RNA-sequencing muscle plasticity to resistance exercise training and disuse in youth and older age

YesMaintenance of skeletal muscle mass and function is critical to health and wellbeing throughout the lifespan. However, disuse through reduced physical activity (e.g., sedentarism), immobilisation, bed rest or microgravity has significant adverse effects on skeletal muscle health. Conversely, resistance exercise training (RET) induces positive muscle mass and strength adaptations. Several studies have employed microarray technology to understand the transcriptional basis of muscle atrophy and hypertrophy after disuse and RET, respectively, to devise fully effective therapeutic interventions. More recently, rapidly falling costs have seen RNA-sequencing (RNA-seq) increasingly applied in exploring muscle adaptations to RET and disuse. The aim of this review is to summarise the transcriptional responses to RET or disuse measured via RNA-seq in young and older adults. We also highlight analytical considerations to maximise the utility of RNA-seq in the context of skeletal muscle research. The limited number of muscle transcriptional signatures obtained thus far with RNA-seq are generally consistent with those obtained with microarrays. However, RNA-seq may provide additional molecular insight, particularly when combined with data-driven approaches such as correlation network analyses. In this context, it is essential to consider the most appropriate study design parameters as well as bioinformatic and statistical approaches. This will facilitate the use of RNA-seq to better understand the transcriptional regulators of skeletal muscle plasticity in response to increased or decreased use

Surface Roughness and Effective Stick-Slip Motion

The effect of random surface roughness on hydrodynamics of viscous incompressible liquid is discussed. Roughness-driven contributions to hydrodynamic flows, energy dissipation, and friction force are calculated in a wide range of parameters. When the hydrodynamic decay length (the viscous wave penetration depth) is larger than the size of random surface inhomogeneities, it is possible to replace a random rough surface by effective stick-slip boundary conditions on a flat surface with two constants: the stick-slip length and the renormalization of viscosity near the boundary. The stick-slip length and the renormalization coefficient are expressed explicitly via the correlation function of random surface inhomogeneities. The effective stick-slip length is always negative signifying the effective slow-down of the hydrodynamic flows by the rough surface (stick rather than slip motion). A simple hydrodynamic model is presented as an illustration of these general hydrodynamic results. The effective boundary parameters are analyzed numerically for Gaussian, power-law and exponentially decaying correlators with various indices. The maximum on the frequency dependence of the dissipation allows one to extract the correlation radius (characteristic size) of the surface inhomogeneities directly from, for example, experiments with torsional quartz oscillators.Comment: RevTeX4, 14 pages, 3 figure

The acute transcriptional response to resistance exercise: impact of age and contraction mode

Optimization of resistance exercise (RE) remains a hotbed of research for muscle building and maintenance. However, the interactions between the contractile components of RE (i.e. concentric (CON) and eccentric (ECC)) and age, are poorly defined. We used transcriptomics to compare age-related molecular responses to acute CON and ECC exercise. Eight young (21±1 y) and eight older (70±1 y) exercise-naïve male volunteers had vastus lateralis biopsies collected at baseline and 5 h post unilateral CON and contralateral ECC exercise. RNA was subjected to next-generation sequencing and differentially expressed (DE) genes tested for pathway enrichment using Gene Ontology (GO). The young transcriptional response to CON and ECC was highly similar and older adults displayed moderate contraction-specific profiles, with no GO enrichment. Age-specific responses to ECC revealed 104 DE genes unique to young, and 170 DE genes in older muscle, with no GO enrichment. Following CON, 15 DE genes were young muscle-specific, whereas older muscle uniquely expressed 147 up-regulated genes enriched for cell adhesion and blood vessel development, and 28 down-regulated genes involved in mitochondrial respiration, amino acid and lipid metabolism. Thus, older age is associated with contraction-specific regulation often without clear functional relevance, perhaps reflecting a degree of stochastic age-related dysregulation.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.CSD was funded by a doctoral training studentship from Bournemouth University. This work was generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA). RMA is generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA) and an EPSRC/BBSRC Innovation Fellowship (EP/S001352/1). We acknowledge the Medical Research Council [grant number MR/P021220/1] [grant number MR/K00414X/1] and Arthritis Research UK [grant number 19891] as part of the MRC-ARUK Centre for Musculoskeletal Ageing Research awarded to the Universities of Nottingham and Birmingham, and the National Institute for Health Research, Nottingham Biomedical Research Centre. This work was supported by the Biotechnology and Biological Sciences Research Council [grant number BB/N015894/1]. This work was supported by a grant from the Swedish Research Council for Sport Science (dnr 2016/125 and dnr 2017/143). C.R.G.W is supported by the Biotechnology and Biological Sciences Research Council-funded South West Biosciences Doctoral Training Partnership [BB/J014400/1; BB/M009122/1].Published versio

Tests of sunspot number sequences: 1. Using ionosonde data

More than 70 years ago it was recognised that ionospheric F2-layer critical frequencies [foF2] had a strong relationship to sunspot number. Using historic datasets from the Slough and Washington ionosondes, we evaluate the best statistical fits of foF2 to sunspot numbers (at each Universal Time [UT] separately) in order to search for drifts and abrupt changes in the fit residuals over Solar Cycles 17-21. This test is carried out for the original composite of the Wolf/Zürich/International sunspot number [R], the new “backbone” group sunspot number [RBB] and the proposed “corrected sunspot number” [RC]. Polynomial fits are made both with and without allowance for the white-light facular area, which has been reported as being associated with cycle-to-cycle changes in the sunspot number - foF2 relationship. Over the interval studied here, R, RBB, and RC largely differ in their allowance for the “Waldmeier discontinuity” around 1945 (the correction factor for which for R, RBB and RC is, respectively, zero, effectively over 20 %, and explicitly 11.6 %). It is shown that for Solar Cycles 18-21, all three sunspot data sequences perform well, but that the fit residuals are lowest and most uniform for RBB. We here use foF2 for those UTs for which R, RBB, and RC all give correlations exceeding 0.99 for intervals both before and after the Waldmeier discontinuity. The error introduced by the Waldmeier discontinuity causes R to underestimate the fitted values based on the foF2 data for 1932-1945 but RBB overestimates them by almost the same factor, implying that the correction for the Waldmeier discontinuity inherent in RBB is too large by a factor of two. Fit residuals are smallest and most uniform for RC and the ionospheric data support the optimum discontinuity multiplicative correction factor derived from the independent Royal Greenwich Observatory (RGO) sunspot group data for the same interval

Excessive growth hormone promotes joint degeneration and chondrocyte metabolic dysfunction in mice

YesMany patients with acromegaly, a hormonal disorder with excessive growth hormone (GH), report pain in joints. The objective of this study is to characterize the joint pathology of mice with over-expression of either bovine GH (bGH) or a GH receptor antagonist (GHa). We also investigate the effect of GH on regulation of chondrocyte cellular metabolism. Knee joints from mice over-expressing bGH or GHa and WT were histologically and μCT analyzed for OA pathologies. Additionally, cartilage from bGH mice was used for metabolomics. Mouse primary chondrocytes from WT or bGH mice with or without Pegvisomant (Peg) treatment were used for Q-PCR and Seahorse Respirometry analysis. Both male and female bGH mice at ~13 months had increased knee joint degeneration, which is characterized by loss of cartilage structure, expansion of hypertrophic chondrocytes, synovitis, and subchondral plate thinning. The joint pathologies were also demonstrated by significantly higher OARSI and Mankin scores in bGH compared with WT mice. Metabolomics revealed changes of a wide range of metabolic pathways in bGH mice including beta-alanine metabolism, tryptophan metabolism, lysine degradation, and ascorbate and aldarate metabolism. Also, bGH chondrocytes upregulated fatty acid oxidation (FAO) and increased expression of Col10a. Joints of GHa mice are remarkably protected from developing age-associated joint degeneration with smooth articular joint surface. These studies uncover that an excessive amount of GH promotes joint degeneration in mice, whereas antagonizing GH action through a GHa protects mice from OA development, which is associated with chondrocyte metabolic dysfunction and hypertrophic changes

Photoproduction of mesons off nuclei

Recent results for the photoproduction of mesons off nuclei are reviewed. These experiments have been performed for two major lines of research related to the properties of the strong interaction. The investigation of nucleon resonances requires light nuclei as targets for the extraction of the isospin composition of the electromagnetic excitations. This is done with quasi-free meson photoproduction off the bound neutron and supplemented with the measurement of coherent photoproduction reactions, serving as spin and/or isospin filters. Furthermore, photoproduction from light and heavy nuclei is a very efficient tool for the study of the interactions of mesons with nuclear matter and the in-medium properties of hadrons. Experiments are currently rapidly developing due to the combination of high quality tagged (and polarized) photon beams with state-of-the-art 4pi detectors and polarized targets

Routine omics collection is a golden opportunity for European human research in space and analog environments

Widespread generation and analysis of omics data have revolutionized molecular medicine on Earth, yet its power to yield new mechanistic insights and improve occupational health during spaceflight is still to be fully realized in humans. Nevertheless, rapid technological advancements and ever-regular spaceflight programs mean that longitudinal, standardized, and cost-effective collection of human space omics data are firmly within reach. Here, we consider the practicality and scientific return of different sampling methods and omic types in the context of human spaceflight. We also appraise ethical and legal considerations pertinent to omics data derived from European astronauts and spaceflight participants (SFPs). Ultimately, we propose that a routine omics collection program in spaceflight and analog environments presents a golden opportunity. Unlocking this bright future of artificial intelligence (AI)-driven analyses and personalized medicine approaches will require further investigation into best practices, including policy design and standardization of omics data, metadata, and sampling methods

Kiyang-yang, a West-African Postwar Idiom of Distress

In 1984, a healing cult for young barren women in southern Guinea Bissau developed into a movement, Kiyang-yang, that shook society to its foundations and had national repercussions. “Idiom of distress” is used here as a heuristic tool to understand how Kiyang-yang was able to link war and post-war-related traumatic stress and suffering on both individual and group levels. An individual experience born from a traumatic origin may be generalized into an idiom that diverse sectors of society could embrace for a range of related reasons. We argue that, for an idiom to be understood and appropriated by others, there has to be resonance at the level of symbolic language and shared experiences as well as at the level of the culturally mediated contingent emotions it communicates. We also argue that through its symbolic references to structural causes of suffering, an idiom of distress entails a danger for those in power. It can continue to exist only if its etiology is not exposed or the social suffering it articulates is not eliminated. We finally argue that idioms of distress are not to be understood as discrete diagnostic categories or as monodimensional expressions of “trauma” that can be addressed

Use of the analysis of the volatile faecal metabolome in screening for colorectal cancer

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT