Spectral analysis of embolic signals

Tese de dout., Engenharia Electrónica e Computação, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2005

Espaços urbanos de festa e a morfologia do lugar: requalificação do Largo da Achada na Camacha (Madeira)

O presente estudo surgiu de acordo com o trabalho que foi realizado durante o período de estágio na Câmara Municipal de Santa Cruz, mais precisamente a requalificação do Largo da Achada localizado na Camacha, freguesia do Concelho de Santa Cruz, Madeira. Este espaço está intimamente ligado a atividades de cariz lúdico e festivo e como tal, houve a necessidade de se realizar uma reflexão sobre o que são espaços urbanos de festa, para poder estabelecer-se a relação existente entre as atividades festivas e o “lugar”, isto é, tentar perceber a influência que estas atividades têm na construção dos espaços urbanos e na sua forma. Esta questão é fundamental para se definirem estratégias de como intervir neste tipo de espaço. Para tal procedeu-se ao estudo de alguns casos distintos onde se faz uma breve análise de algumas festas em espaços diferentes de modo a tentar perceber até que ponto as alterações na morfologia, tanto no interior como na periferia destes, podem introduzir mudanças nas tradições e vice-versa. Para cada estudo de caso identifica-se a principal romaria ou procissão associada ao lugar, de forma a tentar perceber as relações e a influência que o desenho dos espaços abertos e das artérias que os ligam exercem neste tipo de atividades e de que maneiras estas relações interferem com o quotidiano. No decorrer do levantamento bibliográfico chegou-se à conclusão que os autores não eram unânimes quanto à classificação dos diferentes tipos de espaços de festa o que levou à necessidade de propor uma nova classificação que se apresentasse mais de acordo com o espaço que se pretende requalificar. O estudo tem especial enfoque na categoria de espaços de festa consolidados que integra os espaços que têm a sua origem na própria festa, pois são os que melhor se identificam com a requalificação do Largo da Achada. Como resultado deste estudo e da caracterização biofísica, cultural e do espaço urbano, surge então a proposta de requalificação do largo.

Insights into molecular and cellular events involved in normal and pathological vertebral development and fusion using zebrafish as model organism

The vertebral column and its units, the vertebrae, are fundamental features, characteristic of all vertebrates. Developmental segregation of the vertebral bodies as articulated units is an intrinsic requirement to guarantee the proper function of the spine. Whenever these units become fused either during development or postsegmentation, movement is affected in a more or less severe manner, depending on the number of vertebrae affected. Nevertheless, fusion may occur as part of regular development and as a physiological requirement, like in the tetrapod sacrum or in fish posterior vertebrae forming the urostyle. In order to meet the main objective of this PhD project, which aimed to better understand the molecular and cellular events underlying vertebral fusion under physiological and pathological conditions, a detailed characterization of the vertebral fusion occurring in zebrafish caudal fin region was conducted. This showed that fusion in the caudal fin region comprised 5 vertebral bodies, from which, only fusion between [PU1++U1] and ural2 [U2+] was still traceable during development. This involved bone deposition around the notochord sheath while fusion within the remaining vertebral bodies occur at the level of the notochord sheath, as during the early establishment of the vertebral bodies. A comparison approach between the caudal fin vertebrae and the remaining vertebral column showed conserved features such as the presence of mineralization related proteins as Osteocalcin were identified throughout the vertebral column, independently on the mineralization patterns. This unexpected presence of Osteocalcin in notochord sheath, here identified as Oc1, suggested that this gene, opposing to Oc2, generally associated with bone formation and mature osteoblast activity, is potentially associated with early mineralization events including chordacentrum formation. Nevertheless, major differences between caudal fin region and anterior vertebral bodies considering arch histology and mineralization patterns, led us to use RA as an inductive factor for vertebral fusion, allowing a direct comparison of equivalent structures under normal and fusion events. This fusion phenotype was associated with notochord sheath ectopic mineralization instead of ectopic perichordal bone formation related with increased osteoblast activity, as suggested in previous reports. Additionally, alterations in ECM content, cell adhesion and blood coagulation were discussed as potentially related with the fusion phenotype. Finally, Matrix gla protein, upregulated upon RA treatment and shown to be associated with chordacentrum mineralization sites in regular development, was further described considering its potential function in vertebral formation and pathological fusion. Therefore with this work we propose zebrafish caudal fin vertebral fusion as a potential model to study both congenital and postsegmentation fusion and we present candidate factors and genes that may be further explored in order to clarify whether we can prevent vertebral fusion.

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.

Study of the association of Gla Rich Protein (GRP) to human blood cells

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Biomedicina, Universidade do Algarve, 2013

Toxicidade induzida pela digoxina na terapia da insuficiência cardíaca

Dissertação de mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

Interações entre produtos à base de plantas com os medicamentos usados em cardiologia

Dissertação de mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

Functional analysis of a transcriptional variant of matrix gla protein (MGP)

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014

Purification, biochemical characterization and localization at single cell resolution of Matrix Gla Protein (MGP) and Bone Gla Protein (BGP) in the teleost fish Argyrosomus regius

Tese de dout. em Química, Faculdade de Ciências do Mar e do Ambiente, Univ. do Algarve, 2002