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    The mechanism of kainic acid receptor-induced inhibition of I-sAHP in CA1 pyramidal neurones

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    The slow afterhyperpolarisation current (IsAHP) in CA1 pyramidal neurones is reduced in kainic acid-lesioned hippocampus and this effect leads to an increase in cell excitability (Ashwood et al. 1986). We investigated the mechanisms of kainic acid-induced inhibition using whole-cell patch-clamp experiments.Hippocampal slices were obtained from humanely killed 14- to 21-day-old rats. The recordings were made from CA1 pyramidal cells using KMeSO4-containing pipettes. Voltage steps (60 mV for 80 ms) were applied every 20 s to generate IsAHP.Bath application of kainic acid produced concentration-dependent inhibition of IsAHP that reached a plateau of 34 % at 100-200 nM (IC50 = 15 nM; n = 7). The inhibition was not accompanied by an inward current and persisted in the presence of 1 µM TTX + 5 mM TEA (n = 8), suggesting postsynaptic localisation of the receptors. The AMPA/KA blocker CNQX (20 µM; n = 6) abolished the action of kainic acid, whereas a selective antagonist of AMPA receptors, GYKI52466 (100 µM), was ineffective (n = 5). The effect of kainate could be reproduced by domoic acid (200 nM; n = 7), but not by the potent agonist of AMPA receptors (S)-5-fluorowillardiine (300 nM; n = 7). The GluR5 kainate receptor agonist ATPA (2 µM; n = 5) did not produce any inhibition. The results are consistent with an action of kainate mediated by GluR6-containing kainate receptors, and imply that a metabotropic function may be involved as reported for presynaptic kainate receptors (Rodriguez-Moreno &amp; Lerma, 1998). This was tested by pre-incubation of the slices with the protein kinase C inhibitor calphostin C (1 µM); this treatment prevented kainate-induced inhibition (n = 10). Subsequent application of noradrenaline (10 µM; n = 4) blocked IsAHP, demonstrating that PKA-dependent inhibition remained intact. In current-clamp experiments, kainic acid (200 nM) did not reduce either the width or the amplitude of calcium spikes recorded following a brief depolarising step (n = 8). This suggests that kainate inhibition of IsAHP was not due to a reduction in Ca2+ influx.These data indicate that GluR6 kainate receptors on CA1 pyramidal cells not only mediate ionic currents (Bureau et al. 1999) but have metabotropic actions leading to increased cell excitability.This work is supported by The Wellcome Trust. <br/

    Metabotropic regulation of intrinsic excitability by synaptic activation of kainate receptors

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    Prolonged modification of intrinsic neuronal excitability is gaining prominence as an activity-dependent form of plasticity. Here we describe a potential synaptic initiation mechanism for these changes in which release of the transmitter glutamate acts on kainate receptors to regulate the postspike slow afterhyperpolarization (sAHP). This action of synaptically released glutamate was occluded by previous kainate application. Furthermore, inhibition of glutamate uptake enhanced the effects of synaptic activation. Glutamate-mediated kainate receptor inhibition of sAHP current (IsAHP) was blocked by the PKC inhibitor calphostin C, confirming the requirement for a metabotropic signaling cascade. These data describe a new physiological function for glutamate release: activation of metabotropic kainate receptors, which control directly the excitability of pyramidal cells and probably contribute to prolonged excitability changes

    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

    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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