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  • 101
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blum, Arlene -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1117. doi: 10.1126/science.aaf5468. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Arlene Blum is founder and executive director of the Green Science Policy Institute, Berkeley, CA. arlene@GreenSciencePolicy.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965592" target="_blank"〉PubMed〈/a〉
    Keywords: Consumer Product Safety/*legislation & jurisprudence ; Health ; Household Products/*toxicity ; Humans ; Manufactured Materials/*toxicity ; United States
    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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  • 102
    Publication Date: 2016-02-27
    Description: Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limited oxygen availability. Genetic or small-molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured cells and zebrafish models. Chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology, and disease biomarkers in a genetic mouse model of Leigh syndrome, the most common pediatric manifestation of mitochondrial disease. Further preclinical studies are required to assess whether hypoxic exposure can be developed into a safe and effective treatment for human diseases associated with mitochondrial dysfunction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860742/" 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/PMC4860742/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jain, Isha H -- Zazzeron, Luca -- Goli, Rahul -- Alexa, Kristen -- Schatzman-Bone, Stephanie -- Dhillon, Harveen -- Goldberger, Olga -- Peng, Jun -- Shalem, Ophir -- Sanjana, Neville E -- Zhang, Feng -- Goessling, Wolfram -- Zapol, Warren M -- Mootha, Vamsi K -- 1R01-MH110049/MH/NIMH NIH HHS/ -- 5DP1-MH100706/DP/NCCDPHP CDC HHS/ -- 5R01DK097768-03/DK/NIDDK NIH HHS/ -- DP1 MH100706/MH/NIMH NIH HHS/ -- K99 HG008171/HG/NHGRI NIH HHS/ -- K99-HG008171/HG/NHGRI NIH HHS/ -- R01 DK090311/DK/NIDDK NIH HHS/ -- R01 DK097768/DK/NIDDK NIH HHS/ -- R01 MH110049/MH/NIMH NIH HHS/ -- R01DK090311/DK/NIDDK NIH HHS/ -- R24 OD017870/OD/NIH HHS/ -- R24OD017870/OD/NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):54-61. doi: 10.1126/science.aad9642. Epub 2016 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA, USA. Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Broad Institute of Harvard and MIT, Cambridge, MA, USA. ; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA. ; Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ; Broad Institute of Harvard and MIT, Cambridge, MA, USA. McGovern Institute for Brain Research, Cambridge, MA, USA. Department of Brain and Cognitive Sciences and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. ; Broad Institute of Harvard and MIT, Cambridge, MA, USA. Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Stem Cell Institute, Cambridge, MA, USA. ; Department of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA, USA. Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Broad Institute of Harvard and MIT, Cambridge, MA, USA. vamsi@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917594" target="_blank"〉PubMed〈/a〉
    Keywords: Anaerobiosis ; Animals ; Antimycin A/analogs & derivatives/pharmacology ; Bacterial Proteins ; Biomarkers/blood ; Body Temperature ; Body Weight ; Disease Models, Animal ; Electron Transport/drug effects ; Electron Transport Complex I/genetics ; Endonucleases ; Energy Metabolism/drug effects/genetics ; Gene Knockout Techniques ; Genome-Wide Association Study ; Glycine/analogs & derivatives/pharmacology/therapeutic use ; Humans ; Hypoxia-Inducible Factor 1/metabolism ; Isoquinolines/pharmacology/therapeutic use ; K562 Cells ; Leigh Disease/*genetics/pathology/*therapy ; Mice ; Mice, Knockout ; Mitochondria/drug effects/*metabolism ; Oxygen/*metabolism ; Respiration ; Suppression, Genetic ; Von Hippel-Lindau Tumor Suppressor Protein/antagonists & inhibitors/*genetics ; Zebrafish
    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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  • 103
    Publication Date: 2016-04-16
    Description: Increasing incidence of inflammatory bowel diseases, such as Crohn's disease, in developed nations is associated with changes to the microbial environment, such as decreased prevalence of helminth colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the Crohn's disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization by an inflammatory Bacteroides species. Resistance to Bacteroides colonization was dependent on type 2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales. Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota and that deworming treatment reduced levels of Clostridiales and increased Bacteroidales. These results support a model of the hygiene hypothesis in which certain individuals are genetically susceptible to the consequences of a changing microbial environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramanan, Deepshika -- Bowcutt, Rowann -- Lee, Soo Ching -- Tang, Mei San -- Kurtz, Zachary D -- Ding, Yi -- Honda, Kenya -- Gause, William C -- Blaser, Martin J -- Bonneau, Richard A -- Lim, Yvonne A L -- Loke, P'ng -- Cadwell, Ken -- AI007180/AI/NIAID NIH HHS/ -- AI093811/AI/NIAID NIH HHS/ -- AI107588/AI/NIAID NIH HHS/ -- DK090989/DK/NIDDK NIH HHS/ -- DK093668/DK/NIDDK NIH HHS/ -- DK103788/DK/NIDDK NIH HHS/ -- HL123340/HL/NHLBI NIH HHS/ -- P30CA016087/CA/NCI NIH HHS/ -- UL1 TR000038/TR/NCATS NIH HHS/ -- UL1 TR00038/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):608-12. doi: 10.1126/science.aaf3229. Epub 2016 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA. ; Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. ; Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY 10016, USA. Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA. ; Department of Pathology, New York University Langone Medical Center, New York, NY 10016, USA. ; RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa 230-0045, Japan. Japan Agency for Medical Research and Development (AMED)-Core Research for Evolutional Science and Technology (CREST), Tokyo 100-0004, Japan. ; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07101, USA. ; Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10003, USA. Courant Institute of Mathematical Sciences, New York University, New York, NY 10012, USA. Simons Center for Data Analysis, Simons Foundation, New York, NY 10011, USA. ; Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. ken.cadwell@med.nyu.edu png.loke@nyumc.org limailian@um.edu.my. ; Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA. ken.cadwell@med.nyu.edu png.loke@nyumc.org limailian@um.edu.my. ; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA. ken.cadwell@med.nyu.edu png.loke@nyumc.org limailian@um.edu.my.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27080105" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteroides/*immunology ; Bacteroides Infections/*immunology ; Clostridiales/immunology ; Clostridium Infections/immunology ; Crohn Disease/*genetics/immunology ; Gastrointestinal Microbiome/*immunology ; Genetic Predisposition to Disease ; Hygiene Hypothesis ; Intestines/*immunology/microbiology/parasitology ; Mice ; Mice, Mutant Strains ; Nod2 Signaling Adaptor Protein/*genetics ; Trichuriasis/*immunology ; Trichuris/*immunology
    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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  • 104
    Publication Date: 2016-03-26
    Description: Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naive B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naive B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872700/" 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/PMC4872700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jardine, Joseph G -- Kulp, Daniel W -- Havenar-Daughton, Colin -- Sarkar, Anita -- Briney, Bryan -- Sok, Devin -- Sesterhenn, Fabian -- Ereno-Orbea, June -- Kalyuzhniy, Oleksandr -- Deresa, Isaiah -- Hu, Xiaozhen -- Spencer, Skye -- Jones, Meaghan -- Georgeson, Erik -- Adachi, Yumiko -- Kubitz, Michael -- deCamp, Allan C -- Julien, Jean-Philippe -- Wilson, Ian A -- Burton, Dennis R -- Crotty, Shane -- Schief, William R -- P01 AI094419/AI/NIAID NIH HHS/ -- P01 AI110657/AI/NIAID NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1458-63. doi: 10.1126/science.aad9195.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, 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. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Program in Molecular Structure and Function, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Vaccine and Infectious Disease Division, Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, 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. Program in Molecular Structure and Function, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada. Departments of Biochemistry and Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, 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. Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA. schief@scripps.edu shane@lji.org. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. schief@scripps.edu shane@lji.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013733" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; Amino Acid Sequence ; Antibodies, Monoclonal/chemistry/*immunology/isolation & purification ; Antibodies, Neutralizing/chemistry/*immunology/isolation & purification ; Antibody Affinity ; B-Lymphocytes/immunology ; Cell Separation ; Combinatorial Chemistry Techniques ; Epitopes, B-Lymphocyte/chemistry/genetics/*immunology ; Germ Cells/*immunology ; HIV Antibodies/chemistry/*immunology/isolation & purification ; HIV-1/*immunology ; Humans ; Molecular Sequence Data ; Mutation ; Peptide Library ; Precursor Cells, B-Lymphoid/*immunology ; Protein Conformation
    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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  • 105
    Publication Date: 2016-02-26
    Description: Undernourished children exhibit impaired development of their gut microbiota. Transplanting microbiota from 6- and 18-month-old healthy or undernourished Malawian donors into young germ-free mice that were fed a Malawian diet revealed that immature microbiota from undernourished infants and children transmit impaired growth phenotypes. The representation of several age-discriminatory taxa in recipient animals correlated with lean body mass gain; liver, muscle, and brain metabolism; and bone morphology. Mice were cohoused shortly after receiving microbiota from healthy or severely stunted and underweight infants; age- and growth-discriminatory taxa from the microbiota of the former were able to invade that of the latter, which prevented growth impairments in recipient animals. Adding two invasive species, Ruminococcus gnavus and Clostridium symbiosum, to the microbiota from undernourished donors also ameliorated growth and metabolic abnormalities in recipient animals. These results provide evidence that microbiota immaturity is causally related to undernutrition and reveal potential therapeutic targets and agents.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4787260/" 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/PMC4787260/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blanton, Laura V -- Charbonneau, Mark R -- Salih, Tarek -- Barratt, Michael J -- Venkatesh, Siddarth -- Ilkaveya, Olga -- Subramanian, Sathish -- Manary, Mark J -- Trehan, Indi -- Jorgensen, Josh M -- Fan, Yue-Mei -- Henrissat, Bernard -- Leyn, Semen A -- Rodionov, Dmitry A -- Osterman, Andrei L -- Maleta, Kenneth M -- Newgard, Christopher B -- Ashorn, Per -- Dewey, Kathryn G -- Gordon, Jeffrey I -- R37 DK030292/DK/NIDDK NIH HHS/ -- T32 AI007172/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 19;351(6275). pii: aad3311. doi: 10.1126/science.aad3311.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology and Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108, USA. ; Sarah W. Stedman Nutrition and Metabolism Centerand Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA. ; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. School of Public Health and Family Medicine, College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi. ; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. Department of Paediatrics and Child Health, College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi. ; Department of Nutrition and Program in International and Community Nutrition, University of California-Davis, Davis, CA 95616, USA. ; Department for International Health, University of Tampere School of Medicine, Tampere 33014, Finland. ; Architecture et Fonction des Macromolecules Biologiques, Centre National de la Recherche Scientifique and Aix-Marseille Universite, 13288 Marseille Cedex 9, France. Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. ; A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127994, Russia. ; A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127994, Russia. Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. ; Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. ; School of Public Health and Family Medicine, College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi. ; Sarah W. Stedman Nutrition and Metabolism Centerand Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA. Department of Pharmacology and Cancer Biology and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. ; Department for International Health, University of Tampere School of Medicine, Tampere 33014, Finland. Department of Pediatrics, Tampere University Hospital, Tampere 33521, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912898" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria/*classification ; Bifidobacterium/physiology ; Body Weight ; Bone Development ; Clostridiales/physiology ; Disease Models, Animal ; Feces/microbiology ; Femur/growth & development ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Humans ; Infant ; Infant Nutrition Disorders/metabolism/*microbiology ; Malawi ; Male ; Mice ; Mice, Inbred C57BL
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 106
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):14. doi: 10.1126/science.351.6268.14.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721983" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Databases, Genetic/*economics ; Financial Support ; Human Genome Project/*economics ; Humans ; Models, Animal ; National Human Genome Research Institute (U.S.)/*economics ; United States
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  • 107
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richmond, Geraldine -- New York, N.Y. -- Science. 2016 Jan 29;351(6272):427. doi: 10.1126/science.aaf2869. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geraldine Richmond is president of AAAS and Presidential Chair in Science and professor in the Department of Chemistry and Biochemistry at the University of Oregon, Eugene, OR. richmond@oregon.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26823402" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Asia ; *Food Supply ; Humans ; *Internationality ; United States ; *Water Supply
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  • 108
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):20. doi: 10.1126/science.352.6281.20.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034352" target="_blank"〉PubMed〈/a〉
    Keywords: Awards and Prizes ; Biomedical Research/*economics ; *Financing, Government ; National Institute of General Medical Sciences (U.S.) ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 109
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):164-6. doi: 10.1126/science.352.6282.164.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27124448" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Cells/*pathology ; Bystander Effect ; Exosomes/*pathology ; Humans ; Lung Neoplasms/secondary ; Mice ; Neoplasm Invasiveness/*pathology ; Neoplasm Metastasis/*pathology ; Skin Neoplasms/pathology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 110
    Publication Date: 2016-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):325-6. doi: 10.1126/science.351.6271.325.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797992" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*organization & administration ; Federal Government ; Humans ; Neoplasms/*therapy ; Policy ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 111
    Publication Date: 2016-01-09
    Description: The lung is constantly exposed to environmental atmospheric cues. How it senses and responds to these cues is poorly defined. Here, we show that Roundabout receptor (Robo) genes are expressed in pulmonary neuroendocrine cells (PNECs), a rare, innervated epithelial population. Robo inactivation in mouse lung results in an inability of PNECs to cluster into sensory organoids and triggers increased neuropeptide production upon exposure to air. Excess neuropeptides lead to an increase in immune infiltrates, which in turn remodel the matrix and irreversibly simplify the alveoli. We demonstrate in vivo that PNECs act as precise airway sensors that elicit immune responses via neuropeptides. These findings suggest that the PNEC and neuropeptide abnormalities documented in a wide array of pulmonary diseases may profoundly affect symptoms and progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Branchfield, Kelsey -- Nantie, Leah -- Verheyden, Jamie M -- Sui, Pengfei -- Wienhold, Mark D -- Sun, Xin -- 5T32AI007635/AI/NIAID NIH HHS/ -- HL097134/HL/NHLBI NIH HHS/ -- HL122406/HL/NHLBI NIH HHS/ -- R01 HL113870/HL/NHLBI NIH HHS/ -- T32 GM007133/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):707-10. doi: 10.1126/science.aad7969. Epub 2016 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA. ; Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA. ; Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA. xsun@wisc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26743624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Clodronic Acid/pharmacology ; Lung/cytology/*immunology ; Lung Diseases/genetics/immunology ; Macrophages/drug effects/immunology ; Mice ; Mice, Mutant Strains ; Mutation ; Nerve Tissue Proteins/genetics/*physiology ; Neuroendocrine Cells/*immunology/metabolism ; Neuropeptides/*biosynthesis ; Receptors, Immunologic/genetics/*physiology
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  • 112
    Publication Date: 2016-04-23
    Description: The microtubule (MT) cytoskeleton can transmit mechanical signals and resist compression in contracting cardiomyocytes. How MTs perform these roles remains unclear because of difficulties in observing MTs during the rapid contractile cycle. Here, we used high spatial and temporal resolution imaging to characterize MT behavior in beating mouse myocytes. MTs deformed under contractile load into sinusoidal buckles, a behavior dependent on posttranslational "detyrosination" of alpha-tubulin. Detyrosinated MTs associated with desmin at force-generating sarcomeres. When detyrosination was reduced, MTs uncoupled from sarcomeres and buckled less during contraction, which allowed sarcomeres to shorten and stretch with less resistance. Conversely, increased detyrosination promoted MT buckling, stiffened the myocyte, and correlated with impaired function in cardiomyopathy. Thus, detyrosinated MTs represent tunable, compression-resistant elements that may impair cardiac function in disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robison, Patrick -- Caporizzo, Matthew A -- Ahmadzadeh, Hossein -- Bogush, Alexey I -- Chen, Christina Yingxian -- Margulies, Kenneth B -- Shenoy, Vivek B -- Prosser, Benjamin L -- HL089847/HL/NHLBI NIH HHS/ -- HL105993/HL/NHLBI NIH HHS/ -- R00-HL114879/HL/NHLBI NIH HHS/ -- R01EB017753/EB/NIBIB NIH HHS/ -- T32AR053461-09/AR/NIAMS NIH HHS/ -- T32HL007954/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):aaf0659. doi: 10.1126/science.aaf0659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. ; Department of Materials Science and Engineering, University of Pennsylvania School of Engineering and Applied Science, Philadelphia, PA 19104, USA. ; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. ; Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. bpros@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102488" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Desmin/metabolism ; Elasticity ; Heart Failure/metabolism/physiopathology ; Humans ; Male ; Mice ; Microtubules/*metabolism ; Models, Biological ; *Myocardial Contraction ; Myocytes, Cardiac/metabolism/*physiology ; Peptide Synthases/genetics/metabolism ; *Protein Processing, Post-Translational ; RNA, Small Interfering/genetics ; Rats ; Rats, Sprague-Dawley ; Sarcomeres/metabolism ; Tubulin/*metabolism ; Tyrosine/*metabolism
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  • 113
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roman, Joe -- Kraska, James -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1258-60. doi: 10.1126/science.aad4247.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gund Institute for Ecological Economics, University of Vermont, Burlington, VT 05405, USA. jroman@uvm.edu. ; Stockton Center for the Study of International Law, U.S. Naval War College, Newport, RI 02841, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989232" target="_blank"〉PubMed〈/a〉
    Keywords: *Bays ; *Conservation of Natural Resources ; Cuba ; Diplomacy ; United States
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  • 114
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Byrd, Allyson L -- Segre, Julia A -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):224-6. doi: 10.1126/science.aad6753.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. Department of Bioinformatics, Boston University, Boston, MA 02215, USA. ; Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. jsegre@nhgri.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816362" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/adverse effects ; Clostridium difficile/pathogenicity ; Communicable Diseases/chemically induced/*microbiology ; Cross Infection/chemically induced/microbiology ; Diarrhea/chemically induced/microbiology ; Disease Susceptibility/chemically induced/microbiology ; Enterocolitis, Pseudomembranous/chemically induced/microbiology ; *Host-Pathogen Interactions ; Humans ; Mice ; *Microbial Consortia ; Symbiosis/drug effects
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  • 115
    Publication Date: 2016-01-30
    Description: Dietary antigens are normally rendered nonimmunogenic through a poorly understood "oral tolerance" mechanism that involves immunosuppressive regulatory T (Treg) cells, especially Treg cells induced from conventional T cells in the periphery (pTreg cells). Although orally introducing nominal protein antigens is known to induce such pTreg cells, whether a typical diet induces a population of pTreg cells under normal conditions thus far has been unknown. By using germ-free mice raised and bred on an elemental diet devoid of dietary antigens, we demonstrated that under normal conditions, the vast majority of the small intestinal pTreg cells are induced by dietary antigens from solid foods. Moreover, these pTreg cells have a limited life span, are distinguishable from microbiota-induced pTreg cells, and repress underlying strong immunity to ingested protein antigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Kwang Soon -- Hong, Sung-Wook -- Han, Daehee -- Yi, Jaeu -- Jung, Jisun -- Yang, Bo-Gie -- Lee, Jun Young -- Lee, Minji -- Surh, Charles D -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):858-63. doi: 10.1126/science.aac5560. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea. Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea. ; Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea. Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea. Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26822607" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/immunology ; Diet ; Dietary Proteins/*immunology ; Dyspepsia/*immunology ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life ; Immune Tolerance ; Immunity, Mucosal ; Intestine, Small/*immunology/*microbiology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory/*immunology
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  • 116
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruben, Adam -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):110. doi: 10.1126/science.352.6281.110.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Adam Ruben is a molecular biologist, science comedian, and the author of the Science Careers "Experimental Error" column. Learn more at adamruben.net.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034375" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/therapeutic use ; *Art ; *Career Choice ; *Career Mobility ; Humans ; Malaria/drug therapy ; Mice ; Molecular Biology/*education
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  • 117
    Publication Date: 2016-04-02
    Description: Recent studies have implicated long noncoding RNAs (lncRNAs) as regulators of many important biological processes. Here we report on the identification and characterization of a lncRNA, lnc13, that harbors a celiac disease-associated haplotype block and represses expression of certain inflammatory genes under homeostatic conditions. Lnc13 regulates gene expression by binding to hnRNPD, a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). Upon stimulation, lnc13 levels are reduced, thereby allowing increased expression of the repressed genes. Lnc13 levels are significantly decreased in small intestinal biopsy samples from patients with celiac disease, which suggests that down-regulation of lnc13 may contribute to the inflammation seen in this disease. Furthermore, the lnc13 disease-associated variant binds hnRNPD less efficiently than its wild-type counterpart, thus helping to explain how these single-nucleotide polymorphisms contribute to celiac disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Castellanos-Rubio, Ainara -- Fernandez-Jimenez, Nora -- Kratchmarov, Radomir -- Luo, Xiaobing -- Bhagat, Govind -- Green, Peter H R -- Schneider, Robert -- Kiledjian, Megerditch -- Bilbao, Jose Ramon -- Ghosh, Sankar -- R01-AI093985/AI/NIAID NIH HHS/ -- R01-DK102180/DK/NIDDK NIH HHS/ -- R01-GM067005/GM/NIGMS NIH HHS/ -- R37-AI33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):91-5. doi: 10.1126/science.aad0467.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ; Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country (UPV-EHU), BioCruces Research Institute, Leioa 48940, Basque Country, Spain. ; Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ; Center for Celiac Disease, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. ; Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. sg2715@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034373" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Celiac Disease/*genetics/pathology ; Down-Regulation ; Gene Expression Regulation ; *Genetic Predisposition to Disease ; Haplotypes ; Heterogeneous-Nuclear Ribonucleoproteins/genetics ; Humans ; Inflammation/*genetics ; Mice ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/*genetics
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  • 118
    Publication Date: 2016-03-12
    Description: The MYC oncogene codes for a transcription factor that is overexpressed in many human cancers. Here we show that MYC regulates the expression of two immune checkpoint proteins on the tumor cell surface: the innate immune regulator CD47 (cluster of differentiation 47) and the adaptive immune checkpoint PD-L1 (programmed death-ligand 1). Suppression of MYC in mouse tumors and human tumor cells caused a reduction in the levels of CD47 and PD-L1 messenger RNA and protein. MYC was found to bind directly to the promoters of the Cd47 and Pd-l1 genes. MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response. In contrast, when MYC was inactivated in tumors with enforced expression of CD47 or PD-L1, the immune response was suppressed, and tumors continued to grow. Thus, MYC appears to initiate and maintain tumorigenesis, in part, through the modulation of immune regulatory molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Casey, Stephanie C -- Tong, Ling -- Li, Yulin -- Do, Rachel -- Walz, Susanne -- Fitzgerald, Kelly N -- Gouw, Arvin M -- Baylot, Virginie -- Gutgemann, Ines -- Eilers, Martin -- Felsher, Dean W -- 1F32CA177139/CA/NCI NIH HHS/ -- 5T32AI07290/AI/NIAID NIH HHS/ -- CA 089305/CA/NCI NIH HHS/ -- CA 170378/CA/NCI NIH HHS/ -- CA 184384/CA/NCI NIH HHS/ -- U01 CA 114747/CA/NCI NIH HHS/ -- U01 CA 188383/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):227-31. doi: 10.1126/science.aac9935. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany. ; Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany. ; Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany. Theodor Boveri Institute, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany. ; Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. dfelsher@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26966191" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD274/*genetics ; Antigens, CD47/*genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/*immunology ; Down-Regulation ; *Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immune Tolerance/*genetics ; Jurkat Cells ; Lymphoma/genetics/immunology ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics/immunology ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; RNA, Small Interfering/genetics
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  • 119
    Publication Date: 2016-04-02
    Description: Host responses against metazoan parasites or an array of environmental substances elicit type 2 immunity. Despite its protective function, type 2 immunity also drives allergic diseases. The mechanisms that regulate the magnitude of the type 2 response remain largely unknown. Here, we show that genetic ablation of a receptor tyrosine kinase encoded byTyro3in mice or the functional neutralization of its ortholog in human dendritic cells resulted in enhanced type 2 immunity. Furthermore, the TYRO3 agonist PROS1 was induced in T cells by the quintessential type 2 cytokine, interleukin-4. T cell-specificPros1knockouts phenocopied the loss ofTyro3 Thus, a PROS1-mediated feedback from adaptive immunity engages a rheostat, TYRO3, on innate immune cells to limit the intensity of type 2 responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, Pamela Y -- Carrera Silva, Eugenio A -- De Kouchkovsky, Dimitri -- Joannas, Leonel D -- Hao, Liming -- Hu, Donglei -- Huntsman, Scott -- Eng, Celeste -- Licona-Limon, Paula -- Weinstein, Jason S -- Herbert, De'Broski R -- Craft, Joseph E -- Flavell, Richard A -- Repetto, Silvia -- Correale, Jorge -- Burchard, Esteban G -- Torgerson, Dara G -- Ghosh, Sourav -- Rothlin, Carla V -- HL004464/HL/NHLBI NIH HHS/ -- HL078885/HL/NHLBI NIH HHS/ -- HL088133/HL/NHLBI NIH HHS/ -- HL104608/HL/NHLBI NIH HHS/ -- HL117004/HL/NHLBI NIH HHS/ -- MD006902/MD/NIMHD NIH HHS/ -- R01 AI089824/AI/NIAID NIH HHS/ -- T32 AI007019/AI/NIAID NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):99-103. doi: 10.1126/science.aaf1358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. ; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. Laboratorio de Trombosis Experimental, Instituto de Medicina Experimental, Academia Nacional de Medicina-CONICET, Buenos Aires, 1425, Argentina. ; Department of Pathology, School of Medicine, Yale University, New Haven, CT 06520, USA. ; Department of Medicine, University of California San Francisco, CA 94158, USA. ; Department of Experimental Medicine, University of California San Francisco, CA 94158, USA. ; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. Department of Internal Medicine (Rheumatology), School of Medicine, Yale University, New Haven, CT 06520, USA. ; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. Howard Hughes Medical Institute, School of Medicine, Yale University, New Haven, CT 06520, USA. ; Instituto de Investigaciones en Microbiologia y Parasitologia Medica, University of Buenos Aires-CONICET, Buenos Aires, 1121, Argentina. Hospital de Clinicas Jose de San Martin, University of Buenos Aires, 1120, Argentina. ; Center for Research on Neuroimmunological Diseases, Raul Carrea Institute for Neurological Research (FLENI), Buenos Aires 1428, Argentina. ; Department of Medicine, University of California San Francisco, CA 94158, USA. Department of Bioengineering, School of Pharmacy, University of California San Francisco, CA 94158, USA. ; Department of Neurology, School of Medicine, Yale University, New Haven, CT 06520, USA. ; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. carla.rothlin@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034374" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity/*genetics ; Animals ; Asthma/genetics/*immunology ; Blood Proteins/antagonists & inhibitors/genetics/metabolism ; Dendritic Cells/immunology ; Disease Models, Animal ; Gene Knockout Techniques ; Host-Parasite Interactions/genetics/*immunology ; Humans ; Immunity, Innate/*genetics ; Interleukin-4/immunology/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nippostrongylus/immunology ; Pyroglyphidae/immunology ; Receptor Protein-Tyrosine Kinases/genetics/*physiology ; Strongylida Infections/immunology ; T-Lymphocytes/immunology
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  • 120
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-29
    Description: Despite decades of study, there are still many unanswered questions about metastasis, the process by which a localized cancer becomes a systemic disease. One of these questions is the nature of the tumor cells that give rise to metastases. Although conventional models suggest that metastases are seeded by single cells from the primary tumor, there is growing evidence that seeding requires the collective action of tumor cells traveling together in clusters. Here, we review this evidence, which comes from analysis of both experimental models and patient samples. We present a model of metastatic dissemination that highlights the activities of clusters of tumor cells that retain and require their epithelial properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheung, Kevin J -- Ewald, Andrew J -- P30 CA006973/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):167-9. doi: 10.1126/science.aaf6546.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; Departments of Cell Biology, Oncology, and Biomedical Engineering, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA. andrew.ewald@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27124449" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Epithelial Cells/pathology ; Humans ; Mice ; *Models, Biological ; Neoplasm Metastasis/*pathology ; Neoplasm Seeding ; Neoplasms, Experimental/pathology ; Neoplastic Cells, Circulating/*pathology
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  • 121
    Publication Date: 2016-01-02
    Description: Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Qi -- Yan, Menghong -- Cao, Zhonghong -- Li, Xin -- Zhang, Yunfang -- Shi, Junchao -- Feng, Gui-hai -- Peng, Hongying -- Zhang, Xudong -- Zhang, Ying -- Qian, Jingjing -- Duan, Enkui -- Zhai, Qiwei -- Zhou, Qi -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):397-400. doi: 10.1126/science.aad7977. Epub 2015 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89512 USA. ; Key Laboratory of Nutrition and Metabolism, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. University of Chinese Academy of Sciences, Beijing 100049, China. ; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Beijing Royal Integrative Medicine Hospital, Beijing University of Chinese Medicine, Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721680" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA Methylation ; Diet, High-Fat/*adverse effects ; *Epigenesis, Genetic ; Fathers ; GC Rich Sequence ; Male ; Metabolic Diseases/*genetics ; Mice ; Mice, Inbred C57BL ; Models, Animal ; RNA, Transfer/*genetics ; Spermatozoa
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  • 122
    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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  • 123
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kloor, Keith -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):699. doi: 10.1126/science.347.6223.699.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678635" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; Agriculture/*legislation & jurisprudence ; Biotechnology/*legislation & jurisprudence ; Commerce ; Food Labeling/*legislation & jurisprudence ; Food, Genetically Modified/*adverse effects ; Humans ; Research Personnel ; United States ; Universities
    Print ISSN: 0036-8075
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  • 124
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, Rachel -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):269. doi: 10.1126/science.348.6232.269.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883332" target="_blank"〉PubMed〈/a〉
    Keywords: Engineering/*education/manpower ; Faculty/*statistics & numerical data ; Female ; Humans ; Male ; Mathematics/*education/manpower ; Science/*education/manpower ; Sex Factors ; Technology/*education/manpower ; United States ; Women, Working/*statistics & numerical data
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  • 125
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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〉Hackett, Perry -- Carroll, Dana -- P01 HD032652/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1324. doi: 10.1126/science.347.6228.1324.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Cell Biology, and Development, Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. hacke004@umn.edu. ; Department of Biochemistry, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792322" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*legislation & jurisprudence ; Animals ; *Government Regulation ; *Organisms, Genetically Modified ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 126
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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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  • 127
    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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  • 128
    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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  • 129
    Publication Date: 2015-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Merrigan, Kathleen -- Griffin, Timothy -- Wilde, Parke -- Robien, Kimberly -- Goldberg, Jeanne -- Dietz, William -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):165-6. doi: 10.1126/science.aab2031. Epub 2015 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Trachtenberg School of Public Policy and Public Administration, the George Washington University, Washington, DC 20052, USA. kmerrigan@gwu.edu. ; Friedman School of Nutrition Science and Policy, Tufts University, Medford, MA 02155, USA. ; Milken Institute School of Public Health, the George Washington University, Washington, DC 20052, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26429883" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Diet/*standards ; Food Assistance ; Food Technology/*standards ; Humans ; *Nutrition Policy ; United States
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  • 130
    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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  • 131
    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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  • 132
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kohane, Isaac S -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):37-8. doi: 10.1126/science.aab1328. Epub 2015 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. isaac_kohane@harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138968" target="_blank"〉PubMed〈/a〉
    Keywords: *Evidence-Based Medicine ; Genomics/trends ; *Health Policy ; Humans ; Medical Record Linkage ; Reproducibility of Results ; United States
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  • 133
    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
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  • 134
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1454. doi: 10.1126/science.350.6267.1454.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680170" target="_blank"〉PubMed〈/a〉
    Keywords: Contract Services/*economics ; Ecology/*economics ; *Ecosystem ; United States
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  • 135
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kollipara, Puneet -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1403-4. doi: 10.1126/science.347.6229.1403-b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814561" target="_blank"〉PubMed〈/a〉
    Keywords: Agrochemicals ; Chemical Industry/*legislation & jurisprudence ; Conservation of Natural Resources/*legislation & jurisprudence ; Ecotoxicology/*legislation & jurisprudence ; Toxicity Tests ; United States ; United States Environmental Protection Agency
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  • 136
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):896. doi: 10.1126/science.350.6263.896.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586739" target="_blank"〉PubMed〈/a〉
    Keywords: *African Americans ; Biomedical Research/economics ; Biotechnology/*economics/*manpower ; Financial Support ; Government Programs ; Humans ; Laboratory Personnel/*economics ; National Institutes of Health (U.S.)/*economics ; Small Business/economics/trends ; United States
    Print ISSN: 0036-8075
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  • 137
    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
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  • 138
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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
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  • 139
    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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  • 140
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 141
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Sep 25;349(6255):1436-41. doi: 10.1126/science.349.6255.1436. Epub 2015 Sep 24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26404807" target="_blank"〉PubMed〈/a〉
    Keywords: Data Collection ; Environmental Monitoring/*methods/standards ; Foundations ; United States
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  • 142
    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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  • 143
    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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  • 144
    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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  • 145
    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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  • 146
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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〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):574. doi: 10.1126/science.349.6248.574.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250664" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Ecology/*economics ; Ecosystem ; Foundations ; United States
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  • 147
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):225. doi: 10.1126/science.349.6245.225. Epub 2015 Jul 16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26185225" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; Budgets ; National Institutes of Health (U.S.)/*economics ; Salaries and Fringe Benefits/*trends ; United States
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  • 148
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):16. doi: 10.1126/science.349.6243.16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138958" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Age Factors ; Animal Experimentation ; Animals ; *Attitude ; Data Collection ; Female ; Global Warming ; Humans ; Nuclear Energy ; Politics ; *Public Opinion ; *Research ; Sex Factors ; United States
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  • 149
    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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  • 150
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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〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 May 29;348(6238):956. doi: 10.1126/science.348.6238.956.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26023115" target="_blank"〉PubMed〈/a〉
    Keywords: Behavioral Sciences/*economics ; Climate Change/*economics ; Federal Government ; Financing, Government/*legislation & jurisprudence ; Foundations ; Social Sciences/*economics ; United States
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  • 151
    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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  • 152
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Apr 24;348(6233):384. doi: 10.1126/science.348.6233.384.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908803" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/*trends ; Financing, Government ; *National Institutes of Health (U.S.) ; *Peer Review, Research ; United States
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  • 153
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    Publication Date: 2015-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krupic, Julija -- New York, N.Y. -- Science. 2015 Oct 2;350(6256):47. doi: 10.1126/science.aad3002.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK. j.krupic@ucl.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26430112" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; Brain/*physiology/*ultrastructure ; *Distance Perception ; Fourier Analysis ; Humans ; Metric System ; Neurons/*physiology/*ultrastructure ; Rats ; Spatial Navigation/*physiology
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  • 154
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1054. doi: 10.1126/science.347.6226.1054.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745139" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; Biology/*education ; Curriculum ; *Faculty ; Knowledge ; *Professional Competence ; *Religion and Science ; Role ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeMarco, Emily -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):915-7. doi: 10.1126/science.349.6251.915.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315416" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Astacoidea/classification/genetics/physiology ; Coal Mining ; Ecosystem ; *Endangered Species/legislation & jurisprudence ; Environmental Pollution ; Genetic Speciation ; United States ; West Virginia
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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〉DeMarco, Emily -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):570-1. doi: 10.1126/science.349.6248.570.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250661" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Migration ; Animals ; Breeding ; *Butterflies ; *Conservation of Natural Resources ; Female ; Mexico ; Plant Nectar ; Population ; Seasons ; United States
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  • 157
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):602-5. doi: 10.1126/science.347.6222.602.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657228" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Career Mobility ; *Faculty ; Fellowships and Scholarships/*economics ; *Government Programs ; Mathematics/*education ; Science/*education ; United States
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  • 158
    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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  • 159
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):599-601. doi: 10.1126/science.347.6222.599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657226" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; *Financing, Government ; Research/*economics ; United States
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  • 160
    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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  • 161
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):466-7. doi: 10.1126/science.347.6221.466.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635067" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets/*legislation & jurisprudence ; Federal Government ; Financing, Government ; National Institutes of Health (U.S.)/*economics/legislation & jurisprudence ; *Politics ; Public Policy ; Research Support as Topic/legislation & jurisprudence ; United States ; United States Government Agencies/*economics/legislation & jurisprudence ; United States National Aeronautics and Space ; Administration/*economics/legislation & jurisprudence
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  • 162
    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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  • 163
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):221-2. doi: 10.1126/science.349.6245.221. Epub 2015 Jul 16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26185221" target="_blank"〉PubMed〈/a〉
    Keywords: Federal Government ; Humans ; Leadership ; Psychology/*ethics ; *Public Policy ; Security Measures/*ethics ; Social Change ; Societies, Scientific/ethics ; Torture/*ethics ; United States
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  • 164
    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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  • 165
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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〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):263-4. doi: 10.1126/science.350.6258.263.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472886" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/*ultrastructure ; *Computer Simulation ; Investments ; *Models, Neurological ; Neurons/*ultrastructure ; Neurosciences/*economics ; Rats
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  • 166
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):495-7. doi: 10.1126/science.347.6221.495.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635082" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Computer Security ; Financing, Government ; Humans ; *Mathematics ; *Privacy ; Research Support as Topic ; *Security Measures ; Societies ; Trust ; United States ; *United States Department of Defense/economics/ethics ; Universities
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  • 167
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Aubrey -- Birnbaum, Linda -- New York, N.Y. -- Science. 2015 May 15;348(6236):766-7. doi: 10.1126/science.348.6236.766-c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. miller.aubrey@nih.gov. ; National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977543" target="_blank"〉PubMed〈/a〉
    Keywords: Disaster Planning/*methods ; Humans ; National Institute of Environmental Health Sciences (U.S.) ; United States
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  • 168
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hand, Eric -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):813-4. doi: 10.1126/science.347.6224.813.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700494" target="_blank"〉PubMed〈/a〉
    Keywords: *Exobiology ; *Ice Cover ; *Minor Planets ; United States ; United States National Aeronautics and Space Administration
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  • 169
    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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  • 170
    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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  • 171
    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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  • 172
    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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  • 173
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Topik, Christopher -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1263. doi: 10.1126/science.aad4202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Christopher Topik is the director of Restoring America's Forests at The Nature Conservancy North America Region, Arlington, VA. ctopik@tnc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383924" target="_blank"〉PubMed〈/a〉
    Keywords: Disasters/*economics ; Federal Government ; Financial Management/legislation & jurisprudence ; Fires/*economics ; United States
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  • 174
    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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  • 175
    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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  • 176
    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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  • 177
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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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  • 178
    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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  • 179
    Publication Date: 2015-02-24
    Description: An important question in ecology is how mechanistic processes occurring among individuals drive large-scale patterns of community formation and change. Here we show that in two species of bluebirds, cycles of replacement of one by the other emerge as an indirect consequence of maternal influence on offspring behavior in response to local resource availability. Sampling across broad temporal and spatial scales, we found that western bluebirds, the more competitive species, bias the birth order of offspring by sex in a way that influences offspring aggression and dispersal, setting the stage for rapid increases in population density that ultimately result in the replacement of their sister species. Our results provide insight into how predictable community dynamics can occur despite the contingency of local behavioral interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duckworth, Renee A -- Belloni, Virginia -- Anderson, Samantha R -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):875-7. doi: 10.1126/science.1260154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. rad3@email.arizona.edu. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700519" target="_blank"〉PubMed〈/a〉
    Keywords: Androgens/analysis ; Animals ; *Biological Evolution ; Clutch Size ; *Competitive Behavior ; *Ecosystem ; Egg Yolk/chemistry ; Female ; Fires ; Male ; *Maternal Behavior ; Population Density ; Songbirds/*physiology ; United States
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  • 180
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-31
    Description: Massive data collection by businesses and governments calls into question traditional methods for protecting privacy, underpinned by two core principles: (i) notice, that there should be no data collection system whose existence is secret, and (ii) consent, that data collected for one purpose not be used for another without user permission. But notice, designated as a fundamental privacy principle in a different era, makes little sense in situations where collection consists of lots and lots of small amounts of information, whereas consent is no longer realistic, given the complexity and number of decisions that must be made. Thus, efforts to protect privacy by controlling use of data are gaining more attention. I discuss relevant technology, policy, and law, as well as some examples that can illuminate the way.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Landau, Susan -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):504-6. doi: 10.1126/science.aaa4961.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Worcester Polytechnic Institute, Worcester, MA 01609, USA. susan.landau@privacyink.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635089" target="_blank"〉PubMed〈/a〉
    Keywords: *Computer Security ; *Data Collection/legislation & jurisprudence ; Genetic Privacy/legislation & jurisprudence ; Humans ; *Information Dissemination/legislation & jurisprudence ; *Informed Consent ; *Internet/legislation & jurisprudence ; *Privacy/legislation & jurisprudence ; Security Measures ; United States
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  • 181
    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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  • 182
    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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  • 183
    Publication Date: 2015-03-15
    Description: After central nervous system (CNS) injury, inhibitory factors in the lesion scar and poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration of a blood-brain barrier-permeable microtubule-stabilizing drug, epothilone B (epoB), decreased scarring after rodent spinal cord injury (SCI) by abrogating polarization and directed migration of scar-forming fibroblasts. Conversely, epothilone B reactivated neuronal polarization by inducing concerted microtubule polymerization into the axon tip, which propelled axon growth through an inhibitory environment. Together, these drug-elicited effects promoted axon regeneration and improved motor function after SCI. With recent clinical approval, epothilones hold promise for clinical use after CNS injury.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445125/" 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/PMC4445125/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruschel, Jorg -- Hellal, Farida -- Flynn, Kevin C -- Dupraz, Sebastian -- Elliott, David A -- Tedeschi, Andrea -- Bates, Margaret -- Sliwinski, Christopher -- Brook, Gary -- Dobrindt, Kristina -- Peitz, Michael -- Brustle, Oliver -- Norenberg, Michael D -- Blesch, Armin -- Weidner, Norbert -- Bunge, Mary Bartlett -- Bixby, John L -- Bradke, Frank -- R01 HD057632/HD/NICHD NIH HHS/ -- R01 NS059866/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):347-52. doi: 10.1126/science.aaa2958. Epub 2015 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. ; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 Northwest 14th Terrace, Miami, FL33136, USA. ; Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstr. 200A, 69118 Heidelberg, Germany. ; Institute for Neuropathology, RWTH Aachen University, Steinbergweg 20, 52074, Aachen, Germany. Julich-Aachen Research Alliance-Translational Brain Medicine. ; Institute of Reconstructive Neurobiology, Life&Brain Center, University of Bonn and Hertie Foundation, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. ; Departments of Pathology, Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA. ; Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. frank.bradke@dzne.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25765066" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*drug effects/physiology ; Cell Movement/drug effects ; Cell Polarity/drug effects ; Cicatrix/pathology/*prevention & control ; Epothilones/*administration & dosage ; Fibroblasts/drug effects/pathology ; Humans ; Meninges/drug effects/pathology ; Motor Activity/drug effects ; Nerve Regeneration/*drug effects ; Neurons/drug effects/pathology ; Rats ; Spinal Cord Injuries/*drug therapy/pathology/physiopathology ; Tubulin Modulators/*administration & dosage
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  • 184
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breitling, Rainer -- Takano, Eriko -- Gardner, Timothy S -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):107. doi: 10.1126/science.aaa5253.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rainer Breitling is a Professor of Systems Biology at the University of Manchester, Manchester, UK, and an external expert to the European Commission Scientific Committees. rainer.breitling@manchester.ac.uk. ; Eriko Takano is a Professor of Synthetic Biology and Co-Director of the Manchester Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), University of Manchester, Manchester, UK, and an external expert to the European Commission Scientific Committees. eriko.takano@manchester.ac.uk. ; Timothy S. Gardner is Chief Executive Officer of Riffyn, Inc., in Oakland, CA, USA, and an external expert to the European Commission Scientific Committees. tg@riffyn.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25573995" target="_blank"〉PubMed〈/a〉
    Keywords: Europe ; European Union ; Risk Assessment/methods/standards ; Synthetic Biology/*trends ; United States
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  • 185
    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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  • 186
    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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  • 187
    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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  • 188
    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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  • 189
    Publication Date: 2015-03-31
    Description: During intracellular membrane trafficking, N-ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment protein (alpha-SNAP) disassemble the soluble NSF attachment protein receptor (SNARE) complex for recycling of the SNARE proteins. The molecular mechanism by which NSF disassembles the SNARE complex is largely unknown. Using single-molecule fluorescence spectroscopy and magnetic tweezers, we found that NSF disassembled a single SNARE complex in only one round of adenosine triphosphate (ATP) turnover. Upon ATP cleavage, the NSF hexamer developed internal tension with dissociation of phosphate ions. After latent time measuring tens of seconds, NSF released the built-up tension in a burst within 20 milliseconds, resulting in disassembly followed by immediate release of the SNARE proteins. Thus, NSF appears to use a "spring-loaded" mechanism to couple ATP hydrolysis and unfolding of substrate proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441202/" 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/PMC4441202/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ryu, Je-Kyung -- Min, Duyoung -- Rah, Sang-Hyun -- Kim, Soo Jin -- Park, Yongsoo -- Kim, Haesoo -- Hyeon, Changbong -- Kim, Ho Min -- Jahn, Reinhard -- Yoon, Tae-Young -- 3P01GM072694-05S1/GM/NIGMS NIH HHS/ -- P01 GM072694/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1485-9. doi: 10.1126/science.aaa5267.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Creative Research Initiative Center for Single-Molecule Systems Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea. Department of Physics, KAIST, Daejeon 305-701, South Korea. ; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, South Korea. ; Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Korea Institute for Advanced Study, Seoul 130-722, South Korea. ; Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. rjahn@gwdg.de tyyoon@kaist.ac.kr. ; National Creative Research Initiative Center for Single-Molecule Systems Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea. Department of Physics, KAIST, Daejeon 305-701, South Korea. rjahn@gwdg.de tyyoon@kaist.ac.kr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814585" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism ; Animals ; Cattle ; Cricetinae ; Fluorescence Resonance Energy Transfer ; Hydrolysis ; N-Ethylmaleimide-Sensitive Proteins/*metabolism ; Rats ; SNARE Proteins/*metabolism ; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins/*metabolism ; Spectrometry, Fluorescence
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  • 190
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morell, Virginia -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1302-7. doi: 10.1126/science.347.6228.1302.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792312" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Conservation of Natural Resources ; Female ; *Food Chain ; Humans ; Male ; *Predatory Behavior ; Puma ; Ruminants ; United States ; Ursidae ; Wolves
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  • 191
    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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  • 192
    Publication Date: 2015-08-01
    Description: The actin cross-linking domain (ACD) is an actin-specific toxin produced by several pathogens, including life-threatening spp. of Vibrio cholerae, Vibrio vulnificus, and Aeromonas hydrophila. Actin cross-linking by ACD is thought to lead to slow cytoskeleton failure owing to a gradual sequestration of actin in the form of nonfunctional oligomers. Here, we found that ACD converted cytoplasmic actin into highly toxic oligomers that potently "poisoned" the ability of major actin assembly proteins, formins, to sustain actin polymerization. Thus, ACD can target the most abundant cellular protein by using actin oligomers as secondary toxins to efficiently subvert cellular functions of actin while functioning at very low doses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648357/" 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/PMC4648357/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heisler, David B -- Kudryashova, Elena -- Grinevich, Dmitry O -- Suarez, Cristian -- Winkelman, Jonathan D -- Birukov, Konstantin G -- Kotha, Sainath R -- Parinandi, Narasimham L -- Vavylonis, Dimitrios -- Kovar, David R -- Kudryashov, Dmitri S -- R01 GM079265/GM/NIGMS NIH HHS/ -- R01 GM098430/GM/NIGMS NIH HHS/ -- R01 GM114666/GM/NIGMS NIH HHS/ -- R01 HL076259/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 31;349(6247):535-9. doi: 10.1126/science.aab4090.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. kudryashov.1@osu.edu kudryashova.1@osu.edu. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. ; Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA. ; Section of Pulmonary and Critical Care and Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. ; Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA. ; Department of Physics, Lehigh University, Bethlehem, PA 18015, USA. ; Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA. Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. kudryashov.1@osu.edu kudryashova.1@osu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26228148" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Animals ; Antigens, Bacterial/*chemistry/genetics/*toxicity ; Bacterial Toxins/*chemistry/genetics/*toxicity ; Cell Line ; Fetal Proteins/*antagonists & inhibitors ; Intestinal Mucosa/drug effects/metabolism ; Microfilament Proteins/*antagonists & inhibitors ; Nuclear Proteins/*antagonists & inhibitors ; Polymerization/drug effects ; Protein Structure, Tertiary ; Rats
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  • 193
    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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  • 194
    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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  • 195
    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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  • 196
    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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  • 197
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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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  • 198
    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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  • 199
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    Unknown
    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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  • 200
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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