1,721,002 research outputs found

    A newt ribozyme: a catalytic activity in search of a function. Proc Natl Acad Sci U S A

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    We analyzed the cleavage properties and the transcription regulation of the newt (Triturus vulgaris meridionalis) self-cleaving RNA. In vitro self-cleavage of model oligoribonucleotides occurs within a double hammerhead structure. In addition, an entire ribozyme molecule, as well as its catalytic domain, "trans-cleaves" in vitro appropriate oligoribonucleotide substrates. Signals encoded within the ribozyme DNA sequences regulate the ribozyme transcription, which is RNA polymerase II dependent. Finally, the deduced secondary structure of the self-cleaving RNA appears to be conserved in evolutionarily distant newt species. These features suggest that the newt ribozyme could play some role in the cell, possibly related to its cleavage properties

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    PPAR γ agonists inhibit angiogenesis by suppressing PKCα-and CREB-mediated COX-2 expression in the human endothelium

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    AimsThe activation of peroxisome proliferator-activated receptor (PPAR) is known to inhibit angiogenesis. As a potential mechanism for this, we aimed at examining the effects of PPAR agonists on the pro-angiogenic enzyme cyclooxygenase (COX)-2 in human endothelium.Methods and resultsCultured endothelial cells were pre-incubated with the PPAR agonists rosiglitazone (RSG) or GW1929 before stimulation with vascular endothelial growth factor (VEGF) or phorbol myristate acetate (PMA). RSG and GW1929 attenuated VEGF-and PMA-stimulated COX-2 activity, as well as protein and mRNA expression. This effect was abolished by the PPAR antagonists bisphenol A diglycidyl ether and GW9662 as well as by PPAR small-interfering RNAs (siRNAs). Transient transfection experiments revealed that the induction of COX-2 promoter was significantly inhibited by RSG through an interference with the cAMP response element (CRE) site. COX-2 downregulation after siRNA targeting CRE-binding protein (CREB) confirmed the role of CREB in mediating COX-2 transcription. Correspondingly, PPAR agonists attenuated CREB activation. As both protein kinase C (PKC) and are involved in VEGF-induced COX-2 expression and CREB activation, we investigated which isoform(s) of PKC was affected by RSG. RSG only reduced VEGF-and PMA-stimulated PKC membrane translocation.ConclusionVEGF induces CREB-mediated COX-2 expression through a PKC-dependent pathway in human endothelium. The anti-angiogenic effect of PPAR agonists is due, at least in part, to an interference with the VEGF-stimulated PKC-mediated activation of CREB and the related expression of COX-2
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