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Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Increased Mitochondrial Biogenesis Preserves Intestinal Stem Cell Homeostasis And Contributes To Longevity In Indy Mutant Flies, Ryan P. Rogers, Blanka Rogina

UCHC Articles - Research

The Drosophila Indy (I'm Not Dead Yet) gene encodes a plasma membrane transporter of Krebs cycle intermediates, with robust expression in tissues associated with metabolism. Reduced INDY alters metabolism and extends longevity in a manner similar to caloric restriction (CR); however, little is known about the tissue specific physiological effects of INDY reduction. Here we focused on the effects of INDY reduction in the Drosophila midgut due to the importance of intestinal tissue homeostasis in healthy aging and longevity. The expression of Indy mRNA in the midgut changes in response to aging and nutrition. Genetic reduction of Indy expression increases …

The Effects Of Aging And Injury On The Murine Ependymal Barrier And Subventricular Zone, John J. Peters

Honors Scholar Theses

Previous research has shown that numerous age-related changes occur in the subventricular zone (SVZ) and diminish the neurogenic output of the region. Here, various age-related changes in the structure of the lateral ventricle, the ependymal barrier, and the SVZ were examined. It was found that the walls of the lateral ventricles move together, adhere, and eventually fuse. This results in a degradation of the SVZ. Other changes associated with aging were found, including ependymal cell stretching, heightened, ependymal repair, changes in CSF flow velocity and dynamics, and altered ependymal cell polarity. These changes may be related to the process of …

Changes In The Proliferation Of The Subventricular Zone Neural Stem Cell Pool Throughout Aging In The Murine Brain, Olayinka Edwards

Honors Scholar Theses

Previous studies regarding subventricular zone (SVZ) neural stem cells (NSCs) have either observed global changes in the SVZ niche containing NSCs or an impure NSC population. By imaging wholemount preparations of mouse brains and staining with molecular markers specific for proliferating NSC nuclei, the study was able to give a more accurate depiction of the SVZ NSC population than its predecessors. This study will quantify the percentage of proliferating NSCs at various ages of adult murine brain development in order to elucidate a possible correlation between NSC division kinetics and the declining neurogenic output witnessed with aging.

Dopaminergic Innervation Of The Subventricular Zone In The Murine Brain, Linda Beth Drozdowicz

Honors Scholar Theses

The subventricular zone (SVZ) is one of two areas in the brain that, in a healthy mouse, continually generate neurons throughout adulthood. While it was previously thought that only the A9 neurons of the substantia nigra sent dopaminergic afferents to the SVZ, recent studies suggest that the A10 neurons of the ventral tegmental area may innervate this area. This project has aimed to discover which, if either, model is correct.

Examination of the Aphakia (AK) mouse was used to determine the role of distinct midbrain regions in SVZ regulation. Additionally, intraperitoneal injections of the chemical MPTP were used to deduce …

Alterations In The Cellular Composition Of The Mouse Bladder Following Ovariectomy, Partial Bladder Outlet Obstruction, And Aging, Diane Holly Smith

Honors Scholar Theses

Detrusor underactivity (DU) increases susceptibility to urinary retention and accordingly further complicates the management of urinary incontinence. Bladder muscle stretch, a lack of estrogen, and aging are 3 notable DU risk factors. The aim of this research is to better characterize the changes in cellular composition of the bladder that result from these 3 risk factors to gain a better understanding of DU pathogenesis and pathobiology. This research focuses on the effects of a lack of estrogen while also providing an outline for determining the effects of bladder muscle stretch and aging on the cellular composition of the bladder.