Cellular and Molecular Physiology Commons^™

Underlying Mechanism Of Ovarian Reserve Preservation From Gonadotoxicity, Yi Luan

Theses & Dissertations

Cancer therapies often lead to premature ovarian insufficiency by ovarian damage and follicle depletion. However, the oocyte death pathway induced by chemotherapies has been debated. Here we clarified the precise mechanism of ovarian depletion induced by cyclophosphamide and doxorubicin. Cyclophosphamide induced direct apoptosis in oocytes rather than overactivation of primordial follicles. Dormant oocytes instead of activated oocytes with high PI3K activity were more sensitive to cyclophosphamide. Although the ABL inhibitor, GNF2, has been proposed to ameliorate the apoptosis of primordial follicles against cyclophosphamide, GNF2 did not prevent the loss of primordial follicles induced by cyclophosphamide in the systems tested. Oocyte-specific …

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …

Effect Of Umbilical Cord Essential And Toxic Elements, Thyroid Levels, And Vitamin D On Childhood Development, Jesse Cottrell, Chelsea Nelson, Catherine Waldron, Mackenzie Bergeron, Abigail Samson, Monica Valentovic

Biomedical Sciences

Introduction: The in-utero environment has dramatic effects on childhood development. We hypothesized prenatal levels of inorganic agents, thyroid levels, and Vitamin D effect childhood development.

Methods: Umbilical cord blood was collected from April 3, 2013 to January 30, 2014 and analyzed for 20 different elements, thyroid and Vitamin D. A retrospective review (n = 60) was performed of well-child examinations from birth to 5 years old (y.o.).

Results: There were associations with calcium and 4 month BMI (p = <0.01), 12 month language (p = 0.03); Magnesium and 6 month language (p = 0.04) and gross motor skills at 5 years old (y.o.) (p = 0.03); Copper and 12 month fine motor (p = 0.02); Zinc with fine motor (p = <0.01) and language (p = 0.03) at 2 y.o.; Manganese was associated with language development at 2 y.o. (p = 0.02); Molybdenum and fine motor at 12 months of age (p = 0.02); Selenium with gross motor (p = 0.04) and BMI (p = 0.02) at 5 y.o.; Lead with cognitive function at 4 months (p = 0.04) and 2 y.o. (p = 0.01); Mercury with gross motor at 4 months (p = 0.04) and language at 2 y.o. (p = 0.02). Platinum at 12 months of age (p = <.01) as well as multiple associations at 5 y.o. (p = <.01). Thyroid function tests for free T3 were associated with multiple cognitive and physical milestones. T3 Uptake was associated with 5 y.o. gross motor skills (p = 0.02). Total and Free T4 was associated with cognitive development (p = <.01) and fine motor development, respectively. Vitamin D was associated with a delay of fine motor development (p<0.01).

Conclusion: There were multiple associations between umbilical cord essential and toxic elements, thyroid levels, and Vitamin D on childhood development.

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …

Ca2+ Entry Units In A Superfast Fish Muscle, James Matthew Kittelberger, Clara Franzini-Armstrong, Simona Boncompagni

Biology Faculty Publications

Over the past two decades, mounting evidence has demonstrated that a mechanism known as store-operated Ca2+ entry (SOCE) plays a crucial role in sustaining skeletal muscle contractility by facilitating Ca2+ influx from the extracellular space during sarcoplasmic reticulum (SR) Ca2+ depletion. We recently demonstrated that, in exercised fast-twitch muscle from mice, the incidence of Ca2+ entry units (CEUs), newly described intracellular junctions between dead-end longitudinal transverse tubular (T-tubule) extensions and stacks of sarcoplasmic reticulum (SR) flat cisternae, strictly correlate with both the capability of fibers to maintain contractions during fatigue and enhanced Ca2+ influx via SOCE. Here, we tested the …

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …

Unraveling The Effects Of Aerobic Exercise And Erk5 Signaling In The Solid Tumor Microenvironment Using Murine Models, Hannah Savage

Dissertations and Theses (Open Access)

Solid tumors are comprised of multiple cell types which communicate and work together to promote tumor progression. Advances in the treatment of solid tumors have armed clinicians with more efficacious pharmacologic agents and combinations. However, a focus on drug adjuvants in the treatment of solid cancer has left gaps in knowledge regarding non-pharmacologic treatment adjuvants, like aerobic exercise. The current dissertation investigates pharmacologic and non-pharmacologic based approaches to remodel the solid tumor microenvironment landscape and alter therapeutic efficacy. We disassemble compartments of the tumor microenvironment, including tumor vasculature and immune infiltrate, using mouse models and single cell techniques, to elucidate …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Expression Of Claudins In Gill And Opercular Membranes In Relation To Osmoregulation In Euryhaline Atlantic Killifish, Fundulus Heteroclitus, Allison Mcfarland

Graduate Theses and Dissertations

Atlantic killifish (Fundulus heteroclitus) are euryhaline teleosts, which means they can thrive in environments with varying salinities, ranging from concentrated seawater (SW) to dilute fresh water (FW) and thus survive in estuaries. To be able to maintain ionic and osmotic homeostasis in these diverse salinities, osmoregulatory organs like gill and opercular membrane must be able to adjust the permeability and transport of water and ions. The surface epithelia in these organs need to prevent the passive flux of ions and water in a drastically changing environment, while being able to switch between active ion secretion or uptake dependent upon environmental …

Effects Of Chronic Stress On Safety Processing And Physiology In The Medial Prefrontal-Amygdala-Basal Forebrain Circuit, Itamar S. Grunfeld

Dissertations, Theses, and Capstone Projects

Chronic stress increases generalization of fear to non-threatening cues, a key symptom in numerous psychiatric mood disorders. However, the mechanisms through which stress impacts safety learning remain poorly understood. To probe the relationship between stress and safety learning, this dissertation employed multiple behaviors, in conjunction with in-vivo multisite physiology during explicit safety and fear discrimination learning. In Chapter 1, I outline the role of chronic stress in driving neurological adaptations that result in generalized fear and highlight how this occurs because of impaired safety cue encoding. In Chapter 2, I show that chronic stress in the form of social defeat …

From Young To Old: The Effects Of Sedentary-Aging And Exercise Interventions On Structural Plasticity Of Lumbar Motor Neurons, Nmj, And Glial Cell Line-Derived Neurotrophic Factor Expression, Alberto Felipe Cintron-Colon

Dissertations

Neuromuscular weakness has been associated with age progression. A possible reason is a disconnection between muscle and neuron, causing components from both the central and peripheral nervous systems to deteriorate. Exercise, however, has beneficial effects for both muscle and nervous tissue, inducing neuroprotection. Neurotrophic factors are powerful regulators of neuronal maintenance and synaptic strength. Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor that has been shown to be a potent survival factor for somatic motor neurons that innervate skeletal muscle.

This study aims to evaluate changes in structural plasticity of motor neurons in the lumbar spinal cord and …

A Neuromuscular Look Into Genetics Of Muscle Aging, Christina Talley

Master of Science in Integrative Biology Theses

As individuals age throughout their life, they experience muscle tissue loss that impacts their quality of life such as a decrease in their physical capabilities and sometimes even their mental capacity. The process of muscle aging is the key point of this study. This involves the individual’s muscles and the motor neurons that control them. Skeletal muscles are used daily to maintain posture, stand, walk, etc. Throughout a lifetime these muscles undergo damage and need to be repaired. When the muscles are repaired, they express physical changes. The tissue shrinks in size and eventually the composition of the tissue is …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

Preparation Of Proteins And Peptides From Heat-Stabilized Defatted Rice Bran Via Solid State Fermentation And Investigating For Skin Health, Ali A. Bisly

Graduate Theses and Dissertations

Heat-stabilized defatted rice bran (HDRB) is an abundant and inexpensive agro-industrial by-product of rice milling and rice oil extraction process. Furthermore, HDRB is a potential source of proteins. However, the direct protein extraction has low yield of protein due to the impact of heat stabilization and oil extraction process which made the HDRB proteins bound and interact with other components. This research is based on using solid-state fermentation (SSF), which is a natural and cost-effective approach to facilitate protein extraction from HDRB using Bacillus subtilis (natto) Takahashi as a microorganism.

Response surface methodology (RSM) analysis was used with Box-Behnken design …

Exploring Indicator Displacement Assays For Phosphate Detection In Seawater, Francis Radics

Chemistry & Biochemistry Student Scholarship

Francis Radics ’22
Major: Biochemistry
Faculty Mentor: Dr. John Breen, Chemistry and Biochemistry

Indicator displacement assays are based on the optical signal modulation of a noncovalently bound indicator upon dissociation by an analyte species. Our work has focused on exploring the lower detection limits for luminescent displacement assays for inorganic phosphate in seawater using complex ions containing two di(2-picolyl)amine ligands (also called DPA or bis(2-pyridylmethyl)amine), each coordinating a zinc cation. Following the work of B.D. Smith and coworkers, we have prepared three ligands by covalently attaching two DPA moieties, 2,6-bis(chloromethyl) benzene, and 2,6-bis(chloromethyl)-4-methylphenol, and 1,2-phenylenedimethylamine, for assays with 6,7-dihydroxy-4-methanesulfonic acid …

Carbonyl Iron Vs Ferrous Sulfate On Blood Iron Markers In Male Division Iii Cross-Country Athletes, Sam Gunter

Student Scholar Showcase

Competitive distance runners are often predisposed to developing iron deficiency. This study aimed to determine if carbonyl iron was more effective at maintaining blood iron markers and minimizing overall fatigue and GI stress than ferrous sulfate. In this randomized, independent groups study, 7 male, division III cross-country athletes were supplemented with either carbonyl iron or ferrous sulfate for 6 weeks. Blood hemoglobin, hematocrit, subjective GI distress, subjective fatigue, and relative exertion of recent training were assessed at baseline, 3 and 6 weeks. Results will be analyzed via a detailed analysis of variance to determine significant differences in outcome measures. Statistical …

Investigation Of Oncogenic Ras And Endoplasmic Reticulum-Mitochondria Calcium Flux And Their Relationship In The Context Of Tumorigenesis, Emma Anderson

Senior Honors Theses

Intracellular calcium as a signaling molecule is a pervasive feature of cellular pathways, especially those that manage internal homeostasis and transitions through the cell cycle, so much so that regulated, responsive calcium flux between the endoplasmic reticulum (ER) and the mitochondria has been suggested to play a major role in cancer development. Another factor commonly implicated in tumorigenesis is RAS, an oncogene that controls signaling for many pathways that are also regulated by calcium. While both calcium and oncogenic RAS signaling are implicated in cancer development, possible links between them have yet to be determined. The identification of these links …

A Ketogenic Diet Enhances Hippocampal Mitochondrial Efficiency, Cali E. Warren, Erin R. Saito, Benjamin T. Bikman

Library/Life Sciences Undergraduate Poster Competition 2022

Mitochondrial dysfunction and cognitive impairment are common symptoms in many neurologic disorders, as well as in nonpathological aging. Ketones have been suggested as therapeutic for their relevance in epilepsy and other neurodegenerative diseases and psychiatric disorders such as Alzheimer’s and Parkinson’s disease, schizophrenia, and major depressive disorder.

The Coxsackievirus And Adenovirus Receptor Has A Short Half-Life In Epithelial Cells, Poornima Kotha Lakshmi Narayan, James M. Readler, Mahmoud S. Alghamri, Trisha L. Brockman, Ray Yan, Priyanka Sharma, Vladislav Snitsarev, Katherine J.D.A Excoffon, Abimbola O. Kolawole

Department of Biology Faculty Scholarship and Creative Works

The coxsackievirus and adenovirus receptor (CAR) is an essential cellular protein that is involved in cell adhesion, cell signaling, and viral infection. The 8-exon encoded isoform (CAREx8) resides at the apical surface of polarized epithelia, where it is accessible as a receptor for adenovirus entering the airway lumen. Given its pivotal role in viral infection, it is a target for antiviral strategies. To understand the regulation of CAREx8 and determine the feasibility of receptor down regulation, the half-life of total and apical localized CAREx8 was determined and correlated with adenovirus transduction. Total and apical CAREx8 has a relatively short half-life …

Comparative Genomics, Evolutionary Epidemiology, And Rbd-Hace2 Receptor Binding Pattern In B.1.1.7 (Alpha) And B.1.617.2 (Delta) Related To Their Pandemic Response In Uk And India, Chiranjib Chakraborty, Ashish Ranjan Sharma, Manojit Bhattacharya, Bidyut Mallik, Shyam Sundar Nandi, Sang-Soo Lee

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant.

METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, …

T-Lymphocyte Tyrosine Hydroxylase Regulates T H 17 T-Lymphocytes During Repeated Social Defeat Stress, Safwan K. Elkhatib, Cassandra M. Moshfegh, Gabrielle F. Watson, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which results in deleterious changes to psychological and physical health. Patients with PTSD are especially susceptible to life-threatening co-morbid inflammation-driven pathologies, such as autoimmunity, while also demonstrating increased T-helper 17 (T_H17) lymphocyte-driven inflammation. While the exact mechanism of this increased inflammation is unknown, overactivity of the sympathetic nervous system is a hallmark of PTSD. Neurotransmitters of the sympathetic nervous system (i.e., catecholamines) can alter T-lymphocyte function, which we have previously demonstrated to be partially mitochondrial redox-mediated. Furthermore, we have previously elucidated that T-lymphocytes generate their own catecholamines, and strong …

Time-Dependent Alteration In The Chemoreflex Post-Acute Lung Injury, Kajal Kamra, Nikolay Karpuk, Ryan Adam, Irving H. Zucker, Harold D. Schultz, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar-capillary endothelial barrier which impairs gas exchange to induce hypoxemia that reflexively increases respiration. The neural mechanisms underlying the respiratory dysfunction during ALI are not fully understood. The purpose of this study was to investigate the role of the chemoreflex in mediating abnormal ventilation during acute (early) and recovery (late) stages of ALI. We hypothesized that the increase in respiratory rate (fR) during post-ALI is mediated by a sensitized chemoreflex. ALI was induced in male Sprague-Dawley rats using a single intra-tracheal injection of bleomycin (Bleo: low-dose = 1.25 mg/Kg or …

Deciphering The Role Of Mitochondrial Physiology And Thermal Acclimation In Shaping Whole Organismal Performance Of An Invasive Forest Pest, Essa Alrashdi

Masters Theses

Environmental factors such as temperature are substantial determinants of the spongy moth, L. dispar, distribution, reproduction, and growth. Accumulating energy reserves at the larval stage is particularly important to L. dispar, since the larvae metamorphose into a fully-grown, non-feeding adult. As non-feeding adults, the energy balance of the pupae must be adequate, to ensure enough energy reserves for adult dispersal, egg maturation and overall persistence of the species in the region. At this stage, environmental temperature also determines daily metabolic demands, and the overall cost of sustaining ecologically relevant activities. Various hypotheses describing a mismatched growth and metabolic …

Targeting Bcl-2 Family Proteins In Therapy Induced Senescent Cancer Cell Models, Wade Cook

Theses and Dissertations

Non-small Cell Lung Cancer (NSCLC) originates from numerous different cell types in the lungs and is among the deadliest of cancers. Head and Neck Squamous Cell Carcinomas (HNSCC) are derived from the mucosal membranes of the oral cavity, pharynx, and larynx. Both NSCLC and HNSCC are predominately caused by tobacco smoke inhalation and as such mutations in the tumor suppressor gene TP53 are common. Since similarities exist in the root cause of NSCLC and HNSCC, they may also share similarities in treatment methods. Cisplatin is a platinum-based DNA damaging agent that has been used as a cancer chemotherapy for decades. …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

The Role Of Nitric Oxide In Inter- And Intra- Cellular Signaling In Plant Defense, Fan Xia

Theses and Dissertations--Plant Pathology

Plants have evolved a sophisticated immune system to defend themselves against pathogens. This immune response can be triggered in response to pathogen-associated molecular patterns (PAMP) or specialized effectors that are recognized by the plant resistance (R) proteins. The latter, commonly referred to as effector-triggered immunity (ETI), is well known to induce broad-spectrum resistance throughout the plants. This phenomenon known as systemic acquired resistance (SAR) is regulated by several chemical signals including salicylic acid (SA), and free radical nitric oxide (NO) and reactive oxygen species (ROS). These signals operate in two parallel branches with NO/ROS functioning downstream of pipecolic acid (Pip) …

Optimization Of Electrically Driven Fluid Flow Through Tissue Hydrogels, Joseph C. Walker

Electronic Theses and Dissertations

No abstract provided.

Supplemental Peer Instruction In Physiologic Core Concept Education, Austin Choat

Honors Program: Senior Projects (Public)

The objective of my thesis project was to create and research the importance of supplemental learning videos within core physiological concepts identified by the Advancement of Physiological Principles for the purpose of assisting Dr. Kim Hansen in better educating students with less extensive foundational knowledge of chemical and biological sciences. Through researching the benefits of peer instruction, identifying core physiological concepts crucial to wholistic physiology education, and describing a student population hypothesized to benefit substantially from the work, I created educational videos to aid Dr. Hansen in her work as an educator and in the educational research she is striving …