RCAAP Repository

Murid γ-herpesvirus-4 (MuHV-4) promotes polyclonal B cell activation and establishes latency in memory B cells via unclear mechanisms. We aimed at exploring whether B cell receptor specificity plays a role in B cell susceptibility to viral latency and how this is related to B cell activation. We first observed that MuHV-4-specific B cells represent a minority of the latent population, and to better understand the influence of the virus on non-MuHV-4 specific B cells we used the SWHEL mouse model, which produce hen egg lysozyme (HEL)-specific B cells. By tracking HEL+ and HEL- B cells, we showed that in vivo latency was restricted to HEL- B cells while the two populations were equally sensitive to the virus in vitro. Moreover, MuHV-4 induced two waves of B cell activation. While the first wave was characterized by a general B cell activation, as shown by HEL+ and HEL- B cells expansion and upregulation of CD69 expression, the second wave was restricted to the HEL- population, which acquired germinal center (GC) and plasma cell phenotypes. Antigenic stimulation of HEL+ B cells led to the development of HEL+ GC B cells where latent infection remained undetectable, indicating that MuHV-4 does not benefit from acute B cell responses to establish latency in non-virus specific B cells but relies on other mechanisms of the humoral response. These data support a model in which the establishment of latency in B cells by γ-herpesviruses is not stochastic in terms of BCR specificity and is tightly linked to the formation of GCs.

Aim: In this narrative review we aimed to describe how stroke affects emotions and update the readers on the emotional disturbances that occur after stroke. Methods: We searched Medline from 1.1.2013 to 1.7.2019, personal files and references of selected publications. All retrieved systematic reviews and randomized controlled trials were included. Other references were selected by relevance. Summary of review: The emotional response includes a reactive behavior with arousal, somatic, motivational and motor components, and a distinctive cognitive and subjective affective experience. Emotional category responses and experiences after stroke can show dissociations between the behavioral response and the cognitive and affective experiences. Emotional disturbances that often occur after stroke include fear, anger, emotional indifference, lack of understanding of other emotions, and lack of control of emotional expression. Emotional disturbances limit social reintegration of the persons with stroke and are a source of caregiver burnout. The evidence to support the management of the majority of emotional disorders in stroke survivors is currently weak and of low or very low methodologic quality. An exception are the disorders of emotional expression control where antidepressants can have a strong beneficial effect, by reducing the number and duration of the uncontrollable episodes of crying or laughing. Conclusion: Our current knowledge of the emotional disorders that occurs in acute stroke patients and in stroke survivors is heterogeneous and limited. Joint efforts of different research approaches, methodologies and disciplines will improve our current understanding on emotional disorder after stroke and indicate rational pathways to manage them.

Em 2018, a Sociedade Portuguesa de Antropologia e Etnologia (SPAE) celebrou o seu centenário. Nessa altura fui curadora, juntamente com Vítor Oliveira Jorge (arqueólogo, professor aposentado e presidente da SPAE), da exposição A Sociedade Portuguesa de Antropologia e Etnologia, 1918-2018: 100 anos ao serviço da ciência, que decorreu, entre 19 de Novembro de 2018 e 11 de Janeiro de 2019, na Faculdade de Letras da Universidade do Porto (FLUP). Essa ocasião permitiu-me reflectir sobre a contribuição da SPAE para a institucionalização académica da antropologia e o seu papel público como espaço para a difusão do conhecimento, debate e troca de ideias. Como se tratava de dar conta de 100 anos de actividade, foi feita uma selecção de alguns dos seus aspectos principais, ou que mais se destacaram, tal como farei neste texto.

Este ensaio retoma os itinerários planeados e percorridos pelo cientista social brasileiro Gilberto Freyre no império colonial português, entre outubro de 1951 e janeiro de 1952. No decorrer da viagem, Freyre apresentou o conceito de luso-tropicalismo, que o regime do Estado Novo português viria a reutilizar para fins político-ideológicos, interna e externamente, nos anos seguintes, com o acordo ou tolerância da Oposição democrática, e que continuou a ecoar na sociedade portuguesa, após o fim da ditadura e do colonialismo, até aos nossos dias1. Da visita resultaram dois livros: Um Brasileiro em terras portuguesas e Aventura e rotina (ambos de 1953). O primeiro, como o subtítulo esclarece, pretende ser uma «introdução a uma possível luso-tropicologia », acompanhada de conferências e discursos proferidos durante o percurso. O segundo é uma espécie de diário da viagem realizada «à procura das constantes portuguesas de carácter e acção»

Quando, há mais de dez anos atrás, comecei a interessar-me pelo estudo das relações entre Portugal e o Brasil deparei com uma espécie de vazio historiográfico no período que separa o entorno da independência brasileira e os anos 20 já do século XX. E, no entanto, quanto mais lia e investigava sobre o tema, mais me apercebia o quanto das reconfigurações da ideia imperial portuguesa se mantiveram sustentadas em paradigmas herdados do decomposto império luso-brasileiro, não só através da tradição, mas também da imaginação. Na minha pesquisa de doutoramento, que culminou na tese Espelho Fraterno: o Brasil e o republicanismo português na transição para o século XX (2013) que tive a honra de ver premiada com o prémio Vítor de Sá, concentrei-me na dimensão republicana dessa imaginação imperial e consequentemente foquei-me sobretudo nas duas décadas que medeiam os adventos das repúblicas brasileira e portuguesa, 1889 e 1910, respetivamente.

O tropicalismo arranca em 1967, através do corpo: a música de Caetano Veloso e Gilberto Gil, os vestíveis de Hélio Oiticica, as propostas teatrais de José Celso Martinez Corrêa e os cenários de Hélio Eichbauer. Hoje as coisas são um pouco mais complexas. Em tempo de redes sociais, os aspirantes ao poder fazem uso da sua imediatez para suscitarem reações epidérmicas, superficiais, populistas e de grande instantaneidade. A boçalidade triunfa nas caixas de comentários, e com mais alguns perfis falsificados podem manipular-se plebiscitos, movimentos secessionistas, ou, e também censurar-se exposições de arte. Nesta variação do fascismo, a epiderme eletrificada das redes sociais estrutura-se como uma poderosa arena onde se aparenta uma falsa democracia. Talvez a arte continue a ser um reduto para reflexão, mas vemos que a censura se manifesta hoje de modo talvez mais eficaz, silenciando artistas e professores, através da pressão mediatizada, da emoção do momento. Para isto é necessária a atenção consciente da arte, dos artistas, e também dos arte-educadores: enfrenta-se uma massa cada vez mais informe, alienada e despojada de reflexão para além do imediato.

Working paper on the Quality of the European News Ecology.

The Tn antigen (GalNAc-α-1-O-Thr/Ser) is a well-known tumor-associated carbohydrate determinant. The use of glycopeptides that incorporate this structure has become a significant and promising niche of research owing to their potential use as anticancer vaccines. Herein, the conformational preferences of a glycopeptide with an unnatural Tn antigen, characterized by a threonine decorated with an sp2-iminosugar-type α-GalNAc mimic, have been studied both in solution, by combining NMR spectroscopy and molecular dynamics simulations, and in the solid state bound to an anti-mucin-1 (MUC1) antibody, by X-ray crystallography. The Tn surrogate can mimic the main conformer sampled by the natural antigen in solution and exhibits high affinity towards anti-MUC1 antibodies. Encouraged by these data, a cancer vaccine candidate based on this unnatural glycopeptide and conjugated to the carrier protein Keyhole Limpet Hemocyanin (KLH) has been prepared and tested in mice. Significantly, the experiments in vivo have proved that this vaccine elicits higher levels of specific anti-MUC1 IgG antibodies than the analog that bears the natural Tn antigen and that the elicited antibodies recognize human breast cancer cells with high selectivity. Altogether, we compile evidence to confirm that the presentation of the antigen, both in solution and in the bound state, plays a critical role in the efficacy of the designed cancer vaccines. Moreover, the outcomes derived from this vaccine prove that there is room for exploring further adjustments at the carbohydrate level that could contribute to designing more efficient cancer vaccines.

No summary/description provided

Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for proper homeostasis of the organisms, and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are regulatory molecules that can also act as communication signals between cells, being involved in either homeostasis or dysbiosis of the holobionts. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs while using specific extracellular conveyors that travel to the target cell and can be translated into a regulatory response by dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among the cells. This review analyzes current knowledge regarding the role of non-coding RNAs in cell-to-cell communication, with a special focus on the signaling between cells in multi-organism consortia.

Galectin-3 binding protein (LGALS3BP or 90 K) is a secreted glycoprotein found in human body fluids. Deregulated levels were observed in cancer and infection and its study in neurological diseases is more recent. Here, we have investigated 90 K from human cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS, n = 35) and other neurological diseases (n = 23). CSF was fractionated by ultrafiltration/size-exclusion chromatography (SEC) and eluted fractions were analysed by complementary techniques including immunoblotting, electron microscopy and nano-liquid chromatography-tandem mass spectrometry. A fraction of 90 K appeared as nanoparticles of irregular shape with heterogeneous dimensions of 15-60 nm that co-eluted with extracellular vesicles in SEC. Median levels of 90 K quantified by ELISA were not different between ALS patients (215.8 ng/ml) and controls (213.3 ng/ml) in contrast with the benchmark biomarker for ALS phosphoneurofilament heavy chain (1750 and 345 pg/ml, respectively). A multiregression model supported age is the only independent predictor of 90 K level in both groups (p < 0.05). Significant correlation was found between 90 K levels and age for the ALS group (r = 0.366, p = 0.031) and for all subjects (r = 0.392, p = 0.003). In conclusion, this study unveils the presence of 90 K-containing nanoparticles in human CSF and opens novel perspectives to further investigate 90 K as potential aging marker.

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.

No summary/description provided

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.