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  • 101
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Leslie -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):404-5. doi: 10.1126/science.352.6284.404. Epub 2016 Apr 21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102461" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Agricultural Workers' Diseases/drug therapy/*epidemiology/*prevention & control ; Antimalarials/therapeutic use ; Artemisinins/therapeutic use ; Cambodia/epidemiology ; Drug Combinations ; Drug Substitution ; Farmers ; *Hevea ; Human Migration ; Humans ; Malaria, Falciparum/drug therapy/*epidemiology/*prevention & control ; Male ; Mefloquine/therapeutic use ; Mekong Valley/epidemiology ; *Rubber ; Young Adult
    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Leslie -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):403. doi: 10.1126/science.352.6284.403. Epub 2016 Apr 21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102460" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/pharmacology/*therapeutic use ; Artemisinins/pharmacology/*therapeutic use ; Drug Resistance/*genetics ; Humans ; Malaria, Falciparum/*drug therapy/epidemiology/*parasitology ; Mutation ; Myanmar/epidemiology ; Plasmodium falciparum/*drug effects/genetics
    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Leslie -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):398-402, 404-5. doi: 10.1126/science.352.6284.398. Epub 2016 Apr 21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102459" target="_blank"〉PubMed〈/a〉
    Keywords: Antimalarials/*pharmacology/therapeutic use ; Artemisinins/pharmacology/therapeutic use ; Cambodia/epidemiology ; Chloroquine/pharmacology/therapeutic use ; *Disease Eradication ; Drug Resistance, Microbial/*genetics ; Humans ; Malaria, Falciparum/epidemiology/*parasitology/*prevention & control ; Mekong Valley/epidemiology ; Plasmodium falciparum/*drug effects/genetics
    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: 2016-04-23
    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
    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Leslie -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):407. doi: 10.1126/science.352.6284.407. Epub 2016 Apr 21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102463" target="_blank"〉PubMed〈/a〉
    Keywords: Antimalarials/*administration & dosage ; Cambodia/epidemiology ; Disease Eradication/*methods ; Female ; Humans ; Malaria, Falciparum/epidemiology/*prevention & control ; Male ; *Patient Selection ; Pilot Projects ; Plasmodium falciparum/drug effects ; Rural Population
    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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  • 106
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sarrazin, Francois -- Lecomte, Jane -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):422-3. doi: 10.1126/science.352.6284.422-c. Epub 2016 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sorbonne Universites, UPMC Univ. Paris 06, Museum National d'Histoire Naturelle, CNRS, CESCO, UMR 7204, 75005 Paris, France. sarrazin@mnhn.fr. ; Ecologie Systematique Evolution, Univ. Paris-Sud, CNRS, AgroParisTech, Universite Paris-Saclay, 91400 Orsay, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102472" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Conservation of Natural Resources/*methods ; *Extinction, Biological ; Humans
    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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  • 107
    Publication Date: 2016-04-21
    Description: Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871315/" 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/PMC4871315/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beura, Lalit K -- Hamilton, Sara E -- Bi, Kevin -- Schenkel, Jason M -- Odumade, Oludare A -- Casey, Kerry A -- Thompson, Emily A -- Fraser, Kathryn A -- Rosato, Pamela C -- Filali-Mouhim, Ali -- Sekaly, Rafick P -- Jenkins, Marc K -- Vezys, Vaiva -- Haining, W Nicholas -- Jameson, Stephen C -- Masopust, David -- 1R01AI111671/AI/NIAID NIH HHS/ -- R01 AI075168/AI/NIAID NIH HHS/ -- R01 AI084913/AI/NIAID NIH HHS/ -- R01 AI111671/AI/NIAID NIH HHS/ -- R01 AI116678/AI/NIAID NIH HHS/ -- R01AI075168/AI/NIAID NIH HHS/ -- R01AI084913/AI/NIAID NIH HHS/ -- R01AI116678/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Apr 28;532(7600):512-6. doi: 10.1038/nature17655. Epub 2016 Apr 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota 55414, USA. ; Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55414, USA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Pediatric Hematology and Oncology, Children's Hospital, Boston, Massachusetts 02115, USA. ; Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27096360" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animal Husbandry/*methods ; Animals ; Animals, Laboratory/*immunology ; Animals, Wild/*immunology ; Cell Differentiation ; *Environment ; Environmental Exposure ; Female ; Humans ; Immune System/*immunology ; Immunity/*immunology ; Immunity, Innate/immunology ; Immunologic Memory ; Infant, Newborn ; Male ; Mice ; *Models, Animal ; Phenotype ; Specific Pathogen-Free Organisms ; T-Lymphocytes/cytology/immunology ; Virus Diseases/immunology/virology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 108
    Publication Date: 2016-04-21
    Description: Genome-wide association studies (GWAS) have identified numerous genetic variants associated with complex diseases, but mechanistic insights are impeded by a lack of understanding of how specific risk variants functionally contribute to the underlying pathogenesis. It has been proposed that cis-acting effects of non-coding risk variants on gene expression are a major factor for phenotypic variation of complex traits and disease susceptibility. Recent genome-scale epigenetic studies have highlighted the enrichment of GWAS-identified variants in regulatory DNA elements of disease-relevant cell types. Furthermore, single nucleotide polymorphism (SNP)-specific changes in transcription factor binding are correlated with heritable alterations in chromatin state and considered a major mediator of sequence-dependent regulation of gene expression. Here we describe a novel strategy to functionally dissect the cis-acting effect of genetic risk variants in regulatory elements on gene expression by combining genome-wide epigenetic information with clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in human pluripotent stem cells. By generating a genetically precisely controlled experimental system, we identify a common Parkinson's disease associated risk variant in a non-coding distal enhancer element that regulates the expression of alpha-synuclein (SNCA), a key gene implicated in the pathogenesis of Parkinson's disease. Our data suggest that the transcriptional deregulation of SNCA is associated with sequence-dependent binding of the brain-specific transcription factors EMX2 and NKX6-1. This work establishes an experimental paradigm to functionally connect genetic variation with disease-relevant phenotypes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soldner, Frank -- Stelzer, Yonatan -- Shivalila, Chikdu S -- Abraham, Brian J -- Latourelle, Jeanne C -- Barrasa, M Inmaculada -- Goldmann, Johanna -- Myers, Richard H -- Young, Richard A -- Jaenisch, Rudolf -- 1R01NS088538-01/NS/NINDS NIH HHS/ -- 2R01MH104610-15/MH/NIMH NIH HHS/ -- R01 NS088538/NS/NINDS NIH HHS/ -- England -- Nature. 2016 May 5;533(7601):95-9. doi: 10.1038/nature17939. Epub 2016 Apr 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Whitehead Institute, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; Department of Biology, Massachusetts Institute of Technology, 31 Ames Street, Cambridge, Massachusetts 02139, USA. ; Department of Neurology, Boston University School of Medicine, Boston, Masssachusetts 02118, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27096366" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Brain/metabolism ; CRISPR-Cas Systems/genetics ; Enhancer Elements, Genetic/*genetics ; Epigenesis, Genetic/genetics ; *Gene Expression Regulation ; Genetic Engineering ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; Homeodomain Proteins/metabolism ; Humans ; Models, Genetic ; Parkinson Disease/*genetics ; Pluripotent Stem Cells/metabolism ; Risk ; Transcription Factors/metabolism ; alpha-Synuclein/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 109
    Publication Date: 2016-04-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abeliovich, Asa -- Rhinn, Herve -- England -- Nature. 2016 May 5;533(7601):40-1. doi: 10.1038/nature17891. Epub 2016 Apr 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pathology, Cell Biology and Neurology, and the Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27096361" target="_blank"〉PubMed〈/a〉
    Keywords: Enhancer Elements, Genetic/*genetics ; *Gene Expression Regulation ; Genetic Predisposition to Disease/*genetics ; Humans ; Parkinson Disease/*genetics ; alpha-Synuclein/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 110
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Eryn -- England -- Nature. 2016 Apr 7;532(7597):137-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27092378" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Architectural Accessibility ; *Awareness ; Career Choice ; *Disabled Persons/psychology/statistics & numerical data ; *Employment/statistics & numerical data ; Female ; Hemiptera/physiology ; Humans ; Laboratories/manpower ; Male ; *Research Personnel/psychology/statistics & numerical data ; Science/education/*manpower ; *Self-Help Devices ; Social Stigma ; Students/psychology/statistics & numerical data ; Universities/manpower ; Workplace
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 111
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, Andrew -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):280-1. doi: 10.1126/science.352.6283.280.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081048" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeology ; Estonia ; History, Ancient ; Humans ; Ships ; Skeleton ; Slavery/*history ; Sweden
    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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  • 112
    Publication Date: 2016-04-16
    Description: The nuclear pore complex (NPC) controls the transport of macromolecules between the nucleus and cytoplasm, but its molecular architecture has thus far remained poorly defined. We biochemically reconstituted NPC core protomers and elucidated the underlying protein-protein interaction network. Flexible linker sequences, rather than interactions between the structured core scaffold nucleoporins, mediate the assembly of the inner ring complex and its attachment to the NPC coat. X-ray crystallographic analysis of these scaffold nucleoporins revealed the molecular details of their interactions with the flexible linker sequences and enabled construction of full-length atomic structures. By docking these structures into the cryoelectron tomographic reconstruction of the intact human NPC and validating their placement with our nucleoporin interactome, we built a composite structure of the NPC symmetric core that contains ~320,000 residues and accounts for ~56 megadaltons of the NPC's structured mass. Our approach provides a paradigm for the structure determination of similarly complex macromolecular assemblies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Daniel H -- Stuwe, Tobias -- Schilbach, Sandra -- Rundlet, Emily J -- Perriches, Thibaud -- Mobbs, George -- Fan, Yanbin -- Thierbach, Karsten -- Huber, Ferdinand M -- Collins, Leslie N -- Davenport, Andrew M -- Jeon, Young E -- Hoelz, Andre -- 5 T32 GM07616/GM/NIGMS NIH HHS/ -- ACB-12002/PHS HHS/ -- AGM-12006/PHS HHS/ -- R01 GM111461/GM/NIGMS NIH HHS/ -- R01-GM111461/GM/NIGMS NIH HHS/ -- T32 GM007616/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):aaf1015. doi: 10.1126/science.aaf1015. Epub 2016 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA. ; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA. hoelz@caltech.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081075" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Cytoplasm/metabolism ; Electron Microscope Tomography ; Fungal Proteins/chemistry/genetics/metabolism ; Humans ; Molecular Sequence Data ; Nuclear Pore/chemistry/*metabolism/*ultrastructure ; Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism ; *Protein Interaction Maps ; Protein Structure, Tertiary ; Protein Subunits/chemistry/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 113
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):284-7. doi: 10.1126/science.352.6283.284.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081051" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic ; Female ; Fetal Diseases/*prevention & control ; Humans ; Osteogenesis Imperfecta/*prevention & control ; Pregnancy ; *Stem Cell Transplantation ; *Stem Cells
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 114
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):286. doi: 10.1126/science.352.6283.286.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081052" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic ; Female ; Fetal Growth Retardation/*therapy ; Gene Transfer Techniques ; Genetic Therapy/*methods ; Humans ; Placenta ; Pregnancy ; Uterine Artery ; Vascular Endothelial Growth Factor A/*genetics
    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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  • 115
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLaughlin, Kathleen -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):283. doi: 10.1126/science.352.6283.283.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kathleen McLaughlin is a writer in Beijing.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081050" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; Aging ; China/epidemiology ; *Family Relations ; Female ; Human Migration ; Humans ; Male ; Rural Population/*statistics & numerical data ; Sociology ; Suicide/*statistics & numerical data
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 116
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):277-8. doi: 10.1126/science.352.6283.277.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081045" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Brain ; *Datasets as Topic ; European Union ; Humans ; International Cooperation ; Neurosciences/*trends ; United States
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 117
    Publication Date: 2016-04-16
    Description: Drug resistance compromises control of malaria. Here, we show that resistance to a commonly used antimalarial medication, atovaquone, is apparently unable to spread. Atovaquone pressure selects parasites with mutations in cytochrome b, a respiratory protein with low but essential activity in the mammalian blood phase of the parasite life cycle. Resistance mutations rescue parasites from the drug but later prove lethal in the mosquito phase, where parasites require full respiration. Unable to respire efficiently, resistant parasites fail to complete mosquito development, arresting their life cycle. Because cytochrome b is encoded by the maternally inherited parasite mitochondrion, even outcrossing with wild-type strains cannot facilitate spread of resistance. Lack of transmission suggests that resistance will be unable to spread in the field, greatly enhancing the utility of atovaquone in malaria control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goodman, Christopher D -- Siregar, Josephine E -- Mollard, Vanessa -- Vega-Rodriguez, Joel -- Syafruddin, Din -- Matsuoka, Hiroyuki -- Matsuzaki, Motomichi -- Toyama, Tomoko -- Sturm, Angelika -- Cozijnsen, Anton -- Jacobs-Lorena, Marcelo -- Kita, Kiyoshi -- Marzuki, Sangkot -- McFadden, Geoffrey I -- AI031478/AI/NIAID NIH HHS/ -- RR00052/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):349-53. doi: 10.1126/science.aad9279.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. gim@unimelb.edu.au deang@unimelb.edu.au. ; School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia. Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ; School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. ; Johns Hopkins University Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology, Malaria Research Institute, Baltimore, MD 21205, USA. ; Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia. Department of Parasitology, Faculty of Medicine, Hasanuddin University, Jalan Perintis Kemerdekaan Km10, Makassar 90245, Indonesia. ; Division of Medical Zoology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. ; Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ; Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. School of Tropical Medicine and Global Health, Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan. ; Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081071" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/*parasitology ; Antimalarials/*pharmacology/therapeutic use ; Atovaquone/*pharmacology/therapeutic use ; Cell Line ; Cytochromes b/*genetics ; Drug Resistance/*genetics ; Genes, Mitochondrial/genetics ; Humans ; Life Cycle Stages/drug effects/genetics ; Malaria/drug therapy/*parasitology/transmission ; Male ; Mice ; Mitochondria/*genetics ; Mutation ; Plasmodium berghei/*drug effects/genetics/growth & development ; Selection, Genetic
    Print ISSN: 0036-8075
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    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hudson-Edwards, Karen -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):288-90. doi: 10.1126/science.aaf3354.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth and Planetary Sciences, Birkbeck, University of London, London WC1E 7HX, UK. k.hudson-edwards@bbk.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081053" target="_blank"〉PubMed〈/a〉
    Keywords: Environmental Restoration and Remediation/*methods ; Humans ; Industrial Waste/*prevention & control ; *Mining ; *Solid Waste ; Waste Management/*methods
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 119
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, Brian -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):295-6. doi: 10.1126/science.aaf7735.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648 Singapore. brian.burke@imb.a-star.edu.sg.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081057" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Movement ; *DNA Breaks, Double-Stranded ; Endosomal Sorting Complexes Required for Transport/*metabolism ; Humans ; Neoplasms/*pathology ; Nuclear Envelope/*pathology/*ultrastructure ; *Tumor Microenvironment
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  • 120
    Publication Date: 2016-04-16
    Description: Nuclear pore complexes (NPCs) are 110-megadalton assemblies that mediate nucleocytoplasmic transport. NPCs are built from multiple copies of ~30 different nucleoporins, and understanding how these nucleoporins assemble into the NPC scaffold imposes a formidable challenge. Recently, it has been shown how the Y complex, a prominent NPC module, forms the outer rings of the nuclear pore. However, the organization of the inner ring has remained unknown until now. We used molecular modeling combined with cross-linking mass spectrometry and cryo-electron tomography to obtain a composite structure of the inner ring. This architectural map explains the vast majority of the electron density of the scaffold. We conclude that despite obvious differences in morphology and composition, the higher-order structure of the inner and outer rings is unexpectedly similar.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kosinski, Jan -- Mosalaganti, Shyamal -- von Appen, Alexander -- Teimer, Roman -- DiGuilio, Amanda L -- Wan, William -- Bui, Khanh Huy -- Hagen, Wim J H -- Briggs, John A G -- Glavy, Joseph S -- Hurt, Ed -- Beck, Martin -- 1R21AG047433-01/AG/NIA NIH HHS/ -- R21 AG047433/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):363-5. doi: 10.1126/science.aaf0643.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. ; Biochemistry Center of Heidelberg University, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany. ; Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, 507 River Street, Hoboken, NJ 07030, USA. ; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. ; Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081072" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Cryoelectron Microscopy ; Electron Microscope Tomography ; HeLa Cells ; Humans ; Mass Spectrometry ; Models, Molecular ; Nuclear Matrix/metabolism/ultrastructure ; Nuclear Pore/*metabolism/*ultrastructure ; Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levine, Alaina -- England -- Nature. 2016 Apr 14;532(7598):273-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081683" target="_blank"〉PubMed〈/a〉
    Keywords: Archives ; Biomedical Research/*ethics/*legislation & jurisprudence ; Breast Neoplasms/genetics ; Confidentiality/*ethics/*legislation & jurisprudence ; Female ; *Government Regulation ; Humans ; Informed Consent/ethics/legislation & jurisprudence ; Pedigree
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 122
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willyard, Cassandra -- England -- Nature. 2016 Apr 14;532(7598):166-8. doi: 10.1038/532166a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075079" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/economics/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/economics/*therapeutic use ; Clinical Trials as Topic ; DNA Mutational Analysis ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm/*drug effects/genetics ; *Evolution, Molecular ; Female ; Humans ; Immunotherapy, Adoptive/economics/trends ; Mice ; Molecular Targeted Therapy/economics/*methods/trends ; Mutation/*genetics ; Neoplasm Metastasis/drug therapy/genetics/pathology ; Neoplasm Recurrence, Local/chemically induced/genetics/prevention & control ; Neoplasms/*drug therapy/*genetics/pathology ; Selection, Genetic/*drug effects/genetics ; Tumor Microenvironment/drug effects
    Print ISSN: 0028-0836
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  • 123
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Melott, Adrian L -- England -- Nature. 2016 Apr 7;532(7597):40-1. doi: 10.1038/532040a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Astronomy, University of Kansas, Lawrence, Kansas 66045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078562" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Climate Change/history ; *Earth (Planet) ; Extinction, Biological ; Geologic Sediments/chemistry ; History, Ancient ; Humans ; Iron Radioisotopes/*analysis/chemistry ; Stars, Celestial/*chemistry ; Time Factors
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  • 124
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2016 Apr 14;532(7598):155-6. doi: 10.1038/532155a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075072" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/virology ; Angola/epidemiology ; Animals ; Asia/epidemiology ; Child ; Cities/epidemiology ; Disease Outbreaks/statistics & numerical data ; *Fear ; Haplorhini/virology ; Humans ; South America/epidemiology ; Strategic Stockpile/statistics & numerical data ; Vaccination/statistics & numerical data ; World Health Organization ; Yellow Fever/*epidemiology/*transmission/virology ; Yellow Fever Vaccine/administration & dosage/supply & distribution
    Print ISSN: 0028-0836
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  • 125
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roth, Alvin E -- England -- Nature. 2016 Apr 14;532(7598):178. doi: 10.1038/532178a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford University, California, USA. He shared the 2012 Nobel Memorial Prize in Economic Sciences with Lloyd Shapley.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075091" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Economics/*history ; Female ; *Game Theory ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Marketing/history ; Marriage/psychology ; Mathematics/*history ; Nobel Prize ; United States
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  • 126
    Publication Date: 2016-04-15
    Description: Somatic mutations are the driving force of cancer genome evolution. The rate of somatic mutations appears to be greatly variable across the genome due to variations in chromatin organization, DNA accessibility and replication timing. However, other variables that may influence the mutation rate locally are unknown, such as a role for DNA-binding proteins, for example. Here we demonstrate that the rate of somatic mutations in melanomas is highly increased at active transcription factor binding sites and nucleosome embedded DNA, compared to their flanking regions. Using recently available excision-repair sequencing (XR-seq) data, we show that the higher mutation rate at these sites is caused by a decrease of the levels of nucleotide excision repair (NER) activity. Our work demonstrates that DNA-bound proteins interfere with the NER machinery, which results in an increased rate of DNA mutations at the protein binding sites. This finding has important implications for our understanding of mutational and DNA repair processes and in the identification of cancer driver mutations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sabarinathan, Radhakrishnan -- Mularoni, Loris -- Deu-Pons, Jordi -- Gonzalez-Perez, Abel -- Lopez-Bigas, Nuria -- England -- Nature. 2016 Apr 14;532(7598):264-7. doi: 10.1038/nature17661.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain. ; Institucio Catalana de Recerca i Estudis Avancats (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075101" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; DNA/*genetics/*metabolism ; *DNA Repair ; DNA, Neoplasm/genetics/metabolism ; DNA-Binding Proteins/*metabolism ; Gene Expression Regulation, Neoplastic/genetics ; Genome, Human/genetics ; Humans ; Lung Neoplasms/genetics ; Melanoma/*genetics ; Mutagenesis/*genetics ; *Mutation Rate ; Nucleosomes/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding ; Transcription Factors/*metabolism
    Print ISSN: 0028-0836
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  • 127
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Webster, Andrew -- England -- Nature. 2016 Apr 7;532(7597):7. doi: 10.1038/532007a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Director of the Science and Technology Studies Unit (SATSU) at the University of York, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078528" target="_blank"〉PubMed〈/a〉
    Keywords: *Communication ; Great Britain ; Humans ; Lobbying ; *Public Opinion ; Public Policy ; *Research Personnel ; Social Sciences/*trends
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  • 128
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- Abbott, Alison -- England -- Nature. 2016 Apr 7;532(7597):18. doi: 10.1038/nature.2016.19672.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078546" target="_blank"〉PubMed〈/a〉
    Keywords: Brain/*anatomy & histology/cytology/*physiology ; Computer Simulation ; *Computers ; Humans ; Models, Biological ; Neurosciences/*methods/trends ; *Software
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  • 129
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frank, John -- England -- Nature. 2016 Apr 14;532(7598):149. doi: 10.1038/532149a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Edinburgh, UK, and is professor emeritus at the University of Toronto, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075060" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/administration & dosage ; Commerce/statistics & numerical data ; Computers/utilization ; Diet/economics/statistics & numerical data ; *Empirical Research ; Feces/microbiology ; Food/economics/statistics & numerical data ; Humans ; Internationality ; Obesity/economics/*epidemiology/*etiology ; Overweight/economics/epidemiology ; Pandemics/economics/*statistics & numerical data ; Prevalence ; Sedentary Lifestyle ; Television/utilization
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  • 130
    Publication Date: 2016-04-15
    Description: Humans routinely solve problems of immense computational complexity by intuitively forming simple, low-dimensional heuristic strategies. Citizen science (or crowd sourcing) is a way of exploiting this ability by presenting scientific research problems to non-experts. 'Gamification'--the application of game elements in a non-game context--is an effective tool with which to enable citizen scientists to provide solutions to research problems. The citizen science games Foldit, EteRNA and EyeWire have been used successfully to study protein and RNA folding and neuron mapping, but so far gamification has not been applied to problems in quantum physics. Here we report on Quantum Moves, an online platform gamifying optimization problems in quantum physics. We show that human players are able to find solutions to difficult problems associated with the task of quantum computing. Players succeed where purely numerical optimization fails, and analyses of their solutions provide insights into the problem of optimization of a more profound and general nature. Using player strategies, we have thus developed a few-parameter heuristic optimization method that efficiently outperforms the most prominent established numerical methods. The numerical complexity associated with time-optimal solutions increases for shorter process durations. To understand this better, we produced a low-dimensional rendering of the optimization landscape. This rendering reveals why traditional optimization methods fail near the quantum speed limit (that is, the shortest process duration with perfect fidelity). Combined analyses of optimization landscapes and heuristic solution strategies may benefit wider classes of optimization problems in quantum physics and beyond.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sorensen, Jens Jakob W H -- Pedersen, Mads Kock -- Munch, Michael -- Haikka, Pinja -- Jensen, Jesper Halkjaer -- Planke, Tilo -- Andreasen, Morten Ginnerup -- Gajdacz, Miroslav -- Molmer, Klaus -- Lieberoth, Andreas -- Sherson, Jacob F -- England -- Nature. 2016 Apr 14;532(7598):210-3. doi: 10.1038/nature17620.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075097" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; *Crowdsourcing ; *Games, Experimental ; Humans ; *Intuition ; Optical Tweezers ; *Problem Solving ; *Quantum Theory ; Video Games/*psychology
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    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anthes, Emily -- England -- Nature. 2016 Apr 7;532(7597):20-3. doi: 10.1038/532020a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078548" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic ; Depression/prevention & control/psychology/therapy ; Developing Countries ; *Health Services Accessibility ; Humans ; Mental Health/*trends ; Mobile Applications/*trends/utilization ; Pilot Projects ; Psychiatry/instrumentation/*methods ; Public Health/instrumentation/*methods ; Self Care/instrumentation/*methods ; Smartphone/supply & distribution/utilization ; Stress Disorders, Post-Traumatic/psychology/rehabilitation/therapy ; Telemedicine/instrumentation/*trends
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  • 132
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maniscalco, Sabrina -- England -- Nature. 2016 Apr 14;532(7598):184-5. doi: 10.1038/532184a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Turku Centre for Quantum Physics, Department of Physics and Astronomy, University of Turku, Turku 20014, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075093" target="_blank"〉PubMed〈/a〉
    Keywords: *Crowdsourcing ; *Games, Experimental ; Humans ; *Intuition ; *Problem Solving ; *Quantum Theory ; Video Games/*psychology
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  • 133
    Publication Date: 2016-04-15
    Description: Promoters are DNA sequences that have an essential role in controlling gene expression. While recent whole cancer genome analyses have identified numerous hotspots of somatic point mutations within promoters, many have not yet been shown to perturb gene expression or drive cancer development. As such, positive selection alone may not adequately explain the frequency of promoter point mutations in cancer genomes. Here we show that increased mutation density at gene promoters can be linked to promoter activity and differential nucleotide excision repair (NER). By analysing 1,161 human cancer genomes across 14 cancer types, we find evidence for increased local density of somatic point mutations within the centres of DNase I-hypersensitive sites (DHSs) in gene promoters. Mutated DHSs were strongly associated with transcription initiation activity, in which active promoters but not enhancers of equal DNase I hypersensitivity were most mutated relative to their flanking regions. Notably, analysis of genome-wide maps of NER shows that NER is impaired within the DHS centre of active gene promoters, while XPC-deficient skin cancers do not show increased promoter mutation density, pinpointing differential NER as the underlying cause of these mutation hotspots. Consistent with this finding, we observe that melanomas with an ultraviolet-induced DNA damage mutation signature show greatest enrichment of promoter mutations, whereas cancers that are not highly dependent on NER, such as colon cancer, show no sign of such enrichment. Taken together, our analysis has uncovered the presence of a previously unknown mechanism linking transcription initiation and NER as a major contributor of somatic point mutation hotspots at active gene promoters in cancer genomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perera, Dilmi -- Poulos, Rebecca C -- Shah, Anushi -- Beck, Dominik -- Pimanda, John E -- Wong, Jason W H -- England -- Nature. 2016 Apr 14;532(7598):259-63. doi: 10.1038/nature17437.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Prince of Wales Clinical School and Lowy Cancer Research Centre, UNSW Australia, Sydney 2052, Australia. ; Department of Haematology, Prince of Wales Hospital, Sydney 2031, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075100" target="_blank"〉PubMed〈/a〉
    Keywords: Colonic Neoplasms/genetics ; DNA Damage/genetics ; DNA Repair/*genetics/radiation effects ; Deoxyribonuclease I/metabolism ; Enhancer Elements, Genetic/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Genome, Human/*genetics ; Humans ; Lung Neoplasms/genetics ; Melanoma/genetics ; Mutagenesis/*genetics ; *Mutation Rate ; Neoplasms/*genetics ; Point Mutation/genetics ; Promoter Regions, Genetic/*genetics ; *Transcription Initiation, Genetic ; Ultraviolet Rays
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  • 134
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2016 Apr 7;532(7597):16. doi: 10.1038/nature.2016.19655.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078543" target="_blank"〉PubMed〈/a〉
    Keywords: Brain/abnormalities/cytology/metabolism/virology ; Female ; *Fetal Research/economics/legislation & jurisprudence ; Fetus/*abnormalities/*virology ; Humans ; Microcephaly/*etiology/*virology ; Neural Stem Cells/metabolism/virology ; Organoids/metabolism/virology ; Placenta/cytology/metabolism/virology ; Pregnancy ; Proto-Oncogene Proteins/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Tissue and Organ Procurement ; Trophoblasts/metabolism/virology ; Zika Virus/*pathogenicity ; Zika Virus Infection/*complications/congenital/virology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 135
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    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chi, Kelly Rae -- England -- Nature. 2016 Apr 14;532(7598):269-71. doi: 10.1038/532269a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075102" target="_blank"〉PubMed〈/a〉
    Keywords: Aged, 80 and over ; Biopsy/economics/*methods ; Blood Platelets/cytology ; DNA Mutational Analysis/economics/methods ; DNA, Neoplasm/*blood/genetics ; Drug Resistance, Neoplasm/genetics ; Exosomes/genetics ; Female ; Humans ; Neoplasm Metastasis/diagnosis/genetics ; Neoplasm Recurrence, Local/blood/diagnosis/genetics ; Neoplasms/*blood/*diagnosis/drug therapy/genetics ; Neoplastic Cells, Circulating/metabolism ; Phagocytosis ; Polymerase Chain Reaction ; Reproducibility of Results ; Sensitivity and Specificity
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  • 136
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    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khurana, Ekta -- England -- Nature. 2016 Apr 14;532(7598):181-2. doi: 10.1038/532181a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Meyer Cancer Center and Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075092" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*genetics/*metabolism ; DNA Repair/*genetics ; DNA-Binding Proteins/*metabolism ; Genome, Human/*genetics ; Humans ; Melanoma/*genetics ; Mutagenesis/*genetics ; *Mutation Rate ; Neoplasms/*genetics ; Promoter Regions, Genetic/*genetics ; Transcription Factors/*metabolism ; *Transcription Initiation, Genetic
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  • 137
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Pamela Y -- Saxena, Shekhar -- England -- Nature. 2016 Apr 7;532(7597):25-7. doi: 10.1038/532025a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Office for Research on Disparities & Global Mental Health, US National Institute of Mental Health, Bethesda, Maryland, USA. ; Department of Mental Health and Substance Abuse, World Health Organization, Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078549" target="_blank"〉PubMed〈/a〉
    Keywords: Behavioral Research ; Humans ; *International Cooperation ; Mental Health/economics/manpower/*statistics & numerical data ; Mental Health Services/economics/manpower/*organization & administration/supply & ; distribution ; Treatment Outcome ; United Nations ; World Health Organization
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  • 138
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bruggeman, Jeroen -- England -- Nature. 2016 Apr 14;532(7598):177. doi: 10.1038/532177e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Amsterdam, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075089" target="_blank"〉PubMed〈/a〉
    Keywords: *Cooperative Behavior ; Female ; Humans ; *Interpersonal Relations ; Male ; *Morals ; Punishment/*psychology ; *Religion and Psychology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 139
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Apr 14;532(7598):162-4. doi: 10.1038/532162a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075078" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/administration & ; dosage/immunology/pharmacology/therapeutic use ; Antigens, CD40/antagonists & inhibitors ; Antineoplastic Combined Chemotherapy Protocols/administration & ; dosage/pharmacology/*therapeutic use ; CTLA-4 Antigen/antagonists & inhibitors/immunology ; Cancer Vaccines/administration & dosage/immunology/therapeutic use ; Child ; Clinical Trials as Topic ; Endpoint Determination ; Epigenesis, Genetic/drug effects ; Humans ; *Immunotherapy/trends ; Melanoma/drug therapy/immunology ; Mice ; Neoplasms/*drug therapy/*immunology/therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/mortality ; Survivors ; T-Lymphocytes/drug effects/immunology
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 140
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santarem, Frederico -- England -- Nature. 2016 Apr 14;532(7598):177. doi: 10.1038/532177b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Centre in Biodiversity and Genetic Resources (CIBIO/InBIO), Porto, Portugal.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Beekeeping/economics ; Bees/physiology ; Ecosystem ; Europe ; Humans ; *Introduced Species/economics ; *Pollination ; Predatory Behavior/physiology ; Wasps/pathogenicity/*physiology
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  • 141
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    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Apr 7;532(7597):6. doi: 10.1038/532006a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078527" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/economics/*trends ; Developed Countries ; Developing Countries ; Genetics, Medical ; Humans ; Mental Disorders/*economics/*epidemiology/genetics/therapy ; Mental Health/economics/*trends ; Social Stigma ; United Nations ; World Health Organization
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 142
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Apr 7;532(7597):5. doi: 10.1038/532005a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078526" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/virology ; Angola/epidemiology ; Animals ; Ebola Vaccines/supply & distribution ; Hemorrhagic Fever, Ebola/epidemiology/prevention & control ; Humans ; Mosquito Control/*statistics & numerical data/trends ; Strategic Stockpile/economics/*statistics & numerical data ; Vaccination/economics/*statistics & numerical data ; Yellow Fever/*epidemiology/prevention & control ; Yellow Fever Vaccine/economics/supply & distribution
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 143
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibney, Elizabeth -- England -- Nature. 2016 Apr 14;532(7598):160-1. doi: 10.1038/532160a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075076" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; *Games, Experimental ; Humans ; *Intuition ; Mathematics ; Photic Stimulation ; *Problem Solving ; *Quantum Theory ; Video Games/*psychology
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  • 144
    Publication Date: 2016-04-14
    Description: Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes. A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology. Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg(2+)]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago. Given the essential role of Mg(2+) as a cofactor for ATP, a functional consequence of [Mg(2+)]i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg(2+) availability has potential to impact upon many of the cell's more than 600 MgATP-dependent enzymes and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR is regulated through [Mg(2+)]i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feeney, Kevin A -- Hansen, Louise L -- Putker, Marrit -- Olivares-Yanez, Consuelo -- Day, Jason -- Eades, Lorna J -- Larrondo, Luis F -- Hoyle, Nathaniel P -- O'Neill, John S -- van Ooijen, Gerben -- 093734/Z/10/Z/Wellcome Trust/United Kingdom -- MC_UP_1201/4/Medical Research Council/United Kingdom -- England -- Nature. 2016 Apr 21;532(7599):375-9. doi: 10.1038/nature17407. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory for Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; School of Biological Sciences, University of Edinburgh, Max Born Crescent, Edinburgh EH9 3BF, UK. ; Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. ; Department of Earth Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EQ, UK. ; School of Chemistry, University of Edinburgh, David Brewster Road, Edinburgh EH9 3FJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074515" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Cell Line ; Chlorophyta/cytology/metabolism ; Circadian Clocks/genetics/*physiology ; Circadian Rhythm/genetics/*physiology ; *Energy Metabolism ; Feedback, Physiological ; Gene Expression Regulation ; Humans ; Intracellular Space/metabolism ; Magnesium/*metabolism ; Male ; Mice ; TOR Serine-Threonine Kinases/metabolism ; Time Factors
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  • 145
    Publication Date: 2016-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chu, Derrick M -- Aagaard, Kjersti M -- England -- Nature. 2016 Apr 21;532(7599):316-7. doi: 10.1038/nature17887. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Departments of Molecular and Human Genetics, Molecular and Cell Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074514" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Child, Preschool ; Chronic Disease ; Clostridium symbiosum/isolation & purification/physiology ; Diet/adverse effects/methods ; Feces/microbiology ; Female ; Germ-Free Life ; Growth Disorders/*diet therapy/etiology/*microbiology ; Healthy Volunteers ; Humans ; Infant ; Intestines/drug effects/*microbiology ; Liver/metabolism ; Malawi ; Malnutrition/complications/*diet therapy/*microbiology ; Mice ; Microbiota/drug effects/genetics/*physiology ; Milk, Human/chemistry/microbiology ; Mothers ; Oligosaccharides/analysis/pharmacology/therapeutic use ; Ruminococcus/isolation & purification/physiology ; Somatomedins/biosynthesis ; Weight Gain/drug effects
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  • 146
    Publication Date: 2016-04-14
    Description: USP14 is a major regulator of the proteasome and one of three proteasome-associated deubiquitinating enzymes. Its effects on protein turnover are substrate-specific, for unknown reasons. We report that USP14 shows a marked preference for ubiquitin-cyclin B conjugates that carry more than one ubiquitin modification or chain. This specificity is conserved from yeast to humans and is independent of chain linkage type. USP14 has been thought to cleave single ubiquitin groups from the distal tip of a chain, but we find that it removes chains from cyclin B en bloc, proceeding until a single chain remains. The suppression of degradation by USP14's catalytic activity reflects its capacity to act on a millisecond time scale, before the proteasome can initiate degradation of the substrate. In addition, single-molecule studies showed that the dwell time of ubiquitin conjugates at the proteasome was reduced by USP14-dependent deubiquitination. In summary, the specificity of the proteasome can be regulated by rapid ubiquitin chain removal, which resolves substrates based on a novel aspect of ubiquitin conjugate architecture.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844788/" 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/PMC4844788/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Byung-Hoon -- Lu, Ying -- Prado, Miguel A -- Shi, Yuan -- Tian, Geng -- Sun, Shuangwu -- Elsasser, Suzanne -- Gygi, Steven P -- King, Randall W -- Finley, Daniel -- 5R01GM039023-26/GM/NIGMS NIH HHS/ -- R01 GM026875/GM/NIGMS NIH HHS/ -- R01 GM066492/GM/NIGMS NIH HHS/ -- R01GM5660052/GM/NIGMS NIH HHS/ -- R01GM66492-9/GM/NIGMS NIH HHS/ -- R37-GM043601/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Apr 21;532(7599):398-401. doi: 10.1038/nature17433. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA. ; Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. ; Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074503" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Cyclin B/chemistry/metabolism ; Humans ; Kinetics ; Models, Molecular ; Proteasome Endopeptidase Complex/*metabolism ; Proteolysis ; Substrate Specificity ; Ubiquitin/metabolism ; Ubiquitin Thiolesterase/*metabolism ; *Ubiquitination ; Yeasts/enzymology
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  • 147
    Publication Date: 2016-04-09
    Description: Activation of various cell surface receptors triggers the reorganization of downstream signaling molecules into micrometer- or submicrometer-sized clusters. However, the functional consequences of such clustering have been unclear. We biochemically reconstituted a 12-component signaling pathway on model membranes, beginning with T cell receptor (TCR) activation and ending with actin assembly. When TCR phosphorylation was triggered, downstream signaling proteins spontaneously separated into liquid-like clusters that promoted signaling outputs both in vitro and in human Jurkat T cells. Reconstituted clusters were enriched in kinases but excluded phosphatases and enhanced actin filament assembly by recruiting and organizing actin regulators. These results demonstrate that protein phase separation can create a distinct physical and biochemical compartment that facilitates signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, Xiaolei -- Ditlev, Jonathon A -- Hui, Enfu -- Xing, Wenmin -- Banjade, Sudeep -- Okrut, Julia -- King, David S -- Taunton, Jack -- Rosen, Michael K -- Vale, Ronald D -- 5-F32-DK101188/DK/NIDDK NIH HHS/ -- F32 DK101188/DK/NIDDK NIH HHS/ -- R01 GM056322/GM/NIGMS NIH HHS/ -- R01-GM56322/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):595-9. doi: 10.1126/science.aad9964. Epub 2016 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. ; Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; HHMI Mass Spectrometry Laboratory and Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA. ; Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ron.vale@ucsf.edu michael.rosen@utsouthwestern.edu. ; Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. ron.vale@ucsf.edu michael.rosen@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27056844" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Adaptor Proteins, Signal Transducing/*metabolism ; Fluorescence Recovery After Photobleaching ; Humans ; Jurkat Cells ; Membrane Proteins/*metabolism ; Mitogen-Activated Protein Kinase Kinases ; Phosphorylation ; Polymerization ; Receptors, Antigen, T-Cell/*agonists ; Signal Transduction ; T-Lymphocytes/*metabolism
    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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  • 148
    Publication Date: 2016-04-07
    Description: As the last habitable continent colonized by humans, the site of multiple domestication hotspots, and the location of the largest Pleistocene megafaunal extinction, South America is central to human prehistory. Yet remarkably little is known about human population dynamics during colonization, subsequent expansions, and domestication. Here we reconstruct the spatiotemporal patterns of human population growth in South America using a newly aggregated database of 1,147 archaeological sites and 5,464 calibrated radiocarbon dates spanning fourteen thousand to two thousand years ago (ka). We demonstrate that, rather than a steady exponential expansion, the demographic history of South Americans is characterized by two distinct phases. First, humans spread rapidly throughout the continent, but remained at low population sizes for 8,000 years, including a 4,000-year period of 'boom-and-bust' oscillations with no net growth. Supplementation of hunting with domesticated crops and animals had a minimal impact on population carrying capacity. Only with widespread sedentism, beginning ~5 ka, did a second demographic phase begin, with evidence for exponential population growth in cultural hotspots, characteristic of the Neolithic transition worldwide. The unique extent of humanity's ability to modify its environment to markedly increase carrying capacity in South America is therefore an unexpectedly recent phenomenon.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldberg, Amy -- Mychajliw, Alexis M -- Hadly, Elizabeth A -- England -- Nature. 2016 Apr 14;532(7598):232-5. doi: 10.1038/nature17176. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Stanford University, Stanford, California 94305, USA. ; Woods Institute, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049941" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; Archaeology ; Climate ; Geographic Mapping ; History, Ancient ; Human Migration/*history ; Humans ; Population Dynamics/*history ; Radiometric Dating ; Siberia/ethnology ; South America
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  • 149
    Publication Date: 2016-04-07
    Description: Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle. Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833566/" 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/PMC4833566/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seifert, Lena -- Werba, Gregor -- Tiwari, Shaun -- Giao Ly, Nancy Ngoc -- Alothman, Sara -- Alqunaibit, Dalia -- Avanzi, Antonina -- Barilla, Rocky -- Daley, Donnele -- Greco, Stephanie H -- Torres-Hernandez, Alejandro -- Pergamo, Matthew -- Ochi, Atsuo -- Zambirinis, Constantinos P -- Pansari, Mridul -- Rendon, Mauricio -- Tippens, Daniel -- Hundeyin, Mautin -- Mani, Vishnu R -- Hajdu, Cristina -- Engle, Dannielle -- Miller, George -- CA155649/CA/NCI NIH HHS/ -- CA168611/CA/NCI NIH HHS/ -- CA193111/CA/NCI NIH HHS/ -- P30CA016087/CA/NCI NIH HHS/ -- R01 CA168611/CA/NCI NIH HHS/ -- T32 CA193111/CA/NCI NIH HHS/ -- UL1 TR000038/TR/NCATS NIH HHS/ -- England -- Nature. 2016 Apr 14;532(7598):245-9. doi: 10.1038/nature17403. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA. ; Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA. ; Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA. ; Cold Spring Harbor Laboratories, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049944" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/immunology/metabolism/pathology ; Animals ; Apoptosis/drug effects ; *Carcinogenesis/drug effects ; Carcinoma, Pancreatic Ductal/immunology/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chemokine CXCL1/antagonists & inhibitors/*metabolism ; Deoxycytidine/analogs & derivatives/pharmacology ; Disease Progression ; Female ; GTPase-Activating Proteins/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; *Immune Tolerance ; Lectins, C-Type/immunology/*metabolism ; Male ; Membrane Proteins/immunology/*metabolism ; Mice ; Mice, Inbred C57BL ; *Necrosis ; Pancreatic Neoplasms/*immunology/metabolism/*pathology ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; Up-Regulation
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  • 150
    Publication Date: 2016-04-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caron, Marc G -- Gether, Ulrik -- England -- Nature. 2016 Apr 21;532(7599):320-1. doi: 10.1038/nature17883. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Cell Biology, Medicine and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049942" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Serotonin Plasma Membrane Transport Proteins/*chemistry/*metabolism
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  • 151
    Publication Date: 2016-04-07
    Description: In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses-excited by light of one colour and suppressed by another colour. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC), was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joesch, Maximilian -- Meister, Markus -- England -- Nature. 2016 Apr 14;532(7598):236-9. doi: 10.1038/nature17158. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University, 52 Oxford Street, Cambridge, Massachusetts 02138, USA. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049951" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Color ; Color Perception/*physiology/radiation effects ; Color Vision/*physiology/radiation effects ; Darkness ; Female ; Humans ; Male ; Mice ; Models, Neurological ; Neural Pathways/*physiology/radiation effects ; Retinal Cone Photoreceptor Cells/*metabolism/radiation effects ; Retinal Ganglion Cells/metabolism/radiation effects ; Retinal Rod Photoreceptor Cells/*metabolism/radiation effects ; Synapses/metabolism/radiation effects ; Territoriality ; Ultraviolet Rays
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  • 152
    Publication Date: 2016-04-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penn, Bennett H -- Cox, Jeffery S -- England -- Nature. 2016 Apr 21;532(7599):321-2. doi: 10.1038/nature17882. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, California 94143, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720-3370, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049940" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Endoplasmic Reticulum Stress ; Female ; Humans ; Inflammation/*metabolism ; Male ; Nod1 Signaling Adaptor Protein/*metabolism ; Nod2 Signaling Adaptor Protein/*metabolism ; *Signal Transduction
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  • 153
    Publication Date: 2016-04-07
    Description: Cells receive growth and survival stimuli through their attachment to an extracellular matrix (ECM). Overcoming the addiction to ECM-induced signals is required for anchorage-independent growth, a property of most malignant cells. Detachment from ECM is associated with enhanced production of reactive oxygen species (ROS) owing to altered glucose metabolism. Here we identify an unconventional pathway that supports redox homeostasis and growth during adaptation to anchorage independence. We observed that detachment from monolayer culture and growth as anchorage-independent tumour spheroids was accompanied by changes in both glucose and glutamine metabolism. Specifically, oxidation of both nutrients was suppressed in spheroids, whereas reductive formation of citrate from glutamine was enhanced. Reductive glutamine metabolism was highly dependent on cytosolic isocitrate dehydrogenase-1 (IDH1), because the activity was suppressed in cells homozygous null for IDH1 or treated with an IDH1 inhibitor. This activity occurred in absence of hypoxia, a well-known inducer of reductive metabolism. Rather, IDH1 mitigated mitochondrial ROS in spheroids, and suppressing IDH1 reduced spheroid growth through a mechanism requiring mitochondrial ROS. Isotope tracing revealed that in spheroids, isocitrate/citrate produced reductively in the cytosol could enter the mitochondria and participate in oxidative metabolism, including oxidation by IDH2. This generates NADPH in the mitochondria, enabling cells to mitigate mitochondrial ROS and maximize growth. Neither IDH1 nor IDH2 was necessary for monolayer growth, but deleting either one enhanced mitochondrial ROS and reduced spheroid size, as did deletion of the mitochondrial citrate transporter protein. Together, the data indicate that adaptation to anchorage independence requires a fundamental change in citrate metabolism, initiated by IDH1-dependent reductive carboxylation and culminating in suppression of mitochondrial ROS.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860952/" 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/PMC4860952/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Lei -- Shestov, Alexander A -- Swain, Pamela -- Yang, Chendong -- Parker, Seth J -- Wang, Qiong A -- Terada, Lance S -- Adams, Nicholas D -- McCabe, Michael T -- Pietrak, Beth -- Schmidt, Stan -- Metallo, Christian M -- Dranka, Brian P -- Schwartz, Benjamin -- DeBerardinis, Ralph J -- R01 CA157996/CA/NCI NIH HHS/ -- R01 CA188652/CA/NCI NIH HHS/ -- R01CA157996/CA/NCI NIH HHS/ -- R01CA188652/CA/NCI NIH HHS/ -- England -- Nature. 2016 Apr 14;532(7598):255-8. doi: 10.1038/nature17393. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, Texas 75390-8502, USA. ; Department of Radiology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA. ; Seahorse Bioscience, 16 Esquire Road, North Billerica, Massachusetts 01862, USA. ; Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA. ; Touchstone Diabetes Center, UT Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA. ; GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA. ; Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas 75390, USA. ; McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, Texas 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049945" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Adhesion ; Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; Citric Acid/*metabolism ; Contact Inhibition ; Cytosol/enzymology/metabolism ; Extracellular Matrix/metabolism ; Glucose/metabolism ; Glutamic Acid/metabolism ; Glutamine/metabolism ; *Homeostasis ; Humans ; Isocitrate Dehydrogenase/antagonists & inhibitors/deficiency/genetics/*metabolism ; Isocitrates/metabolism ; Mitochondria/*metabolism ; NADP/biosynthesis ; Neoplasms/enzymology/*metabolism/*pathology ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species/*metabolism ; Spheroids, Cellular/metabolism/pathology
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  • 154
    Publication Date: 2016-04-07
    Description: The serotonin transporter (SERT) terminates serotonergic signalling through the sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 A resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coleman, Jonathan A -- Green, Evan M -- Gouaux, Eric -- 5R37MH070039/MH/NIMH NIH HHS/ -- R37 MH070039/MH/NIMH NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Apr 21;532(7599):334-9. doi: 10.1038/nature17629. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Howard Hughes Medical Institute, Oregon Health &Science University, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049939" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/drug effects ; Allosteric Site/drug effects ; Antidepressive Agents/chemistry/metabolism/pharmacology ; Citalopram/chemistry/metabolism/pharmacology ; Crystallography, X-Ray ; Dopamine Plasma Membrane Transport Proteins/chemistry ; Drug Design ; Extracellular Space/metabolism ; Humans ; Immunoglobulin Fab Fragments/immunology ; Intracellular Space/metabolism ; Ions/chemistry/metabolism ; Ligands ; Models, Molecular ; Paroxetine/chemistry/metabolism/pharmacology ; Protein Binding/drug effects ; Protein Conformation/drug effects ; Protein Stability ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/*chemistry/immunology/*metabolism ; Structure-Activity Relationship
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  • 155
    Publication Date: 2016-04-05
    Description: Evidence for human sacrifice is found throughout the archaeological record of early civilizations, the ethnographic records of indigenous world cultures, and the texts of the most prolific contemporary religions. According to the social control hypothesis, human sacrifice legitimizes political authority and social class systems, functioning to stabilize such social stratification. Support for the social control hypothesis is largely limited to historical anecdotes of human sacrifice, where the causal claims have not been subject to rigorous quantitative cross-cultural tests. Here we test the social control hypothesis by applying Bayesian phylogenetic methods to a geographically and socially diverse sample of 93 traditional Austronesian cultures. We find strong support for models in which human sacrifice stabilizes social stratification once stratification has arisen, and promotes a shift to strictly inherited class systems. Whilst evolutionary theories of religion have focused on the functionality of prosocial and moral beliefs, our results reveal a darker link between religion and the evolution of modern hierarchical societies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watts, Joseph -- Sheehan, Oliver -- Atkinson, Quentin D -- Bulbulia, Joseph -- Gray, Russell D -- England -- Nature. 2016 Apr 14;532(7598):228-31. doi: 10.1038/nature17159. Epub 2016 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Psychology, University of Auckland, Auckland 1142, New Zealand. ; Max Planck Institute for the Science of Human History, Jena 07743, Germany. ; School of Art History, Classics and Religious Studies, Victoria University of Wellington, Wellington 6014, New Zealand. ; Research School of the Social Sciences, Australian National University, Canberra 2601, Australia. ; Allan Wilson Centre for Molecular Ecology and Evolution, Palmerston North 4442, New Zealand.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27042932" target="_blank"〉PubMed〈/a〉
    Keywords: Bayes Theorem ; *Ceremonial Behavior ; *Cultural Evolution ; Humans ; Models, Theoretical ; Oceanic Ancestry Group/psychology ; Phylogeny ; Religion and Psychology ; *Social Class ; *Social Control, Formal
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  • 156
    Publication Date: 2016-04-05
    Description: The human sigma1 receptor is an enigmatic endoplasmic-reticulum-resident transmembrane protein implicated in a variety of disorders including depression, drug addiction, and neuropathic pain. Recently, an additional connection to amyotrophic lateral sclerosis has emerged from studies of human genetics and mouse models. Unlike many transmembrane receptors that belong to large, extensively studied families such as G-protein-coupled receptors or ligand-gated ion channels, the sigma1 receptor is an evolutionary isolate with no discernible similarity to any other human protein. Despite its increasingly clear importance in human physiology and disease, the molecular architecture of the sigma1 receptor and its regulation by drug-like compounds remain poorly defined. Here we report crystal structures of the human sigma1 receptor in complex with two chemically divergent ligands, PD144418 and 4-IBP. The structures reveal a trimeric architecture with a single transmembrane domain in each protomer. The carboxy-terminal domain of the receptor shows an extensive flat, hydrophobic membrane-proximal surface, suggesting an intimate association with the cytosolic surface of the endoplasmic reticulum membrane in cells. This domain includes a cupin-like beta-barrel with the ligand-binding site buried at its centre. This large, hydrophobic ligand-binding cavity shows remarkable plasticity in ligand recognition, binding the two ligands in similar positions despite dissimilar chemical structures. Taken together, these results reveal the overall architecture, oligomerization state, and molecular basis for ligand recognition by this important but poorly understood protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, Hayden R -- Zheng, Sanduo -- Gurpinar, Esin -- Koehl, Antoine -- Manglik, Aashish -- Kruse, Andrew C -- T32GM007226/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Apr 28;532(7600):527-30. doi: 10.1038/nature17391. Epub 2016 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27042935" target="_blank"〉PubMed〈/a〉
    Keywords: Benzamides/chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Endoplasmic Reticulum/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Intracellular Membranes/metabolism ; Isoxazoles/chemistry/metabolism ; Ligands ; Models, Molecular ; Piperidines/chemistry/metabolism ; Protein Structure, Tertiary ; Pyridines/chemistry/metabolism ; Receptors, sigma/*chemistry/metabolism ; Substrate Specificity
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  • 157
    Publication Date: 2016-04-05
    Description: Cancer is a disease of ageing. Clinically, aged cancer patients tend to have a poorer prognosis than young. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumour progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression, we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy. Here we find that aged fibroblasts secrete a Wnt antagonist, sFRP2, which activates a multi-step signalling cascade in melanoma cells that results in a decrease in beta-catenin and microphthalmia-associated transcription factor (MITF), and ultimately the loss of a key redox effector, APE1. Loss of APE1 attenuates the response of melanoma cells to DNA damage induced by reactive oxygen species, rendering the cells more resistant to targeted therapy (vemurafenib). Age-related increases in sFRP2 also augment both angiogenesis and metastasis of melanoma cells. These data provide an integrated view of how fibroblasts in the aged microenvironment contribute to tumour progression, offering new possibilities for the design of therapy for the elderly.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833579/" 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/PMC4833579/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaur, Amanpreet -- Webster, Marie R -- Marchbank, Katie -- Behera, Reeti -- Ndoye, Abibatou -- Kugel, Curtis H 3rd -- Dang, Vanessa M -- Appleton, Jessica -- O'Connell, Michael P -- Cheng, Phil -- Valiga, Alexander A -- Morissette, Rachel -- McDonnell, Nazli B -- Ferrucci, Luigi -- Kossenkov, Andrew V -- Meeth, Katrina -- Tang, Hsin-Yao -- Yin, Xiangfan -- Wood, William H 3rd -- Lehrmann, Elin -- Becker, Kevin G -- Flaherty, Keith T -- Frederick, Dennie T -- Wargo, Jennifer A -- Cooper, Zachary A -- Tetzlaff, Michael T -- Hudgens, Courtney -- Aird, Katherine M -- Zhang, Rugang -- Xu, Xiaowei -- Liu, Qin -- Bartlett, Edmund -- Karakousis, Giorgos -- Eroglu, Zeynep -- Lo, Roger S -- Chan, Matthew -- Menzies, Alexander M -- Long, Georgina V -- Johnson, Douglas B -- Sosman, Jeffrey -- Schilling, Bastian -- Schadendorf, Dirk -- Speicher, David W -- Bosenberg, Marcus -- Ribas, Antoni -- Weeraratna, Ashani T -- P01 CA 114046-06/CA/NCI NIH HHS/ -- P01 CA114046/CA/NCI NIH HHS/ -- P30 CA010815/CA/NCI NIH HHS/ -- P50 CA093372/CA/NCI NIH HHS/ -- R01 CA174746/CA/NCI NIH HHS/ -- R01 CA174746-01/CA/NCI NIH HHS/ -- T32 CA009171/CA/NCI NIH HHS/ -- T32 CA9171-36/CA/NCI NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2016 Apr 14;532(7598):250-4. doi: 10.1038/nature17392. Epub 2016 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wistar Institute, Philadelphia, Pennsylvania 19104, USA. ; University of the Sciences, Philadelphia, Pennsylvania 19104, USA. ; Department of Dermatology, University of Zurich, Zurich CH-8006, Switzerland. ; The National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. ; Department of Dermatology and Pathology, Yale University, New Haven, Connecticut 06511, USA. ; Massachusetts General Hospital Cancer Center, Developmental Therapeutics, Boston 02114, Massachusetts, USA. ; Department of Surgical Oncology, MD Anderson Cancer Center, Houston, Texas 77030, USA. ; Departments of Surgery and Pathology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Medical Oncology, City of Hope Medical Center, Duarte, California 91010, USA. ; Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, California 90095, USA. ; Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead 2145, Australia. ; Melanoma Institute Australia and The University of Sydney, Sydney 2000, Australia. ; Department of Medicine, Vanderbilt University Medical Center, Nashville Tennessee 37232, USA. ; Department of Dermatology, University Hospital, West German Cancer Center, University Duesburg-Essen, Essen, Germany. ; German Cancer Consortium (DKTK), Heidelberg 45127, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27042933" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aging/*metabolism ; Animals ; Cell Line, Tumor ; Culture Media, Conditioned/pharmacology ; DNA Damage ; DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism ; Disease Progression ; *Drug Resistance, Neoplasm ; Fibroblasts/secretion ; Humans ; Indoles/pharmacology/therapeutic use ; Male ; Melanoma/blood supply/*drug therapy/genetics/*pathology ; Membrane Proteins/*metabolism/secretion ; Mice ; Microphthalmia-Associated Transcription Factor/metabolism ; Middle Aged ; Molecular Targeted Therapy ; *Neoplasm Metastasis ; Neovascularization, Pathologic ; Oxidative Stress ; Phenotype ; Reactive Oxygen Species/metabolism ; Sulfonamides/pharmacology/therapeutic use ; *Tumor Microenvironment ; Wnt Signaling Pathway ; Wnt1 Protein/antagonists & inhibitors ; beta Catenin/metabolism
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  • 158
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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〉Shoubridge, Eric A -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):31-2. doi: 10.1126/science.aaf5248. Epub 2016 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Montreal Neurological Institute, Department of Human Genetics, McGill University, Montreal, Quebec, Canada. eric@ericpc.mni.mcgill.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034357" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Leigh Disease/*genetics/*therapy ; Mitochondria/*metabolism ; Oxygen/*metabolism ; Von Hippel-Lindau Tumor Suppressor Protein/*genetics
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  • 159
    Publication Date: 2016-04-02
    Description: The recent rapid spread of Zika virus and its unexpected linkage to birth defects and an autoimmune neurological syndrome have generated worldwide concern. Zika virus is a flavivirus like the dengue, yellow fever, and West Nile viruses. We present the 3.8 angstrom resolution structure of mature Zika virus, determined by cryo-electron microscopy (cryo-EM). The structure of Zika virus is similar to other known flavivirus structures, except for the ~10 amino acids that surround the Asn(154) glycosylation site in each of the 180 envelope glycoproteins that make up the icosahedral shell. The carbohydrate moiety associated with this residue, which is recognizable in the cryo-EM electron density, may function as an attachment site of the virus to host cells. This region varies not only among Zika virus strains but also in other flaviviruses, which suggests that differences in this region may influence virus transmission and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845755/" 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/PMC4845755/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sirohi, Devika -- Chen, Zhenguo -- Sun, Lei -- Klose, Thomas -- Pierson, Theodore C -- Rossmann, Michael G -- Kuhn, Richard J -- R01 AI073755/AI/NIAID NIH HHS/ -- R01 AI076331/AI/NIAID NIH HHS/ -- R01AI073755/AI/NIAID NIH HHS/ -- R01AI076331/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):467-70. doi: 10.1126/science.aaf5316. Epub 2016 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA. ; Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27033547" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cryoelectron Microscopy ; Glycosylation ; Humans ; Molecular Sequence Data ; Protein Structure, Tertiary ; Viral Envelope Proteins/chemistry/ultrastructure ; Viral Matrix Proteins/chemistry/ultrastructure ; Zika Virus/*chemistry/*ultrastructure
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  • 160
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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〉Escobar, Herton -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):18. doi: 10.1126/science.352.6281.18.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034350" target="_blank"〉PubMed〈/a〉
    Keywords: *Antineoplastic Agents/chemical synthesis/chemistry/therapeutic use ; Brazil ; Clinical Trials as Topic ; Dosage Forms ; *Drug Approval ; Ethanolamines/chemical synthesis/chemistry/*therapeutic use ; Federal Government ; Humans ; Neoplasms/*drug therapy
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  • 161
    Publication Date: 2016-04-02
    Description: Until recently, programmed cell death was conceived of as a single set of molecular pathways. We now know of several distinct sets of death-inducing mechanisms that lead to differing cell-death processes. In one of them--apoptosis--the dying cell affects others minimally. In contrast, programmed necrotic cell death causes release of immunostimulatory intracellular components after cell-membrane rupture. Defining the in vivo relevance of necrotic death is hampered because the molecules initiating it [such as receptor-interacting protein kinase-1 (RIPK1), RIPK3, or caspase-1] also serve other functions. Proteins that participate in late events in two forms of programmed necrosis [mixed lineage kinase domain-like protein (MLKL) in necroptosis and gasdermin-D in pyroptosis] were recently discovered, bringing us closer to identifying molecules that strictly serve in death mediation, thereby providing probes for better assessing its role in inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wallach, David -- Kang, Tae-Bong -- Dillon, Christopher P -- Green, Douglas R -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):aaf2154. doi: 10.1126/science.aaf2154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomolecular Sciences, The Weizmann Institute of Science, 76100 Rehovot, Israel. d.wallach@weizmann.ac.il douglas.green@stjude.org. ; Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chung-Ju 380-701, Korea. ; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. ; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. d.wallach@weizmann.ac.il douglas.green@stjude.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034377" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Caspase 1/metabolism ; Cytokines/metabolism ; Humans ; Inflammation/*metabolism/*pathology ; Necrosis/pathology ; Neoplasm Proteins/metabolism ; Protein Kinases/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
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  • 162
    Publication Date: 2016-04-02
    Description: Accurate sequence and assembly of genomes is a critical first step for studies of genetic variation. We generated a high-quality assembly of the gorilla genome using single-molecule, real-time sequence technology and a string graph de novo assembly algorithm. The new assembly improves contiguity by two to three orders of magnitude with respect to previously released assemblies, recovering 87% of missing reference exons and incomplete gene models. Although regions of large, high-identity segmental duplications remain largely unresolved, this comprehensive assembly provides new biological insight into genetic diversity, structural variation, gene loss, and representation of repeat structures within the gorilla genome. The approach provides a path forward for the routine assembly of mammalian genomes at a level approaching that of the current quality of the human genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gordon, David -- Huddleston, John -- Chaisson, Mark J P -- Hill, Christopher M -- Kronenberg, Zev N -- Munson, Katherine M -- Malig, Maika -- Raja, Archana -- Fiddes, Ian -- Hillier, LaDeana W -- Dunn, Christopher -- Baker, Carl -- Armstrong, Joel -- Diekhans, Mark -- Paten, Benedict -- Shendure, Jay -- Wilson, Richard K -- Haussler, David -- Chin, Chen-Shan -- Eichler, Evan E -- HG002385/HG/NHGRI NIH HHS/ -- HG003079/HG/NHGRI NIH HHS/ -- HG007234/HG/NHGRI NIH HHS/ -- HG007635/HG/NHGRI NIH HHS/ -- HG007990/HG/NHGRI NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- U41 HG007635/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):aae0344. doi: 10.1126/science.aae0344.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. ; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. ; Genomics Institute, University of California Santa Cruz and Howard Hughes Medical Institute, Santa Cruz, CA 95064, USA. ; McDonnell Genome Institute, Department of Medicine, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA. ; Pacific Biosciences of California, Menlo Park, CA 94025, USA. ; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. eee@gs.washington.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034376" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Contig Mapping ; Evolution, Molecular ; Expressed Sequence Tags ; Female ; Genetic Variation ; Genome, Human ; Genomics ; Gorilla gorilla/*genetics ; Humans ; Sequence Alignment ; Sequence Analysis, DNA/*methods
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  • 163
    Publication Date: 2016-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hicks, Christina C -- Levine, Arielle -- Agrawal, Arun -- Basurto, Xavier -- Breslow, Sara J -- Carothers, Courtney -- Charnley, Susan -- Coulthard, Sarah -- Dolsak, Nives -- Donatuto, Jamie -- Garcia-Quijano, Carlos -- Mascia, Michael B -- Norman, Karma -- Poe, Melissa R -- Satterfield, Terre -- St Martin, Kevin -- Levin, Phillip S -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):38-40. doi: 10.1126/science.aad4977.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Ocean Solutions, Stanford University, CA, USA. Australian Research Council Centre of Excellence for Coral Reef Studies, James Cook University, Australia. Lancaster Environment Centre, Lancaster University, UK. christina.hicks@lancaster.ac.uk. ; Geography, San Diego State University, CA, USA. ; School of Natural Resources and the Environment, University of Michigan, USA. ; Nicholas School of the Environment, Duke University, NC, USA. ; Northwest Fisheries Science Center, NOAA, WA, USA. ; School of Fisheries and Ocean Sciences, University of Alaska Fairbanks, USA. ; U.S. Department of Agriculture, Forest Service, USA. ; Northumbria University, UK. ; School of Marine and Environmental Affairs, University of Washington, USA. ; Swinomish Indian Tribal Community, WA, USA. ; Anthropology and Marine Affairs, University of Rhode Island, USA. ; Moore Center for Science, Conservation International, VA, USA. ; Northwest Fisheries Science Center, NOAA, WA, USA. Washington Sea Grant, University of Washington, USA. ; The Institute for Resources, Environment and Sustainability, University of British Columbia, Canada. ; Department of Geography, Rutgers University, NJ, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034361" target="_blank"〉PubMed〈/a〉
    Keywords: Ecosystem ; Forecasting ; Health ; Humans ; Quality of Life ; *Social Values ; *Value of Life
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  • 164
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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〉Huarte, Maite -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):43-4. doi: 10.1126/science.aaf6015. Epub 2016 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Applied Medical Research (CIMA), Department of Gene Therapy and Regulation of Gene Expression, University of Navarra, Pamplona, Spain, and IdiSNA, Institute of Health Research of Navarra, Pamplona, Spain. maitehuarte@unav.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034364" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Celiac Disease/*genetics ; *Genetic Predisposition to Disease ; Humans ; Inflammation/*genetics ; RNA, Long Noncoding/*genetics
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  • 165
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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〉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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  • 166
    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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  • 167
    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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  • 168
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    Publication Date: 2016-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chatterjee, Rhitu -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):24-7. doi: 10.1126/science.352.6281.24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034354" target="_blank"〉PubMed〈/a〉
    Keywords: Dialysis ; *Farmers ; Female ; Humans ; India/epidemiology ; International Cooperation ; Male ; Occupational Diseases/*etiology/*mortality/therapy ; *Occupational Exposure ; Renal Insufficiency, Chronic/*etiology/*mortality/therapy
    Print ISSN: 0036-8075
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  • 169
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cartwright, Jon -- England -- Nature. 2016 Mar 31;531(7596):669-71.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27035011" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; *Crowdsourcing/instrumentation/methods ; Data Collection/*instrumentation ; Databases, Factual ; Humans ; Mobile Applications/utilization ; Science/*instrumentation/manpower/*methods ; Smartphone/*utilization
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 170
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKinlay, Roger -- England -- Nature. 2016 Mar 31;531(7596):573-5. doi: 10.1038/531573a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Royal Institute of Navigation, and a former head of engineering at Thales UK. He sits on the EPSRC Quantum Technology Strategic Advisory Board.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029262" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cues ; Facility Design and Construction ; Geographic Information Systems/instrumentation/*utilization ; Hippocampus/anatomy & histology/physiology ; Humans ; Maps as Topic ; Orientation/physiology ; Satellite Communications/utilization ; Smartphone/utilization ; Spatial Learning/*physiology ; Spatial Memory/physiology ; Spatial Navigation/*physiology
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  • 171
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    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Briggs, Adam -- England -- Nature. 2016 Mar 31;531(7596):551. doi: 10.1038/531551a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029244" target="_blank"〉PubMed〈/a〉
    Keywords: Beverages/analysis/*economics ; Child ; Dietary Sucrose/*adverse effects ; Food Industry/*economics/*legislation & jurisprudence ; Great Britain ; *Health Policy ; Humans ; *Legislation, Food ; Obesity/epidemiology/prevention & control ; Pediatric Obesity/prevention & control ; Public Health/legislation & jurisprudence ; Taxes/*legislation & jurisprudence
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    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Mar 31;531(7596):549. doi: 10.1038/531549a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029242" target="_blank"〉PubMed〈/a〉
    Keywords: Bullying/prevention & control ; Humans ; *Internet/utilization ; *Moral Development ; *Social Behavior ; Social Media
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  • 173
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    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Mar 31;531(7596):550. doi: 10.1038/531550a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029243" target="_blank"〉PubMed〈/a〉
    Keywords: *Avoidance Learning ; Behavior, Addictive/*psychology ; Cacao ; *Choice Behavior ; *Craving ; Humans
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  • 174
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Mar 31;531(7596):549-50. doi: 10.1038/531549b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029241" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Clocks/physiology ; Circadian Rhythm/*physiology ; Efficiency/physiology ; Humans ; Sleep/physiology ; *Time ; Wakefulness/physiology
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  • 175
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maher, Brendan -- England -- Nature. 2016 Mar 31;531(7596):568-71. doi: 10.1038/531568a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029261" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Bullying/*prevention & control ; Cultural Characteristics ; Humans ; *Internet ; *Machine Learning ; *Peer Influence ; Punishment ; Reinforcement (Psychology) ; Reward ; *Social Behavior ; Teaching/*methods ; Video Games/*psychology/statistics & numerical data
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  • 176
    Publication Date: 2016-04-01
    Description: The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2)) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 A resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cavadini, Simone -- Fischer, Eric S -- Bunker, Richard D -- Potenza, Alessandro -- Lingaraju, Gondichatnahalli M -- Goldie, Kenneth N -- Mohamed, Weaam I -- Faty, Mahamadou -- Petzold, Georg -- Beckwith, Rohan E J -- Tichkule, Ritesh B -- Hassiepen, Ulrich -- Abdulrahman, Wassim -- Pantelic, Radosav S -- Matsumoto, Syota -- Sugasawa, Kaoru -- Stahlberg, Henning -- Thoma, Nicolas H -- England -- Nature. 2016 Mar 31;531(7596):598-603. doi: 10.1038/nature17416.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. ; University of Basel, Petersplatz 10, 4003 Basel, Switzerland. ; Department of Cancer Biology, Dana-Farber Cancer Institute, LC-4312, 360 Longwood Avenue, Boston, Massachusetts 02215, USA. ; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02215, USA. ; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, 4058 Basel, Switzerland. ; Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. ; Novartis Pharma AG, Institutes for Biomedical Research, Novartis Campus, 4056 Basel, Switzerland. ; Gatan R&D, 5974 W. Las Positas Boulevard, Pleasanton, California 94588, USA. ; Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan. ; Graduate School of Science, Kobe University, Kobe, 657-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029275" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Apoproteins/chemistry/metabolism/ultrastructure ; Binding Sites ; *Biocatalysis ; Carrier Proteins/chemistry/metabolism/ultrastructure ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Cullin Proteins/chemistry/metabolism/ultrastructure ; DNA Damage ; DNA-Binding Proteins/chemistry/metabolism/ultrastructure ; Humans ; Kinetics ; Models, Molecular ; Multiprotein Complexes/chemistry/*metabolism/*ultrastructure ; Peptide Hydrolases/chemistry/*metabolism/*ultrastructure ; Protein Binding ; Ubiquitination ; Ubiquitins/metabolism
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  • 177
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2016 Mar 31;531(7596):560. doi: 10.1038/531560a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029280" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adolescent Behavior/*drug effects/physiology/*psychology ; Child ; *Clinical Trials as Topic/economics ; Decision Making ; Gonadotropin-Releasing Hormone/agonists ; Humans ; National Institutes of Health (U.S.)/economics ; Puberty/*drug effects/*physiology/psychology ; Time Factors ; Transgender Persons/*psychology ; Treatment Outcome ; United States
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  • 178
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beekes, Michael -- Thomzig, Achim -- England -- Nature. 2016 Mar 31;531(7596):580. doi: 10.1038/531580a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Robert Koch Institute, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029268" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*etiology ; Animals ; Humans ; *Models, Biological
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  • 179
    Publication Date: 2016-03-31
    Description: Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8(-/-) mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8(-/-) mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okumura, Ryu -- Kurakawa, Takashi -- Nakano, Takashi -- Kayama, Hisako -- Kinoshita, Makoto -- Motooka, Daisuke -- Gotoh, Kazuyoshi -- Kimura, Taishi -- Kamiyama, Naganori -- Kusu, Takashi -- Ueda, Yoshiyasu -- Wu, Hong -- Iijima, Hideki -- Barman, Soumik -- Osawa, Hideki -- Matsuno, Hiroshi -- Nishimura, Junichi -- Ohba, Yusuke -- Nakamura, Shota -- Iida, Tetsuya -- Yamamoto, Masahiro -- Umemoto, Eiji -- Sano, Koichi -- Takeda, Kiyoshi -- England -- Nature. 2016 Apr 7;532(7597):117-21. doi: 10.1038/nature17406. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. ; Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan. ; Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. ; Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. ; Department of Bacteriology, Okayama University Graduate School of Medicine, Okayama 700-8558, Japan. ; Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. ; Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. ; Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. ; Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. ; Laboratory of Immunoparasitology, Research Institute for Microbial Diseases, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027293" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Adhesion ; Caco-2 Cells ; Cell Line ; Colitis/chemically induced/drug therapy/genetics ; Colon/*microbiology ; Dextran Sulfate ; Epithelium/*microbiology ; Female ; *Flagella ; GPI-Linked Proteins/deficiency/genetics/*metabolism/secretion ; Gram-Negative Bacteria/drug effects/metabolism/pathogenicity/*physiology ; Homeostasis ; Humans ; Inflammation/chemically induced/drug therapy/genetics ; Intestinal Mucosa/cytology/metabolism/*microbiology/secretion ; Male ; Mice ; Proteus mirabilis/drug effects/metabolism/pathogenicity ; Symbiosis
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  • 180
    Publication Date: 2016-03-31
    Description: Homo floresiensis, a primitive hominin species discovered in Late Pleistocene sediments at Liang Bua (Flores, Indonesia), has generated wide interest and scientific debate. A major reason this taxon is controversial is because the H. floresiensis-bearing deposits, which include associated stone artefacts and remains of other extinct endemic fauna, were dated to between about 95 and 12 thousand calendar years (kyr) ago. These ages suggested that H. floresiensis survived until long after modern humans reached Australia by ~50 kyr ago. Here we report new stratigraphic and chronological evidence from Liang Bua that does not support the ages inferred previously for the H. floresiensis holotype (LB1), ~18 thousand calibrated radiocarbon years before present (kyr cal. BP), or the time of last appearance of this species (about 17 or 13-11 kyr cal. BP). Instead, the skeletal remains of H. floresiensis and the deposits containing them are dated to between about 100 and 60 kyr ago, whereas stone artefacts attributable to this species range from about 190 to 50 kyr in age. Whether H. floresiensis survived after 50 kyr ago--potentially encountering modern humans on Flores or other hominins dispersing through southeast Asia, such as Denisovans--is an open question.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sutikna, Thomas -- Tocheri, Matthew W -- Morwood, Michael J -- Saptomo, E Wahyu -- Jatmiko -- Awe, Rokus Due -- Wasisto, Sri -- Westaway, Kira E -- Aubert, Maxime -- Li, Bo -- Zhao, Jian-xin -- Storey, Michael -- Alloway, Brent V -- Morley, Mike W -- Meijer, Hanneke J M -- van den Bergh, Gerrit D -- Grun, Rainer -- Dosseto, Anthony -- Brumm, Adam -- Jungers, William L -- Roberts, Richard G -- England -- Nature. 2016 Apr 21;532(7599):366-9. doi: 10.1038/nature17179. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Archaeological Science, School of Earth and Environmental Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia. ; Pusat Penelitian Arkeologi Nasional, Jakarta 12510, Indonesia. ; Department of Anthropology, Lakehead University, Thunder Bay, Ontario P7B 5E1, Canada. ; Human Origins Program, Department of Anthropology, National Museum of Natural History, Smithsonian Institution, Washington DC 20013, USA. ; Traps MQ Luminescence Dating Facility, Department of Environmental Sciences, Macquarie University, Sydney, New South Wales 2109, Australia. ; Research Centre for Human Evolution, Place, Evolution and Rock Art Heritage Unit, Griffith University, Gold Coast, Queensland 4222, Australia. ; School of Earth and Environmental Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia. ; School of Earth Sciences, University of Queensland, Brisbane, Queensland 4072, Australia. ; QUADLAB, Section of Earth and Planetary System Science, Natural History Museum of Denmark, 1350 Copenhagen, Denmark. ; School of Geography, Environment and Earth Sciences, Victoria University of Wellington, Wellington 6012, New Zealand. ; Department of Natural History, University Museum of Bergen, University of Bergen, 5007 Bergen, Norway. ; Research Centre for Human Evolution, Environmental Futures Research Institute, Griffith University, Brisbane, Queensland 4111, Australia. ; Research School of Earth Sciences, Australian National University, Canberra, Australian Capital Territory 0200, Australia. ; GeoQuEST Research Centre, School of Earth and Environmental Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia. ; Department of Anatomical Sciences, Stony Brook University Medical Center, Stony Brook, New York 11794, USA. ; Association Vahatra, BP 3972, Antananarivo 101, Madagascar.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027286" target="_blank"〉PubMed〈/a〉
    Keywords: Aluminum Silicates ; Animals ; *Archaeology ; Australia ; Calibration ; Caves ; *Fossils ; Geologic Sediments/analysis ; Glass ; *Hominidae ; Humans ; Indonesia ; Potassium Compounds ; Quartz ; *Radiometric Dating ; Time Factors ; Uncertainty
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  • 181
    Publication Date: 2016-03-31
    Description: Brown and beige adipose tissues can dissipate chemical energy as heat through thermogenic respiration, which requires uncoupling protein 1 (UCP1). Thermogenesis from these adipocytes can combat obesity and diabetes, encouraging investigation of factors that control UCP1-dependent respiration in vivo. Here we show that acutely activated thermogenesis in brown adipose tissue is defined by a substantial increase in levels of mitochondrial reactive oxygen species (ROS). Remarkably, this process supports in vivo thermogenesis, as pharmacological depletion of mitochondrial ROS results in hypothermia upon cold exposure, and inhibits UCP1-dependent increases in whole-body energy expenditure. We further establish that thermogenic ROS alter the redox status of cysteine thiols in brown adipose tissue to drive increased respiration, and that Cys253 of UCP1 is a key target. UCP1 Cys253 is sulfenylated during thermogenesis, while mutation of this site desensitizes the purine-nucleotide-inhibited state of the carrier to adrenergic activation and uncoupling. These studies identify mitochondrial ROS induction in brown adipose tissue as a mechanism that supports UCP1-dependent thermogenesis and whole-body energy expenditure, which opens the way to improved therapeutic strategies for combating metabolic disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chouchani, Edward T -- Kazak, Lawrence -- Jedrychowski, Mark P -- Lu, Gina Z -- Erickson, Brian K -- Szpyt, John -- Pierce, Kerry A -- Laznik-Bogoslavski, Dina -- Vetrivelan, Ramalingam -- Clish, Clary B -- Robinson, Alan J -- Gygi, Steve P -- Spiegelman, Bruce M -- DK31405/DK/NIDDK NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2016 Apr 7;532(7597):112-6. doi: 10.1038/nature17399. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA. ; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02215, USA. ; MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027295" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue, Brown/chemistry/cytology/metabolism ; Animals ; Cell Respiration ; Cysteine/*chemistry/genetics/metabolism ; *Energy Metabolism/drug effects ; Female ; Humans ; Ion Channels/*chemistry/deficiency/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/drug effects/*metabolism ; Mitochondrial Proteins/*chemistry/deficiency/genetics/*metabolism ; Mutant Proteins/chemistry/genetics/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/*metabolism ; Sulfhydryl Compounds/metabolism ; *Thermogenesis/drug effects
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  • 182
    Publication Date: 2016-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitchell, Aaron P -- England -- Nature. 2016 Apr 7;532(7597):41-2. doi: 10.1038/nature17319. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027285" target="_blank"〉PubMed〈/a〉
    Keywords: Candida albicans/*metabolism/*pathogenicity ; Cytotoxins/*metabolism ; Fungal Proteins/*toxicity ; Humans ; Mycotoxins/*toxicity ; Virulence Factors/*metabolism
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  • 183
    Publication Date: 2016-03-31
    Description: Cerebral cavernous malformations (CCMs) are common inherited and sporadic vascular malformations that cause strokes and seizures in younger individuals. CCMs arise from endothelial cell loss of KRIT1, CCM2 or PDCD10, non-homologous proteins that form an adaptor complex. How disruption of the CCM complex results in disease remains controversial, with numerous signalling pathways (including Rho, SMAD and Wnt/beta-catenin) and processes such as endothelial-mesenchymal transition (EndMT) proposed to have causal roles. CCM2 binds to MEKK3 (refs 7, 8, 9, 10, 11), and we have recently shown that CCM complex regulation of MEKK3 is essential during vertebrate heart development. Here we investigate this mechanism in CCM disease pathogenesis. Using a neonatal mouse model of CCM disease, we show that expression of the MEKK3 target genes Klf2 and Klf4, as well as Rho and ADAMTS protease activity, are increased in the endothelial cells of early CCM lesions. By contrast, we find no evidence of EndMT or increased SMAD or Wnt signalling during early CCM formation. Endothelial-specific loss of Map3k3 (also known as Mekk3), Klf2 or Klf4 markedly prevents lesion formation, reverses the increase in Rho activity, and rescues lethality. Consistent with these findings in mice, we show that endothelial expression of KLF2 and KLF4 is increased in human familial and sporadic CCM lesions, and that a disease-causing human CCM2 mutation abrogates the MEKK3 interaction without affecting CCM complex formation. These studies identify gain of MEKK3 signalling and KLF2/4 function as causal mechanisms for CCM pathogenesis that may be targeted to develop new CCM therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864035/" 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/PMC4864035/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Zinan -- Tang, Alan T -- Wong, Weng-Yew -- Bamezai, Sharika -- Goddard, Lauren M -- Shenkar, Robert -- Zhou, Su -- Yang, Jisheng -- Wright, Alexander C -- Foley, Matthew -- Arthur, J Simon C -- Whitehead, Kevin J -- Awad, Issam A -- Li, Dean Y -- Zheng, Xiangjian -- Kahn, Mark L -- P01 HL075215/HL/NHLBI NIH HHS/ -- P01 HL120846/HL/NHLBI NIH HHS/ -- P01 NS092521/NS/NINDS NIH HHS/ -- P01NS092521/NS/NINDS NIH HHS/ -- R01 HL094326/HL/NHLBI NIH HHS/ -- R01HL-084516/HL/NHLBI NIH HHS/ -- R01HL094326/HL/NHLBI NIH HHS/ -- R01NS075168/NS/NINDS NIH HHS/ -- T32HL07439/HL/NHLBI NIH HHS/ -- England -- Nature. 2016 Apr 7;532(7597):122-6. doi: 10.1038/nature17178. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, Pennsylvania 19104, USA. ; Laboratory of Cardiovascular Signaling, Centenary Institute, Sydney, New South Wales 2050, Australia. ; Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, The University of Chicago Medicine and Biological Sciences, Chicago, Illinois 60637, USA. ; Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA. ; Sydney Microscopy &Microanalysis, University of Sydney, Sydney, New South Wales 2050, Australia. ; Division of Cell Signaling and Immunology, University of Dundee, Dundee DD1 5EH, UK. ; Division of Cardiovascular Medicine and the Program in Molecular Medicine, University of Utah, Salt Lake City, Utah 84112, USA. ; The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China. ; Faculty of Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales 2050, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027284" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins/metabolism ; Animals ; Animals, Newborn ; Carrier Proteins/genetics/metabolism ; Disease Models, Animal ; Endothelial Cells/enzymology/*metabolism ; Female ; Hemangioma, Cavernous, Central Nervous System/etiology/*metabolism/pathology ; Humans ; Kruppel-Like Transcription Factors/deficiency/*metabolism ; MAP Kinase Kinase Kinase 3/deficiency/*metabolism ; *MAP Kinase Signaling System ; Male ; Mice ; Protein Binding ; rho GTP-Binding Proteins/metabolism
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  • 184
    Publication Date: 2016-03-31
    Description: Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name 'Candidalysin' for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851236/" 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/PMC4851236/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moyes, David L -- Wilson, Duncan -- Richardson, Jonathan P -- Mogavero, Selene -- Tang, Shirley X -- Wernecke, Julia -- Hofs, Sarah -- Gratacap, Remi L -- Robbins, Jon -- Runglall, Manohursingh -- Murciano, Celia -- Blagojevic, Mariana -- Thavaraj, Selvam -- Forster, Toni M -- Hebecker, Betty -- Kasper, Lydia -- Vizcay, Gema -- Iancu, Simona I -- Kichik, Nessim -- Hader, Antje -- Kurzai, Oliver -- Luo, Ting -- Kruger, Thomas -- Kniemeyer, Olaf -- Cota, Ernesto -- Bader, Oliver -- Wheeler, Robert T -- Gutsmann, Thomas -- Hube, Bernhard -- Naglik, Julian R -- 097377/Z/11/Z/Wellcome Trust/United Kingdom -- 102549/Z/13/Z/Wellcome Trust/United Kingdom -- BB/J015261/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MR/J008303/1/Medical Research Council/United Kingdom -- MR/M011372/1/Medical Research Council/United Kingdom -- R15 AI094406/AI/NIAID NIH HHS/ -- R15AI094406/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Apr 7;532(7597):64-8. doi: 10.1038/nature17625. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK. ; Department of Microbial Pathogenicity Mechanisms, Hans Knoll Institute, D-07745 Jena, Germany. ; Research Center Borstel, Division of Biophysics, D-23845 Borstel, Germany. ; Deutsches Elektronen-Synchrotron DESY, D-22607 Hamburg, Germany. ; Department of Molecular &Biomedical Sciences, University of Maine, Orono, Maine 04469, USA. ; Wolfson CARD, King's College London, Guy's Campus, London SE1 1UL, UK. ; Research Group Microbial Immunology, Hans Knoll Institute, D-07745 Jena, Germany. ; Centre for Ultrastructural Imaging, King's College London, London SE1 1UL, UK. ; Department of Life Sciences, Imperial College London, London SW7 2AZ, UK. ; Septomics Research Center, Hans-Knoll Institute and Friedrich Schiller University, D-07745 Jena, Germany. ; Department of Molecular and Applied Microbiology, Hans Knoll Institute, D-07745 Jena, Germany. ; Institute for Medical Microbiology, University Medical Center Gottingen, D-37075 Gottingen, Germany. ; Friedrich Schiller University, D-07737 Jena, Germany. ; Integrated Research and Treatment Center, Center for Sepsis Control and Care, D-07747 Jena, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027296" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/metabolism ; Candida albicans/immunology/*metabolism/*pathogenicity ; Candidiasis/metabolism/microbiology/pathology ; Cell Membrane Permeability/drug effects ; Cytotoxins/genetics/*metabolism/secretion/toxicity ; Epithelial Cells/drug effects/immunology/pathology ; Fungal Proteins/genetics/metabolism/secretion/*toxicity ; Host-Pathogen Interactions/immunology ; Humans ; Mucous Membrane/microbiology/pathology ; Mycotoxins/genetics/metabolism/secretion/*toxicity ; Signal Transduction/drug effects ; Virulence/drug effects ; Virulence Factors/genetics/*metabolism/toxicity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 185
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Segal, Rosalind A -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1494. doi: 10.1126/science.351.6280.1494.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rosalind A. Segal is a neurobiology professor at Harvard Medical School and co-chair of cancer biology at the Dana-Farber Cancer Institute in Boston. Send your story to SciCareerEditor@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013735" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; Female ; Humans ; Neurobiology/manpower ; *Sexism ; *Women, Working
    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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  • 186
    Publication Date: 2016-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis S -- Anderson, James M -- Austin, Christopher P -- Battey, James F -- Birnbaum, Linda S -- Briggs, Josephine P -- Clayton, Janine A -- Cuthbert, Bruce -- Eisinger, Robert W -- Fauci, Anthony S -- Gallin, John I -- Gibbons, Gary H -- Glass, Roger I -- Gottesman, Michael M -- Gray, Patricia A -- Green, Eric D -- Greider, Franziska B -- Hodes, Richard -- Hudson, Kathy L -- Humphreys, Betsy -- Katz, Stephen I -- Koob, George F -- Koroshetz, Walter J -- Lauer, Michael S -- Lorsch, Jon R -- Lowy, Douglas R -- McGowan, John J -- Murray, David M -- Nakamura, Richard -- Norris, Andrea -- Perez-Stable, Eliseo J -- Pettigrew, Roderic I -- Riley, William T -- Rodgers, Griffin P -- Sieving, Paul A -- Somerman, Martha J -- Spong, Catherine Y -- Tabak, Lawrence A -- Volkow, Nora D -- Wilder, Elizabeth L -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1405. doi: 10.1126/science.351.6280.1405-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Office of the Director, NIH, Bethesda, MD 20892, USA. collinsf@mail.nih.gov. ; Division of Program Coordination, Planning, and Strategic Initiatives, NIH, Bethesda, MD 20892, USA. ; National Center for Advancing Translational Science, NIH, Rockville, MD 20850, USA. ; National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. ; National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. ; National Center for Complementary and Integrative Health, NIH, Bethesda, MD 20892, USA. ; Office of Research on Women's Health, NIH, Bethesda, MD 20892, USA. ; National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. ; Office of AIDS Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. ; Clinical Center, NIH, Bethesda, MD 20892, USA. ; National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA. ; Fogarty International Center, NIH, Bethesda, MD 20892, USA. ; Office of Intramural Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Nursing Research, NIH, Bethesda, MD 20892, USA. ; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. ; Office of Research Infrastructure Programs, NIH, Bethesda, MD 20892, USA. ; National Institute on Aging, NIH, Bethesda, MD 20892, USA. ; Office of the Director, NIH, Bethesda, MD 20892, USA. ; National Library of Medicine, NIH, Bethesda, MD 20892, USA. ; National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. ; National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA. ; NINDS, NIH, Bethesda, MD 20892, USA. ; Office of Extramural Research, NIH, Bethesda, MD 20892, USA. ; National Institute of General Medical Sciences, NIH, Bethesda, MD 20892, USA. ; National Cancer Institute, NIH, Bethesda, MD 20892, USA. ; Office of Management, NIH, Bethesda, MD 20892, USA. ; Office of Disease Prevention, NIH, Bethesda, MD 20892, USA. ; Center for Scientific Review, NIH, Bethesda, MD 20892, USA. ; Center for Information Technology, NIH, Bethesda, MD 20892, USA. ; National Institute on Minority Health and Health Disparities, NIH, Bethesda, MD 20892, USA. ; National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD 20892, USA. ; Office of Behavioral and Social Sciences Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. ; National Eye Institute, NIH, Bethesda, MD 20892, USA. ; National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA. ; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. ; National Institute on Drug Abuse, NIH, Bethesda, MD 20892, USA. ; Office of Strategic Coordination, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013720" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*economics ; Humans ; National Institutes of Health (U.S.)/*economics
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 187
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Curry, Andrew -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1384-9. doi: 10.1126/science.351.6280.1384.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013711" target="_blank"〉PubMed〈/a〉
    Keywords: Bone and Bones/*injuries ; Germany ; History, Ancient ; Humans ; Military Personnel/*history ; Oceans and Seas ; Rivers ; Skull/injuries ; Violence/*history ; *Warfare ; Weapons/*history
    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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  • 188
    Publication Date: 2016-03-26
    Description: During cancer metastasis, tumor cells penetrate tissues through tight interstitial spaces, which requires extensive deformation of the cell and its nucleus. Here, we investigated mammalian tumor cell migration in confining microenvironments in vitro and in vivo. Nuclear deformation caused localized loss of nuclear envelope (NE) integrity, which led to the uncontrolled exchange of nucleo-cytoplasmic content, herniation of chromatin across the NE, and DNA damage. The incidence of NE rupture increased with cell confinement and with depletion of nuclear lamins, NE proteins that structurally support the nucleus. Cells restored NE integrity using components of the endosomal sorting complexes required for transport III (ESCRT III) machinery. Our findings indicate that cell migration incurs substantial physical stress on the NE and its content and requires efficient NE and DNA damage repair for cell survival.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833568/" 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/PMC4833568/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Denais, Celine M -- Gilbert, Rachel M -- Isermann, Philipp -- McGregor, Alexandra L -- te Lindert, Mariska -- Weigelin, Bettina -- Davidson, Patricia M -- Friedl, Peter -- Wolf, Katarina -- Lammerding, Jan -- R01 HL082792/HL/NHLBI NIH HHS/ -- R01 NS059348/NS/NINDS NIH HHS/ -- S10OD018516/OD/NIH HHS/ -- U54 CA143876/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):353-8. doi: 10.1126/science.aad7297. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nancy E. and Peter C. Meinig School of Biomedical Engineering and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA. ; Department of Cell Biology, Radboud University Medical Center, Nijmegen, Netherlands. ; Department of Cell Biology, Radboud University Medical Center, Nijmegen, Netherlands. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Cancer Genomics Center, Netherlands (CGC.nl). ; Nancy E. and Peter C. Meinig School of Biomedical Engineering and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA. jan.lammerding@cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013428" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; *Cell Movement ; Chromatin/metabolism ; Cytoplasm/metabolism ; DNA Damage ; Endosomal Sorting Complexes Required for Transport/metabolism ; Humans ; Lamins/deficiency ; Neoplasms/metabolism/*pathology ; Nuclear Envelope/metabolism/*pathology ; Stress, Mechanical ; *Tumor Microenvironment
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 189
    Publication Date: 2016-03-26
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838154/" 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/PMC4838154/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dove, Edward S -- Townend, David -- Meslin, Eric M -- Bobrow, Martin -- Littler, Katherine -- Nicol, Dianne -- de Vries, Jantina -- Junker, Anne -- Garattini, Chiara -- Bovenberg, Jasper -- Shabani, Mahsa -- Levesque, Emmanuelle -- Knoppers, Bartha M -- 099313/Wellcome Trust/United Kingdom -- 103360/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1399-400. doi: 10.1126/science.aad5269.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉J. Kenyon Mason Institute for Medicine, Life Sciences and the Law, School of Law, University of Edinburgh, UK. edward.dove@ed.ac.uk. ; Department of Health, Ethics & Society, CAPHRI Research School, Maastricht University, The Netherlands. ; Indiana University Center for Bioethics, Indiana University School of Medicine, Indianapolis, Indiana, USA. ; Honorary Faculty, Wellcome Trust Sanger Institute, Hinxton, UK. Department of Medical Genetics, University of Cambridge, UK. ; Wellcome Trust, London, UK. ; Centre for Law and Genetics, Faculty of Law, University of Tasmania, Australia. ; Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa. ; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. ; Intel Corporation, Health and Life Sciences, London, UK. ; Legal Pathways, Aerdenhout, The Netherlands. ; Centre for Biomedical Ethics and Law, KU Leuven, Leuven, Belgium. ; Centre of Genomics and Policy, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013718" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*ethics ; Datasets as Topic/ethics ; Ethical Review/*standards ; Genetics, Medical ; Genome, Human ; Humans ; Information Dissemination/*ethics ; Internationality ; Neoplasms
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  • 190
    Publication Date: 2016-03-26
    Description: Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faria, Nuno Rodrigues -- Azevedo, Raimunda do Socorro da Silva -- Kraemer, Moritz U G -- Souza, Renato -- Cunha, Mariana Sequetin -- Hill, Sarah C -- Theze, Julien -- Bonsall, Michael B -- Bowden, Thomas A -- Rissanen, Ilona -- Rocco, Iray Maria -- Nogueira, Juliana Silva -- Maeda, Adriana Yurika -- Vasami, Fernanda Giseli da Silva -- Macedo, Fernando Luiz de Lima -- Suzuki, Akemi -- Rodrigues, Sueli Guerreiro -- Cruz, Ana Cecilia Ribeiro -- Nunes, Bruno Tardeli -- Medeiros, Daniele Barbosa de Almeida -- Rodrigues, Daniela Sueli Guerreiro -- Nunes Queiroz, Alice Louize -- da Silva, Eliana Vieira Pinto -- Henriques, Daniele Freitas -- Travassos da Rosa, Elisabeth Salbe -- de Oliveira, Consuelo Silva -- Martins, Livia Caricio -- Vasconcelos, Helena Baldez -- Casseb, Livia Medeiros Neves -- Simith, Darlene de Brito -- Messina, Jane P -- Abade, Leandro -- Lourenco, Jose -- Carlos Junior Alcantara, Luiz -- de Lima, Maricelia Maia -- Giovanetti, Marta -- Hay, Simon I -- de Oliveira, Rodrigo Santos -- Lemos, Poliana da Silva -- de Oliveira, Layanna Freitas -- de Lima, Clayton Pereira Silva -- da Silva, Sandro Patroca -- de Vasconcelos, Janaina Mota -- Franco, Luciano -- Cardoso, Jedson Ferreira -- Vianez-Junior, Joao Lidio da Silva Goncalves -- Mir, Daiana -- Bello, Gonzalo -- Delatorre, Edson -- Khan, Kamran -- Creatore, Marisa -- Coelho, Giovanini Evelim -- de Oliveira, Wanderson Kleber -- Tesh, Robert -- Pybus, Oliver G -- Nunes, Marcio R T -- Vasconcelos, Pedro F C -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095066/Wellcome Trust/United Kingdom -- 102427/Wellcome Trust/United Kingdom -- MR/L009528/1/Medical Research Council/United Kingdom -- R24 AT 120942/AT/NCCIH NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):345-9. doi: 10.1126/science.aaf5036. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Para State, Brazil. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Instituto Adolfo Lutz, University of Sao Paulo, Sao Paulo, Brazil. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. Metabiota, San Francisco, CA 94104, USA. ; Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil. ; Centre of Post Graduation in Collective Health, Department of Health, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil. ; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA 98121, USA. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. ; Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. ; Laboratorio de AIDS and Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. ; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. Department of Medicine, Division of Infectious Diseases, University of Toronto, Toronto, Ontario, Canada. ; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. ; Brazilian Ministry of Health, Brasilia, Brazil. ; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. Metabiota, San Francisco, CA 94104, USA. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br. ; Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br. ; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Para State, Brazil. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013429" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/virology ; Americas/epidemiology ; Animals ; *Disease Outbreaks ; Female ; Genome, Viral/genetics ; Humans ; Incidence ; Insect Vectors/virology ; Microcephaly/*epidemiology/virology ; Molecular Epidemiology ; Molecular Sequence Data ; Mutation ; Pacific Islands/epidemiology ; Phylogeny ; Pregnancy ; RNA, Viral/genetics ; Sequence Analysis, RNA ; Travel ; Zika Virus/classification/*genetics/isolation & purification ; Zika Virus Infection/*epidemiology/transmission/*virology
    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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  • 191
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1377-8. doi: 10.1126/science.351.6280.1377.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013706" target="_blank"〉PubMed〈/a〉
    Keywords: Brazil/epidemiology ; Genome, Viral ; Humans ; *Sports ; *Travel ; Zika Virus/*genetics ; Zika Virus Infection/epidemiology/*transmission/*virology
    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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  • 192
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wala, Jeremiah -- Beroukhim, Rameen -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1398-9. doi: 10.1126/science.aaf5542.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA, and Broad Institute, Cambridge, MA 02142, USA. ; Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA, and Broad Institute, Cambridge, MA 02142, USA. rameen_beroukhim@dfci.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013717" target="_blank"〉PubMed〈/a〉
    Keywords: *Chromosome Aberrations ; *Gene Expression Regulation, Leukemic ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics ; Proto-Oncogenes/*genetics ; *Sequence Deletion ; *Translocation, Genetic
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  • 193
    Publication Date: 2016-03-26
    Description: Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825693/" 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/PMC4825693/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barrera, Luis A -- Vedenko, Anastasia -- Kurland, Jesse V -- Rogers, Julia M -- Gisselbrecht, Stephen S -- Rossin, Elizabeth J -- Woodard, Jaie -- Mariani, Luca -- Kock, Kian Hong -- Inukai, Sachi -- Siggers, Trevor -- Shokri, Leila -- Gordan, Raluca -- Sahni, Nidhi -- Cotsapas, Chris -- Hao, Tong -- Yi, Song -- Kellis, Manolis -- Daly, Mark J -- Vidal, Marc -- Hill, David E -- Bulyk, Martha L -- P50 HG004233/HG/NHGRI NIH HHS/ -- R01 HG003985/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1450-4. doi: 10.1126/science.aad2257. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. ; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA. ; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. Center for Human Genetics Research and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA. Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013732" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Computer Simulation ; DNA/*metabolism ; DNA-Binding Proteins/*genetics/metabolism ; Exome/genetics ; *Gene Expression Regulation ; Genetic Diseases, Inborn/*genetics ; Genetic Variation ; Genome, Human ; Humans ; Mutation ; Polymorphism, Single Nucleotide ; Protein Array Analysis ; Protein Binding ; Sequence Analysis, DNA ; Transcription Factors/*genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 194
    Publication Date: 2016-03-26
    Description: In eukaryotic cells, the nuclear envelope separates the genomic DNA from the cytoplasmic space and regulates protein trafficking between the two compartments. This barrier is only transiently dissolved during mitosis. Here, we found that it also opened at high frequency in migrating mammalian cells during interphase, which allowed nuclear proteins to leak out and cytoplasmic proteins to leak in. This transient opening was caused by nuclear deformation and was rapidly repaired in an ESCRT (endosomal sorting complexes required for transport)-dependent manner. DNA double-strand breaks coincided with nuclear envelope opening events. As a consequence, survival of cells migrating through confining environments depended on efficient nuclear envelope and DNA repair machineries. Nuclear envelope opening in migrating leukocytes could have potentially important consequences for normal and pathological immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raab, M -- Gentili, M -- de Belly, H -- Thiam, H R -- Vargas, P -- Jimenez, A J -- Lautenschlaeger, F -- Voituriez, Raphael -- Lennon-Dumenil, A M -- Manel, N -- Piel, M -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):359-62. doi: 10.1126/science.aad7611. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France. Institut Pierre-Gilles de Gennes, PSL Research University, F-75005 Paris, France. ; Institut Curie, PSL Research University, INSERM, U 932, F-75005 Paris, France. ; Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France. ; Laboratoire de Physique Theorique de la Matiere Condensee, CNRS UMR 7600, Universite Pierre et Marie Curie, Paris, France. Laboratoire Jean Perrin, CNRS UMR 8237, Universite Pierre et Marie Curie, Paris, France. ; Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France. Institut Pierre-Gilles de Gennes, PSL Research University, F-75005 Paris, France. matthieu.piel@curie.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013426" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Death ; *Cell Movement ; Cytoplasm/metabolism ; *DNA Breaks, Double-Stranded ; DNA Repair ; Endosomal Sorting Complexes Required for Transport/genetics/*metabolism ; HeLa Cells ; Humans ; Immunity/genetics ; Interphase ; Leukocytes/immunology/ultrastructure ; Mice ; Nuclear Envelope/*ultrastructure ; Nuclear Proteins/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 195
    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
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 196
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cate, Jamie H D -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1390-2. doi: 10.1126/science.aaf4465.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Molecular and Cell Biology and Chemistry, University of California, Berkeley, CA 94720, USA, and Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. jcate@lbl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013712" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Ribonucleoprotein, U4-U6 Small Nuclear/*chemistry ; Ribonucleoprotein, U5 Small Nuclear/*chemistry
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 197
    Publication Date: 2016-03-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2016 Mar 24;531(7595):422-3. doi: 10.1038/531422a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008946" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Mobile Applications ; Monitoring, Physiologic/*methods/trends ; *Smartphone ; Telemedicine/*trends
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 198
    Publication Date: 2016-03-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2016 Mar 24;531(7595):424-5. doi: 10.1038/nature.2016.19590.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Mapping/trends ; China ; Conservation of Natural Resources/trends ; Environmental Pollution/prevention & control ; Humans ; Neurosciences/trends ; Oceanography/trends ; Science/*trends ; Stem Cell Research
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  • 199
    Publication Date: 2016-03-25
    Description: Focal amplifications of chromosome 3p13-3p14 occur in about 10% of melanomas and are associated with a poor prognosis. The melanoma-specific oncogene MITF resides at the epicentre of this amplicon. However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding RNA (lncRNA) gene SAMMSON is consistently co-gained with MITF. In addition, SAMMSON is a target of the lineage-specific transcription factor SOX10 and its expression is detectable in more than 90% of human melanomas. Whereas exogenous SAMMSON increases the clonogenic potential in trans, SAMMSON knockdown drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state and BRAF, NRAS or TP53 mutational status. Moreover, SAMMSON targeting sensitizes melanoma to MAPK-targeting therapeutics both in vitro and in patient-derived xenograft models. Mechanistically, SAMMSON interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that silencing of the lineage addiction oncogene SAMMSON disrupts vital mitochondrial functions in a cancer-cell-specific manner; this silencing is therefore expected to deliver highly effective and tissue-restricted anti-melanoma therapeutic responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leucci, Eleonora -- Vendramin, Roberto -- Spinazzi, Marco -- Laurette, Patrick -- Fiers, Mark -- Wouters, Jasper -- Radaelli, Enrico -- Eyckerman, Sven -- Leonelli, Carina -- Vanderheyden, Katrien -- Rogiers, Aljosja -- Hermans, Els -- Baatsen, Pieter -- Aerts, Stein -- Amant, Frederic -- Van Aelst, Stefan -- van den Oord, Joost -- de Strooper, Bart -- Davidson, Irwin -- Lafontaine, Denis L J -- Gevaert, Kris -- Vandesompele, Jo -- Mestdagh, Pieter -- Marine, Jean-Christophe -- England -- Nature. 2016 Mar 24;531(7595):518-22. doi: 10.1038/nature17161.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory For Molecular Cancer Biology, Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium. ; Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. ; Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Rue Laurent Fries 1, 67404 Illkirch, France. ; Laboratory of Translational Cell and Tissue Research, Department of Pathology, KULeuven and UZ Leuven, Herestraat 49, 3000 Leuven, Belgium. ; Mouse Histopathology Core Facility, Center for the Biology of Disease, VIB-KULeuven, Herestraat 49, 3000 Leuven, Belgium. ; Medical Biotechnology Center, VIB, Albert Baertsoenkaai 3, 9000 Gent, Belgium. ; Department of Biochemistry, Gent University, Albert Baertsoenkaai 3, 9000 Gent, Belgium. ; Center for Medical Genetics, Gent University, De Pintelaan 185, 9000 Gent, Belgium. ; Cancer Research Institute Gent, Gent University, De Pintelaan 185, 9000 Gent, Belgium. ; Gynaecologische Oncologie, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. ; Laboratory of Computational Biology, Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium. ; Department of Applied Mathematics, Computer Science and Statistics, Gent University, De Pintelaan 185, 9000 Gent, Belgium. ; Department of Mathematics, KU Leuven, Celestijnenlann 200B, 3001 Leuven, Belgium. ; RNA Molecular Biology, Center for Microscopy and Molecular Imaging, Universite Libre de Bruxelles (ULB), rue des Professeurs Jeener et Brachet 12, 6041 Charleroi, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008969" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinogenesis/genetics/pathology ; Cell Lineage ; Cell Proliferation ; Cell Survival ; Chromosomes, Human, Pair 3/genetics ; Clone Cells/metabolism/pathology ; Female ; Gene Amplification/genetics ; Gene Knockdown Techniques ; Humans ; Melanoma/*genetics/*pathology/therapy ; Mice ; Microphthalmia-Associated Transcription Factor/genetics ; Mitochondria/genetics/metabolism/pathology ; Mitochondrial Proteins/metabolism ; Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism ; Molecular Targeted Therapy ; Oncogenes/*genetics ; RNA, Long Noncoding/*genetics/therapeutic use ; SOXE Transcription Factors/metabolism ; Xenograft Model Antitumor Assays
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  • 200
    Publication Date: 2016-03-25
    Description: African dust emission and transport exhibits variability on diurnal to decadal timescales and is known to influence processes such as Amazon productivity, Atlantic climate modes, regional atmospheric composition and radiative balance and precipitation in the Sahel. To elucidate the role of African dust in the climate system, it is necessary to understand the factors governing its emission and transport. However, African dust is correlated with seemingly disparate atmospheric phenomena, including the El Nino/Southern Oscillation, the North Atlantic Oscillation, the meridional position of the intertropical convergence zone, Sahelian rainfall and surface temperatures over the Sahara Desert, all of which obfuscate the connection between dust and climate. Here we show that the surface wind field responsible for most of the variability in North African dust emission reflects the topography of the Sahara, owing to orographic acceleration of the surface flow. As such, the correlations between dust and various climate phenomena probably arise from the projection of the winds associated with these phenomena onto an orographically controlled pattern of wind variability. A 161-year time series of dust from 1851 to 2011, created by projecting this wind field pattern onto surface winds from a historical reanalysis, suggests that the highest concentrations of dust occurred from the 1910s to the 1940s and the 1970s to the 1980s, and that there have been three periods of persistent anomalously low dust concentrations--in the 1860s, 1950s and 2000s. Projections of the wind pattern onto climate models give a statistically significant downward trend in African dust emission and transport as greenhouse gas concentrations increase over the twenty-first century, potentially associated with a slow-down of the tropical circulation. Such a dust feedback, which is not represented in climate models, may be of benefit to human and ecosystem health in West Africa via improved air quality and increased rainfall. This feedback may also enhance warming of the tropical North Atlantic, which would make the basin more suitable for hurricane formation and growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Evan, Amato T -- Flamant, Cyrille -- Gaetani, Marco -- Guichard, Francoise -- England -- Nature. 2016 Mar 24;531(7595):493-5. doi: 10.1038/nature17149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California, USA. ; Laboratoire Atmospheres, Milieux, Observations Spatiales (LATMOS)/IPSL, UPMC Universite Paris 06, Sorbonne Universite, UVSQ, CNRS, Paris, France. ; CNRM-GAME, UMR 3589 CNRS and Meteo-France, Toulouse, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008968" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Atmosphere/chemistry ; *Climate ; Cyclonic Storms ; Desert Climate ; Dust/*analysis ; Ecosystem ; Feedback ; Greenhouse Effect ; Humans ; Models, Theoretical ; Rain ; *Wind
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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