Arene oxidation with malonoyl peroxides

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed

Six-year changes in body mass index and cardiorespiratory fitness of English schoolchildren from an affluent area

We compared values of body mass index (BMI) and cardiorespiratory fitness (20 m shuttle-run test) of n=157 boys and n=150 girls aged 10-11 measured in 2014 with measures from 2008 and 1998. Boys' fitness was lower (d=0.68) in 2014 than 2008, despite a small (d=0.37) decline in BMI. Girl's BMI changed trivially (d=0.08) but cardiorespiratory fitness was lower (d=0.47) in 2014 than 2008. This study suggests fitness is declining at 0.95% per year, which exceeds the 0.8% rate of decline we reported between 1998 and 2008 and is double the global average of 0.43%. Declines in fitness were independent of changes in BMI suggesting continued reductions in English children's habitual physical activity levels

No effect of a whey growth factor extract during resistance training on strength, body composition, or hypertrophic gene expression in resistance-trained young men

Published (online): 01 June 2017Growth factors can be isolated from bovine milk to form a whey growth factor extract (WGFE). This study examined whether WGFE promoted activation of the AKT/mTOR pathway enabling increased lean tissue mass and strength in resistance trained men. Forty six men with >6 months of resistance training (RT) experience performed 12 weeks of RT. Participants consumed 20 g/day of whey protein and were randomised to receive either 1.6 g WGFE/day (WGFE; n = 22) or 1.6 g cellulose/day (control, CONT; n = 24). The primary outcome was leg press one-repetition maximum (LP1-RM) which was assessed at baseline, 6 and 12 weeks. At baseline and 12 weeks body composition was assessed by dual energy x-ray absorptiometry, and muscle protein synthesis and gene expression were assessed (vastus lateralis biopsy) in a sub-sample (WGFE n = 10, CONT n = 10) pre- and 3 hr post-training. RT increased LP1-RM (+34.9%) and lean tissue mass (+2.3%; p 0.48, treatment x time). Post-exercise P70s6k phosphorylation increased acutely, FOXO3a phosphorylation was unaltered. There were no differences in kinase signalling or gene expression between treatments. Compared with CONT, WGFE did not result in greater increases in lean tissue mass or strength in experienced resistance trained men.Michael J. Dale, Alison M. Coates, Peter R.C. Howe, Grant R. Tomkinson, Matthew T. Haren, Andrew Brown, Marissa Caldow, David Cameron-Smith, Jonathan D. Buckle

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Socio-cultural determinants of adiposity and physical activity in preschool children: A cross-sectional study

BACKGROUND: Both individual socio-cultural determinants such as selected parental characteristics (migrant background, low educational level and workload) as well as the regional environment are related to childhood overweight and physical activity (PA). The purpose of the study was to compare the impact of distinct socio-cultural determinants such as the regional environment and selected parental characteristics on adiposity, PA and motor skills in preschool children. METHODS: Forty preschools (N = 542 children) of two culturally different urban regions (German and French speaking part of Switzerland) participated in the study (Ballabeina Study). Outcome measures included adiposity (BMI and skinfold thickness), objectively measured sedentary activities and PA (accelerometers) and agility performance (obstacle course). Parental characteristics (migrant status, educational level and workload) were assessed by questionnaire. RESULTS: Children from the French speaking areas had higher adiposity, lower levels of total and of more intense PA, were more sedentary and less agile than children from the German speaking regions (percent differences for all outcome parameters except for BMI ≥10%; all p ≤ 0.04). Differences in skinfold thickness, sedentary activities and agility, but not in PA, were also found between children of Swiss and migrant parents, though they were ≤8% (p ≤ 0.02). While paternal workload had no effect, maternal workload and parental education resulted in differences in some PA measures and/or agility performance (percent differences in both: ≤9%, p ≤ 0.008), but not in adiposity or sedentary activities (p = NS). Regional differences in skinfold thickness, PA, sedentary activities and agility performance persisted after adjustment for parental socio-cultural characteristics, parental BMI and, where applicable, children's skinfolds (all p ≤ 0.01). CONCLUSIONS: The regional environment, especially the broader social environment, plays a prominent role in determining adiposity, PA and motor skills of young children and should be implicated in the prevention of obesity and promotion of PA in children

Oral steroids for the resolution of otitis media with effusion (OME) in children (OSTRICH): study protocol for a randomised controlled trial

Background Otitis media with effusion (OME) is an accumulation of fluid in the middle ear affecting about 80% of children by the age of 4 years. While OME usually resolves spontaneously, it can affect speech, behaviour and development. Children with persistent hearing loss associated with OME are usually offered hearing aids or insertion of ventilation tubes through the tympanic membrane. Oral steroids may be a safe and effective treatment for OME, which could be delivered in primary care. It has the potential to benefit large numbers of children and reduce the burden of care on them and on health services. However, previous trials have either been too small with too short a follow up period, or of too poor quality to give a definite answer. The aim of the OSTRICH trial is to determine if a short course of oral steroids improves the hearing of children with OME in the short and longer term. Methods/Design 380 participants (children aged 2-8 years) are recruited from Hospital Ear, Nose and Throat departments in Wales and England. A trained clinician seeks informed consent from parents of children with symptoms attributable to OME for at least 3 months and with confirmed bilateral hearing loss at study entry. Participants are randomised to a course of oral steroid or a matched placebo for one week. Outcomes include audiometry, tympanometry and otoscopy assessments, symptoms, adverse effects, functional health status, quality of life, resource use and cost effectiveness. Participants are followed up at 5 weeks, and at 6 and 12 months after the day of randomisation. The primary outcome is audiometry-confirmed satisfactory hearing at 5 weeks. Discussion There is an important evidence gap regarding clinical and cost effectiveness of short courses of oral steroid treatment for OME. Identifying an effective, safe, non-surgical intervention for OME in children for use in primary care would be of great benefit to children, their families and the NHS

IFN-γ, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13

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