Biochemistry Commons^™

The Impact Of Plant Secondary Metabolites On Auxin And Cytokinin Signaling, Timothy E. Shull

Theses and Dissertations--Plant and Soil Sciences

Secondary metabolites are a broad class of specialized compounds that mediate plant-environment interactions and mitigate stress. It is increasingly clear that many phenylalanine-derived secondary metabolites are nearly indispensable for plant survival and that plants adjust their growth according to their secondary metabolic outputs. Consequently, many phenylalanine-derived secondary metabolites have influence over hormone activity. For instance, multiple phenylpropanoid intermediates and catecholamines alter the sensitivity of plants to the central hormone auxin, which in concert with cytokinin directs most aspects of plant growth and development. This dissertation reviews previous research on the influence of phenylpropanoid intermediates and catecholamines on plants, with a …

Structural Basis Of Bacterial Flagellin For Naip5 Binding And Nlrc4 Inflammasome Activation And The Mechanism Of Flagellin Induced Release Of Cytokines In Vivo, Jian Cui

Theses and Dissertations--Chemistry

The bacterial flagellum is a whip-like structure that protrudes from the cell membrane and is one of the most complex and dynamic biological molecular machines that propels bacteria to swim toward beneficial environments and the sites of infection. It is composed of a basal body, a hook, and a long filament. The flagellar filament contains thousands of copies of the protein flagellin (FliC) monomer arranged helically and ending with a filament cap composed of oligomer protein FliD. The overall structure of the filament core is preserved across bacterial species, while the outer domains exhibit high variability, and in some cases …

A Multidisciplinary Characterization Of The Enzymology And Biology Of Reversible Glucan Phosphorylation In Toxoplasma Gondii , Robert Murphy

Theses and Dissertations--Molecular and Cellular Biochemistry

Toxoplasma gondii is an opportunistic, protozoan parasite of all warm-blooded animals, infecting roughly one-third of humans worldwide. Humans acquire infections by consuming T. gondii tissue cysts in undercooked meat or from oocysts shed in cat feces. Encysted parasites convert into rapidly growing tachyzoites that disseminate throughout the body, defining the acute phase of infection. Under host immune pressure, tachyzoites convert into bradyzoites that populate tissue cysts found in CNS or muscle tissue and persist for the lifetime of the host, defining the chronic phase of infection. Tissue cysts are responsible for transmission via carnivory, but also possess the ability to …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Peripheral And Central Glucose Flux In Type I Diabetes, Jelena Anna Juras

Theses and Dissertations--Neuroscience

Diabetes is a complex metabolic disorder, of which high blood glucose concentration is the primary hallmark. Type I diabetes mellitus (T1DM) is characterized by the lack of insulin production, due to a poorly understood autoinflammatory cascade. In the words of historian Barnett “Diabetes may no longer be a death sentence, but for more and more people in the 21st century, it will become a life sentence”, making it the focal point of many research groups. It is estimated that around 20 million individuals worldwide live with T1DM.

Effects of long-term chronically elevated blood glucose are not only seen in micro/macro-vascular …

Apoe Genotype And Cerebral Glucose Metabolism: A Multi-Omics Approach, Holden C. Williams

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is encoded by the APOE gene, present in humans as three main isoforms (E2, E3, and E4). E4 carriers face up to a 15-fold increased risk for developing late-onset Alzheimer’s disease (AD), while E2 carriers are protected. Understanding the risk conferred by E4 has been an extensive research focus for nearly three decades, but the exact mechanism has yet to be proven. Many studies have demonstrated attenuated roles of E4 in classical hallmarks of AD, notably amyloid processing and neurofibrillary formation, which normally present later in disease progression. How APOE influences hallmarks that present much earlier are …

Synthesis Of 6,6- And 7,7-Difluoro-1-Acetamidopyrrolizidines And Their Oxidation Catalyzed By The Nonheme Fe Oxygenase Lolo, Nabin Panth

Theses and Dissertations--Chemistry

One of the remarkable steps in loline alkaloid biosynthesis is the installation of an ether bridge between two unactivated C atoms in 1-exo-acetamidopyrrolizidine (AcAP). LolO, a 2-oxoglutarate-dependent nonheme Fe oxygenase, catalyzes both the hydroxylation of AcAP and the resulting alcohol's cycloetherification to give N-acetylnornoline (NANL). The mechanism of hydroxylation is well understood, but the mechanism of the oxacyclization is not. I synthesized difluorinated analogs of AcAP in an attempt to further understand the mechanism of the unusual cycloetherification step.

I prepared 6,6-F₂-AcAP in eight steps from N,O-protected 4-oxoproline. The key step was a Dieckmann …

Antibiotic Permeation In Gram-Negative Bacteria And Contribution Of Inflammasome Activation And Pyroptosis In Pathogenesis Of Salmonella Systemic Infection, Ankit Pandeya

Theses and Dissertations--Chemistry

Antibiotic resistance is one of the major global issues in the field of public health and medicine. Good antibiotic candidates need to be selectively toxic, inhibit cellular target, and effectively penetrate and accumulate in bacterial cells. The last factor is a formidable barrier in the development of antimicrobials effective in Gram-negative bacteria, due to the presence of two layers of cell envelope. The first half of my thesis focuses on understanding the permeation of small molecules through this formidable cell envelope, distribution inside the cell of Gram-negative bacteria, and design of novel methods to make small molecules effectively cross the …

The Role Of Charge On Dna Packaging And Integrity Within Reconstituted Peptide-Dna Assemblies, Ehigbai Oikeh

Theses and Dissertations--Chemistry

In nature, DNA exists primarily in a highly compacted form. The compaction of DNA in vivo is mediated by cationic proteins; histone in somatic nuclei and arginine-rich peptides called protamines in sperm chromatin. The packaging in the sperm nucleus is significantly higher than somatic nuclei resulting in a final volume roughly 1/20^th that of a somatic nucleus. This tight packaging results in a near crystalline packaging of the DNA helices. While the dense packaging of DNA in sperm nuclei is considered essential for both efficient genetic delivery as well as DNA protection against damage by mutagens and oxidative species, …

Development Of Fluorescence Based Approaches To Understand Astrocyte Biology In The Context Of Nicotine And Nicotinic Receptor Activity, Surya P. Aryal

Theses and Dissertations--Chemistry

Smoking and tobacco use (STU) is a major global health problem and worldwide more than six million people die due to tobacco related diseases each year. Although majority of smokers try to quit smoking several times in their life, traditional therapeutic approaches, which focus only on neuronal cells, have a very low success rate. Understanding the effect of nicotine on glial cells, synaptic communication and blood vasculature in the brain can provide further insights on the neurobiology of substance abuse and can potentially help to design better therapeutic approaches. Glial cells are non-excitable cells in the brain which do not …