The role of hypoxia in the regulation of membrane transporters

ATP binding cassette (ABC) and solute carrier (SLC) transporters are responsible for the majority of the transcellular movement of various substrates, including drugs, among epithelial cells. Despite the well characterized regulation of influx (SLC) and efflux (ABC) transporters by endogenous mediators, such as inflammatory cytokines, little is known about how changes in oxygen levels may affect expression of these transporters. In this study we showed that the expression of SLC22A4, SLC22A5, SLC22A1, SLC02B1, SLC10A2, ABCC2 and ABCC3 transporters is upregulated by hypoxia in HT29 colon carcinoma cells, but not in HepG2 hepatocarcinoma cells. Moreover, OCTN1 (SLC22A4), OCT1 (SLC22A1) and OATP-B (SLC02B1) transporter expression is also induced by inflammatory cytokines but in a smaller extent than in hypoxia. Furthermore our experiments indicate that there is no cross talk between HIF-1 and NF-κB pathways in HT-29 cells, but these two pathways act simultaneously activating common genes, such as, some SLC and ABC transporters. Our preliminary results from studies with an in vivo murine model of colitis, suggest that HIF-1is stabilized and OCTN1 is strongly induced during severe inflammation, which can be relevant for a recovery from the inflammatory process. We have also been interested in the distribution of HIF-1α variants among different ethnic groups as well as their contribution for cancer risk. Thus, we have demonstrated that there is an ethnicity-related variation in the frequency of the C1772T (P582S) single nucleotide polymorphism (SNP) in the HIF-1α gene. Furthermore, we performed a case-control study in a breast cancer population and our results suggest that there is no association between this SNP or the rare G1790A (A588T) SNP and the incidence of breast cancer. Taken together, the results obtained in this study contribute to a better knowledge of drug influx and efflux during hypoxia and inflammation as well as to the understanding of the pharmacogenetic variability of the HIF-1.

Arte-educação : a mediação cultural e o trabalho com equipas criativas

Relatório de estágio de mestrado, Ciências da Educação (Educação Intercultural), Universidade de Lisboa, Instituto de Educação, 2011

Arte e educação : o papel das equipas criativas na mediação cultural

Relatório de estágio de mestrado, Ciências da Educação (Educação Intercultural), Universidade de Lisboa, Instituto de Educação, 2011

O mediador social e pessoal nos cursos de educação e formação de adultos

Trabalho de projecto de mestrado, Ciências da Educação (Formação de Adultos), Universidade de Lisboa, Instituto de Educação, 2011

O mediador nos cursos EFA

Trabalho de projeto de mestrado, Ciências da Educação (Formação de Adultos), Universidade de Lisboa, Instituto de Educação, 2013

Griots cosmopolitas : mobilidade e performance de artistas mandingas entre Lisboa e Guiné-Bissau

Tese de doutoramento, Antropologia (Antropologia da Etnicidade e do Político), Universidade de Lisboa, Instituto de Ciências Sociais, 2014

How hydrogen peroxide and CXCL8 modulate neutrophil recruitment "in vivo"

Tese de doutoramento, Ciências Biomédicas (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Medicina, 2014

Perceived Social Pressures and the Internalization of the Mesomorphic Ideal: the Role of Drive for Muscularity and Autonomy in Physically Active Men

BACKGROUND: Researchers have tested the beliefs of sportspeople and sports medicine specialists that cognitive strategies influence strength performance. Few investigators have synthesised the literature. OBJECTIVES: The specific objectives were to review evidence regarding (a) the cognitive strategy-strength performance relationship; (b) participant skill level as a moderator; and (c) cognitive, motivational, biomechanical/physiological, and emotional mediators. METHOD: Studies were sourced via electronic databases, reference lists of retrieved articles, and manual searches of relevant journals. Studies had to be randomised or counterbalanced experiments with a control group or condition, repeated measures, and a quality control score above 0.5 (out of 1). Cognitive strategies included goal setting, imagery, self-talk, preparatory arousal, and free choice. Dependent variables included maximal strength, local muscular endurance, or muscular power. RESULTS: Globally, cognitive strategies were reliability associated with increased strength performance (results ranged from 61 to 65 %). Results were mixed when examining the effects of specific strategies on particular dependent variables, although no intervention had an overall negative influence. Indeterminate relationships emerged regarding hypothesised mediators (except cognitive variables) and participant skill level as a moderator. CONCLUSIONS: Although cognitive strategies influence strength performance, there are knowledge gaps regarding specific types of strength, especially muscular power. Cognitive variables, such as concentration, show promise as possible mediators.

A relação trabalho-família : o desafio para ontem

Tese de doutoramento, Psicologia (Psicologia dos Recursos Humanos, do Trabalho e das Organizações), Universidade de Lisboa, Faculdade de Psicologia, 2016

Mediadores culturais em Portugal: perfis e trajetórias de um novo grupo ocupacional

O principal objetivo deste artigo é estudar os indivíduos que intervêm em atividades de mediação cultural. A nossa atenção circunscreve-se a mediadores que trabalham em serviços educativos e em programas promovidos por políticas públicas. O estudo recai sobre percursos de um conjunto de mediadores, tendo sido realizadas entrevistas aprofundadas. A análise salienta dois aspetos: por um lado, constata-se que é diverso o grau de centralidade deste trabalho nas trajetórias, e por outro verifica-se uma convergência nos atributos considerados cruciais para o desempenhar. O artigo ensaia um esboço de diversos perfis, ressaltando a heterogeneidade do trabalho de mediação das artes em Portugal.

Deciphering the mechanisms underlying the loss of BDNF neuroprotection in an Alzheimer’s disease model

Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2016

Protein deiminases: new players in the developmentally regulated loss of neural regenerative ability

Spinal cord regenerative ability is lost with development, but the mechanisms underlying this loss are still poorly understood. In chick embryos, effective regeneration does not occur after E13, when spinal cord injury induces extensive apoptotic response and tissue damage. As initial experiments showed that treatment with a calcium chelator after spinal cord injury reduced apoptosis and cavitation, we hypothesized that developmentally regulated mediators of calcium-dependent processes in secondary injury response may contribute to loss of regenerative ability. To this purpose we screened for such changes in chick spinal cords at stages of development permissive (E11) and non-permissive (E15) for regeneration. Among the developmentally regulated calcium-dependent proteins identified was PAD3, a member of the peptidylarginine deiminase (PAD) enzyme family that converts protein arginine residues to citrulline, a process known as deimination or citrullination. This post-translational modification has not been previously associated with response to injury. Following injury, PAD3 up-regulation was greater in spinal cords injured at E15 than at E11. Consistent with these differences in gene expression, deimination was more extensive at the non-regenerating stage, E15, both in the gray and white matter. As deimination paralleled the extent of apoptosis, we investigated the effect of blocking PAD activity on cell death and deiminated-histone 3, one of the PAD targets we identified by mass-spectrometry analysis of spinal cord deiminated proteins. Treatment with the PAD inhibitor, Cl-amidine, reduced the abundance of deiminated-histone 3, consistent with inhibition of PAD activity, and significantly reduced apoptosis and tissue loss following injury at E15. Altogether, our findings identify PADs and deimination as developmentally regulated modulators of secondary injury response, and suggest that PADs might be valuable therapeutic targets for spinal cord injury.

Expanding our therapeutic options: β-blockers for colon cancer?

Supported by U. Porto/Santander Totta (IJUP) (PP-IJUP2011-320)

Multi-agent system for personalization of location-based services

The current ubiquitous network access and increase in network bandwidth are driving the sales of mobile location-aware user devices and, consequently, the development of context-aware applications, namely location-based services. The goal of this project is to provide consumers of location-based services with a richer end-user experience by means of service composition, personalization, device adaptation and continuity of service. Our approach relies on a multi-agent system composed of proxy agents that act as mediators and providers of personalization meta-services, device adaptation and continuity of service for consumers of pre-existing location-based services. These proxy agents, which have Web services interfaces to ensure a high level of interoperability, perform service composition and take in consideration the preferences of the users, the limitations of the user devices, making the usage of different types of devices seamless for the end-user. To validate and evaluate the performance of this approach, use cases were defined, tests were conducted and results gathered which demonstrated that the initial goals were successfully fulfilled.

A mediated moderation study to explain the negative relationship between job insecurity and employee supportive voice

Double degree