1,354,935 research outputs found
K(ATP) channel gene expression is induced by urocortin and mediates its cardioprotective effect
No full textBackground— Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion.
Methods and Results— We have analyzed global changes in gene expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific KATP channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia.
Conclusions— This is, to our knowledge, the first report of the altered expression of a KATP channel subunit induced by a cardioprotective agent and demonstrates that KATP channel opening is essential for the effect of this novel cardioprotective agent
Retracted. ERK and the F-box protein betaTRCP target STAT1 for degradation
No full textThis article has been withdrawn by Paul A. Townsend, Richard A. Knight, Sean P. Barry, David S. Latchman, and Anastasis Stephanou. An investigation at University College London determined that a duplicated blot in Fig. 1, A and B, the GAPDH blot is the same, flipped horizontally. The withdrawing authors sincerely apologize to the scientific community for any confusion or adverse consequences resulting from the publication of the article. Original Abstract:The transcription factor STAT1 has roles in development, homeostasis, cellular differentiation, and apoptosis and has been postulated to function as a tumor suppressor. STAT1 is activated by tyrosine or serine phosphorylation in response to specific cytokines or following a variety of stress-induced stimuli. STAT1 activity is carefully regulated to prevent sustained STAT1-mediated transcription, although the molecular mechanisms involved in the modulation of STAT1 stability are poorly understood. Here we show that activated STAT1 is degraded at the proteasome by a mechanism involving the F-box E3 ligase, SCF(betaTRCP). Active p42/p44 MAPK-ERK phosphorylates STAT1 on serine 727 and targets it for proteasomal degradation. SCF(betaTRCP) binds wild-type STAT1 but not the nonphosphorylatable mutant STAT1(S727A). Moreover, silencing betaTRCP expression or pharmacological inhibition of ERK activity stabilized STAT1 expression. These data suggest that constitutively active ERK may inappropriately degrade STAT1, with loss of its pro-apoptotic and tumor suppressor functions
Brevi periodi di ischemia inducono attivazione caspasica senza condurre a frammentazione del DNA: un'ipotetica soglia ischemica per "l'angina simulata"?
No full textReform of the EU Merger Regulation: Looking Out for the Minority
No full textMinority shareholdings are a common occurrence and, while the vast majority are wholly unproblematic, Ryanair illustrates how different jurisdictional tests can lead to unsatisfactory outcomes. Christian Riis-Madsen, Sophia Stephanou, & Killian Kehoe (O’Melveny & Myers)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Imagens pintadas de Flávio Scholles : evocadores de memórias e narrativas de vida
No full textO estudo concebe as imagens como privilegiados canais de fluxo das memórias, elas mesmas tomadas como narrativas de memórias. Examina as complexas relações entre memória e imagem. Detém-se na análise dessas relações a partir das obras de pintura do artista gaúcho Flávio Scholles, que desde 1976 desenvolve um trabalho artístico de cunho biográfico, podendo ser considerado um guardião de memórias. Discute o significado de suas imagens como disparadoras do exercício de rememorar e a dimensão educativa das mesmas, problematiza em que medida essas pinturas possuem um potencial evocador de memórias individuais e coletivas de sujeitos da região do Vale dos Sinos, RS. Resulta do contato de algumas pessoas com um corpus restrito de imagens produzidas pelo artista, algumas conhecedoras de suas obras, outras tendo o primeiro contato com as mesmas por ocasião da investigação. A pesquisa realizou seis entrevistas e um grupo de conversação envolvendo ao todo 17 sujeitos residentes em vários municípios da Região. As narrativas orais de memórias foram transformadas em documentos e integram o corpus empírico da pesquisa, cujo estudo apóia-se nos referenciais que tematizam os conceitos de imagem e memória. Analisa de que forma os sujeitos se reconheceram nas imagens do artista com as quais se depararam e que conteúdos foram manifestos em suas narrativas a partir desse contato. Para a análise, faz-se acompanhar das reflexões propostas por vários autores, dentre eles Ecléa Bosi, Antoinette Errante, Alberto Manguel, Sandra Jatahy Pesavento, Maria Stephanou e Maria Helena Bastos, entre outros. A estratégia metodológica contempla, além das entrevistas e grupo, a localização e pesquisa junto a documentos escritos, além de conversas com o autor-pintor. A investigação empreendida junto aos sujeitos, que deram voz e vez às suas reminiscências, resultou na organização e análise dos conteúdos produzidos no exercício de rememorar, sendo distribuídos em cinco temas: Trabalho, Família, Educação, Atividades Sociais, Lugares. A compreensão da dimensão educativa das imagens para evocação de memórias individuais e coletivas assenta-se no fato de que as imagens não possuem sentido em si mesmas, mas necessitam de um interlocutor que as decifre, e a partir disso re-signifique a sua própria história de vida. As obras selecionadas no estudo expressam vivências do artista, mas também apresentam conquistas e dilemas do seu grupo de pertencimento, marcados pela defesa da cultura teuto-brasileira na Região do Vale dos Sinos. As obras são plenas de narrativas de infância e juventude, assentadas num contexto histórico, geográfico, social e cultural, ao qual pertencem também os sujeitos narradores, e que por esta proximidade suscitaram muitas identificações, conduzindo-os a refletirem sobre suas próprias vidas, o tempo vivido e o presente que se constrói a partir de tempos idos. Os narradores sensibilizaram-se com cenas, figuras, objetos, e temáticas apresentadas nas pinturas, muitas das quais semelhantes ao universo de coisas e experiências que os cercaram desde a mais tenra idade, que não eram muitas, todavia especiais.On the present study images are conceived as relevant memory flowing channels and seen as memory narratives. It examines the complex relation between the memory and the image. Their analyses is made on the work of the gaucho artist Flávio Scholles, who since 1976 develops an artistic and biographic work, and who deserves to be called a memories guardian. This study questions the meaning of his images as triggers of the remembering exercise, and the educational relation of them. It points out in what measure these pictures have an evocative memorial potential by individuals and collectives on Vale dos Sinos, RS. It shows the contact of a group of people with a restricted corpus of images produced by the artist, some of them knew his art well but others were having the first contact with it. Six interviews and a conversation group with 17 people living in several cities from this region took place during the survey. The oral narratives of their memories became documents and are now part of the empirical corpus of the survey. Its study finds support on the references from the concepts of image and memory. It analyses in which way the subjects recognize themselves on the artist’s images that they had seen and which contend was manifested in their narratives due to this contact. For the analyses were taken in account the ideas proposed by several authors like Ecléa Bosi, Antoinette Errante, Alberto Manguel, Sandra Jatahy Pesavento, Maria Stephanou and Maria Helena Bastos, among others. The methodological strategy used, besides the interviews and group meetings, was the research of written documents, as well as talks with the author-painter. The investigative work with the subjects, resulted on the organization and analyses of the contents produced on the remembering exercise. Those were classified in 5 themes: work, family, education, social activities and places. The comprehension of the educative dimension of the images, evoking the individual and collective memories, lays on the fact that they don’t have a sense by themselves but they need an interlocutor to decode them , and this way finding a new meaning for his/her life story. The masterpieces selected on this study express the artists’ experiences, but also show achievements and dilemmas from his belonging group, known for fighting for the german/brazilian culture on the Vale dos Sinos region. The works are full of childhood and youth narratives placed on an historic, geographic, social and cultural context where the narrator subjects belong to. That’s why many of them identified themselves and had reflections about their own lives, the time lived and the present being built over the past. The narrators felt moved by scenes, figures, objects and themes presented on pictures, many of them similar to the universe they were surrounded by on their early age
BAG-1: a multi-functional pro-survival molecule
No full textBAG-1 is a multi-functional protein that exists as three functionally distinct and differentially localized isoforms which originate from a single mRNA and interact with a wide range of cellular targets. These include heat shock proteins, nuclear hormone receptors, signalling molecules, the anti-apoptotic BCL-2 protein and components of the ubiquitylation/proteasome machinery. Overexpression of BAG-1 isoforms has been demonstrated to regulate apoptosis, proliferation, transcription, metastasis and cell motility in a wide variety of cell systems. Since BAG-1 has a role in many biological pathways there is increasing evidence supporting the view that BAG-1 is an important molecule in disease, for example, potentially modulating both cell survival and response to nuclear hormones in breast cancer, and BAG-1 is a potential molecular target for therapeutic intervention
Variations on the Author
No full text“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
No full textWe 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
The protective effect of moderate hypothermia during intestinal ischemia-reperfusion is associated with modification of hepatic transcription factor activation
No full textBackground/purpose: Moderate hypothermia throughout intestinal ischemia-reperfusion (IIR) injury reduces multiple organ dysfunction. Heat shock proteins (HSPs) have been shown to be protective against ischemia-reperfusion injury, and STAT (Signal Transducers and Activators of Transcription) proteins are pivotal determinants of the cellular response to reperfusion injury. The aim of this study is to investigate the mechanism of hypothermic protection during IIR.Methods: Adult rats underwent intestinal ischemia-reperfusion (IIR), 60-minute ischemia and 60-minute reperfusion, or sham (120 minutes) at either normothermia or moderate hypothermia. Four groups of animals were studied: (1) normothermic sham (NS), (2) normothermic IIR (NIIR), (3) hypothermic sham (HS), and (4) hypothermic IIR (HIIR). Western blotting measured heat shock protein expression, phosphorylated (p-) and total (T-) hepatic STAT-1 and STAT-3.Results: There were no differences in expression of HSPs 27, 47, 60, i70, c70, or 90 between any of the experimental groups. NIIR caused a significant increase in p-STAT-1 compared with normothermic sham (P < .05) and a highly significant increase in p-STAT-3 (P < .001), both these increases were completely abolished by moderate hypothermia (P < .01 v NIIR.)Conclusions: The protective effect of moderate hypothermia on liver is not mediated by HSP expression at this time-point. Hypothermia may act by decreasing hepatic STAT activation, supporting the potential therapeutic role of moderate hypothermia. Modulation of STAT activation may also provide novel therapeutic targets
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