352 resultados para BH3-mimetic
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Nas três narrativas que constituem The New York Trilogy – City of Glass, Ghosts e The Locked Room – Paul Auster emprega e desconstrói os elementos convencionais do romance policial, elaborando uma investigação recorrente da natureza, função e significado da linguagem, mas também da solidão, do encerramento e da problemática da identidade. A produção narrativa de Auster evoca fantasmas logocêntricos tradicionais (como a presença, a realidade e a verdade), que fazem eco do princípio de indissolubilidade entre palavra e significado, apenas para lograr esta identidade através de uma orientação textual para a marcação da ficcionalidade e consequente reforço dos efeitos de significação ilusórios. Auster altera os mecanismos logrando as expectativas do leitor em relação ao epílogo e à transparência textual, que um pacto mimético faria pressupor. O espaço vazio resultante confere ao texto uma liberdade plurissignificativa que dispersa todas as certezas e veicula o poder da criação do caos. Sob a aparência de fluência narrativa, a escrita de Paul Auster esconde uma subversão das premissas básicas da literatura realista e dos signos referenciais, numa poética auto-reflexiva ficcionalizada sobre a estruturação de universos imaginários.
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International audience
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La reconnaissance d’un antigène présenté par les cellules présentatrices d’antigène induit la prolifération et la différenciation des lymphocytes T naïfs en lymphocytes T effecteurs et mémoires. Cette reconnaissance se fait par l’interaction du récepteur des cellules T (TCR) des lymphocytes T et le complexe CMH-peptide présent à la surface des DC. Cependant, des signaux additionnels sont requis, une meilleure activation des lymphocytes T implique des corécepteurs présents à la surface de ces deux types cellulaires. Après l’élimination de l’antigène, la plupart des lymphocytes T effecteurs vont mourir. Une petite population de lymphocytes T va persister pour se différencier en lymphocytes T mémoires capables de protéger l’organisme contre une réinfection. Les signaux qui contrôlent le maintien des lymphocytes T mémoires sont encore mal compris. Pour comprendre le rôle de la molécule de costimulation 4-1BB dans le maintien des lymphocytes T CD8 mémoires, nous avons émis l’hypothèse que l’état de phosphorylation de la protéine adaptatrice TRAF1, qui se lie à 4-1BB, module le maintien des lymphocytes T CD8 mémoires. Ainsi, nous avons montré par des expériences de spectrométrie de masse que TRAF1 s’associe préférentiellement à TBK1 lorsqu’elle n’est pas phosphorylée. Nous avons aussi montré que la présence de TRAF1 est requise pour stabiliser TBK1 au récepteur 4-1BB après stimulation des lymphocytes T. Par ailleurs, les lymphocytes T CD8 OT-I TRAF1-/- reconstituées avec un mutant phospho-déficient de TRAF1 (S139A) et ensuite différenciées en lymphocytes T mémoires in vitro induisent une activation de la voie de signalisation NF-ĸB contrairement à ceux exprimant la forme phospho-mimétique de TRAF1 (S139D). Ces premières études démontrent l’importance de l’état de phosphorylation de TRAF1 en aval de 4-1BB dans les cellules T. Dans la seconde partie, nous avons évalué le rôle d’un autre corécepteur; la neuropiline 1, dans la maturation des DC. A cet effet, nous avons émis l’hypothèse que l’interaction de la neuropiline 1 et ses ligands contribuerait à la fonction des DC. Nous avons démontré que l’absence de la neuropiline 1 n’a pas d’effet sur la maturation au LPS des DC. Cependant, la présence du VEGF (un ligand de Nrp-1) inhibe la maturation des DC dérivées de la moelle osseuse. Notre étude a démontré que VEGF inhibe l’expression des molécules de costimulation, la sécrétion des cytokines pro inflammatoires et la signalisation TLR4 principalement les voies MAP Kinase et NF-ĸB. Contrairement aux résultats avec les cellules WT, VEGF n’est pas capable d’affecter la maturation, la sécrétion des cytokines et la signalisation TLR4 des DC Nrp1-Lyz où la neuropiline 1 est délétée. Ainsi, nos résultats ont démontré que VEGF inhibe la maturation des DC de façon Nrp1-dépendante. Enfin, l’analyse des molécules partenaires de la neuropiline 1 montre que Nrp1, VEGF et TLR4 se retrouvent dans le même complexe. Nos résultats démontrent que VEGF, en présence de la neuropiline 1 est capable d’interagir avec TLR4 pour inhiber la maturation des DC. Toutefois, en absence de la neuropiline1, VEGF n’est pas capable de recruter TLR4 pour réduire l’expression des molécules de costimulation. Ces études sur les corécepteurs pourraient être importantes dans l’élaboration de nouvelles approches vaccinales.
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This is a study concerning in the structure of non governmental organizations, based on the institutional theory. It aims to understand the relation among structure, social projects and environmental influences, analyzing if there is coherence with project social or expresses adaptation to the institutional pressures of the environment. It introduces as theoretical support for the themes, studies about institutional theory and social structure. The research is descriptive and exploratory; it also applies to a study of case, based on the technical procedures. From the research universe, that was compound by non governmental organizations from Natal, RN, Brasil, it was chosen the Casa Renascer, a non governmental organization that works with the combat to the violence and sexual exploration of children and teenagers. The data collection process employed includes documental research, observations and semi structured research devices, guided by the organizational process proposed by Serva (1996) and by the institutional theory. The collected data were qualitatively treated. The analysis was divided into three parts, following the research matters. The social project characterization demonstrated that the organization went by three main phases. The first one, characterized by focus in women and girls education and health; the second shows the emphasis on girls in social risk situation, with preventive approach; and the last one, characterized by victims assistance of violence and sexual exploration. From the analysis using the institutional theory mechanisms, the results showed that exists coherence between structure and environmental influences, but a weak coherence between structure and social projects. It indicates as main determinant of the structure, an aspect forgotten by the institutional theory, the power. It was observed the presence from normative, coercive and mimetic mechanisms, highlighting normative influences
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There is controversy regarding the description of the different regions of the face of the superficial musculoaponeurotic system (SMAS) and its relationship with the superficial mimetic muscles. The purpose of this study is to analyze the development of the platysma muscle and the SMAS in human specimens at 8–17 weeks of development using an optical microscope. Furthermore, we propose to study the relationship of the anlage of the SMAS and the neighbouring superficial mimetic muscles. The facial musculature derives from the mesenchyme of the second arch and migrates towards the different regions of the face while forming premuscular laminae. During the 8th week of development, the cervical, infraorbital, mandibular, and temporal laminae are observed to be on the same plane. The platysma muscle derives from the cervical lamina and its mandibular extension enclosing the lower part of the parotid region and the cheek, while the SMAS derives from the upper region. During the period of development analyzed in this study, we have observed no continuity between the anlage of the SMAS and that of the superficial layer of the temporal fascia and the zygomaticus major muscle. Nor have we observed any structure similar to the SMAS in the labial region.
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The overall objective of this thesis was to study the effects of regular and high (super-) doses of phytase in the gut of broilers, with the aim of documenting the mechanism of their action leading to improvements in animal health. Phytase is often supplemented to commercial broiler diets to facilitate the hydrolysis of plant phytate and release of phosphorus for utilisation. Although not the original intention of its addition, phytase supplementation leads to improvements in growth performance parameters and enhanced nutrient utilisation. Further benefits have also been observed following the addition of super-doses of phytase which are not explained by an increase in phosphorus release, and thus have been termed ‘extra-phosphoric effects’. Using diets formulated to be adequate or marginally deficient in available phosphorus (aP; forming the negative control, NC), phytase was supplemented at 1,500 and 3,000 FTU/kg phytase in the first study (both super-doses) and the partitioning of nutrients within the body was investigated. It appeared that there were some metabolic changes between 1,500 and 3,000 FTU/kg, switching between protein and fat accretion, potentially as a consequence of nutrient availability, although these changes were not reflected by changes in growth performance parameters. However, the loss of the NC treatment without phytase on day 12 limits the comparison of the phytase within the NC treatment, but does allow for comparison of each dose at adequate or low dietary aP levels. As expected, a greater degree of phytate hydrolysis was achieved with 3,000 than with 1,500 FTU/kg phytase, but changes in carcass accretion characteristics were greater with 1,500 than 3,000 FTU/kg. Using these findings and the observation that there were no further changes in the parameters measured by increasing phytase from 1,500 to 3,000 FTU/kg (aside from phytate hydrolysis), 1,500 FTU/kg phytase was selected as the super-dose to be used in subsequent studies. The next study considered the influence of regular (500 FTU/kg) and super doses (1,500 FTU/kg) of phytase from within the gut. Overall, it was observed that changes were occurring to the gut environment, which ultimately would influence the absorptive capacity and conditions for further phytate hydrolysis. Dietary treatment influenced gut conditions such as pH, intestinal morphology and bacterial populations which can subsequently influence nutrient utilisation and potential for growth. The subsequent study was designed to investigate the effects within the gut in more detail. The release of nutrients from phytate hydrolysis and their bioavailability within the digesta can influence conditions within intestine, facilitating enhanced absorption. One of the parameters investigated was the expression of genes involved in the transport of nutrients in the intestine. Overall, there were few significant dietary treatment influences on gene expression in the intestine, however there was a dose-dependent response of phytase on the expression of the jejunual divalent mineral transporter. This indicates a change in divalent mineral bioavailability in the intestine, with correlations with inositol phosphate esters (IPs) being identified. This is likely explained by the IPs produced by phytase hydrolysis and accumulating in the digesta, differing between regular and high doses of phytase. It became apparent that interactions between the products of phytate hydrolysis (IP3, IP4) and minerals in the digesta had the potential to influence the gut environment and subsequent nutrient bioavailability and overall phytase action. The final study was designed to increase the content of the IPs, and investigate the influence of phytase under these conditions. As the complete hydrolysis of phytate to myo-inositol has been reported to be beneficial due to its proposed insulin mimetic effects, myo-inositol was also supplemented to one of the diets to see if any further benefits would be observed when supplemented alongside super-doses of phytase. Neither increased concentrations of the higher IP esters (IP6, IP5 and IP4) nor myo-inositol (myo-) had any effect on broiler growth performance, however there were still apparent beneficial influences of phytase supplementation. The results suggest considerable and important interactions between minerals and IP esters within the digesta, which ultimately have the potential to influence gut conditions and thus nutrient utilisation and growth performance. Reduced concentrations of blood glucose in the high IP ester diet with additional phytase supplementation suggest some insulin-like effects of myo- production. Additionally, the lack of effect of myo- supplementation on blood glucose and insulin concentrations suggests a difference between the structure of phytase-produced myo- and supplemented myo-. Although there were no improvements in growth performance by increasing phytase from 500 to 1,500 FTU/kg, there were changes occurring at the level of the gut and expression of genes in the intestine, influencing nutrient utilisation and the partitioning of nutrients within the body. There are many factors to be considered when supplementing phytase, with dietary nutrient content and nutrient release and IP production during phytate hydrolysis having an influence on phytase action, nutrient absorption and conditions within the gut. Super-doses of phytase may be beneficial for maintaining optimal gut conditions, clearing IP esters from the digesta, reducing their potential to form complexes with minerals and other nutrients, ultimately influencing the efficiency of production.
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The research presented in this paper aims to analyze the representation in the Jesus’ parable The Good Samaritan, specifically, their persons, questioning the character “amimético”/mimetic that narrative category. With brief descriptions of the person of Sophocles' tragedy - Oedipus, the survey highlights the main features of the narratives Greek and Judeo-Christian, to submit their respective characters based on assumptions about mimesis and metaphor. The study indicates an eminently bibliographic research, based on the poetics of Aristotle (1973), assumptions about mimesis, metaphor and parable, studies guided by Costa (1992), Le Guern (1976), Lockyer (2006), Lopes (1987), Sant'anna (2010) and Spina (1967). The survey allowed the perception of speech introduced by literary art, through the representation, so that the parable study demonstrates that the author used a narrative language appropriate to his interlocutors, with daily themes, and therefore constructed a strategy to achieve their educational goals. This art of narrating stories also indicates knowledge moral, philosophical or religious, but this is, in general, unveiled by the representation of social types. In the parable analyzed, the character “metaphored” the moral sense that the narrator pointed, confronting concepts that your listener defended, showing him his "mistake" in the interpretation of Jewish Moral Law.