RCAAP Repository

Hereditary amyloidosis related to transthyretin (hATTR) is a fatal progressive, autosomal dominant disease caused by mutations in the TTR gene. The most common TTR mutation worldwide is the V30M with a neuropathic phenotype, originating early impairment of small fibres responsible for the autonomic and sensory abnormalities frequently found as the first manifestation of disease. Diagnostic tools to assess autonomic function are essential in the diagnosis of small fibre neuropathy (SFNP) in early stages of disease, allowing an early treatment management.

Skeletal muscle cells (myofibers) are rod-shaped multinucleated cells surrounded by an extracellular matrix (ECM) basal lamina. In contrast to other cell types, nuclei in myofibers are positioned just below the plasma membrane at the cell periphery. Peripheral nuclear positioning occurs during myogenesis and is driven by myofibril crosslinking and contraction. Here we show that peripheral nuclear positioning is triggered by local accumulation of fibronectin secreted by myofibroblasts. We demonstrate that fibronectin via α5-integrin mediates peripheral nuclear positioning dependent on FAK and Src activation. Finally, we show that Cdc42, downstream of restricted fibronectin activation, is required for myofibril crosslinking but not myofibril contraction. Thus we identify that local activation of integrin by fibronectin secreted by myofibroblasts activates peripheral nuclear positioning in skeletal myofibers.

This project, situated from the discipline of design, and motivated by the desire to contribute to the decolonization of public spaces and the collective imaginary, aims to make visible the sociocultural tensions that emanate from the presence of monuments that commemorate the colonial-era in the public sphere. In addressing the issue from the perspective of cultural memory studies and postcolonial theory, it shows how Eurocentric epistemic frameworks give the colonial narrative a rationality that normalizes the domination relations imposed by the empires. In turn, it shows how mediums such as monuments, by remaining intact and glorified, end up projecting in time these power structures and reproducing them in the present. Based on the theory of remediation postulates, the principles of Discursive Design and Speculative Design, and seeking to explore the potential offered by new technologies associated with artificial intelligence and image processing on the web, an application was developed based on a fictional scenario, in which some of the most problematic traits observed in European authorities are exacerbated to the point of satire. This process gave birth to Colombot: Bring Your Favorite Colonialist to Life!, a web application that emulates the incarnation of historical figures of colonialism in an artificial intelligence, which aims to provoke debate by revealing the violent and segregating dimensions of the colonial era.

Numa sociedade marcada pelo cariz científico e tecnológico, a educação em ciência assume um papel fundamental para o desenvolvimento do indivíduo. O ensino das ciências deverá promover a apropriação de conhecimentos e o desenvolvimento de capacidades e atitudes essenciais à vida em sociedade. Este estudo pretende compreender se a implementação da Metodologia de Projecto nas aulas de Ciências da Natureza do 2º ciclo do Ensino Básico permite motivar e envolver os alunos activamente na sua aprendizagem com vista à apropriação de conhecimentos científicos e simultaneamente ao desenvolvimento de competências relacionadas com a autonomia, o pensamento crítico, o espírito de entreajuda e o gosto por aprender. Pretendeuse ainda perceber se o trabalho colaborativo desenvolvido com a investigadora num contexto de supervisão, contribuiu para o desenvolvimento profissional da professora participante. Adoptou-se uma abordagem interpretativa, de tipo qualitativo, seguindo a metodologia de estudo de caso. Como métodos de recolha de dados, realizaram-se entrevistas, efectuaram-se observações no âmbito da implementação da Metodologia de Projecto na sala de aula, e analisaram-se diversos documentos, como o Currículo Nacional do Ensino Básico – Competências Essenciais (DEB, 2001), documentos produzidos colaborativamente pela investigadora e a professora, como planificações e materiais inerentes ao trabalho de projecto e ainda os trabalhos desenvolvidos pelos alunos. Os resultados do estudo apoiam a ideia de que a realização de projectos através da Metodologia de Projecto, contribuíram para a aprendizagem de conteúdos científicos numa perspectiva construtivista da aprendizagem e promoveram o desenvolvimento de competências sociais essenciais a uma cidadania responsável e crítica. O trabalho de projecto proporcionou ainda a integração de outras áreas disciplinares e não disciplinares, constituindo uma metodologia integradora de saberes. Também o trabalho colaborativo com a professora participante em contexto de supervisão, parece ter contribuído para o enriquecimento das práticas pedagógicas, revelando-se um elemento facilitador do desenvolvimento profissional das professoras envolvidas.

The present document intends to demonstrate the validity of the structure and strategy of the game in the artistic process, more than drawing a parallel between game and art. Starting by finding the differences, with regard to the antagonism of the seriousness of the game and the work, it unfolds to show that the game has always been and is always (and will be) present in art (and in life) – Chapter I, The game in art and the art in the game. As soon as we get that out of the way, we set out to explain ‘what game is’ and what constitutes it in its genesis – Chapter II, The polarity of the word game – highlighting its particularities and discovering its system while the echo and coincidence increasingly manifests itself – Chapter III, the peculiarity of the game – resulting in one of the points of greatest interest and attraction, an inherent duplicity that inevitably unites game and art – Chapter IV, The double play / the double game. Thus, we move towards that which is the main figure of this paper, the artist, - Chapter V, The Pawn , the artist=naught - the creative subject who moderates realities that aim at doubles. With a sharp approach to a third realm, one that seems to be out of our control, we conclude this investigation talking about chance and data, - Chapter VI, My niece is cold – supporting an idea that revolves around winning and losing. the moment when the game is over (and cyclically renewed). Can the game be considered as artistic process?

This work project aims to demonstrate the usefulness of QR codes in museum collections, having as a case study the Sculpture Storage Room of the Faculty of Fine Arts of the University of Lisbon. This storage room has works of art that emerged from various contexts, with 99% of the collection consisting of plasters and the rest by other materials. In addition to the objects in the storage room, there are many pieces exhibited throughout the faculty which are also part of the collection. Due to several factors, such as the fact that it is a large collection and is inserted in the academic context, there are some issues that need to be solved as they may be of concern in the future. The most worrying and the one addressed in this dissertation is the degradation factor called dissociation. As identifying the location of objects and their connection to a system is one of the ways to combat dissociation, we propose the implementation of a QR code system, which can be read with the cameras of our smartphones, allowing access to a large quantity of information through public or private websites. These codes allow us to create links between objects inside the storage room and the information associated with them, such as inventory sheets, location of the objects and map, thus solving the existing problem. In addition to its usefulness in organizing and managing the storage room, these codes can also be useful in Faculty corridors as a way of providing additional information to the visitor, making it accessible to everyone.

Losses on chromatic and preparation layers are a common problem on easel paintings. When the losses are on flesh zones, there is an additional factor of concern, since this is the region that captures the biggest attention of the art appreciator. The choice of the most appropriate filling mass formulation for this situation is a crucial step. The purpose of this investigation was to understand, how the constituent materials from filler influence chromatic reintegration and how the filling materials can be used to assist in color matching on skin areas. To reach this target, the study was directed to filling and retouching of flesh zones, using a painting as a study case, belonging to Faculdade de Belas-Artes da Universidade de Lisboa – FBAUL collection. It was selected and tested 29 filling formulations (between traditional, synthetic and ready-made formulas) being 21 not pigmented and 8 pigmented on laboratory, applied over a mockup model. The 21 not pigmented samples were covered by distinct inks, usually applied in chromatic reintegration. These samples were compared between each other, as well as the 8 pigmented fillers, on different levels of luminosity. Using non-destructive imaging and analytical techniques, were identified the differences that the tested fillers might present when interacting with the applied color. It is intended to document and understand these interactions so that the reintegration process could begin to be thought from the application of filling materials. Recognition of their influence is so far done empirically. This study is another contribution to the selection of fillers. Using color and reflectance measurement, the samples could be distinguished and classified between themselves according with their similarity, and according to a reference on the painting. After the choice of the best sample, an intervention was made at the painting, in order to confirm the methodology. Based on the results obtained with this research, a protocol was proposed, that could provide some guidelines for the conservators-restorers community, a contribution to studies on chromatic reintegration.

Objective: Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that ultimately leads to bone erosions and joint destruction. Methotrexate (MTX) slows bone damage but the mechanism by which it acts is still unknown. In this study, we aimed to assess the effect of MTX and low-dose prednisolone (PDN) on circulating osteoclast (OC) precursors and OC differentiation in patients with RA. Methods: Patients with RA before and at least 6 months after MTX therapy were analysed and compared with healthy donors. A blood sample was collected in order to assess receptor activator of NF-κβ (RANK) ligand surface expression on circulating leucocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines and OC differentiation assays were performed. Results: Classical activation markers of monocytes and RANK increased in patients with RA at baseline, compared with control healthy donors, and after MTX and low-dose PDN (MTX+PDN) exposure they decreased to control levels. Although the number of OC was not different between groups, the percentage of resorbed area and the resorbed area per pit reduced after treatment. Serum soluble receptor activator of nuclear factor-kappa (RANKL) levels increased at baseline compared with healthy donors and normalised after therapy. Conclusion: Our results suggest that MTX+PDN play an important role in downregulating OC function, which we believe occurs through the decrease in RANK surface expression in monocytes.

Several lines of recent evidence support a role for chromatin in splicing regulation. Here, we show that splicing can also contribute to histone modification, which implies bidirectional communication between epigenetic mechanisms and RNA processing. Genome-wide analysis of histone methylation in human cell lines and mouse primary T cells reveals that intron-containing genes are preferentially marked with histone H3 Lys36 trimethylation (H3K36me3) relative to intronless genes. In intron-containing genes, H3K36me3 marking is proportional to transcriptional activity, whereas in intronless genes, H3K36me3 is always detected at much lower levels. Furthermore, splicing inhibition impairs recruitment of H3K36 methyltransferase HYPB (also known as Setd2) and reduces H3K36me3, whereas splicing activation has the opposite effect. Moreover, the increase of H3K36me3 correlates with the length of the first intron, consistent with the view that splicing enhances H3 methylation. We propose that splicing is mechanistically coupled to recruitment of HYPB/Setd2 to elongating RNA polymerase II.

Trees, including minimum spanning trees (MSTs), are commonly used in phylogenetic studies. But, for the research community, it may be unclear that the presented tree is just a hypothesis, chosen from among many possible alternatives. In this scenario, it is important to quantify our confidence in both the trees and the branches/edges included in such trees. In this paper, we address this problem for MSTs by introducing a new edge betweenness metric for undirected and weighted graphs. This spanning edge betweenness metric is defined as the fraction of equivalent MSTs where a given edge is present. The metric provides a per edge statistic that is similar to that of the bootstrap approach frequently used in phylogenetics to support the grouping of taxa. We provide methods for the exact computation of this metric based on the well known Kirchhoff's matrix tree theorem. Moreover, we implement and make available a module for the PHYLOViZ software and evaluate the proposed metric concerning both effectiveness and computational performance. Analysis of trees generated using multilocus sequence typing data (MLST) and the goeBURST algorithm revealed that the space of possible MSTs in real data sets is extremely large. Selection of the edge to be represented using bootstrap could lead to unreliable results since alternative edges are present in the same fraction of equivalent MSTs. The choice of the MST to be presented, results from criteria implemented in the algorithm that must be based in biologically plausible models.

The origin of cells that generate the blastema following appendage amputation has been a long-standing question in epimorphic regeneration studies. The blastema is thought to originate from either stem (or progenitor) cells or differentiated cells of various tissues that undergo dedifferentiation. Here, we investigate the origin of cells that contribute to the regeneration of zebrafish caudal fin skeletal elements. We provide evidence that the process of lepidotrichia (bony rays) regeneration is initiated as early as 24 hours post-amputation and that differentiated scleroblasts acquire a proliferative state, detach from the lepidotrichia surface, migrate distally, integrate into the blastema and dedifferentiate. These findings provide novel insights into the origin of cells in epimorphic appendage regeneration in zebrafish and suggest conservation of regeneration mechanisms between fish and amphibians.

Plasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination during Plasmodium development in the liver.

Retinal homeostasis relies on intricate coordination of cell death and survival in response to stress and damage. Signaling mechanisms that coordinate this process in the adult retina remain poorly understood. Here we identify Decapentaplegic (Dpp) signaling in Drosophila and its mammalian homologue Transforming Growth Factor-beta (TGFβ) superfamily, that includes TGFβ and Bone Morphogenetic Protein (BMP) signaling arms, as central mediators of retinal neuronal death and tissue survival following acute damage. Using a Drosophila model for UV-induced retinal damage, we show that Dpp released from immune cells promotes tissue loss after UV-induced retinal damage. Interestingly, we find a dynamic response of retinal cells to this signal: in an early phase, Dpp-mediated stimulation of Saxophone/Smox signaling promotes apoptosis, while at a later stage, stimulation of the Thickveins/Mad axis promotes tissue repair and survival. This dual role is conserved in the mammalian retina through the TGFβ/BMP signaling, as supplementation of BMP4 or inhibition of TGFβ using small molecules promotes retinal cell survival, while inhibition of BMP negatively affects cell survival after light-induced photoreceptor damage and NMDA induced inner retinal neuronal damage. Our data identify key evolutionarily conserved mechanisms by which retinal homeostasis is maintained.

No âmbito do Projecto de Engenharia Informática (PEI) surgiu a oportunidade de adquirir experiência e novos conhecimentos sobre ferramentas, tecnologias e metodologias do mundo empresarial, numa das maiores empresas de Sistemas de Informação a nível nacional, a Portugal Telecom – Sistemas de Informação S.A. (PTSI). O estágio foi efectuado na área de Suporte Técnico de Business Intelligence (BI) na qual estão inseridos os maiores projectos de BI do grupo PT. Neste departamento de suporte são efectuadas tarefas como as de identificar, analisar, acompanhar, resolver todos os incidentes e problemas que surjam no âmbito de uma aplicação de BI, a instalação de software correctivo e evolutivo nos ambientes de Qualidade e Produção bem como a implementação de novas ferramentas aplicacionais de modo a garantir a operacionalidade da área com vista a automatizar os nossos processos e a diminuir os tempos de resposta aos problemas/necessidades identificados em cada aplicação. O estágio contou com o desenvolvimento de uma ferramenta para a instalação de software relativamente ao sistema de gestão de base de dados SqlServer2005, com o objectivo de automatizar e melhorar o processo de instalação de software para que houvesse uma diminuição dos tempos de resposta por parte da nossa equipa perante o cliente de negócio. A ferramenta foi elaborada seguindo todas as etapas de desenvolvimento de software impostas pelas metodologias da PTSI.

Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.

How immunity is regulated at distinct epithelial tissues that vary in microbial occupancy and environmental and tissue specific cues isn't clear. Dutzan et al. (2017) report that mechanical-derived signals, not those from micro-organisms, are key to maintaining interleukin-17-expressing T helper (Th17) cells at the oral epithelia.

Cervical cancer (CC) is one of the acquired immunodeficiency syndrome (AIDS) defining diseases and the human immunodeficiency virus (HIV) infection is thought to relate with increased acute toxicity of chemoradiotherapy (CRT). We investigated the effect of HIV status in the incidence of neutropenia associated with cisplatin-based CRT for CC and its impact in treatment completion. This is a single-center retrospective cohort study. Data collection was performed for all the consecutive stage Ib-IV CC women treated with cisplatin-based CRT from 2012 to 2016, and with known HIV status. Sixty-one patients were included, 6 were HIV+. HIV+ patients had a higher risk of neutropenia at any cycle during cisplatin CRT [adjusted odds ratio (OR) 7.3, 95% confidence interval (95% CI) 1.02–52.3; P = .05]. Despite the absolute differences, mean neutrophil count was nonsignificantly lower in HIV+ women, both at baseline [4455/μL (interquartile range, IQR: 1830–6689) vs 6340 (IQR: 1720–18,970) for HIV−, P = .98] and at the end of treatment [1752/μL (IQR: 1100–2930) vs 3147/μL (IQR: 920–18,390) in HIV−; P = .06]. Moreover, when considering the effect of time, CRT seems to induce a consistent drop of neutrophils in both groups (P = .229). No febrile neutropenia events occurred. In HIV+ women, there were more CT cycle delays (P = .013), patients were more prone to use granulocyte colony-stimulating factor (G-CSF; HIV+ 40.0% vs HIV− 4.0%; P = .04) and less likely to complete at least 5 cycles of cisplatin (P = .02). All patients received adequate dose of pelvic RT, regardless of HIV status. HIV+ patients have a significantly increased risk of neutropenia during CRT treatment for CC and are less likely to complete chemotherapy with cisplatin.

Introduction: To date, no valid outcome measure has been developed in European Portuguese (EP) to evaluate the Parkinsons' Disease (PD) patients' (PwP) reports regarding their swallowing disturbances. Objectives: The aim of this study was to translate and cross-culturally adapt the Swallowing Disturbance Questionnaire (SDQ) and the Sialorrhea Clinical Scale for PD (SCS-PD) into EP and to determine its clinimetric properties in PwP. Materials and methods: The original English SDQ and SCS-PD versions were cross-culturally adapted following recommendations established in international guidelines. The validation process involved 75 PwP and 65 healthy sex- and age-matched participants. Results: The EP versions of the SDQ and SCS-PD are equivalent to the original versions (content, depth, and scoring). Statistical analyses for the SDQ tool revealed good feasibility (missing data <5%), acceptability (no floor or ceiling effects), excellent internal consistency (Cronbach´s α = 0.95), good construct validity (78.5% revealed large to moderate loadings), moderate convergent validity (r = 0.60), good divergent validity (r = 0.40), good known-groups validity (p-value < .05) and a fair sensitivity and specificity (AUC = 0.700). Statistical analyses for the SCS-PD tool shows good feasibility, reasonable acceptability (floor effect), good internal consistency (Cronbach´s α = 0.85), good construct validity (85.7% showed between large to moderate loadings), good convergent validity (r = 0.78), good divergent validity (r = 0.39), good known groups validity (p-value < .05) and a fair sensitivity and specificity (AUC = 0.704). Conclusions: The EP versions of the SDQ and SCS-PD maintained the characteristics of the original versions and therefore consistent tools to be used in PwP.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper motor neurons in the motor cortex and lower motor neurons (LMN) in the brainstem and spinal cord, resulting in a progressive functional impairment. Neurophysiology is a diagnostic tool to detect dysfunction of upper motor neurons and LMN, even when the changes are subclinical. Electromyography is the standard neurophysiological investigation to detect LMN changes, which is essential to exclude mimicking disorders and attain early diagnosis. Recently, Awaji criteria was proposed to support ALS diagnosis, in these criteria fasciculation potentials associated with neurogenic motor unit potentials represents a sufficient marker of LMN involvement, in each muscle. Many studies have confirmed that Awaji criteria are more sensitive, permitting earlier diagnosis without loss of specificity when compared with the revised El Escorial criteria. Fasciculations are easily detected by ultrasound; increasingly, this technique has been used to diagnose ALS, combined with electromyography. This combination can increase diagnostic accuracy. Many techniques for estimating the number of motor units have been proposed, they are useful to quantify LMN loss. Electrical impedance myography is an emerging technique with great potential to monitor ALS progression. Neurophysiological investigation of upper motor neuron dysfunction is difficult in ALS, detecting decreased cortical inhibition by threshold tracking cortical magnetic stimulation is a promising method, which needs to be validated in different centers.

Introduction: Functional mobility (FM) is a concept that incorporates the capacity of a person to move independently and safely to accomplish tasks. It has been proposed as a Parkinson's disease (PD) functional and global health outcome. In this study, we aimed to identify which kinematic and clinical outcomes changes better predict FM changes when PD patients are submitted to a specialized multidisciplinary program. Methods: PD patients engaged in a pre-defined specialized multidisciplinary program were assessed at admission and discharge. Change from baseline was calculated for all kinematic and clinical outcomes, and Timed Up and Go (TUG) was defined as the primary outcome for FM. A stepwise multivariate linear regression was performed to identify which outcome measures better predict TUG changes. Results: Twenty-four patients were included in the study. The changes in TUG Cognitive test, supervised step length, and free-living (FL) step time asymmetry were identified as the best predictors of TUG changes. The supervised step length and FL step time asymmetry were able to detect a small to moderate effect of the intervention (d values ranging from -0.26 to 0.42). Conclusions: Our results support the use of kinematic outcome measures to evaluate the efficacy of multidisciplinary interventions on PD FM. The TUG Cognitive, step length, and FL step time asymmetry were identified as having the ability to predict TUG changes. More studies are needed to identify the minimal clinically important difference for step length and FL step time asymmetry in response to a multidisciplinary intervention for PD FM.