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  • 1
    Publication Date: 2002-11-26
    Description: Neuronal PAS domain protein 2 (NPAS2) is a mammalian transcription factor that binds DNA as an obligate dimeric partner of BMAL1 and is implicated in the regulation of circadian rhythm. Here we show that both PAS domains of NPAS2 bind heme as a prosthetic group and that the heme status controls DNA binding in vitro. NPAS2-BMAL1 heterodimers, existing in either the apo (heme-free) or holo (heme-loaded) state, bound DNA avidly under favorably reducing ratios of the reduced and oxidized forms of nicotinamide adenine dinucleotide phosphate. Low micromolar concentrations of carbon monoxide inhibited the DNA binding activity of holo-NPAS2 but not that of apo-NPAS2. Upon exposure to carbon monoxide, inactive BMAL1 homodimers were formed at the expense of NPAS2-BMAL1 heterodimers. These results indicate that the heterodimerization of NPAS2, and presumably the expression of its target genes, are regulated by a gas through the heme-based sensor described here.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dioum, Elhadji M -- Rutter, Jared -- Tuckerman, Jason R -- Gonzalez, Gonzalo -- Gilles-Gonzalez, Marie-Alda -- McKnight, Steven L -- NIH5-T32-GM08-291-12/GM/NIGMS NIH HHS/ -- R01 HL640381/HL/NHLBI NIH HHS/ -- R01 MH5938805/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 20;298(5602):2385-7. Epub 2002 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Biochemistry and Plant Biology and Plant Biotechnology Center, The Ohio State University, 1060 Carmack Road, Columbus, OH 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12446832" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; Carbon Monoxide/*metabolism/pharmacology ; Circadian Rhythm ; DNA/*metabolism ; Dimerization ; Helix-Loop-Helix Motifs ; Heme/chemistry/*metabolism ; Ligands ; Myoglobin/metabolism ; NADP/metabolism ; Nerve Tissue Proteins/*chemistry/*metabolism ; Oxidation-Reduction ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry/metabolism ; Spectrophotometry, Ultraviolet ; Transcription Factors/*chemistry/*metabolism
    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
    ISSN: 1434-1948
    Keywords: Carbene complexes ; Carboxylato complexes ; Density functional calculations ; Palladium ; Rhodium ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The structures of several complexes arising from the interaction between methylene and palladium and rhodium diformates were optimized through density functional calculations. For palladium, mono-, di-, and trimeric complexes were considered. The results obtained show that in all cases the most stable structures correspond to complexes in which methylene has inserted in one of the M-O bonds, while metal-carbene complexes are energy minima only for monomeric palladium diformate and for rhodium diformate. Trimeric palladium formate is thermodynamically stable upon fragmentation. However, when it reacts with methylene, fragmentation becomes favorable. The role of the resulting monomeric complex in the olefin cyclopropanation mechanism catalyzed by palladium dicarboxylates is discussed.
    Additional Material: 7 Ill.
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  • 3
    ISSN: 1434-193X
    Keywords: Cycloadditions ; Carbenes ; Nitrones ; Nitrilimines ; Pyrazolines ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: ---The reaction of tert-butylalkynyl chromium Fischer carbene complex 1 with nitrones 2 affords β-enamino-ketoaldehydes 4 by the light-promoted rearrangement of the corresponding [3+2] cycloadduct carbene complexes 3. On the other hand, [3+2] cycloaddition of chiral nonracemic Fischer alkenyl carbene complexes 19 with nitrilimines 10 yields enantiomerically pure Δ2-pyrazolines with high regio- and diastereoselectivity.
    Additional Material: 3 Ill.
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  • 4
    ISSN: 1434-193X
    Keywords: Carbohydrates ; Glycosides ; Conformation analysis ; Molecular modeling ; Carbohydrates ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: ---The conformational behaviours of several nonhydrolizable lactose analogues, namely methyl α-thiolactoside (1), methyl β-carbalactoside (2) and methyl β-carbaiminolactoside (3) have been studied using a combination of NMR spectroscopy (J and NOE data) and molecular mechanics calculations. Analogies and differences with the natural compounds have been found.Supporting information for this article is available on the WWW under //http://www.wiley-vch.de/contents/jc_2046/2000/99592_s.pdf or from the author.
    Additional Material: 3 Ill.
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  • 5
    Publication Date: 2002-12-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Funes, Soledad -- Davidson, Edgar -- Reyes-Prieto, Adrian -- Magallon, Susana -- Herion, Pascal -- King, Michael P -- Gonzalez-Halphen, Diego -- HL59646/HL/NHLBI NIH HHS/ -- TW01176/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2155.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico (UNAM), 04510 D.F., Mexico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12481129" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apicomplexa/enzymology/*genetics/ultrastructure ; *Biological Evolution ; Cell Nucleus/genetics ; Chlamydomonas reinhardtii/enzymology/genetics ; Chlorophyta/enzymology/*genetics ; Cloning, Molecular ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/chemistry/*genetics ; *Gene Transfer, Horizontal ; Genes ; Genes, Protozoan ; Molecular Sequence Data ; Phylogeny ; Plastids/*genetics ; Symbiosis ; Toxoplasma/enzymology/genetics
    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
    Publication Date: 2001-12-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vecchione, M -- Young, R E -- Guerra, A -- Lindsay, D J -- Clague, D A -- Bernhard, J M -- Sager, W W -- Gonzalez, A F -- Rocha, F J -- Segonzac, M -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2505.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Marine Fisheries Service, Systematics Laboratory, National Museum of Natural History, Washington, DC 20560, USA. vecchione.michael@nmnh.si.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11752567" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Decapodiformes/*anatomy & histology/classification/*physiology ; *Ecosystem ; Escape Reaction ; Locomotion ; Movement ; Oceans and Seas ; Seawater ; Videotape Recording
    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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  • 7
    Publication Date: 2002-05-04
    Description: Extracts of the resin of the guggul tree (Commiphora mukul) lower LDL (low-density lipoprotein) cholesterol levels in humans. The plant sterol guggulsterone [4,17(20)-pregnadiene-3,16-dione] is the active agent in this extract. We show that guggulsterone is a highly efficacious antagonist of the farnesoid X receptor (FXR), a nuclear hormone receptor that is activated by bile acids. Guggulsterone treatment decreases hepatic cholesterol in wild-type mice fed a high-cholesterol diet but is not effective in FXR-null mice. Thus, we propose that inhibition of FXR activation is the basis for the cholesterol-lowering activity of guggulsterone. Other natural products with specific biologic effects may modulate the activity of FXR or other relatively promiscuous nuclear hormone receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Urizar, Nancy L -- Liverman, Amy B -- Dodds, D'Nette T -- Silva, Frank Valentin -- Ordentlich, Peter -- Yan, Yingzhuo -- Gonzalez, Frank J -- Heyman, Richard A -- Mangelsdorf, David J -- Moore, David D -- New York, N.Y. -- Science. 2002 May 31;296(5573):1703-6. Epub 2002 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988537" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Caco-2 Cells ; Carrier Proteins/genetics/metabolism ; Cells, Cultured ; Chenodeoxycholic Acid/pharmacology ; Cholesterol/*metabolism ; Cholesterol, Dietary/administration & dosage ; DNA/metabolism ; DNA-Binding Proteins/*antagonists & inhibitors/chemistry/genetics/*metabolism ; Hepatocytes/metabolism ; Histone Acetyltransferases ; Humans ; *Hydroxysteroid Dehydrogenases ; Hypolipidemic Agents/metabolism/*pharmacology ; Ligands ; Liver/metabolism ; *Membrane Glycoproteins ; Mice ; Nuclear Receptor Coactivator 1 ; Pregnenediones/metabolism/*pharmacology ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors/genetics/metabolism ; Receptors, Steroid/antagonists & inhibitors/metabolism ; Transcription Factors/*antagonists & inhibitors/chemistry/genetics/*metabolism ; Transcriptional Activation/drug effects ; Transfection ; Tumor Cells, Cultured
    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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  • 8
    Publication Date: 2003-03-08
    Description: Mutations in the cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1) gene are a common cause of human primary congenital glaucoma (PCG). Here we show that Cyp1b1-/- mice have ocular drainage structure abnormalities resembling those reported in human PCG patients. Using Cyp1b1-/- mice, we identified the tyrosinase gene (Tyr) as a modifier of the drainage structure phenotype, with Tyr deficiency increasing the magnitude of dysgenesis. The severe dysgenesis in eyes lacking both CYP1B1 and TYR was alleviated by administration of the tyrosinase product dihydroxyphenylalanine (l-dopa). Tyr also modified the drainage structure dysgenesis in mice with a mutant Foxc1 gene, which is also involved in PCG. These experiments raise the possibility that a tyrosinase/l-dopa pathway modifies human PCG, which could open new therapeutic avenues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Libby, Richard T -- Smith, Richard S -- Savinova, Olga V -- Zabaleta, Adriana -- Martin, Janice E -- Gonzalez, Frank J -- John, Simon W M -- CA34196/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Mar 7;299(5612):1578-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jackson Laboratory, Bar Harbor, ME 04609, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12624268" target="_blank"〉PubMed〈/a〉
    Keywords: Albinism, Ocular/genetics/pathology ; Animals ; Anterior Eye Segment/*abnormalities ; Aryl Hydrocarbon Hydroxylases/deficiency/genetics ; Cornea/abnormalities ; Cytochrome P-450 CYP1B1 ; *DNA-Binding Proteins ; Disease Models, Animal ; Female ; Forkhead Transcription Factors ; Glaucoma/*congenital/enzymology/*genetics/pathology ; Intraocular Pressure ; Iris/abnormalities ; Levodopa/administration & dosage/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Monophenol Monooxygenase/deficiency/*genetics/metabolism ; Mutation ; Phenotype ; Pregnancy ; Trabecular Meshwork/abnormalities ; Transcription Factors/genetics
    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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  • 9
    Publication Date: 2004-04-17
    Description: 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〉
    Keywords: 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
    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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  • 10
    Publication Date: 2003-06-07
    Description: The proper development of the central nervous system depends upon a finely tuned balance between cell proliferation and programmed cell death (PCD). Although PCD was initially believed to depend solely on the inability of certain neurons to obtain access to a limited supply of trophic factors, it has become apparent that the local production of death signals is also critical. In this Viewpoint, we discuss several pathways implicated in the survival of cerebellar granule cells- both pathways that protect from apoptosis and pathways that promote apoptosis-and describe how these disparate pathways converge on the final common mediators of PCD. Information on other important pathways implicated in granule cell survival may be found in the Connections Maps.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vaudry, David -- Falluel-Morel, Anthony -- Leuillet, Sebastien -- Vaudry, Hubert -- Gonzalez, Bruno J -- New York, N.Y. -- Science. 2003 Jun 6;300(5625):1532-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Institute for Peptide Research (IFRMP 23), Laboratoryof Cellular and Molecular Neuroendocrinology, INSERM U413, University of Rouen, 76821 Mont-Saint-Aignan, France. david.vaudry@univ-rouen.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12791981" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Caspase 3 ; Caspases/metabolism ; *Cell Survival ; Cerebellar Cortex/*cytology ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/metabolism ; Nerve Growth Factors/metabolism ; Neurons/cytology/*physiology ; *Signal Transduction ; Transforming Growth Factor beta/metabolism ; Tumor Suppressor Protein p53/metabolism
    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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