal intensity despite pharmacological perturbations, and compensation of information transmission occurred. Information transmission to the biological output of neurite extension appeared robust. Cells may use information entropy as information so that messages can be robustly transmitted despite variation in molecular activities among individual cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uda, Shinsuke -- Saito, Takeshi H -- Kudo, Takamasa -- Kokaji, Toshiya -- Tsuchiya, Takaho -- Kubota, Hiroyuki -- Komori, Yasunori -- Ozaki, Yu-ichi -- Kuroda, Shinya -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):558-61. doi: 10.1126/science.1234511.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Bunkyo-ku, Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23908238" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cyclic AMP Response Element-Binding Protein/metabolism ; Early Growth Response Protein 1/metabolism ; Gene Expression/drug effects ; *Information Theory ; Intercellular Signaling Peptides and Proteins/pharmacology ; PC12 Cells ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; *Signal Transduction
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  • 91
    Publication Date: 2013-08-31
    Description: The lateral habenula (LHb) has recently emerged as a key brain region in the pathophysiology of depression. However, the molecular mechanism by which LHb becomes hyperactive in depression remains unknown. Through a quantitative proteomic screen, we found that expression of the beta form of calcium/calmodulin-dependent protein kinase type II (betaCaMKappaIotaIota) was significantly up-regulated in the LHb of animal models of depression and down-regulated by antidepressants. Increasing beta-, but not alpha-, CaMKII in the LHb strongly enhanced the synaptic efficacy and spike output of LHb neurons and was sufficient to produce profound depressive symptoms, including anhedonia and behavioral despair. Down-regulation of betaCaMKII levels, blocking its activity or its target molecule the glutamate receptor GluR1 reversed the depressive symptoms. These results identify betaCaMKII as a powerful regulator of LHb neuron function and a key molecular determinant of depression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932364/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932364/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Kun -- Zhou, Tao -- Liao, Lujian -- Yang, Zhongfei -- Wong, Catherine -- Henn, Fritz -- Malinow, Roberto -- Yates, John R 3rd -- Hu, Hailan -- P41 GM103533/GM/NIGMS NIH HHS/ -- R01 MH067880/MH/NIMH NIH HHS/ -- R01 MH091119/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1016-20. doi: 10.1126/science.1240729.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P R China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990563" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antidepressive Agents/pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & ; inhibitors/*biosynthesis/genetics ; Depressive Disorder, Major/*enzymology/genetics/psychology ; Disease Models, Animal ; Gene Knockdown Techniques ; Habenula/drug effects/*enzymology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects/enzymology ; Promoter Regions, Genetic ; Proteomics ; Rats ; Rats, Sprague-Dawley
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  • 92
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-07-03
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749839/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749839/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nedergaard, Maiken -- R01 MH099578/MH/NIMH NIH HHS/ -- R01 NS075177/NS/NINDS NIH HHS/ -- R01 NS078167/NS/NINDS NIH HHS/ -- R01 NS078304/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1529-30. doi: 10.1126/science.1240514.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY 14642, USA. nedergaard@urmc.rochester.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812703" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquaporin 4/*metabolism ; Brain/*physiopathology ; Cerebrospinal Fluid/metabolism ; Extracellular Fluid/metabolism ; Humans ; Lymphatic Vessels/*metabolism ; Mice ; Neurodegenerative Diseases/cerebrospinal fluid/*physiopathology/*therapy ; Neuroglia/*metabolism ; Neurons/metabolism ; Rats
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  • 93
    Publication Date: 2013-07-28
    Description: The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, aerobic glycolysis is augmented, and glucose is directed toward metabolic pathways that support tissue growth. We show that reprogramming of intestinal glucose metabolism is triggered by the exposure of the Roux limb to undigested nutrients. We demonstrate by positron emission tomography-computed tomography scanning and biodistribution analysis using 2-deoxy-2-[18F]fluoro-D-glucose that reprogramming of intestinal glucose metabolism renders the intestine a major tissue for glucose disposal, contributing to the improvement in glycemic control after RYGB.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068965/" 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/PMC4068965/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saeidi, Nima -- Meoli, Luca -- Nestoridi, Eirini -- Gupta, Nitin K -- Kvas, Stephanie -- Kucharczyk, John -- Bonab, Ali A -- Fischman, Alan J -- Yarmush, Martin L -- Stylopoulos, Nicholas -- DK089503/DK/NIDDK NIH HHS/ -- F32 DK095558/DK/NIDDK NIH HHS/ -- F32DK095558/DK/NIDDK NIH HHS/ -- P50 GM021700/GM/NIGMS NIH HHS/ -- T32DK007191/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):406-10. doi: 10.1126/science.1235103.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Basic and Translational Obesity Research, Division of Endocrinology, Boston Children's 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/23888041" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; Blood Glucose/*metabolism ; Cholesterol/biosynthesis ; Diabetes Mellitus, Experimental/metabolism/surgery ; Digestion ; Energy Metabolism ; Fluorodeoxyglucose F18/metabolism ; *Gastric Bypass ; Gene Expression Regulation ; Glucose/*metabolism ; Glucose Transporter Type 1/metabolism ; Glycolysis ; Jejunum/*metabolism ; Male ; Metabolic Networks and Pathways ; Metabolomics ; Multimodal Imaging ; Pentose Phosphate Pathway ; Positron-Emission Tomography ; Rats ; Rats, Long-Evans ; Signal Transduction ; Tissue Distribution ; Tomography, X-Ray Computed ; Up-Regulation
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  • 94
    Publication Date: 2013-09-28
    Description: A dense mucus layer in the large intestine prevents inflammation by shielding the underlying epithelium from luminal bacteria and food antigens. This mucus barrier is organized around the hyperglycosylated mucin MUC2. Here we show that the small intestine has a porous mucus layer, which permitted the uptake of MUC2 by antigen-sampling dendritic cells (DCs). Glycans associated with MUC2 imprinted DCs with anti-inflammatory properties by assembling a galectin-3-Dectin-1-FcgammaRIIB receptor complex that activated beta-catenin. This transcription factor interfered with DC expression of inflammatory but not tolerogenic cytokines by inhibiting gene transcription through nuclear factor kappaB. MUC2 induced additional conditioning signals in intestinal epithelial cells. Thus, mucus does not merely form a nonspecific physical barrier, but also constrains the immunogenicity of gut antigens by delivering tolerogenic signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005805/" 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/PMC4005805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shan, Meimei -- Gentile, Maurizio -- Yeiser, John R -- Walland, A Cooper -- Bornstein, Victor U -- Chen, Kang -- He, Bing -- Cassis, Linda -- Bigas, Anna -- Cols, Montserrat -- Comerma, Laura -- Huang, Bihui -- Blander, J Magarian -- Xiong, Huabao -- Mayer, Lloyd -- Berin, Cecilia -- Augenlicht, Leonard H -- Velcich, Anna -- Cerutti, Andrea -- AI073899/AI/NIAID NIH HHS/ -- AI095245/AI/NIAID NIH HHS/ -- AI57653/AI/NIAID NIH HHS/ -- AI61093/AI/NIAID NIH HHS/ -- AI74378/AI/NIAID NIH HHS/ -- AI95613/AI/NIAID NIH HHS/ -- AI96187/AI/NIAID NIH HHS/ -- DK072201/DK/NIDDK NIH HHS/ -- P01 AI061093/AI/NIAID NIH HHS/ -- P01 DK072201/DK/NIDDK NIH HHS/ -- P60 DK020541/DK/NIDDK NIH HHS/ -- R01 AI057653/AI/NIAID NIH HHS/ -- R01 AI093577/AI/NIAID NIH HHS/ -- U01 AI095613/AI/NIAID NIH HHS/ -- U19 AI096187/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 25;342(6157):447-53. doi: 10.1126/science.1237910. Epub 2013 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24072822" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Dendritic Cells/immunology ; Galectin 3/genetics/metabolism ; Glycosylation ; *Homeostasis ; Humans ; Immune Tolerance/genetics/*immunology ; Inflammation/immunology ; Intestinal Mucosa/immunology ; Intestine, Small/*immunology ; Lectins, C-Type/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mouth/*immunology ; Mucin-2/genetics/physiology ; Mucus/*immunology ; NF-kappa B/metabolism ; Receptors, IgG/genetics/metabolism ; Transcription, Genetic ; beta Catenin/metabolism
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  • 95
    Publication Date: 2013-01-19
    Description: Environmental stressors during childhood and adolescence influence postnatal brain maturation and human behavioral patterns in adulthood. Accordingly, excess stressors result in adult-onset neuropsychiatric disorders. We describe an underlying mechanism in which glucocorticoids link adolescent stressors to epigenetic controls in neurons. In a mouse model of this phenomenon, a mild isolation stress affects the mesocortical projection of dopaminergic neurons in which DNA hypermethylation of the tyrosine hydroxylase gene is elicited, but only when combined with a relevant genetic risk for neuropsychiatric disorders. These molecular changes are associated with several neurochemical and behavioral deficits that occur in this mouse model, all of which are blocked by a glucocorticoid receptor antagonist. The biology and phenotypes of the mouse models resemble those of psychotic depression, a common and debilitating psychiatric disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617477/" 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/PMC3617477/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Niwa, Minae -- Jaaro-Peled, Hanna -- Tankou, Stephanie -- Seshadri, Saurav -- Hikida, Takatoshi -- Matsumoto, Yurie -- Cascella, Nicola G -- Kano, Shin-ichi -- Ozaki, Norio -- Nabeshima, Toshitaka -- Sawa, Akira -- K99 MH094408/MH/NIMH NIH HHS/ -- K99MH-094408/MH/NIMH NIH HHS/ -- MH-069853/MH/NIMH NIH HHS/ -- MH-084018/MH/NIMH NIH HHS/ -- MH-085226/MH/NIMH NIH HHS/ -- MH-088753/MH/NIMH NIH HHS/ -- MH-092443/MH/NIMH NIH HHS/ -- MH-094268/MH/NIMH NIH HHS/ -- R01 MH092443/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 18;339(6117):335-9. doi: 10.1126/science.1226931.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23329051" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; *Adolescent Behavior ; *Adolescent Development ; Affective Disorders, Psychotic/genetics/*metabolism ; Animals ; Disease Models, Animal ; Dopaminergic Neurons/*metabolism ; *Epigenesis, Genetic ; Glucocorticoids/*metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Tissue Proteins/genetics/metabolism ; Stress, Psychological/genetics/*metabolism
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  • 96
    Publication Date: 2013-09-07
    Description: Epigenetic alterations are increasingly recognized as causes of human cancers and disease. These aberrations are likely to arise during genomic reprogramming in mammalian preimplantation embryos, when their epigenomes are most vulnerable. However, this process is only partially understood because of the experimental inaccessibility of early-stage embryos. Here, we introduce a methodologic advance, probing single cells for various DNA-methylation errors at multiple loci, to reveal failed maintenance of epigenetic mark results in chimeric mice, which display unpredictable phenotypes leading to developmental arrest. Yet we show that mouse pronuclear transfer can be used to ameliorate such reprogramming defects. This study not only details the epigenetic reprogramming dynamics in early mammalian embryos but also suggests diagnostic and potential future therapeutic applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lorthongpanich, Chanchao -- Cheow, Lih Feng -- Balu, Sathish -- Quake, Stephen R -- Knowles, Barbara B -- Burkholder, William F -- Solter, Davor -- Messerschmidt, Daniel M -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 6;341(6150):1110-2. doi: 10.1126/science.1240617.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mammalian Development Group, Institute of Medical Biology, A*STAR, Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24009393" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*metabolism ; Cellular Reprogramming/*genetics ; *Chimerism ; *DNA Methylation ; *Epigenesis, Genetic ; Gene Deletion ; *Gene Expression Regulation, Developmental ; Genetic Loci ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nuclear Proteins/genetics ; Repressor Proteins/genetics ; Single-Cell Analysis
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  • 97
    Publication Date: 2013-05-11
    Description: Brain plasticity as a neurobiological reflection of individuality is difficult to capture in animal models. Inspired by behavioral-genetic investigations of human monozygotic twins reared together, we obtained dense longitudinal activity data on 40 inbred mice living in one large enriched environment. The exploratory activity of the mice diverged over time, resulting in increasing individual differences with advancing age. Individual differences in cumulative roaming entropy, indicating the active coverage of territory, correlated positively with individual differences in adult hippocampal neurogenesis. Our results show that factors unfolding or emerging during development contribute to individual differences in structural brain plasticity and behavior. The paradigm introduced here serves as an animal model for identifying mechanisms of plasticity underlying nonshared environmental contributions to individual differences in behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freund, Julia -- Brandmaier, Andreas M -- Lewejohann, Lars -- Kirste, Imke -- Kritzler, Mareike -- Kruger, Antonio -- Sachser, Norbert -- Lindenberger, Ulman -- Kempermann, Gerd -- New York, N.Y. -- Science. 2013 May 10;340(6133):756-9. doi: 10.1126/science.1235294.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CRTD-DFG Research Center for Regenerative Therapies Dresden, Technische Universitat Dresden, Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661762" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; Body Weight ; Brain/anatomy & histology/embryology/physiology ; Female ; Hippocampus/anatomy & histology/*embryology/physiology ; *Individuality ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Models, Animal ; *Neurogenesis ; Neuronal Plasticity/*genetics ; Organ Size
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  • 98
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-08-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2013 Aug 23;341(6148):833-6. doi: 10.1126/science.341.6148.833.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23970676" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspase 9/genetics/*metabolism ; DNA, Bacterial/*genetics ; Disease Models, Animal ; Food Microbiology ; Gene Knockout Techniques/methods ; Gene Targeting/*methods ; Genome/genetics ; Humans ; Mice ; Rats ; *Streptococcus Phages ; Streptococcus thermophilus/*genetics/*immunology/virology
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  • 99
    Publication Date: 2013-05-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balter, Michael -- New York, N.Y. -- Science. 2013 May 24;340(6135):909. doi: 10.1126/science.340.6135.909.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704541" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; *Cognition ; *Forecasting ; Hippocampus/physiology ; Neurons/physiology ; Neuropsychological Tests ; Rats
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2013-11-02
    Description: Synapse formation in the developing brain depends on the coordinated activity of synaptogenic proteins, some of which have been implicated in a number of neurodevelopmental disorders. Here, we show that the sushi repeat-containing protein X-linked 2 (SRPX2) gene encodes a protein that promotes synaptogenesis in the cerebral cortex. In humans, SRPX2 is an epilepsy- and language-associated gene that is a target of the foxhead box protein P2 (FoxP2) transcription factor. We also show that FoxP2 modulates synapse formation through regulating SRPX2 levels and that SRPX2 reduction impairs development of ultrasonic vocalization in mice. Our results suggest FoxP2 modulates the development of neural circuits through regulating synaptogenesis and that SRPX2 is a synaptogenic factor that plays a role in the pathogenesis of language disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903157/" 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/PMC3903157/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sia, G M -- Clem, R L -- Huganir, R L -- NS050274/NS/NINDS NIH HHS/ -- P30 NS050274/NS/NINDS NIH HHS/ -- P50 MH084020/MH/NIMH NIH HHS/ -- P50MH084020/MH/NIMH NIH HHS/ -- R01 MH095058/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):987-91. doi: 10.1126/science.1245079. Epub 2013 Oct 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24179158" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/cytology ; Epilepsy/genetics ; Forkhead Transcription Factors/genetics/*metabolism ; Humans ; *Language ; Language Disorders/*genetics ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics/*physiology ; Neurons/physiology ; Synapses/*physiology ; Transfection ; *Vocalization, Animal
    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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