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  • 2015-2019  (216)
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  • 1
    Publication Date: 2015-09-01
    Description: Glycerophospholipids, the structural components of cell membranes, have not been considered to be spatial cues for intercellular signaling because of their ubiquitous distribution. We identified lyso-phosphatidyl-beta-D-glucoside (LysoPtdGlc), a hydrophilic glycerophospholipid, and demonstrated its role in modality-specific repulsive guidance of spinal cord sensory axons. LysoPtdGlc is locally synthesized and released by radial glia in a patterned spatial distribution to regulate the targeting of nociceptive but not proprioceptive central axon projections. Library screening identified the G protein-coupled receptor GPR55 as a high-affinity receptor for LysoPtdGlc, and GPR55 deletion or LysoPtdGlc loss of function in vivo caused the misallocation of nociceptive axons into proprioceptive zones. These findings show that LysoPtdGlc/GPR55 is a lipid-based signaling system in glia-neuron communication for neural development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guy, Adam T -- Nagatsuka, Yasuko -- Ooashi, Noriko -- Inoue, Mariko -- Nakata, Asuka -- Greimel, Peter -- Inoue, Asuka -- Nabetani, Takuji -- Murayama, Akiho -- Ohta, Kunihiro -- Ito, Yukishige -- Aoki, Junken -- Hirabayashi, Yoshio -- Kamiguchi, Hiroyuki -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):974-7. doi: 10.1126/science.aab3516.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Lipid Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Sendai, Miyagi 980-8578, Japan. Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. ; Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan. ; Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Sendai, Miyagi 980-8578, Japan. Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), 1-7-1 Otemachi, Chiyoda, Tokyo 100-0004, Japan. ; RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. kamiguchi@brain.riken.jp hirabaya@riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315437" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Chick Embryo ; Coculture Techniques ; Ganglia, Spinal/*cytology/physiology ; Gene Knockout Techniques ; Glycerophospholipids/analysis/metabolism/*physiology ; Glycolipids/analysis/*physiology ; Mice ; Nerve Growth Factor/pharmacology ; Neuroglia/*physiology ; Nociceptors/*physiology ; Receptor, trkA/metabolism ; Receptor, trkC/metabolism ; Receptors, Cannabinoid/genetics/*physiology ; Spinal Cord/*cytology/*embryology ; Tissue Culture Techniques
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-11-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dajani, Rana -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1043. doi: 10.1126/science.350.6264.1043-b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan. rdajani@hu.edu.jo.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612944" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Art ; Equipment Reuse ; Fibroblasts ; Gloves, Protective ; Jordan ; Laboratories ; Mice ; Recycling/*methods ; United States
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  • 3
    Publication Date: 2015-11-14
    Description: The RNA-guided CRISPR-associated protein Cas9 is used for genome editing, transcriptional modulation, and live-cell imaging. Cas9-guide RNA complexes recognize and cleave double-stranded DNA sequences on the basis of 20-nucleotide RNA-DNA complementarity, but the mechanism of target searching in mammalian cells is unknown. Here, we use single-particle tracking to visualize diffusion and chromatin binding of Cas9 in living cells. We show that three-dimensional diffusion dominates Cas9 searching in vivo, and off-target binding events are, on average, short-lived (〈1 second). Searching is dependent on the local chromatin environment, with less sampling and slower movement within heterochromatin. These results reveal how the bacterial Cas9 protein interrogates mammalian genomes and navigates eukaryotic chromatin structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knight, Spencer C -- Xie, Liangqi -- Deng, Wulan -- Guglielmi, Benjamin -- Witkowsky, Lea B -- Bosanac, Lana -- Zhang, Elisa T -- El Beheiry, Mohamed -- Masson, Jean-Baptiste -- Dahan, Maxime -- Liu, Zhe -- Doudna, Jennifer A -- Tjian, Robert -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):823-6. doi: 10.1126/science.aac6572.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley, CA, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. ; Laboratoire Physico-Chimie Curie, Institut Curie, Centre National de la Recherche Scientifique UMR 168, Paris, France. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. ; Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Laboratoire Physico-Chimie Curie, Institut Curie, Centre National de la Recherche Scientifique UMR 168, Paris, France. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu. ; Department of Chemistry, University of California, Berkeley, CA, USA. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Innovative Genomics Initiative, University of California, Berkeley, CA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Li Ka Shing Biomedical and Health Sciences Center, University of California, Berkeley, CA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26564855" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Bacterial Proteins/chemistry/*metabolism ; *CRISPR-Cas Systems ; Chromatin/chemistry/*metabolism/ultrastructure ; Clustered Regularly Interspaced Short Palindromic Repeats ; *DNA Cleavage ; Endonucleases/chemistry/*metabolism ; *Genetic Engineering ; Genome ; Mice ; Single-Cell Analysis
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  • 4
    Publication Date: 2015-05-23
    Description: Sex determination in the mosquito Aedes aegypti is governed by a dominant male-determining factor (M factor) located within a Y chromosome-like region called the M locus. Here, we show that an M-locus gene, Nix, functions as an M factor in A. aegypti. Nix exhibits persistent M linkage and early embryonic expression, two characteristics required of an M factor. Nix knockout with clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 resulted in largely feminized genetic males and the production of female isoforms of two key regulators of sexual differentiation: doublesex and fruitless. Ectopic expression of Nix resulted in genetic females with nearly complete male genitalia. Thus, Nix is both required and sufficient to initiate male development. This study provides a foundation for mosquito control strategies that convert female mosquitoes into harmless males.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hall, Andrew Brantley -- Basu, Sanjay -- Jiang, Xiaofang -- Qi, Yumin -- Timoshevskiy, Vladimir A -- Biedler, James K -- Sharakhova, Maria V -- Elahi, Rubayet -- Anderson, Michelle A E -- Chen, Xiao-Guang -- Sharakhov, Igor V -- Adelman, Zach N -- Tu, Zhijian -- AI113643/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1268-70. doi: 10.1126/science.aaa2850. Epub 2015 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. ; Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. ; Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. ; Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. ; School of Public Health and Tropical Medicine, Southern Medical University, Guangdong, People's Republic of China. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. jaketu@vt.edu zachadel@vt.edu. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. jaketu@vt.edu zachadel@vt.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999371" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/*genetics/*growth & development ; Animals ; Caspase 9 ; Clustered Regularly Interspaced Short Palindromic Repeats ; Female ; Gene Knockout Techniques ; *Genes, Insect ; *Genetic Loci ; Male ; Molecular Sequence Data ; Mosquito Control/methods ; Sex Determination Processes/*genetics
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  • 5
    Publication Date: 2015-03-07
    Description: Human higher cognition is attributed to the evolutionary expansion and elaboration of the human cerebral cortex. However, the genetic mechanisms contributing to these developmental changes are poorly understood. We used comparative epigenetic profiling of human, rhesus macaque, and mouse corticogenesis to identify promoters and enhancers that have gained activity in humans. These gains are significantly enriched in modules of coexpressed genes in the cortex that function in neuronal proliferation, migration, and cortical-map organization. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting that they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes during corticogenesis, providing insight into human cortical evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426903/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426903/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reilly, Steven K -- Yin, Jun -- Ayoub, Albert E -- Emera, Deena -- Leng, Jing -- Cotney, Justin -- Sarro, Richard -- Rakic, Pasko -- Noonan, James P -- 099175/Z/12/Z/Wellcome Trust/United Kingdom -- DA023999/DA/NIDA NIH HHS/ -- F32 GM106628/GM/NIGMS NIH HHS/ -- GM094780/GM/NIGMS NIH HHS/ -- NS014841/NS/NINDS NIH HHS/ -- P30 CA016359/CA/NCI NIH HHS/ -- R01 DA023999/DA/NIDA NIH HHS/ -- R01 GM094780/GM/NIGMS NIH HHS/ -- T32 GM007223/GM/NIGMS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1155-9. doi: 10.1126/science.1260943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. ; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. james.noonan@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745175" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/*growth & development ; Enhancer Elements, Genetic/*genetics ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Humans ; Macaca mulatta ; Mice ; Organogenesis/*genetics ; Promoter Regions, Genetic/*genetics ; Rats
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  • 6
    Publication Date: 2015-01-03
    Description: Adipocytes have been suggested to be immunologically active, but their role in host defense is unclear. We observed rapid proliferation of preadipocytes and expansion of the dermal fat layer after infection of the skin by Staphylococcus aureus. Impaired adipogenesis resulted in increased infection as seen in Zfp423(nur12) mice or in mice given inhibitors of peroxisome proliferator-activated receptor gamma. This host defense function was mediated through the production of cathelicidin antimicrobial peptide from adipocytes because cathelicidin expression was decreased by inhibition of adipogenesis, and adipocytes from Camp(-/-) mice lost the capacity to inhibit bacterial growth. Together, these findings show that the production of an antimicrobial peptide by adipocytes is an important element for protection against S. aureus infection of the skin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318537/" 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/PMC4318537/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ling-juan -- Guerrero-Juarez, Christian F -- Hata, Tissa -- Bapat, Sagar P -- Ramos, Raul -- Plikus, Maksim V -- Gallo, Richard L -- AR052728/AR/NIAMS NIH HHS/ -- DK096828/DK/NIDDK NIH HHS/ -- GM055246/GM/NIGMS NIH HHS/ -- HHSN272201000020C/PHS HHS/ -- P01 HL107150/HL/NHLBI NIH HHS/ -- R01 AI052453/AI/NIAID NIH HHS/ -- R01 AI083358/AI/NIAID NIH HHS/ -- R01 AI116576/AI/NIAID NIH HHS/ -- R01 AR064781/AR/NIAMS NIH HHS/ -- R01 AR067273/AR/NIAMS NIH HHS/ -- R01-AR067273/AR/NIAMS NIH HHS/ -- R01AI052453/AI/NIAID NIH HHS/ -- R25 GM055246/GM/NIGMS NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):67-71. doi: 10.1126/science.1260972.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Dermatology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA. ; Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA. Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA. ; Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, San Diego, La Jolla, CA 92037, USA. ; Division of Dermatology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA. rgallo@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554785" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/*immunology/microbiology ; Adipogenesis/immunology ; Animals ; Antimicrobial Cationic Peptides/immunology ; Cathelicidins/genetics/*immunology ; DNA-Binding Proteins/genetics/immunology ; Dermis/*immunology/microbiology ; Host-Pathogen Interactions/immunology ; Mice ; Mice, Mutant Strains ; Staphylococcal Skin Infections/*immunology ; Staphylococcus aureus/*immunology ; Transcription Factors/genetics/immunology
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  • 7
    Publication Date: 2015-07-15
    Description: Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited. Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with TM3 and TM4 contributing to homotrimerization. The six TMs enclose a V-shaped cavity that can accommodate a diacylglycerol molecule. A homology-based structural model of human Insig-2, together with biochemical characterizations, suggest that the central cavity of Insig-2 accommodates 25-hydroxycholesterol, whereas TM3 and TM4 engage in Scap binding. These analyses provide an important framework for further functional and mechanistic understanding of Insig proteins and the sterol regulatory element-binding protein pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704858/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704858/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, Ruobing -- Zhou, Xinhui -- He, Yuan -- Ke, Meng -- Wu, Jianping -- Liu, Xiaohui -- Yan, Chuangye -- Wu, Yixuan -- Gong, Xin -- Lei, Xiaoguang -- Yan, S Frank -- Radhakrishnan, Arun -- Yan, Nieng -- HL-20948/HL/NHLBI NIH HHS/ -- P01 HL020948/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):187-91. doi: 10.1126/science.aab1091.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. Center for Structural Biology, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China. ; National Institute of Biological Sciences, Beijing 102206, China. ; Molecular Design and Chemical Biology, Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Shanghai, Shanghai 201203, China. ; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160948" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry ; Crystallography, X-Ray ; Diglycerides/chemistry ; Humans ; Hydroxycholesterols/chemistry/*metabolism ; Intracellular Signaling Peptides and Proteins/*chemistry ; Membrane Proteins/*chemistry ; Mycobacterium/*metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Sterol Regulatory Element Binding Proteins/*chemistry
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  • 8
    Publication Date: 2015-04-11
    Description: Protein phosphorylation regulates virtually all biological processes. Although protein kinases are popular drug targets, targeting protein phosphatases remains a challenge. Here, we describe Sephin1 (selective inhibitor of a holophosphatase), a small molecule that safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively bound and inhibited the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis. Thus, regulatory subunits of phosphatases are drug targets, a property exploited here to safely prevent two protein misfolding diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490275/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490275/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Indrajit -- Krzyzosiak, Agnieszka -- Schneider, Kim -- Wrabetz, Lawrence -- D'Antonio, Maurizio -- Barry, Nicholas -- Sigurdardottir, Anna -- Bertolotti, Anne -- 309516/European Research Council/International -- MC_U105185860/Medical Research Council/United Kingdom -- R01-NS55256/NS/NINDS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Apr 10;348(6231):239-42. doi: 10.1126/science.aaa4484.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. ; Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy. ; Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. aberto@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25859045" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; Cells, Cultured ; Charcot-Marie-Tooth Disease/drug therapy/metabolism/pathology ; Disease Models, Animal ; Endoplasmic Reticulum Stress/drug effects ; Enzyme Inhibitors/metabolism/pharmacokinetics/*pharmacology/toxicity ; Guanabenz/*analogs & derivatives/chemical ; synthesis/metabolism/pharmacology/toxicity ; HeLa Cells ; Humans ; Mice ; Mice, Transgenic ; Molecular Targeted Therapy ; Phosphorylation ; Protein Folding ; Protein Phosphatase 1/*antagonists & inhibitors ; Proteostasis Deficiencies/*drug therapy/*prevention & control ; Signal Transduction
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  • 9
    Publication Date: 2015-05-02
    Description: Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1alpha and nuclear lamina-heterochromatin anchoring protein LAP2beta. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494668/" 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/PMC4494668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Weiqi -- Li, Jingyi -- Suzuki, Keiichiro -- Qu, Jing -- Wang, Ping -- Zhou, Junzhi -- Liu, Xiaomeng -- Ren, Ruotong -- Xu, Xiuling -- Ocampo, Alejandro -- Yuan, Tingting -- Yang, Jiping -- Li, Ying -- Shi, Liang -- Guan, Dee -- Pan, Huize -- Duan, Shunlei -- Ding, Zhichao -- Li, Mo -- Yi, Fei -- Bai, Ruijun -- Wang, Yayu -- Chen, Chang -- Yang, Fuquan -- Li, Xiaoyu -- Wang, Zimei -- Aizawa, Emi -- Goebl, April -- Soligalla, Rupa Devi -- Reddy, Pradeep -- Esteban, Concepcion Rodriguez -- Tang, Fuchou -- Liu, Guang-Hui -- Belmonte, Juan Carlos Izpisua -- F32 AG047770/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1160-3. doi: 10.1126/science.aaa1356. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; Diagnosis and Treatment Center for Oral Disease, the 306th Hospital of the PLA, Beijing, China. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; College of Life Sciences, Peking University, Beijing 100871, China. ; The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Universidad Catolica San Antonio de Murcia, Campus de los Jeronimos s/n, 30107 Guadalupe, Murcia, Spain. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Beijing Institute for Brain Disorders, Beijing 100069, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931448" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*metabolism ; Animals ; *Cell Aging ; Cell Differentiation ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; DNA-Binding Proteins/metabolism ; Epigenesis, Genetic ; Exodeoxyribonucleases/genetics/*metabolism ; Gene Knockout Techniques ; HEK293 Cells ; Heterochromatin/chemistry/*metabolism ; Humans ; Membrane Proteins/metabolism ; Mesenchymal Stromal Cells/*metabolism ; Methyltransferases/genetics/metabolism ; Mice ; Models, Biological ; RecQ Helicases/genetics/*metabolism ; Repressor Proteins/genetics/metabolism ; Werner Syndrome/genetics/*metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-06-13
    Description: Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" 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/PMC4481126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yongyou -- Desai, Amar -- Yang, Sung Yeun -- Bae, Ki Beom -- Antczak, Monika I -- Fink, Stephen P -- Tiwari, Shruti -- Willis, Joseph E -- Williams, Noelle S -- Dawson, Dawn M -- Wald, David -- Chen, Wei-Dong -- Wang, Zhenghe -- Kasturi, Lakshmi -- Larusch, Gretchen A -- He, Lucy -- Cominelli, Fabio -- Di Martino, Luca -- Djuric, Zora -- Milne, Ginger L -- Chance, Mark -- Sanabria, Juan -- Dealwis, Chris -- Mikkola, Debra -- Naidoo, Jacinth -- Wei, Shuguang -- Tai, Hsin-Hsiung -- Gerson, Stanton L -- Ready, Joseph M -- Posner, Bruce -- Willson, James K V -- Markowitz, Sanford D -- 1P01CA95471-09/CA/NCI NIH HHS/ -- 5P30 CA142543-03/CA/NCI NIH HHS/ -- P01 CA095471/CA/NCI NIH HHS/ -- P30 CA043703/CA/NCI NIH HHS/ -- P30 CA142543/CA/NCI NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 DK097948/DK/NIDDK NIH HHS/ -- P50 CA130810/CA/NCI NIH HHS/ -- P50 CA150964/CA/NCI NIH HHS/ -- R01 CA127590/CA/NCI NIH HHS/ -- R25 CA148052/CA/NCI NIH HHS/ -- R25CA148052/CA/NCI NIH HHS/ -- U54 HL119810/HL/NHLBI NIH HHS/ -- U54HL119810/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Gastroenterology, Haeundae Paik Hospital, Inje University, Busan 612896, South Korea. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Surgery, Busan Paik Hospital, and Paik Institute of Clinical Research and Ocular Neovascular Research Center, Inje University, Busan, South Korea. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Family Medicine, University of Michigan, Ann Arbor MI 48109, USA. ; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. ; Proteomics Center, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA. ; College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068857" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Transplantation ; Colitis/enzymology/prevention & control ; Dinoprostone/metabolism ; Enzyme Inhibitors/chemistry/pharmacology ; Hematopoiesis/drug effects ; Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/genetics/*physiology ; Liver Regeneration/drug effects ; Mice ; Mice, Knockout ; Prostaglandins/*metabolism ; Pyridines/chemistry/pharmacology ; Regeneration/drug effects/genetics/*physiology ; Thiophenes/chemistry/pharmacology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bilbe, Graeme -- New York, N.Y. -- Science. 2015 May 29;348(6238):974-6. doi: 10.1126/science.aaa3683. Epub 2015 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Drugs for Neglected Diseases Initiative, 15 Chemin Louis Dunant, 1202 Geneva, Switzerland. gbilbe@dndi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26023124" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiprotozoal Agents/adverse effects/*chemistry/therapeutic use ; Chagas Disease/drug therapy/transmission ; Disease Models, Animal ; *Drug Design ; Euglenozoa Infections/*drug therapy/transmission ; Humans ; Kinetoplastida/*drug effects ; Leishmaniasis/drug therapy/transmission ; Mice ; Neglected Diseases/*drug therapy ; Trypanosoma cruzi/drug effects ; Trypanosomiasis, African/drug therapy/transmission
    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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  • 12
    Publication Date: 2015-06-13
    Description: During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richiardi, Jonas -- Altmann, Andre -- Milazzo, Anna-Clare -- Chang, Catie -- Chakravarty, M Mallar -- Banaschewski, Tobias -- Barker, Gareth J -- Bokde, Arun L W -- Bromberg, Uli -- Buchel, Christian -- Conrod, Patricia -- Fauth-Buhler, Mira -- Flor, Herta -- Frouin, Vincent -- Gallinat, Jurgen -- Garavan, Hugh -- Gowland, Penny -- Heinz, Andreas -- Lemaitre, Herve -- Mann, Karl F -- Martinot, Jean-Luc -- Nees, Frauke -- Paus, Tomas -- Pausova, Zdenka -- Rietschel, Marcella -- Robbins, Trevor W -- Smolka, Michael N -- Spanagel, Rainer -- Strohle, Andreas -- Schumann, Gunter -- Hawrylycz, Mike -- Poline, Jean-Baptiste -- Greicius, Michael D -- IMAGEN consortium -- 93558/Medical Research Council/United Kingdom -- R01 MH085772-01A1/MH/NIMH NIH HHS/ -- R01NS073498/NS/NINDS NIH HHS/ -- U54 EB020403/EB/NIBIB NIH HHS/ -- Department of Health/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1241-4. doi: 10.1126/science.1255905. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. Laboratory of Neurology and Imaging of Cognition, Department of Neuroscience, University of Geneva, Geneva, Switzerland. jonas.richiardi@unige.ch greicius@stanford.edu. ; Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. ; The War Related Illness and Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA, USA. Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. ; Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. ; Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada. Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Canada. ; Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. ; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. ; Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Department of Psychiatry, Universite de Montreal, Centre Hospitalier Universitaire (CHU) Ste Justine Hospital, Montreal, Canada. ; Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Neurospin, Commissariat a l'Energie Atomique et aux Energies Alternatives, Paris, France. ; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany. ; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA. ; School of Physics and Astronomy, University of Nottingham, Nottingham, UK. ; Institut National de la Sante et de la Recherche Medicale, INSERM Unit 1000 "Neuroimaging and Psychiatry," University Paris Sud, Orsay, France. INSERM Unit 1000 at Maison de Solenn, Assistance Publique Hopitaux de Paris (APHP), Cochin Hospital, University Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Rotman Research Institute, University of Toronto, Toronto, Canada. School of Psychology, University of Nottingham, Nottingham, UK. ; The Hospital for Sick Children, University of Toronto, Toronto, Canada. ; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK. ; Department of Psychiatry and Psychotherapy, and Neuroimaging Center, Technische Universitat Dresden, Dresden, Germany. ; Department of Psychopharmacology, Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, Mannheim, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK. ; Allen Institute for Brain Science, Seattle, WA, USA. ; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA. ; Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. jonas.richiardi@unige.ch greicius@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068849" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Animals ; Brain/metabolism/*physiology ; Female ; Gene Expression ; Humans ; Ion Channels/*genetics ; Magnetic Resonance Imaging ; Male ; Mice ; Nerve Net/metabolism/*physiology ; Neural Pathways/metabolism/physiology ; Polymorphism, Genetic ; Rest/*physiology ; Synapses/metabolism/physiology ; *Transcriptome ; Young Adult
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  • 13
    Publication Date: 2015-05-16
    Description: PIWI-interacting RNAs (piRNAs) protect the animal germ line by silencing transposons. Primary piRNAs, generated from transcripts of genomic transposon "junkyards" (piRNA clusters), are amplified by the "ping-pong" pathway, yielding secondary piRNAs. We report that secondary piRNAs, bound to the PIWI protein Ago3, can initiate primary piRNA production from cleaved transposon RNAs. The first ~26 nucleotides (nt) of each cleaved RNA becomes a secondary piRNA, but the subsequent ~26 nt become the first in a series of phased primary piRNAs that bind Piwi, allowing piRNAs to spread beyond the site of RNA cleavage. The ping-pong pathway increases only the abundance of piRNAs, whereas production of phased primary piRNAs from cleaved transposon RNAs adds sequence diversity to the piRNA pool, allowing adaptation to changes in transposon sequence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545291/" 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/PMC4545291/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Bo W -- Wang, Wei -- Li, Chengjian -- Weng, Zhiping -- Zamore, Phillip D -- GM62862/GM/NIGMS NIH HHS/ -- GM65236/GM/NIGMS NIH HHS/ -- HG007000/HG/NHGRI NIH HHS/ -- R01 GM065236/GM/NIGMS NIH HHS/ -- R37 GM062862/GM/NIGMS NIH HHS/ -- U41 HG007000/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 15;348(6236):817-21. doi: 10.1126/science.aaa1264.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. ; RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. zhiping.weng@umassmed.edu phillip.zamore@umassmed.edu. ; RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. zhiping.weng@umassmed.edu phillip.zamore@umassmed.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977554" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins/genetics/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*metabolism ; Endoribonucleases/genetics/*metabolism ; Female ; Germ Cells/metabolism ; Male ; Metabolic Networks and Pathways ; Mice ; Ovary/metabolism ; Peptide Initiation Factors/genetics/*metabolism ; *RNA Cleavage ; RNA, Guide/*metabolism ; RNA, Small Interfering/biosynthesis/*metabolism ; *Retroelements ; Testis/metabolism
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  • 14
    Publication Date: 2015-04-18
    Description: Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rinkevich, Yuval -- Walmsley, Graham G -- Hu, Michael S -- Maan, Zeshaan N -- Newman, Aaron M -- Drukker, Micha -- Januszyk, Michael -- Krampitz, Geoffrey W -- Gurtner, Geoffrey C -- Lorenz, H Peter -- Weissman, Irving L -- Longaker, Michael T -- GM07365/GM/NIGMS NIH HHS/ -- R01 GM087609/GM/NIGMS NIH HHS/ -- U01 HL099776/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):aaa2151. doi: 10.1126/science.aaa2151.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883361" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage/genetics ; Cell Separation/*methods ; Cicatrix/metabolism/*pathology ; Disease Models, Animal ; Embryonic Development ; Embryonic Stem Cells/cytology ; Fibroblasts/cytology/pathology/*physiology ; Gene Expression ; Homeodomain Proteins/genetics ; Mice ; Mouth/injuries/pathology/surgery ; Skin/injuries/*pathology ; Translational Medical Research ; *Wound Healing
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  • 15
    Publication Date: 2015-11-07
    Description: The sense of smell allows chemicals to be perceived as diverse scents. We used single-neuron RNA sequencing to explore the developmental mechanisms that shape this ability as nasal olfactory neurons mature in mice. Most mature neurons expressed only one of the ~1000 odorant receptor genes (Olfrs) available, and at a high level. However, many immature neurons expressed low levels of multiple Olfrs. Coexpressed Olfrs localized to overlapping zones of the nasal epithelium, suggesting regional biases, but not to single genomic loci. A single immature neuron could express Olfrs from up to seven different chromosomes. The mature state in which expression of Olfr genes is restricted to one per neuron emerges over a developmental progression that appears to be independent of neuronal activity involving sensory transduction molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanchate, Naresh K -- Kondoh, Kunio -- Lu, Zhonghua -- Kuang, Donghui -- Ye, Xiaolan -- Qiu, Xiaojie -- Pachter, Lior -- Trapnell, Cole -- Buck, Linda B -- DP2 HD088158/DP/NCCDPHP CDC HHS/ -- R01 DC009324/DC/NIDCD NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1251-5. doi: 10.1126/science.aad2456. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98115, USA. Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98115, USA. ; Departments of Mathematics, Molecular and Cell Biology, and Electrical Engineering and Computer Sciences, University of California-Berkeley, Berkeley, CA 94720, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98115, USA. coletrap@uw.edu lbuck@fhcrc.org. ; Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. coletrap@uw.edu lbuck@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541607" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cyclic Nucleotide-Gated Cation Channels/genetics ; *Gene Expression Regulation, Developmental ; Genetic Loci ; Genetic Markers ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/*metabolism ; Neurogenesis/*genetics ; Olfactory Mucosa/innervation ; Olfactory Receptor Neurons/*metabolism ; Receptors, Odorant/*genetics ; Sequence Analysis, RNA ; Single-Cell Analysis ; Smell/*genetics ; Transcriptome
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  • 16
    Publication Date: 2015-08-22
    Description: Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras-dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687752/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687752/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Yong -- Wong, Ching-On -- Cho, Kwang-jin -- van der Hoeven, Dharini -- Liang, Hong -- Thakur, Dhananiay P -- Luo, Jialie -- Babic, Milos -- Zinsmaier, Konrad E -- Zhu, Michael X -- Hu, Hongzhen -- Venkatachalam, Kartik -- Hancock, John F -- R01 NS081301/NS/NINDS NIH HHS/ -- R01NS081301/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):873-6. doi: 10.1126/science.aaa5619.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. ; Department of Diagnostic and Biomedical Sciences, Dental School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA. ; Department of Neuroscience, University of Arizona, Tucson, AZ 85721, USA. ; Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Program in Cell and Regulatory Biology, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. ; Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Program in Cell and Regulatory Biology, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. john.f.hancock@uth.tmc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293964" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Membrane/metabolism/*physiology ; Cricetinae ; Drosophila melanogaster ; Fibroblasts ; *Membrane Potentials ; Mice ; Neurons ; Phosphatidylinositol 4,5-Diphosphate/*metabolism ; Phosphatidylserines/*metabolism ; Signal Transduction ; ras Proteins/*metabolism
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  • 17
    Publication Date: 2015-01-03
    Description: Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complicated membrane protein complexes. The enzyme contributes substantially to oxidative energy conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. We report the x-ray structure of mitochondrial complex I at a resolution of 3.6 to 3.9 angstroms, describing in detail the central subunits that execute the bioenergetic function. A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the "deactive" form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site, providing support for a two-state stabilization-change mechanism of proton pumping.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zickermann, Volker -- Wirth, Christophe -- Nasiri, Hamid -- Siegmund, Karin -- Schwalbe, Harald -- Hunte, Carola -- Brandt, Ulrich -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):44-9. doi: 10.1126/science.1259859.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe-University, 60438 Frankfurt am Main, Germany. Cluster of Excellence Frankfurt "Macromolecular Complexes," Goethe-University, 60438 Frankfurt am Main, Germany. zickermann@med.uni-frankfurt.de carola.hunte@biochemie.uni-freiburg.de ulrich.brandt@radboudumc.nl. ; Institute for Biochemistry and Molecular Biology, ZBMZ, BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. ; Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK. Institute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance, 60438 Frankfurt am Main, Germany. ; Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe-University, 60438 Frankfurt am Main, Germany. ; Cluster of Excellence Frankfurt "Macromolecular Complexes," Goethe-University, 60438 Frankfurt am Main, Germany. Institute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance, 60438 Frankfurt am Main, Germany. ; Institute for Biochemistry and Molecular Biology, ZBMZ, BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. zickermann@med.uni-frankfurt.de carola.hunte@biochemie.uni-freiburg.de ulrich.brandt@radboudumc.nl. ; Cluster of Excellence Frankfurt "Macromolecular Complexes," Goethe-University, 60438 Frankfurt am Main, Germany. Nijmegen Center for Mitochondrial Disorders, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. zickermann@med.uni-frankfurt.de carola.hunte@biochemie.uni-freiburg.de ulrich.brandt@radboudumc.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554780" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; Electron Transport Complex I/*chemistry/ultrastructure ; Mitochondria/*enzymology ; Mitochondrial Membranes/*enzymology ; Protein Structure, Secondary ; Protons ; Ubiquinone/chemistry ; Yarrowia/enzymology
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  • 18
    Publication Date: 2015-09-12
    Description: The function of neural circuits depends on the generation of specific classes of neurons. Neural identity is typically established near the time when neurons exit the cell cycle to become postmitotic cells, and it is generally accepted that, once the identity of a neuron has been established, its fate is maintained throughout life. Here, we show that network activity dynamically modulates the properties of fast-spiking (FS) interneurons through the postmitotic expression of the transcriptional regulator Er81. In the adult cortex, Er81 protein levels define a spectrum of FS basket cells with different properties, whose relative proportions are, however, continuously adjusted in response to neuronal activity. Our findings therefore suggest that interneuron properties are malleable in the adult cortex, at least to a certain extent.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702376/" 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/PMC4702376/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dehorter, Nathalie -- Ciceri, Gabriele -- Bartolini, Giorgia -- Lim, Lynette -- del Pino, Isabel -- Marin, Oscar -- 103714MA/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1216-20. doi: 10.1126/science.aab3415.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Centre for Developmental Neurobiology, Medical Research Council, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, UK. Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas and Universidad Miguel Hernandez, 03550 Sant Joan d'Alacant, Spain. ; Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas and Universidad Miguel Hernandez, 03550 Sant Joan d'Alacant, Spain. ; MRC Centre for Developmental Neurobiology, Medical Research Council, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, UK. Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas and Universidad Miguel Hernandez, 03550 Sant Joan d'Alacant, Spain. oscar.marin@kcl.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26359400" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/cytology/metabolism/*physiology ; DNA-Binding Proteins/genetics/*metabolism ; Interneurons/cytology/metabolism/*physiology ; Mice ; Mice, Mutant Strains ; Mitosis ; Mutation ; Nerve Net/cytology/metabolism/*physiology ; Transcription Factors/genetics/*metabolism ; *Transcription, Genetic
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  • 19
    Publication Date: 2015-02-01
    Description: When exposed to antigens, naive B cells differentiate into different types of effector cells: antibody-producing plasma cells, germinal center cells, or memory cells. Whether an individual naive B cell can produce all of these different cell fates remains unclear. Using a limiting dilution approach, we found that many individual naive B cells produced only one type of effector cell subset, whereas others produced all subsets. The capacity to differentiate into multiple subsets was a characteristic of clonal populations that divided many times and resisted apoptosis, but was independent of isotype switching. Antigen receptor affinity also influenced effector cell differentiation. These findings suggest that diverse effector cell types arise in the primary immune response as a result of heterogeneity in responses by individual naive B cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412594/" 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/PMC4412594/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor, Justin J -- Pape, Kathryn A -- Steach, Holly R -- Jenkins, Marc K -- P01 AI035296/AI/NIAID NIH HHS/ -- P01AI035296/AI/NIAID NIH HHS/ -- P30 CA077598/CA/NCI NIH HHS/ -- R01 AI027998/AI/NIAID NIH HHS/ -- R01 AI039614/AI/NIAID NIH HHS/ -- R01AI036914/AI/NIAID NIH HHS/ -- R37AI027998/AI/NIAID NIH HHS/ -- T32 CA009138/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):784-7. doi: 10.1126/science.aaa1342. Epub 2015 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA. jtaylor3@fhcrc.org. ; Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25636798" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody-Producing Cells/*immunology ; Antigens/immunology ; Apoptosis/*immunology ; B-Lymphocyte Subsets/*immunology ; B-Lymphocytes/*immunology ; Cell Differentiation ; *Immunity, Humoral ; Immunoglobulin Class Switching ; Mice ; Mice, Inbred C57BL
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  • 20
    Publication Date: 2015-06-13
    Description: Blood gas and tissue pH regulation depend on the ability of the brain to sense CO2 and/or H(+) and alter breathing appropriately, a homeostatic process called central respiratory chemosensitivity. We show that selective expression of the proton-activated receptor GPR4 in chemosensory neurons of the mouse retrotrapezoid nucleus (RTN) is required for CO2-stimulated breathing. Genetic deletion of GPR4 disrupted acidosis-dependent activation of RTN neurons, increased apnea frequency, and blunted ventilatory responses to CO2. Reintroduction of GPR4 into RTN neurons restored CO2-dependent RTN neuronal activation and rescued the ventilatory phenotype. Additional elimination of TASK-2 (K(2P)5), a pH-sensitive K(+) channel expressed in RTN neurons, essentially abolished the ventilatory response to CO2. The data identify GPR4 and TASK-2 as distinct, parallel, and essential central mediators of respiratory chemosensitivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, Natasha N -- Velic, Ana -- Soliz, Jorge -- Shi, Yingtang -- Li, Keyong -- Wang, Sheng -- Weaver, Janelle L -- Sen, Josh -- Abbott, Stephen B G -- Lazarenko, Roman M -- Ludwig, Marie-Gabrielle -- Perez-Reyes, Edward -- Mohebbi, Nilufar -- Bettoni, Carla -- Gassmann, Max -- Suply, Thomas -- Seuwen, Klaus -- Guyenet, Patrice G -- Wagner, Carsten A -- Bayliss, Douglas A -- HL074011/HL/NHLBI NIH HHS/ -- HL108609/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1255-60. doi: 10.1126/science.aaa0922. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. ; Institute of Physiology, University of Zurich, Zurich, CH-8057, Switzerland. ; Institute of Veterinary Physiology, University of Zurich, Zurich, CH-8057, Switzerland. Centre de Recherche du CHU de Quebec, Departement de Pediatrie, Faculte de Medecine, Universite Laval, Quebec, QC, Canada. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei, 050017, China. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. School of Medical Sciences, University of New South Wales, New South Wales 2052, Australia. Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA. ; Novartis Institutes for Biomedical Research, Basel, CH-4002, Switzerland. ; Institute of Veterinary Physiology, University of Zurich, Zurich, CH-8057, Switzerland. ; Institute of Physiology, University of Zurich, Zurich, CH-8057, Switzerland. Wagnerca@access.uzh.ch bayliss@virginia.edu. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. Wagnerca@access.uzh.ch bayliss@virginia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068853" target="_blank"〉PubMed〈/a〉
    Keywords: Acidosis, Respiratory/genetics/physiopathology ; Animals ; Carbon Dioxide/*physiology ; Female ; Gene Deletion ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Neurons/metabolism/physiology ; Potassium Channels, Tandem Pore Domain/genetics/*physiology ; Receptors, G-Protein-Coupled/antagonists & inhibitors/genetics/*physiology ; *Respiration ; Trapezoid Body/cytology/metabolism/*physiology
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  • 21
    Publication Date: 2015-03-07
    Description: Immune cells, including natural killer (NK) cells, recognize transformed cells and eliminate them in a process termed immunosurveillance. It is thought that tumor cells evade immunosurveillance by shedding membrane ligands that bind to the NKG2D-activating receptor on NK cells and/or T cells, and desensitize these cells. In contrast, we show that in mice, a shed form of MULT1, a high-affinity NKG2D ligand, causes NK cell activation and tumor rejection. Recombinant soluble MULT1 stimulated tumor rejection in mice. Soluble MULT1 functions, at least in part, by competitively reversing a global desensitization of NK cells imposed by engagement of membrane NKG2D ligands on tumor-associated cells, such as myeloid cells. The results overturn conventional wisdom that soluble ligands are always inhibitory and suggest a new approach for cancer immunotherapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Weiwen -- Gowen, Benjamin G -- Zhang, Li -- Wang, Lin -- Lau, Stephanie -- Iannello, Alexandre -- Xu, Jianfeng -- Rovis, Tihana L -- Xiong, Na -- Raulet, David H -- R01 CA093678/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):136-9. doi: 10.1126/science.1258867. Epub 2015 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, and Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA. ; Center for Proteomics University of Rijeka Faculty of Medicine Brace Branchetta 20, 51000 Rijeka, Croatia. ; Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 115 Henning Building, University Park, PA 16802, USA. ; Department of Molecular and Cell Biology, and Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA. raulet@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745066" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/genetics/*immunology/pharmacology ; Histocompatibility Antigens Class I/genetics/*immunology/pharmacology ; Immunologic Surveillance ; Immunotherapy/methods ; Killer Cells, Natural/*immunology ; Ligands ; Lymphocyte Activation ; Melanoma, Experimental/immunology/therapy ; Mice ; NK Cell Lectin-Like Receptor Subfamily K/*immunology ; Neoplasms/*immunology/therapy ; Recombinant Proteins/genetics/immunology/pharmacology ; T-Lymphocytes/immunology
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  • 22
    Publication Date: 2015-10-17
    Description: Human skin relies on cutaneous receptors that output digital signals for tactile sensing in which the intensity of stimulation is converted to a series of voltage pulses. We present a power-efficient skin-inspired mechanoreceptor with a flexible organic transistor circuit that transduces pressure into digital frequency signals directly. The output frequency ranges between 0 and 200 hertz, with a sublinear response to increasing force stimuli that mimics slow-adapting skin mechanoreceptors. The output of the sensors was further used to stimulate optogenetically engineered mouse somatosensory neurons of mouse cortex in vitro, achieving stimulated pulses in accordance with pressure levels. This work represents a step toward the design and use of large-area organic electronic skins with neural-integrated touch feedback for replacement limbs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tee, Benjamin C-K -- Chortos, Alex -- Berndt, Andre -- Nguyen, Amanda Kim -- Tom, Ariane -- McGuire, Allister -- Lin, Ziliang Carter -- Tien, Kevin -- Bae, Won-Gyu -- Wang, Huiliang -- Mei, Ping -- Chou, Ho-Hsiu -- Cui, Bianxiao -- Deisseroth, Karl -- Ng, Tse Nga -- Bao, Zhenan -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):313-6. doi: 10.1126/science.aaa9306.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical Engineering, Stanford University, Stanford, CA, USA. ; Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. ; Department of Bioengineering, Stanford University, Stanford, CA, USA. ; Department of Chemistry, Stanford University, Stanford, CA, USA. ; Department of Chemical Engineering, Stanford University, Stanford, CA, USA. ; Xerox Palo Alto Research Center, Palo Alto, CA, USA. ; Department of Chemical Engineering, Stanford University, Stanford, CA, USA. zbao@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472906" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/cytology/physiology ; Hand/anatomy & histology/innervation/physiology ; Humans ; In Vitro Techniques ; *Mechanoreceptors ; Mice ; *Neural Prostheses ; Optogenetics ; Pressure ; Skin/*innervation ; *Touch ; Transcutaneous Electric Nerve Stimulation/*methods ; Transistors, Electronic
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  • 23
    Publication Date: 2015-07-04
    Description: Lactic acid racemization is involved in lactate metabolism and cell wall assembly of many microorganisms. Lactate racemase (Lar) requires nickel, but the nickel-binding site and the role of three accessory proteins required for its activation remain enigmatic. We combined mass spectrometry and x-ray crystallography to show that Lar from Lactobacillus plantarum possesses an organometallic nickel-containing prosthetic group. A nicotinic acid mononucleotide derivative is tethered to Lys(184) and forms a tridentate pincer complex that coordinates nickel through one metal-carbon and two metal-sulfur bonds, with His(200) as another ligand. Although similar complexes have been previously synthesized, there was no prior evidence for the existence of pincer cofactors in enzymes. The wide distribution of the accessory proteins without Lar suggests that it may play a role in other enzymes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Desguin, Benoit -- Zhang, Tuo -- Soumillion, Patrice -- Hols, Pascal -- Hu, Jian -- Hausinger, Robert P -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):66-9. doi: 10.1126/science.aab2272.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. ; Institute of Life Sciences, Universite Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA. hujian1@msu.edu hausinge@msu.edu. ; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. hujian1@msu.edu hausinge@msu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138974" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics ; Binding Sites ; Carbon/chemistry ; Catalysis ; Crystallography, X-Ray ; Histidine/chemistry ; Holoenzymes/chemistry ; Lactic Acid/*biosynthesis/chemistry ; Lactobacillus plantarum/*enzymology/genetics ; Ligands ; Lysine/chemistry ; Metalloproteins/*chemistry/genetics ; Niacin/*chemistry ; Nickel/*chemistry ; Nicotinamide Mononucleotide/analogs & derivatives/chemistry ; Protein Processing, Post-Translational ; Protein Structure, Secondary ; Racemases and Epimerases/*chemistry/genetics ; Spectrometry, Mass, Electrospray Ionization ; Sulfur
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  • 24
    Publication Date: 2015-05-23
    Description: Extremophiles, microorganisms thriving in extreme environmental conditions, must have proteins and nucleic acids that are stable at extremes of temperature and pH. The nonenveloped, rod-shaped virus SIRV2 (Sulfolobus islandicus rod-shaped virus 2) infects the hyperthermophilic acidophile Sulfolobus islandicus, which lives at 80 degrees C and pH 3. We have used cryo-electron microscopy to generate a three-dimensional reconstruction of the SIRV2 virion at ~4 angstrom resolution, which revealed a previously unknown form of virion organization. Although almost half of the capsid protein is unstructured in solution, this unstructured region folds in the virion into a single extended alpha helix that wraps around the DNA. The DNA is entirely in the A-form, which suggests a common mechanism with bacterial spores for protecting DNA in the most adverse environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DiMaio, Frank -- Yu, Xiong -- Rensen, Elena -- Krupovic, Mart -- Prangishvili, David -- Egelman, Edward H -- GM035269/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 22;348(6237):914-7. doi: 10.1126/science.aaa4181.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. ; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. ; Institut Pasteur, Department of Microbiology, 25 rue du Dr. Roux, Paris 75015, France. ; Institut Pasteur, Department of Microbiology, 25 rue du Dr. Roux, Paris 75015, France. egelman@virginia.edu david.prangishvili@pasteur.fr. ; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. egelman@virginia.edu david.prangishvili@pasteur.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999507" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cryoelectron Microscopy ; DNA, A-Form/*metabolism ; Molecular Sequence Data ; Protein Multimerization ; Protein Structure, Secondary ; Rudiviridae/*metabolism/ultrastructure ; Spores, Bacterial/genetics/virology ; Sulfolobus/*genetics/*virology ; Virion/*ultrastructure
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  • 25
    Publication Date: 2015-10-10
    Description: Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toh, Shigeo -- Holbrook-Smith, Duncan -- Stogios, Peter J -- Onopriyenko, Olena -- Lumba, Shelley -- Tsuchiya, Yuichiro -- Savchenko, Alexei -- McCourt, Peter -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):203-7. doi: 10.1126/science.aac9476.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto M5S 3B2, Canada. ; Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, 200 College Street, Toronto M5S 3E5, Canada. Center for Structural Genomics of Infectious Diseases, contracted by National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, 200 College Street, Toronto M5S 3E5, Canada. ; Institute of Transformative Bio-Molecules, Nagoya University, Japan, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan. ; Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto M5S 3B2, Canada. peter.mccourt@utoronto.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26450211" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/metabolism ; Catalytic Domain ; Germination/drug effects ; Heterocyclic Compounds, 3-Ring/*metabolism/pharmacology ; Lactones/*metabolism/pharmacology ; Molecular Sequence Data ; Phylogeny ; Plant Growth Regulators/*metabolism/pharmacology ; Plant Proteins/*chemistry/classification/genetics ; Protein Structure, Secondary ; Receptors, Cell Surface/*chemistry/classification/genetics ; Seeds/genetics/growth & development/metabolism ; Striga/genetics/growth & development/*metabolism ; Structure-Activity Relationship
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  • 26
    Publication Date: 2015-06-20
    Description: The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform "identification of direct RNA interacting proteins" (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors-including cohesins, condensins, topoisomerases, RNA helicases, chromatin remodelers, and modifiers-that synergistically repress Xi transcription. Inhibiting two or three interactors destabilizes silencing. Although Xist attracts some interactors, it repels architectural factors. Xist evicts cohesins from the Xi and directs an Xi-specific chromosome conformation. Upon deleting Xist, the Xi acquires the cohesin-binding and chromosomal architecture of the active X. Our study unveils many layers of Xi repression and demonstrates a central role for RNA in the topological organization of mammalian chromosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Minajigi, Anand -- Froberg, John E -- Wei, Chunyao -- Sunwoo, Hongjae -- Kesner, Barry -- Colognori, David -- Lessing, Derek -- Payer, Bernhard -- Boukhali, Myriam -- Haas, Wilhelm -- Lee, Jeannie T -- R01-DA-38695/DA/NIDA NIH HHS/ -- R03-MH97478/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 17;349(6245). pii: aab2276. doi: 10.1126/science.aab2276. Epub 2015 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA. ; Massachusetts General Hospital Cancer Center, Charlestown, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA, USA. ; Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA. lee@molbio.mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089354" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Animals ; Cell Cycle Proteins/*metabolism ; Cells, Cultured ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA-Binding Proteins/metabolism ; Embryonic Stem Cells/metabolism ; Fibroblasts/metabolism ; Gene Knockdown Techniques ; Gene Silencing ; Mice ; Multiprotein Complexes/metabolism ; Nucleic Acid Conformation ; Proteomics ; RNA Helicases/metabolism ; RNA, Long Noncoding/*metabolism ; X Chromosome/chemistry/genetics/*metabolism ; *X Chromosome Inactivation
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  • 27
    Publication Date: 2015-01-13
    Description: The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. The soft implants extracted cortical states in freely behaving animals for brain-machine interface and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Minev, Ivan R -- Musienko, Pavel -- Hirsch, Arthur -- Barraud, Quentin -- Wenger, Nikolaus -- Moraud, Eduardo Martin -- Gandar, Jerome -- Capogrosso, Marco -- Milekovic, Tomislav -- Asboth, Leonie -- Torres, Rafael Fajardo -- Vachicouras, Nicolas -- Liu, Qihan -- Pavlova, Natalia -- Duis, Simone -- Larmagnac, Alexandre -- Voros, Janos -- Micera, Silvestro -- Suo, Zhigang -- Courtine, Gregoire -- Lacour, Stephanie P -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):159-63. doi: 10.1126/science.1260318.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Centre for Neuroprosthetics, Institute of Microengineering and Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland. ; International Paraplegic Foundation Chair in Spinal Cord Repair, Centre for Neuroprosthetics and Brain Mind Institute, EPFL, Switzerland. Pavlov Institute of Physiology, St. Petersburg, Russia. ; International Paraplegic Foundation Chair in Spinal Cord Repair, Centre for Neuroprosthetics and Brain Mind Institute, EPFL, Switzerland. ; Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, EPFL, Lausanne, Switzerland. ; Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Centre for Neuroprosthetics, Institute of Microengineering and Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland. International Paraplegic Foundation Chair in Spinal Cord Repair, Centre for Neuroprosthetics and Brain Mind Institute, EPFL, Switzerland. ; School of Engineering and Applied Sciences, Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, MA, USA. ; Laboratory for Biosensors and Bioelectronics, Institute for Biomedical Engineering, University and ETH Zurich, Switzerland. ; Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, EPFL, Lausanne, Switzerland. The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa 56025, Italy. ; International Paraplegic Foundation Chair in Spinal Cord Repair, Centre for Neuroprosthetics and Brain Mind Institute, EPFL, Switzerland. gregoire.courtine@epfl.ch stephanie.lacour@epfl.ch. ; Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Centre for Neuroprosthetics, Institute of Microengineering and Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland. gregoire.courtine@epfl.ch stephanie.lacour@epfl.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25574019" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocompatible Materials/therapeutic use ; Brain-Computer Interfaces ; Drug Delivery Systems/*methods ; *Dura Mater ; Elasticity ; Electric Stimulation/*methods ; Electrochemotherapy/*methods ; *Electrodes, Implanted ; Locomotion ; Mice ; Mice, Inbred Strains ; Motor Cortex/physiopathology ; Multimodal Imaging ; Neurons/physiology ; Paralysis/etiology/physiopathology/*therapy ; Platinum ; *Prostheses and Implants ; Silicon ; Spinal Cord/physiopathology ; Spinal Cord Injuries/complications/physiopathology/*therapy
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  • 28
    Publication Date: 2015-10-24
    Description: The immune system plays an important role in regulating tumor growth and metastasis. Classical monocytes promote tumorigenesis and cancer metastasis, but how nonclassical "patrolling" monocytes (PMo) interact with tumors is unknown. Here we show that PMo are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack PMo, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient PMo into Nr4a1-deficient mice prevented tumor invasion in the lung. PMo established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature, and promoted natural killer cell recruitment and activation. Thus, PMo contribute to cancer immunosurveillance and may be targets for cancer immunotherapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanna, Richard N -- Cekic, Caglar -- Sag, Duygu -- Tacke, Robert -- Thomas, Graham D -- Nowyhed, Heba -- Herrley, Erica -- Rasquinha, Nicole -- McArdle, Sara -- Wu, Runpei -- Peluso, Esther -- Metzger, Daniel -- Ichinose, Hiroshi -- Shaked, Iftach -- Chodaczek, Grzegorz -- Biswas, Subhra K -- Hedrick, Catherine C -- F32 HL117533-02/HL/NHLBI NIH HHS/ -- R01 CA202987/CA/NCI NIH HHS/ -- R01 HL118765/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):985-90. doi: 10.1126/science.aac9407. Epub 2015 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. rhanna@lji.org hedrick@lji.org. ; Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey. ; Izmir Biomedicine and Genome Center, Dokuz Eylul University, Izmir, Turkey. ; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; Microscopy Core, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Universite de Strasbourg, Illkirch, France. ; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. ; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26494174" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Immunologic Surveillance/*immunology ; Immunotherapy/methods ; Killer Cells, Natural/immunology ; Lung Neoplasms/*immunology/*secondary/therapy ; Mice ; Mice, Mutant Strains ; Monocytes/*immunology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms, Experimental/immunology/secondary ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics
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  • 29
    Publication Date: 2015-03-15
    Description: TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Yin Yao -- Pike, Ashley C W -- Mackenzie, Alexandra -- McClenaghan, Conor -- Aryal, Prafulla -- Dong, Liang -- Quigley, Andrew -- Grieben, Mariana -- Goubin, Solenne -- Mukhopadhyay, Shubhashish -- Ruda, Gian Filippo -- Clausen, Michael V -- Cao, Lishuang -- Brennan, Paul E -- Burgess-Brown, Nicola A -- Sansom, Mark S P -- Tucker, Stephen J -- Carpenter, Elisabeth P -- 084655/Wellcome Trust/United Kingdom -- 092809/Z/10/Z/Wellcome Trust/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1256-9. doi: 10.1126/science.1261512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Pfizer Neusentis, Granta Park, Cambridge CB21 6GS, UK. ; OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766236" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arachidonic Acid/pharmacology ; Binding Sites ; Crystallography, X-Ray ; Fluoxetine/analogs & derivatives/chemistry/metabolism/pharmacology ; Humans ; *Ion Channel Gating ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Potassium/metabolism ; Potassium Channels, Tandem Pore Domain/antagonists & ; inhibitors/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 30
    Publication Date: 2015-10-10
    Description: Phosphatidylinositol 3-kinase Vps34 complexes regulate intracellular membrane trafficking in endocytic sorting, cytokinesis, and autophagy. We present the 4.4 angstrom crystal structure of the 385-kilodalton endosomal complex II (PIK3C3-CII), consisting of Vps34, Vps15 (p150), Vps30/Atg6 (Beclin 1), and Vps38 (UVRAG). The subunits form a Y-shaped complex, centered on the Vps34 C2 domain. Vps34 and Vps15 intertwine in one arm, where the Vps15 kinase domain engages the Vps34 activation loop to regulate its activity. Vps30 and Vps38 form the other arm that brackets the Vps15/Vps34 heterodimer, suggesting a path for complex assembly. We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to reveal conformational changes accompanying membrane binding and identify a Vps30 loop that is critical for the ability of complex II to phosphorylate giant liposomes on which complex I is inactive.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601532/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601532/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rostislavleva, Ksenia -- Soler, Nicolas -- Ohashi, Yohei -- Zhang, Lufei -- Pardon, Els -- Burke, John E -- Masson, Glenn R -- Johnson, Chris -- Steyaert, Jan -- Ktistakis, Nicholas T -- Williams, Roger L -- BB/K019155/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_U105184308/Medical Research Council/United Kingdom -- PG11/109/29247/British Heart Foundation/United Kingdom -- U105184308/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):aac7365. doi: 10.1126/science.aac7365.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Structural Biology Research Center, VIB, B-1050 Brussels, Belgium. Structural Biology Brussels, Vrije Universiteit Brussel, B-1050 Brussels, Belgium. ; The Babraham Institute, Cambridge, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. rlw@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26450213" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/chemistry/*enzymology ; Class III Phosphatidylinositol 3-Kinases/chemistry/*ultrastructure ; Crystallography, X-Ray ; Endosomes/chemistry/*enzymology ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/enzymology ; Vacuolar Sorting Protein VPS15/chemistry/ultrastructure
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  • 31
    Publication Date: 2015-09-19
    Description: Prostate cancer is initially responsive to androgen deprivation, but the effectiveness of androgen receptor (AR) inhibitors in recurrent disease is variable. Biopsy of bone metastases is challenging; hence, sampling circulating tumor cells (CTCs) may reveal drug-resistance mechanisms. We established single-cell RNA-sequencing (RNA-Seq) profiles of 77 intact CTCs isolated from 13 patients (mean six CTCs per patient), by using microfluidic enrichment. Single CTCs from each individual display considerable heterogeneity, including expression of AR gene mutations and splicing variants. Retrospective analysis of CTCs from patients progressing under treatment with an AR inhibitor, compared with untreated cases, indicates activation of noncanonical Wnt signaling (P = 0.0064). Ectopic expression of Wnt5a in prostate cancer cells attenuates the antiproliferative effect of AR inhibition, whereas its suppression in drug-resistant cells restores partial sensitivity, a correlation also evident in an established mouse model. Thus, single-cell analysis of prostate CTCs reveals heterogeneity in signaling pathways that could contribute to treatment failure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miyamoto, David T -- Zheng, Yu -- Wittner, Ben S -- Lee, Richard J -- Zhu, Huili -- Broderick, Katherine T -- Desai, Rushil -- Fox, Douglas B -- Brannigan, Brian W -- Trautwein, Julie -- Arora, Kshitij S -- Desai, Niyati -- Dahl, Douglas M -- Sequist, Lecia V -- Smith, Matthew R -- Kapur, Ravi -- Wu, Chin-Lee -- Shioda, Toshi -- Ramaswamy, Sridhar -- Ting, David T -- Toner, Mehmet -- Maheswaran, Shyamala -- Haber, Daniel A -- 2R01CA129933/CA/NCI NIH HHS/ -- EB008047/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1351-6. doi: 10.1126/science.aab0917.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Urology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Center for Bioengineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. haber@helix.mgh.harvard.edu smaheswaran@mgh.harvard.edu. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. haber@helix.mgh.harvard.edu smaheswaran@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383955" target="_blank"〉PubMed〈/a〉
    Keywords: Androgen Antagonists/pharmacology/*therapeutic use ; Animals ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; Humans ; Male ; Mice ; Neoplastic Cells, Circulating/drug effects/*metabolism ; Phenylthiohydantoin/*analogs & derivatives/pharmacology/therapeutic use ; Prostate/drug effects/metabolism/pathology ; Prostatic Neoplasms/*drug therapy/*pathology ; Proto-Oncogene Proteins/genetics/metabolism ; RNA Splicing ; Receptors, Androgen/*genetics ; Sequence Analysis, RNA/methods ; Signal Transduction ; Single-Cell Analysis/methods ; Transcriptome ; Wnt Proteins/genetics/*metabolism ; Xenograft Model Antitumor Assays
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Travis, John -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1456-7. doi: 10.1126/science.350.6267.1456.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680172" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria/genetics ; *CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; DNA/genetics ; Embryo, Mammalian ; Gene Targeting/*methods ; Genetic Engineering/*methods ; Genome/*genetics ; Humans ; Mice ; Organisms, Genetically Modified
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  • 33
    Publication Date: 2015-11-07
    Description: Understanding the evolution of sex determination in plants requires identifying the mechanisms underlying the transition from monoecious plants, where male and female flowers coexist, to unisexual individuals found in dioecious species. We show that in melon and cucumber, the androecy gene controls female flower development and encodes a limiting enzyme of ethylene biosynthesis, ACS11. ACS11 is expressed in phloem cells connected to flowers programmed to become female, and ACS11 loss-of-function mutants lead to male plants (androecy). CmACS11 represses the expression of the male promoting gene CmWIP1 to control the development and the coexistence of male and female flowers in monoecious species. Because monoecy can lead to dioecy, we show how a combination of alleles of CmACS11 and CmWIP1 can create artificial dioecy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boualem, Adnane -- Troadec, Christelle -- Camps, Celine -- Lemhemdi, Afef -- Morin, Halima -- Sari, Marie-Agnes -- Fraenkel-Zagouri, Rina -- Kovalski, Irina -- Dogimont, Catherine -- Perl-Treves, Rafael -- Bendahmane, Abdelhafid -- New York, N.Y. -- Science. 2015 Nov 6;350(6261):688-91. doi: 10.1126/science.aac8370.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut National de la Recherche Agronomique (INRA), Institute of Plant Sciences Paris-Saclay, CNRS, Universite Paris-Sud, Universite d'Evry, Universite Paris-Diderot, Batiment 630, 91405, Orsay, France. ; Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS, UMR 8601, Universite Rene Descartes, Paris, France. ; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. ; INRA, UR 1052, Unite de Genetique et d'Amelioration des Fruits et Legumes, BP 94, F-84143 Montfavet, France. ; Institut National de la Recherche Agronomique (INRA), Institute of Plant Sciences Paris-Saclay, CNRS, Universite Paris-Sud, Universite d'Evry, Universite Paris-Diderot, Batiment 630, 91405, Orsay, France. bendahm@evry.inra.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26542573" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; *Biological Evolution ; Cucumis sativus/enzymology/genetics/growth & development ; Cucurbitaceae/enzymology/genetics/*growth & development ; Ethylenes/biosynthesis ; Flowers/enzymology/genetics/*growth & development ; Genes, Plant/genetics/physiology ; Lyases/genetics/*physiology ; Molecular Sequence Data ; Phloem/enzymology/genetics/growth & development ; Plant Proteins/genetics/*physiology ; Sex Determination Processes/*genetics
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  • 34
    Publication Date: 2015-10-31
    Description: Light mechanical stimulation of hairy skin can induce a form of itch known as mechanical itch. This itch sensation is normally suppressed by inputs from mechanoreceptors; however, in many forms of chronic itch, including alloknesis, this gating mechanism is lost. Here we demonstrate that a population of spinal inhibitory interneurons that are defined by the expression of neuropeptide Y::Cre (NPY::Cre) act to gate mechanical itch. Mice in which dorsal NPY::Cre-derived neurons are selectively ablated or silenced develop mechanical itch without an increase in sensitivity to chemical itch or pain. This chronic itch state is histamine-independent and is transmitted independently of neurons that express the gastrin-releasing peptide receptor. Thus, our studies reveal a dedicated spinal cord inhibitory pathway that gates the transmission of mechanical itch.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700934/" 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/PMC4700934/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bourane, Steeve -- Duan, Bo -- Koch, Stephanie C -- Dalet, Antoine -- Britz, Olivier -- Garcia-Campmany, Lidia -- Kim, Euiseok -- Cheng, Longzhen -- Ghosh, Anirvan -- Ma, Qiufu -- Goulding, Martyn -- NS072031/NS/NINDS NIH HHS/ -- NS072040/NS/NINDS NIH HHS/ -- NS080586/NS/NINDS NIH HHS/ -- NS086372/NS/NINDS NIH HHS/ -- P01 NS072040/NS/NINDS NIH HHS/ -- P30 NS072031/NS/NINDS NIH HHS/ -- R01 NS 067216/NS/NINDS NIH HHS/ -- R01 NS080586/NS/NINDS NIH HHS/ -- R01 NS086372/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):550-4. doi: 10.1126/science.aac8653.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA. ; Neurobiology Section, Division of Biological Sciences, University of California, San Diego, CA 92093, USA. ; Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA. Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China. ; Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA. goulding@salk.edu qiufu_ma@dfci.harvard.edu. ; Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. goulding@salk.edu qiufu_ma@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516282" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Hair/physiology ; Interneurons/*physiology ; Mechanoreceptors/physiology ; Mechanotransduction, Cellular/genetics/*physiology ; Mice ; Mice, Transgenic ; *Neural Inhibition ; Neuropeptide Y/genetics/physiology ; Pruritus/*physiopathology ; Skin/innervation ; Spinal Cord/*physiology ; *Synaptic Transmission
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  • 35
    Publication Date: 2015-05-16
    Description: In animal gonads, PIWI-clade Argonaute proteins repress transposons sequence-specifically via bound Piwi-interacting RNAs (piRNAs). These are processed from single-stranded precursor RNAs by largely unknown mechanisms. Here we show that primary piRNA biogenesis is a 3'-directed and phased process that, in the Drosophila germ line, is initiated by secondary piRNA-guided transcript cleavage. Phasing results from consecutive endonucleolytic cleavages catalyzed by Zucchini, implying coupled formation of 3' and 5' ends of flanking piRNAs. Unexpectedly, Zucchini also participates in 3' end formation of secondary piRNAs. Its function can, however, be bypassed by downstream piRNA-guided precursor cleavages coupled to exonucleolytic trimming. Our data uncover an evolutionarily conserved piRNA biogenesis mechanism in which Zucchini plays a central role in defining piRNA 5' and 3' ends.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohn, Fabio -- Handler, Dominik -- Brennecke, Julius -- New York, N.Y. -- Science. 2015 May 15;348(6236):812-7. doi: 10.1126/science.aaa1039.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria. ; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria. julius.brennecke@imba.oeaw.ac.at.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977553" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*enzymology/genetics ; Endoribonucleases/genetics/*metabolism ; Evolution, Molecular ; Female ; Germ Cells/enzymology ; Male ; Mice ; Ovary/enzymology ; *RNA Cleavage ; RNA, Guide/*metabolism ; RNA, Small Interfering/biosynthesis/*metabolism ; RNA-Binding Proteins/genetics ; Testis/enzymology ; *Transcription, Genetic ; Uridine/metabolism
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  • 36
    Publication Date: 2015-10-24
    Description: Mammalian sleep comprises rapid eye movement (REM) sleep and non-REM (NREM) sleep. To functionally isolate from the complex mixture of neurons populating the brainstem pons those involved in switching between REM and NREM sleep, we chemogenetically manipulated neurons of a specific embryonic cell lineage in mice. We identified excitatory glutamatergic neurons that inhibit REM sleep and promote NREM sleep. These neurons shared a common developmental origin with neurons promoting wakefulness; both derived from a pool of proneural hindbrain cells expressing Atoh1 at embryonic day 10.5. We also identified inhibitory gamma-aminobutyric acid-releasing neurons that act downstream to inhibit REM sleep. Artificial reduction or prolongation of REM sleep in turn affected slow-wave activity during subsequent NREM sleep, implicating REM sleep in the regulation of NREM sleep.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, Yu -- Kashiwagi, Mitsuaki -- Yasuda, Kosuke -- Ando, Reiko -- Kanuka, Mika -- Sakai, Kazuya -- Itohara, Shigeyoshi -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):957-61. doi: 10.1126/science.aad1023. Epub 2015 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai Tsukuba, Ibaraki 305-8575, Japan. Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan. hayashi.yu.fp@u.tsukuba.ac.jp sitohara@brain.riken.jp. ; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai Tsukuba, Ibaraki 305-8575, Japan. ; Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan. ; Integrative Physiology of the Brain Arousal System, Lyon Neuroscience Research Center, INSERM U1028-CNRS UMR5292, School of Medicine, Claude Bernard University Lyon 1, F-69373 Lyon, France. ; Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan. hayashi.yu.fp@u.tsukuba.ac.jp sitohara@brain.riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26494173" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Brain Stem/cytology/physiology ; Cell Lineage ; Cell Separation ; Female ; Glutamates/metabolism ; Male ; Mice ; Mice, Transgenic ; Neurons/metabolism/*physiology ; Pons/cytology/physiology ; Rhombencephalon/*cytology/*embryology ; Sleep, REM/*physiology ; Wakefulness/*physiology ; gamma-Aminobutyric Acid
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  • 37
    Publication Date: 2015-03-21
    Description: Deterioration of adult stem cells accounts for much of aging-associated compromised tissue maintenance. How stem cells maintain metabolic homeostasis remains elusive. Here, we identified a regulatory branch of the mitochondrial unfolded protein response (UPR(mt)), which is mediated by the interplay of SIRT7 and NRF1 and is coupled to cellular energy metabolism and proliferation. SIRT7 inactivation caused reduced quiescence, increased mitochondrial protein folding stress (PFS(mt)), and compromised regenerative capacity of hematopoietic stem cells (HSCs). SIRT7 expression was reduced in aged HSCs, and SIRT7 up-regulation improved the regenerative capacity of aged HSCs. These findings define the deregulation of a UPR(mt)-mediated metabolic checkpoint as a reversible contributing factor for HSC aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447312/" 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/PMC4447312/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohrin, Mary -- Shin, Jiyung -- Liu, Yufei -- Brown, Katharine -- Luo, Hanzhi -- Xi, Yannan -- Haynes, Cole M -- Chen, Danica -- R01 AG040990/AG/NIA NIH HHS/ -- R01AG040061/AG/NIA NIH HHS/ -- T32 AG000266/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1374-7. doi: 10.1126/science.aaa2361.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Biochemistry, Cell and Molecular Biology Allied Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY, USA. ; Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. danicac@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Aging ; *Cell Cycle Checkpoints ; Energy Metabolism ; HEK293 Cells ; Hematopoietic Stem Cells/metabolism/*physiology ; Humans ; Mice ; Mice, Mutant Strains ; Mitochondria/*metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Nuclear Respiratory Factor 1/*metabolism ; Protein Biosynthesis ; Sirtuins/genetics/*metabolism ; *Unfolded Protein Response
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  • 38
    Publication Date: 2015-08-22
    Description: Elucidating the signaling mechanism of strigolactones has been the key to controlling the devastating problem caused by the parasitic plant Striga hermonthica. To overcome the genetic intractability that has previously interfered with identification of the strigolactone receptor, we developed a fluorescence turn-on probe, Yoshimulactone Green (YLG), which activates strigolactone signaling and illuminates signal perception by the strigolactone receptors. Here we describe how strigolactones bind to and act via ShHTLs, the diverged family of alpha/beta hydrolase-fold proteins in Striga. Live imaging using YLGs revealed that a dynamic wavelike propagation of strigolactone perception wakes up Striga seeds. We conclude that ShHTLs function as the strigolactone receptors mediating seed germination in Striga. Our findings enable access to strigolactone receptors and observation of the regulatory dynamics for strigolactone signal transduction in Striga.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsuchiya, Yuichiro -- Yoshimura, Masahiko -- Sato, Yoshikatsu -- Kuwata, Keiko -- Toh, Shigeo -- Holbrook-Smith, Duncan -- Zhang, Hua -- McCourt, Peter -- Itami, Kenichiro -- Kinoshita, Toshinori -- Hagihara, Shinya -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):864-8. doi: 10.1126/science.aab3831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Department of Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto, Ontario M5S 3B2, Canada. yuichiro@itbm.nagoya-u.ac.jp hagi@itbm.nagoya-u.ac.jp. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Department of Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto, Ontario M5S 3B2, Canada. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Japan Science and Technology Agency-Exploratory Research for Advanced Technology, Itami Molecular Nanocarbon Project, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. yuichiro@itbm.nagoya-u.ac.jp hagi@itbm.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293962" target="_blank"〉PubMed〈/a〉
    Keywords: Fluoresceins/chemistry/metabolism ; Fluorescence ; Fluorescent Dyes/chemistry/metabolism ; *Germination ; Hydrolases/metabolism ; Hydrolysis ; Lactones/*metabolism ; Molecular Imaging/methods ; Molecular Sequence Data ; Plant Growth Regulators/*metabolism ; Plant Proteins/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Seeds/*growth & development/metabolism ; Signal Transduction ; Striga/*growth & development/metabolism
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  • 39
    Publication Date: 2015-01-31
    Description: The mechanistic basis of eukaryotic circadian oscillators in model systems as diverse as Neurospora, Drosophila, and mammalian cells is thought to be a transcription-and-translation-based negative feedback loop, wherein progressive and controlled phosphorylation of one or more negative elements ultimately elicits their own proteasome-mediated degradation, thereby releasing negative feedback and determining circadian period length. The Neurospora crassa circadian negative element FREQUENCY (FRQ) exemplifies such proteins; it is progressively phosphorylated at more than 100 sites, and strains bearing alleles of frq with anomalous phosphorylation display abnormal stability of FRQ that is well correlated with altered periods or apparent arrhythmicity. Unexpectedly, we unveiled normal circadian oscillations that reflect the allelic state of frq but that persist in the absence of typical degradation of FRQ. This manifest uncoupling of negative element turnover from circadian period length determination is not consistent with the consensus eukaryotic circadian model.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432837/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432837/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larrondo, Luis F -- Olivares-Yanez, Consuelo -- Baker, Christopher L -- Loros, Jennifer J -- Dunlap, Jay C -- P01 GM68087/GM/NIGMS NIH HHS/ -- R01 GM034985/GM/NIGMS NIH HHS/ -- R01 GM083336/GM/NIGMS NIH HHS/ -- R01 GM34985/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):1257277. doi: 10.1126/science.1257277.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. jay.c.dunlap@dartmouth.edu llarrondo@bio.puc.cl. ; Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. ; Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. ; Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. ; Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. jay.c.dunlap@dartmouth.edu llarrondo@bio.puc.cl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635104" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/analogs & derivatives/pharmacology ; Alleles ; *Circadian Clocks ; *Circadian Rhythm ; Feedback, Physiological ; Fungal Proteins/biosynthesis/*genetics/*metabolism ; Half-Life ; Neurospora crassa/*physiology ; Phosphorylation ; Proteasome Endopeptidase Complex/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Stability ; Proteolysis ; Signal Transduction
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  • 40
    Publication Date: 2015-09-19
    Description: Throughout life, neural stem cells (NSCs) generate neurons in the mammalian brain. Using photobleaching experiments, we found that during cell division in vitro and within the developing mouse forebrain, NSCs generate a lateral diffusion barrier in the membrane of the endoplasmic reticulum, thereby promoting asymmetric segregation of cellular components. The diffusion barrier weakens with age and in response to impairment of lamin-associated nuclear envelope constituents. Weakening of the diffusion barrier disrupts asymmetric segregation of damaged proteins, a product of aging. Damaged proteins are asymmetrically inherited by the nonstem daughter cell in embryonic and young adult NSC divisions, whereas in the older adult brain, damaged proteins are more symmetrically distributed between progeny. Thus, these data identify a mechanism of how damage that accumulates with age is asymmetrically distributed during somatic stem cell division.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, D L -- Pilz, G A -- Arauzo-Bravo, M J -- Barral, Y -- Jessberger, S -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1334-8. doi: 10.1126/science.aac9868.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland. ; Biodonostia Health Research Institute, 20014 San Sebastian, Spain. IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain. ; Institute of Biochemistry, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland. ; Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland. jessberger@hifo.uzh.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383951" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Aging ; *Cell Division ; Diffusion ; Endoplasmic Reticulum/physiology/ultrastructure ; Intracellular Membranes/physiology/ultrastructure ; Lamin Type A/*metabolism ; Mice ; Neural Stem Cells/*cytology/*metabolism ; Photobleaching ; Prosencephalon/cytology/growth & development/metabolism ; Protein Transport
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  • 41
    Publication Date: 2015-05-30
    Description: Memory consolidation is the process by which a newly formed and unstable memory transforms into a stable long-term memory. It is unknown whether the process of memory consolidation occurs exclusively through the stabilization of memory engrams. By using learning-dependent cell labeling, we identified an increase of synaptic strength and dendritic spine density specifically in consolidated memory engram cells. Although these properties are lacking in engram cells under protein synthesis inhibitor-induced amnesia, direct optogenetic activation of these cells results in memory retrieval, and this correlates with retained engram cell-specific connectivity. We propose that a specific pattern of connectivity of engram cells may be crucial for memory information storage and that strengthened synapses in these cells critically contribute to the memory retrieval process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ryan, Tomas J -- Roy, Dheeraj S -- Pignatelli, Michele -- Arons, Autumn -- Tonegawa, Susumu -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 29;348(6238):1007-13. doi: 10.1126/science.aaa5542. Epub 2015 May 28.〈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, Cambridge, MA 02139, USA. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; 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, Cambridge, MA 02139, USA. ; 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, Cambridge, MA 02139, USA. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. tonegawa@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26023136" target="_blank"〉PubMed〈/a〉
    Keywords: Amnesia, Retrograde/chemically induced/*physiopathology ; Amygdala/chemistry/physiopathology ; Animals ; Conditioning, Classical ; Dendrites/chemistry/pathology/*physiology ; Dentate Gyrus/chemistry/pathology/physiopathology ; Fluorescent Dyes/analysis ; Luminescent Proteins/analysis ; Memory, Long-Term/*physiology ; Mice ; Neuronal Plasticity/physiology ; Protein Synthesis Inhibitors/pharmacology ; Staining and Labeling ; Synapses/physiology
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  • 42
    Publication Date: 2015-03-21
    Description: Neuronal excitation is regulated by energy metabolism, and drug-resistant epilepsy can be suppressed by special diets. Here, we report that seizures and epileptiform activity are reduced by inhibition of the metabolic pathway via lactate dehydrogenase (LDH), a component of the astrocyte-neuron lactate shuttle. Inhibition of the enzyme LDH hyperpolarized neurons, which was reversed by the downstream metabolite pyruvate. LDH inhibition also suppressed seizures in vivo in a mouse model of epilepsy. We further found that stiripentol, a clinically used antiepileptic drug, is an LDH inhibitor. By modifying its chemical structure, we identified a previously unknown LDH inhibitor, which potently suppressed seizures in vivo. We conclude that LDH inhibitors are a promising new group of antiepileptic drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sada, Nagisa -- Lee, Suni -- Katsu, Takashi -- Otsuki, Takemi -- Inoue, Tsuyoshi -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1362-7. doi: 10.1126/science.aaa1299.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. ; Department of Hygiene, Kawasaki Medical School, Kurashiki 701-0192, Japan. ; Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. tinoue@pharm.okayama-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anticonvulsants/chemistry/*pharmacology/therapeutic use ; Dioxolanes/chemistry/*pharmacology/therapeutic use ; Disease Models, Animal ; Enzyme Inhibitors/chemistry/*pharmacology/therapeutic use ; L-Lactate Dehydrogenase/*antagonists & inhibitors ; Membrane Potentials/drug effects ; Mice ; Mice, Inbred ICR ; Neurons/enzymology/physiology ; Patch-Clamp Techniques ; Safrole/chemistry/*pharmacology/therapeutic use ; Seizures/*drug therapy ; Subthalamic Nucleus/enzymology
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  • 43
    Publication Date: 2015-10-17
    Description: Research in the genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. Although the exact identity of many of the genes remains to be discovered, genes identified to date encode proteins that play roles in certain conserved pathways: protein synthesis, transcriptional and epigenetic regulation, and synaptic signaling. The next generation of research in neurodevelopmental disorders must address the neural circuitry underlying the behavioral symptoms and comorbidities, the cell types playing critical roles in these circuits, and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we can leverage the heterogeneity of neurodevelopmental disorders into precision medicine will the mechanism-based therapeutics for these disorders start to unlock success.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739545/" 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/PMC4739545/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sahin, Mustafa -- Sur, Mriganka -- EF1451125/PHS HHS/ -- EY007023/EY/NEI NIH HHS/ -- MH085802/MH/NIMH NIH HHS/ -- NS090473/NS/NINDS NIH HHS/ -- P20 NS080199/NS/NINDS NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- U01 NS082320/NS/NINDS NIH HHS/ -- U54 NS092090/NS/NINDS NIH HHS/ -- U54NS092090/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 20;350(6263). pii: aab3897. doi: 10.1126/science.aab3897. Epub 2015 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉F. M. Kirby Center for Neurobiology, Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA. mustafa.sahin@childrens.harvard.edu msur@mit.edu. ; Simons Center for the Social Brain, Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. mustafa.sahin@childrens.harvard.edu msur@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472761" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/drug therapy/genetics ; Behavior ; Brain/growth & development/metabolism ; Chromatin Assembly and Disassembly ; Clinical Trials as Topic ; Epigenesis, Genetic ; Genes ; *Genetic Predisposition to Disease ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Mutation ; Neural Pathways/metabolism ; Neurodevelopmental Disorders/*drug therapy/*genetics ; Precision Medicine/*methods ; Protein Biosynthesis/genetics ; Transcription, Genetic ; Translational Medical Research
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  • 44
    Publication Date: 2015-07-25
    Description: In eukaryotic cells, phosphatidylserine (PS) is synthesized in the endoplasmic reticulum (ER) but is highly enriched in the plasma membrane (PM), where it contributes negative charge and to specific recruitment of signaling proteins. This distribution relies on transport mechanisms whose nature remains elusive. Here, we found that the PS transporter Osh6p extracted phosphatidylinositol 4-phosphate (PI4P) and exchanged PS for PI4P between two membranes. We solved the crystal structure of Osh6p:PI4P complex and demonstrated that the transport of PS by Osh6p depends on PI4P recognition in vivo. Finally, we showed that the PI4P-phosphatase Sac1p, by maintaining a PI4P gradient at the ER/PM interface, drove PS transport. Thus, PS transport by oxysterol-binding protein-related protein (ORP)/oxysterol-binding homology (Osh) proteins is fueled by PI4P metabolism through PS/PI4P exchange cycles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moser von Filseck, Joachim -- Copic, Alenka -- Delfosse, Vanessa -- Vanni, Stefano -- Jackson, Catherine L -- Bourguet, William -- Drin, Guillaume -- New York, N.Y. -- Science. 2015 Jul 24;349(6246):432-6. doi: 10.1126/science.aab1346. Epub 2015 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice Sophia-Antipolis and CNRS, 660 route des lucioles, 06560 Valbonne, France. ; Institut Jacques Monod, CNRS, UMR 7592, Universite Paris Diderot, Sorbonne Paris Cite, F-75013 Paris, France. ; Inserm U1054, 29 rue de Navacelles, 34090 Montpellier, France. CNRS UMR5048, Centre de Biochimie Structurale, 29 rue de Navacelles, 34090 Montpellier, France. ; Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice Sophia-Antipolis and CNRS, 660 route des lucioles, 06560 Valbonne, France. drin@ipmc.cnrs.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26206936" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport ; Cell Membrane/*metabolism ; Crystallography, X-Ray ; Endoplasmic Reticulum/*metabolism ; Phosphatidylinositol Phosphates/chemistry/*metabolism ; Phosphatidylserines/chemistry/*metabolism ; Phosphoric Monoester Hydrolases/genetics/*metabolism ; Receptors, Steroid/chemistry/genetics/*metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism
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  • 45
    Publication Date: 2015-02-14
    Description: The C-terminal region of Clostridium perfringens enterotoxin (C-CPE) can bind to specific claudins, resulting in the disintegration of tight junctions (TJs) and an increase in the paracellular permeability across epithelial cell sheets. Here we present the structure of mammalian claudin-19 in complex with C-CPE at 3.7 A resolution. The structure shows that C-CPE forms extensive hydrophobic and hydrophilic interactions with the two extracellular segments of claudin-19. The claudin-19/C-CPE complex shows no density of a short extracellular helix that is critical for claudins to assemble into TJ strands. The helix displacement may thus underlie C-CPE-mediated disassembly of TJs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saitoh, Yasunori -- Suzuki, Hiroshi -- Tani, Kazutoshi -- Nishikawa, Kouki -- Irie, Katsumasa -- Ogura, Yuki -- Tamura, Atsushi -- Tsukita, Sachiko -- Fujiyoshi, Yoshinori -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):775-8. doi: 10.1126/science.1261833.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. ; Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan. yoshi@cespi.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678664" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Claudins/*chemistry ; Enterotoxins/*chemistry ; Hydrophobic and Hydrophilic Interactions ; Mice ; Protein Structure, Secondary ; Tight Junctions/chemistry/*ultrastructure
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  • 46
    Publication Date: 2015-02-28
    Description: Ebola virus causes sporadic outbreaks of lethal hemorrhagic fever in humans, but there is no currently approved therapy. Cells take up Ebola virus by macropinocytosis, followed by trafficking through endosomal vesicles. However, few factors controlling endosomal virus movement are known. Here we find that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small-molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule that we tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. Therefore, TPC proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550587/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550587/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakurai, Yasuteru -- Kolokoltsov, Andrey A -- Chen, Cheng-Chang -- Tidwell, Michael W -- Bauta, William E -- Klugbauer, Norbert -- Grimm, Christian -- Wahl-Schott, Christian -- Biel, Martin -- Davey, Robert A -- R01 AI063513/AI/NIAID NIH HHS/ -- R01AI063513/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):995-8. doi: 10.1126/science.1258758.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Texas Biomedical Research Institute, San Antonio, TX, USA. ; The University of Texas Medical Branch, Galveston, TX, USA. ; Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universitat Munchen, Munich, Germany. ; Southwest Research Institute, San Antonio, TX, USA. ; Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-Universitat Freiburg, Freiburg, Germany. ; Texas Biomedical Research Institute, San Antonio, TX, USA. rdavey@txbiomed.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25722412" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/*pharmacology/therapeutic use ; BALB 3T3 Cells ; Benzylisoquinolines/pharmacology/therapeutic use ; Calcium Channel Blockers/*pharmacology/therapeutic use ; Calcium Channels/genetics/*physiology ; Ebolavirus/drug effects/*physiology ; Female ; Gene Knockout Techniques ; HeLa Cells ; Hemorrhagic Fever, Ebola/drug therapy/*therapy/virology ; Humans ; Macrophages/drug effects/virology ; Mice ; *Molecular Targeted Therapy ; NADP/analogs & derivatives/metabolism ; RNA Interference ; Signal Transduction ; Verapamil/pharmacology/therapeutic use ; Virus Internalization/*drug effects
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  • 47
    Publication Date: 2015-07-04
    Description: Larger brains tend to have more folded cortices, but what makes the cortex fold has remained unknown. We show that the degree of cortical folding scales uniformly across lissencephalic and gyrencephalic species, across individuals, and within individual cortices as a function of the product of cortical surface area and the square root of cortical thickness. This relation is derived from the minimization of the effective free energy associated with cortical shape according to a simple physical model, based on known mechanisms of axonal elongation. This model also explains the scaling of the folding index of crumpled paper balls. We discuss the implications of this finding for the evolutionary and developmental origin of folding, including the newfound continuum between lissencephaly and gyrencephaly, and for pathologies such as human lissencephaly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mota, Bruno -- Herculano-Houzel, Suzana -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):74-7. doi: 10.1126/science.aaa9101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. ; Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Instituto Nacional de Neurociencia Translacional, INCT/MCT, Sao Paulo, Brazil. suzanahh@gmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Count ; *Cerebral Cortex/cytology/embryology/pathology ; Humans ; Lissencephaly/*pathology ; Mice ; Models, Neurological ; Neurons/*cytology/pathology ; Rats ; Species Specificity
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):491-2. doi: 10.1126/science.350.6260.491.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516259" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*physiology/ultrastructure ; Brain-Derived Neurotrophic Factor/pharmacology ; Memory, Long-Term/*physiology ; Mice ; Microscopy, Electron ; Nerve Net/*physiology/ultrastructure ; Neurons/drug effects/physiology ; Neurosciences ; Synapses/*physiology/ultrastructure
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  • 49
    Publication Date: 2015-09-26
    Description: Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) detects intracellular DNA and signals through the adapter protein STING to initiate the antiviral response to DNA viruses. Whether DNA viruses can prevent activation of the cGAS-STING pathway remains largely unknown. Here, we identify the oncogenes of the DNA tumor viruses, including E7 from human papillomavirus (HPV) and E1A from adenovirus, as potent and specific inhibitors of the cGAS-STING pathway. We show that the LXCXE motif of these oncoproteins, which is essential for blockade of the retinoblastoma tumor suppressor, is also important for antagonizing DNA sensing. E1A and E7 bind to STING, and silencing of these oncogenes in human tumor cells restores the cGAS-STING pathway. Our findings reveal a host-virus conflict that may have shaped the evolution of viral oncogenes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lau, Laura -- Gray, Elizabeth E -- Brunette, Rebecca L -- Stetson, Daniel B -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):568-71. doi: 10.1126/science.aab3291. Epub 2015 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA. ; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA. stetson@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26405230" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/chemistry/genetics/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; DNA Tumor Viruses/*immunology ; DNA, Neoplasm/immunology ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Evolution, Molecular ; HEK293 Cells ; HeLa Cells ; Host-Pathogen Interactions ; Humans ; Membrane Proteins/*antagonists & inhibitors ; Metabolic Networks and Pathways ; Molecular Sequence Data ; Nucleotides, Cyclic/*antagonists & inhibitors ; Oncogene Proteins, Viral/chemistry/genetics/*metabolism ; Retinoblastoma Protein/antagonists & inhibitors ; *Tumor Escape
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mueller, Kristen L -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):54-5. doi: 10.1126/science.348.6230.54.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25838372" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology/therapeutic use ; Humans ; Immunotherapy ; Mice ; Neoplasms/*immunology/*therapy ; Receptors, Antigen, T-Cell/antagonists & inhibitors/immunology
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  • 51
    Publication Date: 2015-04-25
    Description: Inflammatory CD4(+) T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. Although selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here, we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII(+) ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4(+) T cells in the intestine and suggest that this process is dysregulated in human IBD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449822/" 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/PMC4449822/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hepworth, Matthew R -- Fung, Thomas C -- Masur, Samuel H -- Kelsen, Judith R -- McConnell, Fiona M -- Dubrot, Juan -- Withers, David R -- Hugues, Stephanie -- Farrar, Michael A -- Reith, Walter -- Eberl, Gerard -- Baldassano, Robert N -- Laufer, Terri M -- Elson, Charles O -- Sonnenberg, Gregory F -- DK071176/DK/NIDDK NIH HHS/ -- DP5 OD012116/OD/NIH HHS/ -- DP5OD012116/OD/NIH HHS/ -- UL1-RR024134/RR/NCRR NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 May 29;348(6238):1031-5. doi: 10.1126/science.aaa4812. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. ; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA. ; Medical Research Council, Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. ; Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland. ; Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, MN, USA. ; Institut Pasteur, Microenvironment and Immunity Unit, Paris, France. ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA. ; Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA. ; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. gfsonnenberg@med.cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908663" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/immunology ; Autoimmunity ; Bacteria/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Colon/*microbiology ; Female ; Flagellin/genetics/immunology ; Histocompatibility Antigens Class II/*immunology ; Humans ; *Immunity, Innate ; Inflammatory Bowel Diseases/immunology/*microbiology ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred C57BL ; Symbiosis ; Thymus Gland/immunology
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  • 52
    Publication Date: 2015-09-12
    Description: Podophyllotoxin is the natural product precursor of the chemotherapeutic etoposide, yet only part of its biosynthetic pathway is known. We used transcriptome mining in Podophyllum hexandrum (mayapple) to identify biosynthetic genes in the podophyllotoxin pathway. We selected 29 candidate genes to combinatorially express in Nicotiana benthamiana (tobacco) and identified six pathway enzymes, including an oxoglutarate-dependent dioxygenase that closes the core cyclohexane ring of the aryltetralin scaffold. By coexpressing 10 genes in tobacco-these 6 plus 4 previously discovered-we reconstitute the pathway to (-)-4'-desmethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Our results enable production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lau, Warren -- Sattely, Elizabeth S -- DP2 AT008321/AT/NCCIH NIH HHS/ -- R00 GM089985/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1224-8. doi: 10.1126/science.aac7202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA. ; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA. sattely@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26359402" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biosynthetic Pathways/genetics ; Etoposide/*metabolism ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; *Genetic Engineering ; Methylation ; Mixed Function Oxygenases/genetics/*metabolism ; Molecular Sequence Data ; Podophyllotoxin/*analogs & derivatives/biosynthesis/*metabolism ; Podophyllum peltatum/*enzymology/genetics ; Tobacco/genetics/*metabolism ; Topoisomerase Inhibitors/*metabolism ; Transcriptome
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):575-7. doi: 10.1126/science.349.6248.575.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*cytology ; Caenorhabditis elegans ; Cell Shape ; Humans ; Identity Crisis ; Interneurons/classification ; Mice ; Neuroanatomy/*methods ; Neurons/*classification ; Retina/cytology ; Silver Staining ; Visual Cortex/cytology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 54
    Publication Date: 2015-03-31
    Description: Trypanosoma brucei, a causative agent of African Sleeping Sickness, constantly changes its dense variant surface glycoprotein (VSG) coat to avoid elimination by the immune system of its mammalian host, using an extensive repertoire of dedicated genes. However, the dynamics of VSG expression in T. brucei during an infection are poorly understood. We have developed a method, based on de novo assembly of VSGs, for quantitatively examining the diversity of expressed VSGs in any population of trypanosomes and monitored VSG population dynamics in vivo. Our experiments revealed unexpected diversity within parasite populations and a mechanism for diversifying the genome-encoded VSG repertoire. The interaction between T. brucei and its host is substantially more dynamic and nuanced than previously expected.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514441/" 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/PMC4514441/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mugnier, Monica R -- Cross, George A M -- Papavasiliou, F Nina -- AI085973/AI/NIAID NIH HHS/ -- R01 AI085973/AI/NIAID NIH HHS/ -- R01 AI097127/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1470-3. doi: 10.1126/science.aaa4502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY, USA. Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA. ; Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY, USA. Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA. papavasiliou@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814582" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigenic Variation ; Host-Parasite Interactions/*immunology ; Humans ; Mice ; Mice, Inbred BALB C ; Trypanosoma brucei brucei/*immunology ; Trypanosomiasis, African/*immunology ; Variant Surface Glycoproteins, Trypanosoma/*immunology
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1186-7. doi: 10.1126/science.347.6227.1186.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766212" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/pathology/*therapy ; Animals ; Antineoplastic Agents/administration & dosage ; *Blood-Brain Barrier ; Brain/pathology ; Brain Neoplasms/drug therapy/*therapy ; Clinical Trials, Phase I as Topic ; Disease Models, Animal ; Humans ; Mice ; Microbubbles ; Plaque, Amyloid/pathology/therapy ; *Ultrasonic Therapy
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  • 56
    Publication Date: 2015-12-19
    Description: Microbial sulfate reduction has governed Earth's biogeochemical sulfur cycle for at least 2.5 billion years. However, the enzymatic mechanisms behind this pathway are incompletely understood, particularly for the reduction of sulfite-a key intermediate in the pathway. This critical reaction is performed by DsrAB, a widespread enzyme also involved in other dissimilatory sulfur metabolisms. Using in vitro assays with an archaeal DsrAB, supported with genetic experiments in a bacterial system, we show that the product of sulfite reduction by DsrAB is a protein-based trisulfide, in which a sulfite-derived sulfur is bridging two conserved cysteines of DsrC. Physiological studies also reveal that sulfate reduction rates are determined by cellular levels of DsrC. Dissimilatory sulfate reduction couples the four-electron reduction of the DsrC trisulfide to energy conservation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santos, Andre A -- Venceslau, Sofia S -- Grein, Fabian -- Leavitt, William D -- Dahl, Christiane -- Johnston, David T -- Pereira, Ines A C -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1541-5. doi: 10.1126/science.aad3558.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Tecnologia Quimica e Biologica Antonio Xavier, Universidade Nova de Lisboa, Oeiras, Portugal. ; Department of Earth and Planetary Science, Harvard University, Cambridge, MA, USA. ; Institut fur Mikrobiologie & Biotechnologie, Rheinische Friedrich-Wilhelms-Universitat Bonn, Germany. ; Instituto de Tecnologia Quimica e Biologica Antonio Xavier, Universidade Nova de Lisboa, Oeiras, Portugal. ipereira@itqb.unl.pt.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680199" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeal Proteins/chemistry/*metabolism ; Archaeoglobus fulgidus/*enzymology ; Crystallography, X-Ray ; Cysteine/chemistry/metabolism ; *Energy Metabolism ; Oxidation-Reduction ; Proteins/metabolism ; Sulfates/metabolism ; Sulfides/chemistry/*metabolism ; Sulfites/metabolism ; Sulfur/*metabolism
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  • 57
    Publication Date: 2015-03-07
    Description: Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state-like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor's inactive state.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445376/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445376/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burg, John S -- Ingram, Jessica R -- Venkatakrishnan, A J -- Jude, Kevin M -- Dukkipati, Abhiram -- Feinberg, Evan N -- Angelini, Alessandro -- Waghray, Deepa -- Dror, Ron O -- Ploegh, Hidde L -- Garcia, K Christopher -- DP1 GM106409/GM/NIGMS NIH HHS/ -- R01 GM097015/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1113-7. doi: 10.1126/science.aaa5026.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Computer Science, Stanford University, Stanford, CA 94305, USA. Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA. ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. kcgarcia@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745166" target="_blank"〉PubMed〈/a〉
    Keywords: CCR5 Receptor Antagonists/chemistry ; Chemokine CX3CL1/*chemistry ; Crystallography, X-Ray ; Cyclohexanes/chemistry ; Humans ; Ligands ; Piperidines/chemistry ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, CXCR4/antagonists & inhibitors ; Receptors, Chemokine/agonists/*chemistry ; Triazoles/chemistry ; Viral Proteins/agonists/*chemistry
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  • 58
    Publication Date: 2015-06-13
    Description: Cell division progresses to anaphase only after all chromosomes are connected to spindle microtubules through kinetochores and the spindle assembly checkpoint (SAC) is satisfied. We show that the amino-terminal localization module of the SAC protein kinase MPS1 (monopolar spindle 1) directly interacts with the HEC1 (highly expressed in cancer 1) calponin homology domain in the NDC80 (nuclear division cycle 80) kinetochore complex in vitro, in a phosphorylation-dependent manner. Microtubule polymers disrupted this interaction. In cells, MPS1 binding to kinetochores or to ectopic NDC80 complexes was prevented by end-on microtubule attachment, independent of known kinetochore protein-removal mechanisms. Competition for kinetochore binding between SAC proteins and microtubules provides a direct and perhaps evolutionarily conserved way to detect a properly organized spindle ready for cell division.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hiruma, Yoshitaka -- Sacristan, Carlos -- Pachis, Spyridon T -- Adamopoulos, Athanassios -- Kuijt, Timo -- Ubbink, Marcellus -- von Castelmur, Eleonore -- Perrakis, Anastassis -- Kops, Geert J P L -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1264-7. doi: 10.1126/science.aaa4055. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. ; Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. ; Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. ; Leiden Institute of Chemistry, Leiden University, Post Office Box 9502, 2300 RA Leiden, Netherlands. ; Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. g.j.p.l.kops@umcutrecht.nl a.perrakis@nki.nl. ; Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. g.j.p.l.kops@umcutrecht.nl a.perrakis@nki.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068855" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; Binding, Competitive ; Calcium-Binding Proteins/genetics/metabolism ; *Cell Cycle Checkpoints ; Cell Cycle Proteins/*metabolism ; HeLa Cells ; Humans ; Kinetochores/*metabolism ; Microfilament Proteins/genetics/metabolism ; Microtubules/*metabolism ; Nuclear Proteins/chemistry/*metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/*metabolism ; Protein-Tyrosine Kinases/*metabolism ; Signal Transduction ; Spindle Apparatus/*metabolism
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  • 59
    Publication Date: 2015-03-31
    Description: Dynactin is an essential cofactor for the microtubule motor cytoplasmic dynein-1. We report the structure of the 23-subunit dynactin complex by cryo-electron microscopy to 4.0 angstroms. Our reconstruction reveals how dynactin is built around a filament containing eight copies of the actin-related protein Arp1 and one of beta-actin. The filament is capped at each end by distinct protein complexes, and its length is defined by elongated peptides that emerge from the alpha-helical shoulder domain. A further 8.2 angstrom structure of the complex between dynein, dynactin, and the motility-inducing cargo adaptor Bicaudal-D2 shows how the translational symmetry of the dynein tail matches that of the dynactin filament. The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413427/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413427/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Urnavicius, Linas -- Zhang, Kai -- Diamant, Aristides G -- Motz, Carina -- Schlager, Max A -- Yu, Minmin -- Patel, Nisha A -- Robinson, Carol V -- Carter, Andrew P -- 100387/Wellcome Trust/United Kingdom -- MC_UP_A025_1011/Medical Research Council/United Kingdom -- WT100387/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1441-6. doi: 10.1126/science.aaa4080. Epub 2015 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK. ; Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK. cartera@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814576" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/chemistry ; Animals ; Cryoelectron Microscopy ; Dyneins/*chemistry ; Humans ; Mice ; Microtubule-Associated Proteins/*chemistry ; Multiprotein Complexes/*chemistry ; Protein Interaction Mapping ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Swine
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  • 60
    Publication Date: 2015-10-31
    Description: Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vacchelli, Erika -- Ma, Yuting -- Baracco, Elisa E -- Sistigu, Antonella -- Enot, David P -- Pietrocola, Federico -- Yang, Heng -- Adjemian, Sandy -- Chaba, Kariman -- Semeraro, Michaela -- Signore, Michele -- De Ninno, Adele -- Lucarini, Valeria -- Peschiaroli, Francesca -- Businaro, Luca -- Gerardino, Annamaria -- Manic, Gwenola -- Ulas, Thomas -- Gunther, Patrick -- Schultze, Joachim L -- Kepp, Oliver -- Stoll, Gautier -- Lefebvre, Celine -- Mulot, Claire -- Castoldi, Francesca -- Rusakiewicz, Sylvie -- Ladoire, Sylvain -- Apetoh, Lionel -- Bravo-San Pedro, Jose Manuel -- Lucattelli, Monica -- Delarasse, Cecile -- Boige, Valerie -- Ducreux, Michel -- Delaloge, Suzette -- Borg, Christophe -- Andre, Fabrice -- Schiavoni, Giovanna -- Vitale, Ilio -- Laurent-Puig, Pierre -- Mattei, Fabrizio -- Zitvogel, Laurence -- Kroemer, Guido -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):972-8. doi: 10.1126/science.aad0779. Epub 2015 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, China. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. ; Regina Elena National Cancer Institute, Rome, Italy. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France. ; Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy. ; Italian National Research Council, Institute for Photonics and Nanotechnology, Rome, Italy. ; Genomics and Immunoregulation, Life and Medical Science Center Institute, University of Bonn, Germany. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. ; Universite Paris Sorbonne Cite, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. Sotio, Prague, Czech Republic. ; Department of Medical Oncology, Centre Georges-Francois Leclerc, Dijon, France. Universite Bourgogne Franche-Comte, Dijon, France. Centre Georges Francois Leclerc, Dijon, France. ; Department of Life Sciences, University of Siena, Siena, Italy. ; Institut du Cerveau et de la Moelle Epiniere, ICM CNRS UMR 7225 - INSERM U 1127 - UPMC-P6 UMR S 1127, Equipe Neurogenetique et Physiologie Hopital de la Pitie-Salpetriere, 47, Boulevard de l'Hopital, 75013 Paris, France. ; INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France. ; Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France. ; INSERM, U981, Villejuif, France. Department of Breast Oncology, Gustave Roussy Cancer Campus, Villejuif, France. ; University of Franche-Comte, INSERM 1098, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. Department of Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. ; Regina Elena National Cancer Institute, Rome, Italy. Department of Biology, University of Rome "Tor Vergata," Rome, Italy. ; Universite Paris Sorbonne Cite, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Pole de Biologie, Hopital Europeen Georges Pompidou, AP-HP, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France. kroemer@orange.fr laurence.zitvogel@gustaveroussy.fr. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Pole de Biologie, Hopital Europeen Georges Pompidou, AP-HP, Paris, France. Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, 17176 Stockholm, Sweden. kroemer@orange.fr laurence.zitvogel@gustaveroussy.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516201" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Annexin A1/metabolism/pharmacology ; Anthracyclines/*therapeutic use ; Breast Neoplasms/drug therapy/immunology ; Cell Line, Tumor ; Chemotherapy, Adjuvant ; Colorectal Neoplasms/drug therapy/immunology ; Dendritic Cells/drug effects/immunology ; Female ; Humans ; Immunity, Innate/genetics ; Leukocytes/drug effects/immunology ; Mice ; Neoplasms/*drug therapy/*immunology ; Polymorphism, Single Nucleotide ; Receptors, Formyl Peptide/genetics/*physiology ; T-Lymphocytes/immunology
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  • 61
    Publication Date: 2015-03-31
    Description: The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 x 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoenen, T -- Safronetz, D -- Groseth, A -- Wollenberg, K R -- Koita, O A -- Diarra, B -- Fall, I S -- Haidara, F C -- Diallo, F -- Sanogo, M -- Sarro, Y S -- Kone, A -- Togo, A C G -- Traore, A -- Kodio, M -- Dosseh, A -- Rosenke, K -- de Wit, E -- Feldmann, F -- Ebihara, H -- Munster, V J -- Zoon, K C -- Feldmann, H -- Sow, S -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):117-9. doi: 10.1126/science.aaa5646. Epub 2015 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA. ; Bioinformatics and Computational Biosciences Branch, NIAID, NIH, Bethesda, MD 20892, USA. ; Center of Research and Training for HIV and Tuberculosis, University of Science, Technique and Technologies of Bamako, Mali. ; World Health Organization Office, Bamako, Mali. ; Centre des Operations d'Urgence, Centre pour le Developpement des Vaccins (CVD-Mali), Centre National d'Appui a la lutte contre la Maladie, Ministere de la Sante et de l'Hygiene Publique, Bamako, Mali. ; World Health Organization Inter-Country Support Team, Ouagadougou, Burkina Faso. ; Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA. ; Office of the Scientific Director, NIAID, NIH, Bethesda, MD 20895, USA. ; Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA. feldmannh@niaid.nih.gov ssow@medicine.umaryland.edu. ; Centre des Operations d'Urgence, Centre pour le Developpement des Vaccins (CVD-Mali), Centre National d'Appui a la lutte contre la Maladie, Ministere de la Sante et de l'Hygiene Publique, Bamako, Mali. feldmannh@niaid.nih.gov ssow@medicine.umaryland.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814067" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Disease Outbreaks ; Ebolavirus/classification/*genetics/isolation & purification ; Genotype ; Hemorrhagic Fever, Ebola/epidemiology/*virology ; Humans ; Mali/epidemiology ; Molecular Sequence Data ; *Mutation Rate ; Phylogeny
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 62
    Publication Date: 2015-10-31
    Description: Infections and inflammation can lead to cachexia and wasting of skeletal muscle and fat tissue by as yet poorly understood mechanisms. We observed that gut colonization of mice by a strain of Escherichia coli prevents wasting triggered by infections or physical damage to the intestine. During intestinal infection with the pathogen Salmonella Typhimurium or pneumonic infection with Burkholderia thailandensis, the presence of this E. coli did not alter changes in host metabolism, caloric uptake, or inflammation but instead sustained signaling of the insulin-like growth factor 1/phosphatidylinositol 3-kinase/AKT pathway in skeletal muscle, which is required for prevention of muscle wasting. This effect was dependent on engagement of the NLRC4 inflammasome. Therefore, this commensal promotes tolerance to diverse diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732872/" 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/PMC4732872/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schieber, Alexandria M Palaferri -- Lee, Yujung Michelle -- Chang, Max W -- Leblanc, Mathias -- Collins, Brett -- Downes, Michael -- Evans, Ronald M -- Ayres, Janelle S -- CA014195/CA/NCI NIH HHS/ -- DK0577978/DK/NIDDK NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- R01 AI114929/AI/NIAID NIH HHS/ -- R01AI114929/AI/NIAID NIH HHS/ -- R37 DK057978/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):558-63. doi: 10.1126/science.aac6468.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ; Integrative Genomics and Bioinformatics Core, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ; Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. jayres@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516283" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis Regulatory Proteins/metabolism ; Biosynthetic Pathways ; Burkholderia ; Burkholderia Infections/complications ; Calcium-Binding Proteins/metabolism ; Escherichia coli/*immunology ; Inflammasomes/*immunology ; Insulin-Like Growth Factor I/*metabolism ; Intestines/*microbiology ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Muscle, Skeletal/*metabolism ; Phosphatidylinositol 3-Kinase/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Salmonella Infections/complications ; Salmonella typhimurium ; Wasting Syndrome/etiology/*immunology/*microbiology
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  • 63
    Publication Date: 2015-02-28
    Description: Polycomb and Trithorax group proteins encode the epigenetic memory of cellular positional identity by establishing inheritable domains of repressive and active chromatin within the Hox clusters. Here we demonstrate that the CCCTC-binding factor (CTCF) functions to insulate these adjacent yet antagonistic chromatin domains during embryonic stem cell differentiation into cervical motor neurons. Deletion of CTCF binding sites within the Hox clusters results in the expansion of active chromatin into the repressive domain. CTCF functions as an insulator by organizing Hox clusters into spatially disjoint domains. Ablation of CTCF binding disrupts topological boundaries such that caudal Hox genes leave the repressed domain and become subject to transcriptional activation. Hence, CTCF is required to insulate facultative heterochromatin from impinging euchromatin to produce discrete positional identities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428148/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428148/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narendra, Varun -- Rocha, Pedro P -- An, Disi -- Raviram, Ramya -- Skok, Jane A -- Mazzoni, Esteban O -- Reinberg, Danny -- GM-64844/GM/NIGMS NIH HHS/ -- GM086852/GM/NIGMS NIH HHS/ -- GM112192/GM/NIGMS NIH HHS/ -- P30 CA016087/CA/NCI NIH HHS/ -- R01 GM086852/GM/NIGMS NIH HHS/ -- R01 GM112192/GM/NIGMS NIH HHS/ -- R01 HD079682/HD/NICHD NIH HHS/ -- R01HD079682/HD/NICHD NIH HHS/ -- R37-37120/PHS HHS/ -- T32 GM007238/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):1017-21. doi: 10.1126/science.1262088.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. ; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. ; Department of Biology, New York University, New York, NY 10003, USA. ; Department of Biology, New York University, New York, NY 10003, USA. danny.reinberg@nyumc.org eom204@nyu.edu. ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. danny.reinberg@nyumc.org eom204@nyu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25722416" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/*genetics ; Chromatin/chemistry/genetics/*metabolism ; Dogs ; Embryonic Stem Cells/*cytology ; *Gene Expression Regulation ; *Genes, Homeobox ; Humans ; Mice ; Motor Neurons/*cytology ; Multigene Family ; Neck ; Protein Structure, Tertiary ; Rats ; Repressor Proteins/chemistry/genetics/*metabolism
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  • 64
    Publication Date: 2015-09-01
    Description: DNA strand exchange plays a central role in genetic recombination across all kingdoms of life, but the physical basis for these reactions remains poorly defined. Using single-molecule imaging, we found that bacterial RecA and eukaryotic Rad51 and Dmc1 all stabilize strand exchange intermediates in precise three-nucleotide steps. Each step coincides with an energetic signature (0.3 kBT) that is conserved from bacteria to humans. Triplet recognition is strictly dependent on correct Watson-Crick pairing. Rad51, RecA, and Dmc1 can all step over mismatches, but only Dmc1 can stabilize mismatched triplets. This finding provides insight into why eukaryotes have evolved a meiosis-specific recombinase. We propose that canonical Watson-Crick base triplets serve as the fundamental unit of pairing interactions during DNA recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580133/" 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/PMC4580133/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Ja Yil -- Terakawa, Tsuyoshi -- Qi, Zhi -- Steinfeld, Justin B -- Redding, Sy -- Kwon, YoungHo -- Gaines, William A -- Zhao, Weixing -- Sung, Patrick -- Greene, Eric C -- CA146940/CA/NCI NIH HHS/ -- GM074739/GM/NIGMS NIH HHS/ -- R01 CA146940/CA/NCI NIH HHS/ -- R01 ES015252/ES/NIEHS NIH HHS/ -- R01 GM074739/GM/NIGMS NIH HHS/ -- R01ES015252/ES/NIEHS NIH HHS/ -- T32 GM007367/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):977-81. doi: 10.1126/science.aab2666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Department of Biophysics, Kyoto University, Sakyo, Kyoto, Japan. ; Department of Chemistry, Columbia University, New York, NY, USA. ; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Howard Hughes Medical Institute, Columbia University, New York, NY, USA. ecg2108@cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315438" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Pairing ; Base Sequence ; Cell Cycle Proteins/chemistry/metabolism ; DNA/*chemistry/*metabolism ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/chemistry/metabolism ; Escherichia coli Proteins/chemistry/metabolism ; Evolution, Molecular ; *Homologous Recombination ; Humans ; Meiosis ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Rad51 Recombinase/chemistry/*metabolism ; Rec A Recombinases/chemistry/*metabolism ; Recombinases/chemistry/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Thermodynamics
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  • 65
    Publication Date: 2015-04-04
    Description: MicroRNAs (miRNAs) repress the expression of many genes in metazoans by accelerating messenger RNA degradation and inhibiting translation, thereby reducing the level of protein. However, miRNAs only slightly reduce the mean expression of most targeted proteins, leading to speculation about their role in the variability, or noise, of protein expression. We used mathematical modeling and single-cell reporter assays to show that miRNAs, in conjunction with increased transcription, decrease protein expression noise for lowly expressed genes but increase noise for highly expressed genes. Genes that are regulated by multiple miRNAs show more-pronounced noise reduction. We estimate that hundreds of (lowly expressed) genes in mouse embryonic stem cells have reduced noise due to substantial miRNA regulation. Our findings suggest that miRNAs confer precision to protein expression and thus offer plausible explanations for the commonly observed combinatorial targeting of endogenous genes by multiple miRNAs, as well as the preferential targeting of lowly expressed genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmiedel, Jorn M -- Klemm, Sandy L -- Zheng, Yannan -- Sahay, Apratim -- Bluthgen, Nils -- Marks, Debora S -- van Oudenaarden, Alexander -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):128-32. doi: 10.1126/science.aaa1738.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Integrative Research Institute for the Life Sciences and Institute for Theoretical Biology, Humboldt Universitat, 10115 Berlin, Germany. Institute of Pathology, Charite-Universitatsmedizin, 10117 Berlin, Germany. Department of Physics, Massachusetts Institute of Technology (MIT), Cambridge MA 02139, USA. ; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139, USA. ; Department of Physics, Massachusetts Institute of Technology (MIT), Cambridge MA 02139, USA. ; Integrative Research Institute for the Life Sciences and Institute for Theoretical Biology, Humboldt Universitat, 10115 Berlin, Germany. Institute of Pathology, Charite-Universitatsmedizin, 10117 Berlin, Germany. nils.bluethgen@charite.de debbie@hms.harvard.edu a.vanoudenaarden@hubrecht.eu. ; Department of Systems Biology, Harvard Medical School, Longwood Avenue, Boston, MA 02115, USA. nils.bluethgen@charite.de debbie@hms.harvard.edu a.vanoudenaarden@hubrecht.eu. ; Department of Physics, Massachusetts Institute of Technology (MIT), Cambridge MA 02139, USA. Department of Biology, MIT, Cambridge, MA 02139, USA. Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, Netherlands. nils.bluethgen@charite.de debbie@hms.harvard.edu a.vanoudenaarden@hubrecht.eu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25838385" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics/physiology ; Animals ; Embryonic Stem Cells/metabolism ; *Gene Expression Regulation ; Mice ; MicroRNAs/genetics/*physiology ; Models, Genetic ; Protein Biosynthesis/*genetics ; RNA, Messenger/biosynthesis ; Single-Cell Analysis ; Transcription, Genetic
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  • 66
    Publication Date: 2015-11-21
    Description: Stabilization of the hypoxia-inducible factor 1 (HIF-1) increases life span and health span in nematodes through an unknown mechanism. We report that neuronal stabilization of HIF-1 mediates these effects in Caenorhabditis elegans through a cell nonautonomous signal to the intestine, which results in activation of the xenobiotic detoxification enzyme flavin-containing monooxygenase-2 (FMO-2). This prolongevity signal requires the serotonin biosynthetic enzyme TPH-1 in neurons and the serotonin receptor SER-7 in the intestine. Intestinal FMO-2 is also activated by dietary restriction (DR) and is necessary for DR-mediated life-span extension, which suggests that this enzyme represents a point of convergence for two distinct longevity pathways. FMOs are conserved in eukaryotes and induced by multiple life span-extending interventions in mice, which suggests that these enzymes may play a critical role in promoting health and longevity across phyla.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leiser, Scott F -- Miller, Hillary -- Rossner, Ryan -- Fletcher, Marissa -- Leonard, Alison -- Primitivo, Melissa -- Rintala, Nicholas -- Ramos, Fresnida J -- Miller, Dana L -- Kaeberlein, Matt -- P30AG013280/AG/NIA NIH HHS/ -- R00AGA0033050/PHS HHS/ -- R01AG038518/AG/NIA NIH HHS/ -- T32AG000057/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Dec 11;350(6266):1375-8. doi: 10.1126/science.aac9257. Epub 2015 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Washington, Seattle, WA 98195, USA. ; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. ; Department of Pathology, University of Washington, Seattle, WA 98195, USA. kaeber@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586189" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Caenorhabditis elegans/genetics/metabolism/*physiology ; Caenorhabditis elegans Proteins/chemistry/genetics/metabolism/*physiology ; Diet ; Intestines/*enzymology ; Longevity/genetics/*physiology ; Mice ; Neurons/*metabolism ; Oxygenases/genetics/*physiology ; Protein Stability ; RNA Interference ; Receptors, Serotonin/metabolism ; Signal Transduction ; Transcription Factors/chemistry/*metabolism ; Tryptophan Hydroxylase/metabolism
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  • 67
    Publication Date: 2015-06-06
    Description: Aneuploidy in human eggs is the leading cause of pregnancy loss and several genetic disorders such as Down syndrome. Most aneuploidy results from chromosome segregation errors during the meiotic divisions of an oocyte, the egg's progenitor cell. The basis for particularly error-prone chromosome segregation in human oocytes is not known. We analyzed meiosis in more than 100 live human oocytes and identified an error-prone chromosome-mediated spindle assembly mechanism as a major contributor to chromosome segregation defects. Human oocytes assembled a meiotic spindle independently of either centrosomes or other microtubule organizing centers. Instead, spindle assembly was mediated by chromosomes and the small guanosine triphosphatase Ran in a process requiring ~16 hours. This unusually long spindle assembly period was marked by intrinsic spindle instability and abnormal kinetochore-microtubule attachments, which favor chromosome segregation errors and provide a possible explanation for high rates of aneuploidy in human eggs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477045/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477045/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holubcova, Zuzana -- Blayney, Martyn -- Elder, Kay -- Schuh, Melina -- MC_U105192711/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1143-7. doi: 10.1126/science.aaa9529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK. ; Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. mschuh@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26045437" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; *Aneuploidy ; Animals ; Cells, Cultured ; *Chromosome Segregation ; Female ; Green Fluorescent Proteins/genetics/metabolism ; Humans ; Kinetochores/metabolism ; *Meiosis ; Mice ; Microtubule-Associated Proteins/genetics/metabolism ; Microtubule-Organizing Center/metabolism ; Oocytes/*pathology ; Spindle Apparatus/*metabolism ; ran GTP-Binding Protein/metabolism
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  • 68
    Publication Date: 2015-01-03
    Description: Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380271/" 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/PMC4380271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neafsey, Daniel E -- Waterhouse, Robert M -- Abai, Mohammad R -- Aganezov, Sergey S -- Alekseyev, Max A -- Allen, James E -- Amon, James -- Arca, Bruno -- Arensburger, Peter -- Artemov, Gleb -- Assour, Lauren A -- Basseri, Hamidreza -- Berlin, Aaron -- Birren, Bruce W -- Blandin, Stephanie A -- Brockman, Andrew I -- Burkot, Thomas R -- Burt, Austin -- Chan, Clara S -- Chauve, Cedric -- Chiu, Joanna C -- Christensen, Mikkel -- Costantini, Carlo -- Davidson, Victoria L M -- Deligianni, Elena -- Dottorini, Tania -- Dritsou, Vicky -- Gabriel, Stacey B -- Guelbeogo, Wamdaogo M -- Hall, Andrew B -- Han, Mira V -- Hlaing, Thaung -- Hughes, Daniel S T -- Jenkins, Adam M -- Jiang, Xiaofang -- Jungreis, Irwin -- Kakani, Evdoxia G -- Kamali, Maryam -- Kemppainen, Petri -- Kennedy, Ryan C -- Kirmitzoglou, Ioannis K -- Koekemoer, Lizette L -- Laban, Njoroge -- Langridge, Nicholas -- Lawniczak, Mara K N -- Lirakis, Manolis -- Lobo, Neil F -- Lowy, Ernesto -- MacCallum, Robert M -- Mao, Chunhong -- Maslen, Gareth -- Mbogo, Charles -- McCarthy, Jenny -- Michel, Kristin -- Mitchell, Sara N -- Moore, Wendy -- Murphy, Katherine A -- Naumenko, Anastasia N -- Nolan, Tony -- Novoa, Eva M -- O'Loughlin, Samantha -- Oringanje, Chioma -- Oshaghi, Mohammad A -- Pakpour, Nazzy -- Papathanos, Philippos A -- Peery, Ashley N -- Povelones, Michael -- Prakash, Anil -- Price, David P -- Rajaraman, Ashok -- Reimer, Lisa J -- Rinker, David C -- Rokas, Antonis -- Russell, Tanya L -- Sagnon, N'Fale -- Sharakhova, Maria V -- Shea, Terrance -- Simao, Felipe A -- Simard, Frederic -- Slotman, Michel A -- Somboon, Pradya -- Stegniy, Vladimir -- Struchiner, Claudio J -- Thomas, Gregg W C -- Tojo, Marta -- Topalis, Pantelis -- Tubio, Jose M C -- Unger, Maria F -- Vontas, John -- Walton, Catherine -- Wilding, Craig S -- Willis, Judith H -- Wu, Yi-Chieh -- Yan, Guiyun -- Zdobnov, Evgeny M -- Zhou, Xiaofan -- Catteruccia, Flaminia -- Christophides, George K -- Collins, Frank H -- Cornman, Robert S -- Crisanti, Andrea -- Donnelly, Martin J -- Emrich, Scott J -- Fontaine, Michael C -- Gelbart, William -- Hahn, Matthew W -- Hansen, Immo A -- Howell, Paul I -- Kafatos, Fotis C -- Kellis, Manolis -- Lawson, Daniel -- Louis, Christos -- Luckhart, Shirley -- Muskavitch, Marc A T -- Ribeiro, Jose M -- Riehle, Michael A -- Sharakhov, Igor V -- Tu, Zhijian -- Zwiebel, Laurence J -- Besansky, Nora J -- 092654/Wellcome Trust/United Kingdom -- R01 AI050243/AI/NIAID NIH HHS/ -- R01 AI063508/AI/NIAID NIH HHS/ -- R01 AI073745/AI/NIAID NIH HHS/ -- R01 AI076584/AI/NIAID NIH HHS/ -- R01 AI080799/AI/NIAID NIH HHS/ -- R01 AI104956/AI/NIAID NIH HHS/ -- R21 AI101459/AI/NIAID NIH HHS/ -- R56 AI107263/AI/NIAID NIH HHS/ -- SC1 AI109055/AI/NIAID NIH HHS/ -- U19 AI089686/AI/NIAID NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U41 HG007234/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):1258522. doi: 10.1126/science.1258522. Epub 2014 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. neafsey@broadinstitute.org nbesansk@nd.edu. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Medical Entomology and Vector Control, School of Public Health and Institute of Health Researches, Tehran University of Medical Sciences, Tehran, Iran. ; George Washington University, Department of Mathematics and Computational Biology Institute, 45085 University Drive, Ashburn, VA 20147, USA. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; National Vector Borne Disease Control Programme, Ministry of Health, Tafea Province, Vanuatu. ; Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. ; Department of Biological Sciences, California State Polytechnic-Pomona, 3801 West Temple Avenue, Pomona, CA 91768, USA. ; Tomsk State University, 36 Lenina Avenue, Tomsk, Russia. ; Department of Computer Science and Engineering, Eck Institute for Global Health, 211B Cushing Hall, University of Notre Dame, Notre Dame, IN 46556, USA. ; Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Inserm, U963, F-67084 Strasbourg, France. CNRS, UPR9022, IBMC, F-67084 Strasbourg, France. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. ; Faculty of Medicine, Health and Molecular Science, Australian Institute of Tropical Health Medicine, James Cook University, Cairns 4870, Australia. ; Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. ; Department of Mathematics, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. ; Department of Entomology and Nematology, One Shields Avenue, University of California-Davis, Davis, CA 95616, USA. ; Institut de Recherche pour le Developpement, Unites Mixtes de Recherche Maladies Infectieuses et Vecteurs Ecologie, Genetique, Evolution et Controle, 911, Avenue Agropolis, BP 64501 Montpellier, France. ; Division of Biology, Kansas State University, 271 Chalmers Hall, Manhattan, KS 66506, USA. ; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. ; Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Genomics Platform, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou 01 BP 2208, Burkina Faso. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; School of Life Sciences, University of Nevada, Las Vegas, NV 89154, USA. ; Department of Medical Research, No. 5 Ziwaka Road, Dagon Township, Yangon 11191, Myanmar. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. ; Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita degli Studi di Perugia, Perugia, Italy. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Computational Evolutionary Biology Group, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Bioinformatics Research Laboratory, Department of Biological Sciences, New Campus, University of Cyprus, CY 1678 Nicosia, Cyprus. ; Wits Research Institute for Malaria, Faculty of Health Sciences, and Vector Control Reference Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, Johannesburg, South Africa. ; National Museums of Kenya, P.O. Box 40658-00100, Nairobi, Kenya. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. ; Virginia Bioinformatics Institute, 1015 Life Science Circle, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, P.O. Box 230-80108, Kilifi, Kenya. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. ; Department of Entomology, 1140 East South Campus Drive, Forbes 410, University of Arizona, Tucson, AZ 85721, USA. ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, One Shields Avenue, Davis, CA 95616, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA. ; Regional Medical Research Centre NE, Indian Council of Medical Research, P.O. Box 105, Dibrugarh-786 001, Assam, India. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Entomology, Texas A&M University, College Station, TX 77807, USA. ; Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. ; Fundacao Oswaldo Cruz, Avenida Brasil 4365, RJ Brazil. Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. ; School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Department of Physiology, School of Medicine, Center for Research in Molecular Medicine and Chronic Diseases, Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Santiago de Compostela, A Coruna, Spain. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK. ; School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L3 3AF, UK. ; Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Computer Science, Harvey Mudd College, Claremont, CA 91711, USA. ; Program in Public Health, College of Health Sciences, University of California, Irvine, Hewitt Hall, Irvine, CA 92697, USA. ; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SJ, UK. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. Centre of Evolutionary and Ecological Studies (Marine Evolution and Conservation group), University of Groningen, Nijenborgh 7, NL-9747 AG Groningen, Netherlands. ; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. ; Department of Biology, Indiana University, Bloomington, IN 47405, USA. School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Centers for Disease Control and Prevention, 1600 Clifton Road NE MSG49, Atlanta, GA 30329, USA. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, 12735 Twinbrook Parkway, Rockville, MD 20852, USA. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Departments of Biological Sciences and Pharmacology, Institutes for Chemical Biology, Genetics and Global Health, Vanderbilt University and Medical Center, Nashville, TN 37235, USA. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. neafsey@broadinstitute.org nbesansk@nd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554792" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/classification/*genetics ; Base Sequence ; Chromosomes, Insect/genetics ; Drosophila/genetics ; *Evolution, Molecular ; *Genome, Insect ; Humans ; Insect Vectors/classification/*genetics ; Malaria/*transmission ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment
    Print ISSN: 0036-8075
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  • 69
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Mitch -- New York, N.Y. -- Science. 2015 Nov 6;350(6261):614-5. doi: 10.1126/science.350.6261.614.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26542545" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antigens, CD274/antagonists & inhibitors ; Antineoplastic Agents/*therapeutic use ; Bacteroides/*immunology ; Burkholderia/*immunology ; CTLA-4 Antigen/antagonists & inhibitors ; Gastrointestinal Tract/*microbiology ; Immunotherapy/methods ; Mice ; Microbiota/genetics/*immunology ; Neoplasms/immunology/*therapy ; Probiotics/*therapeutic use ; T-Lymphocytes/drug effects/*immunology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 70
    Publication Date: 2015-09-05
    Description: Growing up on a dairy farm protects children from allergy, hay fever, and asthma. A mechanism linking exposure to this endotoxin (bacterial lipopolysaccharide)-rich environment with protection has remained elusive. Here we show that chronic exposure to low-dose endotoxin or farm dust protects mice from developing house dust mite (HDM)-induced asthma. Endotoxin reduced epithelial cell cytokines that activate dendritic cells (DCs), thus suppressing type 2 immunity to HDMs. Loss of the ubiquitin-modifying enzyme A20 in lung epithelium abolished the protective effect. A single-nucleotide polymorphism in the gene encoding A20 was associated with allergy and asthma risk in children growing up on farms. Thus, the farming environment protects from allergy by modifying the communication between barrier epithelial cells and DCs through A20 induction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schuijs, Martijn J -- Willart, Monique A -- Vergote, Karl -- Gras, Delphine -- Deswarte, Kim -- Ege, Markus J -- Madeira, Filipe Branco -- Beyaert, Rudi -- van Loo, Geert -- Bracher, Franz -- von Mutius, Erika -- Chanez, Pascal -- Lambrecht, Bart N -- Hammad, Hamida -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1106-10. doi: 10.1126/science.aac6623.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium. ; Department of Respiratory Medicine, Assistance Publique Hopitaux de Marseille, UMR INSERM U1067 CNRS 7333, Aix Marseille University, Marseille, France. ; Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universitat, Munich, Germany. ; Unit of Molecular Signal Transduction, VIB Inflammation Research Center, Ghent, Belgium. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. ; Center for Drug Research, Department of Pharmacy, Ludwig Maximilians University, Butenandtstrasse 5-13, D-81377 Munich, Germany. ; Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium. Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, Netherlands. hamida.hammad@ugent.be bart.lambrecht@ugent.be. ; Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium. hamida.hammad@ugent.be bart.lambrecht@ugent.be.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26339029" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Asthma/immunology/prevention & control ; Cells, Cultured ; Child ; DNA-Binding Proteins/*biosynthesis ; Dairying ; Dendritic Cells/immunology ; Dust/*immunology ; Female ; Humans ; Hygiene Hypothesis ; Hypersensitivity/enzymology/immunology/*prevention & control ; Inhalation Exposure ; Intracellular Signaling Peptides and Proteins/*biosynthesis ; Lipopolysaccharides/*immunology ; Lung/*enzymology/immunology ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins/*biosynthesis ; Pyroglyphidae/*immunology ; Respiratory Mucosa/*enzymology/immunology
    Print ISSN: 0036-8075
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  • 71
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Mitch -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1058-9, 1061. doi: 10.1126/science.347.6226.1058.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745143" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/chemistry/immunology/*therapeutic use ; Clinical Trials as Topic ; Drug Approval ; Humans ; Immune System/immunology ; Mice ; Multiple Sclerosis/*therapy ; Myelin Sheath/immunology ; Protein Conformation ; Recombinant Proteins/immunology/*therapeutic use ; United States ; United States Food and Drug Administration
    Print ISSN: 0036-8075
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  • 72
    Publication Date: 2015-10-17
    Description: Transcriptional enhancers direct precise on-off patterns of gene expression during development. To explore the basis for this precision, we conducted a high-throughput analysis of the Otx-a enhancer, which mediates expression in the neural plate of Ciona embryos in response to fibroblast growth factor (FGF) signaling and a localized GATA determinant. We provide evidence that enhancer specificity depends on submaximal recognition motifs having reduced binding affinities ("suboptimization"). Native GATA and ETS (FGF) binding sites contain imperfect matches to consensus motifs. Perfect matches mediate robust but ectopic patterns of gene expression. The native sites are not arranged at optimal intervals, and subtle changes in their spacing alter enhancer activity. Multiple tiers of enhancer suboptimization produce specific, but weak, patterns of expression, and we suggest that clusters of weak enhancers, including certain "superenhancers," circumvent this trade-off in specificity and activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farley, Emma K -- Olson, Katrina M -- Zhang, Wei -- Brandt, Alexander J -- Rokhsar, Daniel S -- Levine, Michael S -- GM46638/GM/NIGMS NIH HHS/ -- NS076542/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):325-8. doi: 10.1126/science.aac6948.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. msl2@princeton.edu ekfarley@princeton.edu. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. ; Department of Medicine, University of California, San Diego, CA 92093-0688, USA. ; Department of Chemistry, University of California, Berkeley, CA 94720-3200, USA. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472909" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Ciona intestinalis/genetics/*growth & development ; Consensus Sequence ; Enhancer Elements, Genetic/genetics/*physiology ; Fas-Associated Death Domain Protein/metabolism ; Fibroblast Growth Factors/*metabolism ; GATA Transcription Factors/*metabolism ; *Gene Expression Regulation, Developmental ; Molecular Sequence Data ; Organ Specificity/genetics/physiology ; Otx Transcription Factors/*metabolism
    Print ISSN: 0036-8075
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  • 73
    Publication Date: 2015-11-07
    Description: Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721659/" 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/PMC4721659/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vetizou, Marie -- Pitt, Jonathan M -- Daillere, Romain -- Lepage, Patricia -- Waldschmitt, Nadine -- Flament, Caroline -- Rusakiewicz, Sylvie -- Routy, Bertrand -- Roberti, Maria P -- Duong, Connie P M -- Poirier-Colame, Vichnou -- Roux, Antoine -- Becharef, Sonia -- Formenti, Silvia -- Golden, Encouse -- Cording, Sascha -- Eberl, Gerard -- Schlitzer, Andreas -- Ginhoux, Florent -- Mani, Sridhar -- Yamazaki, Takahiro -- Jacquelot, Nicolas -- Enot, David P -- Berard, Marion -- Nigou, Jerome -- Opolon, Paule -- Eggermont, Alexander -- Woerther, Paul-Louis -- Chachaty, Elisabeth -- Chaput, Nathalie -- Robert, Caroline -- Mateus, Christina -- Kroemer, Guido -- Raoult, Didier -- Boneca, Ivo Gomperts -- Carbonnel, Franck -- Chamaillard, Mathias -- Zitvogel, Laurence -- R01 CA161879/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1079-84. doi: 10.1126/science.aad1329. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. University of Paris Sud XI, Kremlin-Bicetre, France. ; Institut National de la Recherche Agronomique (INRA), Micalis-UMR1319, 78360 Jouy-en-Josas, France. ; University of Lille, CNRS, INSERM, Centre Hospitalier Regional Universitaire de Lille, Institut Pasteur de Lille, U1019, UMR 8204, Centre d'Infection et d'Immunite de Lille (CIIL), F-59000 Lille, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. University of Paris Sud XI, Kremlin-Bicetre, France. Center of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Department of Radiation Oncology, New York University, New York, NY, USA. ; Microenvironment and Immunity Unit, Institut Pasteur, Paris, France. ; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. ; Department of Genetics and Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Metabolomics Platform, GRCC, Villejuif, France. ; Animalerie Centrale, Institut Pasteur, Paris, France. ; Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France. Universite de Toulouse, Universite Paul Sabatier, IPBS, F-31077 Toulouse, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. ; Service de microbiologie, GRCC, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, GRCC, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. INSERM U981, GRCC, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. ; Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Metabolomics Platform, GRCC, Villejuif, France. INSERM U848, Villejuif, France. Equipe 11 Labellisee-Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France. Pole de Biologie, Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France. ; Unite des Rickettsies, Faculte de Medecine, Universite de la Mediterranee, Marseille, France. ; Institut Pasteur, Unit of Biology and Genetics of the Bacterial Cell Wall, Paris, France. INSERM, Equipe Avenir, Paris, France. ; University of Paris Sud XI, Kremlin-Bicetre, France. Gastroenterology Department, Hopital Bicetre, Assistance Publique-Hopitaux de Paris, Paris, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. University of Paris Sud XI, Kremlin-Bicetre, France. Center of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, France. laurence.zitvogel@gustaveroussy.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541610" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aged, 80 and over ; Animals ; Anti-Bacterial Agents/pharmacology ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Bacteroides/*immunology ; CTLA-4 Antigen/*antagonists & inhibitors/immunology ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/*immunology ; Germ-Free Life/immunology ; Humans ; Immunologic Memory ; Immunotherapy ; Intestines/immunology/microbiology ; Male ; Melanoma/*therapy ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Skin Neoplasms/*therapy ; T-Lymphocytes/immunology
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  • 74
    Publication Date: 2015-01-13
    Description: NADPH/NADP(+) (the reduced form of NADP(+)/nicotinamide adenine dinucleotide phosphate) homeostasis is critical for countering oxidative stress in cells. Nicotinamide nucleotide transhydrogenase (TH), a membrane enzyme present in both bacteria and mitochondria, couples the proton motive force to the generation of NADPH. We present the 2.8 A crystal structure of the transmembrane proton channel domain of TH from Thermus thermophilus and the 6.9 A crystal structure of the entire enzyme (holo-TH). The membrane domain crystallized as a symmetric dimer, with each protomer containing a putative proton channel. The holo-TH is a highly asymmetric dimer with the NADP(H)-binding domain (dIII) in two different orientations. This unusual arrangement suggests a catalytic mechanism in which the two copies of dIII alternatively function in proton translocation and hydride transfer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479213/" 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/PMC4479213/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leung, Josephine H -- Schurig-Briccio, Lici A -- Yamaguchi, Mutsuo -- Moeller, Arne -- Speir, Jeffrey A -- Gennis, Robert B -- Stout, Charles D -- 1R01GM103838-01A1/GM/NIGMS NIH HHS/ -- 5R01GM061545/GM/NIGMS NIH HHS/ -- GM073197/GM/NIGMS NIH HHS/ -- GM095600/GM/NIGMS NIH HHS/ -- P41 GM103310/GM/NIGMS NIH HHS/ -- P41GM103310/GM/NIGMS NIH HHS/ -- R01 GM061545/GM/NIGMS NIH HHS/ -- R01 GM095600/GM/NIGMS NIH HHS/ -- R01 GM103838/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):178-81. doi: 10.1126/science.1260451.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA. ; National Resource for Automated Molecular Microscopy, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. dave@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25574024" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Molecular Sequence Data ; NADP Transhydrogenases/*chemistry ; Protein Multimerization ; Protein Structure, Tertiary ; *Protons ; Thermus thermophilus/enzymology
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  • 75
    Publication Date: 2015-06-27
    Description: Pigment-protein and pigment-pigment interactions are of fundamental importance to the light-harvesting and photoprotective functions essential to oxygenic photosynthesis. The orange carotenoid protein (OCP) functions as both a sensor of light and effector of photoprotective energy dissipation in cyanobacteria. We report the atomic-resolution structure of an active form of the OCP consisting of the N-terminal domain and a single noncovalently bound carotenoid pigment. The crystal structure, combined with additional solution-state structural data, reveals that OCP photoactivation is accompanied by a 12 angstrom translocation of the pigment within the protein and a reconfiguration of carotenoid-protein interactions. Our results identify the origin of the photochromic changes in the OCP triggered by light and reveal the structural determinants required for interaction with the light-harvesting antenna during photoprotection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leverenz, Ryan L -- Sutter, Markus -- Wilson, Adjele -- Gupta, Sayan -- Thurotte, Adrien -- Bourcier de Carbon, Celine -- Petzold, Christopher J -- Ralston, Corie -- Perreau, Francois -- Kirilovsky, Diana -- Kerfeld, Cheryl A -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):1463-6. doi: 10.1126/science.aaa7234.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA. ; MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. ; Commissariat a l'Energie Atomique (CEA), Institut de Biologie et Technologies de Saclay (iBiTec-S), 91191 Gif-sur-Yvette, France. Centre National de la Recherche Scientifique (CNRS), I2BC, UMR 9198, 91191 Gif-sur-Yvette, France. ; Berkeley Center for Structural Biology, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. ; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. ; INRA, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, F-78026 Versailles, France. ; MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA. ckerfeld@lbl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113721" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/metabolism ; Canthaxanthin/*chemistry/metabolism ; Crystallography, X-Ray ; Models, Chemical ; *Photosynthesis ; Phycobilisomes/*chemistry ; Protein Structure, Secondary ; Protein Transport ; Synechocystis/*metabolism
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  • 76
    Publication Date: 2015-07-15
    Description: The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nie, Yonggang -- Speakman, John R -- Wu, Qi -- Zhang, Chenglin -- Hu, Yibo -- Xia, Maohua -- Yan, Li -- Hambly, Catherine -- Wang, Lu -- Wei, Wei -- Zhang, Jinguo -- Wei, Fuwen -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):171-4. doi: 10.1126/science.aab2413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK. ; Beijing Key Laboratory of Captive Wildlife Technologies, Beijing Zoo, Beijing, China. ; Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK. ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. ; Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. weifw@ioz.ac.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160943" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Body Temperature ; Cattle ; Chromosomes, Human, Pair 15/genetics ; Diet/veterinary ; Dogs ; *Eating ; Energy Metabolism/genetics/*physiology ; Gastrointestinal Tract ; Genetic Variation ; Humans ; Mice ; Molecular Sequence Data ; Motor Activity ; NADPH Oxidase/*genetics ; Organ Size ; Sasa ; Thyroxine/blood ; Triiodothyronine/blood ; Ursidae/anatomy & histology/*genetics/*physiology
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  • 77
    Publication Date: 2015-06-27
    Description: Organisms are adapted to the relentless cycles of day and night, because they evolved timekeeping systems called circadian clocks, which regulate biological activities with ~24-hour rhythms. The clock of cyanobacteria is driven by a three-protein oscillator composed of KaiA, KaiB, and KaiC, which together generate a circadian rhythm of KaiC phosphorylation. We show that KaiB flips between two distinct three-dimensional folds, and its rare transition to an active state provides a time delay that is required to match the timing of the oscillator to that of Earth's rotation. Once KaiB switches folds, it binds phosphorylated KaiC and captures KaiA, which initiates a phase transition of the circadian cycle, and it regulates components of the clock-output pathway, which provides the link that joins the timekeeping and signaling functions of the oscillator.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506712/" 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/PMC4506712/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Yong-Gang -- Cohen, Susan E -- Phong, Connie -- Myers, William K -- Kim, Yong-Ick -- Tseng, Roger -- Lin, Jenny -- Zhang, Li -- Boyd, Joseph S -- Lee, Yvonne -- Kang, Shannon -- Lee, David -- Li, Sheng -- Britt, R David -- Rust, Michael J -- Golden, Susan S -- LiWang, Andy -- AI081982/AI/NIAID NIH HHS/ -- AI101436/AI/NIAID NIH HHS/ -- GM062419/GM/NIGMS NIH HHS/ -- GM100116/GM/NIGMS NIH HHS/ -- GM107521/GM/NIGMS NIH HHS/ -- R01 GM062419/GM/NIGMS NIH HHS/ -- R01 GM100116/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):324-8. doi: 10.1126/science.1260031. Epub 2015 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Natural Sciences, University of California, Merced, CA 95343, USA. ; Center for Circadian Biology, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA. ; Department of Chemistry, University of California, Davis, CA 95616, USA. ; School of Natural Sciences, University of California, Merced, CA 95343, USA. Quantitative and Systems Biology, University of California, Merced, CA 95343, USA. ; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. ; Center for Circadian Biology, University of California, San Diego, La Jolla, CA 92093, USA. Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. ; School of Natural Sciences, University of California, Merced, CA 95343, USA. Center for Circadian Biology, University of California, San Diego, La Jolla, CA 92093, USA. Quantitative and Systems Biology, University of California, Merced, CA 95343, USA. Chemistry and Chemical Biology, University of California, Merced, CA 95343, USA. Health Sciences Research Institute, University of California, Merced, CA 95343, USA. aliwang@ucmerced.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113641" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics/*metabolism ; *Circadian Rhythm ; Circadian Rhythm Signaling Peptides and Proteins/*chemistry/genetics/*metabolism ; Phosphorylation ; Protein Folding ; Protein Structure, Secondary ; Synechococcus/metabolism/*physiology
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  • 78
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):261-2. doi: 10.1126/science.350.6258.261.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472885" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cattle ; *Chimera ; *Embryonic Stem Cells ; *Financing, Organized ; Humans ; Mice ; National Institutes of Health (U.S.)/*economics ; Organ Transplantation ; Rats ; Stem Cell Research/*economics ; Swine ; United States
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  • 79
    Publication Date: 2015-07-04
    Description: There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672004/" 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/PMC4672004/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fibriansah, Guntur -- Ibarra, Kristie D -- Ng, Thiam-Seng -- Smith, Scott A -- Tan, Joanne L -- Lim, Xin-Ni -- Ooi, Justin S G -- Kostyuchenko, Victor A -- Wang, Jiaqi -- de Silva, Aravinda M -- Harris, Eva -- Crowe, James E Jr -- Lok, Shee-Mei -- K08 AI103038/AI/NIAID NIH HHS/ -- R01 AI107731/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54 AI065359/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):88-91. doi: 10.1126/science.aaa8651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore. ; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA. ; Department of Medicine, Vanderbilt University, Nashville, TN, USA. The Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA. ; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. ; The Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA. Departments of Pediatrics and Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA. sheemei.lok@duke-nus.edu.sg james.crowe@vanderbilt.edu. ; Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore. sheemei.lok@duke-nus.edu.sg james.crowe@vanderbilt.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138979" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/*ultrastructure ; Antibodies, Neutralizing/*ultrastructure ; Coinfection/immunology ; Cross Reactions ; Cryoelectron Microscopy ; Dengue Virus/*immunology ; Disease Models, Animal ; Epitopes/immunology ; Humans ; Mice ; Serogroup ; Viral Envelope Proteins/*immunology
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  • 80
    Publication Date: 2015-01-31
    Description: The 18-kilodalton translocator protein (TSPO), proposed to be a key player in cholesterol transport into mitochondria, is highly expressed in steroidogenic tissues, metastatic cancer, and inflammatory and neurological diseases such as Alzheimer's and Parkinson's. TSPO ligands, including benzodiazepine drugs, are implicated in regulating apoptosis and are extensively used in diagnostic imaging. We report crystal structures (at 1.8, 2.4, and 2.5 angstrom resolution) of TSPO from Rhodobacter sphaeroides and a mutant that mimics the human Ala(147)--〉Thr(147) polymorphism associated with psychiatric disorders and reduced pregnenolone production. Crystals obtained in the lipidic cubic phase reveal the binding site of an endogenous porphyrin ligand and conformational effects of the mutation. The three crystal structures show the same tightly interacting dimer and provide insights into the controversial physiological role of TSPO and how the mutation affects cholesterol binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Fei -- Liu, Jian -- Zheng, Yi -- Garavito, R Michael -- Ferguson-Miller, Shelagh -- ACB-12002/PHS HHS/ -- AGM-12006/PHS HHS/ -- GM094625/GM/NIGMS NIH HHS/ -- GM26916/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):555-8. doi: 10.1126/science.1260590.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. fergus20@msu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635101" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Cholesterol/metabolism ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Isoquinolines/metabolism ; Ligands ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry ; Polymorphism, Single Nucleotide ; Porphyrins/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protoporphyrins/metabolism ; Receptors, GABA/chemistry/genetics ; Rhodobacter sphaeroides/*chemistry
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  • 81
    Publication Date: 2015-08-15
    Description: Adenosine-to-inosine (A-to-I) editing is a highly prevalent posttranscriptional modification of RNA, mediated by ADAR (adenosine deaminase acting on RNA) enzymes. In addition to RNA editing, additional functions have been proposed for ADAR1. To determine the specific role of RNA editing by ADAR1, we generated mice with an editing-deficient knock-in mutation (Adar1(E861A), where E861A denotes Glu(861)--〉Ala(861)). Adar1(E861A/E861A) embryos died at ~E13.5 (embryonic day 13.5), with activated interferon and double-stranded RNA (dsRNA)-sensing pathways. Genome-wide analysis of the in vivo substrates of ADAR1 identified clustered hyperediting within long dsRNA stem loops within 3' untranslated regions of endogenous transcripts. Finally, embryonic death and phenotypes of Adar1(E861A/E861A) were rescued by concurrent deletion of the cytosolic sensor of dsRNA, MDA5. A-to-I editing of endogenous dsRNA is the essential function of ADAR1, preventing the activation of the cytosolic dsRNA response by endogenous transcripts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liddicoat, Brian J -- Piskol, Robert -- Chalk, Alistair M -- Ramaswami, Gokul -- Higuchi, Miyoko -- Hartner, Jochen C -- Li, Jin Billy -- Seeburg, Peter H -- Walkley, Carl R -- R01GM102484/GM/NIGMS NIH HHS/ -- T32 HG000044/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1115-20. doi: 10.1126/science.aac7049. Epub 2015 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia. ; Department of Genetics, Stanford University, Stanford, CA 94305, USA. ; Department of Molecular Neurobiology, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany. ; Taconic Biosciences, 51063 Cologne, Germany. ; St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia. cwalkley@svi.edu.au.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26275108" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Adenosine/genetics ; Adenosine Deaminase/genetics/*metabolism ; Animals ; DEAD-box RNA Helicases/genetics/*metabolism ; Embryo Loss/*genetics ; Gene Deletion ; Gene Knock-In Techniques ; Inosine/genetics ; Mice ; Mice, Mutant Strains ; Mutation ; Nucleic Acid Conformation ; *RNA Editing ; RNA, Double-Stranded/chemistry/*metabolism ; Transcription, Genetic
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  • 82
    Publication Date: 2015-10-03
    Description: gamma-Aminobutyric acid (GABA) is the major inhibitory transmitter in the mature brain but is excitatory in the developing cortex. We found that mouse zona incerta (ZI) projection neurons form a GABAergic axon plexus in neonatal cortical layer 1, making synapses with neurons in both deep and superficial layers. A similar depolarizing GABAergic plexus exists in the developing human cortex. Selectively silencing mouse ZI GABAergic neurons at birth decreased synaptic activity and apical dendritic complexity of cortical neurons. The ZI GABAergic projection becomes inhibitory with maturation and can block epileptiform activity in the adult brain. These data reveal an early-developing GABAergic projection from the ZI to cortical layer 1 that is essential for proper development of cortical neurons and balances excitation with inhibition in the adult cortex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Jiadong -- Kriegstein, Arnold R -- R37 NS35710/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):554-8. doi: 10.1126/science.aac6472. Epub 2015 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA. jardongchen@gmail.com kriegsteina@stemcell.ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26429884" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Cerebral Cortex/cytology/*embryology ; GABAergic Neurons/*cytology ; Humans ; Inhibitory Postsynaptic Potentials ; Mice ; Mice, Transgenic ; Synaptic Transmission ; Zona Incerta/cytology/*embryology
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  • 83
    Publication Date: 2015-02-28
    Description: Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. In this work, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Florio, Marta -- Albert, Mareike -- Taverna, Elena -- Namba, Takashi -- Brandl, Holger -- Lewitus, Eric -- Haffner, Christiane -- Sykes, Alex -- Wong, Fong Kuan -- Peters, Jula -- Guhr, Elaine -- Klemroth, Sylvia -- Prufer, Kay -- Kelso, Janet -- Naumann, Ronald -- Nusslein, Ina -- Dahl, Andreas -- Lachmann, Robert -- Paabo, Svante -- Huttner, Wieland B -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1465-70. doi: 10.1126/science.aaa1975. Epub 2015 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Pfotenhauerstrasse 108, D-01307 Dresden, Germany. ; Technische Universitat Dresden, Center for Regenerative Therapies Dresden, Fetscherstrasse 105, D-01307 Dresden, Germany. ; Max Planck Institute for Evolutionary Anthropology (MPI-EVA), Deutscher Platz 6, D-04103 Leipzig, Germany. ; Technische Universitat Dresden, Universitatsklinikum Carl Gustav Carus, Klinik und Poliklinik fur Frauenheilkunde und Geburtshilfe, Fetscherstrasse 74, D-01307 Dresden, Germany. ; Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Pfotenhauerstrasse 108, D-01307 Dresden, Germany. huttner@mpi-cbg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25721503" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Separation ; GTPase-Activating Proteins/chemistry/genetics/*physiology ; Gene Duplication ; *Gene Expression Regulation, Developmental ; Humans ; Lateral Ventricles/cytology ; Mice ; Neocortex/cytology/*embryology/metabolism ; Neural Stem Cells/*cytology/metabolism ; Neurogenesis/*genetics ; Neuroglia/cytology/metabolism ; Neurons/cytology/metabolism ; Protein Structure, Tertiary ; Transcriptome
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  • 84
    Publication Date: 2015-06-06
    Description: Retroviruses depend on self-assembly of their capsid proteins (core particle) to yield infectious mature virions. Despite the essential role of the retroviral core, its high polymorphism has hindered high-resolution structural analyses. Here, we report the x-ray structure of the native capsid (CA) protein from bovine leukemia virus. CA is organized as hexamers that deviate substantially from sixfold symmetry, yet adjust to make two-dimensional pseudohexagonal arrays that mimic mature retroviral cores. Intra- and interhexameric quasi-equivalent contacts are uncovered, with flexible trimeric lateral contacts among hexamers, yet preserving very similar dimeric interfaces making the lattice. The conformation of each capsid subunit in the hexamer is therefore dictated by long-range interactions, revealing how the hexamers can also assemble into closed core particles, a relevant feature of retrovirus biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Obal, G -- Trajtenberg, F -- Carrion, F -- Tome, L -- Larrieux, N -- Zhang, X -- Pritsch, O -- Buschiazzo, A -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):95-8. doi: 10.1126/science.aaa5182. Epub 2015 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Pasteur de Montevideo, Unit of Protein Biophysics, Mataojo 2020, 11400, Montevideo, Uruguay. Departamento de Inmunobiologia, Facultad de Medicina, Universidad de la Republica, Avenida General Flores 2125, 11800, Montevideo, Uruguay. ; Institut Pasteur de Montevideo, Unit of Protein Crystallography, Mataojo 2020, 11400, Montevideo, Uruguay. ; Institut Pasteur de Montevideo, Unit of Protein Biophysics, Mataojo 2020, 11400, Montevideo, Uruguay. ; Institut Pasteur, Unite de Virologie Structurale, Departement de Virologie and CNRS Unite Mixte de Recherche 3569, 28, Rue du Docteur Roux, 75015, Paris, France. ; Institut Pasteur de Montevideo, Unit of Protein Biophysics, Mataojo 2020, 11400, Montevideo, Uruguay. Departamento de Inmunobiologia, Facultad de Medicina, Universidad de la Republica, Avenida General Flores 2125, 11800, Montevideo, Uruguay. pritsch@pasteur.edu.uy alebus@pasteur.edu.uy. ; Institut Pasteur de Montevideo, Unit of Protein Crystallography, Mataojo 2020, 11400, Montevideo, Uruguay. Institut Pasteur, Department of Structural Biology and Chemistry, 25, Rue du Dr Roux, 75015, Paris, France. pritsch@pasteur.edu.uy alebus@pasteur.edu.uy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26044299" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Capsid/*chemistry ; Capsid Proteins/*chemistry/genetics ; Cattle ; Crystallography, X-Ray ; Leukemia Virus, Bovine/*chemistry/genetics ; Molecular Sequence Data ; Mutation ; Protein Multimerization ; Protein Structure, Secondary
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  • 85
    Publication Date: 2015-09-05
    Description: During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells are unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8(+) T cell-mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditionally depleted mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8(+) T cell recruitment and effector functions. Collectively, these results suggest that neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8(+) T cell migration and localization in influenza-infected tissues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lim, Kihong -- Hyun, Young-Min -- Lambert-Emo, Kris -- Capece, Tara -- Bae, Seyeon -- Miller, Richard -- Topham, David J -- Kim, Minsoo -- AI102851/AI/NIAID NIH HHS/ -- HHSN272201400005C/PHS HHS/ -- HL087088/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):aaa4352. doi: 10.1126/science.aaa4352.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA. ; Department of Pharmacology, Northwestern University, Chicago, IL, USA. ; Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA. minsoo_kim@urmc.rochester.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26339033" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Chemokine CXCL12/*immunology/pharmacology ; Chemotaxis/*immunology ; Heterocyclic Compounds/pharmacology ; Influenza A virus/*immunology ; Lung/immunology/virology ; Male ; Matrix Metalloproteinase 2/immunology ; Matrix Metalloproteinase 9/immunology ; Mice ; Mice, Inbred C57BL ; Neutropenia/immunology ; Neutrophils/*immunology/virology ; Orthomyxoviridae Infections/*immunology ; Trachea/*immunology/virology
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  • 86
    Publication Date: 2015-03-15
    Description: Wireless deep brain stimulation of well-defined neuronal populations could facilitate the study of intact brain circuits and the treatment of neurological disorders. Here, we demonstrate minimally invasive and remote neural excitation through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic nanoparticles. When exposed to alternating magnetic fields, the nanoparticles dissipate heat generated by hysteresis, triggering widespread and reversible firing of TRPV1(+) neurons. Wireless magnetothermal stimulation in the ventral tegmental area of mice evoked excitation in subpopulations of neurons in the targeted brain region and in structures receiving excitatory projections. The nanoparticles persisted in the brain for over a month, allowing for chronic stimulation without the need for implants and connectors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Ritchie -- Romero, Gabriela -- Christiansen, Michael G -- Mohr, Alan -- Anikeeva, Polina -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1477-80. doi: 10.1126/science.1261821. Epub 2015 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. anikeeva@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25765068" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Deep Brain Stimulation/*methods ; Evoked Potentials ; HEK293 Cells ; Humans ; *Magnetite Nanoparticles ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/physiology ; Rats ; TRPV Cation Channels/agonists ; Ventral Tegmental Area/physiology ; *Wireless Technology
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  • 87
    Publication Date: 2015-02-14
    Description: The identification of active neurons and circuits in vivo is a fundamental challenge in understanding the neural basis of behavior. Genetically encoded calcium (Ca(2+)) indicators (GECIs) enable quantitative monitoring of cellular-resolution activity during behavior. However, such indicators require online monitoring within a limited field of view. Alternatively, post hoc staining of immediate early genes (IEGs) indicates highly active cells within the entire brain, albeit with poor temporal resolution. We designed a fluorescent sensor, CaMPARI, that combines the genetic targetability and quantitative link to neural activity of GECIs with the permanent, large-scale labeling of IEGs, allowing a temporally precise "activity snapshot" of a large tissue volume. CaMPARI undergoes efficient and irreversible green-to-red conversion only when elevated intracellular Ca(2+) and experimenter-controlled illumination coincide. We demonstrate the utility of CaMPARI in freely moving larvae of zebrafish and flies, and in head-fixed mice and adult flies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fosque, Benjamin F -- Sun, Yi -- Dana, Hod -- Yang, Chao-Tsung -- Ohyama, Tomoko -- Tadross, Michael R -- Patel, Ronak -- Zlatic, Marta -- Kim, Douglas S -- Ahrens, Misha B -- Jayaraman, Vivek -- Looger, Loren L -- Schreiter, Eric R -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):755-60. doi: 10.1126/science.1260922.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA. ; Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA. schreitere@janelia.hhmi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678659" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biosensing Techniques ; Calcium/*analysis/metabolism ; Drosophila melanogaster ; Fluorescence ; *Genes, Immediate-Early ; Indicators and Reagents/analysis/metabolism ; Luminescent Proteins/genetics/*metabolism ; Mice ; Neural Pathways/*chemistry/cytology/physiology ; Neuronal Calcium-Sensor Proteins/genetics/*metabolism ; Protein Engineering ; Sensory Receptor Cells/*chemistry/physiology ; Staining and Labeling/*methods ; Zebrafish
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  • 88
    Publication Date: 2015-08-26
    Description: The identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens ("mini-HAs") based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to those of full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever after sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bound a wide range of HAs, competed with human bnAbs for HA stem binding, neutralized H5N1 viruses, and mediated antibody-dependent effector activity. These results represent a proof of concept for the design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Impagliazzo, Antonietta -- Milder, Fin -- Kuipers, Harmjan -- Wagner, Michelle V -- Zhu, Xueyong -- Hoffman, Ryan M B -- van Meersbergen, Ruud -- Huizingh, Jeroen -- Wanningen, Patrick -- Verspuij, Johan -- de Man, Martijn -- Ding, Zhaoqing -- Apetri, Adrian -- Kukrer, Basak -- Sneekes-Vriese, Eveline -- Tomkiewicz, Danuta -- Laursen, Nick S -- Lee, Peter S -- Zakrzewska, Anna -- Dekking, Liesbeth -- Tolboom, Jeroen -- Tettero, Lisanne -- van Meerten, Sander -- Yu, Wenli -- Koudstaal, Wouter -- Goudsmit, Jaap -- Ward, Andrew B -- Meijberg, Wim -- Wilson, Ian A -- Radosevic, Katarina -- P41GM103393/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1301-6. doi: 10.1126/science.aac7263. Epub 2015 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands. aimpagli@its.jnj.com wilson@scripps.edu. ; Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands. ; Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 3210 Merryfield Row, San Diego, CA 92121, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. aimpagli@its.jnj.com wilson@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26303961" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*immunology ; Humans ; Influenza A Virus, H1N1 Subtype/*immunology ; Influenza A Virus, H5N1 Subtype/*immunology ; Influenza Vaccines/*immunology ; Influenza, Human/*prevention & control ; Mice ; Protein Multimerization ; Protein Structure, Secondary
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  • 89
    Publication Date: 2015-02-14
    Description: Acute myeloid leukemia (AML) is the most common form of adult leukemia. The transcription factor fusion CBFbeta-SMMHC (core binding factor beta and the smooth-muscle myosin heavy chain), expressed in AML with the chromosome inversion inv(16)(p13q22), outcompetes wild-type CBFbeta for binding to the transcription factor RUNX1, deregulates RUNX1 activity in hematopoiesis, and induces AML. Current inv(16) AML treatment with nonselective cytotoxic chemotherapy results in a good initial response but limited long-term survival. Here, we report the development of a protein-protein interaction inhibitor, AI-10-49, that selectively binds to CBFbeta-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFbeta-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423805/" 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/PMC4423805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Illendula, Anuradha -- Pulikkan, John A -- Zong, Hongliang -- Grembecka, Jolanta -- Xue, Liting -- Sen, Siddhartha -- Zhou, Yunpeng -- Boulton, Adam -- Kuntimaddi, Aravinda -- Gao, Yan -- Rajewski, Roger A -- Guzman, Monica L -- Castilla, Lucio H -- Bushweller, John H -- 1 DP2 OD007399-01/OD/NIH HHS/ -- DP2 OD007399/OD/NIH HHS/ -- R01 AI039536/AI/NIAID NIH HHS/ -- R01 CA096983/CA/NCI NIH HHS/ -- R01 CA140398/CA/NCI NIH HHS/ -- T32 GM080186/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):779-84. doi: 10.1126/science.aaa0314.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA. ; Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA. ; Department of Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA. ; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. ; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA. ; Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA. jhb4v@virginia.edu Lucio.Castilla@umassmed.edu. ; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA. jhb4v@virginia.edu Lucio.Castilla@umassmed.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/chemistry/*therapeutic use ; Benzimidazoles/chemistry/*therapeutic use ; Cell Line, Tumor ; Core Binding Factor Alpha 2 Subunit/antagonists & inhibitors/metabolism ; Female ; Humans ; Leukemia, Myeloid, Acute/*drug therapy ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Fusion/*antagonists & inhibitors/metabolism ; Protein Interaction Maps ; Small Molecule Libraries/chemistry
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  • 90
    Publication Date: 2015-11-28
    Description: Vibrational spectroscopy has been extensively applied to the study of molecules in gas phase, in condensed phase, and at interfaces. The transition from spectroscopy to spectroscopic imaging of living systems, which allows the spectrum of biomolecules to act as natural contrast, is opening new opportunities to reveal cellular machinery and to enable molecule-based diagnosis. Such a transition, however, involves more than a simple combination of spectrometry and microscopy. We review recent efforts that have pushed the boundary of the vibrational spectroscopic imaging field in terms of spectral acquisition speed, detection sensitivity, spatial resolution, and imaging depth. We further highlight recent applications in functional analysis of single cells and in label-free detection of diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Ji-Xin -- Xie, X Sunney -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):aaa8870. doi: 10.1126/science.aaa8870.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Weldon School of Biomedical Engineering and Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. jcheng@purdue.edu xie@chemistry.harvard.edu. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. jcheng@purdue.edu xie@chemistry.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612955" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Animals ; Biology ; Gases ; Humans ; Medicine ; Mice ; Microscopy/*methods ; Molecular Imaging/*methods ; Sensitivity and Specificity ; Spectrum Analysis, Raman/*methods ; Vibration
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  • 91
    Publication Date: 2015-01-13
    Description: XRCC4 and XLF are two structurally related proteins that function in DNA double-strand break (DSB) repair. Here, we identify human PAXX (PAralog of XRCC4 and XLF, also called C9orf142) as a new XRCC4 superfamily member and show that its crystal structure resembles that of XRCC4. PAXX interacts directly with the DSB-repair protein Ku and is recruited to DNA-damage sites in cells. Using RNA interference and CRISPR-Cas9 to generate PAXX(-/-) cells, we demonstrate that PAXX functions with XRCC4 and XLF to mediate DSB repair and cell survival in response to DSB-inducing agents. Finally, we reveal that PAXX promotes Ku-dependent DNA ligation in vitro and assembly of core nonhomologous end-joining (NHEJ) factors on damaged chromatin in cells. These findings identify PAXX as a new component of the NHEJ machinery.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338599/" 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/PMC4338599/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ochi, Takashi -- Blackford, Andrew N -- Coates, Julia -- Jhujh, Satpal -- Mehmood, Shahid -- Tamura, Naoka -- Travers, Jon -- Wu, Qian -- Draviam, Viji M -- Robinson, Carol V -- Blundell, Tom L -- Jackson, Stephen P -- 11224/Cancer Research UK/United Kingdom -- 268536/European Research Council/International -- A11224/Cancer Research UK/United Kingdom -- C28598/A9787/Cancer Research UK/United Kingdom -- C6/A11224/Cancer Research UK/United Kingdom -- C6946/A14492/Cancer Research UK/United Kingdom -- WT092096/Wellcome Trust/United Kingdom -- WT093167/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):185-8. doi: 10.1126/science.1261971.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK. ; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. ; Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK. ; Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK. ; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK. s.jackson@gurdon.cam.ac.uk tlb20@cam.ac.uk. ; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK. Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. s.jackson@gurdon.cam.ac.uk tlb20@cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25574025" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Nuclear/*metabolism ; Cell Line, Tumor ; Crystallography, X-Ray ; *DNA Breaks, Double-Stranded ; *DNA End-Joining Repair ; DNA Repair Enzymes/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Humans ; Protein Structure, Secondary ; RNA Interference
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  • 92
    Publication Date: 2015-08-08
    Description: Cytoplasmic aggregation of TDP-43, accompanied by its nuclear clearance, is a key common pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). However, a limited understanding of this RNA-binding protein (RBP) impedes the clarification of pathogenic mechanisms underlying TDP-43 proteinopathy. In contrast to RBPs that regulate splicing of conserved exons, we found that TDP-43 repressed the splicing of nonconserved cryptic exons, maintaining intron integrity. When TDP-43 was depleted from mouse embryonic stem cells, these cryptic exons were spliced into messenger RNAs, often disrupting their translation and promoting nonsense-mediated decay. Moreover, enforced repression of cryptic exons prevented cell death in TDP-43-deficient cells. Furthermore, repression of cryptic exons was impaired in ALS-FTD cases, suggesting that this splicing defect could potentially underlie TDP-43 proteinopathy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ling, Jonathan P -- Pletnikova, Olga -- Troncoso, Juan C -- Wong, Philip C -- P50AG05146/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):650-5. doi: 10.1126/science.aab0983.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. wong@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250685" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/*genetics ; Animals ; Base Sequence ; Cells, Cultured ; Cysteine Endopeptidases/genetics ; DNA-Binding Proteins/genetics/*physiology ; Embryonic Stem Cells ; Exons/*genetics ; Frontotemporal Dementia/*genetics ; Gene Knockout Techniques ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Protein Isoforms/genetics ; *RNA Splicing ; RNA Stability ; RNA, Messenger/metabolism ; Sequence Analysis, DNA
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  • 93
    Publication Date: 2015-07-15
    Description: Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (T(H)17) cells and regulatory T cells (T(regs)) in the intestine. Here, we report that microbiota-induced T(regs) express the nuclear hormone receptor RORgammat and differentiate along a pathway that also leads to T(H)17 cells. In the absence of RORgammat(+) T(regs), T(H)2-driven defense against helminths is more efficient, whereas T(H)2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORgammat(+) T(regs) and T(H)17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ohnmacht, Caspar -- Park, Joo-Hong -- Cording, Sascha -- Wing, James B -- Atarashi, Koji -- Obata, Yuuki -- Gaboriau-Routhiau, Valerie -- Marques, Rute -- Dulauroy, Sophie -- Fedoseeva, Maria -- Busslinger, Meinrad -- Cerf-Bensussan, Nadine -- Boneca, Ivo G -- Voehringer, David -- Hase, Koji -- Honda, Kenya -- Sakaguchi, Shimon -- Eberl, Gerard -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):989-93. doi: 10.1126/science.aac4263. Epub 2015 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France. ; Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. ; RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan. ; The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; INSERM, U1163, Laboratory of Intestinal Immunity, Paris, France. Universite Paris Descartes-Sorbonne Paris Cite and Institut Imagine, Paris, France. INRA Micalis UMR1319, Jouy-en-Josas, France. ; Center of Allergy and Environment (ZAUM), Technische Universitat and Helmholtz Zentrum Munchen, Munich, Germany. ; Research Institute of Molecular Pathology, Vienna Biocenter, 1030 Vienna, Austria. ; INSERM, U1163, Laboratory of Intestinal Immunity, Paris, France. Universite Paris Descartes-Sorbonne Paris Cite and Institut Imagine, Paris, France. ; Institut Pasteur, Biology and Genetics of Bacterial Cell Wall, 75724 Paris, France. INSERM, Groupe Avenir, 75015 Paris, France. ; Department of Infection Biology at the Institute of Clinical Microbiology, Immunology and Hygiene, University Clinic Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany. ; RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. CREST, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan. ; Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. ; Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France. gerard.eberl@pasteur.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160380" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Colitis, Ulcerative/immunology ; Colon/immunology/microbiology ; Germ-Free Life ; Homeostasis ; *Immunity, Mucosal ; Intestinal Mucosa/*immunology/*microbiology ; Intestine, Small/immunology/microbiology ; Intestines/immunology/*microbiology ; Mice ; Microbiota/*immunology ; Models, Immunological ; Nematospiroides dubius ; Nuclear Receptor Subfamily 1, Group F, Member 3/*metabolism ; Specific Pathogen-Free Organisms ; Strongylida Infections/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; Th17 Cells/immunology ; Th2 Cells/immunology ; Vitamin A/metabolism
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  • 94
    Publication Date: 2015-07-15
    Description: Human inborn errors of immunity mediated by the cytokines interleukin-17A and interleukin-17F (IL-17A/F) underlie mucocutaneous candidiasis, whereas inborn errors of interferon-gamma (IFN-gamma) immunity underlie mycobacterial disease. We report the discovery of bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional RORgamma and RORgammaT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORgamma- and RORgammaT-deficient individuals also displayed an impaired IFN-gamma response to Mycobacterium. This principally reflected profoundly defective IFN-gamma production by circulating gammadelta T cells and CD4(+)CCR6(+)CXCR3(+) alphabeta T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORgamma, RORgammaT, or both.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668938/" 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/PMC4668938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Satoshi -- Markle, Janet G -- Deenick, Elissa K -- Mele, Federico -- Averbuch, Dina -- Lagos, Macarena -- Alzahrani, Mohammed -- Al-Muhsen, Saleh -- Halwani, Rabih -- Ma, Cindy S -- Wong, Natalie -- Soudais, Claire -- Henderson, Lauren A -- Marzouqa, Hiyam -- Shamma, Jamal -- Gonzalez, Marcela -- Martinez-Barricarte, Ruben -- Okada, Chizuru -- Avery, Danielle T -- Latorre, Daniela -- Deswarte, Caroline -- Jabot-Hanin, Fabienne -- Torrado, Egidio -- Fountain, Jeffrey -- Belkadi, Aziz -- Itan, Yuval -- Boisson, Bertrand -- Migaud, Melanie -- Arlehamn, Cecilia S Lindestam -- Sette, Alessandro -- Breton, Sylvain -- McCluskey, James -- Rossjohn, Jamie -- de Villartay, Jean-Pierre -- Moshous, Despina -- Hambleton, Sophie -- Latour, Sylvain -- Arkwright, Peter D -- Picard, Capucine -- Lantz, Olivier -- Engelhard, Dan -- Kobayashi, Masao -- Abel, Laurent -- Cooper, Andrea M -- Notarangelo, Luigi D -- Boisson-Dupuis, Stephanie -- Puel, Anne -- Sallusto, Federica -- Bustamante, Jacinta -- Tangye, Stuart G -- Casanova, Jean-Laurent -- 8UL1TR000043/TR/NCATS NIH HHS/ -- HHSN272200900044C/AI/NIAID NIH HHS/ -- HHSN272200900044C/PHS HHS/ -- R37 AI095983/AI/NIAID NIH HHS/ -- R37AI095983/AI/NIAID NIH HHS/ -- T32 AI007512/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):606-13. doi: 10.1126/science.aaa4282. Epub 2015 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. jmarkle@rockefeller.edu jean-laurent.casanova@rockefeller.edu. ; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia. ; Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland. ; Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel. ; Department of Immunology, School of Medicine, Universidad de Valparaiso, Santiago, Chile. Department of Pediatrics, Padre Hurtado Hospital and Clinica Alemana, Santiago, Chile. ; Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. ; Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Department of Pediatrics, Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia. ; Department of Pediatrics, Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia. ; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. ; Institut Curie, INSERM U932, Paris, France. ; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA. ; Caritas Baby Hospital, Post Office Box 11535, Jerusalem, Israel. ; Department of Immunology, School of Medicine, Universidad de Valparaiso, Santiago, Chile. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. ; Trudeau Institute, Saranac Lake, NY 12983, USA. ; La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; Department of Radiology, Assistance Publique-Hopitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France. ; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. ; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia. Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK. ; Laboratoire Dynamique du Genome et Systeme Immunitaire, INSERM UMR 1163, Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France. ; Laboratoire Dynamique du Genome et Systeme Immunitaire, INSERM UMR 1163, Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France. Pediatric Hematology-Immunology Unit, AP-HP, Necker Hospital for Sick Children, Paris, France. ; Institute of Cellular Medicine, Newcastle University and Great North Children's Hospital, Newcastle upon Tyne NE4 6BE, UK. ; Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France. ; Department of Paediatric Allergy Immunology, University of Manchester, Royal Manchester Children's Hospital, Manchester, UK. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. Pediatric Hematology-Immunology Unit, AP-HP, Necker Hospital for Sick Children, Paris, France. Center for the Study of Primary Immunodeficiencies, AP-HP, Necker Hospital for Sick Children, Paris, France. ; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. ; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA. Manton Center for Orphan Disease Research, Children's Hospital, Boston, MA 02115, USA. ; Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland. Center of Medical Immunology, Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. Center for the Study of Primary Immunodeficiencies, AP-HP, Necker Hospital for Sick Children, Paris, France. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. Pediatric Hematology-Immunology Unit, AP-HP, Necker Hospital for Sick Children, Paris, France. Howard Hughes Medical Institute, New York, NY 10065, USA. jmarkle@rockefeller.edu jean-laurent.casanova@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160376" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Candida albicans/*immunology ; Candidiasis, Chronic Mucocutaneous/complications/*genetics/immunology ; Cattle ; Child ; Child, Preschool ; DNA Mutational Analysis ; Exome/genetics ; Female ; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor ; Humans ; Immunity/*genetics ; Interferon-gamma/immunology ; Interleukin-17/immunology ; Mice ; Mutation ; Mycobacterium bovis/immunology/isolation & purification ; Mycobacterium tuberculosis/immunology/isolation & purification ; Nuclear Receptor Subfamily 1, Group F, Member 3/*genetics ; Pedigree ; Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology ; Receptors, Antigen, T-Cell, gamma-delta/genetics/immunology ; Severe Combined Immunodeficiency/*genetics ; T-Lymphocytes/immunology ; Thymus Gland/abnormalities/immunology ; Tuberculosis, Bovine/*genetics/immunology ; Tuberculosis, Pulmonary/*genetics/immunology
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  • 95
    Publication Date: 2015-04-18
    Description: Protective CD8(+) T cell-mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. Using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (LEM) that promoted antigen-dependent CD8(+) T cell proliferation, effector function, and memory cell generation in response to infection with lymphocytic choriomeningitis virus. Generation of LEM-deficient mice confirmed these results. Through interaction with CR6 interacting factor (CRIF1), LEM controlled the levels of oxidative phosphorylation (OXPHOS) complexes and respiration, resulting in the production of pro-proliferative mitochondrial reactive oxygen species (mROS). LEM provides a link between immune activation and the expansion of protective CD8(+) T cells driven by OXPHOS and represents a pathway for the restoration of long-term protective immunity based on metabolically modified cytotoxic CD8(+) T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okoye, Isobel -- Wang, Lihui -- Pallmer, Katharina -- Richter, Kirsten -- Ichimura, Takahuru -- Haas, Robert -- Crouse, Josh -- Choi, Onjee -- Heathcote, Dean -- Lovo, Elena -- Mauro, Claudio -- Abdi, Reza -- Oxenius, Annette -- Rutschmann, Sophie -- Ashton-Rickardt, Philip G -- A9995/Cancer Research UK/United Kingdom -- AI091930/AI/NIAID NIH HHS/ -- AI45108/AI/NIAID NIH HHS/ -- FS/12/38/29640/British Heart Foundation/United Kingdom -- G0700795/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 May 29;348(6238):995-1001. doi: 10.1126/science.aaa7516. Epub 2015 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK. ; Institute of Microbiology, Eidgenossische Technische Hochschule Zurich (ETHZ), Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland. ; Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02215, USA. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK. Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02215, USA. p.ashton-rickardt@imperial.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883318" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology/*metabolism ; Cell Cycle Proteins/metabolism ; Cell Respiration ; Immunity, Cellular ; *Immunologic Memory ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/*metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Molecular Sequence Data ; Oxidative Phosphorylation ; Reactive Oxygen Species/metabolism
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  • 96
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Servick, Kelly -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1299. doi: 10.1126/science.347.6228.1299.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792309" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology ; Energy Metabolism ; *Enzyme-Linked Immunosorbent Assay ; Exercise/*physiology ; False Positive Reactions ; Fibronectins/*blood/immunology/metabolism ; Humans ; Mice ; Molecular Targeted Therapy ; Muscle, Skeletal/metabolism ; Obesity/drug therapy/metabolism ; *Reagent Kits, Diagnostic
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  • 97
    Publication Date: 2015-06-27
    Description: Circadian clocks generate slow and ordered cellular dynamics but consist of fast-moving bio-macromolecules; consequently, the origins of the overall slowness remain unclear. We identified the adenosine triphosphate (ATP) catalytic region [adenosine triphosphatase (ATPase)] in the amino-terminal half of the clock protein KaiC as the minimal pacemaker that controls the in vivo frequency of the cyanobacterial clock. Crystal structures of the ATPase revealed that the slowness of this ATPase arises from sequestration of a lytic water molecule in an unfavorable position and coupling of ATP hydrolysis to a peptide isomerization with high activation energy. The slow ATPase is coupled with another ATPase catalyzing autodephosphorylation in the carboxyl-terminal half of KaiC, yielding the circadian response frequency of intermolecular interactions with other clock-related proteins that influences the transcription and translation cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abe, Jun -- Hiyama, Takuya B -- Mukaiyama, Atsushi -- Son, Seyoung -- Mori, Toshifumi -- Saito, Shinji -- Osako, Masato -- Wolanin, Julie -- Yamashita, Eiki -- Kondo, Takao -- Akiyama, Shuji -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):312-6. doi: 10.1126/science.1261040. Epub 2015 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. ; Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Functional Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. ; Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Department of Functional Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. ; Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Functional Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. ; Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. PSL Research University, Chimie ParisTech, 75005 Paris, France. ; Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Suita 565-0871, Japan. ; Research Center of Integrative Molecular Systems (CIMoS), Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. Department of Functional Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan. akiyamas@ims.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113637" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*chemistry/genetics ; Adenosine Triphosphate/chemistry ; Bacterial Proteins/*chemistry/genetics ; Catalysis ; *Catalytic Domain ; Circadian Clocks/*physiology ; *Circadian Rhythm ; Circadian Rhythm Signaling Peptides and Proteins/*chemistry/genetics ; Crystallography, X-Ray ; Hydrolysis ; Synechococcus/enzymology/*physiology
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  • 98
    Publication Date: 2015-06-27
    Description: Cardiac progenitor cells are multipotent and give rise to cardiac endothelium, smooth muscle, and cardiomyocytes. Here, we define and characterize the cardiomyoblast intermediate that is committed to the cardiomyocyte fate, and we characterize the niche signals that regulate commitment. Cardiomyoblasts express Hopx, which functions to coordinate local Bmp signals to inhibit the Wnt pathway, thus promoting cardiomyogenesis. Hopx integrates Bmp and Wnt signaling by physically interacting with activated Smads and repressing Wnt genes. The identification of the committed cardiomyoblast that retains proliferative potential will inform cardiac regenerative therapeutics. In addition, Bmp signals characterize adult stem cell niches in other tissues where Hopx-mediated inhibition of Wnt is likely to contribute to stem cell quiescence and to explain the role of Hopx as a tumor suppressor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jain, Rajan -- Li, Deqiang -- Gupta, Mudit -- Manderfield, Lauren J -- Ifkovits, Jamie L -- Wang, Qiaohong -- Liu, Feiyan -- Liu, Ying -- Poleshko, Andrey -- Padmanabhan, Arun -- Raum, Jeffrey C -- Li, Li -- Morrisey, Edward E -- Lu, Min Min -- Won, Kyoung-Jae -- Epstein, Jonathan A -- 5-T32-GM-007170/GM/NIGMS NIH HHS/ -- K08 HL119553/HL/NHLBI NIH HHS/ -- K08 HL119553-02/HL/NHLBI NIH HHS/ -- R01 HL071546/HL/NHLBI NIH HHS/ -- U01 HL100405/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):aaa6071. doi: 10.1126/science.aaa6071.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Genetics, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. epsteinj@upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113728" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bone Morphogenetic Proteins/genetics/*metabolism ; Cell Lineage/genetics ; Gene Expression ; *Gene Expression Regulation, Developmental ; Heart/*embryology ; Homeodomain Proteins/genetics/*metabolism ; Mice ; Mice, Mutant Strains ; Molecular Sequence Data ; Muscle, Smooth/cytology/metabolism ; Myoblasts, Cardiac/cytology/*metabolism ; Organogenesis/*genetics ; Stem Cell Niche/genetics/physiology ; Tumor Suppressor Proteins/genetics/*metabolism ; Wnt Signaling Pathway/*genetics
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  • 99
    Publication Date: 2015-10-24
    Description: The nucleotide-binding oligomerization domain-like receptor (Nlrp) 6 maintains gut microbiota homeostasis and regulates antibacterial immunity. We now report a role for Nlrp6 in the control of enteric virus infection. Nlrp6(-/-) and control mice systemically challenged with encephalomyocarditis virus had similar mortality; however, the gastrointestinal tract of Nlrp6(-/-) mice exhibited increased viral loads. Nlrp6(-/-) mice orally infected with encephalomyocarditis virus had increased mortality and viremia compared with controls. Similar results were observed with murine norovirus 1. Nlrp6 bound viral RNA via the RNA helicase Dhx15 and interacted with mitochondrial antiviral signaling protein to induce type I/III interferons (IFNs) and IFN-stimulated genes (ISGs). These data demonstrate that Nlrp6 functions with Dhx15 as a viral RNA sensor to induce ISGs, and this effect is especially important in the intestinal tract.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Penghua -- Zhu, Shu -- Yang, Long -- Cui, Shuang -- Pan, Wen -- Jackson, Ruaidhri -- Zheng, Yunjiang -- Rongvaux, Anthony -- Sun, Qiangming -- Yang, Guang -- Gao, Shandian -- Lin, Rongtuan -- You, Fuping -- Flavell, Richard -- Fikrig, Erol -- AI099625/AI/NIAID NIH HHS/ -- AI103807/AI/NIAID NIH HHS/ -- N01-HHSN272201100019C/PHS HHS/ -- R03 AI099625/AI/NIAID NIH HHS/ -- R21 AI103807/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):826-30. doi: 10.1126/science.aab3145. Epub 2015 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA. ; Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. ; Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. ; Department of Genetics, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. ; Lady Davis Institute, Department of Medicine, McGill University, Montreal, Quebec, Canada. ; Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA. richard.flavell@yale.edu erol.fikrig@yale.edu. ; Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA. richard.flavell@yale.edu erol.fikrig@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26494172" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caliciviridae Infections/immunology/virology ; Cardiovirus Infections/immunology/virology ; Cytokines/genetics ; Encephalomyocarditis virus/immunology ; Gastroenteritis/immunology/virology ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Immunity, Innate/*genetics ; Interferon Type I/*immunology ; Intestines/*immunology/*virology ; Mice ; Mice, Mutant Strains ; Norovirus/immunology ; RNA Helicases/*physiology ; RNA, Viral/*immunology ; Receptors, Cell Surface/genetics/*physiology ; Ubiquitins/genetics ; Viremia/genetics/immunology
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  • 100
    Publication Date: 2015-01-09
    Description: The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine with a high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295826/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295826/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Shuyu -- Tsun, Zhi-Yang -- Wolfson, Rachel L -- Shen, Kuang -- Wyant, Gregory A -- Plovanich, Molly E -- Yuan, Elizabeth D -- Jones, Tony D -- Chantranupong, Lynne -- Comb, William -- Wang, Tim -- Bar-Peled, Liron -- Zoncu, Roberto -- Straub, Christoph -- Kim, Choah -- Park, Jiwon -- Sabatini, Bernardo L -- Sabatini, David M -- AI47389/AI/NIAID NIH HHS/ -- F30 CA180754/CA/NCI NIH HHS/ -- F31 AG044064/AG/NIA NIH HHS/ -- F31 CA180271/CA/NCI NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R37 AI047389/AI/NIAID NIH HHS/ -- T32 GM007287/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):188-94. doi: 10.1126/science.1257132. Epub 2015 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Harvard Medical School, 260 Longwood Avenue, Boston, MA 02115, USA. ; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. ; Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. sabatini@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25567906" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Transport Systems/chemistry/genetics/*metabolism ; Arginine/deficiency/*metabolism ; HEK293 Cells ; Humans ; Lysosomes/*enzymology ; Molecular Sequence Data ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes/*metabolism ; Protein Structure, Tertiary ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism
    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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