Androgen Receptor Function Links Human Sexual Dimorphism to DNA Methylation

Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming. We aimed at investigating whether inactivation of the androgen receptor, the key regulator of normal male sex development, is associated with differences of the patterns of DNA methylation marks in genital tissues. To this end, we performed large scale array-based analysis of gene methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males and 26 individuals with androgen insensitivity syndrome (AIS) due to inactivating androgen receptor gene mutations. By this approach we identified differential methylation of 167 CpG loci representing 162 unique human genes. These were significantly enriched for androgen target genes and low CpG content promoter genes. Additional 75 genes showed a significant increase of heterogeneity of methylation in AIS compared to a high homogeneity in normal male controls. Our data show that normal and aber

The role of epigenetics in renal ageing

An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects

Measurement of the associated γ+μ^± production cross section in pp̄ collisions at √s=1.8 TeV

Abstract The cross-section of associated J/ψ-ψ(2S) production in proton-proton collisions at a centre-of-mass energy of $$\sqrt{s}$$ s = 13 TeV is measured using a data sample corresponding to an integrated luminosity of 4.2 fb−1, collected by the LHCb experiment. The measurement is performed for both J/ψ and ψ(2S) mesons having transverse momentum pT&lt; 14 GeV/c and rapidity 2.0 &lt; y &lt; 4.5, assuming negligible polarisation of the J/ψ and ψ(2S) mesons. The production cross-section is measured to be 4.5 ± 0.7 ± 0.3 nb, where the first uncertainty is statistical and the second systematic. The differential cross-sections are measured as functions of several kinematic variables of the J/ψ-ψ(2S) candidates. The results are combined with a measurement of J/ψ-J/ψ production, giving a cross-section ratio between J/ψ-ψ(2S) and J/ψ-J/ψ production of 0.274 ± 0.044 ± 0.008, where the first uncertainty is statistical and the second systematic.</jats:p