Life Sciences Commons^™

Genome-Wide Analyses Of Genomic Variation Regulating Differential Stress Responses In Japanese Quail, Steven Anthony Shumaker

Graduate Theses and Dissertations

As consumer demands for poultry grow, producers work to improve bird productivity in both meat and egg production. This endeavor is multifaceted, as many different factors play a part in influencing the productivity of birds, including environmental conditions, overall health, and genetic potential. One aspect controlled for in all aspects of poultry production optimization is stress management. Mitigation of stress is of primary concern to producers, as improper stress management can have many deleterious effects on chickens. Stress management requires an understanding of poultry stress responses and their physiological mechanisms, which can be more deeply understood through genomic analysis. Chapter …

Pyridine Nucleotide Redox Potential In Coronary Smooth Muscle Couples Myocardial Blood Flow To Cardiac Metabolism., Marc Matthew Dwenger

Electronic Theses and Dissertations

The maintenance of myocardial oxygen supply during stress is essential for sustaining cardiac health. Enhancement of coronary blood flow upon increases in myocardial oxygen demand (i.e., hyperemia) relies on regulation of voltage-gated K⁺ (Kv) channels by their intracellular β subunits (i.e., Kvβ proteins). Considering that, Kvβ proteins are aldo-keto reductases (AKRs) and regulate Kv channel gating, we tested the hypothesis that elevation of myocardial oxygen demand modifies intracellular NAD(H) in arterial myocytes. Furthermore, we tested whether the resultant change in the redox state of the pyridine nucleotide pool directly regulates coronary Kv1 channel activity. High-resolution imaging mass spectrometry and …

Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard

Electronic Theses and Dissertations

Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase, plays a role in DNA damage repair, redox sensing, and metabolism. In the heart, ATM contributes significantly in the myocardial infarction (MI)-induced cardiac remodeling with effects on fibrosis, hypertrophy, apoptosis and inflammation. This study investigates the role of ATM deficiency in 14 weeks Western-type diet (WD)-induced cardiac outcomes prior to and 1-day post-MI in a sex-specific manner using wild-type (WT) and ATM heterozygous knockout (hKO) mice. In male mice, ATM deficiency induced rapid body weight gain and preload-associated dysfunction, while WT mice displayed afterload-associated dysfunction 14 weeks post-WD. Myocyte apoptosis and hypertrophy were …

Targeting Ccn Proteins In The Treatment Of Dermal Fibrosis, Alex Peidl

Electronic Thesis and Dissertation Repository

Fibrotic disorders, including the inflammatory connective tissue disease systemic sclerosis (SSc), contribute to 45% of deaths in the Western world. Currently there is no universally agreed-upon treatment for fibrosis. The CCN family of matricellular proteins are tightly spatiotemporally regulated proteins involved in development and wound healing, and are aberrantly expressed in fibrotic disease, including in SSc. CCN1 and CCN2 are overexpressed in SSc and contribute to the progression of animal models of fibrosis. CCN3 is reciprocally regulated to CCN1 and CCN2 and has been shown to suppress CCN2-mediated fibrogenic activity in kidney fibrosis. This led to the development of therapeutic …

Does Epa Cause A Decrease In Inflammation Of Bend.3 Cells Through Ffar4?, Clay J. Weidenhamer

Masters Theses

Atherosclerosis is an inflammatory disease initiated by low and oscillatory shear stress on the endothelium. The inflammatory process recruits leukocytes to the vessel wall by expression of the adhesion molecule VCAM-1. Activation of the NF-κB inflammatory signaling pathway is responsible for the increase in VCM-1 expression. Omega 3 FAs, such as EPA, reduce the risk of atherosclerosis by decreasing this inflammatory response. The pathway by which omega 3 FAs is proposed to inhibit inflammation includes activating FFAR4 to decrease NF-κB activation thereby reducing expression of adhesion molecules. We hypothesized that treatment of endothelial cells with 30 μM EPA would decrease …

Characterizing The Structural, Biophysical And Functional Effects Of S-Glutathionylation On Stim1 Ca2+ Sensing, Christian Michael Sirko

Electronic Thesis and Dissertation Repository

Stromal interaction molecule 1 (STIM1) is an endo/sarcoplasmic reticulum (ER/SR) calcium (Ca²⁺) sensing protein that initiates cytoplasmic Ca²⁺ influx via store-operated calcium entry (SOCE). STIM1, in conjunction with Orai, a plasma membrane (PM) protein, function as mediators of SOCE through the formation of calcium-release activated calcium (CRAC) channels. S-Glutathionylation of STIM1 at Cys56 has been shown to evoke constitutive Ca²⁺ entry in DT40 cells, however no studies have carefully investigated the biophysical and structural effects of this covalent modification to the luminal domain, which are critical for understanding the molecular mechanism underlying the regulation of …

Investigation Of The Hsp90 Co-Chaperone, Sti1, In Cellular Resilience And Neurodegenerative Diseases, Rachel E. Lackie

Electronic Thesis and Dissertation Repository

In neurodegenerative diseases, certain proteins misfold and form toxic aggregates that cause brain matter atrophy, leading to decline in motor and/or cognitive functions. To maintain cellular proteostasis and survival, molecular chaperones regulate protein maturation and help to prevent aberrant protein aggregation. The molecular chaperone Hsp90 regulates hundreds of proteins and interestingly, several of those are misfolded in neurodegenerative diseases. Stress inducible-phosphoprotein-1 (STI1, STIP1), an Hsp90 co-chaperone, orchestrates client protein transfer between chaperones Hsp70 and Hsp90 through physical interactions with both chaperones. Notably, previous work in yeast, worms, and mouse neurons all showed that STI1 protects organisms against stressors and amyloid-like …

Identifying The Molecular Pathways That Drive Retinal Degeneration In The Childhood Neurodegenerative Disease: Mucolipidosis Type Iv, Michael Pamonag

Masters Theses, 2020-current

Humans, like many other vertebrates, possess five Aristotelian senses (vision, olfaction, hearing, taste, and touch) which we use to experience and navigate our environment. Our visual system is the only source of light detection and light signaling in our bodies. This makes our visual system essential for detecting movement, distance, time of day, and seasonal changes in the length of days within our environment. The visual systems of most animals are designed to capture photons of visible light and convert that energy into a neurological signal (visual signal) to be transmitted to brain regions responsible for visual perception1 . This …

Understanding The Pathogenesis Of Renal Medullary Carcinoma, Melinda Soeung

Dissertations & Theses (Open Access)

Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

MSU Graduate Theses

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Exercise Training Rescues Increased Brain Isf Aβ Caused By Chronic Isolation Stress In App/Ps1 Transgenic Mice, Lydia M. Holtmann

MSU Graduate Theses

Alzheimer’s Disease (AD) is a progressive brain disorder that destroys memory and cognition thought to be initiated through the build-up of the amyloid-beta (A) peptide. The A peptide aggregates, slowly forming into insoluble plaque substances that destroy the brain and worsen patient’s symptoms over time. Studies have shown that chronic isolation stress (CIS) increases the A peptide soluble and insoluble levels in the brain and that exercise training decreases these levels in transgenic mouse models of AD. We sought to determine if an exercise training regimen would rescue the increase in Aβ levels caused by CIS in the APP/PS1 transgenic …

Link Between Muscle And Whole-Body Energetic Responses To Exercise, Christopher M.T. Hayden

Masters Theses

Substantial evidence exists regarding how skeletal muscles use energy and how this affects muscular performance. What remains unclear is how characteristics of muscle energetics affect whole-body energetics during daily living, and what effects this may have on mobility. The goal of this study was to determine the associations between muscle and whole-body energetics including the relationships between: 1) muscle PCr depletion (∆PCr) in response to light intensity isotonic contractions and the oxygen deficit at the onset of a 30-min treadmill walk (30MTW), and, 2) muscle oxidative capacity and excess post-exercise oxygen consumption (EPOC; 30MTW), respiratory exchange ratio (RER; 30MTW), and …

Characterizing The Effects Of Pyrroloquinoline Quinone (Pqq) Supplementation On Skeletal Muscle Mitochondrial Function And Myogenesis During Oxidative Stress And Iugr., Allyson J. Wood

Electronic Thesis and Dissertation Repository

Intrauterine growth restriction (IUGR) affects 10-15% of births and is associated with placental insufficiency (PI), resulting in fetal oxidative stress (OS). This OS is a factor in the predisposition to postnatal noncommunicable disease (NCD) of which muscle mitochondrial dysfunctional is a key aspect. Pyrroloquinoline quinone (PQQ), an antioxidant-like compound, is capable of OS reduction and promotes mitochondrial function, though limited research has focused on its effects in in utero skeletal muscle. This study sought to investigate the impact of in vitro H₂O₂, a model of OS, and an in vivo model of OS associated IUGR, with …

Decreased Activity Of Phosphofructokinase-1 In Flight Muscle Cells Of Hawk Moth Manduca Sexta With Age, Owen G. Alvine

Honors Thesis

The phosphofructokinase-1 (PFK-1) enzyme is important for the catalyzation and regulation of glycolysis, especially in muscle. Investigating age-related changes in PFK-1 activity will provide insights into the metabolism shifts in muscle cells of our muscle aging model. The hawk moth, Manduca sexta, was chosen as the model organism because of its unique endothermic, synchronous flight muscles that are more analogous to vertebrates than invertebrate species. We hypothesized that PFK-1 activity will increase in muscle cells of aged moths due to dysregulation of the mitochondria. This was predicted to change the method of energy production, by hindering oxidative phosphorylation, making glycolysis …

The Potential Influence Of Abiotic Conditions On Mussel Species Abundance In San Francisco Bay, Alexandra G. Farrell, M. Christina Vasquez Dr.

Honors Thesis

Climate change has negatively altered seawater conditions, which may have severe implications for marine ecosystems. Mussels are susceptible to environmental changes since they are primary consumers and filter-feeding bivalves. Two species of particular interest to the West Coast of the U.S. are Mytilus galloprovincialis and M. trossulus. M. trossulus is native to the California Coast and was historically prevalent from Southern California to Washington. However, with increased shipping and rising seawater temperature, M. galloprovincialis, an invasive species from the Mediterranean, pushed the species range of M. trossulus poleward. M. trossulus is more tolerant of cold seawater with variable salinity while …

Investigating Mechanisms In Nociceptors Driving Ongoing Activity And Ongoing Pain, Elia Lopez

Dissertations & Theses (Open Access)

Ongoing (apparently spontaneous) pain at rest is a major complaint of patients suffering from many forms of acute and chronic pain, including acute and persistent postsurgical pain. Accumulating evidence suggests ongoing activity in nociceptors is a major driver of ongoing pain. Ongoing activity can be generated in sensory neurons in the absence of sensory generator potentials if one or more of three neurophysiological alterations occur – prolonged depolarization of resting membrane potential (RMP), hyperpolarization of action potential (AP) threshold, and/or increased amplitude of depolarizing spontaneous fluctuations of membrane potential (DSFs) to bridge the gap between RMP and AP threshold. Cellular …

Cacna1g Transcript Knockdown Analysis Via In Situ Hybridization, Jennifer (Shih-En) Chen

Undergraduate Honors Theses

The pedunculopontine nucleus (PPN) comprises the mesencephalic locomotor region (MLR) of the midbrain. It contains glutamatergic, cholinergic, and GABAergic interneurons, but only glutamatergic neurons influence locomotion, which is our focus here. The PPN receives upstream and downstream input from the basal ganglia. It projects to the reticular formation of the brainstem, which connects to the spinal cord. The PPN is involved in a wide range of physiological and behavioral processes, but our focus is locomotion. We hypothesize that the PPN influences the reticular activating system (RAS) of the medulla and thus the central pattern generators (CPG) in the spinal cord …

Inwardly Rectifying Potassium Channels: Regulators Of Myogenic Tone In Cerebrovascular Smooth Muscle, Jacob Fletcher

Electronic Thesis and Dissertation Repository

In cerebral arteries, inwardly rectifying potassium channels (K_IR) contribute to smooth muscle hyperpolarization to control arterial diameter and tone. Emerging evidence highlighted their regulation by pressure, though the underlying mechanism remains unclear. This thesis explored this concept through examination of K_IR channels in mouse and rat cerebral vascular smooth muscle (VSM). Experiments progressed from isolated cells to whole animals, employing electrophysiology, immunocytochemistry, proximity ligation assay, and arterial spin-labelling MRI techniques. Initial experiments indicated that K_IR activity persists beyond K_IR2.1 knockout in smooth muscle, clarifying their molecular composition. Our subsequent study identified key structural components …

Establishing And Validating Methods To Assess The Influence Of Exercise On Circulating Exosome Profiles In Sedentary Older Adults, Heather Quiriarte

LSU Master's Theses

Aging is associated with progressing cellular structural and functional changes, and sedentary behavior can exacerbate these hallmarks of aging. Routine exercise is known to have beneficial effects on physiological systems, but the exact molecular mechanisms behind the health benefits are unclear. Emerging evidence suggests extracellular vesicles called exosomes are involved in the intercommunication between cells and organs following exercise by delivering their cargo such as proteins and miRNAs. miRNA profiles in older adults following acute and chronic exercise need further exploration. Specifically, the effects of regular low-intensity physical activity (LPA) breaks in sedentary time on proteins and miRNA packaged in …

Myelin, Cpla2, And Azithromycin: Modulation Of Macrophage Activation In Spinal Cord Injury Inflammation, Timothy J. Kopper

Theses and Dissertations--Physiology

Spinal cord injury (SCI) produces a chronic inflammatory state primarily mediated by macrophages consisting of resident microglia and infiltrating monocytes. These chronically activated SCI macrophages adopt a pro-inflammatory, pathological state that continues to cause additional damage after the initial injury and inhibits recovery. While the roles of macrophages in SCI pathophysiology are well documented, the factors contributing to this maladaptive response are poorly understood. Here, we identify the detrimental effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA₂) in myelin- mediated potentiation of pro-inflammatory macrophage activation. Macrophage- mediated inflammatory …

A Novel Review Of Heat Shock Protein 110 Kda: A Basis For Research And Continued Experimentation Through Biochemical Analysis, Crist W. Cuffee

Theses and Dissertations

Heat shock protein 110 kDa, Hsp110, is a distinct cellular protector, different in form and function from Hsp70, a close relative of Hsp110. Functioning primarily as a holdase or in tandem with other molecular chaperones, a review of current accomplishments elucidates the uniqueness of this protein and the continued mysteries that surrounds it. Found only in eukaryotes, Hsp110 has been linked to many diseases, ranging from parasitic infection to neurodegenerative disorders. While still lacking, studies of this protein have provided much in the realm of speculation on the mechanisms behind Hsp110s’ contribution to different pathologies. This review will serve as …

Novel Mammalian Models For Understanding And Treating Spinal Cord Injury, Michael B. Orr

Theses and Dissertations--Physiology

Spinal cord injury (SCI) is devastating and often leaves the injured individual with persistent dysfunction. The injury persists because humans have poor wound repair and there are no pharmacologic treatments to induce wound repair after SCI. The continued efforts to discover therapeutic targets and develop treatments heavily relies on animal models. The purpose of this project is to develop and study novel mammalian models of SCI to provide insights for the development and effective implementation of SCI therapies.

Lab mice (Mus musculus) are a powerful tool for recapitulating the progression and persistent damage evident in human SCI, but …

Analysis Of Circadian Rhythm Irregularities On The Health Of Shift Workers, Sahil Rajan

Williams Honors College, Honors Research Projects

Circadian rhythms involve the natural 24 wake-sleep cycle that governs proper maintenance of biological sleep schedules. Circadian rhythm disruption has been associated with health issues such as diabetes, obesity, and mental health disorders such as bipolar and sleep disorders. In this study, a survey method was utilized in order to analyze specific population demographics to determine whether working day or night shifts predisposed individuals to health issues due to disruptions in their circadian rhythms. This study was also carried out to observe popular coping strategies among night shift workers. Of all the variables tested comparing the difference between day and …

Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen

Theses and Dissertations

Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …

Morphological Changes In Dorsal Root Ganglia Macrophages Associated With Neuropathic Pain Mechanisms Suggest A Novel Target For Chronic Pain Therapy, Emily Kussick

CMC Senior Theses

The present study examined morphological changes in the dorsal root ganglia (DRG) following an innate immune stimulus. The importance of the DRG has increasingly become recognized in pain processing as more than just the home of primary afferent cell bodies. All sensory information passes through the DRG via the primary afferents, and on to the spinal cord. The primary afferents synapse with second-order neurons in the spinal cord that ascend towards the brain, where they transmit the pain signal to the limbic forebrain and/or the somatosensory cortex for processing. The DRG is an interesting niche to study at as it …

Cold-Induced Metabolic Changes In Lean, Nag-1 Transgenic Mice, Rachel J. Davey

All Master's Theses

Obesity is a multifaceted metabolic disorder with severe worldwide public health consequences. While obesity can often be treated using diet and exercise, there are complex genetic interactions driving obesity that don’t always respond to such changes. One important research focus for addressing genetic factors is activating brown adipose tissue which increases thermogenesis, the process of burning stored fats to generate heat. Cold exposure is a known way to activate brown adipose tissue through b3-adrenergic signaling. This signaling pathway causes an upregulation of thermogenesis in brown adipocytes and beige adipocytes, which is white adipose tissue that “browns” and becomes metabolically active. …

Novel Quantification And Localization Of Water And Solute Transporters In The Tissues Of The Spiney Dogfish (Squalus Acanthias), Tolulope B. Ojo

Electronic Theses and Dissertations

The dogfish, Squalus acanthias is a marine cartilaginous elasmobranch found in the North Atlantic and Pacific oceans. Dogfish synthesize and excrete urea as a product of nitrogen metabolism. They also convert ammonia into urea and retain this urea, such that their plasma is isosmotic or slightly hyperosmotic to the surrounding seawater. To facilitate the regulation of body fluid and to maintain ionic concentrations and osmotic pressure, Dogfish use ion and solute transporters (e.g., NCC, UT-1) and aquaporin water channel proteins. Studies have identified some of the aquaporin genes in the elasmobranch genome, but their functions are mostly uncharacterized. Recent transcriptomic …