Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.     

Alternative exon usage selectively determines both tissue distribution and subcellular localization of the acyl-CoA thioesterase 7 gene products

Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of acyl-CoAs to free fatty acids and coenzyme A. Recent studies have demonstrated that one gene named Acot7, reported to be mainly expressed in brain and testis, is transcribed in several different isoforms by alternative usage of first exons. Strongly decreased levels of ACOT7 activity and protein in both mitochondria and cytosol was reported in patients diagnosed with fatty acid oxidation defects, linking ACOT7 function to regulation of fatty acid oxidation in other tissues. In this study, we have identified five possible first exons in mouse Acot7 (Acot7a–e) and show that all five first exons are transcribed in a tissue-specific manner. Taken together, these data show that the Acot7 gene is expressed as multiple isoforms in a tissue-specific manner, and that expression in tissues other than brain and testis is likely to play important roles in fatty acid metabolism. Received 5 February 2007: received after revision 3 April 2007; accepted 19 April 2007     

硼对12Ni3CrMoV高强度钢焊接接头冷裂敏感性的影响

低碳调质高强度钢中添加硼对焊接冷裂敏感性的影响较少有人研究,并存在两种不同意见.本文对含硼量分别为0.005%,0.0014%,0.0028%,0.0035%的12Ni3CrMoV调质高强度钢焊接冷裂敏感性进行研究.试验结果表明:1.插销试验临界应力:含硼钢比无硼钢(含硼0.0005%)高;含硼钢中,临界应力按含硼量0.0014%,0.0028%,0.0035%的顺序递减.2.扫描电镜断口分析:无硼钢有沿晶断裂区、准介理断裂区和韧窝断裂区.含硼钢没有沿晶断裂区,只有准介理断裂区和韧窝断裂区.3.焊条未烘干时,无硼和含硼钢的插销临界应力都降低,无硼钢沿晶断裂区扩大,含硼钢仍无沿晶断裂区.4.硼在HAZ粗晶区中沿奥氏体晶界形成偏聚带,硼相主要沿奥氏体晶界呈不连续点状析出.含硼愈多,沿奥氏体晶界偏聚和硼相析出也愈多.5.C.D.Beachem提出的断口形貌发展过程示意图可以解释无硼钢断裂,不能完全解释含硼钢断裂过程.6.裂纹敏感性成分Pcm值表达式中,硼项系数为" 5"值得商榷.就本文钢材而言,硼项函数应为"负变数".本文对含硼钢延迟裂纹机理作了探讨.     

P pili in uropathogenic E. coli are composite fibres with distinct fibrillar adhesive tips.

Escherichia coli is a frequent cause of several common bacterial infections in humans and animals, including urinary tract infections, bacteraemia and bacteria-related diarrhoea and is also the main cause of neonatal meningitis. Microbial attachment to surfaces is a key event in colonization and infection and results mainly from a stereochemical fit between microbial adhesins and complementary receptors on host cells. Bacterial adhesins required for extracellular colonization by Gram-negative bacteria are often minor components of heteropolymeric fibres called pili which must be oriented in an accessible manner in these structures to be able to bind to specific receptor architectures. P pili mediate the binding of uropathogenic E. coli to a digalactoside receptor determinant present in the urinary tract epithelium. We report here that the adhesin is a component of distinct fibrillar structures present at the tips of the pili. These virulence-associated tip fibrillae are thin, flexible polymers composed mostly of repeating subunits of PapE that frequently terminate with the alpha-D-galactopyranosyl-(1-4)-beta-D-galactopyranose or Gal alpha (1-4)Gal binding PapG adhesin.