The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease

Objective Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression.This work was supported by Brainvectis and E.rare: E-Rare Joint Transnational Call for Proposals 2017 “Transnational Research Projects for Innovative Therapeutic Approaches for Rare Diseases”. CN laboratory is supported by the French Muscular Dystrophy Association (AFM-Téléthon), the Ataxia UK, and the Fundação para a Ciência e Tecnologia (project ALG-01-0145-FEDER-29480 “SeGrPolyQ”). AM is supported by a Ph.D. fellowship from FCT (SFRH/BD/133192/2017)info:eu-repo/semantics/publishedVersio

INFLUENCE OF WOOD STACKING LOCATION ON FOREST TRANSPORT COSTS

Given the importance of forest transportation planning due to its high contribution in wood final cost, the distance between forest plantation stands and the wood final destination should be optimized in order to reduce process cost. The relation between distance and transportation cost is known, yet, it is still necessary to evaluate how much the location of the wood piles inside the stand interferes with its final cost. Thus, we try to evaluate the influence of the wood stacking location on forest transportation costs. The vectorization of the general map of a property located in Minas Gerais state was performed through the QGIS software, by representing the planting areas by polygons, internal and external access roads by lines, and the possible wood-stacking location to be transported by points. In each stand, four wood-stacking sites were considered, each on one side of the stand. Considering this, optimal route simulations were performed based on the criterion of the shortest distance between each pile of wood and a carbonization plant. The results showed a 32% reduction in the final cost of transportation when the wood is stacked in places closer to the carbonization plant. Therefore, the results evidence that the choice of the ideal stacking point, in the aspect of closer proximity to the destination of the wood transportation, can generate savings in this process

Knowledge and practices of biosafety among nursing professors

Objectives: To describe the knowledge of nursing teachers of a nursing course on Norm 32 and on postexposure practices to biological materials and to identify the vaccination status of these teachers. Method: Quantitative descriptive cross-sectional study. Data was collected between September and October 2014, using a questionnaire and analyzed using the SPSS statistical software 21.0. The participants were 35 nursing teachers. Results: 71.4% were female; 100% claimed to have knowledge on biosecurity; 51.4% knew Norm 32; 71.4% were immunized for hepatitis B; 22.9% had accidents involving biological material; only 14.3% cited washing the injury with water and soap after the occurrence of an accident. Conclusion: It was evidenced that there is a weakness in the teachers’ knowledge regarding biosafety actions

MICRO-DESTINO: UMA PERSPECTIVA DE ANÁLISE E GESTÃO PARA O DESENVOLVIMENTO TURÍSTICO

Este artigo apresenta a perspectiva de micro-destino turístico com suas categorias de classificação, assim como, às vantagens do uso desta unidade para a análise e gestão do turismo. Esta perspectiva é contextualizada através do estudo de caso do Destino turístico Gran Canaria-Espanha que definiu uma estruturação de 14 micro-destinos. A identificação de pequenas áreas geográficas nas quais o turismo é uma atividade motriz contribui para o desenvolvimento de políticas e programas mais eficazes que considerem a homogeneização destas áreas, e por consequente a heterogeneidade existente no destino integral. A pesquisa se classifica como qualitativa com método exploratório-descritivo, utilizando dados estatísticos secundários. Os resultados indicam que a categorização dos micro-destinos turísticos analisados seguem os critérios indicados na literatura para sua delimitação. A adoção destas unidades de gestão justificou-se pelos dados de demanda e oferta existente nos locais, pois possibilitou melhor controle, planejamento e co-marketing. Assim, a divisão territorial baseada em micro-destinos demonstra ser uma opção adequada para fins de gestão regional.Palavras-chave: Micro-destino turístico. Gestão estratégica turística. Gran Canaria. ABSTRACTThis paper presents the tourism micro-destination perspective and their categories of classification, as well as, the advantages of using this unit to the analysis and management in the tourism sector. This perspective is contextualized through the case study of Gran Canaria tourism destination, in Spain, which defined 14 micro-destinations in its tourism system. The identification of small geographic areas in which tourism is a driver activity contributes to the development of policies and programs mostly effective because considers the homogenization of these areas, and consequently, the existing heterogeneity in integral destination. The research is performed by an exploratory-descriptive qualitative methodology using secondary data. The results indicate that the categorization of the tourism micro-destinations in Gran Canaria has followed the criteria indicated in the literature to their delimitation. Also, it indicated that the adoption of these management units are justified by demand data and by the tourism offer in these places, allowing better control, planning and co-marketing. Thus, the territorial division based on micro-destinations reveals to be an appropriate option for regional management.Keywords: Tourism Micro-destination. Tourism Management. Gran Canaria

Cordycepin activates autophagy through AMPK phosphorylation to reduce abnormalities in Machado-Joseph disease models

Machado-Joseph disease (MJD) is a neurodegenerative disorder caused by an abnormal expansion of citosine-adenine-guanine trinucleotide repeats in the disease-causing gene. This mutation leads to an abnormal polyglutamine tract in the protein ataxin-3 (Atx3), resulting in formation of mutant Atx3 aggregates. Despite several attempts to develop a therapeutic option for MJD, currently there are no available therapies capable of delaying or stopping disease progression. Recently, our group reported that reducing the expression levels of mutant Atx3 lead to a mitigation of several MJD-related behavior and neuropathological abnormalities. Aiming a more rapid translation to the human clinics, in this study we investigate a pharmacological inhibitor of translation-cordycepin-in several preclinical models. We found that cordycepin treatment significantly reduced (i) the levels of mutant Atx3, (ii) the neuropathological abnormalities in a lentiviral mouse model, (iii) the motor and neuropathological deficits in a transgenic mouse model and (iv) the number of ubiquitin aggregates in a human neural model. We hypothesize that the effect of cordycepin is mediated by the increase of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) levels, which is accompanied by a reduction in the global translation levels and by a significant activation of the autophagy pathway. Overall, this study suggests that cordycepin might constitute an effective and safe therapeutic approach for MJD, and probably for the other polyglutamine diseases.European Union through the European social fund, funds Fundo Europeu de Desenvolvimento Regional through the Competitive Factors Operational Program-COMPETE, POPH and QRENFrench Muscular Dystrophy Association (AFM-Telethon) [18776]Ataxia UKFundacao para a Ciencia e TecnologiaPortuguese Foundation for Science and Technology [SFRH/BD/133192/2017]FCT - Fundacao para a Ciencia e a Tecnologia, I.P. [UID/BIM/04773/2013 CBMR

THE SUSCEPTIBILITY OF RECENT ISOLATES OF Schistosoma mansoni TO PRAZIQUANTEL

Introduction: Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma and its control is dependent on a single drug, praziquantel (PZQ), but concerns over PZQ resistance have renewed interest in evaluating the in vitro susceptibility of recent isolates of Schistosoma mansoni to PZQ in comparison with well-established strains in the laboratory. Material and methods: The in vitro activity of PZQ (6.5-0.003 µg/mL) was evaluated in terms of mortality, reduced motor activity and ultrastructural alterations against S. mansoni. Results: After 3 h of incubation, PZQ, at 6.5 µg/mL, caused 100% mortality of all adult worms in the three types of recent isolates, while PZQ was inactive at concentrations of 0.08-0.003 µg/mL after 3 h of incubation. The results show that the SLM and Sotave isolates basically presented the same pattern of susceptibility, differing only in the concentration of 6.5 µg/mL, where deaths occurred from the range of 1.5 h in Sotave and just in the 3 h range of SLM. Additionally, this article presents ultrastructural evidence of rapid severe PZQ-induced surface membrane damage in S. mansoni after treatment with the drug, such as disintegration, sloughing, and erosion of the surface. Conclusion: According to these results, PZQ is very effective to induce tegument destruction of recent isolates of S. mansoni

Influência dos parâmetros da metaheurística algoritmo genético em um problema de planejamento florestal

Este trabalho objetivou avaliar o comportamento de diferentes parâmetros da metaheurística Algoritmo Genético para solução de problemas do planejamento florestal. O estudo considerou um horizonte de planejamento de 16 anos, analisando-se como parâmetros da metaheurística a utilização de elitismo, o tipo de cruzamento (1 ponto de corte e uniforme), o tipo de seleção dos pais para cruzamento (roleta e torneio) e tipo de mutação (escolha aleatória do gene e gene a gene), totalizando 16 combinações. Adicionalmente foram avaliados o tamanho da população inicial (20, 50 e 80 indivíduos) e o critério de parada (100, 300 e 500 gerações), totalizando 9 combinações. Cada uma dessas combinações foi considerada como um tratamento e processada com 30 repetições. O problema objetivou encontrar um cenário de planejamento da produção florestal que retornasse o máximo valor presente líquido sujeito às restrições de idade de corte (entre 5 e 7 anos), demandas mínima e máxima anual (140.000 m³ e 160.000 m³, respectivamente) e integridade. O processamento foi efetuado utilizando-se o software MeP. Aplicou-se o teste não-paramétrico de Kruskal-Wallis. Os resultados mostram que há diferença estatisticamente significativa, a 5% de probabilidade, entre as combinações dos parâmetros. Conclui-se que a qualidade das soluções geradas pela metaheurística algoritmo genético é dependente da seleção de uma boa configuração de seus parâmetros. A melhor solução foi encontrada utilizando a seguinte configuração: elitismo, cruzamento de 1 ponto, seleção do tipo torneio, mutação do tipo gene a gene, população inicial com 50 indivíduos e critério de parada com 500 gerações

Conhecimentos e condutas de biossegurança entre docentes de enfermagem Knowledge and practices of biosafety among nursing professors

Objetivos: Descrever o conhecimento dos docentes enfermeiros de um curso de enfermagem sobre Norma Regulamentadora 32 e as condutas pós-exposição a materiais biológicos e, identificar a situação vacinal destes docentes. Método: Estudo quantitativo descritivo de corte transversal. Os dados foram coletados, entre setembro e outubro de 2014, através de um questionário e analisados através do Software estatístico SPSS 21.0. Participaram da pesquisa 35 docentes enfermeiros. Resultados: 71,4% eram do sexo feminino; 100% afirmou ter conhecimento sobre biossegurança; 51,4% conheciam a Norma Regulamentadora 32; 71,4% estavam imunizados para hepatite B; 22,9% sofreram acidente envolvendo material biológico; apenas 14,3% citaram a lavagem com água e sabão do ferimento após a ocorrência de acidente. Conclusão: Evidenciou-se que existe uma fragilidade no conhecimento dos docentes relativo às ações de biossegurança

Metabolic profiling and antibacterial activity of Eryngium pristis Cham. & Schltdl. - prospecting for its use in the treatment of bacterial infections

Morbidity and mortality of the infected patients by multidrug-resistant bacteria have increased, emphasizing the urgency of fi ght for the discovery of new innovative antibiotics. In this sense, natural products emerge as valuable sources of bioactive compounds. Among the biodiversity, Eryngium pristis Cham. & Schltdl. (Apiaceae Lindl.) is traditionally used to treat thrush and ulcers of throat and mouth, as diuretic and emmenagogue, but scarcely known as an antimicrobial agent. With this context in mind, the goals of this study were to investigate the metabolic profi le and the antibacterial activity of ethanolic extract (EE-Ep) and hexane (HF-Ep), dichloromethane (DF-Ep), ethyl acetate (EAF-Ep) and butanol (BF-Ep) fractions from E. pristis leaves. Gas Chromatography-Mass Spectrometry (GC-MS) was performed to stablish the metabolic profi le and revealed the presence of 12 and 14 compounds in EAF-Ep and HF-Ep, respectively. β-selinene, spathulenol, globulol, 2-methoxy-4-vinylphenol, α-amyrin, β-amyrin, and lupeol derivative were some of phytochemicals identifi ed. The antibacterial activity was determined by Minimal Inhibitory Concentration (MIC) using the broth micro-dilution against eight ATCC® and fi ve methicillin-resistant Staphylococcus aureus (MRSA) clinical strains. HF-Ep was the most eff ective (MIC ≤ 5,000 μg/μL), being active against the largest part of tested Gram-positive and Gram-negative bacterial strains, including MRSA, with exception of Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 9027) and (ATCC 27853). These results suggest that E. pristis is a natural source of bioactive compounds for the search of new antibiotics which can be an interesting therapeutic approach to recover patients mainly infected by MRSA strains.info:eu-repo/semantics/publishedVersio