A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.

Early loss of splenic Tfh cells in SIV-infected rhesus macaques

Early loss of splenic Tfh cells in SIV-infected rhesus macaques

The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ

Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-y (IFN-y). Mycobacterium avium-infected mice lacking IFN-y signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-y signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-y reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-y displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-y is responsible for the Warburg effect observed in organs infected with M. avium.

Myeloid Sirtuin 2 expression does not impact long-term Mycobacterium tuberculosis control

Sirtuins (Sirts) regulate several cellular mechanisms through deacetylation of several transcription factors and enzymes. Recently, Sirt2 was shown to prevent the development of inflammatory processes and its expression favors acute Listeria monocytogenes infection. The impact of this molecule in the context of chronic infections remains unknown. We found that specific Sirt2 deletion in the myeloid lineage transiently increased Mycobacterium tuberculosis load in the lungs and liver of conditional mice. Sirt2 did not affect long-term infection since no significant differences were observed in the bacterial burden at days 60 and 120 post-infection. The initial increase in M. tuberculosis growth was not due to differences in inflammatory cell infiltrates in the lung, myeloid or CD4+ T cells. The transcription levels of IFN-?, IL-17, TNF, IL-6 and NOS2 were also not affected in the lungs by Sirt2-myeloid specific deletion. Overall, our results demonstrate that Sirt2 expression has a transitory effect in M. tuberculosis infection. Thus, modulation of Sirt2 activity in vivo is not expected to affect chronic infection with M. tuberculosis.

NF-kB pathway controls mitochondrial dynamics

The Optic atrophy 1 protein (OPA1) is a key element in the dynamics and morphology of mitochondria. We demonstrated that the absence of I?B kinase-a, which is a key element of the nonclassical NF-?B pathway, has an impact on the mitochondrial network morphology and OPA1 expression. In contrast, the absence of NF-?B essential modulator (NEMO) or I?B kinase-ß, both of which are essential for the canonical NF-?B pathway, has no impact on mitochondrial dynamics. Whereas Parkin has been reported to positively regulate the expression of OPA1 through NEMO, herein we found that PARK2 overexpression did not modify the expression of OPA1. PARK2 expression reduced the levels of Bax, and it prevented stress-induced cell death only in Bak-deficient mouse embryonic fibroblast cells. Collectively, our results point out a role of the nonclassical NF-?B pathway in the regulation of mitochondrial dynamics and OPA1 expression.

Numerical modeling and assessment of the thermal environment in an industrial premise of automotive components

Dissertação de mestrado em Engenharia Industrial

Intermetallic layer formation and influence in solder joints reliability

Dissertação de mestrado integrado em Materials Engineering

Otimização das características de um chassis tubular de automóvel de competição com tração a duas rodas motrizes

Dissertação de mestrado integrado em Engenharia Mecânica

Numerical simulation of the reflow soldering process

Dissertação de mestrado integrado em Mechanical Engineering

Ki-67 expression in CRC lymph node metastasis does not predict survival

Colorectal cancer is one of the most common malignancies and a leading cause of cancer death worldwide. Molecular markers may improve clinicopathologic staging and provide a basis to guide novel therapeutic strategies which target specific tumourassociated molecules according to individual tumour biology; however, so far, no ideal molecular marker has been found to predict disease progression. We tested Ki-67 proliferation marker in primary and lymph node metastasis of CRC. We observed a statistical significant difference between the positive rates of neoplastic cells positively stained byKi-67 in both sites, with remarkable increased number of Ki-67 positive cells in primary tumor cells compared to cancer cells that invaded lymph nodes. We can speculate that the metastatic CRC in lymph node can be more resistant to the drugs that target cellular division.

Serviços para suporte à gestão de dados científicos: plano de intervenção dos SDUM

Os Serviços de Documentação da Universidade do Minho (SDUM) estabeleceram para os anos de 2014 e 2015 um plano de intervenção para os serviços de suporte à Gestão dos Dados Científicos na UMinho. Esta apresentação pretende resumir o plano traçado e a metodologia para a elaboração desta estratégia de atuação, identificando as áreas e os eixos de intervenção definidos pelos SDUM. Descreve algumas das ações já realizadas ou em desenvolvimento e destaca os principais resultados obtidos através de um estudo diagnóstico, realizado por questionário junto dos investigadores e centros de investigação da universidade, com o intuito de se obter um melhor conhecimento sobre o tipo de dados produzidos, as práticas de gestão associadas e averiguar a pertinência de serviços de suporte neste domínio.

Caso de demonstração de uma framework para automatização do teste de APIs de aplicações SaaS

Dissertação de mestrado integrado em Engenharia e Gestão de Sistemas de Informação

La formación b-learning en el máster de español segunda lengua y lengua extranjera de la Universidade do Minho: innovación pedagógica y desafíos educativos

En el actual marco de creciente innovación pedagógica, debido entre otros factores, a la irrupción de nuevas herramientas informáticas, la enseñanza a distancia (e-learning y/o b-learning) va ocupando cada vez más espacio en la oferta educativa de diversas instituciones. En esta dirección, en la Universidade do Minho, y concretamente en el Área de Estudos Espanhóis e Hispano-Americanos,[1] hemos dedicado considerables esfuerzos a la ampliación de nuestra oferta desde 2010: primero en la elaboración e implementación del Curso de Formación Especializada en Español Lengua Extranjera, modalidad b-learning (3 ediciones; 2010-2013), y, actualmente, con el Máster Universitario en Español Lengua Segunda / Lengua Extranjera (vid. www.melsle.ilch.uminho.pt), también b-learning. En las siguientes páginas, nos proponemos compartir una serie de experiencias y reflexiones que han ido surgiendo durante estos años acerca de la formación universitária de profesores de Español Lengua Extranjera, en general, con recurso a la modalidade b-learning; para ello, nos centraremos en los siguientes aspectos: (i) caracterización general y problematización de la enseñanza a distancia en la Universidade do Minho; (ii) descripción del Máster Universitario en Español Lengua Segunda / Lengua Extranjera, acerca del cual detallaremos algunas prácticas adoptadas, relacionadas com la enseñanza e-learning como, por ejemplo, (iii) la coordinación pedagógica o (iv) los enfoques metodológicos adoptados a partir de la experiencia de una Unidad Curricular concreta.

A novel small-caliber bacterial cellulose vascular prosthesis: production, characterization, and preliminary in vivo testing

Vascular grafts are used to bypass damaged or diseased blood vessels. Bacterial cellulose (BC) has been studied for use as an off-the-shelf graft. Herein, we present a novel, cost-effective, method for the production of small caliber BC grafts with minimal processing or requirements. The morphology of the graft wall produced a tensile strength above that of native vessels, performing similarly to the current commercial alternatives. As a result of the production method, the luminal surface of the graft presents similar topography to that of native vessels. We have also studied the in vivo behavior of these BC graft in order to further demonstrate their viability. In these preliminary studies, 1 month patency was achieved, with the presence of neo-vessels and endothelial cells on the luminal surface of the graft.

Estudo palinostratigráfico dos sectores Martinlongo-Vaqueiros e Malhadinha da Faixa Piritosa Ibérica: enquadramento geológico e paleogeográfico

Dissertação de mestrado em Geociências (área de especialização em Valorização de Recursos Geológicos)