Correlates to Performance on Field Tests of Muscular Strength

Field tests of upper body muscular strength and endurance (UBMSE) are often administered to children, but little is known about the determinants of performance on these tests. Therefore the purpose of this investigation was to examine potential determinants of performance on several common field tests of UBMSE including pull-ups, flexed-arm hang, push-ups, and two types of modified pull-ups. Subjects were 56 girls, and 38 boys, ages 9 to 11 years. Potential determinants assessed were age, height, weight, gender, % fat, physical activity, and laboratory measures of muscular strength and endurance. Multiple regression analysis revealed that the laboratory measures of UBMSE failed to account for significant fractions of variance in performance on four of the five tests. However, % fat was significantly associated with performance on four of five tests. These results indicate that factors other than muscular strength and endurance account for most of the variance in performance, and that % fat appears to be a particularly important determinant of performance

Moduli Stabilisation and de Sitter String Vacua from Magnetised D7 Branes

Anomalous U(1)'s are ubiquitous in 4D chiral string models. Their presence crucially affects the process of moduli stabilisation and cannot be neglected in realistic set-ups. Their net effect in the 4D effective action is to induce a matter field dependence in the non-perturbative superpotential and a Fayet-Iliopoulos D-term. We study flux compactifications of IIB string theory in the presence of magnetised D7 branes. These give rise to anomalous U(1)'s that modify the standard moduli stabilisation procedure. We consider simple orientifold models to determine the matter field spectrum and the form of the effective field theory. We apply our results to one-modulus KKLT and multi-moduli large volume scenarios, in particular to the Calabi-Yau P^4_{[1,1,1,6,9]}. After stabilising the matter fields, the effective action for the Kahler moduli can acquire an extra positive term that can be used for de Sitter lifting with non-vanishing F- and D-terms. This provides an explicit realization of the D-term lifting proposal of hep-th/0309187.Comment: 35 pages, 1 figure. v2: Minor changes, references adde

Guidelines for performing Mendelian randomization investigations

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into nine sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust methods and one on other approaches), data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 18 months

Guidelines for performing Mendelian randomization investigations: update for summer 2023 [version 3; peer review: 2 approved]

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into ten sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust statistical methods and one on other approaches), extensions and additional analyses, data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 24 months

Arsenic Exposure Is Associated with Decreased DNA Repair in Vitro and in Individuals Exposed to Drinking Water Arsenic

The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined the effects of As on DNA repair in a cultured human cell model. Arsenic exposure was associated with decreased expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In addition, lymphocytes from As-exposed individuals showed higher levels of DNA damage, as measured by a comet assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell culture. These data provide further evidence to support the ability of As to inhibit the DNA repair machinery, which is likely to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action

A fragment-based approach to assess the ligandability of ArgB, ArgC, ArgD and ArgF in the L-arginine biosynthetic pathway of Mycobacterium tuberculosis.

The L-arginine biosynthesis pathway consists of eight enzymes that catalyse the conversion of L-glutamate to L-arginine. Arginine auxotrophs (argB/argF deletion mutants) of Mycobacterium tuberculosis are rapidly sterilised in mice, while inhibition of ArgJ with Pranlukast was found to clear chronic M. tuberculosis infection in a mouse model. Enzymes in the arginine biosynthetic pathway have therefore emerged as promising targets for anti-tuberculosis drug discovery. In this work, the ligandability of four enzymes of the pathway ArgB, ArgC, ArgD and ArgF is assessed using a fragment-based approach. We identify several hits against these enzymes validated with biochemical and biophysical assays, as well as X-ray crystallographic data, which in the case of ArgB were further confirmed to have on-target activity against M. tuberculosis. These results demonstrate the potential for more enzymes in this pathway to be targeted with dedicated drug discovery programmes

Research Ethics Recommendations for Whole-Genome Research: Consensus Statement

Interest in whole-genome research has grown substantially over the past few months. This article explores the challenging ethics issues associated with this work

Capacitating Community: The Writing Innovation Symposium

The topic of this symposium, capacitating community, invites CLJ readers to consider what makes community possible. This piece showcases one means, small conferences, via a retrospective on the Writing Innovation Symposium (WIS), a regional event with national scope that has hosted writers and writing educators annually in Milwaukee, WI, since 2018. Through a quilted conversation pieced from hours of small-group discussion, twenty-nine participants across academic and nonacademic ranks, roles, and ranges of experience offer insight into the WIS as well as the nature and value of professional community