The validity of an updated metabolic power algorithm based upon Di Prampero’s theoretical model in Elite soccer players

The aim of this study was to update the metabolic power (MP) algorithm (P.VO2, W·kg−1) related to the kinematics data (PGPS, W·kg−1) in a soccer-specific performance model. For this aim, seventeen professional (Serie A) male soccer players (.VO2max 55.7 ± 3.4 mL·min−1·kg−1) performed a 6 min run at 10.29 km·h−1 to determine linear-running energy cost (Cr). On a separate day, thirteen also performed an 8 min soccer-specific intermittent exercise protocol. For both procedures, a portable Cosmed K4b2 gas-analyzer and GPS (10 Hz) was used to assess the energy cost above resting (C). From this aim, the MP was estimated through a newly derived C equation (PGPSn) and compared with both the commonly used (PGPSo) equation and direct measurement (P.VO2). Both PGPSn and PGPSo correlated with P.VO2 (r = 0.66, p < 0.05). Estimates of fixed bias were negligible (PGPSn = −0.80 W·kg−1 and PGPSo = −1.59 W·kg−1), and the bounds of the 95% CIs show that they were not statistically significant from 0. Proportional bias estimates were negligible (absolute differences from one being 0.03 W·kg−1 for PGPSn and 0.01 W·kg−1 for PGPSo) and not statistically significant as both 95% CIs span 1. All variables were distributed around the line of unity and resulted in an under-or overestimation of PGPSn, while PGPSo routinely underestimated MP across ranges. Repeated-measures ANOVA showed differences over MP conditions (F1,38 = 16.929 and p < 0.001). Following Bonferroni post hoc test significant differences regarding the MP between PGPSo and P.VO2 /PGPSn (p < 0.001) were established, while no differences were found between P.VO2 and PGPSn (p = 0.853). The new approach showed it can help the coaches and the soccer trainers to better monitor external training load during the training seasons.© 2020 by the authors. Licensee MDPI, Basel, Switzerland

Aryloxymaleimides for cysteine modification, disulfide bridging and the dual functionalization of disulfide bonds

Tuning the properties of maleimide reagents holds significant promise in expanding the toolbox of available methods for bioconjugation. Herein we describe aryloxymaleimides which represent 'next generation maleimides' of attenuated reactivity, and demonstrate their ability to enable new methods for protein modification at disulfide bonds

Breakdown of Fermi-liquid theory in a cuprate superconductor

The behaviour of electrons in solids is remarkably well described by Landau's Fermi-liquid theory, which says that even though electrons in a metal interact they can still be treated as well-defined fermions, called ``quasiparticles''. At low temperature, the ability of quasiparticles to transport heat is strictly given by their ability to transport charge, via a universal relation known as the Wiedemann-Franz law, which no material in nature has been known to violate. High-temperature superconductors have long been thought to fall outside the realm of Fermi-liquid theory, as suggested by several anomalous properties, but this has yet to be shown conclusively. Here we report on the first experimental test of the Wiedemann-Franz law in a cuprate superconductor, (Pr,Ce)$_2$CuO$_4$. Our study reveals a clear departure from the universal law and provides compelling evidence for the breakdown of Fermi-liquid theory in high-temperature superconductors.Comment: 7 pages, 3 figure

Knowledge based identification of essential signaling from genome-scale siRNA experiments

<p>Abstract</p> <p>Background</p> <p>A systems biology interpretation of genome-scale RNA interference (RNAi) experiments is complicated by scope, experimental variability and network signaling robustness. Over representation approaches (ORA), such as the Hypergeometric or z-score, are an established statistical framework used to associate RNA interference effectors to biologically annotated gene sets or pathways. These methods, however, do not directly take advantage of our growing understanding of the interactome. Furthermore, these methods can miss partial pathway activation and may be biased by protein complexes. Here we present a novel ORA, protein interaction permutation analysis (PIPA), that takes advantage of canonical pathways and established protein interactions to identify pathways enriched for protein interactions connecting RNAi hits.</p> <p>Results</p> <p>We use PIPA to analyze genome-scale siRNA cell growth screens performed in HeLa and TOV cell lines. First we show that interacting gene pair siRNA hits are more reproducible than single gene hits. Using protein interactions, PIPA identifies enriched pathways not found using the standard Hypergeometric analysis including the FAK <it>cytoskeletal remodeling pathway</it>. Different branches of the <it>FAK </it>pathway are distinctly essential in HeLa versus TOV cell lines while other portions are uneffected by siRNA perturbations. Enriched hits belong to protein interactions associated with cell cycle regulation, anti-apoptosis, and signal transduction.</p> <p>Conclusion</p> <p>PIPA provides an analytical framework to interpret siRNA screen data by merging biologically annotated gene sets with the human interactome. As a result we identify pathways and signaling hypotheses that are statistically enriched to effect cell growth in human cell lines. This method provides a complementary approach to standard gene set enrichment that utilizes the additional knowledge of specific interactions within biological gene sets. </p

The regulation of monoamine oxidase: a gene expression by distinct variable number tandem repeats

The monoamine oxidase A (MAOA) uVNTR (upstream variable number tandem repeat) is one of the most often cited examples of a gene by environment interaction (GxE) in relation to behavioral traits. However, MAOA possesses a second VNTR, 500 bp upstream of the uVNTR, which is termed d- or distal VNTR. Furthermore, genomic analysis indicates that there are a minimum of two transcriptional start sites (TSSs) for MAOA, one of which encompasses the uVNTR within the 5′ untranslated region of one of the isoforms. Through expression analysis in semi-haploid HAP1 cell lines genetically engineered in order to knockout (KO) either the uVNTR, dVNTR, or both VNTRs, we assessed the effect of the two MAOA VNTRs, either alone or in combination, on gene expression directed from the different TSSs. Complementing our functional analysis, we determined the haplotype variation of these VNTRs in the general population. The expression of the two MAOA isoforms was differentially modulated by the two VNTRs located in the promoter region. The most extensively studied uVNTR, previously considered a positive regulator of the MAOA gene, did not modulate the expression of what it is considered the canonical isoform, while we found that the dVNTR positively regulated this isoform in our model. In contrast, both the uVNTR and the dVNTR were found to act as negative regulators of the second less abundant MAOA isoform. The haplotype analysis for these two VNTRs demonstrated a bias against the presence of one of the potential variants. The uVNTR and dVNTR differentially affect expression of distinct MAOA isoforms, and thus, their combined profiling offers new insights into gene-regulation, GxE interaction, and ultimately MAOA-driven behavior

A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways.</p> <p>Methods</p> <p>We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene <it>FANCM </it>(ORs 1.9-2.0, <it>P </it>= 0.003-0.004) and 2 SNPs downstream of the growth hormone gene <it>GH1 </it>(OR 1.6, <it>P </it>= 0.002; OR 0.5, <it>P </it>= 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: <it>MDM2</it>, <it>MPG</it>, <it>FGF2</it>, <it>FGFR3</it>, <it>GNRH2</it>, and <it>IGF1</it>.</p> <p>Conclusions</p> <p>Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings.</p