Life Sciences Commons^™

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 …

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 …

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 …

Effect Of Estrogen Pretreatment On Glial-Like Cell Viability Following Stress Response Hormone Treatment, Bridget N. Smith, Kevin S. Burgess, Kathleen S. Hughes

Georgia Journal of Science

The role of steroid hormones is critical in cellular function. Previous studies have found a positive correlation between the endogenous estrogen 17β-estradiol and cellular protection. Conversely, exogenous conjugated equine estrogens provide less protective mechanisms than endogenous hormones, and little is known about the role of estrogens in cellular protection during a stress response. In the present study, we compare the effects of short-term estrogen pretreatments (alone and in combination) on cell viability when cells with glial cell morphology are exposed to either epinephrine or cortisol. Results showed that 1 µM 17β-estradiol resulted in decreased cell viability following the epinephrine treatment; …

Energetic Cost And Physiological Trade-Offs, Heba A. Ali

FIU Electronic Theses and Dissertations

Understanding how organisms allocate limited resources across physiological systems is a major challenge in biology. This study revealed that high energetic demand of electric signals of male electric fish (Brachyhypopomus gauderio) is matched by a metabolic trade-off with other cellular functions. We used thyroxine (T4) to modulate the fish’s signal metabolism, partitioned the energy budget pharmacologically, and measured energy consumption using oxygen respirometry. In males, total energy consumption was unchanged pre- and post-T4 treatment, while signal metabolism rose and the standard metabolic rate fell in an even trade-off. Total metabolism in females did the opposite. Under T4, the …

Temperature Changes Seen In Lower Extremities After Cpn Local Anesthetic Block, Lora Asberry

Symposium of Student Scholars

Many older patients often suffer from walking issues such as Drop Foot. Drop Foot is caused by the malfunction of nerves in the foot, resulting in the loss of control of the front foot muscle. Within all of our patients, there has been a common fibular palsy, caused by the entrapment of the peroneal nerve. Due to this, they cannot lift up their foot. Some cases are permanent, while others are temporary. In the temporary cases, we have indicated a Phoenix Sign. The Phoenix Sign indicates that a nerve, presumed to be dead, has the capability to be recessed back …

Age-Related Reduction In High-Velocity Power And Myofiber Morphology And Composition, Ben Dalton

Symposium of Student Scholars

Power is diminished more dramatically at higher contraction velocities in older adults. It has been suggested that this may reflect age-related changes in single myofiber morphology or composition. PURPOSE: To examine power, muscle activation, and single myofiber morphology and composition between young (YM) and older (OM) males. METHODS: Power, or torque × velocity, was recorded during isokinetic knee extensions at 60°·s^-1 and 180°·s^-1 in healthy, untrained YM (n=15; 20.7±2.2 yrs) and OM (n=15; 71.6±3.9 yrs). The relative increase in power from 60°·s^-1 to 180°·s^-1 was recorded for each participant. Electromyography amplitude of the vastus lateralis (VL) …

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 …

Threshold Concentration And Random Collision Determine The Growth Of The Huntingtin Inclusion From A Stable Core, Sen Pei, Theresa C. Swayne, Jeffrey F. Morris, Lesley Emtage

Publications and Research

The processes underlying formation and growth of unfolded protein inclusions are relevant to neurodegenerative diseases but poorly characterized in living cells. In S. cerevisiae, inclusions formed by mutant huntingtin (mHtt) have some characteristics of biomolecular condensates but the physical nature and growth mechanisms of inclusion bodies remain unclear. We have probed the relationship between concentration and inclusion growth in vivo and find that growth of mHtt inclusions in living cells is triggered at a cytoplasmic threshold concentration, while reduction in cytoplasmic mHtt causes inclusions to shrink. The growth rate is consistent with incorporation of new material through collision and coalescence. …

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 …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. 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 …

Notch Signaling Represses Cone Photoreceptor Formation Through The Regulation Of Retinal Progenitor Cell States, Xueqing Chen, Mark M. Emerson

Publications and Research

Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized …

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 …

The Effect Of Freeze-Thaw Events On Dna Integrity In The Gray Treefrog (Hyla Versicolor), Georgia Ficarra

Masters Theses & Specialist Projects

Freeze-tolerant gray treefrogs survive winter by producing natural cryoprotectants and accommodating ice formation within extracellular spaces. While frozen, gray treefrogs endure hyperglycemia, dehydration, and anoxia due to the halt of all bodily functions. Upon thawing, the frogs’ anoxic cells receive a rapid influx of oxygen, which can cause oxidative damage to vital macromolecules including DNA. Previous studies have suggested freeze-tolerant frogs avoid oxidative damage after freeze-thaw events by elevating antioxidant activity, but recent work has shown upregulated DNA repair encoding genes in post-freeze frogs. The objective of this thesis is to assess the cellular costs of freezing by measuring oxidative …

High And Low Toxin Producing Strains Of Karenia Brevis Differ Significantly In The Redox Proteome, Lipid Profiles, And Xanthophyll Cycle Pigments, Ricardo Colon

FIU Electronic Theses and Dissertations

The dinoflagellate Karenia brevis, blooms annually in the Gulf of Mexico, producing a suite of neurotoxins known as the brevetoxins. The cellular toxin content of K. brevis, however, is highly variable between or even within strains. I investigated biochemical differences between high (KbHT) and low (KbLT) toxin producing cultures both derived from the Wilson strain, related to energy-dependent quenching (qE) by photosystem II, and the content of reduced thiols of the proteome. By characterizing the xanthophyll content of the two strains I was able to determine that KbLT performs qE inconsistently. To investigate the …

The Effect Of Fluid Flow Shear Stress And Substrate Stiffness On Yes-Associated Protein (Yap) Activity And Osteogenesis In Murine Osteosarcoma Cells, Thomas R. Coughlin, Ali Sana, Kevin Voss, Abhilash Gadi, Upal Basu-Roy, Caroline M. Curtin, Alka Mansukhani, Oran D. Kennedy

Publications and Research

Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/ physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in …

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …

Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina

Biology Faculty Publications

Global climate change has broad-ranging impacts on the natural environment and human civilization. Increasing average temperatures along with more frequent heat waves collectively have negative effects on cultivated crops in agricultural sectors and wild species in natural ecosystems. These aberrantly hot temperatures, together with cold stress, represent major abiotic stresses to plants. Molecular and physiological responses to high and low temperatures are intricately linked to the regulation of important plant hormones. In this review, we shall highlight our current understanding of how changing temperatures regulate plant hormone pathways during immunity, stress responses and development. This article will present an overview …

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 …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing …

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 …