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  • 1
    Publikationsdatum: 2012-10-02
    Beschreibung: Author(s): F. de Campos, O. J. P. Éboli, M. B. Magro, W. Porod, D. Restrepo, S. P. Das, M. Hirsch, and J. W. F. Valle Supersymmetric models with bilinear R -parity violation can account for the observed neutrino masses and mixing parameters indicated by neutrino oscillation data. We consider minimal supergravity versions of bilinear R -parity violation where the lightest supersymmetric particle is a neutralino. This ... [Phys. Rev. D 86, 075001] Published Mon Oct 01, 2012
    Schlagwort(e): Beyond the standard model
    Print ISSN: 0556-2821
    Digitale ISSN: 1089-4918
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2012-05-12
    Beschreibung: An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N(6)-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m(6)A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks--around stop codons and within long internal exons--and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m(6)A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m(6)A has a fundamental role in regulation of gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dominissini, Dan -- Moshitch-Moshkovitz, Sharon -- Schwartz, Schraga -- Salmon-Divon, Mali -- Ungar, Lior -- Osenberg, Sivan -- Cesarkas, Karen -- Jacob-Hirsch, Jasmine -- Amariglio, Ninette -- Kupiec, Martin -- Sorek, Rotem -- Rechavi, Gideon -- England -- Nature. 2012 Apr 29;485(7397):201-6. doi: 10.1038/nature11112.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575960" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine/*analogs & derivatives/*genetics ; Alternative Splicing ; Animals ; Base Sequence ; Cell Line, Tumor ; Conserved Sequence ; Evolution, Molecular ; Hep G2 Cells ; Humans ; *Metabolome/genetics ; Methylation ; Methyltransferases/deficiency/genetics/metabolism ; Mice ; RNA/genetics/*metabolism ; RNA, Ribosomal/genetics/metabolism ; RNA, Transfer/genetics/metabolism ; RNA-Binding Proteins/metabolism ; Transcriptome/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2013-07-05
    Beschreibung: Phosphoinositides serve crucial roles in cell physiology, ranging from cell signalling to membrane traffic. Among the seven eukaryotic phosphoinositides the best studied species is phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), which is concentrated at the plasma membrane where, among other functions, it is required for the nucleation of endocytic clathrin-coated pits. No phosphatidylinositol other than PI(4,5)P2 has been implicated in clathrin-mediated endocytosis, whereas the subsequent endosomal stages of the endocytic pathway are dominated by phosphatidylinositol-3-phosphates(PI(3)P). How phosphatidylinositol conversion from PI(4,5)P2-positive endocytic intermediates to PI(3)P-containing endosomes is achieved is unclear. Here we show that formation of phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) by class II phosphatidylinositol-3-kinase C2alpha (PI(3)K C2alpha) spatiotemporally controls clathrin-mediated endocytosis. Depletion of PI(3,4)P2 or PI(3)K C2alpha impairs the maturation of late-stage clathrin-coated pits before fission. Timed formation of PI(3,4)P2 by PI(3)K C2alpha is required for selective enrichment of the BAR domain protein SNX9 at late-stage endocytic intermediates. These findings provide a mechanistic framework for the role of PI(3,4)P2 in endocytosis and unravel a novel discrete function of PI(3,4)P2 in a central cell physiological process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Posor, York -- Eichhorn-Gruenig, Marielle -- Puchkov, Dmytro -- Schoneberg, Johannes -- Ullrich, Alexander -- Lampe, Andre -- Muller, Rainer -- Zarbakhsh, Sirus -- Gulluni, Federico -- Hirsch, Emilio -- Krauss, Michael -- Schultz, Carsten -- Schmoranzer, Jan -- Noe, Frank -- Haucke, Volker -- England -- Nature. 2013 Jul 11;499(7457):233-7. doi: 10.1038/nature12360. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz Institut fur Molekulare Pharmakologie & Freie Universitat Berlin, Robert-Roessle-Strasse 10, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823722" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; COS Cells ; Cercopithecus aethiops ; Class II Phosphatidylinositol 3-Kinases/metabolism ; Clathrin-Coated Vesicles/metabolism ; *Endocytosis ; HEK293 Cells ; HeLa Cells ; Humans ; Molecular Sequence Data ; Phosphatidylinositol Phosphates/*metabolism ; Phosphoric Monoester Hydrolases/metabolism ; Sorting Nexins/metabolism ; Time Factors
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Publikationsdatum: 2011-10-29
    Beschreibung: Cytotoxic chemotherapy targets elements common to all nucleated human cells, such as DNA and microtubules, yet it selectively kills tumor cells. Here we show that clinical response to these drugs correlates with, and may be partially governed by, the pretreatment proximity of tumor cell mitochondria to the apoptotic threshold, a property called mitochondrial priming. We used BH3 profiling to measure priming in tumor cells from patients with multiple myeloma, acute myelogenous and lymphoblastic leukemia, and ovarian cancer. This assay measures mitochondrial response to peptides derived from proapoptotic BH3 domains of proteins critical for death signaling to mitochondria. Patients with highly primed cancers exhibited superior clinical response to chemotherapy. In contrast, chemoresistant cancers and normal tissues were poorly primed. Manipulation of mitochondrial priming might enhance the efficacy of cytotoxic agents.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280949/" 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/PMC3280949/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ni Chonghaile, Triona -- Sarosiek, Kristopher A -- Vo, Thanh-Trang -- Ryan, Jeremy A -- Tammareddi, Anupama -- Moore, Victoria Del Gaizo -- Deng, Jing -- Anderson, Kenneth C -- Richardson, Paul -- Tai, Yu-Tzu -- Mitsiades, Constantine S -- Matulonis, Ursula A -- Drapkin, Ronny -- Stone, Richard -- Deangelo, Daniel J -- McConkey, David J -- Sallan, Stephen E -- Silverman, Lewis -- Hirsch, Michelle S -- Carrasco, Daniel Ruben -- Letai, Anthony -- P01CA068484/CA/NCI NIH HHS/ -- P01CA139980/CA/NCI NIH HHS/ -- R01 CA129974/CA/NCI NIH HHS/ -- R01 CA129974-05/CA/NCI NIH HHS/ -- R01CA129974/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2011 Nov 25;334(6059):1129-33. doi: 10.1126/science.1206727. Epub 2011 Oct 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22033517" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adult ; Aged ; Animals ; Antineoplastic Agents/*therapeutic use ; *Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Child ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Female ; Humans ; Leukemia, Myeloid, Acute/drug therapy/physiopathology ; Male ; Membrane Potential, Mitochondrial ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Mitochondria/*physiology ; Multiple Myeloma/drug therapy/physiopathology ; Neoplasms/*drug therapy/*physiopathology ; Ovarian Neoplasms/drug therapy/physiopathology ; Peptide Fragments/metabolism ; Permeability ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/physiopathology ; Proto-Oncogene Proteins c-bcl-2/chemistry/metabolism ; Remission Induction ; Signal Transduction
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Publikationsdatum: 2013-04-13
    Beschreibung: Author(s): Carolina Arbeláez, Renato M. Fonseca, Jorge C. Romão, and Martin Hirsch We construct lists of supersymmetric models with extended gauge groups at intermediate steps, all of which are inspired by S O (10) unification. We consider three different kinds of setups: (i) the model has exactly one additional intermediate scale with a left-right (LR) symmetric group; (ii)  S O (10) ... [Phys. Rev. D 87, 075010] Published Fri Apr 12, 2013
    Schlagwort(e): Beyond the standard model
    Print ISSN: 0556-2821
    Digitale ISSN: 1089-4918
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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