Life Sciences Commons^™

Structural And Functional Studies Of The Papain-Like Protease 2 From Mouse Hepatitis Virus, Yafang Chen

Open Access Dissertations

Our goal is to establish a system to investigate how the deubiquitinating (DUB) and deISGylating activities of coronavirus (CoV) papain-like protease domains (PLPs) are involved in virus immune evasion. To this end, we chose PLP2 from mouse hepatitis virus (MHV) as our target of study because MHV has historically served as a model system for the study of CoVs, and it has undeniable advantage of ease in culturing in comparison to human coronaviruses.

It is reported here the expression and purification of a region of MHV nsp3 that contains the catalytic core of the PLP2 domain and its neighboring domains. …

Optimizing The Neural Response To Electrical Stimulation And Exploring New Applications Of Neurostimulation, Kurt Yuqin Qing

Open Access Dissertations

Electrical stimulation has been successful in treating patients who suffer from neurologic and neuropsychiatric disorders that are resistant to standard treatments. For deep brain stimulation (DBS), its official approved use has been limited to mainly motor disorders, such as Parkinson's disease and essential tremor. Alcohol use disorder, and addictive disorders in general, is a prevalent condition that is difficult to treat long-term. To determine whether DBS can reduce alcohol drinking in animals, voluntary alcohol consumption of alcohol-preferring rats before, during, and after stimulation of the nucleus accumbens shell were compared. Intake levels in the low stimulus intensity group (n=3, 100&mgr;A …

The Effect Of Macromolecular Crowding On The Structure Of The Protein Complex Superoxide Dismutase, Ajith Rathnaweera Rajapaksha Mudalige

Open Access Dissertations

Biological environments contain between 7 - 40% macromolecules by volume. This reduces the available volume for macromolecules and elevates the osmotic pressure relative to pure water. Consequently, biological macromolecules in their native environments tend to adopt more compact and dehydrated conformations than those in vitro. This effect is referred to as macromolecular crowding and constitutes an important physical difference between native biological environments and the simple solutions in which biomolecules are usually studied.^ We used small angle scattering (SAS) to measure the effects of macromolecular crowding on the size of a protein complex, superoxide dismutase (SOD). Crowding was induced using …

Effects Of Temperature And Pollinator Availability On Plant Reproductive Success In The Indiana Spring Ephemeral Community, Asya Robertshaw

Open Access Dissertations

Temperature is a key driver of phenology in both plants and insects, and even small changes in temperature can impact the reproductive success of insect-pollinated plants by influencing access to pollinator services. While it is well-established that temperature variation directly impacts the flowering phenology of many plant species, the mechanisms by which it ultimately influences seed production via the pollinator community are not well understood. Climate change has the potential to disrupt the temporal synchrony between plants and their primary pollinators, especially if the two rely on different seasonal cues for the timing of their life history events. If the …

Genetic, Agronomic And Compositional Characterization Of Brown Midrib Sweet Sorghum Lignocellulosic Biomass For Ethanol Production, Luis A. Rivera Burgos

Open Access Dissertations

Sorghum is a promising bioenergy crop due to its unique phenotypic and genotypic attributes. Quality (low lignin and high stem sugar concentration) and quantity (biomass yield, plant height, plant maturity, etc.) biomass traits are key contributors to ethanol yield and production. In this study, a 236 sorghum recombinant inbred line (RIL) population was subjected to genetic, agronomic and compositional characterization for ethanol yield and production. We found that the sweet mutation enhances biomass quantity traits in the RILs which translates to higher ethanol production and biomass quality which improves ethanol yield. The variance components showed from moderate to high heritability …

The Pathological Role Of Acrolein In Experimental Autoimmune Encephalomyelitis And Multiple Sclerosis, Melissa A. Tully

Open Access Dissertations

Multiple sclerosis (MS) is an autoimmune demyelinating neuropathy that affects nearly 2.5 million people worldwide. Despite substantial efforts, few treatments are currently available largely due to limited knowledge of pathogenic mechanisms underlying the disease. The immune-inflammatory nature of the pathology has prompted investigation of the role of oxidative stress in disease development and progression; however targeting reactive oxygen species for neutralization has had marginal success therapeutically, suggesting that an alternate oxidative stress-related target would prove beneficial. Recently, our lab has implicated acrolein, a highly reactive aldehyde that is both a byproduct and catalyst of lipid peroxidation, as a potential therapeutic …

The Role Of Entomology In Environmental And Science Education: Comparing Outreach Methods For Their Impact On Student And Teacher Content Knowledge And Motivation, Faith J. Weeks

Open Access Dissertations

Outreach programming can be an important way for local students and teachers to be exposed to new fields while enhancing classroom learning. University-based outreach programs are offered throughout the country, including most entomology departments as few individuals learn about insects in school and these programs can be excellent sources of entomological education, as well as models to teach environmental and science education. Each department utilizes different instructional delivery methods for teaching about insects, which may impact the way in which students and teachers understand the insect concepts presented. To determine the impact of using entomology to enhance science and environmental …

Paralogous Genes In Arabidopsis Thaliana Contribute To Diversified Phenylpropanoid Metabolism, Li Yi

Open Access Dissertations

Significant evidence supports the idea that gene duplication drives the evolution of new gene function. Besides being silenced, duplicated genes can either neofunctionalize or subfunctionalize under selective pressure or neutral drift. Understanding the trajectory of how each gene is fixed and presumably provides added fitness remains difficult. Plant specialized metabolism provides an attractive platform to study the fixation of genes post duplication and how this process leads to the chemical diversity seen today. Specialized metabolites by definition are thought to be dispensable under normal growth conditions. Thus deleterious mutations occurring in paralogous genes that otherwise would be selected against in …

Modeling, Empirics And Policy Implications Of Firm Heterogeneity In International Trade, Zeynep Akgul

Open Access Dissertations

Computable General Equilibrium (CGE) models are essential computational tools for trade policy analysis. While traditional CGE models based on the Armington assumption of national product differentiation have been successfully applied to various policy scenarios, they also have significant limitations in explaining the firm-level information prevalent in the recent international trade literature. The pioneering work of Melitz (2003) has provided a firm heterogeneity theory that can help address the shortcomings of Armington-based CGE models by introducing additional productivity mechanisms and extensive margin effects. Incorporation of firm heterogeneity in mainstream CGE models offers great potential to improve computational policy analysis. Even though …

Analysis Of Chd Remodelers During Development: A Tale In Two Organisms, Brett Bishop

Open Access Dissertations

The correct development of different organisms requires the precise timing of genes important for development transitions. Organisms have recruited ATP-dependent chromatin remodelers to ensure the correct timing of gene expression during developmental transitions. Here I show how different CHD ATP-dependent chromatin remodelers regulate developmental transitions of different organisms. I show that PICKLE not only promotes H3K27me3 during development to repress developmental genes but also is targeted to these genes. The association of PICKLE to these genes suggests that both repression and H3K27me3 levels is a direct action of PICKLE on these loci. Using zebrafish as a model system, I show …

Undercover Predators: Vegetation Mediates Foraging, Trophic Cascades, And Biological Control By Omnivorous Weed Seed Predators, Carmen K Blubaugh

Open Access Dissertations

Weed pressure is the most costly challenge that vegetable growers face, requiring more labor investment than other production inputs. Vertebrate and invertebrate seed predators destroy a large percentage of weed propagules on the soil surface, and their ecosystem services may ease labor requirements for farmers in herbicide-free systems. Cover provided by living vegetation is an important predictor of seed predator activity, and my dissertation takes a comprehensive approach to understanding the behavior, predator, and environment-mediated mechanisms by which cover impacts weed seed predation in crop environments. ^ First, I performed a meta-analysis of 27 studies to quantitatively evaluate what is …

Consequences Of Short-Term Water Temperature Variability To Fish: Current And Future Climate Change Impacts, David P. Coulter

Open Access Dissertations

Water temperature has a profound influence on aquatic ectotherms by affecting all aspects of biological organization; from chemical and molecular functioning to whole-organism and population-level impacts. Natural processes and anthropogenic activities can create conditions where temperatures vary greatly through space and time. While exposure to temperature changes lasting ≥ 24 hours have been examined in some species, it is unclear how more rapid (< 24 hours; sub-daily) thermal fluctuations affect aquatic ectotherms. I used a combination of field observations, laboratory experiments, and modeling simulations to understand: 1) how habitat quality of aquatic ectotherms is affected in thermally dynamic environments; 2) the role of sub-daily temperature fluctuations on growth, survival, and stress responses in juvenile and adult fish; 3) how fish early life stages are affected by sub-daily temperature fluctuations; and 4) what impact thermally dynamic environments have on a model species at a population-level. A model quantifying habitat quality around power plant thermal discharges indicated that elevated and variable discharge temperatures affected habitat quality over a relatively small spatial area for aquatic ectotherms. Models examining elevated temperatures representing climate warming showed that the effects of industrial discharges and climate warming could have an interactive effect on habitat quality by increasing the spatial area and duration over which industrial thermal effluents impact aquatic ectotherms. Laboratory experiments indicated that closely related fishes can respond differently to the same sub-daily temperature fluctuations. Yellow perch (Perca flavescens) had higher consumption and growth under sub-daily temperature fluctuations but developed skin lesions; an indication of thermal stress. In contrast, these same fluctuations reduced growth in physiologically similar walleye (Sander vitreus) …

Novel Methods For Manipulating Ion Types In The Solution And Gas Phases For The Structural Analysis Of Biomolecules Using Mass Spectrometry, Christine M Fisher

Open Access Dissertations

Mass Spectrometry has become a valuable tool for the analysis of a variety of molecules, making it applicable to many fields. The advent of nanoelectrospray ionization (nESI) as a soft/low energy ionization technique has enabled the analysis of large, intact biomolecules. Most mass spectrometry experiments consist of three main steps: ionization, probe step(s), and mass analysis. The present work focuses on a variety of methods for altering ion types at various stages of the mass spectrometry experiment to affect ion fragmentation. Ion types can be manipulated in the solution/droplet phases using novel nESI emitters, generated from borosilicate theta capillaries. These …

Carrion-Associated Arthropods In Rural And Urban Environments, Serena Daye Gross

Open Access Dissertations

Preferences of arthropods are important in forensic entomology, as the species collected can help determine the postmortem interval or if remains have been moved. This study looked at arthropods that are attracted to pig carcasses in rural and urban habitats in Northwest Indiana. The species and number of carrion-associated arthropods that are found at a carcass vary with habitat type, month, and stage of decomposition. Lucilia sericata (Diptera: Calliphoridae) is a synanthropic species that was found in higher numbers in urban locations for both adults and larvae. Though L. sericata had higher numbers in urban habitats, caution must be exercised …

Elucidation Of Pharmacologically Manipulated Responding In The Delay Discounting Task In High Alcohol Preferring Mice, Meredith Halcomb

Open Access Dissertations

Impulsive behavior is the hallmark of many psychopathologies. Uncovering the neurobiological mechanisms driving impulsivity is paramount in the development of through the delay discounting (DD) task in both human and animal models. The present study is an examination of the predictive validity of the two primary types of DD procedures in animals, the Adjusting Amounts (AA) and within session Increasing Delays (ID) tasks. Methods:Subjects were administered either1.25 mg/kg d-amphetamine (AMP), 1.5 g/kg ethanol (EtOH) or saline and tested in either the AA or ID method for 15 days to evaluate drug effects on impulsive behavior. Results: Stimulant administration resulted …

Characterization Of Hessian Fly From Israel, Alisha J Johnson

Open Access Dissertations

Mayetiola destructor Say, the Hessian fly, is a gall midge and a member of the Dipteran family Cecidomyiidae. It is a common pest of wheat found throughout all of the major wheat growing areas of the world and poses a serious economic threat to the United States (US), particularly in the Southeast winter wheat region. Damage to wheat is done solely by feeding first and second in-star larvae. Hessian fly (Hf) infestations result in a loss in grain yield by the stunting and/or killing of seedling wheat plants in the winter and by causing breakage at the nodes of the …

A Novel In Vivo Tumor Oxygen Profiling Assay: Combining Functional And Molecular Imaging With Multivariate Mathematical Modeling, Chung-Wein Lee

Open Access Dissertations

Purpose: The objective of this study is to develop and test a novel high spatio-temporal in vivo assay to quantify tumor oxygenation and hypoxia. The assay implements a biophysical model of oxygen transport to fuse parameters acquired from in vivo functional and molecular imaging modalities. ^ Introduction: Tumor hypoxia plays an important role in carcinogenesis. It triggers pathological angiogenesis to supply more oxygen to the tumor cells and promotes cancer cell metastasis. Preclinical and clinical evidence show that anti-angiogenic treatment is capable of normalizing the tumor vasculature both structurally and functionally. The resulting normalized vasculature provides a more efficient and …

Quantitative Mrna Detection With Advanced Nonlinear Microscopy, Jing Liu

Open Access Dissertations

Cell-specific information on quantity and localization of key mRNA transcripts in single-cell level are critical to the assessment of cancer risk, therapy efficacy, and effective prevention strategies. While current techniques are not capable to visualize single mRNA transcript beyond the diffraction limit. In this thesis, two nonlinear technologies, second harmonic super-resolution microscopy (SHaSM) and transient absorption microscopy (TAM), are developed to detect and quantify single Human edimer receptor 2 (Her2) mRNA transcripts. The SHaSM is used to detect single mRNA transcript beyond the diffraction limit, while the TAM is employed to detect mRNA without the interference of fluorescence background. The …

Developmentally Regulated Sumoylation In The Ciliate Tetrahymena Thermophila, Amjad M. Nasir

Open Access Dissertations

The Small Ubiquitin-like MOdifier (SUMO) protein regulates numerous nuclear events such as transcription, mitosis and meiosis and DNA repair. These processes are critical to the programmed nuclear events of conjugation in ciliates and provide the potential to investigate developmentally regulated SUMOylation. We predicted a developmental increase in SUMOylation during late conjugation based on the extensive genome remodeling in the developing macronucleus (anlagen) ofTetrahymena thermophila. Immunoblotting of cell lysates from vegetative and mating cells using anti-SUMO antibodies revealed distinct developmental differences and an increased signal correlated with formation of the anlagen. Immunofluorescence of mating Tetrahymena cells with the same antibody …

Profiling Gene Expression During Early Gametophyte Development And Sex Determination In Ceratopteris Richardii, Nadia Atallah

Open Access Dissertations

In the fern Ceratopteris richardii, every spore has the potential to develop as either a male or hermaphroditic gametophyte. Gametophyte sex is determined by a GA-like pheromone (ACE) that is secreted by hermaphrodites approximately 6 days after spore inoculation and induces male development in other juvenile gametophytes. Our goal is to better understand the genetic and molecular mechanisms involved in sex determination and to identify sex determination genes in Ceratopteris. RNA-Seq was used to create de novotranscriptome assemblies from gametophytes grown, with or without ACE, during the time that their sex is determined, and from male gametophytes in early …

Biochemical Investigation Of The Ubiquitin Carboxyl-Terminal Hydrolase Family, Joseph Rashon Chaney

Open Access Dissertations

The proteasome is the machinery in eukaryotic cells that degrades protein and recycles the amino acids. Protein degradation is a highly regulated process which starts by the attachment of chains of ubiquitin, which serves as a tag that marks a protein for degradation. This function involves the work of several proteins at the proteasome that work either as ubiquitin chaperones, ubiquitin binders or cleave ubiquitin from the protein that is to be degraded. As this is a highly regulated process, various irregularities can have deleterious effects including the onset of disease, including cardiovascular, cancer, and neurological. ^ The focus of …

Beta-Lactam Antimicrobial Dosing Optimization In Obese Patients Compared To Non-Obese Patients Using Population Pharmacokinetic/Pharmacodynamic Approach, Eun Kyoung Chung

Open Access Dissertations

Obesity is a significant global health problem and has been associated with altered pharmacokinetics and pharmacodynamics of many drugs. However, little is known regarding the effect of obesity on the pharmacokinetics and pharmacodynamics of many broad-spectrum, beta-lactam antibiotics such as piperacillin/tazobactam, meropenem, and cefepime. The objective of this study is to evaluate the population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam, meropenem, and cefepime in hospitalized obese patients in order to determine dosing regimens that provide similar exposures between obese and non-obese patients. ^ For piperacillin/tazobactam, a retrospective analysis was conducted using prospectively collected serum concentration-time data from two previous studies (Study …

Biology And Ecology Of Bigheaded Carp In An Invaded Ecosystem, Alison Adele Coulter

Open Access Dissertations

Globally, the homogenization of species has become a threat to biodiversity. As species are transported around the world, a portion of these species, released intentionally or accidentally, may become invasive and can produce negative impacts. Great effort has been invested into early identification and prevention of invasions as these are considered less expensive than managing an invasion. Unfortunately, species may exhibit varying characteristics across ecosystems, and so their behavior and potential survival in a new environment may be difficult to predict. Therefore, I examined trends in the biology and behavior of invasive fishes, including the plasticity surrounding these and how …

Development Of Experimental And Instrumental Systems To Study Biological Systems, Amanda J Hemphill

Open Access Dissertations

Chapters 1-4 of this thesis describes the development of an experimental system to measure diffusion-limited reaction kinetics in a biological environment. About 100 years ago, the relationship between reaction rate and diffusion in homogenous solution, ie water or buffer, was described as a linear relationship by Smoluchowski. Applying this theory naively would suggest that since the diffusion coefficients drop by factors of 4-100 then the rates of reaction would drop by the same amount. However, recent theory and simulations suggest that this does not hold. Even though biological diffusion coefficients drop to 0.1-20% of that in buffer, these recent studies …

Role Of Syk In The Regulation Of Cytoskeleton And Stress Granules In Breast Cancer, Mariya Krisenko

Open Access Dissertations

The Syk protein-tyrosine kinase, a well-characterized modulator of immune recognition receptor signaling, also plays important, but poorly characterized, roles in tumor progression, acting as an inhibitor of cellular motility and metastasis in highly invasive cancer cells. Multiharmonic atomic force microscopy (AFM) was used to map nanomechanical properties of live MDA-MB-231 breast cancer cells either lacking or expressing Syk. The expression of Syk dramatically altered the cellular topography, reduced cell height, increased elasticity, increased viscosity, and allowed visualization of a more substantial microtubule network. The microtubules of Syk-expressing cells were more stable to nocodazole-induced depolymerization and were more highly acetylated than …

Genetic Analysis Of Nitrogen Remobilization And Kernel Compositon In Zea Mays L. And Sorghum Bicolor (L.) Moench, Raymond S Lindsey

Open Access Dissertations

Genetic Analysis of Nitrogen Remobilization and Kernel Composition in Zea Mays L. and Sorghum Bicolor (L.) Moench. Major Professor: Mitchell Tuinstra. Modern maize (Zea mays L.) production relies heavily on nitrogen fertilization for high productivity. Over-application of nitrogen fertilizers in cropping systems can have detrimental economic and environmental effects. For this reason, improving Nitrogen Use Efficiency (NUE) is a major goal of breeders and producers. Nitrogen Utilization Efficiency (NUtE) is one component of NUE, and the most important component under N-limited conditions. In this study we examined the genetic controls of the timing and preferential canopy position of leaf N …

Investigation Of Dried Distillers Grains With Solubles (Ddgs) Susceptibility To Red Flour Beetle (Tribolium Castaneum (Herbst)) Infestation, Mahsa Fardisi

Open Access Dissertations

Protecting livestock feed from insect infestation is a common challenge that feed facility managers and farmers have to deal with. It becomes an issue of importance because insect infestation degrades feed quality and quantity. Dried Distillers Grains with Solubles (DDGS) is added to livestock feed because of its high protein content. As DDGS usage in animal feed increases, understanding the susceptibility of DDGS, when mixed with livestock feed, to insect infestation is necessary for safe feed storage. This research addressed four questions. The first looked at the susceptibility of DDGS, when stored as a raw ingredient, to Tribolium castaneum (Herbst) …

The Impact Of Stress History Of Deformable Dry Granules On The Mechanical Properties Of Tablets, Biplob K Mitra

Open Access Dissertations

A mechanistic understanding of the relationship among the granule composition, individual granule property, downstream robust processing, and the final tablet attributes is critical for rational development of a quality tablet. However, in the dry granulation literature, milled granules that are polydisperse in solid fraction, size, and shape are extensively used for compaction studies. Thus, the effect of an individual granule property or an individual component on the compaction properties of dry granules was not adequately separated. To advance the mechanistic understanding of the effect of dry granulation on tensile strength of tablets, individual granule properties such as size, solid fraction, …

Structural And Biophysical Analysis Of The Proteasomal Deubiquitinase, Uch37, Marie Elizabeth Morrow

Open Access Dissertations

Ubiquitin carboxyl-terminal hydrolase 37, or UCH37, is a deubiquitinating enzyme associated with the 26S proteasome, the primary protein degradation machinery in eukaryotic cells. UCH37 is responsible for the disassembly of polymeric ubiquitin chains, or polyubiquitin, which have been ligated onto proteins in order to target them for degradation. The 26S utilizes two associated deubiquitinating enzymes, UCH37 and USP14, and one intrinsic, Rpn11, to remove polyubiquitin chains from substrate proteins as they are unfolded and translocated into the proteolytic core of the proteasome, where proteins are cleaved into small peptides and then released for recycling by the cell. UCH37 associates with …

Communication, Home Bias And Social Capital, Sharon Raszap Skorbiansky

Open Access Dissertations

This dissertation consists of three essays on the effects of communication, home bias and social capital. The first study analyzes three different laboratory treatments that determine if policies that introduce and improve communication are beneficial to a market. The control treatment has no communication. Then, two different types of communication mechanisms are introduced: cheap communication, where subjects are able to lie, and truthful communication, where only honest messages may be sent. The results demonstrate that truthful communication dramatically improves subjects' ability to trade efficiently, ultimately leading to higher social surplus and lower income inequalities. Cheap communication does not produce the …