215 research outputs found

    Efficacy and safety of apixaban in real-life patients at high bleeding risk

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    Ronald Reagan a wyzwania epoki

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    Z wprowadzenia: "Śmierć Ronalda Reagana w czerwcu 2004 r. zamknęła znaczącą epokę w dziejach Europy i świata. Reagan symbolizował pokolenie polityków, którym przyszło działać w czasach szybkiej dekompozycji dwóch, wydawałoby się niepodważalnych pewników politycznych dominujących po drugiej wojnie światowej w świecie zachodnim. Z polityków tych był tym, który przyczynił się w olbrzymiej mierze do podważenia obu z nich."(...

    Social capital, social inclusion and changing school contexts: a Scottish perspective

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    This paper synthesises a collaborative review of social capital theory, with particular regard for its relevance to the changing educational landscape within Scotland. The review considers the common and distinctive elements of social capital, developed by the founding fathers – Putnam, Bourdieu and Coleman – and explores how these might help to understand the changing contexts and pursue opportunities for growth

    The Cytosolic Tail of the Golgi Apyrase Ynd1 Mediates E4orf4-Induced Toxicity in Saccharomyces cerevisiae

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    The adenovirus E4 open reading frame 4 (E4orf4) protein contributes to regulation of the progression of virus infection. When expressed individually, E4orf4 was shown to induce non-classical transformed cell-specific apoptosis in mammalian cells. At least some of the mechanisms underlying E4orf4-induced toxicity are conserved from yeast to mammals, including the requirement for an interaction of E4orf4 with protein phosphatase 2A (PP2A). A genetic screen in yeast revealed that the Golgi apyrase Ynd1 associates with E4orf4 and contributes to E4orf4-induced toxicity, independently of Ynd1 apyrase activity. Ynd1 and PP2A were shown to contribute additively to E4orf4-induced toxicity in yeast, and to interact genetically and physically. A mammalian orthologue of Ynd1 was shown to bind E4orf4 in mammalian cells, confirming the evolutionary conservation of this interaction. Here, we use mutation analysis to identify the cytosolic tail of Ynd1 as the protein domain required for mediation of the E4orf4 toxic signal and for the interaction with E4orf4. We also show that E4orf4 associates with cellular membranes in yeast and is localized at their cytoplasmic face. However, E4orf4 is membrane-associated even in the absence of Ynd1, suggesting that additional membrane proteins may mediate E4orf4 localization. Based on our results and on a previous report describing a collection of Ynd1 protein partners, we propose that the Ynd1 cytoplasmic tail acts as a scaffold, interacting with a multi-protein complex, whose targeting by E4orf4 leads to cell death

    Statistical practices of educational researchers: An analysis of their ANOVA, MANOVA, and ANCOVA analyses

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    Articles published in several prominent educational journals were examined to investigate the use of data-analysis tools by researchers in four research paradigms: between-subjects univariate designs, between-subjects multivariate designs, repeated measures designs, and covariance designs. In addition to examining specific details pertaining to the research design (e.g., sample size, group size equality/inequality) and methods employed for data analysis, we also catalogued whether: (a) validity assumptions were examined, (b) effect size indices were reported, (c) sample sizes were selected based on power considerations, and (d) appropriate textbooks and/or articles were cited to communicate the nature of the analyses that were performed. Our analyses imply that researchers rarely verify that validity assumptions are satisfied and accordingly typically use analyses that are nonrobust to assumption violations. In addition, researchers rarely report effect size statistics, nor do they routinely perform power analyses to determine sample size requirements. We offer many recommendations to rectify these shortcomings.Social Sciences and Humanities Research Counci

    Systematical Detection of Significant Genes in Microarray Data by Incorporating Gene Interaction Relationship in Biological Systems

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    Many methods, including parametric, nonparametric, and Bayesian methods, have been used for detecting differentially expressed genes based on the assumption that biological systems are linear, which ignores the nonlinear characteristics of most biological systems. More importantly, those methods do not simultaneously consider means, variances, and high moments, resulting in relatively high false positive rate. To overcome the limitations, the SWang test is proposed to determine differentially expressed genes according to the equality of distributions between case and control. Our method not only latently incorporates functional relationships among genes to consider nonlinear biological system but also considers the mean, variance, skewness, and kurtosis of expression profiles simultaneously. To illustrate biological significance of high moments, we construct a nonlinear gene interaction model, demonstrating that skewness and kurtosis could contain useful information of function association among genes in microarrays. Simulations and real microarray results show that false positive rate of SWang is lower than currently popular methods (T-test, F-test, SAM, and Fold-change) with much higher statistical power. Additionally, SWang can uniquely detect significant genes in real microarray data with imperceptible differential expression but higher variety in kurtosis and skewness. Those identified genes were confirmed with previous published literature or RT-PCR experiments performed in our lab

    MTF-1-Mediated Repression of the Zinc Transporter Zip10 Is Alleviated by Zinc Restriction

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    The regulation of cellular zinc uptake is a key process in the overall mechanism governing mammalian zinc homeostasis and how zinc participates in cellular functions. We analyzed the zinc transporters of the Zip family in both the brain and liver of zinc-deficient animals and found a large, significant increase in Zip10 expression. Additionally, Zip10 expression decreased in response to zinc repletion. Moreover, isolated mouse hepatocytes, AML12 hepatocytes, and Neuro 2A cells also respond differentially to zinc availability in vitro. Measurement of Zip10 hnRNA and actinomycin D inhibition studies indicate that Zip10 was transcriptionally regulated by zinc deficiency. Through luciferase promoter constructs and ChIP analysis, binding of MTF-1 to a metal response element located 17 bp downstream of the transcription start site was shown to be necessary for zinc-induced repression of Zip10. Furthermore, zinc-activated MTF-1 causes down-regulation of Zip10 transcription by physically blocking Pol II movement through the gene. Lastly, ZIP10 is localized to the plasma membrane of hepatocytes and neuro 2A cells. Collectively, these results reveal a novel repressive role for MTF-1 in the regulation of the Zip10 zinc transporter expression by pausing Pol II transcription. ZIP10 may have roles in control of zinc homeostasis in specific sites particularly those of the brain and liver. Within that context ZIP10 may act as an important survival mechanism during periods of zinc inadequacy

    Plant 45S rDNA Clusters Are Fragile Sites and Their Instability Is Associated with Epigenetic Alterations

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    Our previous study demonstrated that 45S ribosomal DNA (45S rDNA) clusters were chromosome fragile sites expressed spontaneously in Lolium. In this study, fragile phenotypes of 45S rDNA were observed under aphidicolin (APH) incubation in several plant species. Further actinomycin D (ActD) treatment showed that transcriptional stress might interfere with chromatin packaging, resulting in 45S rDNA fragile expression. These data identified 45S rDNA sites as replication-dependent as well as transcription-dependent fragile sites in plants. In the presence of ActD, a dramatic switch to an open chromatin conformation and accumulated incomplete 5′ end of the external transcribed spacer (5′ETS) transcripts were observed, accompanied by decreased DNA methylation, decreased levels of histone H3, and increased histone acetylation and levels of H3K4me2, suggesting that these epigenetic alterations are associated with failure of 45S rDNA condensation. Furthermore, the finding that γ-H2AX was accumulated at 45S rDNA sites following ActD treatment suggested that the DNA damage signaling pathway was associated with the appearance of 45S rDNA fragile phenotypes. Our data provide a link between 45S rDNA transcription and chromatin-packaging defects and open the door for further identifying the molecular mechanism involved
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