SIRT1/2 orchestrate acquisition of DNA methylation and loss of histone H3 activating marks to prevent premature activation of inflammatory genes in macrophages

Altres ajuts: CERCA Programme/Generalitat de Catalunya; [...].Sirtuins 1 and 2 (SIRT1/2) are two NAD-dependent deacetylases with major roles in inflammation. In addition to deacetylating histones and other proteins, SIRT1/2-mediated regulation is coupled with other epigenetic enzymes. Here, we investigate the links between SIRT1/2 activity and DNA methylation in macrophage differentiation due to their relevance in myeloid cells. SIRT1/2 display drastic upregulation during macrophage differentiation and their inhibition impacts the expression of many inflammation-related genes. In this context, SIRT1/2 inhibition abrogates DNA methylation gains, but does not affect demethylation. Inhibition of hypermethylation occurs at many inflammatory loci, which results in more drastic upregulation of their expression upon macrophage polarization following bacterial lipopolysaccharide (LPS) challenge. SIRT1/2-mediated gains of methylation concur with decreases in activating histone marks, and their inhibition revert these histone marks to resemble an open chromatin. Remarkably, specific inhibition of DNA methyltransferases is sufficient to upregulate inflammatory genes that are maintained in a silent state by SIRT1/2. Both SIRT1 and SIRT2 directly interact with DNMT3B, and their binding to proinflammatory genes is lost upon exposure to LPS or through pharmacological inhibition of their activity. In all, we describe a novel role for SIRT1/2 to restrict premature activation of proinflammatory genes

In Vivo Cytotoxicity Induced by 60 Hz Electromagnetic Fields under a High-Voltage Substation Environment

Abstract: Living beings permanently receive electromagnetic radiation, particularly from extremely low-frequency electromagnetic fields (ELF-EMFs), which may cause adverse health effects. In this work, we studied the in vivo cytotoxic effects of exposing BALB/c mice to 60 Hz and 8.8 µT EMFs during 72 h and 240 h in a switchyard area, using animals exposed to 60 Hz and 2.0 mT EMFs or treated with 5 mg/kg mitomycin C (MMC) as positive controls. Micronucleus (MN) frequency and male germ cell analyses were used as cytological endpoints. ELF-EMF exposure was observed to significantly (p < 0.05) increase MN frequency at all conditions tested, with the 2 mT/72 h treatment causing the highest response, as compared with untreated control. In addition, increased sperm counts were observed after switchyard area ELF-EMF exposure, as compared with untreated control. In contrast, low sperm counts were obtained for 72 h/2.0 mT-exposed animals and for MMC-treated mice (p < 0.05), without altering male germ cell morphological characteristics

Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease : Results from the MOPEAD project

The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis. Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care-based protocol for early detection of cognitive decline (PC), and (4) a tertiary care-based pre-screening at diabetologist clinics (DC). A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC). These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD

Actualidad y prospectiva de la investigación científica en el Centro Universitario Amecameca de la Universidad Autónoma del Estado de México

Con responsabilidad, se organizó un programa cuya finalidad fuera publicitar con transparencia dichos avances, a través de un esfuerzo de rendición de cuentas a la comunidad inmediata, la universitaria, y a la comunidad abierta, la sociedad que la principal referencia para tal efecto. El programa se concretiza a través del presente libro, conformado con una inspiración de investigación multidisciplinaria; sin embargo, para llegar a tal fin, el reto es realizar el proceso de búsqueda y generación de conocimiento transitando hacia la colaboración de los cuerpos académicos, que puedan construir nuevos conocimientos fortalecidos por la convergencia de diferentes campos del saber. En consecuencia, la primera etapa de esta estrategia es la publicidad de los trabajos investigativos ejercidos, para hacer un balance al día, pero también proyectar el futuro de cada campo y área del conocimiento. La organización explicativa está organizada por tres bloques representativos del quehacer en la generación de conocimiento del Centro Universitario, un primer bloque centra el interés en las humanidades, educación y sustentabilidad; el segundo bloque lo integra la reflexión científica sobre la construcción democrática, derechos humanos y equidad de género; en el tercer segmento se destina a la seguridad alimentaria, salud pública y sistemas agropecuarios. La actualidad de la investigación eleva la producción lograda y lo que en el momento se encuentra en construcción y los alcances que produce para la docencia, la investigación misma, y para la sociedad en general. La prospectiva es un área que todos los capítulos desarrollan con el propósito de delinear los alcances innovadores por andar en teoría, metodología e incluso en los saberes mismo

SIRT1/2 orchestrate acquisition of DNA methylation and loss of histone H3 activating marks to prevent premature activation of inflammatory genes in macrophages

Altres ajuts: CERCA Programme/Generalitat de Catalunya; [...].Sirtuins 1 and 2 (SIRT1/2) are two NAD-dependent deacetylases with major roles in inflammation. In addition to deacetylating histones and other proteins, SIRT1/2-mediated regulation is coupled with other epigenetic enzymes. Here, we investigate the links between SIRT1/2 activity and DNA methylation in macrophage differentiation due to their relevance in myeloid cells. SIRT1/2 display drastic upregulation during macrophage differentiation and their inhibition impacts the expression of many inflammation-related genes. In this context, SIRT1/2 inhibition abrogates DNA methylation gains, but does not affect demethylation. Inhibition of hypermethylation occurs at many inflammatory loci, which results in more drastic upregulation of their expression upon macrophage polarization following bacterial lipopolysaccharide (LPS) challenge. SIRT1/2-mediated gains of methylation concur with decreases in activating histone marks, and their inhibition revert these histone marks to resemble an open chromatin. Remarkably, specific inhibition of DNA methyltransferases is sufficient to upregulate inflammatory genes that are maintained in a silent state by SIRT1/2. Both SIRT1 and SIRT2 directly interact with DNMT3B, and their binding to proinflammatory genes is lost upon exposure to LPS or through pharmacological inhibition of their activity. In all, we describe a novel role for SIRT1/2 to restrict premature activation of proinflammatory genes

General practitioners' attitude toward early and pre-dementia diagnosis of AD in five European countries-A MOPEAD project survey

Introduction General practitioners (GPs) play a key role in early identification of dementia, yet diagnosis is often missed or delayed in primary care. As part of the multinational Models of Patient Engagement for Alzheimer's Disease project, we assess GPs' attitude toward early and pre-dementia diagnosis of AD and explore barriers to early diagnosis. Methods Our survey covered general attitude toward early diagnosis, diagnostic procedures, resources, and opinion on present and future treatment options across five European countries. Results In total 343 GPs completed the survey; 74% of GPs indicated that an early diagnosis is valuable. There were country-specific differences in GPs' perceptions of reimbursement and time available for the patient. If a drug were available to slow down the progression of AD, 59% of the GPs would change their implementation of early diagnosis. Discussion Our findings provide insight into GPs' attitudes by exploring differences in perception and management of early diagnosis

Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease : Results from the MOPEAD project

Introduction: The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis. Methods: Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care–based protocol for early detection of cognitive decline (PC), and (4) a tertiary care–based pre-screening at diabetologist clinics (DC). Results: A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC). Conclusion: These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD

Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease: Results from the MOPEAD project

Introduction: The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis. Methods: Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care–based protocol for early detection of cognitive decline (PC), and (4) a tertiary care–based pre-screening at diabetologist clinics (DC). Results: A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC). Conclusion: These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD