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W. D. MacRae G. F. Q. Chan Chi-Kit Wat G. H. N. Towers J. Lam 《Cellular and molecular life sciences : CMLS》1980,36(9):1096-1097
Summary -Terthienyl and 5 polyacetylenes were examined for chromosome damaging activity using Syrian hamster cells. None of these naturally occurring compounds induced sister chromatid exchanges and neither -terthienyl nor phenylheptatriyne induced chromosome aberrations.The authors wish to thank the National Science and Engineering Research Council for financial support of this research. 相似文献
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Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy 总被引:20,自引:0,他引:20
Gerull B Heuser A Wichter T Paul M Basson CT McDermott DA Lerman BB Markowitz SM Ellinor PT MacRae CA Peters S Grossmann KS Drenckhahn J Michely B Sasse-Klaassen S Birchmeier W Dietz R Breithardt G Schulze-Bahr E Thierfelder L 《Nature genetics》2004,36(11):1162-1164
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations. 相似文献
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Edith Krugelis MacRae 《Cellular and molecular life sciences : CMLS》1963,19(2):77-78
Résumé Chez les Turbellaires, l'auteur a trouvé de l'uroporphyrine dans les vers des genresDugesia etCura, et de la coproporphyrine dans ceux des genresPhagocata etBdellocephala. Les porphyrines ont été identifiées par la chromatographie sur papier. Elles sont localisées dans les rhabdites des cellules de l'épiderme et du sous-épiderme de ces vers. 相似文献
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Gudbjartsson DF Arnar DO Helgadottir A Gretarsdottir S Holm H Sigurdsson A Jonasdottir A Baker A Thorleifsson G Kristjansson K Palsson A Blondal T Sulem P Backman VM Hardarson GA Palsdottir E Helgason A Sigurjonsdottir R Sverrisson JT Kostulas K Ng MC Baum L So WY Wong KS Chan JC Furie KL Greenberg SM Sale M Kelly P MacRae CA Smith EE Rosand J Hillert J Ma RC Ellinor PT Thorgeirsson G Gulcher JR Kong A Thorsteinsdottir U Stefansson K 《Nature》2007,448(7151):353-357
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality. Recent studies have provided evidence of a genetic contribution to AF. Mutations in potassium-channel genes have been associated with familial AF but account for only a small fraction of all cases of AF. We have performed a genome-wide association scan, followed by replication studies in three populations of European descent and a Chinese population from Hong Kong and find a strong association between two sequence variants on chromosome 4q25 and AF. Here we show that about 35% of individuals of European descent have at least one of the variants and that the risk of AF increases by 1.72 and 1.39 per copy. The association with the stronger variant is replicated in the Chinese population, where it is carried by 75% of individuals and the risk of AF is increased by 1.42 per copy. A stronger association was observed in individuals with typical atrial flutter. Both variants are adjacent to PITX2, which is known to have a critical function in left-right asymmetry of the heart. 相似文献
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Furuhashi M Tuncman G Görgün CZ Makowski L Atsumi G Vaillancourt E Kono K Babaev VR Fazio S Linton MF Sulsky R Robl JA Parker RA Hotamisligil GS 《Nature》2007,447(7147):959-965
Adipocyte fatty-acid-binding protein, aP2 (FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deficient mice have shown that this lipid chaperone has a significant role in several aspects of metabolic syndrome, including type 2 diabetes and atherosclerosis. Here we demonstrate that an orally active small-molecule inhibitor of aP2 is an effective therapeutic agent against severe atherosclerosis and type 2 diabetes in mouse models. In macrophage and adipocyte cell lines with or without aP2, we also show the target specificity of this chemical intervention and its mechanisms of action on metabolic and inflammatory pathways. Our findings demonstrate that targeting aP2 with small-molecule inhibitors is possible and can lead to a new class of powerful therapeutic agents to prevent and treat metabolic diseases such as type 2 diabetes and atherosclerosis. 相似文献
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Anaerobic degradation of the insecticide lindane by Clostridium sp 总被引:11,自引:0,他引:11
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Small heat shock proteins: molecular structure and chaperone function 总被引:17,自引:0,他引:17
Small heat shock proteins (sHSPs) associate with nuclei, cytoskeleton and membranes, and as molecular chaperones they bind
partially denatured proteins, thereby preventing irreversible protein aggregation during stress. sHSP monomers consist of
a conserved α-crystallin domain of approximately 90 amino acid residues, bordered by variable amino- and carboxy-terminal
extensions. The sHSPs undergo dynamic assembly into mono- and poly-disperse oligomers where the rate of disassembly affects
chaperoning. The α-crystallin domain contains several β-strands organized into two β-sheets responsible for dimer formation,
the basic building block of most sHSPS. The amino-terminal extension modulates oligomerization, subunit dynamics and substrate
binding, whereas the flexible carboxy-terminal extension promotes solubility, chaperoning and oligomerization, the latter
by inter-subunit linkage. Crystallization studies have revealed sHSP structure and function. Additionally, site-directed mutagenesis,
biophysical investigations, functional studies and the discovery of relationships between mutated sHSPs and diseases have
illuminated the role of sHSP within cells.
Received 8 May 2005; received after revision 24 June 2005; accepted 19 July 2005 相似文献
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Structure and function of small heat shock/alpha-crystallin proteins: established concepts and emerging ideas 总被引:5,自引:0,他引:5
MacRae TH 《Cellular and molecular life sciences : CMLS》2000,57(6):899-913
Small heat shock/alpha-crystallin proteins are defined by conserved sequence of approximately 90 amino acid residues, termed the alpha-crystallin domain, which is bounded by variable amino- and carboxy-terminal extensions. These proteins form oligomers, most of uncertain quaternary structure, and oligomerization is prerequisite to their function as molecular chaperones. Sequence modelling and physical analyses show that the secondary structure of small heat shock/alpha-crystallin proteins is predominately beta-pleated sheet. Crystallography, site-directed spin-labelling and yeast two-hybrid selection demonstrate regions of secondary structure within the alpha-crystallin domain that interact during oligomer assembly, a process also dependent on the amino terminus. Oligomers are dynamic, exhibiting subunit exchange and organizational plasticity, perhaps leading to functional diversity. Exposure of hydrophobic residues by structural modification facilitates chaperoning where denaturing proteins in the molten globule state associate with oligomers. The flexible carboxy-terminal extension contributes to chaperone activity by enhancing the solubility of small heat shock/alpha-crystallin proteins. Site-directed mutagenesis has yielded proteins where the effect of the change on structure and function depends upon the residue modified, the organism under study and the analytical techniques used. Most revealing, substitution of a conserved arginine residue within the alpha-crystallin domain has a major impact on quaternary structure and chaperone action probably through realignment of beta-sheets. These mutations are linked to inherited diseases. Oligomer size is regulated by a stress-responsive cascade including MAPKAP kinase 2/3 and p38. Phosphorylation of small heat shock/alpha-crystallin proteins has important consequences within stressed cells, especially for microfilaments. 相似文献
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