Digital Commons Network^™

Acute Myeloid Leukemia: Therapy Resistance And A Potential Role For Tetraspanin Membrane Scaffolds, Muskan Floren, Jennifer M. Gillette

Pathology Research and Scholarship

Acute myeloid leukemia (AML) is characterized by the disruption of myeloid differentiation and accumulation of blast cells in the bone marrow. While AML patients respond favorably to induction chemotherapy, long-term outcomes remain poor due to a high rate of chemoresistance. Advances with targeted therapies, which can be used in combination with conventional chemotherapy, have expanded therapeutic options for patients. However, remission is often short-lived and followed by disease relapse and drug resistance. Therefore, there is a substantial need to improve treatment options by identifying novel molecular and cellular targets that regulate AML chemosensitivity. Membrane scaffolds such as the tetraspanin family …

Locating Herbarium Specimens In Online Digital Repositories To Be Used In Future Retrospective Analysis Of Metal Pollutants From Pre- And Post-1960s In The Most Polluted City In The United States, Chattanooga, Tennessee, Megon Stepaniuk

Masters Theses and Doctoral Dissertations

Here we find and analyze herbarium specimens collected throughout the last 100 years from the greater Chattanooga area to future screen them for the presence and concentration of metals. Chattanooga was declared the most polluted city in America in 1969 from the years 1961-1965 due to unchecked industrial emissions. Factories, railroads, coal furnaces, and iron making were only a few of many industrial operations releasing metal particulates and toxicants into the atmosphere. Metals can be deposited atop plant surfaces or soil when they find a sink there. Living plants have been used to assess metal pollution concentrations, though assessing historical …

Multi-Scale And Multi-Group Modeling Techniques Applied To Cholera And Covid-19, Conrad Ratchford

Masters Theses and Doctoral Dissertations

Cholera is an acute intestinal illness caused by infection with the Vibrio cholerae bacteria. The dynamics of the disease transmission are governed by human-human, environment-human, and within-human sub-dynamics. Specifically, the within-host dynamics incorporate virus and immune cell interaction with the vibrios. One model is presented to incorporate all three of these dynamical components. This model is extended to consider the case of a sub-divided population interacting in a spatially heterogeneous environment. In particular, we find that the between-host reproduction number is shaped by the collection of the disease risk factors from all the individual host groups. These multi-patch techniques are …

Dean's Research Newsletter, August 2021, Jerry L. Nadler

SOM Dean's Research Newsletter

No abstract provided.

Development Of Conjugated Polymer Nanoparticles For Applications In Superresolution Imaging And Sensors, Muskendol Novoa Delgado

All Theses

Utilization of conjugated polymer nanoparticles (CPNs) as fluorescent probes has attracted lots of scientific interest due to their exceptional brightness and photostability, particularly there has been considerable interest in developing a photoswitchable nanoparticle based on CPNs. Previous efforts by other groups of researchers, either did not exhibit single-step switching or suffer from poor on/off contrast because of incomplete quenching of the nanoparticle fluorescence. In this work, superresolution imaging via controlled reversible generation and recombination of hole polarons as fluorescence quenchers inside CPNs has been demonstrated resulting in a localization precision of ~0.6nm, which is about 4 times better than the …

Artistically Reshaping Trauma: An Exploration Of Radical Healing In The Lived Experiences And Art Of Marginalized Youth, Anitra R. Alexander

All Theses

Consumption and circulation of police brutality and the death of persons in the marginalized community present major concerns for the psychological well-being and development of marginalized youth. Contemporary events, such as the COVID-19 pandemic, have increased both negative media attention and instances of oppression towards AAPI communities. Not all adolescents are directly exposed to traumatic race-related events online; however, many are likely experiencing the direct effects of such incidents. Despite exposure and effects of these events, marginalized adolescents still demonstrate indicators of healthy coping. Indicators of healthy coping present the need to shift research from negative psychological outcomes to healing …

Evaluation Of Two-Phase Anaerobic Digestion For Increased Sludge Handling Capacity And Energy Production At The F. Wayne Hill Water Resources Center, Julia Ann Funk

All Theses

Two-phase anaerobic digestion (AD) of municipal wastewater separates the hydrolytic-acidogenic phase from the methanogenic phase, resulting in optimization of the respective microbial communities, increased stability, shorter residence times, and increased methane production rates compared to conventional single-phase treatment. Anaerobic co-digestion of fats, oils, and grease (FOG) with municipal wastewater also offers the potential for increased methane production rates; however, FOG can lead to system upsets and overall digester failure if not managed properly. Anaerobic co-digestion in a two-phase system could offer the potential of alleviating many of these upsets, including more efficient conversion of long chain fatty acids (LCFAs) and …

Framing Ludens: Pawn Swapping And Game Mode Alteration In An Unreal Engine Game Level, Jeffrey Paul Martell

All Theses

Knight of Drones is a hybrid twin-stick top-down shooter and side-scrolling platformer that aims to bring vintage gameplay to a contemporary game engine. A single swatch of the top-down game mode and a pair of levels from the side-scrolling game mode will be presented beginning with the player characters and player pawn assets and then extending to the level design and game design assets.

The game deals with the fallout effects of climate change and serves as a cautionary tale against pollution and weaponized AI. This message will appear primarily in the game's atmosphere, literally in the background in some …

Thioredoxin Reductase Is A Major Regulator Of Metabolism In Leukemia Cells, Sheelarani Karunanithi, Ruifu Liu, Yongchun Hou, Giancarlo Gonzalez, Natasha Oldford, Anne Jessica Roe, Nethrie Idipilly, Kalpana Gupta, Chandra Sekhar Amara, Satwikreddy Putluri, Grace Kyueun Lee, Juan Valentin-Goyco, Lindsay Stetson, Stephen A Moreton, Vasanta Putluri, Shyam M Kavuri, Yogen Saunthararajah, Marcos De Lima, Gregory P Tochtrop, Nagireddy Putluri, David N Wald

Faculty, Staff and Students Publications

Despite the fact that AML is the most common acute leukemia in adults, patient outcomes are poor necessitating the development of novel therapies. We identified that inhibition of Thioredoxin Reductase (TrxR) is a promising strategy for AML and report a highly potent and specific inhibitor of TrxR, S-250. Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models. We found that TrxR inhibition leads to a rapid and marked impairment of metabolism in leukemic cells subsequently leading to cell death. TrxR was found to be a major and direct regulator of metabolism in AML …

Deep Learning-Based Mixed-Dimensional Gaussian Mixture Model For Characterizing Variability In Cryo-Em, Muyuan Chen, Steven J Ludtke

Faculty, Staff and Students Publications

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. Cryogenic electron microscopy (cryo-EM) provides direct visualization of individual macromolecules sampling different conformational and compositional states. While numerous methods are available for computational classification of discrete states, characterization of continuous conformational changes or large numbers of discrete state without human supervision remains challenging. Here we present e2gmm, a machine learning algorithm to determine a conformational landscape for proteins or complexes using a three-dimensional Gaussian mixture model mapped onto two-dimensional particle images in known orientations. Using a deep neural network architecture, e2gmm can automatically resolve the …

Transcriptional Milestones In Dictyostelium Development, Mariko Katoh-Kurasawa, Karin Hrovatin, Shigenori Hirose, Amanda Webb, Hsing-I Ho, Blaž Zupan, Gad Shaulsky

Faculty, Staff and Students Publications

Dictyostelium development begins with single-cell starvation and ends with multicellular fruiting bodies. Developmental morphogenesis is accompanied by sweeping transcriptional changes, encompassing nearly half of the 13,000 genes in the genome. We performed time-series RNA-sequencing analyses of the wild type and 20 mutants to explore the relationships between transcription and morphogenesis. These strains show developmental arrest at different stages, accelerated development, or atypical morphologies. Considering eight major morphological transitions, we identified 1371 milestone genes whose expression changes sharply between consecutive transitions. We also identified 1099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite …

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …

Cd148 Deficiency In Fibroblasts Promotes The Development Of Pulmonary Fibrosis, Konstantin Tsoyi, Xiaoliang Liang, Giulia De Rossi, Stefan W Ryter, Kevin Xiong, Sarah G Chu, Xiaoli Liu, Bonna Ith, Lindsay J Celada, Freddy Romero, Matthew J Robertson, Anthony J Esposito, Sergio Poli, Souheil El-Chemaly, Mark A Perrella, Yuanyuan Shi, James Whiteford, Ivan O Rosas

Faculty, Staff and Students Publications

Rationale: CD148/PTRJ (receptor-like protein tyrosine phosphatase η) exerts antifibrotic effects in experimental pulmonary fibrosis via interactions with its ligand syndecan-2; however, the role of CD148 in human pulmonary fibrosis remains incompletely characterized.

Objectives: We investigated the role of CD148 in the profibrotic phenotype of fibroblasts in idiopathic pulmonary fibrosis (IPF).

Methods: Conditional CD148 fibroblast-specific knockout mice were generated and exposed to bleomycin and then assessed for pulmonary fibrosis. Lung fibroblasts (mouse lung and human IPF lung), and precision-cut lung slices from human patients with IPF were isolated and subjected to experimental treatments. A CD148-activating 18-aa mimetic peptide (SDC2-pep) derived from …

Stability Of Hippocampal Subfield Volumes After Trauma And Relationship To Development Of Ptsd Symptoms, C. N. Weis, E. Kate Webb, Ashley A. Huggins, Maddy Kallenbach, Tara A. Miskovich, Jacklynn M. Fitzgerald, Kenneth P. Bennett, Jessica L. Krukowski, Terri A Deroon-Cassini, Christine L. Larson

Psychology Faculty Research and Publications

Background

The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus’ functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample …

Per- And Polyfluorinated Alkyl Substances (Pfas) Cycling Within Michigan: Connections Between Contaminated Sites, Landfills, And Wastewater Treatment Plants, Ross W. Helmer

Masters Theses

The disposal and treatment of Per- and Polyfluorinated Alkyl Substances (PFAS) contaminated solid and liquid wastes, and associated cycling within the natural and engineered environment is a complex topic. PFAS data on contaminated sites, landfill leachates, the influent, effluent, and biosolids from wastewater treatment plants (WWTPs) within Michigan were compiled from publicly available and private sources. Most of the datasets are based on a 28-analyte suite generated using a modified form of the US EPA 537 analytical method, with a subset of data from the 18-analyte ASTM D7979-19 method. Approximately 70% of the 171 contaminated sites in Michigan have maximum …

An Assessment Of Inp/Zns As Potential Anti-Cancer Therapy: Quantum Dot Treatment Induces Stress On Hela Cells, Victoria Grace Davenport

Graduate Theses/Dissertations

Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dots (QDs) are an emerging option in QD technologies for uses of fluorescent imaging as well as targeted drug and anti-cancer therapies based on their customizable properties. In this study we explored effects of InP/ZnS when treated with HeLa cervical cancer cells. We employed XTT viability assays, reactive oxygen species (ROS) analysis, and apoptosis analysis to better understand cytotoxicity extents at different concentrations of InP/ZnS. In addition, we compared the transcriptome profile from the QDtreated HeLa cells with that of untreated HeLa cells to identify changes to the transcriptome in response to the QD. Intracellular …

Investigation Of The Interface Reactions Of Ion Selective Electrode Membranes Using Chromatographic And Spectroscopic Analyses Of Erbium(Iii) Tetraphenylporphyrin, Alexis Rae Miller

Graduate Theses/Dissertations

Ion selective electrodes (ISEs) are analytical sensors that monitor the interactions between an ionophore within a polymeric membrane and ions in various solutions. The sensitivity and selectivity of ISEs is directly related to the chemical components. One type of ionopohore utilized in ISEs are metalloporphyrins. Metalloporphyrins have unique binding characteristics, which make them useful in sensors. The polymeric membranes that are synthesized and used in ISEs consist of a metalloporphyrin complex, polyvinyl chloride, and ortho-nitrophenyl octyl ether. The membrane unique to this project contains erbium (III) tetraphenylporphyrin as the metalloporphyrin ionophore. Various analytical techniques were applied in the investigation …

Why Am I Like This? An Examination Of The Impact Of Early Childhood Experiences On Adult Attachment Style, Amaris Clay

Graduate Theses/Dissertations

Early childhood experiences and parental relationships have a lasting influence on future interpersonal relationships and the associated behaviors (Cortazar and Herreros 2010; Raby et al. 2015; Simons et al. 2014; Treger and Sprecher 2011). The proposed study is investigating the complex links between adverse childhood experiences, parenting style, and attachment style. The purpose of this study was to examine the lasting impact of early childhood factors and how they affect relationships in adulthood. The study intends to replicate previous research on parenting style and attachment style. The results of this study will add to the body of research centered on …

Ecological Correlates Of Alligator Snapping Turtle Bite Performance, Ashley Herrin Gagnon

Graduate Theses/Dissertations

The Alligator Snapping Turtle (Macrochelys temminckii) is one of many turtle species facing conservation challenges. Nearly extirpated in the 1980s, it is currently the subject of a head-start initiative, of which, any lasting behavioral or physiological effects were—until now—unknown! To evaluate the ability of captive-reared individuals to excel in natural habitats, and to foresee any future research or conservation challenges regarding this animal, I explored a suite of variables that influence bite performance and behaviors including captive or free-ranging status, and environmental conditions including body temperature and season. My results indicated that free-ranging M. temminckii outperform those residing …

Investigation Into Bacterial Impairment Of Greene And Polk County Water Systems, John C. Kincaid

Graduate Theses/Dissertations

Bacterial impairment of water systems is a major issue facing mankind. Bacteria that are introduced into a system have the potential to cause harmful diseases to wildlife and humans. In Greene and Polk counties, many water systems have become bacterially impaired over the years. Despite this, little is known about the contamination of known harmful bacteria in this region. To address this issue, I investigated the presence of known human pathogens across water systems in these two counties, many of which have displayed high levels of E. coli and fecal indicator microorganisms over many years. I used a high-throughput sequencing …

Examining Health Inequity In Ancient Egypt, Samantha Rose Gonzalez

Graduate Theses/Dissertations

This thesis explores the history of medicine in ancient Egypt between the Middle and New Kingdoms, and offers a case study highlighting the use of religion and magic in healing and analyzing health inequity. I am interested in medical practices, treatments, diagnosis methods, and access to healthcare in the ancient world. I seek to bridge the gaps and help unify the knowledge surrounding ancient Egyptian medical practices and contribute to the studies in the history of medicine. I explore types of diseases that commonly affected the ancient Egyptians and how they integrated religion and magic into their understanding and treatment …

A Values-Based Self-Management Program For Undergraduate Students With Remote Delivery: Looking At Emotion Regulation, Sara Elizabeth Johnson

Graduate Theses/Dissertations

College students face significant levels of stress (American College Health Association, 2019) and recent data suggests a high prevalence of diagnostic-level mental health concerns being reported by students and treated by mental health professionals (Blanco et al., 2008). College counseling centers are thus facing an increase in demand for services, creating a growing need for innovative treatment options to flexibly accommodate the demand (Center for Collegiate Mental Health, 2016). In response to the unique needs of college students, Acceptance and Commitment Therapy (ACT)-based interventions have received support for their use in increasing wellbeing in engineering students and graduate students (Abiadbe …

Stimuli Responsive Dye-Containing Peg-Pla Block Copolymer Micelles And Computationally Assisted Design Of A Stapled Peptide Bundle, Tyler L. Odom

Graduate Theses/Dissertations

In this thesis, I report the preparation and characterization of dye-containing PEG-b-PLA block copolymer micelles and the computational design of a novel coiled-coil peptide bundle. The PEG-b-PLA micelles encapsulate hydrophobic molecules into their core and have strong potential as nanocontainers or delivery vesicles. In theory, these internalized molecules can be released upon exposure to mechanical forces that disrupt the micellar structures. This force-responsive nature is one of the inherent properties of micellar systems. However, there is a stark lack of research that utilize this property in applications. Along those lines, I have studied the behavior of …

Physiological, Biochemical, And Metabolic Responses Of Wheat (Triticum Aestivum) Exposed To Perfluorooctanesulfonic Acid (Pfos), Polycarp Chidiebere Ofoegbu

Graduate Theses/Dissertations

The effects of perfluorooctanesulfonic acid (PFOS) on agricultural plants is a serious environmental concern that needs to be addressed. PFOS is a member of a class of organic chemical compounds known as per and polyfluoroalkyl substances (PFAS). These compounds are utility chemicals in household, commercial, and industrial items, but have become environmental contaminants of global concern. Full lifecycle and short-term exposure studies of wheat grown in soil amended with 0, 25, and 50 mg/kg PFOS were conducted to assess the impacts of PFOS on wheat. PFOS uptake analysis, physiological assays, elemental analysis, and metabolomics were carried out in the full …

The Co-Requisite Collaboration: Building Self-Confidence, Self-Efficacy, And Rapport Through Dialogue Journals In A Basic Writing Course, Timothy Jacob Pyatt

Graduate Theses/Dissertations

Research on dialogue journals has grown in the last fifty years, but a gap exists in understanding how and why these dialogue journals work. During the fall of 2020, I conducted a study utilizing quantitative data to examine how dialogue journals impact student’s self-confidence, self-efficacy, and rapport. The data has confirmed that dialogue journals are effective classroom tools and that various aspects such as word count and purpose can be impacted in connection to student’s perceptions of themselves. This project responds to the gap in the literature and provides data to support how and why dialogue journals promote growth in …

Neuronal Migration In Developmental Hyperserotonmia: Assessment Of Vesicular Glutamate In The Raphe Nuclei, Trey M. Shupp

Graduate Theses/Dissertations

The neurotransmitter serotonin is involved in the early development of the central nervous system and the organization of neurons throughout the cerebral cortex and cerebellum. It is proposed that serotonin indirectly interacts with cells in the marginal zone of the cerebral cortex known as Cajal-Retizus (CR) cells. These cells secrete the extracellular matrix protein reelin, which is known for its role in neuronal organization and migration during early neural development. It has been observed that low levels of serotonin are associated with similarly low levels of reelin during development and have been reported to result in disorganization of neurons in …

Expression, Purification And Characterization Of The Human Cytochrome P450 Enzyme 4x1 (Cyp4x1) Using Substrate Binding Affinity, Metabolic Assays And Protein Crystallization, Olusegun Adeolu Idowu

Graduate Theses/Dissertations

The human cytochrome P450 enzyme 4X1 (CYP4X1) is among the “orphan” cytochrome P450 meaning there is much unknown about its structure, biological function, and regulation in literature study. Scientific work on this protein has primarily been on identifying its physiological functions and expression sites. A recent study found 2 substrates (arachidonic acid and anandamide) catalyzed by the enzyme. Expression in humans appears to be primarily in the brain, prostate, lungs, and neurovascular systems and research has linked the protein as a potential chemotherapy target in brain cancer. So far, only a few inhibitors have been identified. The goal …

Establishing The Role Of Dc-Sign And Glycoprotein H For Kshv Entry In B Lymphocytes, Nancy Palmerin

Pharmaceutical Sciences (MS) Theses

Kaposi sarcoma-associated herpesvirus, also known as KSHV or HHV-8, is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. KSHV is known to cause four types of malignancies: endothelial-based Kaposi Sarcoma (KS), two rare B cell- based lymphomas; Primary effusion lymphoma, Multicentric Castleman’s disease and a recently characterized inflammatory disorder called KSHV-associated inflammatory cytokine syndrome(KICS). Unfortunately, all of the diseases associated with KSHV infection are fatal, and to this day there is no known cure. The purpose of this study is to understand the viral entry process of KSHV in tonsil-derived B lymphocytes. This study will …

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were …

Modulation Of Antibacterial Activity And Cytotoxicity In Amphipathic Cyclic Peptide [R4w4] Using Histidine Substitution, Ryan Stueber

Pharmaceutical Sciences (MS) Theses

Antibiotics have been the gold standard frontline defense against bacterial infections for decades. At the same time, these infecting bacteria have continued to evolve to resist developed antibiotics in an almost endless cycle. As such, we aim to take an alternative approach utilizing antimicrobial peptides (AMPs) as a means to end this cycle. [R4W4] is among known AMPs that demonstrated antimicrobial activity against methicillin-resistant staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 2.67 μg/mL. This peptide had notably effective antimicrobial activity, especially relative to linear (R4W4). However, it displayed a concerning level of cytotoxicity; eliciting a human embryonic …