Biological Sciences electronic theses and disserations (MU)
Permanent URI for this collection
The items in this collection are the theses and dissertations written by students of the Division of Biological Sciences. Some items may be viewed only by members of the University of Missouri System and/or University of Missouri-Columbia. Click on one of the browse buttons above for a complete listing of the works.
Browse
Recent Submissions
Item Response gene to complement32 in inflammatory smooth muscle transformation(University of Missouri--Columbia, 2025) Zhao, Wen; Chen, Shiyou[EMBARGOED UNTIL 12/01/2026] Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation, extracellular matrix (ECM) degradation, and vascular smooth muscle cell (VSMC) phenotypic switching, yet no effective pharmacological therapies exist to prevent disease progression. The regulatory mechanisms governing VSMC phenotypic plasticity during vascular inflammation remain insufficiently defined. Here, we studied if Response Gene to Complement 32 (RGC32) regulates VSMC phenotype under inflammatory conditions. In human smooth muscle cells (HSMCs), treatment with IL-1β and TNF-α led to a rapid and sustained downregulation of RGC32 expression at both mRNA and protein levels, coinciding with the transition from a contractile to an inflammatory/synthetic state. Overexpression of RGC32 counteracted cytokine-induced loss of contractile markers, restoring α-SMA, 22α, and CNN1 expression. Notably, RGC32 overexpression suppressed MMP2 expression under inflammatory stimulation, suggesting a protective role against ECM breakdown and aortic wall weakening. RNA sequencing further revealed that RGC32 reshapes global gene expression programs, enhancing ECM-related gene signatures (e.g., COL1A1, ELN, C1Q) while modulating chromatin remodeling, RNA processing, and protein turnover pathways. These findings indicate that RGC32 functions may serve as a molecular brake that stabilizes VSMC identity and regulates ECM homeostasis during vascular inflammation.Item Gene expression levels in the central nervous system following intrathecal AAV-mediated gene therapy in dogs with CLN2 neuronal ceroid lipofuscinosis(University of Missouri--Columbia, 2025) Diepeveen, Mitchell; Whiting, Rebecca[EMBARGOED UNTIL 12/01/2026] CLN2 disease is a pediatric neurodegenerative disorder caused by mutations in the TPP1 gene resulting in a deficiency of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). The disease is characterized by progressive cognitive and motor decline, brain atrophy, seizures, visual impairment associated with retinal degeneration, and typically culminates in death by the early teenage years. Canine CLN2 disease is a naturally occurring disorder caused by a mutation in the orthologous TPP1 gene and follows a similar progression over a compressed time scale. Gene therapy is being explored as a potential one-time treatment option to combat CLN2 disease. Previous studies have shown adeno-associated virus (AAV) to be a safe and efficient vector for gene therapy; however, it is important to investigate biodistribution of transduction. RT-qPCR allows high sensitivity transcript detection as well as relative quantification. In this project, we used RT-qPCR to measure hTPP1 expression after intravitreal and intrathecal administration of AAV.hTPP1 gene therapy in CLN2-affected dogs to assess the biodistribution of transgene expression in target and off-target tissues. Treatment variables included AAV serotype, treatment age, and dosage. Dogs that received intrathecal injection showed widespread expression in both brain and visceral tissue with no expression seen in eye tissues. Treating dogs at a young age with AAVrh10 resulted in the highest expression in most brain regions. Dogs that received intravitreal injection exhibited more localized transduction with expression specific to the eyes. Assessment of biodistribution with different therapeutic strategies enables identification of the combination of variables that will lead to the greatest transgene expression in the target tissues. Data suggests that for optimal therapeutic benefit, a combined intrathecal, intravitreal, and intravenous administration of gene therapy may be necessary.Item Effect of morphactins, TIBA and ethrel on the wood anatomy of Hibiscus lasiocarpus (Malvaceae)(University of Missouri--Columbia, 1982) Rodriguez, Kyrsis Raquel; Cumbie, Billy G.The morphactins IT-3456 and hydroxyfluorene carboxylic acid; TIBA and ethrel were found to affect the normal development of the wood of Hibiscus lasiocarpus Cav. In all cases the process of xylogenesis was affected throughout the stem. The reduction in size of the vessel elements caused by IT-3456, TIBA and ethrel was so dramatic that their width, at the treatment areas, is close to that of the fibers. The morphactin hydroxyfluorene carboxylic acid caused a complete inhibition of the vessel element production at the treatment point. This inhibition was temporary and vessel element production was restored after a period of time. Except for TIBA, all the substances tested affected the apical meristems of the stems. IT-3456 and ethrel had an inhibitory effect while hydroxyfluorene carboxylic acid had a promoting effect in the growth in length of the experimental stems. In all cases the development of non-especialized cells like those of the parenchyma tissue was disrupted. The main targets of these substances seem to be the apical and lateral meristems of the stem as well as, any other non-especialized cell present.Item The secretory-excretory system of the nematode Caenorhabditis elegans(University of Missouri--Columbia, 1983) Nelson, F. Kenneth; Riddle, Donald L.The secretory-excretory system of C. elegans, reconstructed from serial-section electron micrographs of larvae, is composed of four cells, whose nuclei lie on the ventral side of the pharynx and adjacent intestine. (1) The first of these, the pore cell, encloses the terminal one-third of the excretory duct which leads to an excretory pore at the ventral midline. This cell, a modified hypodermal cell, secretes the cuticle that lines the excretory duct within the pore cell. Laser ablation of this cell seriously disrupts osmoregulation of the nematode. (2) The second cell, the duct cell, surrounds the duct with a lamellar membrane from the origin of the excretory duct at the excretory sinus to the pore cell boundary. Laser ablation of the duct cell nucleus results in disruption of osmoregulation and prevents the secretion of the duct cuticle within the duct cell. (3) The third cell, the large H-shaped excretory cell, extends bilateral canals anteriorly and posteriorly nearly the entire length of the worm. The excretory sinus within the cell body joins the lumena of the canals with the origin of the duct. Like the pore and duct cell, the excretory cell is essential for osmoregulation. (4) The fourth cell, the binucleate, A-shaped gland cell extends bilateral processes anteriorly from cell bodies located just behind the pharynx. These processes are fused at the anterior tip of the cell, where the cell enters the circumpharyngeal nerve ring. The processes are also joined at the anterior edge of the excretory cell body, where the excretory cell and gland are joined to the duct cell at the origin of the duct. Secretory granules may be concentrated in the gland near this secretory-excretory junction. The dauer larva (a developmentally arrested third-stage larva) uniquely lacks secretory granules, and the gland cytoplasm is displaced by a labyrinth of large, transparent spaces. Exit from the dauer stage results in the return of active secretory morphology in fourth stage larvae. The gland cell is not involved in osmoregulation, in growth control, in fertility, in longevity, or dauer larva formation.Item Pheromone, food, and temperature : environmental cues controlling development of the Caenorhabditis elegans Dauer larva(University of Missouri--Columbia, 1983) Golden, James W.; Riddle, Donald L.Development of the Caenorhabditis elegans dauer larva is influenced by the relative strengths of at least three environmental cues: a pheromone, food, and temperature. The fatty acid like pheromone enhances dauer larva forma�tion and inhibits recovery, and its concentration apparently serves as a measure of the population density. A labile, hydrophillic food-signal has effects opposite those of the pheromone, and its concentration provides a measure of the food-supply. The cues have been used in the analysis of dauer larva formation and recovery of the wild-type strain N2 and mutants affected in dauer larva formation. Dauer-inducing conditions produce a prolongation of the second intermolt period and morphologically distinguishable second stage larvae, called L2d. Unlike L2 larvae, L2d larvae have the potential to form either L3 or dauer larvae, depending on the environmental cues. Worms become committed to non-dauer development around the LI molt when grown in the absence of exogenous pheromone. Commitment to dauer larva formation occurs just before the second molt, at which time a few worms complete development into dauer larvae even if transfered to fresh medium. Incubation temperatures above 20�C enhance wild-type dauer larva formation in the presence of added pheromone, and temperature-shift studies place the temperature-sensitive period around the first molt. Some dauer-constitutive mutants overrespond to the pheromone, and apparently enhance the expression of the wild-type temperature-sensitive process. Two temperature-sensitive dauer-constitutive alleles, daf-4(m72) and daf-7(m62), are suppressed by the amber suppressors up-7(st5), indicating they are nonsense alleles and presumably produce a nonfunctional, rather than temperature-sensitive, gene product.