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  • Base Sequence
  • Chemistry
  • 2010-2014  (270)
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  • 1
    Publication Date: 2014-09-16
    Description: A defining feature governing head patterning of jawed vertebrates is a highly conserved gene regulatory network that integrates hindbrain segmentation with segmentally restricted domains of Hox gene expression. Although non-vertebrate chordates display nested domains of axial Hox expression, they lack hindbrain segmentation. The sea lamprey, a jawless fish, can provide unique insights into vertebrate origins owing to its phylogenetic position at the base of the vertebrate tree. It has been suggested that lamprey may represent an intermediate state where nested Hox expression has not been coupled to the process of hindbrain segmentation. However, little is known about the regulatory network underlying Hox expression in lamprey or its relationship to hindbrain segmentation. Here, using a novel tool that allows cross-species comparisons of regulatory elements between jawed and jawless vertebrates, we report deep conservation of both upstream regulators and segmental activity of enhancer elements across these distant species. Regulatory regions from diverse gnathostomes drive segmental reporter expression in the lamprey hindbrain and require the same transcriptional inputs (for example, Kreisler (also known as Mafba), Krox20 (also known as Egr2a)) in both lamprey and zebrafish. We find that lamprey hox genes display dynamic segmentally restricted domains of expression; we also isolated a conserved exonic hox2 enhancer from lamprey that drives segmental expression in rhombomeres 2 and 4. Our results show that coupling of Hox gene expression to segmentation of the hindbrain is an ancient trait with origin at the base of vertebrates that probably led to the formation of rhombomeric compartments with an underlying Hox code.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209185/" 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/PMC4209185/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, Hugo J -- Bronner, Marianne E -- Krumlauf, Robb -- R01 DE017911/DE/NIDCR NIH HHS/ -- R01 NS086907/NS/NINDS NIH HHS/ -- R01DE017911/DE/NIDCR NIH HHS/ -- R01NS086907/NS/NINDS NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):490-3. doi: 10.1038/nature13723. Epub 2014 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA. ; 1] Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA [2] Department of Anatomy and Cell Biology, Kansas University Medical Center, Kansas City, Kansas 66160, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25219855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Body Patterning/genetics ; Conserved Sequence/*genetics ; Enhancer Elements, Genetic/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks/*genetics ; Genes, Homeobox/*genetics ; Lampreys/embryology/genetics ; Molecular Sequence Data ; Phylogeny ; Rhombencephalon/*embryology/*metabolism ; Vertebrates/*embryology/genetics ; Zebrafish/embryology/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-02-15
    Description: Evolutionary changes in traits involved in both ecological divergence and mate choice may produce reproductive isolation and speciation. However, there are few examples of such dual traits, and the genetic and molecular bases of their evolution have not been identified. We show that methyl-branched cuticular hydrocarbons (mbCHCs) are a dual trait that affects both desiccation resistance and mate choice in Drosophila serrata. We identify a fatty acid synthase mFAS (CG3524) responsible for mbCHC production in Drosophila and find that expression of mFAS is undetectable in oenocytes (cells that produce CHCs) of a closely related, desiccation-sensitive species, D. birchii, due in part to multiple changes in cis-regulatory sequences of mFAS. We suggest that ecologically influenced changes in the production of mbCHCs have contributed to reproductive isolation between the two species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Henry -- Loehlin, David W -- Dufour, Heloise D -- Vaccarro, Kathy -- Millar, Jocelyn G -- Carroll, Sean B -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1148-51. doi: 10.1126/science.1249998. Epub 2014 Feb 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24526311" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Desiccation ; Drosophila/*genetics/physiology ; Ecosystem ; Evolution, Molecular ; Fatty Acid Synthases/*genetics/physiology ; *Genes, Insect ; *Genetic Variation ; Hydrocarbons/*metabolism ; *Mating Preference, Animal ; Molecular Sequence Data ; *Reproductive Isolation
    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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  • 3
    Publication Date: 2014-09-13
    Description: In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000x coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431643/" 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/PMC4431643/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gire, Stephen K -- Goba, Augustine -- Andersen, Kristian G -- Sealfon, Rachel S G -- Park, Daniel J -- Kanneh, Lansana -- Jalloh, Simbirie -- Momoh, Mambu -- Fullah, Mohamed -- Dudas, Gytis -- Wohl, Shirlee -- Moses, Lina M -- Yozwiak, Nathan L -- Winnicki, Sarah -- Matranga, Christian B -- Malboeuf, Christine M -- Qu, James -- Gladden, Adrianne D -- Schaffner, Stephen F -- Yang, Xiao -- Jiang, Pan-Pan -- Nekoui, Mahan -- Colubri, Andres -- Coomber, Moinya Ruth -- Fonnie, Mbalu -- Moigboi, Alex -- Gbakie, Michael -- Kamara, Fatima K -- Tucker, Veronica -- Konuwa, Edwin -- Saffa, Sidiki -- Sellu, Josephine -- Jalloh, Abdul Azziz -- Kovoma, Alice -- Koninga, James -- Mustapha, Ibrahim -- Kargbo, Kandeh -- Foday, Momoh -- Yillah, Mohamed -- Kanneh, Franklyn -- Robert, Willie -- Massally, James L B -- Chapman, Sinead B -- Bochicchio, James -- Murphy, Cheryl -- Nusbaum, Chad -- Young, Sarah -- Birren, Bruce W -- Grant, Donald S -- Scheiffelin, John S -- Lander, Eric S -- Happi, Christian -- Gevao, Sahr M -- Gnirke, Andreas -- Rambaut, Andrew -- Garry, Robert F -- Khan, S Humarr -- Sabeti, Pardis C -- 095831/Wellcome Trust/United Kingdom -- 1DP2OD006514-01/OD/NIH HHS/ -- 1U01HG007480-01/HG/NHGRI NIH HHS/ -- 260864/European Research Council/International -- DP2 OD006514/OD/NIH HHS/ -- GM080177/GM/NIGMS NIH HHS/ -- HHSN272200900049C/AI/NIAID NIH HHS/ -- HHSN272200900049C/PHS HHS/ -- T32 GM080177/GM/NIGMS NIH HHS/ -- U01 HG007480/HG/NHGRI NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U19 AI115589/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1369-72. doi: 10.1126/science.1259657. Epub 2014 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Kenema Government Hospital, Kenema, Sierra Leone. andersen@broadinstitute.org augstgoba@yahoo.com psabeti@oeb.harvard.edu. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. andersen@broadinstitute.org augstgoba@yahoo.com psabeti@oeb.harvard.edu. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Kenema Government Hospital, Kenema, Sierra Leone. ; Kenema Government Hospital, Kenema, Sierra Leone. Eastern Polytechnic College, Kenema, Sierra Leone. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Tulane University Medical Center, New Orleans, LA 70112, USA. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Redeemer's University, Ogun State, Nigeria. ; University of Sierra Leone, Freetown, Sierra Leone. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214632" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Disease Outbreaks ; Ebolavirus/*genetics/isolation & purification ; *Epidemiological Monitoring ; Genetic Variation ; Genome, Viral/genetics ; Genomics/methods ; Hemorrhagic Fever, Ebola/epidemiology/*transmission/*virology ; Humans ; Mutation ; Sequence Analysis, DNA ; Sierra Leone/epidemiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-02-18
    Description: The human neocortex has numerous specialized functional areas whose formation is poorly understood. Here, we describe a 15-base pair deletion mutation in a regulatory element of GPR56 that selectively disrupts human cortex surrounding the Sylvian fissure bilaterally including "Broca's area," the primary language area, by disrupting regional GPR56 expression and blocking RFX transcription factor binding. GPR56 encodes a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor required for normal cortical development and is expressed in cortical progenitor cells. GPR56 expression levels regulate progenitor proliferation. GPR56 splice forms are highly variable between mice and humans, and the regulatory element of gyrencephalic mammals directs restricted lateral cortical expression. Our data reveal a mechanism by which control of GPR56 expression pattern by multiple alternative promoters can influence stem cell proliferation, gyral patterning, and, potentially, neocortex evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480613/" 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/PMC4480613/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bae, Byoung-Il -- Tietjen, Ian -- Atabay, Kutay D -- Evrony, Gilad D -- Johnson, Matthew B -- Asare, Ebenezer -- Wang, Peter P -- Murayama, Ayako Y -- Im, Kiho -- Lisgo, Steven N -- Overman, Lynne -- Sestan, Nenad -- Chang, Bernard S -- Barkovich, A James -- Grant, P Ellen -- Topcu, Meral -- Politsky, Jeffrey -- Okano, Hideyuki -- Piao, Xianhua -- Walsh, Christopher A -- 2R01NS035129/NS/NINDS NIH HHS/ -- G0700089/Medical Research Council/United Kingdom -- GR082557/Wellcome Trust/United Kingdom -- HHSN275200900011C/PHS HHS/ -- N01-HD-9-0011/HD/NICHD NIH HHS/ -- R01 NS035129/NS/NINDS NIH HHS/ -- U01 MH081896/MH/NIMH NIH HHS/ -- U01MH081896/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):764-8. doi: 10.1126/science.1244392.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Broad Institute of MIT and Harvard, and Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531968" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Animals ; Base Sequence ; Biological Evolution ; Body Patterning/*genetics ; Cats ; Cell Proliferation ; Cerebral Cortex/anatomy & histology/cytology/*embryology ; Codon, Nonsense ; Frontal Lobe/anatomy & histology/cytology/embryology ; Genetic Variation ; Haplotypes ; Humans ; Mice ; Molecular Sequence Data ; Neural Stem Cells/cytology/*physiology ; Pedigree ; Promoter Regions, Genetic/genetics ; Receptors, G-Protein-Coupled/*genetics ; Sequence Deletion
    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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  • 5
    Publication Date: 2014-09-13
    Description: Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774895/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774895/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goto, Yoshiyuki -- Obata, Takashi -- Kunisawa, Jun -- Sato, Shintaro -- Ivanov, Ivaylo I -- Lamichhane, Aayam -- Takeyama, Natsumi -- Kamioka, Mariko -- Sakamoto, Mitsuo -- Matsuki, Takahiro -- Setoyama, Hiromi -- Imaoka, Akemi -- Uematsu, Satoshi -- Akira, Shizuo -- Domino, Steven E -- Kulig, Paulina -- Becher, Burkhard -- Renauld, Jean-Christophe -- Sasakawa, Chihiro -- Umesaki, Yoshinori -- Benno, Yoshimi -- Kiyono, Hiroshi -- 1R01DK098378/DK/NIDDK NIH HHS/ -- R01 DK098378/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1254009. doi: 10.1126/science.1254009. Epub 2014 Aug 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka 567-0085, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. ; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Nippon Institute for Biological Science, Tokyo 198-0024, Japan. ; Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Yakult Central Institute, Tokyo 186-8650, Japan. ; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Department of Mucosal Immunology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. ; Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI 48109-5617, USA. ; Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland. ; Ludwig Institute for Cancer Research and Universite Catholique de Louvain, Brussels B-1200, Belgium. ; Nippon Institute for Biological Science, Tokyo 198-0024, Japan. Division of Bacterial Infection, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan. ; Benno Laboratory, Innovation Center, RIKEN, Wako, Saitama 351-0198, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214634" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Disease Models, Animal ; Fucose/*metabolism ; Fucosyltransferases/genetics/metabolism ; Germ-Free Life ; Glycosylation ; Goblet Cells/enzymology/immunology/microbiology ; Ileum/enzymology/immunology/microbiology ; *Immunity, Innate ; Interleukins/immunology ; Intestinal Mucosa/enzymology/*immunology/microbiology ; Lymphocytes/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Microbiota/*immunology ; Molecular Sequence Data ; Paneth Cells/enzymology/immunology/microbiology ; Salmonella Infections/*immunology/microbiology ; *Salmonella typhimurium
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  • 6
    Publication Date: 2014-03-15
    Description: Ecological specialization should minimize niche overlap, yet herbivorous neotropical flies (Blepharoneura) and their lethal parasitic wasps (parasitoids) exhibit both extreme specialization and apparent niche overlap in host plants. From just two plant species at one site in Peru, we collected 3636 flowers yielding 1478 fly pupae representing 14 Blepharoneura fly species, 18 parasitoid species (14 Bellopius species), and parasitoid-host associations, all discovered through analysis of molecular data. Multiple sympatric species specialize on the same sex flowers of the same fly host-plant species-which suggests extreme niche overlap; however, niche partitioning was exposed by interactions between wasps and flies. Most Bellopius species emerged as adults from only one fly species, yet evidence from pupae (preadult emergence samples) show that most Bellopius also attacked additional fly species but never emerged as adults from those flies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Condon, Marty A -- Scheffer, Sonja J -- Lewis, Matthew L -- Wharton, Robert -- Adams, Dean C -- Forbes, Andrew A -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1240-4. doi: 10.1126/science.1245007.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Cornell College, Mount Vernon, IA 52314, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626926" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Biodiversity ; Cucurbitaceae/*parasitology ; Flowers/parasitology ; *Food Chain ; *Herbivory ; Molecular Sequence Data ; Peru ; Pupa/parasitology ; Tephritidae/embryology/*parasitology ; Wasps/*physiology
    Print ISSN: 0036-8075
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  • 7
    Publication Date: 2014-08-30
    Description: The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raghavan, Maanasa -- DeGiorgio, Michael -- Albrechtsen, Anders -- Moltke, Ida -- Skoglund, Pontus -- Korneliussen, Thorfinn S -- Gronnow, Bjarne -- Appelt, Martin -- Gullov, Hans Christian -- Friesen, T Max -- Fitzhugh, William -- Malmstrom, Helena -- Rasmussen, Simon -- Olsen, Jesper -- Melchior, Linea -- Fuller, Benjamin T -- Fahrni, Simon M -- Stafford, Thomas Jr -- Grimes, Vaughan -- Renouf, M A Priscilla -- Cybulski, Jerome -- Lynnerup, Niels -- Lahr, Marta Mirazon -- Britton, Kate -- Knecht, Rick -- Arneborg, Jette -- Metspalu, Mait -- Cornejo, Omar E -- Malaspinas, Anna-Sapfo -- Wang, Yong -- Rasmussen, Morten -- Raghavan, Vibha -- Hansen, Thomas V O -- Khusnutdinova, Elza -- Pierre, Tracey -- Dneprovsky, Kirill -- Andreasen, Claus -- Lange, Hans -- Hayes, M Geoffrey -- Coltrain, Joan -- Spitsyn, Victor A -- Gotherstrom, Anders -- Orlando, Ludovic -- Kivisild, Toomas -- Villems, Richard -- Crawford, Michael H -- Nielsen, Finn C -- Dissing, Jorgen -- Heinemeier, Jan -- Meldgaard, Morten -- Bustamante, Carlos -- O'Rourke, Dennis H -- Jakobsson, Mattias -- Gilbert, M Thomas P -- Nielsen, Rasmus -- Willerslev, Eske -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1255832. doi: 10.1126/science.1255832.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; Department of Biology, Pennsylvania State University, 502 Wartik Laboratory, University Park, PA 16802, USA. ; Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. ; Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. ; Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, 75236 Uppsala, Sweden. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Arctic Centre at the Ethnographic Collections (SILA), National Museum of Denmark, Frederiksholms Kanal 12, 1220 Copenhagen, Denmark. ; Department of Anthropology, University of Toronto, Toronto, Ontario M5S 2S2, Canada. ; Arctic Studies Center, Post Office Box 37012, Department of Anthropology, MRC 112, National Museum of Natural History, Smithsonian Institution, Washington, DC 20013-7012, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, 75236 Uppsala, Sweden. ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, Denmark. ; AMS 14C Dating Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, 8000 Aarhus C, Denmark. ; Anthropological Laboratory, Institute of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Frederik V's Vej 11, 2100 Copenhagen, Denmark. ; Department of Earth System Science, University of California, Irvine, CA 92697, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. AMS 14C Dating Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, 8000 Aarhus C, Denmark. ; Department of Archaeology, Memorial University, Queen's College, 210 Prince Philip Drive, St. John's, Newfoundland, A1C 5S7, Canada. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; Department of Archaeology, Memorial University, Queen's College, 210 Prince Philip Drive, St. John's, Newfoundland, A1C 5S7, Canada. ; Canadian Museum of History, 100 Rue Laurier, Gatineau, Quebec K1A 0M8, Canada. Department of Anthropology, University of Western Ontario, 1151 Richmond Street North, London N6A 5C2, Canada. ; Leverhulme Centre for Human Evolutionary Studies, Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 1QH, UK. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. Department of Archaeology, University of Aberdeen, St. Mary's Building, Elphinstone Road, Aberdeen AB24 3UF, Scotland, UK. ; Department of Archaeology, University of Aberdeen, St. Mary's Building, Elphinstone Road, Aberdeen AB24 3UF, Scotland, UK. ; National Museum of Denmark, Frederiksholms kanal 12, 1220 Copenhagen, Denmark. School of Geosciences, University of Edinburgh, Edinburgh EH8 9XP, UK. ; Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia. ; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA. School of Biological Sciences, Washington State University, Post Office Box 644236, Pullman, WA 99164, USA. ; Department of Integrative Biology, University of California, Berkeley, CA 94720, USA. Ancestry.com DNA LLC, San Francisco, CA 94107, USA. ; Informatics and Bio-computing, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, Ontario, M5G 0A3, Canada. ; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. ; Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Bashkortostan 450074, Russia. ; State Museum for Oriental Art, 12a, Nikitsky Boulevard, Moscow 119019, Russia. ; Greenland National Museum and Archives, Post Office Box 145, 3900 Nuuk, Greenland. ; Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Department of Anthropology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA. Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. ; Department of Anthropology, University of Utah, Salt Lake City, UT 84112, USA. ; Research Centre for Medical Genetics of Russian Academy of Medical Sciences, 1 Moskvorechie, Moscow 115478, Russia. ; Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden. ; Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 1QH, UK. ; Laboratory of Biological Anthropology, University of Kansas, Lawrence, KS 66045, USA. ; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA. ; Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, 75236 Uppsala, Sweden. ; Department of Integrative Biology, University of California, Berkeley, CA 94720, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ewillerslev@snm.ku.dk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170159" target="_blank"〉PubMed〈/a〉
    Keywords: Alaska/ethnology ; Arctic Regions/ethnology ; Base Sequence ; Bone and Bones ; Canada/ethnology ; DNA, Mitochondrial/genetics ; Genome, Human/*genetics ; Greenland/ethnology ; Hair ; History, Ancient ; *Human Migration ; Humans ; Inuits/ethnology/*genetics/history ; Molecular Sequence Data ; Siberia/ethnology ; Survivors/history ; Tooth
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  • 8
    Publication Date: 2014-08-26
    Description: The ethanolamine utilization (eut) locus of Enterococcus faecalis, containing at least 19 genes distributed over four polycistronic messenger RNAs, appears to be regulated by a single adenosyl cobalamine (AdoCbl)-responsive riboswitch. We report that the AdoCbl-binding riboswitch is part of a small, trans-acting RNA, EutX, which additionally contains a dual-hairpin substrate for the RNA binding-response regulator, EutV. In the absence of AdoCbl, EutX uses this structure to sequester EutV. EutV is known to regulate the eut messenger RNAs by binding dual-hairpin structures that overlap terminators and thus prevent transcription termination. In the presence of AdoCbl, EutV cannot bind to EutX and, instead, causes transcriptional read through of multiple eut genes. This work introduces riboswitch-mediated control of protein sequestration as a posttranscriptional mechanism to coordinately regulate gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356242/" 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/PMC4356242/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DebRoy, Sruti -- Gebbie, Margo -- Ramesh, Arati -- Goodson, Jonathan R -- Cruz, Melissa R -- van Hoof, Ambro -- Winkler, Wade C -- Garsin, Danielle A -- P30 DK056338/DK/NIDDK NIH HHS/ -- R01 AI076406/AI/NIAID NIH HHS/ -- R01 AI110432/AI/NIAID NIH HHS/ -- R01 GM099790/GM/NIGMS NIH HHS/ -- R01AI076406/AI/NIAID NIH HHS/ -- R01GM099790/GM/NIGMS NIH HHS/ -- R56 AI110432/AI/NIAID NIH HHS/ -- R56AI110432/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):937-40. doi: 10.1126/science.1255091.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, TX 77030, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. ; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. danielle.a.garsin@uth.tmc.edu wwinkler@umd.edu. ; Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, TX 77030, USA. danielle.a.garsin@uth.tmc.edu wwinkler@umd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25146291" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cobamides/*metabolism ; Enterococcus faecalis/*genetics/metabolism ; Ethanolamine/*metabolism ; *Gene Expression Regulation, Bacterial ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Messenger/chemistry/genetics/*metabolism ; *Response Elements ; Riboswitch/genetics/*physiology ; *Transcription, Genetic
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  • 9
    Publication Date: 2014-08-30
    Description: The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carneiro, Miguel -- Rubin, Carl-Johan -- Di Palma, Federica -- Albert, Frank W -- Alfoldi, Jessica -- Barrio, Alvaro Martinez -- Pielberg, Gerli -- Rafati, Nima -- Sayyab, Shumaila -- Turner-Maier, Jason -- Younis, Shady -- Afonso, Sandra -- Aken, Bronwen -- Alves, Joel M -- Barrell, Daniel -- Bolet, Gerard -- Boucher, Samuel -- Burbano, Hernan A -- Campos, Rita -- Chang, Jean L -- Duranthon, Veronique -- Fontanesi, Luca -- Garreau, Herve -- Heiman, David -- Johnson, Jeremy -- Mage, Rose G -- Peng, Ze -- Queney, Guillaume -- Rogel-Gaillard, Claire -- Ruffier, Magali -- Searle, Steve -- Villafuerte, Rafael -- Xiong, Anqi -- Young, Sarah -- Forsberg-Nilsson, Karin -- Good, Jeffrey M -- Lander, Eric S -- Ferrand, Nuno -- Lindblad-Toh, Kerstin -- Andersson, Leif -- 095908/Wellcome Trust/United Kingdom -- U54 HG003067/HG/NHGRI NIH HHS/ -- WT095908/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1074-9. doi: 10.1126/science.1253714.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CIBIO/InBIO, Centro de Investigacao em Biodiversidade e Recursos Geneticos, Campus Agrario de Vairao, Universidade do Porto, 4485-661, Vairao, Portugal. ; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. ; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. Vertebrate and Health Genomics, The Genome Analysis Centre, Norwich, UK. ; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. ; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden. ; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Department of Animal Production, Ain Shams University, Shoubra El-Kheima, Cairo, Egypt. ; Wellcome Trust Sanger Institute, Hinxton, UK. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; CIBIO/InBIO, Centro de Investigacao em Biodiversidade e Recursos Geneticos, Campus Agrario de Vairao, Universidade do Porto, 4485-661, Vairao, Portugal. Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK. ; Institut National de la Recherche Agronomique (INRA), UMR1388 Genetique, Physiologie et Systemes d'Elevage, F-31326 Castanet-Tolosan, France. ; Labovet Conseil, BP539, 85505 Les Herbiers Cedex, France. ; INRA, UMR1198 Biologie du Developpement et Reproduction, F-78350 Jouy-en-Josas, France. ; Department of Agricultural and Food Sciences, Division of Animal Sciences, University of Bologna, 40127 Bologna, Italy. ; Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA. ; U.S. Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA. ; ANTAGENE, Animal Genomics Laboratory, Lyon, France. ; INRA, UMR1313 Genetique Animale et Biologie Integrative, F- 78350, Jouy-en-Josas, France. ; Wellcome Trust Sanger Institute, Hinxton, UK. ; Instituto de Estudios Sociales Avanzados, (IESA-CSIC) Campo Santo de los Martires 7, Cordoba, Spain. ; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. ; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. Division of Biological Sciences, The University of Montana, Missoula, MT 59812, USA. ; CIBIO/InBIO, Centro de Investigacao em Biodiversidade e Recursos Geneticos, Campus Agrario de Vairao, Universidade do Porto, 4485-661, Vairao, Portugal. Departamento de Biologia, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre sn. 4169-007 Porto, Portugal. ; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. kersli@broadinstitute.org leif.andersson@imbim.uu.se. ; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA. kersli@broadinstitute.org leif.andersson@imbim.uu.se.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170157" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Domestic/anatomy & histology/*genetics/psychology ; Animals, Wild/anatomy & histology/*genetics/psychology ; Base Sequence ; Behavior, Animal ; Breeding ; Evolution, Molecular ; Gene Frequency ; Genetic Loci ; Genome/genetics ; Molecular Sequence Data ; Phenotype ; Polymorphism, Single Nucleotide ; Rabbits/anatomy & histology/*genetics/psychology ; Selection, Genetic ; Sequence Analysis, DNA
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  • 10
    Publication Date: 2014-11-15
    Description: Cellular memory is crucial to many natural biological processes and sophisticated synthetic biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. In this work, we use the DNA of living cell populations as genomic "tape recorders" for the analog and distributed recording of long-term event histories. We describe a platform for generating single-stranded DNA (ssDNA) in vivo in response to arbitrary transcriptional signals. When coexpressed with a recombinase, these intracellularly expressed ssDNAs target specific genomic DNA addresses, resulting in precise mutations that accumulate in cell populations as a function of the magnitude and duration of the inputs. This platform could enable long-term cellular recorders for environmental and biomedical applications, biological state machines, and enhanced genome engineering strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266475/" 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/PMC4266475/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farzadfard, Fahim -- Lu, Timothy K -- 1DP2OD008435/OD/NIH HHS/ -- 1P50GM098792/GM/NIGMS NIH HHS/ -- DP2 OD008435/OD/NIH HHS/ -- P50 GM098792/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):1256272. doi: 10.1126/science.1256272.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Synthetic Biology Group, Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA. MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA 02139, USA. MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. ; Synthetic Biology Group, Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA. MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA 02139, USA. MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. timlu@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395541" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Bioengineering ; Cells ; DNA, Single-Stranded/*genetics ; Escherichia coli/genetics ; *Genetic Code ; Genomics/methods ; Information Storage and Retrieval/*methods ; Memory ; Molecular Sequence Data ; Synthetic Biology ; *Tape Recording ; Transcription, Genetic ; *Writing
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  • 11
    Publication Date: 2014-09-02
    Description: A fundamental feature of immune systems is the ability to distinguish pathogenic from self and commensal elements, and to attack the former but tolerate the latter. Prokaryotic CRISPR-Cas immune systems defend against phage infection by using Cas nucleases and small RNA guides that specify one or more target sites for cleavage of the viral genome. Temperate phages include viruses that can integrate into the bacterial chromosome, and they can carry genes that provide a fitness advantage to the lysogenic host. However, CRISPR-Cas targeting that relies strictly on DNA sequence recognition provides indiscriminate immunity both to lytic and lysogenic infection by temperate phages-compromising the genetic stability of these potentially beneficial elements altogether. Here we show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic infection but tolerate lysogenization by temperate phages. Conditional tolerance is achieved through transcription-dependent DNA targeting, and ensures that targeting is resumed upon induction of the prophage lytic cycle. Our results provide evidence for the functional divergence of CRISPR-Cas systems and highlight the importance of targeting mechanism diversity. In addition, they extend the concept of 'tolerance to non-self' to the prokaryotic branch of adaptive immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214910/" 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/PMC4214910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldberg, Gregory W -- Jiang, Wenyan -- Bikard, David -- Marraffini, Luciano A -- 1DP2AI104556-01/AI/NIAID NIH HHS/ -- DP2 AI104556/AI/NIAID NIH HHS/ -- T32 AI070084/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Oct 30;514(7524):633-7. doi: 10.1038/nature13637. Epub 2014 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Bacteriology, The Rockefeller University, New York, New York 10065, USA. ; 1] Laboratory of Bacteriology, The Rockefeller University, New York, New York 10065, USA [2] Synthetic Biology Group, Institut Pasteur, 28 Rue du Dr. Roux, 75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25174707" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophages/*genetics/immunology/pathogenicity/*physiology ; Base Sequence ; CRISPR-Associated Proteins/immunology/metabolism ; CRISPR-Cas Systems/*genetics/immunology/*physiology ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics/immunology ; DNA, Viral/genetics/immunology/metabolism ; Immune Tolerance ; Lysogeny/genetics/immunology ; Molecular Sequence Data ; Proviruses/genetics/immunology/pathogenicity/physiology ; Staphylococcus epidermidis/*genetics/immunology/*virology ; *Transcription, Genetic
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  • 12
    Publication Date: 2014-06-12
    Description: Cutaneous melanoma is epidemiologically linked to ultraviolet radiation (UVR), but the molecular mechanisms by which UVR drives melanomagenesis remain unclear. The most common somatic mutation in melanoma is a V600E substitution in BRAF, which is an early event. To investigate how UVR accelerates oncogenic BRAF-driven melanomagenesis, we used a BRAF(V600E) mouse model. In mice expressing BRAF(V600E) in their melanocytes, a single dose of UVR that mimicked mild sunburn in humans induced clonal expansion of the melanocytes, and repeated doses of UVR increased melanoma burden. Here we show that sunscreen (UVA superior, UVB sun protection factor (SPF) 50) delayed the onset of UVR-driven melanoma, but only provided partial protection. The UVR-exposed tumours showed increased numbers of single nucleotide variants and we observed mutations (H39Y, S124F, R245C, R270C, C272G) in the Trp53 tumour suppressor in approximately 40% of cases. TP53 is an accepted UVR target in human non-melanoma skin cancer, but is not thought to have a major role in melanoma. However, we show that, in mice, mutant Trp53 accelerated BRAF(V600E)-driven melanomagenesis, and that TP53 mutations are linked to evidence of UVR-induced DNA damage in human melanoma. Thus, we provide mechanistic insight into epidemiological data linking UVR to acquired naevi in humans. Furthermore, we identify TP53/Trp53 as a UVR-target gene that cooperates with BRAF(V600E) to induce melanoma, providing molecular insight into how UVR accelerates melanomagenesis. Our study validates public health campaigns that promote sunscreen protection for individuals at risk of melanoma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112218/" 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/PMC4112218/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Viros, Amaya -- Sanchez-Laorden, Berta -- Pedersen, Malin -- Furney, Simon J -- Rae, Joel -- Hogan, Kate -- Ejiama, Sarah -- Girotti, Maria Romina -- Cook, Martin -- Dhomen, Nathalie -- Marais, Richard -- A12738/Cancer Research UK/United Kingdom -- A13540/Cancer Research UK/United Kingdom -- A17240/Cancer Research UK/United Kingdom -- A7091/Cancer Research UK/United Kingdom -- A7192/Cancer Research UK/United Kingdom -- C107/A10433/Cancer Research UK/United Kingdom -- C5759/A12328/Cancer Research UK/United Kingdom -- England -- Nature. 2014 Jul 24;511(7510):478-82. doi: 10.1038/nature13298. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK [2]. ; 1] Signal Transduction Team, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK [2]. ; Signal Transduction Team, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. ; Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. ; 1] Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK [2] Histopathology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK. ; 1] Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK [2] Signal Transduction Team, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919155" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Transformation, Neoplastic/*genetics/*radiation effects ; DNA Damage/genetics ; Disease Models, Animal ; Female ; Humans ; Melanocytes/metabolism/pathology/radiation effects ; Melanoma/etiology/*genetics/metabolism/*pathology ; Mice ; Mice, Inbred C57BL ; Mutagenesis/genetics/*radiation effects ; Mutation/genetics/radiation effects ; Nevus/etiology/genetics/metabolism/pathology ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Skin Neoplasms/etiology/genetics/metabolism/pathology ; Sunburn/complications/etiology/genetics ; Sunscreening Agents/pharmacology ; Tumor Suppressor Protein p53/*genetics/metabolism ; Ultraviolet Rays/*adverse effects
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  • 13
    Publication Date: 2014-06-12
    Description: High-throughput single-cell transcriptomics offers an unbiased approach for understanding the extent, basis and function of gene expression variation between seemingly identical cells. Here we sequence single-cell RNA-seq libraries prepared from over 1,700 primary mouse bone-marrow-derived dendritic cells spanning several experimental conditions. We find substantial variation between identically stimulated dendritic cells, in both the fraction of cells detectably expressing a given messenger RNA and the transcript's level within expressing cells. Distinct gene modules are characterized by different temporal heterogeneity profiles. In particular, a 'core' module of antiviral genes is expressed very early by a few 'precocious' cells in response to uniform stimulation with a pathogenic component, but is later activated in all cells. By stimulating cells individually in sealed microfluidic chambers, analysing dendritic cells from knockout mice, and modulating secretion and extracellular signalling, we show that this response is coordinated by interferon-mediated paracrine signalling from these precocious cells. Notably, preventing cell-to-cell communication also substantially reduces variability between cells in the expression of an early-induced 'peaked' inflammatory module, suggesting that paracrine signalling additionally represses part of the inflammatory program. Our study highlights the importance of cell-to-cell communication in controlling cellular heterogeneity and reveals general strategies that multicellular populations can use to establish complex dynamic responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193940/" 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/PMC4193940/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shalek, Alex K -- Satija, Rahul -- Shuga, Joe -- Trombetta, John J -- Gennert, Dave -- Lu, Diana -- Chen, Peilin -- Gertner, Rona S -- Gaublomme, Jellert T -- Yosef, Nir -- Schwartz, Schraga -- Fowler, Brian -- Weaver, Suzanne -- Wang, Jing -- Wang, Xiaohui -- Ding, Ruihua -- Raychowdhury, Raktima -- Friedman, Nir -- Hacohen, Nir -- Park, Hongkun -- May, Andrew P -- Regev, Aviv -- 1F32HD075541-01/HD/NICHD NIH HHS/ -- 1P50HG006193-01/HG/NHGRI NIH HHS/ -- 5DP1OD003893-03/OD/NIH HHS/ -- DP1 CA174427/CA/NCI NIH HHS/ -- DP1OD003958-01/OD/NIH HHS/ -- F32 HD075541/HD/NICHD NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- U54 AI057159/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 19;510(7505):363-9. doi: 10.1038/nature13437. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Chemistry & Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA [2] Department of Physics, Harvard University, 17 Oxford Street, Cambridge, Massachusetts 02138, USA [3] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [4]. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2]. ; 1] Fluidigm Corporation, 7000 Shoreline Court, Suite 100, South San Francisco, California 94080, USA [2]. ; Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; Fluidigm Corporation, 7000 Shoreline Court, Suite 100, South San Francisco, California 94080, USA. ; 1] Department of Chemistry & Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA [2] Department of Physics, Harvard University, 17 Oxford Street, Cambridge, Massachusetts 02138, USA. ; School of Computer Science and Engineering, Hebrew University, 91904 Jerusalem, Israel. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Center for Immunology and Inflammatory Diseases & Department of Medicine, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. ; 1] Department of Chemistry & Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA [2] Department of Physics, Harvard University, 17 Oxford Street, Cambridge, Massachusetts 02138, USA [3] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919153" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Viral/pharmacology ; Base Sequence ; Cell Communication ; Dendritic Cells/drug effects/*immunology ; Gene Expression Profiling ; Gene Expression Regulation/*immunology ; Immunity/*genetics ; Interferon-beta/genetics ; Mice ; Microfluidic Analytical Techniques ; *Paracrine Communication ; Principal Component Analysis ; RNA, Messenger/chemistry/genetics ; Single-Cell Analysis
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  • 14
    Publication Date: 2014-03-07
    Description: A hexanucleotide repeat expansion (HRE), (GGGGCC)n, in C9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we identify a molecular mechanism by which structural polymorphism of the HRE leads to ALS/FTD pathology and defects. The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA*DNA hybrids (R-loops). The structural polymorphism causes a repeat-length-dependent accumulation of transcripts aborted in the HRE region. These transcribed repeats bind to ribonucleoproteins in a conformation-dependent manner. Specifically, nucleolin, an essential nucleolar protein, preferentially binds the HRE G-quadruplex, and patient cells show evidence of nucleolar stress. Our results demonstrate that distinct C9orf72 HRE structural polymorphism at both DNA and RNA levels initiates molecular cascades leading to ALS/FTD pathologies, and provide the basis for a mechanistic model for repeat-associated neurodegenerative diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046618/" 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/PMC4046618/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haeusler, Aaron R -- Donnelly, Christopher J -- Periz, Goran -- Simko, Eric A J -- Shaw, Patrick G -- Kim, Min-Sik -- Maragakis, Nicholas J -- Troncoso, Juan C -- Pandey, Akhilesh -- Sattler, Rita -- Rothstein, Jeffrey D -- Wang, Jiou -- 5T32CA009110-36/CA/NCI NIH HHS/ -- NS07432/NS/NINDS NIH HHS/ -- NS085207/NS/NINDS NIH HHS/ -- P30 DK089502/DK/NIDDK NIH HHS/ -- P50 AG005146/AG/NIA NIH HHS/ -- P50AG05146/AG/NIA NIH HHS/ -- R01 NS074324/NS/NINDS NIH HHS/ -- R01 NS085207/NS/NINDS NIH HHS/ -- T32 CA009110/CA/NCI NIH HHS/ -- UL1 TR001079/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Mar 13;507(7491):195-200. doi: 10.1038/nature13124. Epub 2014 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Biology, Johns Hopkins University Baltimore, Maryland 21205, USA [2] Department of Neuroscience, Johns Hopkins University Baltimore, Maryland 21205, USA. ; 1] Department of Neurology, Johns Hopkins University Baltimore, Maryland 21205, USA [2] The Brain Science Institute, Johns Hopkins University Baltimore, Maryland 21205, USA. ; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University Baltimore, Maryland 21205, USA. ; Department of Neurology, Johns Hopkins University Baltimore, Maryland 21205, USA. ; Department of Pathology, Johns Hopkins University Baltimore, Maryland, 21205, USA. ; 1] Department of Neuroscience, Johns Hopkins University Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University Baltimore, Maryland 21205, USA [3] The Brain Science Institute, Johns Hopkins University Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24598541" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/genetics ; B-Lymphocytes ; Base Sequence ; Cell Nucleolus/genetics/pathology ; DNA/genetics/metabolism ; DNA Repeat Expansion/*genetics ; Frontotemporal Dementia/genetics ; G-Quadruplexes ; HEK293 Cells ; Humans ; Models, Molecular ; Neurons ; Open Reading Frames/*genetics ; Phosphoproteins/metabolism ; RNA/biosynthesis/chemistry/genetics/metabolism ; RNA-Binding Proteins/metabolism ; Ribonucleoproteins/metabolism ; Stress, Physiological ; Transcription, Genetic/genetics
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  • 15
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2014 Oct 16;514(7522):282. doi: 10.1038/514282a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25318499" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Databases, Genetic ; Disease/*genetics ; Genetic Association Studies ; Genetic Variation/genetics ; Genetics, Medical ; Humans ; Information Dissemination ; Phenotype ; Sequence Analysis, DNA
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  • 16
    Publication Date: 2014-06-12
    Description: Ligation of tRNAs with their cognate amino acids, by aminoacyl-tRNA synthetases, establishes the genetic code. Throughout evolution, tRNA(Ala) selection by alanyl-tRNA synthetase (AlaRS) has depended predominantly on a single wobble base pair in the acceptor stem, G3*U70, mainly on the kcat level. Here we report the crystal structures of an archaeal AlaRS in complex with tRNA(Ala) with G3*U70 and its A3*U70 variant. AlaRS interacts with both the minor- and the major-groove sides of G3*U70, widening the major groove. The geometry difference between G3*U70 and A3*U70 is transmitted along the acceptor stem to the 3'-CCA region. Thus, the 3'-CCA region of tRNA(Ala) with G3*U70 is oriented to the reactive route that reaches the active site, whereas that of the A3*U70 variant is folded back into the non-reactive route. This novel mechanism enables the single wobble pair to dominantly determine the specificity of tRNA selection, by an approximate 100-fold difference in kcat.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323281/" 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/PMC4323281/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naganuma, Masahiro -- Sekine, Shun-ichi -- Chong, Yeeting Esther -- Guo, Min -- Yang, Xiang-Lei -- Gamper, Howard -- Hou, Ya-Ming -- Schimmel, Paul -- Yokoyama, Shigeyuki -- GM015539/GM/NIGMS NIH HHS/ -- GM023562/GM/NIGMS NIH HHS/ -- NS085092/NS/NINDS NIH HHS/ -- R01 GM015539/GM/NIGMS NIH HHS/ -- R01 GM023562/GM/NIGMS NIH HHS/ -- R01 GM100136/GM/NIGMS NIH HHS/ -- R01 NS085092/NS/NINDS NIH HHS/ -- England -- Nature. 2014 Jun 26;510(7506):507-11. doi: 10.1038/nature13440. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [3] RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; 1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [3] Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; 1] The Skaggs Institute for Chemical Biology and the Department of Cell and Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA [2] aTyr Pharma, 3545 John Hopkins Court, San Diego, California 92121, USA (Y.E.C.); Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, USA (M.G.). ; The Skaggs Institute for Chemical Biology and the Department of Cell and Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. ; 1] The Skaggs Institute for Chemical Biology and the Department of Cell and Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA [2] The Scripps Florida Research Institute, 130 Scripps Way, 3B3 Jupiter, Florida 33458-5284, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919148" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Monophosphate/analogs & derivatives/chemistry ; Alanine-tRNA Ligase/*chemistry ; Archaeoglobus fulgidus/*enzymology/*genetics ; *Base Pairing ; Base Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Kinetics ; Models, Molecular ; RNA, Transfer, Ala/*chemistry/*genetics ; Substrate Specificity ; *Transfer RNA Aminoacylation
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  • 17
    Publication Date: 2014-04-04
    Description: Cancer genome sequencing studies indicate that a single breast cancer typically harbours multiple genetically distinct subclones. As carcinogenesis involves a breakdown in the cell-cell cooperation that normally maintains epithelial tissue architecture, individual subclones within a malignant microenvironment are commonly depicted as self-interested competitors. Alternatively, breast cancer subclones might interact cooperatively to gain a selective growth advantage in some cases. Although interclonal cooperation has been shown to drive tumorigenesis in fruitfly models, definitive evidence for functional cooperation between epithelial tumour cell subclones in mammals is lacking. Here we use mouse models of breast cancer to show that interclonal cooperation can be essential for tumour maintenance. Aberrant expression of the secreted signalling molecule Wnt1 generates mixed-lineage mammary tumours composed of basal and luminal tumour cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumour cell hierarchy. Using somatic Hras mutations as clonal markers, we show that some Wnt tumours indeed conform to a hierarchical configuration, but that others unexpectedly harbour genetically distinct basal Hras mutant and luminal Hras wild-type subclones. Both subclones are required for efficient tumour propagation, which strictly depends on luminally produced Wnt1. When biclonal tumours were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumour regression and relapse revealed that basal subclones recruit heterologous Wnt-producing cells to restore tumour growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolve to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumour cell communities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050741/" 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/PMC4050741/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cleary, Allison S -- Leonard, Travis L -- Gestl, Shelley A -- Gunther, Edward J -- R01 CA152222/CA/NCI NIH HHS/ -- England -- Nature. 2014 Apr 3;508(7494):113-7. doi: 10.1038/nature13187.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA [2] Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA. ; 1] Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA [2] Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA [3] Department of Medicine (Hematology/Oncology), Pennsylvania State University College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695311" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Lineage ; Cell Proliferation ; Clone Cells/metabolism/pathology ; Disease Models, Animal ; Female ; Mice ; Mosaicism ; Mutation ; Neoplasm Recurrence, Local/genetics/metabolism/pathology ; Neoplastic Stem Cells/metabolism/pathology ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Wnt Signaling Pathway ; Wnt1 Protein/deficiency/*metabolism
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  • 18
    Publication Date: 2014-10-03
    Description: The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA-DNA complementarity to identify target sites for sequence-specific double-stranded DNA (dsDNA) cleavage. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, known as the protospacer adjacent motif (PAM), next to and on the strand opposite the twenty-nucleotide target site in dsDNA. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in a large range of prokaryotic and eukaryotic cell types, and in whole organisms, but it has been thought to be incapable of targeting RNA. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalysed DNA cleavage. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous messenger RNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable transcript recognition without the need for tags.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268322/" 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/PMC4268322/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connell, Mitchell R -- Oakes, Benjamin L -- Sternberg, Samuel H -- East-Seletsky, Alexandra -- Kaplan, Matias -- Doudna, Jennifer A -- P50 GM102706/GM/NIGMS NIH HHS/ -- P50GM102706-03/GM/NIGMS NIH HHS/ -- T32 GM007232/GM/NIGMS NIH HHS/ -- T32 GM066698/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 11;516(7530):263-6. doi: 10.1038/nature13769. Epub 2014 Sep 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. ; Department of Chemistry, University of California, Berkeley, California 94720, USA. ; 1] Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA [2] Department of Agricultural and Biological Engineering, University of Florida, Gainesville, Florida 32611, USA. ; 1] Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA [2] Department of Chemistry, University of California, Berkeley, California 94720, USA [3] Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA [4] Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25274302" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; CRISPR-Associated Proteins/*metabolism ; CRISPR-Cas Systems/*physiology ; Cell Extracts ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; DNA/chemistry/genetics/metabolism ; Genetic Engineering/*methods ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/genetics ; HeLa Cells ; Humans ; Nucleotide Motifs ; Oligonucleotides/chemistry/genetics/metabolism ; RNA/chemistry/genetics/*metabolism ; RNA, Guide/chemistry/genetics/metabolism ; RNA, Messenger/genetics/isolation & purification/metabolism ; Substrate Specificity
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  • 19
    Publication Date: 2014-06-10
    Description: RNA is arguably the most functionally diverse biological macromolecule. In some cases a single discrete RNA sequence performs multiple roles, and this can be conferred by a complex three-dimensional structure. Such multifunctionality can also be driven or enhanced by the ability of a given RNA to assume different conformational (and therefore functional) states. Despite its biological importance, a detailed structural understanding of the paradigm of RNA structure-driven multifunctionality is lacking. To address this gap it is useful to study examples from single-stranded positive-sense RNA viruses, a prototype being the tRNA-like structure (TLS) found at the 3' end of the turnip yellow mosaic virus (TYMV). This TLS not only acts like a tRNA to drive aminoacylation of the viral genomic (g)RNA, but also interacts with other structures in the 3' untranslated region of the gRNA, contains the promoter for negative-strand synthesis, and influences several infection-critical processes. TLS RNA can provide a glimpse into the structural basis of RNA multifunctionality and plasticity, but for decades its high-resolution structure has remained elusive. Here we present the crystal structure of the complete TYMV TLS to 2.0 A resolution. Globally, the RNA adopts a shape that mimics tRNA, but it uses a very different set of intramolecular interactions to achieve this shape. These interactions also allow the TLS to readily switch conformations. In addition, the TLS structure is 'two faced': one face closely mimics tRNA and drives aminoacylation, the other face diverges from tRNA and enables additional functionality. The TLS is thus structured to perform several functions and interact with diverse binding partners, and we demonstrate its ability to specifically bind to ribosomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136544/" 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/PMC4136544/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colussi, Timothy M -- Costantino, David A -- Hammond, John A -- Ruehle, Grant M -- Nix, Jay C -- Kieft, Jeffrey S -- GM081346/GM/NIGMS NIH HHS/ -- GM097333/GM/NIGMS NIH HHS/ -- P30 CA046934/CA/NCI NIH HHS/ -- P30CA046934/CA/NCI NIH HHS/ -- R01 GM081346/GM/NIGMS NIH HHS/ -- R01 GM097333/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 17;511(7509):366-9. doi: 10.1038/nature13378. Epub 2014 Jun 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [3] Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA (T.M.C.); Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037, USA (J.A.H.). ; 1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. ; 1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA (T.M.C.); Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037, USA (J.A.H.). ; Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. ; Molecular Biology Consortium, Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24909993" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Amino Acyl-tRNA Synthetases/metabolism ; Aminoacylation ; Base Sequence ; Crystallography, X-Ray ; Models, Molecular ; *Molecular Mimicry ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Protein Binding ; RNA Folding ; RNA, Guide/genetics/metabolism ; RNA, Transfer/*chemistry/genetics/metabolism ; RNA, Viral/*chemistry/genetics/*metabolism ; Ribosomes/chemistry/metabolism ; Tymovirus/*genetics
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  • 20
    Publication Date: 2014-11-05
    Description: Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to identify candidate causal variants for 21 autoimmune diseases from genotyping data. We integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4(+) T-cell subsets, regulatory T cells, CD8(+) T cells, B cells, and monocytes. We find that approximately 90% of causal variants are non-coding, with approximately 60% mapping to immune-cell enhancers, many of which gain histone acetylation and transcribe enhancer-associated RNA upon immune stimulation. Causal variants tend to occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation, but only 10-20% directly alter recognizable transcription factor binding motifs. Rather, most non-coding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336207/" 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/PMC4336207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farh, Kyle Kai-How -- Marson, Alexander -- Zhu, Jiang -- Kleinewietfeld, Markus -- Housley, William J -- Beik, Samantha -- Shoresh, Noam -- Whitton, Holly -- Ryan, Russell J H -- Shishkin, Alexander A -- Hatan, Meital -- Carrasco-Alfonso, Marlene J -- Mayer, Dita -- Luckey, C John -- Patsopoulos, Nikolaos A -- De Jager, Philip L -- Kuchroo, Vijay K -- Epstein, Charles B -- Daly, Mark J -- Hafler, David A -- Bernstein, Bradley E -- 12-0089/Worldwide Cancer Research/United Kingdom -- AI039671/AI/NIAID NIH HHS/ -- AI045757/AI/NIAID NIH HHS/ -- AI046130/AI/NIAID NIH HHS/ -- AI070352/AI/NIAID NIH HHS/ -- ES017155/ES/NIEHS NIH HHS/ -- GM093080/GM/NIGMS NIH HHS/ -- HG004570/HG/NHGRI NIH HHS/ -- NS067305/NS/NINDS NIH HHS/ -- NS24247/NS/NINDS NIH HHS/ -- P01 AI039671/AI/NIAID NIH HHS/ -- P01 AI045757/AI/NIAID NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- R01 NS024247/NS/NINDS NIH HHS/ -- R37 NS024247/NS/NINDS NIH HHS/ -- T32 GM007748/GM/NIGMS NIH HHS/ -- U01 ES017155/ES/NIEHS NIH HHS/ -- U19 AI046130/AI/NIAID NIH HHS/ -- U19 AI070352/AI/NIAID NIH HHS/ -- U54 HG004570/HG/NHGRI NIH HHS/ -- U54 HG006991/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Feb 19;518(7539):337-43. doi: 10.1038/nature13835. Epub 2014 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Diabetes Center and Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, California 94143, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA [3] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA [4] Center for Systems Biology and Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, Connecticut 06511, USA. ; Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, Connecticut 06511, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA. ; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02142, USA [3] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02142, USA. ; Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363779" target="_blank"〉PubMed〈/a〉
    Keywords: Autoimmune Diseases/*genetics/immunology/pathology ; Base Sequence ; Chromatin/genetics ; Consensus Sequence/genetics ; Enhancer Elements, Genetic/genetics ; Epigenesis, Genetic/*genetics ; Epigenomics ; Genome-Wide Association Study ; Humans ; Nucleotide Motifs ; Organ Specificity ; Polymorphism, Single Nucleotide/*genetics ; T-Lymphocytes/immunology/metabolism ; Transcription Factors/metabolism
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  • 21
    Publication Date: 2014-09-12
    Description: The ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garreau de Loubresse, Nicolas -- Prokhorova, Irina -- Holtkamp, Wolf -- Rodnina, Marina V -- Yusupova, Gulnara -- Yusupov, Marat -- 294312/European Research Council/International -- England -- Nature. 2014 Sep 25;513(7519):517-22. doi: 10.1038/nature13737. Epub 2014 Sep 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Universite de Strasbourg, 67404, Illkirch, France. ; Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209664" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites/drug effects ; Crystallography, X-Ray ; Cycloheximide/pharmacology ; Drug Resistance/drug effects ; Eukaryotic Cells/*chemistry/drug effects/enzymology ; Kinetics ; Macrolides/pharmacology ; Models, Molecular ; Molecular Targeted Therapy ; Molecular Weight ; Peptide Chain Elongation, Translational/drug effects ; Peptidyl Transferases/chemistry/metabolism ; Piperidones/pharmacology ; Protein Synthesis Inhibitors/*chemistry/*pharmacology ; RNA, Messenger/genetics/metabolism ; RNA, Transfer/genetics/metabolism ; Ribosome Subunits, Large, Eukaryotic/chemistry/drug effects/metabolism ; Ribosomes/*chemistry/*drug effects/metabolism ; Saccharomyces cerevisiae/*chemistry ; Species Specificity ; Substrate Specificity
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  • 22
    Publication Date: 2014-05-16
    Description: The silkworm Bombyx mori uses a WZ sex determination system that is analogous to the one found in birds and some reptiles. In this system, males have two Z sex chromosomes, whereas females have Z and W sex chromosomes. The silkworm W chromosome has a dominant role in female determination, suggesting the existence of a dominant feminizing gene in this chromosome. However, the W chromosome is almost fully occupied by transposable element sequences, and no functional protein-coding gene has been identified so far. Female-enriched PIWI-interacting RNAs (piRNAs) are the only known transcripts that are produced from the sex-determining region of the W chromosome, but the function(s) of these piRNAs are unknown. Here we show that a W-chromosome-derived, female-specific piRNA is the feminizing factor of B. mori. This piRNA is produced from a piRNA precursor which we named Fem. Fem sequences were arranged in tandem in the sex-determining region of the W chromosome. Inhibition of Fem-derived piRNA-mediated signalling in female embryos led to the production of the male-specific splice variants of B. mori doublesex (Bmdsx), a gene which acts at the downstream end of the sex differentiation cascade. A target gene of Fem-derived piRNA was identified on the Z chromosome of B. mori. This gene, which we named Masc, encoded a CCCH-type zinc finger protein. We show that the silencing of Masc messenger RNA by Fem piRNA is required for the production of female-specific isoforms of Bmdsx in female embryos, and that Masc protein controls both dosage compensation and masculinization in male embryos. Our study characterizes a single small RNA that is responsible for primary sex determination in the WZ sex determination system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kiuchi, Takashi -- Koga, Hikaru -- Kawamoto, Munetaka -- Shoji, Keisuke -- Sakai, Hiroki -- Arai, Yuji -- Ishihara, Genki -- Kawaoka, Shinpei -- Sugano, Sumio -- Shimada, Toru -- Suzuki, Yutaka -- Suzuki, Masataka G -- Katsuma, Susumu -- England -- Nature. 2014 May 29;509(7502):633-6. doi: 10.1038/nature13315. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. ; 1] Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan [2]. ; Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan. ; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828047" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/genetics ; Animals ; Base Sequence ; Bombyx/embryology/*genetics ; Dosage Compensation, Genetic ; Female ; Male ; Molecular Sequence Data ; RNA, Small Interfering/*genetics ; *Sex Characteristics ; Sex Chromosomes/genetics ; Sex Determination Processes/*genetics
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  • 23
    Publication Date: 2014-01-17
    Description: Cells of the osteoblast lineage affect the homing and the number of long-term repopulating haematopoietic stem cells, haematopoietic stem cell mobilization and lineage determination and B cell lymphopoiesis. Osteoblasts were recently implicated in pre-leukaemic conditions in mice. However, a single genetic change in osteoblasts that can induce leukaemogenesis has not been shown. Here we show that an activating mutation of beta-catenin in mouse osteoblasts alters the differentiation potential of myeloid and lymphoid progenitors leading to development of acute myeloid leukaemia with common chromosomal aberrations and cell autonomous progression. Activated beta-catenin stimulates expression of the Notch ligand jagged 1 in osteoblasts. Subsequent activation of Notch signalling in haematopoietic stem cell progenitors induces the malignant changes. Genetic or pharmacological inhibition of Notch signalling ameliorates acute myeloid leukaemia and demonstrates the pathogenic role of the Notch pathway. In 38% of patients with myelodysplastic syndromes or acute myeloid leukaemia, increased beta-catenin signalling and nuclear accumulation was identified in osteoblasts and these patients showed increased Notch signalling in haematopoietic cells. These findings demonstrate that genetic alterations in osteoblasts can induce acute myeloid leukaemia, identify molecular signals leading to this transformation and suggest a potential novel pharmacotherapeutic approach to acute myeloid leukaemia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116754/" 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/PMC4116754/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kode, Aruna -- Manavalan, John S -- Mosialou, Ioanna -- Bhagat, Govind -- Rathinam, Chozha V -- Luo, Na -- Khiabanian, Hossein -- Lee, Albert -- Murty, Vundavalli V -- Friedman, Richard -- Brum, Andrea -- Park, David -- Galili, Naomi -- Mukherjee, Siddhartha -- Teruya-Feldstein, Julie -- Raza, Azra -- Rabadan, Raul -- Berman, Ellin -- Kousteni, Stavroula -- P01 AG032959/AG/NIA NIH HHS/ -- P30 DK063608/DK/NIDDK NIH HHS/ -- R01 AR054447/AR/NIAMS NIH HHS/ -- R01 AR055931/AR/NIAMS NIH HHS/ -- T32 GM082797/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Feb 13;506(7487):240-4. doi: 10.1038/nature12883. Epub 2014 Jan 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Endocrinology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA. ; Department of Pathology and Cell Biology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA. ; Department of Genetics and Development College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA. ; Department of Biomedical Informatics and Center for Computational Biology and Bioinformatics, Columbia University, New York, New York 10032, USA. ; Department of Pathology & Institute for Cancer Genetics Irving Cancer Research Center, Columbia University, New York, New York 10032, USA. ; Biomedical Informatics Shared Resource, Herbert Irving Comprehensive Cancer Center and Department of Biomedical Informatics, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA. ; 1] Department of Medicine, Division of Endocrinology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA [2] Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 50, NL-3015 GE Rotterdam, The Netherlands. ; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. ; Myelodysplastic Syndromes Center, Columbia University New York, New York 10032, USA. ; Departments of Medicine Hematology & Oncology Columbia University New York, New York 10032, USA. ; Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. ; 1] Department of Medicine, Division of Endocrinology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA [2] Department of Physiology & Cellular Biophysics, College of Physicians & Surgeons, 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/24429522" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia/genetics/metabolism/pathology ; Animals ; Base Sequence ; Calcium-Binding Proteins/deficiency/genetics/metabolism ; Cell Differentiation/genetics ; Cell Lineage ; Cell Nucleus/metabolism ; Cell Transformation, Neoplastic/*genetics/pathology ; Chromosome Aberrations ; Female ; Hematopoietic Stem Cells/metabolism/pathology ; Humans ; Intercellular Signaling Peptides and Proteins/deficiency/genetics/metabolism ; Leukemia, Myeloid, Acute/*genetics/metabolism/*pathology ; Ligands ; Male ; Membrane Proteins/deficiency/genetics/metabolism ; Mice ; Mutation/*genetics ; Myelodysplastic Syndromes/genetics/metabolism/pathology ; Myeloid Cells/metabolism/pathology ; Osteoblasts/*metabolism/pathology/secretion ; Receptors, Notch/metabolism ; Signal Transduction ; Tumor Microenvironment/genetics ; beta Catenin/*genetics/*metabolism
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  • 24
    Publication Date: 2014-01-31
    Description: In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic microRNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of 'riboSNitches' versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3' untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973747/" 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/PMC3973747/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wan, Yue -- Qu, Kun -- Zhang, Qiangfeng Cliff -- Flynn, Ryan A -- Manor, Ohad -- Ouyang, Zhengqing -- Zhang, Jiajing -- Spitale, Robert C -- Snyder, Michael P -- Segal, Eran -- Chang, Howard Y -- P30 CA034196/CA/NCI NIH HHS/ -- R01 HG004361/HG/NHGRI NIH HHS/ -- R01-HG004361/HG/NHGRI NIH HHS/ -- T32 CA009302/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 30;505(7485):706-9. doi: 10.1038/nature12946.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Stem Cell and Development, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672 [3]. ; 1] Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2]. ; Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovet 76100, Israel. ; 1] Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] The Jackson Laboratory for Genomic Medicine, 263 Farmington Avenue, ASB Call Box 901 Farmington, Connecticut 06030, USA. ; Department of Genetics, 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/24476892" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; Base Sequence ; Binding Sites ; Child ; Female ; Gene Expression Regulation/genetics ; Genome, Human/genetics ; Humans ; Male ; MicroRNAs/chemistry/genetics/metabolism ; *Nucleic Acid Conformation ; Open Reading Frames/genetics ; Point Mutation/genetics ; RNA/*chemistry/*genetics/metabolism ; RNA Splice Sites/genetics ; RNA-Binding Proteins/metabolism ; Transcriptome/*genetics
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  • 25
    Publication Date: 2014-07-22
    Description: Bone-resorbing osteoclasts significantly contribute to osteoporosis and bone metastases of cancer. MicroRNAs play important roles in physiology and disease, and present tremendous therapeutic potential. Nonetheless, how microRNAs regulate skeletal biology is underexplored. Here we identify miR-34a as a novel and critical suppressor of osteoclastogenesis, bone resorption and the bone metastatic niche. miR-34a is downregulated during osteoclast differentiation. Osteoclastic miR-34a-overexpressing transgenic mice exhibit lower bone resorption and higher bone mass. Conversely, miR-34a knockout and heterozygous mice exhibit elevated bone resorption and reduced bone mass. Consequently, ovariectomy-induced osteoporosis, as well as bone metastasis of breast and skin cancers, are diminished in osteoclastic miR-34a transgenic mice, and can be effectively attenuated by miR-34a nanoparticle treatment. Mechanistically, we identify transforming growth factor-beta-induced factor 2 (Tgif2) as an essential direct miR-34a target that is pro-osteoclastogenic. Tgif2 deletion reduces bone resorption and abolishes miR-34a regulation. Together, using mouse genetic, pharmacological and disease models, we reveal miR-34a as a key osteoclast suppressor and a potential therapeutic strategy to confer skeletal protection and ameliorate bone metastasis of cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149606/" 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/PMC4149606/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krzeszinski, Jing Y -- Wei, Wei -- Huynh, HoangDinh -- Jin, Zixue -- Wang, Xunde -- Chang, Tsung-Cheng -- Xie, Xian-Jin -- He, Lin -- Mangala, Lingegowda S -- Lopez-Berestein, Gabriel -- Sood, Anil K -- Mendell, Joshua T -- Wan, Yihong -- 1P30 CA142543/CA/NCI NIH HHS/ -- 1S10RR02564801/RR/NCRR NIH HHS/ -- P01 CA134292/CA/NCI NIH HHS/ -- P30 CA142543/CA/NCI NIH HHS/ -- R01 CA120185/CA/NCI NIH HHS/ -- R01 CA139067/CA/NCI NIH HHS/ -- R01 DK089113/DK/NIDDK NIH HHS/ -- S10 RR024757/RR/NCRR NIH HHS/ -- S10 RR025648/RR/NCRR NIH HHS/ -- U54 CA151668/CA/NCI NIH HHS/ -- UH2 TR000943/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Aug 28;512(7515):431-5. doi: 10.1038/nature13375. Epub 2014 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; 1] Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Division of Cellular and Developmental Biology, Molecular and Cell Biology Department, University of California at Berkeley, Berkeley, California 94705, USA. ; 1] Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; 1] Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; 1] Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [3] Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; 1] Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; 1] Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043055" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Bone Neoplasms/genetics/pathology/*prevention & control/*secondary ; Bone Resorption/drug therapy/genetics ; Cell Differentiation/drug effects/*genetics ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Gene Deletion ; Homeodomain Proteins/antagonists & inhibitors/genetics/metabolism ; Humans ; Male ; Mammary Neoplasms, Animal/pathology ; Mice ; Mice, Transgenic ; MicroRNAs/*genetics/pharmacology/therapeutic use ; Neoplasm Transplantation ; Organ Size/drug effects ; Osteoclasts/drug effects/*pathology ; Osteoporosis/genetics/pathology/*prevention & control ; Ovariectomy ; Repressor Proteins/antagonists & inhibitors/*deficiency/genetics/metabolism ; Skin Neoplasms/pathology ; Transgenes ; Xenograft Model Antitumor Assays
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  • 26
    Publication Date: 2014-01-31
    Description: Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other 'housekeeping' proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086860/" 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/PMC4086860/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subtelny, Alexander O -- Eichhorn, Stephen W -- Chen, Grace R -- Sive, Hazel -- Bartel, David P -- GM067031/GM/NIGMS NIH HHS/ -- R01 GM067031/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Apr 3;508(7494):66-71. doi: 10.1038/nature13007. Epub 2014 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4] Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA [5]. ; 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4]. ; 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476825" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/genetics ; Base Sequence ; Cell Line ; Drosophila melanogaster/embryology/genetics ; Gastrulation/genetics ; Gene Expression Regulation, Developmental/*genetics ; Humans ; Liver/metabolism ; Mice ; MicroRNAs/genetics/metabolism ; Models, Genetic ; Plant Leaves/genetics ; Poly A/*analysis/genetics ; Protein Biosynthesis/*genetics ; RNA Stability/genetics ; RNA, Messenger/*genetics/metabolism ; Ribosomes/metabolism ; Sequence Analysis, RNA ; Species Specificity ; Transcription, Genetic ; Xenopus/embryology/genetics ; Yeasts/genetics ; Zebrafish/embryology/genetics ; Zygote/metabolism
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  • 27
    Publication Date: 2014-05-16
    Description: MicroRNA and protein sequestration by non-coding RNAs (ncRNAs) has recently generated much interest. In the bacterial Csr/Rsm system, which is considered to be the most general global post-transcriptional regulatory system responsible for bacterial virulence, ncRNAs such as CsrB or RsmZ activate translation initiation by sequestering homodimeric CsrA-type proteins from the ribosome-binding site of a subset of messenger RNAs. However, the mechanism of ncRNA-mediated protein sequestration is not understood at the molecular level. Here we show for Pseudomonas fluorescens that RsmE protein dimers assemble sequentially, specifically and cooperatively onto the ncRNA RsmZ within a narrow affinity range. This assembly yields two different native ribonucleoprotein structures. Using a powerful combination of nuclear magnetic resonance and electron paramagnetic resonance spectroscopy we elucidate these 70-kilodalton solution structures, thereby revealing the molecular mechanism of the sequestration process and how RsmE binding protects the ncRNA from RNase E degradation. Overall, our findings suggest that RsmZ is well-tuned to sequester, store and release RsmE and therefore can be viewed as an ideal protein 'sponge'.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duss, Olivier -- Michel, Erich -- Yulikov, Maxim -- Schubert, Mario -- Jeschke, Gunnar -- Allain, Frederic H-T -- England -- Nature. 2014 May 29;509(7502):588-92. doi: 10.1038/nature13271. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, ETH Zurich, CH-8093 Zurich, Switzerland. ; Laboratory of Physical Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828038" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Electron Spin Resonance Spectroscopy ; Escherichia coli/chemistry/genetics/metabolism ; Escherichia coli Proteins/chemistry/*metabolism ; Methyltransferases/chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Molecular Weight ; Nuclear Magnetic Resonance, Biomolecular ; Nucleic Acid Conformation ; *Protein Binding ; Protein Multimerization ; RNA, Untranslated/chemistry/genetics/*metabolism ; Ribonucleases/metabolism ; Ribonucleoproteins/chemistry/genetics/metabolism
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  • 28
    Publication Date: 2014-06-06
    Description: The mir-34/449 family consists of six homologous miRNAs at three genomic loci. Redundancy of miR-34/449 miRNAs and their dominant expression in multiciliated epithelia suggest a functional significance in ciliogenesis. Here we report that mice deficient for all miR-34/449 miRNAs exhibited postnatal mortality, infertility and strong respiratory dysfunction caused by defective mucociliary clearance. In both mouse and Xenopus, miR-34/449-deficient multiciliated cells (MCCs) exhibited a significant decrease in cilia length and number, due to defective basal body maturation and apical docking. The effect of miR-34/449 on ciliogenesis was mediated, at least in part, by post-transcriptional repression of Cp110, a centriolar protein suppressing cilia assembly. Consistent with this, cp110 knockdown in miR-34/449-deficient MCCs restored ciliogenesis by rescuing basal body maturation and docking. Altogether, our findings elucidate conserved cellular and molecular mechanisms through which miR-34/449 regulate motile ciliogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119886/" 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/PMC4119886/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Rui -- Walentek, Peter -- Sponer, Nicole -- Klimke, Alexander -- Lee, Joon Sub -- Dixon, Gary -- Harland, Richard -- Wan, Ying -- Lishko, Polina -- Lize, Muriel -- Kessel, Michael -- He, Lin -- 1R21CA175560-01/CA/NCI NIH HHS/ -- GM42341/GM/NIGMS NIH HHS/ -- R01 CA139067/CA/NCI NIH HHS/ -- R01 GM042341/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 5;510(7503):115-20. doi: 10.1038/nature13413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2]. ; 1] Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2]. ; Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany. ; Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA. ; Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA. ; The Third Military Medical University, Chongqing 400038, China. ; Department of Molecular Oncology, University of Goettingen, Goettingen 37073, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24899310" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Basal Bodies/metabolism/pathology/ultrastructure ; Base Sequence ; Calmodulin-Binding Proteins/*deficiency/*genetics/metabolism ; Centrioles/metabolism ; Cilia/*genetics/pathology/*physiology/ultrastructure ; Epidermis/embryology/pathology ; Female ; Infertility/genetics/physiopathology ; Kartagener Syndrome/genetics/pathology/physiopathology ; Male ; Mice ; Mice, Knockout ; MicroRNAs/*genetics/metabolism ; Morphogenesis/*genetics ; Phenotype ; Respiratory System/pathology/physiopathology ; Survival Analysis ; Xenopus laevis/embryology
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  • 29
    Publication Date: 2014-08-15
    Description: The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem cells. Here we describe a new method of cancer model generation using the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system in vivo in wild-type mice. We used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs) to the liver that directly target the tumour suppressor genes Pten (ref. 5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology. Simultaneous targeting of Pten and p53 induced liver tumours that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumour tissue revealed insertion or deletion mutations of the tumour suppressor genes, including bi-allelic mutations of both Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring sgRNAs targeting the beta-catenin gene and a single-stranded DNA oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of beta-catenin. This study demonstrates the feasibility of direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199937/" 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/PMC4199937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xue, Wen -- Chen, Sidi -- Yin, Hao -- Tammela, Tuomas -- Papagiannakopoulos, Thales -- Joshi, Nikhil S -- Cai, Wenxin -- Yang, Gillian -- Bronson, Roderick -- Crowley, Denise G -- Zhang, Feng -- Anderson, Daniel G -- Sharp, Phillip A -- Jacks, Tyler -- 1K99CA169512/CA/NCI NIH HHS/ -- 2-P01-CA42063/CA/NCI NIH HHS/ -- 5-U54-CA151884-04/CA/NCI NIH HHS/ -- DP1 MH100706/MH/NIMH NIH HHS/ -- K99 CA169512/CA/NCI NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- R00 CA169512/CA/NCI NIH HHS/ -- R01 DK097768/DK/NIDDK NIH HHS/ -- R01-CA115527/CA/NCI NIH HHS/ -- R01-CA132091/CA/NCI NIH HHS/ -- R01-CA133404/CA/NCI NIH HHS/ -- R01-EB000244/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Oct 16;514(7522):380-4. doi: 10.1038/nature13589. Epub 2014 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2]. ; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; Tufts University and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2] Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3] Harvard-MIT Division of Health Sciences &Technology, Cambridge, Massachusetts 02139, USA [4] Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119044" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *CRISPR-Cas Systems ; Cell Transformation, Neoplastic/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Female ; *Genes, Tumor Suppressor ; Genes, p53/genetics ; Genetic Engineering/*methods ; Hepatocytes/metabolism/pathology ; Lipid Metabolism ; Liver/cytology/*metabolism/pathology ; Liver Neoplasms/genetics/metabolism/pathology ; Mice ; Molecular Sequence Data ; Mutagenesis/*genetics ; Mutation/*genetics ; Oncogenes/*genetics ; PTEN Phosphohydrolase/genetics ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; beta Catenin/genetics
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Dec 18;516(7531):S72. doi: 10.1038/516S72a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517243" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry ; China ; Cities ; Periodicals as Topic/statistics & numerical data ; Research/standards/*statistics & numerical data/trends ; Universities/statistics & numerical data
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  • 31
    Publication Date: 2014-08-01
    Description: The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with silvestrol has powerful therapeutic effects against murine and human leukaemic cells in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5' untranslated region (UTR) sequences such as the 12-nucleotide guanine quartet (CGG)4 motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and silvestrol-sensitive transcripts are a number of oncogenes, superenhancer-associated transcription factors, and epigenetic regulators. Hence, the 5' UTRs of select cancer genes harbour a targetable requirement for the eIF4A RNA helicase.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492470/" 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/PMC4492470/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolfe, Andrew L -- Singh, Kamini -- Zhong, Yi -- Drewe, Philipp -- Rajasekhar, Vinagolu K -- Sanghvi, Viraj R -- Mavrakis, Konstantinos J -- Jiang, Man -- Roderick, Justine E -- Van der Meulen, Joni -- Schatz, Jonathan H -- Rodrigo, Christina M -- Zhao, Chunying -- Rondou, Pieter -- de Stanchina, Elisa -- Teruya-Feldstein, Julie -- Kelliher, Michelle A -- Speleman, Frank -- Porco, John A Jr -- Pelletier, Jerry -- Ratsch, Gunnar -- Wendel, Hans-Guido -- GM-067041/GM/NIGMS NIH HHS/ -- GM-073855/GM/NIGMS NIH HHS/ -- MOP-10653/Canadian Institutes of Health Research/Canada -- P30 CA008748/CA/NCI NIH HHS/ -- R01 CA142798/CA/NCI NIH HHS/ -- R01-CA142798-01/CA/NCI NIH HHS/ -- England -- Nature. 2014 Sep 4;513(7516):65-70. doi: 10.1038/nature13485. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2] Weill Cornell Graduate School of Medical Sciences, New York, New York 10065, USA [3]. ; 1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2]. ; Computational Biology Department, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Stem Cell Center and Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; 1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2] Novartis, Cambridge, Massachusetts 02139, USA (K.J.M.); The University of Arizona Cancer Center, Tucson, Arizona 85719, USA (J.H.S.). ; Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605 USA. ; 1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2] Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. ; 1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2] Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [3] Novartis, Cambridge, Massachusetts 02139, USA (K.J.M.); The University of Arizona Cancer Center, Tucson, Arizona 85719, USA (J.H.S.). ; Department of Chemistry, Center for Chemical Methodology and Library Development, Boston University, Boston, Massachusetts 02215, USA. ; Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. ; Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; 1] Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada [2] Department of Oncology, McGill University, Montreal, Quebec H3G 1Y6, Canada [3] The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3G 1Y6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079319" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/*genetics ; Animals ; Antineoplastic Agents, Phytogenic/pharmacology/therapeutic use ; Base Sequence ; Cell Line, Tumor ; Epigenesis, Genetic ; Eukaryotic Initiation Factor-4A/*metabolism ; Female ; *G-Quadruplexes ; Humans ; Mice ; Mice, Inbred C57BL ; Nucleotide Motifs ; Oncogene Proteins/*biosynthesis/*genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug ; therapy/genetics/*metabolism ; *Protein Biosynthesis/drug effects ; Ribosomes/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects/genetics ; Triterpenes/pharmacology
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  • 32
    Publication Date: 2014-07-22
    Description: Programmed -1 ribosomal frameshift (-1 PRF) signals redirect translating ribosomes to slip back one base on messenger RNAs. Although well characterized in viruses, how these elements may regulate cellular gene expression is not understood. Here we describe a -1 PRF signal in the human mRNA encoding CCR5, the HIV-1 co-receptor. CCR5 mRNA-mediated -1 PRF is directed by an mRNA pseudoknot, and is stimulated by at least two microRNAs. Mapping the mRNA-miRNA interaction suggests that formation of a triplex RNA structure stimulates -1 PRF. A -1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay pathway. At least one additional mRNA decay pathway is also involved. Functional -1 PRF signals that seem to be regulated by miRNAs are also demonstrated in mRNAs encoding six other cytokine receptors, suggesting a novel mode through which immune responses may be fine-tuned in mammalian cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369343/" 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/PMC4369343/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Belew, Ashton Trey -- Meskauskas, Arturas -- Musalgaonkar, Sharmishtha -- Advani, Vivek M -- Sulima, Sergey O -- Kasprzak, Wojciech K -- Shapiro, Bruce A -- Dinman, Jonathan D -- 5 R01GM058859/GM/NIGMS NIH HHS/ -- HHSN261200800001/PHS HHS/ -- R01 GM058859/GM/NIGMS NIH HHS/ -- R01 HL119439/HL/NHLBI NIH HHS/ -- R21 GM068123/GM/NIGMS NIH HHS/ -- R21GM068123/GM/NIGMS NIH HHS/ -- T32 AI051967/AI/NIAID NIH HHS/ -- T32AI051967/AI/NIAID NIH HHS/ -- T32GM080201/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2014 Aug 21;512(7514):265-9. doi: 10.1038/nature13429. Epub 2014 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2]. ; 1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2] Department of Biotechnology and Microbiology, Vilnius University, Vilnius, LT 03101, Lithuania [3]. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA. ; 1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2] VIB Center for the Biology of Disease, KU Leuven, Campus Gasthuisberg, Herestraat 49, bus 602, 3000 Leuven, Belgium. ; Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Basic Research Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043019" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Cell Survival ; Codon, Nonsense/genetics ; Frameshifting, Ribosomal/*genetics ; HeLa Cells ; Humans ; MicroRNAs/*genetics ; Models, Molecular ; Molecular Sequence Data ; *Nonsense Mediated mRNA Decay ; Nucleic Acid Conformation ; RNA, Messenger/chemistry/*genetics/*metabolism ; Receptors, CCR5/*genetics ; Receptors, Interleukin/genetics ; Regulatory Sequences, Ribonucleic Acid ; Ribosomes/metabolism
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  • 33
    Publication Date: 2014-08-15
    Description: Mammalian cells possess mechanisms to detect and defend themselves from invading viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid-inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection. Detection triggers a signalling cascade via the adaptor MAVS that culminates in the production of type I interferons (IFN-alpha and beta; hereafter IFN), which are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA structures and much evidence indicates that RIG-I responds to RNAs bearing a triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region at the 5'-end (reviewed in refs 1, 2, 3). Here we show that RIG-I also mediates antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus, and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis, all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent response to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base-paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a powerful means of self/non-self discrimination by the innate immune system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201573/" 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/PMC4201573/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goubau, Delphine -- Schlee, Martin -- Deddouche, Safia -- Pruijssers, Andrea J -- Zillinger, Thomas -- Goldeck, Marion -- Schuberth, Christine -- Van der Veen, Annemarthe G -- Fujimura, Tsutomu -- Rehwinkel, Jan -- Iskarpatyoti, Jason A -- Barchet, Winfried -- Ludwig, Janos -- Dermody, Terence S -- Hartmann, Gunther -- Reis e Sousa, Caetano -- A3598/Cancer Research UK/United Kingdom -- MC_UU_12010/8/Medical Research Council/United Kingdom -- R01 AI038296/AI/NIAID NIH HHS/ -- R37 AI038296/AI/NIAID NIH HHS/ -- Cancer Research UK/United Kingdom -- England -- Nature. 2014 Oct 16;514(7522):372-5. doi: 10.1038/nature13590. Epub 2014 Aug 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Immunobiology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK [2]. ; 1] Institut fur Klinische Chemie und Klinische Pharmakologie, Universitatsklinikum Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn, Germany [2]. ; 1] Immunobiology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK [2] Drosophila Genetics and Epigenetics, Laboratory of Developmental Biology, CNRS UMR7622, Universite Pierre et Marie Curie, Paris, France (S.D.); Medical Research Council Human Immunology Unit, Radcliffe Department of Medicine, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK (J.R.). ; 1] Department of Pediatrics, Vanderbilt University School of Medicine, D7235 Medical Center North, 1161 21st Avenue South, Nashville, Tennessee 37232-2581, USA [2] Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, D7235 Medical Center North, 1161 21st Avenue South, Nashville, Tennessee 37232-2581, USA. ; Institut fur Klinische Chemie und Klinische Pharmakologie, Universitatsklinikum Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn, Germany. ; Immunobiology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. ; Instituto de Biologia Funcional y Genomica. Consejo Superior de Investigaciones Cientificas/Universidad de Salamanca, Zacarias Gonzalez 2, 37007, Salamanca, Spain. ; 1] Department of Pediatrics, Vanderbilt University School of Medicine, D7235 Medical Center North, 1161 21st Avenue South, Nashville, Tennessee 37232-2581, USA [2] Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, D7235 Medical Center North, 1161 21st Avenue South, Nashville, Tennessee 37232-2581, USA [3] Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, D7235 Medical Center North, 1161 21st Avenue South, Nashville, Tennessee 37232-2581, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119032" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Pairing ; Base Sequence ; DEAD-box RNA Helicases/*metabolism ; Diphosphates/*metabolism ; Female ; Genome, Viral/genetics ; *Immunity, Innate ; Male ; Mice ; RNA, Viral/*chemistry/genetics/*metabolism ; Reoviridae/*genetics/*immunology/physiology
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  • 34
    Publication Date: 2014-11-05
    Description: Thirty years ago it was shown that the non-enzymatic, template-directed polymerization of activated mononucleotides proceeds readily in a homochiral system, but is severely inhibited by the presence of the opposing enantiomer. This finding poses a severe challenge for the spontaneous emergence of RNA-based life, and has led to the suggestion that either RNA was preceded by some other genetic polymer that is not subject to chiral inhibition or chiral symmetry was broken through chemical processes before the origin of RNA-based life. Once an RNA enzyme arose that could catalyse the polymerization of RNA, it would have been possible to distinguish among the two enantiomers, enabling RNA replication and RNA-based evolution to occur. It is commonly thought that the earliest RNA polymerase and its substrates would have been of the same handedness, but this is not necessarily the case. Replicating D- and L-RNA molecules may have emerged together, based on the ability of structured RNAs of one handedness to catalyse the templated polymerization of activated mononucleotides of the opposite handedness. Here we develop such a cross-chiral RNA polymerase, using in vitro evolution starting from a population of random-sequence RNAs. The D-RNA enzyme, consisting of 83 nucleotides, catalyses the joining of L-mono- or oligonucleotide substrates on a complementary L-RNA template, and similar behaviour occurs for the L-enzyme with D-substrates and a D-template. Chiral inhibition is avoided because the 10(6)-fold rate acceleration of the enzyme only pertains to cross-chiral substrates. The enzyme's activity is sufficient to generate full-length copies of its enantiomer through the templated joining of 11 component oligonucleotides.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239201/" 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/PMC4239201/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sczepanski, Jonathan T -- Joyce, Gerald F -- F32 GM101741/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Nov 20;515(7527):440-2. doi: 10.1038/nature13900. Epub 2014 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363769" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Biocatalysis ; Biopolymers/biosynthesis/chemistry/metabolism ; DNA-Directed RNA Polymerases/chemistry/*metabolism ; Directed Molecular Evolution ; Evolution, Chemical ; Kinetics ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligonucleotides/chemistry/metabolism ; Origin of Life ; Polymerization ; RNA/*biosynthesis/*chemistry/metabolism ; RNA, Catalytic/*chemistry/*metabolism ; Stereoisomerism ; Templates, Genetic
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  • 35
    Publication Date: 2014-01-31
    Description: The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA heteroduplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106473/" 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/PMC4106473/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sternberg, Samuel H -- Redding, Sy -- Jinek, Martin -- Greene, Eric C -- Doudna, Jennifer A -- GM074739/GM/NIGMS NIH HHS/ -- R01 GM073794/GM/NIGMS NIH HHS/ -- R01 GM074739/GM/NIGMS NIH HHS/ -- T32 GM066698/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 6;507(7490):62-7. doi: 10.1038/nature13011. Epub 2014 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Chemistry, University of California, Berkeley, California 94720, USA [2]. ; 1] Department of Chemistry, Columbia University, New York, New York 10032, USA [2]. ; 1] Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA [2] Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland. ; Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA. ; 1] Department of Chemistry, University of California, Berkeley, California 94720, USA [2] Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA [3] Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA [4] Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476820" target="_blank"〉PubMed〈/a〉
    Keywords: Apoenzymes/metabolism ; *Base Pairing ; Base Sequence ; Biocatalysis ; CRISPR-Associated Proteins/*metabolism ; *CRISPR-Cas Systems ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; DNA/chemistry/genetics/metabolism ; *DNA Cleavage ; Diffusion ; Endonucleases/*metabolism ; Enzyme Activation ; Genetic Engineering/methods ; Genome/genetics ; Nucleic Acid Denaturation ; Nucleic Acid Heteroduplexes/chemistry/genetics/metabolism ; Nucleotide Motifs ; RNA/chemistry/*genetics/metabolism ; Streptococcus pyogenes/enzymology/immunology ; Substrate Specificity ; Thermodynamics
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  • 36
    Publication Date: 2014-02-18
    Description: A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs and recruits general transcription factors to initiate transcription. The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Maternal to zygotic transition represents the most marked change of the transcriptome repertoire in the vertebrate life cycle. Early embryonic development in zebrafish is characterized by a series of transcriptionally silent cell cycles regulated by inherited maternal gene products: zygotic genome activation commences at the tenth cell cycle, marking the mid-blastula transition. This transition provides a unique opportunity to study the rules of TSS selection and the hierarchy of events linking transcription initiation with key chromatin modifications. We analysed TSS usage during zebrafish early embryonic development at high resolution using cap analysis of gene expression, and determined the positions of H3K4me3-marked promoter-associated nucleosomes. Here we show that the transition from the maternal to zygotic transcriptome is characterized by a switch between two fundamentally different modes of defining transcription initiation, which drive the dynamic change of TSS usage and promoter shape. A maternal-specific TSS selection, which requires an A/T-rich (W-box) motif, is replaced with a zygotic TSS selection grammar characterized by broader patterns of dinucleotide enrichments, precisely aligned with the first downstream (+1) nucleosome. The developmental dynamics of the H3K4me3-marked nucleosomes reveal their DNA-sequence-associated positioning at promoters before zygotic transcription and subsequent transcription-independent adjustment to the final position downstream of the zygotic TSS. The two TSS-defining grammars coexist, often physically overlapping, in core promoters of constitutively expressed genes to enable their expression in the two regulatory environments. The dissection of overlapping core promoter determinants represents a framework for future studies of promoter structure and function across different regulatory contexts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haberle, Vanja -- Li, Nan -- Hadzhiev, Yavor -- Plessy, Charles -- Previti, Christopher -- Nepal, Chirag -- Gehrig, Jochen -- Dong, Xianjun -- Akalin, Altuna -- Suzuki, Ana Maria -- van IJcken, Wilfred F J -- Armant, Olivier -- Ferg, Marco -- Strahle, Uwe -- Carninci, Piero -- Muller, Ferenc -- Lenhard, Boris -- MC_UP_1102/1/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2014 Mar 20;507(7492):381-5. doi: 10.1038/nature12974. Epub 2014 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biology, University of Bergen, Thormohlensgate 53A, N-5008 Bergen, Norway [2] Institute of Clinical Sciences and MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK [3]. ; 1] School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2]. ; School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. ; 1] RIKEN Omics Science Center, Yokohama, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, RIKEN Yokohama Campus, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; 1] Computational Biology Unit, Uni Computing, Uni Research AS, University of Bergen, Thormohlensgate 55, N-5008 Bergen, Norway [2] German Cancer Research Center (DKFZ), Genomics & Proteomics Core Facility (GPCF), Im Neuenheimer Feld 580/TP3, Heidelberg 69120, Germany (C.Pr.); Broegelmann Research Laboratory, The Gade Institute, University of Bergen, The Laboratory Building, Haukeland University Hospital, N-5021 Bergen, Norway (C.N.); Acquifer AG, Sophienstrasse 136, 76135 Karlsruhe, Germany (J.G.); Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA (X.D.); Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland (A.A.). ; 1] School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2] German Cancer Research Center (DKFZ), Genomics & Proteomics Core Facility (GPCF), Im Neuenheimer Feld 580/TP3, Heidelberg 69120, Germany (C.Pr.); Broegelmann Research Laboratory, The Gade Institute, University of Bergen, The Laboratory Building, Haukeland University Hospital, N-5021 Bergen, Norway (C.N.); Acquifer AG, Sophienstrasse 136, 76135 Karlsruhe, Germany (J.G.); Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA (X.D.); Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland (A.A.). ; Erasmus Medical Center, Center for Biomics, Room Ee679b, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. ; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Postfach 3640, 76021 Karlsruhe, Germany. ; 1] Institute of Clinical Sciences and MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK [2] Department of Informatics, University of Bergen, Thormohlensgate 55, N-5008 Bergen, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531765" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Embryo, Nonmammalian/embryology/metabolism ; Female ; Gene Expression Regulation, Developmental/genetics ; Histones/metabolism ; Methylation ; Mothers ; Nucleosomes/genetics ; Promoter Regions, Genetic/*genetics ; *Transcription Initiation Site ; Transcription Initiation, Genetic ; Transcriptome/genetics ; Zebrafish/embryology/*genetics ; Zygote/metabolism
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  • 37
    Publication Date: 2014-02-18
    Description: RNA interference is widely distributed in eukaryotes and has a variety of functions, including antiviral defence and gene regulation. All RNA interference pathways use small single-stranded RNA (ssRNA) molecules that guide proteins of the Argonaute (Ago) family to complementary ssRNA targets: RNA-guided RNA interference. The role of prokaryotic Ago variants has remained elusive, although bioinformatics analysis has suggested their involvement in host defence. Here we demonstrate that Ago of the bacterium Thermus thermophilus (TtAgo) acts as a barrier for the uptake and propagation of foreign DNA. In vivo, TtAgo is loaded with 5'-phosphorylated DNA guides, 13-25 nucleotides in length, that are mostly plasmid derived and have a strong bias for a 5'-end deoxycytidine. These small interfering DNAs guide TtAgo to cleave complementary DNA strands. Hence, despite structural homology to its eukaryotic counterparts, TtAgo functions in host defence by DNA-guided DNA interference.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697943/" 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/PMC4697943/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swarts, Daan C -- Jore, Matthijs M -- Westra, Edze R -- Zhu, Yifan -- Janssen, Jorijn H -- Snijders, Ambrosius P -- Wang, Yanli -- Patel, Dinshaw J -- Berenguer, Jose -- Brouns, Stan J J -- van der Oost, John -- P30 CA008748/CA/NCI NIH HHS/ -- R01 GM104962/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 13;507(7491):258-61. doi: 10.1038/nature12971. Epub 2014 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, the Netherlands [2]. ; Laboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, the Netherlands. ; Clare Hall Laboratories, Cancer Research UK, London Research Institute, South Mimms EN6 3LD, UK. ; Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. ; Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Centro de Biologia Molecular Severo Ochoa, UAM-CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531762" target="_blank"〉PubMed〈/a〉
    Keywords: Argonaute Proteins/*metabolism ; Base Pairing/genetics ; Base Sequence ; DNA/genetics/*metabolism ; *DNA Cleavage ; Deoxycytidine/genetics/metabolism ; *Gene Silencing ; Phosphorylation ; Plasmids/genetics ; Prokaryotic Cells/*metabolism ; Thermus thermophilus/*genetics/*metabolism
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  • 38
    Publication Date: 2014-08-01
    Description: The CRISPR-associated protein Cas9 is an RNA-guided endonuclease that cleaves double-stranded DNA bearing sequences complementary to a 20-nucleotide segment in the guide RNA. Cas9 has emerged as a versatile molecular tool for genome editing and gene expression control. RNA-guided DNA recognition and cleavage strictly require the presence of a protospacer adjacent motif (PAM) in the target DNA. Here we report a crystal structure of Streptococcus pyogenes Cas9 in complex with a single-molecule guide RNA and a target DNA containing a canonical 5'-NGG-3' PAM. The structure reveals that the PAM motif resides in a base-paired DNA duplex. The non-complementary strand GG dinucleotide is read out via major-groove interactions with conserved arginine residues from the carboxy-terminal domain of Cas9. Interactions with the minor groove of the PAM duplex and the phosphodiester group at the +1 position in the target DNA strand contribute to local strand separation immediately upstream of the PAM. These observations suggest a mechanism for PAM-dependent target DNA melting and RNA-DNA hybrid formation. Furthermore, this study establishes a framework for the rational engineering of Cas9 enzymes with novel PAM specificities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176945/" 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/PMC4176945/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anders, Carolin -- Niewoehner, Ole -- Duerst, Alessia -- Jinek, Martin -- 337284/European Research Council/International -- England -- Nature. 2014 Sep 25;513(7519):569-73. doi: 10.1038/nature13579. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079318" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/genetics/metabolism ; *Base Pairing ; Base Sequence ; CRISPR-Associated Proteins/*metabolism ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; Endonucleases/*metabolism ; Models, Molecular ; Nucleic Acid Denaturation ; *Nucleotide Motifs ; Protein Conformation ; RNA, Guide/chemistry/genetics/metabolism ; Streptococcus pyogenes/*enzymology ; Substrate Specificity
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  • 39
    Publication Date: 2014-02-18
    Description: In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes. Here we translate this 'albumin hitchhiking' approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069155/" 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/PMC4069155/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Haipeng -- Moynihan, Kelly D -- Zheng, Yiran -- Szeto, Gregory L -- Li, Adrienne V -- Huang, Bonnie -- Van Egeren, Debra S -- Park, Clara -- Irvine, Darrell J -- AI091693/AI/NIAID NIH HHS/ -- AI095109/AI/NIAID NIH HHS/ -- AI104715/AI/NIAID NIH HHS/ -- F32 CA180586/CA/NCI NIH HHS/ -- P01 AI104715/AI/NIAID NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- R01 AI095109/AI/NIAID NIH HHS/ -- U19 AI091693/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 27;507(7493):519-22. doi: 10.1038/nature12978. Epub 2014 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4] Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, Massachusetts 02139, USA [5] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; CpG Islands/genetics/immunology ; Female ; Lymph Nodes/*immunology ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes/immunology ; Vaccines, Subunit/genetics/*immunology ; Vaccines, Synthetic/genetics/*immunology
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  • 40
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Dec 18;516(7531):S69. doi: 10.1038/516S69a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517242" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry ; China ; Cities ; Periodicals as Topic/statistics & numerical data ; Physics ; Research/standards/*statistics & numerical data/trends ; Universities/statistics & numerical data
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  • 41
    Publication Date: 2014-01-10
    Description: UvrD helicase is required for nucleotide excision repair, although its role in this process is not well defined. Here we show that Escherichia coli UvrD binds RNA polymerase during transcription elongation and, using its helicase/translocase activity, forces RNA polymerase to slide backward along DNA. By inducing backtracking, UvrD exposes DNA lesions shielded by blocked RNA polymerase, allowing nucleotide excision repair enzymes to gain access to sites of damage. Our results establish UvrD as a bona fide transcription elongation factor that contributes to genomic integrity by resolving conflicts between transcription and DNA repair complexes. Furthermore, we show that the elongation factor NusA cooperates with UvrD in coupling transcription to DNA repair by promoting backtracking and recruiting nucleotide excision repair enzymes to exposed lesions. Because backtracking is a shared feature of all cellular RNA polymerases, we propose that this mechanism enables RNA polymerases to function as global DNA damage scanners in bacteria and eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471481/" 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/PMC4471481/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Epshtein, Vitaly -- Kamarthapu, Venu -- McGary, Katelyn -- Svetlov, Vladimir -- Ueberheide, Beatrix -- Proshkin, Sergey -- Mironov, Alexander -- Nudler, Evgeny -- R01 GM058750/GM/NIGMS NIH HHS/ -- T32 GM088118/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 16;505(7483):372-7. doi: 10.1038/nature12928. Epub 2014 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2]. ; 1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA [3]. ; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA. ; State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia. ; 1] State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia [2] Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia. ; 1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24402227" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA/chemistry/metabolism ; DNA Damage ; DNA Helicases/*metabolism ; *DNA Repair ; DNA-Directed RNA Polymerases/chemistry/*metabolism ; Escherichia coli/enzymology/genetics ; Escherichia coli Proteins/*metabolism ; Models, Molecular ; Molecular Sequence Data ; *Movement ; Peptide Elongation Factors/metabolism ; Protein Binding ; Transcription Factors/metabolism ; Transcription, Genetic ; Transcriptional Elongation Factors
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  • 42
    Publication Date: 2014-10-03
    Description: Throughout evolution primate genomes have been modified by waves of retrotransposon insertions. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, transcriptional silencing of retrotransposons requires KAP1 (also known as TRIM28) and its repressive complex, which can be recruited to target sites by KRAB zinc-finger (KZNF) proteins such as murine-specific ZFP809 which binds to integrated murine leukaemia virus DNA elements and recruits KAP1 to repress them. KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons. However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA) and long interspersed nuclear element 1 (L1), is unknown. Here we show that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8-12 million years ago that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until approximately 12.5 million years ago when the L1PA3-subfamily of retrotransposons escaped ZNF93's restriction through the removal of the ZNF93-binding site. Our data support a model where KZNF gene expansion limits the activity of newly emerged retrotransposon classes, and this is followed by mutations in these retrotransposons to evade repression, a cycle of events that could explain the rapid expansion of lineage-specific KZNF genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268317/" 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/PMC4268317/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacobs, Frank M J -- Greenberg, David -- Nguyen, Ngan -- Haeussler, Maximilian -- Ewing, Adam D -- Katzman, Sol -- Paten, Benedict -- Salama, Sofie R -- Haussler, David -- U24 CA143858/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 11;516(7530):242-5. doi: 10.1038/nature13760. Epub 2014 Sep 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA [2] [3] Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam 1098 XH, The Netherlands (F.M.J.J.); Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA (D.G.); Mater Research Institute, University of Queensland, Queensland 4101, Australia (A.D.E.). ; 1] Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA [2] Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA [3] [4] Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam 1098 XH, The Netherlands (F.M.J.J.); Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA (D.G.); Mater Research Institute, University of Queensland, Queensland 4101, Australia (A.D.E.). ; 1] Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA [2] Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA. ; Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA. ; 1] Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA [2] Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam 1098 XH, The Netherlands (F.M.J.J.); Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA (D.G.); Mater Research Institute, University of Queensland, Queensland 4101, Australia (A.D.E.). ; 1] Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA [2] Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, California 95064, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25274305" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Embryonic Stem Cells/cytology/metabolism ; *Evolution, Molecular ; Humans ; Kruppel-Like Transcription Factors/genetics/*metabolism ; Mice ; Mutation/genetics ; Primates/*genetics ; Retroelements/*genetics ; Zinc Fingers
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  • 43
    Publication Date: 2014-03-29
    Description: In plants, post-transcriptional gene silencing (PTGS) is mediated by DICER-LIKE 1 (DCL1)-dependent microRNAs (miRNAs), which also trigger 21-nucleotide secondary short interfering RNAs (siRNAs) via RNA-DEPENDENT RNA POLYMERASE 6 (RDR6), DCL4 and ARGONAUTE 1 (AGO1), whereas transcriptional gene silencing (TGS) of transposons is mediated by 24-nucleotide heterochromatic (het)siRNAs, RDR2, DCL3 and AGO4 (ref. 4). Transposons can also give rise to abundant 21-nucleotide 'epigenetically activated' small interfering RNAs (easiRNAs) in DECREASED DNA METHYLATION 1 (ddm1) and DNA METHYLTRANSFERASE 1 (met1) mutants, as well as in the vegetative nucleus of pollen grains and in dedifferentiated plant cell cultures. Here we show that easiRNAs in Arabidopsis thaliana resemble secondary siRNAs, in that thousands of transposon transcripts are specifically targeted by more than 50 miRNAs for cleavage and processing by RDR6. Loss of RDR6, DCL4 or DCL1 in a ddm1 background results in loss of 21-nucleotide easiRNAs and severe infertility, but 24-nucleotide hetsiRNAs are partially restored, supporting an antagonistic relationship between PTGS and TGS. Thus miRNA-directed easiRNA biogenesis is a latent mechanism that specifically targets transposon transcripts, but only when they are epigenetically reactivated during reprogramming of the germ line. This ancient recognition mechanism may have been retained both by transposons to evade long-term heterochromatic silencing and by their hosts for genome defence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074602/" 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/PMC4074602/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Creasey, Kate M -- Zhai, Jixian -- Borges, Filipe -- Van Ex, Frederic -- Regulski, Michael -- Meyers, Blake C -- Martienssen, Robert A -- P30 CA045508/CA/NCI NIH HHS/ -- R01 GM067014/GM/NIGMS NIH HHS/ -- R01GM067014/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Apr 17;508(7496):411-5. doi: 10.1038/nature13069. Epub 2014 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA. ; Delaware Biotechnology Institute and Department of Plant & Soil Sciences, 15 Innovation Way, University of Delaware, Newark, Delaware 19711, USA. ; 1] Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA [2] Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Cold Spring Harbor Laboratory, New York 11724, USA [3] Chaire Blaise Pascal, Institut de Biologie de l'Ecole Normale Superieure (IBENS), 75230 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670663" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics ; Base Sequence ; Conserved Sequence ; DNA Transposable Elements/genetics ; *Epigenesis, Genetic ; Genome, Plant/genetics ; MicroRNAs/*genetics/metabolism ; Models, Genetic ; Open Reading Frames/genetics ; RNA, Small Interfering/biosynthesis/*genetics ; Retroelements/*genetics
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  • 44
    Publication Date: 2014-03-01
    Description: Understanding the spatial organization of gene expression with single-nucleotide resolution requires localizing the sequences of expressed RNA transcripts within a cell in situ. Here, we describe fluorescent in situ RNA sequencing (FISSEQ), in which stably cross-linked complementary DNA (cDNA) amplicons are sequenced within a biological sample. Using 30-base reads from 8102 genes in situ, we examined RNA expression and localization in human primary fibroblasts with a simulated wound-healing assay. FISSEQ is compatible with tissue sections and whole-mount embryos and reduces the limitations of optical resolution and noisy signals on single-molecule detection. Our platform enables massively parallel detection of genetic elements, including gene transcripts and molecular barcodes, and can be used to investigate cellular phenotype, gene regulation, and environment in situ.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140943/" 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/PMC4140943/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Je Hyuk -- Daugharthy, Evan R -- Scheiman, Jonathan -- Kalhor, Reza -- Yang, Joyce L -- Ferrante, Thomas C -- Terry, Richard -- Jeanty, Sauveur S F -- Li, Chao -- Amamoto, Ryoji -- Peters, Derek T -- Turczyk, Brian M -- Marblestone, Adam H -- Inverso, Samuel A -- Bernard, Amy -- Mali, Prashant -- Rios, Xavier -- Aach, John -- Church, George M -- GM080177/GM/NIGMS NIH HHS/ -- MH098977/MH/NIMH NIH HHS/ -- P50 HG005550/HG/NHGRI NIH HHS/ -- RC2 HL102815/HL/NHLBI NIH HHS/ -- RC2HL102815/HL/NHLBI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32 GM080177/GM/NIGMS NIH HHS/ -- U01 MH098977/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1360-3. doi: 10.1126/science.1250212. Epub 2014 Feb 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wyss Institute, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24578530" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line ; Cells, Cultured ; DNA, Complementary ; Fluorescence ; Gene Expression Profiling/*methods ; Humans ; Induced Pluripotent Stem Cells ; RNA, Messenger/genetics/metabolism ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis ; Transcription Initiation Site ; *Transcriptome ; Wound Healing
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  • 45
    Publication Date: 2014-04-26
    Description: Mutations in the mitochondrial genome are associated with multiple diseases and biological processes; however, little is known about the extent of sequence variation in the mitochondrial transcriptome. By ultra-deeply sequencing mitochondrial RNA (〉6000x) from the whole blood of ~1000 individuals from the CARTaGENE project, we identified remarkable levels of sequence variation within and across individuals, as well as sites that show consistent patterns of posttranscriptional modification. Using a genome-wide association study, we find that posttranscriptional modification of functionally important sites in mitochondrial transfer RNAs (tRNAs) is under strong genetic control, largely driven by a missense mutation in MRPP3 that explains ~22% of the variance. These results reveal a major nuclear genetic determinant of posttranscriptional modification in mitochondria and suggest that tRNA posttranscriptional modification may affect cellular energy production.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hodgkinson, Alan -- Idaghdour, Youssef -- Gbeha, Elias -- Grenier, Jean-Christophe -- Hip-Ki, Elodie -- Bruat, Vanessa -- Goulet, Jean-Philippe -- de Malliard, Thibault -- Awadalla, Philip -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):413-5. doi: 10.1126/science.1251110.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CHU Sainte-Justine Research Centre, Department of Pediatrics, Faculty of Medicine, Universite de Montreal, 3175 Chemin de la Cote-Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763589" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Base Sequence ; DNA, Mitochondrial/chemistry/genetics ; Female ; *Genetic Variation ; *Genome, Mitochondrial ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Methylation ; Middle Aged ; Mutation, Missense ; Polymorphism, Single Nucleotide ; RNA/chemistry/*genetics/metabolism ; RNA Processing, Post-Transcriptional ; RNA, Transfer/chemistry/*genetics/metabolism ; Ribonuclease P/*genetics/metabolism ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Transcriptome
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  • 46
    Publication Date: 2014-03-29
    Description: Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATalpha allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033833/" 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/PMC4033833/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Annaluru, Narayana -- Muller, Heloise -- Mitchell, Leslie A -- Ramalingam, Sivaprakash -- Stracquadanio, Giovanni -- Richardson, Sarah M -- Dymond, Jessica S -- Kuang, Zheng -- Scheifele, Lisa Z -- Cooper, Eric M -- Cai, Yizhi -- Zeller, Karen -- Agmon, Neta -- Han, Jeffrey S -- Hadjithomas, Michalis -- Tullman, Jennifer -- Caravelli, Katrina -- Cirelli, Kimberly -- Guo, Zheyuan -- London, Viktoriya -- Yeluru, Apurva -- Murugan, Sindurathy -- Kandavelou, Karthikeyan -- Agier, Nicolas -- Fischer, Gilles -- Yang, Kun -- Martin, J Andrew -- Bilgel, Murat -- Bohutski, Pavlo -- Boulier, Kristin M -- Capaldo, Brian J -- Chang, Joy -- Charoen, Kristie -- Choi, Woo Jin -- Deng, Peter -- DiCarlo, James E -- Doong, Judy -- Dunn, Jessilyn -- Feinberg, Jason I -- Fernandez, Christopher -- Floria, Charlotte E -- Gladowski, David -- Hadidi, Pasha -- Ishizuka, Isabel -- Jabbari, Javaneh -- Lau, Calvin Y L -- Lee, Pablo A -- Li, Sean -- Lin, Denise -- Linder, Matthias E -- Ling, Jonathan -- Liu, Jaime -- Liu, Jonathan -- London, Mariya -- Ma, Henry -- Mao, Jessica -- McDade, Jessica E -- McMillan, Alexandra -- Moore, Aaron M -- Oh, Won Chan -- Ouyang, Yu -- Patel, Ruchi -- Paul, Marina -- Paulsen, Laura C -- Qiu, Judy -- Rhee, Alex -- Rubashkin, Matthew G -- Soh, Ina Y -- Sotuyo, Nathaniel E -- Srinivas, Venkatesh -- Suarez, Allison -- Wong, Andy -- Wong, Remus -- Xie, Wei Rose -- Xu, Yijie -- Yu, Allen T -- Koszul, Romain -- Bader, Joel S -- Boeke, Jef D -- Chandrasegaran, Srinivasan -- 092076/Wellcome Trust/United Kingdom -- GM077291/GM/NIGMS NIH HHS/ -- R01 GM077291/GM/NIGMS NIH HHS/ -- R01 GM090192/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):55-8. doi: 10.1126/science.1249252. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Health Sciences, Johns Hopkins University (JHU) School of Public Health, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674868" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Chromosomes, Fungal/genetics/metabolism ; DNA, Fungal/genetics ; Genes, Fungal ; Genetic Fitness ; Genome, Fungal ; Genomic Instability ; Introns ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; RNA, Fungal/genetics ; RNA, Transfer/genetics ; Saccharomyces cerevisiae/cytology/*genetics/physiology ; Sequence Analysis, DNA ; Sequence Deletion ; Synthetic Biology/*methods ; Transformation, Genetic
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  • 47
    Publication Date: 2014-02-22
    Description: Robustness, the maintenance of a character in the presence of genetic change, can help preserve adaptive traits but also may hinder evolvability, the ability to bring forth novel adaptations. We used genotype networks to analyze the binding site repertoires of 193 transcription factors from mice and yeast, providing empirical evidence that robustness and evolvability need not be conflicting properties. Network vertices represent binding sites where two sites are connected if they differ in a single nucleotide. We show that the binding sites of larger genotype networks are not only more robust, but the sequences adjacent to such networks can also bind more transcription factors, thus demonstrating that robustness can facilitate evolvability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Payne, Joshua L -- Wagner, Andreas -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):875-7. doi: 10.1126/science.1249046.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Zurich, Institute of Evolutionary Biology and Environmental Studies, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24558158" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites/genetics ; Gene Regulatory Networks ; Mice ; Mutation ; Saccharomyces cerevisiae Proteins/chemistry ; Transcription Factors/*chemistry ; Transcription, Genetic
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  • 48
    Publication Date: 2014-11-15
    Description: In certain human cancers, the expression of critical oncogenes is driven from large regulatory elements, called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). In a subset of T-cell acute lymphoblastic leukemia (T-ALL) cases, we found that heterozygous somatic mutations are acquired that introduce binding motifs for the MYB transcription factor in a precise noncoding site, which creates a super-enhancer upstream of the TAL1 oncogene. MYB binds to this new site and recruits its H3K27 acetylase-binding partner CBP, as well as core components of a major leukemogenic transcriptional complex that contains RUNX1, GATA-3, and TAL1 itself. Additionally, most endogenous super-enhancers found in T-ALL cells are occupied by MYB and CBP, which suggests a general role for MYB in super-enhancer initiation. Thus, this study identifies a genetic mechanism responsible for the generation of oncogenic super-enhancers in malignant cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720521/" 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/PMC4720521/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mansour, Marc R -- Abraham, Brian J -- Anders, Lars -- Berezovskaya, Alla -- Gutierrez, Alejandro -- Durbin, Adam D -- Etchin, Julia -- Lawton, Lee -- Sallan, Stephen E -- Silverman, Lewis B -- Loh, Mignon L -- Hunger, Stephen P -- Sanda, Takaomi -- Young, Richard A -- Look, A Thomas -- 1R01CA176746-01/CA/NCI NIH HHS/ -- 5P01CA109901-08/CA/NCI NIH HHS/ -- 5P01CA68484/CA/NCI NIH HHS/ -- CA114766/CA/NCI NIH HHS/ -- CA120215/CA/NCI NIH HHS/ -- CA167124/CA/NCI NIH HHS/ -- CA29139/CA/NCI NIH HHS/ -- CA30969/CA/NCI NIH HHS/ -- CA98413/CA/NCI NIH HHS/ -- CA98543/CA/NCI NIH HHS/ -- P01 CA109901/CA/NCI NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1373-7. doi: 10.1126/science.1259037. Epub 2014 Nov 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Haematology, UCL Cancer Institute, University College London, London WC1E 6BT, UK. ; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Division of Pediatric Hematology-Oncology, Boston Children's Hospital, MA 02115, USA. ; Department of Pediatrics, Benioff Children's Hospital, University of California San Francisco, CA 94143, USA. ; Pediatric Hematology/Oncology/BMT, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, USA. ; Cancer Science Institute of Singapore, National University of Singapore, and Department of Medicine, Yong Loo Lin School of Medicine, 117599, Singapore. ; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. thomas_look@dfci.harvard.edu young@wi.mit.edu. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Division of Pediatric Hematology-Oncology, Boston Children's Hospital, MA 02115, USA. thomas_look@dfci.harvard.edu young@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25394790" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Binding Sites ; Cell Line, Tumor ; *DNA, Intergenic ; *Enhancer Elements, Genetic ; *Gene Expression Regulation, Neoplastic ; Histones/metabolism ; Humans ; *INDEL Mutation ; Molecular Sequence Data ; *Mutation ; Oncogenes ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics ; Protein Interaction Domains and Motifs ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins c-myb/metabolism
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  • 49
    Publication Date: 2014-02-01
    Description: Plant floral stem cells divide a limited number of times before they stop and terminally differentiate, but the mechanisms that control this timing remain unclear. The precise temporal induction of the Arabidopsis zinc finger repressor KNUCKLES (KNU) is essential for the coordinated growth and differentiation of floral stem cells. We identify an epigenetic mechanism in which the floral homeotic protein AGAMOUS (AG) induces KNU at ~2 days of delay. AG binding sites colocalize with a Polycomb response element in the KNU upstream region. AG binding to the KNU promoter causes the eviction of the Polycomb group proteins from the locus, leading to cell division-dependent induction. These analyses demonstrate that floral stem cells measure developmental timing by a division-dependent epigenetic timer triggered by Polycomb eviction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Bo -- Looi, Liang-Sheng -- Guo, Siyi -- He, Zemiao -- Gan, Eng-Seng -- Huang, Jiangbo -- Xu, Yifeng -- Wee, Wan-Yi -- Ito, Toshiro -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):1248559. doi: 10.1126/science.1248559.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Republic of Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482483" target="_blank"〉PubMed〈/a〉
    Keywords: AGAMOUS Protein, Arabidopsis/genetics/*metabolism ; Arabidopsis/cytology/genetics/*growth & development ; Arabidopsis Proteins/genetics/*metabolism ; Base Sequence ; Carrier Proteins/genetics/*metabolism ; Cell Division/genetics/*physiology ; Epigenesis, Genetic ; Flowers/cytology/genetics/*growth & development ; Gene Expression Regulation, Plant ; Meristem/*cytology ; Molecular Sequence Data ; Plants, Genetically Modified/cytology/growth & development ; Polycomb-Group Proteins/genetics/*metabolism ; Promoter Regions, Genetic ; Stem Cells/*cytology ; Time Factors ; Trans-Activators/genetics/metabolism
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  • 50
    Publication Date: 2014-06-28
    Description: Epistatic interactions between mutations can make evolutionary trajectories contingent on the chance occurrence of initial mutations. We used experimental evolution in Saccharomyces cerevisiae to quantify this contingency, finding differences in adaptability among 64 closely related genotypes. Despite these differences, sequencing of 104 evolved clones showed that initial genotype did not constrain future mutational trajectories. Instead, reconstructed combinations of mutations revealed a pattern of diminishing-returns epistasis: Beneficial mutations have consistently smaller effects in fitter backgrounds. Taken together, these results show that beneficial mutations affecting a variety of biological processes are globally coupled; they interact strongly, but only through their combined effect on fitness. As a consequence, fitness evolution follows a predictable trajectory even though sequence-level adaptation is stochastic.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314286/" 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/PMC4314286/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kryazhimskiy, Sergey -- Rice, Daniel P -- Jerison, Elizabeth R -- Desai, Michael M -- GM104239/GM/NIGMS NIH HHS/ -- R01 GM104239/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1519-22. doi: 10.1126/science.1250939.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. skryazhi@oeb.harvard.edu mdesai@oeb.harvard.edu. ; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. ; Department of Physics, Harvard University, Cambridge, MA 02138, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. ; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Department of Physics, Harvard University, Cambridge, MA 02138, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. skryazhi@oeb.harvard.edu mdesai@oeb.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970088" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Base Sequence ; Directed Molecular Evolution ; *Epistasis, Genetic ; *Evolution, Molecular ; Genes, Fungal ; *Genetic Fitness ; Genome, Fungal ; Genotype ; Models, Genetic ; Molecular Sequence Annotation ; Mutation ; Saccharomyces cerevisiae/*genetics/*physiology ; Sequence Analysis, DNA ; Stochastic Processes
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  • 51
    Publication Date: 2014-10-04
    Description: Cancer genome characterization has revealed driver mutations in genes that govern ubiquitylation; however, the mechanisms by which these alterations promote tumorigenesis remain incompletely characterized. Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. We highlight DEK as a SPOP substrate that exhibited decreases in ubiquitylation and proteasomal degradation resulting from heteromeric complexes of wild-type and mutant SPOP protein. DEK stabilization promoted prostate epithelial cell invasion, which implicated DEK as an oncogenic effector. More generally, these results provide a framework to decipher tumorigenic mechanisms linked to dysregulated ubiquitylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257137/" 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/PMC4257137/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Theurillat, Jean-Philippe P -- Udeshi, Namrata D -- Errington, Wesley J -- Svinkina, Tanya -- Baca, Sylvan C -- Pop, Marius -- Wild, Peter J -- Blattner, Mirjam -- Groner, Anna C -- Rubin, Mark A -- Moch, Holger -- Prive, Gilbert G -- Carr, Steven A -- Garraway, Levi A -- T32 GM007753/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):85-9. doi: 10.1126/science.1250255. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Harvard Medical School, Boston, MA 02115, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. ; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada. ; Harvard Medical School, Boston, MA 02115, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; Institute of Surgical Pathology, University Hospital Zurich, ZH 8091 Zurich, Switzerland. ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Institute for Precision Medicine of Weill Cornell and New York Presbyterian Hospital, New York, NY 10065, USA. ; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Harvard Medical School, Boston, MA 02115, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA 02115, USA. levi_garraway@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278611" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites/genetics ; Carcinogenesis/genetics/metabolism/pathology ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Chromosomal Proteins, Non-Histone/metabolism ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Neoplasm Invasiveness ; Nuclear Proteins/*genetics/metabolism ; Oncogene Proteins/metabolism ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Proteasome Endopeptidase Complex/metabolism ; Repressor Proteins/*genetics/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination/*genetics
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  • 52
    Publication Date: 2014-05-24
    Description: The evolution of the ratite birds has been widely attributed to vicariant speciation, driven by the Cretaceous breakup of the supercontinent Gondwana. The early isolation of Africa and Madagascar implies that the ostrich and extinct Madagascan elephant birds (Aepyornithidae) should be the oldest ratite lineages. We sequenced the mitochondrial genomes of two elephant birds and performed phylogenetic analyses, which revealed that these birds are the closest relatives of the New Zealand kiwi and are distant from the basal ratite lineage of ostriches. This unexpected result strongly contradicts continental vicariance and instead supports flighted dispersal in all major ratite lineages. We suggest that convergence toward gigantism and flightlessness was facilitated by early Tertiary expansion into the diurnal herbivory niche after the extinction of the dinosaurs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitchell, Kieren J -- Llamas, Bastien -- Soubrier, Julien -- Rawlence, Nicolas J -- Worthy, Trevor H -- Wood, Jamie -- Lee, Michael S Y -- Cooper, Alan -- New York, N.Y. -- Science. 2014 May 23;344(6186):898-900. doi: 10.1126/science.1251981.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Australian Centre for Ancient DNA, School of Earth and Environmental Sciences, University of Adelaide, North Terrace Campus, South Australia 5005, Australia. ; School of Biological Sciences, Flinders University, South Australia 5001, Australia. ; Landcare Research, Post Office Box 40, Lincoln 7640, New Zealand. ; Australian Centre for Ancient DNA, School of Earth and Environmental Sciences, University of Adelaide, North Terrace Campus, South Australia 5005, Australia. South Australian Museum, North Terrace, South Australia 5000, Australia. ; Australian Centre for Ancient DNA, School of Earth and Environmental Sciences, University of Adelaide, North Terrace Campus, South Australia 5005, Australia. alan.cooper@adelaide.edu.au.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855267" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Biological Evolution ; DNA/*genetics ; Flight, Animal ; Fossils ; Molecular Sequence Data ; New Zealand ; Palaeognathae/*classification/genetics ; Phylogeny ; Struthioniformes/*classification/genetics
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  • 53
    Publication Date: 2014-05-03
    Description: Transcription by RNA polymerase (RNAP) is interrupted by pauses that play diverse regulatory roles. Although individual pauses have been studied in vitro, the determinants of pauses in vivo and their distribution throughout the bacterial genome remain unknown. Using nascent transcript sequencing, we identified a 16-nucleotide consensus pause sequence in Escherichia coli that accounts for known regulatory pause sites as well as ~20,000 new in vivo pause sites. In vitro single-molecule and ensemble analyses demonstrate that these pauses result from RNAP-nucleic acid interactions that inhibit next-nucleotide addition. The consensus sequence also leads to pausing by RNAPs from diverse lineages and is enriched at translation start sites in both E. coli and Bacillus subtilis. Our results thus reveal a conserved mechanism unifying known and newly identified pause events.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108260/" 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/PMC4108260/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larson, Matthew H -- Mooney, Rachel A -- Peters, Jason M -- Windgassen, Tricia -- Nayak, Dhananjaya -- Gross, Carol A -- Block, Steven M -- Greenleaf, William J -- Landick, Robert -- Weissman, Jonathan S -- F32 GM100611/GM/NIGMS NIH HHS/ -- F32 GM108222/GM/NIGMS NIH HHS/ -- P50 GM102706/GM/NIGMS NIH HHS/ -- R01 GM038660/GM/NIGMS NIH HHS/ -- R01 GM102790/GM/NIGMS NIH HHS/ -- R37 GM057035/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1042-7. doi: 10.1126/science.1251871. Epub 2014 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. ; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biological Sciences, Stanford University, Stanford, CA 94025, USA. Department of Applied Physics; Stanford University, Stanford, CA 94025, USA. ; Department of Genetics, Stanford University, Stanford, CA 94025, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu. ; Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu. ; Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24789973" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Codon, Initiator/*genetics ; Consensus Sequence ; DNA-Directed RNA Polymerases/metabolism ; Escherichia coli/*genetics/*metabolism ; *Gene Expression Regulation, Bacterial ; Peptide Chain Initiation, Translational/*genetics ; *Regulatory Elements, Transcriptional ; *Transcription, Genetic
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  • 54
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brenner, Sydney -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):262. doi: 10.1126/science.1249912.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore, 138673.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436413" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry ; England ; History, 20th Century ; History, 21st Century ; Molecular Biology/*history ; *Nobel Prize ; Sequence Analysis, DNA/*history/methods
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  • 55
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-11-02
    Description: MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. We determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions with the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, whereas an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. These results explain the conserved nucleotide-pairing patterns in animal miRNA target sites first observed over two decades ago.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313529/" 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/PMC4313529/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schirle, Nicole T -- Sheu-Gruttadauria, Jessica -- MacRae, Ian J -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 GM104475/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):608-13. doi: 10.1126/science.1258040.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. macrae@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359968" target="_blank"〉PubMed〈/a〉
    Keywords: Argonaute Proteins/*chemistry/genetics ; Base Sequence ; Catalytic Domain ; Conserved Sequence ; Crystallography, X-Ray ; *Gene Expression Regulation ; Humans ; Magnesium/chemistry ; MicroRNAs/*chemistry/genetics ; Models, Molecular ; Nucleic Acid Conformation ; Protein Structure, Secondary ; RNA, Guide/*chemistry/genetics
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  • 56
    Publication Date: 2014-11-21
    Description: To study the evolutionary dynamics of regulatory DNA, we mapped 〉1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337786/" 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/PMC4337786/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vierstra, Jeff -- Rynes, Eric -- Sandstrom, Richard -- Zhang, Miaohua -- Canfield, Theresa -- Hansen, R Scott -- Stehling-Sun, Sandra -- Sabo, Peter J -- Byron, Rachel -- Humbert, Richard -- Thurman, Robert E -- Johnson, Audra K -- Vong, Shinny -- Lee, Kristen -- Bates, Daniel -- Neri, Fidencio -- Diegel, Morgan -- Giste, Erika -- Haugen, Eric -- Dunn, Douglas -- Wilken, Matthew S -- Josefowicz, Steven -- Samstein, Robert -- Chang, Kai-Hsin -- Eichler, Evan E -- De Bruijn, Marella -- Reh, Thomas A -- Skoultchi, Arthur -- Rudensky, Alexander -- Orkin, Stuart H -- Papayannopoulou, Thalia -- Treuting, Piper M -- Selleri, Licia -- Kaul, Rajinder -- Groudine, Mark -- Bender, M A -- Stamatoyannopoulos, John A -- 1RC2HG005654/HG/NHGRI NIH HHS/ -- 2R01HD04399709/HD/NICHD NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 DK096266/DK/NIDDK NIH HHS/ -- R01 EY021482/EY/NEI NIH HHS/ -- R01 HD043997/HD/NICHD NIH HHS/ -- R37 DK044746/DK/NIDDK NIH HHS/ -- R37DK44746/DK/NIDDK NIH HHS/ -- RC2 HG005654/HG/NHGRI NIH HHS/ -- U54 HG007010/HG/NHGRI NIH HHS/ -- U54HG007010/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):1007-12. doi: 10.1126/science.1246426.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. ; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA. ; Department of Biological Structure, University of Washington, Seattle, WA 98195, USA. ; Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Howard Hughes Medical Institute. ; Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute. ; Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK. ; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ; Howard Hughes Medical Institute. Division of Hematology/Oncology, Children's Hospital Boston and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA. ; Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA. ; Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA. ; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Department of Radiation Oncology, University of Washington, Seattle, WA 98109, USA. ; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Department of Pediatrics, University of Washington, Seattle, WA 98195, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Division of Oncology, Department of Medicine, University of Washington, Seattle, WA 98195, USA. jstam@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25411453" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Conserved Sequence ; DNA/*genetics ; Deoxyribonuclease I ; *Evolution, Molecular ; Genome, Human ; Humans ; Mice ; Regulatory Sequences, Nucleic Acid/*genetics ; Restriction Mapping ; Transcription Factors/*metabolism
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  • 57
    Publication Date: 2014-04-20
    Description: Flaviviruses are emerging human pathogens and worldwide health threats. During infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) are produced by resisting degradation by the 5'--〉3' host cell exonuclease Xrn1 through an unknown RNA structure-based mechanism. Here, we present the crystal structure of a complete Xrn1-resistant flaviviral RNA, which contains interwoven pseudoknots within a compact structure that depends on highly conserved nucleotides. The RNA's three-dimensional topology creates a ringlike conformation, with the 5' end of the resistant structure passing through the ring from one side of the fold to the other. Disruption of this structure prevents formation of sfRNA during flaviviral infection. Thus, sfRNA formation results from an RNA fold that interacts directly with Xrn1, presenting the enzyme with a structure that confounds its helicase activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163914/" 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/PMC4163914/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Erich G -- Costantino, David A -- Rabe, Jennifer L -- Moon, Stephanie L -- Wilusz, Jeffrey -- Nix, Jay C -- Kieft, Jeffrey S -- P30 CA046934/CA/NCI NIH HHS/ -- P30CA046934/CA/NCI NIH HHS/ -- U54 AI-065357/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):307-10. doi: 10.1126/science.1250897.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744377" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Crystallography, X-Ray ; Encephalitis Virus, Murray Valley/*genetics/pathogenicity ; Exoribonucleases/metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; *Nucleic Acid Conformation ; RNA, Viral/*chemistry/genetics/metabolism
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  • 58
    Publication Date: 2014-05-17
    Description: Because of differences in craniofacial morphology and dentition between the earliest American skeletons and modern Native Americans, separate origins have been postulated for them, despite genetic evidence to the contrary. We describe a near-complete human skeleton with an intact cranium and preserved DNA found with extinct fauna in a submerged cave on Mexico's Yucatan Peninsula. This skeleton dates to between 13,000 and 12,000 calendar years ago and has Paleoamerican craniofacial characteristics and a Beringian-derived mitochondrial DNA (mtDNA) haplogroup (D1). Thus, the differences between Paleoamericans and Native Americans probably resulted from in situ evolution rather than separate ancestry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chatters, James C -- Kennett, Douglas J -- Asmerom, Yemane -- Kemp, Brian M -- Polyak, Victor -- Blank, Alberto Nava -- Beddows, Patricia A -- Reinhardt, Eduard -- Arroyo-Cabrales, Joaquin -- Bolnick, Deborah A -- Malhi, Ripan S -- Culleton, Brendan J -- Erreguerena, Pilar Luna -- Rissolo, Dominique -- Morell-Hart, Shanti -- Stafford, Thomas W Jr -- New York, N.Y. -- Science. 2014 May 16;344(6185):750-4. doi: 10.1126/science.1252619.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Applied Paleoscience and DirectAMS, 10322 NE 190th Street, Bothell, WA 98011, USA. paleosci@gmail.com. ; Department of Anthropology and Institutes of Energy and the Environment, Pennsylvania State University, University Park, PA 16802, USA. ; Department of Earth and Planetary Sciences, University of New Mexico, Albuquerque, NM 87131-0001, USA. ; Department of Anthropology and School of Biological Sciences, Washington State University, Pullman, WA 99164, USA. ; Bay Area Underwater Explorers, Berkeley, CA, USA. ; Department of Earth and Planetary Sciences, Northwestern University, Evanston, IL 60208, USA. ; School of Geography and Earth Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada. ; Instituto Nacional Antropologia e Historia, Colonia Centro Historico, 06060, Mexico City, DF, Mexico. ; Department of Anthropology and Population Research Center, University of Texas at Austin, Austin, TX 78712, USA. ; Institute for Genomic Biology, University of Illinois, Urbana-Champaign, IL 61801, USA. ; Subdireccion de Arqueologia Subacuatica, Instituto Nacional de Antropologia e Historia, 06070 Mexico City, Mexico. ; Waitt Institute, La Jolla, CA 92038-1948, USA. ; Department of Anthropology, Stanford University, Stanford, CA 94305, USA. ; Centre for AMS C, Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark, and Centre for GeoGenetics, Natural History Museum of Denmark, Geological Museum, Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833392" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Biological Evolution ; DNA, Mitochondrial/genetics ; Haplotypes ; Humans ; Indians, North American/*genetics ; Mexico ; Molecular Sequence Data ; Paleontology ; Radiometric Dating ; *Skeleton ; Skull/anatomy & histology
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  • 59
    Publication Date: 2014-07-12
    Description: Antiretroviral treatment (ART) of HIV infection suppresses viral replication. Yet if ART is stopped, virus reemerges because of the persistence of infected cells. We evaluated the contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. A total of 534 HIV integration sites (IS) and 63 adjacent HIV env sequences were derived from three study participants over 11.3 to 12.7 years of ART. Each participant had identical viral sequences integrated at the same position in multiple cells, demonstrating infected-cell proliferation. Integrations were overrepresented in genes associated with cancer and favored in 12 genes across multiple participants. Over time on ART, a greater proportion of persisting proviruses were in proliferating cells. HIV integration into specific genes may promote proliferation of HIV-infected cells, slowing viral decay during ART.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230336/" 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/PMC4230336/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wagner, Thor A -- McLaughlin, Sherry -- Garg, Kavita -- Cheung, Charles Y K -- Larsen, Brendan B -- Styrchak, Sheila -- Huang, Hannah C -- Edlefsen, Paul T -- Mullins, James I -- Frenkel, Lisa M -- 201311CVI-322424-244686/Canadian Institutes of Health Research/Canada -- K23 AI077357/AI/NIAID NIH HHS/ -- K23AI077357/AI/NIAID NIH HHS/ -- P30 AI027757/AI/NIAID NIH HHS/ -- R01 AI091550/AI/NIAID NIH HHS/ -- R01 AI111806/AI/NIAID NIH HHS/ -- R01AI091550/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 1;345(6196):570-3. doi: 10.1126/science.1256304. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. University of Washington, Seattle, WA, USA. ; Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; University of Washington, Seattle, WA, USA. ; Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. ; University of Washington, Seattle, WA, USA. Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. University of Washington, Seattle, WA, USA. lfrenkel@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25011556" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-HIV Agents/therapeutic use ; Base Sequence ; Basic-Leucine Zipper Transcription Factors/genetics ; Cell Proliferation ; Chromosomes, Human, Pair 6/genetics ; *Genes, Neoplasm ; Genetic Loci ; HIV Infections/drug therapy/*virology ; HIV-1/genetics/*physiology ; Humans ; Jurkat Cells ; Molecular Sequence Data ; Phylogeny ; *Virus Integration ; *Virus Latency ; Virus Replication ; env Gene Products, Human Immunodeficiency Virus/classification/genetics
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  • 60
    Publication Date: 2014-12-17
    Description: To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405904/" 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/PMC4405904/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jarvis, Erich D -- Mirarab, Siavash -- Aberer, Andre J -- Li, Bo -- Houde, Peter -- Li, Cai -- Ho, Simon Y W -- Faircloth, Brant C -- Nabholz, Benoit -- Howard, Jason T -- Suh, Alexander -- Weber, Claudia C -- da Fonseca, Rute R -- Li, Jianwen -- Zhang, Fang -- Li, Hui -- Zhou, Long -- Narula, Nitish -- Liu, Liang -- Ganapathy, Ganesh -- Boussau, Bastien -- Bayzid, Md Shamsuzzoha -- Zavidovych, Volodymyr -- Subramanian, Sankar -- Gabaldon, Toni -- Capella-Gutierrez, Salvador -- Huerta-Cepas, Jaime -- Rekepalli, Bhanu -- Munch, Kasper -- Schierup, Mikkel -- Lindow, Bent -- Warren, Wesley C -- Ray, David -- Green, Richard E -- Bruford, Michael W -- Zhan, Xiangjiang -- Dixon, Andrew -- Li, Shengbin -- Li, Ning -- Huang, Yinhua -- Derryberry, Elizabeth P -- Bertelsen, Mads Frost -- Sheldon, Frederick H -- Brumfield, Robb T -- Mello, Claudio V -- Lovell, Peter V -- Wirthlin, Morgan -- Schneider, Maria Paula Cruz -- Prosdocimi, Francisco -- Samaniego, Jose Alfredo -- Vargas Velazquez, Amhed Missael -- Alfaro-Nunez, Alonzo -- Campos, Paula F -- Petersen, Bent -- Sicheritz-Ponten, Thomas -- Pas, An -- Bailey, Tom -- Scofield, Paul -- Bunce, Michael -- Lambert, David M -- Zhou, Qi -- Perelman, Polina -- Driskell, Amy C -- Shapiro, Beth -- Xiong, Zijun -- Zeng, Yongli -- Liu, Shiping -- Li, Zhenyu -- Liu, Binghang -- Wu, Kui -- Xiao, Jin -- Yinqi, Xiong -- Zheng, Qiuemei -- Zhang, Yong -- Yang, Huanming -- Wang, Jian -- Smeds, Linnea -- Rheindt, Frank E -- Braun, Michael -- Fjeldsa, Jon -- Orlando, Ludovic -- Barker, F Keith -- Jonsson, Knud Andreas -- Johnson, Warren -- Koepfli, Klaus-Peter -- O'Brien, Stephen -- Haussler, David -- Ryder, Oliver A -- Rahbek, Carsten -- Willerslev, Eske -- Graves, Gary R -- Glenn, Travis C -- McCormack, John -- Burt, Dave -- Ellegren, Hans -- Alstrom, Per -- Edwards, Scott V -- Stamatakis, Alexandros -- Mindell, David P -- Cracraft, Joel -- Braun, Edward L -- Warnow, Tandy -- Jun, Wang -- Gilbert, M Thomas P -- Zhang, Guojie -- DP1 OD000448/OD/NIH HHS/ -- DP1OD000448/OD/NIH HHS/ -- R24 GM092842/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1320-31. doi: 10.1126/science.1253451.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Howard Hughes Medical Institute (HHMI), and Duke University Medical Center, Durham, NC 27710, USA. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn. ; Department of Computer Science, The University of Texas at Austin, Austin, TX 78712, USA. ; Scientific Computing Group, Heidelberg Institute for Theoretical Studies, Heidelberg, Germany. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. College of Medicine and Forensics, Xi'an Jiaotong University Xi'an 710061, China. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; School of Biological Sciences, University of Sydney, Sydney, New South Wales 2006, Australia. ; Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, USA. Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. ; CNRS UMR 5554, Institut des Sciences de l'Evolution de Montpellier, Universite Montpellier II Montpellier, France. ; Department of Neurobiology, Howard Hughes Medical Institute (HHMI), and Duke University Medical Center, Durham, NC 27710, USA. ; Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, SE-752 36 Uppsala Sweden. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. Biodiversity and Biocomplexity Unit, Okinawa Institute of Science and Technology Onna-son, Okinawa 904-0495, Japan. ; Department of Statistics and Institute of Bioinformatics, University of Georgia, Athens, GA 30602, USA. ; Laboratoire de Biometrie et Biologie Evolutive, Centre National de la Recherche Scientifique, Universite de Lyon, F-69622 Villeurbanne, France. ; Environmental Futures Research Institute, Griffith University, Nathan, Queensland 4111, Australia. ; Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Dr. Aiguader 88, 08003 Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. Institucio Catalana de Recerca i Estudis Avancats, Barcelona, Spain. ; Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Dr. Aiguader 88, 08003 Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. ; Joint Institute for Computational Sciences, The University of Tennessee, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. ; Bioinformatics Research Centre, Aarhus University, DK-8000 Aarhus C, Denmark. ; The Genome Institute, Washington University School of Medicine, St Louis, MI 63108, USA. ; Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA. Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA. Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA. ; Department of Ecology and Evolutionary Biology, University of California Santa Cruz (UCSC), Santa Cruz, CA 95064, USA. ; Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University Cardiff CF10 3AX, Wales, UK. ; Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University Cardiff CF10 3AX, Wales, UK. Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; International Wildlife Consultants, Carmarthen SA33 5YL, Wales, UK. ; College of Medicine and Forensics, Xi'an Jiaotong University Xi'an, 710061, China. ; State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, China. ; Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, LA 70118, USA. Museum of Natural Science and Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. ; Center for Zoo and Wild Animal Health, Copenhagen Zoo Roskildevej 38, DK-2000 Frederiksberg, Denmark. ; Museum of Natural Science and Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. ; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA. Brazilian Avian Genome Consortium (CNPq/FAPESPA-SISBIO Aves), Federal University of Para, Belem, Para, Brazil. ; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA. ; Brazilian Avian Genome Consortium (CNPq/FAPESPA-SISBIO Aves), Federal University of Para, Belem, Para, Brazil. Institute of Biological Sciences, Federal University of Para, Belem, Para, Brazil. ; Brazilian Avian Genome Consortium (CNPq/FAPESPA-SISBIO Aves), Federal University of Para, Belem, Para, Brazil. Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro RJ 21941-902, Brazil. ; Centre for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark Kemitorvet 208, 2800 Kgs Lyngby, Denmark. ; Breeding Centre for Endangered Arabian Wildlife, Sharjah, United Arab Emirates. ; Dubai Falcon Hospital, Dubai, United Arab Emirates. ; Canterbury Museum Rolleston Avenue, Christchurch 8050, New Zealand. ; Trace and Environmental DNA Laboratory Department of Environment and Agriculture, Curtin University, Perth, Western Australia 6102, Australia. ; Department of Integrative Biology, University of California, Berkeley, CA 94720, USA. ; Laboratory of Genomic Diversity, National Cancer Institute Frederick, MD 21702, USA. Institute of Molecular and Cellular Biology, SB RAS and Novosibirsk State University, Novosibirsk, Russia. ; Smithsonian Institution National Museum of Natural History, Washington, DC 20013, USA. ; BGI-Shenzhen, Shenzhen 518083, China. ; Department of Biological Sciences, National University of Singapore, Republic of Singapore. ; Department of Vertebrate Zoology, National Museum of Natural History, Smithsonian Suitland, MD 20746, USA. ; Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. ; Bell Museum of Natural History, University of Minnesota, Saint Paul, MN 55108, USA. ; Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. Department of Life Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK. Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, VA 22630, USA. ; Smithsonian Conservation Biology Institute, National Zoological Park, Washington, DC 20008, USA. ; Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia 199004. Oceanographic Center, Nova Southeastern University, Ft Lauderdale, FL 33004, USA. ; Center for Biomolecular Science and Engineering, UCSC, Santa Cruz, CA 95064, USA. ; San Diego Zoo Institute for Conservation Research, Escondido, CA 92027, USA. ; Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. Department of Vertebrate Zoology, MRC-116, National Museum of Natural History, Smithsonian Institution, Washington, DC 20013, USA. ; Department of Environmental Health Science, University of Georgia, Athens, GA 30602, USA. ; Moore Laboratory of Zoology and Department of Biology, Occidental College, Los Angeles, CA 90041, USA. ; Department of Genomics and Genetics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK. ; Swedish Species Information Centre, Swedish University of Agricultural Sciences Box 7007, SE-750 07 Uppsala, Sweden. Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; Department of Organismic and Evolutionary Biology and Museum of Comparative Zoology, Harvard University, Cambridge, MA 02138, USA. ; Scientific Computing Group, Heidelberg Institute for Theoretical Studies, Heidelberg, Germany. Institute of Theoretical Informatics, Department of Informatics, Karlsruhe Institute of Technology, D- 76131 Karlsruhe, Germany. ; Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA. ; Department of Ornithology, American Museum of Natural History, New York, NY 10024, USA. ; Department of Biology and Genetics Institute, University of Florida, Gainesville, FL 32611, USA. ; Department of Computer Science, The University of Texas at Austin, Austin, TX 78712, USA. Departments of Bioengineering and Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn. ; BGI-Shenzhen, Shenzhen 518083, China. Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Macau University of Science and Technology, Avenida Wai long, Taipa, Macau 999078, China. Department of Medicine, University of Hong Kong, Hong Kong. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Trace and Environmental DNA Laboratory Department of Environment and Agriculture, Curtin University, Perth, Western Australia 6102, Australia. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. Centre for Social Evolution, Department of Biology, Universitetsparken 15, University of Copenhagen, DK-2100 Copenhagen, Denmark. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504713" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avian Proteins/genetics ; Base Sequence ; Biological Evolution ; Birds/classification/*genetics ; DNA Transposable Elements ; Genes ; Genetic Speciation ; *Genome ; INDEL Mutation ; Introns ; *Phylogeny ; Sequence Analysis, DNA
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  • 61
    Publication Date: 2014-11-02
    Description: In plants, multiple lineages have evolved sex chromosomes independently, providing a powerful comparative framework, but few specific determinants controlling the expression of a specific sex have been identified. We investigated sex determinants in the Caucasian persimmon, Diospyros lotus, a dioecious plant with heterogametic males (XY). Male-specific short nucleotide sequences were used to define a male-determining region. A combination of transcriptomics and evolutionary approaches detected a Y-specific sex-determinant candidate, OGI, that displays male-specific conservation among Diospyros species. OGI encodes a small RNA targeting the autosomal MeGI gene, a homeodomain transcription factor regulating anther fertility in a dosage-dependent fashion. This identification of a feminizing gene suppressed by a Y-chromosome-encoded small RNA contributes to our understanding of the evolution of sex chromosome systems in higher plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akagi, Takashi -- Henry, Isabelle M -- Tao, Ryutaro -- Comai, Luca -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):646-50. doi: 10.1126/science.1257225. Epub 2014 Oct 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology and Genome Center, University of California Davis, Davis, CA, USA. Laboratory of Pomology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. ; Department of Plant Biology and Genome Center, University of California Davis, Davis, CA, USA. ; Laboratory of Pomology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. rtao@kais.kyoto-u.ac.jp lcomai@ucdavis.edu. ; Department of Plant Biology and Genome Center, University of California Davis, Davis, CA, USA. rtao@kais.kyoto-u.ac.jp lcomai@ucdavis.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359977" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Chromosomes, Plant/*genetics ; Diospyros/*genetics/*physiology ; Molecular Sequence Data ; RNA, Plant/genetics/*physiology ; RNA, Small Interfering/genetics/*physiology
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  • 62
    Publication Date: 2014-11-29
    Description: Cucurbitacins are triterpenoids that confer a bitter taste in cucurbits such as cucumber, melon, watermelon, squash, and pumpkin. These compounds discourage most pests on the plant and have also been shown to have antitumor properties. With genomics and biochemistry, we identified nine cucumber genes in the pathway for biosynthesis of cucurbitacin C and elucidated four catalytic steps. We discovered transcription factors Bl (Bitter leaf) and Bt (Bitter fruit) that regulate this pathway in leaves and fruits, respectively. Traces in genomic signatures indicated that selection imposed on Bt during domestication led to derivation of nonbitter cucurbits from their bitter ancestors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shang, Yi -- Ma, Yongshuo -- Zhou, Yuan -- Zhang, Huimin -- Duan, Lixin -- Chen, Huiming -- Zeng, Jianguo -- Zhou, Qian -- Wang, Shenhao -- Gu, Wenjia -- Liu, Min -- Ren, Jinwei -- Gu, Xingfang -- Zhang, Shengping -- Wang, Ye -- Yasukawa, Ken -- Bouwmeester, Harro J -- Qi, Xiaoquan -- Zhang, Zhonghua -- Lucas, William J -- Huang, Sanwen -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1084-8. doi: 10.1126/science.1259215.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. Agricultural Genomic Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. Horticulture and Landscape College, Hunan Agricultural University, National Chinese Medicinal Herbs Technology Center, Changsha 410128, China. ; Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China. ; Hunan Vegetable Research Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China. ; Horticulture and Landscape College, Hunan Agricultural University, National Chinese Medicinal Herbs Technology Center, Changsha 410128, China. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. College of Life Sciences, Wuhan University, Wuhan 430072, China. ; Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China. ; School of Pharmacy, Nihon University, Tokyo 101-8308, Japan. ; Laboratory of Plant Physiology, Wageningen University, Wageningen 6700, Netherlands. ; Department of Plant Biology, College of Biological Sciences, University of California, Davis, CA 95616, USA. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. Agricultural Genomic Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China. huangsanwen@caas.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25430763" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cucumis sativus/genetics/*metabolism ; Fruit/genetics/*metabolism ; Gene Expression Regulation, Plant ; Genome, Plant ; Molecular Sequence Data ; Plant Leaves/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; *Taste ; Transcription Factors/genetics/*metabolism ; Triterpenes/chemical synthesis/*metabolism
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  • 63
    Publication Date: 2014-12-18
    Description: Gene transcription in animals involves the assembly of RNA polymerase II at core promoters and its cell-type-specific activation by enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has been less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different core promoters might exhibit an intrinsic specificity to certain enhancers. This is conceivable, as various core promoter sequence elements are differentially distributed between genes of different functions, including elements that are predominantly found at either developmentally regulated or at housekeeping genes. Here we show that thousands of enhancers in Drosophila melanogaster S2 and ovarian somatic cells (OSCs) exhibit a marked specificity to one of two core promoters--one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor--and confirm the existence of these two classes for five additional core promoters from genes with diverse functions. Housekeeping enhancers are active across the two cell types, while developmental enhancers exhibit strong cell-type specificity. Both enhancer classes differ in their genomic distribution, the functions of neighbouring genes, and the core promoter elements of these neighbouring genes. In addition, we identify two transcription factors--Dref and Trl--that bind and activate housekeeping versus developmental enhancers, respectively. Our results provide evidence for a sequence-encoded enhancer-core-promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zabidi, Muhammad A -- Arnold, Cosmas D -- Schernhuber, Katharina -- Pagani, Michaela -- Rath, Martina -- Frank, Olga -- Stark, Alexander -- England -- Nature. 2015 Feb 26;518(7540):556-9. doi: 10.1038/nature13994. Epub 2014 Dec 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517091" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; DNA-Binding Proteins/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*embryology/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Genes, Essential/*genetics ; Genome, Insect/genetics ; Models, Genetic ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; Substrate Specificity/genetics ; Transcription Factors/metabolism ; Transcriptional Activation/genetics
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  • 64
    Publication Date: 2014-02-21
    Description: Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050669/" 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/PMC4050669/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, Matthew -- Mohankumar, Kumarasamypet M -- Punchihewa, Chandanamali -- Weinlich, Ricardo -- Dalton, James D -- Li, Yongjin -- Lee, Ryan -- Tatevossian, Ruth G -- Phoenix, Timothy N -- Thiruvenkatam, Radhika -- White, Elsie -- Tang, Bo -- Orisme, Wilda -- Gupta, Kirti -- Rusch, Michael -- Chen, Xiang -- Li, Yuxin -- Nagahawhatte, Panduka -- Hedlund, Erin -- Finkelstein, David -- Wu, Gang -- Shurtleff, Sheila -- Easton, John -- Boggs, Kristy -- Yergeau, Donald -- Vadodaria, Bhavin -- Mulder, Heather L -- Becksfort, Jared -- Gupta, Pankaj -- Huether, Robert -- Ma, Jing -- Song, Guangchun -- Gajjar, Amar -- Merchant, Thomas -- Boop, Frederick -- Smith, Amy A -- Ding, Li -- Lu, Charles -- Ochoa, Kerri -- Zhao, David -- Fulton, Robert S -- Fulton, Lucinda L -- Mardis, Elaine R -- Wilson, Richard K -- Downing, James R -- Green, Douglas R -- Zhang, Jinghui -- Ellison, David W -- Gilbertson, Richard J -- P01 CA096832/CA/NCI NIH HHS/ -- P01CA96832/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- P30CA021765/CA/NCI NIH HHS/ -- R01 CA129541/CA/NCI NIH HHS/ -- R01CA129541/CA/NCI NIH HHS/ -- England -- Nature. 2014 Feb 27;506(7489):451-5. doi: 10.1038/nature13109. Epub 2014 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [3]. ; 1] Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2]. ; 1] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2]. ; 1] Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2]. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2] Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA. ; Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; MD Anderson Cancer Center Orlando, Pediatric Hematology/Oncology, 92 West Miller MP 318, Orlando, Florida 32806, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] The Genome Institute, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA [3] Department of Genetics, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] The Genome Institute, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] The Genome Institute, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA [3] Department of Genetics, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA [4] Siteman Cancer Center, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA. ; Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553141" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/metabolism ; Animals ; Base Sequence ; Brain Neoplasms/genetics/metabolism/pathology ; Cell Line ; Cell Nucleus/metabolism ; *Cell Transformation, Neoplastic/genetics ; Chromosomes, Human, Pair 11/genetics ; Ependymoma/*genetics/*metabolism/pathology ; Female ; Humans ; Mice ; Models, Genetic ; Molecular Sequence Data ; NF-kappa B/genetics/*metabolism ; Neural Stem Cells/metabolism/pathology ; Oncogene Proteins, Fusion/genetics/metabolism ; Phosphoproteins/genetics/metabolism ; Proteins/genetics/*metabolism ; *Signal Transduction ; Transcription Factor RelA/genetics/*metabolism ; Translocation, Genetic/genetics
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  • 65
    Publication Date: 2014-12-04
    Description: The emergence of catalysis in early genetic polymers such as RNA is considered a key transition in the origin of life, pre-dating the appearance of protein enzymes. DNA also demonstrates the capacity to fold into three-dimensional structures and form catalysts in vitro. However, to what degree these natural biopolymers comprise functionally privileged chemical scaffolds for folding or the evolution of catalysis is not known. The ability of synthetic genetic polymers (XNAs) with alternative backbone chemistries not found in nature to fold into defined structures and bind ligands raises the possibility that these too might be capable of forming catalysts (XNAzymes). Here we report the discovery of such XNAzymes, elaborated in four different chemistries (arabino nucleic acids, ANA; 2'-fluoroarabino nucleic acids, FANA; hexitol nucleic acids, HNA; and cyclohexene nucleic acids, CeNA) directly from random XNA oligomer pools, exhibiting in trans RNA endonuclease and ligase activities. We also describe an XNA-XNA ligase metalloenzyme in the FANA framework, establishing catalysis in an entirely synthetic system and enabling the synthesis of FANA oligomers and an active RNA endonuclease FANAzyme from its constituent parts. These results extend catalysis beyond biopolymers and establish technologies for the discovery of catalysts in a wide range of polymer scaffolds not found in nature. Evolution of catalysis independent of any natural polymer has implications for the definition of chemical boundary conditions for the emergence of life on Earth and elsewhere in the Universe.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336857/" 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/PMC4336857/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor, Alexander I -- Pinheiro, Vitor B -- Smola, Matthew J -- Morgunov, Alexey S -- Peak-Chew, Sew -- Cozens, Christopher -- Weeks, Kevin M -- Herdewijn, Piet -- Holliger, Philipp -- MC_U105178804/Medical Research Council/United Kingdom -- MC_U105185859/Medical Research Council/United Kingdom -- T32 GM008570/GM/NIGMS NIH HHS/ -- U105178804/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Feb 19;518(7539):427-30. doi: 10.1038/nature13982. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA. ; 1] KU Leuven, Rega Institute, Minderbroedersstraat 10, B 3000 Leuven, Belgium [2] Universite Evry, Institute of Systems and Synthetic Biology, 5 rue Henri Desbrueres, 91030 Evry Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470036" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Catalysis ; Endonucleases/metabolism ; Ligases/metabolism ; Nucleic Acids/*chemical synthesis/chemistry/*metabolism ; Polymers/*chemical synthesis/*chemistry/metabolism ; RNA/metabolism
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  • 66
    Publication Date: 2013-12-18
    Description: An understanding of ctenophore biology is critical for reconstructing events that occurred early in animal evolution. Toward this goal, we have sequenced, assembled, and annotated the genome of the ctenophore Mnemiopsis leidyi. Our phylogenomic analyses of both amino acid positions and gene content suggest that ctenophores rather than sponges are the sister lineage to all other animals. Mnemiopsis lacks many of the genes found in bilaterian mesodermal cell types, suggesting that these cell types evolved independently. The set of neural genes in Mnemiopsis is similar to that of sponges, indicating that sponges may have lost a nervous system. These results present a newly supported view of early animal evolution that accounts for major losses and/or gains of sophisticated cell types, including nerve and muscle cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920664/" 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/PMC3920664/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ryan, Joseph F -- Pang, Kevin -- Schnitzler, Christine E -- Nguyen, Anh-Dao -- Moreland, R Travis -- Simmons, David K -- Koch, Bernard J -- Francis, Warren R -- Havlak, Paul -- NISC Comparative Sequencing Program -- Smith, Stephen A -- Putnam, Nicholas H -- Haddock, Steven H D -- Dunn, Casey W -- Wolfsberg, Tyra G -- Mullikin, James C -- Martindale, Mark Q -- Baxevanis, Andreas D -- ZIA HG000140-13/Intramural NIH HHS/ -- ZIA HG000140-14/Intramural NIH HHS/ -- ZIA HG000140-15/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1242592. doi: 10.1126/science.1242592.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Technology Branch, Division of Intramural Research, National Human Genome Research Institute, 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/24337300" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Biological Evolution ; Cell Lineage/*genetics ; Ctenophora/classification/*cytology/*genetics ; *Genome ; Mesoderm/cytology ; Molecular Sequence Data ; Muscle Development/genetics ; Neurogenesis/genetics ; Phylogeny
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  • 67
    Publication Date: 2013-07-06
    Description: DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lister, Ryan -- Mukamel, Eran A -- Nery, Joseph R -- Urich, Mark -- Puddifoot, Clare A -- Johnson, Nicholas D -- Lucero, Jacinta -- Huang, Yun -- Dwork, Andrew J -- Schultz, Matthew D -- Yu, Miao -- Tonti-Filippini, Julian -- Heyn, Holger -- Hu, Shijun -- Wu, Joseph C -- Rao, Anjana -- Esteller, Manel -- He, Chuan -- Haghighi, Fatemeh G -- Sejnowski, Terrence J -- Behrens, M Margarita -- Ecker, Joseph R -- AI44432/AI/NIAID NIH HHS/ -- CA151535/CA/NCI NIH HHS/ -- HD065812/HD/NICHD NIH HHS/ -- HG006827/HG/NHGRI NIH HHS/ -- K99NS080911/NS/NINDS NIH HHS/ -- MH094670/MH/NIMH NIH HHS/ -- R01 AI044432/AI/NIAID NIH HHS/ -- R01 CA151535/CA/NCI NIH HHS/ -- R01 HD065812/HD/NICHD NIH HHS/ -- R01 HG006827/HG/NHGRI NIH HHS/ -- R01 MH094670/MH/NIMH NIH HHS/ -- R01 MH094774/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ryan.lister@uwa.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23828890" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Adult ; Animals ; Base Sequence ; Conserved Sequence ; Cytosine/*analogs & derivatives/metabolism ; *DNA Methylation ; *Epigenesis, Genetic ; Epigenomics ; Frontal Lobe/*growth & development ; *Gene Expression Regulation, Developmental ; Genome-Wide Association Study ; Humans ; Longevity ; Mice ; Mice, Inbred C57BL ; X Chromosome Inactivation/genetics
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  • 68
    Publication Date: 2013-07-03
    Description: Gene expression in organisms involves many factors and is tightly controlled. Although much is known about the initial phase of transcription by RNA polymerase III (Pol III), the enzyme that synthesizes the majority of RNA molecules in eukaryotic cells, termination is poorly understood. Here, we show that the extensive structure of Pol III-synthesized transcripts dictates the release of elongation complexes at the end of genes. The poly-T termination signal, which does not cause termination in itself, causes catalytic inactivation and backtracking of Pol III, thus committing the enzyme to termination and transporting it to the nearest RNA secondary structure, which facilitates Pol III release. Similarity between termination mechanisms of Pol III and bacterial RNA polymerase suggests that hairpin-dependent termination may date back to the common ancestor of multisubunit RNA polymerases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760304/" 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/PMC3760304/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nielsen, Soren -- Yuzenkova, Yulia -- Zenkin, Nikolay -- 202994/European Research Council/International -- BB/F013558/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J006378/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1577-80. doi: 10.1126/science.1237934.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812715" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Molecular Sequence Data ; Nucleic Acid Conformation ; Poly T/metabolism ; Poly U/metabolism ; RNA Polymerase III/*metabolism ; RNA, Ribosomal, 5S/chemistry/genetics ; RNA, Transfer, Tyr/chemistry/genetics ; Saccharomyces cerevisiae/*enzymology/genetics ; *Transcription Termination, Genetic
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  • 69
    Publication Date: 2013-03-09
    Description: RNA chaperones are ubiquitous, heterogeneous proteins essential for RNA structural biogenesis and function. We investigated the mechanism of chaperone-mediated RNA folding by following the time-resolved dimerization of the packaging domain of a retroviral RNA at nucleotide resolution. In the absence of the nucleocapsid (NC) chaperone, dimerization proceeded through multiple, slow-folding intermediates. In the presence of NC, dimerization occurred rapidly through a single structural intermediate. The RNA binding domain of heterogeneous nuclear ribonucleoprotein A1 protein, a structurally unrelated chaperone, also accelerated dimerization. Both chaperones interacted primarily with guanosine residues. Replacing guanosine with more weakly pairing inosine yielded an RNA that folded rapidly without a facilitating chaperone. These results show that RNA chaperones can simplify RNA folding landscapes by weakening intramolecular interactions involving guanosine and explain many RNA chaperone activities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338410/" 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/PMC4338410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grohman, Jacob K -- Gorelick, Robert J -- Lickwar, Colin R -- Lieb, Jason D -- Bower, Brian D -- Znosko, Brent M -- Weeks, Kevin M -- GM031819/GM/NIGMS NIH HHS/ -- GM064803/GM/NIGMS NIH HHS/ -- GM072518/GM/NIGMS NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- R01 GM031819/GM/NIGMS NIH HHS/ -- R01 GM064803/GM/NIGMS NIH HHS/ -- T32 GM007092/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 12;340(6129):190-5. doi: 10.1126/science.1230715. Epub 2013 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23470731" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Dimerization ; Guanosine/chemistry/*metabolism ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/chemistry/metabolism ; Inosine/chemistry/metabolism ; Kinetics ; Models, Molecular ; Molecular Chaperones/chemistry/*metabolism ; Moloney murine leukemia virus/genetics/*metabolism ; Nucleic Acid Conformation ; Nucleocapsid Proteins/chemistry/*metabolism ; Protein Binding ; RNA, Viral/*chemistry/metabolism
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  • 70
    Publication Date: 2013-09-07
    Description: Organofluorines represent a rapidly expanding proportion of molecules that are used in pharmaceuticals, diagnostics, agrochemicals, and materials. Despite the prevalence of fluorine in synthetic compounds, the known biological scope is limited to a single pathway that produces fluoroacetate. Here, we demonstrate that this pathway can be exploited as a source of fluorinated building blocks for introduction of fluorine into natural-product scaffolds. Specifically, we have constructed pathways involving two polyketide synthase systems, and we show that fluoroacetate can be used to incorporate fluorine into the polyketide backbone in vitro. We further show that fluorine can be inserted site-selectively and introduced into polyketide products in vivo. These results highlight the prospects for the production of complex fluorinated natural products using synthetic biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057101/" 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/PMC4057101/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walker, Mark C -- Thuronyi, Benjamin W -- Charkoudian, Louise K -- Lowry, Brian -- Khosla, Chaitan -- Chang, Michelle C Y -- 1 DP2 OD008696/OD/NIH HHS/ -- 1 T32 GMO66698/PHS HHS/ -- 1S10RR023679-01/RR/NCRR NIH HHS/ -- F32 CA137994/CA/NCI NIH HHS/ -- R01 GM087934/GM/NIGMS NIH HHS/ -- S10 RR16634-01/RR/NCRR NIH HHS/ -- T32 GM066698/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Sep 6;341(6150):1089-94. doi: 10.1126/science.1242345.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-1460, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24009388" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/genetics/metabolism ; Base Sequence ; Biological Products/chemistry/*metabolism ; Burkholderia/enzymology ; Coenzyme A Ligases/chemistry/genetics/metabolism ; Escherichia coli ; Fluoroacetates/chemistry/*metabolism ; Metabolic Networks and Pathways ; Molecular Sequence Data ; Polyketide Synthases/chemistry/genetics/*metabolism ; Polyketides/chemistry/*metabolism ; Protein Engineering ; Protein Structure, Tertiary ; Streptomyces coelicolor/enzymology
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  • 71
    Publication Date: 2013-02-16
    Description: Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which-together with molecular dynamics simulations-suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586787/" 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/PMC3586787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Sangjin -- Brostromer, Erik -- Xing, Dong -- Jin, Jianshi -- Chong, Shasha -- Ge, Hao -- Wang, Siyuan -- Gu, Chan -- Yang, Lijiang -- Gao, Yi Qin -- Su, Xiao-dong -- Sun, Yujie -- Xie, X Sunney -- DP1 OD000277/OD/NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 15;339(6121):816-9. doi: 10.1126/science.1229223.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413354" target="_blank"〉PubMed〈/a〉
    Keywords: *Allosteric Regulation ; Base Sequence ; Binding Sites ; DNA, B-Form/*chemistry ; DNA-Binding Proteins/*chemistry ; DNA-Directed RNA Polymerases/chemistry ; Escherichia coli/genetics/metabolism ; Gene Expression ; *Gene Expression Regulation, Bacterial ; Lac Repressors/chemistry ; Molecular Dynamics Simulation ; Nucleosomes/chemistry ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Glucocorticoid/chemistry ; Transcription Factors/*chemistry ; Viral Proteins/chemistry
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  • 72
    Publication Date: 2013-10-12
    Description: In antiviral RNA interference (RNAi), the DICER enzyme processes virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that guide ARGONAUTE proteins to silence complementary viral RNA. As a counterdefense, viruses deploy viral suppressors of RNAi (VSRs). Well-established in plants and invertebrates, the existence of antiviral RNAi remains unknown in mammals. Here, we show that undifferentiated mouse cells infected with encephalomyocarditis virus (EMCV) or Nodamura virus (NoV) accumulate ~22-nucleotide RNAs with all the signature features of siRNAs. These derive from viral dsRNA replication intermediates, incorporate into AGO2, are eliminated in Dicer knockout cells, and decrease in abundance upon cell differentiation. Furthermore, genetically ablating a NoV-encoded VSR that antagonizes DICER during authentic infections reduces NoV accumulation, which is rescued in RNAi-deficient mouse cells. We conclude that antiviral RNAi operates in mammalian cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853215/" 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/PMC3853215/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maillard, P V -- Ciaudo, C -- Marchais, A -- Li, Y -- Jay, F -- Ding, S W -- Voinnet, Olivier -- R01 AI052447/AI/NIAID NIH HHS/ -- R01 GM094396/GM/NIGMS NIH HHS/ -- RC1 GM091896/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):235-8. doi: 10.1126/science.1241930.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Swiss Federal Institute of Technology Zurich (ETH-Z), Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24115438" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins/genetics/metabolism ; Base Sequence ; Cardiovirus Infections/*immunology ; Cell Line ; DEAD-box RNA Helicases/genetics/metabolism ; Encephalomyocarditis virus/genetics/*physiology ; Gene Knockout Techniques ; Mice ; Molecular Sequence Data ; Nodaviridae/genetics/*physiology ; RNA Interference/*immunology ; RNA Virus Infections/*immunology ; RNA, Double-Stranded/genetics/*immunology/metabolism ; RNA, Small Interfering/genetics/*immunology/metabolism ; RNA, Viral/genetics/*immunology/metabolism ; Ribonuclease III/genetics/metabolism ; Virus Replication
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  • 73
    Publication Date: 2013-07-23
    Description: Ten years ago, the discovery of Mimivirus, a virus infecting Acanthamoeba, initiated a reappraisal of the upper limits of the viral world, both in terms of particle size (〉0.7 micrometers) and genome complexity (〉1000 genes), dimensions typical of parasitic bacteria. The diversity of these giant viruses (the Megaviridae) was assessed by sampling a variety of aquatic environments and their associated sediments worldwide. We report the isolation of two giant viruses, one off the coast of central Chile, the other from a freshwater pond near Melbourne (Australia), without morphological or genomic resemblance to any previously defined virus families. Their micrometer-sized ovoid particles contain DNA genomes of at least 2.5 and 1.9 megabases, respectively. These viruses are the first members of the proposed "Pandoravirus" genus, a term reflecting their lack of similarity with previously described microorganisms and the surprises expected from their future study.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Philippe, Nadege -- Legendre, Matthieu -- Doutre, Gabriel -- Coute, Yohann -- Poirot, Olivier -- Lescot, Magali -- Arslan, Defne -- Seltzer, Virginie -- Bertaux, Lionel -- Bruley, Christophe -- Garin, Jerome -- Claverie, Jean-Michel -- Abergel, Chantal -- New York, N.Y. -- Science. 2013 Jul 19;341(6143):281-6. doi: 10.1126/science.1239181.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Genomic Information Laboratory, UMR 7256 CNRS Aix-Marseille Universite, 163 Avenue de Luminy, Case 934, 13288 Marseille cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23869018" target="_blank"〉PubMed〈/a〉
    Keywords: Amoeba/*virology ; Base Sequence ; *Evolution, Molecular ; Fresh Water/virology ; *Genome, Viral ; Mimiviridae/*classification/*genetics/isolation & purification/ultrastructure ; Molecular Sequence Data ; Phylogeny ; Proteomics ; Seawater/virology
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  • 74
    Publication Date: 2013-10-12
    Description: The processes that shaped modern European mitochondrial DNA (mtDNA) variation remain unclear. The initial peopling by Palaeolithic hunter-gatherers ~42,000 years ago and the immigration of Neolithic farmers into Europe ~8000 years ago appear to have played important roles but do not explain present-day mtDNA diversity. We generated mtDNA profiles of 364 individuals from prehistoric cultures in Central Europe to perform a chronological study, spanning the Early Neolithic to the Early Bronze Age (5500 to 1550 calibrated years before the common era). We used this transect through time to identify four marked shifts in genetic composition during the Neolithic period, revealing a key role for Late Neolithic cultures in shaping modern Central European genetic diversity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039305/" 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/PMC4039305/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brandt, Guido -- Haak, Wolfgang -- Adler, Christina J -- Roth, Christina -- Szecsenyi-Nagy, Anna -- Karimnia, Sarah -- Moller-Rieker, Sabine -- Meller, Harald -- Ganslmeier, Robert -- Friederich, Susanne -- Dresely, Veit -- Nicklisch, Nicole -- Pickrell, Joseph K -- Sirocko, Frank -- Reich, David -- Cooper, Alan -- Alt, Kurt W -- Genographic Consortium -- R01 GM100233/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):257-61. doi: 10.1126/science.1241844.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Anthropology, Johannes Gutenberg University of Mainz, Mainz, Germany. brandtg@uni-mainz.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24115443" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; Base Sequence ; DNA, Mitochondrial/*genetics/history ; Europe ; *Genetic Drift ; *Genetic Variation ; History, Ancient ; Humans ; Molecular Sequence Data ; Population/*genetics ; Transients and Migrants
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  • 75
    Publication Date: 2013-02-16
    Description: Instances in which natural selection maintains genetic variation in a population over millions of years are thought to be extremely rare. We conducted a genome-wide scan for long-lived balancing selection by looking for combinations of SNPs shared between humans and chimpanzees. In addition to the major histocompatibility complex, we identified 125 regions in which the same haplotypes are segregating in the two species, all but two of which are noncoding. In six cases, there is evidence for an ancestral polymorphism that persisted to the present in humans and chimpanzees. Regions with shared haplotypes are significantly enriched for membrane glycoproteins, and a similar trend is seen among shared coding polymorphisms. These findings indicate that ancient balancing selection has shaped human variation and point to genes involved in host-pathogen interactions as common targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612375/" 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/PMC3612375/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leffler, Ellen M -- Gao, Ziyue -- Pfeifer, Susanne -- Segurel, Laure -- Auton, Adam -- Venn, Oliver -- Bowden, Rory -- Bontrop, Ronald -- Wall, Jeffrey D -- Sella, Guy -- Donnelly, Peter -- McVean, Gilean -- Przeworski, Molly -- 075491/Z/04/B/Wellcome Trust/United Kingdom -- 086084/Z/08/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095552/Wellcome Trust/United Kingdom -- 095552/Z/11/Z/Wellcome Trust/United Kingdom -- GM72861/GM/NIGMS NIH HHS/ -- HG005226/HG/NHGRI NIH HHS/ -- R01 GM072861/GM/NIGMS NIH HHS/ -- T32 GM007197/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1578-82. doi: 10.1126/science.1234070. Epub 2013 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. emleffler@uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413192" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Genetic Association Studies ; Genome, Human/*genetics ; Haplotypes ; Host-Pathogen Interactions/*genetics ; Humans ; Molecular Sequence Data ; Pan troglodytes/*genetics ; Pedigree ; Polymorphism, Single Nucleotide ; *Selection, Genetic
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  • 76
    Publication Date: 2013-10-11
    Description: DNA methylation was first described almost a century ago; however, the rules governing its establishment and maintenance remain elusive. Here we present data demonstrating that active transcription regulates levels of genomic methylation. We identify a novel RNA arising from the CEBPA gene locus that is critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extend the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene-selective demethylation of therapeutic targets in human diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870304/" 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/PMC3870304/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Ruscio, Annalisa -- Ebralidze, Alexander K -- Benoukraf, Touati -- Amabile, Giovanni -- Goff, Loyal A -- Terragni, Jolyon -- Figueroa, Maria Eugenia -- De Figueiredo Pontes, Lorena Lobo -- Alberich-Jorda, Meritxell -- Zhang, Pu -- Wu, Mengchu -- D'Alo, Francesco -- Melnick, Ari -- Leone, Giuseppe -- Ebralidze, Konstantin K -- Pradhan, Sriharsa -- Rinn, John L -- Tenen, Daniel G -- CA118316/CA/NCI NIH HHS/ -- CA66996/CA/NCI NIH HHS/ -- HL56745/HL/NHLBI NIH HHS/ -- P01 CA066996/CA/NCI NIH HHS/ -- R01 CA118316/CA/NCI NIH HHS/ -- R01 HL056745/HL/NHLBI NIH HHS/ -- R01 HL112719/HL/NHLBI NIH HHS/ -- T32 HL007917-11A1/HL/NHLBI NIH HHS/ -- England -- Nature. 2013 Nov 21;503(7476):371-6. doi: 10.1038/nature12598. Epub 2013 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [3] Universita Cattolica del Sacro Cuore, Institute of Hematology, L.go A. Gemelli 8, Rome 00168, Italy [4].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24107992" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; CCAAT-Enhancer-Binding Proteins/*genetics ; Cell Line ; DNA/genetics/metabolism ; DNA (Cytosine-5-)-Methyltransferase/*metabolism ; DNA Methylation/*genetics ; Gene Expression Profiling ; Gene Expression Regulation/*genetics ; Genome, Human/genetics ; Humans ; RNA, Messenger/genetics/metabolism ; RNA, Untranslated/genetics/*metabolism ; RNA-Binding Proteins/metabolism ; Substrate Specificity ; Transcription, Genetic/genetics
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  • 77
    Publication Date: 2013-07-13
    Description: RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929597/" 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/PMC3929597/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ray, Debashish -- Kazan, Hilal -- Cook, Kate B -- Weirauch, Matthew T -- Najafabadi, Hamed S -- Li, Xiao -- Gueroussov, Serge -- Albu, Mihai -- Zheng, Hong -- Yang, Ally -- Na, Hong -- Irimia, Manuel -- Matzat, Leah H -- Dale, Ryan K -- Smith, Sarah A -- Yarosh, Christopher A -- Kelly, Seth M -- Nabet, Behnam -- Mecenas, Desirea -- Li, Weimin -- Laishram, Rakesh S -- Qiao, Mei -- Lipshitz, Howard D -- Piano, Fabio -- Corbett, Anita H -- Carstens, Russ P -- Frey, Brendan J -- Anderson, Richard A -- Lynch, Kristen W -- Penalva, Luiz O F -- Lei, Elissa P -- Fraser, Andrew G -- Blencowe, Benjamin J -- Morris, Quaid D -- Hughes, Timothy R -- 1R01HG00570/HG/NHGRI NIH HHS/ -- DK015602-05/DK/NIDDK NIH HHS/ -- MOP-125894/Canadian Institutes of Health Research/Canada -- MOP-14409/Canadian Institutes of Health Research/Canada -- MOP-49451/Canadian Institutes of Health Research/Canada -- MOP-67011/Canadian Institutes of Health Research/Canada -- MOP-93671/Canadian Institutes of Health Research/Canada -- P30 CA014520/CA/NCI NIH HHS/ -- R01 CA104708/CA/NCI NIH HHS/ -- R01 GM051968/GM/NIGMS NIH HHS/ -- R01 GM084034/GM/NIGMS NIH HHS/ -- R01 HG005700/HG/NHGRI NIH HHS/ -- R01GM084034/GM/NIGMS NIH HHS/ -- T32 GM008061/GM/NIGMS NIH HHS/ -- Z01 DK015602-01/Intramural NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):172-7. doi: 10.1038/nature12311.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23846655" target="_blank"〉PubMed〈/a〉
    Keywords: Autistic Disorder/genetics ; Base Sequence ; Binding Sites/genetics ; Conserved Sequence/genetics ; Eukaryotic Cells/metabolism ; Gene Expression Regulation/*genetics ; Humans ; Molecular Sequence Data ; Nucleotide Motifs/*genetics ; Protein Structure, Tertiary/genetics ; RNA Stability/genetics ; RNA-Binding Proteins/chemistry/genetics/*metabolism
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  • 78
    Publication Date: 2013-02-08
    Description: Several mutations are required for cancer development, and genome sequencing has revealed that many cancers, including breast cancer, have somatic mutation spectra dominated by C-to-T transitions. Most of these mutations occur at hydrolytically disfavoured non-methylated cytosines throughout the genome, and are sometimes clustered. Here we show that the DNA cytosine deaminase APOBEC3B is a probable source of these mutations. APOBEC3B messenger RNA is upregulated in most primary breast tumours and breast cancer cell lines. Tumours that express high levels of APOBEC3B have twice as many mutations as those that express low levels and are more likely to have mutations in TP53. Endogenous APOBEC3B protein is predominantly nuclear and the only detectable source of DNA C-to-U editing activity in breast cancer cell-line extracts. Knockdown experiments show that endogenous APOBEC3B correlates with increased levels of genomic uracil, increased mutation frequencies, and C-to-T transitions. Furthermore, induced APOBEC3B overexpression causes cell cycle deviations, cell death, DNA fragmentation, gamma-H2AX accumulation and C-to-T mutations. Our data suggest a model in which APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers that could select TP53 inactivation and explain how some tumours evolve rapidly and manifest heterogeneity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907282/" 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/PMC3907282/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burns, Michael B -- Lackey, Lela -- Carpenter, Michael A -- Rathore, Anurag -- Land, Allison M -- Leonard, Brandon -- Refsland, Eric W -- Kotandeniya, Delshanee -- Tretyakova, Natalia -- Nikas, Jason B -- Yee, Douglas -- Temiz, Nuri A -- Donohue, Duncan E -- McDougle, Rebecca M -- Brown, William L -- Law, Emily K -- Harris, Reuben S -- 1UL1RR033183/RR/NCRR NIH HHS/ -- F31 DA033186/DA/NIDA NIH HHS/ -- F32 GM095219/GM/NIGMS NIH HHS/ -- KL2 RR033182/RR/NCRR NIH HHS/ -- P01 GM091743/GM/NIGMS NIH HHS/ -- P30 CA77598/CA/NCI NIH HHS/ -- P50 CA101955/CA/NCI NIH HHS/ -- R01 AI064046/AI/NIAID NIH HHS/ -- T32 AI083196/AI/NIAID NIH HHS/ -- T32 CA009138/CA/NCI NIH HHS/ -- UL1 TR000114/TR/NCATS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2013 Feb 21;494(7437):366-70. doi: 10.1038/nature11881. Epub 2013 Feb 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry, Molecular Biology and Biophysics Department, University of Minnesota, Minneapolis, Minnesota 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23389445" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Biocatalysis ; Breast Neoplasms/*enzymology/*genetics/pathology ; Cell Death ; Cell Line, Tumor ; Cytidine Deaminase/genetics/*metabolism ; DNA Damage/genetics ; DNA Fragmentation ; DNA, Neoplasm/genetics/metabolism ; Deamination ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Histones/metabolism ; Humans ; *Mutagenesis/genetics ; Phenotype ; *Point Mutation/genetics ; Tumor Suppressor Protein p53/genetics/metabolism ; Up-Regulation ; Uracil/metabolism
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  • 79
    Publication Date: 2013-07-12
    Description: Riboswitches are cis-acting gene-regulatory RNA elements that can function at the level of transcription, translation and RNA cleavage. The commonly accepted molecular mechanism for riboswitch function proposes a ligand-dependent conformational switch between two mutually exclusive states. According to this mechanism, ligand binding to an aptamer domain induces an allosteric conformational switch of an expression platform, leading to activation or repression of ligand-related gene expression. However, many riboswitch properties cannot be explained by a pure two-state mechanism. Here we show that the regulation mechanism of the adenine-sensing riboswitch, encoded by the add gene on chromosome II of the human Gram-negative pathogenic bacterium Vibrio vulnificus, is notably different from a two-state switch mechanism in that it involves three distinct stable conformations. We characterized the temperature and Mg(2+) dependence of the population ratios of the three conformations and the kinetics of their interconversion at nucleotide resolution. The observed temperature dependence of a pre-equilibrium involving two structurally distinct ligand-free conformations of the add riboswitch conferred efficient regulation over a physiologically relevant temperature range. Such robust switching is a key requirement for gene regulation in bacteria that have to adapt to environments with varying temperatures. The translational adenine-sensing riboswitch represents the first example, to our knowledge, of a temperature-compensated regulatory RNA element.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reining, Anke -- Nozinovic, Senada -- Schlepckow, Kai -- Buhr, Florian -- Furtig, Boris -- Schwalbe, Harald -- England -- Nature. 2013 Jul 18;499(7458):355-9. doi: 10.1038/nature12378. Epub 2013 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Biomolecular Magnetic Resonance, Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-Universitat Frankfurt am Main, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23842498" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/metabolism ; Base Sequence ; *Gene Expression Regulation, Bacterial ; Ligands ; Magnesium/chemistry ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Bacterial/*chemistry/metabolism ; *Riboswitch ; Temperature ; Vibrio vulnificus/genetics
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  • 80
    Publication Date: 2013-06-04
    Description: Rev-Erb-alpha and Rev-Erb-beta are nuclear receptors that regulate the expression of genes involved in the control of circadian rhythm, metabolism and inflammatory responses. Rev-Erbs function as transcriptional repressors by recruiting nuclear receptor co-repressor (NCoR)-HDAC3 complexes to Rev-Erb response elements in enhancers and promoters of target genes, but the molecular basis for cell-specific programs of repression is not known. Here we present evidence that in mouse macrophages Rev-Erbs regulate target gene expression by inhibiting the functions of distal enhancers that are selected by macrophage-lineage-determining factors, thereby establishing a macrophage-specific program of repression. Remarkably, the repressive functions of Rev-Erbs are associated with their ability to inhibit the transcription of enhancer-derived RNAs (eRNAs). Furthermore, targeted degradation of eRNAs at two enhancers subject to negative regulation by Rev-Erbs resulted in reduced expression of nearby messenger RNAs, suggesting a direct role of these eRNAs in enhancer function. By precisely defining eRNA start sites using a modified form of global run-on sequencing that quantifies nascent 5' ends, we show that transfer of full enhancer activity to a target promoter requires both the sequences mediating transcription-factor binding and the specific sequences encoding the eRNA transcript. These studies provide evidence for a direct role of eRNAs in contributing to enhancer functions and suggest that Rev-Erbs act to suppress gene expression at a distance by repressing eRNA transcription.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839578/" 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/PMC3839578/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, Michael T Y -- Cho, Han -- Lesch, Hanna P -- Gosselin, David -- Heinz, Sven -- Tanaka-Oishi, Yumiko -- Benner, Christopher -- Kaikkonen, Minna U -- Kim, Aneeza S -- Kosaka, Mika -- Lee, Cindy Y -- Watt, Andy -- Grossman, Tamar R -- Rosenfeld, Michael G -- Evans, Ronald M -- Glass, Christopher K -- CA014195/CA/NCI NIH HHS/ -- CA17390/CA/NCI NIH HHS/ -- CA52599/CA/NCI NIH HHS/ -- DK057978/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK091183/DK/NIDDK NIH HHS/ -- HL088093/HL/NHLBI NIH HHS/ -- HL105278/HL/NHLBI NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P01 HL088093/HL/NHLBI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- R01 CA052599/CA/NCI NIH HHS/ -- R01 CA173903/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 HL105278/HL/NHLBI NIH HHS/ -- R37 DK057978/DK/NIDDK NIH HHS/ -- T32 GM007198-37/GM/NIGMS NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- U19 DK062434/DK/NIDDK NIH HHS/ -- U19DK62434/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 27;498(7455):511-5. doi: 10.1038/nature12209. Epub 2013 Jun 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23728303" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Binding Sites ; Down-Regulation/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Knockdown Techniques ; Macrophages/*metabolism ; Mice ; Nuclear Receptor Subfamily 1, Group D, Member 1/deficiency/genetics/*metabolism ; Organ Specificity ; Promoter Regions, Genetic/genetics ; RNA, Messenger/genetics/metabolism ; Response Elements/genetics ; Transcription, Genetic/*genetics
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  • 81
    Publication Date: 2013-10-15
    Description: The mechanisms by which genetic variation affects transcription regulation and phenotypes at the nucleotide level are incompletely understood. Here we use natural genetic variation as an in vivo mutagenesis screen to assess the genome-wide effects of sequence variation on lineage-determining and signal-specific transcription factor binding, epigenomics and transcriptional outcomes in primary macrophages from different mouse strains. We find substantial genetic evidence to support the concept that lineage-determining transcription factors define epigenetic and transcriptomic states by selecting enhancer-like regions in the genome in a collaborative fashion and facilitating binding of signal-dependent factors. This hierarchical model of transcription factor function suggests that limited sets of genomic data for lineage-determining transcription factors and informative histone modifications can be used for the prioritization of disease-associated regulatory variants.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994126/" 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/PMC3994126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heinz, S -- Romanoski, C E -- Benner, C -- Allison, K A -- Kaikkonen, M U -- Orozco, L D -- Glass, C K -- 5T32DK007494/DK/NIDDK NIH HHS/ -- CA17390/CA/NCI NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK091183/DK/NIDDK NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- R01 CA173903/CA/NCI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- T32 AR059033/AR/NIAMS NIH HHS/ -- England -- Nature. 2013 Nov 28;503(7477):487-92. doi: 10.1038/nature12615. Epub 2013 Oct 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Mail Code 0651, La Jolla, California 92093, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24121437" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs/genetics ; Animals ; Base Sequence ; Cell Lineage/genetics ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; Genetic Variation/*genetics ; Histones/chemistry/metabolism ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Biological ; Mutation/genetics ; NF-kappa B/metabolism ; Protein Binding ; Reproducibility of Results ; Selection, Genetic/*genetics ; Transcription Factor RelA/metabolism ; Transcription Factors/*metabolism
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  • 82
    Publication Date: 2013-07-03
    Description: During normal translation, the binding of a release factor to one of the three stop codons (UGA, UAA or UAG) results in the termination of protein synthesis. However, modification of the initial uridine to a pseudouridine (Psi) allows efficient recognition and read-through of these stop codons by a transfer RNA (tRNA), although it requires the formation of two normally forbidden purine-purine base pairs. Here we determined the crystal structure at 3.1 A resolution of the 30S ribosomal subunit in complex with the anticodon stem loop of tRNA(Ser) bound to the PsiAG stop codon in the A site. The PsiA base pair at the first position is accompanied by the formation of purine-purine base pairs at the second and third positions of the codon, which show an unusual Watson-Crick/Hoogsteen geometry. The structure shows a previously unsuspected ability of the ribosomal decoding centre to accommodate non-canonical base pairs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732562/" 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/PMC3732562/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fernandez, Israel S -- Ng, Chyan Leong -- Kelley, Ann C -- Wu, Guowei -- Yu, Yi-Tao -- Ramakrishnan, V -- 096570/Wellcome Trust/United Kingdom -- GM104077/GM/NIGMS NIH HHS/ -- MC_U105184332/Medical Research Council/United Kingdom -- R01 GM104077/GM/NIGMS NIH HHS/ -- R21 AG039559/AG/NIA NIH HHS/ -- U105184332/Medical Research Council/United Kingdom -- England -- Nature. 2013 Aug 1;500(7460):107-10. doi: 10.1038/nature12302. Epub 2013 Jun 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812587" target="_blank"〉PubMed〈/a〉
    Keywords: Anticodon/chemistry/genetics/metabolism ; *Base Pairing ; Base Sequence ; Codon, Terminator/chemistry/*genetics/*metabolism ; Crystallography, X-Ray ; Models, Molecular ; Nucleic Acid Conformation ; Protein Conformation ; Pseudouridine/chemistry/genetics/metabolism ; RNA, Transfer, Ser/chemistry/genetics/metabolism ; Ribosome Subunits, Small, Bacterial/chemistry/genetics/metabolism ; Ribosomes/*chemistry/genetics/*metabolism
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  • 83
    Publication Date: 2013-05-07
    Description: Adult stem cells undergo asymmetric cell division to self-renew and give rise to differentiated cells that comprise mature tissue. Sister chromatids may be distinguished and segregated nonrandomly in asymmetrically dividing stem cells, although the underlying mechanism and the purpose it may serve remain elusive. Here we develop the CO-FISH (chromosome orientation fluorescence in situ hybridization) technique with single-chromosome resolution and show that sister chromatids of X and Y chromosomes, but not autosomes, are segregated nonrandomly during asymmetric divisions of Drosophila male germline stem cells. This provides the first direct evidence, to our knowledge, that two sister chromatids containing identical genetic information can be distinguished and segregated nonrandomly during asymmetric stem-cell divisions. We further show that the centrosome, SUN-KASH nuclear envelope proteins and Dnmt2 (also known as Mt2) are required for nonrandom sister chromatid segregation. Our data indicate that the information on X and Y chromosomes that enables nonrandom segregation is primed during gametogenesis in the parents. Moreover, we show that sister chromatid segregation is randomized in germline stem cell overproliferation and dedifferentiated germline stem cells. We propose that nonrandom sister chromatid segregation may serve to transmit distinct information carried on two sister chromatids to the daughters of asymmetrically dividing stem cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711665/" 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/PMC3711665/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yadlapalli, Swathi -- Yamashita, Yukiko M -- 1F31HD071727-01/HD/NICHD NIH HHS/ -- F31 HD071727/HD/NICHD NIH HHS/ -- England -- Nature. 2013 Jun 13;498(7453):251-4. doi: 10.1038/nature12106. Epub 2013 May 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109, USA. swathi@umich.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23644460" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Dedifferentiation ; Cell Division ; Centrosome/metabolism ; Chromatids/genetics/*metabolism ; *Chromosome Segregation ; DNA (Cytosine-5-)-Methyltransferase ; Drosophila Proteins ; Drosophila melanogaster/*cytology/genetics/*metabolism ; Male ; Molecular Sequence Data ; Spermatogonia/cytology ; Stem Cells/*cytology/metabolism ; Testis/cytology ; X Chromosome/genetics/metabolism ; Y Chromosome/genetics/metabolism
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  • 84
    Publication Date: 2013-04-05
    Description: The technological demand to push the gigahertz (10(9) hertz) switching speed limit of today's magnetic memory and logic devices into the terahertz (10(12) hertz) regime underlies the entire field of spin-electronics and integrated multi-functional devices. This challenge is met by all-optical magnetic switching based on coherent spin manipulation. By analogy to femtosecond chemistry and photosynthetic dynamics--in which photoproducts of chemical and biochemical reactions can be influenced by creating suitable superpositions of molecular states--femtosecond-laser-excited coherence between electronic states can switch magnetic order by 'suddenly' breaking the delicate balance between competing phases of correlated materials: for example, manganites exhibiting colossal magneto-resistance suitable for applications. Here we show femtosecond (10(-15) seconds) photo-induced switching from antiferromagnetic to ferromagnetic ordering in Pr0.7Ca0.3MnO3, by observing the establishment (within about 120 femtoseconds) of a huge temperature-dependent magnetization with photo-excitation threshold behaviour absent in the optical reflectivity. The development of ferromagnetic correlations during the femtosecond laser pulse reveals an initial quantum coherent regime of magnetism, distinguished from the picosecond (10(-12) seconds) lattice-heating regime characterized by phase separation without threshold behaviour. Our simulations reproduce the nonlinear femtosecond spin generation and underpin fast quantum spin-flip fluctuations correlated with coherent superpositions of electronic states to initiate local ferromagnetic correlations. These results merge two fields, femtosecond magnetism in metals and band insulators, and non-equilibrium phase transitions of strongly correlated electrons, in which local interactions exceeding the kinetic energy produce a complex balance of competing orders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Tianqi -- Patz, Aaron -- Mouchliadis, Leonidas -- Yan, Jiaqiang -- Lograsso, Thomas A -- Perakis, Ilias E -- Wang, Jigang -- England -- Nature. 2013 Apr 4;496(7443):69-73. doi: 10.1038/nature11934.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23552945" target="_blank"〉PubMed〈/a〉
    Keywords: Biology ; Chemistry ; Circular Dichroism ; Electronics ; Iron/chemistry ; *Magnetic Phenomena ; Magnetics ; Optics and Photonics ; Photosynthesis ; *Quantum Theory ; Temperature ; Time Factors
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  • 85
    Publication Date: 2013-06-01
    Description: Cytosolic DNA arising from intracellular bacterial or viral infections is a powerful pathogen-associated molecular pattern (PAMP) that leads to innate immune host defence by the production of type I interferon and inflammatory cytokines. Recognition of cytosolic DNA by the recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of cGAMP to activate the stimulator of interferon genes (STING). Here we report the crystal structure of cGAS alone and in complex with DNA, ATP and GTP along with functional studies. Our results explain the broad DNA sensing specificity of cGAS, show how cGAS catalyses dinucleotide formation and indicate activation by a DNA-induced structural switch. cGAS possesses a remarkable structural similarity to the antiviral cytosolic double-stranded RNA sensor 2'-5'oligoadenylate synthase (OAS1), but contains a unique zinc thumb that recognizes B-form double-stranded DNA. Our results mechanistically unify dsRNA and dsDNA innate immune sensing by OAS1 and cGAS nucleotidyl transferases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3768140/" 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/PMC3768140/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Civril, Filiz -- Deimling, Tobias -- de Oliveira Mann, Carina C -- Ablasser, Andrea -- Moldt, Manuela -- Witte, Gregor -- Hornung, Veit -- Hopfner, Karl-Peter -- 243046/European Research Council/International -- U19 AI083025/AI/NIAID NIH HHS/ -- U19AI083025/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Jun 20;498(7454):332-7. doi: 10.1038/nature12305. Epub 2013 May 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Gene Center, Ludwig-Maximilians-University, 81377 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23722159" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/chemistry/metabolism ; Animals ; Base Sequence ; Catalytic Domain ; Crystallography, X-Ray ; *Cytosol ; DNA/chemistry/*metabolism/pharmacology ; Guanosine Triphosphate/chemistry/metabolism ; HEK293 Cells ; Humans ; Membrane Proteins/genetics/metabolism ; Mice ; Models, Biological ; Models, Molecular ; Mutation ; Nucleotidyltransferases/*chemistry/genetics/metabolism ; Protein Conformation/drug effects ; Structure-Activity Relationship ; Substrate Specificity ; Swine ; Uridine Triphosphate/chemistry/metabolism ; Zinc/chemistry/metabolism
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  • 86
    Publication Date: 2013-09-24
    Description: Nucleic-acid-binding proteins are generally viewed as either specific or nonspecific, depending on characteristics of their binding sites in DNA or RNA. Most studies have focused on specific proteins, which identify cognate sites by binding with highest affinities to regions with defined signatures in sequence, structure or both. Proteins that bind to sites devoid of defined sequence or structure signatures are considered nonspecific. Substrate binding by these proteins is poorly understood, and it is not known to what extent seemingly nonspecific proteins discriminate between different binding sites, aside from those sequestered by nucleic acid structures. Here we systematically examine substrate binding by the apparently nonspecific RNA-binding protein C5, and find clear discrimination between different binding site variants. C5 is the protein subunit of the transfer RNA processing ribonucleoprotein enzyme RNase P from Escherichia coli. The protein binds 5' leaders of precursor tRNAs at a site without sequence or structure signatures. We measure functional binding of C5 to all possible sequence variants in its substrate binding site, using a high-throughput sequencing kinetics approach (HITS-KIN) that simultaneously follows processing of thousands of RNA species. C5 binds different substrate variants with affinities varying by orders of magnitude. The distribution of functional affinities of C5 for all substrate variants resembles affinity distributions of highly specific nucleic acid binding proteins. Unlike these specific proteins, C5 does not bind its physiological RNA targets with the highest affinity, but with affinities near the median of the distribution, a region that is not associated with a sequence signature. We delineate defined rules governing substrate recognition by C5, which reveal specificity that is hidden in cellular substrates for RNase P. Our findings suggest that apparently nonspecific and specific RNA-binding modes may not differ fundamentally, but represent distinct parts of common affinity distributions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800043/" 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/PMC3800043/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guenther, Ulf-Peter -- Yandek, Lindsay E -- Niland, Courtney N -- Campbell, Frank E -- Anderson, David -- Anderson, Vernon E -- Harris, Michael E -- Jankowsky, Eckhard -- GM056740/GM/NIGMS NIH HHS/ -- GM067700/GM/NIGMS NIH HHS/ -- GM096000/GM/NIGMS NIH HHS/ -- GM099720/GM/NIGMS NIH HHS/ -- R01 GM056740/GM/NIGMS NIH HHS/ -- R01 GM067700/GM/NIGMS NIH HHS/ -- R01 GM096000/GM/NIGMS NIH HHS/ -- R01 GM099720/GM/NIGMS NIH HHS/ -- T32 GM008056/GM/NIGMS NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- UL1RR024989/RR/NCRR NIH HHS/ -- England -- Nature. 2013 Oct 17;502(7471):385-8. doi: 10.1038/nature12543. Epub 2013 Sep 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for RNA Molecular Biology, 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/24056935" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/genetics ; Base Sequence ; Escherichia coli/*enzymology/genetics ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Kinetics ; Nucleic Acid Conformation ; RNA Precursors/chemistry/genetics/metabolism ; RNA, Bacterial/chemistry/genetics/metabolism ; RNA, Transfer/chemistry/genetics/*metabolism ; RNA, Transfer, Met/chemistry/genetics/metabolism ; Ribonuclease P/chemistry/genetics/*metabolism ; Substrate Specificity
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  • 87
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2013-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGee, Harold -- England -- Nature. 2013 Dec 19;504(7480):372-4. doi: 10.1038/504372a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24352277" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aspergillus/metabolism ; Beer/microbiology ; Cheese/microbiology ; Chemistry ; *Fermentation ; *Food Technology ; Microbiology ; Saccharomyces cerevisiae/metabolism
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  • 88
    Publication Date: 2013-05-28
    Description: A complex interaction of signalling events, including the Wnt pathway, regulates sprouting of blood vessels from pre-existing vasculature during angiogenesis. Here we show that two distinct mutations in the (uro)chordate-specific gumby (also called Fam105b) gene cause an embryonic angiogenic phenotype in gumby mice. Gumby interacts with disheveled 2 (DVL2), is expressed in canonical Wnt-responsive endothelial cells and encodes an ovarian tumour domain class of deubiquitinase that specifically cleaves linear ubiquitin linkages. A crystal structure of gumby in complex with linear diubiquitin reveals how the identified mutations adversely affect substrate binding and catalytic function in line with the severity of their angiogenic phenotypes. Gumby interacts with HOIP (also called RNF31), a key component of the linear ubiquitin assembly complex, and decreases linear ubiquitination and activation of NF-kappaB-dependent transcription. This work provides support for the biological importance of linear (de)ubiquitination in angiogenesis, craniofacial and neural development and in modulating Wnt signalling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rivkin, Elena -- Almeida, Stephanie M -- Ceccarelli, Derek F -- Juang, Yu-Chi -- MacLean, Teresa A -- Srikumar, Tharan -- Huang, Hao -- Dunham, Wade H -- Fukumura, Ryutaro -- Xie, Gang -- Gondo, Yoichi -- Raught, Brian -- Gingras, Anne-Claude -- Sicheri, Frank -- Cordes, Sabine P -- IHO 94384/Canadian Institutes of Health Research/Canada -- MOP 111199/Canadian Institutes of Health Research/Canada -- MOP 97966/Canadian Institutes of Health Research/Canada -- MOP119289/Canadian Institutes of Health Research/Canada -- England -- Nature. 2013 Jun 20;498(7454):318-24. doi: 10.1038/nature12296. Epub 2013 May 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23708998" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Alleles ; Amino Acid Sequence ; Animals ; Base Sequence ; Crystallography, X-Ray ; Embryo, Mammalian/blood supply/embryology/metabolism ; Endopeptidases/*chemistry/deficiency/genetics/*metabolism ; Female ; Gene Expression Profiling ; HEK293 Cells ; Humans ; Mice ; Models, Molecular ; Molecular Sequence Data ; *Neovascularization, Physiologic/genetics ; Phenotype ; Phosphoproteins/metabolism ; Protein Conformation ; Ubiquitin/*chemistry/*metabolism ; Ubiquitin-Protein Ligases/metabolism ; *Ubiquitination ; Wnt Signaling Pathway
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  • 89
    Publication Date: 2013-09-10
    Description: Replication fork maintenance pathways preserve chromosomes, but their faulty application at nonallelic repeats could generate rearrangements causing cancer, genomic disorders and speciation. Potential causal mechanisms are homologous recombination and error-free postreplication repair (EF-PRR). Homologous recombination repairs damage-induced DNA double-strand breaks (DSBs) and single-ended DSBs within replication. To facilitate homologous recombination, the recombinase RAD51 and mediator BRCA2 form a filament on the 3' DNA strand at a break to enable annealing to the complementary sister chromatid while the RecQ helicase, BLM (Bloom syndrome mutated) suppresses crossing over to prevent recombination. Homologous recombination also stabilizes and restarts replication forks without a DSB. EF-PRR bypasses DNA incongruities that impede replication by ubiquitinating PCNA (proliferating cell nuclear antigen) using the RAD6-RAD18 and UBC13-MMS2-RAD5 ubiquitin ligase complexes. Some components are common to both homologous recombination and EF-PRR such as RAD51 and RAD18. Here we delineate two pathways that spontaneously fuse inverted repeats to generate unstable chromosomal rearrangements in wild-type mouse embryonic stem (ES) cells. Gamma-radiation induced a BLM-regulated pathway that selectively fused identical, but not mismatched, repeats. By contrast, ultraviolet light induced a RAD18-dependent pathway that efficiently fused mismatched repeats. Furthermore, TREX2 (a 3'--〉5' exonuclease) suppressed identical repeat fusion but enhanced mismatched repeat fusion, clearly separating these pathways. TREX2 associated with UBC13 and enhanced PCNA ubiquitination in response to ultraviolet light, consistent with it being a novel member of EF-PRR. RAD18 and TREX2 also suppressed replication fork stalling in response to nucleotide depletion. Interestingly, replication fork stalling induced fusion for identical and mismatched repeats, implicating faulty replication as a causal mechanism for both pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805358/" 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/PMC3805358/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Lingchuan -- Kim, Tae Moon -- Son, Mi Young -- Kim, Sung-A -- Holland, Cory L -- Tateishi, Satoshi -- Kim, Dong Hyun -- Yew, P Renee -- Montagna, Cristina -- Dumitrache, Lavinia C -- Hasty, Paul -- 1 R01 CA123203-01A1/CA/NCI NIH HHS/ -- 2P01AG017242-12/AG/NIA NIH HHS/ -- P30 CA054174/CA/NCI NIH HHS/ -- P30CA013330/CA/NCI NIH HHS/ -- R01 CA123203/CA/NCI NIH HHS/ -- England -- Nature. 2013 Sep 26;501(7468):569-72. doi: 10.1038/nature12500. Epub 2013 Sep 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Medicine/Institute of Biotechnology, The Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245-3207, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24013173" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosomal Instability/*genetics ; Chromosome Breakage ; Chromosomes, Mammalian/*genetics ; DNA Breaks, Double-Stranded ; DNA Repair/*genetics ; DNA Replication/*genetics ; DNA-Binding Proteins/metabolism ; Embryonic Stem Cells/metabolism ; Exodeoxyribonucleases/metabolism ; Homologous Recombination/*genetics ; Hydroxyurea/pharmacology ; Inverted Repeat Sequences/*genetics ; Mice ; Nucleotides/deficiency/metabolism ; Proliferating Cell Nuclear Antigen/metabolism ; Rad51 Recombinase/metabolism ; RecQ Helicases/metabolism ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitination/radiation effects ; Ultraviolet Rays
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  • 90
    Publication Date: 2013-03-29
    Description: Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ling, Hong-Qing -- Zhao, Shancen -- Liu, Dongcheng -- Wang, Junyi -- Sun, Hua -- Zhang, Chi -- Fan, Huajie -- Li, Dong -- Dong, Lingli -- Tao, Yong -- Gao, Chuan -- Wu, Huilan -- Li, Yiwen -- Cui, Yan -- Guo, Xiaosen -- Zheng, Shusong -- Wang, Biao -- Yu, Kang -- Liang, Qinsi -- Yang, Wenlong -- Lou, Xueyuan -- Chen, Jie -- Feng, Mingji -- Jian, Jianbo -- Zhang, Xiaofei -- Luo, Guangbin -- Jiang, Ying -- Liu, Junjie -- Wang, Zhaobao -- Sha, Yuhui -- Zhang, Bairu -- Wu, Huajun -- Tang, Dingzhong -- Shen, Qianhua -- Xue, Pengya -- Zou, Shenhao -- Wang, Xiujie -- Liu, Xin -- Wang, Famin -- Yang, Yanping -- An, Xueli -- Dong, Zhenying -- Zhang, Kunpu -- Zhang, Xiangqi -- Luo, Ming-Cheng -- Dvorak, Jan -- Tong, Yiping -- Wang, Jian -- Yang, Huanming -- Li, Zhensheng -- Wang, Daowen -- Zhang, Aimin -- Wang, Jun -- England -- Nature. 2013 Apr 4;496(7443):87-90. doi: 10.1038/nature11997. Epub 2013 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23535596" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Brachypodium/genetics ; Crops, Agricultural/classification/genetics ; Diploidy ; Genetic Markers/genetics ; Genome, Plant/*genetics ; Molecular Sequence Data ; Oryza/genetics ; Phylogeny ; Sorghum/genetics ; Synteny/genetics ; Triticum/classification/*genetics ; Zea mays/genetics
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  • 91
    Publication Date: 2013-05-10
    Description: The Saccharomyces cerevisiae Pif1 helicase is the prototypical member of the Pif1 DNA helicase family, which is conserved from bacteria to humans. Here we show that exceptionally potent G-quadruplex unwinding is conserved among Pif1 helicases. Moreover, Pif1 helicases from organisms separated by more than 3 billion years of evolution suppressed DNA damage at G-quadruplex motifs in yeast. The G-quadruplex-induced damage generated in the absence of Pif1 helicases led to new genetic and epigenetic changes. Furthermore, when expressed in yeast, human PIF1 suppressed both G-quadruplex-associated DNA damage and telomere lengthening.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680789/" 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/PMC3680789/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paeschke, Katrin -- Bochman, Matthew L -- Garcia, P Daniela -- Cejka, Petr -- Friedman, Katherine L -- Kowalczykowski, Stephen C -- Zakian, Virginia A -- R01 GM026938/GM/NIGMS NIH HHS/ -- R01 GM041347/GM/NIGMS NIH HHS/ -- R01 GM043265/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 May 23;497(7450):458-62. doi: 10.1038/nature12149. Epub 2013 May 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23657261" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Conserved Sequence ; DNA Damage/genetics ; DNA Helicases/deficiency/genetics/*metabolism ; Epigenesis, Genetic ; Evolution, Molecular ; *G-Quadruplexes ; Gene Silencing ; Genetic Complementation Test ; *Genomic Instability ; Humans ; Molecular Sequence Data ; Mutation Rate ; Saccharomyces cerevisiae/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Telomere Homeostasis/genetics
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  • 92
    Publication Date: 2013-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shechtman, Dan -- England -- Nature. 2013 Oct 17;502(7471):S54-5. doi: 10.1038/502S54a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24132333" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry ; Developing Countries ; Education/statistics & numerical data ; Entrepreneurship/*economics ; Leadership ; Nobel Prize ; Research ; Technology/*economics
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  • 93
    Publication Date: 2013-05-07
    Description: The coordination of stem- and blast-cell behaviours, such as self-renewal, differentiation and quiescence, with physiological changes underlies growth, regeneration and tissue homeostasis. Germline stem and somatic blast cells in newly hatched Caenorhabditis elegans larvae can suspend postembryonic development, which consists of diverse cellular events such as migration, proliferation and differentiation, until the nutritional state becomes favourable (termed L1 diapause). Although previous studies showed that the insulin/insulin-like growth factor (IGF) signalling (IIS) pathway regulates this developmental quiescence, the detailed mechanism by which the IIS pathway enables these multipotent cells to respond to nutrient availability is unknown. Here we show in C. elegans that the microRNA (miRNA) miR-235, a sole orthologue of mammalian miR-92 from the oncogenic miR-17-92 cluster, acts in the hypodermis and glial cells to arrest postembryonic developmental events in both neuroblasts and mesoblasts. Expression of mir-235 persists during L1 diapause, and decreases upon feeding in a manner dependent on the IIS pathway. Upregulation of one of the miR-235 targets, nhr-91, which encodes an orthologue of mammalian germ cell nuclear factor, is responsible for defects caused by loss of the miRNA. Our findings establish a novel role of a miR-92 orthologue in coupling blast-cell behaviours to the nutritional state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasuga, Hidefumi -- Fukuyama, Masamitsu -- Kitazawa, Aya -- Kontani, Kenji -- Katada, Toshiaki -- England -- Nature. 2013 May 23;497(7450):503-6. doi: 10.1038/nature12117. Epub 2013 May 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23644454" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Caenorhabditis elegans/*genetics/growth & development/immunology/*metabolism ; Down-Regulation ; Embryo, Nonmammalian/metabolism ; Food Deprivation ; Humans ; Insulin/metabolism ; Insulin-Like Growth Factor I/metabolism ; Larva/cytology/metabolism ; Lymphocyte Activation/*genetics/physiology ; MicroRNAs/*genetics/*metabolism ; Molecular Sequence Data ; Neural Stem Cells/cytology/metabolism ; Neuroglia/metabolism ; *Nutritional Status/genetics ; Signal Transduction ; Subcutaneous Tissue/metabolism
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  • 94
    Publication Date: 2013-11-26
    Description: RNA structure has critical roles in processes ranging from ligand sensing to the regulation of translation, polyadenylation and splicing. However, a lack of genome-wide in vivo RNA structural data has limited our understanding of how RNA structure regulates gene expression in living cells. Here we present a high-throughput, genome-wide in vivo RNA structure probing method, structure-seq, in which dimethyl sulphate methylation of unprotected adenines and cytosines is identified by next-generation sequencing. Application of this method to Arabidopsis thaliana seedlings yielded the first in vivo genome-wide RNA structure map at nucleotide resolution for any organism, with quantitative structural information across more than 10,000 transcripts. Our analysis reveals a three-nucleotide periodic repeat pattern in the structure of coding regions, as well as a less-structured region immediately upstream of the start codon, and shows that these features are strongly correlated with translation efficiency. We also find patterns of strong and weak secondary structure at sites of alternative polyadenylation, as well as strong secondary structure at 5' splice sites that correlates with unspliced events. Notably, in vivo structures of messenger RNAs annotated for stress responses are poorly predicted in silico, whereas mRNA structures of genes related to cell function maintenance are well predicted. Global comparison of several structural features between these two categories shows that the mRNAs associated with stress responses tend to have more single-strandedness, longer maximal loop length and higher free energy per nucleotide, features that may allow these RNAs to undergo conformational changes in response to environmental conditions. Structure-seq allows the RNA structurome and its biological roles to be interrogated on a genome-wide scale and should be applicable to any organism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Yiliang -- Tang, Yin -- Kwok, Chun Kit -- Zhang, Yu -- Bevilacqua, Philip C -- Assmann, Sarah M -- England -- Nature. 2014 Jan 30;505(7485):696-700. doi: 10.1038/nature12756. Epub 2013 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA [2] Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA [3] Center for RNA Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA [4]. ; 1] Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA [2] Center for RNA Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA [3] Bioinformatics and Genomics Graduate Program, Pennsylvania State University, University Park, Pennsylvania 16802, USA [4]. ; 1] Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA [2] Center for RNA Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA [3]. ; 1] Bioinformatics and Genomics Graduate Program, Pennsylvania State University, University Park, Pennsylvania 16802, USA [2] Department of Statistics, Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA [2] Center for RNA Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA [3] Plant Biology Graduate Program, Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA [2] Center for RNA Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA [3] Bioinformatics and Genomics Graduate Program, Pennsylvania State University, University Park, Pennsylvania 16802, USA [4] Plant Biology Graduate Program, Pennsylvania State University, University Park, Pennsylvania 16802, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24270811" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics ; Base Sequence ; Codon, Initiator/genetics ; Computational Biology ; Genome, Plant/*genetics ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Phylogeny ; Polyadenylation/genetics ; Protein Biosynthesis/genetics ; RNA Splice Sites/genetics ; RNA, Messenger/chemistry/genetics/metabolism ; RNA, Plant/analysis/*chemistry/genetics/*metabolism ; RNA, Ribosomal, 18S/chemistry/genetics/metabolism ; *Regulatory Sequences, Ribonucleic Acid/genetics ; Sequence Analysis, RNA ; Stress, Physiological/genetics ; Structure-Activity Relationship
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  • 95
    Publication Date: 2013-03-01
    Description: Eukaryotic transcription initiation requires the assembly of general transcription factors into a pre-initiation complex that ensures the accurate loading of RNA polymerase II (Pol II) at the transcription start site. The molecular mechanism and function of this assembly have remained elusive due to lack of structural information. Here we have used an in vitro reconstituted system to study the stepwise assembly of human TBP, TFIIA, TFIIB, Pol II, TFIIF, TFIIE and TFIIH onto promoter DNA using cryo-electron microscopy. Our structural analyses provide pseudo-atomic models at various stages of transcription initiation that illuminate critical molecular interactions, including how TFIIF engages Pol II and promoter DNA to stabilize both the closed pre-initiation complex and the open-promoter complex, and to regulate start--initiation complexes, combined with the localization of the TFIIH helicases XPD and XPB, support a DNA translocation model of XPB and explain its essential role in promoter opening.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612373/" 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/PMC3612373/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Yuan -- Fang, Jie -- Taatjes, Dylan J -- Nogales, Eva -- CA127364/CA/NCI NIH HHS/ -- GM63072/GM/NIGMS NIH HHS/ -- R01 CA127364/CA/NCI NIH HHS/ -- R01 GM063072/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Mar 28;495(7442):481-6. doi: 10.1038/nature11991. Epub 2013 Feb 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23446344" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cryoelectron Microscopy ; DNA/chemistry/genetics/metabolism ; DNA Helicases/chemistry/metabolism ; Humans ; Models, Molecular ; Molecular Sequence Data ; Promoter Regions, Genetic/*genetics ; Protein Conformation ; RNA Polymerase II/*chemistry/metabolism/*ultrastructure ; TATA-Box Binding Protein/chemistry/metabolism ; Transcription Factor TFIIH/chemistry/metabolism ; Transcription Factors, TFII/*chemistry/metabolism/*ultrastructure ; Transcription Initiation Site ; Transcription Initiation, Genetic/*physiology
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  • 96
    Publication Date: 2013-07-16
    Description: During animal development, the proper regulation of apoptosis requires the precise spatial and temporal execution of cell-death programs, which can include both caspase-dependent and caspase-independent pathways. Although the mechanisms of caspase-dependent and -independent cell killing have been examined extensively, how these pathways are coordinated within a single cell that is fated to die is unknown. Here we show that the Caenorhabditis elegans Sp1 transcription factor SPTF-3 specifies the programmed cell deaths of at least two cells-the sisters of the pharyngeal M4 motor neuron and the AQR sensory neuron-by transcriptionally activating both caspase-dependent and -independent apoptotic pathways. SPTF-3 directly drives the transcription of the gene egl-1, which encodes a BH3-only protein that promotes apoptosis through the activation of the CED-3 caspase. In addition, SPTF-3 directly drives the transcription of the AMP-activated protein kinase-related gene pig-1, which encodes a protein kinase and functions in apoptosis of the M4 sister and AQR sister independently of the pathway that activates CED-3 (refs 4, 5). Thus, a single transcription factor controls two distinct cell-killing programs that act in parallel to drive apoptosis. Our findings reveal a bivalent regulatory node for caspase-dependent and -independent pathways in the regulation of cell-type-specific apoptosis. We propose that such nodes might act as features of a general mechanism for regulating cell-type-specific apoptosis and could be therapeutic targets for diseases involving the dysregulation of apoptosis through multiple cell-killing mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748152/" 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/PMC3748152/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hirose, Takashi -- Horvitz, H Robert -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Aug 15;500(7462):354-8. doi: 10.1038/nature12329. Epub 2013 Jul 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23851392" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/*genetics ; Base Sequence ; Caenorhabditis elegans/*genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; Caspases/*metabolism ; Gene Expression Regulation, Developmental ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Repressor Proteins/genetics/metabolism ; Sequence Alignment ; Sp1 Transcription Factor/*genetics/*metabolism
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  • 97
    Publication Date: 2013-03-01
    Description: Bacteriophages (or phages) are the most abundant biological entities on earth, and are estimated to outnumber their bacterial prey by tenfold. The constant threat of phage predation has led to the evolution of a broad range of bacterial immunity mechanisms that in turn result in the evolution of diverse phage immune evasion strategies, leading to a dynamic co-evolutionary arms race. Although bacterial innate immune mechanisms against phage abound, the only documented bacterial adaptive immune system is the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system, which provides sequence-specific protection from invading nucleic acids, including phage. Here we show a remarkable turn of events, in which a phage-encoded CRISPR/Cas system is used to counteract a phage inhibitory chromosomal island of the bacterial host. A successful lytic infection by the phage is dependent on sequence identity between CRISPR spacers and the target chromosomal island. In the absence of such targeting, the phage-encoded CRISPR/Cas system can acquire new spacers to evolve rapidly and ensure effective targeting of the chromosomal island to restore phage replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587790/" 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/PMC3587790/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seed, Kimberley D -- Lazinski, David W -- Calderwood, Stephen B -- Camilli, Andrew -- AI045746/AI/NIAID NIH HHS/ -- AI055058/AI/NIAID NIH HHS/ -- AI058935/AI/NIAID NIH HHS/ -- R01 AI045746/AI/NIAID NIH HHS/ -- R01 AI055058/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Feb 28;494(7438):489-91. doi: 10.1038/nature11927.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23446421" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriolysis ; Bacteriophages/*genetics/growth & development/*immunology/pathogenicity ; Base Sequence ; Biological Evolution ; Chromosomes, Bacterial/genetics ; Gene Deletion ; Genes, Viral/*genetics/immunology ; Genome, Viral/genetics ; Genomic Islands/genetics ; *Immunity, Innate ; Inverted Repeat Sequences/genetics ; Molecular Sequence Data ; Substrate Specificity ; Vibrio cholerae/genetics/*immunology/*virology
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  • 98
    Publication Date: 2013-04-09
    Description: TET (ten-eleven-translocation) proteins are Fe(ii)- and alpha-ketoglutarate-dependent dioxygenases that modify the methylation status of DNA by successively oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, potential intermediates in the active erasure of DNA-methylation marks. Here we show that IDAX (also known as CXXC4), a reported inhibitor of Wnt signalling that has been implicated in malignant renal cell carcinoma and colonic villous adenoma, regulates TET2 protein expression. IDAX was originally encoded within an ancestral TET2 gene that underwent a chromosomal gene inversion during evolution, thus separating the TET2 CXXC domain from the catalytic domain. The IDAX CXXC domain binds DNA sequences containing unmethylated CpG dinucleotides, localizes to promoters and CpG islands in genomic DNA and interacts directly with the catalytic domain of TET2. Unexpectedly, IDAX expression results in caspase activation and TET2 protein downregulation, in a manner that depends on DNA binding through the IDAX CXXC domain, suggesting that IDAX recruits TET2 to DNA before degradation. IDAX depletion prevents TET2 downregulation in differentiating mouse embryonic stem cells, and short hairpin RNA against IDAX increases TET2 protein expression in the human monocytic cell line U937. Notably, we find that the expression and activity of TET3 is also regulated through its CXXC domain. Taken together, these results establish the separate and linked CXXC domains of TET2 and TET3, respectively, as previously unknown regulators of caspase activation and TET enzymatic activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643997/" 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/PMC3643997/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ko, Myunggon -- An, Jungeun -- Bandukwala, Hozefa S -- Chavez, Lukas -- Aijo, Tarmo -- Pastor, William A -- Segal, Matthew F -- Li, Huiming -- Koh, Kian Peng -- Lahdesmaki, Harri -- Hogan, Patrick G -- Aravind, L -- Rao, Anjana -- CA151535/CA/NCI NIH HHS/ -- R01 AI040127/AI/NIAID NIH HHS/ -- R01 AI044432/AI/NIAID NIH HHS/ -- R01 AI40127/AI/NIAID NIH HHS/ -- R01 CA151535/CA/NCI NIH HHS/ -- R01 HD065812/HD/NICHD NIH HHS/ -- England -- Nature. 2013 May 2;497(7447):122-6. doi: 10.1038/nature12052. Epub 2013 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Signaling and Gene Expression, La Jolla Institute for Allergy & Immunology, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23563267" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/*metabolism ; Animals ; Base Sequence ; Caspases/metabolism ; Catalytic Domain ; CpG Islands/genetics ; DNA Methylation/genetics ; DNA-Binding Proteins/biosynthesis/*chemistry/deficiency/genetics/*metabolism ; Dioxygenases/chemistry/genetics/metabolism ; Down-Regulation ; Embryonic Stem Cells/metabolism ; Enzyme Activation ; HEK293 Cells ; Humans ; Mice ; Oxidation-Reduction ; Promoter Regions, Genetic/genetics ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/biosynthesis/chemistry/genetics/*metabolism ; Transcription Factors/*chemistry/deficiency/genetics/*metabolism ; U937 Cells
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  • 99
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    Nature Publishing Group (NPG)
    Publication Date: 2013-08-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bobrow, Martin -- England -- Nature. 2013 Aug 8;500(7461):123. doi: 10.1038/500123a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Cambridge, UK. mb238@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23925206" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; Base Sequence ; Confidentiality ; Databases, Factual/standards ; Humans ; *Information Dissemination ; International Cooperation ; Research/economics/standards
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  • 100
    Publication Date: 2013-01-29
    Description: Digital production, transmission and storage have revolutionized how we access and use information but have also made archiving an increasingly complex task that requires active, continuing maintenance of digital media. This challenge has focused some interest on DNA as an attractive target for information storage because of its capacity for high-density information encoding, longevity under easily achieved conditions and proven track record as an information bearer. Previous DNA-based information storage approaches have encoded only trivial amounts of information or were not amenable to scaling-up, and used no robust error-correction and lacked examination of their cost-efficiency for large-scale information archival. Here we describe a scalable method that can reliably store more information than has been handled before. We encoded computer files totalling 739 kilobytes of hard-disk storage and with an estimated Shannon information of 5.2 x 10(6) bits into a DNA code, synthesized this DNA, sequenced it and reconstructed the original files with 100% accuracy. Theoretical analysis indicates that our DNA-based storage scheme could be scaled far beyond current global information volumes and offers a realistic technology for large-scale, long-term and infrequently accessed digital archiving. In fact, current trends in technological advances are reducing DNA synthesis costs at a pace that should make our scheme cost-effective for sub-50-year archiving within a decade.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672958/" 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/PMC3672958/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldman, Nick -- Bertone, Paul -- Chen, Siyuan -- Dessimoz, Christophe -- LeProust, Emily M -- Sipos, Botond -- Birney, Ewan -- 088151/Wellcome Trust/United Kingdom -- England -- Nature. 2013 Feb 7;494(7435):77-80. doi: 10.1038/nature11875. Epub 2013 Jan 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SD, UK. goldman@ebi.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23354052" target="_blank"〉PubMed〈/a〉
    Keywords: *Archives ; Base Sequence ; Computers ; DNA/*chemical synthesis/*chemistry/economics ; Information Management/economics/*methods ; Molecular Sequence Data ; Sequence Analysis, DNA/economics ; Synthetic Biology/economics/methods
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