Hydrodynamic and sediment fluxes through the inlets of the Ria Formosa

Tese de dout., Ciências do Mar, da Terra e do Ambiente (Ciências do Mar-Oceanografia Física), Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2011

Adding value to performance measurement by using system dynamics and multicriteria analysis

Tese de dout., Filosofia, Department of Management Science, University of Strathclyde, 2004

Dynamics of production and mortality of Aurelia SP. in thau lagoon, northwerstern Mediterranean

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

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

The function of drosophila integrin adhesion complexes in pupal hemocyte migration in vivo

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

The role of alpha-synuclein phosphorylation in synucleinopathies

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2014

The role of reciprocal regulation between TAL1 and miRNA expression in T-cell leukemia progression

Tese de doutoramento, Ciências Biomédicas (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Medicina, 2015

O contributo das representações numéricas básicas e da função executiva no desempenho de operações aritméticas : um estudo exploratório

Tese de mestrado, Psicologia (Secção de Cognição Social Aplicada), Universidade de Lisboa, Faculdade de Psicologia, 2014

Characterization of adenosinergic system in Rett syndrome

Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2015

An exploration of pre-attentive visual discrimination using event-related potentials

The Mismatch Negativity (MMN) has been characterised as a ‘pre-attentive’ component of an Event-Related Potential (ERP) that is related to discriminatory processes. Although well established in the auditory domain, characteristics of the MMN are less well characterised in the visual domain. The five main studies presented in this thesis examine visual cortical processing using event-related potentials. Novel methodologies have been used to elicit visual detection and discrimination components in the absence of a behavioural task. Developing paradigms in which a behavioural task is not required may have important clinical applications for populations, such as young children, who cannot comply with the demands of an active task. The ‘pre-attentive’ nature of visual MMN has been investigated by modulating attention. Generators and hemispheric lateralisation of visual MMN have been investigated by using pertinent clinical groups. A three stimulus visual oddball paradigm was used to explore the elicitation of visual discrimination components to a change in the orientation of stimuli in the absence of a behavioural task. Monochrome stimuli based on pacman figures were employed that differed from each other only in terms of the orientation of their elements. One such stimulus formed an illusory figure in order to capture the participant’s attention, either in place of, or alongside, a behavioural task. The elicitation of a P3a to the illusory figure but not to the standard or deviant stimuli provided evidence that the illusory figure captured attention. A visual MMN response was recorded in a paradigm with no task demands. When a behavioural task was incorporated into the paradigm, a P3b component was elicited consistent with the allocation of attentional resources to the task. However, visual discrimination components were attenuated revealing that the illusory figure was unable to command all attentional resources from the standard deviant transition. The results are the first to suggest that the visual MMN is modulated by attention. Using the same three stimulus oddball paradigm, generators of visual MMN were investigated by recording potentials directly from the cortex of an adolescent undergoing pre-surgical evaluation for resection of a right anterior parietal lesion. To date no other study has explicitly recorded activity related to the visual MMN intracranially using an oddball paradigm in the absence of a behavioural task. Results indicated that visual N1 and visual MMN could be temporally and spatially separated, with visual MMN being recorded more anteriorly than N1. The characteristic abnormality in retinal projections in albinism afforded the opportunity to investigate each hemisphere in relative isolation and was used, for the first time, as a model to investigate lateralisation of visual MMN and illusory contour processing. Using the three stimulus oddball paradigm, no visual MMN was elicited in this group, and so no conclusions regarding the lateralisation of visual MMN could be made. Results suggested that both hemispheres were equally capable of processing an illusory figure. As a method of presenting visual test stimuli without conscious perception, a continuous visual stream paradigm was developed that used a briefly presented checkerboard stimulus combined with masking for exploring stimulus detection below and above subjective levels of perception. A correlate of very early cortical processing at a latency of 60-80 ms (CI) was elicited whether stimuli were reported as seen or unseen. Differences in visual processing were only evident at a latency of 90 ms (CII) implying that this component may represent a correlate of visual consciousness/awareness. Finally, an oddball sequence was introduced into the visual stream masking paradigm to investigate whether visual MMN responses could be recorded without conscious perception. The stimuli comprised of black and white checkerboard elements differing only in terms of their orientation to form an x or a +. Visual MMN was not recorded when participants were unable to report seeing the stimulus. Results therefore suggest that behavioural identification of the stimuli was required for the elicitation of visual MMN and that visual MMN may require some attentional resources. On the basis of these studies it is concluded that visual MMN is not entirely independent of attention. Further, the combination of clinical and non-clinical investigations provides a unique opportunity to study the characterisation and localisation of putative mechanisms related to conscious and non-conscious visual processing.

Who gets to play? Investigating equity in musical instrument instruction in Scottish primary schools

There is a widely held view that learning to play a musical instrument is a valuable experience for all children in terms of their personal growth and development. Although there is no statutory obligation for instrumental music provision in Scottish primary schools, there are well-established Instrumental Music Services in Local Education Authorities that have been developed to provide this facility for pupils. This article presents the findings of a study that was aimed at investigating the extent to which the opportunity to undertake instrumental instruction in Scottish primary schools is equitable. The study employed a mixed-methods approach. Data were gathered from 21 Scottish primary schools, a total pupil population of 5122 pupils of whom 323 pupils were receiving instrumental instruction. The analysis involved an investigation of the academic profile of this group, the representation of children with additional support needs (ASN) and the nature of their ASN. A qualitative analysis of policy and guideline documents and interviews with Heads of Instrumental Services, headteachers and instrumental instructors served to explain and illuminate the quantitative data. The findings showed that particular groups of children with ASN were significantly under-represented and offer explanations of the processes by which this occurs.

Estrogen protects the blood–brain barrier from inflammation-induced disruption and increased lymphocyte trafficking

Sex differences have been widely reported in neuroinflammatory disorders, focusing on the contributory role of estrogen. The microvascular endothelium of the brain is a critical component of the blood–brain barrier (BBB) and it is recognized as a major interface for communication between the periphery and the brain. As such, the cerebral capillary endothelium represents an important target for the peripheral estrogen neuroprotective functions, leading us to hypothesize that estrogen can limit BBB breakdown following the onset of peripheral inflammation. Comparison of male and female murine responses to peripheral LPS challenge revealed a short-term inflammation-induced deficit in BBB integrity in males that was not apparent in young females, but was notable in older, reproductively senescent females. Importantly, ovariectomy and hence estrogen loss recapitulated an aged phenotype in young females, which was reversible upon estradiol replacement. Using a well-established model of human cerebrovascular endothelial cells we investigated the effects of estradiol upon key barrier features, namely paracellular permeability, transendothelial electrical resistance, tight junction integrity and lymphocyte transmigration under basal and inflammatory conditions, modeled by treatment with TNFα and IFNγ. In all cases estradiol prevented inflammation-induced defects in barrier function, action mediated in large part through up-regulation of the central coordinator of tight junction integrity, annexin A1. The key role of this protein was then further confirmed in studies of human or murine annexin A1 genetic ablation models. Together, our data provide novel mechanisms for the protective effects of estrogen, and enhance our understanding of the beneficial role it plays in neurovascular/neuroimmune disease.

Assessing residual reasoning ability in overtly non-communicative patients using fMRI

It is now well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are also capable of logical thought. Here, we validate an fMRI paradigm that can detect the neural fingerprint of reasoning processes and moreover, can confirm whether a participant derives logical answers. We demonstrate the efficacy of this approach in a physically non-communicative patient who had been shown to engage in mental imagery in response to simple audi- tory instructions. Our results demonstrate that this individual retains a remarkable capacity for higher cogni- tion, engaging in the reasoning task and deducing logical answers. We suggest that this approach is suitable for detecting residual reasoning ability using neural responses and could readily be adapted to assess other aspects of cognition.

Urocortin – From Parkinson’s disease to the skeleton

Urocortin (Ucn 1), a 40 amino acid long peptide related to corticotropin releasing factor (CRF) was discovered 19 years ago, based on its sequence homology to the parent molecule. Its existence was inferred in the CNS because of anatomical and pharmacological discrepancies between CRF and its two receptor subtypes. Although originally found in the brain, where it has opposing actions to CRF and therefore confers stress-coping mechanisms, Ucn 1 has subsequently been found throughout the periphery including heart, lung, skin, and immune cells. It is now well established that this small peptide is involved in a multitude of physiological and pathophysiological processes, due to its receptor subtype distribution and promiscuity in second messenger signalling pathways. As a result of extensive studies in this field, there are now well over one thousand peer reviewed publications involving Ucn 1. In this review, we intend to highlight some of the less well known actions of Ucn 1 and in particular its role in neuronal cell protection and maintenance of the skeletal system, both by conventional methods of reviewing the literature and using bioinformatics, to highlight further associations between Ucn 1 and disease conditions. Understanding how Ucn 1 works in these tissues, will help to unravel its role in normal and pathophysiological processes. This would ultimately allow the generation of putative medical interventions for the alleviation of important diseases such as Parkinson's disease, arthritis, and osteoporosis.

Environmental exposure to toxicants mixtures from a multi-purpose estuary: perspectives for a biomonitoring study in Portugal

This work was focused on a multi-purpose estuarine environment (river Sado estuary, SW Portugal) around which a number of activities (e.g., fishing, farming, heavy industry, tourism and recreational activities) coexist with urban centres with a total of about 200 000 inhabitants. Based on previous knowledge of the hazardous chemicals within the ecosystem and their potential toxicity to benthic species, this project intended to evaluate the impact of estuarine contaminants on the human and ecosystem health. An integrative methodology based on epidemiological, analytical and biological data and comprising several lines of evidence, namely, human contamination pathways, human health effects, consumption of local produce, estuarine sediments, wells and soils contamination, effects on commercial benthic organisms, and genotoxic potential of sediments, was used. The epidemiological survey confirmed the occurrence of direct and indirect (through food chain) exposure of the local population to estuarine contaminants. Furthermore, the complex mixture of contaminants (e.g., metals, pesticides, polycyclic aromatic hydrocarbons) trapped in the estuary sediments was toxic to human liver cells exposed in vitro, causing cell death, oxidative stress and genotoxic effects that might constitute a risk factor for the development of chronic-degenerative diseases, on the long term. Finally, the integration of data from several endpoints indicated that the estuary is moderately impacted by toxicants that affect also the aquatic biota. Nevertheless, the human health risk can only be correctly assessed through a biomonitoring study including the quantification of contaminants (or metabolites) in biological fluids as well as biomarkers of early biological effects (e.g., biochemical, genetic and omics-based endpoints) and genetic susceptibility in the target population. Data should be supported by a detailed survey to assess the impact of the contaminated seafood and local farm products consumption on human health and, particularly, on metabolic diseases or cancer development.