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  • 1
    ISSN: 0031-9422
    Keywords: Cactaceae ; Cephalocereus senilis ; HPLC. ; aurone ; enzyme induction ; phytoalexin ; suspension culture
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0031-9422
    Keywords: Cactaceae ; Cephalocereus senilis ; HPLC ; aurone ; enzyme induction ; phytoalexin ; suspension culture
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2012-02-22
    Description: Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from alpha-ketoglutarate. Here we report that 2HG-producing IDH mutants can prevent the histone demethylation that is required for lineage-specific progenitor cells to differentiate into terminally differentiated cells. In tumour samples from glioma patients, IDH mutations were associated with a distinct gene expression profile enriched for genes expressed in neural progenitor cells, and this was associated with increased histone methylation. To test whether the ability of IDH mutants to promote histone methylation contributes to a block in cell differentiation in non-transformed cells, we tested the effect of neomorphic IDH mutants on adipocyte differentiation in vitro. Introduction of either mutant IDH or cell-permeable 2HG was associated with repression of the inducible expression of lineage-specific differentiation genes and a block to differentiation. This correlated with a significant increase in repressive histone methylation marks without observable changes in promoter DNA methylation. Gliomas were found to have elevated levels of similar histone repressive marks. Stable transfection of a 2HG-producing mutant IDH into immortalized astrocytes resulted in progressive accumulation of histone methylation. Of the marks examined, increased H3K9 methylation reproducibly preceded a rise in DNA methylation as cells were passaged in culture. Furthermore, we found that the 2HG-inhibitable H3K9 demethylase KDM4C was induced during adipocyte differentiation, and that RNA-interference suppression of KDM4C was sufficient to block differentiation. Together these data demonstrate that 2HG can inhibit histone demethylation and that inhibition of histone demethylation can be sufficient to block the differentiation of non-transformed cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478770/" 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/PMC3478770/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Chao -- Ward, Patrick S -- Kapoor, Gurpreet S -- Rohle, Dan -- Turcan, Sevin -- Abdel-Wahab, Omar -- Edwards, Christopher R -- Khanin, Raya -- Figueroa, Maria E -- Melnick, Ari -- Wellen, Kathryn E -- O'Rourke, Donald M -- Berger, Shelley L -- Chan, Timothy A -- Levine, Ross L -- Mellinghoff, Ingo K -- Thompson, Craig B -- R01 CA078831/CA/NCI NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- U54CA143798/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 15;483(7390):474-8. doi: 10.1038/nature10860.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22343901" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/cytology/drug effects/metabolism ; Animals ; Astrocytes/cytology/drug effects ; Cell Differentiation/drug effects/*genetics ; Cell Line, Tumor ; Cell Lineage/genetics ; DNA Methylation/drug effects ; Enzyme Induction/drug effects ; Gene Expression Regulation/drug effects ; Glioma/enzymology/genetics/pathology ; Glutarates/metabolism/pharmacology ; HEK293 Cells ; Histones/*metabolism ; Humans ; Isocitrate Dehydrogenase/antagonists & inhibitors/*genetics/metabolism ; Jumonji Domain-Containing Histone Demethylases/antagonists & ; inhibitors/deficiency/genetics/metabolism ; Methylation/drug effects ; Mice ; Mutation/*genetics ; Neural Stem Cells/metabolism ; Promoter Regions, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-08-01
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692367/" 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/PMC4692367/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akbari, Omar S -- Bellen, Hugo J -- Bier, Ethan -- Bullock, Simon L -- Burt, Austin -- Church, George M -- Cook, Kevin R -- Duchek, Peter -- Edwards, Owain R -- Esvelt, Kevin M -- Gantz, Valentino M -- Golic, Kent G -- Gratz, Scott J -- Harrison, Melissa M -- Hayes, Keith R -- James, Anthony A -- Kaufman, Thomas C -- Knoblich, Juergen -- Malik, Harmit S -- Matthews, Kathy A -- O'Connor-Giles, Kate M -- Parks, Annette L -- Perrimon, Norbert -- Port, Fillip -- Russell, Steven -- Ueda, Ryu -- Wildonger, Jill -- R01 AI070654/AI/NIAID NIH HHS/ -- R01 AI110713/AI/NIAID NIH HHS/ -- T32 GM007133/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):927-9. doi: 10.1126/science.aac7932. Epub 2015 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Entomology, Univ. of California, Riverside, CA 92507, USA. Center for Disease Vector Research, Institute for Integrative Genome Biology, Univ. of California, Riverside, CA 92507, USA. ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. ; Section of Cell and Developmental Biology, Univ. of California, San Diego, La Jolla, CA 92095, USA. kevin.esvelt@wyss.harvard.edu ebier@ucsd.edu. ; Division of Cell Biology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berks SL5 7PY, UK. ; Wyss Institute for Biologically Inspired Engineering, Harvard Medical School, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Bloomington Drosophila Stock Center, Department of Biology, Indiana Univ., Bloomington, IN 47405, USA. ; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria. ; CSIRO Centre for Environment and Life Sciences, Underwood Avenue, Floreat, WA 6014, Australia. ; Wyss Institute for Biologically Inspired Engineering, Harvard Medical School, Boston, MA 02115, USA. kevin.esvelt@wyss.harvard.edu ebier@ucsd.edu. ; Section of Cell and Developmental Biology, Univ. of California, San Diego, La Jolla, CA 92095, USA. ; Department of Biology, Univ. of Utah, Salt Lake City, UT 84112, USA. ; Laboratory of Genetics, Univ. of Wisconsin-Madison, Madison, WI 53706, USA. ; Department of Biomolecular Chemistry, Univ. of Wisconsin-Madison, Madison, WI 53706, USA. ; CSIRO Biosecurity Flagship, General Post Of ce Box 1538, Hobart, Tasmania, 7001, Australia. ; Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, Univ. of California at Irvine, Irvine, CA 92697, USA. ; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; Laboratory of Genetics, Univ. of Wisconsin-Madison, Madison, WI 53706, USA. Laboratory of Cell and Molecular Biology, Univ. of Wisconsin-Madison, Madison, WI 53706, USA. ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. ; Department of Genetics, Univ. of Cambridge, Cambridge, Cambridgeshire CB2 3EH, UK. ; Department of Genetics, Graduate Univ. for Advanced Studies, Mishima, Shizuoka 411-8540, Japan. NIG-Fly Stock Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan. ; Department of Biochemistry, Univ. of Wisconsin-Madison, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26229113" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; *Containment of Biohazards ; Endonucleases/metabolism ; *Genetic Engineering ; *Genetic Research ; Genome ; *Organisms, Genetically Modified ; *Safety
    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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