Life Sciences Commons^™

Sex Differences In Stroke Recovery: Synaptic Proteins And The Growth Inhibitory Protein Nogo A, Vincent Joseph Borkowski

Dissertations

Ischemic stroke is a major world-wide health problem, resulting in death and disability especially in the older population. A sex difference exists in functional recovery post-stroke, with post-menopausal women having worse functional outcome as compared to age-matched men. Although the mechanisms underlying this sex difference are not entirely clear, it is recommended that any potential therapy for stroke recovery be tested in pre-clinical models including both male and females in order to determine the efficacy of the proposed treatment on the entire population. We have reported a novel therapy to enhance brain plasticity and improve functional recovery after stroke in …

Critical Role Of C-Jun N-Terminal Kinase Signaling In Binge Alcohol-Driven Atrial Arrhythmic Remodeling, Jiajie Yan Yan

Dissertations

Holiday Heart Syndrome (HHS) is cardiac arrhythmia induced by binge alcohol consumption, a drinking pattern affects 38 million adults in our society. Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia in HHS and causes significant morbidity and mortality. Despite the intensive prevention effort nationwide, the binge drinking population keeps rising. However, no effective treatment strategies are available for binge drinking induced AF due to the unknown underlying mechanisms. In this thesis, I aim to elucidate the mechanisms of binge alcohol-promoted atrial arrhythmogenicity by using a mouse model of repeated binge alcohol exposure established in the Ai Lab.

The Ai …

The Amino Terminal Region Of Cardiac Myosin Binding Protein-C Is Necessary For Cardiac Function, Thomas Lawrence Lynch

Dissertations

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that has been suggested to regulate cardiac contraction via its amino terminal (N’) region. Following ischemic injury to the heart, cMyBP-C is cleaved into a predominant N’ fragment consisting of domains C0 through C1 and the first 17 residues of the M-domain that is referred to as C0-C1f. However, the necessity of the N’-C0-C1f region of cMyBP-C in regulating cardiac function in vivo has not been elucidated. I hypothesized that the N’-C0-C1f region of cMyBP-C is critical for normal cardiac function in vivo. To test this hypothesis, transgenic (TG) mice …

Inhibition Of B Lymphopoiesis By Adipocytes And Myeloid-Derived Suppressor Cells, Domenick Kennedy

Dissertations

B lymphopoiesis declines with age in humans, mice, and rabbits. Impaired B lymphopoiesis correlates with increased fat in the bone marrow (BM), suggesting that adipocytes negatively regulate this process. In fact, adipocyte factors were found to inhibit B cell development in BM cultures.

Our goal was to understand the mechanism by which adipocytes inhibit B cell development. Through culturing mouse BM cells on OP9 stromal cells in the presence of adipocyte-conditioned medium (ACM), we found that adipocytes promote the accumulation of CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs). These cells were not simply bystanders, as we report for the first time that …

Mechanism By Which Commensal Bacteria Limit Inflammation, Mallory Paynich

Dissertations

Trillions of bacteria live within the gastrointestinal tract and are critical for maintaining intestinal homeostasis; however, the mechanisms utilized by specific bacterial molecules to contribute to homeostasis are not well understood. We utilize a mouse model in which a single oral dose of the probiotic, Bacillus subtilis, protects mice from acute colitis induced by the enteric pathogen Citrobacter rodentium. Our goal is to elucidate the mechanism by which B. subtilis prevents inflammation.

We identified exopolysaccharides (EPS) to be the active molecule of B. subtilis, and a single dose of EPS protects mice from disease. EPS binds F4/80+CD11b+ peritoneal macrophages, and …

Monocyte-Induced Regulatory T Cell Differentiation, Jessica Genevieve Lee

Dissertations

Immediately after birth, thousands of foreign antigens challenge the newborn immune system. Many of the invaders are harmless, such as food, pollen, and beneficial bacteria. Newborns have a tolerant immune system that keeps them from developing inflammation or allergies to these new antigens. In utero, this immunoregulatory tendency is important for establishing tolerance to self and maternal antigens. Multiple processes contribute to fetal tolerance, including clonal deletion, anergy, changes in antigen presenting cells (APCs), and the generation of regulatory T cells (Tregs). However, the mechanism(s) of fetal Treg differentiation and the specific APCs required are unknown.

Our lab has previously …

Prevalence And Diversity Of The Haemosporidian Blood Parasite Leucocytozoon In Sub-Saharan African Birds, Heather Skeen

Master's Theses

Our knowledge of avian Haemosporidian parasites has increased dramatically with the advent and increased used of molecular technologies. Yet Leucocytozoon, a common avian parasite, remains relatively understudied. Haemosporidian parasite diversity and prevalence has been shown to be dependent on several factors, including host family and habitat, on a microecological scale. In this study I screened 3,375 birds from sub-Saharan Africa for the presence of Leucocytozoon and demonstrate that the patterns of prevalence and diversity continue at a macroecological scale. Using molecular data, I found that the prevalence of Leucocytozoon varied between sampling areas from 3.9% to 62.64% and the diversity …

Predicting Suitable Habitat Decline Of Midwestern United States Amphibians And Quantifying The Consequence Of Declines Using Pond-Breeding Salamanders, Brock Struecker

Master's Theses

With current declines of vertebrate taxa meeting or exceeding those of historic mass extinction events, there is a growing need to investigate the main drivers of declines. Amphibians are perhaps at greatest risk of global climate change and land-use changes than most other vertebrate classes and also have significant roles in ecosystem processes – combined, this creates a cause for concern. I designed a study that would investigate the effects of current and predicted climate change and land-use changes on amphibians using species distribution models and a field study to identify the potential consequences of amphibian species declines by investigating …

Lactobacillus Crispatus Produces A Bacteridical Molecule That Kills Uropathogenic E. Coli, Katherine Diebel

Master's Theses

As many as 1 in 2 women will have at least one urinary tract infection (UTI) in their lifetime. UTIs can cause complications in pregnancy and decrease quality of life, and their treatment and prevention are expensive. Uropathogenic E. coli (UPEC) is the primary cause of UTI. The probiotic and bactericidal capacities of gut and vaginal Lactobacillus isolates have been studied, but the same attention has not been paid to urinary strains. These urinary isolates of L. crispatus appear to have a greater killing capacity against UPEC and this bactericidal activity does not depend on the cells themselves, consistent with …

Investigation Of A Ubiquitous Spore Surface Protein, Justyna Kordzikowska

Master's Theses

All bacterial spores are comprised of concentric shells. All spores are encased in a layer called the coat. Some spores have an additional layer outside of the coat called the exosporium. Presumably, this morphological variation is an adaptation to variation in the environments in which these species can be found. However, spores from species with and without exosporia can often be found in the same niche. We hypothesize, therefore, that spores with and without exosporia share a common surface protein. Bacillus anthracis possess a well characterized surface protein called BclA. A BclA homologue is also present on the surface of …

Characterization Of Il-22-Producing Cells In The Human Thymus And The Mechanism By Which Il-22 Expression Is Modulated By Thymic Epithelial Cells., Nadine N. Morgan

Master's Theses

Thymic epithelial cells (TECs) are indispensable for T cell development and maturation. Therefore, damages to the thymic epithelial cells are detrimental to thymic function and immune response. In young healthy individuals, TECs have a high regenerative potential and are capable of renewal from serious damage; however, the molecular mechanism of this recovery is unclear. A recent study has shown that IL-22-producing ILCs are present in the mouse thymus and can regenerate thymic epithelial cells following radiation induced injuries. However, it is unknown whether IL-22-producing cells are also found in the human thymus. Thus, the goal of this study is to …

Early Round Goby (Neogobius Melanostomus) Invasion Into Lake Michigan Tributaries And Competitive Interactions With Two Native Benthic Fishes., Margaret Ann Malone

Master's Theses

The round goby is a prolific invasive species and is currently spreading into Great Lake tributary streams. There is a high potential for negative impacts on native benthic fishes in these stream habitats and the aim of this study is to assess the impacts of the round goby on two native darter species in particular (johnny darter and blackside darter). I review the history of round goby invasion in the Great Lakes and summarize hypotheses of the invasive characters of the round goby. Using game theory, I provide a G-function approach to understanding the outcomes of the round goby invasion …

Investigating The Regulatory Mechanisms By Which Arabinose And Sypa Control Biofilm Formation In Vibrio Fischeri, Sheila Paris

Master's Theses

Biofilms are surface-associated microbial communities surrounded by an extracellular matrix. Through biofilm formation, many pathogens and symbionts are able to colonize, survive, and persist in their host. A model system used to study biofilm formation is the symbiotic bacterium Vibrio fischeri, which colonizes its host, the squid Euprymna scolopes. Complex signaling between the squid and the bacteria is essential for the proper regulation of biofilm formation as well as for persistent colonization.

The signal(s) that promote host-relevant biofilm formation are as-yet unknown, but recently it was discovered that the sugar, L-arabinose, serves as a unique signal to promote biofilm formation …

Phosphodiesterase Inhibition As A Mechanism Of Ion Channel Modulation By Celecoxib, Christina Jean Robakowski

Master's Theses

The overall objective of this thesis work is to determine the mechanism by which celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells. The central hypothesis of the project is that celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells through inhibition of phosphodiesterase 4 (PDE4, which catalyzes the breakdown of cyclic adenosine monophosphate (cAMP)), thereby activating a cAMP/protein kinase A (PKA) signaling pathway. The aims of this thesis targeted different points in the cAMP/PKA pathway with pharmacological interventions using whole cell perforated patch clamp electrophysiology and biochemical methods.

The data suggest multiple mechanisms by which celecoxib could …

The Role Of C-Abl Kinase In Hcc Development, Lennox Chitsike

Master's Theses

Hepatocellular Carcinoma is the second most lethal cancer after pancreatic cancer. Unresectable HCC tumors carry a poor prognosis and few treatment options are available. The dismal prognosis is mainly due to limited therapy options and molecularly targeted therapy is deemed as solution. Here, we report a novel role of c-Abl in HCC development. We provide evidence of c-Abl activation in human HCC samples compared to normal liver. Using genetic and pharmacological tools, we show that c-Abl plays a vital role in HCC progression in vitro and in vivo. We have identified Axl as an effector in processes mediated by c-Abl. …

Assessing The Success Of Outreach At Preventing The Movement Of Aquatic Invasive Species In Illinois, Ellen Anne Cole

Master's Theses

Overland transport of recreational boats is the major vector of dispersal for aquatic invasive species among North American waterbodies. These species have large economic and ecosystem impacts, and understanding their movement is essential to understanding the biodiversity and functioning of aquatic ecosystems across the continent. I surveyed Illinois boaters to determine patterns of recreational boat movement and the consistency with which boaters perform actions to prevent the spread of invasive species. Although most boaters perform these actions, a large minority do not and the network for invasive species spread on recreational boats still connects most waterbodies. Next, I interviewed managers …

Chronic Toxicity Of Binary Metal Mixtures Of Cadmium-Zinc And Cadmium-Nickelon Daphnia Magna, Edgar Ramiro Perez

Master's Theses

This study characterizes binary-metal mixture effects of cadmium (Cd2+) + zinc (Zn2+) and Cd2+ + nickel (Ni2+) on Daphnia magna. Although acute studies have shown protective Ni2+ (Traudt et al. 2016) and Zn2+ effects (Meyer et al. 2015) against Cd2+ toxicity, no study has fully characterized a protective effect on D. magna at several endpoints (survival, reproduction, growth, and accumulation) on a chronic study. In this study, the titration design was selected to characterize the 21 day (21-d) chronic effects of the binary-metal mixtures on survival, growth, reproduction, and metal accumulation in D. magna. Using this design, increasing concentrations of …

Regulation Of Gonad Morphogenesis In Drosophila Melanogaster By Broad Complex, Tramtrack And Bric À Brac Transcription Factors, Diane Silva

Master's Theses

During embryogenesis, primordial germ cells (PGCs) and somatic gonadal precursor cells (SGPs) migrate and coalesce to form the early gonad. A failure of SGPs and PGCs to form a gonad with the proper architecture not only affects germ cell development, but also can result in infertility. We have characterized the phenotypes of two genes, longitudinals lacking (lola) and ribbon (rib), required for the coalescence and compaction of the embryonic gonad in Drosophila melanogaster. Both rib and lola are expressed in the SGPs and to a lesser extent in the PGCs of the developing gonad, and genetic interaction analysis suggests these …

Adenovirus Evasion Of Cell-Intrinsic Immunity, Andrew Michael Burrage

Dissertations

Virus cell entry represents one of the earliest opportunities for a host to respond to infection. Understanding the processes of pathogen detection and restriction employed by the host, as well as strategies utilized by the virus itself to evade such processes, is critical in developing therapeutics to counter pathogenesis. Adenovirus (Ad) infections are self-limiting in healthy populations, but can be devastating to individuals with compromised immune systems. Currently, no specific antiviral treatments exist to combat Ad infections in susceptible populations. However, because Ad infections are not severe in healthy individuals, employing replication-defective Ads as vaccine vectors is generally regarded as …

Regulation Of The Subunits Of Hypoxia Inducible Factors By Sprouty2 And Its Impact On Different Biological Processes, Kristin Caroline Hicks

Dissertations

The hypoxia inducible factors (HIF1α, HIF2α, HIF1β) promote transcription of genes that regulate glycolysis and cell survival and growth. Sprouty2 (Spry2) is a modulator of receptor tyrosine kinase signaling and inhibits cell proliferation via different mechanisms. Because of the seemingly opposite actions of the HIF and Spry2 on cellular processes, we hypothesized that Spry2 decreases the protein levels of HIF1α, HIF2α and HIF1β by enhancing the proximity of the HIF subunit to an ubiquitin ligase capable of degrading the subunit. Focusing on HIF1α as a prototypical alpha subunit, in a variety of tumor derived cell lines, Spry2 decreases the protein …

Studies Into The Allosteric Regulation Of Adp-Glucose Pyrophosphorylases, Benjamin Luke Hill

Dissertations

The synthesis of glycogen in bacteria and starch in plants is allosterically controlled by the production of ADP-glucose by ADP-glucose pyrophosphorylase. Using computational studies, site directed mutagenesis, and kinetic characterization, and protein crystallography we found a critical region for transmitting the allosteric signal in the Escherichia coli and A. tumefaciens ADP-glucose pyrophosphorylase. Molecular dynamics simulations and structural comparisons with other ADP-glucose pyrophosphorylases provided information to hypothesize communication pathways that link allosteric and active sites, and this was tested by site-directed mutagenesis and kinetic characterization of the mutant enzymes. In addition, the application of x-ray crystallography enabled the pinpointing of the …

Heart And Sole: The Functional Role Of Fast-Skeletal Myosin Binding Protein-C In Cardiac And Skeletal Muscle, Brian Leei Lin

Dissertations

The goal of my dissertation was to compare and contrast the function of all three major isoforms of Myosin Binding Protein-C (MyBP-C): slow-skeletal, fast-skeletal, and cardiac (ssMyBP-C, fsMyBP-C, and cMyBP-C, respectively), with a focus on the least characterized isoform, fsMyBP-C. Using a variety of ex vivo, in vitro, and in silico methods, my research demonstrated that the N-terminal region of all MyBP-C isoforms bind to actin and shift tropomyosin, thus activating the thin filament during contraction. Furthermore, each isoform differentially activated the thin filament over isoform-specific ranges of Ca2+: slow-skeletal activates at low Ca2+, fast-skeletal activates at higher Ca2+, and …

The Impact Of Altered T Cell Receptor—Peptide-Major Histocompatibility Complex Interactions On Antigen Recognition And T Cell Function, Timothy T. Spear

Dissertations

Adoptive cell transfer (ACT) using T cell receptor (TCR) gene-modified T cells is an exciting and rapidly evolving field. Numerous basic science and clinical studies have demonstrated various levels of feasibility, safety, and efficacy using TCR-engineered T cells to treat cancer and viral infections. Genomic instability of targeted diseases, however, requires effective and safe TCRs to cross-recognize mutated antigens while minimizing on- or off-target toxicities. Thus, improvements to T cell-based therapeutics mandate a broader understanding of the principles governing antigen recognition. This dissertation addresses critical biologic questions evaluating which parameters are most important in facilitating antigen recognition, and how alterations …

Development Of "Inside-Out" Pegylated Crosslinked Hemoglobin Polymers: Novel Hemoglobin-Based Oxygen Carriers (Hboc), Kyle Douglas Webster

Dissertations

The development of an effective blood substitute is urgent due to increasingly common blood shortages, the need to type-match donated blood, and communicable diseases (e.g. HIV) posing risks for blood transfusions around the world. There have been many attempts at creating hemoglobin-based oxygen carriers (HBOC) using a variety of techniques centered around the use of polyethylene glycol (PEG) conjugated to hemoglobin (Hb) tetramers. A novel method, “Inside-Out” PEGylation, has been developed by our lab to produce a polyethylene glycol crosslinked hemoglobin (PEG XL-Hb) polymer. This method utilizes a single PEG backbone that is surrounded by multiple proteins, instead of covering …

The Role Of Foxo Transcription Factors In Alcohol-Induced Deficient Fracture Repair, Philip M. Roper

Dissertations

Proper and complete repair of a bone fracture is essential in quality of life maintenance, but poor healing and fracture malunion are still medically and socially relevant problems. Alcohol abuse impairs normal fracture healing, leading to delayed or incomplete union. This dissertation aims to clarify mechanisms behind this alcohol-induced impaired healing, thereby elucidating potential methods of intervention.

Alcohol-induced oxidative stress has been linked to many morbidities associated with alcohol abuse. This dissertation elucidates a potential mechanism through which alcohol inhibits fracture healing by increasing oxidative stress. Using a rodent model, I found that alcohol exposure decreases fracture callus formation and …

Mechanistic Variations Of The Bronsted Linear Free Energy Relationships For Nonezymatic Nucleotidyl Transfer Reactions, Zheng Zhang

Dissertations

As the essential enzymes in human bodies, DNA polymerases play a significant role in DNA replication, repair, genetic recombination, and reverse transcription. In 1956, the enzyme of DNA polymerase I, also named as Pol I, was discovered by Arthur Kornberg and colleagues. Subsequently, the Noble Committee had decided that the Noble Prize in Physiology or Medicine for 1959 was to be awarded to Kornberg for his excellent original work that describes the DNA replication process whereby the DNA polymerase copies the nucleotide sequence of a DNA template strand. Because of the complex enzyme structure in the DNA polymerase, it is …

A Study Of Immune-Regulation Of Microbiota Supernatant On Macrophage Function, An N. Nguyen

Master's Theses

The diverse human microbial ecosystem colonizes many different body sites. The gastrointestinal (GI) tract, especially, is a major region that that harbors a complex microbial community composed of trillions of commensal bacteria. Interactions between the commensal bacteria and the host immune system begin at birth and continue through the human lifespan. In the gut, commensal bacteria help the host to ensure the maintenance of intestinal homeostasis as well as the mucosal barrier structure through host stimulation of mucus and antimicrobial molecules. The secretion of these host factors functions to inhibit pathogenic invasion and maintain the population of commensal bacteria. The …

Cardiac Calcium Atpase Dimerization Measured By Fluorescence Resonance Energy Transfer And Chemical Cross-Linking, Daniel Blackwell

Dissertations

The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homo-oligomers that increase the catalytic rate of calcium transport. We investigated SERCA oligomerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher molecular weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer (FRET) measurements in cells transiently transfected with fluorescently-labeled SERCA2a revealed that SERCA readily forms homo-dimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation …

The Role Of Microrna In Cardioprotection: Ischemic Preconditioning And Mesenchymal Stem Cell Paracrine Effects, Kristin Luther

Dissertations

Changes in gene expression and protein levels are an important aspect of cardioprotection in which short non-coding RNA known as miRNA may play a key regulatory role. We investigated the functions of several miRNAs in the context of two cardioprotective stimuli, ischemic preconditioning (IPC) and mesenchymal stem cell (MSC) paracrine effects. We hypothesized that downregulation of a set of miRNAs (miR-148a/b, miR-30b, and let-7a*) augments expression of protective heat shock proteins during IPC, and that MSC exosomes transfer miR-21 to cardiomyocytes, resulting in downregulation of pro-apoptotic genes and reduction of infarct size.

IPC increased the level of Hsp70, Hsp90, and …

Aquatic Insect Community Structure And Secondary Production In Southcentral Alaska Streams With Contrasting Thermal And Hydrologic Regimes, Samantha D. Hertel

Master's Theses

Streams along the Copper River Delta, southcentral Alaska, exhibit contrasting thermal and hydrologic variability associated with being primarily groundwater-fed (GWF) or surface water-fed (SWF). Groundwater-fed streams are predictable both thermally and hydrologically year round, whereas SWF streams are unpredictable and exhibit more variable thermal and hydrologic regimes. These differences may strongly influence aquatic insect community structure and secondary production. Four streams, two GWF and two SWF, were sampled twice monthly from late April 2013 through August 2013 and once seasonally in fall (September) and early winter (November). Aquatic insect community structure differed markedly in both hydrologic types. Taxa richness was …