Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition.

Background: Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.

Methods: In this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level.

Fracture liaison service (FLS) is associated with lower subsequent fragility fracture risk and mortality: NoFRACT (the Norwegian capture the fracture initiative).

Unlabelled: Subsequent fracture rates and associated mortality were compared before and after the introduction of fracture liaison service (FLS). In 100,198 women and men, FLS was associated with 13% and 10% lower risk of subsequent fragility fractures and 18% and 15% lower mortality. The study suggests that FLS may prevent fractures.

YeeE-like bacterial SoxT proteins mediate sulfur import for oxidation and signal transduction.

Many sulfur-oxidizing prokaryotes oxidize sulfur compounds through a combination of initial extracytoplasmic and downstream cytoplasmic reactions. Facultative sulfur oxidizers adjust transcription to sulfur availability. While sulfur-oxidizing enzymes and transcriptional repressors have been extensively studied, sulfur import into the cytoplasm and how regulators sense external sulfur are poorly understood.