Utility of international normative 20 m shuttle run values for identifying youth at increased cardiometabolic risk

The purpose of this study was to examine the ability of international normative centiles for the 20 m shuttle run test (20mSRT) to identify youth at increased cardiometabolic risk. This was a cross-sectional study involving 961 children aged 10–17 years (53% girls) from the United Kingdom. Receiver operating characteristic (ROC) curves determined the discriminatory ability of cardiorespiratory fitness percentiles for predicting increased cardiometabolic risk. ROC analysis demonstrated a significant but poor discriminatory accuracy of cardiorespiratory fitness in identifying low/high cardiometabolic risk in girls (AUC = 0.58, 95% CI: 0.54–0.63; p = 0.04), and in boys (AUC = 0.59, 95% CI: 0.54–0.63; p = 0.03). The cardiorespiratory fitness cut-off associated with high cardiometabolic risk was the 55th percentile (sensitivity = 33.3%; specificity = 84.5%) in girls and the 60th percentile (sensitivity = 42.9%; specificity = 73.6%) in boys. These 20mSRT percentile thresholds can be used to identify children and adolescents who may benefit from lifestyle intervention. Nonetheless, further work involving different populations and cardiometabolic risk scores comprising of different variables are needed to confirm our initial findings

Drug–excipient interactions in ketoprofen: A vibrational spectroscopy study

Ketoprofen (3-benzoyl-alpha-methylbenzeneacetic acid) is a widely used nonsteroidal anti-inflammatory drug (NSAID), always administered in the form of drug-excipient physical mixtures (PMs). The occurrence of possible interactions between ketoprofen and two commonly used excipients-lactose (LAC) and polyvinylpyrrolidone (PVP)-was evaluated, through vibrational spectroscopy techniques [both Raman and Inelastic Neutron Scattering (INS)]. Spectral evidence of drug:excipient close contacts, which were enhanced by aging, was verified for the (1:1) (w:w) (ketoprofen:PVP) and (ketoprofen:LAC) PMs, both by Raman and INS. These interactions were found to involve mainly the central carbonyl and the terminal methyl-carboxylic moieties of the ketoprofen molecule, this being reflected in particular vibrational modes, such as the methyl torsion, the out-of-plane C-OH bending, and the inter-ring C=O stretching

Digit ratio (2D:4D) and muscular strength in adolescent boys

Using a cross-sectional design, this study quantified the relationship between the digit ratio (2D:4D) and muscular strength in 57 adolescent boys. 2D:4D was very likely a moderate negative correlate of handgrip strength, even after adjustment for age and body size. This result may reflect the organizational benefits of prenatal testosterone

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

Label-free electrochemical monitoring of DNA ligase activity

This study presents a simple, label-free electrochemical technique for the monitoring of DNA ligase activity. DNA ligases are enzymes that catalyze joining of breaks in the backbone of DNA and are of significant scientific interest due to their essential nature in DNA metabolism and their importance to a range of molecular biological methodologies. The electrochemical behavior of DNA at mercury and some amalgam electrodes is strongly influenced by its backbone structure, allowing a perfect discrimination between DNA molecules containing or lacking free ends. This variation in electrochemical behavior has been utilized previously for a sensitive detection of DNA damage involving the sugar-phosphate backbone breakage. Here we show that the same principle can be utilized for monitoring of a reverse process, i.e., the repair of strand breaks by action of the DNA ligases. We demonstrate applications of the electrochemical technique for a distinction between ligatable and unligatable breaks in plasmid DNA using T4 DNA ligase, as well as for studies of the DNA backbone-joining activity in recombinant fragments of E. coli DNA ligase

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