Dissection of the early steps in the assembly of the 20S proteasome in Saccharomyces cerevisiae

Tese de dout., Bioquímica (Biologia Celular e Molecular), Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2010

The role of lymphotoxin-B receptor signaling in t-cell acute lymphoblastic leukemia development

Dissertação de mest., Ciências Biomédicas, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2010

Differential requirements of aPKC activity within different epithelial tissues

Epithelial tissues are essential during morphogenesis and organogenesis. During development, epithelial tissues undergo several different remodeling processes, from cell intercalation to cell change shape. An epithelial cell has a highly polarized structure, which is important to maintain tissue integrity. The mechanisms that regulate and maintain apicobasal polarity and epithelial integrity are mostly conserved among all species and in different tissues within the same organism. aPKC-PAR complex localizes in the apical domain of polarized cells, and its function is essential for apicobasal polarization and epithelial integrity. In this work we characterized two novel alleles of aPKC: a temperature sensitive allele (aPKCTS), which has a point mutation on a kinase domain, and another allele with a point mutation on a highly conserved amino acid within the PB1 domain of aPKC (aPKCPB1). Analysis of the aPKCTS mutant phenotypes, lead us to propose that during development different epithelial tissues have differential requirements of aPKC activity. More specifically, our work suggests de novo formation of adherens junctions (AJs) is particularly sensitive to sub-optimal levels of apkc activity. Analysis of the aPKCPB1 allele, suggests that aPKC is likely to have an apical structural function mostly independent of its kinase activity. Altogether our work suggests that although loss of aPKC function is associated to similar epithelial phenotypes (e.g., loss of apicobasal polarization and epithelial integrity), the requirements of aPKC activity within these tissues are nevertheless likely to vary.

Avaliação neuropsicológica de doentes oncológicos submetidos à quimioterapia: um estudo comparativo

Diversos estudos têm vindo a demonstrar que os doentes oncológicos revelam alterações cognitivas na sequência do tratamento de quimioterapia, apesar de alguns outros estudos terem evidenciado o oposto. O principal objetivo desta investigação é fazer uma caracterização cognitiva geral destes doentes, de forma a contribuir para esclarecer a controvérsia existente na literatura relativa à presença e natureza de defeitos cognitivos decorrentes da quimioterapia. Participaram, neste estudo, 35 mulheres com cancro da mama, tratadas com quimioterapia, e 35 mulheres saudáveis, emparelhadas por idade e escolaridade. Foi aplicado um conjunto de provas que avaliam os principais domínios cognitivos (atenção, memória e funções cognitivas de natureza mais complexa), bem como os níveis de sintomatologia depressiva. O grupo clínico demonstrou pior desempenho na maioria das provas neuropsicológicas aplicadas, em comparação às mulheres do grupo de controlo, embora se situasse em algumas provas num nível médio de funcionamento (atendendo ao seu grupo de referência). As diferenças entre grupos não parecem dever-se ao facto de o grupo clínico apresentar níveis mais graves de sintomatologia depressiva. Os resultados do presente estudo vão ao encontro da literatura, sugerindo que a quimioterapia parece ter um efeito negativo no funcionamento cognitivo, tendo-se verificado um maior comprometimento ao nível da atenção, da memória de trabalho, da flexibilidade cognitiva e da fluência verbal. Por sua vez, não se observaram diferenças entre grupos na prova que avalia as funções visuo-construtivas.

The activity of mouse Cerberus like 2 during cardiogenesis - genetic and morphogenetic studies

Cardiogenesis is a delicate and complex process that requires the coordination of an intricate network of pathways and the different cell types. Therefore, understanding heart development at the morphogenetic level is an essential requirement to uncover the causes of congenital heart disease and to provide insight for disease therapies. Mouse Cerberus like 2 (Cerl2) has been defined as a Nodal antagonist in the node with an important role in the Left-Right (L/R) axis establishment, at the early embryonic development. As expected, Cerl2 knockout mice (Cerl2-/-) showed multiple laterality defects with associated cardiac failure. In order to identify the endogenous role of Cerl2 during heart formation independent of its described functions in the node, we accurately analyzed animals where laterality defects were not present. We thereby unravel the consequences of Cerl2 lossof- function in the heart, namely increased left ventricular thickness due to hyperplasia of cardiomyocytes and de-regulated expression of cardiac genes. Furthermore, the Cerl2 mutant neonates present impaired cardiac function. Once that the cardiac expression of Cerl2 is mostly observed in the left ventricle until around midgestration, this result suggest a specific regulatory role of Cerl2 during the formation of the left ventricular myoarchitecture. Here, we present two possible molecular mechanisms underlying the cardiac Cerl2 function, the regulation of Cerl2 antagonist in activation of the TGFßs/Nodal/Activin/Smad2 signaling identified by increased Smad2 phosphorilation in Cerl2-/- hearts and the negative feedback between Cerl2 and Wnt/ß-catenin signaling in heart formation. In this work and since embryonic stem cells derived from 129 mice strain is extensively used to produce targeted mutants, we also present echocardiographic reference values to progressive use of juveniles and young adult 129/Sv strain in cardiac studies. In addition, we investigate the cardiac physiology of the surviving Cerl2 mutants in 129/Sv background over time through a follow-up study using echocardiographic analysis. Our results revealed that Cerl2-/- mice are able to improve and maintain the diastolic and most of systolic cardiac physiologic parameters as analyzed until young adult age. Since Cerl2 is no longer expressed in the postnatal heart, we suggest that an intrinsic and compensatory mechanism of adaptation may be active for recovering the decreased cardiac function found in Cerl2 mutant neonates. Altogether, these data highlight the role of Cerl2 during embryonic heart development in mice. Furthermore, we also suggest that Cerl2-/- may be an interesting model to uncover the molecular, cellular and physiological mechanisms behind the improvement of the cardiac function, contributing to the development of therapeutic approaches to treat heart failures.

Estudo do papel de CITED2 na diferenciação das células estaminais embrionárias

Dissertação de mestrado, Biologia Molecular e Microbiana, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Importância da informação no controlo da Diabetes Mellitus: estudo caso numa farmácia comunitária

Dissertação de mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Ecologia alimentar, idade e crescimento, relações morfométricas e aspetos reprodutivos de Sardinella aurita (Valenciennes, 1847) e Sardinella maderensis Lowe (1838) na Costa Sul de Angola (Namibe)

Dissertação de Mestrado, Biologia Marinha, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Relé diferencial numérico para proteção de transformadores

Dissertação de Mestrado, Engenharia Elétrica e Eletrónica, Especialização em Sistemas de Energia e Controlo, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015