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  • Amino Acid Sequence  (388)
  • Cell Line  (345)
  • American Association for the Advancement of Science (AAAS)  (665)
  • 2000-2004  (665)
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  • American Association for the Advancement of Science (AAAS)  (665)
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  • 1
    Publikationsdatum: 2004-06-05
    Beschreibung: The mechanisms by which hydrophobic molecules, such as long-chain fatty acids, enter cells are poorly understood. In Gram-negative bacteria, the lipopolysaccharide layer in the outer membrane is an efficient barrier for fatty acids and aromatic hydrocarbons destined for biodegradation. We report crystal structures of the long-chain fatty acid transporter FadL from Escherichia coli at 2.6 and 2.8 angstrom resolution. FadL forms a 14-stranded beta barrel that is occluded by a central hatch domain. The structures suggest that hydrophobic compounds bind to multiple sites in FadL and use a transport mechanism that involves spontaneous conformational changes in the hatch.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van den Berg, Bert -- Black, Paul N -- Clemons, William M Jr -- Rapoport, Tom A -- New York, N.Y. -- Science. 2004 Jun 4;304(5676):1506-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. lvandenberg@hms.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15178802" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Bacterial Outer Membrane Proteins/*chemistry/metabolism ; Binding Sites ; Biological Transport ; Crystallization ; Crystallography, X-Ray ; Escherichia coli/chemistry/metabolism ; Escherichia coli Proteins/*chemistry/metabolism ; Fatty Acid Transport Proteins ; Fatty Acids/*metabolism ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary
    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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  • 2
    Publikationsdatum: 2004-01-06
    Beschreibung: Pairing, synapsis, and recombination are prerequisites for accurate chromosome segregation in meiosis. The phs1 gene in maize is required for pairing to occur between homologous chromosomes. In the phs1 mutant, homologous chromosome synapsis is completely replaced by synapsis between nonhomologous partners. The phs1 gene is also required for installation of the meiotic recombination machinery on chromosomes, as the mutant almost completely lacks chromosomal foci of the recombination protein RAD51. Thus, in the phs1 mutant, synapsis is uncoupled from recombination and pairing. The protein encoded by the phs1 gene likely acts in a multistep process to coordinate pairing, recombination, and synapsis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pawlowski, Wojciech P -- Golubovskaya, Inna N -- Timofejeva, Ljudmilla -- Meeley, Robert B -- Sheridan, William F -- Cande, W Zacheus -- New York, N.Y. -- Science. 2004 Jan 2;303(5654):89-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. wpawlows@nature.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14704428" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Cell Nucleus/metabolism ; *Chromosome Pairing ; Chromosomes, Plant/*physiology ; Cloning, Molecular ; Conserved Sequence ; DNA, Plant/metabolism ; DNA-Binding Proteins ; Genes, Plant ; In Situ Hybridization, Fluorescence ; In Situ Nick-End Labeling/methods ; *Meiosis ; Molecular Sequence Data ; Mutation ; Phenotype ; Plant Proteins/chemistry/genetics/*physiology ; RNA, Ribosomal, 5S/genetics ; Rad51 Recombinase ; *Recombination, Genetic ; Sequence Alignment ; Synaptonemal Complex/metabolism/ultrastructure ; Telomere/physiology ; Zea mays/*genetics/physiology
    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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  • 3
    Publikationsdatum: 2004-01-06
    Beschreibung: MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes. These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vassilev, Lyubomir T -- Vu, Binh T -- Graves, Bradford -- Carvajal, Daisy -- Podlaski, Frank -- Filipovic, Zoran -- Kong, Norman -- Kammlott, Ursula -- Lukacs, Christine -- Klein, Christian -- Fotouhi, Nader -- Liu, Emily A -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):844-8. Epub 2004 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Discovery Oncology, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110, USA. lyubomir.vassilev@roche.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14704432" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Apoptosis/*drug effects ; Binding Sites ; Cell Cycle/drug effects ; Cell Division/*drug effects ; Cell Line ; Cell Line, Tumor ; Cell Survival/drug effects ; Crystallization ; Crystallography, X-Ray ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/metabolism ; Dose-Response Relationship, Drug ; Gene Expression ; Genes, p53 ; Humans ; Hydrophobic and Hydrophilic Interactions ; Imidazoles/chemistry/metabolism/*pharmacology ; Mice ; Mice, Nude ; Models, Molecular ; Molecular Weight ; NIH 3T3 Cells ; Neoplasm Transplantation ; Neoplasms, Experimental/drug therapy/metabolism/*pathology ; *Nuclear Proteins ; Phosphorylation ; Piperazines/chemistry/metabolism/*pharmacology ; Protein Conformation ; Proto-Oncogene Proteins/*antagonists & inhibitors/chemistry/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Stereoisomerism ; Transplantation, Heterologous ; Tumor Suppressor Protein p53/*metabolism
    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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  • 4
    Publikationsdatum: 2004-01-06
    Beschreibung: RNA interference (RNAi) is a widespread silencing mechanism that acts at both the posttranscriptional and transcriptional levels. Here, we describe the purification of an RNAi effector complex termed RITS (RNA-induced initiation of transcriptional gene silencing) that is required for heterochromatin assembly in fission yeast. The RITS complex contains Ago1 (the fission yeast Argonaute homolog), Chp1 (a heterochromatin-associated chromodomain protein), and Tas3 (a novel protein). In addition, the complex contains small RNAs that require the Dicer ribonuclease for their production. These small RNAs are homologous to centromeric repeats and are required for the localization of RITS to heterochromatic domains. The results suggest a mechanism for the role of the RNAi machinery and small RNAs in targeting of heterochromatin complexes and epigenetic gene silencing at specific chromosomal loci.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244756/" 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/PMC3244756/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Verdel, Andre -- Jia, Songtao -- Gerber, Scott -- Sugiyama, Tomoyasu -- Gygi, Steven -- Grewal, Shiv I S -- Moazed, Danesh -- R01 GM072805/GM/NIGMS NIH HHS/ -- R01 GM072805-01/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2004 Jan 30;303(5658):672-6. Epub 2004 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, Boston, MA02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14704433" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Argonaute Proteins ; Cell Cycle Proteins/chemistry/genetics/isolation & purification/*metabolism ; Centromere/metabolism ; Chromosomes, Fungal/metabolism ; Endoribonucleases/chemistry/genetics/isolation & purification/metabolism ; Genes, Reporter ; Heterochromatin/*metabolism ; Mass Spectrometry ; Models, Genetic ; Molecular Sequence Data ; Mutation ; Precipitin Tests ; Protein Binding ; *RNA Interference ; RNA, Fungal/metabolism ; RNA, Small Interfering/metabolism ; RNA-Binding Proteins ; Ribonuclease III/metabolism ; Schizosaccharomyces/*genetics/metabolism ; Schizosaccharomyces pombe Proteins/chemistry/genetics/isolation & ; purification/*metabolism
    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: 2004-02-21
    Beschreibung: We have engineered a pathway for the formation of disulfide bonds. By imposing evolutionary pressure, we isolated mutations that changed thioredoxin, which is a monomeric disulfide reductase, into a [2Fe-2S] bridged dimer capable of catalyzing O2-dependent sulfhydryl oxidation in vitro. Expression of the mutant protein in Escherichia coli with oxidizing cytoplasm and secretion via the Tat pathway restored disulfide bond formation in strains that lacked the complete periplasmic oxidative machinery (DsbA and DsbB). The evolution of [2Fe-2S] thioredoxin illustrates how mutations within an existing scaffold can add a cofactor and markedly change protein function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Masip, Lluis -- Pan, Jonathan L -- Haldar, Suranjana -- Penner-Hahn, James E -- DeLisa, Matthew P -- Georgiou, George -- Bardwell, James C A -- Collet, Jean-Francois -- GM-38047/GM/NIGMS NIH HHS/ -- GM-55090/GM/NIGMS NIH HHS/ -- GM-57039/GM/NIGMS NIH HHS/ -- GM-64662/GM/NIGMS NIH HHS/ -- P41-RR01633/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 20;303(5661):1185-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering and Institute for Cell and Molecular Biology, University of Texas, Austin, TX 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14976313" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Motifs ; Amino Acid Sequence ; Amino Acid Substitution ; Bacterial Proteins/genetics/metabolism ; Cell Membrane/metabolism ; Cysteine/analysis ; Cytoplasm/metabolism ; Dimerization ; Directed Molecular Evolution ; Disulfides/chemistry/*metabolism ; Escherichia coli/genetics/*metabolism/physiology ; Hirudins/chemistry/metabolism ; Iron/analysis ; Membrane Proteins/genetics/metabolism ; Movement ; Mutation ; Oxidation-Reduction ; Oxygen/metabolism ; Protein Disulfide-Isomerases/genetics/metabolism ; *Protein Engineering ; Protein Folding ; Proteins/chemistry/*metabolism ; Sulfides/analysis ; Thioredoxins/*chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 6
    Publikationsdatum: 2004-01-24
    Beschreibung: What are the components that control the assembly of subcellular organelles in eukaryotic cells? Although membranes can clearly be distorted by cytosolic factors, very little is known about the intrinsic mechanisms that control the biogenesis, shape, and organization of organellar membranes. Here, we found that the unconventional phospholipid lysobisphosphatidic acid (LBPA) could induce the formation of multivesicular liposomes that resembled the multivesicular endosomes that exist where this lipid is found in vivo. This process depended on the same pH gradient that exists across endosome membranes in vivo and was selectively controlled by Alix. In turn, Alix regulated the organization of LBPA-containing endosomes in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuo, Hirotami -- Chevallier, Julien -- Mayran, Nathalie -- Le Blanc, Isabelle -- Ferguson, Charles -- Faure, Julien -- Blanc, Nathalie Sartori -- Matile, Stefan -- Dubochet, Jacques -- Sadoul, Remy -- Parton, Robert G -- Vilbois, Francis -- Gruenberg, Jean -- New York, N.Y. -- Science. 2004 Jan 23;303(5657):531-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Geneva, 30 quai Ernest Ansermet, 1211 Geneva 4, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14739459" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Annexin A2/metabolism ; Arylsulfonates/metabolism ; Calcium-Binding Proteins/genetics/*metabolism ; Carrier Proteins/genetics/*metabolism ; Cell Cycle Proteins ; Cell Line ; Coloring Agents/metabolism ; Cytosol/metabolism ; Endocytosis ; Endosomal Sorting Complexes Required for Transport ; Endosomes/*metabolism/ultrastructure ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Lipid Bilayers ; Liposomes/*metabolism ; Lysophospholipids/chemistry/*metabolism ; Membrane Glycoproteins/metabolism ; Molecular Structure ; Monoglycerides ; RNA Interference ; RNA, Small Interfering/metabolism ; Vesicular stomatitis Indiana virus/physiology ; Viral Envelope Proteins/metabolism
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 7
    Publikationsdatum: 2004-11-06
    Beschreibung: Phosphorylation of the human histone variant H2A.X and H2Av, its homolog in Drosophila melanogaster, occurs rapidly at sites of DNA double-strand breaks. Little is known about the function of this phosphorylation or its removal during DNA repair. Here, we demonstrate that the Drosophila Tip60 (dTip60) chromatin-remodeling complex acetylates nucleosomal phospho-H2Av and exchanges it with an unmodified H2Av. Both the histone acetyltransferase dTip60 as well as the adenosine triphosphatase Domino/p400 catalyze the exchange of phospho-H2Av. Thus, these data reveal a previously unknown mechanism for selective histone exchange that uses the concerted action of two distinct chromatin-remodeling enzymes within the same multiprotein complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kusch, Thomas -- Florens, Laurence -- Macdonald, W Hayes -- Swanson, Selene K -- Glaser, Robert L -- Yates, John R 3rd -- Abmayr, Susan M -- Washburn, Michael P -- Workman, Jerry L -- New York, N.Y. -- Science. 2004 Dec 17;306(5704):2084-7. Epub 2004 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. tnk@stowers-institute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15528408" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetyl Coenzyme A/metabolism ; Acetylation ; Acetyltransferases/genetics/*metabolism ; Adenosine Triphosphatases/metabolism ; Animals ; Cell Line ; *DNA Damage ; DNA Repair ; Dimerization ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/embryology/genetics/*metabolism ; Embryo, Nonmammalian/metabolism ; Histone Acetyltransferases ; Histones/*metabolism ; Multiprotein Complexes/*metabolism ; Nucleosomes/*metabolism ; Phosphorylation ; RNA Interference ; Recombinant Proteins/metabolism ; Transcription Factors/metabolism
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 8
    Publikationsdatum: 2004-02-07
    Beschreibung: The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibility that, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closely related HAs in complex with receptor analogs. They explain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gamblin, S J -- Haire, L F -- Russell, R J -- Stevens, D J -- Xiao, B -- Ha, Y -- Vasisht, N -- Steinhauer, D A -- Daniels, R S -- Elliot, A -- Wiley, D C -- Skehel, J J -- AI-13654/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Mar 19;303(5665):1838-42. Epub 2004 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764886" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Binding Sites ; Birds ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*metabolism ; History, 20th Century ; Humans ; Hydrogen Bonding ; Influenza A virus/*immunology/metabolism/pathogenicity ; Influenza, Human/epidemiology/history/*virology ; Membrane Glycoproteins/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Tertiary ; Receptors, Virus/*metabolism ; Sequence Alignment ; Sialic Acids/metabolism ; Species Specificity ; Swine
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    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 2004-04-24
    Beschreibung: The mechanisms controlling axon guidance are of fundamental importance in understanding brain development. Growing corticospinal and somatosensory axons cross the midline in the medulla to reach their targets and thus form the basis of contralateral motor control and sensory input. The motor and sensory projections appeared uncrossed in patients with horizontal gaze palsy with progressive scoliosis (HGPPS). In patients affected with HGPPS, we identified mutations in the ROBO3 gene, which shares homology with roundabout genes important in axon guidance in developing Drosophila, zebrafish, and mouse. Like its murine homolog Rig1/Robo3, but unlike other Robo proteins, ROBO3 is required for hindbrain axon midline crossing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618874/" 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/PMC1618874/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jen, Joanna C -- Chan, Wai-Man -- Bosley, Thomas M -- Wan, Jijun -- Carr, Janai R -- Rub, Udo -- Shattuck, David -- Salamon, Georges -- Kudo, Lili C -- Ou, Jing -- Lin, Doris D M -- Salih, Mustafa A M -- Kansu, Tulay -- Al Dhalaan, Hesham -- Al Zayed, Zayed -- MacDonald, David B -- Stigsby, Bent -- Plaitakis, Andreas -- Dretakis, Emmanuel K -- Gottlob, Irene -- Pieh, Christina -- Traboulsi, Elias I -- Wang, Qing -- Wang, Lejin -- Andrews, Caroline -- Yamada, Koki -- Demer, Joseph L -- Karim, Shaheen -- Alger, Jeffry R -- Geschwind, Daniel H -- Deller, Thomas -- Sicotte, Nancy L -- Nelson, Stanley F -- Baloh, Robert W -- Engle, Elizabeth C -- DC00162/DC/NIDCD NIH HHS/ -- DC05524/DC/NIDCD NIH HHS/ -- EY12498/EY/NEI NIH HHS/ -- EY13583/EY/NEI NIH HHS/ -- EY15298/EY/NEI NIH HHS/ -- EY15311/EY/NEI NIH HHS/ -- MH60233/MH/NIMH NIH HHS/ -- P30 HD 18655/HD/NICHD NIH HHS/ -- R01 EY008313/EY/NEI NIH HHS/ -- R01 EY008313-14/EY/NEI NIH HHS/ -- R01 HL066251/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Jun 4;304(5676):1509-13. Epub 2004 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of California, Los Angeles, CA 90095, USA. jjen@ucla.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15105459" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adult ; Alternative Splicing ; Amino Acid Motifs ; Amino Acid Sequence ; Axons/*physiology ; Evoked Potentials, Motor ; Evoked Potentials, Somatosensory ; Female ; Functional Laterality ; Genetic Linkage ; Humans ; In Situ Hybridization ; Magnetic Resonance Imaging ; Male ; Medulla Oblongata/growth & development/pathology ; Microsatellite Repeats ; Molecular Sequence Data ; Morphogenesis ; Mutation ; Neural Pathways ; Ophthalmoplegia/*genetics/pathology/physiopathology ; Pedigree ; Protein Structure, Tertiary ; Receptors, Immunologic/chemistry/*genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rhombencephalon/*growth & development/pathology ; Scoliosis/*genetics/pathology/physiopathology ; Sequence Analysis, DNA ; Syndrome
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    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 10
    Publikationsdatum: 2004-02-21
    Beschreibung: Feline immunodeficiency virus (FIV) induces a disease similar to acquired immunodeficiency syndrome (AIDS) in cats, yet in contrast to human immunodeficiency virus (HIV), CD4 is not the viral receptor. We identified a primary receptor for FIV as CD134 (OX40), a T cell activation antigen and costimulatory molecule. CD134 expression promotes viral binding and renders cells permissive for viral entry, productive infection, and syncytium formation. Infection is CXCR4-dependent, analogous to infection with X4 strains of HIV. Thus, despite the evolutionary divergence of the feline and human lentiviruses, both viruses use receptors that target the virus to a subset of cells that are pivotal to the acquired immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimojima, Masayuki -- Miyazawa, Takayuki -- Ikeda, Yasuhiro -- McMonagle, Elizabeth L -- Haining, Hayley -- Akashi, Hiroomi -- Takeuchi, Yasuhiro -- Hosie, Margaret J -- Willett, Brian J -- R01 AI49765-01A1/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 20;303(5661):1192-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14976315" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; CD4-Positive T-Lymphocytes/immunology/metabolism/virology ; Cats ; Cell Line ; Cell Line, Tumor ; DNA, Complementary ; Gene Library ; HIV/metabolism ; HeLa Cells ; Heterocyclic Compounds/pharmacology ; Humans ; Immunodeficiency Virus, Feline/*metabolism/pathogenicity ; Mice ; Molecular Sequence Data ; NIH 3T3 Cells ; Receptors, CXCR4/antagonists & inhibitors/metabolism ; Receptors, OX40 ; Receptors, Tumor Necrosis Factor/chemistry/genetics/immunology/*metabolism ; Receptors, Virus/chemistry/genetics/immunology/*metabolism ; Species Specificity ; Transduction, Genetic ; Transfection
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 11
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-06-26
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, Andrew -- New York, N.Y. -- Science. 2004 Jun 25;304(5679):1888.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15218115" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Biomedical Research ; Cell Line ; Humans ; *Politics ; *Research Support as Topic ; *Science ; Stem Cells ; United States
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    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 12
    Publikationsdatum: 2004-01-13
    Beschreibung: A family of unusual proteins is deposited in flat, structural platelets in reflective tissues of the squid Euprymna scolopes. These proteins, which we have named reflectins, are encoded by at least six genes in three subfamilies and have no reported homologs outside of squids. Reflectins possess five repeating domains, which are highly conserved among members of the family. The proteins have a very unusual composition, with four relatively rare residues (tyrosine, methionine, arginine, and tryptophan) comprising approximately 57% of a reflectin, and several common residues (alanine, isoleucine, leucine, and lysine) occurring in none of the family members. These protein-based reflectors in squids provide a marked example of nanofabrication in animal systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crookes, Wendy J -- Ding, Lin-Lin -- Huang, Qing Ling -- Kimbell, Jennifer R -- Horwitz, Joseph -- McFall-Ngai, Margaret J -- NEI R01 EY3897/EY/NEI NIH HHS/ -- R01 A150661/PHS HHS/ -- New York, N.Y. -- Science. 2004 Jan 9;303(5655):235-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kewalo Marine Laboratory, Pacific Biomedical Research Center, University of Hawaii-Manoa, 41 Ahui Street, Honolulu, HI 96813, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14716016" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amino Acids/analysis ; Animals ; DNA, Complementary ; Decapodiformes/anatomy & histology/*chemistry/genetics ; Electrophoresis, Polyacrylamide Gel ; Immunoblotting ; Immunohistochemistry ; *Light ; Microscopy, Immunoelectron ; Molecular Sequence Data ; Polymerase Chain Reaction ; Protein Structure, Tertiary ; Proteins/*analysis/*chemistry/genetics/isolation & purification ; Sequence Alignment ; Solubility
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 13
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-08-18
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Sang-yong -- New York, N.Y. -- Science. 2004 Aug 13;305(5686):944-5; author reply 944-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15310877" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bioethical Issues ; Blastocyst/*cytology ; Cell Line ; Cloning, Organism/*ethics ; Embryo Research/*ethics ; Embryo, Mammalian/cytology ; Ethics Committees ; Ethics Committees, Research ; Humans ; Korea ; *Pluripotent Stem Cells
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 14
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-11-30
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Michalakis, Yannis -- Roze, Denis -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1492-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetique et Evolution des Maladies Infectieuses, UMR CNRS IRD 2724, Montpellier Cedex 5, France. yannis.michalakis@mpl.ird.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15567846" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; *Epistasis, Genetic ; *Evolution, Molecular ; Genes, Viral ; HIV Infections/drug therapy/virology ; HIV Protease/chemistry/genetics ; HIV Reverse Transcriptase/chemistry/genetics ; HIV-1/*genetics/physiology ; Humans ; Models, Genetic ; Mutation ; *Recombination, Genetic ; Reproduction ; Selection, Genetic ; Vesicular stomatitis Indiana virus/*genetics/physiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 15
    Publikationsdatum: 2004-11-30
    Beschreibung: Reproductive strategies such as sexual reproduction and recombination that involve the shuffling of parental genomes for the production of offspring are ubiquitous in nature. However, their evolutionary benefit remains unclear. Many theories have identified potential benefits, but progress is hampered by the scarcity of relevant data. One class of theories is based on the assumption that mutations affecting fitness exhibit negative epistasis. Retroviruses recombine frequently and thus provide a unique opportunity to test these theories. Using amino acid sequence data and fitness values from 9466 human immunodeficiency virus 1 (HIV-1) isolates, we find in contrast to these theories strong statistical evidence for a predominance of positive epistasis in HIV-1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonhoeffer, Sebastian -- Chappey, Colombe -- Parkin, Neil T -- Whitcomb, Jeanette M -- Petropoulos, Christos J -- R43 AI050321/AI/NIAID NIH HHS/ -- R43 AI057068/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1547-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecology and Evolution, ETH Zurich, ETH Zentrum NW, CH-8092 Zurich, Switzerland. seb@env.ethz.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15567861" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amino Acids ; Anti-HIV Agents/pharmacology ; Drug Resistance, Viral ; *Epistasis, Genetic ; *Evolution, Molecular ; Genotype ; HIV Infections/drug therapy/virology ; HIV Protease/chemistry/genetics/metabolism ; HIV Reverse Transcriptase/chemistry/genetics/metabolism ; HIV-1/drug effects/*genetics/physiology ; Humans ; Mutation ; *Recombination, Genetic ; Software ; Virus Replication
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-06-12
    Beschreibung: During embryogenesis, differentiation of skeletal muscle is regulated by transcription factors that include members of the Msx homeoprotein family. By investigating Msx1 function in repression of myogenic gene expression, we identified a physical interaction between Msx1 and H1b, a specific isoform of mouse histone H1. We found that Msx1 and H1b bind to a key regulatory element of MyoD, a central regulator of skeletal muscle differentiation, where they induce repressed chromatin. Moreover, Msx1 and H1b cooperate to inhibit muscle differentiation in cell culture and in Xenopus animal caps. Our findings define a previously unknown function for "linker" histones in gene-specific transcriptional regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Hansol -- Habas, Raymond -- Abate-Shen, Cory -- HD29446/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2004 Jun 11;304(5677):1675-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15192231" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Differentiation ; Cell Line ; Embryo, Nonmammalian/cytology/metabolism ; Enhancer Elements, Genetic ; *Gene Expression Regulation, Developmental ; Histones/genetics/*metabolism ; Homeodomain Proteins/chemistry/genetics/*metabolism ; MSX1 Transcription Factor ; Mice ; Models, Genetic ; *Muscle Development ; Muscle, Skeletal/*cytology/metabolism ; Mutation ; MyoD Protein/genetics ; Myoblasts/*cytology/metabolism ; Precipitin Tests ; Protein Binding ; RNA Interference ; Recombinant Proteins/metabolism ; Regulatory Sequences, Nucleic Acid ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcription, Genetic ; Xenopus/embryology/metabolism ; Xenopus Proteins
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-01-06
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickelgren, Ingrid -- New York, N.Y. -- Science. 2004 Jan 2;303(5654):28-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14704404" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Aplysia/physiology ; Memory/*physiology ; Neurons/*physiology ; Prions/chemistry/metabolism/*physiology ; Protein Biosynthesis ; Protein Conformation ; RNA, Messenger/genetics/metabolism ; Solubility ; Transcription Factors/chemistry/genetics/*metabolism ; Yeasts/genetics/metabolism ; mRNA Cleavage and Polyadenylation Factors/chemistry/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 18
    Publikationsdatum: 2004-04-06
    Beschreibung: Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion. Here, we report that a pathogenic fragment of Htt (Httex1p) can be modified either by small ubiquitin-like modifier (SUMO)-1 or by ubiquitin on identical lysine residues. In cultured cells, SUMOylation stabilizes Httex1p, reduces its ability to form aggregates, and promotes its capacity to repress transcription. In a Drosophila model of HD, SUMOylation of Httex1p exacerbates neurodegeneration, whereas ubiquitination of Httex1p abrogates neurodegeneration. Lysine mutations that prevent both SUMOylation and ubiquitination of Httex1p reduce HD pathology, indicating that the contribution of SUMOylation to HD pathology extends beyond preventing Htt ubiquitination and degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steffan, Joan S -- Agrawal, Namita -- Pallos, Judit -- Rockabrand, Erica -- Trotman, Lloyd C -- Slepko, Natalia -- Illes, Katalin -- Lukacsovich, Tamas -- Zhu, Ya-Zhen -- Cattaneo, Elena -- Pandolfi, Pier Paolo -- Thompson, Leslie Michels -- Marsh, J Lawrence -- CA-62203/CA/NCI NIH HHS/ -- HD36049/HD/NICHD NIH HHS/ -- HD36081/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2004 Apr 2;304(5667):100-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, CA 92697, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15064418" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Animals, Genetically Modified ; Cell Line ; Cell Nucleus/metabolism ; Corpus Striatum/cytology ; Cytoplasm/metabolism ; Drosophila ; Genes, MDR ; HeLa Cells ; Humans ; Huntington Disease/metabolism/*pathology ; Lysine/genetics/metabolism ; Mutation ; Nerve Degeneration ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Neurons/metabolism ; Nuclear Proteins/chemistry/genetics/*metabolism ; Proline/genetics/metabolism ; Promoter Regions, Genetic ; Rats ; Recombinant Fusion Proteins/metabolism ; SUMO-1 Protein/genetics/*metabolism ; Transcription, Genetic ; Transfection ; Ubiquitin/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 19
    Publikationsdatum: 2004-01-24
    Beschreibung: Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moody, D Branch -- Young, David C -- Cheng, Tan-Yun -- Rosat, Jean-Pierre -- Roura-Mir, Carme -- O'Connor, Peter B -- Zajonc, Dirk M -- Walz, Andrew -- Miller, Marvin J -- Levery, Steven B -- Wilson, Ian A -- Costello, Catherine E -- Brenner, Michael B -- AI30988/AI/NIAID NIH HHS/ -- AI50216/AI/NIAID NIH HHS/ -- AR48632/AR/NIAMS NIH HHS/ -- CA58896/CA/NCI NIH HHS/ -- GM25845/GM/NIGMS NIH HHS/ -- GM62116/GM/NIGMS NIH HHS/ -- P20 RR16459/RR/NCRR NIH HHS/ -- P41-RR10888/RR/NCRR NIH HHS/ -- S10-RR10493/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2004 Jan 23;303(5657):527-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Smith Building Room 514, 1 Jimmy Fund Way, Boston, MA 02115, USA. bmoody@rics.bwh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14739458" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Antigen Presentation ; Antigens, Bacterial/chemistry/*immunology/metabolism ; Antigens, CD1/chemistry/immunology/metabolism ; Cell Line ; Chromatography, High Pressure Liquid ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Hydroxylation ; Lipoproteins/chemistry/*immunology/metabolism ; *Lymphocyte Activation ; Models, Molecular ; Mycobacterium tuberculosis/growth & development/*immunology ; Oxazoles/chemistry/*immunology/metabolism ; Protein Conformation ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; T-Lymphocytes/*immunology ; Transfection
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 20
    Publikationsdatum: 2004-08-03
    Beschreibung: Propionibacterium acnes is a major inhabitant of adult human skin, where it resides within sebaceous follicles, usually as a harmless commensal although it has been implicated in acne vulgaris formation. The entire genome sequence of this Gram-positive bacterium encodes 2333 putative genes and revealed numerous gene products involved in degrading host molecules, including sialidases, neuraminidases, endoglycoceramidases, lipases, and pore-forming factors. Surface-associated and other immunogenic factors have been identified, which might be involved in triggering acne inflammation and other P. acnes-associated diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bruggemann, Holger -- Henne, Anke -- Hoster, Frank -- Liesegang, Heiko -- Wiezer, Arnim -- Strittmatter, Axel -- Hujer, Sandra -- Durre, Peter -- Gottschalk, Gerhard -- New York, N.Y. -- Science. 2004 Jul 30;305(5684):671-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gottingen Genomics Laboratory, Institute of Microbiology and Genetics, Georg-August-University Gottingen, Grisebachstrasse 8, 37077 Gottingen, Germany. hbruegg@pasteur.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15286373" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acne Vulgaris/immunology/microbiology ; Amino Acid Motifs ; Amino Acid Sequence ; Antigens, Bacterial/chemistry/genetics ; Bacterial Proteins/chemistry/genetics/immunology ; Base Sequence ; Chromosomes, Bacterial/genetics ; Computational Biology ; Energy Metabolism ; Esterases/genetics/metabolism ; Genes, Bacterial ; *Genome, Bacterial ; Heat-Shock Proteins/chemistry/genetics ; Humans ; Hydrolases/genetics/metabolism ; Lipase/genetics/metabolism ; Molecular Sequence Data ; Oxidative Phosphorylation ; Propionibacterium acnes/*genetics/immunology/physiology ; *Sequence Analysis, DNA ; Skin/*microbiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 21
    Publikationsdatum: 2004-04-17
    Beschreibung: Calmodulin (CaM) interactions with Ca2+ channels mediate both Ca2+ regulation of channels and local Ca2+ triggering of transcription factors implicated in neuronal memory. Crucial to these functions are the number of CaM molecules (CaMs) regulating each channel, and the number of CaMs privy to the local Ca2+ signal from each channel. To resolve these parameters, we fused L-type Ca2+ channels to single CaM molecules. These chimeric molecules revealed that a single CaM directs L-type channel regulation. Similar fusion molecules were used to estimate the local CaM concentration near Ca2+ channels. This estimate indicates marked enrichment of local CaM, as if a "school" of nearby CaMs were poised to enhance the transduction of local Ca2+ entry into diverse signaling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mori, Masayuki X -- Erickson, Michael G -- Yue, David T -- New York, N.Y. -- Science. 2004 Apr 16;304(5669):432-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ca2+ Signals Laboratory, Department of Biomedical Engineering , Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15087548" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Calcium/*metabolism ; Calcium Channels, L-Type/chemistry/*metabolism ; Calcium Signaling ; Calmodulin/chemistry/genetics/*metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Fluorescence Resonance Energy Transfer ; Humans ; Mathematics ; Mutation ; Patch-Clamp Techniques ; Peptides/chemistry/genetics ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Transfection
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 22
    Publikationsdatum: 2004-03-27
    Beschreibung: Heterosexual transmission accounts for the majority of human immunodeficiency virus-1 (HIV-1) infections worldwide, yet the viral properties that determine transmission fitness or outgrowth have not been elucidated. Here we show, for eight heterosexual transmission pairs, that recipient viruses were monophyletic, encoding compact, glycan-restricted envelope glycoproteins. These viruses were also uniquely sensitive to neutralization by antibody from the transmitting partner. Thus, the exposure of neutralizing epitopes, which are lost in chronic infection because of immune escape, appears to be favored in the newly infected host. This reveals characteristics of the envelope glycoprotein that influence HIV-1 transmission and may have implications for vaccine design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Derdeyn, Cynthia A -- Decker, Julie M -- Bibollet-Ruche, Frederic -- Mokili, John L -- Muldoon, Mark -- Denham, Scott A -- Heil, Marintha L -- Kasolo, Francis -- Musonda, Rosemary -- Hahn, Beatrice H -- Shaw, George M -- Korber, Bette T -- Allen, Susan -- Hunter, Eric -- AI-40951/AI/NIAID NIH HHS/ -- AI-51231/AI/NIAID NIH HHS/ -- N01-85338/PHS HHS/ -- U01-AI-41530/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Mar 26;303(5666):2019-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15044802" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): AIDS Vaccines ; Amino Acid Sequence ; Cohort Studies ; Epitopes/immunology ; Female ; Genes, env ; Glycosylation ; HIV Antibodies/*immunology ; HIV Envelope Protein gp120/chemistry/genetics/*immunology ; HIV Infections/*immunology/*transmission/virology ; HIV-1/genetics/*immunology/physiology ; Heterosexuality ; Humans ; Likelihood Functions ; Male ; Molecular Sequence Data ; Neutralization Tests ; Prospective Studies ; Viral Load ; Zambia
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 23
    Publikationsdatum: 2004-02-07
    Beschreibung: The 1918 "Spanish" influenza pandemic represents the largest recorded outbreak of any infectious disease. The crystal structure of the uncleaved precursor of the major surface antigen of the extinct 1918 virus was determined at 3.0 angstrom resolution after reassembly of the hemagglutinin gene from viral RNA fragments preserved in 1918 formalin-fixed lung tissues. A narrow avian-like receptor-binding site, two previously unobserved histidine patches, and a less exposed surface loop at the cleavage site that activates viral membrane fusion reveal structural features primarily found in avian viruses, which may have contributed to the extraordinarily high infectivity and mortality rates observed during 1918.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stevens, James -- Corper, Adam L -- Basler, Christopher F -- Taubenberger, Jeffery K -- Palese, Peter -- Wilson, Ian A -- AI058113/AI/NIAID NIH HHS/ -- AI42266/AI/NIAID NIH HHS/ -- AI50619/AI/NIAID NIH HHS/ -- CA55896/CA/NCI NIH HHS/ -- P50-GM 62411/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Mar 19;303(5665):1866-70. Epub 2004 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764887" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Binding Sites ; Carbohydrate Conformation ; Cloning, Molecular ; Crystallography, X-Ray ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/metabolism ; Histidine/chemistry/metabolism ; History, 20th Century ; Humans ; Hydrogen Bonding ; Influenza A virus/classification/*immunology/pathogenicity ; Influenza, Human/epidemiology/history/virology ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Virus/metabolism ; Sialic Acids/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 24
    Publikationsdatum: 2004-09-14
    Beschreibung: Signaling proteins are tightly regulated spatially and temporally to perform multiple functions. For Cdc42 and other guanosine triphosphatases, the subcellular location of activation is a critical determinant of cell behavior. However, current approaches are limited in their ability to examine the dynamics of Cdc42 activity in living cells. We report the development of a biosensor capable of visualizing the changing activation of endogenous, unlabeled Cdc42 in living cells. With the use of a dye that reports protein interactions, the biosensor revealed localized activation in the trans-Golgi apparatus, microtubule-dependent Cdc42 activation at the cell periphery, and activation kinetics precisely coordinated with cell extension and retraction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nalbant, Perihan -- Hodgson, Louis -- Kraynov, Vadim -- Toutchkine, Alexei -- Hahn, Klaus M -- GM57464/GM/NIGMS NIH HHS/ -- GM64346/GM/NIGMS NIH HHS/ -- R01 GM057464/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Sep 10;305(5690):1615-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7365, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15361624" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Actins/metabolism ; Algorithms ; Animals ; *Biosensing Techniques ; Cell Adhesion ; Cell Line ; Cell Membrane/*metabolism ; Cell Polarity ; Cell Surface Extensions/metabolism/ultrastructure ; Endothelial Cells/metabolism/ultrastructure ; Fibroblasts ; Fluorescence ; Fluorescent Dyes/chemistry/metabolism ; Green Fluorescent Proteins ; Humans ; Luminescent Proteins ; Mice ; Microtubules/metabolism ; Neutrophil Activation ; Neutrophils/*metabolism ; Proteins/chemistry/metabolism ; Pseudopodia/metabolism ; Pyrimidinones/metabolism ; Sensitivity and Specificity ; Wiskott-Aldrich Syndrome Protein ; cdc42 GTP-Binding Protein/*metabolism ; rho GTP-Binding Proteins/metabolism ; trans-Golgi Network/*metabolism/ultrastructure
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 25
    Publikationsdatum: 2004-01-13
    Beschreibung: During genetic recombination and the recombinational repair of chromosome breaks, DNA molecules become linked at points of strand exchange. Branch migration and resolution of these crossovers, or Holliday junctions (HJs), complete the recombination process. Here, we show that extracts from cells carrying mutations in the recombination/repair genes RAD51C or XRCC3 have reduced levels of HJ resolvase activity. Moreover, depletion of RAD51C from fractionated human extracts caused a loss of branch migration and resolution activity, but these functions were restored by complementation with a variety of RAD51 paralog complexes containing RAD51C. We conclude that the RAD51 paralogs are involved in HJ processing in human cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Yilun -- Masson, Jean-Yves -- Shah, Rajvee -- O'Regan, Paul -- West, Stephen C -- New York, N.Y. -- Science. 2004 Jan 9;303(5655):243-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14716019" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Substitution ; Animals ; CHO Cells ; Cell Line ; Cricetinae ; DNA Repair ; DNA, Cruciform/chemistry/*metabolism ; DNA-Binding Proteins/chemistry/genetics/isolation & purification/*metabolism ; Electrophoresis, Polyacrylamide Gel ; Female ; HeLa Cells ; Holliday Junction Resolvases/*metabolism ; Humans ; Mutation ; Protein Structure, Tertiary ; Recombinant Proteins/metabolism ; Recombination, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 26
    Publikationsdatum: 2004-01-24
    Beschreibung: Jun N-terminal kinases (JNKs) are essential for neuronal microtubule assembly and apoptosis. Phosphorylation of the activating protein 1 (AP1) transcription factor c-Jun, at multiple sites within its transactivation domain, is required for JNK-induced neurotoxicity. We report that in neurons the stability of c-Jun is regulated by the E3 ligase SCF(Fbw7), which ubiquitinates phosphorylated c-Jun and facilitates c-Jun degradation. Fbw7 depletion resulted in accumulation of phosphorylated c-Jun, stimulation of AP1 activity, and neuronal apoptosis. SCF(Fbw7) therefore antagonizes the apoptotic c-Jun-dependent effector arm of JNK signaling, allowing neurons to tolerate potentially neurotoxic JNK activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nateri, Abdolrahman S -- Riera-Sans, Lluis -- Da Costa, Clive -- Behrens, Axel -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1374-8. Epub 2004 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14739463" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; *Apoptosis ; Base Sequence ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line ; F-Box Proteins/genetics/*metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System ; Mice ; Mitogen-Activated Protein Kinases/*metabolism ; Molecular Sequence Data ; Neurons/*physiology ; PC12 Cells ; Phosphorylation ; Proto-Oncogene Proteins c-jun/*metabolism ; RNA, Small Interfering/metabolism ; Rats ; Transcription Factor AP-1/metabolism ; Transfection ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 27
    Publikationsdatum: 2004-01-31
    Beschreibung: The lantibiotic lacticin 481 is synthesized on ribosomes as a prepeptide (LctA) and posttranslationally modified to its mature form. These modifications include dehydration of serines and threonines, followed by intramolecular addition of cysteines to the unsaturated amino acids, which generates cyclic thioethers. This process breaks eight chemical bonds and forms six newbonds and is catalyzed by one enzyme, LctM. We have characterized the in vitro activity of LctM, which completely processed a series of LctA mutants, displaying a permissive substrate specificity that holds promise for antibiotic engineering.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xie, Lili -- Miller, Leah M -- Chatterjee, Champak -- Averin, Olga -- Kelleher, Neil L -- van der Donk, Wilfred A -- GM 067725/GM/NIGMS NIH HHS/ -- GM58822/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Jan 30;303(5658):679-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14752162" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Bacterial Proteins/*biosynthesis/genetics ; *Bacteriocins ; Cloning, Molecular ; Cysteine/metabolism ; Enzymes/chemistry/genetics/isolation & purification/*metabolism ; Escherichia coli/genetics ; Lactococcus lactis/enzymology/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Protein Precursors/chemistry/metabolism ; Protein Processing, Post-Translational ; Serine/metabolism ; Spectrometry, Mass, Electrospray Ionization ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Substrate Specificity ; Threonine/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 28
    Publikationsdatum: 2004-06-26
    Beschreibung: The nuclear factor-kappa B (NF-kappaB) family of transcription factors plays a seminal role in inflammation, apoptosis, development, and cancer. Modulation of NF-kappaB-mediated gene expression in response to diverse signals is coordinated by the IkappaB kinase (IKK) complex. We identified ELKS, an essential regulatory subunit of the IKK complex. Silencing ELKS expression by RNA interference blocked induced expression of NF-kappaB target genes, including the NF-kappaB inhibitor IkappaBalpha and proinflammatory genes such as cyclo-oxygenase 2 and interleukin 8. These cells were also not protected from apoptosis in response to cytokines. ELKS likely functions by recruiting IkappaBalpha to the IKK complex and thus serves a regulatory function for IKK activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ducut Sigala, Jeanette L -- Bottero, Virginie -- Young, David B -- Shevchenko, Andrej -- Mercurio, Frank -- Verma, Inder M -- New York, N.Y. -- Science. 2004 Jun 25;304(5679):1963-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute for Biological Sciences, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15218148" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adaptor Proteins, Signal Transducing ; Animals ; Apoptosis ; Carrier Proteins/genetics/*metabolism ; Cell Line ; Cyclooxygenase 2 ; Gene Expression ; Genes, Reporter ; HeLa Cells ; Humans ; I-kappa B Kinase ; I-kappa B Proteins/genetics/metabolism ; Interleukin-1/pharmacology ; Interleukin-8/genetics ; Isoenzymes/genetics ; Membrane Proteins ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; NF-kappa B/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; Phosphorylation ; Precipitin Tests ; Prostaglandin-Endoperoxide Synthases/genetics ; Protein-Serine-Threonine Kinases/*metabolism ; RNA Interference ; Tumor Necrosis Factor-alpha/pharmacology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 29
    Publikationsdatum: 2004-08-07
    Beschreibung: The cascade of events that leads to vaccinia-induced actin polymerization requires Src-dependent tyrosine phosphorylation of the viral membrane protein A36R. We found that a localized outside-in signaling cascade induced by the viral membrane protein B5R is required to potently activate Src and induce A36R phosphorylation at the plasma membrane. In addition, Src-mediated phosphorylation of A36R regulated the ability of virus particles to recruit and release conventional kinesin. Thus, Src activity regulates the transition between cytoplasmic microtubule transport and actin-based motility at the plasma membrane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newsome, Timothy P -- Scaplehorn, Niki -- Way, Michael -- New York, N.Y. -- Science. 2004 Oct 1;306(5693):124-9. Epub 2004 Aug 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Motility Laboratory, Room 529, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15297625" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Actins/*metabolism ; Animals ; Cell Line ; Cell Membrane/metabolism/virology ; Chickens ; Consensus Sequence ; Enzyme Activation ; HeLa Cells ; Humans ; Kinesin/metabolism ; Membrane Glycoproteins/chemistry/metabolism ; Microtubules/*metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Recombinant Fusion Proteins/metabolism ; Vaccinia virus/genetics/*metabolism/physiology ; Viral Envelope Proteins/chemistry/metabolism ; Viral Structural Proteins/*metabolism ; Virion/metabolism ; src-Family Kinases/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 30
    Publikationsdatum: 2004-05-08
    Beschreibung: Prostaglandin E2 (PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype (GlyR alpha3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR alpha3 is distinctly expressed in superficial layers of the spinal cord dorsal horn. Mice deficient in GlyR alpha3 not only lack the inhibition of glycinergic neurotransmission by PGE2 seen in wild-type mice but also show a reduction in pain sensitization induced by spinal PGE2 injection or peripheral inflammation. Thus, GlyR alpha3 may provide a previously unrecognized molecular target in pain therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harvey, Robert J -- Depner, Ulrike B -- Wassle, Heinz -- Ahmadi, Seifollah -- Heindl, Cornelia -- Reinold, Heiko -- Smart, Trevor G -- Harvey, Kirsten -- Schutz, Burkhard -- Abo-Salem, Osama M -- Zimmer, Andreas -- Poisbeau, Pierrick -- Welzl, Hans -- Wolfer, David P -- Betz, Heinrich -- Zeilhofer, Hanns Ulrich -- Muller, Ulrike -- New York, N.Y. -- Science. 2004 May 7;304(5672):884-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15131310" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Cell Line ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dinoprostone/administration & dosage/*metabolism/pharmacology ; Female ; Freund's Adjuvant ; Glycine/metabolism ; Humans ; Inflammation/metabolism/*physiopathology ; Male ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Neurons/metabolism ; Pain/*physiopathology ; Patch-Clamp Techniques ; Phosphorylation ; Posterior Horn Cells/*metabolism ; Receptors, Glycine/chemistry/genetics/*metabolism ; Signal Transduction ; Spinal Cord/*metabolism ; Synaptic Transmission ; Transfection ; Zymosan
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 31
    Publikationsdatum: 2004-01-06
    Beschreibung: A previously unknown maltose transporter is essential for the conversion of starch to sucrose in Arabidopsis leaves at night. The transporter was identified by isolating two allelic mutants with high starch levels and very high maltose, an intermediate of starch breakdown. The mutations affect a gene of previously unknown function, MEX1. We show that MEX1is a maltose transporter that is unrelated to other sugar transporters. The severe mex1 phenotype demonstrates that MEX1is the predominant route of carbohydrate export from chloroplasts at night. Homologous genes in plants including rice and potato indicate that maltose export is of widespread significance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Niittyla, Totte -- Messerli, Gaelle -- Trevisan, Martine -- Chen, Jychian -- Smith, Alison M -- Zeeman, Samuel C -- New York, N.Y. -- Science. 2004 Jan 2;303(5654):87-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Metabolic Biology, John Innes Centre, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14704427" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Biological Transport ; Chloroplasts/metabolism ; Cloning, Molecular ; Crosses, Genetic ; DNA, Complementary ; Genes, Plant ; Glucose/metabolism ; Maltose/*metabolism ; Molecular Sequence Data ; Monosaccharide Transport Proteins/chemistry/genetics/*metabolism ; Mutation ; Phenotype ; Plant Leaves/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; Starch/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 32
    Publikationsdatum: 2004-04-17
    Beschreibung: Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in Alzheimer's disease (AD). Here, we demonstrate that Abeta-binding alcohol dehydrogenase (ABAD) is a direct molecular link from Abeta to mitochondrial toxicity. Abeta interacts with ABAD in the mitochondria of AD patients and transgenic mice. The crystal structure of Abeta-bound ABAD shows substantial deformation of the active site that prevents nicotinamide adenine dinucleotide (NAD) binding. An ABAD peptide specifically inhibits ABAD-Abeta interaction and suppresses Abeta-induced apoptosis and free-radical generation in neurons. Transgenic mice overexpressing ABAD in an Abeta-rich environment manifest exaggerated neuronal oxidative stress and impaired memory. These data suggest that the ABAD-Abeta interaction may be a therapeutic target in AD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lustbader, Joyce W -- Cirilli, Maurizio -- Lin, Chang -- Xu, Hong Wei -- Takuma, Kazuhiro -- Wang, Ning -- Caspersen, Casper -- Chen, Xi -- Pollak, Susan -- Chaney, Michael -- Trinchese, Fabrizio -- Liu, Shumin -- Gunn-Moore, Frank -- Lue, Lih-Fen -- Walker, Douglas G -- Kuppusamy, Periannan -- Zewier, Zay L -- Arancio, Ottavio -- Stern, David -- Yan, Shirley ShiDu -- Wu, Hao -- 1K07AG00959/AG/NIA NIH HHS/ -- AG16736/AG/NIA NIH HHS/ -- AG17490/AG/NIA NIH HHS/ -- NS42855/NS/NINDS NIH HHS/ -- P50AG08702/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2004 Apr 16;304(5669):448-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Reproductive Sciences and Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15087549" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 3-Hydroxyacyl CoA Dehydrogenases/chemistry/*metabolism ; Aged ; Aged, 80 and over ; Alzheimer Disease/*metabolism ; Amino Acid Sequence ; Amyloid beta-Peptides/chemistry/genetics/*metabolism ; Animals ; Binding Sites ; Brain/*metabolism ; Brain Chemistry ; Carrier Proteins/chemistry/*metabolism ; Cells, Cultured ; Cerebral Cortex/chemistry/metabolism ; Crystallization ; DNA Fragmentation ; Hippocampus/physiology ; Humans ; Learning ; Memory ; Mice ; Mice, Transgenic ; Microscopy, Confocal ; Microscopy, Immunoelectron ; Mitochondria/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; NAD/metabolism ; Neurons/metabolism ; Protein Binding ; Protein Conformation ; Reactive Oxygen Species/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 33
    Publikationsdatum: 2004-10-09
    Beschreibung: Nitric oxide (NO) is extremely toxic to Clostridium botulinum, but its molecular targets are unknown. Here, we identify a heme protein sensor (SONO) that displays femtomolar affinity for NO. The crystal structure of the SONO heme domain reveals a previously undescribed fold and a strategically placed tyrosine residue that modulates heme-nitrosyl coordination. Furthermore, the domain architecture of a SONO ortholog cloned from Chlamydomonas reinhardtii indicates that NO signaling through cyclic guanosine monophosphate arose before the origin of multicellular eukaryotes. Our findings have broad implications for understanding bacterial responses to NO, as well as for the activation of mammalian NO-sensitive guanylyl cyclase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nioche, Pierre -- Berka, Vladimir -- Vipond, Julia -- Minton, Nigel -- Tsai, Ah-Lim -- Raman, C S -- AY343540/PHS HHS/ -- R01 AI054444/AI/NIAID NIH HHS/ -- R01 AI054444-05/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1550-3. Epub 2004 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Research Center and Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15472039" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Aerobiosis ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Bacterial Proteins/chemistry/metabolism ; Biological Evolution ; Carrier Proteins/*chemistry/genetics/*metabolism ; Chemotaxis ; Chlamydomonas reinhardtii/chemistry/genetics/metabolism ; Cloning, Molecular ; Clostridium botulinum/*chemistry/genetics/*metabolism ; Crystallography, X-Ray ; Electron Spin Resonance Spectroscopy ; Escherichia coli/genetics/growth & development ; Guanylate Cyclase ; Heme/chemistry/metabolism ; Hemeproteins/*chemistry/genetics/*metabolism ; Humans ; Hydrogen Bonding ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Nitric Oxide/*metabolism ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protoporphyrins/analysis/metabolism ; Receptors, Cytoplasmic and Nuclear/chemistry/metabolism ; Sequence Alignment ; Signal Transduction ; Static Electricity ; Thermoanaerobacter/chemistry
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 34
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-11-06
    Beschreibung: Syntaxin, synaptosome-associated protein of 25 kD (SNAP25), and vesicle-associated membrane protein/synaptobrevin are collectively called SNAP receptor (SNARE) proteins, and they catalyze neuronal exocytosis by forming a "core complex." The steps in core complex formation are unknown. Here, we monitored SNARE complex formation in vivo with the use of a fluorescent version of SNAP25. In PC12 cells, we found evidence for a syntaxin-SNAP25 complex that formed with high affinity, required only the amino-terminal SNARE motif of SNAP25, tolerated a mutation that blocks formation of other syntaxin-SNAP25 complexes, and assembled reversibly when Ca2+ entered cells during depolarization. The complex may represent a precursor to the core complex formed during a Ca2+-dependent priming step of exocytosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉An, Seong J -- Almers, Wolfhard -- MH60600/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2004 Nov 5;306(5698):1042-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute L-474, Oregon Health Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15528447" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adrenal Medulla/cytology ; Animals ; Bacterial Proteins ; Cell Line ; Fluorescence Resonance Energy Transfer ; Green Fluorescent Proteins ; Humans ; Luminescent Proteins ; Membrane Proteins/genetics/physiology ; Nerve Tissue Proteins/genetics/physiology ; PC12 Cells ; Qa-SNARE Proteins ; Rats ; Recombinant Fusion Proteins ; SNARE Proteins ; Synaptosomal-Associated Protein 25 ; Vesicular Transport Proteins/*physiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 35
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-05-15
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Normile, Dennis -- New York, N.Y. -- Science. 2004 May 14;304(5673):945.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15143251" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Authorship ; Cell Line ; Cloning, Organism/*ethics/legislation & jurisprudence ; *Embryo Research ; Embryo, Mammalian/*cytology ; Ethics Committees, Research ; *Ethics, Research ; Female ; Humans ; Korea ; Research Support as Topic ; *Stem Cells ; Tissue Donors
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 36
    Publikationsdatum: 2004-02-14
    Beschreibung: Cell-to-cell communication is a crucial prerequisite for the development and maintenance of multicellular organisms. To date, diverse mechanisms of intercellular exchange of information have been documented, including chemical synapses, gap junctions, and plasmodesmata. Here, we describe highly sensitive nanotubular structures formed de novo between cells that create complex networks. These structures facilitate the selective transfer of membrane vesicles and organelles but seem to impede the flow of small molecules. Accordingly, we propose a novel biological principle of cell-to-cell interaction based on membrane continuity and intercellular transfer of organelles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rustom, Amin -- Saffrich, Rainer -- Markovic, Ivanka -- Walther, Paul -- Gerdes, Hans-Hermann -- New York, N.Y. -- Science. 2004 Feb 13;303(5660):1007-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Interdisciplinary Center of Neuroscience (IZN), Institute of Neurobiology, University of Heidelberg, INF 364, Heidelberg 69120, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14963329" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Actins/metabolism ; Animals ; Biological Transport ; Carbocyanines/metabolism ; *Cell Communication ; Cell Line ; Cell Membrane/metabolism ; Cell Surface Extensions/*metabolism/*ultrastructure ; Endocytosis ; Endosomes/metabolism ; Fluorescent Dyes/metabolism ; Green Fluorescent Proteins ; Luminescent Proteins/metabolism ; Membrane Proteins/metabolism ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Microscopy, Video ; Organelles/*metabolism ; PC12 Cells ; Protein Prenylation ; Protein Transport ; Pseudopodia/metabolism/ultrastructure ; Rats ; Recombinant Fusion Proteins/metabolism ; Synaptophysin/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 37
    Publikationsdatum: 2004-12-18
    Beschreibung: The inositol pyrophosphates IP7 and IP8 contain highly energetic pyrophosphate bonds. Although implicated in various biologic functions, their molecular sites of action have not been clarified. Using radiolabeled IP7, we detected phosphorylation of multiple eukaryotic proteins. We also observed phosphorylation of endogenous proteins by endogenous IP7 in yeast. Phosphorylation by IP7 is nonenzymatic and may represent a novel intracellular signaling mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saiardi, Adolfo -- Bhandari, Rashna -- Resnick, Adam C -- Snowman, Adele M -- Snyder, Solomon H -- DA00074/DA/NIDA NIH HHS/ -- MH068830-02/MH/NIMH NIH HHS/ -- MH18501/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 17;306(5704):2101-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15604408" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Drosophila Proteins/metabolism ; Drosophila melanogaster ; Escherichia coli Proteins/metabolism ; Humans ; Inositol Phosphates/*metabolism ; Kinetics ; Magnesium/metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/chemistry/*metabolism ; Phosphates/metabolism ; Phosphorylation ; Phosphotransferases (Phosphate Group Acceptor)/metabolism ; Protein Kinases/genetics/metabolism ; Proteins/*metabolism ; RNA-Binding Proteins/chemistry/*metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Serine/metabolism ; Signal Transduction ; Temperature
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 38
    Publikationsdatum: 2004-12-14
    Beschreibung: Malaria parasites secrete proteins across the vacuolar membrane into the erythrocyte, inducing modifications linked to disease and parasite survival. We identified an 11-amino acid signal required for the secretion of proteins from the Plasmodium falciparum vacuole to the human erythrocyte. Bioinformatics predicted a secretome of 〉320 proteins and conservation of the signal across parasite species. Functional studies indicated the predictive value of the signal and its role in targeting virulence proteins to the erythrocyte and implicated its recognition by a receptor/transporter. Erythrocyte modification by the parasite may involve plasmodial heat shock proteins and be vastly more complex than hitherto realized.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hiller, N Luisa -- Bhattacharjee, Souvik -- van Ooij, Christiaan -- Liolios, Konstantinos -- Harrison, Travis -- Lopez-Estrano, Carlos -- Haldar, Kasturi -- AI39071/AI/NIAID NIH HHS/ -- HL69630/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 10;306(5703):1934-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pathology and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15591203" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Computational Biology ; Cytosol/metabolism ; Erythrocytes/*metabolism/parasitology ; Genes, Protozoan ; Humans ; Malaria, Falciparum/parasitology ; Membrane Proteins/chemistry/metabolism ; Molecular Sequence Data ; Plasmodium falciparum/genetics/growth & development/*metabolism/*pathogenicity ; *Protein Sorting Signals ; Protein Structure, Tertiary ; Protein Transport ; Protozoan Proteins/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Transgenes ; Vacuoles/metabolism/parasitology ; Virulence Factors/chemistry/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 39
    Publikationsdatum: 2004-09-14
    Beschreibung: The first structure of an ammonia channel from the Amt/MEP/Rh protein superfamily, determined to 1.35 angstrom resolution, shows it to be a channel that spans the membrane 11 times. Two structurally similar halves span the membrane with opposite polarity. Structures with and without ammonia or methyl ammonia show a vestibule that recruits NH4+/NH3, a binding site for NH4+, and a 20 angstrom-long hydrophobic channel that lowers the NH4+ pKa to below 6 and conducts NH3. Favorable interactions for NH3 are seen within the channel and use conserved histidines. Reconstitution of AmtB into vesicles shows that AmtB conducts uncharged NH3.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khademi, Shahram -- O'Connell, Joseph 3rd -- Remis, Jonathan -- Robles-Colmenares, Yaneth -- Miercke, Larry J W -- Stroud, Robert M -- GM24485/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Sep 10;305(5690):1587-94.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, S412C Genentech Hall, University of California-San Francisco, 600 16th Street, San Francisco, CA 94143-2240, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15361618" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Ammonia/*metabolism ; Binding Sites ; Biological Transport ; Cation Transport Proteins/*chemistry/genetics/metabolism ; Cell Membrane/chemistry ; Crystallization ; Crystallography, X-Ray ; Escherichia coli/*chemistry/metabolism ; Escherichia coli Proteins/*chemistry/genetics/metabolism ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Hydrophobic and Hydrophilic Interactions ; Liposomes ; Membrane Potentials ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Quaternary Ammonium Compounds/metabolism ; Rh-Hr Blood-Group System/chemistry/metabolism ; Sequence Alignment ; Water/chemistry/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 40
    Publikationsdatum: 2004-11-20
    Beschreibung: Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zimmermann, Robert -- Strauss, Juliane G -- Haemmerle, Guenter -- Schoiswohl, Gabriele -- Birner-Gruenberger, Ruth -- Riederer, Monika -- Lass, Achim -- Neuberger, Georg -- Eisenhaber, Frank -- Hermetter, Albin -- Zechner, Rudolf -- New York, N.Y. -- Science. 2004 Nov 19;306(5700):1383-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biosciences, University of Graz, Graz, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15550674" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 3T3-L1 Cells ; Adipocytes/enzymology/*metabolism ; Adipose Tissue/enzymology/*metabolism ; Adipose Tissue, Brown/enzymology/metabolism ; Amino Acid Sequence ; Animals ; COS Cells ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytoplasm/enzymology ; DNA, Complementary ; Diglycerides/metabolism ; Fatty Acids/metabolism ; Gene Silencing ; Glycerol/metabolism ; Humans ; Isoproterenol/pharmacology ; *Lipid Mobilization ; Lipolysis ; Lipoprotein Lipase/chemistry/genetics/immunology/*metabolism ; Mice ; Molecular Sequence Data ; Phosphorylation ; Protein Structure, Tertiary ; RNA, Messenger/genetics/metabolism ; Sterol Esterase/genetics/*metabolism ; Substrate Specificity ; Transfection ; Triglycerides/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 41
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-02-21
    Beschreibung: Cyclic nucleotides regulate axonal responses to a number of guidance cues through unknown molecular events. We report here that Drosophila nervy, a member of the myeloid translocation gene family of A kinase anchoring proteins (AKAPs), regulates repulsive axon guidance by linking the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) to the Semaphorin 1a (Sema-1a) receptor Plexin A (PlexA). Nervy and PKA antagonize Sema-1a-PlexA-mediated repulsion, and the AKAP binding region of Nervy is critical for this effect. Thus, Nervy couples cAMP-PKA signaling to PlexA to regulate Sema-1a-mediated axonal repulsion, revealing a simple molecular mechanism that allows growing axons to integrate inputs from multiple guidance cues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Terman, Jonathan R -- Kolodkin, Alex L -- New York, N.Y. -- Science. 2004 Feb 20;303(5661):1204-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins University School of Medicine, 1001 PCTB/725 North Wolfe Street, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14976319" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Animals, Genetically Modified ; Axons/*physiology/ultrastructure ; Carrier Proteins/chemistry/*metabolism ; Central Nervous System/embryology ; Cues ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; Drosophila/cytology/*embryology/genetics/metabolism ; Drosophila Proteins/chemistry/*metabolism ; Embryo, Nonmammalian/cytology/metabolism/physiology ; Molecular Sequence Data ; Motor Neurons/metabolism/*physiology/ultrastructure ; Muscles/embryology/innervation/metabolism ; Mutation ; Nerve Tissue Proteins/*metabolism ; Neural Pathways ; Phenotype ; Receptors, Cell Surface/*metabolism ; Semaphorins/*metabolism ; Signal Transduction ; Transgenes
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 42
    Publikationsdatum: 2004-02-07
    Beschreibung: Microtubule (MT) stabilization is regulated by the small guanosine triphosphate (GTP)-binding protein Rho and its effector, mammalian homolog of Diaphanous (mDia), in migrating cells, but factors responsible for localized stabilization at the leading edge are unknown. We report that integrin-mediated activation of focal adhesion kinase (FAK) at the leading edge is required for MT stabilization by the Rho-mDia signaling pathway in mouse fibroblasts. MT stabilization also involved FAK-regulated localization of a lipid raft marker, ganglioside GM1, to the leading edge. The integrin-FAK signaling pathway may facilitate Rho-mDia signaling through GM1, or through a specialized membrane domain containing GM1, to stabilize MTs in the leading edge of migrating cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palazzo, Alexander F -- Eng, Christina H -- Schlaepfer, David D -- Marcantonio, Eugene E -- Gundersen, Gregg G -- CA87038/CA/NCI NIH HHS/ -- GM 44585/GM/NIGMS NIH HHS/ -- GM 62939/GM/NIGMS NIH HHS/ -- GM 68695/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):836-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764879" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylation ; Animals ; Carrier Proteins/metabolism ; Cell Adhesion ; Cell Line ; Cell Membrane/*metabolism ; Cholesterol/metabolism ; Fibronectins/metabolism/pharmacology ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; G(M1) Ganglioside/metabolism ; Glycosylphosphatidylinositols/metabolism ; Integrins/*metabolism ; Membrane Microdomains/*metabolism ; Mice ; Mice, Knockout ; Microtubules/*metabolism/ultrastructure ; NIH 3T3 Cells ; Phosphorylation ; Protein-Tyrosine Kinases/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Tubulin/metabolism ; rho GTP-Binding Proteins/*metabolism ; rhoA GTP-Binding Protein/genetics/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 43
    Publikationsdatum: 2004-05-08
    Beschreibung: Over 99% of modern animals are members of the evolutionary lineage Bilateria. The evolutionary success of Bilateria is credited partly to the origin of bilateral symmetry. Although animals of the phylum Cnidaria are not within the Bilateria, some representatives, such as the sea anemone Nematostella vectensis, exhibit bilateral symmetry. We show that Nematostella uses homologous genes to achieve bilateral symmetry: Multiple Hox genes are expressed in a staggered fashion along its primary body axis, and the transforming growth factor-beta gene decapentaplegic (dpp) is expressed in an asymmetric fashion about its secondary body axis. These data suggest that bilateral symmetry arose before the evolutionary split of Cnidaria and Bilateria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finnerty, John R -- Pang, Kevin -- Burton, Pat -- Paulson, Dave -- Martindale, Mark Q -- New York, N.Y. -- Science. 2004 May 28;304(5675):1335-7. Epub 2004 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15131263" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Body Patterning ; Endoderm/physiology ; Gene Duplication ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genes ; *Genes, Homeobox ; In Situ Hybridization ; Larva/genetics/growth & development ; Molecular Sequence Data ; Phylogeny ; Sea Anemones/*anatomy & histology/embryology/*genetics/growth & development
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 44
    Publikationsdatum: 2004-12-18
    Beschreibung: Mammalian mitochondrial DNA (mtDNA) replication has long been considered to occur by asymmetric synthesis of the two strands, starting at the multiple origins of the strand-displacement loop (D-loop). We report the discovery of a major replication origin at position 57 in the D-loop of several human cell lines (HeLa, A549, and 143B.TK-) and immortalized lymphocytes. The nascent chains starting at this origin, in contrast to those initiated at the previously described origins, do not terminate prematurely at the 3' end of the D-loop but proceed well beyond this control point, behaving as "true" replicating strands. This origin is mainly responsible for mtDNA maintenance under steady-state conditions, whereas mtDNA synthesis from the formerly identified D-loop origins may be more important for recovery after mtDNA depletion and for accelerating mtDNA replication in response to physiological demands.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fish, Jennifer -- Raule, Nicola -- Attardi, Giuseppe -- GM11726/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 17;306(5704):2098-101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15604407" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Cell Line ; Cell Line, Tumor ; DNA Primers/metabolism ; DNA Probes ; *DNA Replication ; DNA, Mitochondrial/*biosynthesis/chemistry/metabolism ; DNA-Directed DNA Polymerase/metabolism ; Electrophoresis, Polyacrylamide Gel ; Ethidium/pharmacology ; HeLa Cells ; Humans ; Lymphocytes/metabolism ; Nucleic Acid Conformation ; Polymerase Chain Reaction ; *Replication Origin
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 45
    Publikationsdatum: 2004-10-23
    Beschreibung: Despite evidence that protein kinases are regulators of apoptosis, a specific role for phosphatases in regulating cell survival has not been established. Here we show that alpha4, a noncatalytic subunit of protein phosphatase 2A (PP2A), is required to repress apoptosis in murine cells. alpha4 is a nonredundant regulator of the dephosphorylation of the transcription factors c-Jun and p53. As a result of alpha4 deletion, multiple proapoptotic genes were transcribed. Either inhibition of new protein synthesis or Bcl-xL overexpression suppressed apoptosis initiated by alpha4 deletion. Thus, mammalian cell viability depends on repression of transcription-initiated apoptosis mediated by a component of PP2A.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Mei -- Fox, Casey J -- Mu, James -- Solt, Laura -- Xu, Anne -- Cinalli, Ryan M -- Birnbaum, Morris J -- Lindsten, Tullia -- Thompson, Craig B -- New York, N.Y. -- Science. 2004 Oct 22;306(5696):695-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15499020" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adipocytes/cytology ; Animals ; *Apoptosis ; Cell Differentiation ; Cell Line ; Cell Survival ; Cells, Cultured ; Cycloheximide/pharmacology ; Gene Deletion ; Gene Expression Profiling ; Liver/cytology/metabolism ; Mice ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; PPAR gamma/metabolism ; Phosphoprotein Phosphatases/*metabolism ; Phosphoproteins/*metabolism ; Phosphorylation ; Protein Phosphatase 2 ; Protein Synthesis Inhibitors/pharmacology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-jun/metabolism ; Transcription, Genetic ; Tumor Suppressor Protein p53/metabolism ; bcl-X Protein
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 46
    Publikationsdatum: 2004-04-17
    Beschreibung: Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Valente, Enza Maria -- Abou-Sleiman, Patrick M -- Caputo, Viviana -- Muqit, Miratul M K -- Harvey, Kirsten -- Gispert, Suzana -- Ali, Zeeshan -- Del Turco, Domenico -- Bentivoglio, Anna Rita -- Healy, Daniel G -- Albanese, Alberto -- Nussbaum, Robert -- Gonzalez-Maldonado, Rafael -- Deller, Thomas -- Salvi, Sergio -- Cortelli, Pietro -- Gilks, William P -- Latchman, David S -- Harvey, Robert J -- Dallapiccola, Bruno -- Auburger, Georg -- Wood, Nicholas W -- G-4029/Parkinson's UK/United Kingdom -- GGP02089/Telethon/Italy -- New York, N.Y. -- Science. 2004 May 21;304(5674):1158-60. Epub 2004 Apr 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CSS IRCCS, Mendel Institute, viale Regina Margherita 261, 00198 Rome, Italy. e.valente@css-mendel.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15087508" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Apoptosis ; COS Cells ; Cell Line, Tumor ; Codon, Nonsense ; Exons ; Humans ; Leupeptins/pharmacology ; Membrane Potentials ; Mitochondria/enzymology/*metabolism ; Molecular Sequence Data ; *Mutation ; Mutation, Missense ; Neurons/metabolism/physiology ; Oxidative Stress ; Parkinson Disease/enzymology/*genetics/metabolism ; Protein Kinases/chemistry/*genetics/*metabolism ; Protein Structure, Tertiary ; Transfection
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 47
    Publikationsdatum: 2004-12-04
    Beschreibung: The degradation of undesirable cellular components or organelles, including invading microbes, by autophagy is crucial for cell survival. Here, Shigella, an invasive bacteria, was found to be able to escape autophagy by secreting IcsB by means of the type III secretion system. Mutant bacteria lacking IcsB were trapped by autophagy during multiplication within the host cells. IcsB did not directly inhibit autophagy. Rather, Shigella VirG, a protein required for intracellular actin-based motility, induced autophagy by binding to the autophagy protein, Atg5. In nonmutant Shigella, this binding is competitively inhibited by IcsB binding to VirG.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ogawa, Michinaga -- Yoshimori, Tamotsu -- Suzuki, Toshihiko -- Sagara, Hiroshi -- Mizushima, Noboru -- Sasakawa, Chihiro -- New York, N.Y. -- Science. 2005 Feb 4;307(5710):727-31. Epub 2004 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Institute of Medical Science, 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/15576571" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *Autophagy ; Bacterial Proteins/genetics/*metabolism ; Cell Line ; DNA-Binding Proteins/*metabolism ; Humans ; Mice ; Mice, Knockout ; Microscopy, Electron ; Microtubule-Associated Proteins/metabolism ; Phagosomes/metabolism/*microbiology/ultrastructure ; Protein Binding ; Recombinant Fusion Proteins/metabolism ; Shigella flexneri/genetics/growth & development/metabolism/*pathogenicity ; Transcription Factors/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 48
    Publikationsdatum: 2004-08-07
    Beschreibung: Vesicle fusion involves vesicle tethering, docking, and membrane merger. We show that mitofusin, an integral mitochondrial membrane protein, is required on adjacent mitochondria to mediate fusion, which indicates that mitofusin complexes act in trans (that is, between adjacent mitochondria). A heptad repeat region (HR2) mediates mitofusin oligomerization by assembling a dimeric, antiparallel coiled coil. The transmembrane segments are located at opposite ends of the 95 angstrom coiled coil and provide a mechanism for organelle tethering. Consistent with this proposal, truncated mitofusin, in an HR2-dependent manner, causes mitochondria to become apposed with a uniform gap. Our results suggest that HR2 functions as a mitochondrial tether before fusion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koshiba, Takumi -- Detmer, Scott A -- Kaiser, Jens T -- Chen, Hsiuchen -- McCaffery, J Michael -- Chan, David C -- R01 GM62967/GM/NIGMS NIH HHS/ -- S10 RR019409-01/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2004 Aug 6;305(5685):858-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, 1200 East California Boulevard, MC114-96, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15297672" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Cell Line ; Crystallography, X-Ray ; Dimerization ; GTP Phosphohydrolases/*chemistry/*metabolism ; Humans ; Hybrid Cells ; Hydrophobic and Hydrophilic Interactions ; Intracellular Membranes/physiology/ultrastructure ; Membrane Fusion ; Mice ; Mitochondria/*metabolism/ultrastructure ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Structure, Secondary ; Protein Structure, Tertiary
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 49
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-10-23
    Beschreibung: Relatively little is known about the importance of amino acid interactions in protein and phenotypic evolution. Here we examine whether mutations that are pathogenic in Drosophila melanogaster become fixed via epistasis in other Dipteran genomes. Overall divergence at pathogenic amino acid sites is reduced. However, approximately 10% of the substitutions at these sites carry the exact same pathogenic amino acid found in D. melanogaster mutants. Hence compensatory mutation(s) must have evolved. Surprisingly, the fraction 10% is not affected by phylogenetic distance. These results support a selection-driven process that allows compensated amino acid substitutions to become rapidly fixed in taxa with large populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kulathinal, Rob J -- Bettencourt, Brian R -- Hartl, Daniel L -- GM068465/GM/NIGMS NIH HHS/ -- P41-HG00739/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1553-4. Epub 2004 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15498973" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Anopheles gambiae/*genetics ; Codon, Nonsense ; Drosophila/*genetics ; Drosophila melanogaster/*genetics ; Epistasis, Genetic ; *Evolution, Molecular ; Genes, Insect ; *Genome ; Insect Proteins/chemistry/*genetics ; Molecular Sequence Data ; *Mutation ; Mutation, Missense ; Phenotype ; Phylogeny ; Selection, Genetic ; Sequence Alignment
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 50
    Publikationsdatum: 2004-04-03
    Beschreibung: Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Qin -- Goderie, Susan K -- Jin, Li -- Karanth, Nithin -- Sun, Yu -- Abramova, Natalia -- Vincent, Peter -- Pumiglia, Kevin -- Temple, Sally -- R01 CA081419/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2004 May 28;304(5675):1338-40. Epub 2004 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15060285" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Astrocytes/cytology/physiology ; Cattle ; Cell Adhesion ; *Cell Communication ; Cell Differentiation ; Cell Division ; Cell Line ; Cell Lineage ; Cells, Cultured ; Cerebral Cortex/embryology ; Clone Cells/physiology ; Coculture Techniques ; Embryo, Mammalian/cytology ; Endothelial Cells/cytology/*physiology ; Endothelium, Vascular/cytology ; Fibroblast Growth Factor 2/pharmacology ; Mice ; Muscle, Smooth, Vascular/cytology/physiology ; Myocytes, Smooth Muscle/cytology/physiology ; Neurons/cytology/*physiology ; Oligodendroglia/cytology/physiology ; Signal Transduction ; Stem Cells/cytology/*physiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 51
    Publikationsdatum: 2004-11-13
    Beschreibung: Plants under oxidative stress suffer from damages that have been interpreted as unavoidable consequences of injuries inflicted upon plants by toxic levels of reactive oxygen species (ROS). However, this paradigm needs to be modified. Inactivation of a single gene, EXECUTER1, is sufficient to abrogate stress responses of Arabidopsis thaliana caused by the release of singlet oxygen: External conditions under which these stress responses are observed and the amounts of ROS that accumulate in plants exposed to these environmental conditions do not directly cause damages. Instead, seedling lethality and growth inhibition of mature plants result from genetic programs that are activated after the release of singlet oxygen has been perceived by the plant.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wagner, Daniela -- Przybyla, Dominika -- Op den Camp, Roel -- Kim, Chanhong -- Landgraf, Frank -- Lee, Keun Pyo -- Wursch, Marco -- Laloi, Christophe -- Nater, Mena -- Hideg, Eva -- Apel, Klaus -- New York, N.Y. -- Science. 2004 Nov 12;306(5699):1183-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Sciences, Plant Genetics, Swiss Federal Institute of Technology (ETH), CH-8092 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15539603" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Arabidopsis/cytology/*genetics/growth & development/*physiology ; Arabidopsis Proteins/chemistry/*genetics/*physiology ; Cell Death/drug effects ; Chromosome Mapping ; Cloning, Molecular ; Cosmids ; Darkness ; Diuron/pharmacology ; Gene Expression Regulation, Plant ; Genes, Plant ; Genetic Complementation Test ; Light ; Molecular Sequence Data ; Mutation ; Open Reading Frames ; *Oxidative Stress ; Photosystem II Protein Complex/metabolism ; Plant Leaves/cytology/drug effects/metabolism ; Reactive Oxygen Species/metabolism ; Singlet Oxygen/*metabolism ; Transformation, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 52
    Publikationsdatum: 2004-05-25
    Beschreibung: Pathogenic mycobacteria resist lysosomal delivery after uptake into macrophages, allowing them to survive intracellularly. We found that the eukaryotic-like serine/threonine protein kinase G from pathogenic mycobacteria was secreted within macrophage phagosomes, inhibiting phagosome-lysosome fusion and mediating intracellular survival of mycobacteria. Inactivation of protein kinase G by gene disruption or chemical inhibition resulted in lysosomal localization and mycobacterial cell death in infected macrophages. Besides identifying a target for the control of mycobacterial infections, these findings suggest that pathogenic mycobacteria have evolved eukaryotic-like signal transduction mechanisms capable of modulating host cell trafficking pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walburger, Anne -- Koul, Anil -- Ferrari, Giorgio -- Nguyen, Liem -- Prescianotto-Baschong, Cristina -- Huygen, Kris -- Klebl, Bert -- Thompson, Charles -- Bacher, Gerald -- Pieters, Jean -- New York, N.Y. -- Science. 2004 Jun 18;304(5678):1800-4. Epub 2004 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biozentrum, University of Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15155913" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amides/pharmacology ; Animals ; Cell Line ; Cyclic GMP-Dependent Protein Kinases/antagonists & ; inhibitors/genetics/*metabolism ; Enzyme Inhibitors/pharmacology ; Gene Deletion ; Lysosomes/microbiology/physiology ; Macrophages/drug effects/*microbiology/ultrastructure ; Mice ; Mycobacterium bovis/drug effects/*enzymology/*growth & development/pathogenicity ; Mycobacterium smegmatis/enzymology/genetics/pathogenicity/physiology ; Mycobacterium tuberculosis/drug effects/enzymology/growth & ; development/pathogenicity ; Phagosomes/enzymology/*microbiology/physiology ; Signal Transduction ; Thiophenes/pharmacology ; Vacuoles/microbiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 53
    Publikationsdatum: 2004-10-23
    Beschreibung: A waxy protective cuticle coats all primary aerial plant tissues. Its synthesis requires extensive export of lipids from epidermal cells to the plant surface. Arabidopsis cer5 mutants had reduced stem cuticular wax loads and accumulated sheetlike inclusions in the cytoplasm of wax-secreting cells. These inclusions represented abnormal deposits of cuticular wax and resembled inclusions found in a human disorder caused by a defective peroxisomal adenosine triphosphate binding cassette (ABC) transporter. We found that the CER5 gene encodes an ABC transporter localized in the plasma membrane of epidermal cells and conclude that it is required for wax export to the cuticle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pighin, Jamie A -- Zheng, Huanquan -- Balakshin, Laura J -- Goodman, Ian P -- Western, Tamara L -- Jetter, Reinhard -- Kunst, Ljerka -- Samuels, A Lacey -- New York, N.Y. -- Science. 2004 Oct 22;306(5696):702-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Botany, University of British Columbia (UBC), 6270 University Boulevard, Vancouver, BC V6T 1Z4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15499022" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): ATP-Binding Cassette Transporters/chemistry/genetics/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/cytology/genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Biological Transport, Active ; Cell Membrane/metabolism ; Cloning, Molecular ; Dimerization ; Genes, Plant ; Inclusion Bodies/ultrastructure ; *Lipid Metabolism ; Microscopy, Electron ; Molecular Sequence Data ; Mutagenesis, Insertional ; Mutation ; Plant Epidermis/cytology/*metabolism/ultrastructure ; Plant Stems/cytology/metabolism/ultrastructure ; Plants, Genetically Modified ; Recombinant Fusion Proteins/metabolism ; Vacuoles/ultrastructure ; Waxes/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 54
    Publikationsdatum: 2004-06-26
    Beschreibung: Arrestin regulates almost all G protein-coupled receptor (GPCR)-mediated signaling and trafficking. We report that the multidomain protein, spinophilin, antagonizes these multiple arrestin functions. Through blocking G protein receptor kinase 2 (GRK2) association with receptor-Gbetagamma complexes, spinophilin reduces arrestin-stabilized receptor phosphorylation, receptor endocytosis, and the acceleration of mitogen-activated protein kinase (MAPK) activity following endocytosis. Spinophilin knockout mice were more sensitive than wild-type mice to sedation elicited by stimulation of alpha2 adrenergic receptors, whereas arrestin 3 knockout mice were more resistant, indicating that the signal-promoting, rather than the signal-terminating, roles of arrestin are more important for certain response pathways. The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanism for fine-tuning complex receptor-orchestrated cell signaling and responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Qin -- Zhao, Jiali -- Brady, Ashley E -- Feng, Jian -- Allen, Patrick B -- Lefkowitz, Robert J -- Greengard, Paul -- Limbird, Lee E -- DA10044/DA/NIDA NIH HHS/ -- DK43879/DK/NIDDK NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- HL42671/HL/NHLBI NIH HHS/ -- MH40899/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2004 Jun 25;304(5679):1940-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Center of Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15218143" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine/*analogs & derivatives/pharmacology ; Adrenergic alpha-Agonists/pharmacology ; Animals ; Arrestin/*antagonists & inhibitors/*metabolism ; Arrestins/genetics/metabolism ; Cell Line ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Endocytosis ; Enzyme Activation ; Epinephrine/pharmacology ; G-Protein-Coupled Receptor Kinase 3 ; GTP-Binding Proteins/*metabolism ; Humans ; MAP Kinase Signaling System ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microfilament Proteins/genetics/*metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Motor Activity ; Nerve Tissue Proteins/genetics/*metabolism ; Phosphorylation ; Receptors, Adrenergic, alpha-2/*metabolism ; Rotarod Performance Test ; Signal Transduction ; Transfection ; beta-Adrenergic Receptor Kinases
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 55
    Publikationsdatum: 2004-09-04
    Beschreibung: Methylation of arginine (Arg) and lysine residues in histones has been correlated with epigenetic forms of gene regulation. Although histone methyltransferases are known, enzymes that demethylate histones have not been identified. Here, we demonstrate that human peptidylarginine deiminase 4 (PAD4) regulates histone Arg methylation by converting methyl-Arg to citrulline and releasing methylamine. PAD4 targets multiple sites in histones H3 and H4, including those sites methylated by coactivators CARM1 (H3 Arg17) and PRMT1 (H4 Arg3). A decrease of histone Arg methylation, with a concomitant increase of citrullination, requires PAD4 activity in human HL-60 granulocytes. Moreover, PAD4 activity is linked with the transcriptional regulation of estrogen-responsive genes in MCF-7 cells. These data suggest that PAD4 mediates gene expression by regulating Arg methylation and citrullination in histones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yanming -- Wysocka, Joanna -- Sayegh, Joyce -- Lee, Young-Ho -- Perlin, Julie R -- Leonelli, Lauriebeth -- Sonbuchner, Lakshmi S -- McDonald, Charles H -- Cook, Richard G -- Dou, Yali -- Roeder, Robert G -- Clarke, Steven -- Stallcup, Michael R -- Allis, C David -- Coonrod, Scott A -- DK55274/DK/NIDDK NIH HHS/ -- GM R01 26020/GM/NIGMS NIH HHS/ -- GM R01 50659/GM/NIGMS NIH HHS/ -- HD R01 38353/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2004 Oct 8;306(5694):279-83. Epub 2004 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15345777" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Arginine/*metabolism ; Blotting, Western ; Calcimycin/pharmacology ; Cell Line, Tumor ; Citrulline/metabolism ; Gene Expression Regulation ; Genes, Reporter ; HL-60 Cells ; Histones/*metabolism ; Humans ; Hydrolases/*metabolism ; Ionophores/pharmacology ; Membrane Proteins/genetics ; Methylamines/metabolism ; Methylation ; Molecular Sequence Data ; Presenilin-2 ; Promoter Regions, Genetic ; Protein-Arginine N-Methyltransferases/metabolism ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 56
    Publikationsdatum: 2004-12-14
    Beschreibung: Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crabbe, Laure -- Verdun, Ramiro E -- Haggblom, Candy I -- Karlseder, Jan -- GM069525/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 10;306(5703):1951-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15591207" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alleles ; Anaphase ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins ; Cell Line ; Cells, Cultured ; Chromatids/metabolism ; Chromosomes, Human/physiology ; DNA Damage ; DNA Helicases/genetics/*metabolism ; DNA-Binding Proteins ; Exodeoxyribonucleases ; Genomic Instability ; HeLa Cells ; Humans ; In Situ Hybridization, Fluorescence ; Models, Genetic ; Mutation ; Protein-Serine-Threonine Kinases/metabolism ; RecQ Helicases ; S Phase ; Telomerase/metabolism ; Telomere/*metabolism ; Tumor Suppressor Proteins ; Werner Syndrome/*genetics
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 57
    Publikationsdatum: 2004-09-18
    Beschreibung: Cell migration initiates by extension of the actin cytoskeleton at the leading edge. Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed this process is mediated by two spatially colocalized but kinematically, kinetically, molecularly, and functionally distinct actin networks. A lamellipodium network assembled at the leading edge but completely disassembled within 1 to 3 micrometers. It was weakly coupled to the rest of the cytoskeleton and promoted the random protrusion and retraction of the leading edge. Productive cell advance was a function of the second colocalized network, the lamella, where actomyosin contraction was integrated with substrate adhesion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ponti, A -- Machacek, M -- Gupton, S L -- Waterman-Storer, C M -- Danuser, G -- GM67230/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Sep 17;305(5691):1782-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15375270" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Actin Cytoskeleton/drug effects/*physiology ; Actins/*physiology ; Animals ; Cell Line ; *Cell Movement ; Cells, Cultured ; Cytochalasin D/pharmacology ; *Depsipeptides ; Epithelial Cells/*physiology/ultrastructure ; Heterocyclic Compounds with 4 or More Rings/pharmacology ; Kinetics ; Macropodidae ; Microscopy, Fluorescence ; Motion Pictures as Topic ; Peptides, Cyclic/pharmacology ; Pseudopodia/*physiology/ultrastructure ; Salamandridae
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 58
    Publikationsdatum: 2004-04-10
    Beschreibung: Ventricular arrhythmias can cause sudden cardiac death (SCD) in patients with normal hearts and in those with underlying disease such as heart failure. In animals with heart failure and in patients with inherited forms of exercise-induced SCD, depletion of the channel-stabilizing protein calstabin2 (FKBP12.6) from the ryanodine receptor-calcium release channel (RyR2) complex causes an intracellular Ca2+ leak that can trigger fatal cardiac arrhythmias. A derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the closed state of RyR2 and prevented the Ca2+ leak that triggers arrhythmias. Thus, enhancing the binding of calstabin2 to RyR2 may be a therapeutic strategy for common ventricular arrhythmias.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wehrens, Xander H T -- Lehnart, Stephan E -- Reiken, Steven R -- Deng, Shi-Xian -- Vest, John A -- Cervantes, Daniel -- Coromilas, James -- Landry, Donald W -- Marks, Andrew R -- New York, N.Y. -- Science. 2004 Apr 9;304(5668):292-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15073377" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Anti-Arrhythmia Agents/*pharmacology/therapeutic use ; Calcium/metabolism ; Calcium-Transporting ATPases/metabolism ; Cell Line ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Death, Sudden, Cardiac/prevention & control ; Electric Stimulation ; Electrocardiography ; Heart/*drug effects/physiology ; Humans ; Isoproterenol/pharmacology ; Mice ; Myocardial Contraction ; Phosphorylation ; Physical Exertion ; Protein Binding ; Ryanodine Receptor Calcium Release Channel/*metabolism ; Sarcoplasmic Reticulum/metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; Tachycardia, Ventricular/metabolism/*prevention & control ; Tacrolimus Binding Proteins/deficiency/genetics/*metabolism ; Thiazepines/*pharmacology/therapeutic use
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 59
    Publikationsdatum: 2004-07-31
    Beschreibung: Gefitinib (Iressa, Astra Zeneca Pharmaceuticals) is a tyrosine kinase inhibitor that targets the epidermal growth factor receptor (EGFR) and induces dramatic clinical responses in nonsmall cell lung cancers (NSCLCs) with activating mutations within the EGFR kinase domain. We report that these mutant EGFRs selectively activate Akt and signal transduction and activator of transcription (STAT) signaling pathways, which promote cell survival, but have no effect on extracellular signal-regulated kinase signaling, which induces proliferation. NSCLC cells expressing mutant EGFRs underwent extensive apoptosis after small interfering RNA-mediated knockdown of the mutant EGFR or treatment with pharmacological inhibitors of Akt and STAT signaling and were relatively resistant to apoptosis induced by conventional chemotherapeutic drugs. Thus, mutant EGFRs selectively transduce survival signals on which NSCLCs become dependent; inhibition of those signals by gefitinib may contribute to the drug's efficacy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sordella, Raffaella -- Bell, Daphne W -- Haber, Daniel A -- Settleman, Jeffrey -- P01 95281/PHS HHS/ -- New York, N.Y. -- Science. 2004 Aug 20;305(5687):1163-7. Epub 2004 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15284455" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antineoplastic Agents/pharmacology ; *Apoptosis ; Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/pathology ; Catalytic Domain ; Cell Line ; Cell Line, Tumor ; Cell Survival ; DNA-Binding Proteins/antagonists & inhibitors/metabolism ; Enzyme Activation ; Humans ; Lung Neoplasms/drug therapy/*genetics/pathology ; Mice ; *Milk Proteins ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Mutation, Missense ; Phosphorylation ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-akt ; Quinazolines/*pharmacology ; RNA, Small Interfering ; Receptor, Epidermal Growth Factor/*genetics/*metabolism ; STAT5 Transcription Factor ; Sequence Deletion ; Signal Transduction ; Trans-Activators/antagonists & inhibitors/metabolism ; Transfection ; Tyrosine/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 60
    Publikationsdatum: 2004-10-09
    Beschreibung: Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weng, Andrew P -- Ferrando, Adolfo A -- Lee, Woojoong -- Morris, John P 4th -- Silverman, Lewis B -- Sanchez-Irizarry, Cheryll -- Blacklow, Stephen C -- Look, A Thomas -- Aster, Jon C -- CA109901/CA/NCI NIH HHS/ -- CA21765/CA/NCI NIH HHS/ -- CA68484/CA/NCI NIH HHS/ -- CA82308/CA/NCI NIH HHS/ -- CA94233/CA/NCI NIH HHS/ -- CA98093/CA/NCI NIH HHS/ -- P01 CA109901/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2004 Oct 8;306(5694):269-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Brigham and Women'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/15472075" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adolescent ; Alleles ; Amino Acid Sequence ; Amyloid Precursor Protein Secretases ; Aspartic Acid Endopeptidases ; Cell Cycle ; Cell Line, Tumor ; Child ; Dimerization ; Endopeptidases/metabolism ; Frameshift Mutation ; Humans ; Leukemia-Lymphoma, Adult T-Cell/*genetics/metabolism ; Molecular Sequence Data ; *Mutation ; Mutation, Missense ; Point Mutation ; Protease Inhibitors/pharmacology ; Protein Structure, Tertiary ; Receptor, Notch1 ; Receptors, Cell Surface/chemistry/*genetics/metabolism ; Sequence Deletion ; Signal Transduction ; Transcription Factors/chemistry/*genetics/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 61
    Publikationsdatum: 2004-02-07
    Beschreibung: Translocation of the small GTP-binding protein Rac1 to the cell plasma membrane is essential for activating downstream effectors and requires integrin-mediated adhesion of cells to extracellular matrix. We report that active Rac1 binds preferentially to low-density, cholesterol-rich membranes, and specificity is determined at least in part by membrane lipids. Cell detachment triggered internalization of plasma membrane cholesterol and lipid raft markers. Preventing internalization maintained Rac1 membrane targeting and effector activation in nonadherent cells. Regulation of lipid rafts by integrin signals may regulate the location of membrane domains such as lipid rafts and thereby control domain-specific signaling events in anchorage-dependent cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉del Pozo, Miguel A -- Alderson, Nazilla B -- Kiosses, William B -- Chiang, Hui-Hsien -- Anderson, Richard G W -- Schwartz, Martin A -- GM52016/GM/NIGMS NIH HHS/ -- HL 20948/HL/NHLBI NIH HHS/ -- R01 GM47214/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):839-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. mdelpozo@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764880" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antigens, CD29/metabolism ; Binding Sites ; Cell Adhesion ; Cell Line ; Cell Membrane/*metabolism ; Cells, Cultured ; Cholera Toxin/metabolism ; Cholesterol/metabolism ; G(M1) Ganglioside/metabolism ; Glycosylphosphatidylinositols/metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Integrins/*metabolism ; Liposomes/metabolism ; Membrane Microdomains/*metabolism ; Mice ; NIH 3T3 Cells ; Rats ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Transfection ; rac1 GTP-Binding Protein/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 62
    Publikationsdatum: 2004-02-21
    Beschreibung: The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunet, Anne -- Sweeney, Lora B -- Sturgill, J Fitzhugh -- Chua, Katrin F -- Greer, Paul L -- Lin, Yingxi -- Tran, Hien -- Ross, Sarah E -- Mostoslavsky, Raul -- Cohen, Haim Y -- Hu, Linda S -- Cheng, Hwei-Ling -- Jedrychowski, Mark P -- Gygi, Steven P -- Sinclair, David A -- Alt, Frederick W -- Greenberg, Michael E -- NIHP30-HD18655/HD/NICHD NIH HHS/ -- P01 NS35138-17/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2004 Mar 26;303(5666):2011-5. Epub 2004 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Center for Blood Research (CBR) Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14976264" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylation ; Animals ; Apoptosis ; Cell Cycle ; Cell Line ; Cell Nucleus/metabolism ; Cells, Cultured ; Cerebellum/cytology ; Forkhead Transcription Factors ; Gene Expression Profiling ; Gene Expression Regulation ; Histone Deacetylases/genetics/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; Mice ; Mice, Knockout ; Neurons/cytology ; *Oxidative Stress ; Phosphorylation ; Proteins/genetics ; Recombinant Proteins/metabolism ; Sirtuin 1 ; Sirtuins/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 63
    Publikationsdatum: 2004-02-14
    Beschreibung: Legumes can enter into symbiotic relationships with both nitrogen-fixing bacteria (rhizobia) and mycorrhizal fungi. Nodulation by rhizobia results from a signal transduction pathway induced in legume roots by rhizobial Nod factors. DMI3, a Medicago truncatula gene that acts immediately downstream of calcium spiking in this signaling pathway and is required for both nodulation and mycorrhizal infection, has high sequence similarity to genes encoding calcium and calmodulin-dependent protein kinases (CCaMKs). This indicates that calcium spiking is likely an essential component of the signaling cascade leading to nodule development and mycorrhizal infection, and sheds light on the biological role of plant CCaMKs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levy, Julien -- Bres, Cecile -- Geurts, Rene -- Chalhoub, Boulos -- Kulikova, Olga -- Duc, Gerard -- Journet, Etienne-Pascal -- Ane, Jean-Michel -- Lauber, Emmanuelle -- Bisseling, Ton -- Denarie, Jean -- Rosenberg, Charles -- Debelle, Frederic -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1361-4. Epub 2004 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire des Interactions Plantes-Microorganismes INRA-CNRS, BP27, 31326 Castanet-Tolosan Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14963335" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Calcium/metabolism ; Calcium Signaling ; Calcium-Calmodulin-Dependent Protein Kinases/chemistry/genetics/*metabolism ; Calmodulin/metabolism ; Chromosomes, Artificial, Bacterial ; Cloning, Molecular ; EF Hand Motifs ; Expressed Sequence Tags ; Gene Expression Regulation, Plant ; Genes, Plant ; Lipopolysaccharides/metabolism ; Medicago/*enzymology/genetics/microbiology ; Molecular Sequence Data ; Mutation ; Mycorrhizae/*physiology ; Peas/*enzymology/genetics/microbiology ; Plant Roots/enzymology/microbiology ; Protein Structure, Tertiary ; Rhizobium/genetics ; Sinorhizobium meliloti/*physiology ; *Symbiosis ; Transformation, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 64
    Publikationsdatum: 2004-04-24
    Beschreibung: Acting as a signal, hydrogen peroxide circumvents antioxidant defense by overoxidizing peroxiredoxins (Prxs), the enzymes that metabolize peroxides. We show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of Prxs containing Cys-SO(2)H, thus reestablishing the antioxidant firewall. Sestrins contain a predicted redox-active domain homologous to AhpD, the enzyme catalyzing the reduction of a bacterial Prx, AhpC. Purified Hi95 (sestrin 2) protein supports adenosine triphosphate-dependent reduction of overoxidized PrxI in vitro, indicating that unlike AhpD, which is a disulfide reductase, sestrins are cysteine sulfinyl reductases. As modulators of peroxide signaling and antioxidant defense, sestrins constitute potential therapeutic targets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Budanov, Andrei V -- Sablina, Anna A -- Feinstein, Elena -- Koonin, Eugene V -- Chumakov, Peter M -- New York, N.Y. -- Science. 2004 Apr 23;304(5670):596-600.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15105503" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amino Acid Substitution ; Cell Division ; Cell Line, Tumor ; Cell Survival ; Cells, Cultured ; Heat-Shock Proteins/chemistry/genetics/*metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/chemistry/genetics/*metabolism ; Oxidation-Reduction ; Oxidoreductases/genetics/metabolism ; Peroxidases/*chemistry/*metabolism ; Peroxiredoxins ; RNA, Small Interfering ; Reactive Oxygen Species/metabolism ; Recombinant Proteins/metabolism ; Tumor Suppressor Protein p53/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 65
    Publikationsdatum: 2004-12-18
    Beschreibung: Alfalfa mosaic virus genomic RNAs are infectious only when the viral coat protein binds to the RNA 3' termini. The crystal structure of an alfalfa mosaic virus RNA-peptide complex reveals that conserved AUGC repeats and Pro-Thr-x-Arg-Ser-x-x-Tyr coat protein amino acids cofold upon interacting. Alternating AUGC residues have opposite orientation, and they base pair in different adjacent duplexes. Localized RNA backbone reversals stabilized by arginine-guanine interactions place the adenosines and guanines in reverse order in the duplex. The results suggest that a uniform, organized 3' conformation, similar to that found on viral RNAs with transfer RNA-like ends, may be essential for replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1500904/" 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/PMC1500904/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guogas, Laura M -- Filman, David J -- Hogle, James M -- Gehrke, Lee -- AI20566/AI/NIAID NIH HHS/ -- GM42504/GM/NIGMS NIH HHS/ -- R01 AI020566/AI/NIAID NIH HHS/ -- R01 GM042504/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 17;306(5704):2108-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15604410" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 3' Untranslated Regions ; Alfalfa mosaic virus/*chemistry/*physiology ; Amino Acid Sequence ; Base Pairing ; Base Sequence ; Binding Sites ; Capsid Proteins/*chemistry/metabolism ; Crystallization ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Folding ; Protein Structure, Secondary ; RNA, Viral/*chemistry/metabolism ; Repetitive Sequences, Nucleic Acid ; *Virus Replication
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 66
    Publikationsdatum: 2004-02-14
    Beschreibung: Forkhead transcription factors play key roles in the regulation of immune responses. Here, we identify a role for one member of this family, Foxj1, in the regulation of T cell activation and autoreactivity. Foxj1 deficiency resulted in multiorgan systemic inflammation, exaggerated Th1 cytokine production, and T cell proliferation in autologous mixed lymphocyte reactions. Foxj1 suppressed NF-kappaB transcription activity in vitro, and Foxj1-deficient T cells possessed increased NF-kappaB activity in vivo, correlating with the ability of Foxj1 to regulate IkappaB proteins, particularly IkappaBbeta. Thus, Foxj1 likely modulates inflammatory reactions and prevents autoimmunity by antagonizing proinflammatory transcriptional activities. These results suggest a potentially general role for forkhead genes in the enforcement of lymphocyte quiescence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Ling -- Spoor, Melanie S -- Gerth, Andrea J -- Brody, Steven L -- Peng, Stanford L -- AI01803/AI/NIAID NIH HHS/ -- AI057471/AI/NIAID NIH HHS/ -- DK52574/DK/NIDDK NIH HHS/ -- HL56244/HL/NHLBI NIH HHS/ -- HL63988/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 13;303(5660):1017-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14963332" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antigen-Presenting Cells/immunology ; Autoimmunity ; Cell Division ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Chimera ; Cytoplasm/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Forkhead Transcription Factors ; Gene Targeting ; Humans ; I-kappa B Proteins/genetics/metabolism ; *Inflammation ; Interferon-gamma/biosynthesis ; Interleukin-2/immunology ; Interleukins/biosynthesis ; *Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; NF-kappa B/antagonists & inhibitors/*metabolism ; NFATC Transcription Factors ; *Nuclear Proteins ; Th1 Cells/*immunology ; Th2 Cells/immunology ; Transcription Factors/genetics/*metabolism ; Transcriptional Activation
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  • 67
    Publikationsdatum: 2004-02-14
    Beschreibung: The structure of the general transcription factor IIB (TFIIB) in a complex with RNA polymerase II reveals three features crucial for transcription initiation: an N-terminal zinc ribbon domain of TFIIB that contacts the "dock" domain of the polymerase, near the path of RNA exit from a transcribing enzyme; a "finger" domain of TFIIB that is inserted into the polymerase active center; and a C-terminal domain, whose interaction with both the polymerase and with a TATA box-binding protein (TBP)-promoter DNA complex orients the DNA for unwinding and transcription. TFIIB stabilizes an early initiation complex, containing an incomplete RNA-DNA hybrid region. It may interact with the template strand, which sets the location of the transcription start site, and may interfere with RNA exit, which leads to abortive initiation or promoter escape. The trajectory of promoter DNA determined by the C-terminal domain of TFIIB traverses sites of interaction with TFIIE, TFIIF, and TFIIH, serving to define their roles in the transcription initiation process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bushnell, David A -- Westover, Kenneth D -- Davis, Ralph E -- Kornberg, Roger D -- AI21144/AI/NIAID NIH HHS/ -- GM49985/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 13;303(5660):983-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14963322" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Nucleic Acid Hybridization ; Promoter Regions, Genetic ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/chemistry/metabolism ; RNA Polymerase II/*chemistry/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/metabolism ; TATA Box ; TATA-Box Binding Protein/chemistry/metabolism ; Templates, Genetic ; Transcription Factor TFIIB/*chemistry/metabolism ; Transcription Factors, TFII/chemistry/metabolism ; *Transcription, Genetic ; Zinc/chemistry
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 68
    Publikationsdatum: 2004-03-06
    Beschreibung: Self-incompatibility (SI) response in Brassica is initiated by haplotype-specific interactions between the pollen-borne ligand S locus protein 11/SCR and its stigmatic S receptor kinase, SRK. This binding induces autophosphorylation of SRK, which is then thought to trigger a signaling cascade that leads to self-pollen rejection. A recessive mutation of the modifier (m) gene eliminates the SI response in stigma. Positional cloning of M has revealed that it encodes a membrane-anchored cytoplasmic serine/threonine protein kinase, designated M locus protein kinase (MLPK). Transient expression of MLPK restores the ability of mm papilla cells to reject self-pollen, suggesting that MLPK is a positive mediator of Brassica SI signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murase, Kohji -- Shiba, Hiroshi -- Iwano, Megumi -- Che, Fang-Sik -- Watanabe, Masao -- Isogai, Akira -- Takayama, Seiji -- New York, N.Y. -- Science. 2004 Mar 5;303(5663):1516-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0101, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15001779" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amino Acid Substitution ; Brassica rapa/enzymology/genetics/*physiology ; Cell Membrane/*enzymology ; Cloning, Molecular ; Cytoplasm/enzymology ; Flowers/enzymology/*physiology ; Genes, Plant ; Haplotypes ; Membrane Proteins/chemistry/genetics/*metabolism ; Mutation ; Open Reading Frames ; Phosphorylation ; Physical Chromosome Mapping ; Plant Proteins ; Pollen/physiology ; Protein Kinases/*metabolism ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 69
    Publikationsdatum: 2004-07-31
    Beschreibung: Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Jidong -- Carmell, Michelle A -- Rivas, Fabiola V -- Marsden, Carolyn G -- Thomson, J Michael -- Song, Ji-Joon -- Hammond, Scott M -- Joshua-Tor, Leemor -- Hannon, Gregory J -- New York, N.Y. -- Science. 2004 Sep 3;305(5689):1437-41. Epub 2004 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15284456" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Argonaute Proteins ; Catalysis ; Cell Line ; Cells, Cultured ; Central Nervous System/embryology ; Embryonic and Fetal Development ; Eukaryotic Initiation Factor-2 ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Humans ; In Situ Hybridization ; Mice ; MicroRNAs/metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; Oligonucleotide Array Sequence Analysis ; Peptide Initiation Factors/chemistry/*metabolism ; Point Mutation ; *RNA Interference ; RNA, Double-Stranded ; RNA, Messenger/*metabolism ; RNA, Small Interfering/metabolism ; RNA-Induced Silencing Complex/chemistry/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 70
    Publikationsdatum: 2004-01-13
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wyrwicz, Lucjan S -- von Grotthuss, Marcin -- Pas, Jakub -- Rychlewski, Leszek -- New York, N.Y. -- Science. 2004 Jan 9;303(5655):168; author reply 168.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14715990" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Arabidopsis/genetics ; Computational Biology ; DNA, Complementary ; Databases, Nucleic Acid ; Databases, Protein ; *Genome, Plant ; Molecular Sequence Data ; Oryza/*genetics ; Plant Proteins/chemistry/*genetics ; Sequence Homology, Amino Acid ; *Transcription, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 71
    Publikationsdatum: 2004-05-25
    Beschreibung: The herbicide glyphosate is effectively detoxified by N-acetylation. We screened a collection of microbial isolates and discovered enzymes exhibiting glyphosate N-acetyltransferase (GAT) activity. Kinetic properties of the discovered enzymes were insufficient to confer glyphosate tolerance to transgenic organisms. Eleven iterations of DNA shuffling improved enzyme efficiency by nearly four orders of magnitude from 0.87 mM-1 min-1 to 8320 mM-1 min-1. From the fifth iteration and beyond, GAT enzymes conferred increasing glyphosate tolerance to Escherichia coli, Arabidopsis, tobacco, and maize. Glyphosate acetylation provides an alternative strategy for supporting glyphosate use on crops.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Castle, Linda A -- Siehl, Daniel L -- Gorton, Rebecca -- Patten, Phillip A -- Chen, Yong Hong -- Bertain, Sean -- Cho, Hyeon-Je -- Duck, Nicholas -- Wong, James -- Liu, Donglong -- Lassner, Michael W -- New York, N.Y. -- Science. 2004 May 21;304(5674):1151-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verdia, Inc. Redwood City, CA 94063, USA. linda.castle@verdiainc.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15155947" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylation ; Acetyltransferases/chemistry/*genetics/metabolism ; Amino Acid Sequence ; Bacillus/enzymology ; Catalysis ; *DNA Shuffling ; *Directed Molecular Evolution ; Drug Resistance ; Escherichia coli/genetics ; Gene Library ; Genetic Variation ; Glycine/*analogs & derivatives/metabolism/*toxicity ; Herbicides/metabolism/*toxicity ; Kinetics ; Molecular Sequence Data ; Mutagenesis ; *Plants, Genetically Modified/drug effects/genetics ; Recombinant Proteins/metabolism ; Recombination, Genetic ; Tobacco/drug effects/genetics/growth & development ; Transformation, Genetic ; Zea mays/drug effects/genetics/growth & development
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 72
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-03-20
    Beschreibung: The spatial organization of the microtubule cytoskeleton is thought to be directed by steady-state activity gradients of diffusible regulatory molecules. We visualized such intracellular gradients by monitoring the interaction between tubulin and a regulator of microtubule dynamics, stathmin, using a fluorescence resonance energy transfer (FRET) biosensor. These gradients were observed both during interphase in motile membrane protrusions and during mitosis around chromosomes, which suggests that a similar mechanism may contribute to the creation of polarized microtubule structures. These interaction patterns are likely to reflect phosphorylation of stathmin in these areas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Niethammer, Philipp -- Bastiaens, Philippe -- Karsenti, Eric -- New York, N.Y. -- Science. 2004 Mar 19;303(5665):1862-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15031504" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Bacterial Proteins ; Binding Sites ; Cell Line ; *Cell Movement ; Chromosomes/metabolism ; Cytosol/metabolism ; Fluorescence Resonance Energy Transfer ; Green Fluorescent Proteins ; Interphase ; Luminescent Proteins ; *Microtubule Proteins ; Microtubules/metabolism/ultrastructure ; *Mitosis ; Mutation ; Phosphoprotein Phosphatases/metabolism ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Protein Binding ; Recombinant Fusion Proteins/metabolism ; Spindle Apparatus/ultrastructure ; Stathmin ; Swine ; Tetradecanoylphorbol Acetate/pharmacology ; Transfection ; Tubulin/*metabolism ; Xenopus ; Xenopus Proteins
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 73
    Publikationsdatum: 2004-03-16
    Beschreibung: Plants with a winter growth habit flower earlier when exposed for several weeks to cold temperatures, a process called vernalization. We report here the positional cloning of the wheat vernalization gene VRN2, a dominant repressor of flowering that is down-regulated by vernalization. Loss of function of VRN2, whether by natural mutations or deletions, resulted in spring lines, which do not require vernalization to flower. Reduction of the RNA level of VRN2 by RNA interference accelerated the flowering time of transgenic winter-wheat plants by more than a month.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737501/" 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/PMC4737501/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, Liuling -- Loukoianov, Artem -- Blechl, Ann -- Tranquilli, Gabriela -- Ramakrishna, Wusirika -- SanMiguel, Phillip -- Bennetzen, Jeffrey L -- Echenique, Viviana -- Dubcovsky, Jorge -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2004 Mar 12;303(5664):1640-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Agronomy and Range Science, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15016992" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alleles ; Amino Acid Sequence ; Arabidopsis/genetics/growth & development ; Base Sequence ; Chromosome Mapping ; Cloning, Molecular ; *Cold Temperature ; Down-Regulation ; Epistasis, Genetic ; Evolution, Molecular ; Flowers/*growth & development ; Gene Deletion ; *Gene Expression Regulation, Plant ; Genes, Plant ; Genetic Variation ; Hordeum/genetics ; Molecular Sequence Data ; Mutation ; Plant Proteins/chemistry/genetics/physiology ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; RNA Interference ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/metabolism ; Seasons ; Transcription, Genetic ; Triticum/*genetics/*growth & development
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 74
    Publikationsdatum: 2004-05-29
    Beschreibung: "Cross-priming" describes the activation of naive CD8+ T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell-derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Norbury, Christopher C -- Basta, Sameh -- Donohue, Keri B -- Tscharke, David C -- Princiotta, Michael F -- Berglund, Peter -- Gibbs, James -- Bennink, Jack R -- Yewdell, Jonathan W -- AI-056094-01/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 May 28;304(5675):1318-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD, 20892-0440, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15166379" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylcysteine/*analogs & derivatives/pharmacology ; Animals ; *Antigen Presentation ; Antigens/*immunology/metabolism ; Antigens, Viral/immunology/metabolism ; CD8-Positive T-Lymphocytes/*immunology ; Cell Line ; *Cross-Priming ; Cysteine Endopeptidases/*metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Endoplasmic Reticulum/metabolism ; Humans ; Immunization ; Influenza A virus/immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Chaperones/metabolism ; Multienzyme Complexes/*metabolism ; Ovalbumin/immunology/metabolism ; Peptide Fragments/immunology ; Proteasome Endopeptidase Complex ; Recombinant Fusion Proteins/immunology/metabolism ; Vaccines/immunology ; Vaccinia virus/genetics/physiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 75
    Publikationsdatum: 2004-02-28
    Beschreibung: Legionella pneumophila, the bacterial agent of legionnaires' disease, replicates intracellularly within a specialized vacuole of mammalian and protozoan host cells. Little is known about the specialized vacuole except that the Icm/Dot type IV secretion system is essential for its formation and maintenance. The Legionella genome database contains two open reading frames encoding polypeptides (LepA and LepB) with predicted coiled-coil regions and weak homology to SNAREs; these are delivered to host cells by an Icm/Dot-dependent mechanism. Analysis of mutant strains suggests that the Lep proteins may enable the Legionella to commandeer a protozoan exocytic pathway for dissemination of the pathogen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, John -- de Felipe, Karim Suwwan -- Clarke, Margaret -- Lu, Hao -- Anderson, O Roger -- Segal, Gil -- Shuman, Howard A -- NIH-R01 AI23549/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1358-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 West 168th Street, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14988561" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acanthamoeba/*microbiology/physiology/ultrastructure ; Animals ; Bacterial Proteins/genetics/metabolism/*physiology ; Cell Line ; Colony Count, Microbial ; Cyclic AMP/metabolism ; Dictyostelium/*microbiology/physiology/ultrastructure ; Exocytosis ; Genome, Bacterial ; Humans ; Legionella pneumophila/*genetics/growth & development/pathogenicity/*physiology ; Lysosomes/physiology ; Macrophages/microbiology/ultrastructure ; Mutation ; Open Reading Frames ; Phagosomes/physiology ; Recombinant Fusion Proteins/metabolism ; Vacuoles/microbiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 76
    Publikationsdatum: 2004-04-24
    Beschreibung: Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely. Oral administration of curcumin to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect. These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells. Thus, curcumin treatment may be able to correct defects associated with the homozygous expression of DeltaF508 CFTR.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Egan, Marie E -- Pearson, Marilyn -- Weiner, Scott A -- Rajendran, Vanathy -- Rubin, Daniel -- Glockner-Pagel, Judith -- Canny, Susan -- Du, Kai -- Lukacs, Gergely L -- Caplan, Michael J -- DK17433/DK/NIDDK NIH HHS/ -- DK53428/DK/NIDDK NIH HHS/ -- GM42136/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Apr 23;304(5670):600-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208026, New Haven, CT 06520-8026, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15105504" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Calcium/metabolism ; Calnexin/metabolism ; Cell Line ; Cell Membrane/*metabolism ; Cricetinae ; Curcumin/administration & dosage/*pharmacology/therapeutic use ; Cystic Fibrosis/*drug therapy/genetics/physiopathology ; Cystic Fibrosis Transmembrane Conductance ; Regulator/chemistry/genetics/*metabolism ; Electrolytes/pharmacology ; Endoplasmic Reticulum/*metabolism ; Gene Targeting ; Glycosylation ; Humans ; Intestinal Mucosa/drug effects/physiology ; Intestinal Obstruction/prevention & control ; Isoproterenol/pharmacology ; Membrane Potentials/drug effects ; Mice ; Mice, Knockout ; Mutation ; Nasal Mucosa/*drug effects/physiology ; Polyethylene Glycols/pharmacology ; Protein Folding ; Rectum ; Transfection
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 77
    Publikationsdatum: 2004-11-20
    Beschreibung: The observation of the regulation of fast protein dynamics in a cellular context requires the development of reliable technologies. Here, a signal regulation cascade reliant on the stimulus-dependent acceleration of the bidirectional flow of mitogen-activated protein kinase (extracellular signal-regulated kinase) across the nuclear envelope was visualized by reversible protein highlighting. Light-induced conversion between the bright and dark states of a monomeric fluorescent protein engineered from a novel coral protein was employed. Because of its photochromic properties, the protein could be highlighted, erased, and highlighted again in a nondestructive manner, allowing direct observation of regulated fast nucleocytoplasmic shuttling of key signaling molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ando, Ryoko -- Mizuno, Hideaki -- Miyawaki, Atsushi -- New York, N.Y. -- Science. 2004 Nov 19;306(5700):1370-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama, 351-0198, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15550670" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Active Transport, Cell Nucleus ; Amino Acid Sequence ; Animals ; Anthozoa ; COS Cells ; Cell Nucleus/*metabolism ; Cytoplasm/*metabolism ; Epidermal Growth Factor/pharmacology ; Fluorescence ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Light ; Luminescent Proteins/chemistry/*metabolism ; MAP Kinase Signaling System ; Microscopy, Confocal ; Mitogen-Activated Protein Kinase 3/*metabolism ; Molecular Sequence Data ; Nuclear Envelope/*metabolism ; Phosphorylation ; Protein Transport ; Recombinant Proteins/chemistry/metabolism ; Transfection ; beta Karyopherins/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 78
    Publikationsdatum: 2004-05-15
    Beschreibung: Dynamic changes in chromatin structure, induced by posttranslational modification of histones, play a fundamental role in regulating eukaryotic transcription. Here we report that histone H2B is phosphorylated at evolutionarily conserved Ser33 (H2B-S33) by the carboxyl-terminal kinase domain (CTK) of the Drosophila TFIID subunit TAF1. Phosphorylation of H2B-S33 at the promoter of the cell cycle regulatory gene string and the segmentation gene giant coincides with transcriptional activation. Elimination of TAF1 CTK activity in Drosophila cells and embryos reduces transcriptional activation and phosphorylation of H2B-S33. These data reveal that H2B-S33 is a physiological substrate for the TAF1 CTK and that H2B-S33 phosphorylation is essential for transcriptional activation events that promote cell cycle progression and development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maile, Tobias -- Kwoczynski, Simona -- Katzenberger, Rebeccah J -- Wassarman, David A -- Sauer, Frank -- GM066204-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 May 14;304(5673):1010-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of California-Riverside, Riverside, CA 95121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15143281" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylation ; Amino Acid Motifs ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Cell Cycle ; Cell Cycle Proteins ; DNA-Binding Proteins/genetics ; Drosophila/embryology/*genetics/metabolism ; Drosophila Proteins/chemistry/genetics/*metabolism ; Embryo, Nonmammalian/physiology ; Genes, Insect ; Histone Acetyltransferases ; Histones/chemistry/*metabolism ; Homeodomain Proteins/genetics ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Phosphoserine/metabolism ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Protein Tyrosine Phosphatases/genetics ; RNA Interference ; Recombinant Proteins/chemistry/metabolism ; Repressor Proteins/genetics ; TATA-Binding Protein Associated Factors ; Transcription Factor TFIID/chemistry/genetics/*metabolism ; Transcription Factors ; *Transcription, Genetic ; *Transcriptional Activation
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 79
    Publikationsdatum: 2004-05-08
    Beschreibung: Caspases play a central role in apoptosis, a well-studied pathway of programmed cell death. Other programs of death potentially involving necrosis and autophagy may exist, but their relation to apoptosis and mechanisms of regulation remains unclear. We define a new molecular pathway in which activation of the receptor-interacting protein (a serine-threonine kinase) and Jun amino-terminal kinase induced cell death with the morphology of autophagy. Autophagic death required the genes ATG7 and beclin 1 and was induced by caspase-8 inhibition. Clinical therapies involving caspase inhibitors may arrest apoptosis but also have the unanticipated effect of promoting autophagic cell death.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Li -- Alva, Ajjai -- Su, Helen -- Dutt, Parmesh -- Freundt, Eric -- Welsh, Sarah -- Baehrecke, Eric H -- Lenardo, Michael J -- GM59136/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Jun 4;304(5676):1500-2. Epub 2004 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15131264" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Chloromethyl Ketones/pharmacology ; Animals ; Apoptosis Regulatory Proteins ; *Autophagy ; Caspase 8 ; *Caspase Inhibitors ; Caspases/genetics/*metabolism ; *Cell Death ; Cell Line ; Cells, Cultured ; Humans ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Kinase 7 ; MAP Kinase Signaling System ; Membrane Proteins ; Mice ; Mitogen-Activated Protein Kinase Kinases/genetics/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Proteins/genetics/*metabolism ; RNA Interference ; Receptor-Interacting Protein Serine-Threonine Kinases
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 80
    Publikationsdatum: 2004-06-19
    Beschreibung: Salmonella enterica, the cause of food poisoning and typhoid fever, induces actin cytoskeleton rearrangements and membrane ruffling to gain access into nonphagocytic cells, where it can replicate and avoid innate immune defenses. Here, we found that SopB, a phosphoinositide phosphatase that is delivered into host cells by a type III secretion system, was essential for the establishment of Salmonella's intracellular replicative niche. SopB mediated the formation of spacious phagosomes following bacterial entry and was responsible for maintaining high levels of phosphatidylinositol-three-phosphate [PtdIns(3)P] in the membrane of the bacteria-containing vacuoles. Absence of SopB caused a significant defect in the maturation of the Salmonella-containing vacuole and impaired bacterial intracellular growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hernandez, Lorraine D -- Hueffer, Karsten -- Wenk, Markus R -- Galan, Jorge E -- AI055472/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Jun 18;304(5678):1805-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15205533" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Antigens, CD/metabolism ; Bacterial Proteins/genetics/*metabolism ; Cell Line ; Cell Membrane/metabolism/ultrastructure ; Cytoplasmic Vesicles/metabolism/*microbiology/ultrastructure ; Epithelial Cells/microbiology ; Gene Deletion ; Genomic Islands ; Humans ; Intestinal Mucosa/cytology/*microbiology ; Lysosome-Associated Membrane Glycoproteins ; Microscopy, Video ; Mutation ; Phagosomes/metabolism/*microbiology ; Phosphatidylinositol Phosphates/metabolism ; Phosphatidylinositols/*metabolism ; Recombinant Fusion Proteins/metabolism ; Salmonella typhimurium/genetics/growth & development/*metabolism/pathogenicity ; Vacuoles/metabolism/microbiology/ultrastructure
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 81
    Publikationsdatum: 2004-08-18
    Beschreibung: Axonal degeneration is an active program of self-destruction that is observed in many physiological and pathological settings. In Wallerian degeneration slow (wlds) mice, Wallerian degeneration in response to axonal injury is delayed because of a mutation that results in overexpression of a chimeric protein (Wlds) composed of the ubiquitin assembly protein Ufd2a and the nicotinamide adenine dinucleotide (NAD) biosynthetic enzyme Nmnat1. We demonstrate that increased Nmnat activity is responsible for the axon-sparing activity of the Wlds protein. Furthermore, we demonstrate that SIRT1, a mammalian ortholog of Sir2, is the downstream effector of increased Nmnat activity that leads to axonal protection. These findings suggest that novel therapeutic strategies directed at increasing the supply of NAD and/or Sir2 activation may be effective for treatment of diseases characterized by axonopathy and neurodegeneration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Araki, Toshiyuki -- Sasaki, Yo -- Milbrandt, Jeffrey -- AG05681/AG/NIA NIH HHS/ -- AG13730/AG/NIA NIH HHS/ -- NS40745/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2004 Aug 13;305(5686):1010-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15310905" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 3T3 Cells ; Animals ; Axons/drug effects/*physiology ; Axotomy ; Benzamides/pharmacology ; Cell Line ; Cell Nucleus/metabolism ; Cell Survival ; Cells, Cultured ; Ganglia, Spinal/cytology ; Humans ; Lentivirus/genetics/physiology ; Mice ; Mutation ; NAD/*biosynthesis/pharmacology ; Naphthols/pharmacology ; Nerve Tissue Proteins/*metabolism ; Neuroprotective Agents/pharmacology ; Nicotinamide-Nucleotide Adenylyltransferase/*metabolism ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/metabolism ; RNA, Small Interfering ; Sirtuin 1 ; Sirtuins/antagonists & inhibitors/*metabolism ; Stilbenes/pharmacology ; Ubiquitin-Protein Ligases/genetics/metabolism ; Vincristine/pharmacology ; Wallerian Degeneration/metabolism/*physiopathology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 82
    Publikationsdatum: 2004-10-02
    Beschreibung: Nodal proteins, members of the transforming growth factor-beta (TGFbeta) superfamily, have been identified as key endogenous mesoderm inducers in vertebrates. Precise control of Nodal signaling is essential for normal development of embryos. Here, we report that zebrafish dapper2 (dpr2) is expressed in mesoderm precursors during early embryogenesis and is positively regulated by Nodal signals. In vivo functional studies in zebrafish suggest that Dpr2 suppresses mesoderm induction activities of Nodal signaling. Dpr2 is localized in late endosomes, binds to the TGFbeta receptors ALK5 and ALK4, and accelerates lysosomal degradation of these receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Lixia -- Zhou, Hu -- Su, Ying -- Sun, Zhihui -- Zhang, Haiwen -- Zhang, Long -- Zhang, Yu -- Ning, Yuanheng -- Chen, Ye-Guang -- Meng, Anming -- New York, N.Y. -- Science. 2004 Oct 1;306(5693):114-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Developmental Biology, Ministry of Education (MOE), Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15459392" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Activin Receptors, Type I/*metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Embryo, Nonmammalian/embryology/*metabolism ; *Embryonic Induction ; Endosomes/metabolism ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Humans ; In Situ Hybridization ; Intracellular Signaling Peptides and Proteins ; Lysosomes/metabolism ; Mesoderm/*physiology ; Molecular Sequence Data ; Mutation ; Nodal Signaling Ligands ; Oligonucleotides, Antisense ; Protein-Serine-Threonine Kinases ; Proteins/metabolism ; Receptors, Transforming Growth Factor beta/*metabolism ; Signal Transduction ; Transforming Growth Factor beta/genetics/metabolism ; Zebrafish/*embryology/genetics/metabolism ; Zebrafish Proteins/chemistry/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 83
    Publikationsdatum: 2004-07-13
    Beschreibung: Ribonucleotide reductase (RNR) synthesizes the deoxyribonucleotides for DNA synthesis. The R2 protein of normal class I ribonucleotide reductases contains a diiron site that produces a stable tyrosyl free radical, essential for enzymatic activity. Structural and electron paramagnetic resonance studies of R2 from Chlamydia trachomatis reveal a protein lacking a tyrosyl radical site. Instead, the protein yields an iron-coupled radical upon reconstitution. The coordinating structure of the diiron site is similar to that of diiron oxidases/monoxygenases and supports a role for this radical in the RNR mechanism. The specific ligand pattern in the C. trachomatis R2 metal site characterizes a new group of R2 proteins that so far has been found in eight organisms, three of which are human pathogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hogbom, Martin -- Stenmark, Pal -- Voevodskaya, Nina -- McClarty, Grant -- Graslund, Astrid -- Nordlund, Par -- New York, N.Y. -- Science. 2004 Jul 9;305(5681):245-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Stockholm University, Roslagstullsbacken 15, Albanova University Center, SE-10691 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247479" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Chlamydia trachomatis/*enzymology ; Crystallography, X-Ray ; Electron Spin Resonance Spectroscopy ; Free Radicals ; Hydrogen Bonding ; Iron/analysis ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Oxygen/metabolism ; Protein Folding ; Protein Structure, Secondary ; Ribonucleotide Reductases/*chemistry/classification/metabolism ; Tyrosine/analysis
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-01-24
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanabe, K -- Sakihama, N -- Kaneko, A -- New York, N.Y. -- Science. 2004 Jan 23;303(5657):493.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Osaka Institute of Technology, Osaka 535-8585, Japan. kztanabe@ge.oit.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14739451" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alleles ; Amino Acid Sequence ; Animals ; Antigens, Protozoan/chemistry/*genetics ; Antimalarials/pharmacology ; Chloroquine/pharmacology ; Drug Resistance ; Epitopes/genetics ; Genes, Protozoan ; Geography ; Haplotypes ; Humans ; Malaria, Falciparum/parasitology ; Membrane Proteins/chemistry/genetics ; Membrane Transport Proteins ; Merozoite Surface Protein 1/chemistry/genetics ; Molecular Sequence Data ; Plasmodium falciparum/drug effects/*genetics/*immunology ; *Polymorphism, Single Nucleotide ; Protozoan Proteins/chemistry/genetics ; Repetitive Sequences, Nucleic Acid ; Tandem Repeat Sequences ; Vanuatu
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  • 85
    Publikationsdatum: 2004-04-10
    Beschreibung: Apoptosis is triggered by activation of initiator caspases upon complex-mediated clustering of the inactive zymogen, as occurs in the caspase-9-activating apoptosome complex. Likewise, caspase-2, which is involved in stress-induced apoptosis, is recruited into a large protein complex, the molecular composition of which remains elusive. We show that activation of caspase-2 occurs in a complex that contains the death domain-containing protein PIDD, whose expression is induced by p53, and the adaptor protein RAIDD. Increased PIDD expression resulted in spontaneous activation of caspase-2 and sensitization to apoptosis by genotoxic stimuli. Because PIDD functions in p53-mediated apoptosis, the complex assembled by PIDD and caspase-2 is likely to regulate apoptosis induced by genotoxins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tinel, Antoine -- Tschopp, Jurg -- New York, N.Y. -- Science. 2004 May 7;304(5672):843-6. Epub 2004 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15073321" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Adaptor Proteins, Signal Transducing ; *Apoptosis ; CRADD Signaling Adaptor Protein ; Carrier Proteins/chemistry/*metabolism ; Caspase 2 ; Caspases/*metabolism ; Cell Line ; Cell Line, Tumor ; Cloning, Molecular ; *DNA Damage ; Death Domain Receptor Signaling Adaptor Proteins ; Doxorubicin/pharmacology ; Enzyme Activation ; Etoposide/pharmacology ; Humans ; Protein Structure, Tertiary ; Proteins/chemistry/metabolism ; RNA, Small Interfering ; Signal Transduction ; Transfection ; Tumor Suppressor Protein p53/metabolism
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    Standort Signatur Erwartet Verfügbarkeit
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  • 86
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-10-23
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2004 Oct 22;306(5696):586.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15498975" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bioethical Issues ; Cell Line ; Cloning, Organism/ethics/*standards ; *Embryo Research/ethics ; Embryo, Mammalian/*cytology ; Guidelines as Topic ; Humans ; Research Embryo Creation/ethics/*standards ; *Stem Cells ; United States
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 87
    Publikationsdatum: 2004-11-13
    Beschreibung: NKT cells represent a distinct lineage of T cells that coexpress a conserved alphabeta T cell receptor (TCR) and natural killer (NK) receptors. Although the TCR of NKT cells is characteristically autoreactive to CD1d, a lipid-presenting molecule, endogenous ligands for these cells have not been identified. We show that a lysosomal glycosphingolipid of previously unknown function, isoglobotrihexosylceramide (iGb3), is recognized both by mouse and human NKT cells. Impaired generation of lysosomal iGb3 in mice lacking beta-hexosaminidase b results in severe NKT cell deficiency, suggesting that this lipid also mediates development of NKT cells in the mouse. We suggest that expression of iGb3 in peripheral tissues may be involved in controlling NKT cell responses to infections and malignancy and in autoimmunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Dapeng -- Mattner, Jochen -- Cantu, Carlos 3rd -- Schrantz, Nicolas -- Yin, Ning -- Gao, Ying -- Sagiv, Yuval -- Hudspeth, Kelly -- Wu, Yun-Ping -- Yamashita, Tadashi -- Teneberg, Susann -- Wang, Dacheng -- Proia, Richard L -- Levery, Steven B -- Savage, Paul B -- Teyton, Luc -- Bendelac, Albert -- AI053725/AI/NIAID NIH HHS/ -- AI50847/AI/NIAID NIH HHS/ -- P20RR16459/RR/NCRR NIH HHS/ -- R01 AI38339/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 3;306(5702):1786-9. Epub 2004 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Chicago, Department of Pathology, Chicago, IL 60637, USA. dzhou@midway.uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15539565" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antigen Presentation ; Antigens, CD1/immunology/metabolism ; Antigens, CD1d ; Autoimmunity ; Cell Line ; Cell Line, Tumor ; Cells, Cultured ; Dendritic Cells/immunology ; Galactosyltransferases/genetics/metabolism ; Globosides/chemistry/*immunology/metabolism ; Humans ; Hybridomas ; Infection/immunology ; Killer Cells, Natural/*immunology ; Ligands ; Lymphocyte Activation ; Lymphocyte Count ; Lysosomes/*metabolism ; Mice ; Mice, Inbred C57BL ; Neoplasms/immunology ; Plant Lectins/immunology ; Rats ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Saposins/metabolism ; T-Lymphocyte Subsets/*immunology ; beta-N-Acetylhexosaminidases/genetics/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 88
    Publikationsdatum: 2004-03-06
    Beschreibung: Activity-dependent plasticity in the brain arises in part from changes in the number of synaptic AMPA receptors. Synaptic trafficking of AMPA receptors is controlled by stargazin and homologous transmembrane AMPA receptor regulatory proteins (TARPs). We found that TARPs were stable at the plasma membrane, whereas AMPA receptors were internalized in a glutamate-regulated manner. Interaction with AMPA receptors involved both extra- and intracellular determinants of TARPs. Upon binding to glutamate, AMPA receptors detached from TARPs. This did not require ion flux or intracellular second messengers. This allosteric mechanism for AMPA receptor dissociation from TARPs may participate in glutamate-mediated internalization of receptors in synaptic plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomita, Susumu -- Fukata, Masaki -- Nicoll, Roger A -- Bredt, David S -- New York, N.Y. -- Science. 2004 Mar 5;303(5663):1508-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, San Francisco, San Francisco, CA 94143-2140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15001777" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology ; Animals ; Calcium Channels/analysis/*metabolism ; Cell Line ; Cells, Cultured ; Cerebral Cortex/chemistry/cytology ; Endocytosis ; Glutamic Acid/metabolism/pharmacology ; Humans ; Neuronal Plasticity ; Protein Binding ; Protein Structure, Tertiary ; Rats ; Receptors, AMPA/agonists/antagonists & inhibitors/*metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Recombinant Fusion Proteins/metabolism ; Synapses/*metabolism ; Xenopus laevis ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
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    Standort Signatur Erwartet Verfügbarkeit
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  • 89
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-07-27
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2004 Jul 23;305(5683):461.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15273368" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adult ; *Biological Specimen Banks/economics ; Cell Line ; Cloning, Organism ; *Embryo Research/economics ; Embryo, Mammalian/*cytology ; Financing, Government ; Humans ; National Institutes of Health (U.S.) ; Research Support as Topic ; *Stem Cells ; United States
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 90
    Publikationsdatum: 2004-02-07
    Beschreibung: A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Amy Hin Yan -- Lesage, Guillaume -- Bader, Gary D -- Ding, Huiming -- Xu, Hong -- Xin, Xiaofeng -- Young, James -- Berriz, Gabriel F -- Brost, Renee L -- Chang, Michael -- Chen, YiQun -- Cheng, Xin -- Chua, Gordon -- Friesen, Helena -- Goldberg, Debra S -- Haynes, Jennifer -- Humphries, Christine -- He, Grace -- Hussein, Shamiza -- Ke, Lizhu -- Krogan, Nevan -- Li, Zhijian -- Levinson, Joshua N -- Lu, Hong -- Menard, Patrice -- Munyana, Christella -- Parsons, Ainslie B -- Ryan, Owen -- Tonikian, Raffi -- Roberts, Tania -- Sdicu, Anne-Marie -- Shapiro, Jesse -- Sheikh, Bilal -- Suter, Bernhard -- Wong, Sharyl L -- Zhang, Lan V -- Zhu, Hongwei -- Burd, Christopher G -- Munro, Sean -- Sander, Chris -- Rine, Jasper -- Greenblatt, Jack -- Peter, Matthias -- Bretscher, Anthony -- Bell, Graham -- Roth, Frederick P -- Brown, Grant W -- Andrews, Brenda -- Bussey, Howard -- Boone, Charles -- GM39066/GM/NIGMS NIH HHS/ -- GM61221/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):808-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764870" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Computational Biology ; Cystic Fibrosis/genetics ; Gene Deletion ; Genes, Essential ; *Genes, Fungal ; Genetic Diseases, Inborn/genetics ; Genotype ; Humans ; Molecular Sequence Data ; Multifactorial Inheritance ; Mutation ; Phenotype ; Polymorphism, Genetic ; Retinitis Pigmentosa/genetics ; Saccharomyces cerevisiae/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 91
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-05-25
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2004 May 21;304(5674):1088.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15155916" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Cell Line ; *Embryo Research ; Embryo, Mammalian/*cytology ; Financing, Government ; Humans ; *National Institutes of Health (U.S.) ; Public Policy ; *Research Support as Topic ; *Stem Cells ; United States
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 92
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-02-19
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fainzilber, Mike -- New York, N.Y. -- Science. 2004 Feb 13;303(5660):955-7; author reply 955-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14971056" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Line ; *Conotoxins/chemistry/genetics/metabolism ; *Conservation of Natural Resources ; Culture Techniques ; Ecosystem ; Environment ; Gene Library ; *Snails/growth & development
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 93
    facet.materialart.
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-12-25
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- Vogel, Gretchen -- New York, N.Y. -- Science. 2004 Dec 24;306(5705):2174-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15618497" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *Bioethical Issues ; Blastocyst ; Cell Differentiation ; Cell Division ; Cell Fusion ; Cell Line ; Cell Nucleus/physiology ; Cloning, Organism ; Embryo, Mammalian/cytology/physiology ; *Ethics, Research ; Female ; Humans ; Nuclear Transfer Techniques ; Oocytes/physiology ; Parthenogenesis ; Patents as Topic ; *Pluripotent Stem Cells ; Research Embryo Creation ; Stem Cell Transplantation
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 94
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-02-21
    Beschreibung: Mycobacteria have low-permeability outer membranes that render them resistant to most antibiotics. Hydrophilic nutrients can enter by way of transmembrane-channel proteins called porins. An x-ray analysis of the main porin from Mycobacterium smegmatis, MspA, revealed a homooctameric goblet-like conformation with a single central channel. This is the first structure of a mycobacterial outer-membrane protein. No structure-related protein was found in the Protein Data Bank. MspA contains two consecutive beta barrels with nonpolar outer surfaces that form a ribbon around the porin, which is too narrow to fit the thickness of the mycobacterial outer membrane in contemporary models.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faller, Michael -- Niederweis, Michael -- Schulz, Georg E -- New York, N.Y. -- Science. 2004 Feb 20;303(5661):1189-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Organische Chemie und Biochemie, Albert-Ludwigs-Universitat, Albertstrasse 21, 79104 Freiburg im Breisgau, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14976314" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Arginine/chemistry ; Cell Membrane Permeability ; Cloning, Molecular ; Crystallization ; Crystallography, X-Ray ; Electric Conductivity ; Escherichia coli/genetics ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Mycobacterium smegmatis/*chemistry/metabolism ; Porins/*chemistry/genetics/metabolism ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry
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  • 95
    Publikationsdatum: 2004-05-01
    Beschreibung: Receptor tyrosine kinase genes were sequenced in non-small cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinib-insensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paez, J Guillermo -- Janne, Pasi A -- Lee, Jeffrey C -- Tracy, Sean -- Greulich, Heidi -- Gabriel, Stacey -- Herman, Paula -- Kaye, Frederic J -- Lindeman, Neal -- Boggon, Titus J -- Naoki, Katsuhiko -- Sasaki, Hidefumi -- Fujii, Yoshitaka -- Eck, Michael J -- Sellers, William R -- Johnson, Bruce E -- Meyerson, Matthew -- New York, N.Y. -- Science. 2004 Jun 4;304(5676):1497-500. Epub 2004 Apr 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15118125" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenocarcinoma/drug therapy/genetics/metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Amino Acid Substitution ; Antineoplastic Agents/pharmacology/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/metabolism ; Cell Line, Tumor ; Controlled Clinical Trials as Topic ; Enzyme Inhibitors/pharmacology/therapeutic use ; Female ; *Genes, erbB-1 ; Humans ; Japan ; Lung Neoplasms/drug therapy/*genetics/metabolism ; Male ; Molecular Sequence Data ; *Mutation ; Mutation, Missense ; Phosphorylation ; Protein Conformation ; Protein Structure, Tertiary ; Quinazolines/pharmacology/*therapeutic use ; Receptor, Epidermal Growth Factor/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Sequence Deletion ; Treatment Outcome ; United States
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  • 96
    Publikationsdatum: 2004-06-19
    Beschreibung: A major cause of aging is thought to result from the cumulative effects of cell loss over time. In yeast, caloric restriction (CR) delays aging by activating the Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells that are treated with serum from these animals. Insulin and insulin-like growth factor 1 (IGF-1) attenuated this response. SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester the proapoptotic factor Bax away from mitochondria, thereby inhibiting stress-induced apoptotic cell death. Thus, CR could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Haim Y -- Miller, Christine -- Bitterman, Kevin J -- Wall, Nathan R -- Hekking, Brian -- Kessler, Benedikt -- Howitz, Konrad T -- Gorospe, Myriam -- de Cabo, Rafael -- Sinclair, David A -- AG19719-03/AG/NIA NIH HHS/ -- AG19972-02/AG/NIA NIH HHS/ -- F32 CA097802/CA/NCI NIH HHS/ -- P01 AG027916/AG/NIA NIH HHS/ -- R01 AG019719/AG/NIA NIH HHS/ -- R01 AG019972/AG/NIA NIH HHS/ -- R01 AG028730/AG/NIA NIH HHS/ -- R01 GM068072/GM/NIGMS NIH HHS/ -- R37 AG028730/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2004 Jul 16;305(5682):390-2. Epub 2004 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15205477" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylation ; Adipose Tissue/metabolism ; Alleles ; Animals ; Antigens, Nuclear/metabolism ; *Apoptosis ; *Caloric Restriction ; Cell Line ; *Cell Survival ; DNA-Binding Proteins/metabolism ; Histone Deacetylases/genetics/*metabolism ; Humans ; Insulin/metabolism/pharmacology ; Insulin-Like Growth Factor I/metabolism/pharmacology ; Kidney/metabolism ; Liver/metabolism ; Male ; Mitochondria/metabolism ; Mutation ; Proto-Oncogene Proteins/metabolism ; *Proto-Oncogene Proteins c-bcl-2 ; RNA, Small Interfering ; Rats ; Rats, Inbred F344 ; Sirtuin 1 ; Sirtuins/genetics/*metabolism ; bcl-2-Associated X Protein
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  • 97
    Publikationsdatum: 2004-12-14
    Beschreibung: The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 mug/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andries, Koen -- Verhasselt, Peter -- Guillemont, Jerome -- Gohlmann, Hinrich W H -- Neefs, Jean-Marc -- Winkler, Hans -- Van Gestel, Jef -- Timmerman, Philip -- Zhu, Min -- Lee, Ennis -- Williams, Peter -- de Chaffoy, Didier -- Huitric, Emma -- Hoffner, Sven -- Cambau, Emmanuelle -- Truffot-Pernot, Chantal -- Lounis, Nacer -- Jarlier, Vincent -- New York, N.Y. -- Science. 2005 Jan 14;307(5707):223-7. Epub 2004 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium. kandries@prdbe.jnj.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15591164" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Antitubercular Agents/chemistry/pharmacokinetics/*pharmacology/therapeutic use ; Bacterial Proton-Translocating ATPases/*antagonists & ; inhibitors/chemistry/metabolism ; Diarylquinolines ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Enzyme Inhibitors/chemistry/pharmacology/therapeutic use ; Humans ; Male ; Mice ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Mycobacterium smegmatis/drug effects/enzymology/growth & development ; Mycobacterium tuberculosis/*drug effects/enzymology/growth & development ; Point Mutation ; Protein Subunits/antagonists & inhibitors/chemistry ; Quinolines/chemistry/pharmacokinetics/*pharmacology/*therapeutic use ; Tuberculosis/*drug therapy/microbiology ; Tuberculosis, Multidrug-Resistant/drug therapy/microbiology
    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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  • 98
    Publikationsdatum: 2004-12-14
    Beschreibung: CD4+ T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acidification, EBNA1, the dominant CD4+ T cell antigen of latent Epstein-Barr virus infection, slowly accumulated in cytosolic autophagosomes. In addition, inhibition of autophagy decreased recognition by EBNA1-specific CD4+ T cell clones. Thus, lysosomal processing after autophagy may contribute to MHC class II-restricted surveillance of long-lived endogenous antigens including nuclear proteins relevant to disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paludan, Casper -- Schmid, Dorothee -- Landthaler, Markus -- Vockerodt, Martina -- Kube, Dieter -- Tuschl, Thomas -- Munz, Christian -- New York, N.Y. -- Science. 2005 Jan 28;307(5709):593-6. Epub 2004 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Immunobiology, Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15591165" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *Antigen Presentation ; *Autophagy ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cell Line ; Cell Line, Transformed ; Cell Line, Tumor ; Chloroquine/pharmacology ; Epstein-Barr Virus Nuclear Antigens/immunology/*metabolism ; Histocompatibility Antigens Class II/*metabolism ; Humans ; Hydrogen-Ion Concentration ; Lysosomes/immunology/metabolism ; Microsomes/metabolism ; Phagosomes/immunology/*metabolism/ultrastructure ; Proteasome Endopeptidase Complex/metabolism ; Transfection
    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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  • 99
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004-12-25
    Beschreibung: The position-dependent specification of root epidermal cells in Arabidopsis provides an elegant paradigm for cell patterning during development. Here, we describe a new gene, SCRAMBLED (SCM), required for cells to appropriately interpret their location within the developing root epidermis. SCM encodes a receptor-like kinase protein with a predicted extracellular domain of six leucine-rich repeats and an intracellular serine-threonine kinase domain. SCM regulates the expression of the GLABRA2, CAPRICE, WEREWOLF, and ENHANCER OF GLABRA3 transcription factor genes that define the cell fates. Further, the SCM gene is expressed throughout the developing root. Therefore, SCM likely enables developing epidermal cells to detect positional cues and establish an appropriate cell-type pattern.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwak, Su-Hwan -- Shen, Ronglai -- Schiefelbein, John -- New York, N.Y. -- Science. 2005 Feb 18;307(5712):1111-3. Epub 2004 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15618487" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Arabidopsis/cytology/*enzymology/*genetics/growth & development ; Arabidopsis Proteins/chemistry/*genetics/*metabolism ; Cell Division ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Genes, Plant ; Genes, Reporter ; Hydrophobic and Hydrophilic Interactions ; In Situ Hybridization ; Molecular Sequence Data ; Mutation ; Plant Epidermis/cytology/enzymology/growth & development ; Plant Roots/cytology/enzymology/growth & development ; Plants, Genetically Modified ; Protein Sorting Signals ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/*genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/chemistry/*genetics/*metabolism ; *Signal Transduction ; Transcription Factors/genetics/metabolism
    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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  • 100
    Publikationsdatum: 2004-05-25
    Beschreibung: Resistin, founding member of the resistin-like molecule (RELM) hormone family, is secreted selectively from adipocytes and induces liver-specific antagonism of insulin action, thus providing a potential molecular link between obesity and diabetes. Crystal structures of resistin and RELMbeta reveal an unusual multimeric structure. Each protomer comprises a carboxy-terminal disulfide-rich beta-sandwich "head" domain and an amino-terminal alpha-helical "tail" segment. The alpha-helical segments associate to form three-stranded coiled coils, and surface-exposed interchain disulfide linkages mediate the formation of tail-to-tail hexamers. Analysis of serum samples shows that resistin circulates in two distinct assembly states, likely corresponding to hexamers and trimers. Infusion of a resistin mutant, lacking the intertrimer disulfide bonds, in pancreatic-insulin clamp studies reveals substantially more potent effects on hepatic insulin sensitivity than those observed with wild-type resistin. This result suggests that processing of the intertrimer disulfide bonds may reflect an obligatory step toward activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patel, Saurabh D -- Rajala, Michael W -- Rossetti, Luciano -- Scherer, Philipp E -- Shapiro, Lawrence -- New York, N.Y. -- Science. 2004 May 21;304(5674):1154-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15155948" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adipocytes/metabolism ; Adiponectin ; Amino Acid Sequence ; Animals ; Cell Line ; Crystallization ; Crystallography, X-Ray ; Culture Media, Conditioned ; Disulfides/*chemistry ; Glucose/metabolism ; Hormones, Ectopic/*chemistry/genetics/*metabolism/pharmacology ; Humans ; Insulin/administration & dosage/blood ; Insulin Resistance ; *Intercellular Signaling Peptides and Proteins ; Liver/metabolism ; Mice ; Molecular Sequence Data ; Molecular Weight ; Mutation ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proteins/chemistry/metabolism ; Resistin
    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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