Molecular bases of classic galactosemia : searching for new therapeutic strategies

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2014

Synthesis and computer-assisted design of mitochondrial electron transport-chain inhibitors as antimalarial agents

Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Metal cycling in salt marshes and intertidal mudflats : influence of plants, invertebrates and fishes

Tese de doutoramento, Biologia (Ecologia), Universidade de Lisboa, Faculdade de Ciências, 2015

Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment

Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2015

Essential oils as anti-nematode agents and their influence on in vitro nematode

Tese de doutoramento, Biologia (Biotecnologia), Universidade de Lisboa, Faculdade de Ciências, 2015

New methodologies for directed functional connectivity applied to brain neuroimaging research

Tese de doutoramento, Engenharia Biomédica e Biofísica, Universidade de Lisboa, Faculdade de Ciências, 2015

Lessons Learnt From Ragweed and Birch Studies

Here we review some of the most important aspects of recent work on Ragweed (Ambrosia) and birch (Betula) concerning: 1) sources, 2) trends & phenology and 3) dispersion and transformation. Sources: At Northern latitudes the birch fraction in forests usually exceeds 50% of all broadleaved trees and the abundance of birch decreases with latitude from 5%-20% in many mid-latitude regions and down to 0%-2% in more southern areas. Birches are also commonly found in small woodlands or planted as ornamental trees in urban areas. Ragweeds are herbaceous weed species that are associated with areas of disturbance. Ragweed is native to North America, but considered an invasive species in Europe, Australia and China. In Europe, the four main centres are: The Pannonian Plain, Ukraine, The Po Valley (Italy) and the Rhone Valley (France). Trends & Phenology: Birch pollen seasons have started earlier during the last decades. This trend appears have decreased during recent years despite increasing spring temperatures. Ragweed tends to experience less change in flowering date as ragweed flowering depends on photoperiod. Ragweed is increasing its distribution in Europe, but airborne concentrations of ragweed pollen are not universally increasing, e.g. due to control measures or pest attacks. Dispersion & transformation: The beginning of the birch pollen season is often heralded by episodes of Long Distance Transport (LDT) from the south. Similar LDT episodes are intermittently seen for ragweed, which can reach as far north as Scandinavia. Humidity and air pollution can modify pollen grains during atmospheric transport. This can cause a change in allergenic potential of the pollen grain and is a direction for future research including the effect of co-exposure of air pollution and the transformation of aeroallergens.

Non-coding RNAs: multi-tasking molecules in the cell

In the last years it has become increasingly clear that the mammalian transcriptome is highly complex and includes a large number of small non-coding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs). Here we review the biogenesis pathways of the three classes of sncRNAs, namely short interfering RNAs (siRNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs). These ncRNAs have been extensively studied and are involved in pathways leading to specific gene silencing and the protection of genomes against virus and transposons, for example. Also, lncRNAs have emerged as pivotal molecules for the transcriptional and post-transcriptional regulation of gene expression which is supported by their tissue-specific expression patterns, subcellular distribution, and developmental regulation. Therefore, we also focus our attention on their role in differentiation and development. SncRNAs and lncRNAs play critical roles in defining DNA methylation patterns, as well as chromatin remodeling thus having a substantial effect in epigenetics. The identification of some overlaps in their biogenesis pathways and functional roles raises the hypothesis that these molecules play concerted functions in vivo, creating complex regulatory networks where cooperation with regulatory proteins is necessary. We also highlighted the implications of biogenesis and gene expression deregulation of sncRNAs and lncRNAs in human diseases like cancer.

Cellular polarity in aging: role of redox regulation and nutrition

Cellular polarity concerns the spatial asymmetric organization of cellular components and structures. Such organization is important not only for biological behavior at the individual cell level, but also for the 3D organization of tissues and organs in living organisms. Processes like cell migration and motility, asymmetric inheritance, and spatial organization of daughter cells in tissues are all dependent of cell polarity. Many of these processes are compromised during aging and cellular senescence. For example, permeability epithelium barriers are leakier during aging; elderly people have impaired vascular function and increased frequency of cancer, and asymmetrical inheritance is compromised in senescent cells, including stem cells. Here, we review the cellular regulation of polarity, as well as the signaling mechanisms and respective redox regulation of the pathways involved in defining cellular polarity. Emphasis will be put on the role of cytoskeleton and the AMP-activated protein kinase pathway. We also discuss how nutrients can affect polarity-dependent processes, both by direct exposure of the gastrointestinal epithelium to nutrients and by indirect effects elicited by the metabolism of nutrients, such as activation of antioxidant response and phase-II detoxification enzymes through the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In summary, cellular polarity emerges as a key process whose redox deregulation is hypothesized to have a central role in aging and cellular senescence.

Hydrogen peroxide sensing, signaling and regulation of transcription factors

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and, (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M-1s−1 and ≥ 1.3 × 103 M-1s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.

Relações públicas e comunicação a internacionalização da banda Cambatango

O presente trabalho de projeto tem como tema Comunicação e Relações Públicas na internacionalização da banda Cambatango. Os Cambatango são uma orquestra típica de tango argentino que deseja consolidar a sua presença no mercado musical europeu. Assim, a pergunta de partida desta investigação é: como é que uma banda musical de origem argentina consegue promover o seu trabalho em território ibérico? O objetivo principal da investigação é associar as atividades de Relações Públicas à indústria da música. Para este fim, foi escolhido um objeto de estudo real, a orquestra Cambatango e proposto um Plano de Relações Públicas que ajude a: fortalecer a gestão e a imagem do grupo; fomentar a visibilidade da banda na indústria musical internacional; conquistar novos públicos e dinamizar a relação com os stakeholders de forma a impulsionar a presença do grupo em território ibérico. Esta investigação tem uma abordagem predominantemente qualitativa, nesse sentido, os métodos de pesquisa utilizados foram: análise SWOT; análise PEST; mapeamento de stakeholders; entrevistas (e respetiva análise categorial temática); pesquisa documental; auditoria em comunicação e pesquisa informal. As principais conclusões foram: existe uma vertente de Relações Públicas para a música, mas que ainda não é muito explorada pelos artistas independentes; um plano de Relações Públicas elaborado com base nas necessidades e objetivos dos artistas pode ajudar a projetar a sua carreira internacional; a indústria da música tem vindo a mudar face às novas tecnologias e os artistas precisam de acompanhar estas tendências; a comunicação é fundamental para estabelecer o diálogo com os diferentes públicos e ganhar maior projeção e visibilidade internacional.

Cold-water coral communities in the Azores : diversity, habitat and conservation

Tese de Doutoramento, Ciências do Mar (especialidade em Ecologia Marinha), 11 de Setembro de 2015, Universidade dos Açores.

Host-symbiont interactions in the deep-sea vent mussel Bathymodiolus azoricus : a molecular approach

Tese de Doutoramento, Ciências do Mar, especialidade de Biologia Marinha, 19 de Dezembro de 2015, Universidade dos Açores.

Uncertainty assessment approach for composite structures based on global sensitivity indices

The problem of uncertainty propagation in composite laminate structures is studied. An approach based on the optimal design of composite structures to achieve a target reliability level is proposed. Using the Uniform Design Method (UDM), a set of design points is generated over a design domain centred at mean values of random variables, aimed at studying the space variability. The most critical Tsai number, the structural reliability index and the sensitivities are obtained for each UDM design point, using the maximum load obtained from optimal design search. Using the UDM design points as input/output patterns, an Artificial Neural Network (ANN) is developed based on supervised evolutionary learning. Finally, using the developed ANN a Monte Carlo simulation procedure is implemented and the variability of the structural response based on global sensitivity analysis (GSA) is studied. The GSA is based on the first order Sobol indices and relative sensitivities. An appropriate GSA algorithm aiming to obtain Sobol indices is proposed. The most important sources of uncertainty are identified.

Design and evaluation of multi-band RF energy harvesting circuits and antennas for WSNs

Radio frequency (RF) energy harvesting is an emerging technology that will enable to drive the next generation of wireless sensor networks (WSNs) without the need of using batteries. In this paper, we present RF energy harvesting circuits specifically developed for GSM bands (900/1800) and a wearable dual-band antenna suitable for possible implementation within clothes for body worn applications. Besides, we address the development and experimental characterization of three different prototypes of a five-stage Dickson voltage multiplier (with match impedance circuit) responsible for harvesting the RF energy. Different printed circuit board (PCB) fabrication techniques to produce the prototypes result in different values of conversion efficiency. Therefore, we conclude that if the PCB fabrication is achieved by means of a rigorous control in the photo-positive method and chemical bath procedure applied to the PCB it allows for attaining better values for the conversion efficiency. All three prototypes (1, 2 and 3) can power supply the IRIS sensor node for RF received powers of -4 dBm, -6 dBm and -5 dBm, and conversion efficiencies of 20, 32 and 26%, respectively. © 2014 IEEE.