1,720,961 research outputs found
BNIP3: A POTENTIAL TARGET FOR THE TREATMENT OF MITOCHONDRIAL DYSFUNCTION IN HUNTINGTON'S DISEASE.
Full text linkHuntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by the
expansion of a CAG trinucleotide repeat in the IT-15 gene. This disorder is characterized by
progressive neuronal death in the basal ganglia and cortex. Although many years have passed
since the discovery of the HD mutation, no therapy has shown a neuroprotective effect or has been
shown to slow down the disease progression to date. Growing evidence supports a pivotal role for
mitochondrial dysfunction in the death of patients’ neurons but the molecular bases for
mitochondrial impairment have not yet been elucidated. We provide the first evidence of an
abnormal activation of Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNip3) in cells
expressing mutant huntingtin. In the present study we show abnormal accumulation and
dimerization of BNip3 in mitochondria from human HD muscle cells and brain tissues from HD
model mice. Recent results have suggested that cytotoxicity induced by mutant huntingtin is likely
mediated by an alteration in normal mitochondrial dynamics, resulting in increased mitochondrial
fragmentation. According to the literature, when BNip3 is overexpressed or induced, it localizes to
the mitochondria and causes loss of mitochondrial potential, mitochondrial fragmentation and
mitophagy. In this context, BNip3 could have a key role in mediating the impairment of
mitochondrial dynamics in HD cells, and BNip3 blocking could improve mitochondrial function,
representing a new therapeutic strategy for HD. We have characterized the effects of BNip3
blockade in cell culture model of HD by expression of the dominant negative protein BNip3ΔTM.
BNip3ΔTM is a mutant protein deleted of the C-terminal domain that is necessary for BNip3
insertion into the outer mitochondrial membrane.
Importantly, we have demonstrated that blocking BNip3 expression and dimerization was able to
restore normal mitochondrial phenotype in human HD muscle cells. Our data shed light on the
molecular mechanisms underlying mitochondrial dysfunction in HD and point to BNip3 as a new
potential target for neuroprotective therapy in HD
Huntington's Disease: The current State of Research with Peripheral Tissues
No full textHuntington's disease (HD) is a genetically dominant condition caused by expanded CAG repeats. These repeats code for a glutamine tract in the HD gene product huntingtin (htt), which is a protein expressed in almost all tissues. Although most HD symptoms reflect preferential neuronal death in specific brain regions, even before the HD gene was identified numerous reports had described additional abnormalities in the peripheral tissues of HD patients, including weight loss, altered glucose homeostasis, and sub-cellular abnormalities in fibroblasts, lymphocytes and erythrocytes. Several years have elapsed since the HD mutation was discovered, and analyses of peripheral tissues from HD patients have helped to understand the molecular pathogenesis of the disease and revealed that the molecular mechanisms through which mutated htt leads to cell dysfunction are widely shared between central nervous system (CNS) and peripheral tissues. These studies show that in peripheral tissues, mutated htt causes accumulation of intracellular protein aggregates, impairment of energetic metabolism, transcriptional deregulation and hyperactivation of programmed cell-death mechanisms. Here, we review the current knowledge of peripheral tissue alterations in HD patients and in animal models of HD and focus on how this information can be used to identify potential therapeutic possibilities and biomarkers for disease progression
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
Loss of Parkin Protein causes abnormal intracellular calcium levels upon glutamatergic stimulation in neuronal cells
No full textDispelling 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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