Cette étude propose une analyse intégrée de biomarqueurs moléculaires de sols, depuis leur site de production jusqu'à leur archivage sédimentaire lacustre. Un inventaire des lipides neutres est d'abord réalisé sur des sols d'usages contrastés : prairies/pâtures et forêts. Globalement, cette approche permet de distinguer (1) des composés linéaires ubiquistes, et (2) des composés (poly-)cycliques, généralement spécifiques. Parmi ces derniers figurent les acétates de triterpényle et les méthoxyserratènes, respectivement biomarqueurs d'Astéracées et de Pinacées. La persistance de l'empreinte moléculaire d'un ancien usage des sols est aussi démontrée. Ensuite, l'analyse multi-proxy d'une carotte sédimentaire couvrant les 6700 dernières années révèle l'impact prépondérant des activités humaines sur le fonctionnement hydrologique du lac, depuis l'époque gallo-romaine. Les assemblages moléculaires précédemment définis dans les sols sont globalement retrouvés, associés à un nouveau biomarqueur spécifique du chanvre, d'intérêt paléoenvironnemental. Une tentative de reconstitution des anciennes occupations des sols apparaît conforme aux données historiques et paléoenvironnementales antérieures. / This study proposes an integrated analysis of molecular biomarkers of landuse, from their genesis in soils to their archiving in the lacustrine sediment. An inventory of neutral lipids is realized on soils of two contrasted landuses: grassland/pasture and forest. This approach globally allows to distinguish (1) ubiquist linear compounds and (2) (poly-)cyclic compounds, generally specific. Among these ones, triterpenyl acetates and methoxyserratenes are detected and are respectively biomarkers of Asteraceae and Pinaceae. The persistence of a molecular imprint of an ancient landuse is also demonstrated. Then, the multi-proxy analysis of a sedimentary core, covering the last 6700 years, shows the prominent impact of human activities on the hydrologic functioning of the lake since the gallo-roman period. Molecular assemblages previously defined in soils are globally detected in sediments, associated with a new specific biomarker of hemp, of palaeoenvironmental interest. Hypotheses for the reconstitution of past landuses appear to be consistent with previous historical and palaeoenvironmental data.

Orientador: Maria Isabel Nogueira Cano / Resumo: O câncer de pulmão é o câncer que apresenta maior mortalidade no mundo: >1,6 milhões de óbitos por ano segundo a Organização Mundial de Saúde (OMS), sendo o câncer de pulmão de células não pequenas (NSCLC) o tipo mais frequente (~ 85%) de carcinoma pulmonar. O NSCLC apresenta dois subtipos histológicos principais: adenocarcinoma (LUAD) e carcinoma de células escamosas (LUSC). Pesquisas têm sido realizadas objetivando identificar biomarcadores moleculares úteis como alvo terapêuticos em NSCLC e os telômeros têm sido considerado alvos promissores para terapias antitumoral, devido ao seu papel crucial na integridade, estabilidade e manutenção genômica. Telômeros humanos consistem em DNA repetitivo rico em G associado a proteínas do complexo shelterin e mantido pela ação da telomerase. Estudos recentes mostraram que a expressão de TERT (subunidade catalítica da telomerase) e de alguns componentes do complexo shelterin estão alterados em câncer de pulmão. No entanto, a correlação entre alterações na função telomérica e o desenvolvimento e progressão de NSCLC não foi elucidada. Portanto, o objetivo do presente estudo foi verificar alterações na expressão de genes associados aos telômeros, incluindo os ncRNAs associados à regulação e manutenção dos telômeros em NSCLC, no intuito de identificar novos biomarcadores associados ao desenvolvimento e progressão do NSCLC. Para tanto, foram realizadas análises de expressão de 50 genes associados aos telômeros em amostras de tecido tumoral e... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: According to the World Health Organization, lung cancer has a high mortality rate associated with >1.6 million deaths per year, being Non-small cell lung cancer (NSCLC) the most frequent type (~ 85%) of lung carcinoma. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two major histological subtypes of NSCLC. Research efforts have been made to identify molecular biomarkers useful as therapeutic targets in NSCLC and telomere have been considered very promising targets for anticancer therapies due to their crucial role in genome integrity maintenance and stability. Human telomeres consist of repetitive G-rich DNA associated with proteins of the shelterin complex, maintained by the action of telomerase. Recent studies showed that expression of TERT (telomerase reverse transcriptase component) and of some of the shelterin components are altered in lung cancer. However, the mechanisms of telomere deregulation associated with NSCLC development and progression have not been elucidated. Therefore, our aim was to study expression changes affecting telomere-associated genes and ncRNAs associated with telomere regulation and maintenance in NSCLC. Such alterations may represent novel biomarkers associated with NSCLC development and progression. For this purpose, expression analyzes of 50 telomere-associated genes were performed in samples of tumor tissue and normal lung tissue, adjacent to the tumor, from patients with NSCLC. The following techniques were used: 1... (Complete abstract click electronic access below) / Mestre