Repositório RCAAP

During my PhD at Instituto de Medicina Molecular João Lobo Antunes (iMM), I developed web apps for transcriptomic data analyses as free, open-source resources and an app server to deploy them. psichomics Alternative pre-mRNA splicing generates functionally distinct transcripts from the same gene and is involved in the control of multiple cellular processes, with its dysregulation being linked to a variety of pathologies. The advent of next-generation sequencing has enabled global studies of alternative splicing in different physiologic and pathologic contexts. However, bioinformatics tools for alternative splicing analysis from RNA-seq data used to be user-unfriendly, disregard available exon-exon junction quantification or have limited downstream analysis features. To overcome such limitations, we developed psichomics, an R package with an intuitive graphical interface for alternative splicing quantification and integrative analyses of alternative splicing and gene expression from large transcriptomic datasets, including those from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the recount2 project, as well as user-provided data. psichomics assists the user in integrating sample-associated features (molecular and clinical) to perform survival, dimensionality reduction, and differential alternative splicing and gene expression analyses. Since its publication in 2018, psichomics has been used to discover splicing-associated prognostic factors and therapeutic targets, along with studying alternative splicing regulation in physiological and pathological contexts. cTRAP The Connectivity Map (CMap) hosts differential expression profiles associated with thousands of genetic and pharmacologic perturbations (perturbagens) of human cells. We developed the cTRAP R package to identify potentially causal molecular perturbations by comparing user-provided differential gene expression results with those from CMap, using correlation and gene set enrichment scores. cTRAP can also compare against gene expression/drug sensitivity associations derived from the NCI-60 cancer cell line panel, the Cancer Therapeutics Response Portal and the Genomics of Drug Sensitivity in Cancer project, to pinpoint compounds that may target the phenotypes associated with the user-provided differential expression profiles. We envisage cTRAP allowing users to identify putative causal perturbations to better understand the molecular mechanisms associated with the observed phenotypes, as well as to predict therapeutic targets. CompBio app server Both psichomics and cTRAP feature graphical interfaces to assist users in exploring most of their functionality. We set up the CompBio app server based on Docker Compose to deploy our lab’s web apps, publicly available at compbio.imm.medicina.ulisboa. pt.

Antibiotic-resistant bacteria are rapidly emerging, and the number of available therapeutic options to fight them is decreasing. In addition, as a surviving strategy, bacteria can aggregate and form biofilms, a multicellular community embedded in a self-produced matrix of extracellular polymeric substances (EPS), which contributes significantly to the reduced susceptibility of bacteria towards conventional antibiotics and innate host defenses. It has been estimated that biofilms are responsible for most infections in tissues and are also recurrent colonizers of biomedical devices. Hence, the identification of novel antimicrobial agents capable to fight infections caused by resistant bacteria and bacterial biofilms is urgently needed. Antimicrobial peptides (AMPs) have been proposed as promising therapeutic alternatives to conventional antibiotics due to their broad-spectrum activity, fast-killing kinetics, and distinct mechanisms of action. In general, AMPs selectively target and kill bacteria through membrane-disruptive mechanisms, thus their activity is independent of the cellular metabolism. This feature confers AMPs the ability to act on dormant populations, which are frequently found in biofilms and are particularly difficult to target by conventional antibiotics. Taking advantage of the fact that viral proteins are an underexplored source of bioactive peptides with antimicrobial properties and based on the knowledge that cell-penetrating peptides (CPPs) can act as AMPs, the present work identified one viral-derived peptide, vCPP2319, active against bacteria in the planktonic and biofilm forms. The peptide was able to effectively kill bacteria through a mechanism of action involving bacterial membrane permeabilization. Nonetheless, vCPP2319 had a limited effect on the biofilm EPS matrix itself. Thus, biofilm treatment with vCPP2319 and a matrix-degrading enzyme, α-amylase, was studied. This combination did not improve the antibacterial action of the peptide. Given the knowledge that cyclization of bioactive peptides is a promising approach for improving peptides’ stability and bioactivity, the antibiofilm activity of the cyclic peptide, [G1K,K8R]cGm, was investigated against S. aureus biofilms. The peptide was able to kill biofilm-embedded cells in a concentration-dependent manner. Mechanistic studies showed that [G1K,K8R]cGm causes morphological changes on bacterial cells and permeabilizes their membranes with a half time of 65 min. Also, we tested an analogue of [G1K,K8R]cGm without disulfide bonds, and a linear unfolded analogue, and found both to be inactive. This finding suggests that the three dimensional structure of [G1K,K8R]cGm and its stabilization by disulfide bonds are essential for its antibacterial and antibiofilm activities. Overall, this study demonstrates the potential of viral proteins as rich sources of new bioactive peptides with antibacterial and antibiofilm properties. In addition, peptide backbone cyclization proved to be valuable strategy to enhance AMPs activity against preformed biofilms.

A utilização de conhecimento conceptual requere a representação semântica de múltiplas informações sobre objetos, e processos de controlo para aceder aos subconjuntos de conhecimento relevantes em cada tarefa. Notavelmente, pouco se sabe sobre a interação entre estes mecanismos semânticos no envelhecimento saudável. Ao nível cognitivo, o envelhecimento é associado à acumulação de conhecimento e ao declínio do controlo cognitivo, enquanto ao nível neuronal tem sido associado a padrões de sobre-ativação, sobretudo em regiões frontais que mostram atrofia cortical. Com recurso à abordagem da neurociência cognitiva para articular medidas comportamentais, com técnicas de MRI funcional e estrutural, investigámos como é que o cérebro envelhecido produz operações semânticas. No estudo comportamental, jovens e idosos realizaram uma tarefa de categorização de itens que variaram na tipicidade. Os resultados mostraram que os idosos foram melhores do que os jovens na categorização de itens atípicos, indicando que, em idades mais avançadas, as pessoas possuem mais conhecimento que promove a inclusão dos conceitos atípicos nas categorias apropriadas. O declínio no controlo cognitivo observado no envelhecimento não prejudicou a categorização destes itens, que se sabe estarem menos bem integrados no repositório semântico em idades mais jovens. No estudo MRI funcional, jovens e idosos nomearam itens típicos e atípicos. Comparados com os participantes jovens, os idosos sobre-ativaram regiões cerebrais associadas à representação semântica, incluindo as porções anteriores e mediais do lobo temporal. Isto sugere a reorganização da atividade neuronal contingente ao aumento de conhecimento em idades avançadas. A circunvolução orbitofrontal média também revelou sobre-ativação, indicando assim que o processamento de itens atípicos taxa recursos adicionais de controlo nos idosos. Mais ainda, as análises de MRI estrutural revelaram que a idade reverte a relação entre espessura cortical e desempenho semântico particularmente em regiões cerebrais do hemisfério direito. Enquanto os jovens mostraram uma associação negativa na circunvolução frontal inferior direita e na circunvolução temporal média, os idosos mostraram uma tendência de correlação positiva. Isto sugere que a manutenção neurobiológica destas regiões cerebrais pode constituir um recurso para os idosos assegurarem o processamento semântico. Em suma, estes resultados revelam um conjunto de reajustamentos que ocorrem a nível cognitivo, funcional e estrutural ao longo da vida para apoiar a cognição semântica.

The introduction of the digital book led to a paradigm shift in the literary universe, creating several questions around the coexistence of the new format with traditional printed books. After a short period of rapid development, in recent years the digital book has seen a phase of stagnation, with most readers preferring the printed version. Thus, the core objective of this dissertation was to find an explanation and answers to the disinterest in digital book by the public, while finding solutions for this problem. The secondary objectives were addressed through the investigation process, such as un-derstanding the history and introduction of digital books, the coexistence of the two me-diums and their connection with the readers. One of the central themes addressed in this dissertation was the digital book as an ex-perimental object. The digital medium was at its disposition an ample number of func-tions and tools that could promote the development of more engaging publications for the readers. Given the theorical-practical nature of this dissertation, it was proposed the creation of an experimental digital book that utilizes the features of the digital medium to establish moments of interaction with the reader. Prototypes were created with this purpose and a small survey was applied to validate their quality. With the results in mind, the final project consists in the adaptation of a book of the Interactive Fiction genre to a website

This article seeks to discuss the relations between reading and writing against the historical backdrop of the initial affirmation of the studia humanitatis in fifteenth-century renaissance Italy and its initial movement towards the North of Europe. It focuses first on the theory of education and learning expressed in the Treatises of four Italian humanists. These treatises were structured based on the coeval experiments undertaken by extremely famous teachers such as the Byzantine diplomat Chrysoloras (1355–1415), who is generally credited with having initiated humanist pedagogy, Gasparino Barzizza (1360–1430), in the cities of Padua and Pavia, Vittorino da Feltre (1370–1446), in Mantua, and above all, Guarino Guarini da Verona (1374–1460), in Ferrara. The action of these last three teachers led to the consolidation of the introduction into the syllabus of a large number of Latin authors, through which the study of the Greek language and literature was endowed with greater legitimacy. It also tracks the proposals of Valla (1407–1457) and Rodolph Agricola (1444–1485). The options regarding the studies and the methodologies used spread to many schools, which we today call secondary schools and universities. Although this reality is restricted in time and space, the article has the broader goal of contributing to a deeper understanding of a school culture that promotes the real development of creative writing skills among its pupils, and which therefore opposes the civilisational principle that identifies the school model in the contemporary epoch as advocating the possibility to teach everything to everybody and always based on a textbook compiled for use by the pupils.

The current study investigated which time components of rapid automatized naming (RAN) predict group differences between dyslexic and non‐dyslexic readers (matched for age and reading level), and how these components relate to different reading measures. Subjects performed two RAN tasks (letters and objects), and data were analyzed through a response time analysis. Our results demonstrated that impaired RAN performance in dyslexic readers mainly stem from enhanced inter‐item pause times and not from difficulties at the level of post‐access motor production (expressed as articulation rates). Moreover, inter‐item pause times account for a significant proportion of variance in reading ability in addition to the effect of phonological awareness in the dyslexic group. This suggests that non‐phonological factors may lie at the root of the association between RAN inter‐item pauses and reading ability. In normal readers, RAN performance was associated with reading ability only at early ages (i.e. in the reading‐matched controls), and again it was the RAN inter‐item pause times that explain the association.

In the present study, the authors investigate how some visual factors related to early stages of visual-object naming modulate naming performance in dyslexia. The performance of dyslexic children was compared with 2 control groups—normal readers matched for age and normal readers matched for reading level—while performing a discrete naming task in which color and dimensionality of the visually presented objects were manipulated. The results showed that 2-dimensional naming performance improved for color representations in control readers but not in dyslexics. In contrast to control readers, dyslexics were also insensitive to the stimulus’s dimensionality. These findings are unlikely to be explained by a phonological processing problem related to phonological access or retrieval but suggest that dyslexics have a lower capacity for coding and decoding visual surface features of 2-dimensional representations or problems with the integration of visual information stored in long-term memory.

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Uma questão crítica no entendimento da assimetria inter-hemisférica para a linguagem diz respeito ao desenvolvimento da especialização hemisférica esquerda para o processamento do discurso em função da idade. Numerosas investigações realizadas sobre esta temática têm oscilado entre uma perspectiva inata e estanque da lateralização cerebral e uma perspectiva que preconiza ser o seu desenvolvimento progressivo e passível de influências externas. No âmbito do debate recente sobre a influência de factores ambientais neste processo, propusemo-nos investigar o efeito da escolaridade no processo de lateralização inter-hemisférica, recorrendo à técnica da escuta dicótica e comparando crianças que ainda não iniciaram a escolaridade com crianças que frequentam diferentes níveis do ensino básico. No nosso estudo, manipulamos a orientação da atenção (focada à direita ou à esquerda) e a carga verbal dos estímulos utilizados (elevada e baixa carga verbal). Os resultados mostram uma diminuição progressiva das diferenças entre ouvidos com a escolaridade, remetendo para duas explicações possivelmente complementares: 1) uma atenuação com a escolaridade da lateralização cerebral da linguagem; 2) uma melhoria progressiva na capacidade de orientar a atenção exigida pela prova de escuta dicótica.

This article summarizes some of the important findings from research evaluating the relationship between poor rapid naming and impaired reading performance. Substantial evidence shows that dyslexic readers have problems with rapid naming of visual items. Early research assumed that this was a consequence of phonological processing deficits, but recent findings suggest that non-phonological processes may lie at the root of the association between slow naming speed and poor reading. The hypothesis that rapid naming reflects an independent core deficit in dyslexia is supported by the main findings: (1) some dyslexics are characterized by rapid naming difficulties but intact phonological skills; (2) evidence for an independent association between rapid naming and reading competence in the dyslexic readers, when the effect of phonological skills was controlled; (3) rapid naming and phonological processing measures are not reliably correlated. Recent research also reveals greater predictive power of rapid naming, in particular the inter-item pause time, for high-frequency word reading compared to pseudoword reading in developmental dyslexia. Altogether, the results are more consistent with the view that a phonological component alone cannot account for the rapid naming performance in dyslexia. Rather, rapid naming problems may emerge from the inefficiencies in visual-orthographic processing as well as in phonological processing.

Induced abortion up to ten completed weeks has been legal in Portugal since April 2007. In 1984 and 1997,two laws decriminalised abortion in three different situations: (1) For maternal indications (up to 12 completed weeks); (2) For fetal indications (up to 16 completed weeks since 1984, and up to 24 completed weeks since 1997); (3) In case of rape, renamed since 1997 ‘crime against sexual freedom’ (up to 12 completed weeks between 1984 and 1997, up to 16 completed weeks since then).

One implication of the double-deficit hypothesis for dyslexia is that there should be subtypes of dyslexic readers that exhibit rapid naming deficits with or without concomitant phonological processing problems. In the current study, we investigated the validity of this hypothesis for Portuguese orthography, which is more consistent than English orthography, by exploring different cognitive profiles in a sample of dyslexic children. In particular, we were interested in identifying readers characterized by a pure rapid automatized naming deficit. We also examined whether rapid naming and phonological awareness independently account for individual differences in reading performance. We characterized the performance of dyslexic readers and a control group of normal readers matched for age on reading, visual rapid naming and phonological processing tasks. Our results suggest that there is a subgroup of dyslexic readers with intact phonological processing capacity (in terms of both accuracy and speed measures) but poor rapid naming skills. We also provide evidence for an independent association between rapid naming and reading competence in the dyslexic sample, when the effect of phonological skills was controlled. Altogether, the results are more consistent with the view that rapid naming problems in dyslexia represent a second core deficit rather than an exclusive phonological explanation for the rapid naming deficits. Furthermore, additional non-phonological processes, which subserve rapid naming performance, contribute independently to reading development.

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As crenças sobre a carreira e sobre as suas capacidades para lidar com as tarefas vocacionais condicionam os comportamentos dos jovens na transição ensino superior/ trabalho. O presente estudo avalia as crenças de autoeficácia face à transição para o trabalho e as crenças de carreira e empregabilidade em 534 estudantes universitários, 267 homens e 267 mulheres, a quem foram aplicados o Inventário de Crenças de Carreira e Empregabilidade e a Escala de Autoeficácia na Transição para o Trabalho. São analisadas médias, desvios-padrão, correlações e diferenças entre grupos definidos por género. Os resultados revelam médias elevadas nas crenças subjacentes a comportamentos e atitudes adaptativos face às transições de carreira, com diferenças favoráveis ao sexo feminino em Flexibilidade, Desafios e Autonomia.

Previous research has shown that spontaneous trait inferences (STI) made from behaviors are bound to actor’s faces. Additionally, research has shown that inferred traits can also become associated with the faces of communicators of the behaviors through spontaneous trait transference (STT). In this study, we replaced the actors’ pictures by actors’ names, in order to investigate whether names of actors and communicators (e.g., Carl Smith) can also become attached to inferred traits. Under these conditions, evidence of STIs was obtained, but not of STTs. These results show that the association between traits and communicators (STT) is highly dependent on the visual salience of the communicator. In contrast, STIs occur even when actors are not visually salient. Results are discussed in terms of the processes underlying STIs and STTs.

The bias blind spot (BBS) is the tendency for people to perceive themselves as less biased than others. This tendency resembles a self-enhancement effect, but research has mainly focused on other mechanisms that purportedly underlie the BBS. In this paper we present developmental evidence that the BBS and a self-enhancing tendency, namely the better-than-average effect, develop independently (Studies 1 and 2). Children aged 5 to 12-years-old do not believe they are biased (despite evidence that they are). However, while younger children tend to believe others are unbiased, older children believe others are biased (Studies 2 and 3). Importantly, younger children understand that unbiased behavior is better than biased behavior (Study 4). Together, these results converge with the notion that the BBS is not a mere instance of a self-enhancing tendency and suggest that the BBS is the residual part of a bigger illusion that everyone is unbiased.

The bias blind spot (BBS) is the tendency for people to perceive themselves as less biased than others. This tendency resembles a self-enhancement ef fect, but research has mainly focused on other mechanisms that purported ly underlie the BBS. In this article we present developmental evidence that the BBS and a self-enhancing tendency, namely the better-than-average ef fect, develop independently (Studies 1 and 2). Children aged 5 to 12 years old do not believe they are biased (despite evidence that they are). How ever, while younger children tend to believe others are unbiased, older children believe others are biased (Studies 2 and 3). Importantly, younger children understand that unbiased behavior is better than biased behavior (Study 4). Together, these results converge with the notion that the BBS is not a mere instance of a self-enhancing tendency and suggest that the BBS is the residual part of a bigger illusion that everyone is unbiased.

A rights-based approach calls for studies to explore further the extent to which rights’ fulfillment in residential care affects young people’s mental health. A focus on protective factors, such as supportive relations, can inform policies and practices in residential care which is critical for youths’ empowerment and adaptive outcomes. However, existing studies on social support are mainly descriptive and qualitative in nature or focus on the effect of support in mental health. This study builds upon and enhances existing knowledge by exploring the moderating role of social support from educators in residential care and the association between perceived rights and psychological difficulties. A sample of 366 adolescents (53% boys) in residential care (Mage ¼ 14.82; SD ¼ 1.81) were included in this study and completed self-reported measures on perceived rights, support in residential care and psychological difficulties. Social support moderated the relationship between the perception of rights regarding respectful system practices, autonomy and contact with family, as well as psychological difficulties. When greater social support was perceived by the adolescents, higher perceptions of respectful system practices and lower perceptions of autonomy and contact with family were associated with lower levels of psychological difficulties. Results provide evidence for the positive role of rights’ fulfillment in psychological functioning in residential care, as well as the protective role of supportive educators.