浙江城市科技驱动力时空分异研究

 以创新动力论为理论基础,从科技人力支持、科技物质支持、城市创新偏好、城市需求拉动和城市科技服务5个方面,选取18个评价指标,采用时序全局因子分析的方法,对2003-2012年浙江11个城市的科技驱动力进行评价,对城市科技驱动力的动态变化规律进行分析。运用系统聚类方法将城市划分为3个层次,运用梯度分析将城市划分为由低至高的3个梯度,分析显示城市科技驱动力的空间分异原因在于城市创新偏好和城市科技服务。     

模糊可靠性理论在机构运动可靠性分析中的应用

讨论了机构运动模糊可靠性分析的普通方法,给出了将模糊可靠性问题转化为一般所指的可靠性问题,分析了机构运动的模糊可靠性的方法,最后说明了以上方法在曲柄滑块机构可靠性分析中的应用.     

A comparative analysis of the cell biology of senescence and aging

Various intracellular organelles, such as lysosomes, mitochondria, nuclei, and cytoskeletons, change during replicative senescence, but the utility of these changes as general markers of senescence and their significance with respect to functional alterations have not been comprehensively reviewed. Furthermore, the relevance of these alterations to cellular and functional changes in aging animals is poorly understood. In this paper, we review the studies that report these senescence-associated changes in various aging cells and their underlying mechanisms. Changes associated with lysosomes and mitochondria are found not only in cells undergoing replicative or induced senescence but also in postmitotic cells isolated from aged organisms. In contrast, other changes occur mainly in cells undergoing in vitro senescence. Comparison of age-related changes and their underlying mechanisms in in vitro senescent cells and aged postmitotic cells would reveal the relevance of replicative senescence to the physiological processes occurring in postmitotic cells as individuals age.     

Regulation of the Hippo pathway in cancer biology

The Hippo tumor suppressor pathway, which is well conserved from Drosophila to humans, has emerged as the master regulator of organ size, as well as major cellular properties, such as cell proliferation, survival, stemness, and tissue homeostasis. The biological significance and deregulation of the Hippo pathway in tumorigenesis have received a surge of interest in the past decade. In the current review, we present the major discoveries that made substantial contributions to our understanding of the Hippo pathway and discuss how Hippo pathway components contribute to cellular signaling, physiology, and their potential implications in anticancer therapeutics.     

eIF2A,an initiator tRNA carrier refractory to eIF2α kinases,functions synergistically with eIF5B

The initiator tRNA (Met-tRNA _i ^Met ) at the P site of the small ribosomal subunit plays an important role in the recognition of an mRNA start codon. In bacteria, the initiator tRNA carrier, IF2, facilitates the positioning of Met-tRNA _i ^Met on the small ribosomal subunit. Eukarya contain the Met-tRNA _i ^Met carrier, eIF2 (unrelated to IF2), whose carrier activity is inhibited under stress conditions by the phosphorylation of its α-subunit by stress-activated eIF2α kinases. The stress-resistant initiator tRNA carrier, eIF2A, was recently uncovered and shown to load Met-tRNA _i ^Met on the 40S ribosomal subunit associated with a stress-resistant mRNA under stress conditions. Here, we report that eIF2A interacts and functionally cooperates with eIF5B (a homolog of IF2), and we describe the functional domains of eIF2A that are required for its binding of Met-tRNA _i ^Met , eIF5B, and a stress-resistant mRNA. The results indicate that the eukaryotic eIF5B–eIF2A complex functionally mimics the bacterial IF2 containing ribosome-, GTP-, and initiator tRNA-binding domains in a single polypeptide.     

Reestablishment of the inactive X chromosome to the ground state through cell fusion-induced reprogramming

The restricted gene expression pattern of a differentiated cell can be reversed by fusion of the somatic cell with a more developmentally potent cell type, such as an embryonic stem (ES) cell. During this reprogramming process, somatic cells obtain most of the characteristics of pluripotent cells. Reactivation of an inactive X chromosome (Xi) is an important epigenetic marker confirming the pluripotent reprogramming of somatic cells. Female somatic cells contain one active X chromosome (Xa) and one Xi, and following the fusion of these cells with male ES cells, the Xi becomes activated, resulting in XaXaXaY fusion hybrid cells. To monitor Xi reactivation, transgenic female neural stem cells (fNSCs) carrying a green fluorescent protein (GFP) reporter gene expressed on the Xa (X-GFP), but not on the Xi, were used for reprogramming. XaXi^GFP NSCs, whose GFP reporter was silenced, were fused with HM1 ES cells (XY) to induce pluripotent reprogramming. The Xi^GFP of NSCs were found to be activated on day 4 post-fusion, indicating reactivation of the Xi. Hybrid cells showed pluripotent cell-specific characteristics cells including inactivation of the NSC marker Nestin, DNA demethylation of Oct4, DNA methylation of Nestin, and reactivation of the Xi. Following differentiation of the (GFP-positive) hybrid cells through embryoid body formation, the proportion of GFP-negative cells was found to be approximately 26?%, indicating that there was random inactivation of one of the three Xas. Here, we showed that the Xi of somatic cells is reprogrammed to the Xa state and that cellular differentiation occurs randomly, i.e., regardless of the Xa or Xi state, indicating that the memory of the Xi of somatic cells has been erased and reset to the ground state (i.e., inner cell mass-like state), indicating that random X-chromosome inactivation occurs upon differentiation.     

Genome-wide functional analysis of pathogenicity genes in the rice blast fungus

Rapid translation of genome sequences into meaningful biological information hinges on the integration of multiple experimental and informatics methods into a cohesive platform. Despite the explosion in the number of genome sequences available, such a platform does not exist for filamentous fungi. Here we present the development and application of a functional genomics and informatics platform for a model plant pathogenic fungus, Magnaporthe oryzae. In total, we produced 21,070 mutants through large-scale insertional mutagenesis using Agrobacterium tumefaciens-mediated transformation. We used a high-throughput phenotype screening pipeline to detect disruption of seven phenotypes encompassing the fungal life cycle and identified the mutated gene and the nature of mutation for each mutant. Comparative analysis of phenotypes and genotypes of the mutants uncovered 202 new pathogenicity loci. Our findings demonstrate the effectiveness of our platform and provide new insights on the molecular basis of fungal pathogenesis. Our approach promises comprehensive functional genomics in filamentous fungi and beyond.