1,720,966 research outputs found

    Acidosis enhances toxicity induced by kainate and zinc exposure in aged cultured astrocytes

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    A key feature of cerebral ischemia, one of the leading causes of death associated with ageing, is excessive accumulation of glutamate in the synaptic cleft. In some forms of cerebral ischemia, like transient global ischemia, high levels of synaptic glutamate are complemented by a concomitant increase in extracellular Zn2+ as result of the release of the cation that is present in the pre-synaptic vesicles of glutamatergic neurons. Interestingly, while neurons are very sensitive to the toxicity triggered by exposure to either glutamate or Zn2+, astrocytes show less vulnerability to these toxins. We examined the vulnerability of cortical type 1 astrocytes to a combined exposure to the AMPA/kainate receptor agonist kainate and Zn 2+. Astrocytes exposed to 1 mM kainate for 1 h did not exhibit any degeneration in the following 24 h, and addition of 50 μM Zn2+ to the kainate exposure failed to produce any further glial loss. Another hallmark of cerebral ischemia is parechymal acidosis and therefore, we tested the susceptibility of our cultured astrocytes to a kainate/Zn2+ exposure performed under acidotic conditions. We found that the combination of 1 h exposure to 1 mM kainate + 50 μM Zn2+ at pH 6.2 produced a strong increase in intracellular free Zn2+ ([Zn2+]i), and extensive glial injury. Comparing [Zn2+]i rises triggered by kainate/ Zn2+ exposure at pH 7.4 or pH 6.2 we found that acidosis promotes increased toxic [Zn2+]i levels as a result of a lethal combination of both enhanced Zn2+ influx through Zn2+ permeable AMPA/kainate channels and impaired intracellular buffering of the cation

    Zinc Homeostasis and Brain Injury

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    Cumulating evidence suggest that Zn2+ dys/homeostasis can play a major role in promoting brain injury in excitotoxic syndromes. Zn2+ homeostasis in the brain is regulated through highly dynamic pathways and is deeply connected with other major signaling pathways, such as NO- and MAP kinase-dependent systems. Zn2+ signaling in neurons and glia also interplays with proton and Ca2+ homeostasis. Zn2+ appears to promote injury with greater potency compared to Ca2+ and as such the cation may be an underappreciated mediator of excitotoxicity, which for many years has been described mainly as a Ca2+- dependent phenomenon. © 2007 Springer-Verlag US

    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

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    The 1st 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis

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    A truncated form of the Huntington's disease (HD) protein that contains the polyglutamine repeat, Httex1p, causes HD-like phenotypes in multiple model organisms. Molecular signatures of pathogenesis appear to involve distinct domains within this polypeptide. We studied the contribution of each domain, singly or in combination, to sub-cellular localization, aggregation and intracellular Ca2+ ([Ca2+]i) dynamics in cells. We demonstrate that sub-cellular localization is most strongly influenced by the first 17 amino acids, with this sequence critically controlling Httex1p mitochondrial localization and also promoting association with the endoplasmic reticulum (ER) and Golgi. This domain also enhances the formation of visible aggregates and together with the expanded polyQ repeat acutely disrupts [Ca2+]i levels in glutamate-challenged PC12 cells. Isolated cortical mitochondria incubated with Httex1p resulted in uncoupling and depolarization of these organelles, further supporting the idea that Httex1p-dependent mitochondrial dysfunction could be instrumental in promoting acute Ca2+ dyshomeostasis. Interestingly, neither mitochondrial nor ER associations seem to be required to promote long-term [Ca2+]i dyshomeostasis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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