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41.
Yu XQ Li M Zhang H Low HQ Wei X Wang JQ Sun LD Sim KS Li Y Foo JN Wang W Li ZJ Yin XY Tang XQ Fan L Chen J Li RS Wan JX Liu ZS Lou TQ Zhu L Huang XJ Zhang XJ Liu ZH Liu JJ 《Nature genetics》2012,44(2):178-182
We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation. 相似文献
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Today, the time-to-market for plastic products ar e getting shorter, thus the lead-time for making the injection mould is decreasin g. There is potential in timesavings in the mould design stage because the design process that is repeatable for every mould design can be standardized. T he preliminary work of any final plastic injection mould design is to always pro vide an initial design of the mould assembly for product designers (customers) p rior to receiving the final product CAD data. Traditiona... 相似文献
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Chun-Song Chua Huiyu Low Kian-Sim Goo T. S. Sim 《Cellular and molecular life sciences : CMLS》2010,67(10):1675-1686
It is well known that the co-chaperone p23 regulates Hsp90 chaperone activity in protein folding. In Plasmodium falciparum, a putative p23 (Pfp23) has been identified through genome analysis, but its authenticity has remained unconfirmed since
co-immunoprecipitation experiments failed to show its interaction with P. falciparum Hsp90 (PfHsp90). Thus, recombinant Pfp23 and PfHsp90 proteins purified from expressed clones were used in this study. It
was clear that Pfp23 exhibited chaperone activity by virtue of its ability to suppress citrate synthase aggregation at 45°C.
Pfp23 was also shown to interact with PfHsp90 and to suppress its ATPase activity. Analyses of modeled Pfp23-PfHsp90 protein
complex and site-directed mutagenesis further revealed strategically placed amino acid residues, K91, H93, W94 and K96, in
Pfp23 to be crucial for binding PfHsp90. Collectively, this study has provided experimental evidence for the inherent chaperone
function of Pfp23 and its interaction with PfHsp90, a sequel widely required for client protein activation. 相似文献
44.
Despite the absence of classical tyrosine kinases encrypted in the kinome of Plasmodium falciparum, biochemical analyses have detected significant tyrosine phosphorylation in its cell lysates. Supporting such phosphorylation
is critical for parasite development. These observations have thus raised queries regarding the plasmodial enzymes accountable
for tyrosine kinase activities in vivo. In the current investigation, immunoblot analysis intriguingly demonstrated that Pfnek3,
a plasmodial mitogen-activated protein kinase kinase (MAPKK), displayed both serine/threonine and tyrosine kinase activities
in autophosphorylation reactions as well as in phosphorylation of the exogenous myelin basic protein substrate. The results
obtained strongly support Pfnek3 as a novel dual-specificity kinase of the malarial parasite, even though it displays a HGDLKSTN
motif in the catalytic loop that resembles the consensus HRDLKxxN signature found in the serine/threonine kinases. Notably,
its serine/threonine and tyrosine kinase activities were found to be distinctly influenced by Mg2+ and Mn2+ cofactors. Further probing into the regulatory mechanism of Pfnek3 also revealed tyrosine phosphorylation to be a crucial
factor that stimulates its kinase activity. Through biocomputational analyses and functional assays, tyrosine residues Y117,
Y122, Y172, and Y238 were proposed as phosphorylation sites essential for mediating the catalytic activities of Pfnek3. The
discovery of Pfnek3’s dual role in phosphorylation marks its importance in closing the loop for cellular regulation in P. falciparum, which remains elusive to date. 相似文献
45.
Uterine fibroids are a common benign tumor of the female genital tract. We conducted a genome-wide association study in which 457,044 SNPs were analyzed in 1,607 individuals with clinically diagnosed uterine fibroids and 1,428 female controls. SNPs showing suggestive associations (P < 5 × 10(-5)) were further genotyped in 3,466 additional cases and 3,245 female controls. Three loci on chromosomes 10q24.33, 22q13.1 and 11p15.5 revealed genome-wide significant associations with uterine fibroids. The SNPs showing the most significant association in a combination analysis at each of these loci were rs7913069 (P = 8.65 × 10(-14), odds ratio (OR) = 1.47), rs12484776 (P = 2.79 × 10(-12), OR = 1.23) and rs2280543 (P = 3.82 × 10(-12), OR = 1.39), respectively. Subsequent fine mapping of these regions will be necessary to pinpoint the causal variants. Our findings should shed light on the pathogenesis of uterine fibroids. 相似文献
46.
报导 MeV 硅离子注入半绝缘 GaAs 的快退火行为,根据缺陷作用原理分析了硅的不均匀激活和载流子分布特征.指出应按载流子浓度、迁移率、埋层电阻和击穿等特性综合评价深埋层和近表面层的品质,优化注入和退火参数. 相似文献
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阚市文 《北京师范大学学报(自然科学版)》1991,27(3):291-295
探讨了离子注入中的温升问题.这种温升可用试验方法进行测量.研究了几种测温方法(例如低熔点金属法和硬度法).分析了降低注入样品温升的一些途径. 相似文献
50.
de Lau W Barker N Low TY Koo BK Li VS Teunissen H Kujala P Haegebarth A Peters PJ van de Wetering M Stange DE van Es JE Guardavaccaro D Schasfoort RB Mohri Y Nishimori K Mohammed S Heck AJ Clevers H 《Nature》2011,476(7360):293-297
The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments. We find that conditional deletion of both genes in the mouse gut impairs Wnt target gene expression and results in the rapid demise of intestinal crypts, thus phenocopying Wnt pathway inhibition. Mass spectrometry demonstrates that Lgr4 and Lgr5 associate with the Frizzled/Lrp Wnt receptor complex. Each of the four R-spondins, secreted Wnt pathway agonists, can bind to Lgr4, -5 and -6. In HEK293 cells, RSPO1 enhances canonical WNT signals initiated by WNT3A. Removal of LGR4 does not affect WNT3A signalling, but abrogates the RSPO1-mediated signal enhancement, a phenomenon rescued by re-expression of LGR4, -5 or -6. Genetic deletion of Lgr4/5 in mouse intestinal crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway activation. Lgr5 homologues are facultative Wnt receptor components that mediate Wnt signal enhancement by soluble R-spondin proteins. These results will guide future studies towards the application of R-spondins for regenerative purposes of tissues expressing Lgr5 homologues. 相似文献