Life Sciences Commons^™

Effects Of Picrotoxin Application On The Cardiac Ganglion Of The American Lobster, Homarus Americanus, John T. Woolley

Honors Projects

Picrotoxin (PTX) has been employed extensively as a tool within the crustacean stomatogastric nervous system (STNS) for its efficacy in blocking K⁺ and Cl⁺ currents gated by both GABA and glutamate. Through blocking some currents in the STNS, PTX allows for examination of other components without their presence. However, effects of PTX are relatively unknown within the lobster’s cardiac ganglion (CG). As an incredibly small nervous system of only nine neurons, the lobster CG presents an excellent model system for studying neural circuits. Given that the chemical synapses in the CG are mediated by glutamate, the present study …

Defining The Nuanced Nature Of Redox Biology In Post-Traumatic Stress Disorder, Emily C. Reed, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Post-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of …

The Investigation Of Novel Bovine Oocyte-Specific Long Non-Coding Rnas And Their Roles In Oocyte Maturation And Early Embryonic Development, Jaelyn Zoe Current

Graduate Theses, Dissertations, and Problem Reports

Early embryonic loss is a significant factor in livestock species' infertility, resulting in an economic deficit. In cattle, the in vivo fertilization rate is ~90%, with an average calving rate of about 55%, indicating an embryonic-fetal mortality rate of roughly 35%. Further, 70-80% of total embryonic loss in cattle occurs during the first three weeks after insemination, particularly between days 7-16. Growing evidence indicates that the oocyte plays an active role in regulating critical aspects of the reproductive process required for successful fertilization, embryo development, and pregnancy. However, defining oocyte quality remains enigmatic. Recently, many have abandoned the notion that …

Effects Of Altering Physiologically Relevant Cholesterol Levels And Media Types On Porin Gene Expression In Klebsiella Pneumoniae And The Resulting Impact On Antibiotic Resistance, Megan R. Camden

UNF Graduate Theses and Dissertations

Klebsiella pneumoniae is a Gram-negative, non-motile bacterium belonging to the Enterobacteriaceae family. K. pneumoniae is a rising threat in the clinical setting, as there has been a large increase in the presence of antibiotic resistant isolates. While much research is conducted on laboratory and clinical strains of bacteria, not much is known regarding the impact that human physiology can have on bacterial gene expression, and in response, to antibiotic susceptibility. The goal of this study is to determine if physiologically relevant cholesterol levels and media types impact porin gene expression and antibiotic resistance in K. pneumoniae. To accomplish this, …

Enhanced Central Sympathetic Tone Induces Heart Failure With Preserved Ejection Fraction (Hfpef) In Rats, Shyam S. Nandi, Kenichi Katsurada, Michael J. Moulton, Hong Zheng, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome characterized by diastolic dysfunction, concentric cardiac left ventricular (LV) hypertrophy, and myocardial fibrosis with preserved systolic function. However, the underlying mechanisms of HFpEF are not clear. We hypothesize that an enhanced central sympathetic drive is sufficient to induce LV dysfunction and HFpEF in rats. Male Sprague-Dawley rats were subjected to central infusion of either saline controls (saline) or angiotensin II (Ang II, 20 ng/min, i.c.v) via osmotic mini-pumps for 14 days to elicit enhanced sympathetic drive. Echocardiography and invasive cardiac catheterization were used to measure systolic and diastolic …

Elucidation Of The Role Of Agouti-Signaling Protein Throughout Folliculogenesis And Early Embryonic Development In Cattle, Heather L. Chaney

Graduate Theses, Dissertations, and Problem Reports

The oocyte expresses certain genes during folliculogenesis to regulate the acquisition of oocyte competence. Oocyte competence, which refers to the presence of imperative molecular factors in the oocyte that are critical for high oocyte quality, is directly related to the ability of the oocyte to result in a successful pregnancy following fertilization. Over the past few decades, the development and optimization of assisted reproductive technologies, particularly in vitrofertilization, have enabled the beef and dairy industries to advance cattle genetics and productivity. However, only approximately 40% of bovine embryos will develop to the blastocyst stage in vitro. In addition, bovine embryos …

The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto

Williams Honors College, Honors Research Projects

I investigated the effects of diet and sex on zebrafish bone metabolism. Zebrafish were subjected to either a high-calorie or low-calorie diet over a five-week period. After this diet, zebrafish scales were used to measure alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) enzyme activity with a fluorescent substrate. The enzyme activities were markers of the osteoblasts (ALP) and the osteoclasts (TRAP). These data were compared among sex and diet of the zebrafish using a repeated measures ANOVA statistical test. I also measured the number of resorption lacunae per scale (another indicator of osteoclast activity). The results showed higher TRAP …

Repeated Social Defeat Stress Induces An Inflammatory Gut Milieu By Altering The Mucosal Barrier Integrity And Gut Microbiota Homeostasis, Santosh K. Yadav, Rizwan Ahmad, Cassandra M. Moshfegh, Jagadesan Sankarasubramanian, Vineet A. Joshi, Safwan K. Elkhatib, Yashpal S. Chhonker, Goeffrey A. Talmon, Chittibabu Guda, Adam Case, Amar B. Singh

Journal Articles: Cellular & Integrative Physiology

Background

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual’s life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation.

Methods

We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the …

A Critical Role For Staphylococcal Nitric Oxide Synthase In Controlling Flavohemoglobin Toxicity, Ryan M. Singh, Sujata S. Chaudhari, Sasmita Panda, Elizabeth H. Hutfless, Cortney E. Heim, Dhananjay Shinde, Abdulelah A. Alqarzaee, Margaret F. Sladek, Vineet Kumar, Matthew C. Zimmerman, Paul D. Fey, Tammy Kielian, Vinai Chittezham Thomas

Journal Articles: Cellular & Integrative Physiology

Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S. epidermidis produces endogenous NO through its genetically encoded nitric oxide synthase (seNOS) and heavily relies on its activity for growth. In this study, we investigate the basis of the growth advantage attributed to seNOS activity. Our findings reveal that seNOS supports growth by countering Hmp toxicity. S. epidermidis relies on Hmp activity for its survival in the host under NO stress. …

Potential Of Synthetic And Natural Compounds As Novel Histone Deacetylase Inhibitors For The Treatment Of Hematological Malignancies, Dilipkumar Pal, Khushboo Raj, Shyam Sundar Nandi, Surajit Sinha, Abhishek Mishra, Arijit Mondal, Ricardo Lagoa, Jack T. Burcher, Anupam Bishayee

Journal Articles: Cellular & Integrative Physiology

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor …

Elevated Crp And Tnf-Α Levels Are Associated With Blunted Neural Oscillations Serving Fluid Intelligence, Sarah M. Dietz, Mikki Schantell, Rachel K. Spooner, Megan E. Sandal, Amirsalar Mansouri, Yasra Arif, Hannah J. Okelberry, Jason A. John, Ryan Glesinger, Pamela E. May, Elizabeth Heinrichs-Graham, Adam J. Case, Matthew C. Zimmerman, Tony W. Wilson

Journal Articles: Cellular & Integrative Physiology

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf.

METHODS: Seventy adults between the ages of 20-66 years …

Commonalities And Differences In Carotid Body Dysfunction In Hypertension And Heart Failure, Igor S. A. Felippe, Rodrigo Del Río, Harold D. Schultz, Benedito H. Machado, Julian F R Paton

Journal Articles: Cellular & Integrative Physiology

Carotid body pathophysiology is associated with many cardiovascular-respiratory-metabolic diseases. This pathophysiology reflects both hyper-sensitivity and hyper-tonicity. From both animal models and human patients, evidence indicates that amelioration of this pathophysiological signalling improves disease states such as a lowering of blood pressure in hypertension, a reduction of breathing disturbances with improved cardiac function in heart failure (HF) and a re-balancing of autonomic activity with lowered sympathetic discharge. Given this, we have reviewed the mechanisms of carotid body hyper-sensitivity and hyper-tonicity across disease models asking whether there is uniqueness related to specific disease states. Our analysis indicates some commonalities and some potential …

Sound The (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide Pgpp, Areej Malik, Megan A. Hept, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

It has recently become evident that the bacterial stringent response is regulated by a triphosphate alarmone (pGpp) as well as the canonical tetra- and pentaphosphate alarmones ppGpp and pppGpp [together, (p)ppGpp]. Often dismissed in the past as an artifact or degradation product, pGpp has been confirmed as a deliberate endpoint of multiple synthetic pathways utilizing GMP, (p)ppGpp, or GDP/GTP as precursors. Some early studies concluded that pGpp functionally mimics (p)ppGpp and that its biological role is to make alarmone metabolism less dependent on the guanine energy charge of the cell by allowing GMP-dependent synthesis to continue when GDP/GTP has been …

Dimerization Of Dopamine (D2) And Adenosine (A2a) Receptors, Elena Vukovic, Jackson M. Macatol

Williams Honors College, Honors Research Projects

This experiment will aim to explore the heterodimerization of Dopamine (D2) and Adenosine (A2A) receptors in cells when bound to different ligands. Borroto-Escuela et al. (2018) investigated the dimerization of the A2AR-D2R in rats when administered with cocaine, and they found that disrupting the A2AR-D2R complex restores the cocaine reward system in rats. This was a strong influence as to why we chose to investigate A2AR-D2R dimerization in Chinese hamster ovary (CHO) cells.

One goal that we have for this experiment is to combine our current laboratory skills with new laboratory techniques. There are constantly new techniques in labs, and …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

Auctus: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

MSU Graduate Theses

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

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 …

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 …

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 …

Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward

Doctoral Dissertations

Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could …

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. …

Assessing The Role Of Integrins In Contact Guidance By Substratum Topography, Robin S. Hong

Undergraduate Student Research Internships Conference

In this project, the effect of blocking integrin subunits on contact guidance of human periodontal ligament fibroblasts were assessed. Imaging was gathered through Timelapse imaging of live cells as well as immunohistochemistry of fixed cells at designated timepoints.

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 …

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

Dissertations & 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) …

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 …

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

Dissertations & 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 …

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 …

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 …

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 …

Biochemistry Of Trehalose Accumulation In The Spring Field Cricket, Gryllus Veletis, Alyssa R. Stephens

Electronic Thesis and Dissertation Repository

The freeze tolerant spring field cricket, Gryllus veletis, accumulates trehalose in the blood and tissues during cold acclimation. Trehalose is the main blood sugar in insects, thus its blood concentration is tightly regulated, and trehalose is readily metabolized. How do crickets modify their metabolism to accumulate trehalose in their hemolymph and tissues? I hypothesized that trehalose production, transport, and consumption were modified during the cold acclimation to facilitate trehalose accumulation. Trehalose and the trehalose-specific transporter, TRET-1, are distributed among all tissues, and trehalose accumulates in the hemolymph, fat body, Malpighian tubules, and gut. Trehalose production increases during cold acclimation …