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SYNAPTIC AVAILABILITY OF GLUN2A SUBUNIT OF NMDA RECEPTORS FROM PHYSIOLOGICAL MECHANISMS TO 
PATHOLOGY: THE ROLE OF RABPHILIN 3A
Get PDFBackground and Purpose - NMDA receptor subunit composition strictly commands receptor function and pharmacological responses. The identity of the GluN2 subunit regulates biophysical and pharmacological properties of the receptor and influences receptor assembly, signaling and trafficking to the postsynaptic membrane. The number or subunit composition of NMDA receptors vary during activity dependent plasticity and CNS disorders like Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID) where you can find an enhanced extrasynaptic localization of GluN2B-containing NMDA receptors and an increase of the GluN2A/GluN2B ratio at striatal synapses. Recently, a two-hybrid screening to find potential proteins interacting with the C-terminal tail of the GluN2A subunit of the NMDA receptor has highlighted Rabphilin 3A (Rph3A) as a potential partner. Rph3A is a synaptic vesicle-associated protein that was first identified as a binding partner of the GTP-bound Rab3A, a member of the Rab family of GTPases implicated in vesicle docking/fusion reactions. Moreover, different studies have indicated that Rph3A can regulate exo- and endocytosis processes at synaptic sites. Our goal was to characterize Rph3A interaction with GluN2A at postynaptic sites and to assess its relevance in PD and LID.
Methods and Results - Firstly, we verified its interaction with GluN2A by immunoprecipitation and GST pull-down experiments. Subcellular fractionation assays revealed that Rph3A is present in Triton Insoluble Postsynaptic compartment and post-synaptic density (PSD) fractions. Immunofluorescence studies performed in neuronal hippocampal cultures, confirmed biochemical experiments revealing Rph3A colocalization with PSD-95 (marker of the postsynaptic compartment) and GluN2A. Moreover, we found Rph3A to be interacting with a 40AA domain on C-terminal tail of GluN2A between AA 1349 and 1389. Therefore, we designed a cell permeable peptide containing this sequence called TAT-2A-40. This peptide is capable of disrupting the interaction between Rph3A and GluN2A. By doing this, it can reduce the expression of GluN2A in dendritic spines and its surface expression as we show by immunocytochemistry and electrophysiology. Moreover, we have observed an increase of GluN2A/Rph3A interaction in a rat PD model as well as a rat LID model. We have that the TAT-2A-40 was capable of significantly reducing the dyskinetic behavior in these animals.
Conclusions - These results strongly indicate the presence of Rph3A in the PSD compartment and suggest a function of Rph3A in the modulation of NR2A localization. Rph3A could play a crucial role in the stabilization of GluN2A subunits at the plasma membrane in dendritic spines. Therefore, this interaction could be a potential therapeutic target for diseases where NMDAR composition is significantly altered such as Parkinson's Disease and L-DOPA-induced dyskinesia
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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