Life Sciences Commons^™

Myokine Probdnf-P75ntr Signaling In Skeletal Muscle Injury And Sterile Inflammation, Katherine Aby

Dissertations and Theses

Originally discovered in the brain, brain-derived neurotrophic factor (BDNF) has been shown to be expressed and released from skeletal muscle as a myokine. However, the function of myokine BDNF is not fully understood. Of interest to this study is the function of the BDNF precursor proBDNF in skeletal muscle. We first show that skeletal muscle expresses unique BDNF splice variants compared to the brain, and at the protein level, skeletal muscle expresses significantly more proBDNF than mature BDNF under basal conditions. Consistent with this, expression of major protein convertases in skeletal muscle were significantly lower. The role of myokine proBDNF …

The Role Of Uchl1 In Skeletal Muscle Development And Regeneration, Ryan Antony

Dissertations and Theses

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally discovered in neurons. UCHL1 is also expressed in skeletal muscle, but its functions remain to be fully understood. Myogenesis is a critical process involved in embryonic development, growth, and regeneration following injury. Skeletal muscle injury is prevalent in trauma and surgical procedures, and skeletal muscle ischemia-reperfusion (IR) injury is a common yet dangerous public health problem. Here we reported that UCHL1 negatively affects muscle growth during aging as well as the regeneration process following IR injury. First, we observed that UCHL1 knockdown in C2C12 myoblasts resulted in increased …

Investigating The Roles Of Dapk, P53/Cep-1, And Mitochondrial Damage In Necrotic Neurodegeneration In C. Elegans, Anil Singh

Dissertations and Theses

Stroke is one of the leading causes of death in the U.S., with minority groups, suffering higher fatality rates. Stroke is caused by ischemia, where occlusion of blood supply to the brain results in neurodegeneration. Most of the damage is attributed to excitotoxicity, where an accumulation of the neurotransmitter glutamate in the synapse overstimulates postsynaptic neurons and ultimately leads to cell death (largely by necrosis). Stroke treatments are often ineffective, due to the delay between the onset of stroke and the delivery of effective treatment. To address this, we focus our study on putative later-acting mediators of excitotoxicity such as …

Of Transcription Factor And Transformation: Elucidating Gene Function In The Common Ice Plant, Mesembryanthemum Crystallinum, Chinenye Lilian Izuegbunam

Dissertations and Theses

Abiotic stresses negatively affect plant growth and development across the globe, which also affect the production of food, feed, biofuel, and fiber to meet the demands of a growing population. Thus, developing novel strategies to increase abiotic stress tolerance in crops is necessary. One of these strategies is exploring transcription factors (TFs) in Crassulacean Acid Metabolism (CAM) plants to improve plant abiotic stress tolerances. Therefore, the first objective of this dissertation determine the abiotic stress tolerance function of a CAM TF, McHB7opt in Arabidopsis. This study found that McHB7opt increased stress-responsive pathways related to seed germination and early seedling development. …

Molecular Investigation Of Minor Genomic Populations And Biological Exposures In Human Health, Brandon Ned Johnson

Dissertations and Theses

The study of genetics has contributed to countless discoveries related to human health and disease. However, the complexities of human biology reside not only in the genome but also in the contributions from environmental exposures, as measured via the classical twin design. To understand the influence of biological exposures, I implemented study designs to explore both the health associations and propagation of foreign genetic material. Microchimerism has been studied for association with several clinical conditions, and I further investigated if male microchimerism could elucidate the etiology of Mayer-Rokitansky-Küster-Hauser syndrome. Prevalence of male microchimerism in women with no history of pregnancy …

Unraveling The Regulatory Basis Of The Desiccation Tolerance Trait In Selaginella Lepidophylla, Madhavi Anuradha Ariyarathne Hewa Babarandhage

Dissertations and Theses

Desiccation tolerance was a crucial adaptation for plants during their transition to terrestrial environments. Some spike mosses, including S. lepidophylla, have evolved the remarkable ability to tolerate extreme desiccation, enabling survival in arid regions of the world. However, the regulatory basis of this trait remains unknown. This dissertation aims to unravel the genetic basis of desiccation tolerance in Selaginella lepidophylla and its potential for improving crop abiotic stress tolerance. To achieve this goal, three objectives were pursued. Objective 1 focused on determining the regulatory role of the SlbHLH transcription factor (TF) by overexpressing it in Arabidopsis thaliana to assess its …

A Tale Of Two-Hybrids: Investigating The Interactomes Of Cullin-Associated Proteins, Elyse Reitter

Dissertations and Theses

Cul3 is the major component of an E3 ligase in human cells. Cul3 was initially identified in the Singer lab as a protein that binds and degrades cyclin E, and subsequent studies have shown it to be part of a complex that is involved in a multitude of biological functions. The nature of this complex, its constituents, its regulation, and its dynamics is just beginning to be understood. The research presented here utilizes a series of two hybrid screens to identify families of interactomes with Cul3 at the center. This information will complement other work in the lab in which …

Investigation Of Nuclear Envelope-Associated Progeria Proteins During Nuclear Envelope Rupture, Rhiannon Marie Sears

Dissertations and Theses

The nuclear envelope (NE) is a specialized extension of the endoplasmic reticulum critical for the proper protection and organization of the genome. This interphase-only structure is host to several proteins and their interacting constituents that have various and diverse cellular roles. Mutations in NE constituents are associated with several human diseases. A subset of these diseases, known as progeria syndromes, are characterized by the premature presentation of physiological aging in a variety of tissues. Mutations in the genes LMNA and BANF1, which encode the A-type lamins and barrier-to-autointegration factor (BAF), can lead to these multisystem progeroid diseases. Though the underlying …

Molecular Mechanisms Underlying The Suppression Of Cardiomyocyte Necroptosis By The Cop9 Signalosome In Mice, Megan T. Lewno

Dissertations and Theses

Background: Within a large subset of heart failure, cardiac ubiquitin-proteasome system (UPS) inadequacy is causative. A vital UPS regulator is the COP9 signalosome (CSN). The CSN holocomplex is formed by 8 unique protein subunits (COPS1~COPS8) and regulates Cullin-RING ligases via Cullin deneddylation. Cardiomyocyte-restricted knockout (cko) of Cops8 causes massive cardiomyocyte necroptosis via the RIPK1-RIPK3-MLKL pathway, resulting in dilated cardiomyopathy (DCM) and shortened lifespan in mice. CSN’s deneddylase resides in COPS5 and Cops5-cko has not been explored. It is important to investigate how the necroptotic pathway within cardiomyocytes is activated in Cops8-cko mice as cardiomyocyte necroptosis has been shown to play …

Mechanisms Of Substrate Recognition By The Cul3-Based E3 Ligase, Katia Graziella De Oliveira Rebola

Dissertations and Theses

Cul3-based E3 ligase is responsible for regulating a variety of cellular pathways, many of which are known to have profound effects on the proper function of multicellular organisms. Although progress over the past years has been truly impressive, our understanding of the mechanisms of E2 recruitment and selection by the BCR complex and all the roles that Cul3 plays on kidneys remains in its infancy. To explore these aspects, this dissertation aims to analyze the Cul3 complex using two different approaches: (1) We used the powerful tool of chimeric analysis to map the essential domain binding characteristics of Cul3 taking …

Application Of Single Particle Electron Microscopy To Native Lens Gap Junctions And Intrinsically Disordered Signaling Complexes, Janette Bernadette Myers

Dissertations and Theses

Gap junctions are a class of membrane proteins that facilitate cell-to-cell communication by forming channels that directly couple the cytoplasm of neighboring cells. The channels are composed of monomers called connexins. Humans express 21 connexin isoforms in a cell-type specific fashion, and each isoform has distinct mechanisms of permeation and regulation. Co-assembly of multiple isoforms into a single intercellular channel can change channel properties, such as conductance and selectivity to substrates (e.g., ions, metabolites and signaling molecules). However, the mechanistic basis for this functional diversity has remained poorly understood. This lack of mechanistic insight has been due in large part …

Characterizing Chromosomal Aberrations In Cells Deficient For Both Atm And Msh2, Yeliz Inalman

Dissertations and Theses

Ataxia telangiectasia mutated (ATM) and mutS homologue 2 (MSH2) are important DNA repair proteins that participate in DNA repair pathways to maintain genomic integrity. Mice deficient for ATM and MSH2 mice are viable. However, ATM^-/- mice show growth retardation, neurological defects, and spontaneous lymphomagenesis. MSH2^-/- mice suffer from aggressive lymphoid tumors between two to five months of age and have increased microsatellite instability, which predisposes MSH2^-/- mice to carcinomas. However, mice deficient in both ATM and MSH2 are unable to survive beyond postnatal day 21 (P21). The observed lethality in ATM^-/-MSH2^-/- mice may result …

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Dissertations and Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …

Molecular Coevolution Of Pacific Northwest Hantaviruses And Their Host, The Deer Mouse, Peromyscus Maniculatus, Philip Darren Jones

Dissertations and Theses

Sin Nombre virus (SNV, family Bunyaviridae, genus Hantavirus), hosted by the deer mouse, Peromyscus maniculatus (family Cricetidae, Subfamily Neotominae), is the primary etiological agent of Hantavirus pulmonary syndrome (HPS) in the western United States. HPS, with known pathogenicity only to humans and for which there is no cure or prophylaxis, affects the epithelium of the lungs by making the capillaries leaky, thereby resulting in bilateral infiltrates, and eventually leading to respiratory failure and death by drowning in approximately 38% of hospitalized patients.

In the Americas, Peromyscus has been co-evolving with hantaviruses for approximately 12–20 million years, since the first …

Distribution Of R-Banded Chromosome Variants In A Bottlenose Dolphin (Tursiops Truncatus) Population, Kristine Anne Gunter

Dissertations and Theses

When combined with observational and behavioral data, chromosome variant analysis provides a means of assessing population structure in bottlenose dolphins, Tursiops truncatus. In this cytogenetic analysis of thirty-six bottlenose dolphins, a distribution of fluorescent R-band variants was catalogued and used as a way to characterize the genetic structure of a Tursiops population inhabiting the Matagorda Bay, Texas, area. Three different population genetic analytical techniques were evaluated for their usefulness in analyzing cytogenetic data. The chromosome variant data obtained from this study was then compared with cytogenetic data gathered from a resident dolphin population residing near Sarasota, Florida.

The purpose …

Purification And Characterization Of Dihydroorotase From Clostridium Oroticum, A Zinc-Containing Metalloenzyme, William Edward Balch

Dissertations and Theses

Dihydroorotase (4,5-L-dihydro-orotate amidohydrolase, EC 3.5.2.3) which catalyzes the reversible cyclization of N-carbamyl-1-aspartate toL-dihydro-orotate has been purified from orotate-grown Clostridium oroticum by a combination of streptomycin sulfate fractionation, DEAE-Sephadex chromatography, and hydroxylapatite chromatograpy. The enzyme has been shown to be omogeneous when subjected to polyacrylamide gel electrophoresis. Thin-layer gel chromatography with Sephadex G-200 indicated the enzyme to have a molecular weight of 110,000 ± 10,000. Sodium dodecyl sulfate gel electrophoresis using two different buffer systems indicate the enzyme to be composed of two identical subunits with a molecular weight of 56,000 ± 5300. Dihydroorotase has been shown to be a zinc-containing …