1,720,962 research outputs found
Endoplasmic reticulum homeostasis, lipid droplets biogenesis and autophagy in Drosophila models of Hereditary Spastic Paraplegia
Get PDFMutations in the SPG4 gene (Spastin), SPG31 gene (REEP1) and SPG3A gene (Atlastin) are the most common causes of autosomal dominant Hereditary Spastic Paraplegia (HSP), a complex genetic disorder characterized by the axonal degeneration of corticospinal tracts. Interactions between REEP1, Atlastin and Spastin, have a crucial role in modifying ER architecture and lipid metabolism, two important emerging cellular aspects potentially underlying HSP pathological mechanism. The role of lipid droplets (LDs) in HSP has been highlighted by recent evidence that proteins such as Seipin/SPG17, Erlin2/SPG18, Atlastin/SPG3A, Spartin/SPG20, REEP1/SPG31 and Spastin/SPG4 affect cellular LD turnover. Moreover, the authophagy/lysosomes degradative pathway is another important process that crosses LD and ER homeostasis. Different studies have shown that Spastin modulates the endosomal tubule fission and has a crucial role in the tethering of cellular organelles such as LDs, endosomes and peroxisomes. The depletion of spastin alters the ER-endosome contacts, impairs endosomal tubule fission and induces lysosome abnormalities. Furthermore, spastin reduces the LD-peroxisome contacts and affects the fatty acid (FA) trafficking from LDs to peroxisomes. In spite of these findings, the relationship between ER homeostasis and the lipid pathway, with the related implications for neuronal dysfunction in HSP, still remains unknown.
In this work we used the common fruit fly, Drosophila melanogaster, as model organism to perform in vivo studies aimed at describing ReepA function in endoplasmic reticulum homeostasis and morphology and, establishing the role of ReepA and Dspastin in LD biogenesis and autophagy. In order to investigate these pathways, we manipulated the expression of Drosophila REEPA and Spastin by using loss of function alleles and RNA interference approaches. Since immunostaining experiments have shown that loss of ReepA function modifies ER morphology. We investigated the role of ReepA in ER homeostasis, quantifying the mRNA levels of the main genes involved in unfolded protein response (UPR). The results indicate that absence of ReepA triggers a selective activation of the Ire1 and Atf6 branches of UPR. Drosophila lacking ReepA exhibit locomotor dysfunction and shortened lifespan and display a decrease in LD number and size in nerves and muscles phenotypes reminiscent of those caused by Dspastin-RNAi. In order to understand the link between ER homeostasis and LD turnover, we quantified the relative mRNA expression of genes (Mino and Mdy) involved in lipid metabolism. Both HSP models displayed a reduction of Mino and Mdy mRNA levels suggesting a role for Spastin and ReepA in LD biogenesis. Moreover, we investigated the formation of early and late autophagosomes, lysosomes and autolysosomes using fluorescent monomeric tandem constructs that allow the visualization of autophagosomes and lysosomes in vivo. Loss of ReepA and Spastin function impaired the autophagic flux, increasing the number of early/immature and late autophagosomes. Moreover, we showed that loss of DSpastin and ReepA function produces larger lysosomes, consistent with the studies in mammalian models. We also found that naringenin, a flavonoid that possesses strong antioxidant activity and is considered a neuroprotective phytochemical, is able to rescue the cellular phenotypes, the lifespan and locomotor disability associated with loss of ReepA and Dspastin-RNAi. Our data highlight the importance of ER homeostasis in nervous system functionality and in HSP neurodegenerative mechanisms opening new avenues for HSP treatment
Addressing the social and economic challenges of Orphan Drugs: a managerial perspective
Get PDFThe work aims to propose preliminary reflections upon a managerial view concerning the open issue of Orphan Drugs. After an overview of the scenario of Orphan Drugs at an international level and a short literature review, the work highlights a dominant economic rationality, which essentially follows a ‘linear’ logic, in the approach to frame the problem of Orphan Drugs both from a policy making and a scientific perspective.
By widening the view in the framing of the problem, a more radical change appears to be required in order to overcome the dilemma of reconciling the economic and the social perspectives and be able to address the issue of Orphan Drugs accordingly. A deep rethinking of business models within the context of the worldwide engagement for a more sustainable and inclusive world is at the basis of a new Inclusive Development strategy, which is outlined as a possible pathway to reconcile the economic and social perspectives in the management of businesses
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
- …
