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  • Mice, Inbred C57BL  (207)
  • American Association for the Advancement of Science (AAAS)  (207)
  • 2010-2014  (207)
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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
    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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  • 2
    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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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    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
    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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  • 4
    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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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    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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  • 11
    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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  • 12
    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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  • 13
    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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  • 14
    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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  • 15
    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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  • 16
    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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  • 17
    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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  • 18
    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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  • 19
    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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  • 20
    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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  • 21
    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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  • 22
    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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  • 23
    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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  • 24
    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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  • 25
    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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  • 26
    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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  • 27
    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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  • 28
    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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  • 29
    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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  • 30
    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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  • 31
    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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  • 32
    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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  • 33
    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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  • 34
    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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  • 35
    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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  • 36
    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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  • 37
    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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  • 38
    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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  • 39
    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
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  • 40
    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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  • 41
    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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  • 42
    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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  • 43
    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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  • 44
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 45
    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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  • 46
    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
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  • 47
    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
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  • 48
    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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  • 49
    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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  • 50
    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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  • 51
    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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  • 52
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 53
    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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  • 54
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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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  • 55
    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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  • 56
    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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  • 57
    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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  • 58
    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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  • 59
    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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  • 60
    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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  • 61
    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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  • 62
    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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  • 63
    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
    Print ISSN: 0036-8075
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  • 64
    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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  • 65
    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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  • 66
    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
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  • 67
    Publication Date: 2013-02-09
    Description: Changes in the microbial community structure are observed in individuals with intestinal inflammatory disorders. These changes are often characterized by a depletion of obligate anaerobic bacteria, whereas the relative abundance of facultative anaerobic Enterobacteriaceae increases. The mechanisms by which the host response shapes the microbial community structure, however, remain unknown. We show that nitrate generated as a by-product of the inflammatory response conferred a growth advantage to the commensal bacterium Escherichia coli in the large intestine of mice. Mice deficient in inducible nitric oxide synthase did not support the growth of E. coli by nitrate respiration, suggesting that the nitrate generated during inflammation was host-derived. Thus, the inflammatory host response selectively enhances the growth of commensal Enterobacteriaceae by generating electron acceptors for anaerobic respiration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004111/" 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/PMC4004111/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winter, Sebastian E -- Winter, Maria G -- Xavier, Mariana N -- Thiennimitr, Parameth -- Poon, Victor -- Keestra, A Marijke -- Laughlin, Richard C -- Gomez, Gabriel -- Wu, Jing -- Lawhon, Sara D -- Popova, Ina E -- Parikh, Sanjai J -- Adams, L Garry -- Tsolis, Renee M -- Stewart, Valley J -- Baumler, Andreas J -- AI076246/AI/NIAID NIH HHS/ -- AI088122/AI/NIAID NIH HHS/ -- AI090387/AI/NIAID NIH HHS/ -- R21 AI107393/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 8;339(6120):708-11. doi: 10.1126/science.1232467.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23393266" target="_blank"〉PubMed〈/a〉
    Keywords: Anaerobiosis ; Animals ; Cattle ; Colitis/*metabolism/*microbiology ; Escherichia coli/genetics/*growth & development/*metabolism ; Ileum/microbiology ; Intestine, Large/*microbiology ; Mice ; Mice, Inbred C57BL ; Mutation ; Nitrates/*metabolism ; Nitric Oxide Synthase Type II/antagonists & inhibitors/deficiency/metabolism
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  • 68
    Publication Date: 2013-03-16
    Description: During hematopoiesis, lineage- and stage-specific transcription factors work in concert with chromatin modifiers to direct the differentiation of all blood cells. We explored the role of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor KAP1 in this process. In mice, hematopoietic-restricted deletion of Kap1 resulted in severe hypoproliferative anemia. Kap1-deleted erythroblasts failed to induce mitophagy-associated genes and retained mitochondria. This was due to persistent expression of microRNAs (miRNAs) targeting mitophagy transcripts, itself secondary to a lack of repression by stage-specific KRAB-ZFPs. The KRAB/KAP1-miRNA regulatory cascade is evolutionarily conserved, as it also controls mitophagy during human erythropoiesis. Thus, a multilayered transcription regulatory system is present, in which protein- and RNA-based repressors are superimposed in combinatorial fashion to govern the timely triggering of an important differentiation event.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678075/" 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/PMC3678075/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barde, Isabelle -- Rauwel, Benjamin -- Marin-Florez, Ray Marcel -- Corsinotti, Andrea -- Laurenti, Elisa -- Verp, Sonia -- Offner, Sandra -- Marquis, Julien -- Kapopoulou, Adamandia -- Vanicek, Jiri -- Trono, Didier -- 268721/European Research Council/International -- New York, N.Y. -- Science. 2013 Apr 19;340(6130):350-3. doi: 10.1126/science.1232398. Epub 2013 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23493425" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia/genetics ; Animals ; Autophagy/*genetics ; Erythroblasts/*metabolism/ultrastructure ; Erythropoiesis/*genetics ; Female ; Male ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/genetics/*metabolism ; Mitochondria/genetics/*physiology ; Mitochondrial Proteins/metabolism ; Nuclear Proteins/genetics/*metabolism ; Repressor Proteins/genetics/*metabolism ; Transcription Factors/*metabolism ; *Zinc Fingers
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  • 69
    Publication Date: 2013-03-02
    Description: The initial phase in the development of a migraine is still poorly understood. Here, we describe a previously unknown signaling pathway between stressed neurons and trigeminal afferents during cortical spreading depression (CSD), the putative cause of migraine aura and headache. CSD caused neuronal Pannexin1 (Panx1) megachannel opening and caspase-1 activation followed by high-mobility group box 1 (HMGB1) release from neurons and nuclear factor kappaB activation in astrocytes. Suppression of this cascade abolished CSD-induced trigeminovascular activation, dural mast cell degranulation, and headache. CSD-induced neuronal megachannel opening may promote sustained activation of trigeminal afferents via parenchymal inflammatory cascades reaching glia limitans. This pathway may function to alarm an organism with headache when neurons are stressed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karatas, Hulya -- Erdener, Sefik Evren -- Gursoy-Ozdemir, Yasemin -- Lule, Sevda -- Eren-Kocak, Emine -- Sen, Zumrut Duygu -- Dalkara, Turgay -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1092-5. doi: 10.1126/science.1231897.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23449592" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways ; Animals ; Astrocytes/metabolism/physiology ; Caspase 1/metabolism ; Connexins/antagonists & inhibitors/*biosynthesis ; *Cortical Spreading Depression ; HMGB1 Protein/metabolism ; Mice ; Mice, Inbred C57BL ; Migraine Disorders/metabolism/*physiopathology ; NF-kappa B/metabolism ; Nerve Fibers/physiology ; Nerve Tissue Proteins/antagonists & inhibitors/*biosynthesis ; Neurons/metabolism/*physiology ; Protein Transport ; Signal Transduction ; Trigeminal Nerve/metabolism/*physiopathology
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  • 70
    Publication Date: 2013-07-06
    Description: Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807819/" 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/PMC3807819/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Patrick M -- Howitt, Michael R -- Panikov, Nicolai -- Michaud, Monia -- Gallini, Carey Ann -- Bohlooly-Y, Mohammad -- Glickman, Jonathan N -- Garrett, Wendy S -- F32 DK095506/DK/NIDDK NIH HHS/ -- F32 DK098826/DK/NIDDK NIH HHS/ -- F32DK095506/DK/NIDDK NIH HHS/ -- F32DK098826/DK/NIDDK NIH HHS/ -- K08 AI078942/AI/NIAID NIH HHS/ -- K08AI078942/AI/NIAID NIH HHS/ -- P30 DK034854/DK/NIDDK NIH HHS/ -- R01 CA154426/CA/NCI NIH HHS/ -- R01 GM099537/GM/NIGMS NIH HHS/ -- R01CA154426/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):569-73. doi: 10.1126/science.1241165. Epub 2013 Jul 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23828891" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria/*metabolism ; Colitis/metabolism ; Colon/*microbiology ; DNA-Binding Proteins/genetics ; Fatty Acids, Volatile/administration & dosage/*metabolism ; Fermentation ; Germ-Free Life ; *Homeostasis ; Humans ; *Metagenome ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Receptors, G-Protein-Coupled/genetics/metabolism ; T-Lymphocytes, Regulatory/*physiology/transplantation
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  • 71
    Publication Date: 2013-06-08
    Description: Hox genes are major determinants of the animal body plan, where they organize structures along both the trunk and appendicular axes. During mouse limb development, Hoxd genes are transcribed in two waves: early on, when the arm and forearm are specified, and later, when digits form. The transition between early and late regulations involves a functional switch between two opposite topological domains. This switch is reflected by a subset of Hoxd genes mapping centrally into the cluster, which initially interact with the telomeric domain and subsequently swing toward the centromeric domain, where they establish new contacts. This transition between independent regulatory landscapes illustrates both the modularity of the limbs and the distinct evolutionary histories of its various pieces. It also allows the formation of an intermediate area of low HOX proteins content, which develops into the wrist, the transition between our arms and our hands. This regulatory strategy accounts for collinear Hox gene regulation in land vertebrate appendages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andrey, Guillaume -- Montavon, Thomas -- Mascrez, Benedicte -- Gonzalez, Federico -- Noordermeer, Daan -- Leleu, Marion -- Trono, Didier -- Spitz, Francois -- Duboule, Denis -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1234167. doi: 10.1126/science.1234167.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Life Sciences, Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744951" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Forelimb/*embryology ; *Gene Expression Regulation, Developmental ; *Gene Order ; *Genes, Homeobox ; *Genes, Switch ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; *Multigene Family ; Telomere/genetics ; *Transcription, Genetic
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  • 72
    Publication Date: 2013-09-14
    Description: Inflammatory caspases, such as caspase-1 and -11, mediate innate immune detection of pathogens. Caspase-11 induces pyroptosis, a form of programmed cell death, and specifically defends against bacterial pathogens that invade the cytosol. During endotoxemia, however, excessive caspase-11 activation causes shock. We report that contamination of the cytoplasm by lipopolysaccharide (LPS) is the signal that triggers caspase-11 activation in mice. Specifically, caspase-11 responds to penta- and hexa-acylated lipid A, whereas tetra-acylated lipid A is not detected, providing a mechanism of evasion for cytosol-invasive Francisella. Priming the caspase-11 pathway in vivo resulted in extreme sensitivity to subsequent LPS challenge in both wild-type and Tlr4-deficient mice, whereas Casp11-deficient mice were relatively resistant. Together, our data reveal a new pathway for detecting cytoplasmic LPS.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931427/" 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/PMC3931427/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagar, Jon A -- Powell, Daniel A -- Aachoui, Youssef -- Ernst, Robert K -- Miao, Edward A -- AI007273/AI/NIAID NIH HHS/ -- AI057141/AI/NIAID NIH HHS/ -- AI097518/AI/NIAID NIH HHS/ -- AI101685/AI/NIAID NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- R01 AI097518/AI/NIAID NIH HHS/ -- R21 AI101685/AI/NIAID NIH HHS/ -- T32 AI007273/AI/NIAID NIH HHS/ -- U54 AI057141/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Sep 13;341(6151):1250-3. doi: 10.1126/science.1240988.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, 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/24031018" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis Regulatory Proteins/genetics ; Calcium-Binding Proteins/genetics ; Caspases/*biosynthesis/genetics ; Cross-Priming ; Enzyme Activation ; Francisella ; Gram-Negative Bacterial Infections/immunology ; Lipid A/*immunology ; Mice ; Mice, Inbred C57BL ; Poly I-C/immunology ; Salmonella ; Salmonella Infections/immunology ; Shock, Septic/*immunology ; Toll-Like Receptor 4/genetics/*immunology
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  • 73
    Publication Date: 2013-03-16
    Description: Upon infection, antigen-specific CD8(+) T lymphocyte responses display a highly reproducible pattern of expansion and contraction that is thought to reflect a uniform behavior of individual cells. We tracked the progeny of individual mouse CD8(+) T cells by in vivo lineage tracing and demonstrated that, even for T cells bearing identical T cell receptors, both clonal expansion and differentiation patterns are heterogeneous. As a consequence, individual naive T lymphocytes contributed differentially to short- and long-term protection, as revealed by participation of their progeny during primary versus recall infections. The discordance in fate of individual naive T cells argues against asymmetric division as a singular driver of CD8(+) T cell heterogeneity and demonstrates that reproducibility of CD8(+) T cell responses is achieved through population averaging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerlach, Carmen -- Rohr, Jan C -- Perie, Leila -- van Rooij, Nienke -- van Heijst, Jeroen W J -- Velds, Arno -- Urbanus, Jos -- Naik, Shalin H -- Jacobs, Heinz -- Beltman, Joost B -- de Boer, Rob J -- Schumacher, Ton N M -- New York, N.Y. -- Science. 2013 May 3;340(6132):635-9. doi: 10.1126/science.1235487. Epub 2013 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23493421" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Asymmetric Cell Division ; CD8-Positive T-Lymphocytes/*cytology/*immunology ; *Cell Differentiation ; Cell Lineage ; Cell Proliferation ; *Immunity, Cellular ; *Immunologic Memory ; Immunophenotyping ; Listeria monocytogenes ; Listeriosis/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Immunological ; Receptors, Antigen, T-Cell/immunology ; Single-Cell Analysis ; Stochastic Processes ; T-Lymphocyte Subsets/cytology/*immunology
    Print ISSN: 0036-8075
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  • 74
    Publication Date: 2013-07-23
    Description: Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource, with potential for studying disease and use in regenerative medicine. However, genetic manipulation and technically challenging strategies such as nuclear transfer used in reprogramming limit their clinical applications. Here, we show that pluripotent stem cells can be generated from mouse somatic cells at a frequency up to 0.2% using a combination of seven small-molecule compounds. The chemically induced pluripotent stem cells resemble embryonic stem cells in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. By using small molecules, exogenous "master genes" are dispensable for cell fate reprogramming. This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hou, Pingping -- Li, Yanqin -- Zhang, Xu -- Liu, Chun -- Guan, Jingyang -- Li, Honggang -- Zhao, Ting -- Ye, Junqing -- Yang, Weifeng -- Liu, Kang -- Ge, Jian -- Xu, Jun -- Zhang, Qiang -- Zhao, Yang -- Deng, Hongkui -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):651-4. doi: 10.1126/science.1239278. Epub 2013 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉College of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23868920" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cadherins/genetics ; Cell Engineering/*methods ; Cellular Reprogramming/*drug effects/genetics ; Epithelial-Mesenchymal Transition/drug effects/genetics ; Fibroblasts/cytology/*drug effects ; Gene Expression Profiling ; Green Fluorescent Proteins/genetics ; Induced Pluripotent Stem Cells/*cytology/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Octamer Transcription Factor-3/genetics/metabolism ; Promoter Regions, Genetic/drug effects ; Small Molecule Libraries/chemistry/*pharmacology
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  • 75
    Publication Date: 2013-08-21
    Description: Excessive intake of dietary fats leads to diminished brain dopaminergic function. It has been proposed that dopamine deficiency exacerbates obesity by provoking compensatory overfeeding as one way to restore reward sensitivity. However, the physiological mechanisms linking prolonged high-fat intake to dopamine deficiency remain elusive. We show that administering oleoylethanolamine, a gastrointestinal lipid messenger whose synthesis is suppressed after prolonged high-fat exposure, is sufficient to restore gut-stimulated dopamine release in high-fat-fed mice. Administering oleoylethanolamine to high-fat-fed mice also eliminated motivation deficits during flavorless intragastric feeding and increased oral intake of low-fat emulsions. Our findings suggest that high-fat-induced gastrointestinal dysfunctions play a key role in dopamine deficiency and that restoring gut-generated lipid signaling may increase the reward value of less palatable, yet healthier, foods.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tellez, Luis A -- Medina, Sara -- Han, Wenfei -- Ferreira, Jozelia G -- Licona-Limon, Paula -- Ren, Xueying -- Lam, Tukiet T -- Schwartz, Gary J -- de Araujo, Ivan E -- DC009997/DC/NIDCD NIH HHS/ -- DK020541/DK/NIDDK NIH HHS/ -- DK026687/DK/NIDDK NIH HHS/ -- DK085579/DK/NIDDK NIH HHS/ -- P30 DK026687/DK/NIDDK NIH HHS/ -- UL1RR024139/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 16;341(6147):800-2. doi: 10.1126/science.1239275.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The John B. Pierce Laboratory, New Haven, CT 06519, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23950538" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Appetite ; Corpus Striatum/*metabolism ; Dietary Fats/*administration & dosage ; Dopamine/deficiency/*metabolism ; Endocannabinoids/*administration & dosage/biosynthesis/*physiology ; Energy Intake ; Ethanolamines/*administration & dosage ; Feeding Behavior ; Gastrointestinal Tract/*metabolism ; Homeostasis ; Intestine, Small/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Oleic Acids/*administration & dosage/biosynthesis/*physiology ; PPAR alpha/genetics/metabolism ; Reward ; Signal Transduction ; Vagus Nerve/physiology
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  • 76
    Publication Date: 2013-07-03
    Description: The textbook description of mitochondrial respiratory complexes (RCs) views them as free-moving entities linked by the mobile carriers coenzyme Q (CoQ) and cytochrome c (cyt c). This model (known as the fluid model) is challenged by the proposal that all RCs except complex II can associate in supercomplexes (SCs). The proposed SCs are the respirasome (complexes I, III, and IV), complexes I and III, and complexes III and IV. The role of SCs is unclear, and their existence is debated. By genetic modulation of interactions between complexes I and III and III and IV, we show that these associations define dedicated CoQ and cyt c pools and that SC assembly is dynamic and organizes electron flux to optimize the use of available substrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lapuente-Brun, Esther -- Moreno-Loshuertos, Raquel -- Acin-Perez, Rebeca -- Latorre-Pellicer, Ana -- Colas, Carmen -- Balsa, Eduardo -- Perales-Clemente, Ester -- Quiros, Pedro M -- Calvo, Enrique -- Rodriguez-Hernandez, M A -- Navas, Placido -- Cruz, Raquel -- Carracedo, Angel -- Lopez-Otin, Carlos -- Perez-Martos, Acisclo -- Fernandez-Silva, Patricio -- Fernandez-Vizarra, Erika -- Enriquez, Jose Antonio -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1567-70. doi: 10.1126/science.1230381.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812712" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cells, Cultured ; Cytochromes c/*metabolism ; Electron Transport ; Electron Transport Complex I/genetics/*metabolism ; Electron Transport Complex III/genetics/*metabolism ; Electron Transport Complex IV/genetics/*metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Mice ; Mice, Inbred C57BL ; Mitochondria/*enzymology ; Molecular Sequence Data ; Ubiquinone/*metabolism
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  • 77
    Publication Date: 2013-12-07
    Description: The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting the plasma membrane and directing cytotoxic granules for secretion at the immunological synapse. Centrosome docking at the plasma membrane also occurs during cilia formation. The primary cilium, formed in nonhematopoietic cells, is essential for vertebrate Hedgehog (Hh) signaling. Lymphocytes do not form primary cilia, but we found and describe here that Hh signaling played an important role in CTL killing. T cell receptor activation, which "prearms" CTLs with cytotoxic granules, also initiated Hh signaling. Hh pathway activation occurred intracellularly and triggered Rac1 synthesis. These events "prearmed" CTLs for action by promoting the actin remodeling required for centrosome polarization and granule release. Thus, Hh signaling plays a role in CTL function, and the immunological synapse may represent a modified cilium.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022134/" 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/PMC4022134/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de la Roche, Maike -- Ritter, Alex T -- Angus, Karen L -- Dinsmore, Colin -- Earnshaw, Charles H -- Reiter, Jeremy F -- Griffiths, Gillian M -- 075880/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- R01 AR054396/AR/NIAMS NIH HHS/ -- R01 GM095941/GM/NIGMS NIH HHS/ -- R01AR05439/AR/NIAMS NIH HHS/ -- R01GM095941/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1247-50. doi: 10.1126/science.1244689.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24311692" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology/metabolism ; Cell Polarity ; Cells, Cultured ; Centrosome/metabolism ; *Cytotoxicity, Immunologic ; Hedgehog Proteins/*metabolism ; *Immunological Synapses ; Kruppel-Like Transcription Factors/genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Immunological ; Neuropeptides/genetics/metabolism ; Receptors, Antigen, T-Cell/immunology/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, G-Protein-Coupled/metabolism ; *Signal Transduction ; T-Lymphocytes, Cytotoxic/*immunology/metabolism ; rac1 GTP-Binding Protein/genetics/metabolism
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  • 78
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-05-25
    Description: Itch is triggered by somatosensory neurons expressing the ion channel TRPV1 (transient receptor potential cation channel subfamily V member 1), but the mechanisms underlying this nociceptive response remain poorly understood. Here, we show that the neuropeptide natriuretic polypeptide b (Nppb) is expressed in a subset of TRPV1 neurons and found that Nppb(-/-) mice selectively lose almost all behavioral responses to itch-inducing agents. Nppb triggered potent scratching when injected intrathecally in wild-type and Nppb(-/-) mice, showing that this neuropeptide evokes itch when released from somatosensory neurons. Itch responses were blocked by toxin-mediated ablation of Nppb-receptor-expressing cells, but a second neuropeptide, gastrin-releasing peptide, still induced strong responses in the toxin-treated animals. Thus, our results define the primary pruriceptive neurons, characterize Nppb as an itch-selective neuropeptide, and reveal the next two stages of this dedicated neuronal pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670709/" 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/PMC3670709/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mishra, Santosh K -- Hoon, Mark A -- ZIA DE000721-04/Intramural NIH HHS/ -- ZIA DE000721-05/Intramural NIH HHS/ -- ZIA DE000721-06/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 24;340(6135):968-71. doi: 10.1126/science.1233765.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics Unit, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research/NIH, 49 Convent Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704570" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chloroquine/pharmacology ; Endothelin-1/pharmacology ; Gastrin-Releasing Peptide/metabolism/pharmacology ; Histamine/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Natriuretic Peptide, Brain/genetics/*metabolism/pharmacology ; *Nociception ; Phospholipase C beta ; Pruritus/chemically induced/metabolism/*physiopathology ; Receptors, Atrial Natriuretic Factor/metabolism ; Sensory Receptor Cells/drug effects/*metabolism ; Spinal Cord/drug effects/pathology/physiopathology ; TRPV Cation Channels/metabolism
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  • 79
    Publication Date: 2013-09-07
    Description: The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829625/" 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/PMC3829625/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ridaura, Vanessa K -- Faith, Jeremiah J -- Rey, Federico E -- Cheng, Jiye -- Duncan, Alexis E -- Kau, Andrew L -- Griffin, Nicholas W -- Lombard, Vincent -- Henrissat, Bernard -- Bain, James R -- Muehlbauer, Michael J -- Ilkayeva, Olga -- Semenkovich, Clay F -- Funai, Katsuhiko -- Hayashi, David K -- Lyle, Barbara J -- Martini, Margaret C -- Ursell, Luke K -- Clemente, Jose C -- Van Treuren, William -- Walters, William A -- Knight, Rob -- Newgard, Christopher B -- Heath, Andrew C -- Gordon, Jeffrey I -- DK078669/DK/NIDDK NIH HHS/ -- DK58398/DK/NIDDK NIH HHS/ -- DK70977/DK/NIDDK NIH HHS/ -- F32 DK091044/DK/NIDDK NIH HHS/ -- K01 DK095774/DK/NIDDK NIH HHS/ -- K05 AA017688/AA/NIAAA NIH HHS/ -- P01 DK078669/DK/NIDDK NIH HHS/ -- P30 AG028716/AG/NIA NIH HHS/ -- P30 DK020579/DK/NIDDK NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30-AG028716/AG/NIA NIH HHS/ -- R01 DK070977/DK/NIDDK NIH HHS/ -- R01 DK076729/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 6;341(6150):1241214. doi: 10.1126/science.1241214.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24009397" target="_blank"〉PubMed〈/a〉
    Keywords: *Adiposity ; Adult ; Animals ; Bacteroidetes/genetics/*physiology ; Cecum/metabolism/microbiology ; Diet, Fat-Restricted ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Metabolome ; Metagenome/genetics/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/genetics/*metabolism ; Thinness/microbiology ; Twins ; Weight Gain ; Young Adult
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  • 80
    Publication Date: 2013-09-28
    Description: Drug-evoked synaptic plasticity in the mesolimbic system reshapes circuit function and drives drug-adaptive behavior. Much research has focused on excitatory transmission in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). How drug-evoked synaptic plasticity of inhibitory transmission affects circuit adaptations remains unknown. We found that medium spiny neurons expressing dopamine (DA) receptor type 1 (D1R-MSNs) of the NAc project to the VTA, strongly preferring the GABA neurons of the VTA. Repeated in vivo exposure to cocaine evoked synaptic potentiation at this synapse, occluding homosynaptic inhibitory long-term potentiation. The activity of the VTA GABA neurons was thus reduced and DA neurons were disinhibited. Cocaine-evoked potentiation of GABA release from D1R-MSNs affected drug-adaptive behavior, which identifies these neurons as a promising target for novel addiction treatments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bocklisch, Christina -- Pascoli, Vincent -- Wong, Jovi C Y -- House, David R C -- Yvon, Cedric -- de Roo, Mathias -- Tan, Kelly R -- Luscher, Christian -- New York, N.Y. -- Science. 2013 Sep 27;341(6153):1521-5. doi: 10.1126/science.1237059.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24072923" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cocaine/*pharmacology ; Cocaine-Related Disorders/physiopathology ; Dopaminergic Neurons/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuronal Plasticity/drug effects ; Synaptic Transmission/drug effects/physiology ; Ventral Tegmental Area/*metabolism ; gamma-Aminobutyric Acid/*drug effects/metabolism
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  • 81
    Publication Date: 2013-03-16
    Description: A core feature of protective T cell responses to infection is the robust expansion and diversification of naive antigen-specific T cell populations into short-lived effector and long-lived memory subsets. By means of in vivo fate mapping, we found a striking variability of immune responses derived from individual CD8(+) T cells and show that robust acute and recall immunity requires the initial recruitment of multiple precursors. Unbiased mathematical modeling identifies the random integration of multiple differentiation and division events as the driving force behind this variability. Within this probabilistic framework, cell fate is specified along a linear developmental path that progresses from slowly proliferating long-lived to rapidly expanding short-lived subsets. These data provide insights into how complex biological systems implement stochastic processes to guarantee robust outcomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchholz, Veit R -- Flossdorf, Michael -- Hensel, Inge -- Kretschmer, Lorenz -- Weissbrich, Bianca -- Graf, Patricia -- Verschoor, Admar -- Schiemann, Matthias -- Hofer, Thomas -- Busch, Dirk H -- New York, N.Y. -- Science. 2013 May 3;340(6132):630-5. doi: 10.1126/science.1235454. Epub 2013 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich 81675, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23493420" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; CD8-Positive T-Lymphocytes/*immunology ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Clonal Selection, Antigen-Mediated ; Computer Simulation ; *Immunity, Cellular ; *Immunologic Memory ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Interleukin-2/biosynthesis ; Listeria monocytogenes ; Listeriosis/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Immunological ; Single-Cell Analysis ; Stochastic Processes ; T-Cell Antigen Receptor Specificity ; T-Lymphocyte Subsets/*immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 82
    Publication Date: 2013-11-23
    Description: The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression, and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here, we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy. In antibiotics-treated or germ-free mice, tumor-infiltrating myeloid-derived cells responded poorly to therapy, resulting in lower cytokine production and tumor necrosis after CpG-oligonucleotide treatment and deficient production of reactive oxygen species and cytotoxicity after chemotherapy. Thus, optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects by modulating myeloid-derived cell functions in the tumor microenvironment. These findings underscore the importance of the microbiota in the outcome of disease treatment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iida, Noriho -- Dzutsev, Amiran -- Stewart, C Andrew -- Smith, Loretta -- Bouladoux, Nicolas -- Weingarten, Rebecca A -- Molina, Daniel A -- Salcedo, Rosalba -- Back, Timothy -- Cramer, Sarah -- Dai, Ren-Ming -- Kiu, Hiu -- Cardone, Marco -- Naik, Shruti -- Patri, Anil K -- Wang, Ena -- Marincola, Francesco M -- Frank, Karen M -- Belkaid, Yasmine -- Trinchieri, Giorgio -- Goldszmid, Romina S -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):967-70. doi: 10.1126/science.1240527.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24264989" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/administration & dosage ; Antigen Presentation/genetics ; Antineoplastic Agents/therapeutic use ; Bacteria/drug effects ; Bacterial Physiological Phenomena/drug effects ; Down-Regulation ; Gene Expression Regulation ; Germ-Free Life ; Immunotherapy ; Inflammation/genetics ; Intestines/*microbiology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Microbiota/drug effects/*physiology ; Neoplasm Transplantation ; Neoplasms/*immunology/microbiology/*therapy ; Oligodeoxyribonucleotides/therapeutic use ; Organoplatinum Compounds/therapeutic use ; Phagocytosis/genetics ; Reactive Oxygen Species/metabolism ; Symbiosis ; Tumor Microenvironment/*immunology ; Tumor Necrosis Factor-alpha/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 83
    Publication Date: 2013-12-07
    Description: The yellow fever vaccine YF-17D is one of the most successful vaccines ever developed in humans. Despite its efficacy and widespread use in more than 600 million people, the mechanisms by which it stimulates protective immunity remain poorly understood. Recent studies using systems biology approaches in humans have revealed that YF-17D-induced early expression of general control nonderepressible 2 kinase (GCN2) in the blood strongly correlates with the magnitude of the later CD8(+) T cell response. We demonstrate a key role for virus-induced GCN2 activation in programming dendritic cells to initiate autophagy and enhanced antigen presentation to both CD4(+) and CD8(+) T cells. These results reveal an unappreciated link between virus-induced integrated stress response in dendritic cells and the adaptive immune response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048998/" 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/PMC4048998/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ravindran, Rajesh -- Khan, Nooruddin -- Nakaya, Helder I -- Li, Shuzhao -- Loebbermann, Jens -- Maddur, Mohan S -- Park, Youngja -- Jones, Dean P -- Chappert, Pascal -- Davoust, Jean -- Weiss, David S -- Virgin, Herbert W -- Ron, David -- Pulendran, Bali -- 084812/Wellcome Trust/United Kingdom -- 084812/Z/08/Z/Wellcome Trust/United Kingdom -- N01 AI50019/AI/NIAID NIH HHS/ -- N01 AI50025/AI/NIAID NIH HHS/ -- P51 OD011132/OD/NIH HHS/ -- R37 AI048638/AI/NIAID NIH HHS/ -- R37 DK057665/DK/NIDDK NIH HHS/ -- R56 AI048638/AI/NIAID NIH HHS/ -- U19 AI057266/AI/NIAID NIH HHS/ -- U19 AI090023/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54 AI057160/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):313-7. doi: 10.1126/science.1246829. Epub 2013 Dec 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24310610" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Cricetinae ; Dendritic Cells/enzymology/*immunology ; Enzyme Activation ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Microtubule-Associated Proteins/genetics ; Protein-Serine-Threonine Kinases/*biosynthesis/genetics ; Yellow Fever Vaccine/*immunology
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  • 84
    Publication Date: 2012-03-24
    Description: Phenotypic variability in genetic disease is usually attributed to genetic background variation or environmental influence. Here, we show that deletion of a single gene, Trim28 (Kap1 or Tif1beta), from the maternal germ line alone, on an otherwise identical genetic background, results in severe phenotypic and epigenetic variability that leads to embryonic lethality. We identify early and minute epigenetic variations in blastomeres of the preimplantation embryo of these animals, suggesting that the embryonic lethality may result from the misregulation of genomic imprinting in mice lacking maternal Trim28. Our results reveal the long-range effects of a maternal gene deletion on epigenetic memory and illustrate the delicate equilibrium of maternal and zygotic factors during nuclear reprogramming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Messerschmidt, Daniel M -- de Vries, Wilhelmine -- Ito, Mitsuteru -- Solter, Davor -- Ferguson-Smith, Anne -- Knowles, Barbara B -- 079249/Wellcome Trust/United Kingdom -- 095606/Wellcome Trust/United Kingdom -- MR/J001597/1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Mar 23;335(6075):1499-502. doi: 10.1126/science.1216154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mammalian Development Group, Institute of Medical Biology, Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22442485" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/physiology ; DNA Methylation ; Down-Regulation ; *Embryo Loss ; Embryo, Mammalian/*physiology ; Embryonic Development ; *Epigenesis, Genetic ; Female ; Gene Expression Regulation, Developmental ; *Genomic Imprinting ; Insulin-Like Growth Factor II/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins/*genetics/*physiology ; Oligonucleotide Array Sequence Analysis ; Oocytes/*physiology ; Phenotype ; RNA, Long Noncoding ; RNA, Untranslated/genetics/metabolism ; Repressor Proteins/*genetics/*physiology
    Print ISSN: 0036-8075
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  • 85
    Publication Date: 2012-03-31
    Description: Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin-mediated suppression of hepatic gluconeogenesis. Further, decreased mTORC1 signaling was sufficient to extend life span independently from changes in glucose homeostasis, as female mice heterozygous for both mTOR and mLST8 exhibited decreased mTORC1 activity and extended life span but had normal glucose tolerance and insulin sensitivity. Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324089/" 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/PMC3324089/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lamming, Dudley W -- Ye, Lan -- Katajisto, Pekka -- Goncalves, Marcus D -- Saitoh, Maki -- Stevens, Deanna M -- Davis, James G -- Salmon, Adam B -- Richardson, Arlan -- Ahima, Rexford S -- Guertin, David A -- Sabatini, David M -- Baur, Joseph A -- 1F32AG032833-01A1/AG/NIA NIH HHS/ -- CA129105/CA/NCI NIH HHS/ -- F32 AG032833/AG/NIA NIH HHS/ -- P30DK19525/DK/NIDDK NIH HHS/ -- R01 CA129105/CA/NCI NIH HHS/ -- R01 CA129105-05/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Mar 30;335(6076):1638-43. doi: 10.1126/science.1215135.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22461615" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue, White/metabolism ; Animals ; Carrier Proteins/genetics/metabolism ; Female ; Gluconeogenesis ; Glucose/metabolism ; Glucose Clamp Technique ; Homeostasis ; Insulin/administration & dosage/blood ; *Insulin Resistance ; Liver/metabolism ; *Longevity ; Male ; Mice ; Mice, Inbred C57BL ; Multiprotein Complexes ; Muscle, Skeletal/metabolism ; Phosphorylation ; Proteins/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases/genetics/metabolism
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  • 86
    Publication Date: 2012-07-24
    Description: Diseases of the esophageal epithelium (EE), such as reflux esophagitis and cancer, are rising in incidence. Despite this, the cellular behaviors underlying EE homeostasis and repair remain controversial. Here, we show that in mice, EE is maintained by a single population of cells that divide stochastically to generate proliferating and differentiating daughters with equal probability. In response to challenge with all-trans retinoic acid (atRA), the balance of daughter cell fate is unaltered, but the rate of cell division increases. However, after wounding, cells reversibly switch to producing an excess of proliferating daughters until the wound has closed. Such fate-switching enables a single progenitor population to both maintain and repair tissue without the need for a "reserve" slow-cycling stem cell pool.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527005/" 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/PMC3527005/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doupe, David P -- Alcolea, Maria P -- Roshan, Amit -- Zhang, Gen -- Klein, Allon M -- Simons, Benjamin D -- Jones, Philip H -- 079249/Wellcome Trust/United Kingdom -- 092096/Wellcome Trust/United Kingdom -- G0601740/Medical Research Council/United Kingdom -- G0700600/1/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom -- G0800784/Medical Research Council/United Kingdom -- MC_U105370181/Medical Research Council/United Kingdom -- U.1053.00.010(70181)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Aug 31;337(6098):1091-3. doi: 10.1126/science.1218835. Epub 2012 Jul 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Cancer Cell Unit, Hutchison-MRC Research Centre, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22821983" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers/analysis ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Doxycycline/pharmacology ; Epithelial Cells/*physiology ; Epithelium/drug effects/metabolism/*physiology ; Esophagus/*cytology/*physiology ; Green Fluorescent Proteins/biosynthesis ; Histones/biosynthesis ; Mice ; Mice, Inbred C57BL ; Recombinant Fusion Proteins/biosynthesis ; *Regeneration ; Stem Cells/metabolism/*physiology
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  • 87
    Publication Date: 2012-01-24
    Description: Synaptic inputs on dendrites are nonlinearly converted to action potential outputs, yet the spatiotemporal patterns of dendritic activation remain to be elucidated at single-synapse resolution. In rodents, we optically imaged synaptic activities from hundreds of dendritic spines in hippocampal and neocortical pyramidal neurons ex vivo and in vivo. Adjacent spines were frequently synchronized in spontaneously active networks, thereby forming dendritic foci that received locally convergent inputs from presynaptic cell assemblies. This precise subcellular geometry manifested itself during N-methyl-D-aspartate receptor-dependent circuit remodeling. Thus, clustered synaptic plasticity is innately programmed to compartmentalize correlated inputs along dendrites and may reify nonlinear synaptic integration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, Naoya -- Kitamura, Kazuo -- Matsuo, Naoki -- Mayford, Mark -- Kano, Masanobu -- Matsuki, Norio -- Ikegaya, Yuji -- New York, N.Y. -- Science. 2012 Jan 20;335(6066):353-6. doi: 10.1126/science.1210362.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22267814" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; CA3 Region, Hippocampal/cytology/physiology ; Calcium/metabolism ; Dendritic Spines/*physiology/ultrastructure ; Excitatory Postsynaptic Potentials ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Net/*physiology ; Neuronal Plasticity ; Organ Culture Techniques ; Patch-Clamp Techniques ; Pyramidal Cells/*physiology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Somatosensory Cortex/cytology/physiology ; Synapses/*physiology
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  • 88
    Publication Date: 2012-03-03
    Description: Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection, or immunodepletion. However, the mechanisms governing this regeneration remain poorly understood. We detail such a mechanism, centered on interleukin-22 (IL-22) and triggered by the depletion of CD4(+)CD8(+) double-positive thymocytes. Intrathymic levels of IL-22 were increased after thymic insult, and thymic recovery was impaired in IL-22-deficient mice. IL-22, which signaled through thymic epithelial cells and promoted their proliferation and survival, was up-regulated by radio-resistant RORgamma(t)(+)CCR6(+)NKp46(-) lymphoid tissue inducer cells after thymic injury in an IL-23-dependent manner. Administration of IL-22 enhanced thymic recovery after total body irradiation. These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616391/" 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/PMC3616391/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dudakov, Jarrod A -- Hanash, Alan M -- Jenq, Robert R -- Young, Lauren F -- Ghosh, Arnab -- Singer, Natalie V -- West, Mallory L -- Smith, Odette M -- Holland, Amanda M -- Tsai, Jennifer J -- Boyd, Richard L -- van den Brink, Marcel R M -- AI080455/AI/NIAID NIH HHS/ -- CA107096/CA/NCI NIH HHS/ -- HL069929/HL/NHLBI NIH HHS/ -- HL095075/HL/NHLBI NIH HHS/ -- R01 AI080455/AI/NIAID NIH HHS/ -- R01 CA107096/CA/NCI NIH HHS/ -- R01 HL069929/HL/NHLBI NIH HHS/ -- R01 HL095075/HL/NHLBI NIH HHS/ -- T32 CA009207/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2012 Apr 6;336(6077):91-5. doi: 10.1126/science.1218004. Epub 2012 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. dudakovj@mskcc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383805" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Count ; Cell Proliferation ; Cell Survival ; Dendritic Cells/physiology ; Epithelial Cells/cytology/physiology ; Interleukin-23/metabolism ; Interleukins/administration & dosage/deficiency/genetics/*metabolism ; Lymphocytes/cytology/physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics/metabolism ; Radiation Dosage ; Receptors, Interleukin/metabolism ; Recombinant Proteins/administration & dosage ; *Regeneration ; Signal Transduction ; Thymocytes/*physiology ; Thymus Gland/cytology/immunology/*physiology/radiation effects ; Up-Regulation ; Whole-Body Irradiation
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  • 89
    Publication Date: 2012-01-28
    Description: During the activation of humoral immune responses, B cells acquire antigen for subsequent presentation to cognate T cells. Here we show that after mouse B cells accumulate antigen, it is maintained in a polarized distribution for extended periods in vivo. Using high-throughput imaging flow cytometry, we observed that this polarization is preserved during B cell division, promoting asymmetric antigen segregation among progeny. Antigen inheritance correlates with the ability of progeny to activate T cells: Daughter cells receiving larger antigen stores exhibit a prolonged capacity to present antigen, which renders them more effective in competing for T cell help. The generation of progeny with differential capacities for antigen presentation may have implications for somatic hypermutation and class switching during affinity maturation and as B cells commit to effector cell fates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thaunat, Olivier -- Granja, Aitor G -- Barral, Patricia -- Filby, Andrew -- Montaner, Beatriz -- Collinson, Lucy -- Martinez-Martin, Nuria -- Harwood, Naomi E -- Bruckbauer, Andreas -- Batista, Facundo D -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2012 Jan 27;335(6067):475-9. doi: 10.1126/science.1214100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22282815" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigen Presentation ; Antigens/*analysis/*immunology ; B-Lymphocytes/cytology/*immunology ; Cell Division ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Computer Simulation ; Flow Cytometry ; *Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Immunological ; Muramidase/analysis/immunology ; T-Lymphocytes/*immunology
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  • 90
    Publication Date: 2012-12-15
    Description: Many mammals use scent marking for sexual and competitive advertisement, but little is known about the mechanism by which scents are used to locate mates and competitors. We show that darcin, an involatile protein sex pheromone in male mouse urine, can rapidly condition preference for its remembered location among females and competitor males so that animals prefer to spend time in the site even when scent is absent. Learned spatial preference is conditioned through contact with darcin in a single trial and remembered for approximately 14 days. This pheromone-induced learning allows animals to relocate sites of particular social relevance and provides proof that pheromones such as darcin can be highly potent stimuli for social learning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Sarah A -- Davidson, Amanda J -- McLean, Lynn -- Beynon, Robert J -- Hurst, Jane L -- BB/J002631/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC503897/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2012 Dec 14;338(6113):1462-5. doi: 10.1126/science.1225638.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mammalian Behaviour and Evolution Group, Institute of Integrative Biology, University of Liverpool, Leahurst Campus, Neston CH64 7TE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23239735" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Competitive Behavior/drug effects/*physiology ; Conditioning (Psychology)/drug effects/physiology ; Female ; Male ; Maze Learning/drug effects/*physiology ; Mice ; Mice, Inbred C57BL ; Proteins/pharmacology/*physiology ; Sex Attractants/pharmacology/*physiology/urine ; Smell/drug effects/physiology ; Spatial Behavior/drug effects/*physiology
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  • 91
    Publication Date: 2012-03-10
    Description: Electrically coupled inhibitory interneurons dynamically control network excitability, yet little is known about how chemical and electrical synapses regulate their activity. Using two-photon glutamate uncaging and dendritic patch-clamp recordings, we found that the dendrites of cerebellar Golgi interneurons acted as passive cables. They conferred distance-dependent sublinear synaptic integration and weakened distal excitatory inputs. Gap junctions were present at a higher density on distal dendrites and contributed substantially to membrane conductance. Depolarization of one Golgi cell increased firing in its neighbors, and inclusion of dendritic gap junctions in interneuron network models enabled distal excitatory synapses to drive network activity more effectively. Our results suggest that dendritic gap junctions counteract sublinear dendritic integration by enabling excitatory synaptic charge to spread into the dendrites of neighboring inhibitory interneurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587282/" 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/PMC3587282/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vervaeke, Koen -- Lorincz, Andrea -- Nusser, Zoltan -- Silver, R Angus -- 064413/Wellcome Trust/United Kingdom -- 090197/Wellcome Trust/United Kingdom -- 095667/Wellcome Trust/United Kingdom -- 293681/European Research Council/International -- 294667/European Research Council/International -- BB/F005490/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- F005490/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0400598/Medical Research Council/United Kingdom -- G0400598(71261)/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2012 Mar 30;335(6076):1624-8. doi: 10.1126/science.1215101. Epub 2012 Mar 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22403180" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/physiology ; Cerebellar Cortex/cytology ; Computer Simulation ; Dendrites/*physiology/*ultrastructure ; Electrical Synapses/*physiology/ultrastructure ; Excitatory Postsynaptic Potentials ; Interneurons/*physiology ; Ion Channels/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Neurological ; Nerve Net/*physiology/ultrastructure ; *Neural Inhibition ; Patch-Clamp Techniques ; Synapses/physiology ; Synaptic Transmission
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  • 92
    Publication Date: 2012-05-15
    Description: The virulence mechanisms that allow pathogens to colonize the intestine remain unclear. Here, we show that germ-free animals are unable to eradicate Citrobacter rodentium, a model for human infections with attaching and effacing bacteria. Early in infection, virulence genes were expressed and required for pathogen growth in conventionally raised mice but not germ-free mice. Virulence gene expression was down-regulated during the late phase of infection, which led to relocation of the pathogen to the intestinal lumen where it was outcompeted by commensals. The ability of commensals to outcompete C. rodentium was determined, at least in part, by the capacity of the pathogen and commensals to grow on structurally similar carbohydrates. Thus, pathogen colonization is controlled by bacterial virulence and through competition with metabolically related commensals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439148/" 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/PMC3439148/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kamada, Nobuhiko -- Kim, Yun-Gi -- Sham, Ho Pan -- Vallance, Bruce A -- Puente, Jose L -- Martens, Eric C -- Nunez, Gabriel -- DK091191/DK/NIDDK NIH HHS/ -- DK61707/DK/NIDDK NIH HHS/ -- R01 DK061707/DK/NIDDK NIH HHS/ -- R01 DK091191/DK/NIDDK NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2012 Jun 8;336(6086):1325-9. doi: 10.1126/science.1222195. Epub 2012 May 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22582016" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Load ; Bacterial Proteins/genetics/metabolism ; Bacteroides/*growth & development ; Citrobacter rodentium/genetics/growth & development/immunology/*pathogenicity ; Enterobacteriaceae Infections/immunology/*microbiology ; Escherichia coli/*growth & development ; Feces/microbiology ; Gene Expression Regulation, Bacterial ; Germ-Free Life ; Intestinal Mucosa/*microbiology ; Intestines/*microbiology ; *Metagenome ; Mice ; Mice, Inbred C57BL ; *Microbial Interactions ; Specific Pathogen-Free Organisms ; Virulence Factors/genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 93
    Publication Date: 2012-03-01
    Description: Posttraumatic stress disorder (PTSD) is characterized by a hypermnesia of the trauma and by a memory impairment that decreases the ability to restrict fear to the appropriate context. Infusion of glucocorticoids in the hippocampus after fear conditioning induces PTSD-like memory impairments and an altered pattern of neural activation in the hippocampal-amygdalar circuit. Mice become unable to identify the context as the correct predictor of the threat and show fear responses to a discrete cue not predicting the threat in normal conditions. These data demonstrate PTSD-like memory impairments in rodents and identify a potential pathophysiological mechanism of this condition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaouane, Nadia -- Porte, Yves -- Vallee, Monique -- Brayda-Bruno, Laurent -- Mons, Nicole -- Calandreau, Ludovic -- Marighetto, Aline -- Piazza, Pier Vincenzo -- Desmedt, Aline -- New York, N.Y. -- Science. 2012 Mar 23;335(6075):1510-3. doi: 10.1126/science.1207615. Epub 2012 Feb 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS UMR 5228, Centre de Neurosciences Integratives et Cognitives, Talence, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22362879" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/*physiopathology ; Animals ; Conditioning (Psychology) ; Corticosterone/*administration & dosage/blood/metabolism/pharmacology ; Cues ; Electroshock ; *Fear ; Hippocampus/*physiopathology ; Male ; Memory Disorders/chemically induced/*physiopathology ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-fos/metabolism ; Restraint, Physical ; Stress Disorders, Post-Traumatic/*physiopathology ; Stress, Psychological
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  • 94
    Publication Date: 2012-03-24
    Description: Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal-but not adult-GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437652/" 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/PMC3437652/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olszak, Torsten -- An, Dingding -- Zeissig, Sebastian -- Vera, Miguel Pinilla -- Richter, Julia -- Franke, Andre -- Glickman, Jonathan N -- Siebert, Reiner -- Baron, Rebecca M -- Kasper, Dennis L -- Blumberg, Richard S -- AI090102/AI/NIAID NIH HHS/ -- DK034854/DK/NIDDK NIH HHS/ -- DK44319/DK/NIDDK NIH HHS/ -- DK51362/DK/NIDDK NIH HHS/ -- DK53056/DK/NIDDK NIH HHS/ -- DK88199/DK/NIDDK NIH HHS/ -- P30 DK034854/DK/NIDDK NIH HHS/ -- R01 DK044319/DK/NIDDK NIH HHS/ -- R01 DK088199/DK/NIDDK NIH HHS/ -- R37 DK044319/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2012 Apr 27;336(6080):489-93. doi: 10.1126/science.1219328. Epub 2012 Mar 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women'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/22442383" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Animals, Newborn ; Antigens, CD1d/immunology ; Asthma/*immunology ; Bacteria/*growth & development ; Chemokine CXCL6/genetics/metabolism ; Colitis, Ulcerative/chemically induced/*immunology ; Colon/immunology/microbiology ; DNA Methylation ; Disease Models, Animal ; Disease Susceptibility ; Germ-Free Life ; Intestinal Mucosa/*immunology ; Intestines/immunology/*microbiology ; Lung/*immunology ; Mice ; Mice, Inbred C57BL ; Natural Killer T-Cells/*immunology ; Oxazolone ; Receptors, CXCR/genetics/metabolism ; Specific Pathogen-Free Organisms
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  • 95
    Publication Date: 2012-03-10
    Description: We have identified tens of thousands of short extrachromosomal circular DNAs (microDNA) in mouse tissues as well as mouse and human cell lines. These microDNAs are 200 to 400 base pairs long, are derived from unique nonrepetitive sequence, and are enriched in the 5'-untranslated regions of genes, exons, and CpG islands. Chromosomal loci that are enriched sources of microDNA in the adult brain are somatically mosaic for microdeletions that appear to arise from the excision of microDNAs. Germline microdeletions identified by the "Thousand Genomes" project may also arise from the excision of microDNAs in the germline lineage. We have thus identified a previously unknown DNA entity in mammalian cells and provide evidence that their generation leaves behind deletions in different genomic loci.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703515/" 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/PMC3703515/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shibata, Yoshiyuki -- Kumar, Pankaj -- Layer, Ryan -- Willcox, Smaranda -- Gagan, Jeffrey R -- Griffith, Jack D -- Dutta, Anindya -- ES013773/ES/NIEHS NIH HHS/ -- GM31819/GM/NIGMS NIH HHS/ -- GM84465/GM/NIGMS NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- R01 CA060499/CA/NCI NIH HHS/ -- R01 CA060499-18/CA/NCI NIH HHS/ -- R01 CA60499/CA/NCI NIH HHS/ -- R01 ES013773/ES/NIEHS NIH HHS/ -- R01 GM031819/GM/NIGMS NIH HHS/ -- R01 GM084465/GM/NIGMS NIH HHS/ -- R01 GM084465-04/GM/NIGMS NIH HHS/ -- T32 GM008136/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Apr 6;336(6077):82-6. doi: 10.1126/science.1213307. Epub 2012 Mar 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22403181" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions ; Animals ; Base Pairing ; Base Sequence ; Brain/*embryology ; Brain Chemistry ; Cell Line ; Cell Line, Tumor ; *Chromosome Deletion ; Chromosomes, Human/*genetics ; Chromosomes, Mammalian/*genetics ; CpG Islands ; DNA Replication ; *DNA, Circular/analysis/chemistry/isolation & purification/metabolism ; Exons ; Germ Cells/chemistry ; Heart/embryology ; Humans ; Liver/chemistry/embryology ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron ; Molecular Sequence Data ; Polymerase Chain Reaction ; Repetitive Sequences, Nucleic Acid
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  • 96
    Publication Date: 2012-01-28
    Description: The adult dentate gyrus generates new granule cells (GCs) that develop over several weeks and integrate into the preexisting network. Although adult hippocampal neurogenesis has been implicated in learning and memory, the specific role of new GCs remains unclear. We examined whether immature adult-born neurons contribute to information encoding. By combining calcium imaging and electrophysiology in acute slices, we found that weak afferent activity recruits few mature GCs while activating a substantial proportion of the immature neurons. These different activation thresholds are dictated by an enhanced excitation/inhibition balance transiently expressed in immature GCs. Immature GCs exhibit low input specificity that switches with time toward a highly specific responsiveness. Therefore, activity patterns entering the dentate gyrus can undergo differential decoding by a heterogeneous population of GCs originated at different times.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385415/" 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/PMC3385415/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marin-Burgin, Antonia -- Mongiat, Lucas A -- Pardi, M Belen -- Schinder, Alejandro F -- 55005963/Howard Hughes Medical Institute/ -- R03 TW008607/TW/FIC NIH HHS/ -- R03TW008607-01/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2012 Mar 9;335(6073):1238-42. doi: 10.1126/science.1214956. Epub 2012 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratorio de Plasticidad Neuronal, Instituto Leloir, Instituto de Investigaciones Bioquimicas de Buenos Aires-Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Avenida Patricias Argentinas 435, 1405 Buenos Aires, Argentina.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22282476" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dentate Gyrus/*cytology/*physiology ; Electric Stimulation ; Entorhinal Cortex/cytology/physiology ; Excitatory Postsynaptic Potentials ; Female ; GABAergic Neurons/physiology ; Glutamic Acid/metabolism ; Inhibitory Postsynaptic Potentials ; Mice ; Mice, Inbred C57BL ; *Neural Inhibition ; *Neurogenesis ; Neuronal Plasticity ; Neurons/cytology/*physiology ; Patch-Clamp Techniques ; Perforant Pathway ; Synapses/physiology ; *Synaptic Potentials
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-09-22
    Description: The blood-testis barrier includes strands of tight junctions between somatic Sertoli cells that restricts solutes from crossing the paracellular space, creating a microenvironment within seminiferous tubules and providing immune privilege to meiotic and postmeiotic cells. Large cysts of germ cells transit the Sertoli cell tight junctions (SCTJs) without compromising their integrity. We used confocal microscopy to visualize SCTJ components during germ cell cyst migration across the SCTJs. Cysts become enclosed within a network of transient compartments fully bounded by old and new tight junctions. Dissolution of the old tight junctions releases the germ cells into the adluminal compartment, thus completing transit across the blood-testis barrier. Claudin 3, a tight junction protein, is transiently incorporated into new tight junctions and then replaced by claudin 11.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694388/" 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/PMC3694388/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Benjamin E -- Braun, Robert E -- CA34196/CA/NCI NIH HHS/ -- HD12629/HD/NICHD NIH HHS/ -- P30 CA034196/CA/NCI NIH HHS/ -- U54 HD012629/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2012 Nov 9;338(6108):798-802. doi: 10.1126/science.1219969. Epub 2012 Sep 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22997133" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood-Testis Barrier/*ultrastructure ; *Cell Movement ; Claudin-3/analysis/metabolism ; Claudins/analysis/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Models, Biological ; Seminiferous Tubules/chemistry/ultrastructure ; Sertoli Cells/chemistry/physiology/*ultrastructure ; Spermatocytes/*physiology/ultrastructure ; Spermatogenesis ; Tight Junctions/chemistry/physiology/*ultrastructure
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  • 98
    Publication Date: 2012-09-18
    Description: Interferon regulatory factor 4 (IRF4) and IRF8 regulate B, T, macrophage, and dendritic cell differentiation. They are recruited to cis-regulatory Ets-IRF composite elements by PU.1 or Spi-B. How these IRFs target genes in most T cells is enigmatic given the absence of specific Ets partners. Chromatin immunoprecipitation sequencing in T helper 17 (T(H)17) cells reveals that IRF4 targets sequences enriched for activating protein 1 (AP-1)-IRF composite elements (AICEs) that are co-bound by BATF, an AP-1 factor required for T(H)17, B, and dendritic cell differentiation. IRF4 and BATF bind cooperatively to structurally divergent AICEs to promote gene activation and T(H)17 differentiation. The AICE motif directs assembly of IRF4 or IRF8 with BATF heterodimers and is also used in T(H)2, B, and dendritic cells. This genomic regulatory element and cognate factors appear to have evolved to integrate diverse immunomodulatory signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glasmacher, Elke -- Agrawal, Smita -- Chang, Abraham B -- Murphy, Theresa L -- Zeng, Wenwen -- Vander Lugt, Bryan -- Khan, Aly A -- Ciofani, Maria -- Spooner, Chauncey J -- Rutz, Sascha -- Hackney, Jason -- Nurieva, Roza -- Escalante, Carlos R -- Ouyang, Wenjun -- Littman, Dan R -- Murphy, Kenneth M -- Singh, Harinder -- RC1 AI087266/AI/NIAID NIH HHS/ -- RC4 AI092765/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Nov 16;338(6109):975-80. doi: 10.1126/science.1228309. Epub 2012 Sep 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Discovery Immunology, Genentech, Incorporated, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22983707" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic-Leucine Zipper Transcription Factors/metabolism ; Cell Differentiation/genetics ; Chromatin Immunoprecipitation ; Humans ; Immunomodulation/*genetics ; Interferon Regulatory Factors/*metabolism ; Mice ; Mice, Inbred C57BL ; *Regulatory Elements, Transcriptional ; Th17 Cells/*immunology ; Transcription Factor AP-1/*metabolism ; *Transcriptional Activation
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  • 99
    Publication Date: 2012-06-30
    Description: Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non-AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons. CUG/Leu-tRNA initiation was independent of the canonical initiator tRNA (AUG/Met-tRNA(i)(Met)) pathway but required expression of eukaryotic initiation factor 2A. Thus, a tRNA-based translation initiation mechanism allows non-AUG-initiated protein synthesis and supplies peptides for presentation by MHC class I molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Starck, Shelley R -- Jiang, Vivian -- Pavon-Eternod, Mariana -- Prasad, Sharanya -- McCarthy, Brian -- Pan, Tao -- Shastri, Nilabh -- New York, N.Y. -- Science. 2012 Jun 29;336(6089):1719-23. doi: 10.1126/science.1220270.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22745432" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation/*genetics ; Antigen-Presenting Cells/immunology ; COS Cells ; Cercopithecus aethiops ; *Codon, Initiator ; HeLa Cells ; Histocompatibility Antigens Class I/*genetics/*immunology ; Humans ; Hybridomas/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Peptide Chain Initiation, Translational ; Protein Biosynthesis/*genetics ; *RNA, Transfer, Leu ; T-Lymphocytes/immunology
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  • 100
    Publication Date: 2012-02-11
    Description: Alzheimer's disease (AD) is associated with impaired clearance of beta-amyloid (Abeta) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Abeta within hours in an apoE-dependent manner. Abeta plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Abeta clearance mechanisms, resulting in the rapid reversal of a broad range of Abeta-induced deficits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651582/" 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/PMC3651582/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cramer, Paige E -- Cirrito, John R -- Wesson, Daniel W -- Lee, C Y Daniel -- Karlo, J Colleen -- Zinn, Adriana E -- Casali, Brad T -- Restivo, Jessica L -- Goebel, Whitney D -- James, Michael J -- Brunden, Kurt R -- Wilson, Donald A -- Landreth, Gary E -- AG030482-03S1/AG/NIA NIH HHS/ -- DC003906/DC/NIDCD NIH HHS/ -- K01 AG029524/AG/NIA NIH HHS/ -- P50-AG005681/AG/NIA NIH HHS/ -- R01 AG030482/AG/NIA NIH HHS/ -- R01 AG037693/AG/NIA NIH HHS/ -- R01 DC003906/DC/NIDCD NIH HHS/ -- R01-AG037693/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2012 Mar 23;335(6075):1503-6. doi: 10.1126/science.1217697. Epub 2012 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323736" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*drug therapy/*metabolism ; Amyloid beta-Peptides/*metabolism ; Amyloidosis/drug therapy/metabolism ; Animals ; Apolipoproteins E/*metabolism ; Astrocytes/drug effects/metabolism ; Behavior, Animal/drug effects ; Brain/drug effects/*metabolism ; Disease Models, Animal ; Extracellular Fluid/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia/drug effects/metabolism ; Molecular Targeted Therapy ; Odors ; Olfactory Pathways/drug effects/physiology ; Orphan Nuclear Receptors/metabolism ; PPAR gamma/metabolism ; Phagocytosis ; Plaque, Amyloid/drug therapy ; Retinoid X Receptors/agonists/metabolism ; Tetrahydronaphthalenes/*pharmacology/*therapeutic use
    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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