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Articles 1 - 12 of 12
Full-Text Articles in Life Sciences
The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams
The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams
Electronic Thesis and Dissertation Repository
B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …
Understanding Neonicotinoid Related Immunosuppression: A Potential For Beneficial Bacterial Intervention, John A. Chmiel
Understanding Neonicotinoid Related Immunosuppression: A Potential For Beneficial Bacterial Intervention, John A. Chmiel
Electronic Thesis and Dissertation Repository
The use of neonicotinoid pesticides has been implicated in the recent decrease of honey bee (Apis mellifera) populations. In this thesis, a Drosophila melanogaster model was used to characterize immune impairment associated with imidacloprid (neonicotinoid) exposure and test the ability of beneficial bacteria (lactobacilli) to alleviate these harmful effects. The experiments outlined in chapters 2 and 3 demonstrate that imidacloprid alters the gut microbiota by exploiting the cooperation between gut immune pathways. The pesticide reduces expression of Duox via dysregulation of the immune deficiency pathway resulting in decreased hydrogen peroxide production. This contributes to the microbiota changes but …
Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco
Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco
Electronic Thesis and Dissertation Repository
Congenital heart defects are the most prevalent birth defect, and maternal cigarette smoking is a known risk factor. Nicotine replacement therapies are recommended to pregnant women who smoke to aid in smoking cessation, as this alternative is thought to be much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in …
Reactive Oxygen Species And The Regulation Of Cerebral Vascular Myogenic Tone, Neil Mazumdar
Reactive Oxygen Species And The Regulation Of Cerebral Vascular Myogenic Tone, Neil Mazumdar
Electronic Thesis and Dissertation Repository
The myogenic response refers to the intrinsic ability of arteries to constrict to elevated pressure, developing “tone”. The underlying mechanism has yet to be elucidated but recent evidence suggests that the angiotensin II type 1 receptor (AT1R) is a key mechanosensor, linking intravascular pressure to tone development. One intriguing aspect of this receptor is its ability to activate NADPH oxidase (Nox), an enzyme responsible for the production of reactive oxygen species (ROS). The goal of this study was to ascertain the role of Nox in myogenic tone development. Isolated rat cerebral arteries were mounted in a myograph, pressurized to 60mmHg …
Investigating The Protective Effects Of Telomerase Reverse Transcriptase On Neuronal Metabolism And Resistance To Amyloid-Beta, Olivia Singh
Investigating The Protective Effects Of Telomerase Reverse Transcriptase On Neuronal Metabolism And Resistance To Amyloid-Beta, Olivia Singh
Electronic Thesis and Dissertation Repository
Maintenance of telomere length during cell division is dependent on the catalytic subunit telomerase reverse transcriptase (TERT), which adds TTAGGG repeats to the ends of chromosomes to prevent telomere shortening during DNA replication. However, non-telomeric roles of TERT have emerged under oxidative stress whereby TERT translocates from the nucleus to the mitochondria and protects against mitochondrial dysfunction through a poorly defined mechanism. A major pathological feature of Alzheimer’s Disease (AD) is the progressive accumulation of amyloid-beta (Aβ) peptide within the cortex and hippocampus. Aβ can directly interfere with mitochondrial respiration and promote mitochondrial dysfunction, ROS production, and neuronal cell death. …
The Long Haul: Migratory Flight Preparation And Performance In Songbirds, Morag F. Dick
The Long Haul: Migratory Flight Preparation And Performance In Songbirds, Morag F. Dick
Electronic Thesis and Dissertation Repository
Migration requires birds to sustain high intensity endurance exercise for periods lasting from hours to days. Similar to athletes, preparation and nutrition is key to success. Birds seasonally prepare for migration, which includes increasing the capacity to oxidize fat in the flight muscles. Beyond fuelling migration, n-3 long-chain polyunsaturated fatty acids (PUFA) are hypothesized to be natural doping agents and increase endurance and fatty acid oxidative capacity. I examined how birds prepare for and sustain migratory flight and directly tested the role of n-3 PUFA. Using yellow-rumped warblers (Setophaga coronata) as a model species, I first examined the …
Pregestational Diabetes And Congenital Heart Defects: Role Of Reactive Oxygen Species, Hoda Moazzen
Pregestational Diabetes And Congenital Heart Defects: Role Of Reactive Oxygen Species, Hoda Moazzen
Electronic Thesis and Dissertation Repository
Women with pregestational diabetes are at a high risk of having babies with congenital heart defects (CHDs). The mechanisms of CHD induction in the offspring of women with pregestational diabetes remain elusive. With an ever-increasing rate of diabetes in young adults, there is a pressing need to understand the underlying mechanisms and initiate effective preventative strategies. The aim of this thesis is to study the role of reactive oxygen species (ROS) signalling in heart morphogenesis, unravel molecular mechanisms of CHDs induced by pregestational diabetes and provide new insights on potential therapeutic strategies. To this end, a mouse model of pregestational …
Ilk Modulates Stress-Induced Apoptosis In Epidermal Keratinocytes, Michelle Im
Ilk Modulates Stress-Induced Apoptosis In Epidermal Keratinocytes, Michelle Im
Electronic Thesis and Dissertation Repository
Integrin-linked kinase (ILK) is a ubiquitous scaffold protein that mediates cellular responses to integrin stimulation by extracellular matrix proteins. Mice with inactivation of the Ilk gene in squamous epithelia display defects in skin regeneration after injury, failure to thrive, and perinatal death. ILK-deficient epidermis exhibits reduced adhesion to the basement membrane and impaired hair follicle morphogenesis. In culture, ILK-deficient keratinocytes fail to attach and spread efficiently, and demonstrate decreased survival. We now show that ILK-deficient keratinocytes exhibit lower proliferative capacity and increased apoptosis in the absence or presence of growth factors. This reduced viability appears to be independent of the …
Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington
Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …
The Effects Of Telomerase Inhibition On Cellular Senescence In Fetal Guinea Pig Muscle Cells, Stephanie E. Hallows
The Effects Of Telomerase Inhibition On Cellular Senescence In Fetal Guinea Pig Muscle Cells, Stephanie E. Hallows
Electronic Thesis and Dissertation Repository
Low birth weight infants have a higher risk of developing metabolic syndrome, including Type II Diabetes. Fetal muscle is growth restricted in low birth weight infants and is the main tissue for determining insulin resistance. Recent studies indicate premature senescence in low birth weight rodents, which could lead to adult disease. In utero environments may play a role in the development of senescence through increased reactive oxygen species (ROS). Telomerase is present at high levels during development and protects cells from cellular stress and apoptosis. We postulate that telomerase protects cells from DNA damage and premature senescence. A primary culture …
The Role Of Pex11-Beta In Peroxisome Biogenesis, Intracellular Relationship To Reactive Oxygen Species Levels And Redox-Sensitive Cell Signaling, Mark A. Fox
Electronic Thesis and Dissertation Repository
Peroxisomes are organelles whose roles in fatty acid metabolism and reactive oxygen species (ROS) elimination have contributed much attention in understanding their origin and biogenesis. Many studies have shown that de novo peroxisome biogenesis is an important regulatory process, while yeast studies suggest that total peroxisome numbers are in part regulated by proteins such as Pex11, which can facilitate the division of existing peroxisomes. Although de novo biogenesis and divisions are likely important mechanisms to peroxisome functioning, the regulation of peroxisome numbers during embryonic development is poorly understood. Peroxisome number and function are particularly crucial in oviparous animals such as …
Mitochondrial Metabolic Suppression And Reactive Oxygen Species Production During Hypometabolism In Mammals, Jason Cl Brown
Mitochondrial Metabolic Suppression And Reactive Oxygen Species Production During Hypometabolism In Mammals, Jason Cl Brown
Electronic Thesis and Dissertation Repository
During hibernation, daily torpor, and fasting, mammals reduce metabolic rate (MR) up to 99%, 95%, and 30%, respectively, compared to resting levels. Mitochondrial metabolic suppression likely contributes to this MR reduction, and the first objective of this study was to determine the relative contributions of active, regulated inhibition and passive thermal effects as body temperature (Tb) falls, to mitochondrial metabolic suppression, and to examine the mechanisms involved using top-down elasticity analysis and novel statistical approach. The second objective of this study was to determine how mitochondrial metabolic suppression affects mitochondrial reactive oxygen species (ROS) production, a topic which …