Life Sciences Commons^™

Primary Kinetic Isotope Effect For Substrate Hydroxylation And Iron Binding Regulation In Factor Inhibiting Hif-1, Michael A. Mingroni

Doctoral Dissertations

The hypoxic response is a vast and complex system, delicately designed through evolution to allow our tissues to rapidly adapt and survive fluctuations in pO2. HIF1α, the master regulator of oxygen, is tightly controlled through oxygen-dependent, post-translational hydroxylation via PHD2 and FIH1.The aberrant stabilization of HIF1α is an adverse consequence of disease states, but can also occur under normoxia in the presence of ROS or in iron depletion. The extensive transcriptional network regulated by HIF1α makes the HIF pathway an attractive therapeutic target, particularly through the inhibition of the hydroxylases, PHD2 and FIH, however the active site chemistry is mechanistically …

Extracellular Polymeric Substances In Oxygenic Photogranules: Investigation Of Their Role In Photogranulation In A Hydrostatic Environment, Wenye Camilla Kuo-Dahab

Doctoral Dissertations

The purpose of this dissertation was to assess the critical role of extracellular polymeric substances (EPS) in the photogranulation of activated sludge, in a hydrostatic environment. The first section evaluates the fate and dynamics of different fractions of EPS in sludge-based photogranulation under hydrostatic conditions. The study shows that during the transformation of activated sludge into a photogranular biomass, sludge’s base-extractable proteins selectively degrade. Strong correlations between base-extracted proteins and the growth of chlorophyll a and chlorophyll a/b ratio suggest that the bioavailability of this organic nitrogen is linked with selection and enrichment of filamentous cyanobacteria under hydrostatic conditions. The …

Structural Analysis Of Protein Therapeutics By Hydrogen Deuterium Exchange And Covalent Labeling Mass Spectrometry, Catherine Yvonne Tremblay

Doctoral Dissertations

This dissertation focuses on the use of mass spectrometry (MS) to study therapeutic protein higher order structure (HOS) by encoding the structure into the mass of the protein. As therapeutic proteins become more common in the pharmaceutical industry, the need for methods that accurately determine their HOS has grown. Two methods applied here are hydrogen deuterium exchange (HDX) MS and diethylpyrocarbonate (DEPC) covalent labeling (CL) MS. We demonstrate how these two methods provide complementary, and sometimes synergistic, information about protein HOS. HDX/MS reports on both changes in solvent exposure and changes in protein dynamics, and as a result it can …

Interseeding Native Warm-Season Grass Pastures, Jonathan D. Richwine

Doctoral Dissertations

Cool-season annual (CSA) grass and legume species, as well as warm-season forbs, can enhance established native warm-season grass (NWSG) pastures by extending the grazing season, reducing supplemental feed costs, suppressing weeds, increasing herbage production and overall forage quality, and increasing food and cover resources for pollinators and wildlife. Therefore, two NWSG experiments were conducted near Spring Hill, TN, 2018-2020, to assess three CSA seeding options (cereal rye monoculture, a cereal rye, ‘Purple Top’ turnip, ‘Trophy’ rape, ‘Frosty’ berseem clover, and ‘Dixie’ crimson clover polyculture, or non-planted control) and two warm-season N rates (0 or 67 kg N ha^-1) …

Insights Into Steinernema Carpocapsae-Xenorhabdus Nematophila Specificity And The Role Of Adult Nematode Colonization, Erin Mans

Doctoral Dissertations

The gut microbiota can provide the host with several benefits such as the production of secondary metabolites, essential amino acids, as well as the breakdown of food or protection from pathogens. The host in turn provides the microbiota with shelter and nutrients. Given the benefits that the host and microbiota receive from their association, humans and the microbiota have evolved mechanisms of selection and specificity to assure the proper symbionts colonize a host with high fidelity. Chapter two will explore mechanisms by which Xenorhabdus nematophila nematode intestinal localization (nil) genes interact with and adhere to the nematode intestinal …

Anti-Inflammatory And Chemopreventive Activity Of Lunasin From Tofu Whey For The Management Of Gastrointestinal Diseases, Cindy Andrea Nieto Veloza

Doctoral Dissertations

Gastrointestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are pathological conditions associated with chronic inflammation, characterized by intestinal damage, debilitating symptoms, and detrimental health consequences. The increased risk of CRC in IBD patients, and the adverse effects associated with current therapeutic strategies, point out the need for safer alternatives to reduce chronic inflammation in the bowel. Lunasin is a bioactive peptide naturally occurring in soybeans, with chemopreventive and anti-inflammatory properties demonstrated in several extra-intestinal diseases. However, to date, there is no evidence of the biological activity of lunasin on the gastrointestinal tract as a target site. …

Understanding The Novel Role Of Checkpoint Protein Rough Deal In Homolog Orientation And Centromeric Cohesion In Drosophila Male Meiosis, Qiutao He

Doctoral Dissertations

Meiosis is a central mechanism in sexual reproduction, through which the diploid precursor cells in the germline produce haploid gametes. After fertilization, a new set of diploid genome forms in the offspring with the characteristics of mother and father. The faithful transmission of genetic material to next generation relies on the fidelity of chromosome segregation during meiosis. A variety of mechanisms regulate the chromosome segregations in meiosis, including homolog interaction, chromosome cohesion, and sister-chromatid orientation. In most eukaryotic organisms, homolog interactions are built by the formation of chiasmata resulted from crossovers, but it is absent in male Drosophila in which …

Impacts Of Soil Management On Microbial Assemblages Involved In Nitrogen Transformations In Agroecosystems In Tennessee, Usa, Jialin Hu

Doctoral Dissertations

Nutrient reduction, particularly with respect to nitrogen (N) losses, is an important goal for sustainably managed agroecosystems. Soil N-cycling microbial populations that modulate these processes are affected by agricultural management regimes. This research focused on the controls and dynamics of the major N-cycling microbial populations in high-input cotton field under agricultural management regimes and low-input native C₄ forage grass systems under pasture management practices to determine the effects of management regimes on in situ seasonal dynamics of the functional microbes responsible for N fixation, nitrification, and denitrification processes. Molecular microbial ecology methods were combined with soil physicochemical properties and …

Modulation Of Protein Dynamics By Ligand Binding And Solvent Composition, Richard J. Lindsay

Doctoral Dissertations

Many proteins undergo conformational switching in order to perform their cellular functions. A multitude of factors may shift the energy landscape and alter protein dynamics with varying effects on the conformations they explore. We apply atomistic molecular dynamics simulations to a variety of biomolecular systems in order to investigate how factors such as pressure, the chemical environment, and ligand binding at distant binding pockets affect the structure and dynamics of these protein systems. Further, we examine how such changes should be characterized. We first investigate how pressure and solvent modulate ligand access to the active site of a bacterial lipase …

The Role Of Cdc42 Regulation In Cell Growth Pattern And Timing, Julie Robinson

Doctoral Dissertations

In fission yeast, polarized cell growth stops during division and resumes after cell separation at the end that existed in the previous generation. It is unclear how growth occurs specifically at this end after cell division. Via a pedigree analysis of mutant cells which display a unique polarity phenotype, we show the existence of a memory of growth. This memory of growth exists at the pre-existing cell end, which grew in the previous generation, and facilitates growth at that end in the next generation. This memory of growth gives the pre-existing end some advantage in a competition for active Cdc42, …

Birds And Bioenergy: A Modeling Framework For Managed Landscapes At Multiple Spatial Scales, Jasmine Asha Kreig

Doctoral Dissertations

This dissertation examines the design and management of bioenergy landscapes at multiple spatial scales given numerous objectives. Objectives include biodiversity outcomes, biomass feedstock yields, and economic value.

Our study examined biodiversity metrics for 25 avian species in Iowa, including subsets of these species related to ecosystem services. We used our species distribution model (SDM) framework to determine the importance of predictors related to switchgrass production on species richness. We found that distance to water, mean diurnal temperature range, and herbicide application rate were the three most important predictors of biodiversity overall. We found that 76% of species responded positively to …

The Effects Of Maturation On Acl Loading, Muscle Coordination, And Metabolic Cost In Adolescent Female Soccer Players, Lauren E. Schroeder

Doctoral Dissertations

Anterior cruciate ligament (ACL) injuries remain a significant, season-ending injury in youth soccer, with young female athletes exhibiting higher incidence rates compared to young male athletes. ACL injury rates increase with older ages, with female soccer players 15 years or older being at an almost twofold increased rate of injury compared to young female soccer players. Several biomechanical and neuromuscular changes occur during the maturation process, becoming more prevalent in young females, that can place them at an increased risk for ACL injury. These biomechanical and neuromuscular changes can affect how efficient young females are when completing high-risk, dynamic tasks …

Identification And Functional Characterization Of Plant Small Secreted Proteins During Arbuscular Mycorrhizal Symbiosis, Xiaoli Hu

Doctoral Dissertations

Plant small secreted proteins (SSPs) are sequences of 50 – 250 amino acids in size which are transported out of cells to fulfill multiple functions related to plant growth and development and response to various stresses. With the development of more accurate and affordable genome sequencing technology, an increasing number of SSPs have been predicted using diverse computational tools based on machine learning. Although experimentally validated plant SSPs are still limited, some studies have reported that plant SSPs can be induced and involved in mutualistic relationships between plants and microbes. In Chapter I, known SSPs and their functions in various …

The Histone Variant H2av Regulates Stress Responses And Tissue Development Through Interactions With Chromatin Insulator Proteins In Drosophila Melanogaster, James Ryan Simmons

Doctoral Dissertations

The ability of a cell to sense and respond to various forms of stress is essential to maintain integrity of the genome. Numerous pathways have been implicated in cellular responses to environmental and genotoxic stresses, often involving proteins and complexes that bind DNA directly to orchestrate changes in transcription and genome organization. Chromatin insulators describe a class of protein complex that bind specific sequences in the genome and work through two classically described functions: to restrict communication between enhancers and promoters through physical separation into different genomic domains and to prevent the spread of heterochromatin into euchromatic regions of the …

Improvement Of Solubility, Stability, And Bioaccessibility Of Curcumin Using Colloidal Delivery Systems, Bingjing Zheng

Doctoral Dissertations

Curcumin is a yellow-orange crystalline substance found in certain foods (turmeric) that is claimed to exhibit a broad range of biological activities. Its application as a nutraceutical in functional foods and beverages is often limited by its relatively low solubility in aqueous media, its chemical instability, and its low bioavailability. Recent research suggests that colloidal delivery systems can overcome these hurdles and improve the efficacy and commercial value of curcumin in the food, supplement, and pharmaceutical fields. The purpose of this research was to develop colloidal delivery systems to improve the application of curcumin as a nutraceutical in foods. First, …

Investigation On The Factors Impacting The Bioaccessibility Of Oil-Soluble Vitamins: Food Matrix Effects, Yunbing Tan

Doctoral Dissertations

Food, nutrition, and pharmaceutical scientists are trying to elucidate the major factors impacting the bioavailability of macronutrients (e.g., lipids), micronutrients (e.g., vitamins), and nutraceuticals (e.g., carotenoids) so as to improve their efficacy. Currently, however, there is a limited understanding of how food matrix effects impact nutrient digestion and bioavailability. In this thesis, the impact of food matrix effects was elucidated by systematically examining the influence of several important factors (including oil type, oil concentration, droplet size, emulsifier type, and nutrient type) on lipid digestion and the bioaccessibility of hydrophobic bioactive agents. Oil-in-water emulsions were used as model …

Formation, Characterization, And Utilization Of Multilayer Nanoemulsions In Foods, Jorge L. Muriel Mundo

Doctoral Dissertations

Multilayer coatings have been proposed as a promising nanotechnology for improving the performance of emulsion-based products in numerous research fields. In foods, these multilayer coatings can be used to improve the encapsulation and protection of bioactive ingredients in delivery systems during storage and passage through the gastrointestinal tract (1, 2). Therefore, there is strong interest in understanding the formation, properties, and performance of these novel coatings. Multilayer coatings are formed by layer-by-layer electrostatic deposition of oppositely charged biopolymers, such as proteins and polysaccharides. A better understanding of the formation and properties of biopolymer multilayer coatings could lead to …

Environmental Drivers Of Jaguar Distribution, Activity, And Abundance In Santa Rosa National Park, Costa Rica, Victor Montalvo

Doctoral Dissertations

Jaguars (Panthera onca) are a landscape species persisting in less than 54% of their historical distribution range; thus, the understanding of abiotic and biotic environmental factors affecting ecological interactions of this top predator in seasonal ecosystems such the dry forest is crucial for their conservation. In addition to factors affecting species ecology, some methodological constraints also could affect jaguar study outcomes leading to wrong decision-making. Data gathered from available jaguar peer-reviewed literature showed that there are large number of variables and techniques used to model jaguar distribution that did not contribute substantially to descriptions of jaguar distribution. Using …

Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng

Doctoral Dissertations

Cell surface harbors rich information regarding the status of cell health. Being able to monitor and detect its changes in response to stimuli will provide crucial information in drug discovery, disease diagnosis, and human health. Despite the efforts and breakthroughs made possible through the specific sensing approach, there are significant challenges in extracting the information on the cell surface in a quantitative and reliable way. To address this challenge, I took the approach of array-based, hypothesis-free sensing in which the engineered sensors selectively interact with target analytes, producing a distinct pattern of response that enables analyte identification. This signature-based pattern …

Novel Approaches Towards Improved Purity In High Yield Transcription Reactions, Elvan Cavac

Doctoral Dissertations

High yields of RNA (e.g., mRNA, gRNA, lncRNA) are routinely prepared following a two-step approach: high yield in vitro transcription using T7 RNA polymerase, followed by extensive purification using gel or chromatic methods. In high yield transcription reactions, as RNA accumulates in solution, T7 RNA polymerase rebinds and extends the encoded RNA (using the RNA as a template), resulting in a product pool contaminated with longer than desired, (partially) double stranded impurities. Current purification methods often fail to fully eliminate these impurities which, if present in therapeutics, can stimulate the innate immune response with potentially fatal consequences. This study establishes …

Pharmacological Chaperoning Of Human Lysosomal Neuraminidase 1, Di Chu

Doctoral Dissertations

Human lysosomal neuraminidase 1 (hNEU1) is an exo-a-sialidase which cleaves a(2-3) and a(2-6) linked sialic acids on glycoproteins in the lysosome. Deficiency of hNEU1 in the lysosome results in sialidosis, a lysosomal storage disease. Currently there is no effective treatment for sialidosis, which leads to a rising interest in discovering potential therapies. Here we presented a small molecule, α-D-N-acetylneuraminic acid (NANA), increases the protein amount and activity of both wild-type hNEU1 and three different hNEU1 mutations found in sialidosis patients in our mammalian cell system, suggesting that NANA works as a potential pharmacological chaperone for hNEU1 and provides …

Investigative Mechanisms To Exploit Caspase-Induced Apoptosis Using Polymeric Nanogels, Francesca Edith Anson

Doctoral Dissertations

Cysteine aspartate proteases (caspases) act as the molecular scissors of cell death, disintegrating diverse cellular components necessary for survival and growth via proteolysis. Caspases are tightly regulated through a myriad of mechanisms including proteolytic processing, structural changes, post-translational modifications and metal binding. Correspondingly, cancers have evolved numerous resistance and desensitization mechanisms upstream or within the caspase pathway to avoid death signals. These mechanisms are extremely diverse and are not fully understood however, the field overwhelming suggests caspase activity and caspase inhibition antagonism to be critical for efficacious cancer therapies. Accordingly, exploiting the role of caspases in apoptosis has become an …

The Hidden Life Of Tropical Roots: Functional Root Traits And Their Response To Climatic Disturbances, Daniela Yaffar

Doctoral Dissertations

Roots play a critical role in plant nutrition, and terrestrial carbon cycling. However, they are often understudied compared to their aboveground counterparts; especially in the tropics, where more carbon is cycled than in any other ecosystem. Some tropical forests, like in Puerto Rico, are more represented in scientific studies than others. However, this information is sparse, complicating the interpretation of root trait patterns. Trees in Puerto Rico have adapted mechanisms for withstanding hurricane disturbances, including in their roots. Additionally, as many tropical forests, some in Puerto Rico have low available phosphorus (P); thus, trees rely on root traits to enhance …

Applications Of Comparative Genomics And Data Science To Agricultural And Clinical Research, Katrina A. Schlum

Doctoral Dissertations

The advent of inexpensive, high-throughput whole genome sequencing (WGS) technologies has led to the generation of thousands of related genomes, even from a single study. Large-scale genome analysis has resulted in hypothesis-generating approaches in the fields of clinical, human and agriculture genomics. Additionally, population-level genomic sampling has resulted in a decrease in false positives in genotype-phenotype associations and an increase in understanding of the basis of disease, antibiotic and pesticide resistance. Deeper understanding of migration, genetic divergence and evolution has also been made possible due to WGS. This research applies comparative genomics, population genomics and data science approaches to whole …

The Effects Of High Temperatures On Mating Communication In Songbirds, Casey Marie Coomes

Doctoral Dissertations

Due to climate change, animals around the globe are experiencing the negative impacts of hot temperature extremes. Hot temperatures can affect animals is by inducing behavioral changes. Some of these behavioral changes include reductions in important, fitness-related behaviors such as foraging and mating. One aspect of mating behaviors that high temperatures can impact is communication. In many systems, mating communication consists of a male signaler transmitting a signal to a female receiver, who then uses the signal to assess the male’s quality as a potential mate. High temperatures can impact this process at the level of the signaler, the receiver, …

Biofabricated Constructs Of Carbon-Based Nanoparticles With Mesenchymal Stem Cells For Orthopedic Repair, Steven D. Newby

Doctoral Dissertations

Breakthroughs in tissue engineering are moving at a rapid rate especially in the regenerative bone biofabrication. Technology growth in the field of additive manufacturing (AM) such 3D bioprinting which provides the ability to create biocompatible 3D construct on which a cell source could be seeded is an encouraging substitute to autologous grafts.

This present research aims to biofabricate a construct for bone tissue engineering using AM technology. The biocompatible material was chosen corresponding to bones extracellular matrix (ECM) composition, which demonstrates an inorganic and organic development phase: Poly (lactic-glycolic acid) was chosen as the polymeric matrix of the compound, due …

Engineering Modularity Of Ester Biosynthesis Across Biological Scales, Hyeongmin Seo

Doctoral Dissertations

Metabolic engineering and synthetic biology enable controlled manipulation of whole-cell biocatalysts to produce valuable chemicals from renewable feedstocks in a rapid and efficient manner, helping reduce our reliance on the conventional petroleum-based chemical synthesis. However, strain engineering process is costly and time-consuming that developing economically competitive bioprocess at industrial scale is still challenging. To accelerate the strain engineering process, modular cell engineering has been proposed as an innovative approach that harnesses modularity of metabolism for designing microbial cell factories. It is important to understand biological modularity and to develop design principles for effective implementation of modular cell engineering. In this …

The Effects Of Urbanization On The Avian Gut Microbiome, Mae Berlow

Doctoral Dissertations

The gut microbiome influences and is influenced by the host, and can affect the host organism by contributing to health, development and immunity. Similarly, the host can influence this community; it’s makeup can vary with host species, locality, diet, social stressors, and environmental stressors. Some of these environmental stressors have arisen due to human-induced rapid environmental change, like urbanization. The physiology and behaviors of organisms that are able to persist in urban environments are often different from their non-urban congeners. Nutrition, development, and immunity—all of which are affected by the gut microbiome—are important factors that can determine survival in urban …

Biotic And Abiotic Dehalogenation Of Halogenated Methanes: Trichlorofluoromethane, Dichlorodifluoromethane, And Tetrachloromethane, Briana M. Mcdowell

Doctoral Dissertations

Trichlorofluoromethane (CFC-11), dichlorofluoromethane (CFC-12), and tetrachloromethane (CT) are fully halogenated methanes that were produced as refrigerants in the early part of the 1900s and later used in many industrial processes. They are ozone-depleting agents and common groundwater contaminants. They are volatile chemicals that are moderately soluble in water. Due to their volatility when released to the environment, they are predominantly found in the atmosphere, though they also dissolve into the groundwater. In anaerobic environments, they can undergo dehalogenation reactions with several redox-active compounds. This dissertation presents results from two treatability studies from sites contaminated with CFC-11, CFC-12, and CT. Additionally, …

Characterization And Management Of Glyphosate-Resistant Junglerice, Clay M. Perkins

Doctoral Dissertations

Junglerice has become a major weed in Tennessee and across the mid-south. Glyphosate resistance and dicamba antagonism has resulted in the reported control failures and rise in prevalence. Junglerice was the most prevalent weed escape in cotton and soybean fields across Tennessee from 2018 to 2020. In all, 13% of the junglerice accessions could no longer be effectively controlled with glyphosate. Due to poor in-crop control, it has been recommended to start clean when trying to control junglerice and other grasses. Therefore, research was conducted to determine the best burndown methods utilizing dicamba, glufosinate, or paraquat. A sequential application of …