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Changes In Rna Expression Of Hut78 Cells Resulting From The Hiv-1 Viral Protein R R77q Mutation, Joshua S. Ramsey
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 …
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 …
Natural Product Berbamine Enhances The Efficacy Of Doxorubicin Treatment For Triple Negative Breast Cancer, Jake Tyler
Natural Product Berbamine Enhances The Efficacy Of Doxorubicin Treatment For Triple Negative Breast Cancer, Jake Tyler
Theses and Dissertations
According to breast cancer statistics, 279,100 new cases are expected in the United States in 2020 (Siegel et al., 2020). Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a significantly shorter median overall survival compared to other subtypes of breast cancer. Unlike hormone-positive or HER2-positve breast cancers with effective hormonal or targeted therapies available, there has been very little clinical success from targeted therapies for TNBC. Doxorubicin (Dox) is one of the most used chemotherapy drugs. The only limitation of Dox treatment is its cytotoxicity. Berbamine dihydrochloride (BBM) is a natural benzylisoquinoline alkaloid that …
Effects Of Global Warming On Gonadal Functions, Cellular Apoptosis, And Oxidative Stress In The American Oyster, Sarah B. Nash
Effects Of Global Warming On Gonadal Functions, Cellular Apoptosis, And Oxidative Stress In The American Oyster, Sarah B. Nash
Theses and Dissertations
Global warming due to climate change is predicted to intensify the heat stress in marine and coastal organisms, affecting their development, growth and reproductive functions. In this study. I analyzed gonadal development, heat shock protein 70 (HSP70), nitrotyrosine protein (NTP), dinitrophenyl (DNP) expressions, cellular apoptosis, and coelomic fluid (CF) conditions in American oyster. Oysters were placed in six aquariums and exposed to control (24°C), medium (28°C), and high (32°C) temperatures for one week. Higher temperature significantly decreased the number of eggs and sperm. CF protein concentrations also declined compared to control. In contrast, CF pH and HSP70 expression in gonad …
Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh
Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh
Theses and Dissertations
Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …
Apoptotic And Necrotizing Mechanisms Of Recombinant Panton-Valentine Leukocidin In Thp1 Monocytes., Heriberto Deleon Iii
Apoptotic And Necrotizing Mechanisms Of Recombinant Panton-Valentine Leukocidin In Thp1 Monocytes., Heriberto Deleon Iii
Theses and Dissertations
The Panton-Valentine Leukocidin (PVL) is a highly specialized bacterial exotoxin produced by Staphylococcus aureus. The increased degree of invasiveness of community associated methicillin resistant Staphylococcus aureus (CAMRSA) has been attributed to the relatively high rates of PVL produced by the pathogen, thus increasing pathogenicity and virulence. The increased rates of PVL encoding CAMRSA infections have been correlated with increased rates of necrotizing fasciitis, invasive osteomyelitis and invasive necrotizing pneumococcal infections. Previous research as revealed that PVL has the ability to induce apoptosis at low concentration (5nM-10nM) and necrosis (50-100nM) at high concentrations, with little detail on the mechanism of initiation. …
Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez
Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez
Theses and Dissertations
Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis …
Exploring The Antibacterial, Antioxidant, And Anticancerproperties Of Lichen Metabolites, Gajendra Shrestha
Exploring The Antibacterial, Antioxidant, And Anticancerproperties Of Lichen Metabolites, Gajendra Shrestha
Theses and Dissertations
Natural products have been a significant source of new drugs, especially in treating cancer, infectious diseases, hypertension, and neurological disorders. Although many natural metabolites have been screened and yielded pharmaceutically important drugs, many potential sources of natural product drug therapies still need to be investigated, including lichens. Lichens are symbiotic systems consisting of a filamentous fungus and a photosynthetic partner (an eukaryotic alga and/or cyanobacterium). Lichens produce an impressive variety of unique secondary compounds and have been used as ingredients in folk medicines for centuries. Demonstrated biological roles based on lichen chemistry include: antibiotics, anti-proliferative, antioxidants, anti-HIV, anti-cancer, immunomodulation, and …
Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden
Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden
Theses and Dissertations
Receptors for advanced glycation end-products (RAGE) are pattern recognition receptors of the immunoglobulin superfamily highly expressed in the lung. Likely functions include the modulation of pulmonary inflammation during disease. However, the contributions of RAGE in the developing lung in cases where secondhand smoke (SHS) exposure occurs are unknown. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, we exposed gestating dams to a controlled dose of SHS during the last four critical days of in utero lung morphogenesis. We discovered that both maternal and fetal lungs respond to SHS by up-regulating RAGE. Exposed fetuses were markedly …
Inhibition Of Pim And Axl Kinases As Potential Treatments For A Variety Of Hematological Malignancies And Solid Tumors, Kent James Carpenter
Inhibition Of Pim And Axl Kinases As Potential Treatments For A Variety Of Hematological Malignancies And Solid Tumors, Kent James Carpenter
Theses and Dissertations
This thesis is divided into three chapters. In each case, the goal is to achieve inhibition of a growth kinase (PIM or AXL) and subsequent arrest of cell growth and induction of apoptosis (in vitro cell culture models) or decrease in tumor volume (in vivo xenograft studies). Chapter one and chapter two discuss inhibition of proviral integration site for Moloneymurine leukemia virus (PIM) kinases. The three PIM kinases, PIM-1, PIM-2, and PIM-3, are a subfamily of serine/threonine kinases that are known to be involved in signaling pathways as downstream effectors of signal transducer and activator of transcription-5 (STAT5) signaling and …
The Cytotoxic Effect Of The Bcl-2 Family Of Proteins In Breast Cancer Cells, Yamileth Chin
The Cytotoxic Effect Of The Bcl-2 Family Of Proteins In Breast Cancer Cells, Yamileth Chin
Theses and Dissertations
Breast cancer is the second leading cause of death amongst women ages 20 to 59. Despite advancements in cancer therapies, more research is necessary to improve the diagnoses and treatment of several types of breast cancer. Paclitaxel (Taxol) is a commonly utilized anti-cancer drug for various types of solid tumors. However, the molecular mechanism utilized by paclitaxel to induce cell death is still elusive. Previous studies in our laboratory have shown that the pro-apoptotic BCL-2 family protein, BAK (BCL-2 homologous antagonist/killer) plays an important role in paclitaxel-induced cell death. In untreated breast cancer cells, BAK is associated with the anti-apoptotic …
Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons
Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons
Theses and Dissertations
Secretory phospholipase A2 hydrolyzes phospholipids at a lipid-water interface, resulting in pro-inflammatory products being released from cell membranes. Healthy cells are resistant to cleavage by this enzyme, but apoptotic cells become susceptible to its activity. Only bilayers with certain characteristics are able to be hydrolyzed. Most recently, studies in this lab have emphasized the idea that the biophysical state of the bilayer (in terms of lipid order, spacing, and fluidity) is relevant in determining the probability of one phospholipid escaping the membrane to be hydrolyzed. Prior to this study, it had been shown that apoptotic cells undergo biophysical alterations that …
Promoter Polymorphisms In Interferon Regulatory Factor 5, Daniel N. Clark
Promoter Polymorphisms In Interferon Regulatory Factor 5, Daniel N. Clark
Theses and Dissertations
The promoter region of interferon regulatory factor 5 (IRF5) contains the rs2004640 T or G single nucleotide polymorphism (SNP) and a CGGGG indel. Both of these polymorphisms have been implicated as genetic risk factors for several autoimmune diseases, including systemic lupus erythematosus, whose pathology involves altered apoptosis and cytokine signaling. The polymorphisms' overall effect is to increase IRF5 levels. IRF5 is a transcription factor of several cytokines, including interferon, and is pro-apoptotic. Thus an alteration of cytokine levels and apoptosis signaling due to high IRF5 levels is the proposed source of autoimmune risk. Each of IRF5's four first exons (1A, …
Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill
Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill
Theses and Dissertations
Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors highly expressed in the lung that modulate pulmonary inflammation during disease. However, the contributions of RAGE signaling are unknown during pulmonary organogenesis. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, conditional transgenic mice were generated that over-express RAGE in alveolar type II cells of the lung. When RAGE is over-expressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. Flow cytometry and immunohistochemistry employing cell-specific markers for various distal cell types demonstrated anomalies in key epithelial cell populations resulting from RAGE up-regulation through …
The Effect Of Cobalt Protoporphyrin And Cobalt Chloride On Heme Oxygenase Expression And Protection From Deoxycholate-Induced Apoptosis, Tina Lawson
Theses and Dissertations
The inner surface of the stomach is lined by a mucous membrane known as the gastric mucosa. The integrity of the gastric mucosa is critical for protecting the stomach from the low pH and proteolytic environment within the lumen. Both clinically and experimentally, exposure of gastric mucosal cells to bile salts is known to cause injury. Bile salts present in duodenogastric reflux are thought to play a significant role in gastric ulcer formation and alkaline gastritis. In vitro, studies using physiologic concentrations of the secondary bile salt, deoxycholic acid, indicate that bile salts can induce apoptosis in cultured human gastric …
Generation Of Macrophage Chemotactic Factors By Spla2, Andria Chambers
Generation Of Macrophage Chemotactic Factors By Spla2, Andria Chambers
Theses and Dissertations
Removal of apoptotic cells by macrophages is required in order to prevent autoimmune responses. Previous studies have reported that group IIA secretory phospholipase A2 (sPLA2) preferentially binds to apoptotic cells and induces a chemotactic factor which promotes the migration of macrophages to apoptotic cells. Based on these observations, we hypothesized that the pool of sPLA2 trapped on apoptotic cells produces chemoattractant lipids that recruit macrophages to phagocytose the apoptotic cells. To test this hypothesis, Jurkat cells were cultured under normal conditions and induced to undergo early apoptosis through treatment with D,L-threo-dihydrosphingosine. Live and early apoptotic cells were incubated with catalytically …
Mechanisms By Which Apoptotic Membranes Become Susceptible To Secretory Phospholipase A2, Rachel Williams Bailey
Mechanisms By Which Apoptotic Membranes Become Susceptible To Secretory Phospholipase A2, Rachel Williams Bailey
Theses and Dissertations
During apoptosis, changes occur in T-lymphocyte membranes that render them susceptible to hydrolysis by secretory phospholipase A2 (sPLA2). To study the relevant mechanisms, a simplified model of apoptosis using a calcium ionophore was first applied. Kinetic and flow cytometry experiments provided key observations regarding ionophore treatment: initial hydrolysis rate was elevated, total reaction product was increased four-fold, and adsorption of the enzyme to the membrane surface was unaltered. Analysis of these results suggested that susceptibility during calcium-induced apoptosis is limited by substrate availability rather than enzyme adsorption. Fluorescence experiments identified three membrane alterations that might affect substrate access to the …
The Effect Of Febrile Temperature On Plasmodium Falciparum, Heidi Sue Porter
The Effect Of Febrile Temperature On Plasmodium Falciparum, Heidi Sue Porter
Theses and Dissertations
Previously it has been shown that cultures of Plasmodium falciparum died following exposure to a febrile temperature of 40°C, as demonstrated by a decrease in parasitemia of the following generation. In the current study, the effect of 40°C treatment on culture media, erythrocytes, and parasite glucose consumption, were ruled out as possible influences on parasite death, demonstrating that 40°C impacted the parasites directly. Metabolic profiling of DNA synthesis, protein synthesis, and glucose utilization during exposure to 40°C clearly indicated that febrile temperatures had direct effect on major metabolic pathways and parasite development, beginning 20-24 hr after erythrocyte invasion. The ring …
Novel Cancer Therapeutics, The Generation Of Ros, And Cell Survival, Clint Mitchell
Novel Cancer Therapeutics, The Generation Of Ros, And Cell Survival, Clint Mitchell
Theses and Dissertations
The impact of Ad.mda-7 on the survival of renal cell carcinoma lines (RCC), primary renal epithelial cells, glioblastoma multiforme lines (GBM), and primary rodent astrocytes is unknown. The present studies examine whether the GST fusion protein, GST-MDA-7, and the adenovirus, Ad.mda-7, altered the growth and survival of the A498 and UOK121N RCC lines or radiosensitized GBM, respectively. Due to previous findings that the RCC lines, but not primary renal epithelial cells, were resistant to type 5 adenoviral infection, we used purified GST-MDA-7 protein to show that GST-MDA-7, but not GST, caused a dose-dependent reduction in A498 and UOK121N proliferation but …
Phospholipase A2 Induced Monocyte Chemotaxis To Apoptotic Cells, Kwasi Karikari
Phospholipase A2 Induced Monocyte Chemotaxis To Apoptotic Cells, Kwasi Karikari
Theses and Dissertations
Apoptosis is a form of programmed cell death that is essential in such processes as organ and tissue remodeling and maturation of hematopoietic cells. The clearance of apoptotic cells is essential to prevent autoimmune responses to sequestered antigens. This process is mediated by phagocytes of the monocyte lineage. Before phagocytosis can occur, macrophages must be recruited to the apoptotic cells through chemotaxis. Products of the reaction catalyzed by the phospholipases A2 (PLA2) have been shown to induce monocyte chemotaxis either directly or indirectly. Some investigators have implicated a cytosolic calcium-independent PLA2 (iPLA2) in the production of these products during apoptosis. …
Assessment Of Cell Death Parameters In Bovine Parvovirus-Infected Ebtr Cells, Lubna Salah Eldin Abdel Latif
Assessment Of Cell Death Parameters In Bovine Parvovirus-Infected Ebtr Cells, Lubna Salah Eldin Abdel Latif
Theses and Dissertations
Bovine parvovirus (BPV) is a helper-independent parvovirus. It has a small icosahedral capsid with a single stranded DNA genome. It is a highly stable virus with a narrow host range. It causes acute gastroenteritis in calves. It is considered to be a cytolytic virus because it kills the host cells. However, the mechanism by which the virus causes cell death is not known. The work described in this thesis assessed different parameters of cell death in BPV infected embryonic bovine tracheal (EBTr) cells. There are several ways for viruses to induce cell death. Viruses can induce apoptosis in the infected …
Type-5 Phosphodiesterase Inhibition In The Prevention Of Doxorubicin Cardiomyopathy, Patrick William Fisher
Type-5 Phosphodiesterase Inhibition In The Prevention Of Doxorubicin Cardiomyopathy, Patrick William Fisher
Theses and Dissertations
Prior studies have demonstrated the effect of diazoxide in protecting against apoptosis via mitochondrial KATP channel opening in vitro. The current investigations are designed to determine if sildenafil, a phosphodiesterase-5 inhibitor and known mitochondrial KATP channel opener, would protect against chronic doxorubicin cardiomyopathy both in vivo and in vitro.Male ICR mice were randomized to 1 of 4 treatments: saline, sildenafil (0.7 mg/kg IP), doxorubicin (5 mg/kg IP), and sildenafil (0.7 mg/kg IP)+doxorubicin. Apoptosis was determined using the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling and in situ oligo ligation methods. Desmin distribution was determined via immunofluorescence. Bcl-2 was analyzed by …
Identification Of The Rna Cis-Elements That Interact With Srp30a To Regulate The Alternative Splicing Of Caspase 9 Pre-Mrna, Prabhat Mukerjee
Identification Of The Rna Cis-Elements That Interact With Srp30a To Regulate The Alternative Splicing Of Caspase 9 Pre-Mrna, Prabhat Mukerjee
Theses and Dissertations
Studies have shown that the alternative splicing of caspase 9 and the phospho-status of SR proteins, a conserved family of splicing factors, are regulated by chemotherapy and de novo ceramide via the action of protein phosphatase-1 (PP1). Two RNA splice variants are derived from the caspase 9 gene, pro-apoptotic caspase 9a and anti-apoptotic caspase 9b, via alternative splicing by either the inclusion or exclusion of an exon 3, 4, 5, and 6 cassette. In this study, the link between SR proteins and the alternative splicing of caspase 9 was established. Sequence analysis of the exon 3, 4, 5, and 6 …