1,720,970 research outputs found
Analysis of the R451C Neuroligin3 Knock-In mouse, a model of a monogenic form of autism
Full text linkAutism Spectrum Disorders (ASDs) are neurodevelopmental syndromes, in which several environmental risk factors act on a vulnerable genetic background. Among genes whose mutations have been associated with ASDs, the R451C substitution in the synaptic protein Neuroligin3 (NLGN3) has been highly characterized.
It is known from in vitro studies, that the mutation affects folding of the extracellular domain of the protein, causing its retention in the Endoplasmic Reticulum (ER) and the activation of the Unfolded Protein Response (UPR). It has been shown both in vitro and in vivo, that only ~10% of the mutant protein reach the synapse, causing loss of NLGN3 on the cell surface and leading to alterations in synaptic neurotransmission.
In this work, we have evaluated whether UPR was activated in vivo, in the brain of the knock-in mouse model carrying the R451C mutation in the endogenous NLGN3. We showed a selective increase of UPR markers levels in the cerebellum of the R451C mice, along with an increase in the frequency of the miniature excitatory currents in the Purkinje cells, that resulted to be UPR-dependent.
At the same time, in order to find a strategy to rescue NLGN3 folding and expression on the cell surface, we have generated and characterized a new cell-based model system that allowed studying NLGN3 protein trafficking. By using this system, we have screened an FDA-approved library of compounds for improving impaired protein folding. Among the compounds that have been tested, several members of the glucocorticoid family showed efficacy in increasing mutant protein trafficking and restoring membrane localization.
Collectively, our data indicated that the ER-retention of R451C NLGN3 in vivo, caused UPR activation and alterations of synaptic function in the cerebellum of a mouse model of a monogenic form of autism. Furthermore, we identified compounds improving NLGN3 folding and rescuing impaired trafficking
Aflatoxin B1 Cytotoxicity on Neurons in culture
No full textAflatoxin B-1(AFB(1)), a metabolite produced by Aspergillus flavus and Aspergillus parasiticus, is mainly known for its strong hepatotoxic and hepatocarcinogenic actions. Acute and reversible effects due to exposure to aflatoxin and the presence of aflatoxins in various human tissues and organs have also been reported. In particular, aflatoxin M(1) (a metabolite of AFB(1)) has been identified in human brain tissue, and a syndrome characterised by encephalopathy has been observed in humans poisoned by AFB(1). As a first approach to the study of the neurotoxicity of AFB(1), we used the human neuronal cell lines, SKNMC and SKNSH. The data reported show clearly that AFB(1) is capable of interacting directly with neuronal cells and causing a decrease in cell number following the addition of toxin to the culture. Decrease in cell survival is dependent on the toxin concentration, on time of exposure, and on cell density. The cytotoxic response of these cells has been compared to the effects of AFB(1) on hepatoma cells and spinal cord motor neurons. Postmitotic neurons are also susceptible to AFB(1) toxicity, although to a lower extent than proliferating cells. A non-proliferating state thus appears to lower, but not destroy, neuron sensitivity to the toxin
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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