Epigenetic regulation of nitric oxide synthase 2, inducible (Nos2) by NLRC4 inflammasomes involves PARP1 cleavage

Nitric oxide synthase 2, inducible (Nos2) expression is necessary for the microbicidal activity of macrophages. However, NOS2 over-activation causes multiple inflammatory disorders, suggesting a tight gene regulation is necessary. Using cytosolic flagellin as a model for inflammasome-dependent NOS2 activation, we discovered a surprising new role for NLRC4/caspase-1 axis in regulating chromatin accessibility of the Nos2 promoter. We found that activation of two independent mechanisms is necessary for NOS2 expression by cytosolic flagellin: caspase-1 and NF-kappa B activation. NF-kappa B activation was necessary, but not sufficient, for NOS2 expression. Conversely, caspase-1 was necessary for NOS2 expression, but dispensable for NF-kappa B activation, indicating that this protease acts downstream NF-kappa B activation. We demonstrated that epigenetic regulation of Nos2 by caspase-1 involves cleavage of the chromatin regulator PARP1 (also known as ARTD1) and chromatin accessibility of the NF-kappa B binding sites located at the Nos2 promoter. Remarkably, caspase-1-mediated Nos2 transcription and NO production contribute to the resistance of macrophages to Salmonella typhimurium infection. Our results uncover the molecular mechanism behind the constricted regulation of Nos2 expression and open new therapeutic opportunities based on epigenetic activities of caspase-1 against infectious and inflammatory diseases.Kanton of ZurichUniversity Research Priority Program (URPP) in Translational Cancer Biology at the University of ZurichSwiss National Science FoundationCancer Research SocietyCanadian Cancer SocietyNSERCOntario Institute for Cancer Research (OICR)province of OntarioPrincess Margaret Cancer FoundationUniversity of Toronto McLaughlin CentreFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP - Brazil)Brazilian Research Council (CNPq-Brazil)CAPESINCTVUniv Fed Sao Paulo, Ctr Terapia Celular & Mol CTC Mol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, BrazilUniv Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, CanadaUniv Sao Paulo, Inst Ciencias Biomed, Sao Paulo & Inst Invest Imunol, Inst Nacl Ciencia Tecnol INCT 3, Sao Paulo, BrazilInst Nacl Ciencia Tecnol INCT III, Inst Invest Imunol, Sao Paulo, BrazilUniv Zurich, Dept Mol Mech Dis, Zurich, SwitzerlandUniv Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, CanadaUniv Fed Sao Paulo, Ctr Terapia Celular & Mol CTC Mol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, BrazilSwiss National Science Foundation: 310030B_138667Cancer Research Society: CRS19092Cancer Research Society: CRS19091Canadian Cancer Society: CCSRI 703279Canadian Cancer Society CCSRI 703716NSERC: 489073University of Toronto McLaughlin Centre: MC-2015-02FAPESP: 2013/16010-5FAPESP: 2015/18003-1Web of Scienc

Estimation and classification of popping expansion capacity in popcorn breeding programs using NIR spectroscopy

One of the most important quality traits in popcorn breeding programs is the popping expansion (PE) capacity of the kernel, which is the ratio of the volume of the popcorn to the weight of the kernel. In this study, we evaluated whether near infrared spectroscopy (NIR spectroscopy) could be used as a tool in popcorn breeding programs to routinely predict and/or discriminate popcorn genotypes on the basis of their PE. Three generations (F1, F2, and F2:3) were developed in three planting seasons by manual cross-pollination and self-pollination. A total of 376 ears from the F2:3 generation were selected, shelled, and subjected to phenotypic analysis. Genetic variability was observed in the F2 and F2:3 generations, and their average PE value was 31.5 ± 6.7 mL.g-1. PE prediction models using partial least square (PLS) regression were developed, and the root mean square error of calibration (RMSEC) was 6.08 mL.g-1, while the coefficient of determination (RC 2) was 0.26. The model developed by principal component analysis with quadratic discriminant analysis (PCA-QDA) was the best for discriminating the kernels with low PE (≤ 30 mL.g-1) from those with high PE (> 30 mL.g-1) with an accuracy of 78%, sensitivity of 81.2%, and specificity of 72.2%. Although NIR spectroscopy appears to be a promising non-destructive method for assessing the PE of intact popcorn kernels for narrow breeding populations, greater variability and larger sample sizes would help improve the robustness of the predictive and classificatory models

Bicistronic DNA vaccines simultaneously encoding HIV, HSV and HPV antigens promote CD8⁺ T cell responses and protective immunity

Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8⁺ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8⁺ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.CNPqINCTVFAPESPUS

Síntese e caracterização de filmes finos biodegradáveis a base de bambu funcionalizados com óxido de ferro: uma análise de verificação de propriedades mecânicas, informações das superfícies e a absorção e emissão dos elementos / Synthesis and characterization of biodegradable bamboo-based thin films functionalized with iron oxide: a verification analysis of mechanical properties, surface information and the absorption and emission of elements

Guadua Weber-Baueri Pilger popularmente conhecido por bambu (taboca), encontrado na região Amazônica, Acre. Foram sintetizadas nanopartículas de óxido de ferro pelo método de coprecipitação. A Carboximetilcelulose (CMC) foi obtida pela síntese de Williamson (reação de substituição) a partir do colmo do bambu. Preparou-se os filmes finos em base bambu dispersando a CMC em água destilada nas concentrações diferentes de Polietilenoglicol (PEG) 2,5%, 5% e 7,5%, as misturas ficaram em agitação magnética e adicionados nos nanocompósitos o óxido de ferro com 1% e 5%, através de um banho ultrassom as soluções foram misturadas e adicionadas a placa petri para uma secagem completa na estufa incubadora, resultando nos filmes finos funcionalizados com óxido de ferro (FFOF). Os filmes finos funcionalizados com óxido de ferro foram caracterizados seguindo os Ensaios de Tração em que a tensão normal mostra que os filmes finos por serem poliméricos apresentam uma boa resistência mecânica, a Microscopia Eletrônica de Varredura (MEV) dá informações das superfícies com 1% e 5% as amostras apresentam similaridade onde a presença das nanopartículas magnéticas (NPM) não afetou as morfologias das suas superfícies, a Espectroscopia por Energia Dispersiva (EDS) é possível verificar a concentração de NPM visível na amostra indicando o revestimento a totalidade da superfície. Com base nos resultados obtidos foram possíveis obter resultados satisfatórios das análises dos (FFOF) apresentando um novo material nanoestruturado com diversas aplicações tecnológicas na engenharia dos materiais

Optical fiber relative humidity sensor based on a FBG with a di-ureasil coating

In this work we proposed a relative humidity (RH) sensor based on a Bragg grating written in an optical fiber, associated with a coating of organo-silica hybrid material prepared by the sol-gel method. The organo-silica-based coating has a strong adhesion to the optical fiber and its expansion is reversibly affected by the change in the RH values (15.0–95.0%) of the surrounding environment, allowing an increased sensitivity (22.2 pm/%RH) and durability due to the presence of a siliceous-based inorganic component. The developed sensor was tested in a real structure health monitoring essay, in which the RH inside two concrete blocks with different porosity values was measured over 1 year. The results demonstrated the potential of the proposed optical sensor in the monitoring of civil engineering structures

Erratum to: The study of cardiovascular risk in adolescents – ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents

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