Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75)

The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75). Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation, is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75 or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75) is a physiologically significant mechanism of regulating intracellular Src activity.     

自调式镦压挤胀复合液压机的研制

从力学原理、设计原理、整机结构、关键零部件的设计和工作程序,系统地介绍了自调式镦压挤胀复合液压机．由于压机设计了顶出缸对下活动横梁调节限位结构,回程拉杆对上镦压横梁的复位结构及镦压缸和气液储能器之间的连通协调结构,这不仅使该液压机结构紧凑,同时节省了上镦压横梁的回程液压缸、下活动横梁的镦压缸,并简化了上凸模与上镦压模分设的液压系统,而且解决了直齿圆柱齿轮在塑性成形过程中齿顶难以充满、齿根易出现微裂纹,以及成形压力过大和模具寿命过低的问题．     

An Analysis of an SIRS Epidemic Model with General Direct Immunization in Networks北大核心CSCD

We consider an SIRS epidemic model with a general direct immunization rate on networks. By constructing suitable Lyapunov functions, we find that the dynamical behvaior of the model is completely determined by the epidemic threshold λc. When λ≤λc, the disease-free equilibrium is globally asymptotically stable; when λ>λc, the endemic equilibrium is globally asymptotically stable. In addition, we propose a uniform direct immunization and a targeted direct immunization. The results show that under the same average immunization rate s there exists a critical immunization-lost rate δc so that the epidemic threshold of the targeted direct immunization is smaller (larger) than that of the uniform direct immunization if δ<δc(δ>δc). © 2017, The Journal of Agency of Complex Systems and Complexity Science. All right reserved.     

Impact of bolus volume on small intestinal intra-luminal impedance in healthy subjects

AIM: To assess the impact of bolus volume on the characteristics of small intestinal (SI) impedance signals.METHODS: Concurrent SI manometry-impedance measurements were performed on 12 healthy volunteers to assess the pattern of proximal jejunal fluid bolus movement over a 14 cm-segment.Each subject was given 34 boluses of normal saline (volume from 1 to 30 mL) via the feeding tube placed immediately above the proximal margin of the studied segment.A bolus-induced impedance event occurred if there was &gt; 12%...     

Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms.

The stable propagation of genetic information requires that the entire genome of an organism be faithfully replicated once and only once each cell cycle. In eukaryotes, this replication is initiated at hundreds to thousands of replication origins distributed over the genome, each of which must be prohibited from re-initiating DNA replication within every cell cycle. How cells prevent re-initiation has been a long-standing question in cell biology. In several eukaryotes, cyclin-dependent kinases (CDKs) have been implicated in promoting the block to re-initiation, but exactly how they perform this function is unclear. Here we show that B-type CDKs in Saccharomyces cerevisiae prevent re-initiation through multiple overlapping mechanisms, including phosphorylation of the origin recognition complex (ORC), downregulation of Cdc6 activity, and nuclear exclusion of the Mcm2-7 complex. Only when all three inhibitory pathways are disrupted do origins re-initiate DNA replication in G2/M cells. These studies show that each of these three independent mechanisms of regulation is functionally important.     

Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli

When present in single-stranded DNA, palindromic or quasi-palindromic sequences have the potential to form complex secondary structures, including hairpins, which may facilitate interstrand misalignment of direct repeats and be responsible for diverse types of replication-based mutations, including deletions, additions, frameshifts and duplications. In regions of palindromic symmetry, specific deletion events may involve the formation of a hairpin or other DNA secondary structures which can stabilize the misalignment of direct repeats. One model suggests that these deletions occur during DNA replication by slippage of the template strand and misalignment with the progeny strand. The concurrent DNA replication model, involving an asymmetric dimeric DNA polymerase III complex which replicates the leading and lagging strands, has significant implications for mutagenesis. The intermittent looping of the lagging strand template, and the fact that the lagging strand template may contain a region of single-stranded DNA the length of an Okazaki fragment, provides an opportunity for DNA secondary-structure formation and misalignment. Here we report our design of a palindromic fragment to create an 'asymmetric palindromic insert' in the chloramphenicol acetyltransferase gene of plasmid pBR325. The frequency with which the insert was deleted in Escherichia coli depends on the orientation of the gene in the plasmid. Our results suggest that replication-dependent deletion between direct repeats may occur preferentially in the lagging strand.     

利用Mahalanobis距离进行人脸表情的识别

提出了利用Mahalanobis距离进行人脸表情识别的方法.首先将待分类的图像样本集进行坐标变换,使得变换以后类间离散度尽可能大而类内离散度尽可能小,即使变换以后的Fisher准则函数取得极大值,在新的坐标下求每个待分类样本到各类均值向量的Mahalanobis距离,从而将待分类的样本归到Mahalanobis距离最小的类中去,通过实验得到了平均80.25%的识别率.     

基质金属蛋白酶-26(MMP-26)在小鼠胚胎植入过程中的作用

基质金属蛋白酶-26（MMP-26，又称Endometase或基质水解素-2）是MMPs家族的一个新成员，它可在胎盘，子宫以及不同肿瘤细胞系中表达，采用子宫角注射，免疫组化，原位杂交，胚泡与子宫上皮单层培养，免疫印迹，RT-PCR和RNA印迹等多种体内外实验方法研究并报道了MMP-26在小鼠胚胎中的表达以及MMP-26抗体在胚胎植入中的作用，研究表明，MMP-26的mRNA与蛋白在小鼠胚泡中均有强烈的表达，此外，体内研究显示，MMP-26抗体能显著抑制小鼠胚胎的着床；在体外培养体系中，MMP-26抗体可显著抑制小鼠胚泡在子宫上皮单层上的黏附与扩展；同时，MMP-26抗体以剂量依赖关系抑制整合素αV亚基mRNA和蛋白的表达，研究提示，MMP-26可能直接或间接参与滋养层细胞侵入子宫内膜的过程，促使小鼠胚泡成功植入。