Cellular and Molecular Physiology Commons^™

Exposure To Pm2.5 And Aging., Daniel Chris Gomes

Electronic Theses and Dissertations

Inhalation of fine airborne particulate matter (PM_2.5) is an environmental risk factor for numerous health disorders, including cardiovascular diseases (CVD). While several studies have shown that PM_2.5 exposure can induce oxidative stress, DNA damage, and inflammation, the underlying mechanisms that translate these effects into systemic pathology remain poorly understood. Some recent studies have shown that PM_2.5 exposure can lead to telomere shortening in leukocytes, but the generality of this outcome and contribution to endothelial dysfunction has not yet been fully explored. We hypothesized that PM_2.5inhalation accelerates cellular aging and senescence in both circulating peripheral …

Establishing Procedures For Primary Human Myoblast Cell Culture, Erica Duffy

Biomedical Engineering

Peripheral Artery Disease (PAD) affects an estimated 200 million people worldwide and is the leading cause of amputation in the United States. PAD is characterized by atherosclerotic narrowing of arteries, resulting in ischemia from reduced blood flow to distal tissues. Although surgical and percutaneous interventions can restore perfusion, fewer than 50% of patients experience sustained benefit, highlighting the need for alternative therapeutic strategies. One promising approach is promoting arteriogenesis, the growth and outward remodeling of pre-existing collateral vessels that improve blood flow around the occluded arteries. Arteriogenesis is regulated by regenerative, M2-polarized macrophages, making macrophage polarization a key therapeutic target. …

Rebound Bursting Selectively Enables Fast Dynamics In Dopamine Midbrain Neurons Projecting To The Dorsolateral Striatum, Strahinja Stojanovic, Christopher J. Knowlton, Richard Egger-Mackrodt, Johanna Mankel, Josef Shin, Stephan Lammel, Carmen C. Canavier, Jochen Roeper

School of Graduate Studies Faculty Publications

Dopamine (DA) midbrain neurons are involved in a wide array of key brain functions including movement control and reward-based learning. They are also critical for major brain disorders such as Parkinson's disease or schizophrenia. DA neurons projecting to distinct striatal territories are diverse with regard to their molecular makeup and cellular physiology, which are likely to contribute to the observed differences in temporal DA dynamics. Among these regions, the dorsolateral striatum (DLS) displays the fastest DA dynamics, which might control the moment-to-moment vigor and variability of voluntary movements. However, the underlying mechanisms for these DLS-specific fast DA fluctuations are unresolved. …

Female Cardioprotection In A Mouse Model Of Alcohol-Associated Cardiomyopathy, Joshua M. Edavettal, Meagan Donovan, Nicholas R. Harris, Xavier R. Chapa-Dubocq, Keishla M. Rodríguez-Graciani, Janos Paloczi, Liz Simon, Bysani Chandrasekar, Jason D. Gardner

School of Graduate Studies Faculty Publications

Chronic alcohol misuse is the leading cause of non-ischemic dilated cardiomyopathy, and the molecular mechanisms underlying the development of alcohol-associated cardiomyopathy (ACM), particularly regarding sex-specific susceptibility and mitochondrial contributions, are not fully known. In this study, we utilized a preclinical model of chronic + binge ethanol consumption to investigate sex differences in disease severity and mitochondrial function. Male and female C57BL/6J mice were fed ethanol or control liquid diets for 30 days, with 2 binge episodes on days 10 and 30. Cardiac morphology was assessed via echocardiography and cardiac function via left ventricular pressure-volume catheterization. Mitochondrial function was evaluated ex …

Alphasperm Data, Seth J. Parks, Timothy G. Jenkins

ScholarsArchive Data

Data from a prospective cohort study of sperm DNA methylation, semen analysis, and DNA fragmentation in fertile and infertile men before and after treatment with a male fertility antioxidant supplement.

A Novel Sialylation Pathway Mediated By Extracellular Vesicles In Aggressive Prostate Cancer, Camila A. Bach, Md Niamat Hossain, Ishan J. Chaudhari, Cecilia E. Verrillo, Nicole M. Naranjo, Isabella Amoroso, Anna Testa, Samuel Sey, W. Kevin Kelly, Susan L. Bellis, Aurelio Lorico, Ada G. Blidner, Gabriel A. Rabinovich, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Altered cell surface glycosylation is a hallmark of cancer; among aberrant glycan structures, hypersialylated proteins contribute to disease progression. The enzyme ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) mediates α2,6-linked sialylation of N-glycosylated proteins and is upregulated in many cancers, including prostate cancer (PrCa). We propose that ST6GAL1 may be released by cancer cells in small extracellular vesicles (sEVs) in the PrCa tumor microenvironment to potentially modulate cell surface sialylation in recipient cells. We isolated sEVs from PrCa cells by density gradient separation and characterized them by nanoparticle tracking analysis using ZetaView and immunoblotting analysis. We identified ST6GAL1 in both its membrane-bound …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Asymmetric Fgf Receptor Dimerization: Implications For Fgf23 Biology And Drug Discovery, Mohammed S. Razzaque, Moosa Mohammadi

School of Medicine Publications

Fibroblast growth factor 23 (FGF23) requires both αKlotho and heparan sulfate proteoglycans (HSPGs) as obligatory coreceptors to bind, dimerize, and activate its FGF receptors (FGFRs) in the kidney, thereby regulating mineral ion and vitamin D homeostasis. Cryogenic electron microscopy studies reveal that FGF23 signaling proceeds through an asymmetric 1:2:1:1 FGF23–FGFR–αKlotho–HS assembly. According to this structural model, αKlotho simultaneously anchors FGF23 and one FGFR chain, referred to as the primary receptor (FGFRP), to form a 1:1:1 FGF23-FGFRP-αKlotho triplex, which boosts FGF23-FGFRP interaction. Subsequently, the HS coreceptor aids the triplex in recruiting a second FGFR chain, or secondary receptor (FGFRS), leading to …

Advanced Interactions Of Directed Energy With Retinal Pigment Epithelial Cells And Their Photochemical And Photothermal Responses, Jin B. Ha

Theses & Dissertations

Excess optical radiation can injure the retina through either rapid heat deposition (photothermal damage) or cumulative photo‑oxidative stress (photochemical damage), yet current laser‑safety limits treat these mechanisms as independent. To test that assumption, this dissertation integrated systematic wavelength, duration and temperature‑controlled laser exposures with live/dead fluorescence imaging in a melanin‑loaded hTERT‑RPE1 monolayer model. First, concurrent 447 nm (blue) and 2 µm (infra‑red) beams delivered for 200 s demonstrated a strong thermal–photochemical synergy: each beam alone was sub‑threshold (≤25 % lethality) but together produced 100 % RPE death without exceeding 50 °C, proving that modest heating markedly lowers the photon dose …

Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells

Electronic Theses and Dissertations

Cardiac fibroblasts are central effectors of cardiac repair after myocardial infarction (MI). In response to signaling cues, they differentiate to a range of phenotypes with robust capacities to synthesize and secrete extracellular matrix (ECM) and signaling molecules. Although activated fibroblast phenotypes are associated with pronounced changes in metabolism, it remains unclear how the metabolic network upholds the effector functions of fibroblasts in the post-infarcted heart. Here, we identified that critical enzymes in the phosphoenolpyruvate (PEP) cycle, i.e. pyruvate kinase muscle-2 (PKM2) and phosphoenolpyruvate carboxykinase-2 (PCK2), are elevated in the heart after MI and examined their role in regulating post-MI remodeling …

Identification Of Serum Exosome Proteins In Systemic Sclerosis With Interstitial Lung Disease By Aptamer Proteomics, Sonsoles Piera-Velazquez, Simon T. Dillon, Xuesong Gu, Towia A. Libermann, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A major unmet need for Systemic Sclerosis (SSc) clinical management is the absence of well validated biomarkers for early diagnosis of SSc-associated interstitial lung disease (SSc-ILD). The objective of this study was to identify proteins contained within serum exosomes that may serve as potential biomarkers to differentiate patients with Diffuse SSc without SSc-ILD from patients with Diffuse SSc with SSc-ILD employing aptamer-based proteomics.

METHODS: Serum exosomes were isolated from two cohorts of patients. The first cohort included 15 patients with Diffuse SSc without SSc-ILD and 14 patients with Diffuse SSc with SSc-ILD and the second cohort included 12 patients …

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige Boneski, Hiromi Sesaki, Ruteja Barve, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Breaking The Rules: Post-Translational Modifications And Proteome Dynamics During Anoxia, Chelsea Jordan Hughes

Dissertations and Theses

Most organisms are ill-equipped to survive anoxia, but some organisms have developed molecular strategies to mitigate the cellular stressors associated with a lack of oxygen. While it is established that anoxic survival is contingent on metabolic suppression, it is unclear what mechanisms support this change in gene expression. Gene expression is regulated by a variety of mechanisms within the cell, including alteration of chromatin structure through histone modifications and protein modifications which contribute to the ever-changing proteomic landscape of the cell. Protein modifications such as ubiquitylation can lead to the degradation of proteins, while modifications to transcription factors can change …

The Role Of G6pd Variants And 3d Genomic Structure In The Development Of Pulmonary Hypertension, Christina M. Signoretti Ph.D.

NYMC Student Theses and Dissertations

Pulmonary hypertension is an under-recognized global health epidemic which is estimated to affect 1% of the population. It is associated with sustained mean pulmonary artery pressure greater than 20 mmHg, pulmonary artery remodeling, smooth muscle and endothelial cell proliferation and subsequent increased right ventricle hypertrophy due to increased afterload. Glucose-6-phosphate dehydrogenase (G6PD) is one of the key enzymes in the pentose phosphate pathway and has been previously linked to the development of pulmonary hypertension. G6PD deficiency is the most common human enzymopathy which affects approximately 400 million people worldwide and is a result of agricultural and epidemiological evolution in different …

Mechanisms Of Placental Impairment And The Upregulation Of Fetuin-B During Maternal Undernourishment, Mia Camilliere

NYMC Student Theses and Dissertations

Proper nutrition is crucial during pregnancy to support fetal and placental development. Failure to meet these nutritional needs can result in adverse health outcomes for both mother and baby. Despite its high prevalence in underdeveloped countries, maternal undernourishment is a public health issue worldwide. There are several possible causes of maternal undernourishment, and these can occur alone or in combination, such as poor access to nutrition, hyperemesis gravidarum, and drug use. This condition can adversely affect placental development and function to the extent of placental insufficiency, perturbing the entire pregnancy. The placenta is responsible not only for hormonally and physically …

Ammonia Regulation In Aedes Taeniorhynchus, A Salt-Water Mosquito, Joseph Edmonds

Undergraduate Honors Theses

The salt tolerant mosquito species Aedes taeniorhynchus has been observed in high salinity and ammonia conditions. Previous studies indicate Na+/K+ ATPase (NKA), the proton pump vacuolar-type H+ ATPase (VHA) and sodium-dependent cation-chloride cotransporters (NKCC’s) in sodium secretion in larval Aedes taeniorhynchus. However ammonia transporter such as Rh-protein, Amt1, and Amt2 have only been characterized in Aedes taeniorhynchus’s fresh water relative Aedes aegypti. Our research exhibits the expression of these transporters in A.taeniorhynchus using immunohistochemistry techniques. Evidence of VHA and NKA function in ammonia transport was characterized in vivo using drug antagonists in varying saline and ammonia concentrations. Ammonia flux rates …

The Antioxidant Potential Of Rosemary Leaf-Derived Nanovesicles, Shani Akila Griffin

Master's Theses

Human dermal fibroblasts are essential for maintaining skin homeostasis. However, exposure to exogenous and endogenous stressors can lead to fibroblast instability, extracellular matrix degradation, and excessive reactive oxygen species (ROS) production. These factors contribute to skin aging and ROS-induced skin disorders leading to hair loss. Adverse effects from synthetic treatments have driven interest in natural alternatives like plant extracts for skin therapy. However, the polyphenols in these treatments require an effective delivery system to ensure their stability and targeted application. Plant derived nanovesicles (PDNVs) are emerging as a promising natural alternative for therapeutic applications. Their biocompatibility, stability, and encapsulated compounds …

Ion-Dna Interactions As A Key Determinant Of Uracil Dna Glycosylase Activity., Sharon N Greenwood, Alexis N Dispensa, Matthew Wang, Justin R Bauer, Timothy D Vaden, Zhiwei Liu, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Because of their ubiquitous presence, ions interact with numerous macromolecules in the cell and affect critical biological processes. Here, we discuss how cations including Mg²⁺ alter the enzymatic activity of a DNA glycosylase by tuning its affinity for DNA. The response of uracil DNA glycosylase (UNG2) to Mg²⁺ ions in solution is biphasic and paradoxical, where low concentrations of the ion stimulate the enzyme, but high concentrations inhibit the enzyme. We analyzed this phenomenon by modeling experimental data with a statistical framework that we empirically derived to understand molecular systems that display biphasic behaviors. Parameters from our statistical …

Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins

Biomedical Sciences ETDs

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …

Chronic Inflammation: The Link Between A High Added Sugar Diet And Disease, Anna Collins

Senior Honors Theses

The modern diet includes many processed foods that contain added sugars, resulting in a significant increase in daily glucose and fructose consumption. Considering this, there is an increased effort to uncover the effects of excess sugar intake on the body’s health and metabolism. Strong evidence supports the connection between a high added sugar diet and the presence of chronic, low-grade inflammation due to cellular distress and metabolic dysfunction. Prolonged inflammatory responses are linked to tissue damage and the development of various metabolic diseases that are prevalent in modern society, such as obesity, fatty liver disease, cardiovascular disease, and type 2 …

Neuronal Tol-1 Integrates Microbial And Metabolic Cues To Modulate Feeding And Aversion In C. Elegans, Gursimran Singh Gujral

Theses, Dissertations and Culminating Projects

Toll-like receptors (TLRs) are key mediators of innate immunity, but emerging evidence suggests that they also play critical roles in the functioning of the central nervous system. This thesis explores the function of TOL-1, the Caenorhabditis elegans homolog of mammalian TLRs, in sensory neurobiology and behavioral responses to nutritive food. In particular, carbon dioxide and ethanol are commonly encountered in microbial environments and can signal metabolically active food sources or potential pathogens. Using tol-1 loss-of-function mutants, neuronal rescue lines, and a combination of molecular, tissue imaging, and behavioral assays, we demonstrate that TOL-1 functions in chemosensory neurons to regulate feeding …

Hypoxia Induced Ribosomal Rna Fragmentation Mediated By Rnase L, Vanessa Kristina Pizutelli, Dimitri G Pestov

Rowan-Virtua Research Day

Ischemic injury contributes to a range of global pathologies. Ischemia/Reperfusion Injury (IRI) is a paradoxical phenomenon that involves an initial restriction of blood flow followed by a sudden restoration of perfusion. This type of injury takes place in conditions such as myocardial infarction, acute kidney disease, and ischemic stroke and often leads to cellular death. Additionally, IRI exacerbates post-surgical outcomes and plays a role in graft dysfunction and transplant rejection. Despite efforts to develop therapies targeting known IRI pathways, clinical trials have largely been unsuccessful, underscoring the need for alternative mechanisms and biomarkers associated with IRI-induced apoptosis. Reactive oxygen species …

Stromal Cells In The Small Intestine: Physiology, Localization, Function, And Alterations Induced By Chronic Arsenic Exposure, Scott Ventrello

All Dissertations

Arsenic is a prevalent toxicant found to affect around 94 to 240 million individuals in over fifty countries who are exposed to levels above the EPA and WHO standard of 10 ppb. As one of WHO’s top ten chemicals of public health concern, it is linked to several chronic diseases including diabetes, obesity, cancers, and inflammatory bowel diseases. Arsenic increases inflammation and disrupts the intestinal barrier in the small intestine and colon. Further, previous studies found that arsenic decreased secretory cell lineage and stromal cell gene expression markers in the small intestine. Thus, our goal was to investigate arsenic’s effect …

Implications Of Type Iv Pilus Retraction For Dna Uptake By Acinetobacter Baumannii, Yafan Yu

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Horizontal gene transfer (HGT) via natural competence allows bacteria to incorporate extracellular DNA (eDNA) into their genomes, facilitating genetic diversity and adaptation. In Acinetobacter species, natural competence depends on DNA binding and uptake mediated by type IV pili (T4P). T4P are dynamic extracellular filaments composed primarily of the major pilin subunit PilA, along with a few minor subunits. T4P drive a range of cellular functions including twitching motility, biofilm formation, and DNA uptake, with some functions dependent on pilus retraction and others not. However, how Acinetobacter T4P bind DNA and how T4P/eDNA interactions impact biofilm formation remain unclear. Here, I …

Investigating The Effects Of Hepatocyte Growth Factor On Primary Myoblast Proliferation, Grace Heller

Biomedical Engineering

Peripheral artery occlusive disease (PAOD) is a progressive vascular condition that affects over 200 million people worldwide and approximately 8 million in the United States. It is characterized by atherosclerotic narrowing of peripheral arteries, leading to reduced blood flow, ischemia, and, in severe cases, tissue loss and limb amputation. Although surgical revascularization is the gold standard, many patients—particularly those with comorbidities like diabetes— continue to experience poor outcomes, emphasizing the need for alternative therapies. One promising strategy is to enhance collateral arteriogenesis, the remodeling and enlargement of collateral arterioles that naturally bypass occluded vessels. Satellite cells (SCs), which give rise …

Metabolite Analysis To Understand Factors Limiting Microbial Fermentation At High Substrate Concentrations, Bishal D. Sharma

Dartmouth College Ph.D Dissertations

Clostridium thermocellum, a thermophilic anaerobic bacterium, holds promise as a biocatalyst for conversion of lignocellulosic biomass into biofuels. This microbe has been subjected to various metabolic engineering strategies, including the deletion of genes encoding secondary fermentation products such as H₂, formate, acetate, and lactate, as well as the expression of heterologous genes to redirect carbon flux toward ethanol production. Despite these efforts, achieving economically viable ethanol titers remains a challenge. We hypothesized that studying how intracellular metabolite concentrations change as fermentation stops could reveal metabolic bottlenecks or regulatory mechanisms limiting ethanol production at high titers. However, metabolomics studies at …

Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie

LSU Doctoral Dissertations

Embryos of Artemia franciscana survive harsh conditions in diapause and anoxia-induced quiescence for years by undergoing deep metabolic transitions. I investigated the relationship between phosphorylation of pyruvate dehydrogenase (PDH) and carbon flux to the tricarboxylic acid (TCA) cycle during metabolic depression. The difference in catalytic activity of the PDH complex (PDC) in maximally phosphorylated and dephosphorylated samples was 16.5-fold. Western blot analysis confirmed the changes in phosphorylation of PDH. Analysis of PDH expression in diapause and post-diapause embryos via phospho-PDH showed no significant differences. Investigation of post-diapause embryos under anoxia showed that phosphorylation of PDH decreased and activated the enzyme. …

Adipocyte-Derived Cchamide-1, Eiger, Growth-Blocking Peptide 3, And Unpaired 2 Regulate Drosophila Melanogaster Oogenesis, Chad Simmons, Isaiah Williams, Tancia Bradshaw, Alissa R. Armstrong

Faculty Publications

In addition to energy storage, adipose tissue communication to other organs plays a key role in regulating organismal physiology. While the link between adipose tissue dysfunction and pathophysiology, including diabetes, chronic inflammation, and infertility, is clear, the molecular mechanisms that underlie these associations have not been fully described. We use Drosophila melanogaster as a model to better understand how adipose tissue communicates to the ovary. In this study, we utilized D. melanogaster’s robust genetic toolkit to examine the role of five adipokines known to control larval growth during development, CCHamide-1, CCHamide-2, eiger, Growth-blocking peptide 3, and unpaired 2 in regulating …

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …

Editorial: Frontiers In The Midlands Society Of Physiological Sciences (2023-2024), Sathish Kumar Natarajan, Hong Zheng, Surabhi Chandra, Harold D. Schultz, William C.W. Chen

Journal Articles: Cellular & Integrative Physiology

No abstract provided.