Dissertationen zum Thema „DiCre“
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Loubens, Manon. „Analyse fonctionnelle de protéines des organites apicaux chez les sporozoïtes de Plasmodium“. Electronic Thesis or Diss., Sorbonne université, 2021. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2021SORUS245.pdf.
Der volle Inhalt der QuelleInfection with Plasmodium, the parasite responsible for malaria, begins with the inoculation of invasive sporozoites by a female Anopheles mosquito. Sporozoites infect liver cells and develop into merozoites which, once released into the bloodstream, undergo asexual multiplication cycles in red blood cells. Host cell invasion involves the secretion of apical organelles (micronemes and rhoptries) and the formation of a unique structure (moving junction) that leads to the internalization of the parasite within a parasitophorous vacuole. However, the molecular mechanisms involved during invasion of hepatocytes by sporozoites remain unknown. Apical secretory organelles contain proteins specifically expressed in sporozoites (including 6-cysteine domain proteins), and proteins also expressed in merozoites (such as AMA1, RONs or CLAMP), which are involved in the formation of the moving junction. Our work revealed the essential role of a 6-cysteine domain protein, B9, in the invasion of hepatocytes by sporozoites. Using a conditional mutagenesis strategy, we also demonstrated the role of AMA1, RON2, RON4 and CLAMP in sporozoites, not only for hepatocyte invasion in the mammalian host but also for salivary gland colonization in the mosquito. Our results support the hypothesis of a functional compartmentalization of microneme proteins in Plasmodium sporozoites. This work contributes to a better understanding of the molecular mechanisms involved during infection of hepatocytes and identifies new potential targets to block malaria liver infection
Frohnecke, Nora. „Funktionelle Charakterisierung des Ferredoxin Redoxsystems von Toxoplasma gondii“. Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19075.
Der volle Inhalt der QuelleToxoplasmosis is one of the most common parasitic zoonoses world-wide, around 30% of human beings are infected. Toxoplasma gondii (phylum: Apicomplexa) contains a unique intracellular organelle derived from plastids, called apicoplast. The only known redox system in the apicoplast consists of the ferredoxin NADP+-reductase and its redox partner, ferredoxin (Fd). The latter donates electrons to different essential metabolic pathways in the apicoplast like the last two enzymes of the isoprenoid precursor biosynthesis and the lipoic acid synthesis. To dissect protein protein interactions for an electron transfer a bacterial reverse two hybrid system was used. The physical interaction of both proteins TgFd and TgLipA could be shown. Fd is supposed to play an important role in diverse metabolic pathways, hence a knock-out of the Fd gene is expected to generate a complex biochemical phenotype and be lethal to the parasite. Therefore two complementary approaches were used to analyze the role of TgFd in this context. The first strategy shall verify the essentiality of TgFd for the survival of T. gondii. It is based on the DiCre system whereby a defined genetic knock out of TgFd is produced. Respectives parasites have been generated, but at the end no genetic Fd knock out could be produced. In the second approach a conditional knock-down was generated, where the expression of the TgFd gene is repressed after induction. The Fd deficiency has wide ranging effects on T. gondii: The fatty acid synthesis of the apicoplast-synthesized fatty acids is reduced as well as the motility is decreased due to an affected isoprenoid synthesis. In total this leads to a dramatic inhibition of parasite growth. Both metabolic pathways depend upon the electron carrier Fd and thus are affected by Fd deficiency. The results underline the essential role of the ferredoxin redoxsystem of T. gondii.
Holden, Damien James. „Generalised Brans-Dicke cosmology“. Thesis, University of Portsmouth, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247071.
Der volle Inhalt der QuelleCoirault-Neuburger, Sylvie. „Dire la croyance“. Paris 5, 1994. http://www.theses.fr/1994PA05H094.
Der volle Inhalt der QuelleWhat is believing? Believing is neither knowing, nor plain imagination. One’s belief expresses itself so as to develop a world of original relations. Dialogue is not always possible there. Its logics admit impossible. Are signs and speeches that express belief faithful? Relations with other people, with the object of belief demand to go on ways leading from meeting to recognition
Thibau, Tereza Cristina Sorice Baracho. „A legitimação ativa nas ações coletivas: um contributo para o estudo da substituição processual“. Universidade Federal de Minas Gerais, 2003. http://hdl.handle.net/1843/DIRE-5SFJMX.
Der volle Inhalt der QuelleO trabalho visa a analisar os possíveis caminhos a serem traçados na interpretação do Direito nacional contemporâneo, que vem se empenhando na tarefa de promover a proteção dos novos direitos ou interesses de terceira geração, denominados metaindividuais, os quais forma elevados à categoria de garantias findamentais. As discussões jurídico-processuais impostas pelos conflitos de massa que hoje se verificam como reflexo dos fenômenos da globalização, coletivização e massificação imprimidas nas relações sociais, levam a pensar na privatização do direito público e na publicização do direito privado. Buscou-se então uma análise desta situação, focalizando inicialmente a doutrina jurídica tradicional, e posteriormente os novos enfoques que precisam ser a esta dirigidos, para adequá-las às necessidades do direito atual. Dentro deste panorama, surgiu a necessidade de se examinar a legitimação ativa dos entes intermediários, aos quais a lei conferiu a tarefa de representação das coletividades em juízo. Assumindo a posição de parte (autor ideológico) no processo coletivo, os entes intermediários estão afetados por todos os direitos e deveres que tal condição processual lhes destina. E, em princípio, poder-se-ia imaginar para estes a condição também de substitutos processuais (legitimação extraordinária) da coletividade. A natureza jurídica da legitimação ativa destes entes é matéria que ainda está em construção; há tendência da doutrina em diferenciá-la conforme a espécie de interesse metaindividual que se visa a proteger (difuso, coletivo ou individual homogêneo). Acredita-se que tal natureza é de ligitimação institucional coletiva, como um terium genus, a qual se caracteriza por apresentar traços da legitimação ordinária, extraordinária e coletiva, simultaneamente. E, visto que há mais de um ente legitimado a atuar em juízo em nome da coletividade, esta legitimação será também concorrente e disjuntiva. Além da legitimação para agir, examina-se o grau de interesse para agir, que tais entes precisam demonstrar, para que estejam completas as condições para o exercício do direito de ação destes. Tal interesse processual é medido pela adequação da escolha política que a lei fez ao indicar o Ministério Público, os entes públicos, as entidades e órgãos da administração pública direta ou indireta, e as associações (sidicatos), como representantes da coletividade. Esta escolha fundou-se tanto na relevância social dos bens jurídicos tutelados nas ações coletivas, como na força e capacidade de atuação que tais corpos podem significar nesta seara. Partindo-se do exame das circunstâncias processuais que cercam a legitimação ativa e o interesse de agir dos entes intermediários, além do objeto e dos efeitos da coisa julgada nas ações coletivas, verifica-se que não existe uma perfeita adequação da figura da substituição processual como inerente à posição ocupada no processo por tais entes. Todavia, não se pode negar que também existam semelhanças entre a figura do substituto processual e a condição de 'representante' institucional da coletividade àqueles referentes. A própria lei processual, assim como está, não facilita interpretações muito seguras neste campo. Entretanto, o que se verifica de concreto é que houve uma modificação, por ficção jurídica, no conceito de 'parte', passando a ser concebido como aquele que foi legitimado a intentar a ação, e tal fato tornou-se indispensável para que o direito processual pudesse acobertar os conflitos coletivos. Por outro lado, existe no direito brasileiro um sistema integrado de defesa dos direitos e interesses metaindividuais representado essencialmente pela ação popular, ação civil pública e ações coletivas do Código de Defesa do Consumidor, que garantem satisfatóriamente o acesso destes à justiça. Sem se esquecer da via individual que se mantém aberta e sobre a qual, o uso da via coletiva não induzirá litispendência. É necessário que os operadores do direito obedeçam a tal sistema, para evitar que ocorram desvios e enganos em relação à relevância que o tema merece, embora, quanto a este, continue palpitante e aberta as discussões doutrinárias e legislativas.
Roberto, Giordano Bruno Soares. „O Direito Civil nas Academias Jurídicas do Império“. Universidade Federal de Minas Gerais, 2008. http://hdl.handle.net/1843/DIRE-7PYKYE.
Der volle Inhalt der QuelleO presente trabalho pretende analisar o modo como se deram o ensino e a produção bibliográfica de direito civil nas Academias Jurídicas do Império. Inicialmente, oferece informações sobre a fundação dos cursos jurídicos no Brasil. Em seguida, indica os principais dados sobre a carreira e a produção bibliográfica dos professores que ocuparam as cátedras destinadas à matéria em ambas as Escolas. Por fim, proporciona reflexões sobre qualidade e relevância tanto do ensino quanto da produção bibliográfica de direito civil nos espaços e no período anteriormente indicados.
Faria, Juliana Cordeiro de. „Seguro facultativo de responsabilidade civil: a problemática do direito de ação da vítima contra a seguradora na perspectiva do código civil de 2002“. Universidade Federal de Minas Gerais, 2004. http://hdl.handle.net/1843/DIRE-6APTKV.
Der volle Inhalt der QuelleHertz, Géraldine. „Dire Dieu, le dire de Dieu chez Philon, Plutarque et «Basilide»“. Thesis, Paris Est, 2013. http://www.theses.fr/2013PEST0015.
Der volle Inhalt der QuelleCan one make statements about God ? Does God speak and does hemake statements about himself ? These two questions are intimately related: iflanguage is taken to be a reality extraneous to God’s nature, it might be consideredunsuitable for expression of his nature. This dissertation explores the question of thearticulation between discourse (λόγος) and the divine (θεός) that became a prominentlocus of debate in early imperial Platonism. The clearest sign of this new-foundinterest in the relationship between discursivity and divinity is the growth in the motifof “ineffable God” (θεὸς ἄρρητος). The study looks at three authors – Philo,Plutarch, and the author presented in the Elenchos (VII, 14-27, X, 14) as “Basilides” –linked by a common adherence to the idea that God escapes verbal apprehension.Their respective way of expressing this idea is by no means uniform, however : ifPlutarch seems reticent to declare God “ineffable”, Philo declares this moreemphatically; “Basilides”, meanwhile, reckoning that declaring God “ineffable” isstill saying something about him, goes even further by declaring him “not evenineffable”. In order to understand these differences we must examine the ontological,gnoseological, and linguistic facts that explain the respective positions of theseauthors on the expression of the divine. This inquiry starts with a preliminary chapterwhich situates the debate about the gulf between discourse and God in its context –Middle Platonism – and seeks its premises in the thinking of Plato, Aristotle andPythagoreanizing speculation
Klinder, Jens Simon [Verfasser]. „Vom dynamischen Phasenübergang im offenen Dicke Modell zum Dicke-Hubbard Modell / Jens Simon Klinder“. München : Verlag Dr. Hut, 2016. http://d-nb.info/1084386984/34.
Der volle Inhalt der QuelleCuellar, Trinna Lee. „The role of Dicer in post-mitotic dopaminoceptive neurons and turnover of Dicer generated microRNAs“. Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3359544.
Der volle Inhalt der QuelleMeneksegil, Anouk. „Le dire et l'indicible“. Paris 4, 1992. http://www.theses.fr/1991PA040185.
Der volle Inhalt der QuelleAssuming that the inexpressible is fundamentally undisable, how can one grasp it without being tempted to shroud it in the obscure and untouchable aura of mysteries? From morphological point of view, the Latin privative prefix which expressive the lack or the absence of something disrupts the field it applies to, tightening and restraining it into its limits. One can be mistaken about the meaning and tonality of an apparent pattern of the inexpressible on the expressible thus extrapolating the inexpressible from the expressible which already exist. When one thinks about it, one becomes aware that the secret and prior presence of the inexpressible seems to make the expressible we end up in turn up again
Klaue, Yvonne. „Analysis of Dicer homologues in Arabidopsis“. Thesis, University of East Anglia, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423797.
Der volle Inhalt der QuelleLeclerc-Olive, Michèle. „Le dire de l'évènement (biographique)“. Lille 1, 1993. http://www.theses.fr/1993LIL12003.
Der volle Inhalt der QuellePanassiti, Antonio. „General relativity limit of Brans-Dicke gravity“. Master's thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amslaurea.unibo.it/23344/.
Der volle Inhalt der QuelleKörner, Swen. „Dicke Kinder - revisited zur Kommunikation juveniler Körperkrisen“. Bielefeld Transcript, 2007. http://d-nb.info/988749025/04.
Der volle Inhalt der QuelleTong, Xiaohui. „Rôle de la synthèse des miARN par le tissu adipeux dans les pathologies de vieillissement“. Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30332.
Der volle Inhalt der QuelleOn the one part, dicer, the RNase III endoribonuclease responsible for microRNAs maturation, has been reported to be decreased in adipocytes during ageing. With the use of tamoxifen inducible dicerlox/lox/ adiponectin-CreERT2 mice, we found that adipocyte dicer deficiency promoted the onset of some of the age-related complications such as reduced adipocyte sizes and dysfunctions in systemic metabolism. The abrogation of white adipocyte markers such as Pparγ, Glut4 or Hsl, indicated that dicer is indispensible for the maintainance of white adipocyte identity. In addition, the results that there were lipid accumulation and fibrosis in liver in tamoxifen treated dicerlox/lox/ adiponectin-CreERT2+ mice, indicated that adipocyte dicer deficiency might contribute to liver aging. Mechanistically, mitochondrial function seemed to be upregulated due to adipocyte dicer deficiency, indicated by increased protein levels of OXPHOS components and PGC1α. In line, mitochondria repressors FOXO1 and FOXO3 were phosphorylated and inactivated, whose downstream antioxidant targets Catalase and Sod were also decreased. Moreover, P16, a marker of senescence, exhibited a trend to be increased due to adipocyte dicer deficiency. Since mitochondrial ROS surplus can lead to DNA damage and senescence, we assured that adipocyte dicer deficiency might induce a combination of mitochondrial activation and reduction in detoxification reduction possibly mediated by the inactivation of FOXO1 and FOXO3a. Finally, the result that nutrient restriction positively regulated dicer level in adipocytes further supported that there is a conserved aging pathway in adipocytes involving dicer. On the other part, through microarray screen and RT-qPCR validation, we reported that aging increased mir-1949 in adipocytes in wild type mice and possibly promoted its secretion from perigonadal adipose tissue in vitro. Correspondingly, in vitro results also suggested that senescence increased mir-1949 production and secretion from adipocytes. Functionally, upregulation of mir-1949 in 3T3-F442A adipocytes negatively regulated mitochondrial complex II protein level and oxygen consumption capability, associated with lipid accumulation. Interestingly, sustained upregulation of mir-1949 during adipogenesis of 3T3-F442A preadipocytes, tended to increase white adipocyte markers, such as Leptin, Glut4 or Hsl. Finally, combined with the results that 24h fasting significantly increased mir-1949 in perigonadal adipose tissue as well as that upregulation of mir-1949 exhibited a trend to increase lipid accumulation in senescent 3T3-F442A adipocytes, we assured that aging increases mir-1949 expression in adipocytes which might try to rescue age-related dysfunctions in adipocytes, such as impaired lipid storage. Nevertheless, the precise actions of mir-1949 need to be validated in vivo by injection of AAV-aP2-mir-1949 mimic into aged mice
Tamas, Jennifer. „Dire de ne pas dire : du silence éloquent à l'énonciation tragique des déclarations d'amour chez Racine“. Thesis, Paris 4, 2012. http://www.theses.fr/2012PA040268.
Der volle Inhalt der QuelleI argue that Racine represents the fight against the unspoken. Each play reveals something that is unacceptable and impossible to articulate. How does one state all that cannot be stated? Above all, how to avoid stirring the terror of the listener? Silence, whether it represents a pure absence of words or a murmuring of voices that inhibit an answer, finds itself at the core of the discursive exchange. The declaration of love emerges from the unsaid and brings about a permanent tension between « the spoken word » and « silence. » This study is based on the following paradox: speech is impossible, but the reticence to speak, once overcome, induces an irreversible process. The declaration of love is the symbol of this process. Its utterance represents the ultimate tragic enunciation as it engenders Fate. To show one’s love is to condemn the other.The fatal oracle expresses itself through the words of characters in love.Racine inaugurates a new theater of love in which the declaration corresponds to a deep existential crisis. The Racinian character asserts his subjectivity by expressing his love, though it violates the other
Lane, Tasha Ann. „Gender and the Voir Dire Process“. PDXScholar, 2019. https://pdxscholar.library.pdx.edu/open_access_etds/5068.
Der volle Inhalt der QuelleBonnet, Agathe. „Dire et faire dire l'indicible : Entre secret et stigmate, l'analyse d'un processus d'enquête sociologique sur le ballonnement“. Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00689002.
Der volle Inhalt der QuelleBonnet, Agathe. „Dire et faire dire l'indicible : Entre secret et stigmate, l’analyse d’un processus d’enquête sociologique sur le ballonnement“. Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05H003/document.
Der volle Inhalt der QuelleThis thesis concerns methodological matters existing in the situation of fieldwork. Here the qualitative survey realized in the frame of this research was to explore minor health issues. The survey conducted on bloating issue does notably shed light on the ‘interactional game’ between a female interviewee and a female interviewer revealing the key concepts of stigma and secrecy. Indeed, the analysis of social interactions between both actors incites to perceive the notion of fieldwork as a process where different phases decline and interact altogether. From the recruitment procedure to the closure of the survey, the effects of the investigation are observed and analyzed through a dual “eye”, the interviewee and interviewer. We qualify this methodological approach as “interactive observation”. This “interactive observation” feeds its very principle within the methodology relative to the ideas of participative-observation and the tradition of symbolic interactionism. A reflection is lead on the effects of reciprocity between the elaboration of the fieldwork’s strategies and the unfolding of the study submitted to the unpredictability of the fieldwork
Lai, Yiu-yan, und 黎耀恩. „Charged generalised Brans-Dicke theory in quantum cosmology“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31221087.
Der volle Inhalt der QuelleSantos, Sérgio Mittmann dos. „Cordas cósmicas girantes na gravitação de Brans-Dicke“. Universidade Estadual Paulista (UNESP), 2018. http://hdl.handle.net/11449/153631.
Der volle Inhalt der QuelleRejected by Pamella Benevides Gonçalves null (pamella@feg.unesp.br), reason: Solicitamos que realize correções na submissão seguindo as orientações abaixo: É necessário revisar a formatação das referências seguindo a ABNT 6023:2003, por exemplo, o que ocorre em sua Tese é a ausência da indicação de autoria segundo as normas, abaixo orientação da ABNT. entre outros elementos. 8.1.1 Autor pessoal Indica(m)-se o(s) autor(es), de modo geral, pelo último sobrenome, em maiúsculas, seguido do(s) prenome(s) e outros sobrenomes, abreviado(s) ou não. Recomenda-se, tanto quanto possível, o mesmo padrão para abreviação de nomes e sobrenomes, usados na mesma lista de referências. Os nomes devem ser separados por ponto-e-vírgula, seguido de espaço. Sobre a elaboração das referencias e citações favor solicitar orientação com a bibliotecária Juciene (juciene@feg.unesp.br) Agradecemos a compreensão. on 2018-04-16T18:47:09Z (GMT)
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A partir da teoria da gravitação de Brans-Dicke, são obtidas soluções exatas para as cordas cósmicas girantes. As soluções são para cordas retas, que preservam a simetria de Lorentz ao longo do eixo longitudinal de simetria, e para as não retas, com simetria aproximadamente cilíndrica e que violam a simetria de Lorentz. Essas soluções permitem verificar se os espaços-tempos das cordas são regulares ou apresentam singularidades. Além disso, a possibilidade de que as cordas sejam fontes de curvas tipo-tempo fechadas também é analisada. Exclusivamente para as cordas retas, é verificado se essas se mantiveram estáveis após as suas eventuais formações, e se uma escolha adequada para as constantes de integração das soluções impede a existência das curvas tipo-tempo fechadas. Desde a década de 1930, as observações mostram que as velocidades tangenciais das estrelas das galáxias têm um comportamento que contraria o que é previsto quando se considera somente a presença de matéria visível: à medida que as distâncias até os centros das galáxias aumentam, as velocidades também aumentam, até que começam a tender para valores aproximadamente constantes. A razão para esse fenômeno ainda está sob debate. Por enquanto, é justificado pela presença de matéria escura nos halos das galáxias, mas a própria matéria escura ainda não é bem entendida. Em 1980, para 21 galáxias do tipo Sc, as observações mostraram que esse crescimento das velocidades até atingirem os valores constantes ocorre quando as distâncias crescem por 2 a 3 ordens de grandeza. Com as soluções da teoria de Brans-Dicke para as cordas não retas, é proposto um espaço-tempo com a mesma simetria aproximadamente cilíndrica, que descreve adequadamente esse comportamento nas velocidades das estrelas daquelas 21 galáxias
From the Brans-Dicke theory of gravitation, exact solutions are obtained for the spinning cosmic strings. The solutions are for straight strings, which preserve the Lorentz symmetry along the longitudinal axis of symmetry, and for the non-straight strings, with nearly cylindrical symmetry and which violate the Lorentz symmetry. These solutions allow us to verify if the spacetimes of the strings are regular or have singularities. In addition, the possibility that the strings are sources of closed timelike curves is also analyzed. Only for the straight strings, it is verified if these have remained stable after their eventual formations, and if a suitable choice for the integration constants of the solutions prevents the existence of the closed timelike curves. Since the 1930s, observations have shown that the tangential velocities of galaxies’ stars have a behavior that goes against what is predicted when considering only the presence of visible matter: as distances to the centers of galaxies increase, velocities also increase until they begin to tend to approximately constant values. The reason for this phenomenon is still under discussion. For now, it is justified by the presence of dark matter in the halos of galaxies, but the dark matter itself is still not well understood. In 1980, for 21 Sc-type galaxies, observations showed that such velocities growth until reaching constant values occurs when distances grow by 2 to 3 orders of magnitude. With the solutions of the Brans-Dicke theory for the non-straight strings, a spacetime with the same nearly cylindrical symmetry is proposed, which adequately describes this behavior in the velocities of the stars of those 21 galaxies
Taylor, David W. Jr. „Structural Basis for RNA Processing by Human Dicer“. Thesis, Yale University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3578460.
Der volle Inhalt der QuelleDicer plays a central role in RNA interference pathways by cleaving double-stranded RNAs (dsRNAs) to produce small regulatory RNAs. Human Dicer can process long double-stranded and hairpin precursor RNAs to yield short interfering RNAs (siRNAs) or microRNAs (miRNAs), respectively. In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and either the RNA-binding protein TRBP or PACT to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs from Dicer to AGO2. Here, I have used electron microscopy and single particle analysis of human Dicer-RNA complexes and the RLC to gain insight into the structural basis for human Dicer's substrate preference and RISC-loading. My studies show that Dicer traps pre-siRNAs in a non-productive conformation, while interactions of Dicer with pre-miRNAs and dsRNA binding proteins induce structural changes in the enzyme that enable productive substrate recognition in the central catalytic channel. The RLC Dicer's N-terminal DExH/D domain, located in a short base branch, interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2.
Lima, Sarah Azoubel 1987. „Estudo do metabolismo de microRNAs na resistência de células leucêmicas“. [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314036.
Der volle Inhalt der QuelleDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A resistência à quimioterápicos é um dos principais obstáculos para a terapia do câncer. Na leucemia mielóide crônica (CML) o tratamento é frequentemente ineficiente devido à aquisição de resistência aos quimioterápicos utilizados. Dessa forma, o estudo comparativo de linhagens celulares de CML resistentes e susceptíveis a drogas é de extrema importância para o entendimento dos mecanismos moleculares da resistência e para a evolução de novos protocolos terapêuticos. Um número cada vez maior de evidências indica que os microRNAs apresentam importante papel no processo de carcinogênese e na agressividade tumoral. Nesse trabalho o principal objetivo é melhor esclarecer o papel da maquinaria de processamento de microRNAs no fénotipo MDR (multi-drug resistance), utilizando principalmente as linhagens de CML K562 (susceptível) e Lucena (fenótipo MDR). Nossos resultados revelaram que as células Lucena apresentam altos níveis da endonuclease Dicer e que os microRNAs let-7a e miR-145 são intensamente regulados em relação à K562. Além disso, a linhagem Lucena se tornou mais sensível ao quimioterápico vincristina após o silenciamento de Dicer. Experimentos com outras linhagens celulares mostraram que a resistência frente à cisplatina e doxorrubicina possui correlação significativa com os níveis de Dicer. A identificação de ligantes dessa endonuclease nas linhagens de CML ressalta a possibilidade desta enzima estar cumprindo novos papéis no fenótipo MDR. Entre os ligantes exclusivos da linhagem resistente, estão proteínas envolvidas na promoção de defesa anti-oxidante, proliferação celular e metabolismo de lipídios e hormônios esteróides. De acordo, dados de proteoma das duas linhagens enfatizam a importância do metabolismo lipídico para aquisição da resistência, bem como de um intenso remodelamento do citoesqueleto. Nossos dados reforçam o caráter complexo e multifatorial da resistência à múltiplas drogas, contribuindo para o entendimento do ação de miRNAs e de Dicer nesse processo
Abstract: Drug resistance is one of the main obstacles in cancer therapy. Frequently, the treatment of chronic myelogenous leukemia (CML) becomes inefficient due to the emergence of a resistant population of cancer cells. Therefore, comparative studies of resistant and non-resistant CML cell lines is extremely important to the understanding of molecular mechanisms involved in the acquisition of resistance and also to the evolution of new therapeutic protocols. A growing number of evidence supports an important role for microRNAs in carcinogenesis and tumoral aggressiveness. This study aims to better understand the role of microRNAs and their biosynthetic pathway in the phenotype of multi-drug resistance (MDR) of CML cells. To this purpose we worked with the leukemic cell lines K562 (non-resistant) and Lucena (MDR phenotype). The results obtained revealed that Lucena expresses high levels of Dicer endonuclease and intensely regulates microRNAs let-7a and miR-145 when compared to K562. Also, Dicer silencing in MDR cells enhanced sensitivity to the chemotherapic drug vincristine. Experiments with different cells lines showed that resistance to cisplatin and doxorubicin are correlated to Dicer expression levels. In CML cell lines, the identification of Dicer ligands points to the possibility of alternative roles for this endonuclease in the MDR phenotype. Among the newly found interactors in the resistant cell line are proteins involved in antioxidant defense, proliferation and metabolism of fatty acids and steroids. Accordingly, proteome data from K562 and Lucena cells emphasizes the importance of lipid metabolism and structural remodeling to the resistant phenotype. Overall, our data contributes to the understanding of the role played by microRNAs and Dicer in the complex and multifactorial MDR phenotype
Mestrado
Bioquimica
Mestre em Biologia Funcional e Molecular
Paulo, Walter de Oliveira. „Gravitação newtoniana modificada a partir da teoria gravitacional de Brans-Dicke“. Universidade Federal de Roraima, 2011. http://www.bdtd.ufrr.br/tde_busca/arquivo.php?codArquivo=52.
Der volle Inhalt der QuelleInvestigamos inicialmente o problema da obtenção de uma gravitação newtoniana modificada no caso da teoria da Relatividade Geral. Na sequência, encontramos uma solução geral com simetria esférica para um campo gravitacional fraco no contexto da Teoria de Brans-Dicke. Esta solução é independente de qualquer condição de coordenada. Então, para uma escolha conveniente da função f(r) na métrica de Brans-Dicke, exibimos uma fórmula modificada para a gravitação newtoniana, a qual pode descrever a gravidade em uma escala de comprimento pequena. Discutimos os resultados em comparação com o caso da Relatividade Geral
We investigate initially the problem of obtaining a modified newtonian gravitation in the case of General Relativity theory. Following, we find a general solution with spherical symmetry for a weak gravitational field in the context of Brans-Dicke theory. This solution is independent of any coordinate condition. Then, for a convenient choice of the function f(r) in Brans-Dicke metric, we exhibit a modified formula to newtonian gravity, which can describe gravity in a small length scale. We discuss the results in comparison with the case of General Relativity
Tran, Thi Phuong Anh. „Conception, synthèse et évaluation biologique de nouveaux ligands d'ARN en tant qu'inhibiteurs de la production de microARN oncogènes“. Thesis, Université Côte d'Azur (ComUE), 2016. http://www.theses.fr/2016AZUR4076/document.
Der volle Inhalt der QuelleMicroRNAs (miRs) are a class of small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. Increasing evidence has indicated that the deregulation of miR expression is linked to various human cancers and therefore, miRs represent a new class of potential drug targets. In this context, my PhD project focused on the discovery of new inhibitors of oncogenic miRs production. Toward this aim, two different but complementary approaches were followed: (i) the screening of small libraries of compounds and (ii) the design and synthesis of new classes of conjugates as binders of miRNA precursors (pre-miRs). In particular, we focused our attention on miR-372 and miR-373, two oncogenic miRs overexpressed in various cancers, such as gastric cancer. We showed that some of the screened or of the newly synthesized compounds are able to efficiently bind to stem-loop structured precursors of the targeted miRs with high affinity, thus inhibiting the production of their corresponding mature miRs at the level of Dicer cleavage. Moreover, we found compounds bearing a specific anti-proliferative activity in gastric cancer cells overexpressing targeted miRs and this activity is directly linked to a decrease in the production of oncogenic miR-372 and -373 and to the restoration of normal mRNA translation
Montiglio, Silvia. „Dire le silence au pays du logos“. Paris, EHESS, 1995. http://www.theses.fr/1995EHES0014.
Der volle Inhalt der QuelleIn the civilisation of ancient greece, where speaking occupied a central place in the very definition of human identity and action, silence is imbued with deep and consequential meaning : as a mark of exclusion, as an arm of agression, as the invisible messenger of ill events. Since silence is also a major instrument of cunning intelligence, it can grant succes to those who know how to articulate, according to the impelling kairos, silence, words and action
Jalenques-Vigouroux, Béatrice. „Dire l'environnement : le métarécit environnemental en question“. Paris 4, 2006. http://www.theses.fr/2006PA040124.
Der volle Inhalt der QuelleThis thesis analyses how organisations build the environment into their discourses and how the narrative participates in this construction. Our position is that environment thinking is understood as a part of the crisis in “economic ideology”. It studies three kinds of organisations : a firm, SITA France (SUEZ); a public institution, Agence de l’Environnement et de la Maîtrise de l’Energie (ADEME); and a non-profit organisation, France Nature Environnement (FNE). In addition, it examines a communication organ constituted by these three types of organisations. The criteria used to select these organisations were that they identified themselves as environmental players. More than exhaustivity, our object permits us to measure the amplitude of the discourse used to construct the environment. The study of these French organisations uncovers the fact that the environment is constructed via two distinct types of discourse, the economic type and the environmental type. The study of the social representations associated with frequently-used words within the environmental type of discourse brings to light certain “fermenting agents in a developing narrative”. These “fermenting agents in a developing narrative” allow us to reconstitute the components of a particular potential story, the “meta narrative”: “action”, “anonymous heroes”, “a great peril”, “a lofty ideal”, and “supreme value”, all of which constitute the environmental “metanarrative”
Noonan, Eric S. „Slice—n—Dice Algorithm Implementation in JPF“. BYU ScholarsArchive, 2014. https://scholarsarchive.byu.edu/etd/4147.
Der volle Inhalt der QuelleFellman, Laura Suzanne. „The Genetic Algorithm and Maximum Entropy Dice“. PDXScholar, 1996. https://pdxscholar.library.pdx.edu/open_access_etds/5247.
Der volle Inhalt der QuelleHe, Qiwei. „Le dire-vrai chrétien selon Michel Foucault“. Thesis, Lyon, 2019. http://www.theses.fr/2019LYSEN075/document.
Der volle Inhalt der QuelleThe Foucaldian reading of the Church Fathers in the 1980s occupies a central place in his project of genealogy of the modern subject. One of its most important axes is the analysis of the Christian notion of truth-telling. The formation of an analytic discourse of self, combined with the obligation of total obedience to the other, is an essential part of Christian subjectivity. Our analysis focuses on the various forms of the basic obligation to manifest one's truth in the three Christian practices of baptism, penance, and the direction of consciousness. We propose a critical reading of the Foucauldian analysis of the Christian truth-telling in the course of 1980, On the Government of the living, Wrong-doing, Truth-telling and Confessions of the Flesh, by examining the singularity of its method compared to historians. We also retrace the evolution of the way Foucault problematizes his analysis of Christianity and broadens the historical context. Finally, we propose a comparative reading of the notion of truth-telling both in Confucian philosophy and early Christianity
MUSI, ELISABETTA. „Dire il mondo Abitare pedagogicamente le parole“. Doctoral thesis, Università degli Studi di Milano-Bicocca, 2021. http://hdl.handle.net/10281/315632.
Der volle Inhalt der QuelleThe word reveals our relationship with existence, it speaks of drifts and bewilderments or, on the contrary, of firm and conscious existential postures. Lacking words with which to talk about oneself, about one's relationship with the world, is to lack a grip on reality. Whoever dedicates himself to the tasks of education and care should do so by first of all paying attention to the words with which the subject represents himself and his relationship with the reality that surrounds him. But what makes a word educational? Phenomenological-existential pedagogy constitutes the hermeneutic horizon of reference from which the research began. It aimed to verify the validity of its theoretical assumptions by analysing the use of words in three declared or implicitly educational contexts: educational services for children, prisons and hospitals. The exploratory research began with the realisation of some focus groups that involved - a group of nursery educators and preschool teachers, - a group of nursery school teachers and nursery school teachers, the leaders of storytelling and autobiographical writing workshops in prison, - a group of doctors and health workers. These comparisons provided useful indications for the construction of three types of questionnaires which were then sent to the same operators and their colleagues. From the elaboration of the answers, thought stimuli and operational indications emerged for the construction of a critical theory capable of defining conditions and characteristics so that the word can be effectively educational.
Lapointe, Francis. „Analyse sémantique et description lexicographique de marqueurs pragmatiques construits avec VRAI en français québécois vraiment, pas vraiment, pour de vrai, pour dire vrai, à vrai dire et à dire vrai“. Mémoire, Université de Sherbrooke, 2005. http://savoirs.usherbrooke.ca/handle/11143/2455.
Der volle Inhalt der QuelleLapointe, Francis. „Analyse sémantique et description lexicographique de marqueurs pragmatiques construits avec VRAI en français québécois vraiment, pas vraiment, pour de vrai, pour dire vrai, à vrai dire et à dire vrai /“. [S.l. : s.n.], 2005.
Den vollen Inhalt der Quelle findenBenoit, Matthieu. „Etudes biophysiques de l'interaction entre la protéine humaine TRBP et un précurseur de microARN oncogène“. Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-01038628.
Der volle Inhalt der QuelleAbel, Yoann. „Caractérisation structurale et fonctionnelle d’une nouvelle interaction entre les protéines RPAP3 et TRBP“. Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0285/document.
Der volle Inhalt der QuelleRecently, several studies have described a possible link between snoRNA and microRNA maturation, two ncRNA families involved in the maturation of other RNAs, such as rRNA, and in the regulation of gene expression, respectively. Indeed, these studies have shown that some microRNAs could be maturated from a snoRNA precursor, forming a new class of ncRNAs, the sdRNAs (snoRNA-derived RNAs). The mechanism of sdRNA maturation are still poorly understood. Therefore, we have performed a two-hybrid screen in the yeast S. cerevisiae between different proteins involved in microRNAs and snoRNAs biogenesis. Interestingly, we observed a novel interaction between TRBP, involved in the maturation of microRNAs, and RPAP3, a member of the hR2TP complex. The observation of this interaction raises several questions, such as its possible involvement in the maturation of microRNAs from snoARN precursors, or on the possible involvement of TRBP or RPAP3 in snoRNP or microRNA biogenesis, respectively. Using various molecular biology and biochemical approaches, we undertook the functional and structural characterization of the TRBP/RPAP3 interaction. First, we confirmed the interaction both in vitro and in vivo and we identified the TRBP and RPAP3 domains involved in the interaction, as well as several interesting mutations in the binding interface. Using these mutants should allow us to study the effects of this mutations on the maturation of differents ncRNAs. Additionally, we showed that the interaction between TRBP and RPAP3 and between TRBP and the RNase Dicer were mutually exclusive. Interestingly, it was shown that in the absence of TRBP, Dicer processig resulted, in some cases, in the generation of microRNAs with different ends, and thus, with altered specificity(iso-miRs). The interaction between TRBP and RPAP3 could therefore also constitute a possible way to regulate the availability of TRBP, and eventually the activity of Dicer
Nadimpalli, Hima Priyanka 1988. „Insights into cytoplasmatic polyadenylation mediated by Drosophila Dicer-2“. Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/664810.
Der volle Inhalt der QuelleLa poliadenilación citoplasmática es un mecanismo de control de la traducción extendido a lo largo de la escala animal. En vertebrados, este mecanismo requiere dos secuencias en el extremo 3’ no traducido (UTR) del mRNA, el elemento de poliadenilación citoplasmática rico en uridinas (CPE) y el hexanucleótido de poliadenilación AAUAAA (HN). En embriones tempranos de Drosophila, la poliadenilación de Toll, sin embargo, ocurre independientemente de estas secuencias, y requiere al menos dos factores: Dicer-2, una proteína previamente implicada en interferencia de RNA (RNAi), y la poly(A) polimerasa Wispy. Para entender esta nueva función de Dicer-2 en poliadenilación citoplasmática y traducción, nos propusimos diseccionar los elementos en el extremo 3’ UTR de Toll relevantes para este mecanismo de poliadenilación no canónica, así como identificar proteínas y mRNAs que interaccionan con Dicer-2 a gran escala. Nuestros resultados indican que el extremo 3’ UTR de Toll contiene varias secuencias implicadas en poliadenilación, y que el mecanismo no canónico es dominante en embriones tempranos, probablemente porque los elementos canónicos (CPE y HN) se encuentran activamente reprimidos. El estudio del interactoma de Dicer-2, realizado por purificación por afinidad e identificación por espectrometría de masas, reveló numerosas proteínas que no están implicadas en RNAi. Entre ellas, encontramos factores previamente relacionados con control de la longitud del poly(A) o con interacción con PABP y traducción, sugiriendo que estos factores podrían actuar x como co-factores de Dicer-2 en poliadenilación citoplasmática. Análisis de mRNA targets mediante RIP-Seq reveló multiples tránscritos que previamente fueron identificados como targets de Wispy. Estos resultados sugieren una función extendida de Dicer-2 en poliadenilación citoplasmática, y establecen una base sólida para investigaciones futuras.
Engl, Johanna Pia Magdalena. „Festigkeit und Dicke des hyalinen Knorpels am equinen Talus“. Giessen : VVB Laufersweiler, 2007. http://geb.uni-giessen.de/geb/volltexte/2007/4748/index.html.
Der volle Inhalt der QuelleWong, Pui Man. „The role of Dicer and microRNAs in lymphocyte development“. Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608452.
Der volle Inhalt der Quelle張礎恆 und Chor-hang Paul Cheung. „Solutions of wormhole in the generalized Brans-Dicke theory“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31215075.
Der volle Inhalt der QuelleMatusiak, Raphaël. „TWEAK : un nouveau régulateur de la ribonucléase III Dicer“. Thesis, Université Laval, 2014. http://www.theses.ulaval.ca/2014/30612/30612.pdf.
Der volle Inhalt der QuelleCamargo, Junior Fausto de. „Manifestações do caos no modelo do Maser de Dicke“. [s.n.], 1995. http://repositorio.unicamp.br/jspui/handle/REPOSIP/278173.
Der volle Inhalt der QuelleTese (doutorado) - Universidade Estadual de Campinas, Instituto de Fisica "Gleb Wataghin"
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Resumo: Estudamos os efeitos da não-integrabilidade no modelo do Maser de Dicke, através da observação nas alterações dos padrões de distribuições de valores esperados nos auto-estados de energia de alguns operadores relevantes ao sistema, graficados contra os autovalores de energia. A densidade de estados semiclássica e os valores médios de observáveis, do ponto de vista do ensemble microcanônico, são obtidos e comparados com o padrão de distribuição dos valores médios quânticos com uma boa concordância tanto no caso regular como no caso com caos. A análise das flutuações em torno dos valores médios semiclássicos são feitas através de seções de Poincaré clássicas e mostramos evidências de que existe uma conexão com o comportamento das órbitas periódicas clássicas e suas estabilidades. Calculamos também, na aproximação de campo médio, grandezas termodinâmicas, como o calor específico para o modelo como função da temperatura. Esta função mostra uma descontinuidade com a temperatura de transição de fase superradiante Tc, para interações suficientemente forte, e também o fato de que este resultado não é sensível à presença do caos. A análise dos pontos fixos da dinâmica à temperatura finita é feita tanto para o caso regular como para o caso com caos, e a estabilidade das soluções são discutidas
Abstract: We study the effects of nonintegrability in the Dicke Maser Model by observing the modifications in the patterns of distribution of expectation values in the energy eigenstates of some selected operators plotted against energy eigenvalues. The semiclassical density of states and the mean values of observables in the microcanonical ensemble are obtained and compared with the quantum plots with a very good agreement for both regular and chaotic case. Analysis of fluctuations around the semiclassical mean values are made by means of classical Poincaré sections, and evidences of its connections with the behaviour of the classical periodic orbits and their stabilities are shown. We have also calculated, in the mean field approximation, the quantities like the specific heat of the model as a function of the temperature. Such a function displays a discontinuity at the superradiant transition temperature Tc for large enough interaction, and the fact that this result is not sensitive to the presence of chaos. The fixed point analysis of the dynamics at finite temperature is done for regular and chaotic cases and their stability conditions are discussed.
Doutorado
Física
Doutor em Ciências
MORENO, FILHO Marcos George Magalhães. „Dicke states: production from EPR pairs and entanglement analysis“. Universidade Federal de Pernambuco, 2017. https://repositorio.ufpe.br/handle/123456789/27714.
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CNPq
In this work we analyze the problem of creation of Dicke states through the process of entanglement swapping. First we deal with the tripartite case, presenting a deterministic protocol based on a source of EPR pairs. Still in this topic we show that it is possible to create perfect W states (tripartite Dicke states), even when the EPR source does not yield maximally entangled pairs, with a finite success rate. Subsequently we cope with the n-partite case, for which we present a probabilistic procedure, also employing EPR-pair sources, where the output, whenever successful, is perfect. The analysis of this protocol reveals a critical transition for the success probability, which is characterized in the framework of Landau theory of second order phase-transitions. Finally we proceed with a study of the entanglement between bipartitions of systems described by Dicke states, which allows for the implementation of entanglement witnesses. For each Dicke state we present a highly sensitive witness.
Neste trabalho analisamos o problema de criação de estados de Dicke através de um processo de entanglement swapping. Inicialmente tratamos o caso tripartite, para o qual apresentamos um protocolo determinístico empregando uma fonte de estados EPR. Ainda nesse tópico, mostramos que, com uma taxa de sucesso finita, é possível produzir estados W (estados de Dicke tripartite) perfeitos mesmo quando utilizamos uma fonte de estados EPR não maximamente emaranhados. Em seguida consideramos o caso de n partes, para o qual apresentamos um procedimento probabilístico, também fazendo uso de uma fonte de estados EPR, em que o resultado, sempre que bem-sucedido, é perfeito. A análise deste protocolo revela uma transição crítica, que é caracterizada no contexto da teoria de transição de fase de segunda ordem de Landau. Por ultimo fazemos um estudo do emaranhamento entre bipartições de sistemas descritos por estados de Dicke, que nos permite a implementação de testemunhas de emaranhamento. Para cada estado de Dicke, apresentamos uma testemunha com alta sensibilidade.
Silva, João de Ribamar. „Gravitacionismo no contexto da teoria gravitacional de Brans-Dicke“. Universidade Federal de Roraima, 2010. http://www.bdtd.ufrr.br/tde_busca/arquivo.php?codArquivo=63.
Der volle Inhalt der QuelleIn this work we develop the formalism of the gravitomagnetism in the context of the Brans-Dicke theory of gravity. We write the field equations in a type-Maxwell form while considering the approximations of weak field and of low speed of rotation of the source. We examine the effect of Lense-Thirring precession of inertial frames and obtained the equation of motion for a particle. We have also introduced a model with the angular momentum of the source varying linearly with time, calculating the gravitomagnetic time delay due. The results were compared with the predictions of the theory of General Relativity.
Neste trabalho desenvolvemos o formalismo do gravitacionismo no contexto da teoria gravitacional de Brans-Dicke. Escrevemos as equações de campo em uma forma tipo-Maxwell ao considerarmos as aproximações de campo fraco e de baixa velocidade de rotação da fonte. Examinamos o efeito Lense-Thiring de pressão dos referenciais inerciais e obtivemos a equação de movimento para uma partícula. Introduzimos ainda um modelo com o momento angular da fonte variando linearmente no tempo, calculando o atraso do tempo gravitomagnético decorrente. Os resultados obtidos foram comparados com as previsões da teoria da Relatividade Geral.
Weiss, Andreas. „Le diacre permanent dans le diocese de rotenburg-stuttgart“. Université Marc Bloch (Strasbourg) (1971-2008), 1990. http://www.theses.fr/1990STR20046.
Der volle Inhalt der QuelleStowe, Heather Marguerite. „Cloning and expression of porcine Dicer and Argonaute-2“. Connect to this title online, 2009. http://etd.lib.clemson.edu/documents/1263408510/.
Der volle Inhalt der QuelleCheung, Chor-hang Paul. „Solutions of wormhole in the generalized Brans-Dicke theory /“. Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19737968.
Der volle Inhalt der QuelleYamanaka, Laís Eiko. „Caracterização da DICER-LIKE 2 (TrDCL2) de Trypanosoma rangeli“. reponame:Repositório Institucional da UFSC, 2016. https://repositorio.ufsc.br/xmlui/handle/123456789/168303.
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O mecanismo de RNA de interferência (RNAi) é um sistema pós-transcricional de silenciamento gênico com ampla distribuição nos organismos eucariotos. Os pequenos RNA (siRNA e miRNA) são considerados moléculas chaves nesse mecanismo, os quais são gerados pela proteína Dicer. A presença desse sistema parece não seguir um padrão de distribuição filogenético e a sua evolução ainda não foi compreendida. Entre os protozoários, o mecanismo de RNAi está muito bem caracterizado em Trypanosoma brucei, entretanto é ausente em Trypanosoma cruzi e em muitas espécies de Leishmania. O Trypanosoma rangeli não possui vários componentes da maquinaria de RNAi, tornando-a não funcional. Entretanto, o gene que codifica para a Dicer- Like2 (DCL2) foi encontrado completo em seu genoma, enquanto os demais genes codificantes para as outras proteínas da maquinaria estão truncados (pseudogenes). No presente estudo realizamos a caracterização do gene DCL2 de T. rangeli (TrDCL2), o qual apresentou-se como cópia única no genoma do parasito, possuindo uma janela aberta de leitura com 2.667 pb que codifica para uma proteína de 889 aminoácidos (±100 kDa). Foram reveladas diferenças nas sequências aminoacídicas da TrDCL2 entre as cepas KP1(+) e KP1(-) de T. rangeli e devido uma mudança na fase de leitura não é possível identificar os domínios RNAse III nas cepas KP1(-). O gene TrDCL2 é transcrito nas cepas KP1(+), sendo que os níveis de mRNA não apresentam alterações significativas durante o processo de diferenciação celular in vitro do parasito. Visando a avaliação da atividade enzimática e análise da presença e níveis proteicos, realizamos a expressão heteróloga de dois fragmentos e da proteína TrDCL2 inteira. Um dos fragmentos foi utilizado para a produção de um antissoro policlonal anti-TrDCL2. Este antissoro reconheceu uma proteína do tamanho esperado (±100 kDa) nos extratos proteicos totais das formas epimastigotas e tripomastigotas de T. rangeli. Os ensaios de imunofluorescência indireta, utilizando o mesmo antissoro, revelaram uma distribuição difusa da proteína pelo citoplasma de ambas as formas do parasito. A TrDCL2 é expressa em algumas cepas do T. rangeli, entretanto a determinação do seu papel biológico neste parasito ainda permanece a ser elucidada.
Abstract : The interference RNA mechanism (RNAi) is a system of post-transcriptional gene silencing with wide distribution in the eukaryotes. Small RNA (siRNA e miRNA) are considered key molecules in this mechanism, which are generated by Dicer protein. The presence of this system seems not follow a pattern of phylogenetic distribution and its evolution is still not understood. Between trypanosomatids, the RNAi mechanism is well described in Trypanosoma brucei, but is absent in Trypanosoma cruzi and some Leishmania species. Trypanosoma rangeli does not have many components of RNAi machinery, making it not functional. However, the Dicer-Like2 (DCL2) coding gene was fully encountered in its genome, while the other genes of this machinery are truncated (pseudogenes). In the present study, we have realized the characterization of DLC2 gene of T. rangeli (TrDCL2), which presented a single copy in the parasite genome, having an open reading frame with 2.667 bp that encodes a protein with 889 amino acids (±100 kDa). Differences in aminoacidic sequences were revealed between strains KP1(+) and KP1(-) of T. rangeli and due to a change in the reading phase it was not possible to identify RNAse III domains in the KP1(-) strains. TrDCL2 gene is transcripted in the KP1(+), the mRNA levels do not show significant alterations during the process of cellular differentiation in vitro. Aiming the evaluation of the enzymatic activity and the analysis of the presence of the protein and its levels, we realized the heterologous expression of two fragments and the whole protein TrDCL2. One of the fragments was used to produce a polyclonal antiserum anti-TrDCL2. This antiserum recognized a protein with the expected size (±100 kDa) in the total protein extracts of the epimastigotes and trypomastigotes of T. rangeli. Imunofluorescence assays, using the same antiserum, revealed a diffuse distribution of the protein in the cytoplasm in both forms of the parasite. The TrDCL2 is expressed in some strains of T. rangeli, but the determination of its biological role in this parasite still needs to be elucidated.
Pelegri, Kristic Andrea Paz. „Approche fonctionnaliste de la langue au théâtre. Pour une version chilienne du Chant du Dire-Dire de Daniel Danis“. Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20487.
Der volle Inhalt der QuelleShamandi, Nahid. „Functional analysis of plant RNaseIII enzymes“. Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112157/document.
Der volle Inhalt der QuelleSmall RNAs, including miRNA and siRNA, play essential regulatory roles in genome stability, development and stress responses in most eukaryotes. Plants encode four DICER-LIKE (DCL) RNaseIII enzymes. DCL1 produces miRNAs, while DCL2, DCL3 and DCL4 produce diverse size classes of siRNA. Plants also encode RNASE THREE-LIKE (RTL) enzymes that lack DCL-specific domains and whose function is largely unknown. Arabidopsis plants over-expressing RTL1 exhibit morphological defects and lack all types of small RNAs produced by DCL2, DCL3 and DCL4, indicating that RTL1 is a general suppressor of plant siRNA pathways. RTL1 activity requires a functional RNaseIII domain. RTL1 is naturally expressed only weakly in roots, but virus infection strongly induces its expression in leaves, suggesting that RTL1 induction is a general strategy used by viruses to counteract the siRNA-based plant antiviral defense. Accordingly, transgenic plants over-expressing RTL1 are more sensitive to TYMV infection than wild-type plants, likely because RTL1 prevents the production of antiviral siRNAs. However, TCV, TVCV and CMV, which encode stronger suppressors of RNA silencing (VSR) than TYMV, are insensitive to RTL1 over-expression. Indeed, TCV VSR inhibits RTL1 activity, suggesting that inducing RTL1 expression and dampening RTL1 activity is a dual strategy used by viruses to establish a successful infection. Plants over-expressing RTL2 and rtl2 mutants do not exhibit morphological defects and do not show major changes in the endogenous small RNA repertoire. However, RTL2 over-expression enhances the accumulation of exogenous siRNAs in transient assays, and this activity requires a functional RNaseIII domain. Therefore, it is possible that plant RTL2 processes certain substrates to facilitate the action of DCL enzymes