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  • 1
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    Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2 (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-11-01
    Description: Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Wen G -- Chang, Qiang -- Lin, Yingxi -- Meissner, Alexander -- West, Anne E -- Griffith, Eric C -- Jaenisch, Rudolf -- Greenberg, Michael E -- HD 18655/HD/NICHD NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):885-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593183" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Derived Neurotrophic Factor/*genetics ; Calcium/*metabolism ; Cell Membrane/physiology ; Cells, Cultured ; *Chromosomal Proteins, Non-Histone ; Cloning, Molecular ; CpG Islands ; DNA Methylation ; DNA-Binding Proteins/*metabolism ; Electrophoretic Mobility Shift Assay ; *Gene Expression Regulation ; Gene Silencing ; Histones/metabolism ; Methyl-CpG-Binding Protein 2 ; Methylation ; Mice ; Mice, Knockout ; Neurons/metabolism/physiology ; Phosphorylation ; Potassium Chloride/pharmacology ; Precipitin Tests ; Promoter Regions, Genetic ; Rats ; *Repressor Proteins ; Rett Syndrome/genetics ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Evidence for the exposure of water ice on Titan's surface (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-04-26
    Description: The smoggy stratosphere of Saturn's largest moon, Titan, veils its surface from view, except at narrow wavelengths centered at 0.83, 0.94, 1.07, 1.28, 1.58, 2.0, 2.9, and 5.0 micrometers. We derived a spectrum of Titan's surface within these "windows" and detected features characteristic of water ice. Therefore, despite the hundreds of meters of organic liquids and solids hypothesized to exist on Titan's surface, its icy bedrock lies extensively exposed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffith, Caitlin A -- Owen, Tobias -- Geballe, Thomas R -- Rayner, John -- Rannou, Pascal -- New York, N.Y. -- Science. 2003 Apr 25;300(5619):628-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Planetary Sciences, University of Arizona, 1629 East University Boulevard, Tucson, AZ 85721-0092, USA. griffith@lpl.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12714742" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere ; Carbon Monoxide ; Extraterrestrial Environment ; *Ice ; Methane ; Organic Chemicals ; *Saturn ; Water
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    The Genome sequence of the SARS-associated coronavirus (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-05-06
    Description: We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marra, Marco A -- Jones, Steven J M -- Astell, Caroline R -- Holt, Robert A -- Brooks-Wilson, Angela -- Butterfield, Yaron S N -- Khattra, Jaswinder -- Asano, Jennifer K -- Barber, Sarah A -- Chan, Susanna Y -- Cloutier, Alison -- Coughlin, Shaun M -- Freeman, Doug -- Girn, Noreen -- Griffith, Obi L -- Leach, Stephen R -- Mayo, Michael -- McDonald, Helen -- Montgomery, Stephen B -- Pandoh, Pawan K -- Petrescu, Anca S -- Robertson, A Gordon -- Schein, Jacqueline E -- Siddiqui, Asim -- Smailus, Duane E -- Stott, Jeff M -- Yang, George S -- Plummer, Francis -- Andonov, Anton -- Artsob, Harvey -- Bastien, Nathalie -- Bernard, Kathy -- Booth, Timothy F -- Bowness, Donnie -- Czub, Martin -- Drebot, Michael -- Fernando, Lisa -- Flick, Ramon -- Garbutt, Michael -- Gray, Michael -- Grolla, Allen -- Jones, Steven -- Feldmann, Heinz -- Meyers, Adrienne -- Kabani, Amin -- Li, Yan -- Normand, Susan -- Stroher, Ute -- Tipples, Graham A -- Tyler, Shaun -- Vogrig, Robert -- Ward, Diane -- Watson, Brynn -- Brunham, Robert C -- Krajden, Mel -- Petric, Martin -- Skowronski, Danuta M -- Upton, Chris -- Roper, Rachel L -- New York, N.Y. -- Science. 2003 May 30;300(5624):1399-404. Epub 2003 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉British Columbia Cancer Agency (BCCA) Genome Sciences Centre, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. mmarra@bccgsc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12730501" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; 5' Untranslated Regions ; Animals ; Base Sequence ; Conserved Sequence ; Coronavirus/classification/genetics ; DNA, Complementary ; Frameshifting, Ribosomal ; *Genome, Viral ; Humans ; Membrane Glycoproteins/chemistry/genetics ; Nucleocapsid Proteins/chemistry/genetics ; Open Reading Frames ; Phylogeny ; RNA Replicase/chemistry/genetics ; RNA, Viral/*genetics/isolation & purification ; Regulatory Sequences, Nucleic Acid ; SARS Virus/classification/*genetics/isolation & purification ; Sequence Analysis, DNA ; Severe Acute Respiratory Syndrome/virology ; Spike Glycoprotein, Coronavirus ; Viral Envelope Proteins/chemistry/genetics ; Viral Matrix Proteins/chemistry/genetics ; Viral Proteins/chemistry/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    PDGFRA activating mutations in gastrointestinal stromal tumors (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-01-11
    Description: Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that approximately 35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heinrich, Michael C -- Corless, Christopher L -- Duensing, Anette -- McGreevey, Laura -- Chen, Chang-Jie -- Joseph, Nora -- Singer, Samuel -- Griffith, Diana J -- Haley, Andrea -- Town, Ajia -- Demetri, George D -- Fletcher, Christopher D M -- Fletcher, Jonathan A -- New York, N.Y. -- Science. 2003 Jan 31;299(5607):708-10. Epub 2003 Jan 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Department of Pathology, Oregon Health & Science University Cancer Institute and Portland VA Medical Center, Portland, OR 97201, USA. heinrich@ohsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12522257" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CHO Cells ; Chromosome Aberrations ; Cricetinae ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; Exons ; Gastrointestinal Neoplasms/*genetics/metabolism ; Humans ; Karyotyping ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Oncogenes ; Phosphorylation ; *Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-kit/*genetics/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/*genetics/metabolism ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; Signal Transduction ; Trans-Activators/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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