Efeitos da neuregulina-1 nas alterações metabólicas induzidas pela hipertensão arterial pulmonar

Pulmonary arterial hypertension (PAH) is a chronic rare disease, characterized by increased pulmonary vascular resistance (PVR) with progressive overload and remodelling of the right ventricle (RV), that eventually leads to right ventricular heart failure (RVHF). These derangements arise from a metabolic switch from glucose oxidation towards glycolysis, the Warburg effect, affecting glucose metabolism at the systemic level. The neuregulin-1 (NRG1), a protein that has been shown to play beneficial effects on PAH and RV hypertrophy, has also been associated with the regulation of glucose metabolism given its role in modulating the expression of glucose transporters (GLUTs). In this study we aimed to evaluate the effect of rhNRG1 chronic treatment on glycolysis pathway genes expression in the RV and skeletal muscle in a monocrotaline (MCT)-induced PAH animal model and in chronic hypoxia/Sugen5416 model that also reproduces key pathophysiological features from human PAH. We have found that RV GLUT1 and GLUT4 mRNA expression is altered in PAH and was similar between the MCT and hypoxia/Sugen5416 animal models, being this related with the development of RV hypertrophy (RVH). However, the treatment with rhNRG1 only attenuated GLUTs expression toward normal values in MCT-induced PAH model. The expression of GLUT1 and GLUT4 is correlated with cardiac markers of disease, while the glycolytic pathway genes are correlated with the morphophysiological changes resulting from the development of PAH in MCT model. From the analysis of some glycolytic pathway genes, we conclude that beyond GLUTs, several genes are related, not only with the Warburg effect, but also with the disease progression. We also found that the treatment with rhNRG1 attenuated the changes in some glycolytic pathway genes, resulting in an improvement of glucose metabolism. The glucose tolerance evaluation revealed that the animals with PAH from both models are insulin resistant and that the treatment with rhNRG1 regulated systemic glucose concentration in both animal models. In conclusion, the therapeutic effects of NRG1 in experimental PAH may be due, in part, to the regulation of metabolic changes associated with PAH progression and RV dysfunction, which were reflected in the reversion of the ventricular phenotype of the disease.A hipertensão arterial pulmonar (HAP) é uma doença crónica rara, caracterizada pelo aumento da resistência vascular pulmonar (RVP) com sobrecarga progressiva e remodelagem do ventrículo direito (VD), o que pode levar à insuficiência cardíaca do ventrículo direito (ICVD). Estas perturbações surgem na sequência de uma alteração metabólica na oxidação da glicose, um processo designado por efeito de Warburg, que afeta o metabolismo da glicose a nível sistémico. A neuregulina-1 (NRG1), uma proteína que demonstrou ter efeitos benéficos na hipertrofia do VD causada pela HAP, está também associada à regulação do metabolismo da glicose dado seu papel na modulação da expressão dos transportadores de glicose (GLUTs). Neste estudo, o nosso objetivo tinha por base a avaliação do efeito do tratamento crónico com rhNRG1 na expressão de genes da via da glicólise no VD e em músculo esquelético num modelo animal de HAP induzida por monocrotalina (MCT) e num um modelo crónico de hipoxia/Sugen5416, que reproduz algumas das principais características fisiopatológicas da HAP humana. Verificamos que a expressão de mRNA do GLUT1 e do GLUT4 no VD está alterada na HAP e que se demonstrou semelhante entre os modelos animais MCT e hipoxia/Sugen5416, estando relacionada com o desenvolvimento de hipertrofia do VD (HVD). No entanto, o tratamento com rhNRG1 apenas atenuou a expressão dos GLUTs para valores próximos aos normais no modelo de HAP induzida por MCT. Enquanto que a expressão do GLUT1 e do GLUT4 está correlacionada com marcadores cardíacos da doença, os genes da via glicolítica demonstraram estar correlacionados com as alterações morfofisiológicas resultantes do desenvolvimento da HAP no modelo MCT. A partir da análise de alguns genes da via glicolítica, concluímos que, para além dos GLUTs, alguns genes estão relacionados, não só com o efeito de Warburg, mas também com a progressão da doença. Verificamos também que o tratamento com rhNRG1 atenuou as alterações de expressão em alguns genes da via glicolítica, resultando numa melhoria do metabolismo da glicose. A avaliação da tolerância à glicose revelou que os animais com HAP de ambos os modelos são resistentes à insulina e que o tratamento com rhNRG1 regulou a concentração sistémica de glicose em ambos os modelos animais. Em conclusão, os efeitos terapêuticos da NRG1 na HAP experimental podem dever-se, em parte, à regulação das alterações metabólicas que estão associadas à progressão da HAP e à disfunção do VD, e que se refletiram na reversão do fenótipo ventricular da doença.Mestrado em Biologia Molecular e Celula

Considerações jurídico-penais sobre o homicídio como reação à "tirania doméstica"

Quando se trata de uma vítima de violência doméstica a matar o tirano na tentativa desesperada de colocar fim ao sofrimento vivido nas mãos do mesmo, questiona-se se estaremos no âmbito da figura da legítima defesa, devendo a agora homicida ser absolvida por se encontrar excluída a ilicitude da conduta pela ordem jurídica. Até mesmo quando o pressuposto da atualidade não está preenchido poderemos aplicar a figura da legítima defesa preventiva? Ou poderemos enquadrar o crime no tipo legal do homicídio privilegiado, uma vez que a homicida se encontra num contexto de violência e num estado de afeto que devem ser ponderados em sede de culpa? Pretendemos esclarecer nesta dissertação quando ambas as figuras se devem aplicar.When it comes to a victim of domestic violence killing the aggressor in a desperate attempt to put an end to the suffering experienced at his hands, it is questioned whether we are within the scope of the figure of self-defense, and the now murderer should be acquitted for being excluded illegality in the legal order. Even when the current assumption is not met, can we apply the figure of preventive self-defense? Or can we frame the crime in the legal type of privileged homicide since the murderer is in a context of violence and in a state of affection that must be considered in terms of guilt? We intend to clarify in this dissertation when both figures should apply

Plano de marketing internacional para empresa Inês Barbosa

Mestrado em MarketingO presente projeto pretende elaborar um plano de marketing capaz de apoiar a internacionalização da empresa Inês Barbosa para o mercado japonês. O objetivo principal deste projeto consiste na recolha de informação relevante para a compreensão de conceitos, processos, fases, estratégias, métricas de desempenho, mercado, clientes, variáveis incontroláveis e assistir a empresa no processo de entrada no mercado japonês. O plano será construído com fundamentado na literatura adiante e a estrutura do mesmo terá como base a estrutura proposta pelos autores McDonald (2015), Wood (2007) e Cateora, Gilly e Graham (2011). A empresa Inês Barbosa foi fundada em 1993 pela Inês Barbosa (fundadora e diretora geral), 5º geração de uma família de ourives, e o seu foco de negócios consiste no fabrico de Ourivesaria Tradicional Portuguesa, em especial na filigrana artesanal e atua principalmente na área B2B.This project aims to develop a marketing plan capable of supporting the internationalization of the company Inês Barbosa to the Japanese market. The main objective of this project is to gather relevant information to understand concepts, processes, phases, strategies, performance metrics, market, customers, uncontrollable variables and assist the company in the process of entering the Japanese market. The plan will be built based on the literature below and its structure will be based on the structure proposed by the authors McDonald (2015), Wood (2007) and Cateora, Gilly & Graham (2011). The company Inês Barbosa was founded in 1993 by Inês Barbosa (founder and manager), 5th generation of a family of goldsmiths, and its business focus is the manufacture of Traditional Portuguese Goldsmiths, with special focus to handcrafted filigree and operates mainly in B2B, having clients in Portugal, USA, Spain and China.info:eu-repo/semantics/publishedVersio

The MOVE.TE Falls Prevention and Management Program: lessons learnt in the Portuguese context

MOVE.TE is a non-profit participatory physiotherapy platform that aims at translating knowledge in the field of physiotherapy and developing freely available evidence-based physiotherapy programmes targeting the primary care services of the Portuguese National Health service. A group of volunteer academics and clinicians collaborated at different stages and time points to create the first ever falls prevention and management programme and guidance for Physiotherapy in primary care, in Portugal. This report describes this seven-step process. In spite of many challenges, this project constitutes an example of advocacy in physiotherapy for the promotion of better healthcare for older adults.info:eu-repo/semantics/publishedVersio

Author Correction: Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities.

This Article contains an error in the description of the data presented in Figure 2. Each blot demonstrating a protein of interest, or of its phosphorylated form, is matched with the expression of β-actin, used as loading control. The majority of the proteins were separated in different gels, apart from proteins p105, p50 and Bcl-xL which were run in the same gel and have the same loading control. As a result, the Figure 2 legend, “Ionizing radiation induces macrophage NF-κB activation and increases Bcl-xL expression. (A) Evaluation of RelA phosphorylation (Ser536) and RelB, cRel, p100/p52 and p105/p50 subunit expression, 1 and 6 h after irradiation (2, 6 and 10 Gy). (B) RelB nuclear translocation 6 h after macrophage irradiation (10 Gy). Histone deacetylase 1 (HDAC1) and β-actin were used as loading controls for nuclear and cytoplasmic fractions, respectively. (C) Evaluation of Bcl2 and Bcl-xL expression after macrophage irradiation. Western blot images are representative of protein expression/phosphorylation status in distinct donors (at least n = 4), evaluated in two independent experiments.” should read: “Ionizing radiation induces macrophage NF-κB activation and increases Bcl-xL expression. (A) Evaluation of RelA phosphorylation (Ser536) and RelB, cRel, p100/p52 and p105/p50 subunit expression, 1 and 6 h after irradiation (2, 6 and 10 Gy). (B) RelB nuclear translocation 6 h after macrophage irradiation (10 Gy). Histone deacetylase 1 (HDAC1) and β-actin were used as loading controls for nuclear and cytoplasmic fractions, respectively. (C) Evaluation of Bcl2 and Bcl-xL expression after macrophage irradiation. Western blot images are representative of protein expression/phosphorylation status in distinct donors (at least n = 4), evaluated in two independent experiments. The β-actin loading control of the panels comprised by p105, p50 (2A) and Bcl-xL (2C) is the same, since proteins were separated in the same gel electrophoresis.

Análise das interações entre dados climáticos e o processo de desertificação no núcleo de desertificação de Cabrobó-PE, Brasil

This study assessed the dynamics of the Land Use and Land Cover Changes in the desertification hotspot of Cabrobó-PE using an approach that includes the space-time variation of environmental and climate data. To achieve this goal, the ArcGis software and the Google Earth Engine Platform were used. This platform combines a catalog of satellite imagery and geospatial datasets with planetary-scale analysis capabilities and makes it available for scientists, researchers, and developers allowing the detection of changes, map trends, and quantify differences on the Earth's surface. Results showed that forested areas decreased 54% between 2000 and 2016, being replaced by areas of bare soil and degraded areas. The degraded areas were characterized by higher land surface temperature (37.5% °C) and by an increase of 1°C in the period 2009 to 2016. The increase in land surface temperature may be associated with the water stress, which usually worsens in areas with a high degree of soil degradation. The combination of the information analyzed in the present study allows the monitoring of heterogeneous areas, identifying hotspots that require immediate recovery actions and the improved of soil management.No presente estudo avaliou-se a dinâmica das mudanças de usos e cobertura da terra no núcleo de desertificação de Cabrobó-PE, a partir de abordagem que inclui a variação espaço-temporal de dados ambientais e de clima. Para a execução do trabalho, utilizaram-se o software ArcGis e a Plataforma do Google Earth Engine. Essa plataforma combina um catálogo de imagens de satélite e conjuntos de dados geoespaciais com recursos de análise em escala planetária e os disponibiliza a cientistas, pesquisadores e desenvolvedores, o que possibilita detectar mudanças, mapear tendências e quantificar diferenças de alterações na superfície terrestre. De acordo com os resultados obtidos, foi possível constatar que as áreas de floresta no núcleo de Cabrobó diminuíram 54%, sendo estas substituídas por áreas de solo exposto e áreas degradadas no período de 2000 a 2016. As áreas degradadas foram caracterizadas por apresentarem temperatura de superfície mais elevada (37,5oC), tendo aumentado em 1oC no período de 2009 a 2016. O aumento da temperatura da superfície pode estar associado ao estresse hídrico que tende a se agravar em áreas com alto grau de degradação do solo. A combinação das informações analisadas no presente estudo permite monitorar áreas heterogêneas, identificando pontos críticos (hotspots) que requerem ações imediatas de recuperação e implementação de manejo adequado

Chemical composition and antioxidant potential of essential oils from different Ocimum species (Basil) / Composição química e atividade antioxidante de óleos essenciais de diferentes espécies de Ocimum (Manjericão)

Plants of the genus Ocimum are widely used in cooking, cosmetics and folk medicine, mainly antibacterial, antifungal and antioxidant properties. This article examines the chemical composition and antioxidant capacity of essential oils of Ocimum varieties. The chemical composition was analyzed by gas chromatography/mass spectrometry (GC/MS). For the evaluation of the antioxidant capacities, three different methods were used: the 2,20-diphenyl-1-picrylhydrazyl radical scavenging method (DPPH), ABTS (2,2?-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) antiradical method and ?-carotene/peroxyl radicals (LOO•) systems. There was a great variability in the composition and some species had a high eugenol content: O. tenuiflorum>O. campechianum>O. basilicum var. ball>O. gratissimum >O. basilicum var. greek. Methyl chavicol, neral and geranial were components found in other Ocimum species. Better antioxidant efficiency was found in species with a higher eugenol content as Ocimum tenuiflorum by DPPH IC50 2.31±0.02 µg.mL-1, ABTS IC50 2.22±0.23 µg.mL-1 and ?-carotene/linolenic acid system IC50 16.11±3.59 µg.mL-1, equally statistically significant when compared to pure eugenol. Basil essential oils had higher eugenol content in five species with strong antioxidant potential, adding a differential value to the Food Industry in the production of new functional foods or biofilms for foods with functionalities of preservation or control of chronic diseases

Intricate macrophage-colorectal cancer cell communication in response to radiation

Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively. Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar fractionated scheme to that used during cancer patients' treatment (2 Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co-culture with macrophages increased the mRNA expression of metabolism- and survival-related genes more in SW1463 than in RKO. The presence of macrophages also upregulated glucose transporter 1 expression in irradiated SW1463, but not in RKO cells. In addition, the influence of cancer cells on the expression of pro- and anti-inflammatory macrophage markers, upon radiation exposure, was also evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti-inflammatory CCL18. However, RKO cells induce an increase of macrophage pro-inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data demonstrated that macrophages and cancer cells mutually influence their response to radiation. Notably, conditioned medium from irradiated co-cultures increased non-irradiated RKO cell migration and invasion and did not impact on angiogenesis in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of primary human macrophage-cancer cell co-cultures revealed an intricate cell communication in response to ionizing radiation, which should be considered when developing therapies adjuvant to radiotherapy

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio