Biology subjects

Mizener, A.

Publications and source records attributed to Mizener, A..

4 recordsLinked to original sources

bioRxiv2025

A Model to Simulate the Interference Effects of Acute Aerobic Exercise on Rate of Force Development in Weightlifters

Compelling data supports the concept that concurrent strength and aerobic training can interfere with adaptations to strength training related to speed, power, and rate of force development (RFD). Studies on this topic have primarily utilized non-athlete participants, with data subsequently extrapolated to athlete populations. Since there may be hesitancy to have athletes involved in research on the interference effects of aerobic exercise on strength specific adaptations, we built a model to simulate these effects and develop an equation to predict interference. The hypothesis tested in this project was that aerobic exercise is the main driver of interference on weightlifting-associated RFD, and that this interference can be modeled to generate an equation to predict changes in RFD. Python software was used to generate the model, perform the simulation and optimize variables that contribute to the interference effect. A nonlinear exponential interference model was created that simulates the changes in RFD from a force-time curve in response to acute aerobic exercise lasting from 2-minutes to 60-minutes in duration. RFD sensitivity to aerobic exercise was modeled such that values were reduced by approximately 70% after aerobic exercise less than 10 minutes, with further reduction to 80% with durations greater than 10-minutes. The prediction equation can be used by strength coaches to predict the interference of acute aerobic exercise on RFD and subsequently allow the coach to make informed decisions on training program design if there is a need to include aerobic exercise in a strength and/or power-based periodized plan.

physiology↗

bioRxiv2025

ACE-031, a Soluble Activin Type IIB Receptor, Increases Muscle Mass and Strength in the Common Marmoset (Callithrix jacchus)

AimPharmacological blockade of ligands for the activin receptor type IIB (ActRIIB) e.g., myostatin and activin A is associated with improvements in murine skeletal muscle mass and function. The efficacy of a similar treatment approach in a non-human primate (NHP) model would suggest a greater likelihood of success in the treatment of humans suffering from chronic myopathies. In the present study, we elucidate the potential therapeutic benefit of ACE-031, a therapeutic protein consisting of the ActRIIB extracellular region fused to human IgG1, in the common marmoset (Callithrix jacchus). MethodsMarmosets were randomized to receive ACE-031 or vehicle control (10 mM Tris buffered saline; TBS) for 14 weeks. Body composition was measured weekly throughout the experimental period and morphometric analysis and contractile properties of skeletal muscle were assessed terminally. ResultsMarmosets administered ACE-031 showed a significant increase in body weight and lean body mass from baseline, while no change was seen in the vehicle-treated controls. Biceps brachii exhibited a significant increase in the cross-sectional area of both type I and type II fibers and ex vivo contractile properties of the EDL showed an increase in absolute and specific force production. ConclusionThe efficacy of ACE-031 in non-human primates provides optimism that a therapeutic strategy that targets multiple negative regulators of skeletal muscle may be beneficial in treating myopathies in humans.

physiology↗

bioRxiv2025

Differential Bioenergetic Profile of Human Glioblastoma following Transplantation of Myocyte-derived Mitochondria

Glioblastoma (GBM) exhibits profound plasticity, enabling adaptation to fluctuating microenvironmental stressors such as hypoxia and nutrient deprivation. However, this metabolic rewiring also creates subtype-specific vulnerabilities that may be exploited therapeutically. Here, we investigate whether mitochondrial transplantation using non-neoplastic, human myocyte-derived mitochondria alters the metabolic architecture of GBM cells and modulates their response to ionizing radiation. Using a cell-penetrating peptide-mediated delivery system, we successfully introduced mitochondria into two mesenchymal-subtype GBM cell lines, U3035 and U3046. Transplanted cells exhibited enhanced mitochondrial polarization and respiratory function, particularly in the metabolically flexible U3035 line. Bioenergetic profiling revealed significant increases in basal respiration, spare respiratory capacity, and glycolytic reserve in U3035 cells post-transplantation, whereas U3046 cells showed minimal bioenergetic augmentation. Transcriptomic analyses using oxidative phosphorylation (OXPHOS) and glycolysis gene sets confirmed these functional findings. At baseline, U3035 cells expressed high levels of both glycolytic and OXPHOS genes, while U3046 cells were metabolically suppressed. Following radiation, U3035 cells downregulated key OXPHOS and glycolysis genes, suggesting metabolic collapse. In contrast, U3046 cells transcriptionally upregulated both pathways, indicating compensatory adaptation. These results identify and establish mitochondrial transplantation as a metabolic priming strategy that sensitizes adaptable GBM subtypes like U3035 to therapeutic stress by inducing bioenergetic overextension. Conversely, rigid subtypes like U3046 may require inhibition of post-radiation metabolic compensation for effective targeting. Our findings support a novel stratified approach to GBM treatment which integrates metabolic subtype profiling with bioenergetic modulation.

neuroscience↗

bioRxiv2024

Enhancing Radiation-induced Reactive Oxygen Species Generation Through Mitochondrial Transplantation in Human Glioblastoma

Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increasing mitochondrial density in GBM cells, potentially boosting reactive oxygen species (ROS) production and promoting radiation-induced cell death. Using cell-penetrating peptides (CPPs), mitochondria were transplanted into GBM cell lines U3020 and U3035. Transplanted mitochondria were successfully incorporated into recipient cells, increasing mitochondrial density significantly. Mitochondrial chimeric cells demonstrated enhanced ROS generation post-irradiation, as evidenced by increased electron paramagnetic resonance (EPR) signal intensity and fluorescent ROS assays. The transplanted mitochondria retained functionality and viability for up to 14 days, with mitochondrial DNA (mtDNA) sequencing confirming high transfection and retention rates. Notably, mitochondrial transplantation was feasible in radiation-resistant GBM cells, suggesting potential clinical applicability. These findings support mitochondrial transplantation as a promising strategy to overcome therapeutic resistance in GBM by amplifying ROS-mediated cytotoxicity, warranting further investigation into its efficacy and mechanisms in vivo.

cancer biology↗