砜基碳负离子的选择性环合反应

比较1，1－双（2－叔丁基砜乙基）十二烷基苯基砜（1）双碳负离子在不同条件下的环合反应结果，控制反应条件，在铁催化下可以生成偶联糁烯化的环烯产物（2）为主要产物；不加催化剂，加热回流反应得到分子内亲核取代反应产物环丙烷化合物（3）。     

Swimming and bipedal bottom-running in the pig-nosed turtle Carettochelys insculpta Ramsay, 1886

The pig-nosed freshwater turtle Carettochelys insculpta Ramsay, 1886 has paddle-shaped foreflippers that resemble those of sea turtles. These turtles exhibit a wide range of swimming capabilities. As well as swimming by the action of synchronized foreflippers alone, they sometimes used alternate hindlimb action at the same time. They could swim by ipsilaterally synchronized action of all four limbs, or by hindlimb action alone (combined with stabilizer/lift function of the foreflippers). The turtles also showed flexibility in bottom-walking. Besides the ipsilaterally synchronized quadrupedal action characteristic of other freshwater turtles, they exhibited a bipedal walking mechanism never previously described. Propelled by alternate action of the hindlimbs, the animals held the head and plastron above the substratum, with the large foreflippers acting to provide anterior lift and stability against roll and yaw. Because both hindlimbs were sometimes off the substratum simultaneously during bipedal locomotion, their duty factors were < 0.5, implying a bipedal run.     

Human CtIP promotes DNA end resection

In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.     

你可以承担多少风险

<正>世上有两种企业家,你需要知道你属于哪一种。根据我26年的从商经历,我意识到开办公司的有两种人:喜欢冒险的人和不喜欢冒险的人。无论你属于哪一种,如果你想创立自己的商业王国,必然要面对很大的挑战。第一种企业家最好控制自己,不要屡屡涉险,否则很有可能因决策失误而使公司陷入困境。第二种企业家必须明白,如果毫不冒险也很难有所建树。问题的关键在于:你能承担多少风险和你为了达到目的应该承担多少风险?     

Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.     

Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment

The pathways of intracellular traffic involved in antigen processing and presentation have been defined by immunoelectron microscopy. The export pathway for class II histocompatibility molecules and the antigen import pathway meet in a peripheral endocytic compartment having all the molecular machinery believed to be required for antigen processing and presentation, including internalized surface immunoglobulins, proteolytic enzymes and invariant chains. This compartment defines a site where peptides from endocytosed antigen can bind class II molecules en route to the cell surface for presentation to T cells.     

Dialyzable serum factors alter cellular immunity in pregnancy

Summary Lymphocyte responsiveness was found to be decreased in pregnant and increased in habitually aborting women. This is attributed to a dialyzable serum factor(s), that can be removed from the surface of lymphocytes by repeated washing.     

Active genes are tri-methylated at K4 of histone H3

Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.     

Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.