1,720,987 research outputs found

    Association of AMPA receptors with a subset of glutamate receptor-interacting protein in vivo

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    The NMDA and AMPA classes of ionotropic glutamate receptors are concentrated at postsynaptic sites in excitatory synapses. NMDA receptors interact via their NR2 subunits with PSD-95/SAP90 family proteins, whereas AMPA receptors bind via their GluR2/3 subunits to glutamate receptor-interacting protein (GRIP), AMPA receptor-binding protein (ABP), and protein interacting with C kinase 1 (PICK1). We report here a novel cDNA (termed ABP-L/GRIP2) that is virtually identical to ABP except for additional GRIP-like sequences at the N-terminal and G-terminal ends. Like GRIP (which we now term GR(PI), AEP-L/GRIP2 contains a seventh PDZ domain at its C terminus. Using antibodies that recognize both these proteins, we examined the subcellular localization of GRIP1 and ABP-L/GRIP2 (collectively termed GRIP) and their biochemical association with AMPA receptors. Immunogold electron microscopy revealed the presence of GRIP at excitatory synapses and also at nonsynaptic membranes and within intracellular compartments. The association of native GRIP and AMPA receptors was confirmed biochemically by coimmunoprecipitation from rat brain extracts. A majority of detergent-extractable GluR2/3 was complexed with GRIP in the brain. However, only approximately half of GRIP was associated with AMPA receptors. Unexpectedly, immunocytochemistry of cultured hippocampal neurons and rat brain at the light microscopic level showed enrichment of GRIP in GABAergic neurons and in GABAergic nerve terminals. Thus GRIP is associated with inhibitory as well as excitatory synapses. Collectively, these findings support a role for GRIP in the synaptic anchoring of AMPA receptors but also suggest that GRIP has additional functions unrelated to the binding of AMPA receptors

    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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    Striatal cholinergic dysfunction as a unifying theme in the pathophysiology of dystonia

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    Dystonia is a movement disorder of both genetic and non-genetic causes, which typically results in twisted posturing due to abnormal muscle contraction. Evidence from dystonia patients and animal models of dystonia indicate a crucial role for the striatal cholinergic system in the pathophysiology of dystonia. In this review, we focus on striatal circuitry and the centrality of the acetylcholine system in the function of the basal ganglia in the control of voluntary movement and ultimately clinical manifestation of movement disorders. We consider the impact of cholinergic interneurons (ChIs) on dopamine-acetylcholine interactions and examine new evidence for impairment of ChIs in dysfunction of the motor systems producing dystonic movements, particularly in animal models. We have observed paradoxical excitation of ChIs in the presence of dopamine D2 receptor agonists and impairment of striatal synaptic plasticity in a mouse model of DYT1 dystonia, which are improved by administration of recently developed M1 receptor antagonists. These findings have been confirmed across multiple animal models of DYT1 dystonia and may represent a common endophenotype by which to investigate dystonia induced by other types of genetic and non-genetic causes and to investigate the potential effectiveness of pharmacotherapeutics and other strategies to improve dystonia

    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

    Altered responses to dopaminergic D2 receptor activation and N-type calcium currents in striatal cholinergic interneurons in a mouse model of DYT1 dystonia

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    Early-onset torsion dystonia (DYT1) is an autosomal dominant disease caused by a deletion in the gene encoding the protein torsinA. Recently, a transgenic mouse model of DYT1 has been described, expressing either the human wild-type torsinA (hWT) or mutant torsinA (hMT). We recorded the activity of striatal cholinergic interneurons of hWT, hMT, and control mice. In slice preparations, no significant differences were observed in resting membrane potential (RMP), firing activity, action potential duration or Ih current. Quinpirole, a D2-like dopamine receptor agonist, did not produce detectable effects on RMP of cholinergic interneurons in control mice and hWT mice, but in the hMT mice caused membrane depolarization and an increase in the firing rate. D2 receptor activation inhibits N-type high-voltage-activated calcium currents. We found that, in isolated interneurons from hMT mice, the quinpirole-mediated inhibition of N-type currents was significantly larger than in hWT and controls. Moreover, the N-type component was significantly over-represented in hMT mice. The altered sensitivity of N-type channels in hMT mice could account for the paradoxical excitatory effect of D2 stimulation. Our data support the existence of an imbalance between striatal dopaminergic and cholinergic signaling in DYT1 dystonia. © 2006 Elsevier Inc. All rights reserved
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