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Plasma soluble Receptor for Advanced Glycation End-products (sRAGE) is a strong marker of vascular outcomes although evidence on the direction of association is mixed. Compared to whites, blacks have lower levels of sRAGE. We hypothesized that genetic determinants of sRAGE would help clarify the causal role of sRAGE and the black-white difference in sRAGE levels. We conducted a genome-wide analysis of sRAGE in whites and blacks from the Atherosclerosis Risk in Communities Study. Median plasma sRAGE levels were lower in blacks than whites (728 vs. 1067 pg/ml; P<0.0001). The T (vs. C) allele of rs2070600, a missense variant in AGER, the gene encoding RAGE, was associated with approximately 50% lower sRAGE levels in both whites (N = 1,737; P = 7.26x10-16; minor allele frequency (MAF) = 0.04) and blacks (N = 581; P = 0.02; MAF = 0.01). In blacks, the T (vs. C) allele of rs2071288, intronic to AGER, was associated with 43% lower sRAGE levels (P = 2.22x10-8; MAF = 0.10) and was nearly absent in whites. These AGER SNPs explained 21.5% and 26% of the variation in sRAGE in blacks and whites, respectively, but did not explain the black-white difference in sRAGE. These SNPs were not significantly associated with incident death, coronary heart disease, diabetes, heart failure, or chronic kidney disease in whites (N = 8,130–9,017) or blacks (N = 2,293–2,871) (median follow up ~20 years). We identified strong genetic determinants of sRAGE that did not explain the large black-white difference in sRAGE levels or clearly influence risk of clinical outcomes, suggesting that sRAGE may not be a causal factor in development of these outcomes.  相似文献   
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This paper examines the patterns of the US and Australian immigration geography and the process of regional population diversification and the emergence of new immigrant concentrations at the regional level. It presents a new approach in the context of human migration studies, focusing on spatial relatedness between individual foreign-born groups as revealed from the analysis of their joint spatial concentrations. The approach employs a simple assumption that the more frequently the members of two population groups concentrate in the same locations the higher is the probability that these two groups can be related. Based on detailed data on the spatial distribution of foreign-born groups in US counties (2000–2010) and Australian postal areas (2006–2011) we firstly quantify the spatial relatedness between all pairs of foreign-born groups and model the aggregate patterns of US and Australian immigration systems conceptualized as the undirected networks of foreign-born groups linked by their spatial relatedness. Secondly, adopting a more dynamic perspective, we assume that immigrant groups with higher spatial relatedness to those groups already concentrated in a region are also more likely to settle in this region in future. As the ultimate goal of the paper, we examine the power of spatial relatedness measures in projecting the emergence of new immigrant concentrations in the US and Australian regions. The results corroborate that the spatial relatedness measures can serve as useful instruments in the analysis of the patterns of population structure and prediction of regional population change. More generally, this paper demonstrates that information contained in spatial patterns (relatedness in space) of population composition has yet to be fully utilized in population forecasting.  相似文献   
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Brain Cell Biology - This paper describes the early stages of impregnation by the Golgi method. Sections of aldehyde-fixed and potassium dichromate-treated cerebral cortex were mounted on glass...  相似文献   
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Huntington''s disease (HD) is an inherited neurodegenerative disorder with progressive impairment of motor, behavioral and cognitive functions. The clinical features of HD are closely related to the degeneration of the basal ganglia, predominantly the striatum. The main striatal output structure, the globus pallidus, strongly accumulates metalloprotein-bound iron, which was recently shown to influence the diffusion tensor scalar values. To test the hypothesis that this effect dominates in the iron-rich basal ganglia of HD patients, we examined the globus pallidus using DTI and T2 relaxometry sequences. Quantitative magnetic resonance (MR), clinical and genetic data (number of CAG repeats) were obtained from 14 HD patients. MR parameters such as the T2 relaxation rate (RR), fractional anisotropy (FA) and mean diffusivity (MD) were analysed. A positive correlation was found between RR and FA (R2=0.84), between CAG and RR (R2=0.59) and between CAG and FA (R2=0.44). A negative correlation was observed between RR and MD (R2=0.66). A trend towards correlation between CAG and MD was noted. No correlation between MR and clinical parameters was found. Our results indicate that especially magnetic resonance FA measurements in the globus pallidus of HD patients may be strongly affected by metalloprotein-bound iron accumulation.  相似文献   
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