Chemicals and Drugs Commons^™

Utilizing Ultra-Performance Chromatography High-Resolution Mass Spectrometry To Investigate Fatty Acid Mediated Antibiotic Tolerance, Brittni Woodall

Doctoral Dissertations

The lipid membrane is the first component necessary to sustain life. To maintain homeostasis, segregate cellular machinery, provide protection from the environment, and reproduce, an organism must establish a boundary in which the processes can occur. Throughout the last two decades, research has propelled our knowledge of lipid membranes much beyond original hypotheses. Once thought of to be static and uniform, the understanding of the lipid membrane has evolved to encompass a structure that is responsive, unique, and intricately constructed by the organism itself. By chance or by choice, organisms adapt the lipid membrane according to the environment for which …

Development Of Surface-Modified Liposomes For Drug Delivery Applications, Megan Louise Qualls

Doctoral Dissertations

Liposomes are spherical vesicles composed of a lipid bilayer membrane that assembles around an internal aqueous core. This duality gives liposomes the ability to encapsulate both hydrophobic cargo within the lipid bilayer and hydrophilic cargo in the aqueous core, making them versatile molecular carriers for drug delivery. Liposome platforms have many advantages and are promising drug delivery carriers, and research is ongoing to improve their designs for continued clinical applications. Many liposome types have been developed, but further work is needed to improve surface modification, site-specific targeting, and triggered cargo release in order to further the therapeutic applications of these …

The Effects Of Clonidine On Neonatal Abstinence Syndrome Patient Outcomes, Claire E. Flatt

Chancellor’s Honors Program Projects

No abstract provided.

Identification Of The Type Eleven Secretion System (T11ss) And Characterization Of T11ss-Dependent Effector Proteins, Alex S. Grossman

Doctoral Dissertations

Host-associated microbes live in dangerous environments as a result of host immune killing, nutrient provisioning, and physiological conditions. Bacteria have evolved a host of surface and secreted proteins to help interact with this host environment and overcome nutrient limitation. The studies included within this dissertation describe the identification of a novel bacterial secretion system which has evolved to transport these symbiosis mediating proteins. This system, termed the type eleven secretion system (T11SS), is present throughout the Gram negative phylum Proteobacteria, including many human pathogens such as Neisseria meningitidis, Acinetobacter baumanii, Haemophilus haemolyticus, and Proteus vulgaris. Furthermore, …

Synthesis Of A Functionalized Trans-Cyclooctene (Tco) For Selective Protein Isolation After Bioorthogonal Labeling With Tetrazine, Thaddeus Lawrence Puzdrakiewicz, Dillon P. Mcbee, Joshua A. Baccile

Chancellor’s Honors Program Projects

No abstract provided.

Anti-Inflammatory And Chemopreventive Activity Of Lunasin From Tofu Whey For The Management Of Gastrointestinal Diseases, Cindy Andrea Nieto Veloza

Doctoral Dissertations

Gastrointestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are pathological conditions associated with chronic inflammation, characterized by intestinal damage, debilitating symptoms, and detrimental health consequences. The increased risk of CRC in IBD patients, and the adverse effects associated with current therapeutic strategies, point out the need for safer alternatives to reduce chronic inflammation in the bowel. Lunasin is a bioactive peptide naturally occurring in soybeans, with chemopreventive and anti-inflammatory properties demonstrated in several extra-intestinal diseases. However, to date, there is no evidence of the biological activity of lunasin on the gastrointestinal tract as a target site. …

Assessment Of The Use Of Low Molecular Weight Diblock Copolymers For The Formation Of Stable, Tunable Droplet Interface Bilayers, Joseph Tawfik

Masters Theses

This thesis presents the use of diblock copolymers, poly(butadiene)-b-poly(ethylene oxide) (PB_m PEO_n) and poly(isoprene)-b-poly(ethylene oxide) (PI_mPEO_n), as amphiphilic molecular building blocks for the formation of synthetic polymer bilayer membranes using the droplet interface bilayer (DIB) technique. The DIB technique makes use of the self-assembly of amphiphilic macromolecules along oil-water droplet interfaces that can then be physically connected for the construction of liquid supported macromolecular bilayers at the droplet interface. These bilayer membranes are capable of hosting both naturally occurring and synthetic protein channels. This technique has been used to form synthetic bilayer membranes …

Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes

Chancellor’s Honors Program Projects

No abstract provided.

Design And Development Of A Quartz Crystal Microbalance Immunosensor For Exosomes, Wesley Cox

Chancellor’s Honors Program Projects

No abstract provided.

Investigating The Regulation Of Indole-3-Acetic Acid Production By The Plant Associated Microbe Pantoea Sp. Yr343, Kasey Noel Estenson

Doctoral Dissertations

The auxin indole-3-acetic acid (IAA) plays a central role in plant growth and development and many plant-associated microbes produce IAA. Several IAA biosynthetic pathways have been identified in microbes which use the precursor tryptophan. Pantoea sp. YR343, which was isolated from the Populus deltoides rhizosphere, is a robust plant root colonizer that produces IAA. Using genomic and metabolomics analyses, we predicted that the indole-3-pyruvate (IPA) pathway is the major pathway in Pantoea sp. YR343 for IAA production. To better understand IAA biosynthesis and the effects of IAA exposure on cell physiology, we performed proteomics on Pantoea sp. YR343 grown in …

Using The Suprachiasmatic Nucleus As A Model System To Assess Tolerance And Withdrawal To Alcohol, Jonathan Houghton Lindsay

Doctoral Dissertations

Alcohol abuse induces many disorders including depression, metabolic syndrome, and sleep disturbances. The strong link between alcohol abuse and sleep problems, along with the close connection between sleep and circadian rhythms, led us to investigate ethanol’s effects on the circadian clock. Previous work has shown that acute ethanol blocks photic phase shifts in vivo and glutamatergic phase shifts in vitro. However, neural systems become tolerant to ethanol across different timeframes. Despite both ethanol tolerance and ethanol withdrawal syndrome being listed as criteria for developing alcohol use disorders, little is known about how ethanol tolerance and withdrawal induced hyperexcitability develop and …

Effects Of Nicotine On The Cyp6a8 Gene Promoter Of Drosophila Melanogaster, Leslie M. Stroud

Chancellor’s Honors Program Projects

No abstract provided.

Using Poincaré And Coefficient Analyses To Assess Changes In Variability In Respiration As A Function Of Leptin Status, Sex, And Buprenorphine In Mice, Wateen Hussein Alami

Chancellor’s Honors Program Projects

No abstract provided.

Protein Studies: The Function Of Constitutive Androstane Receptor (Car) And Its Associated Ligands, Jacob M. Amburn

Chancellor’s Honors Program Projects

No abstract provided.

The Characterization Of Amyloid Fibrils And Novel Synthetic Heparin-Binding Peptides Binding To Cell Surfaces, Nicole Marie Hackenbrack

Chancellor’s Honors Program Projects

No abstract provided.

Effects Of Different Brands Of Coffee On The Transcriptional Activity Of Drosophila Cyp6a8 Gene Promoter, Marie Ashley Scott

Chancellor’s Honors Program Projects

No abstract provided.

Syntheses Of Precursors To Fluorine-18 Labeled Pet Imaging Agents, Lindsay B. Boling

Chancellor’s Honors Program Projects

No abstract provided.

Design And Synthesis Of Novel Sultams As Non-Nucleoside Inhibitors Of Hiv Reverse Transcriptase, Brian Chadwick Lecroix

Doctoral Dissertations

The compound 2-methyl-3-phenyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (NSC 108406) was identified as an HIV-1 reverse transcriptase inhibitor by the National Cancer Institute. Using this lead, the Baker group has developed a series of analogues with various groups at the 3-position that show a spectrum of biological activities. In the end, the substituents used could not compare to the biological activity of the inhibitor efavirenz (Sustiva^® [trademark]), and so it was decided to synthesize sultams with alkylethynyl substituents at the 3-position of the sultams in an attempt to mimic the activity of efavirenz.

Previous research analyzed the proposed novel sultams in the modeling …

Safety And Immunoreactivity Of A Xenogeneic Dna Plasmid Vaccine Expressing Human Tyrosinase In Tumor-Bearing Horses, Luis Miguel Lembcke Perez Prieto

Doctoral Dissertations

Melanomas are among the most common skin tumors in horses (second only to sarcoids), with prevalence rates reaching as high as 80% in adult gray horses. Despite the wide availability of measures of local control, there are currently no systemic therapies that can effectively prevent spread, or treat metastatic or locally advanced/non-resectable melanoma in horses. A form of gene immunotherapy based on a plasmid DNA construct containing a xenogeneic form of the antigen tyrosinase have been developed and optimized for targeting cancer in both humans and dogs; and have demonstrated significant immunoreactivity and clinical benefit in the treatment of melanocytic …

Functional Analysis Of Corazonin And Its Receptor In Drosophila Melanogaster, Kai Sha

Doctoral Dissertations

Corazonin (Crz) is an amidated undecapeptide originally isolated from the American cockroach. It has been shown to affect diverse physiological functions in a species-specific manner. However, the functionality of Crz in Drosophila melanogaster has not yet been determined. To gain insight into the role of Crz signaling in vivo, Crz and CrzR null alleles were obtained by transposable element mobilization. Flies carrying a deficiency uncovering Crz and pr-set7 loci were generated via P-element excision, and the latter was rescued by wild-type pr-set7 transgene. A mutation of Crz receptor (CrzR) was generated by Minos-element mobilization from …

Comparison Of Methodologies For Synthesis Of 3-(Cyclopropylethynyl)Benzisothiazole 1,1-Dioxide, Rachel Lee Naramore

Chancellor’s Honors Program Projects

No abstract provided.

Asymmetric Total Synthesis Of Congeners Of Hydramycin, An Anthraquinone-Type Antitumor Agent, Costyl Ngnouomeuchi Njiojob

Doctoral Dissertations

Hydramycin is an antitumor antibiotic isolated from Streptomyces violaceus. It is a pyranoanthraquinone-type antitumor agent that has shown broad-spectrum activity against a variety of human-derived cancer cell lines. Among tumors evaluated at the National Cancer Institute (lung, colon, melanoma, breast and prostate), GI₅₀s were <10⁻¹⁰ M in the NCI's 60-cell-line panel. We embarked on the synthesis and evaluation of a simplified congener 2-(1-hydroxy-1-(oxiran-2-yl)ethyl)-4H-naphtho[2,3-h]chromene-4,7,12-trione(17), which would facilitate synthesis while retaining the potent activity. Hydramycin has two chiral centers, and our goal is to design and synthesize all the possible enantiomers (four in …

Chemical Tools To Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes, Meng Meng Rowland

Doctoral Dissertations

Signaling lipids such as diacylglycerol (DAG) and the phosphatidylinositol polyphosphates (PIP_ns) play crucial roles in numerous cellular pathways. However, characterization of their activities is hindered by the complexity of associated signaling pathways and of the membrane environment. To address this issue, we have developed lipid probes that are effective for characterizing biological events using different applications, including activity-based probing (PIP_ns and DAG) and microarray analysis (PIP_ns). The activity-based probes have been applied to label receptor targets in multiple cancer cell proteomes through photocrosslinking followed by click reactions. The probes were found to label several …

Determination Of Important Ligand Sites For The Interaction With Aminoglycoside Acetyltransferase(3)-Iiib By Nmr, Katherine Jane Woodruff

Chancellor’s Honors Program Projects

No abstract provided.

“Effects Of N-3 And N-6 Polyunsaturated Fatty Acids On Human Promyelocytic Hl- 60 Cells, Robert Clements Gillis

Doctoral Dissertations

Enteral nutrition with eicosapentaenoic acid (EPA; 20:5 n-3) and γ-linolenic acid (GLA; 18:3 n-6) decreased pulmonary inflammation by reducing neutrophil counts and chemotactic factors in bronchoalveolar lavage fluid during acute respiratory distress syndrome (ARDS). We hypothesize that the antiinflammatory effects of EPA and GLA may be due, in part, to induction of neutrophil apoptosis. Neutrophil apoptosis is an important physiological process in the resolution of pulmonary inflammation. Furthermore, pro-inflammatory eicosanoids formed from arachidonic acid (AA) by lipoxygenase (LO) and cyclooxygenase (COX) pathways have been shown to inhibit apoptosis in certain cell types. The purpose of this dissertation is to determine …