Biochemistry, Biophysics, and Structural Biology Commons^™

An Investigation Into The Mechanism Of Proteasome Dysfunction In Neurodegenerative Disease And The Biological Impact Of Proteasome Hyperactivation In C. Elegans, Raymond T. Anderson

Graduate Theses, Dissertations, and Problem Reports

Aging is an inevitable process that occurs as humans grow older. It is characterized by the chronological accumulation of cellular damage over time leading to functional decline as an organism grows older. Several processes are thought to contribute to the aging phenomenon, but one of the most prolific of these is the disruption of protein homeostasis (proteostasis). The collapse of proteostasis can lead to accelerated aging and the development of age-related diseases including devastating neurodegenerative diseases (NDs) like Alzheimer and Parkinson disease. Virtually all NDs are characterized by the buildup of proteins in and around neurons resulting in neuronal death …

The Musashi Rna Binding Proteins Are Regulators Of Alternative Splicing And Protein Expression In Photoreceptor Cells, Fatimah Kh. Matalkah

Graduate Theses, Dissertations, and Problem Reports

The Musashi (Msi) family of RNA binding proteins consists of two paralogs, Msi1 and Msi2, that are highly conserved across species. The two paralogs have emerged as factors that promote stem cell proliferation by post-transcriptionally regulating translation. In addition to their expression in stem cells, the Musashi proteins are also expressed in postmitotic neurons, including the photoreceptor cells. The Musashi proteins have been observed to maintain high expression levels in the postmitotic photoreceptors within the eye of both invertebrates and vertebrates. These observations suggest an additional role in the maintenance of terminally differentiated neurons.

Building upon these observations, we investigated …

Elucidating The Proteasomal Regulatory Mechanism Of Proteasome Activator Pa28Γ /Regγ, Taylor Ann Thomas

Graduate Theses, Dissertations, and Problem Reports

Virtually all cellular processes are precisely regulated by the proteasome which is the primary enzyme responsible for the degradation of misfolded, damaged, or no longer necessary soluble proteins. To prevent any untimely degradation of these target protein substrates and protect the cell, the proteasome is tightly regulated via adaptor proteins, known as proteasomal regulators. There are many classes of proteasomal regulators each with their own unique structures, functions, and effects on protein degradation through the proteasome. One such class is the 11S family of proteasomal regulators which are also referred to as PA26/28, or REG. The 11S family are ATP-independent …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …

Transitions Between The Steps Of Group Iic Intron Forward And Reverse Splicing And Integration Into Dna, Claire Mae Smathers

Graduate Theses, Dissertations, and Problem Reports

Group II introns are ancient ribozymes capable of self-excision and mobility into new genomic locations. As the ancestors of both the eukaryotic spliceosome and eukaryotic retroelements, these simple RNA machines serve as excellent models for understanding the mechanisms of both gene splicing and retroelement activity in eukaryotes. Although group II introns have been studied for decades, knowledge of the most unique and arguably evolutionarily relevant class of group II introns, IIC, is limited. Our knowledge is especially limited in terms of understanding how IIC introns mediate the transition between the two transesterification steps of forward splicing and reverse splicing into …

Getting To The Root Cause: The Genetic Underpinnings Of Root System Architecture And Rhizodeposition In Sorghum, Farren Smith

Graduate Theses, Dissertations, and Problem Reports

Plants are some of the most diverse organisms on earth, consisting of more than 350,000 different species. To understand the underlying processes that contributed to plant diversification, it is fundamental to identify the genetic and genomic components that facilitated various adaptations over evolutionary history. Most studies to date have focused on the underlying controls of above-ground traits such as grain and vegetation; however, little is known about the “hidden half” of plants. Root systems comprise half of the total plant structure and provide vital functions such as anchorage, resource acquisition, and storage of energy reserves. The execution of these key …

Amelioration Of Mitochondrial Bioenergetic Dysfunction In Diabetes Mellitus: Delving Into Specialized And Non-Specific Therapeutics For The Ailing Heart, Andrya Jean Durr

Graduate Theses, Dissertations, and Problem Reports

Morbidity and mortality of the diabetic population is influenced by many confounding factors, but cardiovascular disease (CVD), remains the leading cause of death. Mitochondrial dysfunction is central in the development of cardiac contractile dysfunction, with decreased mitochondrial bioenergetic function, increased dependence on free fatty acid utilization, and a decrease in glucose utilization having been shown to contribute to contractile dysfunction. Strategies targeting the amelioration of mitochondrial bioenergetic function are attractive for limiting diabetes-induced heart failure, and preserving health-span. The goals of this dissertation were to assess two mitochondrial-centric approaches for the amelioration of mitochondrial and cardiac contractile dysfunction in diabetes …