1,720,958 research outputs found

    Relationship between Vitamin B6, DNA damage and diabetes

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    The active form of vitamin B6, the pyridoxal-5’ phosphate (PLP) is a cofactor for more than 150 reactions involved in protein, carbohydrate and lipid metabolism. In addition, it is able to counteract Reactive Oxygen Species (ROS) and Advanced Glycation End products (AGEs). In eucaryotes PLP is produced, in the salvage pathway, by the concerted action of pyridoxal kinase (PDXK) and pyridoxamine/pyridoxine oxidase (PNPO) which recycle PLP precursor from food. PLP has been associated to different pathologies including diabetes and cancer although underlying mechanisms remain in large part still unknown. It has been previously demonstrated that mutations in Drosophila Pdxkgene (dPdxk1) cause diabetes and chromosome aberrations (CABs) and also that these phenotypes are linked by a causeeffect relationship. The first aim of this thesis has been to verify whether also the inactivation of the other gene of the salvage pathway, PNPO, encoded by sgll gene, produced the same phenotypes observed in dPdxk1 mutants. To this purpose we silenced sgll gene by RNA interference and characterized the resulting phenotypes. This analysis revealed a significant frequency of CABs and diabetic phenotypes such as hyperglycemia, small body size, impaired lipid storage and accumulation of AGEs associated to Sgll depletion. These results allowed us to confirm the hypothesis that PLP deficiency produces CABs through the genotoxic effect of AGEs in turn triggered by high glucose. Our second aim has been to investigate whether human PDXK variants present in the population can impact on DNA integrity and can be considered predictive of cancer risk. For this purpose, we expressed four human PDXK variants (carrying missense mutations) into dPdxk1 mutant flies and tested them for CABs as well as for diabetic phenotypes, finding that none of them was able to completely rescue the CAB phenotype, hyperglycemia nor AGE accumulation. Biochemical analysis of these variants revealed a compromised catalytic activity and/or a reduced affinity for their substrates, which explained their “loss of function” behaviour. These results suggested that mutations in PDXK human gene can impact on genome integrity via AGEs and predispose to cancer. Our third purpose was to test whether low PLP levels can impact on cancer in Drosophila. Thus we tested the effects of the PLP inhibitor 4-deoxypyridoxine (4-DP) on Ras and Ras/Scr cancer models generated by mosaic analysis with repressible marker (MARCM) strategy. This analysis showed that 4-DP caused enlargement of primary tumors as well as appearance of secondary tumors in both cancer models. Taken together all the results collected in this work have contributed to confirm and elucidate the relationship between vitamin B6 diabetes and cancer

    Allergic contact dermatitis to topical steroids

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    The diagnosis of allergic contact dermatitis to topical corticosteroids is often difficult owing to the overlapping between the clinical features of allergic contact dermatitis and many dermatoses. Allergic contact dermatitis can be suspected when a dermatosis duly treated with topical corticosteroids fails to improve or even worsens. In a series of 6,285 patients tested from January 1997 to May 2001, according to the SIDAPA (former GIRD-CA) standard series, supplemented with tixocortole pevalate, budesonide and hydrocortisone 17-butyrrate, 65 (1.03%) showed sensitization to one or more topical corticosteroids. These data underline the importance of introducing molecules, which are "markers" of sensitization to topical corticosteroids, in patch test standard series. Patients suffering from allergic contact dermatitis to topical corticosteroids can be treated with low-sensitizing corticosteroids such as betametasone and other compounds classified in the "C" Coopman class

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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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