Cell Biology Commons^™

Dapagliflozin Attenuates Cisplatin-Induced Nephrotoxicity In Rats Through Modulation Of Ros/Nf-Κb, Bcl2/Bax And Pink1/Parkin Signaling Pathways, Esraa K. Khallaf, Eman A. Ramadan, Mohey M. Elmazar, Marwa M. Safar

Pharmacy

Dapagliflozin (DPG), an anti-diabetic drug, has gained attention for its renal protective effects through multiple molecular pathways, yet its impact on mitophagy in cisplatin (CIS) nephrotoxicity remains unclear. This study aimed to examine the impact of DPG against CIS-induced nephrotoxicity in rats, targeting mainly PINK1/Parkin-mediated mitophagy and inflammatory/apoptotic pathways. Male Sprague Dawley rats received DPG (10 mg/kg; p.o) daily for 14 consecutive days and AKI was induced by a single injection of CIS (7 mg/kg; i.p) on day 10. Blood glucose, serum levels of creatinine and urea nitrogen, oxidative stress, inflammatory, apoptotic, mitophagy markers, and histological changes were assessed. DPG …

Elevated Trna Halves In Olfactory Epithelial Cells Of Patients With Schizophrenia, Justin T. Gumas, Megumi Shigematsu, Karin E. Borgmann-Winter, C. G. Hahn, Yohei Kirino

Computational Medicine Center Faculty Papers

Schizophrenia patients' olfactory epithelial cells contain abundant immune-activating tRNA fragments, linking small RNA biology to inflammation and suggesting avenues for diagnostics.

Selective Deletion Of Slc2a1 From The Rpe Reveals That Rods But Not Cones Depend On Glucose Transport Across The Outer Blood-Retinal Barrier, Lauren L. Daniele, John Y.S. Han, Minzhong Yu, Ravi A. Sangani, Craig D. Beight, Cyrus Rostami, Philip D. Kiser, Neal S. Peachy, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

GLUT1 facilitates a continuous flow of glucose across the inner and outer blood-retinal barriers (BRBs) to support vision. To understand the extent to which photoreceptors rely on glucose transport across the outer BRB, we generated a tamoxifen-inducible conditional knockout of Slc2a1 in the retinal pigment epithelium (RPE) (RPE-iΔGlut1). In the RPE-iΔGlut1 mice, rod photoreceptors exhibited impaired outer segment renewal and decreased the expression of proteins involved in phototransduction and ciliary transport. Proteins regulating the retinal stress response increased. Cone photoreceptors were functional and viable 15 months post-tamoxifen treatment in the RPE-iΔGlut1 mice, while 70% of the rods died. …

Decoupling Of Reproduction And Lifespan Trade-Off In Caenorhabditis Elegans Through Microbial Programming, Nora M. Villafuerte

LSU Master's Theses

The microbiome is increasingly recognized as a major regulator of host physiology. Using the Caenorhabditis elegans model, we investigated how natural commensal bacteria modulate host reproduction and lifespan through internal egg hatching, a phenotype in which retained embryos hatch within the maternal body. Screening strains from the CeMbio collection identified four focal strains Ochrobactrum BH3, Lelliottia JUb66, Pantoea BIGb0393, and Enterobacter CEent1 that significantly increased internal egg hatching during the late reproductive period. This contrasts with pathogenic bacteria, which induce early-onset internal egg hatching. Across the focal strains, worms exhibited reduced total brood size but an expanded reproductive window relative …

Inhomogeneous Branching Random Walks: Incorporating Genealogy And Density Effects, Lauren Ajax, Beatrice Durham, Pratima Hebbar, Cade Johnston, Jiayi Zhang

Spora: A Journal of Biomathematics

We introduce a novel framework using inhomogeneous branching random walks (BRWs) to model biological processes, specifically by introducing genealogy-dependence in branching rates and displacement distributions to model bacterial colony growth. Current stochastic models often either assume independent and identical behavior of individual agents or incorporate only spatiotemporal inhomogeneity, ignoring the effect of genealogy-based inhomogeneity on the long-time behavior of these processes. Such asymptotics are of independent mathematical interest and are crucial in understanding the emergence of patterns. We propose several inhomogeneous BRW models in 2D space where displacement distributions and branching rates vary with time, space, and genealogy. A combined …

Investigating The Presence Of Amyloid In The C. Elegans Germline And Embryos, Sereen M. El Jamal

Biochemistry and Molecular Biology

Amyloids, insoluble protein aggregates of cross ß-sheet structure, are commonly associated with amyloidosis diseases. However, more recent studies support that some amyloids serve essential functions evolutionarily conserved across several taxa, particularly in reproduction. The nematode Caenorhabditis elegans serves as an excellent model organism in reproductive research. Prior to this study, no research has investigated the presence of functional amyloid in the C. elegans reproductive system. We hypothesize that similar to the presence of functional amyloid in the eggshells and epididymides of other organisms, functional amyloid will also be present in the germline and embryos of C. elegans. Using immunostaining, …

Cell Surface Expansion And Tension Regulation: How Cellular Forces Shape Embryonic Development, Samantha A. Pressman, Sophia M. Micale, Bing He

Wetterhahn Science Symposium Posters

Congenital birth deformities often arise during epithelial morphogenesis, displaying the need to understand the mechanisms underlying this process. Cell shape changes that mediate morphogenesis often require cell surface expansion to accommodate shifts in 3D tissue geometry. Our lab has identified Four Wheel Drive (Fwd), a Golgi-localized phosphatidylinositol 4-kinase (PI4K) IIIβ ortholog, as a regulator for cell surface expansion during Drosophila ventral furrow formation, a well-characterized model for epithelial folding. We hypothesize that Fwd and Rab11, a regulator of exocytosis and endocytic recycling, coordinate the trans-Golgi network and recycling endosomes to promote vesicle trafficking. Using live imaging of fluorescently tagged Fwd …

Mitochondria In Local Control Of Programmed Cell Killing & Resilience, Rashna Sharmin

Biology Dissertations - Archive

Specialized cells are commonplace and defined by different compartments. Organelle transport across cell compartments is critical for cell function, as in morphologically complex neurons. Specialized cells can undergo programmed elimination, an essential facet of normal development. My central thesis question asks how intracellular transport of mitochondria, the cell’s energy producers, regulate fated elimination of complex cells. I explored this using the specialized tail-spike cell (TSC) of the roundworm C. elegans. The TSC dies embryonically through the novel ‘tripartite’ developmental killing program, Compartmentalized Cell Elimination (CCE).  In my study, I defined and characterized events at the CCE initiation compartment of the …

Long Acting Beta2-Adrenergic Receptor Agonists Reverse Diabetic Nephropathy And Liver Steatosis In Murine Models Of Diabetes And Are Associated With Protection In Retrospective Human Studies, Brennan Winkler

MUSC Theses and Dissertations

Diabetes Mellitus (DM) affects 13.9% of men and 14.3% of women worldwide, a total of approximately 828 million people. Patients with diabetes are at risk of several complications including diabetic nephropathy (DN) and metabolic-associated steatohepatitis (MASH). These diseases eventually lead to end stage kidney disease (ESKD) and liver failure requiring dialysis and organ transplantation. In addition, diabetes exacerbates disease severity of autosomal dominant polycystic kidney disease (ADPKD), the most common potentially lethal genetic disease to affect humans with a prevalence of 1 in 500-1000. Therefore, a therapeutic approach that can attenuate organ damage and restore function in patients with DM, …

The Impact Of The Different Vdac Isoforms On Hbv Replication And Hbx Localization, Cody Mcumber

MUSC Theses and Dissertations

Chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma worldwide. Despite the availability of a preventative vaccine, there are approximately 254 million people living with a chronic HBV infection. There are 9 known HBV genotypes, each with their own clinical impacts and manifestation in infected patients. HBx is the only regulatory protein encoded by the HBV genome and is required for efficient viral replication. HBx has many effects in infected hepatocytes besides known effects on HBV replication, such as localization to the mitochondria. HBx is also known to have impacts on mitochondrial membrane potential, mitochondrial permeability …

Generating A Gfp Reporter Via Crispr To Visualize Ssa4 Export, Aara Khairollahi, Rebecca Adams

SPARK Symposium Presentations

In eukaryotic cells, the transport of mRNA from the nucleus to the cytoplasm is a very regulated process controlled by nuclear pore complexes (NPCs). During stress conditions, such as heat shock, most mRNA export is inhibited in Saccharomyces cerevisiae, yet the transcript for SSA4, a gene responsible for refolding denatured essential proteins, is exported. The mechanism behind this selective export remains unknown. To investigate this, we used CRISPR-Cas9 to generate a reporter strain in which the SSA4 open reading frame was replaced or inserted with green fluorescent protein (GFP). This reporter is designed to produce GFP only under conditions that …

Exploring The Synergistic Effects Of Cisplatin And Curcumin In Osteosarcoma Cells, Ellis Stafford, Alexa Cabral, Andrea Florian Ph.D., Reese Nagy

SPARK Symposium Presentations

Osteosarcoma (OS) is a highly aggressive bone cancer characterized by rapid metastasis, which drastically reduces patient survival rates from 70% in localized cases to 30% upon metastasis. Current treatments combining chemotherapy with cisplatin and surgical intervention are often ineffective against metastatic OS and are associated with significant side effects. Cisplatin targets cancer cells by binding to DNA, disrupting transcription and replication, and inducing apoptosis. To address the challenges associated with current treatments, this study investigates the potential of combining cisplatin with curcumin, the bioactive compound derived from turmeric, as a novel therapeutic approach. Curcumin has shown anticancer properties by inducing …

Fgf Signaling Is Necessary For Newt Lens Regeneration, Leo Alexander Napoleon

Honors Theses and Capstones

The Iberian ribbed newt Pleurodeles waltl can regenerate the lens by transdifferentiating iris pigmented epithelial (IPE) cells into lens epithelial cells (LECs), but the mechanism by which this occurs remains largely uncharacterized. We aim to mechanistically show an early and critical role for FGF signaling by using small molecules to inhibit FGF receptors and observe the histological and intracellular effects. Two inhibitors were found to completely stall lens regeneration. Cell cycle analysis revealed decreased DNA synthesis and uniformly low but unchanged entry to mitosis under signaling inhibition by staining for EdU incorporation and phospho-histone H3 (pH3), respectively. Western blot revealed …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Investigating The Effects Of Nucleopore Defects On The Cellular Response To Stress In Als/Ftd Ipsc-Derived Neurons, Alicia Christine Collins

Open Access Dissertations

Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a progressive neurodegenerative disease spectrum characterized by motor dysfunction, cognitive decline, and death within a few years of clinical onset. Hallmark features of ALS/FTD include defects in nucleocytoplasmic transport (NCT) and abnormal cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43, both of which have been shown to be exasperated by oxidative stress (OS). It remains unclear how these processes are connected and how they collectively contribute to neurodegeneration. To fill this gap of knowledge, we used human embryonic kidney cells, neuroblastoma cells, and induced pluripotent stem cell-derived cortical neurons harboring the ALS/FTD C9ORF72 …

The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey

Honors Undergraduate Theses

Stress profoundly influences brain function through neuromodulatory hormones that regulate synaptic plasticity, yet how temporal patterns of hormone exposure shape excitatory synapse formation remains poorly understood. This study investigates how exposure to stress hormones, norepinephrine and cortisol, affects excitatory synapse development. While existing research primarily compares concentration models, real-world stress occurs in variable patterns that may produce distinct neural outcomes. To address this gap, differentiated Neuro2A neuronal cells are exposed to norepinephrine or cortisol under a continuous treatment paradigm designed to model chronic stress conditions. Following treatment, immunofluorescence imaging is utilized to quantify excitatory synapse formation through analysis of presynaptic …

Perfluorooctane Sulfonate (Pfos)-Induced Disruption Of Mitochondrial Activity And Cell Adhesion In Liver Cells, Phuong Dam Nam Tran

Graduate Theses/Dissertations

Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant associated with potential hepatoxic effects and other health risks. Despite its widespread distribution, the mechanisms underlying its toxicities remain to be fully understood. To investigate PFOS toxicology, my study utilized HepG2 and THLE-2 human hepatic cell models to replicate conditions reflecting PFOS accumulation in the liver. Cell viability, cell stress, and cell death assays were conducted to assess the toxicological influence of the chemical on both cell lines. Total RNA extraction was performed, followed by cDNA sequencing, and RT-qPCR. The XTT viability assay revealed a dose-dependent decrease in number of viable cells …

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 …

Magnesium-Based Metal Matrix Nanocomposite Implants And Nanobubble-Based Delivery Systems: Integrated Strategies For Bone Loss Treatment With Cytocompatibility Evaluation, Lucas José Martinho Bizuti

Honors Undergraduate Theses

This thesis intends to investigate the development of different multimodal therapeutic strategies for combating bone loss. Most specifically, this paper will emphasize the utilization of Magnesium-Based Metal Matrix Nanocomposite Implants (MMNC) and Nanobubble-Based Delivery Systems as options for future treatment focus. The effects of biodegradable magnesium implants were evaluated for cytotoxicity and cytocompatibility via Hematoxylin and Eosin, and Masson’s Trichrome staining, as well as radiological images. The Nanobubble-Based Delivery System is being developed and optimized as a delivery system to target osteoclast activity. This paper focused on optimizing experimental parameters, which include Rotational speeds for nanobubble stimulation under microgravity conditions …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …