Variant histone H3.3 is incorporated into nucleosomes by a mechanism that does not require DNA replication and has also been implicated as a potential mediator of epigenetic memory of active transcriptional states. In this study, we have used chromatin immunoprecipitation analysis to show that H3.3 is found mainly at the promoters of transcriptionally active genes. We also show that H3.3 combines with H3 acetylation and K4 methylation to form a stable mark that persists during mitosis. Our results suggest that H3.3 is deposited principally through the action of chromatin-remodelling complexes associated with transcriptional initiation, with deposition mediated by RNA polymerase II elongation having only a minor role.

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BackgroundEarly screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM.Methods and FindingsWe conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge's g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37).ConclusionsOur systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients.

The development of new materials that mimic cartilage and its function is an unmet need that will allow replacing the damaged parts of the joints, instead of the whole joint. Polyvinyl alcohol (PVA) hydrogels have raised special interest for this application due to their biocompatibility, high swelling capacity and chemical stability. In this work, the effect of post-processing treatments (annealing, high hydrostatic pressure (HHP) and gamma-radiation) on the performance of PVA gels obtained by cast-drying was investigated and, their ability to be used as delivery vehicles of the anti-inflammatories diclofenac or ketorolac was evaluated. HHP damaged the hydrogels, breaking some bonds in the polymeric matrix, and therefore led to poor mechanical and tribological properties. The remaining treatments, in general, improved the performance of the materials, increasing their crystallinity. Annealing at 150 °C generated the best mechanical and tribological results: higher resistance to compressive and tensile loads, lower friction coefficients and ability to support higher loads in sliding movement. This material was loaded with the anti-inflammatories, both without and with vitamin E (Vit.E) or Vit.E + cetalkonium chloride (CKC). Vit.E + CKC helped to control the release of the drugs which occurred in 24 h. The material did not induce irritability or cytotoxicity and, therefore, shows high potential to be used in cartilage replacement with a therapeutic effect in the immediate postoperative period.

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