2014 UMKC Dissertations - Freely Available Online
Permanent URI for this collection
This community contains the collections of dissertations submitted electronically to the School of Graduate Studies by doctoral degree candidates at the University of Missouri-Kansas City in the spring, summer, and fall semesters of 2014. The items in this collection are dissertations that are available to the general public.
Browse
Recent Submissions
Item 364 Days: Suite for Jazz Orchestra(2014) Chapman, Jonathan Eric; Simpson, Reynold364 Days: Suite for Jazz Orchestra was composed for a standard seventeen-piece (5/4/4/4) jazz orchestra. The suite is comprised of five pieces- And I Think of You; Goodnight; What Ifs; 364 Days; The Dreamer and The Realist - and were recorded for the album J.E. Chapman, 364 Days: music for large ensembles. Each movement of the suite is intended to work as a part of the larger work or out of context as an individual performance piece. The sections of the suite are connected through an "affiliated motif". Each piece is tied together through intervallic commonalities, common melodic contour, and "spirit" but are unique enough in their own individuality to posses their own personality. While the intent is for the suite to be performed as a complete work I took great effort in creating five works that could be performed separately and yet still sound complete; each piece has its own unique formal structure and distinctive rhythmic and style elements that allow them to succeed as part of a set or as an isolated work. These compositions blend modern jazz harmonies and non-traditional formal structures; staying connected to and extending the tradition of jazz composition.Item Regulation of Gene Expression by Non-coding RNAs in Arabidopsis and Brachypodium(2014) Wang, Hsiao-Lin V.; Chekanova, JuliaExpansion of high-throughput sequencing technology has increased our understanding in the importance of pervasive transcription and the resulting indispensable molecules, noncoding RNAs (ncRNAs). A significant effort has been made in determining the biological relevance of ncRNAs, including the small RNAs (smRNAs) and long ncRNAs (lncRNAs). Studies have shown that ncRNAs can have very important regulatory functions such as the establishment and maintenance of the epigenetic architecture of eukaryotic genomes. However, these studies have only revealed the surface of ncRNAs’ functions in cells. Motivated by the previously “hidden” transcriptome regulated by the Arabidopsis exosome, we examined the role of ncRNAs in regulation of gene expression in two plant model systems, Arabidopsis and Brachypodium. We set out to investigate whether the Arabidopsis exosome complex modulates gene expression through regulating ncRNAs, including both smRNAs and lncRNAs. Thus, the role of Arabidopsis exosome complex in regulating smRNA metabolism was extensively investigated and we revealed the differences between Arabidopsis core exosome, yeast and human exosomes in modulating smRNAs. Although we have only begun to categorize the lncRNAs regulated by the Arabidopsis exosome, our data so far has led to intriguing speculations, including the possible role of exosome in transcriptional regulation via controlling lncRNAs. The challenges still remain, including establishing the regulatory role of specific lncRNAs regulated by the exosome and other factors at transcriptional or post-transcriptional levels in different cellular contexts, and most importantly, how the interaction between these lncRNAs and the chromatin is mediated. We also investigated the role of smRNAs in biotic and abiotic stress responses in Brachypodium. We identified a group of endogenous, stress-induced small interfering RNAs, sutr-siRNAs, and its novel mechanism in targeting cis elements involved in splice site selection. This finding will stimulate research of smRNA mediated stress responses in agricultural important crops. It also provides a framework for more suitable experimental systems, such as the Drosophila and mammalian cell cultures, to further investigate the associated mechanistic details of sutr-siRNAs. In this dissertation, we revealed new insights and detailed molecular mechanisms of the Arabidopsis exosome complex in regulation of gene expression, as well as provided a novel regulatory mechanism of endogenous siRNAs by being involved in splicing. Although many challenges still remain to fully determine the mechanistic details and biological significance of plant ncRNAs, the work presented in this dissertation has added to our understanding in regulation of gene expression through ncRNAs in plants.Item Disconnecting a Role for DNA Repair in the Pathogenicity of the Human pathogen Cryptococcus neoformans(2014) Verma, Surbhi; Idnurm, AlexanderC. neoformans is an opportunistic fungal pathogen causing fatal meningitis and lung infections. Worldwide every year around 625,000 deaths occur due to Cryptococcosis. A basic understanding of Cryptococcus virulence mechanisms and survival strategies is required to combat the infections and develop therapies through translational research. Considering the evidence of a role of DNA repair in pathogenesis, I investigated DNA repair strategies adopted by Cryptococcus to survive in the environment and to cause successful infection. The repair of UV induced DNA damage was studied for two genes: UVE1 and RAD23, parts of base excision repair and nucleotide excision repair pathways, respectively. My findings suggest that UVE1 is required to combat UV induced stress. Uve1 is a mitochondrially-localized enzyme that functions to protect the mitochondrial genome from the deleterious effects of UV-induced DNA damage. Another aspect explored was the regulation of UVE1 by the Bwc1-Bwc2 photoreceptor complex. UVE1 is a direct downstream target of Bwc1-Bwc2 and is responsible for the UV sensitivity phenotype governed by this complex, without affecting mating or virulence. The regulation of UVE1 iv through the Bwc1-Bwc2 photoreceptor was also extended to two other fungal lineages, ascomycetes and zygomycetes. The second DNA repair gene, RAD23, codes for a dual function protein acting in nucleotide excision repair and as an ubiquitin receptor. Those two functions were uncoupled by creating mutant alleles and testing the strains carrying them for their virulence. The DNA repair function of the Rad23 is dispensable for virulence. Hence, specific DNA repair pathways do not necessarily have a major role in the virulence of Cryptococcus. However, ancillary functions of a DNA repair protein can contribute to virulence.Item Mating Type Specific Roles During The Sexual Cycle Of Phycomyces Blakesleeanus(2014) Shakya, Viplendra Pratap Singh; Idnurm, AlexanderPhycomyces blakesleeanus is a filamentous fungus that belongs in the order Mucorales. It can propagate through both sexual and asexual reproduction. The asexual structures of Phycomyces called sporangiophores have served as a model for phototropism and many other sensory aspects. The MadA-MadB protein complex (homologs of WC proteins) is essential for phototropism. Light also inhibits sexual reproduction in P. blakesleeanus but the mechanism by which inhibition occurs has remained uncharacterized. In this study the role of the MadA-MadB complex was tested. Three genes that are required for pheromone biosynthesis or cell type determination in the sex locus are regulated by light, and require MadA and MadB. However, this regulation acts through only one of the two mating types, plus (+), by inhibiting the expression of the sexP gene that encodes an HMG-domain transcription factor that confers the (+) mating type properties. This suggests that the inhibitory effect of light on mating can be executed through the plus partner. These results provide an example of convergence in the mechanisms underlying signal transduction for mating in fungi. This study further investigated the role of mating type genes in the mating related process of mitochondrial inheritance. Due to isogamous fusion of cells in mating in this fungus, the initial expectation was that Phycomyces would demonstrate biparental inheritance but instead uniparental inheritance (UPI) was observed. Analysis of progeny from a series of genetic crosses between wild type strains of Phycomyces revealed a correlation between the individual genes in the mating type locus and UPI of mitochondria. Inheritance is from the (+) sex type and is associated with degradation of the mtDNA from the minus (−) parent. These findings suggest that UPI can be directly controlled by genes that determine sex identity, independent of cell size or the complexity of the genetic composition of a sex chromosome. Similar regulation may exist in other eukaryotes or was important at one stage of their evolution in establishing this system of inheritance. This investigation on the genetic regulation of mating and mating-related process of mitochondrial inheritance P. blakesleeanus demonstrates a prominent role of the sexP gene in both phenomena.Item Evaluation Of HIF Inhibitors For The Treatment of Ocular Neovascular Diseases(2015-06-02) Vavilala, Divya Teja; Mukherji, MridulHypoxia-inducible-factor (HIF)-mediated expression of pro-angiogenic genes under hypoxia is the fundamental cause of pathological neovascularization in ocular diseases and cancers. Thus, the inhibitors of the HIF pathway or key regulators such as histone demethylases (KDMs), that amplify HIF signaling, can have profound therapeutic value for these diseases. This dissertation reports findings about phytochemical molecules - honokiol and berberine and shows them to be potent inhibitors of the HIF pathway as well as hypoxiainduced expression of KDMs in a number of cancer and retinal pigment epithelial cell lines. The results provide an evidence-based scientific explanation for therapeutic benefits observed with honokiol and berberine. On comparing the anti-HIF effect of both these compounds honokiol was found to possess a better efficacy that exhibited it's effect on the HIF pathway by inhibiting HIF binding to the HRE. Further in this study honokiol was compared with two other recently identified HIF inhibitors from natural sources - digoxin and doxorubicin. The results show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Therefore honokiol was chosen as candidate molecule for further clinical evaluation for the treatment of pathological ocular neovascularization. Honokiol inhibited hypoxic - mediated secretion of VEGF by retinal pigment epithelial cells. Hence honokiol’s anti-angiogenic activity was evaluated using various in vitro angiogenesis assays that mimic ocular neovascularization. A robust inhibition of human retinal micro vascular endothelial cell (hRMVEC) activation and proliferation was observed with honokiol treatment. Also, hRMVEC cells lost their ability to migrate and form wellnetworked tubes essential for pathological ocular neovascularization. Further, it is shown for the first time that daily intraperitoneally injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration a characteristic feature of the OIR model. Honokiol also enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.