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Changes In Rna Expression Of Hut78 Cells Resulting From The Hiv-1 Viral Protein R R77q Mutation, Joshua S. Ramsey

Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1) is the causative virus for acquired immunodeficiency syndrome (AIDS). AIDS is characterized by chronic inflammation and reduction of CD4+ T-cells in the blood. This leads to the patient becoming immunocompromised and much more susceptible to disease in general. Different phenotypes in the progression of AIDS have been observed in patients in either progressing to AIDS faster as a Rapid Progressor (RP), or slower as a Long-Term Non-Progressor (LTNP). Researching elements that result in the LTNP phenotype is of interest as it has the potential to offer alternative treatments and therapies to those suffering from …

Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe

Electronic Thesis and Dissertation Repository

Maternal diabetes increases congenital malformations due to teratogenic effects of glucose on the developing embryo. High glucose culture alters preimplantation embryo development and is associated with increased oxidative stress. Apoptosis and autophagy are programmed cell death and survival mechanisms induced by oxidative stress, but their role in preimplantation diabetic embryopathy is poorly elucidated. It was hypothesized that high glucose culture would alter autophagic and apoptotic responses, and that they are dependent on the timing of high glucose culture initiation. Embryos were cultured with 0.2 mM (control) or 25 mM (high glucose) of D-glucose starting from the early (36 hpi) or …

Is Vdac1 A Novel Bcl2 Family Member That Binds Bax?, Claire Pearson

Honors Theses

Apoptosis is a type of regulated cell death important for normal embryonic development and maintenance of adult tissues by removing excess or dysfunctional cells to ensure proper functioning of organs. The Bcl-2 family of proteins determines whether apoptosis remains suppressed or becomes activated through the balance of interactions among pro-survival and pro-death members. A defining feature of the Bcl-2 family is a BH3 domain that drives interactions between the family members. Isoform 1 of the voltage dependent anion channel (VDAC1) has an important role in metabolism, but was recently found to have high homology with known BH3 domains. This study …

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 …

Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif

Student Research Submissions

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H⁺ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku

Biotechnology Theses

Lung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the …

Bis-Indolyl Compounds And The Induction Of Apoptosis In T98g Glioblastoma Multiforme Cells, Margot C. Brown

Seton Hall University Dissertations and Theses (ETDs)

1,1-bis(3’idolyl)-1(aryl)methane compounds (BIM compounds) have been shown to have anti-cancer properties in colon cancer, bladder cancer, and leukemia cells. The purpose of this work was to determine if BIM compounds could be an effective treatment of glioblastoma multiforme. Sulforhodamine B (SRB) assays showed that 20µM of the BIM compounds could inhibit cellular proliferation of the T98G glioblastoma multiforme cell line over 72 hours. Then immunoblotting was used to analyze the molecular pathway induced by BIM compounds. An increase in the expression of both BAX and cleaved caspase 3 suggest BIM compounds activate programmed cell death, or apoptosis in glioblastoma cells. …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

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 …

A Functional Study Of Topological Dna Problem In Human T Cells During Chronic Viral Infection, Xindi Dang

Electronic Theses and Dissertations

T cells play an important role in adaptive immune system against viral infections, while premature aging and dysfunction of T cells induced by unrepaired DNA damages are always non-negligible snags during the long-term of fighting with chronic viral infections, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV) infection. In this dissertation, we investigated the role of topological DNA damage in reprogramming telomeric DNA damage responses (DDR), mitochondrial metabolisms, and T cell functions using CD4+ T cells derived from individuals with chronic viral infections or healthy subjects treated with topoisomerase inhibitors. The healthy human …

The Effects Of Polymorphisms Of Viral Protein R Of Hiv-1 On The Induction Of Apoptosis In Primary Cells And The Characterization Of Twelve Novel Bacillus Anthracis Bacteriophage, Jacob D. Fairholm

Theses and Dissertations

Viral protein r (Vpr) of Human immunodeficiency virus type 1 (HIV-1) plays an important role in the ability of the virus to infect cells and cause disease. Two polymorphisms to Vpr have been shown to result in differences in disease progression in infected individuals. R36W tends to result in rapid disease progression while R77Q results in long-term non-progression. In order to better understand how these polymorphisms result in these different disease phenotypes, our lab has recently shown that in cell culture, the R36W polymorphism results in increased viral replication and greater induction of cell death. On the other hand, infection …

Targeting Delivery Of Bcl-2 Family Protein Inhibitor Has The Potential To Treat Cancer And Fibrosis, Mohammad Nurul Huda

Open Access Theses & Dissertations

Apoptosis is a naturally occurring cell death mechanism to remove the selective cell population. B-cell leukemia/lymphoma-2 (BCL-2) family protein plays a critical role in activating the upstream apoptosis signaling pathway, primarily the intrinsic apoptosis pathway. The BCL-2 family consists of both pro-and anti-apoptotic proteins, which are structurally and functionally similar, containing up to four BCL-2 homologies (BH) motifs (BH1-4). Defecting apoptosis along this signaling pathway can lead to various events, including malignant cell transformation, tumor metastasis, tissue fibrosis, and drug resistance. In fibrosis, the aberrant apoptosis signaling also activates multiple effector proteins and growth factors, such as TGF-β, CTGF, and …

In Vitro Investigation Of Tumor Selective Piperidones As Therapeutic Agents Against Leukemia Cancer Cells, Lisett Contreras

Open Access Theses & Dissertations

Cancer is a continuous global health issue. It is the second leading cause of death behind heart disease. Disparities across the emergence of cancer and resulting fatalities raise the importance of researching the disease. Treatments are available for certain types of cancers. However, these are typically accompanied by residual problems including side effects and the possibility for relapse. Some treatments attack all cells, leading to unwarranted side effects that make the possibility of living a comfortable life nearly impossible. Other treatments are specific to certain genetic alterations, making them only useful for a small percentage of patients. Not one treatment …

The Effects Of Triaminopyrimidine Analogs And Gold(I) Chloride Compounds On Cell Proliferation And Apoptosis In Mda-Mb-231 Human Breast Cancer Cells, Robin Redline

College of Science and Health Theses and Dissertations

Breast cancer is a common disease that affects both women and men all over the world. Triple negative breast cancer is an aggressive subtype of breast cancer with poor survival statistics and few available treatment options. Uncontrolled cell proliferation and the ability to avoid programmed cell death, apoptosis, are two shared hallmarks of cancers. Previous research has shown a group of heterocyclic molecules called triaminopyrimidines, not tested in this study, may be effective antiproliferative agents. Previous research has also shown that some gold(I) complexes not tested in this study, may be promising anticancer agents. In this study, a few chemicals …

An Assessment Of Inp/Zns As Potential Anti-Cancer Therapy: Quantum Dot Treatment Induces Stress On Hela Cells, Victoria Grace Davenport

MSU Graduate Theses

Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dots (QDs) are an emerging option in QD technologies for uses of fluorescent imaging as well as targeted drug and anti-cancer therapies based on their customizable properties. In this study we explored effects of InP/ZnS when treated with HeLa cervical cancer cells. We employed XTT viability assays, reactive oxygen species (ROS) analysis, and apoptosis analysis to better understand cytotoxicity extents at different concentrations of InP/ZnS. In addition, we compared the transcriptome profile from the QDtreated HeLa cells with that of untreated HeLa cells to identify changes to the transcriptome in response to the QD. Intracellular …

Molecular Mechanisims Underlying The Anti-Cancer Activity Of Gum Arabic From Acacia Sp. In Triple-Negative Breast Cancer Cells., Sawsan Yaslam Alyafii

Theses

Metastatic breast cancer is the leading cause of cancer-related deaths among women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive, accounting for 15-20% of all breast cancer cases. As TNBC cells lack the expression of hormone receptors estrogen receptors (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2), TNBCs are unresponsive to hormonal therapy and often become highly resistant when exposed to standard chemotherapy, which has been identifies as a major obstacle in TNBC treatment. Gum Arabic, a natural exudate produced from plants, is widely used traditionally for religious, cosmetics as well as medical purposes …

Molecular Mechanisims Underlying The Anti-Cancer Activity Of Gum Arabic From Acacia Sp. In Triple-Negative Breast Cancer Cells, Sawsan Yaslam Hussein Alyafii

Theses

Metastatic breast cancer is the leading cause of cancer-related deaths among women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive, accounting for 15-20% of all breast cancer cases. As TNBC cells lack the expression of hormone receptors estrogen receptors (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2), TNBCs are unresponsive to hormonal therapy and often become highly resistant when exposed to standard chemotherapy, which has been identified as a major obstacle in TNBC treatment. Gum Arabic, a natural exudate produced from plants, is widely used traditionally for religious, cosmetics as well as medicinal purposes …

Investigative Mechanisms To Exploit Caspase-Induced Apoptosis Using Polymeric Nanogels, Francesca Edith Anson

Doctoral Dissertations

Cysteine aspartate proteases (caspases) act as the molecular scissors of cell death, disintegrating diverse cellular components necessary for survival and growth via proteolysis. Caspases are tightly regulated through a myriad of mechanisms including proteolytic processing, structural changes, post-translational modifications and metal binding. Correspondingly, cancers have evolved numerous resistance and desensitization mechanisms upstream or within the caspase pathway to avoid death signals. These mechanisms are extremely diverse and are not fully understood however, the field overwhelming suggests caspase activity and caspase inhibition antagonism to be critical for efficacious cancer therapies. Accordingly, exploiting the role of caspases in apoptosis has become an …

Novel Insights Into The Role Of Pyruvate Kinase M2 In Podocyte Homeostasis And Function, Mohammed Alquraishi

Doctoral Dissertations

Background: Renal diseases are major health concerns and among the top ten leading causes of death in the US. A large number of these diseases are characterized by deterioration in glomerular structure and function, leading to reduced filtration capacity and proteinuria. Glomerulus podocytes are epithelial cells that maintain glomerular integrity and act as a defense mechanism against proteinuria. Recent advances in renal research suggested a novel role of glycolysis and its related enzymes, pyruvate kinase M2 (PKM2) in particular, in the progression of renal diseases. However, the precise role of PKM2 in podocyte homeostasis and its contribution to glomerular function …

The Impacts Of Psychological Stress On Innate-Like Invariant T Cell Survival, Phenotype, And Function, Patrick Rudak

Electronic Thesis and Dissertation Repository

The nervous system serves numerous critical roles in the regulation of immune responses. Consequently, psychological stress can result in immunosuppressive states that are conducive to the development of infection and cancer. Yet, whether stress impacts the functions of innate-like T lymphocytes including invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, which participate in early host defense against pathogens and tumors, remains poorly understood. In this thesis, I leveraged multiple established methods with which to induce psychological stress in mice. I demonstrate that T_H1- and T_H2-type immune responses initiated by iNKT …

Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration, Sandeep Saxena

Theses and Dissertations--Biology

Mammalian system consists of stress-sensing molecules that regulates their cellular response against damage, injury and oncogenic stress. During vertebrate regeneration, cells responding to injury re-enter the cell cycle and proliferate to form new tissue. Cell cycle re-entry or arrest is at least partly regulated by cellular senescence which negatively impacts the proliferative pool of cells during regeneration. What remains unclear is whether cells in regenerating systems possess an increased propensity to proliferate and are refractory to signals that induce senescence. My thesis work has focused on how fibroblasts from the ear pinna differentially regulate healing in highly regenerative mammals (e.g., …

Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka

Legacy Theses & Dissertations (2009 - 2024)

Ricin is a highly lethal protein toxin derived from the seeds of the castor plant, Ricinus communis. It is a Type II ribosome inactivating protein (RIP), meaning it is a heterodimer with one subunit, ricin toxin B (RTB), that mediates cell surface attachment and intracellular trafficking and a second subunit, ricin toxin A (RTA), that irreversibly shuts down protein synthesis in the cytosol. During trafficking, RTA and RTB necessarily separate in the endoplasmic reticulum, wherein RTA unfolds and translocates into the cytosol where it refolds into an enzymatically active conformation. RTA is remarkably fast acting and efficient, with few molecules …

Potential Drug Treatment For Duchenne Muscular Dystrophy Which Could Be Through Upregulation Of Lipin1, Rajsi Y. Thaker

Browse all Theses and Dissertations

Duchenne muscular dystrophy (DMD) is a genetic disorder leading to progressive muscle degeneration and weakness due to mutation in dystrophin gene, which is very important for maintaining muscle membrane integrity. Dystrophin is the largest gene in the human genome therefore more prone to mutation. There is currently no cure for DMD. Our lab recently found that Lipin1 deficient myofibers showed upregulation of necroptosis correlated with the loss of muscle membrane integrity. Our primary approach for ameliorating dystrophic phenotype in DMD is through reduction of necroptosis using drugs which can potentially upregulate Lipin1 expression. In this study, we identified two drugs …

Tunel Apoptotic Cell Detection In Stony Coral Tissue Loss Disease (Sctld): Evaluation Of Potential And Improvements, E. Murphy Mcdonald

All HCAS Student Capstones, Theses, and Dissertations

Stony coral tissue loss disease (SCTLD) is a highly lethal coral disease that has caused a dramatic loss of coral tissue along the Florida Reef Tract and throughout the Wider Caribbean. This study seeks to understand whether programmed cell death (apoptosis) is involved in the pathology of the highly virulent SCTLD tissue loss lesion. Tissues from diseased colonies of Pseudodiploria strigosa collected in 2018 and 2020 were stained using the terminal deoxyribonucleotidyltransferase (TdT) mediated dUTP-biotin nick end labeling (TUNEL) assay to visualize areas of programmed cell death. The archived tissue samples collected in 2018 exhibited a significantly higher degree of …

Investigating The Role Of Lin-35 And The Dream Complex In Preserving Fertility Under Stress In C. Elegans, Frances Virginia Compere

Master's Theses (2009 -)

Organisms are subjected to environments that can fluctuate and cause them stress. Therefore, organisms must have the ability to adapt to the stress to survive and propagate. Temperature stress is becoming an increasingly relevant type of stress due to climate change and is known to affect fertility in many types of organisms including the model organism Caenorhabditis elegans. Here we examine the role of LIN-35, the single C. elegans homolog of the tumor suppressor Retinoblastoma (pRB), in fertility under moderate temperature stress. We found that lin-35 mutants lose fertility more drastically under moderate temperature stress than wildtype worms, and that …

Dimers Of Isatin Derived Spirocyclic Nf-Κb Inhibitor Exhibit Potent Anticancer Activity By Inducing Upr Mediated Apoptosis, Smit Kour

Theses & Dissertations

Activation of NFκB pathway has been implicated in several malignancies and plays a role in many key processes including tumor initiation and progression. The NFκB pathway is activated when TNFα in the tumor microenvironment binds to its receptor, eventually leading to the phosphorylation of the kinase IKKβ. Once active, IKKβ phosphorylates IκBα, a protein that functions to sequester NFκB in the cytosol of resting cells. The phosphorylation of IκBα leads to its degradation in the proteasome and allows NFκB to translocate to the nucleus where it can drive gene transcription. The sulfhydryl groups on solvent-exposed cysteine (Cys) residues of the …

Evaluation Of The Bax-Vdac Interaction And Their Influence On Apoptosis In Drosophila Melanogaster, Frances Marie Gatlin

Honors Theses

Apoptosis, also known as programmed cell death, is a cellular process used for development or for when cells undergo injury or stress. The Bcl2 family of proteins includes both pro-apoptotic and anti-apoptotic proteins that control the intrinsic pathway of apoptosis. Understanding the mechanisms and influence these proteins have on apoptosis is an important area of research focused on in Dr. Jones’s lab. Evidence shows a homology amongst the Bcl2 family of proteins at the BH3 domain. Dr. Jekabsons' lab has found a potential homology amongst VDAC 1-3 and the Bcl2 family at the BH3 domain.

Specifically, our lab is using …

Novel Regulatory Roles Of Endocytic Membrane Trafficking Proteins In Mitochondrial Homeostasis, Trey Farmer

Theses & Dissertations

Endocytic membrane trafficking is a basic cell process that is critical for regulating the transport of lipids and proteins. Our lab focuses on the cellular functions and mechanisms of the proteins that regulate these pathways. A key family of regulatory proteins is the C-terminal Eps15 Homology Domain (EHD) protein family. The EHD family includes EHD1-4, which are ubiquitously expressed in mammalian tissues. While these isoforms do have some overlapping functions, each protein also has distinct activities in regulating the shape and fission of membranes throughout the endocytic pathways. Specifically, EHD1 uses ATP hydrolysis to induce constriction and fission of endocytic …

Novel Cyanoximates As An Alternative In Cancer Chemotherapy, Kafayat Aderonke Yusuf

MSU Graduate Theses

Chemotherapy is one of the most effective treatment plans for several cancer types. The recurrent side effects derived from chemotherapy agents have warranted the search for novel chemical compounds with better efficacy and minimal side effects. In line with this idea, I investigated effects of a group of newly synthesized metal based chemical compounds called cyanoximates on HeLa human cancer cells. Cyanoximates used were Pt(DECO)₂, Pt(MCO)₂, and Pd(DECO)₂ along with the chemotherapy drug cisplatin as a positive control. I found that the metal cyanoximates reduced cell viability via apoptosis, and that Pt(DECO)₂ was most …