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Background & Aims: Identification of inflammatory bowel disease (IBD) susceptibility genes is key to understanding pathogenic mechanisms. Recently, the North American IBD Genetics Consortium provided compelling evidence for an association between ileal Crohn’s disease (CD) and the IL23R gene using genome-wide association scanning. External replication is a priority, both to confirm this finding in other populations and to validate this new technique. We tested for association between IL23R and IBD in a large independent UK panel to determine the size of the effect and explore subphenotype correlation and interaction with CARD15. Methods: Eight single nucleotide polymorphism markers in IL23R tested in the North American study were genotyped in 1902 cases of Crohn’s disease (CD), 975 cases of ulcerative colitis (UC), and 1345 controls using MassARRAY. Data were analyzed using χ2 statistics, and subgroup association was sought. Results: A highly significant association with CD was observed, with the strongest signal at coding variant Arg381Gln (allele frequency, 2.5% in CD vs 6.2% in controls [P = 1.1 × 10−12]; odds ratio, 0.38; 95% confidence interval, 0.29–0.50). A weaker effect was seen in UC (allele frequency, 4.6%; odds ratio, 0.73; 95% confidence interval, 0.55–0.96). Analysis accounting for Arg381Gln suggested that other loci within IL23R also influence IBD susceptibility. Within CD, there were no subphenotype associations or evidence of interaction with CARD15. Conclusions: This study shows an association between IL23R and all subphenotypes of CD with a smaller effect on UC. This extends the findings of the North American study, providing clear evidence that genome-wide association scanning can successfully identify true complex disease genes. [Copyright &y& Elsevier]

Summary: Pten-/- cells display a partially defective checkpoint in response to ionizing radiation (IR). The checkpoint defect was traced to the ability of AKT to phosphorylate CHK1 at serine 280, since a nonphosphorylated mutant of CHK1 (S280A) complemented the checkpoint defect and restored CDC25A degradation. CHK1 phosphorylation at serine 280 led to covalent binding of 1 to 2 molecules of ubiquitin and cytoplasmic CHK1 localization. Primary breast carcinomas lacking PTEN expression and having elevated AKT phosphorylation had increased cytoplasmic CHK1 and displayed aneuploidy (p < 0.005). We conclude that loss of PTEN and subsequent activation of AKT impair CHK1 through phosphorylation, ubiquitination, and reduced nuclear localization to promote genomic instability in tumor cells. [Copyright &y& Elsevier]

A serine protease gene designated Pyrenopeziza brassicae serine protease 2 (Psp2) was cloned from the plant pathogenic fungus Pyrenopeziza brassicae and its expression analysed. Psp2 was transcribed in equal levels during both vegetative growth and sexual development and showed no differential expression in the presence of exogenous protein or during starvation. [Copyright &y& Elsevier]

Summary We and others have recently reported that the SMC protein Smchd1 is a regulator of chromosome conformation. Smchd1 is critical for the structure of the inactive X chromosome and at autosomal targets such as the Hox genes. However, it is unknown how Smchd1 is recruited to these sites. Here, we report that Smchd1 localizes to the inactive X via the Xist -HnrnpK-PRC1 (polycomb repressive complex 1) pathway. Contrary to previous reports, Smchd1 does not bind Xist or other RNA molecules with any specificity. Rather, the localization of Smchd1 to the inactive X is H2AK119ub dependent. Following perturbation of this interaction, Smchd1 is destabilized, which has consequences for gene silencing genome-wide. Our work adds Smchd1 to the PRC1 silencing pathway for X chromosome inactivation. Graphical Abstract Highlights • Smchd1 does not bind endogenous RNA with detectable sequence specificity • Smchd1 depends on the Xist-HnrpnK-PRC1 pathway for recruitment to the inactive X • Smchd1 depends on histone H2A lysine 119 ubiquitination for inactive X localization • Smchd1 protein stability depends on histone H2A lysine 119 ubiquitination Jansz et al. report that the chromatin protein Smchd1 depends on polycomb repressive complex 1-mediated ubiquitylation of histone H2A for its recruitment to the inactive X chromosome and for its protein stability. These data have implications for Smchd1 targeting genome-wide. [ABSTRACT FROM AUTHOR]

Abstract: Melamine–urea–formaldehyde resins are very important commercially, yet little is known about their structures, and the techniques that have been available to examine this are quite limited. In this manuscript we describe the use of 1H–15N HMQC NMR spectroscopy and the development of a doubly-selective 1H–15N–13C CP INEPT NMR experiment, to establish for the first time that melamine and urea co-polymerize with formaldehyde and to identify the 1H, 15N and 13C chemical shifts of the bridging units. This methodology makes it possible to examine co-condensation in industrial preparations of melamine–urea–formaldehyde resins, in order to correlate structure and function and optimize the manufacturing process. [Copyright &y& Elsevier]