1,720,969 research outputs found
Functional Characterization of an AMPA receptor auxiliary subunit GSG1L in vivo
No full textAMPA receptors (AMPAR) are key mediators of fast excitatory neurotransmission within the brain. The functional identity of AMPAR at the synapses strongly contributes to molecular mechanisms of learning and memory. At the synapse, AMPARs are bound to their auxiliary subunits, which have a profound effect on AMPAR biogenesis. GSG1L is a recently identified auxiliary subunit that has a strong AMPAR regulatory function, unlike any known auxiliary subunit. The work presented in this dissertation aimed to determine the postsynaptic function of GSG1L. We report that AMPA receptor auxiliary subunit GSG1L controls short-term plasticity in anterior thalamic synapses
that receive inputs from the cortex, but not in those receiving inputs from other pathways. A canonical auxiliary subunit stargazin co-exists in these neurons but is functionally absent from corticothalamic synapses. In GSG1L knockout mice, anterior thalamic neurons exhibit hyperexcitability and the animals have increased susceptibility to seizures, consistent with a negative regulatory role of GSG1L. We hypothesize that negative regulation of synaptic function by GSG1L plays a critical role in maintaining optimal excitation in the anterior thalamus
Regulation of Glucose-6-Phosphatase Catalytic Subunit 2 (G6PC2) Expression and Activity
No full textMultiple studies have shown that elevated fasting blood glucose (FBG) levels are associated with increased risk of heart disease, type 2 diabetes, and many other conditions. Given the biological importance of FBG, genetic studies were performed to identify genes that regulate FBG levels. These analyses identified common, naturally occurring variants in ~30 genes with the strongest association being identified in G6PC2. G6PC2 is an enzyme that catalyzes the conversion of glucose-6-phosphate to glucose and free phosphate and is predominantly expressed in pancreatic islet beta cells—the cells responsible for insulin secretion. Insulin is the most important factor controlling blood glucose levels. These genetic data implicate G6PC2 as a target for therapies designed to lower FBG levels. Mouse studies have shown that G6pc2 deletion results in decreased FBG due to an increase in the sensitivity of glucose-stimulated insulin secretion (GSIS) to glucose. The first part of this dissertation will probe the impact of several mutations in G6PC2 on the expression and activity of the protein and determine the effect of mutations that alter function on human glucose levels using the Vanderbilt biobank, BioVU.
G6PC2 is found in the endoplasmic reticulum (ER) membrane with the active site oriented to the ER lumen, but until recently only low-resolution biochemical data were available for G6PC2. Recent publication of the AlphaFold2 algorithm has resulted in the generation of a predicted structure for G6PC2, allowing for the generation of new hypotheses investigating the structure-function relationship of the protein. Part two of this dissertation investigates several important structural motifs in the G6PC2 protein, as predicted by the AlphaFold2 algorithm and sequence analysis. Part three of this dissertation determines the therapeutic potential of a previously identified small molecule inhibitor of G6PC2. The performed studies elucidated key residues required for G6PC2 activity, support G6PC2 as a novel target for lowering FBG, and will aid in the future development of optimized G6PC2 inhibitors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
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