RCAAP Repository

Background: The role of cardiovascular risk factors in amyotrophic lateral sclerosis (ALS) is controversial. A favourable profile has been found in ALS patients, but previous studies have not specifically considered the profile in different disease phenotypes. Methods: Demographic data, smoking habits, lifetime exercise, and medical history including diabetes mellitus, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, stroke, and cardiac events, were analysed in ALS patients and in controls with other neurological disorders, utilising a standardized questionnaire applied by the same neurologist. In ALS patients the results were analysed according to their different phenotypes. Univariate analyses and multinomial logistic models were applied to estimate the odds ratios (ORs) and confidence intervals (CIs) for covariates, to test potential modifiers and their effects. Results: 500 consecutively assessed adult ALS patients (mean age 65.6, 47% women, and 136 bulbar-onset) and 327 age and gender-matched controls were studied. Patients with spinal-onset ALS took more exercise (p = 0.012), reported less hypertension (p = 0.002) and had fewer cardiac events (p = 0.012). Multinomial regression analysis showed that men without hypertension have a higher risk of having spinal-onset ALS (p < 0.001) while female with hypertension have a higher risk of having bulbar-onset ALS (p = 0.033). Conclusions: Risk-factors in ALS can be influenced by gender and phenotype. This study suggests that men with spinal ALS are healthier, exercise more and have lower rate of hypertension, but females with bulbar-onset ALS are more prone to hypertension. The complex interplay between exercise, diet and comorbidities with ALS phenotype requires further investigation.

Thrombosis of the cerebral veins and sinuses (CVT) is a distinct cerebrovascular disorder that, unlike arterial stroke, most often affects children and young adults, especially women. In this review, we will summarize recent advances on the knowledge of patients with CVT.

Background and aims: The role of inflammation in atherosclerosis development and expression in different arterial territories is unclear. Soluble CD40 ligand (sCD40L) mediates inflammation and atherogenesis. Through a systematic review and meta-analysis, we assessed whether sCD40L was dysregulated in stable atherosclerosis, irrespective of the diseased arterial territory, and whether this dysregulation differed according to the specific territory. Methods: Systematic literature searches were performed in MEDLINE, Cochrane Library, Web of Science, and Embase for studies reporting circulating sCD40L levels in individuals with and without stable atherosclerosis. sCD40L levels were compared using random-effects meta-analysis, weighted by the inverse variance method (study protocol: PROSPERO CRD42020181392). Results: Fifty-four studies (59 estimates) including 7705 patients and 7841 controls were analyzed. sCD40L levels were found to be increased in patients with atherosclerosis, irrespective of the territory (standardized mean difference [SMD] 0.43, 95% CI 0.29-0.57; 59 estimates; χ2 heterogeneity p < 0.001; I2 = 92%). SMD was greatest in carotid atherosclerosis (SMD 0.58, 95% CI 0.30-0.86; 17 estimates), followed by coronary (SMD 0.43, 95% CI 0.24-0.62; 33 estimates), lower extremity (SMD 0.26, 95% CI -0.02-0.54; 7 estimates), and renal atherosclerosis (SMD -0.07, 95% CI -2.77-2.64; 2 estimates) (χ2 heterogeneity p < 0.001; I2 ≥ 80% for all). Subgroup analysis revealed that sCD40L levels were increased in clinical, but not subclinical, atherosclerosis. Conclusions: sCD40L levels were increased in stable atherosclerosis, particularly in the carotid and coronary territories. These novel data support sCD40L as a marker of systemic atherosclerosis, possibly with differential roles in specific territories.

A revista Gama parece agir como um revelador de imagens latentes: a sua ação é uma ativação social, sempre de reforço simbólico, que permite auxiliar a discernir, e a identificar, aquilo a que todos chamamos de arte. É um projeto de legitimação apoiado nos criadores: que sejam os artistas a apontar os caminhos da arte, onde eles se escondem, onde ela pode passar a ser. Como em Espinosa, na ‘Ética,’ a arte pode ser uma ‘qualia’ de uma substância potente, que ao ser percebida e reconhecida, nas páginas do número 14 da revista Gama, nos seus 16 artigos, se percebe como coisa, ocorrência valiosa, ou melhor, ‘valente.’

Entre Lisboa e a América, encontra-se o pretexto para o conhecimento mútuo, para descobrir autores e artistas: a viagem torna-nos diferentes. A revista GAMA galga os muros e procura o reconhecimanto. O resultado, um acervo de informação sobre a arte de cá e de lá do Atlântico, de ontem, ou de há pouco. A revista GAMA não ficou no Quintal: saltou muros, brincou com os novos vizinhos, esfolou os joelhos, roubou laranjas. O resultado, uma aventura de conhecimento. A liberdade está na possibilidade da viagem e do conhecimento. Tenho que saber quem sou, tenho de saber quem és.

Esta dissertação é sobre a experiência da pintura (a experiência de pintar) na era da pós-internet e estrutura-se nos resultados de pesquisas das sociedades educadas ocidentais. Como é que o acesso efetivo às tecnologias da informação afeta o trabalho artístico e criativo? Como é que interfere nas escolhas de cada indivíduo e no seu desenvolvimento artístico? E porque é que o processo de crescimento e de independência é tão importante para o auto-conhecimento (pessoal e artístico)? Para responder a estas perguntas e aos assuntos que lhes são inerentes é necessário contextualizar sobre qual foi a minha área de interesse pessoal nos últimos dois anos, que passei em Portugal. Portanto, minhas experiências pessoais e as respectivas pesquisas plásticas, teóricas e conceptuais sobre os vários temas que me interessam fundem-se e vêm sublinhar a investigação pela pintura como um campo de questionamento criativo e artístico. Para salientar o aspecto pessoal, tomo a liberdade de falar na primeira pessoa ao longo de todo o documento. A investigação que se segue está ligada a uma série de pinturas que vão ser expostas na Faculdade de Belas-Artes de Lisboa entre 8 e 18 de Junho de 2021. A selecção desta série de oito pinturas é especial porque mostra o resultado do meu desenvolvimento artístico durante os últimos 2 anos, em Lisboa; reflecte os meus interesses, o desenvolvimento técnico pictórico e a minha forte ligação à pintura figurativa nos dias de hoje. Um dos meus objectivos nesta investigação foi pensar sobre a pintura que desenvolvo e que vou apresentar. Neste sentido, apresento o leque de informações que é inerente ao meu projecto pictórico, primeiro, para documentar e reforçar as motivações pessoais que o originaram e, depois, para ajudar o leitor ou observador identificar-me como o autor destas pinturas, especificamente, e neste movimento compreender quais os temas e conceitos que me interessam.

Aim Habitat diversity has been linked to the diversity and structure of island communities, however, little is known about patterns and processes within habitats. Here we aim to determine the contributions of habitat type and inferred dispersal frequency to the differences in taxonomic structure between assemblages in the same island habitat. Location The Macaronesian archipelagos (Azores, Madeira, the Canary Islands and Cabo Verde). Taxon Spiders (Araneae). Methods We established forest and dry habitat sites (each with five plots) on two islands per archipelago. We collected spiders using standardised sampling protocols. We tested the differences in beta diversity separately for each habitat and for each inferred category of ballooning (an aerial dispersal strategy) frequency across geographic scales through nested non-parametric permutational multivariate analyses of variance. We then tested whether ballooning and habitat influenced heterogeneity in species composition (dispersion in beta diversity) in the two habitat types. We analysed the effects of habitat and ballooning on species abundance distribution (SAD) and rarity by fitting Gambin models and evaluating the contribution of ballooning categories to SAD. Results Communities of the same archipelago and habitat were taxonomically more similar, and beta diversity increased with geographic scale, being greater in dry habitats. There was greater species replacement among assemblages in dry habitats than in forests, with greater differences for rare ballooners. There were no differences in SAD between habitats although dry habitat sites seemed to harbour more species with low abundances (rare species) than forests. Main conclusions Habitat type does not only condition the differences between spider assemblages of the same habitat but also the scale at which they occur. These differences may be determined by the heterogeneity in the physical structure of each habitat as well as how much this structure facilitates aerial dispersal (ballooning), and should be considered in theories/hypotheses on island community assembly as well as in conservation strategies.

The invasive Vespa velutina has been widely referred as an effective predator of honeybees. Despite the potential risk to pollination services provision and honey production, there is no accurate quantification and assessment of its real consequences for honeybees. To date, the identification of the honeybee and other insects in the diet of V. velutina has been investigated by direct observation of adult foraging or examination of food pellets. To overcome these limitations, in this study we used a DNA metabarcoding approach to evaluate the usefulness of different types of sample (jaws and stomachs collected from workers and larval faecal pellets taken from the hornet comb) to investigate the predation of V. velutina upon honeybees, and potentially on other insects. Honeybee DNA was identified in all types of samples, but larval faecal pellets retrieved the higher number of reads of honeybee DNA and the largest diversity at all taxonomic levels. Over all samples we could identify 4 orders, 9 families, 6 genera and 1 species of prey. We estimate that collecting 6 workers is sufficient to identify honeybee predation by a colony using worker’s jaws. Stomachs were the least useful sample type to detect honeybee DNA. The presence of honeybee DNA in all analysed colonies irrespective of collection site, and the variety of insect orders detected in the diet support current concerns over the acknowledged negative impact of V. velutina on managed honeybees and its potential threat to pollination services provision.

Lichens are classified into different functional groups depending on their ecological and physiological response to a given environmental stressor. However, knowledge on lichen response to the synergistic effect of multiple environmental factors is extremely scarce, although vital to get a comprehensive understanding of the effects of global change. We exposed six lichen species belonging to different functional groups to the combined effects of two nitrogen (N) doses and direct sunlight involving both high temperatures and ultraviolet (UV) radiation for 58 days. Irrespective of their functional group, all species showed a homogenous response to N with cumulative, detrimental effects and an inability to recover following sunlight, UV exposure. Moreover, solar radiation made a tolerant species more prone to N pollution’s effects. Our results draw attention to the combined effects of global change and other environmental drivers on canopy defoliation and tree death, with consequences for the protection of ecosystems.

The merging of community ecology and phylogenetic biology allows us to link broader evolutionary processes to local ecological processes, thereby increasing our understanding of community assembly. A recurrent way to test how species assemblages respond to diferent abiotic conditions and evaluate the role of evolutionary constraints in community assembly is through using environmental gradients as natural treatments. Here, we combine phylogenetic and trait-based methods to evaluate how the phylogenetic diversity and composition of bird assemblages and their community-weighted traits vary along an elevational gradient in the Swiss Alps. For this purpose, we used four life-history traits considered to be key indicators of individual species response to environmental changes: clutch size, number of breeding attempts, dispersal capacity and lifespan. Controlling for phylogeny, we determined whether environmental flters (elevation, habitat type) act on these traits independently of the level of relatedness among species. We found that phylogenetic dispersion decreases with elevation, but the signature of phylogenetic clustering was weak. Phylogenetic fuzzy weighting showed that the distribution of bird species across plots was related to the two environmental gradients; nonetheless, such infuence was not determined by the phylogenetic relationships in either case. That is, there are no specifc clades associated with particular elevation or habitat types. We also found that high elevation communities around the treeline were composed of species with lower reproductive rates, reduced lifespan, and lower dispersal capacity, which would make them less resilient to environmental change. Although traits showed moderate phylogenetic signal, only the lifespan was phylogenetically structured. In the remaining cases, the trait-environment association was not mediated by the phylogenetic relationships among taxa. Our study indicates that evolutionary constraints do not represent a signifcant driver of community assembly in Alpine bird communities and support the notion that phylogeny may often not be a good proxy for traits subject to environmental fltering.

Annually millions of animals are killed as a result of human-wildlife impacts. Each year the NGO Associação Mata Ciliar (NGOMC), in Southeastern Brazil, receives and rehabilitates thousands of animals. We evaluated how natural and anthropogenic characteristics affect the risk of different types of human-wildlife impacts for mammals that arrive at the NGOMC; and explore the relationship between both the animal's size and the type of human-wildlife impact event, survival rates and the likelihood that these animals can be fully rehabilitated. To test our hypotheses regarding the drivers and consequences of the total number of human-wildlife impact events, traffic collisions, electrocutions, and requested removals, we used records of the mammals that arrived at the NGOMC between 2012 and 2018, and obtained data on environmental attributes and anthropogenic factors at the municipality level, as well as species weights. The total number of human-wildlife impact events and of requested removals were both positively correlated with deforestation rate and urban area. The number of traffic collisions was positively related to the number of fires. Municipalities with larger urban areas were more likely to have at least one electrocuted mammal. Temporally, the number of fires two months before was positively correlated with the number of human-wildlife impact events. Traffic collisions and electrocutions more frequently resulted in the death of the animal, than did other events. Animals that died were heavier on average than those that remained in captivity or were successfully released back into the wild. We conclude that human-wildlife impact event rates should decline with lower rates of deforestation, less anthropogenic fires and the adoption of other specific measures to avoid both traffic collisions with fauna and electrocutions.

Population density data on depleted and endangered wildlife species are essential to assure their effective management and, ultimately, conservation. The European wildcat is an elusive and threatened species inhabiting the Iberian Peninsula, with fragmented populations and living in low densities. We fitted spatial capture–recapture models on camera-trap data, to provide the first estimate of wildcat density for Portugal and assess the most influential drivers determining it. The study was implemented in Montesinho Natural Park (NE Portugal), where we identified nine individuals, over a total effort of 3,477 trap-nights. The mean density estimate was 0.032 ± 0.012 wildcat/km2 , and density tended to increase with distance to humanized areas, often linked to lower human disturbance and domestic cat presence, with forest and herbaceous vegetation cover and with European rabbit abundance. Although, this density estimate is within the range of values estimated for protected areas elsewhere in the Iberian Peninsula, our estimates are low at the European level. When put in context, our results highlight that European wildcats may be living in low population densities across the Iberian Mediterranean biogeographic region. No phenotypic domestic or hybrid cats were detected, suggesting potentially low admixture rates between the two species, although genetic sampling would be required to corroborate this assertion. We provide evidence that Montesinho Natural Park may be a suitable area to host a healthy wildcat population, and thus be an important protected area in this species' conservation context.

Esta Newsletter (NL) resulta de uma parceria entre o Instituto de Saúde Baseada na Evidência e a Cochrane Portugal, e tem como objectivo disponibilizar informação sobre áreas interessantes para a prática clínica, com base na melhor evidência científica. São incluídos estudos relevantes, criticamente avaliados pela sua validade, importância dos resultados e aplicabilidade prática, resumidos numa óptica de suporte à decisão. É dada prioridade a estudos de causalidade incluindo-se ainda, quando justificado, estudos qualitativos e metodológicos, assim como revisões científicas. O conteúdo da NL é da exclusiva responsabilidade do(s) seu(s) autor(es).

Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here, we found that γδ T cell subsets making either interferon-γ (IFN-γ) or interleukin (IL)-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during thymic development and were stably maintained in the periphery and within tumors. Moreover, pro-tumoral IL-17+ γδ T cells selectively showed high lipid uptake and intracellular lipid storage and were expanded in obesity and in tumors of obese mice. Conversely, glucose supplementation enhanced the antitumor functions of IFN-γ+ γδ T cells and reduced tumor growth upon adoptive transfer. These findings have important implications for the differentiation of effector γδ T cells and their manipulation in cancer immunotherapy.

Objective: To investigate the cutaneous silent period (CSP) by measuring its onset latency, duration and amount signal suppression in patients with motor neuron disease (MND) grouped according to the intensity of upper motor neuron involvement (UMN), and to test the effect of contralateral hand contraction. Methods: Painful stimulation was applied at the V finger, and contraction recorded from the abductor digiti minimi (ADM) muscle (baseline condition). Afterwards, CSP was studied during strong contralateral ADM contraction (test condition). 10-15 consecutive traces were recorded for each condition, signals were rectified, averaged, and analyzed offline. Results: 46 patients were investigated, 15 with progressive muscular atrophy (PMA), 16 with typical amyotrophic lateral sclerosis (ALS), 15 with primary lateral sclerosis/predominant UMN-ALS (PLS+UMN-ALS), and 28 controls. In the baseline condition, all MND groups showed delayed onset latencies (p = 0.001). There was no significant difference in the CSP duration. Suppression was lower in the PLS + UMN-ALS group (p = 0.004). In the control group, contralateral contraction did not change CSP, but onset latency shortened significantly in the PMA group. Conclusions: CSP onset latency is delayed in all investigated groups of MND, including in PMA, indicating subclinical UMN involvement. Changes in CSP can indicate UMN lesion in MND. Significance: CSP should be explored to identify UMN involvement in MND.

Twenty years ago, in the middle 1990s, a pending debate in the RNA cell biology field concerned the nuclear organization of pre-mRNA splicing. Localization studies using antibodies to detect proteins of the spliceosome and oligonucleotide probes that hybridized with the spliceosomal small nuclear RNAs had revealed that practically all building blocks of the splicing machinery were not uniformly distributed in the nucleus but rather appeared concentrated in defined regions. These regions were termed “nuclear speckles” or “splicing domains” due to the local enrichment in splicing factors. Whether or not pre-mRNA splicing occurred within these domains remained controversial.

Eimeria vermiformis is a tissue specific, intracellular protozoan that infects the murine small intestinal epithelia, which has been widely used as a coccidian model to study mucosal immunology. This mouse infection model is valuable to investigate the mechanisms of host protection against primary and secondary infection in the small intestine. Here, we describe the generation of an E. vermiformis stock solution, preparation of sporulated E. vermiformis to infect mice and determination of oocysts burden. This protocol should help to establish a highly reproducible natural infection challenge model to study immunity in the small intestine. The information obtained from using this mouse model can reveal fundamental mechanisms of interaction between the pathogen and the immune response, e.g., provided by intraepithelial lymphocytes (IEL) at the basolateral site of epithelial cells but also a variety of other immune cell populations present in the gut.

Previous results indicated that miR-146b-5p is downregulated by TAL1, a transcription factor critical for early hematopoiesis that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an oncogenic role. Here, we confirmed that miR-146b-5p expression is lower in TAL1-positive patient samples than in other T-ALL cases. Furthermore, leukemia T-cells display decreased levels of miR-146b-5p as compared to normal T-cells, thymocytes and other hematopoietic progenitors. MiR-146b-5p silencing enhances the in vitro migration and invasion of T-ALL cells, associated with increased levels of filamentous actin and chemokinesis. In vivo, miR-146b overexpression in a TAL1-positive cell line extends mouse survival in a xenotransplant model of human T-ALL. In contrast, knockdown of miR-146b-5p results in leukemia acceleration and decreased mouse overall survival, paralleled by faster tumor infiltration of the central nervous system. Our results suggest that miR-146b-5p is a functionally relevant microRNA gene in the context of T-ALL, whose negative regulation by TAL1 and possibly other oncogenes contributes to disease progression by modulating leukemia cell motility and disease aggressiveness.

DNA replication ensures accurate duplication of the original genetic information present in a cell in order for it to be properly transmitted to daughter cells. However, replication can be perturbed, for instance in rapidly dividing cancer cells, in a process referred to as replication stress (RS). Checkpoint kinase 1 (CHK1) is an essential component of the ATR-dependent DNA damageresponse pathway that protect cells from RS by preventing replication fork collapse and activating homologous DNA repair. The ATR-CHK1 pathway is triggered upon exposure of single-stranded DNA that arises with the stalling of replication forks, and it is required to reset proper origin firing, and to promote fork stability and checkpoint activation, delaying mitosis until replication is completed and thereby avoiding mitotic catastrophe.

Ultrasound (US) is a physical property, designated as such when the oscillating sound pressure is above the upper limit of the human hearing rate (20 kHz), and has been explored in many areas of the human activity, from military life to medicine. Medical ultrasonography is able to capture size and structure of internal organs, tendons, muscle and nerves, it does not involve the use of ionizing radiation, and in addition is rapid and costs are relatively low. In neuromuscular disorders, US was first used as a treatment option for pain.