Physiology
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Item Open Access Skeletal Muscle Undergoes Fiber Type Metabolic Switch Without Myosin Heavy Chain Switch in Response to Defective Fatty Acid Oxidation(2022-02-09) Pereyra, Andrea S.; Lin, Chien-Te; Spangenburg, Espen E.; Neufer, P. Darrell; Fisher-Wellman, Kelsey; Ellis, Jessica M.; Sanchez, Daniela Mesa; Laskin, JuliaItem Open Access High Fat Diet Induces Obesity in Adult Mice but Fails to Develop Pre-Penile and Penile Vascular Dysfunction(2022-04-06) Odom, Michael R.; Hunt, Trevor C.; Pak, Elena S.; Hannan, Johanna L.Item Open Access Respiratory and Cardiovascular Effects of Ambient Particulate Matter from Dust Storm and Non‑Dust Storm Periods in Kuwait(2022-01-01) Walters, D. M.; Selim, M. I.; Al‑Khulaifi, N. M.; Rushing, B. R.Item Open Access Isometric Skeletal Muscle Contractile Properties in Common Strains of Male Laboratory Mice(2022-10-04) Minchew, Everett C.; Williamson, Nicholas C.; Readyoff, Andrew T.; McClung, Joseph M.; Spangenburg, Espen E.Item Open Access Bioenergetic Phenotyping of DEN-Induced Hepatocellular Carcinoma Reveals a Link Between Adenylate Kinase Isoform Expression and Reduced Complex I-Supported Respiration(2022-06-08) McLaughlin, Kelsey L.; Nelson, Margaret A.M.; Coalson, Hannah S.; Hagen, James T.; Montgomery, McLane M.; Fisher-Wellman, Kelsey H.; Wooten, Ashley R.; Zeczycki, Tonya N.; Vohra, Nasreen A.Item Open Access Human Studies of Mitochondrial Biology Demonstrate an Overall Lack of Binary Sex Differences: A Multivariate Meta-Analysis(2022) Fisher-Wellman, Kelsey H.; Neufer, P. Darrell; Junker, AlexItem Open Access Alterations in Sphingolipid Composition and Mitochondrial Bioenergetics Represent Synergistic Therapeutic Vulnerabilities Linked to Multidrug Resistance in Leukemia(2022-01) Fisher-Wellman, Kelsey H.; Hagen, James T.; Nelson, Margaret A. M.; McLaughlin, Kelsey L.; Coalson, Hannah S.; Kassai, Miki; Kao, Li-Pin; Cabot, Myles C.Item Open Access Consensus Guidelines on the Construct Validity of Rodent Models of Restless Legs Syndrome(2022) Clemens, Stefan; Salminen, Aaro V.Item Open Access Interventional- and Amputation-Stage Muscle Proteomes in the Chronically Threatened Ischemic Limb(2022) Green, Thomas D.; Karnekar, Reema; Fisher-Wellman, Kelsey H.; Yamaguchi, Dean J.; McClung, Joseph M.Item Open Access CVD and COVID-19: Emerging Roles of Cardiac Fibroblasts and Myofibroblasts(2022-04-13) Katwa, Laxmansa C.; Mendoza, Chelsea; Clements, MadisonItem Open Access Increased Level of Tumor Necrosis Factor-Alpha (TNF-α) Leads to Downregulation of Nitrergic Neurons Following Bilateral Cavernous Nerve Injury and Modulates Penile Smooth Tone(2021) Hannan, Johanna L.; Matsui, Hotaka; Sopko, Nikolai; Campbell, Jeffery D.; Liu, Xiaopu; Reinhardt, Allison; Weyne, Emmanuel; Castiglione, Fabio; Albersen, Maarten; Bivalacqua, Trinity J.Item Open Access Genetically Increasing Flux Through b-Oxidation in Skeletal Muscle Increases Mitochondrial Reductive Stress and Glucose Intolerance(2021) Smith, Cody D.; Lin, Chien-Te; McMillin, Shawna L.; Weyrauch, Luke A.; Schmidt, Cameron A.; Smith, Cheryl A.; Witczak, Carol; Neufer, P. Darrell; Kurland, Irwin J.Item Open Access Acyl-CoA Synthetase 6 is Required for Brain Docosahexaenoic Acid Retention and Neuroprotection During Aging(2021-06-08) Fernandez, Regina F.; Pereyra, Andrea S.; Diaz, Victoria; Wilson, Emily S.; Litwa, Karen A.; Martínez-Gardeazabal, Jonatan; Jackson, Shelley N.; Brenna, Thomas; Hermann, Brian P.; Eells, Jeffrey B.; Ellis, Jessica M.Item Open Access The Role of Ethanolamine Phosphate Phospholyase in Regulation of Astrocyte Lipid Homeostasis(2021-05-26) Ellis, Jessica M.; White, Cory J.; Wolfgang, Michael J.Item Open Access Octanoate is Differentially Metabolized in Liver and Muscle and Fails to Rescue Cardiomyopathy in CPT2 Deficiency(2021) Pereyra, Andrea S.; Ellis, Jessica M.; Fisher-Wellman, Kelsey H.; Harris, Kate L.; Soepriatna, Arvin H.; Waterbury, Quin A.; Bharathi, Sivakama S.; Zhang, Yuxun; Goergen, Craig J.; Goetzman, Eric S.Item Open Access Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery(2021-10-06) Dohm, G. Lynis; Barberio, Matthew D.; Pories, Walter J.; Gadaleta, Natalie A.; Houmard, Joseph A.; Nadler, Evan P.; Hubal, Monica J.Item Open Access Preference and Detrimental Effects of High Fat, Sugar, and Salt Diet in Wild-Caught Drosophila Simulans are Reversed by Flight Exercise(2021) Murashov, Alexander K.; Pak, Elena S.; Chien-Te Lin, Chien-Te; Boykov, Ilya N.; Katherine A. Buddo, Katherine A.; Jordan Mar, Jordan; Krishna M. Bhat, Krishna M.; Neufer, Peter DarrellItem Open Access Intrinsic OXPHOS Limitations Underlie Cellular Bioenergetics in Leukemia(2021) Nelson, Margaret AM; McLaughlin, Kelsey L.; Hagen, James T.; Coalson, Hannah S.; Schmidt, Cameron; Kassai, Miki; Kew, Kimberly A.; McClung, Joseph M.; Neufer, P. DarrellItem Open Access Operations Perspective to Competency-Based Medical Education: Experiences of IUPS-ICMR Physiology Education Workshop series (2018-2019) conducted in India(2021-10) Chandran, Dinu S.; Muthukrishnan, Suriya Prakash; Barman, Susan M.; Peltonen, Liisa M.; Ghosh, Sarmishtha; Sharma, Renuka; Bhattacharjee, Manasi; Rathore, Bharti Bhandari; Carroll, Robert G.; Sengupta, Jayasree; Chan, Julie Y.H.; Ghosh, DebabrataItem Open Access Muscle Mitochondria in Vascular Disease: A Novel Genetic Target for Limb Salvage(East Carolina University, 2022-04-19) Goldberg, Emma Joy; McClung, Joseph M; PhysiologyPeripheral arterial occlusive disease (PAD) is a manifestation of systemic atherosclerosis defined by an occlusion in the peripheral arteries, most commonly those supplying blood to the lower extremities. Chronic limb threatening ischemia (CLTI) is the most severe clinical manifestation of PAD, and is associated with high rates of limb loss, mortality, and reduced quality of life. Despite increasing PAD prevalence, treatments have been largely stalled over the past two decades, and therapeutics aimed at restoring residual blood flow have been largely unsuccessful in improving limb outcomes, especially for patients with CLTI, suggesting that the restoration of blood flow may not be enough to restore muscle functional ability. Exercise rehabilitation has established efficacy in lessening functional impairments observed in PAD patients who can tolerate it, making it only accessible to patients with less severe PAD manifestations. These findings indicate that targeting and improving ischemic skeletal muscle quality could provide great benefits to patients with PAD. Further supporting this idea, ex vivo studies of skeletal muscle myofibers from patients with PAD demonstrate decreased oxygen consumption and enzyme activity indicative of a unique and intrinsic skeletal muscle bioenergetic dysfunction. The overall aim of this dissertation was to establish whether the restoration of blood flow necessarily guarantees recovery of muscle contractile function, and to determine the role of a specific mitochondrial protein, Cox6a2, in skeletal muscle bioenergetic function. This dissertation ties together multiple in vivo studies using preclinical animal models of PAD, as well as a novel, inducible mouse model of skeletal muscle Cox6a2 loss (Cox6a2 KO). The overarching hypothesis is that the myopathy observed in preclinical models of PAD and in the clinical PAD population is due to dysfunctional skeletal muscle mitochondrial bioenergetics, not perfusion recovery. Further, we hypothesize that skeletal muscle Cox6a2 is required for normal skeletal muscle mitochondrial function, and that its loss will result in a preclinical phenotype that mimics the bioenergetic phenotype observed in the clinical population. Our results establish that the restoration of tissue perfusion does not guarantee the recovery of muscle contractile function or structure in a preclinical model of PAD, and that the loss of Cox6a2 in mature skeletal muscle results in a mitochondrial bioenergetic phenotype.