Digital Commons Network^™

Development And Evaluation Of Biocompatible Engineered Nanoparticles For Use In Ophthalmology, Bedia Begum Karakocak

McKelvey School of Engineering Graduate Student Theses & Dissertations

The synthesis and design of biocompatible nanoparticles for targeted drug delivery and bioimaging requires knowledge of both their potential toxicity and their transport. For both practical and ethical reasons, evaluating exposure via cell studies is a logical precursor to in vivo tests. As a step towards clinical trials, this work extensively investigated the toxicity of gold nanoparticles (Au NPs) and carbon dot (CD) nanoparticles as a prelude to their in vivo application, focusing specifically on ocular cells. As a further step, it also evaluated their whole-body transport in mice. The research pursued two approaches in assessing the toxicity of engineered …

Methods To Record Transcription Factor Binding And Enhancer Activity Throughout Cellular Differentiation, Zongtai Qi

Arts & Sciences Graduate Student Theses and Dissertations

The ability to create distinct cell types is fundamental for the development of multicellular organisms. Since all cells in an organism contain the same genes, cellular diversity is achieved through the transcriptional network where transcription factors (TFs) interacts with cis-regulatory elements, leading to the selective transcription of different sets of genes. To better understand the functions of TFs and regulatory elements underlying cell fate decisions, we developed methods that are able to record their activities throughout cellular differentiation. In Chapter 2, we developed a degradation domain based induction system for ҃alling CardsӠmethod which maps the binding sites of TFs using …

Transcriptional Signatures Of Host Susceptibility In Urinary Tract Infections, Lu Yu

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTI) caused by uropathogenic Escherichia coli (UPEC) are common and highly recurrent. Two important non-behavioral risk factors for UTI in women are genetics and history of two or more episodes of previous UTI. However, specific mechanisms of how these two factors modulate host susceptibility to UTI remain unclear. Concordantly, inbred mice of various genotypes and with different infection histories exhibit different susceptibilities to acute and chronic bladder infection (cystitis), which recapitulates a range of clinical UTI outcomes observed in women. Early host-pathogen interactions have been shown to determine UTI outcomes in mouse models. Here, we used two …

The Role Of Mesenchymal Stromal Cells And Classical Dendritic Cells In The Maintenance And Regulation Of The Bone Marrow Niche, Jingzhu Zhang

Arts & Sciences Graduate Student Theses and Dissertations

The bone marrow niche is an important microenvironment for the regulation of normal and malignant hematopoiesis. The first discovered niche component is mesenchymal stromal cells, which are the major source for the production and secretion of multiple niche factors. Mesenchymal stromal cells are heterogeneous and various transgenes have been used to target non-identical but overlapping subpopulations. To further characterize the heterogeneity of mesenchymal stromal cells, we tested the targeting specificity of three tissue-specific Cre-recombinase transgenes. We show that in addition to osteoblasts, Ocn-Cre targets a majority of Cxcl12-abundant reticular (CAR) cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset …

Plant Metabolic Pathways And Regulatory Networks For Aromatic Amino Acids And Hormones, Cynthia Holland

Arts & Sciences Graduate Student Theses and Dissertations

Unlike humans and other metazoans, organisms such as fungi, bacteria, and plants have retained the enzymatic machinery necessary to synthesize their aromatic amino acids de novo. Chorismate, the final product of the shikimate pathway, is the precursor to the three aromatic amino acidsѠtryptophan, tyrosine, and phenylalanineѠand is upstream of a number of plant growth hormones, including auxins and benzoates. Phenylalanine and tyrosine both stem from the precursor prephenate, which is formed from chorismate by chorismate mutase, and use dehydrogenases, aminotransferases, and dehydratases in their biosynthetic pathways. Although aromatic amino acid biosynthesis is important for protein synthesis, secondary metabolism, and human …

Evaluation Of Neurobiological Risk Factors For Alcohol Consumption; Convergent Evidence For Predispositional Effects Of Brain Volume, David Baranger

Arts & Sciences Graduate Student Theses and Dissertations

Alcohol is one of the most widely used psychoactive substances and accounts for 5% of global disease burden. The goal of the present work is to help advance efforts to both identify prognostic markers of risk, and to understand the mechanisms by which alcohol consumption impacts health. Early life stress is one of the strongest predictors of mental illness, including alcohol dependence, and has been hypothesized to impact risk via modulation of striatal reward functions and reward learning. Studies examined the effect of stress on reward learning and processing, and tested for moderation by genetic and environmental risk. Results were …

The Mechanism Of Hyper Daptomycin Resistance In Corynebacterium Striatum And Daptomycinճ Mechanism Of Action, Nicholas Kevork Goldner

Arts & Sciences Graduate Student Theses and Dissertations

Daptomycin, a last line-of-defense antibiotic for treating Gram-positive infections, is experiencing clinical failure against important infectious agents, including Corynebacterium striatum. The recent transition of daptomycin to generic antibiotic status is projected to dramatically increase availability, use, and clinical failure. Despite daptomycinճ more than 30-year history as an important antibiotic, four major questions were left unanswered. 1) How do bacteria become hyper-resistant to daptomycin? 2) What is the in vivo membrane target of daptomycin? 3) How does daptomycin interact with the membrane? 4) What is daptomycinճ mechanism of killing? These four questions have plagued the daptomycin field, and even now conflicting …

A Mechanism Of Antimicrobial Resistance And A Mitigation Strategy, Christopher Bulow

Arts & Sciences Graduate Student Theses and Dissertations

ABSTRACT OF THE DISSERTATIONA Mechanism of Antimicrobial Resistance and a Mitigation StrategybyChristopher BulowDoctor of Philosophy in Biology and Biomedical SciencesMolecular Genetics and GenomicsWashington University in St. Louis, 2018Professor Gautam Dantas, ChairThe ability to treat infections, perform surgery, and administer immunosuppressants and chemotherapy depends on effective antibiotics. The emergence and spread of antimicrobial resistance is far outpacing the development of new therapies1-3 threatening to thrust medicine into a post-antibiotic era4. Many mechanisms of antimicrobial action and of antimicrobial resistance remain poorly understood as drug development struggles to keep pace. As resistance develops, the human gut serves as a reservoir and provides …

The Role Of Personality In The Development Of Health Disparities During Late-Mid Life, Juliette Mcclendon Iacovino

Arts & Sciences Graduate Student Theses and Dissertations

Objectives: The current study examined race/gender disparities in initial levels and trajectories of self-reported physical and mental health, and health care utilization, as well as the impact of personality and stressful life events on race/gender disparities. We hypothesized that health disparities would remain stable or decrease over time; that at-risk personality traits (e.g., high neuroticism) would have a more robust negative impact on health for black participants; that trust would mediate racial disparities in health; and that personality traits would moderate the association between stressful life events and health trajectories differentially across race/gender. Methods: Analyses utilized the first six waves …

Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh

Arts & Sciences Graduate Student Theses and Dissertations

Protective immune responses to Mycobacterium tuberculosis (Mtb) must induce bactericidal functions while minimizing damage to the lung. Such responses require precise control of pro- and anti-inflammatory factors to regulate the recruitment and function of protective immune cells but the mechanisms by which this control is exerted remain incompletely defined. Basic helix-loop-helix family, member e40 (Bhlhe40) is a transcription factor known to regulate production of pro- and anti-inflammatory cytokines that affect protective immunity to Mtb. Immune-responsive Gene 1 (Irg1) is an enzyme that generates itaconate, a metabolite with potential anti-inflammatory and antibacterial roles during Mtb infection. The impact of Bhlhe40 and …

Smooth As Silk: Translating Discoveries To New Therapies In Amyotrophic Lateral Sclerosis, Wade Self

Arts & Sciences Graduate Student Theses and Dissertations

No effective therapies exist for the treatment of patients suffering from amyotrophic lateral sclerosis, a devastating neurodegenerative disease characterized by motor neuron loss, paralysis, and death on average 3 Р5 years after diagnosis. Although multiple promising candidates have emerged from preclinical experiments in disease models, failure rates of randomized control trials assessing efficacy in humans are over 95%, demonstrating a need to improve the translation of preclinical findings to human biology. In this dissertation, I present original work investigating amyotrophic lateral sclerosis caused by mutations in SOD1 (ALSSOD1) for the successful translation of SOD1-targeting strategies into meaningful treatment options for …

Hemodynamic Effects On Embryonic Arterial Growth And Matrix Remodeling, Maria Gabriela Espinosa

McKelvey School of Engineering Graduate Student Theses & Dissertations

Hemodynamic forces drive cardiovascular morphogenesis and remodeling in the developing embryo. Changes to the embryonic hemodynamic environment have been shown to induce a variety of congenital heart defects, but little attention has been given to vasculature-specific defects. Although vascular development has been widely studied in the context of genetics and molecular biology, this work investigates the impact of hemodynamic forces on arterial development and mechanics.

The dorsal aorta (DA) is the first intraembryonic vessel to form. Its passive mechanical properties are determined by the deposition of extracellular matrix (ECM) proteins, a hallmark of arterial maturation. We hypothesized that hemodynamic changes …

Lignin Conversion To Value-Added Products Via Heterogeneous Catalysts, Yu Gao

McKelvey School of Engineering Graduate Student Theses & Dissertations

Increasing world population has led to great demands for fuels, chemicals, and materials, and has raised concerns over the depletion of non-renewable resources and the environmental impacts of their processing and utilization. However, the biorefinery concept suggests lignocellulosic biomass can be used as an alternative resource for producing a range of fuels, chemicals and materials to fulfill these demands in a sustainable way. Hence, fermentation technologies are widely developed to efficiently utilize lignocellulosic carbohydrates. However, the non-carbohydrate fraction of biomass, lignin, is still considered as waste and is under-utilized as low-grade fuel, mainly for local heat and electricity production. Since …

Kdm6b Is Required For Self-Renewal Of Normal And Leukemic Mouse Stem Cells Under Proliferative Stress, Cates Mallaney

Arts & Sciences Graduate Student Theses and Dissertations

KDM6B (JMJD3) is one of two known epigenetic modifiers responsible for the removal of the repressive histone mark, histone-3 lysine-27 trimethylation (H3K27me3), and has been shown to play a role in development, differentiation, and inflammatory stress response. Unlike the other H3K27me3 demethylase, UTX (KDM6A), which is frequently mutated in hematopoietic malignancies, KDM6B is upregulated in a myriad of blood disorders. This suggests that it may have important functions in the pathogenesis of hematopoietic cancers. Here, we examined the role of Kdm6b in hematopoietic stem cell (HSC) fate decisions under normal and malignant conditions to evaluate its potential as a therapeutic …

Preventing Extinction Of At-Risk Plant Species In A Complex World, Holly Lee Bernardo

Arts & Sciences Graduate Student Theses and Dissertations

Earthճ current biodiversity crisis is now considered a true mass extinction event, with species level extinction rates well above background rates and population level extinction rates orders of magnitude more common that species extinctions. There are many threats driving this loss of biodiversity. How each threat impacts the viability of a species is highly context dependent, but all are anthropogenic in origin and so as the human population continues to increase, so too will the pressure of these threats on our natural systems. Ultimately, how much a threat decreases the viability of a species depends on how that threat influences …

Breath Biomarkers And An Expanded Role For Isoprenoids In Plasmodium Falciparum, Chad Louis Schaber

Arts & Sciences Graduate Student Theses and Dissertations

Malaria remains one of the deadliest infectious diseases worldwide, and efforts to combat it require novel insights into diagnostics, vector transmission, and drug inhibitor targets. Previous studies suggest that malaria infection causes hosts to preferentially attract the transmission vector, the Anopheles mosquito, but the mechanism and wider implication of these findings were not known. By analyzing the headspace above malaria parasite cultures, we identified several molecules that might engender mosquito attraction. We demonstrated that several of these molecules activate mosquito odorant receptors, including the known plant-emitted mosquito attractant _-pinene. During patient studies involving two independent pediatric clinical populations from Malawi, …

In Vivo Vascular Imaging With Photoacoustic Microscopy, Hsun-Chia Hsu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) tomography (PAT) has received extensive attention in the last decade for its capability to provide label-free structural and functional imaging in biological tissue with highly scalable spatial resolution and penetration depth. Compared to modern optical modalities, PAT offers speckle-free images and is more sensitive to optical absorption contrast (with 100% relative sensitivity). By implementing different regimes of optical wavelength, PAT can be used to image diverse light-absorbing biomolecules. For example, hemoglobin is of particular interest in the visible wavelength regime owing to its dominant absorption, and lipids and water are more commonly studied in the near-infrared regime.

In …

Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai

Arts & Sciences Graduate Student Theses and Dissertations

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cells responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. Here, we addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg responses during homeostasis and Teff responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis. In fact, 4/6 Treg TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the marked expansion …

The Role Of Membrane Excitability In Insulin Regulation, Christopher Howard Emfinger

Arts & Sciences Graduate Student Theses and Dissertations

In mammals, ATP-sensitive K+ (KATP) channels are essential regulators of insulin secretion from pancreatic islet [beta]-cells, illustrated by the finding that gain-of-function mutations in KATP channels (KATP-GOF) cause neonatal diabetes mellitus (NDM). However, variability in symptom severity and effectiveness of treatment is seen in NDM, even for those with the same mutation and in the same family. Short-term treatment of mice expressing KATP-GOF mutations in [beta]-cells (KATP-GOF mice) with the KATP blocker glibenclamide during disease onset results in two outcomes: one subset becomes severely diabetic (non-remitters), whereas the other subset remains below the glucose levels at which significant side effects …

A High-Content Screen Identifies Hsp90 As A Component Of Axon Injury Signaling, Scott Karney-Grobe

Arts & Sciences Graduate Student Theses and Dissertations

Axons are unique compartments of neurons that extend tremendous distances throughout the body. Neurodegenerative or traumatic damage to axons destroys neuronal function and thus necessitates axonal repair. Mammalian peripheral neurons can regrow their axons following injury, providing a robust system to study the molecular mechanisms of axon regeneration. Injury induces a large transcriptional program that drives regeneration. While many regeneration-associated genes are known, the mechanisms by which injury activates them are less well understood. Identification of new injury signals has been limited by in vivo approaches. To address this challenge, I developed and performed a loss-of-function pharmacological screen in cultured …

Characterization Of The Celf6 Rna Binding Protein: Effects On Mouse Vocal Behavior And Biochemical Function, Michael A. Rieger

Arts & Sciences Graduate Student Theses and Dissertations

Behavior in higher eukaryotes is a complex process which integrates signals in the environment, the genetic makeup of the organism, and connectivity in the nervous system to produce extremely diverse adaptations to the phenomenon of existence. Unraveling the subcellular components that contribute to behavioral output is important for both understanding how behavior occurs in an unperturbed state, as well as understanding how behavior changes when the underlying systems that generate it are altered. Of the numerous molecular species that make up a cell, the regulation of messenger RNAs (mRNAs), the coding template of all proteins, is of key importance to …

Novel 2d Structure Nanomaterials Synthesis And Ir Absorption, Suming Wang

Dissertations and Theses

Nanomaterials have gained much attention as in energy storage application for its unique electrical properties. Many research groups have developed various methods to fabricate nanomaterials for various applications. However, there exists much possibilities of developing cost-effective methods for nanomaterial fabrication. No one has studied using natural organic compound A as solution base for wet process nanomaterial synthesis.

In this study, a new method of fabricating two-dimensional structure nanomaterials is proposed. This method is applicable for multiple metal elements such as copper oxide, copper hydroxide, and iron oxide. The two dimensional structure nanomaterials have prestige properties because of their large surface …

Learning Onboard Rwu’S Research Vessel, Jill Rodrigues

Featured News Story

With the start of the Fall semester, that means students will be launching hands-on science lessons aboard the new research vessel, the InVincebleSpirit.

Pesticides And The Environment Ent 411/511, Michael Cerbo

Library Impact Statements

No abstract provided.

Service Via Invitation, Taylor University

2018 Website News Stories

No abstract provided.

Fluorescent Labeled Inhibitors, Christopher D. Spilling, Benjamin Martin, Stephane Canaan, Jean-Francois Cavalier

UMSL Patents

Provided herein are a series of fluorescently labeled phosphonate and phosphate compounds such as can be used for affinity probes to detect certain enzymes including lipases. Also provided are methods of making and using such compounds.

For the most up-to-date information about these patents, including the availability of Certificates of Correction, be sure to check the United States Patent and Trademark Office's free, publicly accessible database: Patent Public Search https://ppubs.uspto.gov/pubwebapp/static/pages/landing.html

Regium Bonds Between Mn Clusters (M=Cu,Ag,Au And N=2-6) And Nucleophiles Nh3 And Hcn, Wiktor Zierkiewicz, Mariusz Michalczyk, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

The most stable geometries of the coinagemetal (or regium) atom (Cu, Ag, Au) clusters Mn for n up to 6 are all planar, and adopt the lowest possible spin multiplicity. Clusters with even numbers of M atoms are thus singlets, while those with odd n are open-shell doublets. Examination of the molecular electrostatic potential (MEP) of each cluster provides strong indications of the most likely site of attack by an approaching nucleophile, generally one of two positions. A nucleophile (NH3 or HCN) most favorably approaches one particular M atom of each cluster, rather than a bond midpoint or face. In …

2018 – 2020 Key Strategic Issues List, Antulio J. Echevarria Ii

Articles & Editorials

No abstract provided.

The Legal Treatment Of Informal Caregivers Of The Elderly In Canada And Australia: The Importance Of Recognizing Relations In Creating Reforms, Sara Nicole Pon

LLM Theses

This thesis examines the policy implications of the legal treatment of caregivers of the elderly in Canada and Australia and how this can inform law and policy reforms in Canada. Legislation and policy on the formal care system and supports for informal caregivers of the elderly in Canada and Australia are described, with a focus on BC and Ontario in Canada. These supports are analyzed and evaluated through the lens of relational autonomy. Australia for the most part has more supports than Canada, although improvements can be made to these supports to make them more effective in supporting informal caregivers …

Crop Pests And Predators Exhibit Inconsistent Responses To Surrounding Landscape Composition, Daniel S. Karp, Rebecca Chaplin-Kramer, Timothy D. Meehan, Emily A. Martin, Fabrice Declerck, Heather Grab, Claudio Gratton, Lauren Hunt, Ashley E. Larsen, Alejandra Martínez-Salinas, Megan E. O’Rourke, Adrien Rusch, Katja Poveda, Mattias Jonsson, Jay A. Rosenheim, Nancy A. Schellhorn, Teja Tscharntke, Stephen D. Wratten, Wei Zhang, Aaron L. Iverson, Lynn S. Adler, Matthias Albrecht, Audrey Alignier, Gina M. Angelella, Muhammad Zubair Anjum, Jacques Avelino, Péter Batáry, Johannes M. Baveco, Felix J. J. A. Bianchi, Klaus Birkhofer, David J. Gonthier

Entomology Faculty Publications

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop …