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Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde Jan 2023

Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde

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Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies with a five-year survival of ~10%. Recent studies in the US population suggest PDAC as the fourth leading cause of cancer-related deaths in 2022. ST6 β-galactoside α2,6-sialyltransferase (ST6GAL1) is a glycosyltransferase which is known to be upregulated in cancer. It acts as a master regulator of a cell by being the predominant sialyltransferase catalyzing the addition of a bulky negatively charged sialic acid to the galactose sugar in an α2,6-linkage. Due to this, the sialic acid changes the structure and function of cell surface receptor proteins and regulates signal …

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Plasticity Characteristics Of Cxcr5+ Cd4+ T Memory Cells And Cxcr5- Non-Tfh Memory Cells, Ching-En Lee Jan 2023

Plasticity Characteristics Of Cxcr5+ Cd4+ T Memory Cells And Cxcr5- Non-Tfh Memory Cells, Ching-En Lee

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iv ability to differentiate into CXCR5- and CXCR5+ effector cells between the CCR7- and CCR7+ CXCR5+ CD4+ T memory cells, between WT and μMT CXCR5+ CD4+ T memory cells, as well as between Bcl6- and Bcl6+ CXCR5- non-Tfh memory cells. This finding did not support the hypothesis that the heterogeneous characteristics within CXCR5- non-Tfh memory cells and CXCR5+ CD4+ T memory cells significantly affect their abilities to differentiate into CXCR5- and CXCR5+ effector cells during recall responses.

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Investigating The Effects Of Immune Checkpoint Inhibition And Combined Treatment With Evofosfamide On The Tumor Microenvironment Through Hypoxia Imaging, Kaytlyn Carter Mcneal Jan 2023

Investigating The Effects Of Immune Checkpoint Inhibition And Combined Treatment With Evofosfamide On The Tumor Microenvironment Through Hypoxia Imaging, Kaytlyn Carter Mcneal

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Colorectal cancer (CRC) is a prevalent and deadly cancer worldwide. While immunotherapy, particularly immune checkpoint inhibition, shows promise in various cancers, its efficacy in CRC and other tumor types is limited. Hypoxia, characterized by inadequate tissue oxygenation, critically drives cancer progression, promoting tumor growth, metastasis, chemotherapy resistance, and poor prognosis. Evofosfamide, a hypoxia-activating prodrug, is being evaluated in clinical trials for combined use with checkpoint blockade as a potential therapeutic strategy. This study investigates the impact of hypoxia on immune checkpoint inhibition, evofosfamide, and combination therapy, while utilizing non-invasive molecular imaging to develop analytical methods for quantifying and characterizing tumor …

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Comparison Of Crown Fracture And Wear Resistence Of Resin 3d Printed Permanent Crown And Other Restorative Materials, Victor Moncada Jan 2023

Comparison Of Crown Fracture And Wear Resistence Of Resin 3d Printed Permanent Crown And Other Restorative Materials, Victor Moncada

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Statement of Problem: The resin for 3D printing permanent crowns is a recently approved material with limited literature evidence to support its in vitro properties. Comparing the mechanical properties such as fracture load (N) and wear resistance for 3D printing permanent restorations resins would represent a very good reference to consider future clinical decisions. Purpose: To investigate the fracture load (N) and wear resistance of the resins for 3D printing permanent crowns available in the U.S. dental market and to compare amongst them using lithium disilicate as a reference. Materials and Methods: for the crown fracture test, the experimental design …

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Respiratory Symptoms And Psychological Distress In Farmers Living With Copd, Prasert Kham-Ai Jan 2023

Respiratory Symptoms And Psychological Distress In Farmers Living With Copd, Prasert Kham-Ai

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Farmers are susceptible to both Chronic Obstructive Pulmonary Disease (COPD) and psychological distress. It is known that psychological distress is associated with increased respiratory symptoms and triggers COPD exacerbation. Therefore, farmers who have COPD may experience worsening respiratory symptoms as a result of psychological distress. Since no known studies revealed the association between the frequency of respiratory symptoms and the level of psychological distress among farmers with COPD, this study aimed to explore (1) the frequency of respiratory symptoms and the level of psychological distress, (2) the factors related to increased respiratory symptoms and psychological distress, and (3) the association …

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The Molecular And Structural Basis Of B Cell Epitope Targeting In Transplant Rejection, John T. Killian Jan 2023

The Molecular And Structural Basis Of B Cell Epitope Targeting In Transplant Rejection, John T. Killian

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HLA-reactive antibodies (HLA-Abs) to mismatched polymorphic HLA molecules are one of the major barriers to successful organ transplantation. However, key knowledge gaps remain surrounding the immunology of the anti-HLA B cell response in transplant rejection. This lack of understanding regarding the phenotype and specificity of the anti- HLA B cell response means that the field cannot develop optimal therapies to treat B-cell mediated donor-specific responses and that it lacks the tools to optimally match donors and recipients to prevent rejection events. Therefore, this dissertation aimed to explore the clinical factors associated with the formation of donor-specific antibodies and the molecular …

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Large-Scale Mining Of Dense Subgraphs: Algorithms And Systems, Jalal Khalil Jan 2023

Large-Scale Mining Of Dense Subgraphs: Algorithms And Systems, Jalal Khalil

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Quasi-cliques and k-plexes are dense structures with established significance in graph mining, offering flexibility and resilience to data anomalies. However, mining these structures poses computational challenges due to their NP-hardness. In this study, we address these challenges and propose solutions for efficient mining, in addition to visualization tools for tuning and analysis. For quasi-clique mining, we adapted the distributed solution (G-thinker) [1] to a sharedmemory multi-core environment, making it accessible to average users. Our solution is two orders of magnitude faster than the recent solution by [2], and it scales almost ideally with the number of CPU cores. To facilitate …

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Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones Jan 2023

Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones

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Treatment options for the universally lethal brain tumor, glioblastoma (GBM), are severely limited and often unsuccessful in fully eradicating the disease. Extremely aggressive in nature, GBM cells often implore suppressive mechanisms to evade therapeutic detection which aids in the dismal 15-month median survival rate. Facilitating disease severity and more importantly, disease recurrence, are the immunosuppressive and chemoresistant phenotypes of GBM cells. Specifically, the DNA alkylating agent, temozolomide (TMZ) possesses lymphodepleting properties shunting robust immune cell infiltration into an immunologically cold tumor microenvironment. Additionally, through inherent or acquired mechanisms, GBM tumors commonly become resistant to the DNA damaging effects of TMZ …

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The Long Non-Coding Rna Neat1 Mediates Astrocyte Gene Expression And Hippocampus-Dependent Memory In Aging And Alzheimer's Disease, Ashleigh Burns Irwin Jan 2023

The Long Non-Coding Rna Neat1 Mediates Astrocyte Gene Expression And Hippocampus-Dependent Memory In Aging And Alzheimer's Disease, Ashleigh Burns Irwin

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Dysregulation of long non-coding RNAs (lncRNAs) is increasingly associated with cognitive dysfunction and neurodegenerative disorders such as Alzheimer’s disease (AD). The highly evolutionarily conserved lncRNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) is expressed not only in a tissue- and temporally-specific manner, but also celltype specific manner. Despite the predominance of NEAT1 in glial populations, and the significant role astrocytes play in memory, relatively little is known about Neat1 regulation of astrocyte transcriptomics during age-related memory. Here, we report a crucial role of the lncRNA Neat1 in astrocyte dysfunction and memory deficits associated with both normal aging and AD. Expression of Neat1 …

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Optimization Of Progranulin Gene Therapy, A Potential Treatment For Frontotemporal Dementia, Shreya Natesh Kashyap Jan 2023

Optimization Of Progranulin Gene Therapy, A Potential Treatment For Frontotemporal Dementia, Shreya Natesh Kashyap

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Heterozygous loss of function mutations in the progranulin gene cause frontotemporal dementia, characterized by deficits in social behavior, language comprehension and motor function. Almost every frontotemporal dementia-related progranulin mutation is loss of function and results in progranulin haploinsufficiency. For this reason, progranulin replacement is a conceptually straightforward therapeutic strategy for patients with frontotemporal dementia caused by progranulin mutations. Here, we outline progranulin biology, progranulin deficient mouse models of frontotemporal dementia and preclinical interventions centered around increasing brain progranulin levels. We have demonstrated that blocking the progranulin C-terminus, which harbors the sortilin binding site, improves the cross-correctional capacity of neurotropic progranulin …

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Alternating Current Electrospinning And Characterization Of Nanofibrous Fish Skin Gelatin As An Innovative Biomaterial Platform, Amanda Kennell Jan 2023

Alternating Current Electrospinning And Characterization Of Nanofibrous Fish Skin Gelatin As An Innovative Biomaterial Platform, Amanda Kennell

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A biomaterial for tissue repair is globally sought after, as transplant surgeries and general wound healing have a strong need for a manufactured scaffold that mimics the natural body’s tissue in morphology, composition, and properties. This research presents a nanofibrous (NF) fish skin gelatin-based (FSG) substrate fabricated through an uncommon high-yield method of Alternating Current electrospinning that mimics that can mimic the natural body’s extracellular matrix (ECM). An ECM is the first step in tissue repair. Fabrication through electrospinning gave the NF FSG substrate an identical mimic of the natural body’s extracellular matrix morphology with nanofiber diameter on the order …

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Molecular Influences Of Racial Disparities In Pancreatic Neuroendocrine Tumors, Brendon Herring Jan 2023

Molecular Influences Of Racial Disparities In Pancreatic Neuroendocrine Tumors, Brendon Herring

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Pancreatic Neuroendocrine Tumors (PNETs) are highly heterogeneous neoplasms arising from the hormone-secreting cells of the endocrine pancreas. PNETs are broadly categorized as functional and non-functional based on the presence of symptoms associated with hormone secretion, which occurs in approximately 30% of cases. While functional tumors are all considered for resection because of these symptoms and their associated sequelae, non-functional tumors > 2cm are currently resected based on increased risk of developing metastatic disease. However, this criterion is based on data from predominantly White patients. Recent studies have shown that Black patients have much higher rates of lymph node metastatic disease at …

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Investigating Scientific Self-Concept In The General Chemistry Laboratory While Performing Course-Based Undergraduate Research Throughout A Pandemic, Josh Forakis Jan 2023

Investigating Scientific Self-Concept In The General Chemistry Laboratory While Performing Course-Based Undergraduate Research Throughout A Pandemic, Josh Forakis

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Climate change, waste management crises, and global pandemics emphasize the need for a thriving science, technology, engineering, and mathematics (STEM) workforce, and one of the jobs of STEM educators is to provide meaningful educational experiences that engage STEM students in scientific practices, broaden their worldview, and prepare them for a future career in the scientific field. Undergraduate research experiences have been shown to benefit STEM students, but few students can participate, especially at early stages in their undergraduate studies. To broaden participation in undergraduate research, an honors general chemistry laboratory course was converted into a course-based undergraduate research experience (CURE) …

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An Examination Of Clinical Pain Severity, Sleep Quality, And Neighborhood Disadvantage In A Racially/Ethically Diverse Sample Of Adults With Symptomatic Knee Osteoarthritis, Cesar Emmanuel Gonzalez Jan 2023

An Examination Of Clinical Pain Severity, Sleep Quality, And Neighborhood Disadvantage In A Racially/Ethically Diverse Sample Of Adults With Symptomatic Knee Osteoarthritis, Cesar Emmanuel Gonzalez

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Knee osteoarthritis (OA) is often accompanied by insomnia symptoms, character-ized by difficulty falling asleep, maintaining sleep, or both. Among individuals with knee OA, up to 31% report significant difficulty falling asleep, 81% have difficulties staying asleep, and up to 77% report any sleep problem. However, the sleep and pain relationship has also rarely been evaluated using objective and subjective sleep measures. Thus, this study attempted to characterize objective and subjective sleep variables in a diverse sam-ple of individuals with symptomatic knee OA. Further, the impact of objective and sub-jective sleep quality on clinical pain severity, movement-evoked pain, and physical func-tion …

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Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher Jan 2023

Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher

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Only ten percent of drugs in clinical trials are ultimately approved by the Food and Drug Administration (FDA). With many diseases and disorders needing therapeutic options, computational drug repurposing methodologies are great alternatives to some drug discovery methods due to quicker FDA approval and lower cost. We sought to gain insights to improve the identification of drug repurposing candidates that will be safe and effective to increase the success of computational drug repurposing approaches. In regards to identifying safe drug candidates, pharmacovigilance studies of adverse event case reports identified that women are more likely to experience an adverse event, and …

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Inkjet-Printed Reseroir Computing Network For In Situ Sensor Predictions, Steven D. Gardner Jan 2023

Inkjet-Printed Reseroir Computing Network For In Situ Sensor Predictions, Steven D. Gardner

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The technological achievements made with silicon-based transistors have led to nearly all the computing seen today, complete with benefits such as maximized operating speeds, parallel/tensor processing, minimized power overhead, etc. The silicon electronics industry is foundational to scientific progression with its profound impact on modeling, simulations, and fast/reliable computing. However, silicon-based transistors have evolved to meet their physical limitations and have saturated fields of innovation. New fields in computing outside of silicon-based methods have emerged as exotic materials enter the research domain. The suite of super-performing materials like Graphene, Carbon Nanotubes, and Molybdenum Disulfide have chaotic, non-linear behaviors that make …

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Modular Regulation And Function Of The Polypyrimidine Tract Binding Protein 1 (Ptbp1), Christine Carico Jan 2023

Modular Regulation And Function Of The Polypyrimidine Tract Binding Protein 1 (Ptbp1), Christine Carico

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RNA binding proteins (RBPs) are critical regulators of gene expression as they are responsible for the chaperoning and processing of every nascent RNA transcript. Many studies have investigated mechanisms of specificity of RBP function and have identified factors such as cell-specific expression of RBPs and differential preferences for RNA secondary structure. However, RBPs are often multi-domain proteins that contain repeats of various RNA binding domains (e.g., RNA recognition motif) and little work in the genomic era of transcriptomic interrogation has been done to define the contribution of individual domains to the overall protein function. Polypyrimidine tract binding protein 1 (PTBP1) …

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The Effects Of Alzheimer's Disease-Associated Variants And Ligands On The Structure And Function Of Trem2, Hunter Byron Dean Jan 2023

The Effects Of Alzheimer's Disease-Associated Variants And Ligands On The Structure And Function Of Trem2, Hunter Byron Dean

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Alzheimer’s disease (AD) is a devastating, complex form of dementia. Contributions from genetics make up almost 70% of a person’s risk of developing AD, but the mechanisms by which this occurs are not well understood. Attempts to tease apart the risk contributions from individual genes have identified lipid processing and activation of innate immunity as convergent pathways for many of the known genetic risk factors. One of the strongest known risk factors, TREM2, codes for a transmembrane receptor that activates a protective immune response when it detects bound lipids. Variants in TREM2 that control AD risk have been identified, but …

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Reduction Of Sphingomyelinases Associated With Progranulin Deficiency And Frontotemporal Dementia, Nicholas R. Boyle Jan 2023

Reduction Of Sphingomyelinases Associated With Progranulin Deficiency And Frontotemporal Dementia, Nicholas R. Boyle

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Frontotemporal dementia (FTD) is a leading cause of early-onset dementia and has a significant socioeconomic burden due to difficulties in diagnosis and delay to diagnosis. FTD is a clinically, pathologically, and genetically heterogeneous disorder. The pathological changes associated with FTD are termed frontotemporal lobar degeneration (FTLD). Protein aggregates are always present in FTLD, with >90% of cases presenting with either TDP-43 or tau pathology. Most cases of FTD are sporadic, but familial cases account for up to 25% of FTD. All familial FTD is inherited in an autosomal dominant fashion with most cases being caused by mutations in tau (MAPT), …

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Investigation Into The Structure And Function Of Tyrosyl-Dna Phosphodiesterase I'S N-Terminal Domain, Evan J. Brettrager Jan 2023

Investigation Into The Structure And Function Of Tyrosyl-Dna Phosphodiesterase I'S N-Terminal Domain, Evan J. Brettrager

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Tyrosyl-DNA phosphodiesterase I (Tdp1) is a eukaryotic DNA repair enzyme that removes adducts from DNA ends via hydrolysis of a phosphodiester bond. These adducts consist of damaged nucleotides or trapped protein-DNA complexes. Tdp1 hydrolyzes the phosphodiester bond utilizing two catalytic histidines and forming a Tdp1-DNA covalent intermediate. Mutations of these catalytic histidines have been shown to increase the stability of the Tdp1-DNA covalent intermediate and cause Topoisomerase I dependent toxicity in cells. We use these toxic Tdp1 mutant enzymes to study the function of Tdp1’s N-terminal domain (NTD). Full-length Tdp1 has proven difficult to purify due to degradation of the …

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Aging With Hiv And Comorbid Chronic Obstructive Pulmonary Disease, Jun Yeong Byun Jan 2023

Aging With Hiv And Comorbid Chronic Obstructive Pulmonary Disease, Jun Yeong Byun

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Older adults with human immunodeficiency virus (HIV) experience a high prevalence of chronic obstructive pulmonary disease (COPD). Considering having either HIV or COPD is related to worse health outcomes in older adults, aging with both HIV and COPD may synergistically and negatively affect the health outcomes of older people with HIV (PWH) and comorbid COPD. The purpose of this dissertation was to explore the aging of PWH with COPD. This purpose was accomplished through three articles: 1) an adaptation of a gerontological model investigating what is known about the aging of PWH and people with COPD and extrapolating that to …

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Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer Jan 2023

Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer

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During the process of malignant transformation, cells have striking changes in their cell surface glycosylation. One of these changes is an enrichment for α2,6 sialic acid which is added by the sialyltransferase, ST6GAL1. ST6GAL1 is upregulated in numerous malignancies and acts by adding an α2,6 sialic acid onto receptors bound for the plasma membrane. This sialic acid, in turn, modulates the activity of the receptor by regulating conformation, clustering, and cell surface retention. The work presented in this dissertation focuses on how ST6GAL1-mediated sialylation of a specific cell surface receptor, epidermal growth factor receptor (EGFR), regulates many of its properties. …

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Macrophage Ipla2ss-Derived Lipid Signaling Contributes To Type 1 Diabetes Development, Abdulaziz Saad Almutairi Jan 2023

Macrophage Ipla2ss-Derived Lipid Signaling Contributes To Type 1 Diabetes Development, Abdulaziz Saad Almutairi

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Type 1 Diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-secreting pancreatic β-cells that leads to hyperglycemia; however, the mechanism of β-cells destruction remains elusive. Ca2+-independent phospholipase A2β (iPLA2β), which hydrolyzes membrane phospholipids at the sn-2 position and releases bioactive lipids, modulates polarization of macrophages (M ). Data from our lab suggests that selective iPLA2β-derived lipid signals (iDLs) (i.e., PGs, HETEs, DHETs, LTB4) produced by M from spontaneous-T1D prone nonobese diabetic mice (NOD) are high during the pre-diabetic phase. However, the impact of macrophage-derived iDLs in T1D remains unclear. Therefore, we generated a NOD mouse model with …

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Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty Jan 2023

Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty

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Streptococcus parasanguinis is an oral commensal bacterium that produces hydrogen peroxide. Hydrogen peroxide can react with endogenous molecules such as nitrite to form reactive nitrogen intermediates (RNI). These S. parasanguinis-mediated RNI have been shown to inhibit oral pathogens such as Streptococcus mutans, Enterococcus faecalis, and Aggregatibacter actinomycetemcomitans. As such, S. parasanguinis plays a protective role in the oral microbial ecosystem by antagonizing and preventing colonization by oral pathogens. In addition to being an important organism for the health of the oral cavity, S. parasanguinis has also been associated with improved outcomes for people with cystic fibrosis. There are two explanations …

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Exploring The Regulatory Mechanisms Of Ire1 Signaling In Biotic And Abiotic Stress Responses In Arabidopsis, Taiaba Afrin Jan 2023

Exploring The Regulatory Mechanisms Of Ire1 Signaling In Biotic And Abiotic Stress Responses In Arabidopsis, Taiaba Afrin

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Given their immobility, plants have various survival strategies, including the critical ability to recognize and respond to stressors. Exposure to different environmental and intracellular signals triggers significant modifications in stress response regulators' expression. These changes often occur in the endoplasmic reticulum (ER), where a rise in protein synthesis can overwhelm the system, accumulating misfolded proteins and activating a mechanism known as the unfolded protein response (UPR). UPR is a complex regulatory network with three primary branches in eukaryotic systems. The IRE1-mediated pathway is the most conserved among UPR signaling branches. In Arabidopsis, IRE1 splices bZIP60 mRNA and produces a functional …

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Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen Jan 2023

Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen

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Autoimmune diseases are a classification of more than eighty diseases where the immune system recognizes a self-antigen and mistakenly attacks the body’s own tissue, inducing inflammation a nd p otentially l eading t o d amage. Autoimmune diseases disproportionately affect women and develop at any age depending on the disease. The prevalence of some autoimmune diseases is increased in minority populations. Despite this, research into higher-risk populations is lacking. This highlights the need to contribute research into understanding autoimmune disease pathogenesis in diverse studies to understand why disease is more severe in these populations. We analyzed transcriptomes and methylomes of …

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Gain Of Keratinized Muscosa Around Dental Implants Using A Combination Of Strip Gingival Graft And Acellular Dermal Matrix - A Prospective Case Study, Louai Haddad Jan 2023

Gain Of Keratinized Muscosa Around Dental Implants Using A Combination Of Strip Gingival Graft And Acellular Dermal Matrix - A Prospective Case Study, Louai Haddad

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Several surgical techniques have been described to increase keratinized tissue (KT) around implants and teeth. Despite various methods, the bulk of evidence reported that the use of keratinized autogenous graft (i.e., Free Gingival Grafts (FGG)), harvested from the patient’s palate, remained the gold standard in soft tissue augmentation procedures and provided more predictable results. However, soft tissue autograft supply can be limited, and its harvesting is associated by increased patient morbidity. Several clinical studies have demonstrated the effectiveness of using allogenic soft tissue grafts such as Acellular Dermal Matrix Allograft (ADMA) instead of FGG to augment keratinized tissue (KT). This …

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Failure Modes Of Different Zirconia Crown Heights And Materials On Titanium Base Abutments, Aikaterini Anastasaki Jan 2023

Failure Modes Of Different Zirconia Crown Heights And Materials On Titanium Base Abutments, Aikaterini Anastasaki

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Statement of the Problem: The existing scientific literature lacks comprehensive information regarding the influence of zirconia crown height on debonding and fracture occurrences between zirconia crowns and titanium base abutments. Additionally, there is a lack of comparative studies evaluating different zirconia materials as restorative options for screw-retained restorations. Purpose: The purpose of this study was to assess the failure modes of the zirconia crown/titanium implant abutment complex by investigating the impact of increasing zirconia crown heights and different zirconia materials. Materials and Methods: The experimental design encompassed six groups, each consisting of 10 specimens. Group 1 included 10 non-anatomical crowns …

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The Role Of Runx2 And Sp7 In Ameloblast Differentiation And Postnasal Enamel Synthesis, Reem Alhefdhi Jan 2023

The Role Of Runx2 And Sp7 In Ameloblast Differentiation And Postnasal Enamel Synthesis, Reem Alhefdhi

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In mammals, the mineralized tissues include bone, dentin, enamel, and cementum. Runx2 and its downstream target Sp7 are essential transcription factors for the osteoblast differentiation and formation of bone tissue. However, transcription factors that regulate ameloblast differentiation and enamel secretion are less understood. To uncover the role of Runx2 and Sp7 in ameloblasts differentiation and enamel synthesis, we established a colony of Runx2 and Sp7 floxed mice. Both genes were deleted specifically in ameloblasts using K14-Cre transgenic mice. The successful deletion of Runx2 and Sp7 genes in the epithelium, including ameloblasts, was confirmed using Td-Tomato and GFP reporter, respectively. Histological …

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Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano Jan 2023

Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano

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The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays a critical role in nervous system processes. This includes the maintenance of cellular homeostasis in neurons (1). It also includes synaptic efficacy and plasticity as well as protein turnover, presynaptic vesicle transport, and neuronal protesostasis. Proteasome function is impaired as a consequence of aging, which is aggravated by conditions like Alzheimer's Disease and Related-Dementias (AD, ADRD) (2). According to earlier work from our lab the proteasome is critical to how quickly AD progresses. In Drosophila, human cells, and …

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