5-methylcytosine turnover: Mechanisms and therapeutic implications in cancer.

DNA methylation at the fifth position of cytosine (5mC) is one of the most studied epigenetic mechanisms essential for the control of gene expression and for many other biological processes including genomic imprinting, X chromosome inactivation and genome stability. Over the last years, accumulating evidence suggest that DNA methylation is a highly dynamic mechanism driven by a balance between methylation by DNMTs and TET-mediated demethylation processes. However, one of the main challenges is to understand the dynamics underlying steady state DNA methylation levels. In this review article, we give an overview of the latest advances highlighting DNA methylation as a dynamic cycling process with a continuous turnover of cytosine modifications. We describe the cooperative actions of DNMT and TET enzymes which combine with many additional parameters including chromatin environment and protein partners to govern 5mC turnover. We also discuss how mathematical models can be used to address variable methylation levels during development and explain cell-type epigenetic heterogeneity locally but also at the genome scale. Finally, we review the therapeutic implications of these discoveries with the use of both epigenetic clocks as predictors and the development of epidrugs that target the DNA methylation/demethylation machinery. Together, these discoveries unveil with unprecedented detail how dynamic is DNA methylation during development, underlying the establishment of heterogeneous DNA methylation landscapes which could be altered in aging, diseases and cancer.

TET2-mediated epigenetic reprogramming of breast cancer cells impairs lysosome biogenesis.

Methylation and demethylation of cytosines in DNA are believed to act as keystones of cell-specific gene expression by controlling the chromatin structure and accessibility to transcription factors. Cancer cells have their own transcriptional programs, and we sought to alter such a cancer-specific program by enforcing expression of the catalytic domain (CD) of the methylcytosine dioxygenase TET2 in breast cancer cells. The TET2 CD decreased the tumorigenic potential of cancer cells through both activation and repression of a repertoire of genes that, interestingly, differed in part from the one observed upon treatment with the hypomethylating agent decitabine. In addition to promoting the establishment of an antiviral state, TET2 activated 5mC turnover at thousands of MYC-binding motifs and down-regulated a panel of known MYC-repressed genes involved in lysosome biogenesis and function. Thus, an extensive cross-talk between TET2 and the oncogenic transcription factor MYC establishes a lysosomal storage disease-like state that contributes to an exacerbated sensitivity to autophagy inducers.

Lower limb venous and arterial peripheral diseases and work conditions: systematic review.

OBJECTIVES: The individual peripheral vascular disease risk factors are well documented, but the role of work conditions remains equivocal. This systematic review aims to assess relationships between lower limb peripheral venous diseases (lower limb varicose veins (LLVV), venous thromboembolism (VTE) comprising deep vein thrombosis and pulmonary embolism), peripheral arterial disease (intermittent claudication, aortic dissection, aortic aneurysm) and occupational constraints among working adults. METHODS: Several databases were systematically searched until February 2019 for observational studies and clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was used for article selection. Quality assessment and risk of bias were evaluated using Strengthening the Reporting of Observational Studies in Epidemiology and Newcastle-Ottawa scales. RESULTS: Among the 720 screened articles, 37 remained after full-text evaluation. Among the 21 studies on LLVV, prolonged standing was significantly associated to a higher risk of varicose veins with a threshold probably around >3 to 4 hours/day but exposure duration in years was not sufficiently considered. Seated immobility was often observed in workers, with no sufficient evidence to prove that prolonged sitting at work is related to VTE. Carrying heavy loads, stress at work and exposure to high temperatures have emerged more recently notably in relation to varicose veins but need to be better explored. Only three studies discussed the potential role of work on peripheral arterial disease development. CONCLUSIONS: Although some observational studies showed that prolonged standing can be related to varicose veins and that seated immobility at work could be linked to VTE, very little is known about peripheral arterial disease and occupational constraints. Clinical trials to determine preventive strategies at work are needed. PROSPERO REGISTRATION NUMBER: CRD42019127652.

Biohydrogen production from used diapers: Evaluation of effect of temperature and substrate conditioning.

This research assessed the viability to use disposable diapers as a substrate for the production of biohydrogen, a valuable clean-energy source. The important content of cellulose of disposable diapers indicates that this waste could be an attractive substrate for biofuel production. Two incubation temperatures (35 °C and 55 °C) and three diaper conditioning methods (whole diapers with faeces, urine, and plastics, WD; diapers without plastic components, with urine and faeces, DWP; diapers with urine but without faeces and plastic, MSD) were tested in batch bioreactors. The bioreactors were operated in the solid substrate anaerobic hydrogenogenic fermentation with intermittent venting mode (SSAHF-IV). The batch reactors were loaded with the substrate at ca. 25% of total solids and 10% w/w inoculum. The average cumulative bioH2 production followed the order WD > MSD > DWP. The bio-H2 production using MSD was unexpectedly higher than DWP; the presence of plastics in the first was expected to be associated to lower degradability and H2 yield. BioH2 production at 55 °C was superior to that of 35 °C, probably owing to a more rapid microbial metabolism in the thermophilic regime. The results of this work showed low yields in the production of H2 at both temperatures compared with those reported in the literature for municipal and agricultural organic waste. The studied process could improve the ability to dispose of this residue with H2 generation as the value-added product. Research is ongoing to increase the yield of biohydrogen production from waste disposable diapers.

Disposable diapers biodegradation by the fungus Pleurotus ostreatus.

This research assesses the feasibility of degrading used disposable diapers, an important component (5-15% in weight) of urban solid waste in Mexico, by the activity of the fungus Pleurotus ostreatus, also known as oyster mushroom. Disposable diapers contain polyethylene, polypropylene and a super absorbent polymer. Nevertheless, its main component is cellulose, which degrades slowly. P. ostreatus has been utilized extensively to degrade cellulosic materials of agroindustrial sources, using in situ techniques. The practice has been extended to the commercial farming of the mushroom. This degradation capacity was assayed to reduce mass and volume of used disposable diapers. Pilot laboratory assays were performed to estimate the usefulness of the following variables on conditioning of used diapers before they act as substrate for P. ostreatus: (1) permanence vs removal of plastic cover; (2) shredding vs grinding; (3) addition of grape wastes to improve structure, nitrogen and trace elements content. Wheat straw was used as a positive control. After 68 days, decrease of the mass of diapers and productivity of fungus was measured. Weight and volume of degradable materials was reduced up to 90%. Cellulose content was diminished in 50% and lignine content in 47%. The highest efficiency for degradation of cellulosic materials corresponded to the substrates that showed highest biological efficiency, which varied from 0% to 34%. Harvested mushrooms had good appearance and protein content and were free of human disease pathogens. This research indicates that growing P. ostreatus on disposable diapers could be a good alternative for two current problems: reduction of urban solid waste and availability of high protein food sources.

Diseño, construcción e instalación de un lisimetro

Investiga la contaminación por el lixiviado de relleno sanitario y la falta de seguridad en los cálculos para el diseño y construcción de los mismos. Señala la caracterización del biogás y de los lixiviados generados en los rellenos sanitarios y determina los parámetros nacionales para su diseño. Propone instalar tres prototipos o lisimetros con las mismas características de construcción y de relleno. Este trabajo describe el diseño, construcción e instalación del primer lisimetro