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Targeting The Dimerization Of Erbb Receptor Tyrosine Kinases, Rob Yang

All Theses and Dissertations (ETDs)

The epidermal growth factor receptor: EGFR) is a membrane receptor tyrosine kinase whose over-activation has been implicated to cause many human cancers. Novel strategies to inhibit the activation of EGF receptors other than the conventional antibody-based and tyrosine kinase inhibitors are virtually non-existent but could provide benefits both in the laboratory and clinical settings. In an effort to expand the current approaches, this thesis focused on targeting the homodimerization of the EGF receptors themselves and the heterodimerization of EGF receptors with the related ErbB2 receptor. Three sub-projects were completed in the process. The first project explored the feasibility of inhibiting …

Development Of Shell-Crosslinked Knedel-Like Nanoparticles As Intracellular Delivery Vehicles And Gene Regulation Agents, Ke Zhang

All Theses and Dissertations (ETDs)

This dissertation focuses on the development of polymer-based nanomaterials, termed shell-crosslinked knedel-like: SCK) nanoparticles, as vehicles to carry specific guest molecules or guest structures into the cell. Detailed synthetic procedures for and characterization of well-defined block copolymers, as well as the nanostructures resulted from their self-assembly are reported. The nanoparticles exhibited different but controlled sizes and shapes, depending on the conditions for their preparation. To incorporate functionality into these materials, both pre- and post-particle functionalization methods, as well as their combination, were used. The nanostructures involved in this dissertation include protein transduction domain: PTD)-functionalized SCK, folate-functionalized SCK and cationic SCK: …

Investigations Into Building Block Structure And Method Of Preparation On The Properties Of Nanomaterials, Zicheng Li

All Theses and Dissertations (ETDs)

This dissertation research is primarily focused on the preparation of polymer-based nanostructures as potential diagnostic agents and therapeutics delivery vehicles. Various polymers, nanoparticles and conjugation techniques were developed to meet the specific requirements of each application. Shell crosslinked nanoparticles: SCKs) are characterized by their structural integrity and available functionality to attach multiple agents on the shell, such as receptor-recognizing or receptor-specific ligands, .imaging agents, Cell transduction components, etc. In this work, SCKs derived from amphiphilic poly(acrylic acid)-block-polystyrene: PAA-b-PS) have been studied as potential diagnostic and therapeutic agent delivery vehicles: Chapters 2 and 4). SCK nanoparticles bearing a cyclic KCRGDC peptide …

In Vivo Function Of Otopetrin 1 In The Vestibular Sensory Epithelium, Euysoo Kim

All Theses and Dissertations (ETDs)

Otopetrin family genes encode multi-transmembrane domain proteins with three highly conserved domains. In mice, three Otopetrin paralogues are found. One of its members, Otopetrin 1: Otop1) has been previously shown to be essential for the formation of otoconia in the vestibular system of the inner ear. Otoconia are calcium carbonate biominerals that are required for normal balance and the sensation of linear acceleration with respect to gravity. The mechanism by which OTOP1 mediates otoconia biosynthesis is not known, but the ability of OTOP1 to modulate [Ca2+]i in response to purinergic signals in heterologous systems suggest that OTOP1 may be involved …

Runx1 In Primitive Hematopoiesis And Characterization Of Hematopoietic Stem Cells In A Mouse Chronic Inflammatory Arthritis Model, Yunglin Ma

All Theses and Dissertations (ETDs)

Hematopoietic cells are essential for growth and survival throughout adult life. Two different aspects of hematopoiesis are addressed in this dissertation. I. The regulation of primitive hematopoiesis by Runx1 and TGF-beta signaling. Primitive hematopoiesis, occurring exclusively in the yolk sac, is characterized by its transient nature. As the primitive hematopoiesis declines in the yolk sac, definitive hematopoietic progenitors generated in the yolk sac and/or embryo take over in blood cell production. Whether the transition from primitive to definitive hematopoietic program reflects a mere shift in hematopoietic sites or whether it is an actively regulated process is currently unknown. Runx1 is …

Regulation Of Bax/Bak-Dependent Cell Death Program, Hyungjin Kim

All Theses and Dissertations (ETDs)

Mammals have evolved an intricate regulation of a genetically programmed apoptotic cell death that involves mitochondria. Diverse apoptotic signals converge on mitochondria, which causes the release of cytochrome c into the cytosol to activate Apaf-1. This initiates caspase activation, which results in irreversible cellular demise. The BCL-2 family proteins constitute a critical checkpoint in mitochondrion-dependent apoptosis. Multidomain proapoptotic BAX/BAK promotes mitochondrial outer membrane permeabilization, whereas anti-apoptotic BCL-2/BCL-X_L/MCL-1 protects mitochondrial integrity and prevents cytochrome c release. The proapoptotic activity of BAX/BAK is triggered by BH3-only molecules: BH3s) which are upregulated by upstream death signals. However, how these subfamilies interact …

Evolution Of Endosperm Starch Synthesis Pathway Genes In The Context Of Rice: Oryza Sativa) Domestication, Guoqin Yu

All Theses and Dissertations (ETDs)

The evolution of metabolic pathways is a fundamental but poorly understood aspect of evolutionary change. The rice endosperm starch biosynthetic pathway is one of the most thoroughly characterized biosynthesis pathways in plants, and starch is a trait that has evolved in response to strong selection during rice domestication and subsequent crop improvement. In this study, I have examined six key genes in the rice endosperm starch biosynthesis pathway to investigate the evolution of this pathway before rice domestication and during rice domestication. Oryza rufipogon is the wild ancestor of cultivated rice: Oryza sativa). Oryza sativa has five variety groups: aus, …

The Evolution And Regulation Of Dna-Binding By The Nickel-Dependent Transcription Factor Nikr, Erin Benanti

All Theses and Dissertations (ETDs)

Transition metal homeostasis is critical for all cells to balance cellular metal requirements with metal availability. One common homeostatic mechanism in bacteria is metal-dependent transcriptional regulation. The Ni2+-dependent transcription factor NikR is a member of the ribbon-helix-helix: RHH) family of DNA-binding proteins and is widespread among bacteria and archea with vastly different nickel physiologies. The goal of this thesis was to better understand basic aspects of cellular transition metal homeostasis by examining the activity and regulatory properties of NikR family members from different bacterial species. One organism that exhibits a prominent and well-defined nickel physiology is Helicobacter pylori, making it …

Quality Of Life And Affect Across The Adult Lifespan, Patrick Brown

All Theses and Dissertations (ETDs)

The premise of this dissertation is based on the work of M. Powell Lawton, in particular his theories of Environmental Press: Lawton and Nahemow, 1973) and the Dual-Channel Hypothesis: Lawton, 1996; Lawton, Winter, Kleban, & Ruckdeschel, 1999). Study 1 used a correlational approach to test Lawton and colleagues: 1999) model in a community sample of people across the adult lifespan, thereby expanding previous findings to individuals under age 60. Study 2 used an experimental approach to determine if individuals are affectively susceptible to differing environmental conditions based on their performance on a cognitive task. Whereas Study 1 provided a naturalistic …

Mammalian Postcranial Evolution And Primate Extinction In The Middle Eocene Of North America, Rachel Dunn

All Theses and Dissertations (ETDs)

Primates constituted a dominant part of the mammalian faunas of North America during the early and middle parts of the Eocene: 55-46 ma). Beginning in the Uintan North American Land Mammal Age: 46-42 ma) primates declined in diversity and abundance in the Rocky Mountain region. This decline has been linked to the recession of tropical rain forests out of northern latitudes at that time. Climatic change of this magnitude would presumably have an impact on the contemporary mammalian faunas, with reduction or extinction of forest groups like primates, but perhaps radiation of mammals that preferred more open habitats such as …

Mechanisms Of Feedback In The Visual System, Adam Eggebrecht

All Theses and Dissertations (ETDs)

Feedback is an ubiquitous feature of neural systems though there is little consensus on the roles of mechanisms involved with feedback. We set up an in vivo preparation to study and characterize an accessible and isolated feedback loop within the visual system of the leopard frog, Rana pipiens. We recorded extracellularly within the nucleus isthmi, a nucleus providing direct topographic feedback to the optic tectum, a nucleus that receives the vast majority of retinal output. The optic tectum and nucleus isthmi of the amphibian are homologous structures to the superior colliculus and parabigeminal nucleus in mammals, respectively. We formulated a …

A Phenotypic And Genetic Characterization Of The Cell Adhesion Molecules Echinoid And Friend-Of-Echinoid In The Directed Cell Movements Of Ommatidial Rotation During Drosophila Eye Development., Jennifer Fetting

All Theses and Dissertations (ETDs)

Correct development of multicellular organisms relies on the precise patterning of cells, which must respond to and interpret specific cues that instruct the cells to differentiate and often undergo directed cell movements and rearrangements to give rise to functional tissues and organs. Differential adhesion between the stationary and mobile cells permits and promotes these cellular movements, effecting patterning of cells and tissues. During Drosophila eye development, groups of cells, the ommatidial precursors, undergo a 90° rotational movement within a matrix of stationary cells, providing the cell motility readout of tissue polarity. The mechanisms that regulate ommatidial rotation are not well …

A Quest For Meaning In Spontaneous Brain Activity - From Fmri To Electrophysiology To Complexity Science, Biyu He

All Theses and Dissertations (ETDs)

The brain is not a silent, complex input/output system waiting to be driven by external stimuli; instead, it is a closed, self-referential system operating on its own with sensory information modulating rather than determining its activity. Ongoing spontaneous brain activity costs the majority of the brain's energy budget, maintains the brain's functional architecture, and makes predictions about the environment and the future. I have completed three separate studies on the functional significance and the organization of spontaneous brain activity. The first study showed that strokes disrupt large-scale network coherence in the spontaneous functional magnetic resonance imaging: fMRI) signals, and that …

Discovery Of A Novel Metalloregular Family: Structure/Function Studies Of E. Coli Rcnr, Jeffrey Iwig

All Theses and Dissertations (ETDs)

The first row transition metal ions- Mn, Fe, Co, Ni, Cu and Zn are vital cofactors for proteins involved in diverse processes including photosynthesis, oxidative respiration and protein translation. Despite these essential functions, excess metal ions can lead to cell death through the generation of oxidative damage or the occupation of non-native metal sites. Acquiring metal ions from the environment while limiting possible toxic effects requires the coordinated regulation of metal uptake, trafficking and efflux, which in bacteria is often carried out by metal-responsive transcription factors: metalloregulators). Nickel homeostasis in E. coli is an ideal model system for understanding the …

Medial Temporal Lobe Structure And Function, Meghana Karnik

All Theses and Dissertations (ETDs)

Medial Temporal Lobe Structure and Function by Meghana Sunil Karnik Doctor of Philosophy in Biology and Biomedical Sciences: Neuroscience) Washington University in St. Louis, 2009 Professor John G. Csernansky, Chairperson My main goal was to examine the relationship between brain structure and function, specifically medial temporal lobe structure and episodic memory, in various groups of subjects who had schizophrenia, were at risk for schizophrenia because of genetic and disease influences, or who were healthy, in order to explore the influence of genetic and disease influences on brain structure-function relationships. Most of what is known about the neural structures thought to …

Discounting Of Delayed And Probabilistic Rewards By Women With And Without Binge Eating Disorder, Jamie Manwaring

All Theses and Dissertations (ETDs)

Obese individuals with binge eating disorder: BED) exhibit more general and eating-disordered psychopathology than obese individuals without BED. Binge eating also impedes weight-loss efforts, already difficult in an obese population. A better basic understanding of binge eating and obesity is needed to refine treatments for both conditions. Discounting, an experimental paradigm that examines changes in the value of delayed or uncertain outcomes, may provide an objective assessment of impulsive behavior. Impulsivity may perpetuate binge eating, but discounting tasks have never been evaluated with eating disordered individuals. A discounting procedure could help differentiate individuals with eating/weight problems from controls in terms …

Analysis Of The Arabidopsis Polyadenylation Factors Pap1, Cstf64 And Cstf77 And Their Characteristic Inter-Relationship, Amrita Bandyopadhyay

University of Kentucky Master's Theses

3’-end modification by polyadenylation is a ubiquitous feature of almost all eukaryotic mRNA species and is catalyzed by a consortium of enzymes, the polyadenylation factors. Poly(A) polymerase (PAP), the enzyme catalyzing the addition of adenosine residues during the polyadenylation stage, exists in four isoforms within Arabidopsis. In silico and yeast two-hybrid studies showed that PAP1 has unique expression and interaction pattern in Arabidopsis, suggesting non-canonical functions of PAP1. Its exclusive interaction with PAP4 has not been reported in other living systems until now and hints at a difference in polyadenylation in plants with respect to mammals and yeast. …

Remediating Impacts Of Global Climate Change-Induced Submergence On Salt Marsh Ecosystem Functions, Camille Lafosse Stagg

LSU Doctoral Dissertations

Impacts of global climate change, such as sea level rise and severe drought, have altered the hydrology of coastal salt marshes resulting in submergence and subsequent degradation of ecosystem function. A potential method of rehabilitating these systems is the addition of sediment-slurries to increase the elevation of the marsh surface, thus ameliorating the effects of excessive inundation. Although this technique is growing in popularity, the successful restoration of ecological function after sediment addition has received little attention. The purpose of this research was to determine if sediment subsidized salt marshes are functionally equivalent to natural marshes and whether salt marshes …

Bacterial Characterization Of Louisiana Groundwater Contaminated By Dnapl-Containing Chloroethanes And Other Solvents, Kimberly Bowman

LSU Doctoral Dissertations

In support of an effort to determine the feasibility of using an in-situ bioremediation strategy for cleanup of groundwater in an area containing chlorinated solvents present as a dense non-aqueous phase liquid (DNAPL), the bacterial population in the groundwater at a Superfund site located near Baton Rouge, Louisiana was characterized. More than 3¡Á107 cells/mL in the groundwater were observed via microscopy. Universal bacterial and ¡°Dehalococcoides¡±-specific 16S rRNA gene libraries were constructed and analyzed. Universal clones grouped into 18 operational taxonomic units (OTUs), as defined by sequence similarity ¡Ý97.0%, which included several as yet undescribed organisms. Multiple unique sequences closely related …

Synthesis And Characterization Of Transition Metal And Metal Oxide Nanoparticles Using Dendritic Complexes, Elisabeta Mitran

LSU Doctoral Dissertations

The research in this dissertation focuses on the synthesis and characterization of metal/metal oxide nanoparticles in solution and on surfaces with a high degree of control over size and size dispersity; such well-defined nanoparticles were made using metal ion-dendrimer complexes and silica-supported organometallic dendrimers. The metal oxide-based materials can be used as laboratory surrogates for combustion-generated nanoparticles to assess their role in mediating pollutant formation. Nickel nanoparticles with low size dispersity were prepared by a dendrimer-ligand-based method employing five generations amine-terminated poly(propylene imine) dendrimer, DAB-Amn. After coordination, borohydride reduction of Ni(II) ion-dendrimer complexes yielded Ni(0) nanoparticles, as determined by X-ray …

Ananda Devi's Narrative Strategies And Subversions., Ritu Tyagi

LSU Doctoral Dissertations

This dissertation proposes a feminist narratological study of texts by Ananda Devi, a contemporary Francophone writer from Mauritius. I examine three principle narrative strategies that allow Devi to challenge the dominant androcentric discourses. These discourses ignore the feminine world of domesticity and impose images of submission on women, thereby curbing feminine expression and quest. Inspired by the efforts of critics such as Alison Case, Robyn Warhol, Susan Lanser to study narrative structures in the context of cultural constructions of gender, I argue that Devi employs narrative strategies that allow her marginalized narrators to intervene in dominant structures of narrative construction …

Expression Of The Edwardsiella Ictaluri Type Iii Secretion System And Its Relationship To The Native Plasmids, Matthew Lee Rogge

LSU Doctoral Dissertations

Edwardsiella ictaluri encodes a type III secretion system (T3SS) required for intracellular replication. Analysis of in vitro gene expression indicates the T3SS translocon proteins express and secrete in acidic pH. Expression of other T3SS genes, however, requires that phosphate be limited in the culture media, in addition to acidic pH. Responses to environmental stimuli are mediated through the T3SS-encoded regulatory proteins EsrA, EsrB, and EsrC. Mutations in these genes result in differing phenotypes. Mutation of EsrA results in moderately reduced expression of T3SS genes, but translocon protein secretion is retained in the mutant. However, the EsrA mutant is attenuated intracellularly …

Nanoidentation Behavior Of Clay Minerals And Clay-Based Nonstructured Multilayers, Zhongxin Wei

LSU Doctoral Dissertations

Clay minerals, ubiquitous in the geosphere, are hydrous layered silicates or phyllosilicates that are made of nanometer-thick 2:1 or 1:1 layers. Understanding their mechanical properties of clay minerals is of vital importance to a variety of disciplines, such as geomechanics, geophysics, mineral physics, and nanocomposites. Owing to their complex crystal structure and size, however, accurate determination of their mechanical properties is a significant challenge. This dissertation presents the first research effort to study systematically the fundamental mechanical properties along the c-axis (e.g., elastic modulus, hardness) of a wide range of phyllosilicates with varying crystal structure and chemical compositions. To explore …

Cbod₅ Treatment And Nitrogen Transformations Of The Marshland Upwelling System In Intermediate And Saltwater Marshes, Lorna Anne Putnam

LSU Doctoral Dissertations

The marshland upwelling system (MUS) was designed to treat domestic wastewater from coastal dwellings where conventional methods are inadequate due to high water tables, poor hydraulic soil conditions, anaerobic soils, and saline groundwater. Currently there is no adequate treatment system available and coastal dwellings are contributing to water quality problems. This study focused on determining the treatment effectiveness of the MUS for organic matter and understanding the specific processes involved in nitrogen treatment.

The treatment of organic matter, measured as five-day carbonaceous biological oxygen demand (CBOD₅), was effective in field tests for both saltwater and intermediate marshes. Global …

Characterization Of The 'Glutamate Effect' On The Solution Thermodynamics And Function Of The Large Fragments Of The Type I Dna Polymerases From E.Coli And T.Aquaticus, Daniel J. Deredge

LSU Doctoral Dissertations

In this study, it is shown that the large fragments of the type I DNA polymerase from E.coli (Klenow) and T.aquaticus (Klentaq) display enhanced DNA binding affinity in glutamate vs. chloride. Across the relatively narrow salt concentration ranges often used to obtain salt linkage data, Klenow also displays an apparently decreased linked ion released (¦¤n_ions) in Kglutamate vs. KCl while Klentaq does not display such an effect. The osmotic stress technique reveals that Klenow and Klentaq DNA binding is associated with the release of ~500 to 600 waters in KCl. For both proteins, replacing chloride with glutamate results …

Distribution, Diversity And Ecology Of Aerobic Carbon Monoxide-Oxidizing Bacteria In Hawaiian Volcanic Deposits, Carolyn Frances Weber

LSU Doctoral Dissertations

Carbon monoxide-oxidizing bacteria are among the first colonists of recently formed volcanic deposits despite environmental conditions that challenge their survival, such as oscillating water regimes and lack of endogenous sources of organic carbon and nitrogen. Activity assessments and molecular surveys of the coxL gene (large subunit carbon monoxide dehydrogenase) across a vegetation gradient on a 1959 volcanic deposit on Kilauea Volcano (Hawai’i) indicated that CO-oxidizing communities continue to expand, diversify and remain competitive during ecosystem development. Distinct compositional shifts occurred across the gradient with Firmicutes-like coxL sequences dominating clone libraries from unvegetated sites (Bare) and Proteobacteria coxL sequences dominating libraries …

Bullying In Public Schools In Missouri, David A. Copeland

Doctoral Dissertations and Projects

The research conducted sought to find evidence and data to support or lack of support to the following questions: Do school administrators perceive a problem with bullying in their schools in Missouri? Is there a relationship between the victim of bullying and the learning process? Do female adolescents engage in cyber bullying more than male adolescents? Do public schools in Missouri have policies in place that address bullying? The researcher used the Olweus Bullying Prevention Program survey on bullying. The study examined the perceptions and beliefs of the superintendents in the State of Missouri concerning bullying and student responses from …

Dna Topoisomerases I From Pseudomonas Aeruginosa And Vaccinia Virus And Their Use As Drug Targets, Teesta Jain

LSU Doctoral Dissertations

Pseudomonas aeruginosa encodes a putative topoisomerase with sequence similarity to the type IB topoisomerase enzyme from vaccinia virus. Residues in the active site are conserved, notably Tyr292 which would be predicted to form the transient covalent bond to DNA. The gene encoding the P. aeruginosa topoisomerase I (PAT) was cloned and expressed in E. coli. The enzyme relaxes supercoiled DNA, while a mutant of P. aeruginosa containing a Tyr292 to Phe substitution at the active site was found to be catalytically inert. This is consistent with the role of Tyr in forming the covalent intermediate. Like vaccinia topoisomerase (VT), PAT …

The Economic Importance And Management Of Mercury Contamination In Pelagic Fisheries, Tina Marie Willson

LSU Doctoral Dissertations

The presence of mercury in the U.S. fish supply is a growing public health concern. At high levels, mercury can be harmful to humans and ecosystems, and represents a growing threat not only to public health, but also to the economic and ecological viability of many fisheries. This research examined the economic issues surrounding mercury contamination in fish, developed a population dynamics and bioeconomic model to investigate the problem, and compared a variety of management actions to reduce consumer exposure to contaminants. The dissertation begins with an overview of contamination issues in U.S. fisheries, including a review of the historical …

Physical And Chemical Factors Controlling Carbon Gas Emissions And Organic Matter Transformation In Coastal Wetlands, Syam Kumar Dodla

LSU Doctoral Dissertations

Wetlands are important sinks for the atmospheric carbon (C) and play a major role in the global carbon cycle. However, factors impacting wetland soil C transformations and C gas production are not yet well understood. Elucidating these influences is especially important to Louisiana as wetlands are being impacted by salt water intrusion, subsidence and Mississippi river water diversion activities. This study evaluates, the effects of salinity, ions in river and sea water (K+, Ca2+) , clays and electron acceptors (NO3-, SO42-) on soil C transformations as well as C gas production from Louisiana coastal wetlands. Wetland soils were collected from …