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Articles 1 - 27 of 27
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The Characterization Of Inflammatory Extracellular Vesicles, Barak Balva
The Characterization Of Inflammatory Extracellular Vesicles, Barak Balva
Master's Theses
One of the driving factors behind innate immunity is the early response of inflammation. While beneficial in controlling infections, when uncontrolled it can lead to a plethora of disorders. Thus, it is essential to understand the driving factors behind inflammation. a cell's ability to recycle, discard, or transfer proteins is integral for survival and intercellular communication. It has been appreciated that inflammatory components, such as caspase-1, play a huge role in driving protein secretion. Thus, inflammation also plays a role in the distribution of proteins released from cells. These proteins are released via non-conventional secretory pathways, and our lab is …
Investigating The Role Of Hypusine In Viral Translation And Infection, Jeremy Joseph Esin
Investigating The Role Of Hypusine In Viral Translation And Infection, Jeremy Joseph Esin
Master's Theses
Polyamines are small, positively charged, molecules found in eukaryotic cells with roles in cellular function and viral infection. in previous work we have shown RNa viruses, including bunyaviruses, to be sensitive to polyamine depletion, but exact mechanisms are unknown. Bunyaviruses are emerging pathogens that cause encephalitis, hemorrhagic fevers, and meningitis. Rift Valley Fever Virus is a bunyavirus that infects both humans and livestock with severe mortality and morbidity. in previous work done with Rift Valley Fever Virus polyamine depleted results in noninfectious interfering particles without affecting the shape or size of the particles. Here, I investigate a specific metabolic pathway …
Transforming Growth Factor Beta Suppression Of Cd8+ T Cell Proliferation, Shena Geisinger
Transforming Growth Factor Beta Suppression Of Cd8+ T Cell Proliferation, Shena Geisinger
Master's Theses
Transforming Growth Factor Beta (TGF-beta) is highly suppressive to both CD4+ and CD8+ T cell proliferation and function. in tumor microenvironments, TGF-beta has been described as immune suppressive, particularly to CD8+ T cells, however, the molecular mechanism behind how TGF-beta signaling controls T cell growth is not fully understood. Here, we report that TGF-beta inhibits CD8+ T cell proliferation and reduces expression of the CARMA1/BCL10/MALT1 (CBM) signalosome complex in activated CD8+ T cells. the CBM signalosome is an essential scaffold that forms after T cell receptor (TCR) stimulation, leading to the activation of NF-kB and AP-1. This observed reduction in …
The Effect Of Plastic On Leaf Litter Breakdown In Urban Streams, Lisa Haneul Kim
The Effect Of Plastic On Leaf Litter Breakdown In Urban Streams, Lisa Haneul Kim
Master's Theses
The plastic component of anthropogenic litter (AL) is an emerging ecological concern and has been a focus of research, as it is long-lived, mobile, interacts with physical and chemical components of aquatic ecosystems, and breaks down into smaller pieces (i.e., microplastic, <5mm particles). Rivers are considered a major source of plastic to oceans, but little is known about plastic's abundance, distribution, and effects on ecological processes in urban streams. Previous studies report plastic is abundant in freshwater systems, especially in naturally occurring debris dam structures and overhanging vegetation which accumulate high quantities of AL, especially plastic items (i.e. bags, wrappers, packaging material), along with leaf litter and other coarse particulate organic matter. in temperate, forested streams, leaf litter is a critical food source and plays an essential role in the stream food web. the rate at which leaves break down is affected by many variables such as hydrology, water chemistry, and macroinvertebrate and microbial communities. We predicted that plastic accumulation along with leaf litter can slow leaf breakdown by reducing diversity and abundance of microbial decomposers, as well as macroinvertebrate consumers. We measured leaf breakdown, and characterized macroinvertebrate and microbial (i.e., bacterial, fungal, algal) communities in 3 litter bag treatments: leaves alone, plastic alone, and leaves mixed with plastic. Although plastic did not reduce leaf breakdown rates or have a significant effect on macroinvertebrate consumer communities, it showed distinct microbial communities compared to leaf substrates. Results will provide a new understanding of how plastic and microbial communities interact, and set the framework for future studies to look at microbial succession and macroinvertebrate diversity on other synthetic substrates in freshwater systems.
Zika Virus Inactivates Polyamine Catabolism Via Alternative Splicing To Enhance Infection, Marion Lea Graham
Zika Virus Inactivates Polyamine Catabolism Via Alternative Splicing To Enhance Infection, Marion Lea Graham
Master's Theses
During viral infection, the virus and host must compete for resources inside the cell. One of these resources is polyamines. Polyamines are small, positively charged molecules that are found in all eukaryotic cells. They play a key role in several cellular functions including growth and proliferation, transcription and translation, and membrane stability. Viruses also rely polyamines for productive replication, utilizing them during DNA/RNa polymerization, nucleic acid packaging, and protein synthesis. in response to a virus infecting a host cell, the host cell will begin to regulate polyamine levels as a way to combat the infection. Polyamine levels are regulated by …
Investigating Dispersal Ability To Infer Diversification In The Birds Of Madagascar, Robert D. Lauer
Investigating Dispersal Ability To Infer Diversification In The Birds Of Madagascar, Robert D. Lauer
Master's Theses
The objective of this study was to investigate whether dispersal ability, as measured by a proxy of hand-wing index 2, influenced diversification of the birds of Madagascar at two scales. Madagascar is home to several avian lineages that have diversified greatly while other lineages are only represented by a single species. a key question in evolutionary biology is why some of these lineages diversified while others did not. One way to address this is to examine what features of these lineages promotes their diversification. Recent studies have focused on the relative importance of dispersal ability to diversification at the continental …
Optimizing Gene Expression Prediction And Omics Integration In Populations Of African Ancestry, Paul Chukwuebuka Okoro
Optimizing Gene Expression Prediction And Omics Integration In Populations Of African Ancestry, Paul Chukwuebuka Okoro
Master's Theses
Popular transcriptome imputation methods such as PrediXcan and FUSIon use parametric linear assumptions, and thus are unable to flexibly model the complex genetic architecture of the transcriptome. Although non-linear modeling has been shown to improve imputation performance, replicability and potential cross-population differences have not been adequately studied. Therefore, to optimize imputation performance across global populations, we used the non-linear machine learning (ML) models random forest (RF), support vector regression (SVR), and K nearest neighbor (KNN) to build transcriptome imputation models, and evaluated their performance in comparison to elastic net (EN). We trained gene expression prediction models using genotype and blood …
Characterization Of Caspase 1 Substrate Specificity Utilizing Luminescent Reporter Constructs, Nicholas Rohlfes
Characterization Of Caspase 1 Substrate Specificity Utilizing Luminescent Reporter Constructs, Nicholas Rohlfes
Master's Theses
Inflammation is the bodies first response to defend itself against foreign pathogens and damage. Cellular sensors are constantly monitoring the body and checking for homeostatic disruption. Microbial pathogens and tissue damage are sensed by pattern recognition receptors (PRRs), which sense pathogen associated molecular patterns and damage associated molecular patterns, termed PAMPs and DAMPs respectively. Within the family of PRRs are sensors that can induce the formation of the multi-protein complex termed the inflammasome following activation. the inflammasome complex is a molecular platform for which caspase 1, a cysteine protease, is incorporated and is responsible for the maturation of pro-inflammatory cytokines …
Enabling The Clinical Detection Of Human Papilloma Virus (Hpv) To Enhance Effective Diagnosis And Research, Jennifer Sackey
Enabling The Clinical Detection Of Human Papilloma Virus (Hpv) To Enhance Effective Diagnosis And Research, Jennifer Sackey
Master's Theses
Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections. There are over 150 different genotypes of HPV. Some cause benign warts, while others cause several types of cancer. Subunit vaccines comprised of the capsid protein from an increasing number of HPV genotypes have been developed; however, the vaccines are prophylactic and are documented to protect against only 9 of the HPV genotypes. Importantly, there are also significant limitations in the clinical detection of HPV. Current clinical tests can only specifically identify HPV16 and HPV18. One of the test also detects 12 of the other high-oncogenic risk …
A Susceptibility Study Of Urinary Isolates To Methenamine Hippurate And Its Metabolites, Nancy Sloan
A Susceptibility Study Of Urinary Isolates To Methenamine Hippurate And Its Metabolites, Nancy Sloan
Master's Theses
Urinary Tract Infection (UTI) is one of the most common bacterial infections in adult women. Treatment is one of the most common reasons for antibiotic prescription. the rise of antibiotic-resistant infections coupled with the shortage of new antibiotics creates an urgent need for alternative non-antibiotic treatments. One alternative is methenamine hippurate (MH), which is a non-antibiotic prophylaxis. It is reported to be active against some common uropathogens including Escherichia coli and Enterococcus species, but its effects on the newly discovered bladder microbiota (urobiome) are undocumented. Given this knowledge gap, this study aimed to evaluate the drug's spectrum of susceptibility on …
Induction Of Zika And Dengue Virus-Specific Cd8+ T Cells By Means Of Dna Vaccine, Natalie Jachym
Induction Of Zika And Dengue Virus-Specific Cd8+ T Cells By Means Of Dna Vaccine, Natalie Jachym
Master's Theses
Zika virus (ZIKV) and Dengue virus (DENV) are flaviviruses that circulate in the same endemic regions and can co-infect the same individual. While primary infection by DENV leads to life-long immunity to the infecting serotype, it does not provide immunity to other serotypes. Moreover, ZIKV and DENV antibodies can be cross-reactive and potentially enhance infection of the other virus through a process known as antibody-dependent enhancement (ADE). In this mechanism, antibodies weakly bind the infecting virus and direct virions to immunoglobulin Fc receptors on macrophages. This promotes viral uptake and infection rather than neutralize the virus. Due to this mechanism, …
Determining Interactions Between Bacteriophage And Urinary Microbiome Lysogens, Michael Bochert
Determining Interactions Between Bacteriophage And Urinary Microbiome Lysogens, Michael Bochert
Master's Theses
Bacteriophages (phages) are viruses that infect bacteria. They are the most abundant life forms on earth. It is estimated that there are approximately 10³⁰ phages on the planet (Chibani-Chennoufi et al. 2004). They outnumber their bacterial hosts approximately 10 to 1. Bacteria inhabit most niches on the planet including the human body, where they play critical roles in health and disease. Since phages shape bacterial populations the same way that viruses, such as smallpox and measles, shaped human populations, it is important to understand how they interact with their bacterial hosts. The majority of the phages that we know of …
Reducing Reperfusion Injury In An Adult Rat Stroke Model With St-115 Treatment, Morgan Rae Lenz
Reducing Reperfusion Injury In An Adult Rat Stroke Model With St-115 Treatment, Morgan Rae Lenz
Master's Theses
The restoration of blood flow to ischemic cerebral tissue can result in reperfusion injury, and blocking reperfusion injury can significantly aid in recovery of ischemic tissue. Bradykinin has been shown to exhibit protective effects, but does not reach protective levels during reperfusion due to inactivation by aminopeptidase P2 (APP2). Therefore, inhibiting APP2 during reperfusion is a potential therapeutic strategy to aid in the reduction of reperfusion injury, leading to the development of ST-115, an APP2 inhibitor. It was hypothesized that administration of ST-115 during ischemic stroke, and just prior to reperfusion, will result in reduced neurological injury and increased functional …
Dna Methylation Patterns Of Repetitive Elements On Hc21, Navy Neang
Dna Methylation Patterns Of Repetitive Elements On Hc21, Navy Neang
Master's Theses
Cancer is one of the most prominent diseases resulting in death, thus the need for early detection remains essential to its treatments. It is usually associated with DNA methylation changes during tumorigenesis. While many studies focus on euchromatin, some studies have looked at the methylation changes in heterochromatin, since the methylation changes of repetitive elements is common and they contribute to karyotypic instability leading to enhanced chances for more mutations in tumor progression. Using bisulfite PCR and HC21 as a model, this study examines the DNA methylation changes of three repetitive elements in prostate cancer, NBL2, satellite I subfamilies, and …
Behavioral Ecology And Physiological Health Of Managed Populations Of Juvenile Blanding's Turtles (Emydoidea Blandingii) In Urban Wetlands, Armand Andre' Cann
Behavioral Ecology And Physiological Health Of Managed Populations Of Juvenile Blanding's Turtles (Emydoidea Blandingii) In Urban Wetlands, Armand Andre' Cann
Master's Theses
Substantial threats to reptile species biodiversity have become apparent in the last few decades. This is partly caused by significant losses in grasslands and their associate prairie-wetland ecosystems. One Midwestern prairie-wetland species, Blanding's Turtles (Emydoidea blandingii), are at risk of extirpation due to habitat loss, fragmentation, and increased predator populations. Consequently, significant head-starting efforts, a form of reintroduction conservation using captive-reared and then released turtles, have been conducted to recover populations of E. blandingii in northeastern Illinois. However, the success of these programs both locally and range-wide have not been fully quantified. Unfortunately, many approaches to guaging success involve long-term …
Selectivity For Allosteric Effectors Of Bacterial Adp-Glucose Pyrophosphorylase: Structural And Functional Studies, Mashael Alghamdi
Selectivity For Allosteric Effectors Of Bacterial Adp-Glucose Pyrophosphorylase: Structural And Functional Studies, Mashael Alghamdi
Dissertations
The biosynthesis of the intracellular polysaccharide in bacteria and plants, glycogen and starch, respectively, controlled by the key regulatory step that catalyzed by ADP-Glucose Pyrophosphorylase (ADP-Glc PPase). ADP-Glc PPase is an allosteric enzyme regulated by metabolites produced of the principle carbon assimilation pathway in each organism. Agrobacterium tumefaciens enzyme activated by fructose 6-phosphate (Fru6P) and pyruvate, whereas Escherichia coli enzyme activated by fructose 1,6-bisphosphate (FBP), and both enzymes inhibited by AMP. Here, we targeted the allosteric regulation of the A. tumefaciens enzyme, examined some residues that may impact the regulation mechanism (Ser72, His71, Arg75, Ser351, Ser334, Arg368, Asn350, and Asp291), …
Investigating The Mechanism Of The Coronavirus Endoribonuclease In Antagonizing Innate Immune Signaling, Matthew Hackbart
Investigating The Mechanism Of The Coronavirus Endoribonuclease In Antagonizing Innate Immune Signaling, Matthew Hackbart
Dissertations
Coronaviruses (CoVs) are positive-sense RNa viruses that can emerge from endemic reservoirs and infect zoonotically, causing significant morbidity and mortality. CoVs encode an endoribonuclease (EndoU) that cleaves RNa in biochemical assays, but the target and function of EndoU activity during viral replication was not known. My work focused on characterizing the functions of EndoU during infection. I report that EndoU is an innate immune antagonist. to function as an immune antagonist, EndoU cleaves the 5'-Poly-Uridines from Negative-sense viral RNA, termed PUN RNA, which is the product of polyA-templated RNa synthesis. Using a virus containing an EndoU catalytic-inactive mutation, I detected …
Elucidating The Impact And Mechanism Of Hepatitis C Virus Cell-To-Cell Spread, Karina Durso-Cain
Elucidating The Impact And Mechanism Of Hepatitis C Virus Cell-To-Cell Spread, Karina Durso-Cain
Dissertations
Virus cell-to-cell spread has been implicated in the establishment of persistent infection and has been shown to be involved in the transmission of antiviral resistant mutants. However, relatively little is known about how virus cell-to-cell spread impacts infection or the specific mechanisms by which cell-to-cell spread occurs. as such, this dissertation focused on investigating HCV cell-to-cell spread not only to learn more about this medically important virus, but also to determine the broader impact cell-to-cell spread has on viral infection dynamics, identify the cellular factors involved, and perhaps ultimately provide insight into antiviral strategies that might enhance the barrier to …
Suffocated Cd8 T Cells In The Hypoxic Tumor Microenvironment, Lourdes Beatriz Plaza Rojas
Suffocated Cd8 T Cells In The Hypoxic Tumor Microenvironment, Lourdes Beatriz Plaza Rojas
Dissertations
Hypoxia is a common feature of solid tumors that plays an important role in angiogenesis, malignant progression and metastatic development. However, its impact on T cell anti-tumor responses is less known. We determined that CD8 tumor infiltrating lymphocytes (TILs) tend to localize to non-hypoxic tumor areas, suggesting a susceptibility to tumor-associated hypoxia. This led us to further study the effects of hypoxia in vitro by culturing spleen-derived mouse T cells in a humidified chamber at 0.5% O2, 5% CO2 and 37 °C. We found that T cell proliferation and effector function are reduced by hypoxia, severely affecting inflammatory cytokine production. …
Distinct Roles For Carbohydrate And Protein Receptors In Coronavirus Infection, Enya Qing
Distinct Roles For Carbohydrate And Protein Receptors In Coronavirus Infection, Enya Qing
Dissertations
Coronaviruses (CoVs) are common human and animal pathogens. in humans, four endemic CoV species together account for one third of mild respiratory infections worldwide. More severe and frequently fatal respiratory pathologies are caused by recent CoV outbreaks that resulted from occasional zoonotic spillover from animal CoV reservoirs, namely, SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Because CoVs threaten global health, any chance of relieving CoV's threat on human populations would rely heavily on our understanding of the mechanistic requirements for CoV tropism, whose major determinant is at the level of viral entry. CoVs have evolved to use …
Developing Caspase-1 Biosensors To Monitor Inflammation In Vitro And In Vivo, Sarah Talley
Developing Caspase-1 Biosensors To Monitor Inflammation In Vitro And In Vivo, Sarah Talley
Dissertations
Inflammation is central to the pathogenesis of numerous human diseases. in many contexts, inflammation drives immune responses which are critical to protection against many pathogens. However, uncontrolled inflammation can drive the pathology of numerous diseases, including neurodegenerative diseases, intestinal disorders, cancer, and autoimmune diseases. a primary mediator of inflammation is the inflammasome complex, which drives the release of inflammatory mediators through caspase-1 activation. Our goal was to develop a tool that would allow us to monitor caspase-1 activation in vitro and ultimately in vivo. to this end, we employed a circularly permuted form of luciferase in which the N- and …
Human Isocitrate Dehydrogenase Enzymes, Joseph Valentein Roman
Human Isocitrate Dehydrogenase Enzymes, Joseph Valentein Roman
Dissertations
Mammals have three forms of isocitrate dehydrogenase (ICDH) that each catalyze the oxidative decarboxylation of isocitrate forming alpha-ketoglutarate (AKG), carbon dioxide and reduced pyridine nucleotide. The intra-mitochondrial, citric acid cycle enzyme is ICDH III that exists as a hetero tetramer and uses NAD+ as a substrate. ICDH I and ICDH II are both dimeric enzymes that reside in the cytosol and use NADP+. While, the precise function of the cytosolic ICDHs is not known, active site variants of both ICDH I and II cause a variety of cancers. The R132H variant of ICDH1 is one of the most common alterations. …
Estrogen Regulation Of Mir-9-5p And Mir-9-3p Stability And Localization In The Aging Female Brain, Chun Kim
Estrogen Regulation Of Mir-9-5p And Mir-9-3p Stability And Localization In The Aging Female Brain, Chun Kim
Dissertations
In females, levels of estrogens fluctuate across the lifespan and rapidly decline during menopause. Hormone replacement therapy (HRT) has been introduced as a clinical alternative to replenish systemic levels of 17β-estradiol (E2), the primary estrogen in circulation. However, studies from the Women's Health Initiative revealed a critical period immediately following the onset of menopause where HRT is efficacious. Here, we identified the differential regulation of miRNAs, small non-coding RNAs that inhibit translation, as a potential mechanism for this temporal switch in estrogen action. Specifically, early - but not late - E2 administration following ovariectomy in a rat model of menopause …
Cellular And Molecular Mechanism Underlying Alcohol Inhibition Of Bone Fracture Healing, Jonathan Michael Eby
Cellular And Molecular Mechanism Underlying Alcohol Inhibition Of Bone Fracture Healing, Jonathan Michael Eby
Dissertations
Alcohol consumption is associated with increased risk taking and injuries leading to bone fracture. During bone fracture repair mesenchymal stem cells (MSCs) located at the site of injury differentiate into chondrocytes and osteoblasts to form a fracture callus. While most fractures heal without complication, studies show that alcohol abuse can lead to delayed fracture healing and fracture callus formation in both people and animals. Despite what is known about alcohol consumption in pre-injury pathologies like osteopenia and osteoporosis, the cellular and molecular mechanisms by which alcohol consumption inhibits fracture callus formation following orthopaedic injury remain to be elucidated. Here, we …
Determining The Genetic And Phenotypic Profile Of Cord Blood Derived T Regulatory Cells And The Effect Of Calcitriol On Immune Suppression, Anya Nikolai-Yogerst
Determining The Genetic And Phenotypic Profile Of Cord Blood Derived T Regulatory Cells And The Effect Of Calcitriol On Immune Suppression, Anya Nikolai-Yogerst
Dissertations
Recent outbreaks in vertically transmitted viruses, such as Zika virus and HIV, have rejuvenated interest in fetal and neonatal immune tolerance. Babies are susceptible to vertically transmitted viruses because fetal and neonatal immune systems are considered to be immune-privileged and will tolerate antigens presented to them by their mother. Thus, understanding the mechanisms of this tolerance is important to design effective treatments for infected mothers to protect their offspring. Here, I define a novel Treg, a type of T cell that mediates tolerance, named bidirectional T cells (BiT), found in human umbilical cord blood (UCB). These cells are induced by …
Effects Of Pharmaceutical Contamination On Sedment Microbial Communities In Streams, Benjamin Joseph Lorentz
Effects Of Pharmaceutical Contamination On Sedment Microbial Communities In Streams, Benjamin Joseph Lorentz
Master's Theses
The objective of this study was to examine the interaction of pharmaceuticals and personal care products (PPCP) and microbial communities in freshwater ecosystems. This study included two components. The first component consisted of an artificial stream study in which sediment was exposed to environmentally relevant concentrations of three different pharmaceuticals (diphenhydramine, ciprofloxacin, and fluoxetine) individually and as a mixture. Pharmaceutical exposure had no effect on denitrification rates or respiration rates in the sediments, and sediment microbial community composition showed only slight differences between streams dosed with pharmaceuticals and control streams. The second component consisted of a field study in which …
Elucidating The Targets And Function Of The Mlr Compass-Like Complex During Development, David Joseph Ford
Elucidating The Targets And Function Of The Mlr Compass-Like Complex During Development, David Joseph Ford
Dissertations
MLR COMPASS-like complexes are highly-conserved epigenetic regulators required for enhancer establishment and subsequent reprogramming during differentiation and development. Mutation of MLR complex subunits in humans is associated with cancer and developmental disorder, yet much remains to be determined concerning both the healthy and disease-altered functions of these complexes. Using the developmental model Drosophila melanogaster, I further elucidate the functions of the MLR complex during in vivo organ development as well as stress response. I characterize the miRNa bantam as a regulatory target of the complex, required for proper tissue patterning during wing and compound eye formation. in the same systems …