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  • 1
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    Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-09-05
    Description: We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yuan, M -- Konstantopoulos, N -- Lee, J -- Hansen, L -- Li, Z W -- Karin, M -- Shoelson, S E -- AI43477/AI/NIAID NIH HHS/ -- DK45493/DK/NIDDK NIH HHS/ -- DK51729/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1673-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533494" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Aspirin/administration & dosage/*pharmacology ; Blood Glucose/metabolism ; Cell Line ; Dietary Fats/*administration & dosage ; Gene Deletion ; Gene Targeting ; Glucose Tolerance Test ; I-kappa B Kinase ; Insulin/administration & dosage/blood/*metabolism/pharmacology ; *Insulin Resistance ; Lipids/blood ; Liver/metabolism ; Male ; Mice ; Mice, Obese ; Muscles/metabolism ; Obesity/metabolism/*physiopathology ; Phosphorylation ; Prostaglandin-Endoperoxide Synthases/genetics/metabolism ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism ; Rats ; Rats, Zucker ; Receptor, Insulin/metabolism ; Signal Transduction ; Sodium Salicylate/administration & dosage/*pharmacology ; Tumor Necrosis Factor-alpha/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Resistance to an herbivore through engineered cyanogenic glucoside synthesis (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-07-28
    Description: The entire pathway for synthesis of the tyrosine-derived cyanogenic glucoside dhurrin has been transferred from Sorghum bicolor to Arabidopsis thaliana. Here, we document that genetically engineered plants are able to synthesize and store large amounts of new natural products. The presence of dhurrin in the transgenic A. thaliana plants confers resistance to the flea beetle Phyllotreta nemorum, which is a natural pest of other members of the crucifer group, demonstrating the potential utility of cyanogenic glucosides in plant defense.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tattersall, D B -- Bak, S -- Jones, P R -- Olsen, C E -- Nielsen, J K -- Hansen, M L -- Hoj, P B -- Moller, B L -- New York, N.Y. -- Science. 2001 Sep 7;293(5536):1826-8. Epub 2001 Jul 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Biochemistry Laboratory, Department of Plant Biology, Centre for Molecular Plant Physiology, Department of Chemistry, Royal Veterinary and Agricultural University, 40 Thorvaldsensvej, DK-1871, Frederiksberg C, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11474068" target="_blank"〉PubMed〈/a〉
    Keywords: Angiosperms/*enzymology/genetics ; Animals ; Arabidopsis/genetics/*metabolism ; Beetles/*physiology ; Chromatography, High Pressure Liquid ; Cytochrome P-450 Enzyme System/genetics/metabolism ; *Eating ; Food Chain ; *Genetic Engineering ; Glucosides/analysis/biosynthesis ; Mixed Function Oxygenases/genetics/metabolism ; Nitriles/analysis/*metabolism ; Pest Control, Biological/*methods ; Plant Leaves/genetics/metabolism ; Plants, Genetically Modified
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Conservation conflicts across Africa (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-04-03
    Description: There is increasing evidence that areas of outstanding conservation importance may coincide with dense human settlement or impact. We tested the generality of these findings using 1 degree-resolution data for sub-Saharan Africa. We find that human population density is positively correlated with species richness of birds, mammals, snakes, and amphibians. This association holds for widespread, narrowly endemic, and threatened species and looks set to persist in the face of foreseeable population growth. Our results contradict earlier expectations of low conflict based on the idea that species richness decreases and human impact increases with primary productivity. We find that across Africa, both variables instead exhibit unimodal relationships with productivity. Modifying priority-setting to take account of human density shows that, at this scale, conflicts between conservation and development are not easily avoided, because many densely inhabited grid cells contain species found nowhere else.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balmford, A -- Moore, J L -- Brooks, T -- Burgess, N -- Hansen, L A -- Williams, P -- Rahbek, C -- New York, N.Y. -- Science. 2001 Mar 30;291(5513):2616-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Conservation Biology Group, Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK. a.balmford@zoo.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11283376" target="_blank"〉PubMed〈/a〉
    Keywords: Africa South of the Sahara ; Amphibians ; Animals ; Birds ; *Conservation of Natural Resources ; *Ecosystem ; Humans ; Mammals ; Population Density ; Population Growth ; Snakes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-01-08
    Description: Immunoglobulin G (IgG) responses require major histocompatibility complex (MHC)-restricted recognition of peptide fragments by conventional CD4(+) helper T cells. Immunoglobulin G responses to glycosylphosphatidylinositol (GPI)- anchored protein antigens, however, were found to be regulated in part through CD1d-restricted recognition of the GPI moiety by thymus-dependent, interleukin-4-producing CD4(+), natural killer cell antigen 1.1 [(NK1.1)+] helper T cells. The CD1-NKT cell pathway regulated immunogobulin G responses to the GPI-anchored surface antigens of Plasmodium and Trypanosoma and may be a general mechanism for rapid, MHC-unrestricted antibody responses to diverse pathogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schofield, L -- McConville, M J -- Hansen, D -- Campbell, A S -- Fraser-Reid, B -- Grusby, M J -- Tachado, S D -- AI-40171/AI/NIAID NIH HHS/ -- GM 41071/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Jan 8;283(5399):225-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia. schofield@wehi.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9880256" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; Antigens/analysis ; Antigens, CD1/*immunology ; Antigens, Ly ; Antigens, Protozoan/*immunology ; Antigens, Surface ; Cells, Cultured ; Glycosylphosphatidylinositols/*immunology ; Immunoglobulin G/*biosynthesis ; Interleukin-4/biosynthesis ; Lectins, C-Type ; Leishmania mexicana/immunology ; Major Histocompatibility Complex ; Mice ; Mice, Inbred Strains ; NK Cell Lectin-Like Receptor Subfamily B ; Plasmodium/immunology ; Proteins/analysis ; Protozoan Proteins/immunology ; T-Lymphocyte Subsets/*immunology ; T-Lymphocytes, Helper-Inducer/*immunology ; Trypanosoma brucei brucei/immunology ; Variant Surface Glycoproteins, Trypanosoma/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Human origins and ancient human DNA (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-06-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cooper, A -- Rambaut, A -- Macaulay, V -- Willerslev, E -- Hansen, A J -- Stringer, C -- New York, N.Y. -- Science. 2001 Jun 1;292(5522):1655-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11388352" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Animals ; Australia ; Base Sequence ; Biological Evolution ; DNA Damage ; DNA, Mitochondrial/*genetics ; Hominidae/*genetics ; Humans ; *Paleontology ; *Phylogeny ; Specimen Handling
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    LNA-mediated microRNA silencing in non-human primates (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-03-28
    Description: microRNAs (miRNAs) are small regulatory RNAs that are important in development and disease and therefore represent a potential new class of targets for therapeutic intervention. Despite recent progress in silencing of miRNAs in rodents, the development of effective and safe approaches for sequence-specific antagonism of miRNAs in vivo remains a significant scientific and therapeutic challenge. Moreover, there are no reports of miRNA antagonism in primates. Here we show that the simple systemic delivery of a unconjugated, PBS-formulated locked-nucleic-acid-modified oligonucleotide (LNA-antimiR) effectively antagonizes the liver-expressed miR-122 in non-human primates. Acute administration by intravenous injections of 3 or 10 mg kg(-1) LNA-antimiR to African green monkeys resulted in uptake of the LNA-antimiR in the cytoplasm of primate hepatocytes and formation of stable heteroduplexes between the LNA-antimiR and miR-122. This was accompanied by depletion of mature miR-122 and dose-dependent lowering of plasma cholesterol. Efficient silencing of miR-122 was achieved in primates by three doses of 10 mg kg(-1) LNA-antimiR, leading to a long-lasting and reversible decrease in total plasma cholesterol without any evidence for LNA-associated toxicities or histopathological changes in the study animals. Our findings demonstrate the utility of systemically administered LNA-antimiRs in exploring miRNA function in rodents and primates, and support the potential of these compounds as a new class of therapeutics for disease-associated miRNAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elmen, Joacim -- Lindow, Morten -- Schutz, Sylvia -- Lawrence, Matthew -- Petri, Andreas -- Obad, Susanna -- Lindholm, Marie -- Hedtjarn, Maj -- Hansen, Henrik Frydenlund -- Berger, Urs -- Gullans, Steven -- Kearney, Phil -- Sarnow, Peter -- Straarup, Ellen Marie -- Kauppinen, Sakari -- England -- Nature. 2008 Apr 17;452(7189):896-9. doi: 10.1038/nature06783. Epub 2008 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Santaris Pharma, Boge Alle 3, DK-2970 Horsholm, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368051" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cercopithecus aethiops/*genetics ; Female ; *Gene Silencing ; Mice ; Mice, Inbred C57BL ; MicroRNAs/*genetics ; Oligonucleotides/administration & dosage/adverse effects/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    CBP/p300-mediated acetylation of histone H3 on lysine 56 (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-03-10
    Description: Acetylation within the globular core domain of histone H3 on lysine 56 (H3K56) has recently been shown to have a critical role in packaging DNA into chromatin following DNA replication and repair in budding yeast. However, the function or occurrence of this specific histone mark has not been studied in multicellular eukaryotes, mainly because the Rtt109 enzyme that is known to mediate acetylation of H3K56 (H3K56ac) is fungal-specific. Here we demonstrate that the histone acetyl transferase CBP (also known as Nejire) in flies and CBP and p300 (Ep300) in humans acetylate H3K56, whereas Drosophila Sir2 and human SIRT1 and SIRT2 deacetylate H3K56ac. The histone chaperones ASF1A in humans and Asf1 in Drosophila are required for acetylation of H3K56 in vivo, whereas the histone chaperone CAF-1 (chromatin assembly factor 1) in humans and Caf1 in Drosophila are required for the incorporation of histones bearing this mark into chromatin. We show that, in response to DNA damage, histones bearing acetylated K56 are assembled into chromatin in Drosophila and human cells, forming foci that colocalize with sites of DNA repair. Furthermore, acetylation of H3K56 is increased in multiple types of cancer, correlating with increased levels of ASF1A in these tumours. Our identification of multiple proteins regulating the levels of H3K56 acetylation in metazoans will allow future studies of this critical and unique histone modification that couples chromatin assembly to DNA synthesis, cell proliferation and cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756583/" 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/PMC2756583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Chandrima -- Lucia, M Scott -- Hansen, Kirk C -- Tyler, Jessica K -- CA95641/CA/NCI NIH HHS/ -- GM64475/GM/NIGMS NIH HHS/ -- R01 CA095641/CA/NCI NIH HHS/ -- R01 CA095641-07/CA/NCI NIH HHS/ -- R01 GM064475/GM/NIGMS NIH HHS/ -- R01 GM064475-07/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 May 7;459(7243):113-7. doi: 10.1038/nature07861. Epub 2009 Mar 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, PO Box 6511, Aurora Colorado 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19270680" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Cycle Proteins/metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Damage/physiology ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*enzymology ; HeLa Cells ; Histone Deacetylases/metabolism ; Histones/*metabolism ; Humans ; Lysine/*metabolism ; Molecular Chaperones/metabolism ; Retinoblastoma-Binding Protein 4 ; Sirtuin 1 ; Sirtuin 2 ; Sirtuins/metabolism ; p300-CBP Transcription Factors/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    A safe operating space for humanity (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rockstrom, Johan -- Steffen, Will -- Noone, Kevin -- Persson, Asa -- Chapin, F Stuart 3rd -- Lambin, Eric F -- Lenton, Timothy M -- Scheffer, Marten -- Folke, Carl -- Schellnhuber, Hans Joachim -- Nykvist, Bjorn -- de Wit, Cynthia A -- Hughes, Terry -- van der Leeuw, Sander -- Rodhe, Henning -- Sorlin, Sverker -- Snyder, Peter K -- Costanza, Robert -- Svedin, Uno -- Falkenmark, Malin -- Karlberg, Louise -- Corell, Robert W -- Fabry, Victoria J -- Hansen, James -- Walker, Brian -- Liverman, Diana -- Richardson, Katherine -- Crutzen, Paul -- Foley, Jonathan A -- England -- Nature. 2009 Sep 24;461(7263):472-5. doi: 10.1038/461472a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stockholm Resilience Centre, Stockholm University, Kraftriket 2B, 10691 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779433" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Civilization ; Conservation of Natural Resources/*methods/trends ; *Earth (Planet) ; Ecology/*methods/*trends ; *Ecosystem ; Extinction, Biological ; Fossils ; Green Chemistry Technology/*methods/trends ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; History, Ancient ; *Human Activities/history ; Humans ; Nitrogen/metabolism ; Phosphorus/metabolism
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Mechanisms promoting translocations in editing and switching peripheral B cells (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-07-10
    Description: Variable, diversity and joining gene segment (V(D)J) recombination assembles immunoglobulin heavy or light chain (IgH or IgL) variable region exons in developing bone marrow B cells, whereas class switch recombination (CSR) exchanges IgH constant region exons in peripheral B cells. Both processes use directed DNA double-strand breaks (DSBs) repaired by non-homologous end-joining (NHEJ). Errors in either V(D)J recombination or CSR can initiate chromosomal translocations, including oncogenic IgH locus (Igh) to c-myc (also known as Myc) translocations of peripheral B cell lymphomas. Collaboration between these processes has also been proposed to initiate translocations. However, the occurrence of V(D)J recombination in peripheral B cells is controversial. Here we show that activated NHEJ-deficient splenic B cells accumulate V(D)J-recombination-associated breaks at the lambda IgL locus (Igl), as well as CSR-associated Igh breaks, often in the same cell. Moreover, Igl and Igh breaks are frequently joined to form translocations, a phenomenon associated with specific Igh-Igl co-localization. Igh and c-myc also co-localize in these cells; correspondingly, the introduction of frequent c-myc DSBs robustly promotes Igh-c-myc translocations. Our studies show peripheral B cells that attempt secondary V(D)J recombination, and determine a role for mechanistic factors in promoting recurrent translocations in tumours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907259/" 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/PMC2907259/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Jing H -- Gostissa, Monica -- Yan, Catherine T -- Goff, Peter -- Hickernell, Thomas -- Hansen, Erica -- Difilippantonio, Simone -- Wesemann, Duane R -- Zarrin, Ali A -- Rajewsky, Klaus -- Nussenzweig, Andre -- Alt, Frederick W -- 5P01CA92625/CA/NCI NIH HHS/ -- P01 CA092625/CA/NCI NIH HHS/ -- P01 CA092625-010001/CA/NCI NIH HHS/ -- P01 CA092625-020001/CA/NCI NIH HHS/ -- P01 CA092625-060006/CA/NCI NIH HHS/ -- P01 CA092625-070006/CA/NCI NIH HHS/ -- P01 CA092625-080006/CA/NCI NIH HHS/ -- P01 CA092625-090006/CA/NCI NIH HHS/ -- R01 AI077595/AI/NIAID NIH HHS/ -- R01 AI077595-02/AI/NIAID NIH HHS/ -- T32 CA009382/CA/NCI NIH HHS/ -- T32 CA009382-27/CA/NCI NIH HHS/ -- T32 CA009382-28/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2009 Jul 9;460(7252):231-6. doi: 10.1038/nature08159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*metabolism ; Cytidine Deaminase/deficiency/genetics/metabolism ; DNA Breaks, Double-Stranded ; DNA-Binding Proteins/deficiency/metabolism ; Female ; Gene Rearrangement, B-Lymphocyte/*genetics ; Genes, Immunoglobulin/*genetics ; Genes, myc/genetics ; Homeodomain Proteins/metabolism ; Immunoglobulin Class Switching/*genetics ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin kappa-Chains/genetics ; Immunoglobulin lambda-Chains/genetics ; Integrases/genetics/metabolism ; Interphase ; Lymphocyte Activation ; Male ; Mice ; Receptors, Complement 3d/genetics ; Recombination, Genetic/genetics ; Spleen/cytology/immunology ; Translocation, Genetic/*genetics
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-12-20
    Description: Dimerization among transcription factors has become a recurrent theme in the regulation of eukaryotic gene expression. Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a homeodomain-containing protein that functions as a dimer. A dimerization cofactor of HNF-1 alpha (DCoH) was identified that displayed a restricted tissue distribution and did not bind to DNA, but, rather, selectively stabilized HNF-1 alpha dimers. The formation of a stable tetrameric DCoH-HNF-1 alpha complex, which required the dimerization domain of HNF-1 alpha, did not change the DNA binding characteristics of HNF-1 alpha, but enhanced its transcriptional activity. However, DCoH did not confer transcriptional activation to the GAL4 DNA binding domain. These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mendel, D B -- Khavari, P A -- Conley, P B -- Graves, M K -- Hansen, L P -- Admon, A -- Crabtree, G R -- CA 09302/CA/NCI NIH HHS/ -- HD 07201/HD/NICHD NIH HHS/ -- HL 33942/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1991 Dec 20;254(5039):1762-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1763325" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Nucleus/physiology ; Chromosome Deletion ; DNA-Binding Proteins/*metabolism ; Gene Library ; Hepatocyte Nuclear Factor 1 ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocyte Nuclear Factor 1-beta ; Humans ; *Hydro-Lyases ; Liver/physiology ; Macromolecular Substances ; Mice ; Molecular Sequence Data ; *Nuclear Proteins ; Protein Biosynthesis ; RNA, Messenger/genetics ; Rabbits ; Rats ; Reticulocytes/metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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