Intercalation of small molecules into DNA in chromatin is primarily controlled by superhelical constraint

The restricted access of regulatory factors to their binding sites on DNA wrapped around the nucleosomes is generally interpreted in terms of molecular shielding exerted by nucleosomal structure and internucleosomal interactions. Binding of proteins to DNA often includes intercalation of hydrophobic amino acids into the DNA. To assess the role of constrained superhelicity in limiting these interactions, we studied the binding of small molecule intercalators to chromatin in close to native conditions by laser scanning cytometry. We demonstrate that the nucleosome-constrained superhelical configuration of DNA is the main barrier to intercalation. As a result, intercalating compounds are virtually excluded from the nucleosome-occupied regions of the chromatin. Binding of intercalators to extranucleosomal regions is limited to a smaller degree, in line with the existence of net supercoiling in the regions comprising linker and nucleosome free DNA. Its relaxation by inducing as few as a single nick per ~50 kb increases intercalation in the entire chromatin loop, demonstrating the possibility for long-distance effects of regulatory potential

Quantification of training load distribution in mixed martial arts athletes: A lack of periodisation and load management.

The aim of this study was to quantify typical training load and periodisation practices of MMA athletes. MMA competitors (n = 14; age = 22.4 ± 4.4 years; body mass = 71.3 ± 7.7 kg; stature = 171 ±9.9 cm) were observed during training for 8 consecutive weeks without intervention. Seven athletes were training for competitive bouts whilst the remaining 7 were not. Daily training duration, intensity (RPE), load (sRPE and segRPE), fatigue (short questionnaire of fatigue) and body region soreness (CR10 scale) were recorded. Using Bayesian analyses (BF10≥3), data demonstrate that training duration (weekly mean range = 3.9-5.3 hours), sRPE (weekly mean range = 1,287-1,791 AU), strain (weekly mean range = 1,143-1,819 AU), monotony (weekly mean range = 0.63-0.83 AU), fatigue (weekly mean range = 16-20 AU) and soreness did not change within or between weeks. Between weeks monotony (2.3 ± 0.7 AU) supported little variance in weekly training load. There were no differences in any variable between participants who competed and those who did not with the except of the final week before the bout, where an abrupt step taper occurred leading to no between group differences in fatigue. Training intensity distribution corresponding to high, moderate and low was 20, 33 and 47%, respectively. Striking drills accounted for the largest portion of weekly training time (20-32%), with MMA sparring the least (2-7%). Only striking sparring and wrestling sparring displayed statistical weekly differences in duration or load. Athletes reported MMA sparring and wrestling sparring as high intensity (RPE≥7), BJJ sparring, striking sparring and wrestling drills as moderate intensity (RPE 5-6), and striking drills and BJJ drills as low intensity (RPE≤4). We conclude that periodisation of training load was largely absent in this cohort of MMA athletes, as is the case within and between weekly microcycles

Maternal vitamin D status during pregnancy: the Mediterranean reality

Vitamin D status during pregnancy is linked to bone mineralization of developing fetus, which justifies targeting sufficient levels of vitamin D in pregnant women. Despite high level of sunshine in the Mediterranean regions, maternal hypovitaminosis D remain common in these countries. The aim of this narrative review was to provide potential explanations for this phenomenon in an effort to guide future public health policies and vitamin D intakes during pregnancy. We searched Medline for publications regarding hypovitaminosis D during pregnancy in the Mediterranean region. Available studies confirmed the high prevalence of hypovitaminosis D among pregnant women in the Mediterranean regions (50-65% in most studies), resulting in severe skeletal and nonskeletal health events among the offspring. Reasons for this may rely on maternal darker skin pigmentation, poor dietary vitamin D intake, veiled clothing and reduced sunshine exposure, health policies and increased prevalence of obesity. Public health organizations should be aware of this phenomenon and develop specific policies to prevent hypovitaminosis D and its adverse outcomes in maternal and neonatal health