Repositório RCAAP

Os gregos fizeram descoberta surpreendente: uma pedra metálica escura, que podia repelir ou atrair objectos de ferro - era a origem do estudo do magnetismo. Na época das grandes navegações, não se conseguia localizar um navio no mar pelas duas coordenadas, a latitude e a longitude; a determinação desta exigia um relógio a bordo que indicasse a hora exacta no meridiano de referência, e a determinação astronómica da longitude dava erros inaceitáveis. Durante a viagem até à Índia, D. João de Castro levou a cabo um conjunto de experiências que conseguiu detectar fenómenos, nomeadamente relacionados com o magnetismo e com as agulhas magnéticas a bordo. É de supor que devia esses conhecimentos a Pedro Nunes, naturalmente o directo inspirador de todas as observações que realizou nas suas viagens. Quando em 5 de Agosto de 1538, D. João de Castro decidiu determinar a latitude de Moçambique, encontrou a causa que ditava o «espantoso desconcerto» das agulhas: notou o desvio da agulha, descobrindo-o 128 anos antes de Guillaume Dennis (1666), de Nieppe, o qual é registado na História da Navegação como se fosse o primeiro a conhecer esse fenómeno. A sua observação nas proximidades de Baçaim, em 22 de Dezembro de 1538, de um fenómeno magnético, pelo qual se verificavam variações da agulha devido à proximidade de certos rochedos, confirmadas quatro séculos mais tarde, foi denominado atracção local. D. João de Castro refutou a teoria de que a variação da declinação magnética não se fazia por meridianos geográficos. As suas observações são o mais importante registo de valores da declinação magnética no Atlântico e no Índico, no século XVI, e úteis para o estudo do magnetismo terrestre. Foi uma das personalidades da ciência experimental europeia desse século, relacionando a importância desse estudo com as navegações. O seu nome ficou ligado à ciência pelas suas obras que evidenciavam uma tendência para o moderno espírito científico.

O presente estudo tem como finalidade analisar os estados emocionais dos candidatos ao primeiro ano da Academia Militar, nomeadamente a ansiedade, a depressão e o stress, explorando e tentando compreender o papel das Estratégias de Coping. Adoptou-se o Modelo de Lazarus e Folkman (1984) como fundamento relativamente à problemática de stress e coping. A amostra é constituída por 192 candidatos à Academia Militar, com idades compreendias entre os 17 e os 26 anos. Para a recolha dos dados foram utilizados dois questionários de auto-relato, a saber: a Escala de Depressão, Ansiedade e Stress (EADS) (Lovibond & Lovibond, 1995) e o Ways of Coping Questionnaire (Folkman & Lazarus, 1988b). Os resultados obtidos, revelam baixos níveis de ansiedade, depressão e stress quer para o sexo masculino, quer para o sexo feminino. Este facto pode dever-se à utilização de estratégias de coping direccionadas para o problema, sendo que a estratégia de Resolução Planeada do Problema, apresenta um valor elevado, para o sexo masculino e feminino, quando comparado com as restantes estratégias de coping. Verificou-se também que não existem diferenças significativas entre os sexos, no que respeita ao tipo de estratégias de coping utilizadas. Todavia, quando analisados os níveis de ansiedade, depressão e stress entre os sexos, verificam-se níveis significativamente mais elevados de stress e ansiedade para o sexo feminino. Os resultados permitem conhecer em maior profundidade os candidatos à Academia Militar e a forma como lidam com o processo de transição/adaptação, assim como permite verificar as estratégias mais utilizadas pelos mesmos.

Background: How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue. Results: Specific deletion of Smarcad1 in the mouse intestinal epithelium leads to colitis resistance and substantial changes in gene expression, including a striking increase of expression of several genes linked to innate immunity. Absence of Smarcad1 leads to changes in chromatin accessibility and significant changes in histone H3K9me3 over many sites, including genes that are differentially regulated upon Smarcad1 deletion. We identify candidate members of the gut microbiome that elicit a Smarcad1-dependent colitis response, including members of the poorly understood TM7 phylum. Conclusions: Our study sheds light onto the role of the chromatin remodeling machinery in intestinal epithelial cells in the colitis response and shows how a highly conserved chromatin remodeling factor has a distinct role in anti-microbial defense. This work highlights the importance of the intestinal epithelium in the colitis response and the potential of microbial species as pharmacological and probiotic targets in the context of inflammatory diseases.

Background: Hereditary Transthyretin Amyloidosis Polyneuropathy is a rare life-threatening neurologic disease that imposes considerable mortality and it is associated with progressive related disabilities. In this study, we aimed to assess the effect of the disease across health-related quality of life dimensions, in both carriers of the mutation and patients, to compare health-related quality of life with general population, as well as to explore health-related quality of life prognostic factors among patients, including disease progression and treatment. Methods: This study was a multi-institutional, longitudinal, prospective, observational study of hereditary Transthyretin Amyloidosis Polyneuropathy Portuguese adult subjects (621 asymptomatic carriers and 733 symptomatic patients) enrolled in the Transthyretin Amyloidosis Outcomes Survey. Health-related quality of life was captured with the preference-based instrument EQ-5D-3 L. For general population the dataset included all subjects enrolled in a representative national study (n = 1500). Different econometric models were specified; multivariate probit, generalized linear model and generalized estimating equations model; including demographic and clinical covariates. Results: Hereditary Transthyretin Amyloidosis Polyneuropathy patients have their health status severely impaired in all quality of life dimensions and more anxiety/depression problems were found among asymptomatic carriers. No differences on utility were found between carriers and general population (p = 0.209). Among patients, the utility value is estimated to be 0.51 (0.021), a decrement of 0.27 as compared with general population utility. Higher disease duration, advanced disease stage and not receiving treatment are associated with impaired health-related quality of life. No differences were found between genders (p = 0.910) or between late (≥50 years) and early-onset patients (p = 0.254). The utility estimate ranged from 0.63 (0.009) in stage I to 0.01 (0.005) in stage IV. Conclusions: Hereditary Transthyretin Amyloidosis Polyneuropathy symptoms and progressive associated disabilities substantially decrease patient's health-related quality of life. Clinical strategies focused on health-related quality of life preservation such as close follow-up of asymptomatic carriers, prompt diagnosis and adequate, early treatment would benefit patient's long-term outcomes, slowing the progressive decline in health-related quality of life.

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Dengue virus (DENV) represents a public health threat and economic burden in affected countries. The availability of genomic data is key to understanding viral evolution and dynamics, supporting improved control strategies. Currently, the use of high-throughput sequencing (HTS) technologies, which can be applied both directly to patient samples (shotgun metagenomics) and to PCR-amplified viral sequences (amplicon sequencing), is potentially the most informative approach to monitor viral dissemination and genetic diversity by providing, in a single methodological step, identification and characterization of the whole viral genome at the nucleotide level. Despite many advantages, these technologies require bioinformatics expertise and appropriate infrastructure for the analysis and interpretation of the resulting data. In addition, the many software solutions available can hamper the reproducibility and comparison of results. Here we present DEN-IM, a one-stop, user-friendly, containerized and reproducible workflow for the analysis of DENV short-read sequencing data from both amplicon and shotgun metagenomics approaches. It is able to infer the DENV coding sequence (CDS), identify the serotype and genotype, and generate a phylogenetic tree. It can easily be run on any UNIX-like system, from local machines to high-performance computing clusters, performing a comprehensive analysis without the requirement for extensive bioinformatics expertise. Using DEN-IM, we successfully analysed two types of DENV datasets. The first comprised 25 shotgun metagenomic sequencing samples from patients with variable serotypes and genotypes, including an in vitro spiked sample containing the four known serotypes. The second consisted of 106 paired-end and 76 single-end amplicon sequences of DENV 3 genotype III and DENV 1 genotype I, respectively, where DEN-IM allowed detection of the intra-genotype diversity. The DEN-IM workflow, parameters and execution configuration files, and documentation are freely available at https://github.com/B-UMMI/DEN-IM).

No summary/description provided

Background: Ischemic stroke is a frequent neurologic complication of infective endocarditis. This systematic review aims to evaluate the efficacy and safety of thrombectomy in comparison to thrombolysis and to combined treatment in patients with infective endocarditis associated acute ischemic stroke. Methods: A systematic literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review included case reports, cases series, cross-sectional studies, case control studies, randomized controlled trials or nonrandomized controlled trials, which reported the treatment of endocarditis-related acute ischemic stroke with mechanical thrombectomy, intravenous or intra-arterial thrombolysis in adult patients. Data sources: Scielo, b-on, Pubmed and Cochrane, from inception to April 2019. Reference lists were also checked. We compared the efficacy (independence, neurological improvement) and safety (intracranial bleeding, death) of acute ischemic stroke treatment with thrombolysis, thrombectomy and combined therapy. Results: Through systematic review 37 articles describing 52 patients met criteria. The risk of intracranial hemorrhage was 4.14 times higher in patients treated with intravenous thrombolysis (P = .001) and 4.67 times higher in patients treated with combined treatment (P = .01). There was trend for independence (P = .09) and neurological improvement (P = .07) in favor of thrombectomy, when comparing this group to the group treated with intravenous thrombolysis. Conclusions: With the limitation of the low quality of the available evidence, thrombectomy in infective endocarditis associated stroke appears to be safer than thrombolysis, or combined treatment. These results may be useful to guide clinical decisions, in selected patients.

The epigenetic and functional reprogramming of immune genes during induction of trained immunity is accompanied by the metabolic rewiring of cellular state. This memory is induced in the hematopoietic niche and propagated to daughter cells, generating epigenetically and metabolically reprogrammed innate immune cells that are greatly enhanced in their capacity to resolve inflammation. In particular, these cells show accumulation of H3K4me3 and H3K27Ac epigenetic marks on multiple immune gene promoters and associated enhancers. However, the mechanism governing how these epigenetic marks accumulate at discrete immune gene loci has been poorly understood, until now. Here, we discuss some recent advances in the regulation of trained immunity, with a particular focus on the mechanistic role of a novel class of long non-coding RNAs in the establishment of epigenetic marks on trained immune gene promoters.

No summary/description provided

Background: Acquired perforating dermatosis (APD) comprises an uncommon group of skin disorders that develop in adulthood in association with systemic diseases. The aim of this study was to characterize clinicopathologic features and treatment outcomes in a series of patients diagnosed with APD. Methods: Retrospective study of all patients diagnosed with an APD over a 10-year period (2009-2018) at a tertiary teaching hospital in Lisbon, Portugal. Results: Fifty-seven patients with APD were identified. Thirty-five patients presented lesions in multiple anatomic areas (61.4%), and the lower limbs were the most common location. Forty-six patients reported pruritus (80.7%), which was classified as severe in 21 of them (36.8%). An underlying systemic disease was identified in 53 patients (93.0%). Diabetes mellitus (DM) and chronic kidney disease (CKD) were the most common associated systemic diseases, but psychiatric disorders, malignancies, and chronic infections were present in a significant number of patients. The combination of topical steroids with antihistamines was the most prescribed initial treatment, but only 37.8% of the patients had a complete response. Acitretin, systemic steroids, and phototherapy were the treatments associated with the best outcome. Conclusion: Acquired perforating dermatosis can be associated with many systemic disorders that have pruritus as a common factor. Chronic viral infections and an occult malignancy should be sought, particularly in the absence of DM and CKD. The management of APD is challenging and is best achieved with the control of the underlying systemic diseases.

Kidney transplant (KT) recipients have an increased risk for urothelial carcinoma. A role for JC virus (JCV) in human cancers is not yet proved but there is an increasingly reported association between BK virus (BKV) nephropathy and renourinary neoplasms. We report a KT recipient who developed a high-grade urothelial carcinoma 5 years after a diagnosis of JCV nephropathy and 9 years after kidney transplantation. Neoplastic tissue was positive for JCV DNA by real-time polymerase chain reaction (PCR). Immunochemical staining showed strong positivity for cell cycle markers (p16, p53, and Ki67) and for early viral protein JCV large T antigen (JCV LTag; using a broad polyomavirus antibody); however, late viral protein (VP1) stained negative. In contrast, in non-neoplastic urothelium, JCV DNA and all immunochemical markers were negative. These facts suggest that malignancy was induced by JCV. To the best of our knowledge, this is the first report of urothelial high-grade carcinoma associated with JCV nephropathy in a KT recipient.

O Modelo da Complementaridade Paradigmática segue uma perspectiva integrativa e conceptualiza sete pares de necessidades psicológicas (Vaz-Velho, Vasco & Conceição, 2011; Vaz-Velho & Vasco, 2010; Vasco, 2011, 2010, 2009a, 2009b), concebendo o bem-estar como resultante da regulação de satisfação das necessidades através de um processo contínuo de negociação e equilíbrio dos pares dialécticos. Com base na literatura da área da produtividade e do lazer, numa perspectiva psicológica, construiu-se uma escala de avaliação do grau de regulação do par de necessidades Produtividade/Lazer. Esta escala foi aplicada a 562 participantes através de uma plataforma Web e os resultados foram relacionados com as escalas de Bem-Estar Psicológico e Distress Psicológico, do Inventário de Saúde Mental (ISM). Os resultados apoiam a consistência interna dos instrumentos e mostram o contributo das variáveis na variância dos resultados, revelando a relação positiva da Produtividade e do Lazer com o Bem-Estar Psicológico e negativa com o Distress Psicológico. Dividindo os sujeitos por 4 grupos com base nas medianas dos resultados no par de necessidades Produtividade/Lazer, o grupo de resultados mais elevados nos dois pólos revela resultados mais elevados de Bem-Estar Psicológico e mais baixos de Distress Psicológico, quando comparado com os restantes grupos. Apresentam-se as limitações do estudo, as implicações dos resultados para futuras investigações e para a prática psicoterapêutica e sugerem-se linhas de investigação futuras.

Protein behavior is closely regulated by a plethora of post-translational modifications (PTMs). It is therefore desirable to develop approaches to design rational PTMs to modulate specific protein functions. Here, we report one such method, and we illustrate its successful implementation by potentiating the anti-aggregation activity of a molecular chaperone. Molecular chaperones are a multifaceted class of proteins essential to protein homeostasis, and one of their major functions is to combat protein misfolding and aggregation, a phenomenon linked to a number of human disorders. In this work, we conjugated a small-molecule inhibitor of the aggregation of α-synuclein, a process associated with Parkinson's disease (PD), to a specific cysteine residue on human Hsp70, a molecular chaperone with five free cysteines. We show that this regioselective conjugation augments in vitro the anti-aggregation activity of Hsp70 in a synergistic manner. This Hsp70 variant also displays in vivo an enhanced suppression of α-synuclein aggregation and its associated toxicity in a Caenorhabditis elegans model of PD.

No summary/description provided

Background: Staphylococcus epidermidis is a common skin commensal that has emerged as a pathogen in hospitals, mainly related to medical devices-associated infections. Noteworthy, infection rates by S. epidermidis have the tendency to rise steeply in next decades together with medical devices use and immunocompromized population growth. Staphylococcus epidermidis population structure includes two major clonal lineages (A/C and B) that present contrasting pathogenic potentials. To address this distinction and explore the basis of increased pathogenicity of A/C lineage, we performed a detailed comparative analysis using phylogenetic and integrated pangenome-wide-association study (panGWAS) approaches and compared the lineages's phenotypes in in vitro conditions mimicking carriage and infection. Results: Each S. epidermidis lineage had distinct phenotypic signatures in skin and infection conditions and differed in genomic content. Combination of phenotypic and genotypic data revealed that both lineages were well adapted to skin environmental cues. However, they appear to occupy different skin niches, perform distinct biological functions in the skin and use different mechanisms to complete the same function: lineage B strains showed evidence of specialization to survival in microaerobic and lipid rich environment, characteristic of hair follicle and sebaceous glands; lineage A/C strains showed evidence for adaption to diverse osmotic and pH conditions, potentially allowing them to occupy a broader and more superficial skin niche. In infection conditions, A/C strains had an advantage, having the potential to bind blood-associated host matrix proteins, form biofilms at blood pH, resist antibiotics and macrophage acidity and to produce proteases. These features were observed to be rare in the lineage B strains. PanGWAS analysis produced a catalog of putative S. epidermidis virulence factors and identified an epidemiological molecular marker for the more pathogenic lineage. Conclusion: The prevalence of A/C lineage in infection is probably related to a higher metabolic and genomic versatility that allows rapid adaptation during transition from a commensal to a pathogenic lifestyle. The putative virulence and phenotypic factors associated to A/C lineage constitute a reliable framework for future studies on S. epidermidis pathogenesis and the finding of an epidemiological marker for the more pathogenic lineage is an asset for the management of S. epidermidis infections.

No summary/description provided

Tachyplesin I, II and III are host defense peptides from horseshoe crab species with antimicrobial and anticancer activities. They have an amphipathic β-hairpin structure, are highly positively-charged and differ by only one or two amino acid residues. In this study, we compared the structure and activity of the three tachyplesin peptides alongside their backbone cyclized analogues. We assessed the peptide structures using nuclear magnetic resonance (NMR) spectroscopy, then compared the activity against bacteria (both in the planktonic and biofilm forms) and a panel of cancerous cells. The importance of peptide-lipid interactions was examined using surface plasmon resonance and fluorescence spectroscopy methodologies. Our studies showed that tachyplesin peptides and their cyclic analogues were most potent against Gram-negative bacteria and melanoma cell lines, and showed a preference for binding to negatively-charged lipid membranes. Backbone cyclization did not improve potency, but improved peptide stability in human serum and reduced toxicity toward human red blood cells. Peptide-lipid binding affinity, orientation within the membrane, and ability to disrupt lipid bilayers differed between the cyclized peptide and the parent counterpart. We show that tachyplesin peptides and cyclized analogues have similarly potent antimicrobial and anticancer properties, but that backbone cyclization improves their stability and therapeutic potential.

Amyotrophic lateral sclerosis (ALS) is usually sporadic, but 20% of European ancestry cases have a family history of ALS or frontotemporal dementia (FTD). More than 30 genes confer a higher risk for ALS, and C9orf72, TARDBP, SOD1 and FUS account for nearly 70% of all familial (fALS) cases. Tank-binding kinase 1 (TBK1) is an established causal gene associated with 1% of fALS and/or FTD. It codes for a multifunctional kinase involved in multiple cellular processes, such as neuroinflammation and autophagy. Both loss-of-function (LoF) and missense mutations are associated with an increased risk for ALS-FTD spectrum and mutations that cause a 50% reduction of TBK1 protein levels are considered pathogenic.

A memória precisa dos que a motivam e dos que a visitam. Uns, criadores no seu tempo, escrevem as suas delicadas articulações sem saber o seu destino. Outros, nos tempos vindouros, tentam captar a intentio auctoris sabendo que ela se esconde no tecido da criação, nos processos dos artistas. Estes talvez possam ter um ponto de vista que acrescenta algo de novo á matéria do conhecimento. A cultura, a memória dos outros, é também a nossa memória, aqui considerada em perigo. Para salvaguardar a memória pode-se revisitá-la, registá-la, criticá-la, revivê-la. Os espaços discursivos não são assim tantos, mas decerto que a Revista Gama é um deles: aqui se guardam visitas a criadores, se anotam e registam, aqui se resiste. Assim se convocam os artigos que compõem este número da revista Gama. O objetivo é presente: criar discursos de salvaguarda das propostas artísticas mais ou menos dispersas, mais ou menos em perigo, mais ou menos em desligamento. São reativações, renovações de olhares, releituras