Fidelity in planar cell polarity signalling

The polarity of Drosophila wing hairs displays remarkable fidelity. Each of the approximately 30,000 wing epithelial cells constructs an actin-rich prehair that protrudes from its distal vertex and points distally. The distal location and orientation of the hairs is virtually error free, thus forming a nearly perfect parallel array. This process is controlled by the planar cell polarity signalling pathway. Here we show that interaction between two tiers of the planar cell polarity signalling mechanism results in the observed high fidelity. The first tier, mediated by the cadherin Fat, dictates global orientation by transducing a directional signal to individual cells. The second tier, orchestrated by the 7-pass transmembrane receptor Frizzled, aligns each cell's polarity with that of its neighbours through the action of an intercellular feedback loop, enabling polarity to propagate from cell to cell. We show that all cells need not respond correctly to the presumably subtle signal transmitted by Fat. Subsequent action of the Frizzled feedback loop is sufficient to align all the cells cooperatively. This economical system is therefore highly robust, and produces virtually error-free arrays.     

PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates

In addition to the apical-basal polarity pathway operating in epithelial cells, a planar cell polarity (PCP) pathway establishes polarity within the plane of epithelial tissues and is conserved from Drosophila to mammals. In Drosophila, a 'core' group of PCP genes including frizzled (fz), flamingo/starry night, dishevelled (dsh), Van Gogh/strabismus and prickle, function to regulate wing hair, bristle and ommatidial polarity. In vertebrates, the PCP pathway regulates convergent extension movements and neural tube closure, as well as the orientation of stereociliary bundles of sensory hair cells in the inner ear. Here we show that a mutation in the mouse protein tyrosine kinase 7 (PTK7) gene, which encodes an evolutionarily conserved transmembrane protein with tyrosine kinase homology, disrupts neural tube closure and stereociliary bundle orientation, and shows genetic interactions with a mutation in the mouse Van Gogh homologue vangl2. We also show that PTK7 is dynamically localized during hair cell polarization, and that the Xenopus homologue of PTK7 is required for neural convergent extension and neural tube closure. These results identify PTK7 as a novel regulator of PCP in vertebrates.     

Identification of susceptibility genes loci associated with type 2 diabetes

In this study, we selected 10 susceptible SNPs loci to investigate their contribution to susceptibility to type 2 diabetes in Han Chinese among Hubei population. We genotyped SNPs rs5219, rs1801282, rs1470579, rs1111875, rs1081661, rs7754840, rs4506565, rs13266634, rs4402960, and rs5643981 by using the method of polymerase chain reaction-ligase detection reaction (PCR-LDR). In a case-control study, we have genotyped the 10 candidate susceptibility SNP loci, and here, we reported that the SNP rs5219 in KCNJ1...     

平面2T1R并联机构无过约束构型设计

基于螺旋理论和集合论原理,根据动平台所受约束与支链约束之间的关系,分析平面2T1R并联机构无过约束构型条件,得到了6种3支链结构的约束配置方式.根据支链约束要求,采用转动副和移动副设计具体的支链结构,并按不同支链间约束配置方式确定各支链运动副轴线的几何布置,综合出了一类新的完全对称结构和非完全对称结构无过约束平面2T1R并联机构.     

Selection pressure drives the co-evolution of several lipid metabolism genes in mammals

Adipose tissue is an important endocrine organ and energy supplier.Its physiological effect on the regulation of the energy balance is considered an important factor underlying the evolution of mammals.To test whether the genes controlling lipid metabolism have undergone adaptive molecular change in the evolution of mammals,in this study,we used the orthologous gene sequences of 12 important lipid metabolism proteins (leptin,OB-RL,RXRA,RXRB,RXRG,PPARA,PPARB/D,PPARG,PNLIP,ADIPOQ,LPL and UCP1) from NCBI’s databases.We found evidence that 4 of the corresponding genes (leptin,ADIPOQ,PNLIP and PPARA) have undergone positive selection in their evolutionary history and that most adaptive changes occurred during the evolution of the super-clades Laurasiatheria (placentals) and suborders within Euarchontoglires (primates and rodents).Comparisons across sets of genes showed that in a third of cases,bursts of positive selection,more than would be expected by chance,occurred on corresponding branches.We propose that the positive selection drives adaptive changes in some lipid metabolism genes in or within Laurasiatheria and Euarchontoglires clades.Along with evidence from earlier studies,our results show that co-evolution among interacting lipid metabolism proteins has taken place.     

Regulation of segment polarity genes in the Drosophila blastoderm by fushi tarazu and even skipped

During the late cellular blastoderm stage of Drosophila embryo-genesis the segmentation genes engrailed, en, and wingless, wg, become expressed in two series of 14 stripes which will subsequently coincide with the anterior and posterior limits of each parasegment. Previous studies have shown that the establishment of the pattern of en stripes depends upon the activity of the homoeobox-containing pair-rule genes fushi tarazu, ftz and even skipped, eve. Here we show that these two genes also control the spatial expression of wg. Whereas ftz and eve behave as activators of en we find that both genes are required to repress wg expression, so that wg becomes expressed only in the narrow stripes of cells which come to separate the ftz and eve bands at the end of the blastoderm stage. In contrast, we propose that the precise positioning of the en stripes depends upon signals generated in a combinatorial manner by the overlaps between the ftz or eve domains and those of other pair rule genes, specifically odd paired, opa and paired, prd.     

Interaction between peptide growth factors and homoeobox genes in the establishment of antero-posterior polarity in frog embryos

The expression of the Xenopus homoeobox gene xhox3 is an early response to mesoderm induction by peptide growth factors and the level of xhox3 expression marks the antero-posterior character of the induced mesoderm. Different peptide growth factors specify different antero-posterior mesodermal cell fates as seen by the level of xhox3 expression and the capacity to induce specific secondary neural/epidermal structures. These factors and homoeobox genes thus form part of the mechanism necessary for establishing antero-posterior polarity in the frog embryo.     

2n-1次Hamilton系统的临界周期分岔

作者研究了一类只含有奇数次项的Hamilton系统的临界周期分岔.作者首先确定了细中心的阶数,然后证明了至多产生m-1个局部临界周期,并且最大个数m-1可达.     

Identification of nesfatin-1 as a satiety molecule in the hypothalamus

The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour. Here we show that nesfatin, corresponding to NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus.     

Identification of CRE1 as a cytokinin receptor from Arabidopsis

Cytokinins are a class of plant hormones that are central to the regulation of cell division and differentiation in plants. It has been proposed that they are detected by a two-component system, because overexpression of the histidine kinase gene CKI1 induces typical cytokinin responses and genes for a set of response regulators of two-component systems can be induced by cytokinins. Two-component systems use a histidine kinase as an environmental sensor and rely on a phosphorelay for signal transduction. They are common in microorganisms, and are also emerging as important signal detection routes in plants. Here we report the identification of a cytokinin receptor. We identified Arabidopsis cre1 (cytokinin response 1) mutants, which exhibited reduced responses to cytokinins. The mutated gene CRE1 encodes a histidine kinase. CRE1 expression conferred a cytokinin-dependent growth phenotype on a yeast mutant that lacked the endogenous histidine kinase SLN1 (ref. 10), providing direct evidence that CRE1 is a cytokinin receptor. We also provide evidence that cytokinins can activate CRE1 to initiate phosphorelay signalling.     

菠菜SoSWEET蛋白家族基因鉴定与表达分析

以现有菠菜基因组信息为基础,通过生物信息学方法筛选鉴定16个菠菜SoSWEET蛋白家族成员,命名为SoSWEET1~SoSWEET16.氨基酸残基数量在648~1 140之间,分子质量在54 070.32~95 868.64 u之间,理论等电点（pI）在5.06~5.19之间.亚细胞定位预测有6个SoSWEET蛋白定位于细胞膜,5个SoSWEET蛋白定位于内质网,5个SoSWEET蛋白定位于细胞膜、内质网.系统进化分析将菠菜SoSWEET蛋白家族分成4个亚族,在此基础上对基因结构、保守基序、顺式作用调控元件等进行分析.共鉴定了10个高度保守基序,其中所有菠菜SoSWEET蛋白都包含基序1,2和4,是构成菠菜SoSWEET蛋白中最高度保守的部分.所有菠菜SoSWEET蛋白家族成员都含MtN3_slv和PQ-loop superfamily结构域.大多数SoSWEET蛋白家族的基因含有5个内含子.顺式作用元件预测结果表明,菠菜SoSWEET基因启动子上包含光响应、生长发育、植物激素响应和逆境胁迫响应等顺式作用元件.组织表达分析表明,所有SoSWEET基因在根、茎、叶和叶柄中都有表达,霜霉病胁迫处理后16个基因表现出不同响应变化.本研究为后续深入研究菠菜SoSWEET蛋白家族成员的功能提供了重要参考.     

A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity

The PAR-4 and PAR-1 kinases are necessary for the formation of the anterior-posterior (A-P) axis in Caenorhabditis elegans. PAR-1 is also required for A-P axis determination in Drosophila. Here we show that the Drosophila par-4 homologue, lkb1, is required for the early A-P polarity of the oocyte, and for the repolarization of the oocyte cytoskeleton that defines the embryonic A-P axis. LKB1 is phosphorylated by PAR-1 in vitro, and overexpression of LKB1 partially rescues the par-1 phenotype. These two kinases therefore function in a conserved pathway for axis formation in flies and worms. lkb1 mutant clones also disrupt apical-basal epithelial polarity, suggesting a general role in cell polarization. The human homologue, LKB1, is mutated in Peutz-Jeghers syndrome and is regulated by prenylation and by phosphorylation by protein kinase A. We show that protein kinase A phosphorylates Drosophila LKB1 on a conserved site that is important for its activity. Thus, Drosophila and human LKB1 may be functional homologues, suggesting that loss of cell polarity may contribute to tumour formation in individuals with Peutz-Jeghers syndrome.     

具有预后价值的乳腺癌发病关键基因鉴别研究

目的:筛选与乳腺癌发病相关的关键基因,为研究乳腺癌的诊疗提供新的潜在分子靶标.方法:使用GEO2R在线工具比较乳腺癌与正常乳腺组织基因表达情况,进行差异显著性分析,利用基因功能注释工具DAVID对差异基因进行GO和KEGG富集分析.通过STRING数据库构建差异基因的蛋白互作网络,基于最大团中心性(maximal clique centrality,MCC)算法鉴别关键基因,利用Kaplan Meier生存分析验证关键基因对患者生存时间的影响.结果:乳腺癌基因表达差异分析共产生491个差异基因,其中有254个上调,237个下调.GO富集分析表明差异基因显著富集于肿瘤相关的生物学过程、细胞组分和分子功能,KEGG通路富集分析主要集中于PI3K-Akt信号通路、黏附斑和癌症通路.基于MCC算法共选取10个关键基因,其中的4个基因(ISG15,IFIT1,GBP1和IFI27)过表达与患者生存时间显著降低密切相关(P0.05).结论:共鉴别了4个与乳腺癌发病密切相关的关键基因,相关研究结果可为研究乳腺癌的诊疗提供新的潜在分子靶标.     

一圈谐振平面图的构造

如果连通图G是一圈谐振平面图,那么(G+P)(x,y)未必是一圈谐振平面图。从苯环型碳氢化合物的碳原子结构图——六角系统出发,在K圈谐振图的基础上引出了一圈谐振可约链的概念及其相关结论,并给出了确定(G+P)(x,y)是一圈谐振平面图的条件。