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Schwob, Étienne. "Methionyl-trna synthetase mitochondriale de saccharomyces cerevisiae : purification et tentative de clonage de son gene, caracterisation des genes rpk1 codant pour une proteine-kinase et act2 codant pour une nouvelle forme d'actine." Université Louis Pasteur (Strasbourg) (1971-2008), 1988. http://www.theses.fr/1988STR13195.
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Carniel, Fagner. "O telejornal que "Fala pra gente, mas não fala da gente"." reponame:Repositório Institucional da UFPR, 2012. http://hdl.handle.net/1884/28028.
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Resumo: Entendendo que o discurso hegemônico do telejornalismo rural, especificamente na figura do Globo Rural, atua na promoção da modernização agrícola, procuro refletir neste trabalho sobre o papel da televisão nos processos de (re)construção do meio rural em Dois Vizinhos (PR). A hipótese é de que a "presença" da televisão neste contexto acirra a revisão e ressignificação das atividades e condições de vida no contato com experiências e estilos de vida rurais altamente inseridos no mercado e no consumo, veiculados pelo telejornalismo rural. São dinâmicas sociais que configuram a própria agricultura familiar a partir de processos identitários híbridos, forjados no encontro da vida local com a sociedade envolvente. Ativada para designar uma identidade aberta às tensões estabelecidas entre o que se vê na televisão e o que se vive nas comunidades, a agricultura familiar marca a própria diversidade do rural na região, tanto na (re)produção como na representação da vida familiar, abrigando uma polissemia de perspectivas e estratégias identitárias que disputam espaço e ligitimidade nos contextos locais de Dois Vizinhos.
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Yogalingam, Gouri. "Molecular characterisation of feline MPS VI and evaluation of gene therapy /." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phy54.pdf.
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Jokubka, Ramūnas. "Kiaulių genetinių žymenų įtaka produktyvumo savybėms." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2005. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2005~D_20051122_142646-74982.
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The study presents evaluation of pig genetic markers (MHS and MC4R) associated with performance traits in the Lithuanian White pig breed. The study presents a direct approach the testing and explanation of the quantitative part of the trait and QTL with marker based on estimated breeding values in the Lithuanian White population. Information about the strategies for association analysis and improvement can be applied for further characterization of the Lithuanian White population. The use of breeding values instead of single measurements reduces the bias in the recorded performance traits, therefore, the results obtained by using the marker for the Lithuanian White population gives animal breeders the opportunities for realization of a short-term goal in their selection criteria.
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Pradhan, Anjala Vinayak. "Genes differentially expressed in adult familial myelodysplastic syndromes (MDS)." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418063.
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Silva, Ivanilde da. "De quem nós/a gente está(mos) falando afinal?" Florianópolis, SC, 2004. http://repositorio.ufsc.br/xmlui/handle/123456789/87528.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-graduação em LinguísticaMade available in DSpace on 2012-10-21T21:28:10Z (GMT). No. of bitstreams: 1 208785.pdf: 934005 bytes, checksum: 08257673dc8164a3f70b3da098a590d3 (MD5)
O objetivo deste trabalho é descrever e analisar a intercambialidade de nós e a gente (e suas respectivas realizações #mos e zero) atrelada à peculiaridade de serem pronomes multirreferenciais, podendo designar, dentro de uma escala de possibilidades, desde as pessoas do discurso a referentes genéricos, a ponto de não se precisar o referente. A análise está apoiada nas concepções teóricas de Benveniste (1988 e 1989) no que se refere às discussões sobre pronomes e subjetividade das pessoas do discurso; nos processos de referenciação e de categorização de referentes do discurso, baseados na abordagem lingüística e sócio-cognitiva de Mondada e Dubois (1995/2003), Apothéloz (1995/2003) e Milner (1995/2003) principalmente, e nos pressupostos teóricos e metodológicos da sociolingüística variacionista. As amostras da pesquisa foram constituídas por 32 entrevistas, 16 colhidas na cidade de Blumenau/SC, da fala de profissionais, muitos deles vinculados a um hospital da mesma cidade, e os demais dados de fala foram colhidos do Programa do Jô, atração televisiva veiculada pela Rede Globo de Televisão. As entrevistas, coletadas na cidade catarinense foram realizadas entre os anos de 2001 e 2002 e as exibidas pelo Programa do Jô no período de 2003 a 2004. As amostras possuem a mesma distribuição de informantes, conforme dito acima, todos com grau de escolaridade superior, classificados de acordo com o sexo e duas faixas etárias. Os resultados gerais da utilização dos pronomes nós e a gente indicam mudança: na medida em que o pronome a gente se estabiliza como pronome pessoal, ele disputa cada vez mais espaço no campo da determinação, concorrendo com o pronome nós.
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Lenormand, Jean-Luc. "Proto-oncogène c-mos et différenciation myogénique." Paris 6, 1994. http://www.theses.fr/1994PA066626.
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Le proto-oncogène c-mos, l'homologue cellulaire de la séquence transformante du virus de souris du sarcome de Moloney, code pour une serine/thréonine kinase cytoplasmique. Nous avons mis en évidence une expression du proto-oncogène c-mos au cours de la myogenèse in vitro dans des cellules musculaires l6 de rat. Nous montrons également qu'il existe une accumulation concomitante du messager et de la protéine c-mos au cours de sa maturation du muscle squelettique chez le rat. Une analyse fine réalisée à partir du muscle squelettique de rat adulte, indique que la protéine mos de 43kda n'est pas associée a un des constituants de la matrice musculaire, mais a deux polypeptides de 80kda et 34kda. Par différentes approches expérimentales, le peptide de 34kda se révèle être la protéine p34cdc2 qui intervient dans la régulation du cycle cellulaire dans tous les organismes étudiés. Nous démontrons, pour la première fois que dans des cellules et tissus somatiques non transformes, une association entre un des éléments indispensables à la régulation du cycle cellulaire et un proto-oncogène. Cette association entre ces deux facteurs dans le muscle squelettique adulte, reflète une activité cytostatique (csf) pour la protéine p43c-mos, qui en inhibant l'activité de la protéine p34cdc2, empêcherait les cellules différenciées de réinitier un cycle cellulaire.
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Li, Xingru. "Wilms' tumor gene 1 in different types of cancer." Doctoral thesis, Umeå universitet, Institutionen för medicinsk biovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-103389.
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The Wilms’ tumor gene 1 (WT1) was first reported as a tumor suppressor gene in Wilms’ tumor. However, later studies have shown the oncogenic properties of WT1 in a variety of tumors. It was recently proposed that WT1 was a chameleon gene, due to its dual functions in tumorigenesis. We aimed to investigate the clinical significance of WT1 as biomarker in acute myeloid leukemia (AML) and clear cell renal cell carcinoma (ccRCC) and to elucidate the function of WT1 as an oncogene in squamous cell carcinoma of head and neck (SCCHN). In AML, it was suggested that WT1 expression was an applicable marker of minimal residual disease (MRD). In adult patients with AML, we found a good correlation between WT1 expression levels normalized to two control genes, β-actin and ABL. Outcome could be predicted by a reduction in WT1 expression in bone marrow (≥ 1-log) detected less than 1 month after diagnosis, when β-actin was used as control. Also, irrespective of the control gene used, outcome could be predicted by a reduction in WT1 expression in peripheral blood (≥ 2-log) detected between 1 and 6 months after treatment initiation. Previous studies in RCC demonstrated that WT1 acted as a tumor suppressor. Thus, we tested whether single nucleotide polymorphisms (SNPs) or mutations in WT1 might be associated with WT1 expression and clinical outcome in patients with ccRCC. We performed sequencing analysis on 10 exons of the WT1 gene in a total of 182 patient samples, and we identified six different SNPs in the WT1 gene. We found that at least one or two copies of the minor allele were present in 61% of ccRCC tumor samples. However, no correlation was observed between WT1 SNP genotypes and RNA expression levels. Moreover, none of the previously reported WT1 mutations were found in ccRCC. Nevertheless, we found that a favorable outcome was associated the homozygous minor allele for WT1 SNP. We then further investigated whether WT1 methylation was related to WT1 expression and its clinical significance. Methylation array and pyrosequencing analyses showed that the WT1 promoter region CpG site, cg22975913, was the most frequently hypermethylated CpG site. We found a trend that showed nearly significant correlation between WT1 mRNA levels and hypermethylation in the 5’-untranslated region. Hypermethylation in the WT1 CpG site, cg22975913, was found to be associated with patient age and a worse prognosis. One previous study reported that WT1 was overexpressed in SCCHN. That finding suggested that WT1 might play a role in oncogenesis. We found that both WT1 and p63 could promote cell proliferation. A positive correlation between WT1 and p63 expression was observed, and we identified p63 as a WT1 target gene. Furthermore, several known WT1 and p63 target genes were affected by knocking down WT1. Also, co-immunoprecipitation analyses demonstrated a protein interaction between WT1 and p53. In summary, WT1 gene expression can provide useful information for MRD detection during treatment of patients with AML. In RCC, our results suggested that the prognostic impact of WT1 SNPs was limited to the subgroup of patients that were homozygous for the minor allele, and that WT1 promoter hypermethylation could be used as a prognostic biomarker. In SCCHN, WT1 and p63 acted as oncogenes by affecting multiple genes involved in cancer cell growth.
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Pereira, Monalessa Fábia. "Estudo funcional do gene que codifica um transportador de membrana MFS em Colletotrichum lindemuthianum." Universidade Federal de Viçosa, 2011. http://locus.ufv.br/handle/123456789/5341.
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Previous issue date: 2011-02-18Conselho Nacional de Desenvolvimento Científico e Tecnológico
Colletotrichum lindemuthianum is the causal agent of common bean antracnose. This fungus, like other phytopatogens, is constantly exposed to several toxic compounds from many sources, what makes indispensable the development of protection strategies against these products. One of these strategies is related to membrane transporters proteins like the Major Facilitator Superfamily (MFS), that could provide protection against toxic compounds or minimizing its action, being essential for the fungal cellular viability maintenance. In this context, this work aimed to inactivate the mfs1 gene encoding a MFS membrane transporter and investigate the phenotypic alterations entailed in an isolate C. lindemuthianum mutant LV49 (race 89) for this gene. To obtain the mutant, it was necessary to confirm if mfs1 gene was organized as a single copy in the C. lindemuthianum genome. The mfs1 gene can be organized in a cluster in view that a second open reading frame, which corresponds to a transcription factor superfamily containing a Zn2-Cys6 domain, identified as clft1, was observed in 3` downstream region of this gene. The mfs1 promoter analysis revealed a putative mfs1 element that is recognized by proteins of this family, what suggests that this protein could be related to the mfs1 expression regulation. The Split-Marker technique proved to be efficient in C. lindemuthianum mfs1 gene inactivation enabling the study of mfs1 function in a mutant by specific integrations without ectopic integrations. The Δmfs1 mutant showed no differences in drug sensibility profile when commonly drugs employed in antracnose control was used and in relation to pathogenicity, the mutant symptoms started earlier on susceptible bean leaves, showing a stress situation due to the genic product absence. It was also observed that mfs1 presents a primordial role in C. lindemuthianum cellular viability maintenance, what was confirmed by the altered conidiation observed, confirming that this gene encodes for a specific hexose membrane transporter, specifically carbon sources like glucose, mannose and fructose. The protein Mfs1 phylogenetic analysis allow us to conclude that this transporter is a SP family member and the MFS proteins are strongly related with the transported substance. Studies conducted with MFS transporters are important to broaden the knowledge of these proteins and to understand the cell viability in C. lindemuthianum.
O fungo Colletotrichum lindemuthianum é o agente causal da antracnose do feijoeiro comum. Este fungo, assim como outros fungos fitopatógenos estão constantemente expostos a uma grande variedade de compostos tóxicos provenientes de várias fontes, o que torna imprescindível para estes o desenvolvimento de mecanismos de proteção contra estes produtos. Uma dessas estratégias está relacionada com a presença de proteínas transportadoras de membrana, como as pertencentes à Principal Superfamília Facilitadora (MFS), que podem fornecer aos fungos proteção contra compostos tóxicos evitando ou minimizando a ação destes, sendo em sua maioria essenciais para a manutenção da viabilidade celular. Este trabalho teve como objetivo inativar o gene mfs1 que codifica para um transportador de membrana da família MFS e investigar as alterações fenotípicas ocasionadas em um mutante C. lindemuthianum isolado LV49 (raça 89) para este gene. Para a obtenção do mutante foi necessário confirmar que o gene mfs1 encontrava-se presente em cópia única no genoma de C. lindemuthianum. O gene mfs1 pode estar organizado em um conjunto de genes com funções relacionadas, uma vez que downstream à região 3’ deste foi identificada uma segunda janela aberta de leitura correspondente a uma proteína da superfamília de fatores de transcrição contendo o domínio Zn2-Cys6, identificado como clft1. A análise do promotor do gene mfs1 revelou um putativo cis elemento de reconhecimento por proteínas desta família, o que sugere que esta proteína possa estar relacionada à regulação da expressão de mfs1. A técnica de Split- Marker mostrou-se eficiente na inativação do gene mfs1 de C. lindemuthianum, possibilitando o estudo da função do gene mfs1, em um mutante com integração específica e livre de integrações ectópicas. O mutante Δmfs1 não mostrou diferenças no perfil de sensibilidade a drogas comumente empregadas no controle da antracnose e em relação à patogenicidade, o mutante induziu mais precocemente os sintomas em folhas de feijoeiro susceptível, evidenciando uma situação de estresse decorrente da ausência do produto gênico. Foi observado também que o gene mfs1 exerce um papel primordial na manutenção da viabilidade celular de C. lindemuthianum, fato este confirmado pela conidiação alterada e pela confirmação de que este gene codifica para um transportador de membrana específico no transporte de hexoses, especificamente glicose, manose e frutose, uma vez que o mutante Δmfs1 mostrou crescimento reduzido quando cultivado em meios contendo apenas glicose, manose e frutose como fontes de carbono. A análise filogenética da proteína Mfs1 associada aos outros resultados obtidos nos sugere que este transportador é um membro da família SP, e que as proteínas MFS estão fortemente relacionadas com o tipo de substância que é transportada. Estudos de natureza básica sobre transportadores MFS são importantes para ampliar os conhecimentos sobre estas proteínas e a viabilidade celular em C. lindemuthianum.
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Croft, S. M. "Mammalian-wide interspersed repeats (MIRs) and their role in mammalian gene function and evolution." Thesis, Nottingham Trent University, 2009. http://irep.ntu.ac.uk/id/eprint/104/.
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Transposable elements (TEs) are ubiquitous components of plant and animal genomes and constitute more than ~45% of the human genome. Though originally considered as 'parasitic' or 'junk' DNA, TEs are now thought to have played a role in shaping genomes during evolution, contributing to genome plasticity and diversity. All classes of retrotransposons accumulate in the genome via a process termed retrotransposition, wherein the elements are reverse transcribed into RNA and inserted into the genome as DNA. Exaptation of these elements can provide additional or novel function for endogenous genes. Mammalian-wide interspersed repeats (MIRs) are short interspersed nuclear elements (SINEs), belonging to the non-autonomous class of retroelements and are found in all mammals. The recruitment of an MIR element by a gene may provide insight into mammalian evolution and gene function. The human genome was screened for genes that have exaptated MIR elements and the compiled dataset was analysed to determine any commonality which may suggest conserved function(s). Subsequently 1359 genes were identified that have exaptated MIR elements, constituting 5% of the total genes in the human genome. MIR elements may be multifunctional, as 1% of the total human genes contain MIRs that are spliced and/or are contributing to protein coding sequences. Subsequently sequence motifs were identified in the MIR consensus sequences which resemble canonical mammalian splice sites; therefore MIR elements recruited in the 5'-UTR and coding sequence may be a result of the exonisation of intronic elements. The MIR-containing transcripts are frequently expressed in neurological tissue, suggesting a role in neuronal function. Moreover a number of MIR-containing mRNA transcripts are known to be localised to the dendritic compartment of the neurone, and ciliated region of photoreceptors. Some of the localised mRNAs contain putative microRNA binding sites within the MIR sequence, and possible dsRNA structures were noted between MIR elements. It is proposed that exaptated MIR elements may be a source of cis-acting regulatory elements, involved in post-transcriptional control of gene expression, including localisation of mRNA to distinct intracellular compartments.
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Robledo, Brenda. "An in vitro and in vivo evaluation of the capacity of the gene mms6 to be an MRI reporter gene." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/53387.
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Magnetic resonance imaging (MRI) reporter genes produce MRI signal in response to the molecular environment of the cells in which they are expressed. With an MRI scanner, the signal is detected and used to produce an image of the cells. We hypothesized that the magnetotactic bacterial gene mms6 has the potential to function as an MRI reporter gene. Magnetotactic bacteria produce magnetic iron oxide crystals in intracellular organelles called magnetosomes. mms6 encodes an iron-binding, magnetosome membrane protein Mms6, which plays a role in regulating the size and shape of the iron oxide crystals found within the magnetosomes. To test our hypothesis, several mammalian cell lines were transfected with mms6, and mms6-positive clones were genetically engineered. We then used MRI to image these clones in vitro. When the cells were incubated with iron-supplemented culture media, the mms6-positive clones produced more MRI image contrast than mms6-negative cells. Through a systematic process of elimination, the mms6-positive clone that generated the most in vitro MRI image contrast was identified. This clone, named 9L4S, was composed of mms6-positive rat glioma (9L) cells and was used for intracellular iron studies and in vivo imaging. The results of electron microscopy and optical emission spectrometry support the theory that mms6-positive clones enhance MRI image contrast due to an increase in intracellular iron. The main objective of this research was to assess the ability of mms6 to function as an in vivo MRI reporter gene, so a flank tumor animal model was created. Without any exogenous iron supplementation, tumors composed of mms6-positive cells produced greater negative contrast on an MRI image than mms6-negative cells. These results demonstrate that mms6 can be considered for use in studies requiring an MRI reporter gene.
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Udy, Garry Bernard. "Genetic manipulation of c-mos, the mOR gene and krox-24 in murine ES cells." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239733.
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Sabbag, Samantha. ""Porque a gente tem um corpo né... mas a gente só lembra do corpo quando ele dói"." reponame:Repositório Institucional da UFSC, 2017. https://repositorio.ufsc.br/xmlui/handle/123456789/182792.
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Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Educação, Programa de Pós-Graduação em Educação, Florianópolis, 2017.Made available in DSpace on 2018-01-23T03:16:06Z (GMT). No. of bitstreams: 1 349692.pdf: 1801190 bytes, checksum: a800f53787d474778d35875eb6b1d9b8 (MD5) Previous issue date: 2017
A presente pesquisa, em nível de doutorado, teve como problemática investigar: de que forma o corpo constitui a docência na Educação Infantil e como é constituído pelas relações educativas com crianças pequenas?Intencionando a aproximação da problemática definiu-se como objetivo geral: conhecer a centralidade do corpo na constituição da docência na Educação Infantil. A partir de uma perspectiva interpretativa os dados foram obtidos por meio de questionários e entrevistas. Os questionários foram respondidos por 45 docentes de 12 municípios da região metropolitana de Florianópolis e as entrevistas foram realizadas com 13 dessas professoras de 4 municípios da mesma região, todas elas atuavam em creches e pré-escolas municipais. Os dados qualitativos foram categorizados por meio da Técnica de Análise de Conteúdo e os quantitativos serviram para dar suporte às discussões. Por meio do agrupamento das unidades de sentido emergiram duas categorias principais: As especificidades da docência na Educação Infantil e a centralidade do corpo; O corpo como constituído e constituidor da docência na Educação Infantil. Como referencial teórico para as análises partiu-se de uma concepção de docência como uma atitude relacional (Tardif, 2002; Teixeira, 2007; Tardif, Lessard, 2009) e consideraram-se as especificidades da Educação Infantil (Rocha, 1999; Schmitt, 2008; 2014). Destacando a centralidade do corpo nas relações docentes refletimos sobre o corpo como simultaneamente físico e simbólico, produto da natureza e cultura, ancorado por um momento histórico e político (Hughes, Lock, 1987; Vigarello, 2003; Le Breton, 2003; 2006; 2009; Buss-Simão, 2012). As análises revelam que, embora o corpo seja um elemento central nas relações docentes nesta etapa educativa, as professoras pouco direcionam sua atenção a ele. O corpo das professoras é afetado pelas demandas profissionais e como reflexo, afeta as relações estabelecidas com as crianças. Dentre os principais fatores que contribuem para o desgaste corporal identificaram-se a inadequação dos espaços e das materialidades para o corpo dos adultos nos contextos de Educação Infantil e uma lacuna nas formações iniciais e continuadas de professores no tocante ao corpo.
Abstract : The present research, at doctoral level, had as problematic to discover: in what way the body constitutes the teaching in the early childhood education and how it is constituted by the educative relations with small children? Intending to approach the problem defined for the present research was defined as a general objective: to know the centrality of the body in the constitution of teaching in early childhood education. From an interpretative perspective the data were obtained through questionnaires and interviews. The questionnaires were answered by 45 teachers from 12 municipalities in the metropolitan region of Florianópolis and the interviews were conducted with 13 of these teachers from 4 municipalities in the same region, all of them working in kindergartens and public kindergarten. Qualitative data were categorized using the Content Analysis Technique and the quantitative data served to support the discussions. From the process of emersion the two main categories were: The specificities of teaching in early childhood education and the centrality of the body; The body as constituted and constituent of teaching in early childhood education. As a theoretical reference for the analyzes, a conception of teaching as a relational attitude (Tardif, 2002; Teixeira, 2007; Tardif, Lessard, 2009) was considered and the specificities of early childhood education were considered (Rocha, 1999; Schmitt, 2008, 2014). Highlighting the centrality of the body in teacher relations we reflect on the body as simultaneously physical and symbolic, product of nature and culture, anchored by a historical and political moment (Hughes, Lock, 1987; Le Breton, 2003; 2006; 2009; Buss-Simão, 2012) The analyzes reveal that, although the body is a central element in teacher relations at this stage of education, the teachers do not direct their attention to it. The teachers' body is affected by professional demands and, as a reflex, affects the relations established with the children. Among the main factors that contributed to the corporal exhaustion were identified the inadequacy of the spaces and materialities for the adult bodies in the contexts of early childhood education and a gap in the initial and continued formations of teachers regarding the body.
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Ahrabi, Sara. "Genetic analysis of DNA double-strand break mis-repair mechanisms using the human endogenous HPRT gene." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:2ebfaf6f-cc69-4b1c-918b-9be2280b51ff.
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DNA double strand breaks (DSBs) are the most lethal radiation-induced lesions in response to which cells employ either the error free homologous recombination (HR) repair pathway or error prone mechanisms, such as non homologous end joining (NHEJ) and microhomology- mediated end joining (MMEJ). While MMEJ is suppressed by C-NHEJ, the relationship between HR and MMEJ is less clear. In this thesis, I have exploited the human endogenous HPRT gene to develop a novel genetic technology to detect mutation frequencies and signatures in response to DNA DSBs in different genetic backgrounds. Using a sensitive HPRT assay we describe a role for HR genes in suppressing MMEJ in human cells. By monitoring DSB mis-repair, we found that depletion of HR proteins, including RAD51, BRCA2, BRCA1 or SETD2, resulted in a distinct mutational signature associated with significant increases in break-induced mutation frequencies, deletion lengths and the annealing of short regions of microhomology (2 - 6 bp) across the break-site. This signature was dependent on CtIP, MRE11, POLQ and PARP, and thus indicative of MMEJ. In contrast to CtIP or MRE11, depletion of BRCA1 resulted in increased partial resection and MMEJ, thus revealing a functional distinction between these early acting HR factors. Together these findings indicate that HR factors suppress mutagenic MMEJ following DSB resection. Further, I have defined a role for the SETD2 histone methyltransferase in suppressing break-induced mutations, and have shown that CRISPR/Cas9 and ISceI- induced DSBs resulted in different repair profiles.
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Reid, Alasdair Ian. "Expression and mis-expression of hox genes during morphogenesis of the chick skin." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620553.
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Ogez, Brittney Dawn. "Efficacy of AAV2 and AAV8 to cross the blood brain barrier in the MPS IIIA mouse model." Oklahoma City : [s.n.], 2009.
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LIDEREAU, WEINSTEIN ROSETTE. "La variabilite genetique des proto-oncogenes ras, myc et mos comme marqueur de predisposition et d'evolution dans le cancer du sein." Paris 7, 1987. http://www.theses.fr/1987PA077129.
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Zickler, Antje Maria [Verfasser], and Peter A. [Akademischer Betreuer] Horn. "α-Catenin is a dosage-dependent tumor suppressor gene in MDS / Antje Maria Zickler ; Betreuer: Peter A. Horn." Duisburg, 2018. http://d-nb.info/1171705069/34.
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Severmann, Julia [Verfasser], and Peter A. [Akademischer Betreuer] Horn. "Cell cycle-dependent gene expression by Mybl2 - a tumor suppressor in MDS / Julia Severmann ; Betreuer: Peter A. Horn." Duisburg, 2018. http://d-nb.info/1161341358/34.
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Sinha, Ritwik. "EFFICIENT CONFIDENCE SETS FOR DISEASE GENE LOCATIONS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1173464878.
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Langford-Smith, Alexander William Walker. "Lentiviral vector mediated haematopoietic stem cell gene therapy for mucopolysaccharidosis type IIIA." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/lentiviral-vector-mediated-haematopoietic-stem-cell-gene-therapy-for-mucopolysaccharidosis-type-iiia(89f8e108-58f3-42bb-8b80-0e0a1fe45fd7).html.
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Mucopolysaccharidosis type III (Sanfilippo) is comprised of four phenotypically similar lysosomal storage disorders (MPS IIIA-D) caused by the deficiency of enzymes that catabolise heparan sulphate (HS). Progressive accumulation of HS results in abnormal behaviour, progressive cognitive and motor impairment and death in mid-teens. There are currently no treatments for MPS III. To assess the effect of novel therapeutics in the mouse models of MPS III it is necessary to examine the effect on primary storage of HS, secondary storage and behaviour. The reported behaviour of MPS IIIA and B mice is conflicting therefore we developed a one-hour open field test, performed at the same time of day during a period of hyperactivity observed in a previous circadian rhythm study of MPS IIIB mice. At 8 months of age MPS IIIB mice were hyperactive, with increased rapid exploratory behaviour and a reduction in immobility time. The MPS IIIA mice presented with the same behavioural phenotype as the MPS IIIB mice and were significantly hyperactive at 4 and 6 months of age and also displayed a reduced sense of danger. The hyperactivity and reduced sense of danger observed in the mice is consistent with the patient phenotype. Whilst haematopoietic stem cell transplant (HSCT) is the standard therapy used to treat the similar HS storage disorder MPS I Hurler, it is ineffectual in MPS IIIA. We hypothesise that HSCT failure in MPS IIIA is due to insufficient enzyme production in the brain by donor-derived microglial cells. By increasing expression of N-sulphoglucosamine sulphohydrolase (SGSH) we may be able to treat MPS IIIA. Therefore we compared the effect of HSCT using normal haematopoietic stem cells (WT-HSCT) to lentiviral overexpression of SGSH in normal cells (LV-WT-HSCT) or MPS IIIA cells (LV-IIIA-HSCT) in MPS IIIA mice, using the behavioural tests developed.SGSH activity in the brain of MPS IIIA recipients was not significantly increased by WT-HSCT, but was significantly increased by LV-IIIA-HSCT and LV-WT-HSCT. HS was significantly reduced by all transplants but the best treatment was LV-WT-HSCT. Neuroinflammation, indicated by the number of microglia in the brain, was significantly reduced by all treatments but remains significantly elevated. GM2 gangliosides were significantly reduced by WT-HSCT and LV-WT-HSCT and were no longer significantly elevated, but LV-IIIA-HSCT had no significant effect. Critically LV-WT-HSCT corrected the behaviour at 4 and 6 months of age whilst the other treatments had no significant effect. LV-WT-HSCT and WT-HSCT reduced GM2 gangliosides and neuroinflammation equally but only LV-WT-HSCT corrected behaviour and primary HS storage, suggesting they are the important factors in MPS IIIA pathology. LV-WT-HSCT corrects the neurological phenotype in MPS IIIA mice and is a clinically viable approach to treat MPS IIIA and other neuropathic lysosomal storage disorders.
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Woodward, Eleanor. "The use of gene expression profiling to identify novel minimal residual disease markers (MRD) in acute myeloid leukaemia (AML)." Thesis, Cardiff University, 2010. http://orca.cf.ac.uk/55179/.
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Acute myeloid leukaemia (AML) is a heterogeneous disorder characterised by the accumulation of immature haematopoietic cells blocked at various stages of differentiation. Despite improved survival rates over the past decade, relapse occurs in approximately 70% patients undergoing chemotherapy. A potential reason for this is that current clinical protocols do not take account of the level of residual disease present at remission. Therefore, one strategy to reduce relapse rates is to monitor minimal residual disease and continue to treat until the patient is minimal residual disease negative. Current minimal residual disease markers are available for patients with characterised fusion genes but approximately 50% of patients have no detectable chromosomal aberration and therefore are without markers. Gene expression profiling is a powerful tool for disease classification, prognosis and therapeutic predictions. This study aimed to investigate the use gene expression profiling to identify novel minimal residual disease markers for specific AML sub-groups. Patient diagnostic samples were profiled to identify genes specific to AML patients with a favourable translocation in order to establish the "proof-of-principle". Several genes identified were followed in patient diagnostic and follow- up samples and compared to the markers currently used. Continuing with normal karyotype AML, genes were identified as specific to this sub-group. Several homeobox (HOX) genes and the Wilms' tumour (WT1) gene were identified and their MRD levels followed in diagnostic and follow-up samples. Only WT1 identified as specific to normal karyotype AML met the necessary criteria to be an MRD marker. Although the majority of genes selected from the GEP in this study proved unsuitable as markers, the identification and validation of a marker already used for MRD monitoring, WT1, demonstrates the ability of gene expression profiling to identify potential minimal residual disease markers in normal karyotype AML.
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Wang, Wenchao. "Control of germline development and the germ-soma decision by the Caenorhabditis elegans mes genes." [Bloomington, Ind.] : Indiana University, 2008. 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:3334994.
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SANTOS, Francisco Gleidson Vieira dos. "A gente vive assim, mas a gente precisa de uma luz : as experiências religiosas das prostitutas que batalham na Praça do Diário Recife - PE." Universidade Federal de Pernambuco, 2010. https://repositorio.ufpe.br/handle/123456789/1065.
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Previous issue date: 2010Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Este estudo se debruça sobre as experiências religiosas das prostitutas que batalham na Praça do Diário, localizada no centro da cidade do Recife-PE. O foco da análise recai sobre os significados que tais mulheres atribuem à dimensão religiosa em suas vidas. Para tanto, por meio da observação etnográfica no referido local, e de entrevistas com enfoque biográfico, investigou-se as matrizes religiosas que as informantes se sentem pertencentes, quais os sentidos, a partir das suas perspectivas, que suas religiões atribuem à carreira de profissional do sexo. Por fim, buscou-se perceber como estas mulheres articulam suas práticas profissionais com o sagrado. A hipótese que conduziu o trabalho de investigação vislumbrou a possibilidade das mulheres prostitutas possuírem algum tipo de relação com a Pomba-gira. Por instrumentalizarem o aspecto mais intocável das religiões cristãs, a carne, as mulheres prostitutas não encontram aceitação/legitimidade para as suas práticas profissionais/sexuais nas religiões cristãs. Nesta perspectiva, apoiando-me em Geertz, no que se refere à noção de religião como sistema cultural, a Pomba-gira, símbolo sagrado disponibilizado pelos panoramas das religiões afrobrasileiras, emergiria como modelo para situar e mesmo organizar as condutas das mulheres prostitutas diante no mundo. Paradoxos a parte, as religiões acentuadas pelas prostitutas entrevistadas estão inseridas no segmento evangélico pentecostal. Entretanto, por não se conformarem às normas de sexo/ gênero/ elas não se ligam formalmente a tais religiões. Articulam estrategicamente o que lhes é "conveniente", desligam-se da instituição e passam a pessoalmente transacionar com Deus. Concernente à Pomba-gira, a hipótese não pode ser totalmente refutada, visto que no cotidiano da Praça do Diário, em diferentes contextos, a menção à entidade se faz presente, o que pode ser interpretado, como sugere Otávio Velho, não simplesmente como recursos lingüísticos, mas atingindo as esferas das crenças de comportamentos pessoais
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Gugolati, Maica. "Pretty Mas’, visuality and performance in Trinidad and Tobago’s contemporary carnival, West Indies." Thesis, Paris Sciences et Lettres (ComUE), 2018. http://www.theses.fr/2018PSLEH050/document.
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Cette recherche traite de la forme la plus contemporaine de mascarade du carnaval de Trinidad (République de Trinidad-et-Tobago, Caraïbe Anglophone), connue sous l’appellation Pretty Mas’. Cette dernière s’imprègne d’une esthétique nommée Bikini & Beads, pratiquée en majorité par les femmes et de jeunes participants. C’est la forme de mascarade la plus commerciale du pays et le modèle de carnavals diasporiques à travers le monde. L’objet de cette recherche est d’expliquer comment l’aspect visuel de la mascarade tend à transformer cette performance carnavalesque en spectacle.Je montre que la valeur historique de la pratique du carnaval évolue dans la forme contemporaine Bikini & Beads, où les joueurs portent de simples bikinis en guise de costumes. Cette recherche aborde également la question de la représentation de soi à travers ce style de carnaval où le corps des participants se substitue au costume. Les joueurs y affirment leur individualité et leur volonté d’interpréter des histoires autoréférentielles. La visibilité du joueur et de la joueuse devient un moyen d’affirmation de soi, ce qui modifie la pratique performative de la mascarade. J’analyse ensuite l’impact du visuel sur le management de ce style de mascarade. La recherche de visibilité des joueurs et la nécessité d’impressionner les publics modifient l’organisation des groupes de carnaval et la création des costumes. Le désir de reconnaissance publique des participants influe sur la pratique performative et représentationnelle de la mascarade. En privilégiant l’aspect visuel de l’évènement, la performance carnavalesque devient prévisible et reproductible pour son exportation dans les festivals internationauxThis research is about the most current form of carnival masquerade on the island of Trinidad (Republic of Trinidad and Tobago, West Indies), known as Pretty Mas'. Pretty Mas' is imbued with a masquerade style named Bikini & Beads, which is mostly practiced by women and young participants. It is the most commercial form of masquerade in the country and is the model for diaspora carnivals around the world. The object of this research is to explain how the visual aspect of this masquerade tends to transform the carnival performance into a spectacle.I show how the historical value of carnival practice has evolved into the contemporary form of Bikini & Beads, where players wear simple bikinis as costumes. This research deals with the question of self-representation through this masquerade style where the participants' bodies replace the costumes. In doing so players affirm their individuality and willingness to interpret self-referential stories. The player's visibility becomes a mean of asserting oneself, which modifies the performative practice of the masquerade. I then analyze the visual impact on the management of this form of performance and costuming. The players' search for visibility and their need to impress the public have changed the organization of carnival groups and the creation of costumes. The participants' desire for public recognition influences the performative and representational practice of the masquerade. I conclude by affirming that the emphasis on the visual aspect of the event makes the carnival performance more predictable and reproducible so it can be exported to the international festivals
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Pimentel, Renata Lucia Vieira. "Efeitos da deleção genética dos genes que codificam ECA2 e o receptor mas na evoluçãoda gravdez em camndongos." Universidade Federal de Minas Gerais, 2010. http://hdl.handle.net/1843/BUOS-8E3PMX.
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BACKGROUND: Pregnancy is characterized by an increase in many of the different components of the circulating renin-angiotensin system (RAS). During normal gestation, pregnant woman are normotensive because there is an increased activity of RAS. This could be due, at least in part, to the increased activity of the ACE2/Ang-(1-7)/Mas axis, the vasodilator arm of the RAS. However, it is not clear if the deficiency in this vasodilator axis is a consequence or contributing factor in the development of abnormalities in pregnancy. AIM: The aim of this study was to evaluate the effect of genetic deletion of MAS receptor or ACE2 in the RAS activity and in the hemodynamic changes present in the evolution of regnancy in mice. MATERIALS AND METHODS: To directly investigate this possibility the phenotypic alterations induced by ACE2 or MAS deficiency in C57Bl/6 and FVB/N were determined in pregnant mice. Twelve - twenty weeks old C57Bl/6 ACE2-/-, C57Bl/6 MAS-/-, FVB/N MAS-/-, and WT female mice were used for mating with males of similar background and genetic modification. Blood pressure was measured, by telemetry, before, during the pregnancy and until 3 days after delivery. The endothelial function was examined using isolated vessel preparations. The pups and placenta weight were assessed, as well as placental gene expression for RAS components and protein expression for VEGF- receptor. We also analyzed the hemodynamic of umbilical artery, on 19th pregnancy day, by ultrasound, as well as a renal function and a cytokine circulating levels. RESULTS: The female mice FVB/N MAS KO presented an increased, time-dependent, in the blood pressure levels, during the pregnancy; tendency to increased umbilical arteries resistivity index, fetal growth restriction, proteinuria, oliguria, increase in cytokines andendothelial dysfunction similar to some of the clinical manifestations found in the development of preeclampsia. Concomitantly with this finding, the deficiency in the MAS KO mice, in the genetic background C57Bl/6, resulted in the normal blood pressure levels, in the beginning, which remained until the end of pregnancy, although without the presence of proteinuria. However, in late pregnancy these females showed a pressure peak, with marked proteinuria, oliguria, increased cytokines, endothelial dysfunction, as well as a fetal growth restriction, demonstrating that the consequences of the MAS deletion, in pregnancy, is background dependent. In addition in the vasodilator axis of theRAS, the ACE2 deletion caused, in females, increased blood pressure before pregnancy. This phenotype was kept throughout the gestational period, associated, also, with striking fractional excretion of protein and fetal growth restriction, featuring some of the clinical symptoms observed in the context of women who develop preeclampsia superimposed onthe chronic arterial hypertension. CONCLUSION: The genetic deletion of the RAS-vasodilatatory axis components leads to abnormal hemodynamic adjustment during pregnancy, mainly characterized by elevated blood pressure in late pregnancy and fetal growth restriction in mice. These data support an important role of the ACE2 / Ang-(1-7) / Mas axis in the fetal development and hemodynamic adjustment during pregnancy, suggesting that this axis may be an important therapeutic target for the treatment of existing changes during pregnancy.INTRODUÇÃO: A gravidez é caracterizada por um aumento em muitos dos diferentes componentes do sistema renina-angiotensina (SRA) circulante. Durante a gravidez normal, as gestantes são normotensas graças a uma atividade aumentada do SRA. Este perfil pode ser devido, pelo menos em parte, a uma aumentada atividade do eixo ECA2 /Ang-(1-7) / MAS, o braço vasodilatador do SRA. Entretanto, não se sabe ainda se a deficiência nesse eixo vasodilatador seria uma conseqüência ou um fator contribuinte no desenvolvimento de alterações que ocorrem na gravidez. OBJETIVO: O objetivo deste trabalho foi avaliar o efeito da deleção genética do receptor MAS ou da ECA2 no comportamento do SRA e nas alterações hemodinâmicas presentes na evolução da gravidez em camundongos. MATERIAIS E MÉTODOS: Para avaliar diretamente essa possibilidade, alterações fenotípicas induzidas pela deficiência da ECA2 ou do MAS em camundongos C57Bl/6 e FVB/N foram determinadas na gravidez. Para isso utilizamos fêmeas C57Bl/6 ECA2-/-, C57Bl/6 MAS -/-, FVB/N MAS -/- e fêmeas controles WT, entre 12 e 20 semanas de vida, para acasalamento com machos de mesmo background e modificação genética. A pressão arterial foi mensurada por sistema de telemetria, antes e durante a gravidez, bem como até 3 dias após o parto. A função endotelial foi examinada usando a preparação de vaso isolado. O peso dos fetos e da placenta, bem como as expressões gênica placentária para componentes do SRA e protéica placentária para o receptor de VEGF foram avaliados. Também foi analisada a hemodinâmica da artéria umbilical no 19º dia gestacional, por meio de ultrassonografia, além da função renal e dos níveis circulantes de citocinas. RESULTADOS: As fêmeas FVB/N KO MAS apresentaram uma elevação tempodependente da pressão arterial durante a gestação; tendência a aumentado índice de resistividade das artérias umbilicais; restrição de crescimento fetal; proteinúria; oligúria;aumento de citocinas circulantes e disfunção endotelial, características essas similares a algumas das manifestações clínicas encontradas no desenvolvimento de Pré-Eclâmpsia. Concomitantemente a esse achado, a deficiência do MAS em camundongos no background genético C57Bl/6 provocou, a princípio, níveis pressóricos normais, que se mantiveram até o final da gestação, embora sem a presença de proteinúria. No entanto, ao final da gravidez essas fêmeas apresentaram um pico pressórico, com marcante proteinúria, oligúria, aumento de citocinas circulantes, bem como disfunção endotelial e restrição de crescimento fetal, demonstrando que as conseqüências da deleção do MAS, na gravidez, é background dependente. Ainda em relação ao eixo vasodilatador do SRA, a deleção da ECA2 causou, nas fêmeas, aumentados níveis pressóricos antes da gravidez. Esse fenótipo foi mantido durante todo o período gestacional, associado, ainda, com marcante excreção fracional protéica e restrição de crescimento fetal, caracterizando alguns dos sintomas clínicos verificados no quadro de mulheres que desenvolvem a Pré- Eclâmpsia sobreposta à hipertensão arterial crônica. CONCLUSÃO: A deleção genética de componentes do eixo vasodilatador do SRA causou ajustes hemodinâmicos alterados durante a gravidez, caracterizados, principalmente, por elevação da pressão arterial no final da gestação e restrição de crescimento fetal em camundongos. Estes dados suportam um importante papel do eixoECA2 / Ang-(1-7) / MAS no desenvolvimento fetal e no ajuste hemodinâmico durante a gestação, sugerindo que esse eixo possa ser um importante alvo terapêutico para o tratamento de alterações existentes durante o período gestacional.
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Chanet, Audrey. "Impact des flavanones des agrumes sur la prévention de l'athérosclérose et mécanismes d'action mis en jeu." Thesis, Clermont-Ferrand 1, 2011. http://www.theses.fr/2011CLF1MM02.
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Les maladies cardiovasculaires représentent l’une des principales causes de mortalitédans le monde et leur prévention constitue un enjeu majeur de santé publique. Les études épidémiologiques montrent que la consommation de fruits et légumes est associée à un moindre risque cardiovasculaire. Ces effets pourraient être expliqués par leur richesse en micronutriments et plus particulièrement en polyphénols. La consommation de flavanones, une classe de polyphénols présente spécifiquement et en grandes quantités dans les agrumes, a été inversement associée au risque d’accidents coronaires et d’accidents vasculaires cérébraux. Des données expérimentales obtenues in vivo et in vitro suggèrent que les flavanones (hespéridine ou naringine) possèdent des propriétés hypolipémiantes, hypotensives et anti-inflammatoires. Ces effets pourraient notamment être médiés par une modulation de l’expression de gènes par les flavanones. Cependant jusqu’à présent, l’action anti-athérogène des flavanones in vivo n’a été explorée qu’à des doses supra-nutritionnelles et les mécanismes responsables de ces effets sont encore largement méconnus. Par ailleurs, les données mécanistiques in vitro sont peu informatives, car obtenues avec des formes de flavanones non présentes dans l’organisme. Les objectifs de cette thèse ont donc été : (1) d’évaluer l’impact d’une consommation de flavanones (naringine et hespéridine) à dose nutritionnelle sur le développement de la lésion athéromateuse chez différents modèles murins d’hypercholestérolémie et d’appréhender les mécanismes moléculaires mis en jeu par une approche transcriptomique ; (2) de déterminer l’impact des métabolites circulants sur la fonction des cellules endothéliales et d’identifier les mécanismes moléculaires sous-jacents. In vivo, nous avons montré que seule la supplémentation en naringine (0,02%), la flavanone majoritaire du pamplemousse, réduisait la progression des lésions athéromateuses dans un modèle murin d’athérosclérose induite par l’alimentation (souris C57Bl/6J sous régime riche en graisse et en cholestérol). Cet effet était associé à une réduction des concentrations plasmatiques de non HDL-Chol et de biomarqueurs de la dysfonctionendothéliale, mais semblait indépendant d’une modulation du statut anti-oxydant. Une analyse transcriptomique pangénomique de l’aorte de ces animaux, a montré, que la supplémentation en naringine induisait une variation de l’expression de gènes impliqués dans des processus, tels que l’adhésion cellulaire ou l’organisation du cytosquelette, qui sont impliqués dans la migration trans-endothéliale des leucocytes. Ces résultats mettent en évidence de nouvelles cibles moléculaires d’action des flavanones qui ont été plus largement abordées in vitro. Les données obtenues in vitro montrent que l’exposition de cellules endothéliales(HUVEC) à des concentrations physiologiques de métabolites circulants de la naringénine(dérivés glucuronidés) ou de l’hespérétine (dérivés glucuronidés et sulfatés) diminue l’adhésion des monocytes (U937) aux cellules endothéliales, une étape clé de la migrationtrans-endothéliale. En accord avec ces résultats, une analyse TaqMan Low Density Array a montré que l’exposition des cellules endothéliales aux métabolites circulants de flavanones affectait l’expression de gènes impliqués dans l’inflammation, le chimiotactisme, l’adhésion ou encore la migration trans-endothéliale des leucocytes. Pris dans leur ensemble, les résultats de ce travail de thèse montrent que les effets antiathérogènesdes flavanones ne découlent pas exclusivement d’un effet hypolipémiant, mais aussi d’une action directe sur des étapes clés du développement de l’athérosclérose au niveau de l’endothélium, en particulier les processus d’adhésion et migration trans-endothélialeCardiovascular disease is a major cause of mortality worldwide and its prevention is a major public health issue. Epidemiological studies have shown that fruit and vegetables consumption is associated with a lower cardiovascular risk. These effects could be explainedby their richness in micronutrients, especially polyphenols. Consumption of flavanones, a class of polyphenols present specifically and in large amounts in citrus fruits, was inversely associated with risk of coronary events and stroke. Experimental data obtained in vivo and invitro suggest that the flavanones (hesperidin or naringin) have lipid-lowering, hypotensive and anti-inflammatory properties. These effects could be mediated via modulation of gene expression by these bioactives. However, the anti-atherogenic effect of flavanones in vivo has been only explored at supra-nutritional doses and the mechanisms responsible for these effects are largely unknown. Furthermore, in vitro mechanistic data are questionable as they have been obtained using native forms of flavanones which are not present in the body.The objectives of this thesis were: (1) to assess the impact of consumption of flavanones (naringin and hesperidin) at nutritional doses on the development of atherosclerotic lesions indifferent mouse models of hypercholesterolemia and decipher molecular mechanisms brought into play, using a transcriptomic approach, (2) to determine the impact of physiological concentrations of plasma flavanone metabolites on endothelial cell function and theunderlying molecular mechanisms. In vivo, we showed that only naringin supplementation (0.02%), the major flavanonein grapefruit, reduced the progression of atherosclerotic lesions in a mouse model of dietinduced atherosclerosis (C57BL/6J mice fed an enriched diet in fat and cholesterol). Thiseffect was associated with a reduction in plasma non-HDL-Chol and biomarkers ofendothelial dysfunction, but appeared independent of a modulation of antioxidant status. Agenome-wide transcriptome analysis of the aorta of these animals showed that naringin supplementation modulated expression of genes involved in processes such as cell adhesion and cytoskeleton organization; these latter being involved in leukocytes trans-endothelialmigration. These results reveal new molecular targets of action of flavanones that have beenfurther studied in vitro.The in vitro data showed that exposure of endothelial cells (HUVEC) to physiological concentrations of circulating metabolites of naringenin (glucuronides) or hesperetin(glucuronides and sulfate) decreased the adhesion of monocytes (U937) to endothelial cells, a key step in the trans-endothelial migration. Consistent with these results, a TaqMan Low Density Array analysis showed that exposure of endothelial cells to these flavanone metabolites affected the expression of genes involved in inflammation, chemotaxis, adhesionas well as leukocytes trans-endothelial migration. Overall, the results of this work show that the anti-atherogenic effect of flavanones is not exclusively derived from lipid-lowering effect, but also due to a direct action on the endothelium by modulating key processes of atherosclerosis development, particularly adhesion and trans-endothelial migration
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Grabowski, Monika. "Positionsklonierung des Locus für das Myoklonus-Dystonia-Syndrom (MDS) und Untersuchung des Epsilon-Sarkoglykan-Gens (SGCE) auf genomische Prägung." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-26578.
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Cubizolle, Aurélie. "Etude de l'efficacité du transfert du gène de la beta-D-glucuronidase dans le SNC de chiens atteints de mucopolysaccharidose de type VII." Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20220/document.
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La mucopolysaccharidose de type VII (MPS VII) est une maladie génétique de surcharge lysosomale provoquée par une déficience en β-D-glucuronidase (β-glu). β-glu est impliquée dans la cascade de dégradation et de recyclage des glycosaminoglycannes (GAGs). Sa déficience provoque une accumulation vésiculaire de GAGs non dégradés engendrant in fine la mort cellulaire. Notre but est de développer et de tester la pertinence des vecteurs adénoviraux canins helper-dépendant (HD-CAV-2) pour traiter la neurodégénération provoquée par la MPS VII dans le cadre d'une thérapie génique dans le SNC de chien. Parce que les vecteurs CAV-2 transduisent préférentiellement les neurones et qu'ils sont transportés de manière rétrograde le long des axones, leurs distributions dans tout le SNC permettraient de délivrer largement la β-glu dans tout le parenchyme cérébral. Nous avons alors étudié la sureté, la durée d'expression, l'efficacité et la possible réversion du phénotype après injections dans le SNC de chiens MPS VII d'un HD-CAV-2 exprimant le gène humain de la GUSB : HD-RIGIE. Des études préliminaires ont montré la faisabilité du transfert des vecteurs HD-CAV-2 dans le SNC, qu'ils induisaient une réponse immunitaire minimale et qu'ils transduisaient préférentiellement, efficacement et largement les neurones.Nous avons produit un HD-RIGIE de qualité pour les injections intracérébrales et nous avons analysé son efficacité sur l'accumulation de GAGs non dégradés. Les injections de HD-RIGIE montrent une augmentation générale de l'activité β-glu dans tout le SNC des chiens MPS VII (sites d'injections et structures éloignées comme le cortex) et ce 1 mois ou 4 mois après les injections. L'analyse de la GFP confirme une distribution globale de HD-RIGIE dans le SNC d'animaux de grande taille. De plus, grâce aux propriétés intrinsèques de la β-glu (transport rétrograde et phénomène de libération/recapture), nous avons observé une diminution générale de l'accumulation vésiculaire neuronale des GAGs non dégradés dans tout le parenchyme cérébral. D'autre part grâce à la stratégie d'isolement et de non vaccination des chiens MPS VII, nous n'observons ni de réponse immunitaire humorale, ni d'aggravation de l'inflammation du parenchymeMucopolysaccharidosis type VII (MPS VII) is a rare inherited lysosomal storage disease caused by β-D-glucuronidase (β-glu) deficiency. β-glu is involved in the physiological turnover of glycosaminoglycans (GAGs). Its deficiency causes accumulation of undegraded GAGs inside vesicles leading to cell death. Our goals are to develop and test the clinical relevance of helper-dependant (HD) canine adenovirus type 2 (CAV-2) vectors to treat neural degeneration caused by MPS VII in a dog model. Because CAV-2 targets preferentially neurons and traffics via axons, the distribution of the transgene throughout the CNS will allow widespread delivery of the missing lysosomal enzyme in these disorders with a minimum number of injections. We tested a HD-CAV-2 vector expressing the human GUS gene in the canine model of MPS VII for their safety, efficacy, duration of expression and possible reversion of the MPS VII induced symptoms.A previous study based on HD-CAV-EGFP vector injections in MPS VII-/- and healthy dogs showed that we are now able to inject HD-CAV-2 in the dog brain, have a minimal induction of the immune response, an efficient transduction of the neurons and an efficient biodistribution of transduced cells. After the production of a suitable vector (HD-RIGIE) for injections in the CNS of MPS VII dogs we analysed its efficiency on GAGS storage in neurons.Injections of HD-RIGIE showed after 1 month or 4 months post injections a widespread increase in general level of β-glu activity, in the sites of injections and in distant areas such as cortex. Analysis of GFP, also permit to observe a widespread biodistribution of the vector. Because of β-glu property of cross-correction we observed a global decreased in GAGs storage in the entire MPS VII brains. Finally, the dogs did not present humoral immune response and no aggravation of inflammation
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Barreta, Marcos Henrique. "Caracterização molecular dos componentes do sistema angiotensina-(1-7) durante a divergência folicular e expressão de genes de reparo da fita dupla de dna em embriões bovinos." Universidade Federal de Santa Maria, 2012. http://repositorio.ufsm.br/handle/1/4061.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThe first study characterized the expression of MAS receptor and key enzymes for Ang-(1-7) production, such as, ACE2, NEP and PEP during follicular development. Furthermore, the regulation of local Ang1-7 system was evaluated after the intrafollicular injection of fulvestrant (an estradiolreceptor inhibitor) in the dominant follicle. Cows were ovariectomized when the size between the largest (F1) and the second largest follicle (F2) was not statistically different (Day 2), slightly different (Day 3), or markedly different (Day 4). The mRNA abundance of genes encoding MAS receptor, ACE2, NEP and PEP was evaluated in the follicular cells from F1 and F2. The mRNA expression of MAS receptor was upregulated in the granulosa cells of F2 after the establishment of follicular deviation (Day 4), while PEP mRNA increased during (Day 3) and after (Day 4) the deviation process. However, the mRNA expression of ACE2 was upregulated in the granulosa cells of F1 during and after the deviation process. The mRNA expression of NEP was not regulated in F1 and F2. The MAS receptor was immunolocated in the granulosa and theca cells of F1 and F2 during follicular deviation. Moreover, MAS receptor gene expression increased when the F1 was treated with the estrogen receptor-antagonist in vivo. In conclusion, the expression profile of MAS receptor, ACE2, NEP and PEP in dominant and subordinate follicles indicated that Ang-(1-7) play a role in the regulation of the follicular dominance in cattle. A second study was performed to investigate the expression of genes that control homologous recombination (HR; 53BP1, ATM, RAD50, RAD51, RAD52, BRCA1, BRCA2 and NBS1), and non-homologous end-joining (NHEJ; KU70, KU80 and DNAPK), DNArepair pathways in bovine embryos with high, intermediate or low developmental competence. We also evaluated whether bovine embryos can respond to DNA double-stranded breaks (DSBs) induced by ultraviolet (UV) irradiation by regulating the expression of genes involved in the HR and NHEJ repair pathways. Embryos with high, intermediate or low developmental competence were selected based on the cleavage time after in vitro fertilization and were removed from in vitro culture before (36 h), during (72 h) and after (96 h) the expected period of embryonic genome activation (EGA). All studied genes were expressed before, during and after the EGA period regardless the developmental competence of the embryos. Higher mRNA expression of 53BP1 and RAD52 was found before EGA in embryos with low developmental competence. Expression of 53BP1, RAD51 and KU70 was downregulated at 72 h and upregulated at 168 h post-fertilization in bovine embryos with DSBs induced by UV irradiation. In conclusion, important genes controlling HR and NHEJ repair pathways are expressed in bovine embryos before, during or after EGA. Lower developmental competence seems to be associated with a higher mRNA expression of 53BP1 and RAD52. Bovine embryos can response to UV-induced DSBs after the EGA but HR and NHEJ repair pathways seem to be particularly regulated at the blastocyst stage.
O primeiro estudo caracterizou a expressão do receptor MAS e de enzimas responsáveis pela produção de Ang-(1-7), tais como, enzima conversora de angiotensina 2 (ACE2), endopeptidase neutra (NEP) e prolil endopeptidase (PEP) durante o desenvolvimento folicular. Além disso, a regulação local do sistema Ang-(1-7) foi avaliada após a injeção intrafolicular de fulvestrant (inibidor do receptor de estradiol) no folículo dominante. As vacas foram ovariectomizadas quando o tamanho entre o maior (F1) e o segundo maior folículo (F2) não era estatisticamente diferente (D2), ligeiramente (D3) ou marcadamente diferente (D4). A expressão de RNAm do receptor MAS, ACE2, NEP e PEP foi avaliada nas células foliculares do F1 e F2. O receptor MAS foi mais expresso nas células da granulosa do F2 após o estabelecimento da divergência folicular (D4), enquanto a expressão de PEP aumentou durante (D3) e após (D4) o processo de divergência. Entretanto, a expressão de ACE2 foi maior nas células da granulosa do F1 durante e após a divergência. A expressão de PEP não foi regulada no F1 e F2. O receptor MAS foi imunolocalizado nas células da teca e granulosa do F1 e F2 durante a divergência folicular. A expressão de RNAm do receptor MAS aumentou quando o F1 foi tratado com fulvestrant in vivo. Em conclusão, o perfil de expressão do receptor MAS, ACE2, NEP e PEP nos folículos dominante e subordinado indicam que a Ang-(1-7) apresenta uma função na regulação da dominância folicular em bovinos. Em um segundo estudo investigamos a expressão de genes que controlam o reparo do DNA através das vias de recombinação homóloga (HR; 53BP1, ATM, RAD50, RAD51, RAD52, BRCA1, BRCA2, NBS1) e união terminal não homóloga (NHEJ; KU70, KU80, DNAPK) em embriões bovinos com alta, média ou baixa competência de desenvolvimento. Foi também avaliado se embriões bovinos podem responder a quebra na fita dupla de DNA (DSBs), induzida por irradiação UV, através da regulação de genes envolvidos nas vias de reparo HR e NHEJ. Embriões com alta, média ou baixa competência de desenvolvimento foram selecionados pelo tempo de clivagem após a fertilização in vitro e foram removidos do cultivo antes (36 h), durante (72 h) ou após (96 h) o momento esperado para a ativação do genoma embrionário (AGE). Todos os genes foram expressos antes, durante e após a AGE independentemente da competência de desenvolvimento dos embriões. A expressão de 53BP1 e RAD52 foi maior antes da AGE em embriões com baixa competência de desenvolvimento. A expressão de 53BP1, RAD51 e KU70 foi mais baixa as 72 h e maior as 168 h pós fertilização em embriões com DSBs induzida por irradiação UV. Em conclusão, genes importantes para o controle das vias de reparo HR e NHEJ são expressos em embriões bovinos independentemente do tempo de cultivo ou da competência de desenvolvimento. A menor competência de desenvolvimento embrionário parece estar associada com maior expressão de 53BP1 e RAD52. Os embriões bovinos respondem a DSBs após a AGE mas as vias HR e NHEJ são reguladas principalmente no estágio de blastocisto.
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Marcerou, Philippe. "André Antoine, fondateur et directeur du Théâtre Antoine (1897-1906) : thèses présentée et soutenue le 4 mars 2002." Besançon, 2002. http://www.theses.fr/2002BESA1021.
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André Antoine (1858-1943) a créé le Théâtre libre en 1887, une scène d'amateurs, où, s'inspirant des recommandations de Zola, il a renouvelé le répertoire, regroupé les comédiens en une troupe homogène, fait émerger la fonction d'un metteur en scène chargé de coordonner la représentation. En 1897, Antoine fonde un théâtre privé, le Théâtre Antoine, qu'il dirige de 1897 à 1906. Il y poursuit du Théâtre libre, menant de front une ambition artistique, une ambition financière et une ambition personnelle, se fixant pour objectif de faire "un théâtre littéraire à bon marché", qui offre au public "du bon théâtre, bien joué". Le théâtre Antoine produit un théâtre du quotidien qui décrit la société, en montre les limites et en dénonce les scandales. Le drame et la pièce sociale (Brieux, Curel, Ibsen, Hauptmann) tiennent la première place jusqu'en 1902. Après cette date, Antoine crée surtout des pièces à grandes mises en scène (La Terre, Le Roi Lear). . .
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Rudi, Nderim. "An ex ante economic impact analysis of developing low cost technologies for pyramiding useful genes from wild relatives into elite progenitors of cassava." Thesis, Virginia Tech, 2008. http://hdl.handle.net/10919/34145.
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This study conducts an ex-ante economic impact evaluation of developing low cost technologies for pyramiding useful genes from wild relatives into elite progenitors of cassava in Nigeria, Ghana and Uganda. More specifically, it estimates the change in economic surplus generated by introducing cassava varieties with tolerance to cassava mosaic disease, green mites, whiteflies, and delayed post-harvest deterioration. It compares the economic benefits of marker-assisted selection (MAS) to conventional breeding for these traits. Results indicate that varieties developed with marker-assisted breeding that incorporate all three traits are worth US$2.89 billion in Nigeria, $854 million in Ghana, and $280 million in Uganda over 20 years. If these varieties were to be developed with tolerance to CMD and Green mites alone they would be worth US$1.49 billion in Nigeria, $675 million in Ghana, and $52 million in Uganda if developed through MAS. If developed solely by conventional breeding they would be worth about US$676 million in Nigeria, $304 million in Ghana, and $18 million in Uganda. The difference is mostly due to the faster timing of release for the varieties developed with MAS and the higher probability of success. Several sensitivity analyses were conducted and benefits for MAS range from US$1.7 billion to US$4.3 billion for all three traits depending on assumptions. In all cases, the research investment is highly profitable from a societal standpoint.Master of Science
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Araujo, Fabiana Itaci Corrêa de. "...Mas a gente não sabe que roupa dever usar : um estudo sobre a prática do psicólogo no Centro de Referência de Assistência Social." Pontifícia Universidade Católica de São Paulo, 2010. https://tede2.pucsp.br/handle/handle/17415.
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The present research aims to analyze the pratical of psychologists of Social Assistance Centers (CRAS) in its implication with the subjectivity as a dimension of action in the Social Security Politics. The qualitative study was developed from the perspective of the Critical Social Psychology Theory, with a historical dialectical materialist basis. In order to accomplish our objective, three psychologists had been interviewed (half-directed interview). They worked at the public, municipal service, servers of the CRAS for, at least, six months. From the stories produced with the interviews, units of sense had been raised. Hence, those units were collated having as reference the norms of Social Security and the principles of Critical Social Psychology. This was done in dialog with others researches of NEXIN that were about similar themes. In this process it is evident the importance attributed to the practical knowledge developed by the Social Service, the daily attendance to the demands of the population, the importance of the group as privileged unit of work and the purpose attributed for the psychologist for its practical professional in this social-occupational space. The results point the character of process in the construction of a proper place of Psychology in the Social Assistance, and demonstrate the political difficulties joined during the formation and organization of the work of accomplishing the objectives of the basic social protection. This construction is crossed by the contradictions that determine the Social Assistance as an area of public politic, understood in the movement of the production and reproduction of the social life, and of the historical constitution of Psychology as an area of knowledge and practical professional
A presente pesquisa tem como objetivo analisar a prática do psicólogo nos Centros de Referência da Assistência Social (CRAS) em sua implicação com a subjetividade como dimensão de ação da Política de Assistência Social. Trata-se de um estudo qualitativo desenvolvido a partir do referencial teórico-metodológico da Psicologia Social crítica, de base materialista histórica dialética. Para tanto, foram entrevistados (entrevista semi-dirigida) três psicólogos, servidores públicos municipais, trabalhadores do CRAS, há, no mínimo, seis meses. A partir dos relatos produzidos com as entrevistas foram levantadas as unidades de sentido de cada sujeito. Essas foram confrontadas tendo como referência as normatizações da Assistência Social e os pressupostos da Psicologia Social Crítica, em diálogo com as pesquisas já desenvolvidas pelo NEXIN com uma temática próxima à desta. Nesse processo destacam-se a importância atribuída aos conhecimentos e práticas desenvolvidas pelo Serviço Social ao atendimento cotidiano às demandas da população, a importância do grupo como unidade de trabalho privilegiada e a finalidade atribuída pelo psicólogo para sua prática profissional neste espaço sócio-ocupacional. Os resultados apontam para o caráter processual da construção de um lugar próprio da Psicologia na Assistência Social e as dificuldades encontradas de ordem política, de formação e de organização do trabalho, na consecução dos objetivos da proteção social básica. Essa construção é atravessada pelas contradições que determinam a Assistência Social como área da política pública, entendida no movimento de produção e reprodução da vida social, e da constituição histórica da Psicologia como área do conhecimento e prática profissional
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Sousa, Anne Gabriele Lima. "“Eu sou de rua, mas também sou gente” : intersubjetividade e construção de identidades dos indivíduos em situação de rua de João Pessoa-PB." Universidade Federal de Pernambuco, 2012. https://repositorio.ufpe.br/handle/123456789/11303.
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Capes
Esta tese teve como objetivo compreender as bases para a construção de identidades entre os indivíduos adultos em situação de rua. O marco teórico que deu subsídios para a realização desse estudo consistiu nas contribuições teóricas de Taylor sobre a constituição da identidade do self, em diálogo com as reflexões de Bourdieu sobre as distinções na sociedade contemporânea e de Goffman sobre as interações vivenciadas por indivíduos estigmatizados. A pesquisa foi realizada através de um trabalho de campo no centro da cidade de João Pessoa-PB, onde foram realizadas observações espontânea e participante, além de entrevistas em profundidade com 18 indivíduos em situação de rua que habitam os espaços de maior concentração dessa população. A análise qualitativa das entrevistas buscou assimilar tanto os aspectos objetivos como os aspectos subjetivos que permeiam as identidades dos indivíduos na rua. Para entender a dimensão estrutural sob a qual essas identidades são delineadas a rua foi tratada como um campo, no interior do qual os indivíduos estão situados em posições desiguais e participam de relações de poder específicas, inclusive por meio de marcadores estigmatizantes. A subjetividade inerente ao modo como os indivíduos interpretam sua condição e assumem identidades nesse contexto foi buscada através do ordenamento daqueles elementos valorizados por cada um deles em função da avaliação de suas situações objetivas. Conclui-se que, embora as condições socioestruturais nas quais esses indivíduos estão posicionados sejam responsáveis por localizá-los em um contexto que estabelece os limites e possibilidades de seu estar-no-mundo, as identidades pessoais reivindicadas por eles rompem com qualquer determinismo estrutural, fazendo com que empreendam distinções na vida de rua e se autoavaliem a partir de um ordenamento de valores que confere sentido à sua existência e ao seu ambiente.
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Kubaski, Francyne. "Padronização de um protocolo para identificação de mutações no gene da GALNS em pacientes com MPS IVA através das técnicas de PCR-ARMS (Amplification Refractory Mutation System) e sequenciamento." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/67647.
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Introdução: Mucopolissacaridose IVA ou Síndrome de Morquio A é uma doença autossômica recessiva causada pela deficiência da enzima lisossomal Nacetilgalactosamina- 6-sulfatase (GALNS), que resulta no acúmulo lisossomal dos glicosaminoglicanos: Queratan sulfato e Condroitin-6-sulfato nos tecidos causando as manifestações clínicas. Os fenótipos variam da forma clássica à forma atenuada, ambas sem comprometimento cognitivo. A prevalência de MPS IVA varia de 1/76.000 a 1/640.000 nascidos vivos. Objetivos: Analisar e caracterizar o genótipo de pacientes brasileiros com MPS IVA através de estudos de mutações no gene da GALNS, possibilitando a estimativa de frequência de mutações recorrentes e o estabelecimento um protocolo de rotina para triagem dessas mutações. Métodos: Análise molecular do gene da GALNS foi realizada em 26 pacientes brasileiros inicialmente através de PCR-ARMS para detecção de seis mutações recorrentes (p.G116S/ p.G139S/ p.L307P/ p.N164T/ p.R386C e p.S341R) seguidas pela amplificação de regiões codificantes por PCR e sequenciamento. Resultados: Essas mutações foram encontradas em 61,5% da nossa amostra, com uma frequência alélica de 55,8%. Destas, a mutação mais frequente foi p.S341R (26,9%), seguida de p.R386C (21,1%) e p.G116S (7,7%). As mutações p.N164T, p.G139S, p.L307P não foram encontradas em nossa amostra. Além destas, foi encontrada por sequenciamento do éxon 5 uma mutação nova p.C165Y. Conclusão: O protocolo usado para detecção de mutações comuns mostrou-se adequado como um screening inicial de mutações no gene da GALNS, identificando mutações em 61,5% dos pacientes e permitiu a caracterização de 55,8% dos alelos. A mutação p.S341R foi encontrada apenas em pacientes do Nordeste. A identificação de indivíduos heterozigotos nessas famílias será importante para aconselhamento genético e para estimar a prevalência da doença nessa região. Estudos adicionais para identificação da origem dessa mutação, incluindo análises de segregação e haplótipo estão em andamento, e serão avaliadas em conjunto com dados epidemiológicos.Background: Mucopolysaccharidosis IVA or Morquio A syndrome, is an autosomal recessive disorder caused by deficiency of lysosomal enzyme Nacetylgalactosamine- 6-sulfatase (GALNS), which results in lysosomal storage of glycosaminoglycans: Keratan sulfate and Chondroitin-6-sulfate in tissues causing clinical manifestations. The phenotypes vary from the classical to attenuated form, both without cognitive impairment. The prevalence of MPS IVA ranges from 1/76.000 to 1/640.000 live births. Objective: To analyze and characterize the genotype of Brazilian patients with MPS IVA, through molecular study of mutations in the GALNS gene, enabling the estimative of frequency of recurrent mutations and the establishment of a protocol for routine screening of these mutations. Methods: Molecular analysis of GALNS gene was performed in 26 Brazilian patients initially by ARMS-PCR to detect six recurrent mutations (p.G116S/ p.G139S/ p.L307P/ p.N164T/ p.R386C and p.S341R) followed by amplification of coding regions by PCR and sequencing. Results: These mutations were found in 61.5% of our sample, which were present in 55.8% of the alleles. The most frequent mutation was p.RS341R (26.9%), followed by p.R386C (21.1%) and p.G116S (7.7%). Mutations p.N164T, p.G139S, p.L307P were not found in our sample. A novel mutation p.C165Y was found after sequencing of exon 5. Conclusion: The protocol used for detection of common mutations was shown to be adequate for a first screening of mutations at the GALNS gene, once it identified the genotype in 61.5% of patients and allowed the characterization of 55.8% of alleles. The p.S341R was found only in patients from the Northeast. The identification of heterozygous individuals within these families will be important for genetic counseling and for estimating the disease prevalence in this region. Further studies to identify the origin of this mutation, including haplotype and segregation analyses are in progress, and will be evaluated in conjunction with epidemiological data.
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Souza, Márcia Alves de. "Avaliação do desempenho da PCR Multiplex alelo específico para detecção de genes de Mycobacterium tuberculosis associados à resistência a Rifampicina e Isoniazida, a partir de amostra clínica." Universidade Federal do Amazonas, 2013. http://tede.ufam.edu.br/handle/tede/2565.
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A Tuberculose (TB) é uma doença infecciosa causada pelo complexo Mycobacterium tuberculosis, sendo considerada um grave problema de saúde pública mundial. Atualmente, isolados de M. tuberculosis resistentes a pelo menos um medicamento utilizado no tratamento da TB tem sido documentados em todos os países. De acordo com a Organização Mundial de Saúde (OMS) a TB multirresistente (TBMR) é definida quando, isolados de M. tuberculosis de pacientes apresentam resistência a pelo menos Isoniazida e Rifampicina, os dois fármacos fundamentais no tratamento da TB. A resistência à Rifampicina tem sido associada às mutações gênicas no bacilo, no gene rpoB (referentes aos códons 531, 526 e 516). Para a Isoniazida, as mutações associadas à resistência têm sido relatadas nos genes katG, inhA, ahpC e kasA, sendo que a mutação no gene katG, referente ao códon 315, tem sido a mais citada para resistência a este fármaco. Neste contexto, métodos moleculares têm sido propostos pra detecção de mutações gênicas, em isolados de M. tuberculosis, que possam estar associadas à resistência aos fármacos. O presente estudo avaliou o desempenho da PCR multiplex alelo específico (PCR-MAS), diretamente em 86 amostras de escarro de pacientes com TB pulmonar multibacilares (n=42) e paucibacilares (n=44) da Policlínica Cardoso Fonte. A PCR-MAS teve como alvos: os genes katG ,inhA e rpoB. A concordância entre a PCR-MAS e o Método de Redução de Nitrato foi avaliada utilizando o teste kappa e a associação entre as mutações gênicas e a resistência fenotípica aos fármacos foi realizada pelo teste exato de Fisher. A análise de concordância, pelo teste kappa, foi realizada entre as PCR-MAS a partir de amostra de escarro e de isolados de M. tuberculosis. A PCR-MAS apresentou fraca concordância com o Método de Redução de Nitrato, pois de 18 amostras resistentes à Isoniazida, apenas em 4 (22,2%) foram detectadas as mutações para o gene katG ou inhA. No entanto, a avaliação da sensibilidade fenotípica à Rifampicina, apresentou boa concordância com a PCR-MAS (kappa = 0,7237), quando as amostras foram de pacientes de TB pulmonar multibacilar. Além disso, houve associação da presença de mutações no gene rpoB com resistência fenotípica à Rifampicina (p = 0.0014). Em relação a concordância entre as PCR-MAS, de amostras de escarro e seus respectivos isolados de M. tuberculosis, o desempenho foi excelente quando testados em amostras de pacientes com TB pulmonar multibacilar, para detecção de mutações no gene rpoB (kappa = 0,7742). Portanto, os resultados obtidos com a PCR-MAS, a partir de amostras de escarros, foram satisfatórios e poderão ser utilizados para monitorar e pesquisar as mutações associada à resistência à Rifampicina em pacientes de TB multibacilar na rede básica de saúde, pois é um teste rápido, reprodutível e de menor custo.
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Dornelles, Clara Zeni Camargo. "A gente não quer ser tradicional, mas... como e que faz, dai? : a inovação curricular e o debate popularizado sobre lingua portuguesa e ensino." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/269359.
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Orientador: Ines SignoriniTese (doutorado) - Universidade Estadual de Campinas, Instituto de Estudos da Linguagem
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Resumo: Esta pesquisa se insere no campo da lingüística aplicada transdisciplinar de orientação crítica e etnográfica e resulta da busca pela compreensão das relações entre o debate popularizado sobre língua portuguesa e ensino e as demandas de inovação curricular ocasionadas pelo projeto de desenvolvimento e modernização do país. O problema de pesquisa foi articulado a partir da minha experiência enquanto formadora e professora de lingüística em um curso de Letras de uma universidade privada no interior de Santa Catarina. Um dos objetivos da tese foi analisar as condições sócio-históricas e políticas de produção do debate e sua relação com a demanda globalizante de inovação curricular. Para atingir esse objetivo, focalizei as obras produzidas, no período de 1997 a 2007, por dois dos protagonistas do debate: Marcos Bagno e Pasquale Cipro Neto. A análise do debate em escala nacional evidenciou que Bagno faz uso estratégico dos enquadres científico, polarizador, militante e pedagógico para construir autoridade ¿em nome da ciência¿, frente ao público em geral, e, mais recentemente, para analisar e propor políticas de educação lingüística, frente à academia e aos professores de língua portuguesa. Já Pasquale, faz uso dos enquadres científico, normativo e lúdico, para se aproximar da ciência e dos discursos oficiais de renovação do ensino e, assim, afastar-se da imagem de professor de português tradicional. Os resultados sugerem que, apesar dos esforços de Bagno por atuar no modelo polarizador, Pasquale constantemente desfaz as fronteiras entre lingüística e tradição gramatical popularizada, evidenciando que o debate se desenvolve em campos de forças e de lutas marcados por tensões para manter ou mudar a ordem e as hierarquias disciplinares. O outro objetivo da tese foi examinar a configuração da demanda por inovação no curso de Letras a partir de onde realizei minha investigação. Os dados para esta análise resultaram sobretudo do trabalho de campo realizado em 2003 e 2004, período em que o curso passava pela reforma de seu próprio currículo. Tal análise evidenciou que as forças produtoras da demanda local por inovação no estudo/ensino de língua portuguesa eram múltiplas: o mercado, a escola, o Estado, a divulgação científica e a mídia. A análise também mostrou que os agentes re/con/textualizam metadiscursos vistos como tradicionais, acionando os enquadres pedagógico e científico, para compatibilizar as tensões entre o novo e o velho no processo de construção de seus objetos de ensino. Nesse contexto, os conceitos e argumentos oriundos do debate nacional sobre língua portuguesa e ensino assumem valor específico, em função dos recursos disponíveis, das urgências institucionais e das relações locais de poder. Ainda que as mudanças institucionais se estruturem sobre demandas nacionais e oficiais, localmente as inovações nem sempre se configuram da forma como prevê o projeto acadêmico de esclarecimento ou de inovação respaldado pelo Estado
Abstract: This research was developed within the field of applied linguistics of critical and ethnographic orientation. It results from my search to understand the relations between the popularized debate about portuguese language and teaching and curriculum innovation demands. The research question was articulated to my experience as a teacher educator and professor of linguistics in the Curso de Letras in a private university in the interior of Santa Catarina. One of the objectives of the thesis was to analyze the historical, social and political conditions of production of the debate and its relations to the national demands for curricular innovation. This analysis focused the work of Marcos Bagno and Pasquale Cipro Neto, produced from 1997 to 2007. The analysis of the national scale debate showed that Bagno makes strategic use of the scientific, polarized, militant and pedagogical frames to construct authority ¿on the name of science¿, when interacting with the general public, and more recently, to analyze and propose language education politics, when interacting with the academic public and portuguese language teachers. Pasquale makes use of the scientific, normative and ludic frames, in order to approximate science and the official discourses on curricular innovation. This way he gets rid of the image of a traditional portuguese language teacher. The results suggest that, despite Bagno¿s efforts to act on the polarized model, Pasquale constantly pull down the borders between linguistics and the popularized grammatical tradition. The debate is developed within fields of forces and fights marked by tensions to maintain or change disciplinary order and hierarquies. The other objective was to examine the configuration of the innovation demands in the Curso de Letras that was my locus of research. I then found out that the local demands establish connections with national and international curricular politics, which are associated to politics of economical development and modernization of the country. The analysis also showed that the agents re/con/textualize metadiscourses seen as traditional within pedagogical and scientific frames, in a way to make the tensions between the new and the old converge. In this context, the concepts and arguments from the national debate about portuguese language and teaching assume specific values, because of the avaliable resources, the institutional urgencies and the local relations of power. In spite of the fact that the institutional changes are structured on national and official demands, locally, innovations are not always established the ways that are previewed by the enlightenment academic project or the state innovation project
Doutorado
Lingua Materna
Doutor em Linguística Aplicada
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Costa, Cesar Augusto Sam Tiago Vilanova. "Avaliação da expressão de genes de resistência às múltiplas drogas (MDRs) e de metabolização em diferentes linhagens celulares tratadas com complexos metálicos de rutênio." Universidade Federal de Goiás, 2013. http://repositorio.bc.ufg.br/tede/handle/tede/3769.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Não consta resumo em outro idioma.
Foi com a descoberta da atividade antimitótica da cisplatina por Rosenberg na década se 1960 e 70, em seu célebre estudo com bactérias Escherichia coli, que surgiu o interesse em sintetizar e entender as bases moleculares responsáveis pelo mecanismo de ação biológica dos compostos metálicos, visto que a própria cisplatina foi inicialmente sintetizada por Peyrone nos idos de 1840. Os primeiros estudos envolvendo o uso de complexos metálicos de rutênio como agentes antitumorais foram realizados por Tochter no final dos anos 1980 (Dale et al., 1992). Àquela época, foi inferido que todos os compostos de rutênio apresentavam como mecanismo de ação, a sua ligação com o DNA, formando adutos e desencadeando processos celulares de natureza deletéria que, por fim, levariam a morte celular. É interessante lembrar que esse é o mesmo mecanismo de ação dos compostos de platina mais aceitos nos dias atuais. Sadler e Dyson (2003) estudando compostos de rutênio que continham cloro em sua estrutura, como o cloreto de cis-(dicloro)tetraaminorutênio(III) [cis-[RuCl2(NH3)4]Cl], observaram que estes compostos apresentavam mecanismos de ação biológica muito parecidos com os apresentados pela cisplatina [Pt(NH3)2Cl2], onde a hidrólise da ligação Ru–Cl pode ser fortemente influenciada pela natureza dos coligantes presentes na estrutura do rutenato, como grupamentos amino ou até mesmo pela presença de átomos de carbono. A alta concentração de cloretos no sangue permite a esses compostos metálicos, levados por proteínas séricas, chegar até as células e atravessar sua membrana celular e nuclear. Uma vez no interior do núcleo, a ligação Ru–Cl é hidrolisada, devido a queda abrupta da concentração de cloretos (que é cerca de 25 vezes menor), levando o composto a se ligar ao DNA, mais especificamente à posição N7 da base nitrogenada guanina. Por outro lado, compostos que não possuem cloro em sua estrutura, parecem apresentar mecanismos de ação diferentes ao padrão "ligação ao DNA". Sabe-se que compostos que apresentam carboxilatos em sua molécula, como a carboplatina, oxaliplatina e o próprio ditionato de cis-tetraammino(oxalato)rutênio(III) [Cis-[Ru(C2O2)(NH3)4]2(S2O6)], uma vez no interior das células, são hidrolisados muito mais lentamente do que os compostos ricos em cloretos, o que leva a um acúmulo desses compostos no citoplasma, diminuindo sua migração até o núcleo e, assim reduzindo a sua capacidade de se ligar ao DNA. Mas se o DNA não é o alvo desses compostos, então, quem poderia ser? Essa pergunta está sendo respondida com recentes estudos, que revelaram a interação desses compostos, ricos em carboxilatos, com uma miríade de proteínas e enzimas, que vão desde catepsinas, chegando até mesmo à Pgp (Melchart & Sadler, 2008). Estudos realizados por Dyson e colaboradores (2007), utilizando alguns inibidores da proteína Pgp, como fenoxazinas e antracenos, coordenados com compostos de rutênio, observaram que estes novos complexos não somente inibiram a ação da enzima, como também induziram morte celular, demonstrando uma multifuncionalidade. Seguindo essa linha de pensamento, acreditamos que a capacidade do composto ditionato de cistetraammino(oxalato)rutênio(III) em induzir apoptose nas células tumorais, assim como os baixos níveis de expressão de Pgp apresentados pelas células tratadas, corroboram os resultados previamente observados por outros grupos, utilizando compostos de rutênio similares. A resistência a fármacos mediada por Pgp é o mecanismo de MDR mais estudado atualmente. Apesar do desenvolvimento de novos agentes antitumorais, a MDR mediada pela Pgp protege as células de possíveis agentes citotóxicos, limitando a eficácia dos tratamentos quimioterápicos em pacientes com câncer. Atualmente, a extensa maioria dos inibidores da Pgp disponíveis estão associados a vários inconvenientes, que limitam o seu uso no reestabelecimento da eficácia da quimioterapia antineoplásica, após o aparecimento do fenótipo MDR. A procura de inibidores de Pgp alternativos, com um processo sintético exequível e efeitos secundários reduzidos, continua a ser um desafio para os químicos, farmacêuticos e pesquisadores. É nesse contexto que estão sendo desenvolvidos e estudados novos agentes antitumorais que possam agir como inibidores de Pgp, apresentando um efeito dual, ou até mesmo multifuncional, no tratamento clínico das neoplasias malignas. Muito tem se discutido que a próxima geração de fármacos antitumorais poderá ser formada por substâncias que se ligam a mais do que um único alvo terapêutico, o que poderia acelerar tratamento contra a doença, reduzindo o número e a concentração de fármacos que deveriam ser administrados, como os coquetéis atualmente utilizados, e até mesmo aumentando a adesão ao tratamento por parte do paciente. No presente trabalho, estudamos dois complexos de rutênio, o cloreto e o ditionato de rutênio(III), que se apresentam como promissores no possível desenvolvimento de um novo fármaco antitumoral. Essa promessa transparece no fato de ambos serem de síntese química relativamente simples (processo sintético exequível) e, principalmente, por apresentarem efeito biológico de interesse em células tumorais, como citotoxicidade e indução de morte celular, especialmente por apoptose. Pelo que foi observado nos resultados de nossa pesquisa, os complexos aqui estudados, podem constituir um modelo para o estudo de novos agentes anticancerígenos com concomitante capacidade de não induzir MDR. Esta característica se mostrou muito evidente sobre a linhagem leucêmica K-562, onde os níveis de expressão de MDR1, após o tratamento com os rutenatos, foram muito inferiores aos apresentados pelas células tumorais tratadas com o fármaco controle Cisplatina. Ainda, é importante pontuar que o composto ditionato de cistetraammino(oxalato)rutênio(III) apresentou efeito citotóxico em ambas as linhagens tumorais K-562 e A549, sem contudo induzir altos níveis de expressão de Pgp (MDR1), apresentados pelos fármacos platinados. Assim, estudos mais aprofundados sobre a estrutura e funcionamento biológico desses complexos de rutênio, representam um ponto de partida interessante para o desenvolvimento de fármacos multifuncionais e de efeito desejável, auxiliando na delineação de estudos clínicos dirigidos a grupos selecionados de pacientes que reúnam características genotípicas e fenotípicas preditivas de máxima resposta terapêutica com mínima toxicidade. Posteriormente, estes estudos podem levar às realizações de testes diagnósticos e farmacológicos mais eficazes que poderão ser estabelecidos como rotina voltada para uma melhor definição de tratamentos. Isso traria um maior sucesso no teste de novos medicamentos e reduziria os custos e riscos, minimizando o tempo gasto para aprovação de um novo medicamento e a sua disponibilização para a sociedade.
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Vencatto, Rudy Nick. "Mas com isso a gente começou duas vezes no meio do mato : memórias dos desapropriados do Parque Nacional do Iguaçu (Oeste do Paraná, 1970-2009)." Universidade Estadual do Oeste do Paraná, 2010. http://tede.unioeste.br:8080/tede/handle/tede/1765.
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Previous issue date: 2010-09-17Esta investigación analiza el proceso histórico de expropriación de los colonos agricultores que vivian dentro del Parque Nacional de Iguazú (PNI) en el Oeste de Paraná, que se produjo en la década de 1970. En este sentido, investiga las memórias y dinámicas socioculturales relacionados con la institución del parque como una zona de protección ambiental. Aunque oficialmente decretado desde 1939, por el entonces Gobierno de Getulio Vargas, fue recién en la década de 1960, en el proceso más amplio de la ocupación de la frontera, que muchas familias, principalmente de los estados de Santa Catarina y Rio Grande do Sul ocuparan y colonizaran este el espacio. En este proceso, algunas familias han establecido asentamientos en la zona delimitada en el parque, que fueron expulsados más tarde por el entonces IBDF y el INCRA. Situado en una región fronteriza entre Brasil y Argentina, su formación se relaciona con el preocupación del Estado aos domíneos de la frontera nacional. Por esa razón, la investigación historiza las discusiones ambientales que llegó a prevalecer en el Brasil de finales del siglo XIX, motivado por cuestiones externas vividas por el país. Así, también, discute el movimiento intelectual y político, que a lo largo de los siglos XIX y XX, comenzaron a construir los valores y significados acerca de la naturaleza, que posteriormente la definiran en su relación con la cultura como instancias dicotómicos. Metodológicamente, se utiliza la Historia Oral, que permitió pensar las diferentes maneras como los propios agricultores colonos recordan las experiencias de expropiación vividas en aqueles años. En la dinámica del conflicto, las memorias posiblen poner los ojos sobre la ocupación del Oeste de Paraná, así como para las trayectorias de los expropriados. Através de narraciones orales y otros documentos oficiales, la investigación, se evalúa para comprender las relaciones específicas envolvidas en el proceso de el reasentamiento de los antiguos residentes de PNI, cuando empezaron a construir nuevas relaciones de pertenencias y otros vínculos de reciprocidad
Esta pesquisa problematiza historicamente o processo de expropriação de agricultores colonos que viviam no interior do Parque Nacional do Iguaçu (PNI), no Oeste do Paraná, ocorrido na década de 1970. Nessa direção, investiga memórias e dinâmicas socioculturais relacionadas à instituição do parque enquanto área de proteção ambiental. Apesar de oficialmente decretado desde 1939, pelo então Governo de Getúlio Vargas, foi somente na década de 1960, no processo mais amplo de ocupação das fronteiras, que muitas famílias, oriundas, principalmente dos Estados de Santa Catarina e Rio Grande do Sul, ocuparam/colonizaram esse espaço. Nesse processo, algumas famílias estabeleceram núcleos populacionais na área demarcada do parque, que depois foram desapropriados pelo então IBDF e o INCRA. Situado numa região de fronteira entre Brasil e Argentina, sua constituição encontra-se relacionada às preocupações do Estado quanto aos domínios dessa fronteira nacional. Para isso, a pesquisa historiciza discussões ambientais que passaram a vigorar no Brasil a partir do final do século XIX, motivadas por embates e questões externas vividas pelo país. Assim, também, discute o movimento intelectual e político, que ao longo dos séculos XIX e XX, passou a construir valores e sentidos sobre natureza, que posteriormente a definiria em sua relação com a cultura enquanto instâncias dicotômicas. Metodologicamente, utiliza-se da História Oral, o que possibilitou pensar as diferentes maneiras como os próprios agricultores colonos rememoram as experiências da desapropriação vivida naqueles anos. Na dinâmica dos conflitos, as memórias possibilitam lançar olhares sobre a ocupação do Oeste do Paraná, assim como para as trajetórias dos desapropriados. Através de narrativas orais e outros documentos oficiais, a pesquisa se colocou a perceber as relações específicas envolvidas no processo de re-assentamento dos antigos moradores do PNI, quando passaram a construir novas relações de pertencimentos e outros laços de reciprocidade
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Deckers, Rolandus Hubertus Robertus. "Le rôle des ultrasons, de l’IRM et de l’imagerie optique dans le cadre de l’activation locale de gènes et du dépôt local de médicaments." Thesis, Bordeaux 1, 2009. http://www.theses.fr/2008BOR13757/document.
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Dans la première partie de cette thèse, les ultrasons focalisés (HIFU) guidés par Imagerie par Résonance Magnétique (IRM) sont utilisés pour l’activation locale transgénique in vivo. Une souris transgénique avec un gène luciferase sous contrôle d’un promoteur thermosensible est utilisée comme modèle biologique. L’hyperthermie locale est induite par une sonde HIFU et contrôlée via un IRM. Dans la seconde partie de ce travail de thèse, les ultrasons sont utilisés pour améliorer le dépôt local de médicaments dans les cellules et les tissus. Le suivi du médicament est effectué à l’aide de différentes techniques d’imageries telles que l’IRM ou l’imagerie par fluorescenceIn the first part of the thesis magnetic resonance imaging (MRI) guided high intensity focused ultrasound (HIFU) is used for the local activation of a transgene in vivo. A transgenic mouse with a luciferase gene under control of a heat sensitive promoter is used as biological model. Local hyperthermia is induced by HIFU and monitored and controlled via MRI. In the second part of the thesis (focused) ultrasound is used for improving local drug delivery in cells and tissue. The fate of the drug is followed by different imaging techniques such as MRI and fluorescence imaging
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Seeger, Karlheinz. "Rezidive von akuten lymphoblastischen Leukämien im Kindesalter." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2003. http://dx.doi.org/10.18452/13899.
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Die akute lymphoblastische Leukämie (ALL) ist die häufigste maligne Erkrankung im Kindesalter. Trotz risikoadaptierter Chemotherapie erleiden 25 - 30 % der Kinder mit ALL ein Rezidiv. Im Rezidivfall liegen die Heilungschancen trotz intensivierter Therapie nur bei 35- 40%. In retrospektiven und prospektiven Analysen konnten wir einerseits prognostisch-relevante, genetische Merkmale in den Leukämiezellen von Kindern mit ALL-Rezidiv erstmals identifizieren. Diese leukämiespezifischen Merkmale umfassen sowohl Translokations-assoziierte Fusionsgene (TEL-AML1, BCR-ABL, MLL-Aberrationen, E2A-PBX1), Deletionen von Tumorsuppressorgenen (p15, p16, p18) als auch Mutationen in DNA-Reparaturgenen (NBS1). Zusammen mit der sensitiven molekularen Bestimmung der Kinetik der Leukämiezellreduktion (Reaktion auf die Therapie, (MRD, minimal residual disease)) läßt sich die Prognose der Kinder mit ALL-Rezidiv durch die Verwendung dieser Marker zuverlässiger bewerten. Andererseits zeigen unsere Analysen, dass das Ansprechen auf die Therapie und die Prognose von wirtseigenen Faktoren (medikamenten metabolisierenden Enzyme) und von der Interaktion zwischen Leukämie- und Stromazellen und löslichen Wachstumsfaktoren (Zytokinen) abhängt. Eine adäquatere Behandlung dieser Patientengruppe, die bereits eine intensive Therapie erhalten hat und wesentlich risikoreichere, mit einer hohen Akut- und Spättoxizität behaftete Therapieverfahren einschließt, lässt sich durch die Berücksichtigung dieser Ergebnisse erreichen. Die genetische Typisierung und die sensitive Quantifizierung des molekularen Ansprechens auf die Therapie ergänzen heute die klinischen Determinanten zur Risikostratifizierung der Kinder mit ALL-Rezidiv der derzeitigen Therapieoptimierungsstudie ALL-REZ BFM 2002 (Berlin-Frankfurt-Münster).Acute lymphoblastic leukemia is the most common malignancy in childhood. Although the prognosis for pediatric ALL with risk-adapted chemotherapy has improved dramatically, 25-30% of the children suffer a relapse. The prognosis for relapsed ALL remains poor (35-40%). In retrospective and prospective studies, we identified prognostic-relevant genetic features in leukemic blasts from children with ALL relapse. These leukemia-specific aberrations include translocation-associated fusion genes (TEL-AML1, BCR-ABL, MLL changes, E2A-PBX1), deletions of tumor suppressor genes (p15, p16, p18) and point mutations in DNA repair genes (NBS1). Together with the sensitive quantitative assessment of the molecular response to therapy (MRD, minimal residual disease), prediction of outcome is now more reliable. Furthermore, response to therapy and, thus, prognosis is significantly dependent on modifying host factors (drug-metabolizing enzymes) and interactions between leukemic and stromal cells as well as soluble growth factors (cytokines). Today, the genetic characterization of leukemic cells as well as the molecular quantification of response to therapy complement prognostic significant clinical determinants allowing a more precise risk stratification of children with ALL relapse in the relapse trial ALL-REZ BFM 2002 of the BFM (Berlin-Frankfurt-Münster) study group.
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Rajput, Abdul Mateen. "Histone modifications after DNA damage affect survival in Schizosaccharomyces pombe." Thesis, Södertörns högskola, Institutionen för livsvetenskaper, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-6886.
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S. cerevisiae Ada2 and Bre1 has a role in histone post-translational modifications. Deletion of these genes causes deficiency in acetylation (Ada2) or ubiquitination (Bre1) of histones. Further, mutants lacking these genes or homologous genes showed different phenotypes in human and S. cerevisiae while treated with DNA damaging agents 4-NQO and MMS. Bre1 deficient cells showed 4-NQO sensitivity in S. cerevisiae and resistance in human cells. Since it has been shown that S. pombe is more close to mammals in chromatin regulation we wanted to examine S. pombe response against MMS and 4-NQO. By homologous recombination, genes were deleted and mutants were treated with different concentration of both the genotoxins. In accordance with a previous study, Ada2Δ showed sensitivity to MMS while Brl1Δ & Brl2Δ grew as wild type. Surprisingly, unlike S. cerevisiae, S. pombe showed resistance to 4-NQO and has a phenotype similar to the one found in human cells.
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Shepard, Samuel Steven. "The Characterization and Utilization of Middle-range Sequence Patterns within the Human Genome." University of Toledo Health Science Campus / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1271271172.
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Persson, Badé Ewa. "Avoir une double culture franco-maghrébine : Étude de problèmes d’intégrations dans deux oeuvres : Mes mauvaises pensées de Nina Bouraoui et Le Parfum des fleurs la nuit de Leïla Slimani." Thesis, Högskolan Dalarna, Institutionen för språk, litteratur och lärande, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:du-37751.
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Dans ce mémoire nous analysons deux oeuvres littéraires : Mes mauvaises pensées de Nina Bouraoui et Le Parfum des fleurs la nuit de Leïla Slimani. Le but de l’analyse est de savoir comment une double culture franco-maghrébine peut être vécue par des femmes nées dans des familles de mariages mixtes. Ce mémoire analyse ces oeuvres à partir des théories sur les genres littéraires, roman beur et autobiographie, et les lit à travers une perspective genrée pour voir comment nos écrivaines se situent dans les sociétés. Nous avons jugé intéressant de faire la comparaison avec le roman beur, qui évoque les problèmes d’intégration des beurs en France, alors que ces écrivaines ne sont pas des Beurettes puisqu’elles ont vécu au Maghreb et en France et elles traitent des problèmes rencontrés dans les deux endroits. En plus elles ont pu maitriser parfaitement les codes dans les sociétés grâce à leurs parents et il ne devrait pas y avoir de difficultés d’intégration alors qu’elles décrivent leurs rapports avec les deux cultures comme problématiques puisqu’elles se sentent toujours comme des étrangères partout. Le but principal n’est donc pas d’inscrire les récits étudiés ici dans un genre littéraire mais de montrer que beaucoup de problèmes d’intégration sont valables dans les deux cultures et les femmes ont encore plus de problèmes pour se faire respecter si elles ne respectent pas les traditions. Nous pouvons dire que ces écrivaines mettent au défi le roman beur comme elles ne montrent pas uniquement les problèmes d’intégration des Maghrébins en France mais aussi les problèmes pour se faire accepter parmi les Maghrébins pour ceux qui ne vivent pas conformément aux coutumes. Les problèmes liés à la binarité de sexes ont un rôle central. Bouraoui et Slimani donnent dans ces oeuvres la parole aux plus opprimés dans la culture maghrébine, les femmes, les homosexuels et les personnes qui ne suivent pas les traditions en même temps qu’elles traitent les problèmes d’intégration en France. Notre conclusion est que le bagage historique et la culture mixte ont influencé leur choix de métier. Le fait de prendre la parole et d’écrire des oeuvres introspectives les a aidées dans leurs propres analyses de soi. Ces analyses avec les descriptions des milieux aident aussi le lecteur à comprendre la situation dans les sociétés et les messages des écrivaines.In this paper two literary works are analysed: Mes mauvaises pensées by Nina Bouraoui and Le Parfum des fleurs la nuit by Leïla Slimani. The aim of the analysis is to understand how a dual French and North African culture could be experienced by women in families characterized by mixed marriages. The literary works are analysed from theories based on literary genres, “roman beur” and the notion of biography. The study is based on a gender perspective and I try to understand how the authors are experiencing the societies. Comparing with the “roman beur” is interesting, since they raise the integration issues for second generation North African immigrants in France, but the authors are not likely to be seen as second generation migrants from North Africa since they have been living in the Maghreb region and in France, they are telling stories from both places. In addition, they have perfectly mastered the codes of both societies thanks to their parents and should not experience integration issues but nevertheless they feel like strangers. The main objective is not to classify the literary genres but to create an understanding and raise the issues that both cultures are facing regarding the integration into society, focusing on how women have a hard time trying to be respected when not following traditions. The authors challenge the “roman beur” since they not only reproduce the integration problems of North African immigrants in France but also the problems of being accepted among the North African community for those who do not live according to traditions. Issues related to the binary gender roles in society play a central role. Bouraoui and Slimani give in these works voices to the most oppressed individuals in the North African culture: women, homosexuals and people who do not follow traditions at the same time as they are dealing with the integration problems in France. The conclusion is that the historical background and the mixed culture influence the choice of the authors’ profession. Speaking up and writing in an introspective way helped them in their own self-analysis. These analyses also help the reader to understand the situation in the societies and the messages of the writers.
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Papadopoulou, Dimitria. "La Journée Internationale de la Femme dans la presse écrite hellénique : médiatisation d’un événement." Thesis, Paris Est, 2011. http://www.theses.fr/2011PEST0029/document.
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Cette étude a comme objet la médiatisation de la Journée Internationale de la femme dans la presse écrite hellénique pendant deux périodes distinctes, les années 1980-1985 et les années 2000-2005. Le corpus de notre travail est constitué de la presse écrite nationale, plus précisément de huit journaux quotidiens, représentatifs des forces politiques qui existent dans le paysage politique hellénique. Les différentes interprétations assignées à l’événement et véhiculées dans l’espace public nous ont incités à étudier comparativement la médiatisation de l’événement pendant chaque période et au sein de chaque quotidien. L’objectif est de montrer comment un événement qualifié en termes de mobilisation et de revendication se transforme en fête anodine à travers les procédés discursifs qui sont utilisés lors de sa médiatisation. Ainsi, nous examinons le cadrage interprétatif tel qu’il se forme à travers la visibilité, la thématique choisie, les genres journalistiques et les modes énonciatifs utilisés pour la légitimation et l’évaluation de la JIDF en mettant en œuvre une analyse de contenu ainsi qu’une analyse énonciative des articles étudiés. Se situant dans le cadre de l’analyse du discours, notre but final est d’examiner le discours portant sur la JIDF dans son articulation avec le contexte sociopolitique de son énonciation. Nous étudions donc la médiatisation de la JIDF et les diversifications que celle-ci présente au cours des années et au sein de chaque dispositif médiatique sur la base des facteurs sociopolitiques et institutionnels : à savoir l’évolution et les tendances idéologiques du mouvement des femmes en Grèce, l’actualité politique de chaque période étudiée et « l’identité discursive » de chaque dispositif médiatique. Selon notre hypothèse de recherche, le traitement médiatique de la JIDF au cours des années constitue la résultante d’un « jeu » complexe d’interactions entre les acteurs d’ordre politique, médiatique et associatif qui essaient de s’emparer les uns les autres afin de mettre en valeur leur propre définition de l’événement. Il s’agit en fait d’un processus plutôt interactif et transversal qui met en jeu de nombreux acteurs, dont le poids fluctue au gré des conjonctures historiques, politiques et socialesPas de résumé anglais
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Karki, Surya B. "Non-thermal Miniature Dielectric Barrier Discharge Plasma for Treatment ofLung Carcinoma Cells." University of Toledo / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1523017849495564.
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Li, Jiaying. "Le langage mis en scène et en questions : étude du jeu verbal chez Alfred Jarry, Eugène Ionesco, Jean Tardieu, Valère Novarina." Thesis, Paris 10, 2018. http://www.theses.fr/2018PA100176.
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Partant de la conjecture selon laquelle le « théâtre du verbe » de Valère Novarina est moins un phénomène singulier dans le paysage théâtral contemporain qu’une forme d’aboutissement des tentatives d’avant-garde précédentes en quête d’un théâtre dédramatisé fondé sur un langage « inhumanisé », cette étude retrace le chemin spirituel qui relie la pataphysique de Jarry à la logodynamique de Novarina, en passant par le nonsense chez Ionesco et chez Tardieu, chemin sous le signe du jeu verbal. En situant cette dernière notion dans la perspective moderne (anti-utilitaire et anti-anthropocentriste) du langage et du théâtre, le travail s’interroge, dans un premier temps, sur les relations particulières entre le jeu verbal et le théâtre « non dramatique » du XXe siècle. En examinant, dans un second temps, les quatre formes de jeu verbal chez Jarry, Ionesco, Tardieu et Novarina, aussi bien dans les écritures que dans des explorations scéniques, la thèse invite à comprendre le jeu verbal comme une manifestation du doute sur le langage, un pouvoir critique vis-à-vis des conformismes, un appel au changement de perception et au mouvement de toutes les « règles de jeu »Starting with the conjecture that Valère Novarina’s “theatre of the verb” is less a singular phenomenon in the contemporary theatrical landscape than a form of culmination of previous attempts to search for a dedramatized theatre based on a “dehumanized” language, this study retraces the spiritual path that connects Jarry’s pataphysics to Novarina’s logodynamics, via the nonsense in Ionesco and Tardieu’s writings, path under the sign of verbal game. By situating this last notion in the modern perspective (anti-utilitarian and anti-anthropocentric) of language and theatre, the study questions, firstly, the particular relations between the verbal game and the “non-dramatic” theatre of the twentieth century. Next, by examining the four forms of verbal game in Jarry, Ionesco, Tardieu and Novarina’s works, both in the scriptures and in scenic explorations, the thesis invites the readers to understand the verbal game as a manifestation of the doubt about the language, a critical power towards conformism, a call for change of perception and for movement of all “rules of the game”
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Paudel, Rajan. "An Investigation into the Evolution of Nucleotide Composition in the Human Genome." University of Toledo Health Science Campus / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=mco1564404055416097.
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Maruani, Anna. "Exploration de l'hétérogénéité phénotypique des Troubles du Spectre Autistique." Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/MARUANI_Anna_2_va_20181123.pdf.
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Les troubles du spectre autistique (TSA) sont définis par des déficits persistants dans la communication sociale et l'interaction sociale ainsi que par l’aspect restreint et répétitif des comportements et des intérêts. Cette entité recouvre des situations cliniques très hétérogènes, tant par le spectre de sévérité des symptômes que par la variété des comorbidités et des signes associés. Si l’étiologie génétique semble prépondérante, les mécanismes impliqués sont complexes et hétérogènes. Une stratégie possible pour décomposer cette hétérogénéité consiste à s’appuyer sur l’étude des relations phénotype-génotype et de façon plus large sur l’étude de sous-groupes phénotypiques comme les particularités sensorielles, les comorbidités ou les particularités neuro-anatomiques, afin de définir des catégories plus homogènes. L’objectif de la thèse a été d’explorer de façon multimodale l’hétérogénéité de ces troubles. La première partie de ma thèse a porté sur l’exploration des relations phénotype-génotype. La première étude a porté sur l’exploration du syndrome de Jacobsen (JS, délétion en 11q24.2-25) caractérisé par une déficience intellectuelle (DI) et un risque plus élevé de TSA. Dans cette région critique 11q24.2-25, nous avons supposé que l’haplo-insuffisance de la Neurotrimine (NTM) (molécule d'adhésion cellulaire neuronale) pourrait augmenter le risque de TSA et pourrait affecter les volumes des structures du cerveau. Si au final, NTM n’a pu être incriminé comme gène de susceptibilité pour les TSA, les explorations ont fourni de nouvelles informations sur l'impact de la délétion 11q24.2-25 sur l'anatomie du cerveau. En effet, en utilisant la segmentation automatique nous avons exploré la macrocéphalie chez un patient porteur d’une grande délétion de novo touchant NTM et présentant un phénotype clinique de JS : nous avons observé, chez ce patient, un volume accru de structures sous-corticales mais une diminution de la matière grise occipitale. La deuxième étude a porté sur les gènes CNTN5 et CNTN6 qui codent des molécules d'adhésion cellulaire neuronale des voies neuronales sensori-motrices. Les investigations cliniques des patients porteurs de variants délétères de CNTN5 et/ou CNTN6 ont montré que ces patients étaient hypersensibles aux sons et que leurs potentiels évoqués auditifs (PEAs) montraient des changements dans les temps de latence. Ces résultats apportent une nouvelle lumière sur les gènes en lien avec les particularités sensorielles dans les TSA. Je présenterai enfin les résultats préliminaires d’une troisième étude, de liaison, chez une famille multiplexe avec TSA et synesthésie. Dans, la deuxième partie de la thèse j’exposerai une étude exploratoire dans laquelle nous avons émis l'hypothèse que les concentrations plasmatiques abaissées de mélatonine observées chez nos patients TSA (vs contrôles et apparentés) pourraient être liées à une diminution du volume de la glande pinéale (VGP). Les VGP ont été mesurés avec une méthode de mesure volumétrique à base de voxel à partir de l’imagerie par résonance magnétique (IRM). Pour mieux comprendre la relation entre le VGP et les taux de mélatonine plasmatique dans notre population, nous avons généré un modèle normatif. Le déficit en mélatonine semblait plus lié au statut du sujet vis à vis du TSA qu’au VGP. Cette étude nous a conduit à faire l’hypothèse que les variations de la mélatonine dans les TSA pourraient être principalement causées par la dérégulation de la voie de la mélatonine. En conclusion, l’ensemble de ces travaux montre l’importance d’une approche multimodale pour la compréhension des TSA pour ouvrir de nouvelles pistes en terme de stratégie thérapeutiqueAutism Spectrum Disorder (ASD) are defined by persistent deficits in social communication and social interaction as well as by the restricted and repetitive nature of behaviors and interests. This entity covers very heterogeneous clinical situations, as much by the spectrum of severity of symptoms as by the variety of comorbidities and associated signs. If the genetic etiology seems preponderant, the mechanisms involved are complex and heterogeneous. One possible strategy to break down this heterogeneity is to rely on the study of phenotype-genotype relationships and more broadly on the study of phenotypic subgroups such as sensory peculiarities, co-morbidities or neuro-anatomical peculiarities, in order to to define more homogeneous categories. The aim of the thesis was to explore multi-modally the heterogeneity of these disorders.The first part of my thesis focused on the exploration of phenotype-genotype relationships. The first study focused on the exploration of Jacobsen syndrome (JS, 11q24.2-25 deletion) characterized by intellectual disability (ID) and a higher risk of ASD. In this critical region 11q24.2-25, we hypothesized that haploinsufficiency of neurotrimin (NTM) (neuronal cell adhesion molecule) may increase the risk of ASD and may affect volumes of brain structures. In the end, NTM could not be incriminated as a susceptibility gene for ASD, but the explorations provided new information on the impact of the 11q24.2-25 deletion on brain anatomy. Indeed, using automatic segmentation we explored macrocephaly in a patient with a large NTM deletion with NTM and a clinical phenotype of JS: we observed an increased volume of subcortical structures in this patient. But a decrease in the occipital gray matter. The second study focused on the CNTN5 and CNTN6 genes that encode neuronal cell adhesion molecules of the sensory-motor neural pathways. Clinical investigations of patients with deleterious variants of CNTN5 and / or CNTN6 showed that these patients were hypersensitive to sound and that their auditory evoked potentials (ABRs) showed changes in latency. These results shed new light on genes related to sensory peculiarities in ASDs. I will present the preliminary results of a third linkage study in a multiplexed family with TSA and synesthesia.In the second part of the thesis, I will expose an exploratory study in which we hypothesized that the lowered plasma concentrations of melatonin observed in our ASD patients (vs controls and related) could be related to a decrease in the volume of the pineal gland (PGV). The PGV were measured with a voxel-based volumetric measurement method from magnetic resonance imaging (MRI). To better understand the relationship between VGP and plasma melatonin levels in our population, we generated a normative model. The melatonin deficiency seemed more related to the subject's status with respect to ASD than to VGP. This study led us to hypothesize that melatonin variations in ASD may be mainly caused by deregulation of the melatonin pathway.In conclusion, all of this work shows the importance of a multimodal approach for understanding ASD to open new avenues in terms of therapeutic strategy
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Leroux, Patrick. "Le Québec en autoreprésentation : le passage d’une dramaturgie de l’identitaire à celle de l’individu." Thesis, Paris 3, 2009. http://www.theses.fr/2009PA030033/document.
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Cette thèse trace et interroge le passage qui s’est opéré au cours des quarante dernières années dans la dramaturgie québécoise, soit le passage d’une écriture de l’identitaire à celle de l’individu. La lecture privilégiée sera de l’ordre de la sociocritique du texte dramatique et elle permettra d’identifier les stratégies discursives et poétiques autoréflexives d’une pratique théâtrale qui puise ses tropes aux littératures de l’intime. Ainsi, les pièces à caractère biographiques et les relectures historiques sont étudiées au même titre que celles qui se revendiquent de l’autobiographie, de l’autofiction et de l’autoreprésentation. Ces dernières caractérisent la production théâtrale québécoise récente. Après avoir été résolument politique et axée sur la langue, la dramaturgie québécoise, longtemps considérée écriture-miroir d’un peuple dont la nation est en perpétuel devenir, aujourd’hui s’intéresse d’abord à elle-même, à sa littérarisation, voire à ses praticiens préoccupés par la place qu’ils occupent dans un milieu plus exiguë, plus marginalisé dans l’ensemble de la société québécoise. Le devenir sociétal a-t-il été substitué par la préoccupation du devenir individuel, non pas comme exemplum, mais comme manifestation d’un sentiment d’unicité? La thèse examine l’émergence d’une dramaturgie tributaire des pratiques autographiques de ses praticiens. Le discours théâtral est à nouveau en accord avec le discours social, sauf que cette fois, le reflet que renvoie le miroir est celui d’une société d’individus préoccupés par leur propre devenirThis thesis traces and investigates the transition in Quebec drama over the last forty years from writing driven by collective identity to writing driven by the individual. The reading of the dramatic texts draws on a socio-critical approach, identifying discursive strategies and the poetics of self-representation in a theatrical tradition seen to be borrowing its devices from intimate literature. Consequently, biographically inflected plays and epic plays reinterpreting history are studied alongside the more explicitly autobiographical, autofictional, and self-reflective works that have come to typify recent Quebec theatre production. After having been resolutely political and language-based, Quebec drama—long considered reflective of the national aspirations of a people in a state of ongoing redefinition—is now interested primarily in itself as a literary trope. Theatre practitioners have become preoccupied with the narrowing space they occupy in Quebec society. Has the social process of becoming [“le devenir” in the Deleuzian sense] been replaced by an overwhelming preoccupation with the individual sense of becoming, not as a stated exemplum, but rather as the manifestation of a sense of uniqueness? The thesis examines the emergence of a self-reflective dramaturgy celebrating the autobiographical practices its artists are engaged in. Thus theatrical discourse is again in step with social discourse in Quebec, except that the dramatic mirror is reflecting a society of individuals preoccupied with their own personal sense of accomplishment