Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells

<p>Abstract</p> <p>Background</p> <p>Neuropeptide Y (NPY) is emerging as a modulator of communication between the brain and the immune system. However, in spite of increasing evidence that supports a role for NPY in the modulation of microglial cell responses to inflammatory conditions, there is no consistent information regarding the action of NPY on microglial phagocytic activity, a vital component of the inflammatory response in brain injury. Taking this into consideration, we sought to assess a potential new role for NPY as a modulator of phagocytosis by microglial cells.</p> <p>Methods</p> <p>The N9 murine microglial cell line was used to evaluate the role of NPY in phagocytosis. For that purpose, an IgG-opsonized latex bead assay was performed in the presence of lipopolysaccharide (LPS) and an interleukin-1β (IL-1β) challenge, and upon NPY treatment. A pharmacological approach using NPY receptor agonists and antagonists followed to uncover which NPY receptor was involved. Moreover, western blotting and immunocytochemical studies were performed to evaluate expression of p38 mitogen-activated protein kinase (MAPK) and heat shock protein 27 (HSP27), in an inflammatory context, upon NPY treatment.</p> <p>Results</p> <p>Here, we show that NPY inhibits phagocytosis of opsonized latex beads and inhibits actin cytoskeleton reorganization triggered by LPS stimulation. Co-stimulation of microglia with LPS and adenosine triphosphate also resulted in increased phagocytosis, an effect inhibited by an interleukin-1 receptor antagonist, suggesting involvement of IL-1β signaling. Furthermore, direct application of LPS or IL-1β activated downstream signaling molecules, including p38 MAPK and HSP27, and these effects were inhibited by NPY. Moreover, we also observed that the inhibitory effect of NPY on phagocytosis was mediated <it>via </it>Y₁receptor activation.</p> <p>Conclusions</p> <p>Altogether, we have identified a novel role for NPY in the regulation of microglial phagocytic properties, in an inflammatory context.</p

Casa como lar:: entre descanso e movimento

Propomos nesse texto um exercício de pensar os sentidos da mobilidade e lugar no cenário contemporâneo na interface da tradição da geografia humanista. Para tal feito, albergamos a geografia têmporo-espacial acompanhada pelas trajetórias de vida de Torsten Hägerstrand e pelo balé do lugar desenvolvido por David Seamon. Acreditamos que as biografias de vida são elementos fundamentais para pensar a problemática da mobilidade na contemporaneidade, pois elas envolvem todo arranjo situacional da existência. São pelas biografias de vida que as mobilidades e as danças dos lugares se inserem no bojo das relações vividas cotidianamente. O objetivo deste texto se insere na possibilidade de arrolar pensamentos da tradição da geografia humanista ainda pouco trabalhados na contemporaneidade. Fazendo, com isso, um alargamento dos sentidos da mobilidade e do lugar pela tarefa investigativa da geografia humanista

Is There a Surplus of Non-Specialist Physicians in Portugal or Just Poor Human Resources Planning?

N/A

Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel damage response pathways in Trypanosoma brucei

All cells are subject to structural damage that must be addressed for continued growth. A wide range of damage affects the genome, meaning multiple pathways have evolved to repair or bypass the resulting DNA lesions. Though many repair pathways are conserved, their presence or function can reflect the life style of individual organisms. To identify genome maintenance pathways in a divergent eukaryote and important parasite, Trypanosoma brucei, we performed RNAi screens to identify genes important for survival following exposure to the alkylating agent methyl methanesulphonate. Amongst a cohort of broadly conserved and, therefore, early evolved repair pathways, we reveal multiple activities not so far examined functionally in T. brucei, including DNA polymerases, DNA helicases and chromatin factors. In addition, the screens reveal Trypanosoma- or kinetoplastid-specific repair-associated activities. We also provide focused analyses of repair-associated protein kinases and show that loss of at least nine, and potentially as many as 30 protein kinases, including a nuclear aurora kinase, sensitises T. brucei to alkylation damage. Our results demonstrate the potential for synthetic lethal genome-wide screening of gene function in T. brucei and provide an evolutionary perspective on the repair pathways that underpin effective responses to damage, with particular relevance for related kinetoplastid pathogens. By revealing that a large number of diverse T. brucei protein kinases act in the response to damage, we expand the range of eukaryotic signalling factors implicated in genome maintenance activities

Histamine stimulates neurogenesis in the rodent subventricular zone

Neural stem/progenitor cells present in the subventricular zone (SVZ) are a potential source of repairing cells after injury. Therefore, the identification of novel players that modulate neural stem cells differentiation can have a huge impact in stem cell-based therapies. Herein, we describe a unique role of histamine in inducing functional neuronal differentiation from cultured mouse SVZ stem/progenitor cells. This proneurogenic effect depends on histamine 1 receptor activation and involves epigenetic modifications and increased expression of Mash1, Dlx2, and Ngn1 genes. Biocompatible poly (lactic-co-glycolic acid) microparticles, engineered to release histamine in a controlled and prolonged manner, also triggered robust neuronal differentiation in vitro. Preconditioning with histamine-loaded microparticles facilitated neuronal differentiation of SVZ-GFP cells grafted in hippocampal slices and in in vivo rodent brain. We propose that neuronal commitment triggered by histamine per se or released from biomaterial-derived vehicles may represent a new tool for brain repair strategies. STEM CELLS 2012; 30:773784Fundacao para a Ciencia e a Tecnologia-Portugal [SFRH/BD/42848/2008, SFRH/BPD/34841/2007, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, PTDC/CTM/099659/2008]; Fundacao Calouste Gulbenkian [96542]info:eu-repo/semantics/publishedVersio

Using data mining algorithms to predict the bond strength of NSM FRP systems in concrete

This paper presents the effectiveness of soft computing algorithms in analyzing the bond behavior of fiber reinforced polymer (FRP) systems inserted in the cover of concrete elements, commonly known as the near-surface mounted (NSM) technique. It focuses on the use of Data Mining (DM) algorithms as an alternative to the existing guidelines’ models to predict the bond strength of NSM FRP systems. To ease and spread the use of DM algorithms, a web-based tool is presented. This tool was developed to allow an easy use of the DM prediction models presented in this work, where the user simply provides the values of the input variables, the same as those used by the guidelines, in order to get the predictions. The results presented herein show that the DM based models are robust and more accurate than the guidelines’ models and can be considered as a relevant alternative to those analytical methods

Conhecimento dos enfermeiros sobre o novo protocolo de ressuscitação cardiopulmonar

Objetivo: Avaliar o conhecimento de enfermeiros sobre o atendimento à parada cardiorrespiratória (PCR), suporte básico e avançado de vida cardiovascular, tendo como base as novas diretrizes de Ressuscitação Cardiopulmonar (RCP) da American Heart Association (AHA) do ano de 2015. Métodos: Trata-se de um estudo descritivo de abordagem quantitativa, realizado no hospital escola de um município do interior de Minas Gerais, através da aplicação de um questionário fechado, elaborado pelas pesquisadoras. Os dados coletados foram processados pelo Statistical Package for the Social Sciences (SPSS) versão 20. Resultados: Participaram do estudo 19 enfermeiros. O número de acertos dos participantes no questionário oscilou entre 0 a 100%, com média de 4,2 e desvio padrão de 3,2. Foi classificado, como conhecimento satisfatório, o número de acertos superior e/ou igual a 70% e o conhecimento insatisfatório, o número inferior a 70%. Apenas 26,4% dos enfermeiros obtiveram conhecimento satisfatório. Conclusão: Constatou-se que enfermeiros não possuem conhecimento satisfatório sobre as mudanças propostas pelas novas diretrizes de RCP da AHA de 2015

Jovens Solistas da Metropolitana

Brochura de sala do concerto realizado pelos Jovens Solistas da Metropolitana a 24 de Novembro de 2022 no ÂMBITO CULTURAL, PISO 6 do EL CORTE INGLÉS em Lisboa no âmbito da Temporada 2022/2023 da Metropolitana dedicada a 30º aniversário da instituição. O programa do concerto foi preenchido com obras Arnold, Mozart, Beethoven, Ewald e Hindemith. Desenvolvendo uma ponte pedagógica inédita entre a prática e o ensino musical, a ANSO é a única escola do país que forma maestros, instrumentistas de orquestra e pianistas vocacionados para música de câmara. Ao longo dos seus quase 30 anos, mudou o panorama cultural em Portugal, sendo muitos os seus alunos a entrar nas mais exigentes instituições de ensino e formações internacionais. Mais premiada escola nacional desta área, as novas gerações de intérpretes e diretores musicais que lança são reconhecidas pela qualidade. A música de câmara é uma das vertentes fundamentais da Academia Nacional Superior de Orquestra, que todos os anos apresenta o ciclo Jovens Solistas da Metropolitana.N/