Life Sciences Commons^™

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Circadian Rhythmicity And Melatonin Sensitivity In The Human Gut Commensal Bacterium Klebsiella Aerogenes, Kinga Graniczkowska

Theses and Dissertations--Biology

While the expression of circadian rhythms is nearly universal among multicellular eukaryotic organisms, demonstration of this phenomenon in prokaryotes has been largely restricted to photosynthetic cyanobacteria until very recently. Further, growing interest in gastrointestinal microbiomes has revealed a complex temporal relationship between the gastrointestinal clock and the bacterial microbiome within. At least one member of the gut microbiome, Klebsiella (née Enterobacter) aerogenes, responds to the indoleamine hormone melatonin, secreted by the gastrointestinal system itself. Further research revealed that K. aerogenes also expresses a circadian rhythm in motility and gene expression that is temperature compensated. Although rhythmicity is unaltered …

Mechanisms Of Cadmium-Induced And Epidermal Growth Factor Receptor Mutation-Driven Lung Tumorigenesis, Hsuan-Pei Lin

Theses and Dissertations--Toxicology and Cancer Biology

Cadmium (Cd) is a ubiquitous pollutant in the environment and a known carcinogen for lung cancer. Cd has been shown to act as a weak mutagen, which suggests that it may exert tumorigenic effect through non-genotoxic ways, such as epigenetic mechanisms. The goal of this project is to investigate the mechanisms of Cd carcinogenesis focusing on the role of lncRNA dysregulations. The Cd-exposed cells formed significantly more colonies in soft agar, displayed cancer stem cell (CSC)-like property and formed tumors in nude mice. Mechanistically, the lncRNA microarray analysis revealed that chronic Cd exposure dysregulates lncRNA expressions. Q-PCR analysis confirmed the …

Genetic Mouse Models Of Liver Disease: Potential Roles Of Zhx2 (Afr1) And Afr2 In Damage And Regeneration, Courtney P. Turpin

Theses and Dissertations--Pharmacology and Nutritional Sciences

The liver is the largest internal organ in mammals and responsible for carrying out various processes, including lipid and carbohydrate metabolism, detoxification of chemicals, and production of serum proteins. Liver damage, which can be caused by a variety of agents including viral infection, environmental toxins, alcohol and excessive dietary fats, can cause dysregulation of these critical functions, leading to worsening liver pathophysiology and impacting health. However, the liver has the remarkable ability to regenerate when damaged. Hepatocytes, which comprise a majority of liver cells, are relatively quiescent under healthy conditions. Upon injury, remaining hepatocytes can proliferate to recover from liver …

Molecular Mechanisms Regulating Optic Fissure Fusion During Zebrafish Eye Development, Megan Weaver

Theses and Dissertations--Biology

Vertebrate retinal development requires timely and precise fusion of the optic fissure. Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed optic fissure fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a^-/- embryos fail to accumulate F-actin in the optic fissure prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a^-/- embryos. When examining the connection …

Southern Pine Beetle-Specific Rna Interference Demonstrates No Effects On Nontarget Insects, Hannah Marie Hollowell

Theses and Dissertations--Entomology

The endemic southern pine beetle (SPB), Dendroctonus frontalis Zimmermann, is a highly destructive bark beetle that has devastated coniferous forests of the southern United States for decades. Traditional management strategies have been unable to respond effectively to largescale SPB outbreaks, prompting exploration of novel techniques including RNA interference (RNAi). Double-stranded RNAs (dsRNAs) are effective at triggering gene silencing and inducing mortality in SPB, but determining delivery methods and demonstrating specificity of the treatments is necessary before this technology may progress to deployment.

I evaluated three SPB-specific dsRNAs on model nontarget insects to assess potential lethal effects, sublethal effects such as …