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Identification And Characterization Of Genes Involved In Metabolism Of N5 Monoene Precursors To N5 Anacardic Acids In The Trichomes Of Pelargonium X Hortorum., Richa A. Singhal Dec 2016

Identification And Characterization Of Genes Involved In Metabolism Of N5 Monoene Precursors To N5 Anacardic Acids In The Trichomes Of Pelargonium X Hortorum., Richa A. Singhal

Electronic Theses and Dissertations

Unusual monoenoic fatty acids (UMFA’s) and specialized metabolites called anacardic acids (AnAc) are produced in glandular trichomes of Pelargonium ´ hortorum (geranium). The UMFA’s, 16:1∆11 and 18:1∆13 are precursors for the synthesis of unsaturated AnAc 22:1n5and 24:1n5 that contribute to pest resistance in geraniums. UMFAs and their derived AnAc metabolites not only provide a useful biological marker that differentiates the biosynthetic pathway for unusual mononenes from the common fatty acids (i.e. stearic, palmitic, oleic, linoleic and linolenic) but also have industrial, medical and agricultural applications. Fatty acid biosynthesis enzymes like acyl carrier proteins (ACPs); thioesterases (TEs) and β-ketoacyl-ACP …


Identification Of Residual Descending Pathways After Human Spinal Cord Injury., Darryn A. Atkinson Dec 2016

Identification Of Residual Descending Pathways After Human Spinal Cord Injury., Darryn A. Atkinson

Electronic Theses and Dissertations

Spinal Cord Injury (SCI) in humans is a heterogeneous diagnosis, resulting in variable paralysis and paresthesia based on the mechanism, rostro-caudal location, and severity of injury. Both neurophysiological and anatomical studies have suggested that subclinical residual supraspinal-spinal connectivity exists in a subset of individuals deemed to have motor and sensory complete injuries. Recent reports of volitional movement in chronic, motor complete individuals during epidural spinal stimulation have provided compelling evidence that these residual projections may be capable of mediating volitional movement when the functional state of spinal circuitry is electrically modulated. It was the goal of this project to identify …


Retinoic Acid Signaling Regulates Krt5 Independently Of Stem Cell Markers In Submandibular Salivary Gland Epithelium., Timur Maratovich Abashev Dec 2016

Retinoic Acid Signaling Regulates Krt5 Independently Of Stem Cell Markers In Submandibular Salivary Gland Epithelium., Timur Maratovich Abashev

Electronic Theses and Dissertations

Vitamin A metabolism, which produces the signaling molecule Retinoic Acid (RA), has been demonstrated to be important for growth and branching morphogenesis of mammalian embryonic salivary gland epithelium. However, it is not known whether RA functions directly within epithelial cells or in associated tissues that influence morphogenesis of salivary epithelium. Moreover, downstream targets of RA transcriptional regulation have not been identified. Here we show that canonical RA signaling occurs in multiple tissues of embryonic mouse salivary glands, including epithelium, associated parasympathetic ganglion neurons, and non‑neuronal mesenchyme. By culturing epithelium explants in isolation from other tissues we demonstrate that RA influences …


Examination Of The Relevance Of Pi3k And Pten Pathway In Ustilago Maydis., Nathaniel Edward Dalton Dec 2016

Examination Of The Relevance Of Pi3k And Pten Pathway In Ustilago Maydis., Nathaniel Edward Dalton

Electronic Theses and Dissertations

Ustilago maydis is a fungal pathogen that is an obligate parasite on Zea mays (Corn) in order to undergo and complete its sexual life cycle. The cells grow as a haploid form until they meet a compatible partner and undergo a dimorphic switch from a budding yeast-like cell type to a filamentous dikaryon. Infection of the host plant is characterized by leaf chlorosis, anthocyanin content, and formation of large galls that develop on the stem, leaves, cobs, and flowers. Many signaling cascades such as MAPK and PKA are involved in the regulation of the infection lifecycle. The Phosphatidylinosotiol 3 Kinase/ …


Approaches To Arthropod Conservation : Landscape Genetics, Community Assessment, And Prediction Of Extinction Risk., Victoria Annette Prescott Dec 2016

Approaches To Arthropod Conservation : Landscape Genetics, Community Assessment, And Prediction Of Extinction Risk., Victoria Annette Prescott

Electronic Theses and Dissertations

Although urbanization is a leading cause of species extinction throughout the world, the impact of urban development on arthropods is little studied and, as a result, poorly understood. I used three distinct approaches to studying arthropod conservation in North America. First, I used landscape genetics techniques to study the impact of urbanization on gene flow among populations of Rabidosa rabida, the rabid wolf spider. While gene flow was not detrimentally reduced, urban development correlated with a reduction in migration rates among populations, and to my knowledge, this is the first study to document isolation by resistance in spiders. Next, …


Spreading Speeds Along Shifting Resource Gradients In Reaction-Diffusion Models And Lattice Differential Equations., Jin Shang Dec 2016

Spreading Speeds Along Shifting Resource Gradients In Reaction-Diffusion Models And Lattice Differential Equations., Jin Shang

Electronic Theses and Dissertations

A reaction-diffusion model and a lattice differential equation are introduced to describe the persistence and spread of a species along a shifting habitat gradient. The species is assumed to grow everywhere in space and its growth rate is assumed to be monotone and positive along the habitat region. We show that the persistence and spreading dynamics of a species are dependent on the speed of the shifting edge of the favorable habitat, c, as well as c*(∞) and c*(−∞), which are formulated in terms of the dispersal kernel and species growth rates in both directions. When …


Using A Mouse Model To Investigate Male Bias In Autism Spectrum Disorder Incidence., Elizabeth Ann Gordon Dec 2016

Using A Mouse Model To Investigate Male Bias In Autism Spectrum Disorder Incidence., Elizabeth Ann Gordon

Electronic Theses and Dissertations

The review (Chapter 1) overviews our current understanding of the sex bias in autism spectrum disorders (ASD), whereby males are 4 times more likely to develop the condition. The longstanding uncertainty surrounding the etiology of autism can be informed by inclusion of both sexes in future research to better understand the mechanism responsible for this sex bias. Both clinical studies and animal models are useful tools to elucidate the underlying cause(s) of sexual dimorphic morphological, physiological, and behavioral differences in the ASD phenotype. Sex differences in social behaviors are common across species, underscoring the importance of assessing baseline sex differences …


Dietary Resource Utilization Patterns And Head Morphology Among Three Sympatric Watersnake Species., Micah Warren Perkins Dec 2016

Dietary Resource Utilization Patterns And Head Morphology Among Three Sympatric Watersnake Species., Micah Warren Perkins

Electronic Theses and Dissertations

The coexistence of similar species may be related to a variety of resource utilization differences. Dietary resource utilization variation may be the most important difference allowing for the coexistence of sympatric snake species. Many watersnakes (Nerodia spp.) live in sympatry and use similar aquatic habitats feeding on similar prey. While these sympatric watersnakes may have different general foraging patterns, snake diet may be affected by a variety of factors. Therefore, I initiated an investigation to understand the coexistence of sympatric plain-bellied (N. erythrogaster), diamondback (N. rhombifer) and northern (N. sipedon) watersnakes by addressing …


Plant Community Responses To The Removal Of Lonicera Maackii From An Urban Woodland Park., Elihu H. Levine Dec 2016

Plant Community Responses To The Removal Of Lonicera Maackii From An Urban Woodland Park., Elihu H. Levine

Electronic Theses and Dissertations

Impacts of Lonicera maackii on native forest communities have been widely researched, but long-term responses of plant communities to the removal of this exotic shrub have not been extensively evaluated. The Louisville Olmsted Parks Conservancy removes exotic shrubs and vines to restore ecological processes and native species in the woodlands of Cherokee Park. Paired-plots were established in 2008 to gather baseline herb, vine, tree, and shrub community data. Honeysuckle was removed from one plot of each pair in 2009 and community data were gathered again in 2013. Native herb cover and richness, vine cover, and tree sapling abundance increased where …


Tnf-Like Weak Inducer Of Apoptosis (Tweak) : Not So Weak After All., Joseph Dekward Mcmillan Iv Dec 2016

Tnf-Like Weak Inducer Of Apoptosis (Tweak) : Not So Weak After All., Joseph Dekward Mcmillan Iv

Electronic Theses and Dissertations

Background: Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine belonging to the TNF super family. TWEAK produces a variety of cellular responses through the binding to fibroblast growth factor inducible 14 (Fn14), a member of TNF receptor superfamily. Although Fn14 lacks a death domain, TWEAK has been found to induce apoptosis in some cell types by perturbing the activity of certain pathways such as TNF-receptor signaling. TWEAK is also known to regulate proliferation and differentiation of myogenic cells. We have previously reported that the TWEAK-Fn14 system causes skeletal muscle wasting both in vitro and in …


Transient Receptor Potential Cation Channel, Subfamilies V, Member 1 (Trpv1) And M, Member 1 (Trpm1) Contribute To Neural Signaling In Mouse Retina., Jennifer Noel Dec 2016

Transient Receptor Potential Cation Channel, Subfamilies V, Member 1 (Trpv1) And M, Member 1 (Trpm1) Contribute To Neural Signaling In Mouse Retina., Jennifer Noel

Electronic Theses and Dissertations

The retina processes light information through parallel pathways in order to extract and encode the visual scene. Light information is transmitted to the brain through approximately 30 ganglion cells (GCs), the retinal output neurons. Trp channels modulate the responses of retinal neurons within specific pathways. The study of the expression and function of the majority of Trp channels in the retina is largely in its infancy. My dissertation first investigated the expression and function of the transient receptor potential vanilloid-1 (TRPV1) receptor/channel in the retina. TRPV1, the first cloned and most highly studied Trp channel in the peripheral nervous system, …


Glutathione S-Transferase P In Glucose Homeostasis In Mice., Shubha Ghosh Dastidar Dec 2016

Glutathione S-Transferase P In Glucose Homeostasis In Mice., Shubha Ghosh Dastidar

Electronic Theses and Dissertations

High calorie diets have fostered the current pandemic of obesity and comorbid conditions of non-alcoholic fatty liver disease (NAFLD), systemic insulin resistance (IR) and type 2 diabetes (T2D). Hepatic glutathione S-transferases (GSTs) are dysregulated in obesity, NAFLD and diabetes. The multifunctional GST pi isoform (GSTP) catalyzes acrolein metabolism and inhibits JNK (c-Jun NH2-terminal kinase). The purpose of this study was to test specifically whether GSTP deficiency disturbs glucose homeostasis in mice. Hepatic GST proteins were downregulated by short-term high fat diet (HFD) in wild type (WT) mice concomitant with glucose intolerance, increased hepatic JNK activation and protein-acrolein …


Impact Of Luminance And Spatial Parameters On The Generation Of The Human Pattern Electroretinogram., Kate A. Godwin Aug 2016

Impact Of Luminance And Spatial Parameters On The Generation Of The Human Pattern Electroretinogram., Kate A. Godwin

Electronic Theses and Dissertations

The current work assessed some of the key hypotheses behind the generation of the pattern electroretinogram (PERG) response. The first of these hypotheses states that the PERG response is the result of linear cancellation of simultaneous increment and decrement retinal responses, as generated by the retinal ON- and OFF-pathways. Experiment 1 evaluated the possibility of simulating the PERG by summing the ERG responses elicited by increment and decrement flashes, and found that it was indeed possible to simulate the PERG from these responses. However, only the steady-state PERG could be modeled consistently. The second hypothesis evaluated a theory that the …


The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka Aug 2016

The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka

Electronic Theses and Dissertations

Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the …


Cannabinoids Suppress The Innate Immune Response To Periodontal Pathogen Porphyromonas Gingivalis In Gingival Epithelial Cells., Rajarshi Guha Niyogi Aug 2016

Cannabinoids Suppress The Innate Immune Response To Periodontal Pathogen Porphyromonas Gingivalis In Gingival Epithelial Cells., Rajarshi Guha Niyogi

Electronic Theses and Dissertations

Marijuana is widely used in the United States for recreational and medicinal purposes. Despite the proposed beneficial effects of cannabis on certain medical conditions, there is also a concern there is also a concern over negative health consequences of marijuana smoking. Recently, cannabis use has been established as a dose related risk factor for chronic periodontitis. Although the induction / exacerbation of chronic periodontitis in marijuana users has been established epidemiologically, the mechanisms underlying such predisposition are still unknown. It has long been suggested that marijuana has anti-inflammatory properties, while human epithelial cells are known to express cannabinoid receptor type …


Effects Of Glyceollin On Mrna Expression In The Female Mouse Brain., Sanaya Firdaus Bamji Aug 2016

Effects Of Glyceollin On Mrna Expression In The Female Mouse Brain., Sanaya Firdaus Bamji

Electronic Theses and Dissertations

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Glys exhibit mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Glys on brain physiology and function are unknown. The purpose of the experiments summarized in this dissertation was to gain an understanding of the effects of Gly on brain-related functions in the female mouse brain through the observation of changes in gene expression. For our initial studies, we treated ovariectomized Swiss Webster (CFW) …


Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp Aug 2016

Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp

Electronic Theses and Dissertations

The rapid and recent increase in the global epidemic of diabetes and cardiovascular disease suggests a strong component of the environment is contributing. Benzene is a ubiquitous volatile pollutant generated by cigarette smoke, automobile exhaust, wildfires and industrial activities. Consequently, it is found in almost all urban and rural air samples. Benzene is known to cause hematotoxicity and its metabolism generates oxidative stress. Although, benzene has been studied for many years, few investigations have probed what influence benzene exposure may have on other physiological processes. Here we hypothesize that benzene metabolism by hepatic-CYP450 2E1 generates oxidative stress and inflammation, which …


Effect Of Migration, Carrying Capacity, And Fecundity On The Formation Of Clinal Patterns During Range Expansions., Neha J. Angal Aug 2016

Effect Of Migration, Carrying Capacity, And Fecundity On The Formation Of Clinal Patterns During Range Expansions., Neha J. Angal

Electronic Theses and Dissertations

Range expansions, empirically and in simulations, lead to clinal patterns of genetic diversity. Clines are often used as spatial markers of past migrations. This study investigated the effects of migration, growth, and carrying capacities on clinal patterns during range expansions, using forward-time simulations in Nemo. Initial results show, in the absence of prior population structure, range expansions result in a loss of diversity strongly affected by migration, growth, and carrying capacity. This loss of diversity did not persist to the final generation, corresponding to 10,000 years, indicating clinal patterns are less durable than previously assumed—challenging the utility of clinal patterns …


Effects Of Invasive Shrub Honeysuckle (Lonicera Maackii) And Forest Composition On Bird Communities In Woodland Stands., Katie Rae Lynch Aug 2016

Effects Of Invasive Shrub Honeysuckle (Lonicera Maackii) And Forest Composition On Bird Communities In Woodland Stands., Katie Rae Lynch

Electronic Theses and Dissertations

Invasive species pose a threat to aquatic and terrestrial ecosystems by decreasing biodiversity (Didham et al. 2005). Amur bush honeysuckle (Lonicera maackii) has typically reduced native plant diversity and altered animal communities by influencing animal abundance and activity (Collier and Vankat 2002). This study was intended to determine whether honeysuckle density or other characteristics of forested stands influence avian diversity, whether impacts are seasonally dependent, and whether correlations exist between attributes of forested stands and honeysuckle density. In order to test the hypotheses, thirteen forest stands within the Louisville Metropolitan Area were selected. They had similar tree composition …


Air Pollution, Pulmonary Oxidative Stress, And The Endothelin System In The Development Of Cardiovascular Injury., Jordan B. Finch Aug 2016

Air Pollution, Pulmonary Oxidative Stress, And The Endothelin System In The Development Of Cardiovascular Injury., Jordan B. Finch

Electronic Theses and Dissertations

The goal of this project was to examine the role of endothelin-1 (ET-1) as a mediator in the pathway between air pollution exposure and the development of vascular injury. A human cohort and male mice (C57BL/6 and ecSOD-Tg) were used to evaluate changes in the ET-1 system in response to exposures of fine particulate matter (PM2.5). Human ET-1 levels were significantly associated with environmental factors and markers of vascular change, but were decreased with increased PM2.5. No association was seen between ET-1 and endothelial progenitor cells (EPCs) except for EPC-4, possibly indicating a regulatory relationship with this specific population. In …


Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney Aug 2016

Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR undergoes clathrin-mediated endocytosis. This spatial regulation of the receptor is an important regulator of receptor expression as it mediates its degradation. Endocytosis also has implications on EGFR downstream signaling, though the details are not fully understood. The goal of this thesis is to develop a method to isolate early endosomes in order to study downstream effectors associated with activated EGFR in this compartment. HeLa cells were used to test various …


Effects Of Neonatal Capsaicin On Formalin-Induced Atf3 Expression In The Adult Rat., Sarah Krupp Aug 2016

Effects Of Neonatal Capsaicin On Formalin-Induced Atf3 Expression In The Adult Rat., Sarah Krupp

Electronic Theses and Dissertations

Acute and chronic pain can be extremely debilitating conditions, and a better understanding of their underlying pathology is necessary to provide effective treatment. C-Fibers are responsible for transmission of the majority of nociceptive signals, with TRPV1+ C-Fibers being specific to noxious heat. Formalin, an inflammatory agent, acts through TRPA1+ C-Fibers, which have a high degree of co-localization with TRPV1. Using a neonatal capsaicin preparation, which irreversibly ablates the majority of TRPV1+ C-Fibers, formalin- induced inflammation and subsequent ATF3 expression was investigated. Results provide evidence that in addition to a lack of thermal nociception, animals treated with neonatal capsaicin had a …


Structure-Function Analysis And Characterization Of Metalloproteins., Sen Yao Aug 2016

Structure-Function Analysis And Characterization Of Metalloproteins., Sen Yao

Electronic Theses and Dissertations

Metalloproteins are proteins that can bind at least one metal ion as a cofactor. They utilize metal ions for a variety of biological purposes, and are essential for all domains of life. Due to the ubiquity of metalloprotein’s involvement across these processes across all domains of life, how proteins coordinate metal ions for different biochemical functions is of great relevance to understanding the implementation of these biological processes. One of the most important aspects of metal binding is its coordination geometry (CG), which often implies functional activities. Most of the current studies are based on the assumption of previously reported …


The Role Of The Nucleolus In Neurodegeneration., Justin Lauren Hallgren Aug 2016

The Role Of The Nucleolus In Neurodegeneration., Justin Lauren Hallgren

Electronic Theses and Dissertations

The overarching goal of my studies was to determine the role of the nucleolus in neurodegenerative disease. Numerous studies suggest the impairment of ribosomal biogenesis in neurodegenerative disease and such a condition may contribute to neuronal dysfunction in two ways, loss of function and stress response. Ribosomal biogenesis has been demonstrated to play an essential role in both neuronal growth and maintenance. Therefore insufficient levels of ribosomal biogenesis would be expected to produce atrophy and synapse loss. Moreover, the fidelity of ribosomal biogenesis is monitored by nucleolar and ribosomal stress responses which induce apoptosis and/or cell cycle arrest. Therefore, I …


A Systems Biology Approach Identifies A Gene Regulatory Network In Parotid Acinar Cell Differentiation., Melissa Ann Metzler Aug 2016

A Systems Biology Approach Identifies A Gene Regulatory Network In Parotid Acinar Cell Differentiation., Melissa Ann Metzler

Electronic Theses and Dissertations

Objective: This project sought to understand the gene regulatory networks that drive parotid salivary gland acinar cells to terminally differentiate, and drive expression of terminal differentiation genes in dedifferentiated ParC5 cells. Methodology: Laser capture microdissection was used to isolate acinar cells at multiple time points during differentiation. This important step allowed us to measure gene expression in a single and important cell type. A systems biology approach was taken to measure global mRNA and microRNA expression across acinar cell terminal differentiation in the rat parotid salivary gland. In ParC5 cells, the ER stress activator tunicamycin was used to stimulate Xbp1 …


Role Of Microrna-21 In Atherogenesis., Rihab Hamed-Berair May 2016

Role Of Microrna-21 In Atherogenesis., Rihab Hamed-Berair

Electronic Theses and Dissertations

MicroRNA-21 (miR-21) is an evolutionarily conserved microRNA, abundant in most cardiovascular tissues. It has been implicated in the pathogenesis of several cardiovascular diseases including restenosis, myocardial infarction, and heart failure. However, little is known about the contribution of miR-21 in atherosclerosis. My data show that expression of miR-21 is increased by >1.5-fold in murine atherosclerotic lesions and by 1.5-2.0-fold in the macrophages of Western diet (WD)-fed LDLR-KO mice (for 12-20 weeks). In vitro, LDL, oxidized LDL, acetylated LDL and LPS induced miR-21 by 2-4-fold and down-regulated its target protein, PDCD4, in bone marrow-derived macrophages. Basally, macrophages isolated from miR-21-KO …


Analyzing The Phenologic Dynamics Of Kudzu (Pueraria Montana) Infestations Using Remote Sensing And The Normalized Difference Vegetation Index., Faye Peters May 2016

Analyzing The Phenologic Dynamics Of Kudzu (Pueraria Montana) Infestations Using Remote Sensing And The Normalized Difference Vegetation Index., Faye Peters

Electronic Theses and Dissertations

Non-native invasive species are one of the major threats to worldwide ecosystems. Kudzu (Pueraria montana) is a fast-growing vine native to Asia that has invaded regions in the United States making management of this species an important issue. Estimated normalized difference vegetation index (NDVI) values for the years 2000 to 2015 were calculated using data collected by Landsat and MODIS platforms for three infestation sites in Kentucky. The STARFM image-fusing algorithm was used to combine Landsat- and MODIS-derived NDVI into time series with a 30 m spatial resolution and 16 day temporal resolution. The fused time series was …


Congenic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Saasha Le May 2016

Congenic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Saasha Le

Electronic Theses and Dissertations

Breast cancer is a complex disease affected by genetic, epigenetic and environmental factors. The genetic architecture of breast cancer comprises of high to low penetrance alleles. Although low penetrance alleles associate with a small change in an individual’s risk to breast cancer, the total number of variants present and the high population frequency attributes to a much greater population based impact compared to rare high penetrance alleles. Animal models have been used to study these low penetrance modifier alleles in breast cancer. Different rat strains vary in their susceptibility to 7,12- dimethybenzanthracene (DMBA) induced mammary carcinogenesis, with the Wistar- Furth …


Integrated Analysis Of Mirna/Mrna Expression And Gene Methylation Using Sparse Canonical Correlation Analysis., Dake Yang May 2016

Integrated Analysis Of Mirna/Mrna Expression And Gene Methylation Using Sparse Canonical Correlation Analysis., Dake Yang

Electronic Theses and Dissertations

MicroRNAs (miRNAs) are a large number of small endogenous non-coding RNA molecules (18-25 nucleotides in length) which regulate expression of genes post-transcriptionally. While a variety of algorithms exist for determining the targets of miRNAs, they are generally based on sequence information and frequently produce lists consisting of thousands of genes. Canonical correlation analysis (CCA) is a multivariate statistical method that can be used to find linear relationships between two data sets, and here we apply CCA to find the linear combination of differentially expressed miRNAs and their corresponding target genes having maximal negative correlation. Due to the high dimensionality, sparse …


Sa-4-1bbl As A Modulator Of Innate, Adaptive, And Regulatory Immunity : Implications For Cancer Prevention And Treatment., Hampartsoum Barsoumian May 2016

Sa-4-1bbl As A Modulator Of Innate, Adaptive, And Regulatory Immunity : Implications For Cancer Prevention And Treatment., Hampartsoum Barsoumian

Electronic Theses and Dissertations

SA-4-1BBL is a recombinant costimulatory molecule that is active in its soluble form and has pleiotropic effects on the functions of innate, adaptive, and regulatory immune cells. We have previously shown that SA-4-1BBL makes CD4+ T conventional cells (Tconvs) resistant to suppression by CD4+CD25+Foxp3+ T regulatory cells (Tregs). The mechanistic basis of this observation is the subject of this study. We demonstrate that Tconvs, but not Tregs, are the direct targets of SA-4-1BBL-mediated evasion of Treg suppression without contribution from antigen presenting cells (APCs). SA-4-1BBL engagement with its receptor, 4-1BB, on Tconvs resulted in the production of high levels of …