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Adolescent Binge Alcohol Exposure Effects On Heart Structure And Function, Lizhuo Ai
Adolescent Binge Alcohol Exposure Effects On Heart Structure And Function, Lizhuo Ai
Master's Theses
More than 5 million underage Americans report binge drinking at least once per month. While the effects of alcohol consumption on the adult heart have been well studied, the impact to the adolescent heart is almost entirely unknown. Adolescents primarily consume alcohol in a binge pattern, which elevates blood alcohol content (BAC) to 0.08 g/dL within 2 hours. During adolescence the body grows rapidly, and the heart must also grow by cellular hypertrophy to meet this increasing demand. Our goal was to determine the impact of adolescent binge alcohol exposure on the heart, using an outbred rat model. This thesis …
Modulation Of Coxsackievirus Protease Activity By Polyamines, Courtney Noelle Dial
Modulation Of Coxsackievirus Protease Activity By Polyamines, Courtney Noelle Dial
Master's Theses
Coxsackievirus type B (CVB3) is one of the six serotypes of the Coxsackievirus family of non-enveloped, linear, and positive-sense single-stranded RNA viruses. It is a pathogenic enterovirus that belongs to the same genus as the notable pathogen poliovirus. CVB3 can cause a range of illnesses from a fever to gastrointestinal distress but is most noteworthy for the ability to cause viral myocarditis, a swelling of the heart muscle. Coxsackievirus, like all RNA viruses, tends to develop mutations rapidly due to its error prone polymerase and lack of proofreading activity. These mutations can be advantageous for the virus, allowing it to …
A Possible Role Of Clostridium Difficile Association With The Gi Tract In Relapsing Clostridium Difficile Infection, Asiyya Ashraf
A Possible Role Of Clostridium Difficile Association With The Gi Tract In Relapsing Clostridium Difficile Infection, Asiyya Ashraf
Master's Theses
Clostridium difficile infection (CDI), caused by the anaerobic spore-former C. difficile, is a major cause of health-care associated morbidity. CDI occurs in individuals that have a disrupted GI tract microbiota, typically in patients who are on antibiotic therapy. After recovery from an episode of CDI, approximately, 15-30% of patients experience relapse of disease. The mechanism of relapse is not well understood. It is plausible for relapse to occur if C. difficile cells and spores associate with the GI tract mucosa during infection and persist after infection. However, little is known about the association of cells and spores with the GI …
Role Of Daxx As A Predictive Biomarker In Breast Cancer, Michelle Lucia Fernandez
Role Of Daxx As A Predictive Biomarker In Breast Cancer, Michelle Lucia Fernandez
Master's Theses
Breast cancer is the most commonly diagnosed form of cancer in women, besides skin cancer, and second only to lung cancer for cause of mortality. It is divided into three subtypes, depending on different molecular or pathologic characteristics, including estrogen or progesterone receptor-positive (ER/PR+), human epidermal growth factor receptor-2-positive (HER2+) and triple negative breast cancer (TNBC). There are several therapies used to target these subtypes, but there is still a chance that the cancer will recur into a more aggressive, resistant form even if the therapies were successful before. This recurrence is believed to be due to the Cancer Stem …
The Role Of Polyamines In Enteroviral Attachment, Thomas Mckenzie Kicmal
The Role Of Polyamines In Enteroviral Attachment, Thomas Mckenzie Kicmal
Master's Theses
Polyamines are small polycationic molecules with flexible carbon chains that are found in all eukaryotic cells. Polyamines are involved in the regulation of many host processes and have been shown to be implicated in viral replication. Depletion of polyamine pools in cells with FDA approved drugs restricts replication of diverse RNA viruses. Viruses can exploit host polyamines to facilitate packaging, transcription, translation, and protease activity but other mechanisms remain largely unknown. Picornaviruses, including Coxsackievirus B3 (CVB3), are sensitive to depletion of polyamines and remain a significant public health threat. We employed CVB3 as a model system to investigate a potential …
Mllt3 Regulates Expression Of Genes Critical To Liver Metabolic Homeostasis, Jonathan Richard Dixit
Mllt3 Regulates Expression Of Genes Critical To Liver Metabolic Homeostasis, Jonathan Richard Dixit
Master's Theses
Hepatic steatosis (fatty liver) is increasingly prevalent in the US, and is characterized by triglyceride accumulation within hepatocytes. This is a direct result of an imbalance between lipid import, export, de novo lipogenesis, and beta oxidation. Hepatic steatosis can also progress to nonalcoholic steatohepatitis (NASH) which is characterized by increased hepatocyte damage, inflammation, and fibrosis. Further progression can lead to liver failure or hepatocellular carcinoma, requiring liver transplant or causing death. Our lab recently created Mllt3 conditional whole body knockout mice. These mice developed hepatic steatosis and NASH following Mllt3 deletion. MLLT3 is a master gene regulator that is part …
Habitat Associations And Community Interactions Of Non-Native Species In The Southern Basin Of Lake Michigan, Erin O'Shaughnessey
Habitat Associations And Community Interactions Of Non-Native Species In The Southern Basin Of Lake Michigan, Erin O'Shaughnessey
Master's Theses
Non-native crayfishes, mollusks, and macrophytes can have large impacts on biodiversity and damage ecosystem services in freshwaters. In 2015 we discovered an established population of the globally widespread invader red swamp crayfish (Procambarus clarkii) in the North Shore Channel of the Chicago Area Waterway System. This population overlaps with a population of rusty crayfish (Faxonius rusticus), a previous invader that is widely distributed and usually the dominant crayfish species across the Great Lakes region. I studied the interactions between these two species while directly competing over shelter and food. In the field, each species was studied to determine the rate …
Dissecting A Role For Polyamines In Rift Valley Fever Virus Infection, Vincent Mastrodomenico
Dissecting A Role For Polyamines In Rift Valley Fever Virus Infection, Vincent Mastrodomenico
Master's Theses
Bunyaviruses are emerging viral pathogens that cause encephalitis, hemorrhagic fevers, and meningitis. Rift Valley fever virus is a particularly devastating bunyavirus, infecting both humans and livestock with significant morbidity and mortality. By coordinating several host and viral processes Rift Valley fever virus is able to produce infectious virions. Polyamines are small, positively-charged host-derived molecules that play diverse roles in human cells and in infection. We previously demonstrated that polyamines are crucial for RNA viruses; however, the mechanisms by which polyamines function remain unknown. Here, we investigated polyamines' role in the replication of the Rift Valley fever virus (vaccine strain MP-12). …
Microplastic In Aquatic Food Webs: Museum Specimens And Ingestion Experiments Reveal Controls On Microplastic Ingestion By Freshwater Fish, Loren Hou
Master's Theses
Plastic is pervasive in modern economies and ecosystems. Early research suggests freshwater fish commonly ingest microplastic (particles < 5 mm), which may influence fish digestive tissues, but no studies have examined historical patterns in microplastic consumption or rates of microplastic retention in fish. We measured microplastic in digestive tissue of specimens collected and preserved over the last century (Field Museum, Chicago). We selected Micropterus salmoides (largemouth bass), Notropis stramineus (sand shiner), Ictalurus punctatus (channel catfish), and Neogobius melanostomus (round goby) because each was well represented in the museum collection, with specimens from urban rivers. Specimens from 1900-2018 showed increases in microplastic concentration from the 1950's to present. in a second project, we collected round gobies from Lake Michigan in Chicago to conduct feeding experiments to measure microplastic ingestion and retention rates. the majority of microplastic was excreted within 72 hours of ingestion. Results will aid in understanding ecological interactions of microplastic and freshwater fish, informing further work on the movement of microplastic in aquatic food webs.
Binge Alcohol Drinking Exacerbates Ulcerative Colitis Flare, Abigail Cannon
Binge Alcohol Drinking Exacerbates Ulcerative Colitis Flare, Abigail Cannon
Dissertations
Inflammatory Bowel Disease (IBD) remains a prominent medical concern affecting over 1.4 million people in the U.S. One of the most common forms of the disease is ulcerative colitis (UC), and UC patients will often head doctor's advice to refrain from drinking alcohol. However, whether this phenomenon of alcohol exacerbating UC symptoms occurs is still unknown, which necessitated the generation of a mouse model of UC and binge alcohol. Therefore, we examined a range of DSS concentrations (2-4%) and 2 alcohol paradigms in C57BL/6 mice. Mice receiving 2% DSS ad libitum for five days with a three-day alcohol binge had …
Regulation Of Acetyl Phosphate-Dependent Acetylation And Identification Of Novel Lysine Acetyltransferases In Escherichia Coli, David George Christensen
Regulation Of Acetyl Phosphate-Dependent Acetylation And Identification Of Novel Lysine Acetyltransferases In Escherichia Coli, David George Christensen
Dissertations
Over billions of years, organisms have organized chemical reactions into metabolic pathways to sustain life. However, metabolic substrates can undergo many uncatalyzed, extra-metabolic reactions. Acetyl phosphate (AcP), an intermediate of the acetate fermentation pathway in E. coli, is one such metabolite that has been shown to non-enzymatically acetylate hundreds of proteins. This diverse set of targets suggests that acetylation could be a way for the cell to sense its nutritional status and regulate protein activity accordingly. However, how E. coli regulates acetylation, if at all, is unknown.Previous work showed that acetylation becomes pronounced in stationary phase cells. I determined that …
Membrane Microdomains As Platforms For Extra-Cellular Fusions, Michael Hantak
Membrane Microdomains As Platforms For Extra-Cellular Fusions, Michael Hantak
Dissertations
Life requires biological membranes. Membrane-enclosed compartments separate and unite through dynamic fission and fusion reactions. These are catalyzed processes that are central in organismal biogenesis. This dissertation focuses on extracellular membrane fusions, which are central to several processes. (1) Enveloped viruses enter cells through membrane fusions. (2) Extracellular vesicles (EVs) also deliver molecules into cells through membrane fusions. (3) Entire cells also fuse together, generating fertilized zygotes, skeletal muscles, and giant cell macrophages.Mechanisms of extracellular membrane fusion are poorly understood. This dissertation aimed to further define these mechanisms. We focused on regulatory cofactors, including tetraspanins, transmembrane proteins that cluster into …
Structure-Guided T Cell Receptor Mutations That Alter Antigen Specificity, Cross-Reactivity, And Polyfunctional Phenotypes In Gene-Modified T Cells, Kendra Foley
Dissertations
Adoptive cell transfer of T cell receptor (TCR) gene-modified T cells targeting specific tumor antigens is currently in clinical trials for patients with advanced malignancies. Despite the clinical responses, there are still hurdles to be overcome in achieving an effective and safe therapy. One of the limitations in the success of this type of therapy is the potential for cross-reactivity and unanticipated off-target reactivity which could lead to autoimmunity. Adverse events encompassing these "off-target, off-tumor" cross-reactivities leading to autoimmunity have been seen in patients in different clinical trials. Here, we demonstrate a novel approach to improve antigen specific reactivity and …
Staphylococcus Aureus Evasion Of The Innate Immune System, James Paul Grayczyk
Staphylococcus Aureus Evasion Of The Innate Immune System, James Paul Grayczyk
Dissertations
Upon entry into the host, pathogens must overcome innate immunity in order to cause disease. The innate immune system represents a fast-acting initial line of defense to prevent infection. In order to withstand innate defenses, bacterial pathogens like the Gram-positive bacterium Staphylococcus aureus, produce a wide array of virulence factors that can inhibit innate immune cell recruitment and antimicrobial activity, or directly target and kill phagocytic leukocytes thereby facilitating pathogenesis. Infection with S. aureus can cause disease in virtually any tissue site and is a significant burden to human health. In this dissertation, we sought to understand how S. aureus …
Determination Of Transforming Growth Factor-Β Signaling Targets In Activated T Cells, Ramiah Jacks
Determination Of Transforming Growth Factor-Β Signaling Targets In Activated T Cells, Ramiah Jacks
Dissertations
T lymphocytes are a critical component of the adaptive immune system and their responses in pathogenic and steady state conditions require strict regulation. One mechanism involved in this regulation is Transforming Growth Factor-β (TGF-β) signaling. TGF-β can act on activated T cells to facilitate the differentiation of TGF-β dependent T helper subsets or the suppression of T cell activation and proliferation. However, the molecular mechanism(s) by which TGF-β signaling controls T cell differentiation vs T cell suppression remain poorly understood.TGF-β signaling is propagated by initially binding to the TGF-β type II receptor, which subsequently activates TGF-β type I receptor (TGF-βRI) …
Aerococcus Urinae: Establishing The Pathogenesis Of An Emerging Uropathogen, Evann E. Hilt
Aerococcus Urinae: Establishing The Pathogenesis Of An Emerging Uropathogen, Evann E. Hilt
Dissertations
Urinary tract infection (UTI) is the world's most common bacterial infection. Much is known about the infectious process (pathogenesis) of a few of the bacteria that cause these infections, especially E. coli. Unfortunately, the pathogenesis of E. coli and other uropathogenic bacteria was explored almost exclusively in the belief that the bladder is supposed to be sterile. Our recent evidence, however, debunks this dogma. We used modern methods to reveal diverse bacterial communities in the bladders of adult women. These communities differ in women with and without lower urinary tract symptoms (LUTS), including UTI and urinary incontinence (UI). Many bacteria …
Modulating The Tumor Microenvironment To Induce Cross-Priming For Cancer Immunotherapy, Erica Fleming-Trujillo
Modulating The Tumor Microenvironment To Induce Cross-Priming For Cancer Immunotherapy, Erica Fleming-Trujillo
Dissertations
Adoptive cell transfer (ACT) using T cells engineered to express tumor-specific T cell receptors (TCR) holds great promise in treating cancer patients. ACT involves the in vitro generation of large numbers of tumor-specific T cells, which are then administered back to the patient, to establish an in vivo response and effective tumor control. Our lab conducted a phase I clinical trial in which metastatic melanoma patients received systemic infusions of autologous T cells transduced to express a tyrosinase-specific TCR (TIL 1383I). We observed tumor regression in one of seven patients and the development of vitiligo, indicative of T cell-mediated killing …
Alcohol Induced Bacterial Changes In The Setting Of Colitis, Paulius Kuprys
Alcohol Induced Bacterial Changes In The Setting Of Colitis, Paulius Kuprys
Dissertations
Inflammatory bowel diseases (IBD) affect a large number of individuals around the world. This group of diseases is largely composed of two types: Crohn's disease (CD) and ulcerative colitis (UC). Upon development of IBD, patients experience cyclical episodes of inflammation, known as flares. Flare induction appears to arise from multiple factors, which can also vary on a person-to-person basis. Alcohol has been shown to trigger IBD flares and onset, though the underlying mechanism has not been established.Defining factors of the IBD intestinal environment include an altered microbiome, bacterial infiltration of the intestinal epithelium, and increased leakage of proinflammatory bacterial byproducts. …
Protection From Staphylococcus Aureus Bloodstream Infection By Probiotic Exopolysaccharide, Wonbeom Paik
Protection From Staphylococcus Aureus Bloodstream Infection By Probiotic Exopolysaccharide, Wonbeom Paik
Dissertations
Staphylococcus aureus is known to cause severe systemic infection with high mortality rates. Antibiotics are the only approved therapy for patients, but the widespread prevalence of antibiotic resistant strains limits treatment efficacy, and many patients succumb to the disease. Many probiotic agents are commercially available, but the mechanisms by which they benefit are not known. Understanding these mechanisms will help develop novel therapeutics that can improve healthcare, including systemic infections by S. aureus. Bacillus subtilis is a probiotic bacterium that produces an exopolysaccharide (EPS) that induces anti inflammatory macrophages (MΦ). We tested if EPS could be used for systemic S. …
Daxx As A Restrictor Of Tumor Initiating Cell Survival In Er+ Breast Cancer And Its Therapeutic Implications, Daniel Seamus Peiffer
Daxx As A Restrictor Of Tumor Initiating Cell Survival In Er+ Breast Cancer And Its Therapeutic Implications, Daniel Seamus Peiffer
Dissertations
Breast cancer overall is the second most common cause of cancer related death in women, with one in eight women being diagnosed during their lifetime. Breast cancer itself is divided into subtypes based on the expression levels of the hormone receptors including the estrogen receptor (ER) and the progesterone receptor (PR), as well as expression of the growth factor receptor epidermal growth factor receptor 2 (HER2). ER+ breast cancer is the most common breast cancer diagnosis, and these tumors are defined as being initially dependent on activation of the receptor for growth. Based on this, targeted endocrine therapies (ETs) have …
Assessing The Temporal Dynamics Of The Lower Urinary Tract Microbiota And The Effects Of Lifestyle, Travis Kyle Price
Assessing The Temporal Dynamics Of The Lower Urinary Tract Microbiota And The Effects Of Lifestyle, Travis Kyle Price
Dissertations
Urinary tract infections (UTIs) are among the most common bacterial infections in humans, accounting for $3.5 billion in health care expenditures yearly in the United States alone. Yet, treatments for UTI have seen little innovation over the past decade. As demonstrated in other body sites, such as the vagina and gastrointestinal (GI) tract, acute and infectious diseases often have indirect microbial contributions which serve as intriguing new targets for therapies. The recent discovery of the existence of a resident community of bacteria (i.e., microbiota) in the bladders of both women and men, represents a novel avenue for targeting UTIs. However, …
Generating Biologic And Genetic Research Tools To Investigate Serotype I Feline Coronaviruses, Robert Christian Mettelman
Generating Biologic And Genetic Research Tools To Investigate Serotype I Feline Coronaviruses, Robert Christian Mettelman
Dissertations
Serotype I feline infectious peritonitis virus (FIPV) is an alphacoronavirus of high veterinary importance due to the 99% mortality rate observed in cats. Since the 1980s, robust experimentation on these viruses has been limited by availability of culturable pathogenic strains, few permissive cell lines, and a lack of standardized methods to study their basic virology. These complications have resulted in variable and conflicting literature reports, have slowed study of clinical strains and hindered effective vaccine design. The goal of this dissertation was to develop a laboratory "toolbox" containing standardized methods, permissive cell lines and genetic techniques to alleviate some of …
Yczr, A New Case Of Plp-Dependent Mocr/Gabr Type Transcription Regulator In Klebsiella Pneumonia, Yuanzhang Zheng
Yczr, A New Case Of Plp-Dependent Mocr/Gabr Type Transcription Regulator In Klebsiella Pneumonia, Yuanzhang Zheng
Dissertations
Increasing number of genes encoding PLP-dependent transcription regulators, MocR/GabR type regulators, have been identified in various bacterial genomes. However, only a handful of them, including MocR, PdxR and GabR have been studied experimentally. They control different aspects of the bacterial metabolism. Only GabR has reported crystallographic structures. MocR/GabR regulators possess a chimeric structure consisted of a WHTH DNA binding domain and an Aminotransferase-like regulation domain, which can bind PLP as an effector in transcription regulation. Such a chimeric construct presents an interesting case in molecular evolution. The regulation domains of All MocR/GabR type regulators loss their catalytic capacity during evolution …
Elucidation Of The Molecular Mechanisms Of Electrically-Induced Cardioprotection, Anne Elizabeth Roessler
Elucidation Of The Molecular Mechanisms Of Electrically-Induced Cardioprotection, Anne Elizabeth Roessler
Dissertations
Cardiovascular disease is the leading cause of death worldwide. A myocardial infarction (MI), commonly known as a heart attack, is a major event in cardiovascular disease characterized by reduced blood flow to the heart. The ischemia and reperfusion (I/R) injury associated with an MI results in a region of dead tissue in the heart called an infarct, the size of which influences patient prognosis. In the 1980s, it was discovered that short, non-lethal episodes of I/R, termed ischemic preconditioning (IPC), can protect the heart against a subsequent MI. Ischemic preconditioning demonstrated the phenomenon of endogenous cardioprotection. Cardioprotection has great potential …
Characterization Of The Effects Of Sex And Estrogen Receptor Signaling On Antigen-Specific T Cells For Immunotherapy, Flor Cecilia Navarro Negredo
Characterization Of The Effects Of Sex And Estrogen Receptor Signaling On Antigen-Specific T Cells For Immunotherapy, Flor Cecilia Navarro Negredo
Dissertations
Adoptive cell transfer (ACT) immunotherapy using antigen (Ag)-specific T cells is partially effective treating several malignancies but numerous challenges remain in order to improve its therapeutic potential. The roles of host factors, such as sex hormone receptor signaling, that can affect the T cell anti-tumor function remain understudied. The work performed in this dissertation characterized the role of estrogen signaling on T cell function in vitro, and during ACT immunotherapy against hepatocellular carcinoma (HCC) in vivo. Estrogen signaling through ERa enhanced the expression and secretion of Type I effector cytokines including IFNg, TNFa, and Granzyme B in male and female …
Longitudinal Urinary Microbiome Studies: A Need To Transition To Voided Urine, Baylie Hochstedler
Longitudinal Urinary Microbiome Studies: A Need To Transition To Voided Urine, Baylie Hochstedler
Master's Theses
It is now established that the bladder is not sterile; it contains communities of microbes (microbiota). While the healthy bladder microbiota have been defined using expanded quantitative urine culture (EQUC) and urines obtained by transurethral catheterization (TUC), longitudinal and population studies have not previously been possible. These studies cannot be done using TUC urines, as it would be impractical to catheterize participants daily. Instead, we must transition to using voided urines.In order to make this switch, we have addressed three main issues raised by using voided urine. First, we showed that EQUC out performs standard urine culture on voided urines …