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11.
Romeo S Pennacchio LA Fu Y Boerwinkle E Tybjaerg-Hansen A Hobbs HH Cohen JC 《Nature genetics》2007,39(4):513-516
Resequencing genes provides the opportunity to assess the full spectrum of variants that influence complex traits. Here we report the first application of resequencing to a large population (n = 3,551) to examine the role of the adipokine ANGPTL4 in lipid metabolism. Nonsynonymous variants in ANGPTL4 were more prevalent in individuals with triglyceride levels in the lowest quartile than in individuals with levels in the highest quartile (P = 0.016). One variant (E40K), present in approximately 3% of European Americans, was associated with significantly lower plasma levels of triglyceride and higher levels of high-density lipoprotein cholesterol in European Americans from the Atherosclerosis Risk in Communities Study and in Danes from the Copenhagen City Heart Study. The ratio of nonsynonymous to synonymous variants was higher in European Americans than in African Americans (4:1 versus 1.3:1), suggesting population-specific relaxation of purifying selection. Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history. 相似文献
12.
Hellgren M Strömberg P Gallego O Martras S Farrés J Persson B Parés X Höög JO 《Cellular and molecular life sciences : CMLS》2007,64(4):498-505
The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2
(ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with
an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined Km values ranged from 0.05 to 0.3 μM and kcat values from 2.3 to 17.6 min−1, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities
were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup.
This mutation increased the retinoid activity up to 100-fold. The Km values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic
retinol oxidation at physiological concentrations.
Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007 相似文献
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17.
W. Jadassohn E. Cherbuliez P. Boymond H. Isler 《Cellular and molecular life sciences : CMLS》1948,4(6):225-226
Summary The authors show the antibiotic activity of water-insoluble salts of hydrosoluble antibiotics in the case of penicillin G (salts of iron, copper, silver, gold, and uranium) and streptomycin (oleate). 相似文献
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Komen JC Distelmaier F Koopman WJ Wanders RJ Smeitink J Willems PH 《Cellular and molecular life sciences : CMLS》2007,64(24):3271-3281
Refsum disease is a rare, inherited neurodegenerative disorder characterized by accumulation of the dietary branched-chain
fatty acid phytanic acid in plasma and tissues caused by a defect in the alphaoxidation pathway. The accumulation of phytanic
acid is believed to be the main pathophysiological cause of the disease. However, the exact mechanism(s) by which phytanic
acid exerts its toxicity have not been resolved. In this study, the effect of phytanic acid on mitochondrial respiration was
investigated. The results show that in digitonin-permeabilized fibroblasts, phytanic acid decreases ATP synthesis, whereas
substrate oxidation per se is not affected. Importantly, studies in intact fibroblasts revealed that phytanic acid decreases both the mitochondrial
membrane potential and NAD(P)H autofluorescence. Taken together, the results described here show that unesterified phytanic
acid exerts its toxic effect mainly through its protonophoric action, at least in human skin fibroblasts.
Received 4 August 2007; received after revision 26 September 2007; accepted 10 October 2007
J. C. Komen, F. Distelmaier: These authors contributed equally to this work. 相似文献
20.
1 Results Oxy-apatite materials are thought as zirconia-substitutes in Solid Oxide Fuel Cells due to their fast ionic conduction. However, the well known difficulties related to their densification prevent them from being used as such. This study presents strategies to obtain oxy-apatite dense materials and the influence of elaboration route on transport properties. Particular emphasis is put on the microstructure effect on ion conduction. By the combined use of freeze-drying and conventional or spark p... 相似文献