1,720,967 research outputs found
Autism associated misfolding mutation in Neurolign 3 and activation of the unfolded protein response.
No full textNicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice
No full textWe have recently reported nicotine-induced stimulation of reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression levels in the brain of heterozygous reeler mice (HRM), a putative animal model for the study of symptoms relevant to major behavioral disorders. We aimed to evaluate long-term behavioral effects and brain molecular changes as a result of adaptations to nicotine exposure in the developing HRM males. Adolescent mice (pnd 37-42) were exposed to oral nicotine (10 mg/l) in a 6-day free-choice drinking schedule. As expected, no differences in total nicotine intake between WT (wild-type) mice and HRM were found. Long-term behavioral effects and brain molecular changes, as a consequence of nicotine exposure during adolescence, were only evidenced in HRM. Indeed, HRM perseverative exploratory behavior and poor cognitive performance were modulated to WT levels by subchronic exposure to nicotine during development. Furthermore, the expected reduction in the expression of mRNA of reelin and GAD67 in behaviorally relevant brain areas of HRM appeared persistently restored by nicotine. For brain-derived neurotrophic factor (BDNF) mRNA expression, no genotype-dependent changes appeared. However, expression levels were increased by previous nicotine in brains from both genotypes. The mRNA encoding for nicotine receptor subunits (alpha 7, beta 2 and alpha 4) did not differ between genotypes and as a result of previous nicotine exposure. These findings support the hypothesis of pre-existing vulnerability (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative short- and long-term effects associated with nicotine modulation
LINKING ENDOPLASMIC RETICULUM STRESS TO NEURODEVELOPMENTAL DISORDERS
No full textAutism spectrum disorders are a group of neurodevelopmental
disorders with a strong genetic background. One of the most
characterized autism-linked mutations is the R451C substitution
in the synaptic protein Neuroligin3 (NLGN3). The mutation
induces a local misfolding in the extracellular domain causing
the retention of NLGN3 in the Endoplasmic Reticulum (ER)1.
The presence of misfolded protein in the ER can lead to the activation
of the Unfolded Protein Response (UPR), implicated in
several neurological diseases and in the regulation of neurotransmission
and plasticity2. Our aim is to ascertain whether the
ER retention of the R451C NLGN3 mutant protein activates
the UPR. We have generated a new PC12 Tet-On model system
with inducible expression of NLGN3, either wild type or R451C
proteins, for studying the UPR signaling in time-course experiments.
PC12 clones were characterized for NLGN3 expression,
by western blots and immunofluorescence. Wild type NLGN3
protein is correctly trafficked to the cell surface, with the
R451C NLGN3 being retained in the ER, as shown by sensitivity
to endoglycosidase H. Our results indicate that PC12 clones
expressing the R451C mutant NLGN3, activate all UPR signaling
pathways downstream of the ATF6, IRE1 and PERK stress
sensors. Synthesis of R451C NLGN3 induces the up-regulation
of UPR target genes, such as BiP and CHOP, before and after
differentiating the cells to a neuronal phenotype. In order to
understand the potential role of UPR in neurodevelopmental
disorders, we are currently investigating its activation in the
Knock In mouse model of autism, carrying the R451C mutation
in the NLGN3 endogenous gene. Our data represent the first evidence
on the effects of the R451C NLGN3 in activating the
UPR and represent a solid link between UPR and neurodevelopmental
disorders characterized by the retention of misfolded
proteins in the ER
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
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