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    Implicación del factor de transcripción Nrf2 en la expresión de mediadores inflamatorios involucrados en el desarrollo de la artritis reumatoide: efecto de una dieta antioxidante

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    [Resumen] La artritis reumatoide (AR) es una enfermedad inflamatoria crónica de carácter autoinmune que afecta aproximadamente al 1% de la población mundial. Su estrategia terapéutica se basa en fármacos dirigidos a reducir la inflamación de las articulaciones; sin embargo, debido al carácter crónico de esta enfermedad, estos tratamientos tienen importantes efectos adversos, además de un alto coste. Esto ha motivado un gran auge en el estudio del potencial terapéutico de antioxidantes naturales, como el resveratrol (RSV), como nuevas y complementarias oportunidades de tratamiento. Previamente, nuestro grupo ha demostrado que la suplementación oral de RSV podría reducir los principales signos de la patología de la AR, como son una reducción de la hiperplasia sinovial, del infiltrado inmune en la articulación y de la producción de mediadores inflamatorios, además del estrés y daño oxidativo típicos de una articulación artrítica, previniendo así la progresión de la enfermedad. Continuando con este estudio, el objetivo de este trabajo ha sido evaluar en un modelo in vivo de artritis inducida por antígeno (AIA) si el RSV es capaz de modular la expresión del factor de transcripción Nrf2, que se ha erigido como el más importante mecanismo de transcripción implicado en el incremento de la expresión de genes antioxidantes y en el mantenimiento del equilibrio redox; así como los procesos de angiogénesis y autofagia, mecanismos claves en el control de la proliferación anormal que caracteriza el tejido sinovial AR. Asimismo, mediante análisis in vitro se realizó el silenciamiento del factor de transcripción Nrf2 en sinoviocitos para valorar su implicación en el control de la respuesta inflamatoria y si el RSV ejerce el efecto protector a través de la inducción de Nrf2. Los resultados demostraron que el RSV fue capaz de activar el factor de transcripción Nrf2, y modular la expresión de marcadores autofágicos y angiogénicos. Todo ello sugiere que el RSV es capaz de modular la hiperplasia sinovial incrementando la muerte celular por autofagia, y limitando el proceso angiogénico, y apoya el uso de RSV como una nueva estrategia terapéutica en el tratamiento de la AR.[Resumo] A artrite reumatoide (AR) é una doenza inflamatoria e crónica de carácter autoinmune que afecta aproximadamente ó 1% da población mundial. A súa estratexia terapéutica basase en fármacos dirixidos a reducir a inflamación das articulacións; sin embargo, debido ó carácter crónico desta doenza, ditos tratamentos teñen importantes efectos adversos, ademais dun custo elevado. Isto ha motivado un gran auxe no estudio do potencial terapéutico de antioxidantes naturais, como o resveratrol (RSV), como novas e complementarias oportunidades de tratamento. Previamente, noso grupo ha demostrado que a suplementación oral de RSV podería reducir os principais signos da patoloxía da AR, como son una reducción da hiperplasia sinovial, do ilfiltrado inmune na articulación y da producción de mediadores inflamatorios, ademáis do estrés e daño oxidativo típicos dunha articulación artrítica, previniendo así a progresión da enfermidade. Continuando con este estudo, o obxectivo deste traballo foi avaliar nun modelo in vivo de artrite inducida por antíxeno (AIA) se o RSV é capaz de modular a expresión do factor de transcripción Nrf2, que se ha erixido como o más importante mecanismo de transcripción implicado no incremento da expresión de xenes antioxidantes e no mantemento do equilibrio redox; así coma os procesos de anxioxénese e autofaxia, mecanismos claves no control da proliferación anormal que caracteriza o texido sinovial AR. Así mesmo, mediante análise in vitro realizouse o silenciamento do factor de transcripción Nrf2 en sinoviocitos para avaliar a súa implicación no control da respuesta inflamatoria e si o RSV exerce o efecto protector a través da inducción de Nrf2. Os resultados desmostraron que o RSV foi capaz de activar o factor de transcripción Nrf2, e modular a expresión de marcadores autofáxicos e anxioxénicos. Todo isto suxire que o RSV é capaz de modular a hiperplasia sinovial incrementando a norte celular por autofaxia, e limitanto o proceso anxioxénico, e apoya o uso de RSV como unha nova estratexia terapéutica no tratamento da AR.[Abstract] Rheumatoid arthritis (RA) is an inflammatory, chronic and autoimmune joint disease that affects approximately 1% of the population. Its therapeutic strategy is based on drugs aimed at reducing inflammation of the joints; however, due to the chronic nature of this disease, these treatments have significant side effects, and a high cost. This has motivated an increase in the study of the therapeutic potential of natural antioxidants such as resveratrol (RSV), as new and complementary treatment opportunities. Previously, our group has shown that oral supplementation of RSV could reduce the main signs of the pathology of RA, such as a reduction in synovial hyperplasia, immune infiltrate in the joint and the production of inflammatory mediators, in addition to the stress and oxidative damage typical of an arthritic joint, thus preventing disease progression. Carrying on with this study, the aim of this proyect was to evaluate in an in vivo antigen-induced arthritis model (AIA) if the RSV is able to modulate the expression of the Nrf2 transcription factor, which has emerged as the most important mechanism transcription involved in the increased expression of antioxidant genes and in maintaining the redox balance; as well as angiogenesis and autophagy processes, key mechanisms in controlling abnormal proliferation that characterizes RA synovium. Furthermore, in vitro analysis by silencing Nrf2 transcription factor in synoviocytes was performed to evaluate its involvement in controlling the inflammatory response and if the RSV exerts the protective effect by inducing Nrf2. The results showed that RSV was able to activate Nrf2 transcription factor, and modulate the expression of autophagic and angiogenic markers. This suggests that RSV is able to modulate synovial hyperplasia increasing autophagic cell death, and limiting the angiogenic process, and supports the use of RSV as a new therapeutic strategy in the treatment of RA.Traballo fin de mestrado (UDC.FCS). Asistencia e investigación sanitaria. Especialidade en Fundamentos de la Investigación Biomédica. Curso 2015/2016

    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

    Differential Protein-Coding Gene Expression Profile in Patients with Prostate Cancer

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    Esta investigación fue financiada parcialmente por la Universidad de La Frontera, Proyecto GI23-0021, Universidad de La Frontera, Proyecto DI22-0007, y Universidad de La Frontera, Proyecto PDT22-0001 y ANID, Proyecto FONDECYT INI 11240623

    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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