Publications by authors named "Bailey Mclagan"

2 Publications

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Changes in neural drive to calf muscles during steady submaximal contractions after repeated static stretches.

J Physiol 2021 Sep 13;599(18):4321-4336. Epub 2021 Aug 13.

Department of Integrative Physiology, University of Colorado, Boulder, CO, USA.

Key Points: Repeated static-stretching interventions consistently increase the range of motion about a joint and decrease total joint stiffness, but findings on the changes in muscle and connective-tissue properties are mixed. The influence of these stretch-induced changes on muscle function at submaximal forces is unknown. To address this gap in knowledge, the changes in neural drive to the plantar flexor muscles after a static-stretch intervention were estimated. Neural drive to the plantar flexor muscles during a low-force contraction increased after repeated static stretches. These findings suggest that adjustments in motor unit activity are necessary at low forces to accommodate reductions in the force-generating and transmission capabilities of the muscle-tendon unit after repeated static stretches of the calf muscles.

Abstract: Static stretching decreases stiffness about a joint, but its influence on muscle-tendon unit function and muscle activation is unclear. We investigated the influence of three static stretches on changes in neural drive to the plantar flexor muscles, both after a stretch intervention and after a set of maximal voluntary contractions (MVCs). Estimates of neural drive were obtained during submaximal isometric contractions by decomposing high-density electromyographic signals into the activity of individual motor units from medial gastrocnemius, lateral gastrocnemius and soleus. Motor units were matched across contractions and an estimate of neural drive to the plantar flexors was calculated by normalizing the cumulative spike train to the number of active motor units (normalized neural drive). Mean discharge rate increased after the stretch intervention during the 10% MVC task for all recorded motor units and those matched across conditions (all, P = 0.0046; matched only, P = 0.002), recruitment threshold decreased for motor units matched across contractions (P = 0.022), and discharge rate at recruitment was elevated (P = 0.004). Similarly, the estimate of normalized neural drive was significantly greater after the stretch intervention at 10% MVC torque (P = 0.029), but not at 35% MVC torque. The adjustments in motor unit activity required to complete the 10% MVC task after stretch may have been partially attenuated by a set of plantar flexor MVCs. The increase in neural drive required to produce low plantar-flexion torques after repeated static stretches of the calf muscles suggests stretch-induced changes in muscle and connective tissue properties.
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http://dx.doi.org/10.1113/JP281875DOI Listing
September 2021

Derangement of hepatic polyamine, folate, and methionine cycle metabolism in cystathionine beta-synthase-deficient homocystinuria in the presence and absence of treatment: Possible implications for pathogenesis.

Mol Genet Metab 2021 02 11;132(2):128-138. Epub 2021 Jan 11.

Medicine and University of Colorado School of Medicine, Aurora, CO 80045, USA.

Cystathionine beta-synthase deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. Our knowledge of the metabolic changes induced in HCU are based almost exclusively on data derived from plasma. In the present study, we present a comprehensive analysis on the effects of HCU upon the hepatic metabolites and enzyme expression levels of the methionine-folate cycles in a mouse model of HCU. HCU induced a 10-fold increase in hepatic total homocysteine and in contrast to plasma, this metabolite was only lowered by approximately 20% by betaine treatment indicating that this toxic metabolite remains unacceptably elevated. Hepatic methionine, S-adenosylmethionine, S-adenosylhomocysteine, N-acetlymethionine, N-formylmethionine, methionine sulfoxide, S-methylcysteine, serine, N-acetylserine, taurocyamine and N-acetyltaurine levels were also significantly increased by HCU while cysteine, N-acetylcysteine and hypotaurine were all significantly decreased. In terms of polyamine metabolism, HCU significantly decreased spermine and spermidine levels while increasing 5'-methylthioadenosine. Betaine treatment restored normal spermine and spermidine levels but further increased 5'-methylthioadenosine. HCU induced a 2-fold induction in expression of both S-adenosylhomocysteine hydrolase and methylenetetrahydrofolate reductase. Induction of this latter enzyme was accompanied by a 10-fold accumulation of its product, 5-methyl-tetrahydrofolate, with the potential to significantly perturb one‑carbon metabolism. Expression of the cytoplasmic isoform of serine hydroxymethyltransferase was unaffected by HCU but the mitochondrial isoform was repressed indicating differential regulation of one‑carbon metabolism in different sub-cellular compartments. All HCU-induced changes in enzyme expression were completely reversed by either betaine or taurine treatment. Collectively, our data show significant alterations of polyamine, folate and methionine cycle metabolism in HCU hepatic tissues that in some cases, differ significantly from those observed in plasma, and have the potential to contribute to multiple aspects of pathogenesis.
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http://dx.doi.org/10.1016/j.ymgme.2021.01.003DOI Listing
February 2021
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