1,720,955 research outputs found
Glutamate receptors potentiate single K-ATP channels through intracellular ATP changes
Get PDFRett Syndrome (RTT) is a neurodevelopmental disorder caused primarily by mutations in a Mecp2 gene and exclusively affects females. RTT is one of the prevalent developmental disorders with a high frequency of occurrence (about 1:15,000 to 1:10,000) and patients are prone to gastro-intestinal disorders and about 80% have seizures. Although the genetic defect in the Mecp2 gene defines RTT, the insights from recent studies have highlighted the complex pathophysiological mechanisms that point to developmental disorder. A better understanding of the interplay of these pathophysiological mechanisms is one of the challenges in establishing of effective therapeutic strategies. In the present study, we used Mecp2-null mice as a model to examine the physiological and/or pathophysiological cellular mechanism pathways that can play important role in the development of Rett Syndrome.
The main aspect of this study was to reveal the role of glutamate receptors (GluR) /K-ATP channels crosstalk in the development of RTT. Accordingly, the activities of these channels were examined in neurons from wild type (WT) and Mecp2-null mice that represent physiological and pathophysiological examples, respectively. Excessive stimulation of glutamatergic receptors can overexcite neurons. This can be dampened by K-ATP channels linking metabolic and neuronal activities. The crosstalk has not yet been examined on the single channel level. I aimed to examine how K-ATP channel activity changes after stimulation of neuronal glutamate receptors and whether those effects may be mediated through variations in the intracellular ATP levels.
In the hippocampal neurons, GluR agonists augmented the open state probability (Popen) of K-ATP channels with relative efficacy: Kainate = AMPA > NMDA > t-ACPD. Inhibition of calcium influx and chelation of intracellular calcium did not modify the GluR effects. Kainate did not augment production of reactive oxygen species measured with roGFP1. The oxidant H2O2 increased Popen about 2-fold within 1 min but the subsequent application of AMPA/Kainate produced further potentiation; in the same proportion as in the control. The data indicate that changes in the activity of K-ATP channels due to ROS and GluR stimulation have different mechanisms. GluR actions were abolished in Na+-free solutions and after blockade of Na+-K+-ATPase. GluR stimulation enhanced ATP consumption that decreased submembrane ATP levels, whereas metabolic poisoning diminished bulk ATP.
Increase of the K-ATP channel open state probabilities after GluR stimulation less in Mecp2 -/y hippocampal neurons. It allows to speculate whether protective role attributed commonly to K-ATP channels in RTT hippocampal neurons may be less effective.
I examined the role of GluR and K-ATP channels cross-talk in relation to mechanisms of epilepsy. In hippocampal organotypic slices using well established model, a seizure-like activity was evoked by removal of magnesium from bath. This was accompanied by calcium and ATP changes. The ATP responses were distinctly different in specific hippocampal regions: in dentate gyrus (DG) the neurons possessed higher ATP resting levels and showed smaller changes to epileptogenic stimuli in comparison with CA1 and CA3 areas.
ATP levels in RTT neurons were significantly higher than those measured in WT cells. This corroborates well with observations of diminished K-ATP channel open state probability. We propose that K-ATP channels and GluRs are functionally coupled and can regulate long-lasting changes of neuronal activity in the CNS neurons.
The obtained data indicate that RTT symptom as propensity to seizures can be essentially contributed by improper K-ATP channel functioning
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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