Physiology
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Item Embargo Characterization of pelvic floor and genitourinary tissue in a preclinical model of classical Ehlers-Danlos Syndrome(East Carolina University, July 2024) Kamath, SoumyaClassical Ehlers-Danlos syndrome (cEDS) is an inherited connective tissue disorder characterized by collagen abnormalities, leading to tissue fragility. Individuals with cEDS often experience urinary incontinence, pelvic pain, and sexual dysfunction, with these symptoms occurring at a higher prevalence in women (73-89%). This subtype of EDS arises from mutations in the collagen type V (COL5a1) gene, pivotal in fibrillogenesis regulation. The goal of our study is to determine the role of collagen V in the genitourinary tissue of both male and female col5a1 heterozygous mice. We hypothesize lower collagen V levels in cEDS mice would lead to more frequent voiding, decreased bladder contraction, and decreased genital tissue contraction. In chapter two, we attempted to characterize the bladder and vaginal function of the col5a1 heterozygous (HET) mice at 16-weeks by comparing them to their wild-type (WT) counterparts. We found no disparity in voiding frequency or bladder contraction between the two genotypes. However, we noticed that the HET mice exhibited lower bladder contraction rates upon the release of endogenous neurotransmitters. Interestingly, in the vagina, they displayed higher contraction responses to adrenergic stimulation and were more sensitive to nitic oxide mediated relaxation. We also assessed contractility of the iliococcygeus skeletal muscle of the pelvic floor and found no changes between the HET and WT mice. In chapter three, we repeated these experiments with male col5a1 heterozygous mice, focusing on bladder and penile smooth muscle function. Our findings mirrored those of the females as both genotypes voided at comparable rates. Additionally, both genotypes had no change in carbachol mediated contractions. However, the HET male bladders consistently contracted at lower rates to electrical field stimulation (EFS) which is mediated by the release of endogenous neurotransmitters. Interestingly, their penises exhibited higher contraction rates in response to adrenergic stimulation and showed no difference in relaxation rates. In conclusion, our findings suggest that the col5a1 heterozygous mouse model holds considerable potential as an animal model for replicating the genitourinary issues observed in clinical cEDS. Our study has established a foundational framework for future research endeavors to further understand the pathophysiological mechanisms and assess potential therapies to improve cEDS urogenital symptoms.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, Debabrata