63 resultados para 12079
Resumo:
UANL
Resumo:
Les récepteurs nucléaires (RN) sont des facteurs de transcription ligand dépendants qui contrôlent une grande variété de processus biologiques de la physiologie humaine, ce qui a fait d'eux des cibles pharmacologiques privilégiées pour de nombreuses maladies. L'un de ces récepteurs, le récepteur de l’œstrogène alpha (ERα), peut activer la prolifération cellulaire dans certaines sections de l'épithélium mammaire tandis qu’un autre, le récepteur de l'acide rétinoïque alpha (RARα), peut provoquer un arrêt de la croissance et la différenciation cellulaire. La signalisation de ces deux récepteurs peut être altérée dans le cancer du sein, contribuant à la tumorigénèse mammaire. L’activité d’ERα peut être bloquée par les anti-oestrogènes (AE) pour inhiber la prolifération des cellules tumorales mammaires. Par contre, l’activation des voies de RARα avec des rétinoïdes dans un contexte clinique a rencontré peu de succès. Ceci pourrait résulter du manque de spécificité des ligands testés pour RARα et/ou de leur activité seulement dans certains sous-types de tumeurs mammaires. Puisque les récepteurs nucléaires forment des homo- et hétéro-dimères, nous avons cherché à développer de nouveaux essais pharmacologiques pour étudier l'activité de complexes dimériques spécifiques, leur dynamique d’association et la structure quaternaire des récepteurs des œstrogènes. Nous décrivons ici une nouvelle technique FRET, surnommée BRET avec renforcement de fluorescence par transferts combinés (BRETFect), qui permet de détecter la formation de complexes de récepteurs nucléaires ternaires. Le BRETFect peut suivre l'activation des hétérodimères ERα-ERβ et met en évidence un mécanisme allostérique d'activation que chaque récepteur exerce sur son partenaire de dimérisation. L'utilisation de BRETFect en combinaison avec le PCA nous a permis d'observer la formation de multimères d’ERα fonctionnels dans des cellules vivantes pour la première fois. La formation de multimères est favorisée par les AE induisant la dégradation du récepteur des oestrogènes, ce qui pourrait contribuer à leurs propriétés spécifiques. Ces essais de BRET apportent une nette amélioration par rapport aux tests de vecteurs rapporteur luciférase classique, en fournissant des informations spécifiques aux récepteurs en temps réel sans aucune interférence par d'autres processus tels que la transcription et de la traduction. L'utilisation de ces tests nous a permis de caractériser les propriétés de modulation de l’activité des récepteurs nucléaires d’une nouvelle classe de molécules hybrides qui peuvent à la fois lier ERa ou RAR et inhiber les HDACs, conduisant au développement de nouvelles molécules prometteuses bifonctionnelles telles que la molécule hybride RAR-agoniste/HDACi TTNN-HA.
Resumo:
Resumen de las autoras
Resumo:
O presente trabalho busca analisar as mudanças econômicas e de perfil produtivo ocorridas em Santo André, município integrante da Região Metropolitana de São Paulo (RMSP), com transformações em seu perfil eminentemente industrial para o incremento do setor de serviços, parcialmente decorrente dos processos de desconcentração industrial vividos em maior escala no país. Partindo-se da formação histórico-econômica local e da identificação de fenômenos globais, como a reestruturação produtiva vivida na indústria, a pesquisa procurou observar os impactos particulares desta reorganização econômica em Santo André, cujo índices apontam para maior retração industrial em comparação com outros municípios da RMSP, no período analisado que compreende os anos de 1990 a 2010. Além disso, o trabalho analisa a particular situação arrecadatória do município, tendo em vista a queda relativa de um de seus principais impostos - o ICMS – apontando questões no que se refere à gestão tributária e otimização dos recursos disponíveis no orçamento municipal. Por fim, diante da situação problema apresentada, a saber, a fragilidade financeira do poder público em contexto de perda de relevância econômica em Santo André, a pesquisa apresenta um quadro de sugestões relativas a diferentes instâncias estratégicas e estruturais, que visam à dinamização e incremento das finanças e desenvolvimento econômico andreenses. A metodologia utilizada para a construção do trabalho contou não apenas com o acesso a textos e análises de especialistas, relativos aos temas indicados, como entrevistas com diversos atores municipais e regionais, entre os quais incluem-se representantes do poder público municipal, lideranças locais de entidades públicas e privadas e pesquisadores acadêmicos.
Resumo:
The central interest of this thesis is to comprehend how the public action impels the formation and transformation of the tourist destinies. The research was based on the premise that the public actions are the result of the mediation process of state and non-state actors considered important in a section, which interact aiming for prevailing their interests and world visions above the others. The case of Porto de Galinhas beach, in Pernambuco, locus of the investigation of this thesis, allowed the analysis of a multiplicity of actors on the formation and implementation of local actions toward the development of the tourism between the years 1970 and 2010, as well as permitted the comprehension of the construction of the referential on the interventions made. This thesis, of a qualitative nature, has as theoretical support the cognitive approach of analysis of the public policies developed in France, and it has as main exponents the authors Bruno Jobert and Pierre Muller. This choice was made by the emphasis on the cognitive and normative factors of the politics, which aspects are not very explored in the studies of public policies in Brazil. As the source of the data collection, documental, bibliographic and field researches were utilized to the (re)constitution of the formation and transformation in the site concerned. The analysis techniques applied were the content and the documental analysis. To trace the public action referential, it started by the characterization of the touristic section frontiers and the creation of images by the main international body: the World Tourism Organization, of which analysis of the minutes of the meetings underscored guidelines to the member countries, including Brazil, which compounds the global-sectorial reference of the section. As from the analysis of the evolution of the tourism in the country, was identified that public policies in Brazil passed by transformations in their organization over the years, indicating changes in the referential that guided the interventions. These guidelines and transformations were identified in the construction of the tourist destination of Porto de Galinhas, of which data was systematized and presented in four historical periods, in which were discussed the values, the standard, the algorithms, the images and the important mediators. It has been revealed that the State worked in different roles in the decades analyzed in local tourism. From the 1990s, however, new actors were inserted in the formulation and implementation of policies developed, especially for local hotelkeepers. These, through their association, establishes a leadership relation in the local touristic section, thereby, they could set their hegemony and spread their own interest. The leadership acquired by a group of actors, in the case of Porto de Galinhas, does not mean that trade within the industry were neutralized, but that there is a cognitive framework that confronts the actors involved. In spite of the advances achieved by the work of the mediators in the last decades, that resulted in an amplification and diversification of the activity in the area, as well as the consolidation at the beach, as a tourist destiny of national standout, the position of the place is instable, concerned to the competitiveness, once that there is an situation of social and environmental unsustainability
Resumo:
OBJECTIVE: To assess structural and functional cardiac changes in asymptomatic pregnant women with chronic arterial hypertension (CAH). METHODS: One hundred pregnant women with CAH underwent conventional Doppler echocardiography. The Student t test was used to compare them with 29 normotensive pregnant women (NT) in their third gestational trimester. RESULTS: Systolic (SBP; mmHg) and diastolic (DBP; mmHg) blood pressure values were higher (p<0.001) in the CAH pregnant women (SBP: 139±19 and DBP: 92± 18) as compared with those of the NT group (SBP: 112±10 and DBP: 74±9). A significant enlargement of the left atrium (4.10±0.48 cm vs 3.6±0.3 cm; p<0.001) and of the left ventricular normalized mass (59.6±19.7 g/cm2,7 vs 41.9±3.4 g/cm2,7; p<0.001) was observed. Cardiac output (CO, L/min) and systolic volume (SV, mL) were significantly higher in the CAH group (CO: 6.0±1.54 vs 4.9±2.1, p<0.01; SV: 77.3±19.8 vs 56.5±25.8, p<0.001). CONCLUSION: Chronic hypertensive pregnant women have structural and functional cardiac changes that justify routine cardiologic assessment, even in the absence of cardiopulmonary symptoms.
Resumo:
Incluye Bibliografía
Resumo:
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Resumo:
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Resumo:
Obiettivo della tesi è stato quello di studiare il ruolo svolto dall’ipotalamo laterale (LH) nella regolazione dei processi di integrazione dell’attività autonomica e termoregolatoria con quella degli stati di veglia e sonno. A questo scopo, l’attività dell’LH è stata inibita per 6 ore (Esperimento A) mediante microiniezioni locali dell’agonista GABAA muscimolo nel ratto libero di muoversi, nel quale sono stati monitorati in continuo l’elelttroencefalogramma, l’elettromiogramma nucale, la pressione arteriosa (PA) e la temperatura ipotalamica (Thy) e cutanea. Gli animali sono stati studiati a temperatura ambientale (Ta) di 24°C e 10°C. I risultati hanno mostrato che l’inibizione acuta dell’LH riduce l’attività di veglia e sopprime la comparsa del sonno REM. Ciò avviene attraverso l’induzione di uno stato di sonno NREM caratterizzato da ipersincronizzazione corticale, con scomparsa degli stati transizionali al sonno REM. Quando l’animale è esposto a bassa Ta, tali alterazioni si associano a un ampio calo della Thy, che viene compensato da meccanismi vicarianti solo dopo un paio d’ore dall’iniezione. Sulla base di tali risultati, si è proceduto ad un ulteriore studio (Esperimento B) volto ad indagare il ruolo del neuropeptide ipocretina (prodotto in modo esclusivo a livello dell’LH) nei processi termoregolatori, mediante microiniezioni del medesimo nel bulbo rostrale ventromediale (RVMM), stazione cruciale della rete nervosa preposta all’attivazione dei processi termogenetici. La somministrazione di ipocretina è stata in grado di attivare la termogenesi e di potenziare la comparsa della veglia, con concomitante lieve incremento della PA e della frequenza cardiaca, quando effettuata alle Ta di 24°C o di 10°C, ma non alla Ta di 32°C. In conclusione, i risultati indicano che l’LH svolge un ruolo cruciale nella promozione degli stati di veglia e di sonno REM e, per tramite dell’ipocretina, interviene in modo coplesso a livello del RVMM nella regolazione dei processi di coordinamento dell'attività di veglia con quella termoregolatoria.
Resumo:
Chlamydophila (C.) abortus is the most common infectious abortigenic agent in small domestic ruminants in Switzerland. In contrast, the knowledge about chlamydiae in wild ruminants is scarce. As interactions between livestock and Alpine ibex (Capra i. ibex) occur on alpine pastures, the question raises if wild ruminants could play a role as carriers of chlamydiae. Thus, we investigated the prevalence of chlamydiae in Alpine ibex in Switzerland. In total, 624 sera, 676 eye swabs, 84 organ samples and 51 faecal samples from 664 ibex were investigated. Serum samples were tested by two commercial ELISA kits specific for C. abortus. Eye swabs, organs and faecal samples were examined by a Chlamydiaceae-specific real-time polymerase chain reaction (PCR). Positive cases were further investigated by the ArrayTube (AT) microarray method for chlamydial species determination. Of 624 serum samples investigated, 612 animals were negative, whereas nine sera (1.5%) reacted positively in one of the two tests and three sera showed an inconclusive result. Eye swabs of seven out of 412 ibex (1.7%) were tested positive for Chlamydiaceae by real-time PCR. By AT microarray, Chlamydophila (C.) pecorum was identified in two animals, Chlamydophila (C.) pneumoniae was detected in one animal and a mixed infection with C. abortus and C. pecorum was found in four animals. Organs and faecal samples were all negative by real-time PCR analysis. In summary, we conclude that C. abortus is not a common infectious agent in the Swiss ibex population. To our knowledge, this is the first description of C. pneumoniae in ibex. Further studies are necessary to elucidate the situation in other species of wild ruminants as chamois (Rupicapra r. rupicapra), red deer (Cervus elaphus) and roe deer (Capreolus c. capreolus) in Switzerland.
Resumo:
Der Beitrag beschreibt eine doppelte, verfremdete und letztendlich tragische Spiegelung in der Wahrnehmung von Architektur zwischen Europa und Indien: zwischen 1780 und 1856 entstanden in der nordindischen Stadt Lucknow mehrere große Baukomplexe, die von den indisch-islamischen Herrschern der Stadt in europäisch-klassizistischen Formen gestaltet wurden. Nach dem indischen Aufstand, der in den Jahren 1857 und 1858 gegen die britische Herrschaft in Lucknow losbrach, wurden diese Bauten zum Gegenstand einer scharfen europäischen Architekturkritik. Der erste Abschnitt – "Das Eigene und das Fremde" – betrachtet die westliche Rezeption dieser europäisch-klassizistischen Bauten, die über Jahrzehnte durch ein Negativurteil bestimmt war, das sich aus der politischen Interpretation des indischen Aufstands erklärt. Der zweite Abschnitt – "Kopie und Synthese" – geht auf die Suche nach den Zusammenhängen für die positive Europarezeption in Lucknow und für die negative Kritik dieser Bauten in Europa. Es erweist sich, dass die Praxis von Architekturkopie und die Wahrnehmung europäischer Stilformen bei der Übernahme klassizistischer Motive in Indien deutlich anders war als das exakte und moralisch überhöhte Verständnis von Stilformen im Europa nach 1850.