Study of influence of regulatory polymorphisms of expression in development of breast cancer

The human genome has millions of genetics variants that can affect gene expression. These variants are known as cis-regulatory variants and are responsible for intra-species phenotypic differences and individual susceptibility to disease. One of the diseases affected by cis-regulatory variants is breast cancer. Breast cancer is one of the most common cancers, with approximately 4500 new cases each year in Portugal. Breast cancer has many genes mutated and TP53 has been shown to be relevant for this disease. TP53 is one of the most commonly mutated genes in human cancer and it is involved in cell cycle regulation and apoptosis. Previous work by Maia et al has shown that TP53 has differential allelic expression (DAE), which suggests that this gene may be under the influence of cis-regulatory variants. Also, its DAE pattern is totally altered in breast tumours with normal copy number. We hypothesized that cis-regulatory variants affecting TP53 may have a role in breast cancer development and treatment. The present work aims to identify the cis-regulatory variants playing a role in TP53 expression, using in silico, in vitro and in vivo approaches. By bioinformatic tools we have identified candidate cis-regulatory variants and predicted the possible transcription factor binding sites that they affect. By EMSA we studied DNA-protein interactions in this region of TP53. The in silico analysis allowed us to identified three candidate cis-regulatory SNPs which may affect the binding of seven transcription factors. However, the EMSA experiments have not been conclusive and we have not yet confirmed whether any of the identified SNPs are associated with gene expression control of TP53. We will carry out further experiments to validate our findings.

Ecological niche modeling, cytogenetics and phylogeography of the genera Geomalacus and Letourneuxia (Gastropoda, Pulmonata) from the Iberian-Moroccan region

First described more that 150 years ago, the systematics of the genera Geomalacus and Letourneuxia (Arionidae, Gastropoda, Pulmonata) is still challenging. The taxonomic classification of arionid species is based on extremely labile characters such as body size or color that depends both on diet and environment, as well as age. Moreover, there is little information on the genetic diversity and population structure of the Iberian slugs that could provide extra clues to disentangle their problematic classification. The present work uses different analytical tools such as habitat suitability (Ecological Niche Modeling - ENM), cytogenetic analysis and phylogeography to establish the geographical distribution and evolutionary history of these pulmonate slugs. The potential distribution of the four Geomalacus species was modeled using ENM, which allowed the identification of new locations for G. malagensis, including a first report in Portugal. Also, it was predicted a much wider distribution for G. malagensis and G. oliveirae than previously known. Classical cytogenetic analyses were assayed with reproductive and a novel use of somatic tissues (mouth and tentacles) returning the number of chromosomes for the four Geomalacus species and L. numidica (n = 31, 2n = 62) and the respective karyotypes. G. malagensis and L. numidica present similar chromosome morphologies and karyotypic formulae, being more similar to each other than the Geomalacus among themselves. We further reconstructed the phylogeny of the genera Geomalacus and Letourneuxia using partial sequences of the mitochondrial cytochrome oxidase subunit I (COI) and the nuclear ribosomal small subunit (18S rRNA), and applied an independent evolutionary rate method, the indicator vectors correlation, to evaluate the existence of cryptic diversity within species. The five nominal species of Geomalacus and Letourneuxia comprise 14 well-supported cryptic lineages. Letourneuxia numidica was retrieved as a sister group of G. malagensis. G. oliveirae is paraphyletic with respect to G. anguiformis. According to our dating estimates, the most recent common ancestor of Geomalacus dates back to the Middle Miocene (end of the Serravallian stage). The major lineage splitting events within Geomalacus occurred during the dry periods of the Zanclean stage (5.3-3.6 million years) and some lineages were confined to more humid mountain areas of the Iberian Peninsula, which lead to a highly geographically structured mitochondrial genetic diversity. The major findings of this are the following: (1) provides updated species distribution maps for the Iberian Geomalacus expanding the known geographic distribution of the concerned species, (2) unravels the cryptic diversity within the genera Geomalacus and Letourneuxia, (3) Geomalacus oliveirae is paraphyletic with G. anguiformis and (4) Letourneuxia numidica is sister group of G. malagensis.

Produções cerâmicas no cabeço de Porto Marinho (Rio Maior) no contexto da Pré-História recente na Estremadura

Dissertação de mestrado, Arqueologia, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2015

Aprender história através da arte : a identidade civilizacional da Europa Ocidental

Relatório da Prática de Ensino Supervisionada, Mestrado em Ensino de História e de Geografia no 3º Ciclo do Ensino Básico e Ensino Secundário, Universidade de Lisboa, 2011

Aplicação didáctica do documento no ensino da história em contexto de sala de aula : absolutismo régio - sociedade e política

Relatório da Prática de Ensino Supervisionada, Mestrado em Ensino de História e de Geografia no 3º Ciclo do Ensino Básico e Ensino Secundário, Universidade de Lisboa, 2011

Expansão e mudança nos séculos XV e XVI : contributos da aprendizagem da história para a formação da cidadania

Relatório da prática de ensino supervisionada, Mestrado em Ensino de História e Geografia no 3.º Ciclo do Ensino Básico e Ensino Secundário, Universidade de Lisboa, 2011

De como o pícaro chegou a Portugal e aí se apresentou:contributo para a história da recepção do romance picaresco espanhol no sistema literário português

Tese de doutoramento, Tradução (História da Tradução), Universidade de Lisboa, Faculdade de Letras, 2012

Geometria descritiva : história e didática - novas perspetivas

Tese de doutoramento, Belas-Artes (Geometria), Universidade de Lisboa, Faculdade de Belas-Artes, 2014

Para a história da educação de infância em Portugal : o caso de Bragança (1934-1986)

Tese de doutoramento, Educação (História da Educação), Universidade de Lisboa, Instituto de Educação, 2014

Abrir a história : a imagem de arquivo e o movimento desacelarado : um estudo teórico-prático a partir dos filmes Natureza Morta e 48

Tese de doutoramento, Belas-Artes (Audiovisuais), Universidade de Lisboa, Faculdade de Belas-Artes, 2014

Aspectos psicológicos da fibromialgia : personalidade e história de vida

Tese de doutoramento, Psicologia (Psicologia Clínica), Universidade de Lisboa, Faculdade de Psicologia, 2013

Contribuição para a história social da biotecnologia em Portugal

Tese de doutoramento, Sociologia (Sociologia da Ciência e Tecnologia), Universidade de Lisboa, Instituto de Ciências Sociais, 2014

História da filosofia da educação em Portugal : dos programas de ensino ao campo disciplinar : (1976-2006)

Tese de doutoramento, Educação (História da Educação), Universidade de Lisboa, Instituto de Educação, 2014

Poetizando a história nacional : ficcionalização da história e método historiográfico em José de Alencar

Tese de doutoramento, História (História e Cultura do Brasil), Universidade de Lisboa, Faculdade de Letras, 2014

Base genética da hipercolesterolemia familiar

Tese de doutoramento, Bioquímica (Genética Molecular), Universidade de Lisboa, Faculdade de Ciências, 2014