1,721,638 research outputs found

    The function and regulation of retinoids and their receptors in hepatic stellate cells

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    The effects of the retinoid all-trans retinoic acid (RA) on HSC proliferation and expression of HSC activation markers are investigated in vitro. Despite effectively inhibiting HSC proliferation, all-trans RA had no effects on expression of the activation markers gelatinase A, pro-collagen I, tissue inhibitor of matrix metalloproteinase-1, and -2, β1-integrin and α-smooth muscle actin (α-SMA). However, other retinoids produced by HSC may modulate genes that regulate their fibrogenic and fibrolytic properties. Therefore, reverse-phase high performance liquid chromatography was used to examine retinoids produced by HSC during progressive activation. It was demonstrated that, although retinyl palmitate decreased with activation, HSC generated all-trans RA and other retinoic acid derivatives, including 13-cis RA. Retinoids mediate their responses via nuclear retinoid receptors. However, little is known about expression of these receptors in HSC. As different retinoid receptors control different functions, the phenotypic response of HSC to retinoids may change during transformation due to different or altered levels of expression of these receptors. The expression of one of these receptors, retinoic acid receptor beta (RARβ), was therefore examined during the transformation of HSC from a quiescent to an activated phenotype. Whilst RARβ mRNA was consistently detected by northern hybridisation in freshly isolated HSC, expression dropped rapidly during HSC activation such that the mRNA became undetectable over 2-12 days of culture activation. In contrast, western blotting data showed that synthesis of RARβ protein actually increased during this time.The potential role of RARβ in regulating growth and differentiation of HSC was examined using a RARβ selective antagonist. This antagonist was found to decrease HSC proliferation and expression of α-SMA. This suggests RARβ may be one of the major factors responsible for the progression of HSC activation and a potential, novel HSC directed therapeutic target for liver fibrosis.</p

    Imaging LexA degradation in cells explains regulatory mechanisms and heterogeneity of the SOS response

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    Data associated with publication "Imaging LexA degradation in cells explains regulatory mechanisms and heterogeneity of the SOS response" by E.C. Jones and S. Uphof

    Student Transition, Sense of Belonging and Habitus

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    This chapter focuses upon students’ experiences of law school during a period of online remote learning necessitated by COVID-19. It considers the results of a survey conducted at the University of Sheffield School of Law which explored students’ sense of belonging, engagement and self-confidence. The chapter uses Bourdieu’s concepts of field and habitus to theorise these results. It argues that the disruption to the habitus caused by the global pandemic provides opportunities to develop new understandings and challenge potentially harmful norms that existed in the habitus of the pre-pandemic law school. This allows for a longer-term, sustainable transition to a post-pandemic law school that engages with belonging and associated concepts in a way which enhances law student wellbeing

    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
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