1,721,013 research outputs found
Protective effects of olive oil antioxidant phenols on mercury-induced phosphatidylserine externalization in erythrocyte membrane: Insights into scramblase and flippase activity
Full text linkIn several physiopathological processes, phosphatidylserine (PS), normally sequestered to the inner leaflet of the plasma membrane, becomes exposed to the cell surface. In erythrocytes (RBC), PS externalization is a crucial event for the removal of aged/damaged cells but can also be associated with increased prothrombotic activity. Structurally related olive oil antioxidants, including hydroxytyrosol (HT), are able to significantly reduce the percentage of PS-exposing RBC, when cells are exposed to toxic compounds such as the heavy metal mercury (Hg). The aim of the present study was to identify the molecular mechanisms underlying the protective effect, with a focus on two different phospholipid translocases, the ATP-dependent flippase ATP11C and the calcium-dependent scramblase PLSCR1, which are responsible for PS internalization and exposure, respectively. In addition to HT, its monophenol analogue, tyrosol, and its in vivo metabolite, homovanillic alcohol, were also tested. Our investigation revealed that exposure of human intact RBC to HgCl2 induced a decrease in flippase activity and an increase in scramblase activity, and that all the selected phenols restored the control activity, regardless of their different scavenging properties. Interestingly, all phenols restored the ATP level of control cells, which were significantly reduced by HgCl2 treatment. Conversely, no variation in intracellular calcium was observed under our experimental conditions. Additionally, all phenols restored the glutathione levels, significantly reduced in the presence of HgCl2. In line with the data on the enzymatic activity, Western blotting analysis indicated changes in the membrane expression of the two enzymes, alterations prevented by antioxidant pre-treatment. Finally, molecular docking analysis suggests that the tested antioxidants may be able to directly interact with ATP11C. Our findings provide an experimental basis for the use of olive oil bioactive compounds in nutritional/nutraceutical strategies for the prevention of Hg-related toxicity, particularly in relation to the cardiovascular tissues
Molecular Underpinnings of MMP-13 Selective Inhibition by Arylsulfonamido Hydroxamate Analogues as Potential Therapeutic Agents in Osteoarthritis
No full textMDM2/4 inhibitors as novel therapeutic strategy to enhance 5-FU induced nucleolar stress and apoptosis in colon cancer cells
No full textDiscovery of a new subnanomolar Tumor Necrosis Factor-alpha Converting Enzyme (TACE) inhibitor as antiinvasive agent
No full textBest Matching Protein Conformations and Docking Programs for a Virtual Screening Campaign Against SMO Receptor
No full textSMO receptor is one of the main components of the Hedgehog biochemical pathway. In the last decades compelling body of evidence demonstrated that this receptor is a pertinent target for the treatment of various types of solid tumors. Recently, the X-ray determination of the three-dimensional structure of SMO in complex with different antagonists opened up the way for the structure-based design of new antagonists for this receptor that could possibly overcome the limitations connected with the induction of acquired tumor resistance. Herein, taking advantage of three different docking software (namely Glide, PLANTS, and Vina) and of the available SMO structures we set up a retrospective virtual screening (VS) protocol. A database, made up by known SMO antagonists and compounds with no alleged activity against the receptor was created and screened against the different SMO structures. To evaluate the performance of the ranking in VS calculations different statistical metrics (EF, AUAC and BEDROC) were employed allowing to identify the best performing VS docking protocol. Results of these studies will serve as a platform for the application of structure-based VS against the pharmaceutically relevant SMO receptor
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
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