IMPDH1 catalyzes the rate limiting step of de novo guanine synthesis. cGMP is a critical signaling molecule involved in phototransduction in rod and cone photoreceptors. In humans, nine mutations in IMPDH1 lead to Retinitis Pigmentosa and Leber's Congenital Amaurosis; however, the cause of retinal degeneration is unknown. In zebrafish, IMPDH1a is the major variant in the retina, exclusively expressed in rod and cone photoreceptors. To understand the function of IMPDH1, we utilized an IMPDH1a knock-out (KO) zebrafish line. Loss of IMPDH1a does not lead to retinal degeneration, and cGMP levels remain unchanged. However, retinas lacking IMPDH1a show a 61.6% reduction in guanine. Since photoreceptors do not undergo cell division, mitochondrial DNA (mtDNA) synthesis would be a major use of guanine during mitochondrial biogenesis and turnover. Under normal conditions, the amount of mtDNA between the KO and WT zebrafish was the same. To eliminate the potential that KO fish could supplement guanine from their diet, fish were starved for 24 hours. Starved IMPDH1a KO showed a trend of increased mtDNA compared to WT fish. Interestingly, starved fish had about four times the amount of mtDNA for both WT and KO compared to fed fish. Starvation may increase mitochondrial DNA copy number to increase efficiency of ATP production by increased utilization of oxidative phosphorylation. Reducing guanine levels by knocking out IMPDH1a in zebrafish retina does not affect mtDNA or nDNA levels, and the photoreceptor cells appear healthy. Although more research is needed, silencing the gene encoding for IMPDH1 could be a possible therapy for those suffering from the effects of its mutation.

Pigs often have an anterior crossbite (underbite), where the maxillary incisors (upper anterior teeth) are positioned behind the mandibular incisors (lower anterior teeth) instead of in front as found in a normal dental relationship. In humans, when this condition is severe, proper feeding, speaking, and breathing can be impeded. An anterior crossbite can occur due to dental and/or skeletal malformations. Retro-inclination of the maxillary incisors or excessive pro-inclination of the mandibular incisors are dental contributors to this problem, whereas excessive growth of the mandible (lower jaw) or deficient growth of the maxilla (upper jaw) are skeletal causes. Pigs are a novel model for anterior crossbites in humans, yet it is unclear which dental or skeletal condition is the primary cause in pigs. Therefore, it is necessary to characterize this condition in pigs to translate this model to humans effectively. The purpose of this project is to determine if improper inclination of the incisors, mandibular prognathism, or maxillary retrognathism is the primary cause of anterior crossbites in pigs. A total of 150 pig skulls (120 dry skulls and 30 CT images) were included in this study. The angle of inclination of maxillary and mandibular incisors, length of the mandible, and length of the maxilla (estimated by the length of the hard palate) were measured in dry skulls using a metric protractor and ruler to the nearest degree or mm. The same measurements were taken on CT images using ImageJ software. Measurements will be compared between normal and affected pigs using t-tests and correlated to the severity of anterior crossbite using Pearson correlations. Based on the data I have acquired, I expect that the primary cause of anterior crossbites in pigs is maxillary retrognathism, also termed maxillary hypoplasia, and thus serves as a model for this specific condition in humans.

Better understanding the circulation of the ocean's deepest waters is critical to predicting how the world ocean will respond to a rapidly heating atmosphere. The deep and abyssal circulation across 30°S in the Brazil Basin is inferred from multiple decades of full-depth CTD data by an angular momentum and salt conserving inverse model which parameterizes mixing across ocean layers as a function of the roughness of the seafloor. This inverse model was originally designed by my advisor for use in the North East Pacific basin. My work was writing an extensible software library in Python to apply the same inverse technique to other ocean basins like the Brazil basin. From this inverse we learned the Brazil basin exhibits strong diapycnal mixing especially towards its boundaries, and weak lateral mixing. The largest transport outside of boundary currents across 30°S is the southward flow of Antarctic Bottom Water (AABW) at a rate of ~10^10 kg s-1. AABW flows northward through the Vema Channel and southward in the interior of the basin creating a cyclonic circulation around the Rio Grande Rise. Flow along -30°S is westward in the Antarctic Intermediate Water (AAIW) and Upper Circumpolar Deep Water (UCDW), and eastward in the North Atlantic Deep Water (NADW). Southward east of the Rio Grande Rise would have large impacts on the mixing and heat budgets of the Brazil basin.