1,721,188 research outputs found
Connection between astrocytes, cholesterol and synaptic dysfunction in Huntington’s disease
No full textHuntington's disease (HD) is a genetic, neurodegenerative disorder caused by a CAG repeat expansion in the gene encoding the huntingtin (HTT) protein. Clinically, HD is characterized by motor, cognitive, and psychiatric disturbances and is associated with neuronal and synaptic dysfunction and progressive loss of striatal and cortical neurons.
Several molecular and cellular dysfunctions have been identified in HD, and one affected pathway implicates brain cholesterol. Brain cholesterol biosynthesis is reduced across different HD animal models suggesting that newly cholesterol is less available to neurons. This might be detrimental for neuronal cells, especially given that locally synthesized cholesterol is implicated in neurite outgrowth, synapses formation, maintenance and activity, and optimal neurotransmitter release.
Here I will present our recent findings suggesting that astrocytes carrying the HD mutation are the major responsible of cholesterol dysfunction in HD as they contribute to supply less cholesterol to the surrounding neurons. Finally, I will show our in vivo studies demonstrating that delivery of exogenous cholesterol supplementation in the brain of HD mice rescues molecular, functional and behavioral aspects of the disease
Cholesterol dysfunction in neurodegenerative diseases : is Huntington's disease in the list?
No full textBrain cholesterol is an essential component of cell membranes, and involved in a number of biological functions such as membrane trafficking, signal transduction, myelin formation and synaptogenesis. Given these widespread activities and the knowledge that all brain cholesterol derives from local synthesis, it is not surprising that dysfunctions in cholesterol synthesis, storage, transport and removal may lead to human brain diseases. Some of these diseases emerge as a consequence of genetic defects in the enzymes involved in cholesterol biosynthesis; in other cases, such as Alzheimer's disease, there is a link between cholesterol metabolism and the formation and deposition of amyloid-beta peptide. Emerging evidence indicates that changes in cholesterol synthesis may also occur in Huntington's disease, an inherited, autosomal dominant neurodegenerative disorder that primarily affects striatal neurons of the brain. We here provide an overview of the involvement of cholesterol in normal brain function and its impact on neurodegenerative diseases. In particular, we consider the available clinical, biological and molecular evidence indicating a potential dysregulation of cholesterol homeostasis in Huntington's diseas
Sviluppo di tecnologia "ultra-low NOx" per combustori di turbina a gas alimentati a combustibile liquido
No full textEmerging roles for cholesterol in Huntington's disease
No full textRecent findings suggest that alterations in cholesterol homeostasis might be associated with Huntington's disease (HD). Although alterations in cholesterol content have been detected in cell models and several rodent models of HD, it is currently unclear what the potential mechanisms underlying cholesterol perturbations are. Furthermore, it remains to be determined whether these observed changes in cholesterol homeostasis are involved in the pathogenesis of HD or occur as a secondary event. In this review, we provide an overview of current studies that have begun to address these issues and discuss recent findings suggesting that normal huntingtin protein might participate in regulating cholesterol biosynthesis. A better understanding of how alterations in cholesterol levels contribute to the pathophysiology of HD is likely to have significant therapeutic implications for the treatment of this debilitating neurodegenerative disorder
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
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