Sewanee Senior Theses 2024
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Item Review of Literature of Small Dams with a Case Study on the South Cumberland Plateau(University of the South, 2024-05-01) Almon, MollySmall dams (<5m high) are found abundantly across the world due to limited or absent regulation and a variety of uses including agriculture, flood-prevention, water control, drinking water, wildfire prevention, recreation, and aesthetics. Though often thought to have less of an impact downstream because of their size, they can acutely alter downstream habitat, and their frequency suggests that these impacts could accumulate to have larger effects. Small dams change abiotic dynamics like flow, water temperature, pH, geomorphology, chemical and nutrient transportation, and oxygenation based on their operation. The biotic communities respond to these shifts by altering behaviors and population dynamics around the physical structure of the dam. We investigated the frequency with which streams on the southern Cumberland Plateau in Tennessee are impacted and reviewed the literature to identify key questions about the environmental impacts of small dams. Although small dams can cause negative downstream change, their presence can also have positive environmental impacts, and we sought to identify characteristics that benefit or degrade the surrounding ecosystems. More research needs to be done to address the variations of small dams and propel regulation and monitoring accordingly by state and federal agencies. This includes research into the effects on specific species and regions, assessing different types of small dams, and cumulative effects on the biota.Item Diesel Particulate Matter Induces Toxicity Within Caenorhabditis elegans in a Manner Distinct from Protein Misfolding(University of the South, 2024-05-01) Studivant, JeremiahNeurodegenerative diseases are characterized by the age-dependent failure of the proteostasis network (PN)—a critical regulator of protein folding, trafficking, and degradation—leading to an inability to maintain protein folding homeostasis (proteostasis) and eventually resulting in accelerated loss of neurons. Huntington’s disease (HD) is a neurodegenerative disorder caused by a mutation within the huntingtin gene, encoding an expansion of a glutamine (polyQ) repeat. This polyQ expansion is prone to misfolding, perturbing proteostasis. While significant advances have been achieved in understanding risk factors for neurodegenerative diseases, the impact of air pollution on their progression represents a novel and emerging area of concern. Despite the global prevalence of pollutant exposure, our understanding of its effect on the progression of neurodegenerative diseases is limited. Previous work has demonstrated that nanoparticulate matter (nPM) exacerbates proteostasis failure, increasing polyQ protein toxicity in C. elegans. Yet, the variable composition of nPM, influenced by factors such as collection time and geographic location, can result in inconsistent bioactivity assessments for experimental reproduction. Therefore, we began focusing on the effect of a more refined particle, specifically, investigating the effect of commercially available diesel particulate matter (dPM) on proteostasis. To examine proteostasis integrity we employed a C. elegans model expressing a polyQ sequence, fused to a yellow fluorescent protein (YFP), as a sensor of the protein folding environment. Surprisingly, we found that dPM induces cellular toxicity in a manner that is independent of polyQ misfolding. Identifying the effect dPM has on proteostasis offers new insight into how nano pollutants may influence the progression of neurodegenerative diseases.Item Examining the impacts of regenerative agriculture on soil carbon: A community-based participatory study.(University of the South, 2024-05-01) Graf, Paige; Deborah McGrath (Honors Thesis Advisor)Innovative farmers in the southeastern Cumberland Plateau region are stewarding their lands using regenerative practices, such as improved cover cropping and rotational grazing. These practices have been shown to increase and sequester soil carbon, offering an important tool for mitigating climate change caused by rising atmospheric CO2 concentrations. In partnership with the Southeast Tennessee Young Farmers (SeTNYF) Coalition, we initiated a pilot project to examine the impact of rotational grazing and cover cropping on soil carbon on seven local small farms. We employed a community-based participatory approach to design the research around the needs of the local community and to ensure that farmers were consulted at every step. We compared soil carbon at two depths (0-15 and 15-30 cm) between parcels managed with regenerative practices (rotational grazing or cover cropping) and adjacent non-regenerative plots on seven farms. Using the sampling protocol employed by the Soil Inventory Project, we sampled at a minimum density of 3 samples per acre, although on some farms we sampled more, for a total of 406 samples. We hypothesized that soils under rotational grazing or cover crops would have higher organic carbon than adjacent non-regeneratively managed land. Despite the fact that farms had been rotationally grazed for at least five years, we found no significant difference in soil carbon between rotational grazing and adjacent plots. Only on one farm did we find significantly higher carbon under soils that had been cover cropped. Our interviews with farmers suggested that the sampling density may not have been high enough to detect changes in carbon resulting from highly localized regenerative practices, especially given the inherent heterogeneity of soils, compounded by differing land use histories. More research on other factors influencing soil is crucial for future carbon studies to better understand the environmental benefits of regenerative agriculture. While we found no effect of rotational grazing on soil in this study, these data provide a baseline for continued research on small farms which has been enhanced through our use of the community-based participatory approach.Item Synthesis, characterization, and transfer hydrogenation catalysis of mid-row transition metals and the investigations of regulatory mechanisms of the OAS-RNase Land PKR pathways for RNA sensing(University of the South, 2024-05) Keuk, ChannitaA. The synthesis of a series of chlorine-substituted acetylacetonate cobalt(III) complexes was attempted by varying the stoichiometric ratios of the starting materials in solution. Following the synthesis, the complexes were purified using column chromatography and subsequently characterized using ultraviolet-visible, infrared, and nuclear magnetic spectroscopy and x-ray crystallography to analyze the effects of these chlorine substitutions on the Co(III) metal center. Based on the spectroscopic analysis of the complexes, these substitutions yielded discernible differences in the electronic properties of the Co(III) center. Characterization of these complexes can lead to its potential applications in catalysis and photochemical studies. B. Alcohols play an extremely important role in the synthesis of larger organic compounds such as perfumes, sweeteners, and pharmaceuticals. The reduction of ketones to alcohols via traditional metal-catalyzed hydrogenation has multiple drawbacks such as the use of pressurized hydrogen gas and requiring high temperatures. Organometallic catalysts can eliminate some of these by utilizing alternative reaction conditions that are more environmentally friendly and can occur at much lower temperatures. Ruthenium(II) metal complexes with 4-aminopyridine (ampy) and diphenylphosphinobutane (dppb) were synthesized with the replacement of the para-hydrogen on the pyridine ring with a chlorine (Cl) group and a methoxy (OMe) group to study the effects of electron withdrawing groups (EWG) and electron donating groups (EDG) on the electronic profiles of the ruthenium center. NMR spectroscopy, UV-Vis spectroscopy, cyclic voltammetry, and X-ray crystallography were used to characterize each compound. Studies have shown that the ampy based ruthenium(II) metal complexes are capable of isomerization; thus, the rates of trans-to-cis isomerization were. The transfer hydrogenation catalysis data shows that these ampy-ruthenium(II) systems are highly capable of transfer hydrogenation, with selectivity for ketone functional groups. C. N-Heterocyclic carbenes (NHC) are excellent ligands for the coordination and reactivity of cobalt complexes in the transfer hydrogenation catalysis of ketone substrates. The traditional synthesis of such ligands is a time-consuming process that hinders efficient synthesis of metal complexes. Thus, an alternative synthetic method via a microwave reactor for several N-substituted imidazole-based NHC pincer ligands was developed to reduce reaction time from three days to under two hours. Seven different compounds were synthesized and characterized using 1H and 13C nuclear magnetic resonance spectroscopy. Several compounds resulted in mixtures of unreacted starting material and the desired products, which were then cleanly isolated using column chromatography purification. D. Transfer hydrogenation offers an alternative to selectively target specific functional groups on a molecule while keeping the others intact. An abundance of previously published research focuses on expensive transition metal catalysts of ruthenium, platinum, and more. Given the reactivity of ruthenium(II) systems in transfer hydrogenation, the shift to utilizing cobalt(II)-based catalysts systems allows for a more cost-efficient method due to the natural abundance of these first-row transition metals. The synthesis of a series of imidazole-based N-heterocyclic carbene (NHC) cobalt(II) complexes are being explored in order to generate a diverse range of metal complexes with varying electron-donating and withdrawing substitutions, as well as sterically bulky R-groups, on the imidazole ligand. Catalytic studies are also being done to determine if these changes in electron density around the metal center can have an effect on the rates of catalysis. E. In the field of transition metal catalysis, specific analytical techniques must be employed in order to quantitatively assess the rates and percent yield of catalytic conversion of the substrates. For studies involving paramagnetic metal complex species, the common method of NMR spectroscopy proves to be challenging as it requires various additional steps for sample preparation. Thus, an alternatively strategy using the gas chromatography mass spectrometer (GC-MS) allows for quantitative assessment of the amount of product converted by the catalyst through the use of a calibration curve. A series of calibration curves using benzophenone and benzhydrol were generated in an attempt to accurately assess the percent yields of the products in Co(II) imidazole-NHC catalyzed transfer hydrogenation. Studies are currently still ongoing to find the optimal sample preparation techniques to generate an accurate calibration curve. F. The vaccinia virus (VACV) utilizes the hypophosphorylation of serine/arginine-rich (SR) proteins, which are essential to the host alternative RNA splicing machinery, to induce host shut-off. In response to viral infections, the Protein Kinase R (PKR) pathway is activated in order to prevent viral RNA translation. To explore whether defects in RNA splicing generates ligands for PKR activation, western blots were used to probe for PKR activation in A549 cells during SR inhibition. Upon treatment with SR inhibitors and infection with the vaccinia virus for 24 hours, A549 cells were collected and probed for PKR activity via western blot. Contrary to published literature, it was found that VACV infection did not suppress SR phosphorylation based on the western blot analysis, and chemical inhibition of SR proteins do not induce PKR activation. G. As dsRNAs are the hallmark of viral infections, RNA sensing becomes an important component of host innate immunity. The oligoadenylate synthetase (OAS)-RNase L system, a dsRNA-sensing pathway of interest, provides a mechanism of action against dsRNAs within the body. Given the potency of its activation, this pathway is not only highly regulated through cellular mechanisms but also heavily antagonized by viruses. To test whether regulation of the OAS/RNase L pathway occurs at the post translational level, RNase L wildtype and K684R mutant plasmids were generated to test the effect of acetylation of the enzyme and its overexpression on its activation using bioanalyzer assays. Based on the assays conducted, there appears to be no activation of RNase L due to overexpression of the mutant plasmids. However, due to experimental errors, the assays comparing the transfection of PCDEF3 empty vector, wildtype RNase L, and RNase L K684R mutant followed by polyIC and 2-5A treatments failed to show any discernable differences in RNA degradation. Further studies are needed in order to accurately assess the RNA integrity in the bioanalyzer assays studying the effects of hyperacetylation of RNase L on its activation.Item Synthesis and Characterization of Potential Anti-Cancer Platinum Complexes with Indazole and its Derivative(University of the South, 2024-05) Humeniuk, YulliaIn 1978, the FDA marked a milestone with the clinical approval of Cisplatin, the pioneering metal-based anticancer chemotherapeutic. Its effectiveness sparked great interest in understanding its behavior and developing new platinum pharmaceuticals. Platinum(II) complexes dominate a majority of drug discovery research to date; however, platinum(IV) complexes have also begun to be explored in the belief that they will allow new therapy avenues with fewer side effects, acting as potential prodrugs. This exploration extends beyond platinum, delving into various metal systems, such as ruthenium. Inspired by the ruthenium anticancer complex (KP1019) and the scarcity of metal complexes featuring indazole, we explore the chemistry of platinum-indazole complexes. In recent years, our group yielded a library of new bisindazole Pt(IV) and Pt(II) complexes, enriching the landscape of potential anti-cancer agents. These complexes have been characterized via spectroscopy and crystallography, and the initial experiments suggest at least one new compound interacts with a DNA model.