Physiology Commons^™

Modulating Oran Nitrate-Reducing Bacteria To Enhance Nitric Oxide Bioavailability As A Therapeutic Target For Atherosclerosis, Donovan C. Davidson

CMC Senior Theses

Atherosclerosis remains the primary driver of global cardiovascular disease, yet clinical interventions are largely restricted to high-cost, invasive procedures only after it has reached a critical stage. Recent research has identified a connection between the oral microbiome and vascular health via the enterosalivary nitrate-nitrite-nitic oxide (NO) pathway. Oral nitrate-reducing bacteria (ONRB) drive the synthesization of NO by reducing dietary nitrate into nitrite, which is then converted into bioavailable NO. NO is a potent vasodilator that maintains endothelial health by suppressing inflammation through inhibiting the expression of adhesion molecules VCAM-1 and ICAM-1. However, this pathway is easily compromised by dysbiotic oral …

Acid-Base Regulation Mechanisms In The West African Lungfish Protopterus Annectens: An Investigation Into The Role Of The Sodium Proton Exchanger (Nhe), Victor H. Q. Pham-Ho Msc

Theses and Dissertations (Comprehensive)

The lungfish possesses a primitive lung and underdeveloped gills, making use of bimodal respiration. Like other freshwater fishes they must regulate ion- and acid-base equilibrium through active ion uptake (driven by pumps and ion transporters), albeit with challenges due to their underdeveloped gills. My thesis aimed to elucidate the role of the sodium proton exchangers (NHE), encoded by the genes slc9a1/nhe1, slc9a2/nhe2 and slc9a3/nhe3, which are hypothesized to contribute towards acid-base regulation. Pharmacologically, amiloride, a sodium-transport inhibitor, and 5-(N-Ethyl N-isopropyl)-Amiloride (EIPA), an NHE specific inhibitor, affected whole-animal titratable acidity and ammonia fluxes, supporting a physiological function of the NHE. Next, …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

Expanding The Role Of Muscle Stem Cell Fusion In Muscle Under Hypertrophic Stimulus, Jensen Goh Zhong Sheng

Theses and Dissertations--Physiology

Muscle stem cells (MuSCs) are a unique stem cell population that can activate in response to both injury and growth stimuli. Studies on muscle regeneration have shown MuSC activation follows a uniform progression through proliferation, differentiation, and fusion. Therefore, to determine whether MuSC replication is a prerequisite for differentiation under hypertrophic stimulus, I used a lineage-tracking mouse model (Pax7^rtTA; TRE-H2B-GFP) to label MuSC nuclei and simultaneously tracked DNA synthesis via EdU incorporation. This dual-labeling approach allowed us to not only distinguish MuSC-derived nuclei but also demarcate which MuSC had proliferated prior to fusion. I then employed a mechanical …

A Tale Of Two Serpins: Pathologic And Protective Roles Of Agt And Pai-1 In Metabolic And Cardiovascular Disease, Alex C. Pettey

Theses and Dissertations--Physiology

Metabolic and cardiovascular diseases are leading causes of morbidity and mortality worldwide. Conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), aortic aneurysm, and cardiac fibrosis have limited pharmacological therapies, underscoring the need for deeper mechanistic investigations. Serine protease inhibitors (serpins) have been implicated in these pathologies and represent potential therapeutic targets. Despite structural homology, serpins regulate diverse physiological processes through both protease inhibition and non-inhibitory mechanisms. This dissertation examines the roles of two serpins, angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1), in preclinical models of metabolic and cardiovascular disease to identify novel mechanisms that may inform future therapeutic strategies. …

Severity And Duration-Dependent Aortic Stiffening In A Rabbit Coarctation Model Identifies Constitutive Material Parameters As Promising Regional Biomarkers For Hypertension Progression, Arash Ghorbannia, Jamasp Azarnoosh, John F. Ladisa Jr.

VMASC Publications

Coarctation of the aorta (CoA) alters hemodynamics and drives regional remodeling, yet the influence of severity and duration on constitutive properties is undefined. We quantified mechanical responses from CoA to identify constitutive parameters capturing stiffening across clinical severities and durations. Mild (≤ 12 mmHg), intermediate (13–20 mmHg), and severe (> 20 mmHg) CoA was created in rabbits for short, long, and prolonged durations (~ 1, 3, or 22 weeks, respectively). Stress–stretch curves from proximal and distal regions were fit with multiple constitutive models (Linear Elastic, Neo-Hookean, Yeoh, Ogden, Mooney–Rivlin, Holzapfel). Model performance was evaluated by normalized RMSE and R², with …

Systematics Of Disk-Winged Bats (Thyroptera), Courtney L. Klumpp

Capstone Showcase

This thesis investigates the evolutionary relationships among disk-winged bats in the genus Thyroptera, a small group of Neotropical bats known for the adhesive suction disks on their wings and feet that allow them to roost inside tightly rolled leaves. The distinctive morphology and behavior of these bats have not been extensively documented, and their phylogenetic relationships remain only partially resolved. The goal of this research is to better understand how these species are related to one another and to determine whether the five recognized species of Thyroptera form a single monophyletic group. To address this question, morphological and genetic …

Bmal1 Mediates Sex-Specific Circadian Regulation Of Cardiac Ion Channels And Temporal Arrhythmia Vulnerability, Brian P. Delisle, Ezekiel Rozmus, Abhilash Prabhat, Spencer B. Procopio, Xiping Zhang, Emilia Entcheva, Karyn A. Esser, Elizabeth Schroder

Physiology Faculty Publications

No abstract provided.

C/Ebpα Is Essential For Gonadal But Not Inguinal White Adipose Tissue Formation In Mice, Krista Y. Hu, Yu-Lin Ma, Esme A. Dodge, Olivia A. B. Maguire, Caio V. Matias, Ryan K. Barney, Hector S. Himede, Juliana Gomez Pardo, Miriam Cepeda, Scott M. Gordon, Robert C. Bauer

Physiology Faculty Publications

Objective: The distribution of excess white adipose tissue (WAT) in obesity correlates with risk for comorbidities. Thus, understanding depot-specific WAT developmental mechanisms is translationally relevant. SNPs near the gene CEBPA associate with waist to hip ratio, and while C/EBPα is a recognized regulator of adipogenesis, there is no previously known role for C/EBPα in regulating adipose distribution.

Methods: We crossed Cebpa floxed mice to the AdipoQ-Cre transgenic mouse strain, generating mice with adipocyte-specific knockout of Cebpa (Cebpa_ASKO). Mice were phenotyped on a chow diet and after prolonged high-fat diet (HFD) feeding.

Results: Cebpa_ASKO mice almost entirely lack gonadal …

Dim Light At Night Worsens Cardiac Autonomic Dysregulation In Female Diabetic Mice, Abhilash Prabhat, Shrishti Naidu, Isabel G. Stumpf, Tanya S. Seward, Elizabeth A. Schroder, Brian P. Delisle

Physiology Faculty Publications

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. CAN is characterized by impaired cardiovascular autonomic control and is associated with increased mortality, especially among women with type 2 diabetes. Identifying environmental factors that exacerbate the CAN-associated phenotype may reveal modifiable strategies to reduce cardiovascular risk.

Nighttime light exposure is a novel cardiovascular risk factor. Among ∼90,000 individuals, greater nighttime light exposure correlated with increased atrial fibrillation and heart failure risk. Light at night disrupts sympathovagal balance and elevates nocturnal heart rate in humans. Dim light at night similarly disrupts autonomic regulation of heart rate in mice. We …

Early Microglial Response To Amyloid Plaques Drives Sleep Loss In Alzheimer’S Disease, Nicholas J. Constantino, Riley E. Irmen, Matthew J. Lanning, Sierra M. Turner, Clair C. Ashley, Caitlin M. Carroll, Evan M. Neary, Dave Rubinow, J. Andy Snipes, Shannon L. Macauley

Physiology Faculty Publications

Introduction: Sleep disruption is an early feature of Alzheimer's disease (AD), but the cellular mechanisms linking amyloid pathology to sleep loss remain unclear.

Methods: Electroencephalography/electromyography (EEG/EMG) recordings, quantitative EEG analysis, and sleep deprivation were performed in APPswe/PSEN1dE9 (APP/PS1) mice at different stages of pathology relative to normal aging. Amyloid burden and microglial density were quantified with whole-brain light-sheet microscopy. CSF1R-mediated microglial depletion explored effects of microglia on sleep loss.

Results: Amyloid plaques caused non–rapid eye movement (NREM) sleep loss that did not worsen with increased plaque burden. Aging reduced REM sleep and eliminated sleep rebound. Amyloid pathology was associated with …

Ultrasound-Derived Liver Composition And Metabolic Flexibility Under Exercise Stress, Rhodes Van Houten

All Master's Theses

Metabolic Associated Fatty Liver Disease (MAFLD) is characterized by abnormal liver fat accumulation in conjunction with metabolic syndromes. MAFLD affects 33% of individuals worldwide, though little is known about how increased liver fat impacts physiological responses to exercise. This study aimed to analyze the relationship between liver composition and metabolic flexibility during a graded exercise test.  Body composition was analyzed via dual-energy X-ray absorptiometry. Liver ultrasound was evaluated for echogenicity, where elevated mean gray volume (MGV) indicates abnormal liver tissue. Rates of fat (FATox) and carbohydrate (CHOox) oxidation (g/min), respiratory exchange ratio (RER), and blood lactate concentrations ([LA^-], …

Low Energy Availability And Dietary Factors In High School Runners, Natalie E. Allik

All Master's Theses

Context: Low energy availability (LEA) is associated with adverse health and performance outcomes in athletes and may be particularly concerning during adolescence when growth and bone development are ongoing. Although inadequate carbohydrate (CHO) intake has been proposed as a contributor to LEA, limited research has examined this relationship in adolescent endurance athletes. Objective: To examine dietary intake, bone mineral density (BMD), and eating disorder (ED) risk in adolescent distance runners with and without LEA. Methods: Eighteen adolescent distance runners (15.7 ± 1.2 years; 7 males, 11 females) completed baseline assessments including anthropometrics, dual-energy X-ray absorptiometry (DXA), a 24-hour dietary recall, …

Human Plasma Extracellular Vesicles As An Exercise Mimetic To Preserve Skeletal Muscle Plasticity During Disuse, Alexander M. Fliflet, Yanqi Tan, Takeshi M. Barnes, Ane Nishitha Vijayan, Sung Jun Choi

Kinesiology & Sport Management Scholarship

The purpose of this study was to determine the extent to which extracellular vesicles (EVs) circulating in blood after exercise training act as an effective mimetic to maintain skeletal muscle mass during unloading and/or accelerate recovery after disuse. Ten healthy males (27.7 ± 7.1 y) were recruited for a 6-week progressive resistance and endurance training program. EVs were isolated from blood before (EVs) or immediately after training (ExerVs). EVs were intraperitoneally injected into male mice (4×; 3 × 108 particles/injection) during 14 days of hindlimb unloading (HU), then the muscles were collected immediately or 7 days after HU. ExerVs did …

How Effective Is Online Teaching Of Physiology Modules? Perception Of Rwandan Health Sciences Students, Abdullateef Isiaka Alagbonsi, Mojeed Akorede Gbadamosi, Mathieu Nemerimana, Makinde V. Olubiyi, Olufunke Onaadepo, Akaninyene Ubong Ime, Abdul-Rahuf Aderemi Feyitimi, Ruth Wanjiru Mungai, Florent Rutagarama, Simiat Elias

Biomedical Sciences, East Africa

Background: While blended teaching is approved in Rwandan medical education, the perceived effectiveness of online-only delivery for physiology modules remains unclear. This uncertainty limits its continued use. The present study assessed Rwandan health sciences students’ perceptions of the effectiveness of online teaching for physiology modules.

Methods: A total of 528 students from medicine and surgery (n = 300), pharmacy (n = 99), dentistry (n = 89), and clinical psychology (n = 40) programs at the University of Rwanda completed an online questionnaire. Data were analyzed using multivariable logistic regression and non-parametric tests (Mann-Whitney U, Kruskal-Wallis) with corresponding effect …

Spiders In The World Of Pesticides: A Review, Jackson L. Mendillo

Williams Honors College, Honors Research Projects

Pesticides and other agrochemicals have varying effects on spiders depending on their mechanism of action and dosage, ranging from behavioral changes and ataxia, to reproductive changes and physiological stress, to lethal non-target effects. Additionally, peptide Hv1a has promising effects as a more narrow-spectrum pesticide.

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …

Feeding Mode Is Associated With Infant Night Sleep Trajectories During The First Postnatal Year, Magdalena Olson, Li Liu, Elizabeth Reifsnider, Dean V. Coonrod, Sarada S. Panchanathan, Megan E. Petrov, Corrie M. Whisner

Ellmer School of Nursing Faculty Publications

Background: Short sleep and formula feeding during infancy are associated with increased risk of childhood obesity. Feeding practices and sleep arrangements vary during infancy and may also be dynamic, yet their impact on infant night sleep duration remains unclear. Understanding these relationships is crucial for formulating recommendations to support breastfeeding and address sleep concerns. Objective: We examined the association between feeding mode and parent-reported infant night sleep duration during the first postnatal year, while additionally evaluating night-weaning and bedsharing as contextual sleep-related practices. Methods: Infants in the Phoenix Metropolitan Area (n = 193) were followed up at 3, 8, 13, …

Estrogen Deprivation During Primate (Papio Anubis) Pregnancy: Impact On Systemic Microvascular Flow And Cardiovascular Development And Function After Birth In Offspring, Sifa Turan, Jeffery S. Babischkin, Graham W. Aberdeen, Gerald J. Pepe, Eugene D. Albrecht

Department of Biomedical and Translational Sciences Faculty Publications

Background

Suppressing estradiol (E₂) during baboon pregnancy lowers offspring skeletal muscle capillary density, vital for insulin-mediated glucose uptake, and induces insulin resistance. We examined whether E₂ deprivation also impairs microvascular flow and cardiac function.

Methods

Offspring of untreated baboons, letrozole-treated baboons, or letrozole plus E₂ (maternal s.c. injections during the second half of gestation) underwent contrast-enhanced microbubble ultrasonography to quantify microvessel flow and echocardiography to assess cardiac performance.

Results

Letrozole reduced maternal serum E₂ by 95% (p <  0.01). In letrozole offspring, microbubble flux rate (β) fell 55% (p <  0.02), replenishment was 5 s slower (p <  0.03), and microvessel flow declined 40% (p = 0.05); all were restored by added E₂. Indices of systolic (isovolumic contraction), diastolic (isovolumic relaxation), global performance (Tei index), and cardiac output were unchanged.

Conclusion

Prolonged gestational E₂ deprivation programs a reduction in microvascular flow without altering cardiac function; maternal E₂ prevents this, supporting E₂'s role in …

The Histamine-3 Receptor In Cardiac Fibrosis: A Novel Role In Fibroblast Function, Heather Linsky

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the United States, heart failure affects approximately 6.7 million individuals. Despite a number of available therapies, heart failure prevalence continues to grow, suggesting the need for a broader range of effective therapies. More specifically, heart failure with preserved ejection fraction comprises approximately 50% of all heart failure cases and, as the name suggests, is a disease of diastolic dysfunction as opposed to systolic dysfunction. A hallmark of heart failure with preserved ejection fraction is myocardial fibrosis, which is a key contributor to diastolic dysfunction, and is the major focus of this dissertation work. In the heart, histamine-3 receptor activation …