Development of sandwich panels of customized functionalities for the rehabilitation of the built patrimony

Dissertação de International Master in Sustainable Built Environment

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.

Resolving the ancestry of Austronesian‑speaking populations

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion.

Caracterização dos pais das crianças com NEE e análise do sistema de apoio: um estudo exploratório na cidade de Manaus

Dissertação de mestrado em Educação Especial (área de especialização em Dificuldades de Aprendizagem Específicas)

FISHji: new ImageJ macros for the quantification of fluorescence in epifluorescence images

Fluorescence in situ hybridization (FISH) is based on the use of fluorescent staining dyes, however, the signal intensity of the images obtained by microscopy is seldom quantified with accuracy by the researcher. The development of innovative digital image processing programs and tools has been trying to overcome this problem, however, the determination of fluorescent intensity in microscopy images still has issues due to the lack of precision in the results and the complexity of existing software. This work presents FISHji, a set of new ImageJ methods for automated quantification of fluorescence in images obtained by epifluorescence microscopy. To validate the methods, results obtained by FISHji were compared with results obtained by flow cytometry. The mean correlation between FISHji and flow cytometry was high and significant, showing that the imaging methods are able to accurately assess the signal intensity of fluorescence images. FISHji are available for non-commercial use at http://paginas.fe.up.pt/nazevedo/.

An R package for the integrated analysis of metabolomics and spectral data

Recently, there has been a growing interest in the field of metabolomics, materialized by a remarkable growth in experimental techniques, available data and related biological applications. Indeed, techniques as Nuclear Magnetic Resonance, Gas or Liquid Chromatography, Mass Spectrometry, Infrared and UV-visible spectroscopies have provided extensive datasets that can help in tasks as biological and biomedical discovery, biotechnology and drug development. However, as it happens with other omics data, the analysis of metabolomics datasets provides multiple challenges, both in terms of methodologies and in the development of appropriate computational tools. Indeed, from the available software tools, none addresses the multiplicity of existing techniques and data analysis tasks. In this work, we make available a novel R package, named specmine, which provides a set of methods for metabolomics data analysis, including data loading in different formats, pre-processing, metabolite identification, univariate and multivariate data analysis, machine learning, and feature selection. Importantly, the implemented methods provide adequate support for the analysis of data from diverse experimental techniques, integrating a large set of functions from several R packages in a powerful, yet simple to use environment. The package, already available in CRAN, is accompanied by a web site where users can deposit datasets, scripts and analysis reports to be shared with the community, promoting the efficient sharing of metabolomics data analysis pipelines.

O papel dos fisioterapeutas na equipe multidisciplinar atuantes no complexo municipal André Vidal de Araújo em Manaus

Dissertação de mestrado em Educação Especial (área de especialização em Dificuldades de Aprendizagem Específicas)

Psychosocial adjustment and physical health in children of divorce

Objective: To review the literature on the effects of parental divorce over the psychological maladjustment and physical health problems in children of divorced parents, thus contributing to the integration of existing scientific knowledge based on the biopsychosocial model of the impact of divorce on children’s physical health as proposed by Troxel and Matthews (2004). Sources: Review of the literature using MEDLINE and PsycInfo (1980-2007) databases, selecting the most representative articles on the subject. Special attention was paid to contributions by internationally renowned investigators on the subject. Summary of the findings: Divorce may be responsible for a decline of physical and psychological health in children. The developmental maladjustment of children is not triggered by divorce itself, but rather by other risk factors associated with it, such as interparental conflict, parental psychopathology, decline in socio-economic level, inconsistency in parenting styles, a parallel and conflicting co-parenting relationship between parents and low levels of social support. Such risk factors trigger maladjusted developmental pathways, marked by psychopathological symptoms, poor academic performance, worst levels of physical health, risk behavior, exacerbated psychophysiological responses to stress and weakening of the immune system. Conclusions: Clear links were observed between experiencing parental divorce and facing problems of physical and psychological maladjustment in children. Divorce is a stressor that should be considered by health professionals as potentially responsible for maladjusted neuropsychobiological responses and for decline in children’s physical health.

Pervasive decision support to predict football corners and goals by means of data mining

Football is considered nowadays one of the most popular sports. In the betting world, it has acquired an outstanding position, which moves millions of euros during the period of a single football match. The lack of profitability of football betting users has been stressed as a problem. This lack gave origin to this research proposal, which it is going to analyse the possibility of existing a way to support the users to increase their profits on their bets. Data mining models were induced with the purpose of supporting the gamblers to increase their profits in the medium/long term. Being conscience that the models can fail, the results achieved by four of the seven targets in the models are encouraging and suggest that the system can help to increase the profits. All defined targets have two possible classes to predict, for example, if there are more or less than 7.5 corners in a single game. The data mining models of the targets, more or less than 7.5 corners, 8.5 corners, 1.5 goals and 3.5 goals achieved the pre-defined thresholds. The models were implemented in a prototype, which it is a pervasive decision support system. This system was developed with the purpose to be an interface for any user, both for an expert user as to a user who has no knowledge in football games.

Quantifying the legacy of the Chinese Neolithic on the maternal genetic heritage of Taiwan and Island Southeast Asia

There has been a long-standing debate concerning the extent to which the spread of Neolithic ceramics and Malay-Polynesian languages in Island Southeast Asia (ISEA) were coupled to an agriculturally driven demic dispersal out of Taiwan 4000 years ago (4 ka). We previously addressed this question using founder analysis of mitochondrial DNA (mtDNA) control-region sequences to identify major lineage clusters most likely to have dispersed from Taiwan into ISEA, proposing that the dispersal had a relatively minor impact on the extant genetic structure of ISEA, and that the role of agriculture in the expansion of the Austronesian languages was therefore likely to have been correspondingly minor. Here we test these conclusions by sequencing whole mtDNAs from across Taiwan and ISEA, using their higher chronological precision to resolve the overall proportion that participated in the "out-of-Taiwan" mid-Holocene dispersal as opposed to earlier, postglacial expansions in the Early Holocene. We show that, in total, about 20 % of mtDNA lineages in the modern ISEA pool result from the "out-of-Taiwan" dispersal, with most of the remainder signifying earlier processes, mainly due to sea-level rises after the Last Glacial Maximum. Notably, we show that every one of these founder clusters previously entered Taiwan from China, 6-7 ka, where rice-farming originated, and remained distinct from the indigenous Taiwanese population until after the subsequent dispersal into ISEA.