Life Sciences Commons^™

Utilizing Galectin 3 As A Marker Of Ruptured Vesicles In Vivo, Jonathan London

Master's Theses

Ruptured vesicles have been associated with pathological forms of α-synuclein during the development of PD. Galectin 3 (Gal3) is readily recruited to these ruptured vesicles, making it a potentially useful marker of vesicle rupture in PD and other diseases associated with vesicle rupture and lysosomal dysfunction. We were able to visualize and quantify the differences in Gal3 levels during infection with pathological α-synuclein in the rat brain. Having significantly high basal levels of Gal3, we found that the differentiated monocytes showed a nearly100 percent increase in intercellular levels of Gal3 after treatment with pathological α-synuclein. By expressing only the Carbohydrate …

The Effects Of Stress And Alcohol On Hiv-1 Latency, Sarah Ilene Talley

Master's Theses

A major barrier to HIV eradication is the persistence of latent viral reservoirs that exist despite antiretroviral therapy. In order to develop effective therapeutics, a comprehensive understanding of latency and factors driving the formation of the latent reservoir is needed. As stress and alcohol are common comorbidities associated with HIV infection, the goal of this research was to determine how stress and alcohol could affect HIV-latency. Specifically, we hypothesized that the ability of latent proviruses to be reactivated by “shock and kill” approaches would be altered by glucocorticoid and ethanol treatments, and prolonged ethanol exposure would affect the size of …

Role Of Heat Shock Proteins In Maintenance Of The Gut Barrier Following Burn Injury, Abigail Rhea Cannon

Master's Theses

Introduction: Burn injury remains a prominent clinical problem. Patients suffering from burns often succumb to secondary infectious complications leading to sepsis and widespread tissue injury ending in Multiple Organ Dysfunction. However, the mechanism behind the onset of these extraneous symptoms following burn injury is not fully understood. The integrity of the gut barrier is of critical importance as it harbors the largest bacterial reservoir in the body. Following burn injury, we observed a breakdown of the gut barrier resulting in increased gut leakiness and bacterial translocation. Under homeostatic conditions, heat shock proteins (HSPs) stabilize tight junction proteins. Particularly, HSP72 is …

Emetine As An Anti-Cancer Therapeutic In Bladder Cancer, Valerie Davidson

Master's Theses

Bladder cancer is a serious health concern among the older population, as it is responsible for thousands of deaths annually in the United States. Patients that are diagnosed with muscle-invasive disease have a 5-year survival rate of only 20 percent. Additionally, muscle-invasive disease has a high metastatic potential; half of all patients develop metastatic disease within 3 years. Patients with muscle-invasive disease are presented with few treatment options aside from surgery. The current standard of care is a chemotherapeutic combination therapy of cisplatin and gemcitabine. This therapy is highly toxic, and due to the high instance of co-morbidities in these …

The Role Of Pidd Protein In Adenoviral Induction Of Apoptosis, Iris Teresa Figueroa

Master's Theses

The Adenovirus E1A gene sensitizes cells to genetic insults and apoptosis, most notably in response to cytotoxic factors from innate immune cells. The mechanisms by which E1A sensitizes cells to apoptotic stressors have not been fully elucidated, however E1A actively represses NF-κB anti-apoptotic defenses, thereby sensitizing cells to alternative apoptotic cascades. Recent studies alternatively indicate that E1A also actively induces Caspase-2 activation and mitochondrial injury in the presence of certain cytotoxic injuries.

Caspase-2 is cleaved and activated in a large complex consisting of p53-inducible protein with a death domain (PIDD), an adaptor protein RAIDD, and pro-caspase 2. PIDD auto-proteolyzes into …

The Contribution Of The Female Urinary Microbiota To Lower Urinary Tract Symptoms, Travis Kyle Price

Master's Theses

The recent finding that urine is not sterile raises a lot of questions: first and foremost, what microorganisms are present, and are these microorganisms correlated with clinical urinary symptoms? Recent work on the female urinary microbiota (FUM) found that the communities of microorganisms differ between women with no lower urinary tract symptoms (LUTS) and those with Urgency Urinary Incontinence (UUI) a form of over-active bladder syndrome. Specifically, a diverse or dysbiotic urinary microbiota was found to be associated with symptomatic women. This suggests the possibility that the FUM can be contributing to urinary symptoms. Conversely, it could also suggest that …

Malaria Transmission Blocking Vaccines, Lukasz Jacek Sewera

Master's Theses

Malaria affects 198 million people and kills 584,000 each year, predominantly in Sub-Saharan Africa (WHO). The most severe form of malaria is caused by the protozoan parasite Plasmodium falciparum. Development of a vaccine against P. falciparum has been hindered by its complex life cycle with multiple antigenically distinct human and mosquito stages. To effectively prevent disease and reduce the parasite burden in populations, a vaccine will need to target multiple stages, including blocking transmission at the mosquito stage.

Antibodies generated against P. falciparum mosquito stage antigen Pfs25 can prevent parasite transmission from humans to mosquitoes. However, Pfs25 is poorly immunogenic …

The Role Of Central Metabolism And Electron Transport In Biofilm Formation By Vibrio Fischeri, Jakob Michael Ondrey

Master's Theses

Biofilms protect bacteria from environmental threats, including antibiotics; thus, biofilms formed during infections pose an increasing threat to human health. A natural model used to study biofilm formation in the context of a host is the symbiosis between Vibrio fischeri and its host, the squid Euprymna scolopes. Successful colonization depends on the formation of a biofilm and genes involved in making the polysaccharide matrix component, syp. In culture, biofilm phenotypes, including the formation of wrinkled colonies, similarly depend on syp. However, little is known about other factors that contribute to this phenotype. To expand the utility of currently available genetic …

Tcr Modifications To Enhance Expression, Chain Pairing, And Antigen Recognition For Adoptive T Cell Transfer, Kendra Foley

Master's Theses

T cell receptor (TCR) gene modified T cells for adoptive T cell transfer therapy have been shown to have clinical success in treating melanoma and other malignancies by redirecting the specificity of peripheral blood lymphocytes (PBL) to recognize tumor and/or viral associated antigens of choice. One of the challenges in using TCR gene modified T cells is the potential mispairing between endogenous and introduced alpha and beta TCR chains, allowing for unwanted off-target reactivity, autoimmunity, or impaired therapeutic efficacy. One approach to augment proper TCR chain pairing and to enhance T cell function involves the modification of the introduced TCR …

Experimental Evolution Of Specialism In A Wild Virus, Alexander Kula

Master's Theses

A pathogen's ability to successfully replicate and persist within a new host population is fraught with obstacles. While an expanded host-range allows for a greater chance at successful replication, such generalists are typically outcompeted by species which have specialized and adapted host-specific features. Although the most ubiquitous species on earth, very few bacteria-infecting viral species (bacteriophages) with truly broad host-ranges have been identified; this is partially due to the fact that only a small fraction of bacteria (and thus likely hosts) are amenable to laboratory conditions. Nevertheless, the processes of expanding as well as narrowing host-range are not well understood …

Characterization Of Exopolysaccharide (Eps) Produced By Bacillus Subtilis Mutants, Alexander Argianas

Master's Theses

Bacillus subtilis is a probiotic bacterium that can protect against the murine-

specific attaching and effacing (A/E) pathogen Citrobacter rodentium. C. rodentium displays many features observed with the human pathogen enteropathogenic E. coli (EPEC). Protection by B. subtilis is mediated by exopolysaccharide (EPS), which is encoded by the epsA-O operon that contains 15 genes. Disruption of one of these genes, epsH, which appears to encode a putative glycosyltransferase, leads to the loss of protective capacity by B. subtilis and by EPS. EPS is a major component of the B. subtilis biofilm and the ΔepsH mutant is unable to form a …

Investigating The Role Of Cysteine In Biofilm Formation By Vibrio Fischeri, Priyanka Abhishek Singh

Master's Theses

Biofilms are an important area of medical research because bacterial biofilms can form on implants such as catheters and are highly resistant to antibiotics and other antimicrobials. The symbiosis between Vibrio fischeri-Euprymna scolopes, is good model to study biofilm. V. fischeri has 18 gene polysaccharide locus, syp, that is required for biofilm formation and colonization. A recent mutant study suggested the possibility that cysteine biosynthetic genes were involved in biofilm formation by V. fischeri, including cysH, cysJ, cysK, and cysN. My results supported a role for cysK and, to a lesser extent, cysH in biofilm formation. Finally, I have data …

Anthropogenic Litter And Microplastic In Urban Streams: Abundance, Source, And Fate, Amanda Rae Mccormick

Master's Theses

The accumulation and ecological effects of anthropogenic litter (AL) and microplastic are well-documented in marine ecosystems, but these materials’ abundances in rivers is unknown. AL enters rivers from recreation, runoff, and illegal dumping. Microplastic fibers and pellets are abundant in wastewater treatment plant (WWTP) effluent which enters rivers. Our objectives were to: (1) quantify AL abundance and composition in urban streams, (2) measure AL flux, accumulation, and export, and (3) measure riverine microplastic concentration and analyze its bacterial communities. We collected AL from 5 urban streams and observed greater AL density in riparian habitats and greater mass in benthic habitats. …

Dna Methylation Patterns Of Specific L1 Loci On The Short Arm Of Chromosome 21, Sarah Ann Tincher

Master's Theses

While 10-15% of the human genome is composed of heterochromatic DNA, these regions are not included in the completed genome sequence. The short arm of chromosome 21 (HC21p) serves as a model for understanding the structure and function of heterochromatin. LINE-1 (L1) retrotransposons are underrepresented in heterochromatin, including HC21p, and have not been extensively studied in these regions. However, there are disproportionately more full length L1s on HC21p than in euchromatic genomic regions. Decreased DNA methylation in the promoters of these L1s on HC21p may allow them to facilitate heterochromatin formation, which would be analogous to their proposed role in …