Cell Biology Commons^™

Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta

Graduate Theses/Dissertations

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent …

The Role Of Host Factor Sptbn1 In Hiv-1 Capsid Uncoating In Human Microglial Cells, Callie Marie Fry

Graduate Theses/Dissertations

HIV-1 is the virus that causes acquired immunodeficiency syndrome (AIDS), and currently, there is no cure once an individual is infected. The development of new drugs targeting HIV-1 replication steps is essential for keeping viral loads low or undetectable to prevent further transmission. An attractive replication step for new drug targets is viral capsid uncoating, where the virus loses the protein structure encapsulating the genome. The exact mechanism of capsid uncoating is unknown; however, several host-factors may be involved including protein SPTBN1. Recent studies have shown a significant decrease in viral infectivity when SPTBN1 is knocked down, yet its role …

Phenotype Specific Nuclear Lamina Remodeling In Hipsc Derived Cardiomyocytes Bearing Tnnt2 Sarcomeric Variants, Isabella Leite Coscarella, Olalekan H. Usman, Lili Wang, Maicon Landim-Vieira, Lillian Wirstiuk, Amber N. Brown, Diego A. R. Zorio, Brian K. Washburn, Cynthia Vied, Bjorn C. Knollmann, Christopher Solís, Vitold E. Galkin, P. Bryant Chase, J. Travis Hinson, Jerome Irianto, Jose Renato Pinto

Department of Biomedical and Translational Sciences Faculty Publications

[Summary] Cardiomyocytes endure physical stress from the myocardium environment while generating their own mechanical strains. The force generated by sarcomeres is transmitted both longitudinally to adjacent sarcomeres and laterally to the cytoskeleton via intermediate filaments. This mechanical stimulus impacts other organelles, including the nucleus, thus playing a vital role in sensing and signaling nuclear adaptations. However, there is limited understanding of how changes in cardiac contractility affect nuclear mechanics. Here, we sought to investigate the effects of hyper- and hypo-contractility in nuclei of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) bearing TNNT2 pathogenic variants associated with hypertrophic (HCM) or dilated …

Penta Ef-Hand Protein Alg-2 Regulates Copii Activity At Eres In Response To Calcium Signaling, Jacob Ryan Lapka

Graduate Student Theses, Dissertations, & Professional Papers

Intracellular protein trafficking is critical for maintaining cellular homeostasis, relying on highly regulated vesicular transport pathways originating from the endoplasmic reticulum (ER). Central to this process is the COPII coat complex, which governs cargo export at ER exit sites (ERES) by selectively packaging secretory proteins into transport vesicles. Recent studies highlight the regulatory role of calcium (Ca²⁺) signaling at ERES, where the Ca²⁺-binding Penta EF-hand proteins ALG-2 and peflin modulate COPII coat dynamics and cargo sorting in a context-dependent manner. In Chapter 2, we show that knockdown of the Inositol 1,4,5-trisphosphate receptor-3 (IP3R-3) in normal rat …

Dusp8 Gene Expression Is Increased Upon The Stimulation Of Hek293 Cells, Oanh Vo, Lukas Macha

Student Summer Scholars Manuscripts

Dual specificity phosphatase 8 (DUSP8) is one of the phosphatases that oppose the activity of mitogen-activated protein kinases. Previous mouse studies have demonstrated the functional role of DUSP8 in regulating cardiomyocyte growth. However, it is still unclear how the activity of DUSP8 is regulated, and little is known about the regulation of DUSP8 at the gene level. The goal of this study is to determine whether the DUSP8 gene is immediately transcribed upon MAPK activation in the cells. Here, we found that the expression of the DUSP8 gene was significantly increased after stimulation of cells for 30, 60, 90, and …

Biomechanics Of The Atherosclerotic Lipidome: (Un)Expected Statin Interactions And Membrane Remodelling, Ethan M. Fong

Pomona Senior Theses

Statins interact with lipid membranes in ways that shape their pharmacokinetics, off-target effects, and pleiotropic actions, yet these interactions' mechanical and biophysical consequences remain poorly understood. This thesis employs a combination of surface plasmon resonance (SPR), quartz crystal microbalance with dissipation monitoring (QCM-D), and rheological modelling to characterize how representative statins intercalate within biomimetic supported lipid bilayers (SLBs) of healthy and diseased composition. SPR reveals that lipophilic statins exhibit higher apparent affinities and slower dissociation kinetics, especially in cholesterol- and anionic lipid-rich membranes. QCM-D analyses demonstrate that statins alter membrane mass, dissipation, and interfacial stiffness in a statin- and membrane-dependent …

Temporal Dynamics Of Programmed Genome Rearrangement In Sea Lamprey Embryogenesis: A Deep Learning & Lightsheet Imaging Approach To Studying Early Developmental Transitions, Kasturi Rajandran

Theses and Dissertations--Biology

Programmed genome rearrangement (PGR) in the sea lamprey (Petromyzon marinus) leads to the elimination of ~0.5Gb (20%) of the germline genome during early embryogenesis, yet its timing relative to the maternal-to-zygotic transition (MZT) remains unclear. In this study, we imaged embryos cleared at 3-hour intervals (up to 72 hours post fertilization (hpf)) using high-resolution lightsheet fluorescence microscopy and a custom deep-learning image-analysis pipeline (~80% accuracy) to quantify nuclei and micronuclei counts. Micronuclei, which are the hallmarks of PGR first appear between 24 to 27hpf (vs ~36hpf previously reported) indicating PGR starts earlier than previously reported in the sea …

The Role Of Metabolic Gate Keepers In Cell Fate Decision Making, Brian Kelly

Theses and Dissertations--Biology

Maintaining cellular energy balance and redox stability is crucial to cell survival, with glutamine metabolism playing a central role. While extensively studied in cancer, where it supports biosynthesis and reduces oxidative stress to promote tumor growth, its function in non-cancerous contexts like tissue development and muscle regeneration remains less understood. A key aspect of stem cell biology is quiescence, a metabolically dormant state that preserves the stem cell pool, yet the mechanisms regulating this state are not fully clear. Here, we identify glutamine metabolism as a critical factor governing myoblast proliferation and quiescence through a metabolic program distinct from that …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at …

Inductions Of Long-Term Potentiation With Biomimetic Electromagnetic Fields In Primary Neurons, Cooper E. Kansala

Theses and Dissertations (Comprehensive)

Endogenous brain rhythms guide neural communication and plasticity, raising the question of whether weak, temporally structured electromagnetic fields (EMFs) that mimic these rhythms can modulate neuronal activity in a targeted, biomimetic manner. This thesis investigates whether patterned EMFs designed to reflect the temporal structure of hippocampal long-term potentiation (LTP) are more effective at inducing neural plasticity than conventional sinusoidal fields or no stimulation at all. Cortical neurons cultured from postnatal rats were exposed to patterned EMFs for 30 minutes and assessed across three distinct experimental domains. In Chapter 2, microelectrode array (MEA) recordings revealed that the LTP-patterned field significantly increased …

Using Abandoned Model Systems And Historical Literature To Teach Modern Concepts And Techniques In Cell Biology, Leocadia V. Paliulis, Gunar Fabig, Sandra Stein, Silke Tulok, Anja Nobst, Chukwuebuka William Okafornta, Thomas Kurth, Thomas Müller-Reichert

Faculty Journal Articles

The cell biology literature of the 19th and early-to-mid 20th centuries is full of the seminal works that were critical for the development of our current understanding of biology but were done using model systems that are no longer commonly used. We argue that these historical papers are ideal for the development of course-based research experiences, both because the background work is conceptually and technically straightforward, and because the study of the abandoned systems stopped prior to the availability of modern techniques. These abandoned systems offer outstanding opportunities for teaching modern light and electron microscopy techniques, thus providing students with …

Leukocyte Infiltration Profiles At The Site Of Intradermal Injection Of Silikon-1000 In Scleroderma-Prone Ucd200/206 And Healthy White Leghorn Chickens, Katee L. Johnson, Jossie M. Santamaria, Chrysta N. Beck, Gisela F. Erf

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Intradermal injections of silicone-based fillers for the face and body may cause chronic inflammation and fibrotic reactions in some individuals. Chickens from the UCD 200/206 White Leghorn (WL) line spontaneously develop a fibrotic autoimmune disease known as scleroderma/systemic sclerosis (SSc). Using the SSc-prone UCD and healthy WL chickens, a longitudinal study was conducted to examine the cellular inflammatory responses to intradermal (i.d.) injections of sterile SILIKON-1000. Specifically, the pulp (a skin derivative) of growing feathers (GFs) was i.d. injected with sterile SILIKON-1000 or phosphate-buffered saline (PBS) as injection control (8 and 3 birds/line, respectively; 10 µL/GF; 20 GFs/bird). Two GFs …

Unleashing Serine Palmitoyltransferase In Test Tubes And Mice, Matthew W. Peart

Theses and Dissertations

Canonically known both for structural contributions to lipid bilayers and roles in cell signaling, the sphingolipids comprise a dynamic, multifaceted class of molecules which are studied to understand homeostatic cell biology as well as pathophysiology. Sphingolipids contribute to tissue-specific structures such as myelin, a multilayer membrane that allows for rapid conduction of action potentials along neuronal axons. All sphingolipids are downstream products of the rate-limiting and initiating enzyme in the de novo sphingolipid synthesis pathway, Serine palmitoyltransferase (SPT). Demonstrative of its status as the enzyme that catalyzes a crucial step in a biochemical pathway, SPT activity is strictly regulated. This …

Repositioning Antimalarial Drugs As Anticancer Agents: Focus On Tafenoquine, Chris Barton

Funded Scholarship

Due to the expensive and lengthy process of drug design and approval, drug repurposing (or repositioning) has become another option for identifying preexisting molecules that may be used for alternative purposes. Recently, some antimalarial compounds have been shown to display efficacy against cancer cell proliferation. In this study, we provide evidence to suggest that multiple preexisting antimalarial drugs can reduce the viability of human cancer cells in culture. Furthermore, we provide the first evidence that one antimalarial, Tafenoquine (LD50 = 9.6 μM in HCT116 cells), is capable of decreasing viability with an efficacy comparable to Etoposide (LD50 = 15.2 μM …

Reversible Degradation Of Peptidoglycan By Lytic Transglycosylases, Aaron Devereaux

Theses and Dissertations (Comprehensive)

Antimicrobial resistance continues to be a burden on the global healthcare system with an estimated cost of billions of dollars and millions of deaths each year. Recently, there has been little to no development on new antibiotics to treat bacterial infection, and any that are developed become resisted to within a few years. Both Gram-positive and Gram-negative bacteria contain a mesh-like layer called peptidoglycan (PG) that surrounds their cells providing strength, cell shape, and protection from their environments. This layer is a polymer of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) connected via a b-1,4-glycosidic bond, with each strand being cross-linked …

Investigating The Role And Expression Of Aquaporin 10 Paralogs In Spiny Dogfish (Squalus Acanthias), Esosa Omoregie

College of Graduate Studies: Theses & Dissertations

Aquaporins (AQPs) are integral membrane proteins that facilitate the selective transport of water and small solutes across cell membranes, playing essential roles in maintaining osmotic balance in vertebrates. Among them, aquaglyceroporins such as AQP10 are capable of transporting water, glycerol, and urea, contributing to osmoregulatory and metabolic processes. This study investigated the expression, localization, and potential physiological roles of two AQP10 paralogs, AQP10C1 and AQP10C2, in the spiny dogfish (Squalus acanthias), a marine elasmobranch that maintains osmotic equilibrium through urea retention and ion regulation. Using RT-PCR, quantitative PCR, Western blotting and immunohistochemistry the study identified tissue-specific expression patterns of …

Micro- And Nano-Plastics Preparation And Their Impact On Cobetia Marina, Lauren Lamothe

Open Access Master's Theses

Plastic pollution has become an increasing threat to marine and coastal environments. Macroplastics derived from consumer waste are broken down by chemical and physical degradation processes, resulting in micro- and nano-plastics (MPs and NPs). This thesis presents an investigation into the MP and NP pollution in the sea surface microlayer (SSML). The SSML contains surface active compounds and natural and anthropogenic matter. This study provides insight into the deeper impacts on the transport and fate of MPs and NPs and on marine bacteria. The first chapter works through the breakdown of plastic particles with the use of a top-down approach …

Plastics And Their Interactions With Bacterial Biofilms Of Synechococcus Sp. Pcc 7002 And Escherichia Coli Nissle 1917, Jackson Zmich

Open Access Master's Theses

Plastic waste is a leading global pollutant with increasing concerns, as recent studies have shown that these wastes are not only concentrated on a macro scale but on a micro and nano scale. These micro- and nano- sized plastic particles, denoted as MPs and NPs, have been measured in marine and freshwater sources, air, food products, and within biosolids expelled from organisms, including humans. Due to their small size, MNPs are entering organisms through inhalation, ingestion, or dermal absorption. [1] Humans are ingesting MNPs daily, with median rates of approximately 200 ng/capita/day for children and 600 ng/capita/day for adults. [2] …

Characterization Of Dietary And Hormonal Influences On Renal Sodium Transporters And Channels In Rodent Models, Evelyn Chan

Scripps Senior Theses

Within kidneys, a diverse array of renal epithelial cells works to maintain electrolyte and water balance to regulate blood pressure and pH. These cells contain varying types of sodium transporters that adjust sodium reabsorption according to the body’s needs. Previous studies have observed sex-specific differences in renal sodium transporter regulation, which are thought to optimize reproduction in females. In this study, we performed high resolution microscopy and detailed characterization of cell type-specific expression and localization of major sodium transporters and channels in rodents in response to dietary and hormonal influences. Specifically, we examined the impact of dietary salt intake and …

Cell Competition Eliminates Aneuploid Human Pluripotent Stem Cells, Amanda I. Ya

Dartmouth College Ph.D Dissertations

Aberrant mitotic chromosome segregation results in the generation of cells with aneuploidy, an incorrect number of chromosomes. Aneuploidy can compromise the viability of the developing embryo and is the leading cause of pregnancy loss, failed embryo implantation, and congenital birth defects. Yet, widescale analysis of human embryos from in vitro fertilization (IVF) clinics suggests that aneuploidy is common, with upwards of 70% of preimplantation embryos being aneuploid.

Mitotic chromosome missegregation during post-zygotic development results in mosaic embryos made up of both diploid and aneuploid cells. Strikingly, upon transplant for pregnancy, mosaic embryos have been reported to result in healthy birth …