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Articles 1 - 30 of 104
Full-Text Articles in Medicine and Health Sciences
Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi
Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi
Electronic Theses and Dissertations
Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …
Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson
Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson
Electronic Theses and Dissertations
Alcohol-associated liver disease (ALD) is a broad spectrum of diseases ranging from steatosis to severe hepatic cirrhosis, none of which have any FDA approved therapies. Downregulation of hepatic Sirtuin 1 (Sirt1) activity by ethanol has been shown to lead to an upregulation of the pro-lipogenic gene targets under its jurisdiction, resulting in increased lipogenesis and triglyceride accumulation. It was hypothesized that ethanol acts on α4*-nicotinic acetylcholine receptors (α4*-nAChRs) in hepatocytes to decrease Sirt1 expression, which ultimately dysregulates lipid metabolic homeostasis. Ethanol’s effects were investigated in cultured AML12 hepatocytes and in WT primary mouse hepatocytes acutely exposed to ethanol. Consistent with …
Investigation Of Heterocyclic Amines And N-Acetyltransferase 2 Genetic Polymorphism In The Dysregulation Of Hepatic Energy Homeostasis: A Gene-Environment Approach., Kennedy M Walls
Electronic Theses and Dissertations
Heterocyclic amines (HCAs) are mutagens generated when cooking meat for prolonged periods of time or until well-done. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes. However, no previous studies have examined if HCAs, independent of meat consumption, contributes to pathogenesis of insulin resistance or metabolic disease. It is well known that HCAs require hepatic bioactivation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans that, depending on the combination of NAT2 alleles, correlate to rapid, intermediate, or slow acetylator phenotypes that exhibit differential …
Injury Induced Neuroplasticity And Cell Specific Targeting Of The Lumbar Enlargement For Gene Therapy., Brandon Lee Brown
Injury Induced Neuroplasticity And Cell Specific Targeting Of The Lumbar Enlargement For Gene Therapy., Brandon Lee Brown
Electronic Theses and Dissertations
This dissertation is an examination of spinal cord injury induced neuroplasticity and tests whether noninvasive gene therapy can successfully target neurons in the lumbar spinal cord. It begins with an overview of neural control of locomotion and a brief summary of therapeutics that are used and/or in development for treating spinal anatomically characterize s subset of neurons in the spinal cord, long ascending propriospinal neurons, that are involved in interlimb coordination. Characterization of these neurons allows for subsequent evaluation of their potential involvement in injury induced neuroplasticity. This dissertation is divided into five chapters, covering spinal cord injury and therapeutics. …
Impact Of Lyophilization On Porcine Hemoglobin Properties., Mustafa Almosawi
Impact Of Lyophilization On Porcine Hemoglobin Properties., Mustafa Almosawi
College of Arts & Sciences Senior Honors Theses
Blood transfusion is the single most often performed lifesaving procedure in hospitals worldwide. Unfortunately, packed red blood cells (RBCs) used for transfusion can only be stored for 42 days at 4 °C before being discarded due to irreversible damage that occurs during storage. Any reduction in available RBCs for an extended period can lead to blood shortages. To increase the shelf-life of RBCs, we investigated freeze-drying (lyophilizing) in the presence of the non-toxic sugar trehalose as a method for long-term preservation. However, the oxidative stress of the lyophilization and storage processes can compromise the functionality of these cells, and the …
Irreversible Electroporation Potentiates Beta Glucan Induced Trained Innate Immunity: A Novel Combination Treatment For Pancreatic Adenocarcinoma., Matthew Woeste
Electronic Theses and Dissertations
Pancreatic cancer (PC) is a challenging diagnosis yet to benefit from advances in immune oncologic treatments. Irreversible electroporation, a non-thermal method of tumor ablation, is used in treatment of select patients with locally advanced unresectable PC and has potentiated the effect of certain immunotherapies. Yeast-derived particulate β-glucan induces trained innate immunity and successfully reduces murine PC tumor burden. This study tests the hypothesis that IRE may augment β-glucan-induced trained immunity in the treatment of PC. β-Glucan-trained pancreatic myeloid cells were evaluated ex vivo for trained responses and anti-tumor function after exposure to ablated and un-ablated tumor conditioned media. β-Glucan and …
Toward A Comprehensive Account Of Orientation Selectivity In The Retina., Megan Zipperer
Toward A Comprehensive Account Of Orientation Selectivity In The Retina., Megan Zipperer
Electronic Theses and Dissertations
Retinal Ganglion Cells (RGCs) form functionally distinct signaling channels that selectively encode features of the visual input including direction of motion, contrast polarity, size, and color. A highly conserved visual channel amongst vertebrates conveys orientation selectivity, i.e., the selective firing of neuronal cells in response to elongated stimuli along a preferred orientation. Orientation selectivity is an apparent critical computation and several studies have reported aspects of it, including cell type identity in anatomical reconstructions, and functional characterization of at least four different identified RGC types. But how cell types in the different studies relate is not well resolved; the mechanisms …
Examining The Effects Of Npra Antagonist Anantin On Sci-Induced Ployuria., Lindsey Zipperer
Examining The Effects Of Npra Antagonist Anantin On Sci-Induced Ployuria., Lindsey Zipperer
Electronic Theses and Dissertations
Polyuria, or the over production of urine, is a prevalent condition that significantly impacts the quality of life in individuals suffering from a spinal cord injury (SCI). Post-SCI induced polyuria is thought to have been associated with altered levels of vasopressin (AVP), atrial natriuretic peptide (ANP), and natriuretic peptide receptor A (NPRA). In the present study, the function of NPRA was analyzed in the rat contusion model using anantin, an NPRA antagonist. A daily dose of either 100 µg of anantin or vehicle was administered intraperitoneally immediately following the SCI surgery and continued until termination, 4 weeks post injury (wpi). …
Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury
Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury
Electronic Theses and Dissertations
Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …
Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum
Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum
Electronic Theses and Dissertations
Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …
Stromal Vascular Fraction Restores Vasodilatory Function By Reversing Mitochondrial Dysfunction And Oxidative Stress In Aging-Induced Coronary Microvascular Disease., Evan Paul Tracy
Electronic Theses and Dissertations
Background: Coronary Microvascular Disease (CMD) presents in aging post-menopausal women with chronic angina due to microvascular hyperconstriction. The objective was to identify mechanisms of adipose stromal vascular fraction’s (SVF) restorative effects on vasodilation. We hypothesize aging-induced CMD is caused by a) abrogated flow-mediated dilation (FMD) due to loss of nitric oxide signaling and b) ROS-dependent βADR desensitization & internalization, reversible by ameliorating mitochondrial dysfunction and oxidative stress with SVF. Methods: Coronary microvessels were isolated from female rats either young, old, or old with SVF tail-vein injection (OSVF). Pressure myography, RNA-sequencing, immunofluorescence, Western blotting, and morphological analysis were performed to …
Adipose-Derived Stromal Vascular Fraction Therapy Improves Age-Related Adrenergic Mediated Microvascular Dysfunction And Increases Revascularization Potential Following Injury., Gabrielle Brown
Electronic Theses and Dissertations
The role of the microcirculation is to balance blood flow and oxygen delivery to meet local metabolic and oxygen demands. With advancing age, the health of the endothelium declines leading to improper augmentation of the microcirculation; decreasing vasoreactivity and angiogenic potential which can further increase the risk of ischemia. The multiple contributing factors that drive the decline in endothelial health with age make traditional pharmacological interventions challenging whereas cell-based therapies can exert multifactorial gains. Adipose-derived stromal vascular fraction (SVF) is an emerging therapeutic for its easily accessible, autologous, anti-inflammatory, and angiogenic properties. It is a heterogenous population comprised of leukocyte …
The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen
The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen
Electronic Theses and Dissertations
Early-onset colon cancer (EOCC) is a leading cause of cancer death among people younger than 50 years of age in the United States and is associated with metabolic dysfunction and obesity. Anti-inflammatory tumor-associated macrophages (TAM) and low Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene expression in colon cancer (CC) tissue promote tumor progression and decreased patient survival. Obesity-related hormones, such as leptin and adiponectin, have the potential to affect gene expression in TAM to promote CC progression and thereby link obesity and EOCC. The aim of this project was to identify target genes in human CC and to investigate the …
The Impact Of Volume Of Tissue Activation On Cortical-Striatal Networks And Verbal Fluency Declines In Post-Deep Brain Stimulation Parkinson's Disease Patients., Alexander Luke Alley
The Impact Of Volume Of Tissue Activation On Cortical-Striatal Networks And Verbal Fluency Declines In Post-Deep Brain Stimulation Parkinson's Disease Patients., Alexander Luke Alley
Electronic Theses and Dissertations
This study investigated the cortical-striatal networks of verbal fluency declines in 6-month, post-operative, deep brain stimulation Parkinson’s Disease patients. Nine Parkinson’s disease participants with implanted STN or GPi DBS systems were recruited for this study. Verbal fluency data was obtained from each patient preoperatively and 6- months post implantation. The stimulation-based volume of tissue activated area (VTA) of each target site (STN or GPi) was analyzed using Lead-DBS and Lead-Group. The white matter tracks intersecting each patient’s VTA, terminating in the pre-SMA, SMA, caudate nucleus, and anterior cingulate were investigated and correlated with verbal fluency declines. We found statistically significant …
Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge
Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge
Electronic Theses and Dissertations
It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …
Preclinical Development Of Epicertin, A Novel Biotherapeutic For The Treatment Of Ulcerative Colitis., Micaela Ann Reeves
Preclinical Development Of Epicertin, A Novel Biotherapeutic For The Treatment Of Ulcerative Colitis., Micaela Ann Reeves
Electronic Theses and Dissertations
Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit with a C-terminal KDEL endoplasmic retention motif. Previously, orally administered EPT demonstrated mucosal healing activity in acute and chronic dextran sulfate sodium colitis models, indicating its therapeutic potential for ulcerative colitis (UC) treatment. However, oral dosing with EPT requires neutralization of gastric acid prior to administration, hindering its facile application in the treatment of chronic diseases like UC. One solution to this issue is that EPT may also be administered intracolonically without losing efficacy. This work describes the determination of a target intracolonic dose of EPT for future …
Assessing The Role Of Arsenic Exposure And Mirna-186 In Skin Tumorigenesis And Chromosomal Instability., Angeliki Lykoudi
Assessing The Role Of Arsenic Exposure And Mirna-186 In Skin Tumorigenesis And Chromosomal Instability., Angeliki Lykoudi
Electronic Theses and Dissertations
Chronic arsenic exposure through drinking water is a global health issue, affecting more than 200 million people. Arsenic is a group I human carcinogen and causes chromosomal instability (CIN). Arsenic exposure is the second most cause of skin cancer after UV radiation. MiR-186 is overexpressed in arsenic-induced squamous cell carcinoma relative to premalignant hyperkeratosis. Predicted targets of miR-186 are cell cycle regulators. Thus, we hypothesize that miR-186 overexpression drives malignant transformation of HaCaT cells by induction of CIN. Stable clones of HaCaT transfected with pEP-miR-186 expression vector or empty vector were maintained under puromycin selection were exposed to 0 or …
An Analysis Of Taste Neuron Morphological Variability: Influences Of Neuron Type And Plasticity., Lisa Christina Ohman
An Analysis Of Taste Neuron Morphological Variability: Influences Of Neuron Type And Plasticity., Lisa Christina Ohman
Electronic Theses and Dissertations
Taste neurons are functionally and molecularly diverse, but their morphological diversity was, until recently, completely unexplored. Taste neurons were considered relay cells, communicating information from taste-transducing cells to the brain without variation in morphology. Instead, individual taste neurons are tremendously morphologically variable. To determine how differences in branching relate to the number and types of taste-transducing cells providing neuronal input, I combined sparse cell genetic labeling with a whole-mount immunohistochemistry and analysis workflow. I found that the maximum number of taste-transducing cells capable of providing convergent input onto individual gustatory neurons varied with a range of 1-22 taste-transducing cells. Consistently, …
Effects Of Chemosensory Experience And Context On Consummatory Behaviors., Saphira M. Chiu
Effects Of Chemosensory Experience And Context On Consummatory Behaviors., Saphira M. Chiu
Electronic Theses and Dissertations
Eating food generates associations between odors and tastes (i.e., flavor) that guide future choices. Experience with an odor-taste mixture links an odor with a taste’s quality and hedonic value, resulting in a preference for an odor paired with a palatable taste over an odor paired with an unpalatable taste. However, experience with a neutral stimulus (i.e., latent inhibition) or environment (i.e., context) can influence the formation of conditioned associations. Here, I used a two-bottle brief-access task to determine whether rats display an innate preference between unpaired odors (isoamyl acetate and benzaldehyde), how preexposure to the unpaired odors impacts mixture-dependent consummatory …
Oligodendrocyte Responses After Spinal Cord Injury., George Zach Wei
Oligodendrocyte Responses After Spinal Cord Injury., George Zach Wei
Electronic Theses and Dissertations
Recent studies demonstrate that neuroprotection strategies targeting the proteostasis network and components of its effector signaling pathways improve cell survival and motor recovery outcomes in several models of neuronal injury and degeneration. However, the individual contributions of these signaling pathways to the pathogenesis of spinal cord injury (SCI), white matter damage, and motor recovery have not yet been determined. Here, I explored the role of the HIF prolyl hydroxylase domain proteins (PHD/EGLN), effectors that can modulate stress responses activated by the proteostasis network, on motor function recovery after SCI. Furthermore, I identified previously unknown candidate mechanisms in an unbiased manner …
Decreased Kidney Mitochondrial Content And Pgc-1Α Following Repeated Low-Dose Cisplatin-Induced Kidney Injury., Andrew Joseph Orwick
Decreased Kidney Mitochondrial Content And Pgc-1Α Following Repeated Low-Dose Cisplatin-Induced Kidney Injury., Andrew Joseph Orwick
Electronic Theses and Dissertations
Cisplatin is highly effective and one of the most commonly used chemotherapeutic agents in the treatment of a number of different solid organ tumors. Unfortunately, the dose-limiting nephrotoxicity occurs in up to 30% of patients, which requires alterations to treatment regimens that are often less effective. The kidney’s function is to provide fluid homeostasis, and this is an energy-intensive process. Proper renal function is dependent on functional mitochondria. PGC-1α regulates mitochondrial number, respiratory capacity, and mitochondrial proteins in proximal tubule cells. We delivered low-dose cisplatin to mice via intraperitoneal injections once a week for 4 weeks. The mice were then …
Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe
Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe
Electronic Theses and Dissertations
Tumor-associated macrophages polarized to an M2 phenotype (M2-TAMs) promote neo-angiogenesis, tumor-stromal matrix remodeling, and immuno-evasion, which, collectively, contribute to immunotherapeutic resistance and reduced cancer patient survival. Highly glycolytic “Warburg” cancer cells produce lactate that independently drives naïve M0→immunosuppressive M2 (M0→M2) macrophage polarization, but the mechanisms have not been fully elucidated. The atypical cytokine macrophage migration inhibitory factor (MIF) is a fundamental underlying requirement for immunosuppressive M2 macrophage polarization. Still, it is unknown whether a molecular link exists between lactate-supported and MIF-dependent M2 macrophage polarization. Using a combination of gene expression assays, chromatin immunoprecipitation, and metabolomic analyses, we identified that M2 …
The Importance Of Noncapped Viral Genomic Rna To Alphaviral Infection And Pathogenesis., Autumn Lapointe
The Importance Of Noncapped Viral Genomic Rna To Alphaviral Infection And Pathogenesis., Autumn Lapointe
Electronic Theses and Dissertations
Alphaviruses are mosquito-borne arboviruses that have a positive sense, single-stranded RNA genome, which are capable of causing severe disease and thus pose a significant burden to public health. During alphaviral replication, significant quantities of viral genomic RNAs that lack the canonical alphaviral 5’ cap structure are produced and packaged into viral particles, despite the fact that these noncapped genomes cannot be translated and are essentially noninfectious. The production and packaging of the noncapped genomes has been found to be true for infections across multiple vertebrate and invertebrate cell lines and alphavirus species, although the proportion of ncgRNA produced differs. Despite …
Sex-Based Differences In Microbiota Composition And Metabolomic Profiles Associated With Altered Macrophage Function And Protection From Lupus In Bwf1 Mice., James William Harder
Sex-Based Differences In Microbiota Composition And Metabolomic Profiles Associated With Altered Macrophage Function And Protection From Lupus In Bwf1 Mice., James William Harder
Electronic Theses and Dissertations
Systemic lupus erythematosus (SLE) is a complex and an insidious disease that is still not completely understood, and has very few treatment options. Those that are available are ineffective and/or have serious side effects. Both genetic and environmental factors contribute to the susceptibility and resistance to SLE, and understanding the environmental factors underlying this disease could lead to more effective prevention and/or treatment strategies. Like most autoimmune diseases, SLE is much more prevalent in females than males. While there are numerous factors that contribute to this lupus susceptibility, there is increasing evidence that the microbiota can strongly influence lupus progression, …
Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller
Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller
Electronic Theses and Dissertations
Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …
Pde4 Inhibition: A Novel Therapeutic Strategy In Liver Fibrosis., Mohamed Elnagdy
Pde4 Inhibition: A Novel Therapeutic Strategy In Liver Fibrosis., Mohamed Elnagdy
Electronic Theses and Dissertations
Background: Liver fibrosis is accumulation of extracellular matrix (ECM) proteins due to chronic liver injury. Chronic hepatic damage can occur due to multiple causes including, alcohol, non-alcoholic steatohepatitis and chronic viral hepatitis. Liver fibrosis is a critical problem worldwide due to the extremely high incidence of alcohol associated liver damage and chronic viral hepatitis. Moreover, there is no FDA approved therapy for liver fibrosis. Activation and transdifferentiation of quiecent hepatic stellate cells (HSCs) to myofibroblasts (MFBs) is the main event contributing to liver fibrosis. This process involves two phases, the initiation and the perpetuation phases. Hepatocyte injury and inflammatory response …
Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)
Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)
Electronic Theses and Dissertations
The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Electronic Theses and Dissertations
Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11bHi Ly6CHi Ly6G- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of …
Mechanisms Of Chromate-Induced Suppression Of Rad51: A One Environmental Health Approach., Rachel M. Speer
Mechanisms Of Chromate-Induced Suppression Of Rad51: A One Environmental Health Approach., Rachel M. Speer
Electronic Theses and Dissertations
Lung cancer is the leading cause of cancer death. Lung cancer is commonly associated with smoking, however, 1 in 5 women and 1 in 12 men who develop lung cancer are never-smokers. Environmental exposures, therefore, account for a significant portion of lung cancer cases. Hexavalent chromium [Cr(VI)] is a global environmental contaminant and known human lung carcinogen. Cr(VI) and other carcinogenic metals induce chromosome instability, an early event in lung cancer. Structural chromosome instability arises in part due to failed DNA repair. Particulate Cr(VI), the most potent form of Cr(VI), induces DNA double strand breaks and inhibits the high-fidelity DNA …
N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil
N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil
Electronic Theses and Dissertations
Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …