Cell Biology Commons^™

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Syntaxin-3 Mediates Baseline And Stimulated Mucin Secretion, Brianne Wharton

Dissertations & Theses (Open Access)

There are two rates at which airway epithelial cells secrete mucin. The low baseline rate accounts for ciliary clearance, and the high stimulated rate obstructs airways in protection from helminths or in obstructive pulmonary diseases. The exocytosis of mucins occurs via the four-helix SNARE complex. The SNARE proteins contributing helices are the vesicle-SNARE VAMP, and the target-SNAREs SNAP and Syntaxin. Coiling of the complex fuses the granule and plasma membranes to release mucins into the extracellular space. The VAMP and SNAP isoforms mediating baseline and stimulated secretion are known, but the Syntaxin (Stx) isoform remains unknown.

Three candidate exocytic Stx, …

Qualitative Assessment Of Human Embryonic- And Induced Pluripotent Stem Cell Derived Neural Stem Cells Under Cgmp Methods, Michelle Hernandez

Electronic Theses, Projects, and Dissertations

Neural stem cell therapies represent a promising tool for the development of regenerative medicine and are being tested in clinical trials for several neurological disorders. However, the clinical applicability of stem cell therapies is dependent on the implementation of current good manufacturing practices (cGMPs) to ensure the quality, safety, and consistency that stem cell products need to meet FDA regulatory requirements. As such, there is a need for a shift to xeno-free methodologies so experimental conditions are cGMP compliant. The purpose of this study is to test a GMP compatible production method to generate multipotent neural stem cells (NSCs) from …

Atlas-Based Analysis Of The Neural Projections From The Lateral Hypothalamic Area To The Lower Brainstem In The Adult Male Rat, Jessica Valeria Salcido Padilla

Open Access Theses & Dissertations

Within the last decade, the number of diseases associated with dysregulation of the neural circuits responsible for energy balance, glucosensing, and feeding control has increased. One brain region containing these circuits is the lateral hypothalamic area (LHA), which plays an important role in the sleep/wake cycle, energy balance, and motivated behavior. Although the LHA has been termed a â??feeding centerâ??, other regions within the hindbrain are known for the regulation of similar functions including energy balance, glucosensing, and feeding control. While many studies have explored and reported projections from the LHA to the hindbrain, few have further investigated the interconnections …

The Anti-Diabetic Drug Metformin Disrupts Feeding And Sleeping Behaviors In Drosophila Melanogaster., Lucas Fitzgerald

College of Arts & Sciences Senior Honors Theses

Dimethylbiguanide, also known as metformin, is the single most prescribed oral treatment for non-insulin dependent diabetes mellitus, or type 2 diabetes, in Western countries. The primary mechanism of action that metformin acts through is the activation of AMP kinase, an important regulator of energy homeostasis. While the anti-diabetic effects of metformin are well documented, its effects on feeding and sleeping behaviors are not well characterized. Using the model organism Drosophila melanogaster, the mean daily quantity of food consumed was measured and compared between groups treated with several dosages of metformin. Feeding interactions such as meal frequency and length were …

Ammonium Chemotaxis In Chlamydomonas Reinhardtii, Gabela Nelson

LSU Doctoral Dissertations

Analysis of ammonium chemotaxis in Chlamydomonas reinhardtii is largely hindered, compared to that of phototaxis, despite equal importance on flagellated microalgal physiology. A major contribution of this shortfall is the lack of proper assay method. We developed a simple Petri dish assay method in which light is homogenously exposed while patterns of the cellular migration are tracked with a function of time. Using the method, new findings were revealed. First, this research presented that a strain lacking the eyespot organelle required for light gradient-sensing exhibits similar chemotactic behavior compared to a wild-type strain, suggesting Chlamydomonas sense an ammonium gradient not …

Pulsed Electric Fields Sensitize Methicillin-Resistant Staphylococcus Aureus To Antibacterial Therapies And Stimulate Host Immune Responses, Alexandra E. Chittams-Miles

Biomedical Sciences Theses & Dissertations

This research explores the impact of nanosecond pulsed electric fields (nsPEF) on two fronts: their immune stimulatory effects and their potential as a novel strategy to enhance the sensitivity of Methicillin-resistant Staphylococcus aureus (MRSA) to clinically relevant antibiotics. While pulsed electric fields have been reported to have an immune stimulatory effect, the mechanisms responsible for these effects have yet to be determined.

Our investigation addresses the rising concern of MRSA derived skin and soft tissue infections (SSTIs). Consistent with other publications, we found that nsPEF alone cause modest inactivation of planktonic MRSA. We then investigated the effects of nsPEF in …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya

Open Access Theses & Dissertations

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …

Breaking Virulent: The Coincidental Evolution Of Virulence Factors In Bacteria., Rhiannon Emmanuelle Cecil

Electronic Theses and Dissertations

Understanding how innocuous organisms can evolve to be pathogenic to humans is of increasing global concern. Further, understanding how existing pathogens may evolved to be more virulent is also vital to our ability to provide healthcare to people afflicted with diseases that promote chronic bacterial infections, such as cystic fibrosis. With the rise of antibiotic resistance in both bacteria and fungi it is paramount that new therapeutics are identified. Understanding what mutations occur that result in increased virulence in microbes can potentially provide new targets for antimicrobial drugs to combat antibiotic resistance. The Coincidental Evolution Hypothesis is a fundamental hypothesis …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …

Overexpression Of Sox18 Increased Cell Proliferation, Migration And Colony Formation In Pediatric Sarcomas, Jack Ojile

Honors Program Theses and Research Projects

Cancer has become one of the leading causes for premature deaths and continues to increase in rank across the world. An estimated 19.3 million new cases of cancer were reported in 2020 and 10 million cancer related deaths occurred worldwide. Ewing sarcoma and Rhabdomyosarcoma are two pediatric cancers that have not made significant improvements to patient survival for a metastatic diagnosis and the current chemotherapy regiment can cause several undesirable side effects immediately after treatment or later in life. SOX18 has been observed to play some role in various tumorigenic properties like proliferation, invasion, and resisting cell death signals in …

Investigating The Absence Of A Dietary Response At The Neuromuscular Junction In Larval Drosophila Melanogaster, Suzanna Marbach

Honors Program Theses and Research Projects

Research in Drosophila melanogaster (D. melanogaster) has been growing in order to identify the fundamental processes of human disorders of the central nervous system such as Alzheimer’s disease, diabetes, and other neurological disorders at a molecular level. Altered insulin signaling itself has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathies, and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on nervous system function is still incomplete. The focus behind investigating the insulin signaling pathway is derived from our observations in the adult D. melanogaster neuromuscular junction (NMJ) to changes in …

Does Vdac2 Have A Bh3 Domain?, Lillian Ferkany

Honors Theses

Mitochondrial outer membrane permeabilization (MOMP) by Bax oligomerization triggers apoptosis. BCl-2 family proteins, classified as BH3 only proteins, pro-survival proteins, or pro-apoptotic proteins, control apoptosis partly through their agonist or antagonistic effects on Bax, which are mediated by their conserved BH3 domains. All BH3 domains form an alpha helix containing 5-7 conserved hydrophobic residues, designated H0-H5, and one conserved aspartic acid that drive interaction with Bax and other ‘multi-domain’ BCl-2 members. BH3 agonists induce Bax oligomerization, while BH3 antagonists sequester Bax to prevent MOMP. We discovered that voltage dependent anion channels (VDACs) in the MOM contain a putative BH3-like domain …

Investigation Of The Role Of Dax-1 In The Hpa Axis In Human Adrenal Cells, Katerina N. Fargas

Undergraduate Honors Theses

DAX-1 is a nuclear hormone orphan receptor that plays a key role in the development of reproductive tissues and steroid hormone production. The hypothalamic-pituitary-adrenal axis is the pathway for steroid hormone production, primarily glucocorticoids, mineralocorticoids, and adrenal androgens, in the human body. The mechanisms of DAX-1 in hormone production in the adrenal cortex of the HPA axis are not completely understood and, therefore, were the focus of this honors thesis research project. Due to the high level of DAX-1 expression, SW13 adrenal carcinoma cells were conducted for these experiments. We investigated whether glucocorticoids, specifically the synthetic glucocorticoid dexamethasone, had any …

Examining Transcriptional Regulators During Muscle Development In Drosophila Melanogaster, Chaamy Yapa

Student Theses and Dissertations

In Drosophila melanogaster embryos, a distinct approach to study the transcriptional regulation is to examine the larval somatic muscle development. Transcription factors are essential regulatory proteins that help to control gene expression and respond to signaling pathways and various cues. Today, there are at least twenty transcription factors that have been discovered to contribute to the development of the 30 distinct larval somatic muscles in each abdominal hemisegment of Drosophila melanogaster. Several studies have already been conducted on muscle regulatory transcription factors including midline and apterous. These transcription factors were shown to control the development of muscles through mutant …

Understanding The Expression And Role Of Pros-1 In The Male Gonad Of C. Elegans, Jack Bozik

Undergraduate Theses

The gene pros-1 is a transcription factor that is highly expressed within neuronal sheath cells, glial cells, and excretory canal cells. pros-1 plays a role in cell determination of those cell types in the nematode C. elegans, which promotes organismal development. But the degree to which pros-1 presence is important is still not fully understood, because there are many genes involved in development that when mutated or damaged can result in unexpected phenotypes or even total loss of function to a certain developmental mechanism. What makes pros-1 valuable to research is that it is a functional homologue to a …

Transcriptional Silencing Of Cdk18 And Its Role In Lung Carcinogenesis Of Brg1-Mutant Lung Cancers, Loryn M. Phillips

Biology ETDs

BRG1 is mutated in 10% of lung cancers, making this mutation clinically relevant. The downstream effects of BRG1 included significantly affecting the cell cycle control and chromosomal replication pathway. CDK18, a cyclin-dependent kinase, was determined to be the gene with significantly decreased expression (p

Characterization And Genomic Analysis Of Two Escherichia Coli O157:H7 Bacteriophages Isolated From Pigeons, Mohamad I. Alolama

Dissertations

Enterohemorrhagic Escherichia coli, also known as EHEC, is a subset of Shiga toxin-producing E. coli (STEC), and it has recently been identified as one of the principal foodborne pathogens. E. coli O157:H7 is the most important serotype of STEC for its role in causing foodborne illnesses. E. coli O157:H7 could cause various gastroenteritis symptoms such as diarrhea, hemolytic uremic syndrome, hemorrhagic colitis, and thrombotic thrombocytopenic purpura and may cause death. Elimination of E. coli O157:H7 during food processing and storage is a possible solution. Bacteriophages have a significant impact on bacterial populations in nature due to their ability to …

Dissecting The Role Of Selenoprotein P And Thioredoxin Reductase In Pancreatic Cancer Metabolism, Alyssa A. Abbas

Dissertations, Master's Theses and Master's Reports

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of US cancer-related deaths, has a stark 5-year survival rate of 9%, emphasizing an urgent need for effective therapies. A well-established characteristic of cancer, metabolic dysregulation, presents an opportunity for developing therapies that target specific metabolic susceptibilities inherent in cancer cells. Our recent studies have discovered a susceptibility in PDAC; deprivation of cystine or blocking its uptake by erastin (a cystine transport inhibitor) triggers significant lipid peroxidation, thereby inducing ferroptosis specifically in the mesenchymal subtype of PDAC, but not in the epithelial subtype. This study aims to elucidate the roles of Selenoprotein …

Endogenous Antioxidant Response And Lipid Peroxidation Levels In Muscle Tissue Of The Cownose Ray (Rhinoptera Bonasus), Bailey Berry

Electronic Theses and Dissertations

Oxidative stress is the result of an imbalance between reactive oxygen species (ROS) and antioxidant response within cells. ROS generation is a natural consequence of ETC activity within the mitochondria and is associated with aerobic metabolism. Oxidative stress data on elasmobranch muscle is limited, with previous studies primarily focusing on mammalian and teleost muscle. Elasmobranch skeletal muscle is generally composed of large proportions of white muscle fibers (anaerobic), low proportions of red muscle fibers (aerobic), and low proportions of pink muscle fibers (anaerobic). The cownose ray, a benthopelagic batoid species, presents an interesting model of study because it contains relatively …

Exploring The Molecular Basis Of Touch: A Comparative Analysis Of Gene Expression In Sensory Corpuscle-Rich And Corpuscle-Poor Skin Regions In The Duck, Thomas Hart

Theses and Dissertations--Biology

Cutaneous touch is facilitated by discrete cellular complexes composed of non-neuronal cells associated with mechanoreceptor neuron endings. The non-neuronal cells of these cutaneous end organ complexes (CEOCs) are believed to contribute to touch, but their role in touch sensation remains unclear. To better understand the function of CEOC cells, we sought to characterize the transcriptional profile of CEOC-rich tissue and identify genes expressed in CEOC cells. Bill skin of the tactile foraging Pekin duck (Anas platyrhynchos) is dense with CEOCs, specifically the avian analogs of mammalian Pacinian and Meissner corpuscles, while corpuscles in duck foot skin are scarce. Using RNA …

The Role Of Cort And Anaphase Promoting Complex/Cyclosome (Apc/C) In Drosophila Sex Determination And Meiosis, Abuzar Sikander Malik

Electronic Theses and Dissertations

The E3 ubiquitin ligase, APC/C, is essential for the completion cell cycle; along with its co-activators it allows mitotic exit and maintenance of G1. APC/C marks various substrates with ubiquitin chains; marked substrates are subsequently destroyed via the 26S proteasome pathway. Cort is a Drosophila female meiosis specific activator of APC/C. Cort works within meiosis in conjunction with Fzy to mediate Securin and cyclin destruction. A C-terminal IR-tail motif and a N-terminal C-box support Cort-APC/C interaction, whereas short motifs like D-box and KEN-box on the target protein impart substrate recognition to Cort. Cort expression is tightly controlled in the female …

Cul3 Negatively Regulates Nlrp12-Mediated Inhibition Of The Canonical Nf-Κb Signaling Pathway, Inyeong Lee

MSU Graduate Theses

Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is mainly known for its inhibitory function on NF-κB signaling in innate immune cells, and more recently, for its ability to regulate chemokine signaling and ubiquitination of the immune receptor RIG-I. Through a yeast 2-hybrid screen, the Lupfer lab previously discovered that NLRP12 interacts with other ubiquitin-associated proteins including Cullin 3 (CUL3) and RING finger protein 2 (RNF2). This research was conducted to mainly investigate the interaction between NLRP12 and CUL3 in human cells and examine the role in regulating NF-κB signaling. Previously, co-immunoprecipitation, followed by western blot analysis, and confocal microscopy …

Evaluation Of Leishmanicidal Activities Of 4-Thiazolidinones Against Leishmania Major, The Causative Agent Of Human Cutaneous Leishmaniasis, Kiera Bush

All Master's Theses

The leishmaniases are a group of vector-borne parasitic diseases that affect many developing countries including parts of Africa, India, and the Middle East in addition to Southern Europe and the Americas. It is estimated that worldwide, there are about 3 million new cases of leishmaniases each year leading to as many as 50,000 fatalities annually. The parasites that cause leishmaniasis belong to the genus Leishmania spp and are transmitted by the female phlebotomine sand fly. There are three clinical forms of the infection: visceral, mucocutaneous, and cutaneous. However, the focus of this paper is on cutaneous leishmaniasis that causes skin …

Characterization Of Parp1-Dependent Poly-Adp-Ribosylation Of Sprtn, Quincee Simonson

Electronic Theses and Dissertations

DNA-protein crosslinks (DPCs) are a type of DNA lesion that form when proteins become covalently linked to DNA. It is estimated that replicating cells experience approximately 6,000 DPCs per day per genome during exponential growth (Ruggiano & Ramadan, 2021). If left unrepaired, DPCs can be lethal to cells. For this reason, cells have evolved multiple pathways to repair or bypass DPCs to survive. One such pathway involves SPRTN, a nuclear metalloprotease that plays a key role in the repair of DPCs through direct proteolysis (Lopez-Mosqueda et al., 2016; Vaz et al., 2016). Once SPRTN degrades the bulky protein component of …

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 …

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

Electronic Theses and Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess

Open Access Theses & Dissertations

Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …