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Articles 1 - 10 of 10
Full-Text Articles in Life Sciences
The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson
The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson
Electronic Thesis and Dissertation Repository
Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted …
Reactive Oxygen Species Damage And Consequences For Mitochondrial Function In The Hibernating Thirteen-Lined Ground Squirrel, Ictidomys Tridecemlineatus, Brynne Duffy
Electronic Thesis and Dissertation Repository
Hibernators experience changes in blood flow, similar to ischemia-reperfusion injury, which may lead to oxidative damage. I hypothesized that suppression of mitochondrial metabolism during hibernation protects against such damage. I compared oxidative damage and antioxidant capacity in tissues and isolated liver mitochondria among summer, torpid, and interbout euthermic thirteen-lined ground squirrels (TLGS). I found less oxidative tissue damage during summer than hibernation, but no mitochondrial differences. I also compared metabolic activity of isolated mitochondria before and after five minutes of anoxia, followed by reoxygenation, among hibernation states and rats. Anoxia-reoxygenation decreased state-three respiration (ST3) in all groups, with rat mitochondria …
An Approach For The In-Vivo Characterization Of Brain And Heart Inflammation In Duchenne Muscular Dystrophy, Joanne Tang
An Approach For The In-Vivo Characterization Of Brain And Heart Inflammation In Duchenne Muscular Dystrophy, Joanne Tang
Electronic Thesis and Dissertation Repository
Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss—notably within muscles and CNS neurons. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies improved life expectancy, but this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, there is an increasing need to both better understand and track disease pathophysiology in the dystrophic heart and brain prior to onset of severe degenerative symptoms. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration, however chronic neuroinflammation’s role is largely unknown in …
Characterization Of Mechanotransduction In Annulus Fibrosus Cells, Min Kyu M. Kim
Characterization Of Mechanotransduction In Annulus Fibrosus Cells, Min Kyu M. Kim
Electronic Thesis and Dissertation Repository
IVD degeneration is a multifactorial pathological process associated with back pain. While biomechanical factors are important regulators of IVD homeostasis, mechanical loading also contribute to the onset of IVD degeneration. Importantly, the mechanotransduction pathways that mediate cell type-specific responses to mechanical loading are not well understood. Transient receptor potential vanilloid 4 (TRPV4) is a multimodally activated cell surface cation channel implicated as a mechanoreceptor regulating the mechano-response in other musculoskeletal cell types. Using both in vitro and in vivo models, the current study aimed to characterize the role of TRPV4 in annulus fibrosus (AF) cell mechanotransduction. Using a mechanically dynamic …
Mechanisms Of Beta-Cell Deficiency In Gestational Diabetes And Strategies To Reverse Hyperglycemia, Sandra K. Szlapinski
Mechanisms Of Beta-Cell Deficiency In Gestational Diabetes And Strategies To Reverse Hyperglycemia, Sandra K. Szlapinski
Electronic Thesis and Dissertation Repository
Gestational diabetes mellitus (GDM) is an increasingly prevalent form of diabetes that first appears during pregnancy, and reverses after parturition in most cases. Nonetheless, GDM is associated with adverse maternal and fetal health outcomes. There is currently no reliable method of intervention for GDM and a limited understanding of the mechanisms of impaired endocrine adaptability in GDM. In this thesis, I aimed to address these knowledge gaps by establishing a mouse model for the study of suboptimal endocrine adaptations during pregnancy. This was accomplished using a dietary low protein (LP) insult during fetal and neonatal development, which programs for suboptimal …
The Role Of Regulator Of G Protein Signaling 2 In Inflammatory Cytokine Release In Endotoxemia In Mice, Xin Tong Ma
The Role Of Regulator Of G Protein Signaling 2 In Inflammatory Cytokine Release In Endotoxemia In Mice, Xin Tong Ma
Electronic Thesis and Dissertation Repository
In sepsis, lipopolysaccharide (LPS) activates toll-like receptor 4 to stimulate the release of inflammatory cytokines (e.g. tumor necrosis factor-alpha, TNF-α), leading to cardiac dysfunction. Regulator of G protein signaling 2 (RGS2) limits G protein-coupled receptor signaling by increasing the rate of G protein deactivation or inhibiting G protein-effector interactions. We hypothesized that RGS2 deficiency would enhance proinflammatory responses in endotoxemia. Adult wild-type and RGS2-/- C57BL/6 mice and neonatal cardiomyocytes were treated with LPS and assessed for inflammatory responses and cardiac function. Myocardial TNF-α expression was higher in RGS2-/- mice during endotoxemia. Additionally, cardiac function was impaired in …
Understanding The Effects Of Physical Activity On Executive Functioning And Psycho-Emotional Well-Being In Children With Adhd, Hannah B. Bigelow
Understanding The Effects Of Physical Activity On Executive Functioning And Psycho-Emotional Well-Being In Children With Adhd, Hannah B. Bigelow
Electronic Thesis and Dissertation Repository
A short bout of physical activity has been shown to improve executive functioning in children. However, the implications for children with Attention Deficit Hyperactivity Disorder (ADHD) has been understudied. We examined the impact of a 10min bout of physical activity on executive functioning and psycho-emotional well-being in children with ADHD. Participants engaged in two lab-based sessions separated by 1-week: a physical activity session and a control session. The physical activity session included a 10min bout of moderate-intensity biking, with a pre-post battery of cognitive and psycho-emotional assessments. The control session consisted of 10mins of silent reading. We used functional imaging …
Regulators Of Ectopic Calcification In A Mouse Model Of Dish: A Multi-Omics Perspective, Matthew A. Veras
Regulators Of Ectopic Calcification In A Mouse Model Of Dish: A Multi-Omics Perspective, Matthew A. Veras
Electronic Thesis and Dissertation Repository
Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory spondyloarthropathy and the second most common form of arthritis characterized by formation of ectopic mineral along the spine. Pathological findings in DISH include regional calcification of the anterior longitudinal ligament, paraspinal connective tissues, and annulus fibrosus (AF) of the intervertebral disc (IVD). Clinical symptoms of DISH include increased spine stiffness, decreased spinal range of motion, and in severe cases dysphagia and spinal cord/nerve root compression. The molecular pathways responsible for DISH have not been delineated and as such, there are no disease-modifying treatments. Clinical treatment for DISH is limited to surgical resection …
The Amino Terminal Domains Of Sheep Cx46 Or Cx50 Determine Their Gap Junction Channel Open Stability And Unitary Channel Conductance, Benny Yue
Electronic Thesis and Dissertation Repository
Connexins form intercellular communication channels known as gap junctions (GJs), which are found throughout the vertebrate species. GJs formed by different connexins harbor unique channel properties that have not been fully defined. High-resolution structures of native Cx46 and Cx50 GJs from sheep (sCx46 and sCx50) were recently resolved. Molecular dynamics studies identified the NT domains, especially the 9th position, as key determinants in the differences of energetic barrier to K+ permeation in sCx46 and sCx50 GJs. We studied functional properties of GJs formed by sCx46, sCx50, NT domain swapped chimeras (sCx46-50NT and sCx50-46NT), and point variants at the …
Investigating The Role Of Nuclear Receptor Peroxisome Proliferator-Activated Receptor Δ In Obesity-Associated Osteoarthritis, Bethia C. To
Investigating The Role Of Nuclear Receptor Peroxisome Proliferator-Activated Receptor Δ In Obesity-Associated Osteoarthritis, Bethia C. To
Electronic Thesis and Dissertation Repository
Osteoarthritis (OA) is a heterogeneous disease, differentiated based by risk factors that drive joint damage. Peroxisome proliferator-activated receptor delta (PPARd) is a nuclear receptor previously implicated in cartilage damage in OA. Given its deleterious role in post-traumatic OA and in regulating metabolism, we hypothesized that PPARd inhibition will protect against obesity-associated OA. Diet-induced obesity was used to induce OA in mice. Mice fed the western diet for 40 weeks exhibited mild OA, with subchondral bone remodelling occurring alongside cartilage damage. Cartilage-specific Ppard knockout (KO) mice were generated to study its role in metabolic OA. Both wildtype and PPARd KO mice …