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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 …

Investigating The Antibacterial And Immunomodulatory Effects Of Resolvin D2 On Monocytes And Macrophages, Cristina Maria Padovani

Theses and Dissertations

In the late phase of sepsis, immunosuppression occurs, where the host is unable to clear the pre-existing infection and is susceptible to secondary infections. It is believed that the ideal treatments for sepsis should attenuate immunosuppression so that the host can get back to homeostasis. Specialized Pro-resolving Mediators (SPMs) are endogenously- produced fatty acids that resolve infectious inflammation without being immunosuppressive. We hypothesize that an SPM – Resolvin D2 (RvD2) – can augment exhausted macrophage function during the immunosuppressive phase of sepsis. We developed a two-hit model to establish macrophage exhaustion in vitro, and found that RvD2 increased NF-κB activity, …

Neuroinflammation Levels Measured By Microglial Cell Activation, Emma G. Whitlock, Linda S. Yasui

Honors Capstones

Neuroinflammation is an inflammatory response in the brain that can be caused by different stressors such as diseases and/or external factors such as traumatic brain injuries. It is important to note duration and intensity of neuroinflammation levels when determining the impacts of these stressors to the brain environment. During neuroinflammation, a type of immune cell that becomes activated in the brain is called microglial cells. Microglial cells play a role in progression of the pathophysiological effects from the brain stressor. Studying changes in microglial cell shape provides evidence of the degree of neuroinflammation in the brain. Researchers can quantify neuroinflammation …

Role Of Atp-Binding Cassette (Abc) Transporters As A Protector Of Testis Stem Cell Niche From Chemotherapy Drugs In Drosophila Melanogaster, Swagata Maity

Master's Theses

In chemotherapy treatments most tumor cells are destroyed by drugs, but some tumor cells are drug resistant, and these are known as cancer stem cells (CSCs). Normal adult stem cells are also chemo resistant. Therefore, investigation of normal stem cells can be useful to provide further knowledge of CSCs. One of the primary ways that CSCs achieve drug resistance is by drug efflux through transmembrane pumps called ATP-binding cassette (ABC) transporters. Many studies on ABC transporters have been performed in vitro using cultured cell lines, but very few studies have been performed on normal stem cell populations in vivo. Drosophila …

Towards Understanding The Function Of An Ets-Like Gene In Nematostella Vectensis: Generation Of A Knockout Mutant Line And A Transgenic Reporter Line, Emily Bullock

Biological Sciences Undergraduate Honors Theses

Due to their unique phylogenic position as sister to Bilateria, Cnidaria are often credited with the utility of allowing for reconstruction of ancestral biology based on characteristics shared with bilaterians and other animals. This factor makes investigation into the nervous systems of cnidarians critical in understanding early neural evolution. Wamides, a class of neuropeptides, have been shown to play a regulatory role in life cycle transitions across many different species. The cnidarian specific Wamide neuropeptide, GLWamide, has previously been identified to play an accelerator role in the metamorphic timing of a specific species of sea anemone, Nematostella vectensis. However, …

Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna

Dissertations & Theses (Open Access)

As the leading cause of cancer-related deaths worldwide, the development of targeted therapeutics to treat lung cancer remains crucial. Non-small cell lung cancer (NSCLC), the most common histological subtype predominantly comprises lung adenocarcinoma with driver mutations in the K-ras oncogene (KM-LUAD). KM-LUAD progression partly occurs through activation of the NF-κB pathway initiating an inflammatory response and creating a pro-tumor microenvironment. Notably, the pro-inflammatory cytokine IL-1β a potent activator and product of the NF-κB pathway is elevated in the lungs and sera of KM-LUAD patients. We have shown that IL-1β blockade promotes an anti-tumor immune phenotype in a mouse model of …

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations & Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations & Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …

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 …

Uncovering Novel Small Regulatory Rna In Protostome, Sweta Khanal

Dissertations

Small RNAs play pivotal roles in post-transcriptional gene regulation across diverse phylum of protostomes. In this study, we investigate the functional significance of atypical miRNAs, mirtron miR-1017 in Drosophila. Through ectopic expression in neuronal cells, we demonstrate that miR-1017 extends lifespan by targeting its host transcript, acetylcholine receptor Dα2, and influencing its splicing. This novel trans-regulatory function suggests a mechanism for mirtron evolution, highlighting the interplay between splicing and post-transcriptional regulation. Additionally, we profile small RNA populations in the polychaete developmental model Capitella teleta, shedding light on the small RNA landscape in annelid worms. Our analysis reveals a rich …

Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi

Pharmaceutical Sciences (PhD) Dissertations

Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation mechanisms. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using in-situ hybridization (ISH), we identified the subcellular localization of miR-17 in both cilia and cell bodies. We confirmed the importance …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

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, …

The Development Of A New Water-Soluble Zinc Porphyrin, Zntpp--5ap, For Photodynamic Therapy, Kaylee Johnson

Honors Theses

This research focuses on synthesizing a new water-soluble porphyrin with a zinc core that can be used as a photosensitizing agent in photodynamic therapy. Photodynamic therapy is a process in which light is used to activate a photosensitizer to cause cell death. For this study, the porphyrin was synthesized by adding 5-amino-1-pentanol to the ZnTPPC. Once the porphyrin was synthesized it was purified using column chromatography through Sephadex LH-20 and G-50. The structure of the purified ZnTPP-5AP was then analyzed using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), and ultraviolet-visible spectroscopy (UV-vis). Purity of the ZnTPP-5AP was tested using …

Developing Zntpp-4ab As A Potential Photodynamic Therapy Agent, Kennedy Johnson

Honors Theses

Photodynamic therapy is a fairly new technique used in cancer treatment involving the use of a photosensitizer and light exposure to kill malignant cells. In this research, the use of ZnTPP-4AB as a photosensitizer and red light as a source of radiant light energy was explored in terms of cytotoxicity in the A549 lung cancer cell line. ZnTPP-4AB was synthesized by replacing the carbonyl functional groups on the ZnTPPC porphyrin with 4-amino-1-butanol. Following synthesis, the new porphyrin was purified through the use of Sephadex LH-20 and G-50 in column chromatography in order to remove impurities. To confirm the identity and …

The Anatomical Embodiment Of Morning Routines In The Reduction Of Anxiety: An Intervention, Natalie Wright

Expressive Therapies Capstone Theses

The topic under investigation is whether physically embodying a morning routine that was designed through the lens of Laban Bartenieff Movement Analysis (LBMA) will reduce daily symptoms of individuals diagnosed with Generalized Anxiety Disorder.

Since morning routines play a significant part in one’s preparation for the day, I created an individualized LBMA morning routine for a specific client to embody. In addition to the routine, the client documented the process of their anxiety levels on a weekly basis. This client was a white, female, 19-year-old, lesbian college student who was previously diagnosed with Generalized Anxiety Disorder (GAD). The movement analysis …

Synthesis Of Zntpp-Il As A Potential Photodynamic Therapy Agent, Addison White

Honors Theses

Photodynamic Therapy is a new technique used in cancer treatment involving the use of a photosensitizer—a porphyrin—and light exposure to kill malignant cells. In this research, ZnTPP-IL was used as a photosensitizer with white light as a possible source of treatment of NIH 3T3 fibroblast and A549 lung cancer cell lines, with preliminary DNA testing on MYC-22 and G-quadruplex samples. ZnTPP-IL was synthesized by the reaction of the porphyrin ZnTPPC with isoleucinol. The new porphyrin was then purified by column chromatography using Sephadex LH-20 and G-50. ZnTPP-IL was characterized through NMR, IR, UV-vis, and fluorescence spectroscopies. The purity of the …

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 …

The Roles Of Fabp3 In Endothelial Dysfunction And The Transcriptomic Insights Into Cardiovascular Disease, Chi Hien Nguyen

Electronic Thesis and Dissertation Repository

Heart-type fatty acid binding protein (FABP3) is an effective biomarker for cardiac injuries. However, it has also been tested as a biomarker in patients with peripheral artery diseases; these conditions are complications of atherosclerosis, which is driven by endothelial dysfunction. As FABP3 release is not exclusive to the heart but appears to characterize cardiovascular events, whether FABP3 influences endothelial function is not known. Additionally, the transcriptomic profiles of endothelial cells during cardiovascular stresses remain under-investigated. This thesis investigates the multifaceted role of FABP3 and the transcriptomic alterations in endothelial cells under different cardiovascular stressors, offering novel insights into endothelial dysfunction …

Deciphering The Functional Connections Between The Nuclear Paraspeckle And Rad51 Homologous Recombination Proteins Using A Yeast Protein Interaction System, Eric J. Nutz

Senior Theses

Homologous recombination (HR) is a repair pathway for DNA double-stranded breaks. Mutations in HR genes contribute to genomic instability and increase the prevalence of cancer. Exploiting HR deficiency in tumor cells has led to improved synthetic lethality outcomes. RAD51 paralogue protein complexes are known to be involved with HR. Proteomic analysis of RAD51 paralogues reveals a connection to the nuclear paraspeckle. A paraspeckle is a little-known, specialized organelle found in the interchromatin space of the nucleus in mammalian cells. Its three central protein components include SFPQ, NONO, and PSPC1. RAD51D is an HR protein shown previously to interact with SFPQ …

Investigating The Escape Mechanism Of Sre Bearing Mrna Transcripts During Viral Host Shutoff, Daniel Macveigh-Fierro

Doctoral Dissertations

During viral infection, the virus and host clash for control over gene expression in an evolutionarily arms race that has raged for thousands of years. During lytic replication, Kaposi’s sarcoma associated herpesvirus (KSHV) triggers a massive RNA decay event known as host shut off. This causes over 70% of all RNA to be degraded suppressing the host antiviral response while freeing resources for viral replication. Our lab focuses on a subset of transcripts that escape from this viral degradation event using a cis acting 3’ UTR element known as a “SOX resistant element” or SRE. Although we have identified a …

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

Identification And Characterization Of Isoflavone Reductase Family Members In Soybean, Negin Azizkhani

Electronic Thesis and Dissertation Repository

Soybean’s yield is threatened by Phytophthora sojae, a pathogen responsible for stem and root rot disease. Glyceollins, unique antimicrobial agents specific to soybeans in partially preventing P. sojae infection, are derived from the isoflavonoid branch of the general phenylpropanoid pathway. One pivotal enzyme exclusively involved in glyceollin synthesis in soybean is the isoflavone reductase (GmIFR), which catalyzes the 2'-hydroxydaidzein conversion to 2'-hydroxy-2,3-dihydrodaidzein as a precursor for glyceollin biosynthesis. To comprehensively identify all members of the GmIFR gene family within the soybean genome, keyword and blast protein searches were conducted, identifying 98 putative GmIFRs. Among these candidates, …

Species Delimitation Of Slimy Salamanders, Plethodon Kisatchie And Plethodon Mississippi, Across The Lower Mississippi River, Brock Hunter Stevenson

Master's Theses

Species are fundamental units of biodiversity yet delimiting species can be challenging. Slimy Salamanders of the Plethodon glutinosus species complex are a classic example of cryptic species for which species boundaries and relationships have proved difficult to determine. Once thought to be a single species ranging across the eastern United States, protein analysis revealed high genetic divergences among geographically distinct groups of populations, leading to 16 species being recognized within the group. Two of these species, the Louisiana Slimy Salamander (Plethodon kisatchie) and the Mississippi Slimy Salamander (Plethodon mississippi), are closely related but occur on opposite sides of the Mississippi …

Characterizing Hypoxia, Neutrophil Persistence And Revascularization In The Murine Db/Db Model Of Type Ii Diabetic Impaired Skin Healing, Michael R. Grynyshyn

Electronic Thesis and Dissertation Repository

Impaired skin healing represents a significant clinical burden. In the diabetic, inflammatory aberrations, hypoxia and insufficient angiogenesis all result in negative wound healing outcomes - repeated infections, poor perfusion and ultimately amputation. Previous research has reported comparable levels of neutrophils in closed wounds up to 4-12 weeks old. Our study interest was in investigating the dynamics of hypoxia resolution, neutrophil persistence and angiogenic response in the db/db model. Contrary to our hypothesis, we observed significantly higher hypoxic load in the wild types at days 3 and 7. Additionally, we observed significantly elevated neutrophil numbers at day 7 db/db wound bed …

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 …

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

Estrogen Receptor (Er) Alpha Regulatory Mechanisms And Therapeutic Strategies In Er+ Breast Cancer, Bianca A. Romo

Dartmouth College Ph.D Dissertations

Breast cancer is among the most frequently diagnosed cancers in the U.S. and is one of the leading causes of cancer-related mortalities, second to lung cancer. Estrogen receptor alpha-positive (ER+) breast cancer accounts for 2/3 of diagnosed cases. Patients diagnosed with this subtype of breast cancer typically undergo endocrine therapy that aims to mitigate the growth-promoting effects of estrogen/ER. While therapies are effective, 1/3 of patients will experience recurrence. To begin addressing this drug-resistant patient population, we investigated potential drug targets involved in response to treatment.

Coregulators have been implicated in the regulation of ER transcriptional activity and subsequently affecting …

Assessing Lipid Composition Of Cell Membrane In Escherichia Coli Under Aerobic And Anaerobic Conditions, Isabelle Johnson

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Escherichia coli is a highly studied model organism that is tightly tied to the mammalian gastrointestinal system. This microorganism has the capability to be a beneficial gut microbe or a life-threatening pathogen. In this study, the lipid membrane of Escherichia coli was investigated using Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) to observe the change in its composition in aerobic and anaerobic conditions. Evidence of desaturation was discovered in the spectra, though more investigation is needed to understand the metabolic processes and drives that result in this change. Elucidation of these pathways in the future could result in …