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Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy (2022)
Journal Article
Ellwood, R. A., Slade, L., Lewis, J., Torregrossa, R., Sudevan, S., Piasecki, M., …Szewczyk, N. J. (2022). Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy. Communications Biology, 5(1), Article 1255. https://doi.org/10.1038/s42003-022-04212-z

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), a common muscle disease that manifests with muscle weakness, wasting, and degeneration. An emerging theme in DMD pathophysiology is an intramuscular deficit in the gasotransmit... Read More about Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy.

Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization (2022)
Journal Article
Shur, N. F., Simpson, E. J., Crossland, H., Chivaka, P. K., Constantin, D., Cordon, S. M., …Greenhaff, P. L. (2022). Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization. Journal of Cachexia, Sarcopenia and Muscle, 13(6), 2999-3013. https://doi.org/10.1002/jcsm.13075

Background: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers... Read More about Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.

Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy (2021)
Journal Article
Ellwood, R. A., Piasecki, M., & Szewczyk, N. J. (2021). Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy. International Journal of Molecular Sciences, 22(9), Article 4891. https://doi.org/10.3390/ijms22094891

The nematode worm Caenorhabditis elegans has been used extensively to enhance our understanding of the human neuromuscular disorder Duchenne Muscular Dystrophy (DMD). With new arising clinically relevant models, technologies and treatments, there is... Read More about Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy.

Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model (2021)
Journal Article
Ellwood, R. A., Hewitt, J. E., Torregrossa, R., Philp, A. M., Hardee, J. P., Hughes, S., …Szewczyk, N. J. (2021). Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model. Proceedings of the National Academy of Sciences, 118(9), Article e2018342118. https://doi.org/10.1073/pnas.2018342118

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle degeneration and weakness due to mutations in the dystrophin gene. The symptoms of DMD share similarities with those of accelerated aging. Recentl... Read More about Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model.

Network analysis of human muscle adaptation to aging and contraction (2020)
Journal Article
Etheridge, T., Willis, C., Atherton, P., Ames, R., Szewczyk, N., Deane, C., …Lund, J. (2020). Network analysis of human muscle adaptation to aging and contraction. Aging, 12(1), 740-755. https://doi.org/10.18632/aging.102653

Resistance exercise (RE) remains a primary approach for minimising aging muscle decline. Understanding muscle adaptation to individual contractile components of RE (eccentric, concentric) might optimise RE-based intervention strategies. Herein, we em... Read More about Network analysis of human muscle adaptation to aging and contraction.

Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men (2019)
Journal Article
Gharahdaghi, N., Rudrappa, S., Brook, M. S., Idris, I., Crossland, H., Hamrock, C., …Atherton, P. J. (2019). Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men. Journal of Cachexia, Sarcopenia and Muscle, 10(6), 1276-1294. https://doi.org/10.1002/jcsm.12472

Background: The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia) and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RE... Read More about Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men.

Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans (2019)
Journal Article
Sudevan, S., Takiura, M., Kubota, Y., Higashitani, N., Cooke, M., Ellwood, R. A., …Higashitani, A. (2019). Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans. FASEB Journal, 33(8), 9540-9550. https://doi.org/10.1096/fj.201802298r

Mitochondrial dysfunction impairs muscle health and causes subsequent muscle wasting. This study explores the role of mitochondrial dysfunction as an intramuscular signal for the extracellular matrix (ECM)–based proteolysis and, consequentially, musc... Read More about Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans.

The acute transcriptional response to resistance exercise: impact of age and contraction mode (2019)
Journal Article
Deane, C. S., Ames, R. M., Phillips, B. E., Weedon, M. N., Willis, C. R., Boereboom, C., …Etheridge, T. (2019). The acute transcriptional response to resistance exercise: impact of age and contraction mode. Aging, 11(7), 2111-2126. https://doi.org/10.18632/aging.101904

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... Read More about The acute transcriptional response to resistance exercise: impact of age and contraction mode.

Worms in space for outreach on earth: space life science activities for the classroom (2018)
Journal Article
Gaffney, C. J., Pollard, A. K., Deane, C. S., Cooke, M., Balsamo, M., Hewitt, J., …Phillips, B. E. (2018). Worms in space for outreach on earth: space life science activities for the classroom. Gravitational and space research : publication of the American Society for Gravitational and Space Research, 6(2), 74-82

Long term spaceflight is associated with the loss of skeletal muscle mass and function. The Molecular Muscle Experiment (MME) seeks to identify the causes of muscle decline in space and test potential therapies to attenuate this in the microscopic wo... Read More about Worms in space for outreach on earth: space life science activities for the classroom.

Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans (2018)
Journal Article
Gaffney, C. J., Pollard, A., Barratt, T. F., Constantin-Teodosiu, D., Greenhaff, P. L., & Szewczyk, N. J. (2018). Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans. Aging, 10(11), 3382-3396. https://doi.org/10.18632/aging.101654

Sarcopenia, the age-related decline of muscle, is a significant and growing public health burden. C. elegans, a model organism for investigating the mechanisms of ageing, also displays sarcopenia, but the underlying mechanism(s) remain elusive. Here,... Read More about Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans.

Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs (2018)
Journal Article
Hewitt, J. E., Pollard, A. K., Lesanpezeshki, L., Deane, C. S., Gaffney, C. J., Etheridge, T., …Vanapalli, S. A. (2018). Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs. Disease Models and Mechanisms, 11(12), https://doi.org/10.1242/dmm.036137

Muscle strength is a key clinical parameter used to monitor the progression of human muscular dystrophies including Duchenne and Becker muscular dystrophies. Although Caenorhabditis elegans is an established genetic model for studying mechanisms and... Read More about Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs.

Levels of acid sphingomyelinase (ASM) in Caenorhabditis elegans in microgravity (2018)
Journal Article
Gravely, A., Vlasov, A., Freeman, A., Wu, K., Szewczyk, N. J., D'Cruz, R., & Batt, J. (2018). Levels of acid sphingomyelinase (ASM) in Caenorhabditis elegans in microgravity. Gravitational and space research : publication of the American Society for Gravitational and Space Research, 6(1), 27-36

Both Amyotrophic Lateral Sclerosis (ALS) patients and astronauts in spaceflight suffer from muscle atrophy. Previous research suggests that the enzyme acid sphingomyelinase (ASM) may be involved in the pathogenesis of ALS, but it is not known if ASM... Read More about Levels of acid sphingomyelinase (ASM) in Caenorhabditis elegans in microgravity.

NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans (2018)
Journal Article
Rahman, M., Hewitt, J. E., Van-Bussell, F., Edwards, H., Blawzdziewicz, J., Szewczyk, N. J., …Vanapalli, S. A. (2018). NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans. Lab on a Chip, 15, https://doi.org/10.1039/C8LC00103K

Muscle strength is a functional measure of quality of life in humans. Declines in muscle strength are manifested in diseases as well as during inactivity, aging, and space travel. With conserved muscle biology, the simple genetic model C. elegans is... Read More about NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans.

A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle (2017)
Journal Article
Brook, M. S., Wilkinson, D., Mitchell, W. K., Lund, J. N., Phillips, B. E., Szewczyk, N. J., …Atherton, P. J. (2017). A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle. AJP - Endocrinology and Metabolism, 313(6), Article E681-E689. https://doi.org/10.1152/ajpendo.00157.2017

Current methods to quantify in vivo RNA dynamics are limited. Here, we developed a novel stable isotope (D2O) methodology to quantify RNA synthesis (i.e., ribosomal biogenesis) in cells, animal models, and humans. First, proliferating C2C12 cells wer... Read More about A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle.

Functional phosphatome requirement for protein homeostasis, networked mitochondria, and sarcomere structure in C. elegans muscle (2017)
Journal Article
Lehmann, S., Bass, J. J., Barratt, T. F., Ali, M. Z., & Szewczyk, N. J. (2017). Functional phosphatome requirement for protein homeostasis, networked mitochondria, and sarcomere structure in C. elegans muscle. Journal of Cachexia, Sarcopenia and Muscle, 8(4), 660-672. https://doi.org/10.1002/jcsm.12196

Background: Skeletal muscle is central to locomotion and metabolic homeostasis. The laboratory worm C. elegans has been developed into a genomic model for assessing the genes and signals that regulate muscle development and protein degradation. Past... Read More about Functional phosphatome requirement for protein homeostasis, networked mitochondria, and sarcomere structure in C. elegans muscle.

An overview of technical considerations for Western blotting applications to physiological research (2016)
Journal Article
Bass, J. J., Wilkinson, D. J., Rankin, D., Phillips, B. E., Szewczyk, N. J., Smith, K., & Atherton, P. J. (in press). An overview of technical considerations for Western blotting applications to physiological research. Scandinavian Journal of Medicine and Science in Sports, 27(1), https://doi.org/10.1111/sms.12702

The applications of Western/immuno-blotting (WB) techniques have reached multiple layers of the scientific community and are now considered routine procedures in the field of physiology. This is none more so than in relation to skeletal muscle physio... Read More about An overview of technical considerations for Western blotting applications to physiological research.

Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development (2016)
Journal Article
Mora-Lorca, J. A., Sáenz-Narciso, B., Gaffney, C. J., Naranjo-Galindo, F. J., Pedrajas, J. R., Guerrero-Gómez, D., …Miranda-Vizuete, A. (in press). Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development. Free Radical Biology and Medicine, 96, https://doi.org/10.1016/j.freeradbiomed.2016.04.017

Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1... Read More about Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development.

Methods to Assess Subcellular Compartments of Muscle in C. elegans (2014)
Journal Article
Gaffney, C. J., Bass, J. J., Barratt, T. F., & Szewczyk, N. J. (in press). Methods to Assess Subcellular Compartments of Muscle in C. elegans. Journal of Visualized Experiments, doi:10.3791/52043

Skeletal muscle is essential for locomotion and is the bodies’ main protein store. Muscle health measurements within C. elegans are described. Prospective changes to muscle structure and function are assessed using localized GFP and cationic dyes.

The neurodegenerative effects of selenium are inhibited by FOXO and PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in Caenorhabditis elegans (2014)
Journal Article
Estevez, A. O., Morgan, K. L., Szewczyk, N. J., Gems, D., & Estevez, M. (2014). The neurodegenerative effects of selenium are inhibited by FOXO and PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in Caenorhabditis elegans. NeuroToxicology, 41, 28-43. https://doi.org/10.1016/j.neuro.2013.12.012

A validation of the application of D2O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans (2013)
Journal Article
Wilkinson, D. J., Franchi, M. V., Brook, M. S., Narici, M. V., Williams, J. P., Mitchell, W. K., …Smith, K. (2014). A validation of the application of D2O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans. AJP - Endocrinology and Metabolism, 306(5), Article E571-E579. https://doi.org/10.1152/ajpendo.00650.2013

Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control of muscle mass. Traditional [13C]amino acid tracer methodologies necessitate sustained bed rest and intravenous cannulation(s), restricting studies t... Read More about A validation of the application of D2O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans.