Sirtuins and proteolytic systems: implications for pathogenesis of synucleinopathies

Insoluble and fibrillar forms of a-synuclein are the major components of Lewy bodies, a hallmark of several sporadic and inherited neurodegenerative diseases known as synucleinopathies. a-Synuclein is a natural unfolded and aggregation-prone protein that can be degraded by the ubiquitin-proteasomal system and the lysosomal degradation pathways. a-Synuclein is a target of the main cellular proteolytic systems, but it is also able to alter their function further, contributing to the progression of neurodegeneration. Aging, a major risk for synucleinopathies, is associated with a decrease activity of the proteolytic systems, further aggravating this toxic looping cycle. Here, the current literature on the basic aspects of the routes for a-synuclein clearance, as well as the consequences of the proteolytic systems collapse, will be discussed. Finally, particular focus will be given to the sirtuins's role on proteostasis regulation, since their modulation emerged as a promising therapeutic strategy to rescue cells from a-synuclein toxicity. The controversial reports on the potential role of sirtuins in the degradation of a-synuclein will be discussed. Connection between sirtuins and proteolytic systems is definitely worth of further studies to increase the knowledge that will allow its proper exploration as new avenue to fight synucleinopathies.

Time-variations of equivalent water heights'from Grace Mission and in-situ river stages in the Amazon basin

Gravity Recovery and Climate Experiment (GRACE) mission is dedicated to measuring temporal variations of the Earth's gravity field. In this study, the Stokes coefficients made available by Groupe de Recherche en Géodésie Spatiale (GRGS) at a 10-day interval were converted into equivalent water height (EWH) for a ~4-year period in the Amazon basin (from July-2002 to May-2006). The seasonal amplitudes of EWH signal are the largest on the surface of Earth and reach ~ 1250mm at that basin's center. Error budget represents ~130 mm of EWH, including formal errors on Stokes coefficient, leakage errors (12 ~ 21 mm) and spectrum truncation (10 ~ 15 mm). Comparison between in situ river level time series measured at 233 ground-based hydrometric stations (HS) in the Amazon basin and vertically-integrated EWH derived from GRACE is carried out in this paper. Although EWH and HS measure different water bodies, in most of the cases a high correlation (up to ~80%) is detected between the HS series and EWH series at the same site. This correlation allows adjusting linear relationships between in situ and GRACE-based series for the major tributaries of the Amazon river. The regression coefficients decrease from up to down stream along the rivers reaching the theoretical value 1 at the Amazon's mouth in the Atlantic Ocean. The variation of the regression coefficients versus the distance from estuary is analysed for the largest rivers in the basin. In a second step, a classification of the proportionality between in situ and GRACE time-series is proposed.

A radiofrequency identification system for the 60 GHz ISM band

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Eletrónica Médica)

Perplexidades e incertezas da regulação dos media na Europa

A regulação dos media tem ganho relevo nas agendas nacionais e internacionais mas nem sempre a utilização corrente do conceito é consistente, correndo o risco de significar tudo e nada em simultâneo. Independentemente do intenso e profícuo debate concetual que o tema suscita na comunidade académica, julgamos pertinente o estudo das estruturas de regulação mediática que operam no terreno da União Europeia. Este trabalho reflete sobre as entidades de regulação mediática que atuam na defesa do interesse público, ainda que existam as mais diversas modalidades de enunciação e de defesa desse interesse pelos vários estados, e decorre de um esforço de investigação coletivo, enquadrado no projeto “Regulação dos Media em Portugal: O Caso da ERC”, que agregou elementos sobre os organismos reguladores dos media na Europa.

The mineralogy and chemistry of the German and Portuguese tiles used to face a historic building in the Amazon region and their natural susceptibility to tropical weathering

During the 19th century, the most prominent buildings of the city of Belém were faced entirely with tiles manufactured in Portugal and Germany, which now exhibit distinct degrees of degradation. The Pinho mansion is one of the most important of these buildings and was selected for the investigation of the action of the tropical Amazonian climate on the degradation of the tiles. To achieve this objective, the tiles were mapped for organic and inorganic degradation, and samples were collected for analysis. The minerals were determined by XRD, the chemical composition by classical wet methods and SEM/EDS, and the microorganisms under the microscope. The results show that the German and Portuguese tiles are quite different in their composition. While both ceramic bodies are composed of SiO2 and Al2O3, CaO was found only in the Portuguese tile. The low Na2O and K2O contents indicate the addition of materials to reduce the fusion temperature. SiO2 and PbO are the main constituents of the glaze, with CoO and FeO being added as pigment. The ceramic body of the German tiles is constituted of quartz, mullite, and cristobalite, in contrast with the Portuguese tiles, which are made of quartz, gehlenite, diopside, calcite, and feldspars. The glazes are XRD-amorphous. The chemical and mineralogical differences between the German and Portuguese tiles indicate that they were produced from different raw materials under distinct thermal processes. The most prominent weathering-related modifications are the thin layers (German tiles), oxidation stains, dark stains, the detachment of the tile (Portuguese tiles), loss of the glaze and powdering of the ceramic body (Portuguese tiles) through the establishment of Cyanophyta and Bacillariophyta.. The distinct degradation patterns of the tiles exposed to the tropical Amazon climate are a consequence of their distinct mineralogy and chemistry.

Caracterização do microbioma e dos perfis de resistência nos afluentes e efluentes de ETAR

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Importance of anatomical leaf features for characterization of three species of Mapania (Mapanioideae, Cyperaceae) from the Amazon Forest, Brazil

Mapania belongs to Mapanioideae, a quite controversial subfamily in Cyperaceae due to the existence of unusual characters in both reproductive and vegetative organs. The genus is represented by seven species in Northern Brazil but taxonomic valuable information related to the leaf organs is still unknown. The present study aimed the anatomical description of the leaf organs (either basal leaves or cataphylls and involucral bracts) of three representative Brazilian species of Mapania. Samples of cataphylls, basal leaves and involucral bracts were sectioned and stained for observations under light microscopy. The involucral bracts provide the most elucidative characters (ten) to distinguish the three species The basal leaves provides six distinguishing characters and are useful to M. macrophylla and M. pycnostachya, as they are absent in M. sylvatica. Mesophyll arrangement in the involucral bracts supports the circumscription of M. macrophylla and M. pycnostachya in M. sect. Pycnocephala and of M. sylvatica in M. sect. Mapania. Some features as thin-walled epidermal cells, stomata level and aerenchyma were considered to be adaptive to the humid environment in which the species occur. The translucent cells are here considered as aerenchyma precursors and a supportive function is assumed for the bulliform cells on the basal leaves and involucral bracts. No silica bodies were found which confirm it as a diagnostic character of Mapania among Hypolytreae genera.

Paragéneses contrastantes no campo pegmatítico de Arga (NW de Portugal): diversidade e equilíbrio

Dissertação de mestrado Ordenamento e Valorização de Recursos Geológicos

Estratégia para a incorporação de impactes ambientais, sociais e económicos específicos num método de Avaliação da Sustentabilidade de Edifícios de Saúde (HBSA)

The healthcare project design requires a several number of concerns with the satisfaction and well‐being of the working team, patient and administrators, has a strong social responsibility and impact on the city. Due to various design requirements, these buildings are not designed and used in a sustainable way, because there are still no effective methods to support designers in this context. Consequently, they do not know what the best criteria to be followed and their managers are not aware of the measuresthatshould be adopted for efficient use. Furthermore, the aim of this study is to present a proposal for a Healthcare Building Sustainability Assessment (HBSA) method adapted for the Portuguese context and considering the work developed so far in the standardization bodies (CEN and ISO). For this, the chosen methodology is analysed and compared the most relevant building sustainability assessment tools in the context of healthcare buildings.  

Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development

Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. In vitro analyses were performed on Sprague-Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) α, β and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up-regulation of RARα and RARγ.

A cooperação transfronteiriça como oportunidade de desenvolvimento das regiões de fronteira. Da Raia Ibérica à euroregião Galiza-Norte de Portugal

Tese de Doutoramento em Geografia Humana.

Avaliação do transporte sedimentar na bacia do rio Lima baseada em ferramentas de modelação

Dissertação de mestrado integrado em Engenharia Civil

Implementação de metodologias BIM na Direção de Engenharia de Barragens da EDP: casos de estudo de projeto de estruturas em obras hidroelétricas

Dissertação de mestrado integrado em Engenharia Civil

A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

O hospital da misericórdia de Penafiel (1600-1850)

Tese de Doutoramento em História - Especialidade de Idade Moderna