936 research outputs found

    The Wavelet-Based Cluster Analysis for Temporal Gene Expression Data

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    A variety of high-throughput methods have made it possible to generate detailed temporal expression data for a single gene or large numbers of genes. Common methods for analysis of these large data sets can be problematic. One challenge is the comparison of temporal expression data obtained from different growth conditions where the patterns of expression may be shifted in time. We propose the use of wavelet analysis to transform the data obtained under different growth conditions to permit comparison of expression patterns from experiments that have time shifts or delays. We demonstrate this approach using detailed temporal data for a single bacterial gene obtained under 72 different growth conditions. This general strategy can be applied in the analysis of data sets of thousands of genes under different conditions

    Dynamics of Dynamin during Clathrin Mediated Endocytosis in PC12 Cells

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    Members of the dynamin super-family of GTPases are involved in disparate cellular pathways. Dynamin1 and dynamin2 have been implicated in clathrin-mediated endocytosis. While some models suggest that dynamin functions specifically at the point of vesicle fission, evidence also exists for a role prior to fission during vesicle formation and it is unknown if there is a role for dynamin after vesicle fission. Although dynamin2 is ubiquitously expressed, dynamin1 is restricted to the nervous system. These two structurally similar endocytic accessory proteins have not been studied in cells that endogenously express both.The present study quantitatively assesses the dynamics of dynamin1 and dynamin2 during clathrin-mediated endocytosis in PC12 cells, which endogenously express both proteins. Both dynamin isoforms co-localized with clathrin and showed sharp increases in fluorescence intensity immediately prior to internalization of the nascent clathrin-coated vesicle. The fluorescence intensity of both proteins then decreased with two time constants. The slower time constant closely matched the time constant for the decrease of clathrin intensity and likely represents vesicle movement away from the membrane. The faster rate may reflect release of dynamin at the neck of nascent vesicle following GTP hydrolysis.This study analyses the role of dynamin in clathrin-mediated endocytosis in a model for cellular neuroscience and these results may provide direct evidence for the existence of two populations of dynamin associated with nascent clathrin-coated vesicles

    中国上市公司治理结构的实证研究

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    我国上市公司的市场价值与其治理结构有无联系?投资者愿为治理良好的公司付出多大的溢价?本文旨在对上述两大问题进行全面和系统的实证研究,揭示当前上市公司存在的治理弊病,为建立具有中国特色的公司治理体系提供依据。为此,我们充分考虑了公司治理的内外部机制,并结合中国的市场环境,归纳出一系列变量来描述公司治理在我国的具体实践。基于这个变量体系,我们运用主元因素分析法编制了一个可反映上市公司治理水平的综合指标 - G指标。我们的实证研究发现:(1)治理水平高的企业其市场价值也高;(2)投资者愿为治理良好的公司付出相当可观的溢价。postprin

    Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer.

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    Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer

    ZnO-based film bulk acoustic resonator for high sensitivity biosensor applications

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    Author name used in this publication: G. K. H. Pang2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

    In vitro degradation behavior and cytocompatibility of Mg–Zn–Zr alloys

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    Zinc and zirconium were selected as the alloying elements in biodegradable magnesium alloys, considering their strengthening effect and good biocompatibility. The degradation rate, hydrogen evolution, ion release, surface layer and in vitro cytotoxicity of two Mg–Zn–Zr alloys, i.e. ZK30 and ZK60, and a WE-type alloy (Mg–Y–RE–Zr) were investigated by means of long-term static immersion testing in Hank’s solution, non-static immersion testing in Hank’s solution and cell-material interaction analysis. It was found that, among these three magnesium alloys, ZK30 had the lowest degradation rate and the least hydrogen evolution. A magnesium calcium phosphate layer was formed on the surface of ZK30 sample during non-static immersion and its degradation caused minute changes in the ion concentrations and pH value of Hank’s solution. In addition, the ZK30 alloy showed insignificant cytotoxicity against bone marrow stromal cells as compared with biocompatible hydroxyapatite (HA) and the WE-type alloy. After prolonged incubation for 7 days, a stimulatory effect on cell proliferation was observed. The results of the present study suggested that ZK30 could be a promising material for biodegradable orthopedic implants and worth further investigation to evaluate its in vitro and in vivo degradation behavior

    Ageing in rural China: migration and care circulation

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    This article applies the concept of care circulation (Baldassar and Merla, Transnational families, migration and the circulation of care: understanding mobility and absence in family life, 2013) to the processes involved in the care of old people in rural China,an area which has hitherto been predominantly located in a quantitatively based intergenerational transfer framework. Drawing upon a qualitative study of rural families in the context of rural to urban migration, this article examines the multidirectional and asymmetrical exchanges of caregiving and care-receiving and seeks to provide a more nuanced understanding of the impact of migration upon ageing and familial care in rural China. First, going beyond a unidirectional flow or two-way transfer, this article reveals that care circulates between different family members, in different locations, to differing degrees, over the life course. This circulation framework enables an examination of intra-generational dynamics as well as intergenerational relations. Second, this article draws attention to the mediating factors that impact upon the ways in which adult children care for the older generation. It reveals how the employment status of migrating adult children, the temporal dimension of migration and family life cycle of migrating children as well as family relations between the older generation and adult child generation are critical factors. These factors also contribute to the quality of care provided. Finally, while confirming existing scholarship that gender is an important dimension in structuring old age support in rural China, this article calls for a more differentiated approach among generations of women and between regions, revealing the ways in which local migration history interacts with intergenerational dynamics to determine the cohort of women that endure the greatest burden of care

    The RhoGEF Trio Functions in Sculpting Class Specific Dendrite Morphogenesis in Drosophila Sensory Neurons

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    As the primary sites of synaptic or sensory input in the nervous system, dendrites play an essential role in processing neuronal and sensory information. Moreover, the specification of class specific dendrite arborization is critically important in establishing neural connectivity and the formation of functional networks. Cytoskeletal modulation provides a key mechanism for establishing, as well as reorganizing, dendritic morphology among distinct neuronal subtypes. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures.Here we demonstrate that the RhoGEF Trio is required for the specification of class specific dendritic morphology in dendritic arborization (da) sensory neurons of the Drosophila peripheral nervous system (PNS). Trio is expressed in all da neuron subclasses and loss-of-function analyses indicate that Trio functions cell-autonomously in promoting dendritic branching, field coverage, and refining dendritic outgrowth in various da neuron subtypes. Moreover, overexpression studies demonstrate that Trio acts to promote higher order dendritic branching, including the formation of dendritic filopodia, through Trio GEF1-dependent interactions with Rac1, whereas Trio GEF-2-dependent interactions with Rho1 serve to restrict dendritic extension and higher order branching in da neurons. Finally, we show that de novo dendritic branching, induced by the homeodomain transcription factor Cut, requires Trio activity suggesting these molecules may act in a pathway to mediate dendrite morphogenesis.Collectively, our analyses implicate Trio as an important regulator of class specific da neuron dendrite morphogenesis via interactions with Rac1 and Rho1 and indicate that Trio is required as downstream effector in Cut-mediated regulation of dendrite branching and filopodia formation

    Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway

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    Memory formation is modulated by pre- and post-synaptic signaling events in neurons. The neuronal protein kinase Cyclin-Dependent Kinase 5 (Cdk5) phosphorylates a variety of synaptic substrates and is implicated in memory formation. It has also been shown to play a role in homeostatic regulation of synaptic plasticity in cultured neurons. Surprisingly, we found that Cdk5 loss of function in hippocampal circuits results in severe impairments in memory formation and retrieval. Moreover, Cdk5 loss of function in the hippocampus disrupts cAMP signaling due to an aberrant increase in phosphodiesterase (PDE) proteins. Dysregulation of cAMP is associated with defective CREB phosphorylation and disrupted composition of synaptic proteins in Cdk5-deficient mice. Rolipram, a PDE4 inhibitor that prevents cAMP depletion, restores synaptic plasticity and memory formation in Cdk5-deficient mice. Collectively, our results demonstrate a critical role for Cdk5 in the regulation of cAMP-mediated hippocampal functions essential for synaptic plasticity and memory formation.Norman B. Leventhal FellowshipUnited States. National Institutes of Health (NIH T32 MH074249)United States. National Institutes of Health (NIH RO1 NS051874
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