A20 deficiency causes spontaneous neuroinflammation in mice

Background: A20 (TNFAIP3) is a pleiotropic NFκB-dependent gene that terminates NFκB activation in response to inflammatory stimuli. The potent anti-inflammatory properties of A20 are well characterized in several organs. However, little is known about its role in the brain. In this study, we investigated the brain phenotype of A20 heterozygous (HT) and knockout (KO) mice. Methods: The inflammatory status of A20 wild type (WT), HT and KO brain was determined by immunostaining, quantitative PCR, and Western blot analysis. Cytokines secretion was evaluated by ELISA. Quantitative results were statistically analyzed by ANOVA followed by a post-hoc test. Results: Total loss of A20 caused remarkable reactive microgliosis and astrogliosis, as determined by F4/80 and GFAP immunostaining. Glial activation correlated with significantly higher mRNA and protein levels of the pro-inflammatory molecules TNF, IL-6, and MCP-1 in cerebral cortex and hippocampus of A20 KO, as compared to WT. Basal and TNF/LPS-induced cytokine production was significantly higher in A20 deficient mouse primary astrocytes and in a mouse microglia cell line. Brain endothelium of A20 KO mice demonstrated baseline activation as shown by increased vascular immunostaining for ICAM-1 and VCAM-1, and mRNA levels of E-selectin. In addition, total loss of A20 increased basal brain oxidative/nitrosative stress, as indicated by higher iNOS and NADPH oxidase subunit gp91phox levels, correlating with increased protein nitration, gauged by nitrotyrosine immunostaining. Notably, we also observed lower neurofilaments immunostaining in A20 KO brains, suggesting higher susceptibility to axonal injury. Importantly, A20 HT brains showed an intermediate phenotype, exhibiting considerable, albeit not statistically significant, increase in markers of basal inflammation when compared to WT. Conclusions: This is the first characterization of spontaneous neuroinflammation caused by total or partial loss of A20, suggesting its key role in maintenance of nervous tissue homeostasis, particularly control of inflammation. Remarkably, mere partial loss of A20 was sufficient to cause chronic, spontaneous low-grade cerebral inflammation, which could sensitize these animals to neurodegenerative diseases. These findings carry strong clinical relevance in that they question implication of identified A20 SNPs that lower A20 expression/function (phenocopying A20 HT mice) in the pathophysiology of neuroinflammatory diseases

Antibodies Against Glycolipids Enhance Antifungal Activity of Macrophages and Reduce Fungal Burden After Infection with Paracoccidioides brasiliensis

Paracoccidioidomycosis is a fungal disease endemic in Latin America. Polyclonal antibodies to acidic glycosphingolipids (GSLs) from Paracoccidioides brasiliensis opsonized yeast forms in vitro increasing phagocytosis and reduced the fungal burden of infected animals. Antibodies to GSL were active in both prophylactic and therapeutic protocols using a murine intratracheal infection model. Pathological examination of the lungs of animals treated with antibodies to GSL showed well-organized granulomas and minimally damaged parenchyma compared to the untreated control. Murine peritoneal macrophages activated by IFN-gamma and incubated with antibodies against acidic GSLs more effectively phagocytosed and killed P brasiliensis yeast cells as well as produced more nitric oxide compared to controls. The present work discloses a novel target of protective antibodies against P brasiliensis adding to other well-studied mediators of the immune response to this fungus.CapesFAPESPUniv Sao Paulo, Dept Microbiol, Inst Biomed Sci, Sao Paulo, BrazilUniv Sao Paulo, Lab Med Mycol IMTSP LIM53, Sao Paulo, BrazilAlbert Einstein Coll Med, Dept Med, New York, NY USAAlbert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USAUniv Fed Fluminense, Niteroi, RJ, BrazilUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilFAPESP: 2011/17267-4FAPESP: 2013/18655-3Web of Scienc

Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

<p>Abstract</p> <p>Background</p> <p>Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB) and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO) affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE) and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs) from <it>M. bovis </it>BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection.</p> <p>Results</p> <p>The 2DE proteomic map of <it>M. bovis </it>BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa), Rv1926c (BCG1965c, Mpb63) and Rv1886c (BCG1923c, Ag85B) in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2) and Rv0350 (BCG0389, DnaK), show the opposite pattern.</p> <p>Conclusions</p> <p>Here we report the detailed 2DE profile of CFPs from <it>M. bovis </it>BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.</p

How does the replacement of rice flour with flours of higher nutritional quality impact the texture and sensory profile and acceptance of gluten-free chocolate cakes?

Gluten-free bakery products usually use rice flour as substitute for wheat flour. This paper aims to evaluate whether and how the substitution of rice flour for sorghum and teff flour changes the overall acceptance, texture and sensory profile of gluten-free chocolate cakes. An experimental design composed of three factors (rice, sorghum and teff flours) was developed, and formulations were analysed by acceptance test and fibre content. Four formulations were submitted to sensory descriptive analysis. The formulations did not show significant differences in the overall acceptance although the sensory profile has changed. The texture was affected by the type of flour, being the optimised formulation the softer among the samples. From these data, it can be concluded that it is possible to replace rice flour with sorghum and teff flour in chocolate cake formulations, since the change in the sensory profile did not affect the acceptance of the products.info:eu-repo/semantics/publishedVersio

Prevenção à intoxicação por produtos químicos de uso doméstico

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Biodisponibilidade de Cd em latossolo acrescido de lodo de esgoto

This study was carried out to obtain the bioavailability of cadmium in a latosol increased of a single dose of sewage sludge. Representative samples of Bw horizon of a latosol, from Duque de Caxias city - RJ, and sewage sludge from ETE Ilha do Governador, in Rio de Janeiro city were collected. These materials were characterized due to its chemical, physical and mineralogical characteristics. Latter on, the samples were mixed together and bioavailability tests were accomplished. The results show that cadmium became bioavailable in the solution in the first hour of assay. After this interval the concentration of the available metal in solution it diminished, occurring stabilization in the subsequent hours of collection.O presente trabalho trata do estudo da biodisponibilidade de Cd no horizonte Bw de latossolo acrescido de uma única dose de lodo de esgoto. As amostras de latossolo e de lodo, respectivamente, foram coletadas no município de Duque de Caxias - RJ e na estação de tratamento de esgoto da Ilha do Governador (ETE Ilha), no município do Rio de Janeiro. A parte preliminar do estudo consistiu na caracterização dos materiais em laboratório por meio de ensaios físicos (granulometria, massa específica dos grãos, limites de Atterberg), químicos e físico-químicos (pH, carbono orgânico, CTC, ataque sulfúrico, fertilidade, análise química total) e mineralógicos (mineralogia por difração de raios-X). O lodo posteriormente foi incorporado ao latossolo e avaliou-se a biodisponibilidade do Cd na fração solúvel da mistura em questão. Os resultados mostraram que o Cd tornou-se biodisponível na solução na primeira hora de ensaio. Depois deste intervalo a concentração do metal disponível em solução diminuiu, ocorrendo uma estabilização nas horas subseqüentes de coleta

Ewing Sarcoma/Pnet pre-sacral: case report

Ewing’s sarcoma is a type of bone tumor that has aggressive behavior, which mainly affects individuals below 30 years and predominantly in males. The family of tumors includes Ewing a spectrum of neuroectodermal of primitive cells tumors which are embryonic cells migrating from the neural crest. In this report we present a male patient, 19 years, admitted to the emergency room with back pain, weakness of the lower limbs, difficulty urinating and right femur fracture a year ago. Requested magnetic resonance imaging of the pelvis and lumbosacral spine showed a presacral mass lesion and extramedullary and intradural lesions. Patient has been subjected to the pathological examination that showed Ewing’s sarcoma / primitive neuroectodermal tumor. Surgery for spinal decompression and subsequent radiotherapy and chemotherapy have been conducted.O sarcoma de Ewing é um tipo de tumor ósseo, de comportamento agressivo, que acomete principalmente indivíduos abaixo dos 30 anos e com predomínio no sexo masculino. A família de tumores de Ewing compreende um espectro de neoplasias de células neuroectodérmicas primitivas as quais são células embrionárias que migram da crista neural. Neste relato apresenta-se paciente do sexo masculino, 19 anos, admitido na emergência com quadro de lombalgia, fraqueza de membros inferiores, dificuldade de urinar e fratura de fêmur direito há um ano. Solicitada ressonância magnética da pelve e coluna lombosacra que evidenciaram lesão expansiva pré-sacral e lesões extramedulares e intradurais. Paciente submetido a exame anatomopatológico que evidenciou sarcoma de Ewing/Tumor Neuroectodérmico Primitivo. Realizado tratamento cirúrgico para descompressão medular e posterior radioterapia e quimioterapi