Cell Biology Commons^™

Effect Of Partial Ablation Of Skeletal Dynamin Related Protein 1 On Mitochondrial Health, Inflammation, And Fibrosis In A Mouse Model Of Duchenne Muscular Dystrophy, Tessa L. Duzz

Graduate Masters Theses

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder characterized by muscle weakness, degeneration, fibrosis, and impaired muscle regeneration. Mitochondrial dysfunction is an early pathological feature of DMD and has been linked to excessive mitochondrial fission. Dynamin-related protein 1 (Drp1) is a central regulator of mitochondrial fission, a key process in regulating mitochondrial quality and function. Inhibition of Drp1-mediated mitochondrial fission has shown promise as a potential therapeutic target for alleviating pathology and dysfunction in dystrophic muscle. The objective of this study was to determine whether partial skeletal muscle-specific ablation of Drp1 could improve muscle pathology and mitochondrial health in …

The Role Of Seed Mix Characteristics And Soil Amendments During Post-Agricultural Prairie Restoration, Valerie N. Thurston, Michaela J. Woods, Madelaine Gregory, Mary C. Lloyd, Ryan W. Mcewan

Biology Faculty Publications

Introduction: Prairie restoration on degraded lands may be influenced by seed mix characteristics, including species richness and legume establishment. Soil amendments may facilitate restoration; however, the practical usefulness of techniques such as applications of whole soil and leaf mulch remains relatively unclear.

Objectives: We assessed whether increasing species richness and legume content in seed mixes enhances prairie restoration success and examined how soil amendments interact with seed mix composition to influence cover, species richness, diversity, and legume establishment.

Methods: We conducted a field experiment on a 12-ha post-agricultural site in Ohio, U.S.A. Twenty 50 × 50 m plots received one …

Antimicrobial Responses Of Staphylococcus Aureus In Simulated Spaceflight Conditions, Mikayla Dutkiewicz, Yegor Bushnev

Discovery Day - Daytona Beach

Microbial persistence in confined environments, such as spacecraft, can pose challenges to astronaut health and habitat maintenance. This project investigates Staphylococcus aureus, a Gram-positive bacterium commonly associated with human microbiota and opportunistic infections, in spaceflight-relevant environmental conditions. Further, this project will assess the influence of the antimicrobial/antioxidant compound quercetin to assess its effects on bacterial growth and virulence under standard Earth gravity and simulated International Space Station (ISS) conditions. This approach will assess whether spaceflight-relevant stressors, including microgravity and radiation, alter treatment efficacy by influencing microbial physiology and antimicrobial susceptibility. Data collection and analysis are ongoing, and results are expected …

Assessing Non-Thermal Plasma In Cutaneous Regeneration, Arden Rodriguez, Meliah Martin, Graeme Grainger, Arineh Shahbazi

Discovery Day - Daytona Beach

Chronic and acute wounds remain a significant clinical challenge, particularly in austere and resource-limited environments where access to advanced care is restricted. Non-Thermal Plasma (NTP) has emerged as a promising, non-invasive modality with reported antimicrobial and regenerative properties; however, its mechanisms of action and effects on human skin tissue require further characterization. The scope of this project is to engineer and utilize a 3D human skin epithelial model to evaluate the effects of NTP on wound healing. We will first build a 3D epithelial tissue model that will simulate human skin, followed by modeling and evaluation of wound pathology and …

The Osteocyte-Osteoblast Network Requires Dynamic Mechanical Loading For Key Functions, Kevin Kowalski

Discovery Day - Daytona Beach

Spaceflight investigations have demonstrated that reduction in gravity-induced loading regimes is detrimental to maintenance Earth-normal bone and marrow. Mechanistically, however, there are still gaps in knowledge about how the reduction in gravity influences the different niches within the tissue. For example, cortical bone is a stable semi-solid structure that allows for only minor deformations before failure, while marrow is a viscous hydrogel-like material that can resist significant fluidic and compressive forces. We hypothesize that maintenance of different niches within the bone microenvironment are dependent on different loading regimes, and that the collective impact if gravity-induced loading needs to be considered …

The Rpm-1/Phr Signaling Hub Modulates Tau-Induced Neurodegeneration Through Regulation Of Microtubule Stability And Mapk Pathways In C. Elegans, Xinxing Ding

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, are characterized by the accumulation of pathological tau proteins and progressive neuronal loss. Although research regarding tau-mediated toxicity is extensive, the specific pathology that determine whether neurons maintain homeostasis or succumb to collapse under tau-induced stress remain incompletely elucidated. A central, yet still insufficiently understood, feature of these diseases is the disruption of the microtubule (MT) cytoskeleton . The PHR protein family is evolutionarily highly conserved; within this family, RPM-1 in C. elegans functions as an intracellular signaling hub that regulates axon development, synapse formation, axon termination, and various microtubule-associated processes. This …

Oxidative Stress Mediated Glutamate Release And Nmda Receptor-Dependent Synaptic Remodeling In Radiation-Induced Cognitive Dysfunction, Thanh Lam

Dissertations and Theses (Open Access)

In children younger than 14 years old, the brain and other parts of the central nervous system are the most common sites for solid tumors. Radiotherapy is an effective treatment for central nervous system (CNS) tumors. However, it often causes a progressive decline in cognitive functions, which is especially devastating for pediatric patients. Although post-mitotic neurons are generally considered resistant to radiation-induced immediate cell death, ionizing radiation causes complex neurochemical and structural changes that damage synaptic integrity. In this study, we examined the molecular cascades following a 10 Gy radiation dose applied to mouse cortical neurons. We found that radiation-induced …

Homocysteine Thiolactone From Translation Proofreading Is An Endogenous Ligand For Cell-Cell Signaling By The Receptor Sdia, Lorenzo Eugenio Leiva, Roberto A. Zúñiga, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Several widespread mechanisms enable cellular communication and coordinate the behavior of bacterial populations. The modules responsible for cellular communication are often found in matching pairs: an enzyme that synthesizes a signal molecule and a specific receptor that decodes it. A notable exception is Escherichia coli SdiA, a homolog of known N-acyl-homoserine lactone (AHL) receptors, for which no corresponding AHL synthase exists. SdiA is an orphan receptor that enables cross-talk by sensing AHLs from other bacterial species. In this work, we investigated whether homocysteine thiolactone (HTL), an AHL-like molecule arising from a proofreading reaction of methionyl tRNA synthetase (MetRS) to correct …

Antioxidant Potential Of A Non-Heme Iron Complex: Mitigating H2O2-Induced Cellular Damage, Magy A. Mekhail, David M. Freire, Cameron Bowers, Grant Elam, Nora Del Bosque, Hannah K. Pyle, Sarah K. Dunn, Spencer Lanyon, Timothy J. Hubin, Giridhar Akkaraju, Kayla N. Green

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Iron complexes with antioxidant activity have garnered significant interest for both general and medical applications, yet few studies have yielded functional nonheme iron-based mimics for H₂O₂ mitigation in aqueous environments. Here, we investigate water-soluble nonheme iron complexes derived from 12-membered pyridinophanes (^CF₃PyN₃, PyN₃, ^NMe₂PyN₃, and Py₂N₂) to evaluate the impact of ligand scaffolds on H₂O₂ decomposition activity both in vitro and in a cellular model. Speciation and kinetic analyses reveal that both electronic and geometric modulation of the macrocyclic …

A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin

Electronic Theses and Dissertations

Caveolae are specialized, flask-shaped membrane invaginations highly expressed in endothelium and dysregulated in atherosclerosis. Caveolae play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. Thus, we sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. However, cell culturing, the backbone of human-focused biological research, does not standardly do well to model physiologically relevant cell behaviors such as migration or polarity-based tissue formation, particularly for punctate proteins and structures like caveolae. Micropatterns are cell-adhesive shapes that biophysically confine cell(s) to a user defined geometry which stereotype organelle …

Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni

Biochemistry and Molecular Biology

Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …

Loss Of Mct1 Mediated Lactate Uptake Causes Delayed Endplate Maturation And Intervertebral Disc Degeneration, Maria Tsingas, Konstantinos Tsingas, Mei Smyers, Wujuan Zhang, Aaron R. Goldman, Eulisa Lawrence, John A. Collins, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

During skeletal growth, it is thought that the lactate secreted by the glycolytic nucleus pulposus (NP) cells exits the intervertebral disc into circulation via endplates. Our current studies challenge this long-held notion. Mice with early postnatal, endplate, and annulus fibrosus-specific deletion of lactate importer, MCT1, exhibited disc degeneration characterized by NP cell loss and pronounced endplate structural changes. Using metabolic and transcriptomic approaches, we demonstrate that MCT1 loss inhibits endplate chondrocyte differentiation and that lactate serves both as a crucial TCA metabolite and promotes protein and histone lactylation and gene expression. These findings suggest that during skeletal growth, NP-derived lactate …

The Impact Of Tgfβ Conditioning And Socs3 Expression On Cytokine Signal Transduction And Inflammatory Gene Expression In Fibroblasts, Morgan Anderson-Crannage

NYMC Student Theses and Dissertations

Inflammation is a major driver in many aspects of recessive dystrophic epidermolysis bullosa (RDEB) pathology, including impaired wound healing, fibrosis, and potentially cutaneous squamous cell carcinoma development. Fibroblasts, as key stromal cells in the dermis, are responsible for orchestrating inflammatory responses through the secretion of cytokines and chemokines upon stimulation with IL-1α or IL-6. Suppressor of Cytokine Signaling 3 (SOCS3) functions as a negative feedback regulator of cytokine signaling and has emerged as a key modulator of inflammatory responses in immune cells and fibroblasts. Transforming Growth Factor Beta (TGFβ), a known driver of fibrosis in RDEB, has been implicated in …

In Vitro Reversal Of Abc Transporter Mediated Multidrug Resistance In Human Ovarian And Non-Small Cell Lung Cancer Models, Alison K. Kellom, Pia D. Vogel

Biological Sciences Theses and Dissertations

One of the major causes of treatment failure in aggressive cancers is multidrug resistance (MDR), which is linked to the overexpression of membrane efflux proteins that export chemotherapeutics from cancer cells. This mechanism prevents chemotherapeutic drugs from reaching cytotoxic concentrations intracellularly, allowing the cancer to survive. Two primary mediators of this mechanism are P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). P-gp and BCRP are transmembrane ATP-binding cassette (ABC) transporters that are frequently overexpressed in MDR cancers. They utilize the binding and hydrolysis of ATP to transport a diverse range of amphipathic molecules of varying size (Schinkel and Jonker, 2003), …

Mllt1 Is Required To Maintain B-Lymphopoiesis, Janani Prakash

Dissertations

MLLT1 (also named ENL) is an epigenetic reader protein that binds to crotonylated or acetylated lysine residues of histone 3 through its N-terminal YEATS domain. Positive and negative regulatory complexes compete for binding to C-terminal MLLT1, and promote transcription elongation (SEC, Super elongation complex; DOT1L) or transcriptional repression (PRC1, Polycomb repressive complex 1). MLLT1 was initially identified as a chromosomal translocation partner to MLL(KMT2A) in a subset of MLL-rearranged leukemias. MLL-ENL fusion protein causes both lymphoid (predominantly B-ALL) and mixed lineage leukemias. MLLT1 has been implicated in leukemic stem cell survival in MLL-rearranged cell lines but its role in normal …

Potential Innate And Adaptive Roles Played By Γδ T Cells In A Bacterial Immunization Model, Lee Anne Talbot

Seton Hall University Dissertations and Theses (ETDs)

Francisella tularensis is a highly infectious intracellular bacterium and the causative agent of tularemia, with pulmonary infection resulting in severe disease and high mortality if untreated. While protective immunity to F. tularensis has been largely attributed to CD4⁺ T cell–mediated IFN-γ responses, the contribution of γδ T cells to mucosal immunity and vaccine-induced protection remains poorly defined. The objective of this study was to characterize the role of γδ T cells during primary pulmonary infection with F. tularensis live vaccine strain (LVS) and following intranasal immunization with inactivated F. tularensis (iFt) prior to LVS challenge.

Using a murine intranasal infection …

Junctional Actin As A Mechanical Hub For Supracellular Actomyosin Force Transmission During Apical Constriction, Jasneet Brar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Apical constriction is a conserved morphogenetic mechanism that drives epithelial folding during development. During ventral furrow formation in Drosophila melanogaster, contractile actomyosin networks generate forces that reduce apical cell area resulting in tissue invagination. For these cell-scale forces to produce coordinated tissue-scale changes, contractile networks must be mechanically integrated across neighboring cells. Although adherens junctions are known to mediate this coupling, it is unclear how junctions are integrated into cortical actin cytoskeleton, which directly determines cell, and consequently tissue, shape. This thesis tests the hypothesis that supracellular actomyosin organization during apical constriction depends on distinct adherens junction based mechanical couplings: …

Thrombin-Induced Myofibroblast Differentiation Is Regulated By Myocardin And Novel Effector Genes In Ipf Fibroblasts, Christiana Okeke

Biotechnology Theses

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by fibroblast activation, excessive extracellular matrix (ECM) deposition, and irreversible respiratory decline. In this study, we investigated the role of myocardin and its downstream effectors, RGS5, DLGAP5, and TAGLN, in thrombin-induced myofibroblast differentiation and ECM remodeling using primary human IPF fibroblasts. Myocardin knockdown significantly attenuated thrombin-induced expression of profibrotic genes, including FN1, COL1A1, PAI-1, ACTA2, and CNN1, as well as the novel effectors RGS5, DLGAP5, and TAGLN, confirming myocardin as a central regulator of fibrotic signaling. Silencing RGS5 produced minimal effects on gene and protein expression despite minor downward …

The Dynamics Of Synchrony On Replicating Biological Populations, Montse Torres Garcia, Kevin Mcgoff, Francis Motta, Breschine Cummins, Steve Haase

Biology and Medicine Through Mathematics Conference

No abstract provided.

Everolimus And Sirna-Mediated Mtor Inhibition Reduces Proliferation And Promotes Apoptosis In Ewing Sarcoma Cells, Dylan Calvert, Malorie Martinez, Alexa Miner, Ellis Quiroga, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcoma (ES) is an aggressive pediatric bone cancer characterized by rapid cell proliferation and poor prognosis, making the identification of therapeutic targets critical. One of  the mechanistic targets is rapamycin (mTOR) signaling pathway, which is critical for regulating cell growth, proliferation, and survival. Abnormal activation of the mTOR signaling pathway has been linked to the progression of ES, as it drives uncontrolled cell growth and apoptosis resistance. Because mTOR represents a promising therapeutic target for ES treatment, we hypothesized that inhibiting mTOR activity through an siRNA-mediated knockdown or through Everolimus drug treatment, would reduce cell proliferation and promote ES …