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Catalytic activity of the imitation switch (ISWI) family of remodelers is critical for nucleosomal organization and DNA binding of certain transcription factors, including the insulator protein CTCF. Here we define the contribution of individual subcomplexes by deriving a panel of isogenic mouse stem cell lines, each lacking one of six ISWI accessory subunits. Individual deletions of subunits of either CERF, RSF, ACF, WICH or NoRC subcomplexes only moderately affect the chromatin landscape, while removal of the NURF-specific subunit BPTF leads to a strong reduction in chromatin accessibility and SNF2H ATPase localization around CTCF sites. This affects adjacent nucleosome occupancy and CTCF binding. At a group of sites with reduced chromatin accessibility, CTCF binding persists but cohesin occupancy is reduced, resulting in decreased insulation. These results suggest that CTCF binding can be separated from its function as an insulator in nuclear organization and identify a specific role for NURF in mediating SNF2H localization and chromatin opening at bound CTCF sites., (© 2024. The Author(s).)

Chromatin accessibility is a hallmark of regulatory regions, entails transcription factor (TF) binding and requires nucleosomal reorganization. However, it remains unclear how dynamic this process is. In the present study, we use small-molecule inhibition of the catalytic subunit of the mouse SWI/SNF remodeler complex to show that accessibility and reduced nucleosome presence at TF-binding sites rely on persistent activity of nucleosome remodelers. Within minutes of remodeler inhibition, accessibility and TF binding decrease. Although this is irrespective of TF function, we show that the activating TF OCT4 (POU5F1) exhibits a faster response than the repressive TF REST. Accessibility, nucleosome depletion and gene expression are rapidly restored on inhibitor removal, suggesting that accessible chromatin is regenerated continuously and in a largely cell-autonomous fashion. We postulate that TF binding to chromatin and remodeler-mediated nucleosomal removal do not represent a stable situation, but instead accessible chromatin reflects an average of a dynamic process under continued renewal.

Aim: The effect of a supernumerary X chromosome on bones has not been reported, and this study evaluated bone mineral status and metabolism in nonmosaic triple X syndrome., Methods: This cross-sectional study comprised 19 girls, with a median age of 10.9 years, with nonmosaic triple X syndrome and a control group matched for age and body size. We studied ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels and urinary deoxypyridinoline concentrations. We also measured the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) Z-scores., Results: Patients with nonmosaic triple X syndrome showed significantly reduced AD-SoS (p < 0.005) and BTT Z-scores (p < 0.0001) compared to the control group, and these results persisted when we divided the sample into prepubertal and pubertal patients (p < 0.05). These patients also had significantly reduced ionised calcium (p < 0.005) and 25(OH)D levels (p < 0.005) and higher phosphate (p < 0.0001) and PTH (p < 0.0001) levels., Conclusion: Subjects with nonmosaic triple X syndrome exhibited a significant impairment in bone mineral status and metabolism similar to other X polisomy, such as Klinefelter's syndrome. This suggests the presence of a primary bone deficit and the need for regular and close monitoring of these subjects., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome., Design: Cross-sectional study with retrospective analysis., Setting: University pediatric hospital., Patient(s): Fifteen prepubertal subjects (median age 9.0 years, range 6.9-11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9-11.6 years)., Intervention(s): None., Main Outcome Measure(s): We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test., Result(s): All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients., Conclusion(s): Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The authors describe a new case of infantile acute haemorrhagic oedema in a six-month-old child. Even being a vasculitis the authors do not retain to assimilate it to the Schönlein-Henoch syndrome.

The Pediatrician is daily in contact with a large number of adolescents, and therefore is able to recognize those who display behavioural problems. The Pediatrician is often asked for advice in order to solve practical problems such as the choice of school, the practice of sports, ecc. His advice is somehow conditioned by his previous experiences as an adolescent and, if he is a parent himself, by his present familial situation. In the last years, the problems of the adolescents and the fears of their parents have changed, the main concern being today the one for work, due to the high levels of unemployment and underemployment affecting our society. In this situation, some of the most frequent attitudes of parents towards adolescents seem to be erroneous, such as asking them for social success at any cost (e.g. attending unwelcome studies or performing inappropriate sports). This leads to failures that often prove to be unbearable for young people not trained to face and overcome frustration. Parents also seem often to underestimate the possibility of their own "child" being involved in episodes of hooliganism, shoplifting, violence like the ones daily described by the media. The excessive idealization of adolescents by their parents seems to be one of the main causes of this situation. The Pediatrician can intervene with advice, in order to orientate adolescents towards realistic life objectives and a satisfactory development of their personality.