Biology subjects

Bass, J. J.

Publications and source records attributed to Bass, J. J..

3 recordsLinked to original sources

bioRxiv2022

Motor unit dysregulation following 15 days of unilateral lower limb immobilisation

Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. Ten young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation with intramuscular EMG (iEMG) recorded from the vastus lateralis during knee extensor contractions normalised to maximal voluntary contraction (MVC) pre and post disuse. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in MU discharge and MU potential (MUP) characteristics. Vastus lateralis (VL) CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change in either parameter in the non-immobilised VL. Parameters of MUP size were largely reduced with immobilisation, while neuromuscular junction (NMJ) transmission instability increased, and MU firing rate decreased at several contraction levels. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU discharge rate and instability of transmission at the NMJ which may underpin the disproportionate reductions of strength relative to muscle size. Key pointsO_LIMuscle mass and function decline rapidly in situations of disuse such as bed rest and limb immobilisation. C_LIO_LIThe reduction in muscle function commonly exceeds that of muscle mass, which may be associated with the dysregulation of neural input to the muscle. C_LIO_LIWe have used intramuscular electromyography to sample individual motor unit and near fibre potentials from the vastus lateralis following 15 days of unilateral limb immobilisation. Following disuse, the disproportionate loss of muscle strength when compared to size was associated with suppressed motor unit firing rate and increased markers of neuromuscular junction transmission instability. C_LIO_LIThese central and peripheral motor unit adaptations were observed at multiple contraction levels and in the immobilised limb only. Our findings demonstrate neural dysregulation as a key component of functional loss following muscle disuse in humans. C_LI

physiology↗

bioRxiv2020

NASA GeneLab RNA-Seq Consensus Pipeline: Standardized Processing of Short-Read RNA-Seq Data

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from spaceflight-associated experiments. The pipeline includes quality control, read trimming, mapping, and gene quantification steps, culminating in the detection of differentially expressed genes. This data analysis pipeline and the results of its execution using data submitted to GeneLab are now all publicly available through the GeneLab database. We present here the full details and rationale for the construction of this pipeline in order to promote transparency, reproducibility and reusability of pipeline data, to provide a template for data processing of future spaceflight-relevant datasets, and to encourage cross-analysis of data from other databases with the data available in GeneLab.

bioinformatics↗

bioRxiv2019

The Vitamin D Receptor (VDR) Regulates Mitochondrial Function in C2C12 Myoblasts

Vitamin D deficiency has been linked to a reduction in skeletal muscle function and oxidative capacity, however, the mechanistic basis of these impairments are poorly understood. The biological actions of vitamin D are carried out via the binding of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to the vitamin D receptor (VDR). Recent evidence has linked 1,25(OH)2D3 to the regulation of skeletal muscle mitochondrial function in vitro, however, little is known with regard to the role of the VDR in this process. To examine the regulatory role of the VDR in skeletal muscle mitochondrial function, we utilised lentiviral mediated shRNA silencing of the VDR in C2C12 myoblasts (VDR-KD) and examined mitochondrial respiration and protein content compared to shRNA scrambled control. VDR protein content was reduced by ~95% in myoblasts and myotubes (P < 0.001). VDR-KD myoblasts displayed a 30%, 30% and 36% reduction in basal, coupled and maximal respiration respectively (P < 0.05). This phenotype was maintained in VDR-KD myotubes, displaying a 34%, 33% and 48% reduction in basal, coupled and maximal respiration (P < 0.05). Furthermore, ATP production derived from oxidative phosphorylation (ATPox) was reduced by 20% suggesting intrinsic impairments within the mitochondria following VDR-KD. However, despite the observed functional decrements, mitochondrial protein content as well as markers of fusion and fission were unchanged. In summary, we highlight a direct role for the VDR in regulating skeletal muscle mitochondrial respiration in vitro, providing a potential mechanism as to how vitamin D deficiency might impact upon skeletal muscle oxidative capacity.

physiology↗