Thesis (Ph. D.)--Washington State University, August 2008. / Includes bibliographical references.

Zugl.: Bonn, Univ., Diss., 2007

Thesis (M.S.) -- University of Montana, 2008. / Title from author supplied metadata. Description based on contents viewed on June 20, 2009. ETD number: etd-12192008-143539. Includes bibliographical references.

University, Diss., 2004--Köln.

Texte remanié de: Thèse 3# cycle--Lettres--Paris IV, 1970. / Bibliogr. des œuvres de l'auteur, p. 13-14. Thèse soutenue sous le titre : "Julien Le Sage, Lettres d'Érasme à Eusébie, 1757-1832"

Este texto se ocupa de dos volúmenes de la obra de Heidegger: el curso sobre Parménides de 1942 y la recopilación De camino al habla de 1950-1959. El curso sobre Parménides trabaja los términos griegos mythos, logos y epos, y los determina como los mismos” –lo que no precisamente corresponde a la identidad–. En sus diferencias mismas, remiten a la palabra” (das Wort). Varios años después, la palabra” es invocada en la triple denominación de Sprache, Wort y Sage que, en sí mismos, no dependen de ninguna lógica de la identidad, sino más bien de una lógica de la tautología”: la poesía misma.

Orientadores: Fernando Ferreira Costa, Anderson Ferreira da Cunha / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T20:38:21Z (GMT). No. of bitstreams: 1 Brugnerotto_AnaFlavia_M.pdf: 5508751 bytes, checksum: b177c8643fd6a6d948194049324253a1 (MD5) Previous issue date: 2010 / Resumo: As síndromes talassêmicas compreendem um grupo heterogêneo de doenças hereditárias em que existe uma redução no ritmo de síntese de uma ou mais cadeias polipeptídicas da hemoglobina. Nas talassemias ß ocorre a supressão total ou parcial da produção de cadeias ß. O estado homozigótico da maioria das variantes genéticas da talassemia ß produz o quadro clínico da talassemia maior. Esses pacientes apresentam acentuada anemia e necessitam de transfusões sanguíneas regulares para sobreviverem. Os indivíduos heterozigotos para a talassemia ß apresentam, com raras exceções, apenas discreta anemia. Existem ainda alguns quadros clínicos não tão graves quanto à forma homozigótica clássica, geralmente não dependem de transfusões, que são denominados de talassemia intermediária. Os genes responsáveis pela síntese das cadeias da ß globina estão organizados em um cluster localizado no braço curto do cromossomo 11. Quase 200 alelos de talassemia ß já foram caracaterizados. Destes, 125 representam mutações pontuais em regiões funcionalmente importantes do gene, uma de particular interesse ao nosso estudo, é a mutação Cd 39 (C--T). Este trabalho teve como objetivo analisar o perfil global de expressão gênica de células CD 34+ de pacientes com talassemia ß, portadores da mesma mutação genética (Cd 39), mas com evoluções clínicas distintas, maior e intermediária, pelo método de SAGE (Serial Analysis of Gene Expression). Foram gerados 2718 trancritos únicos para o perfil de talassemia ß intermediária e 3052 para o perfil de talassemia ß maior, os quais foram classificados como genes identifcados, no matches, ESTs e outras sequências preditas e anotadas. As expressões de 14 genes foram quantificadas pela reação em cadeia da polimerase em tempo real nas amostras de células CD34+ dos pacientes talassêmicos intermediário e maior, com intuito de validar os resultados obtidos pelo SAGE. As expressões foram concordantes em 57,14% dos genes (ABCB10, APEX1, APOC1, EYA3, HMBS, OAZ1, SRGN, TAGLN2) e discordantes nos demais 42,85% (EIF5a, GRIN2C, HMGB1, NAE1, PCBP2, RAD23B). Quando ambos os perfis foram comparados entre si, 42 transcritos foram ditos como diferencialmente expresso (p<0,05). A análise funcional comparativa dos 42 transcritos diferencialmente expressos foi realizada de acordo com o Gene Ontology Consortium afim de obtermos a classificação funcional destes transcritos. Em conjunto, os resultados podem colaborar na identificação de transcritos importantes, que possam auxiliar na melhor compreensão da fisiopatologia desta doença e desempenhar papéis moduladores no fenótipo em talassemia ß / Abstract: Thalassemia syndromes are a heterogeneous group of hereditary diseases in which there is a reduction in the synthesis of one or more hemoglobin chains. In ß-thalassemia there is a reduction or total suppression of the expression of ß globin genes. The homozygous state of most ß-thalassemia genetic variants produces the clinical evolution of thalassemia major. These patients present severe anemia and require regular blood transfusions in order to survive. Heterozygous individuals present, with exceptions, discret anemia. There are some clinical evolutions that are not as severe as the classic homozygous form, which are often blood transfusion independent, named ß-thalassemia intemedia. The gene responsible for the synthesis of ß the globin chain is arranged in a cluster located on the short arm of cromossome 11. Nearly 200 ß-thalassemia alleles have been characterized. Of these, 125 represent mutations in functionally-important regions of the gene. A nonsense mutation, ie base substitution, which introduces a premature stop codon, destroying the normal reading and interfering in mRNA translation, is of particular interest to our study, especially the Cd 39 mutations (C--T). The aim of this study was to evaluate the global gene expression pattern of CD34+ culture cells from patients with ß-thalassemia, carrying the same genetic mutation (Cd 39) but with different phenotypes (major and intermedia), using Serial Analysis of Gene Expression (SAGE). Two SAGE profiles were gerated: INT and MAIOR. Comparison of the 2718 an 3052 distinct tags from the INT and MAIOR profiles, represented by identified trnacripts and novel tags, 42 tags demonstrated with a differential expression at a statistically significant level (p<0,05) and corresponded to known genes, ESTs or no matches. The expression of 14 genes was further investigated by the real-time polymerase chain reaction in cells cultured from patients with ß-thalassemia intermedia and major, with the purpose of to validating the results obtained by the SAGE method. Similar expressions were seen in 57.14% (ABCB10, APEX1, APOC1, EYA3, HMBS, OAZ1, SRGN, TAGLN2) and discordant expressions were seen in 42.85% (EIF5a, GRIN2C, HMGB1, NAE1, PCBP2, RAD23B). The functional classification was performed according to the Gene Ontology Consortium and a total of a 42 transcripts were submitted to functional classification. Together, our results may contribute to identify important transcripts that may play roles in modulating phenotype in ß-thalassemia and to better understand the pathophysiology of this disease / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

Numerous studies have demonstrated that tumour cells have the ability to alter immune function to create an immune suppressed environment. This allows tumour cells to escape immune surveillance and consequently the tumour can progress. Dendritic and T cells have critical roles in immune activation and tolerance and are thus major targets of tumour-mediated immune suppression. Understanding the mechanism(s) by which tumour cells modulate the immune system will facilitate the development of immune system-based therapies for cancer treatments. In this study we sought to determine the nature of, and cellular and molecular mechanisms underlying, changes in immune status during tumour progression using mouse models of prostate cancer. Detailed analysis of the immunological status in a mouse prostate dysplasia model (12T-7slow) revealed that immune suppression accompanied tumour progression. We found that T cells isolated from tumour-bearing hosts were hypo-responsive to antigen stimulation. Furthermore, we demonstrated that CD4+CD25+ regulatory T cells were responsible, at least in part, for this alteration. Anti-CD25 antibody treatment reduced, but did not prevent, tumour growth in either a transplanted prostate tumour model or a spontaneously developing prostate tumour model. In addition, an altered dendritic cell phenotype and an elevated frequency of CD4+CD25+ regulatory T cells were observed within the tumour mass. Similar alterations were observed in the prostate-specific Pten knockout mice which develop advanced prostate adenocarcinoma. Interestingly, evidence of immune activation, such as an increased frequency of activated T cells, was detected in the tumour microenvironment in both mouse prostate tumour models. To identify factors that may play critical roles in the altered immune cell phenotype observed in the tumour microenvironment, a global gene expression profiling analysis was carried out to evaluate the changes in immune-related gene expression patterns. This analysis provided additional evidence for the co-existence of immune suppression and immune activation. Moreover, subsequent analyses suggested that one differentially expressed transcript, interferon regulatory factor 7, and its target genes might be involved in modulating immune cells and/or tumour progression. Taken together, these studies have important implications for designing specific and effective anti-tumour immune therapy strategies that involve manipulation of tumour cells, dendritic cells and regulatory T cells. / Medicine, Faculty of / Medicine, Department of / Experimental Medicine, Division of / Graduate

Serial Analysis of Gene Expression (SAGE) on Caenorhabditis elegans RNA from FACS sorted embryonic body wall muscle cells has identified nearly 8000 genes expressed in nematode body wall muscle. Approximately 60% of these are genes are expressed at low levels (<5 tags/~50,000-100,000 tag library). Low-abundance transcripts have typically been overlooked since most are considered experimental or contamination errors. Consequently, research has been focused on transcripts that are most enriched in the particular tissue of interest. Here I focus on the analysis of low-expressed transcripts in the muscle SAGE libraries in order to investigate what percentage of these are in fact expressed in muscle and are not false positives. Most well characterized C. elegans body wall muscle genes are not expressed at low levels, therefore I anticipate that focusing on these rarely expressed genes will allow for the identification of muscle components that have been previously unrecognized. RT-PCR was performed on RNA isolated from purified body wall muscle cells to initially estimate what fraction of these low abundance transcripts present in the SAGE data are indeed expressed in muscle. I examined 128 genes, of which 84 were represented by a single SAGE tag. From this initial list, 38% of the low-expressed transcripts were verified for their presence in body wall muscle. Subsequently, reporter GFP fusions were used to deduce if these low-expressed transcripts are indeed expressed in vivo within muscle. Of the low-expressed genes that tested positive via RT-PCR, 42% showed in vivo expression in body wall muscle. When the results from the RT-PCR and in vivo expression experiments are combined, I can extrapolate that at least 16% of low-expressed genes identified by the SAGE libraries are in fact expressed in muscle and are not false positives. RNAi and knockout analysis were performed in order to investigate the role of low-expressed muscle genes in myofilament structure. RNAi results show that 14/34 (41%) of the genes screened had mild defects in myofilament organization. The SAGE libraries identified 6388 low-expressed transcripts, this work suggests that at least 16% (1022 genes) of these are in fact expressed in muscle and may reveal new components previously overlooked by other approaches. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Proporciona los pasos y procedimientos para acceder al recurso Journal of Hospitality & Tourism Research.