Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome

By exome sequencing, we found de novo SMARCB1 mutations in two of five individuals with typical Coffin-Siris syndrome (CSS), a rare autosomal dominant anomaly syndrome. As SMARCB1 encodes a subunit of the SWItch/Sucrose NonFermenting (SWI/SNF) complex, we screened 15 other genes encoding subunits of this complex in 23 individuals with CSS. Twenty affected individuals (87%) each had a germline mutation in one of six SWI/SNF subunit genes, including SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B.     

Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese

We have previously reported multiple loci associated with prostate cancer susceptibility in a Japanese population using a genome-wide association study (GWAS). To identify additional prostate cancer susceptibility loci, we genotyped nine SNPs that were nominally associated with prostate cancer (P < 1 × 10(-4)) in our previous GWAS in three independent studies of prostate cancer in Japanese men (2,557 individuals with prostate cancer (cases) and 3,003 controls). In a meta-analysis of our previous GWAS and the replication studies, which included a total of 7,141 prostate cancer cases and 11,804 controls from a single ancestry group, three new loci reached genome-wide significance on chromosomes 11q12 (rs1938781; P = 1.10 × 10(-10); FAM111A-FAM111B), 10q26 (rs2252004; P = 1.98 × 10(-8)) and 3p11.2 (rs2055109; P = 3.94 × 10(-8)). We also found suggestive evidence of association at a previously reported prostate cancer susceptibility locus at 2p11 (rs2028898; P = 1.08 × 10(-7)). The identification of three new susceptibility loci should provide additional insight into the pathogenesis of prostate cancer and emphasizes the importance of conducting GWAS in diverse populations.     

Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta

Apoptosis, or cellular suicide, is important for normal development and tissue homeostasis, but too much or too little apoptosis can also cause disease. The family of cysteine proteases, the so- called caspases, are critical mediators of programmed cell death, and thus far 14 family members have been identified. Some of these, such as caspase-8, mediate signal transduction downstream of death receptors located on the plasma membrane. Others, such as caspase-9, mediate apoptotic signals after mitochondrial damage. Stress in the endoplasmic reticulum (ER) can also result in apoptosis. Here we show that caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals. Mice that are deficient in caspase-12 are resistant to ER stress-induced apoptosis, but their cells undergo apoptosis in response to other death stimuli. Furthermore, we show that caspase-12-deficient cortical neurons are defective in apoptosis induced by amyloid-beta protein but not by staurosporine or trophic factor deprivation. Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-beta neurotoxicity.     

Comparative potency of gibberellins in inducing parthenocarpic fruit growth inMalus sylvestris mill

Zusammenfassung Die biologische Wirksamkeit der Gibberelline A₁ bis A₁₀, A₁₃ und A₁₄ wurde bei der Einsetzung von Parthenokarpie inMalus sylvestris Mill. festgestellt. Die Gibberelline A₄ und A₇ waren sehr wirksam, A₁, A₂, A₃, A₉, A₁₀, A₁₃ und A₁₄ waren von mittelmässiger Wirksamkeit, während A₅, A₆ und A₈ waren unwirksam. Die mehr wirksamen Gibberelline besitzen, vom molekularen Standpunkt betrachtet, in der Stellung 7 keine OH-Gruppe.

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On leave from Osaka Prefecture University, Osaka, Japan.     

Calcium and magnesium deficiency-induced atrophy of muscle and calcium accumulation in the spinal cord

After severe dietary calcium-magnesium deficiency in rats, succinic dehydrogenase and acetylcholinesterase enzyme activity of gastrocnemius muscle showed a neurogenic atrophy. This alteration was associated with a high concentration of calcium in the spinal cord.     

Contraction of the large conductance coronary artery produced by acetylcholine in the mini pig

Summary In the mini pig, acetylcholine reduced the coronary blood flow and constricted the large coronary artery. These effects were abolished by atropine, but not by phentolamine, suggesting that cholinergic mechanisms may be involved in coronary artery vasoconstriction.     

Study on Preventive Software Rejuvenation Policy for Two Kinds of Bugs

A new preventive software rejuvenation policy is proposed in this paper. This technique is implemented when additive consumption of physical memory has reached some level. Using the theory of cumulative damage process, two models are given for two kinds of bugs. For the first model, aging-related bug is considered only and consumption of physical memory could be known by tests made at periodic times, optimal preventive rejuvenation policy is analytically derived and numerical example is given. As an extended preventive software rejuvenation policy, Heisenbug and aging-related bug are considered meanwhile in the second model.     

Discovery of the short gamma-ray burst GRB 050709

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.