Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, 2023 University of Texas at Tyler
Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari
Biotechnology Theses
The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …
Elafibranor Modulates Ileal Macrophage Polarization To Restore Intestinal Integrity In Nash: Potential Crosstalk Between Ileal Il-10/Stat3 And Hepatic Tlr4/Nf-Κb Axes, 2023 The British University in Egypt
Elafibranor Modulates Ileal Macrophage Polarization To Restore Intestinal Integrity In Nash: Potential Crosstalk Between Ileal Il-10/Stat3 And Hepatic Tlr4/Nf-Κb Axes, Andrew Hakeem, Mohamed M. Kamal, Rasha A. Radwan, Basma A. Abdelrahman, Olfat A. Hammam, Mohey M. Elmazar, Aiman S. El-Khatib, Yasmeen M. Attia
Pharmacy
Experimental and clinical evidence implicate disrupted gut barrier integrity in provoking innate immune responses, specifically macrophages, towards the progression of non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptors (PPARs), a subset of the nuclear receptor superfamily, act to fine-tune several metabolic and inflammatory processes implicated in NASH. As such, the current study was carried out to decipher the potential role of dual PPAR α/δ activation using elafibranor (ELA) on ileal macrophage polarization (MP) and its likely impact on the liver in a NASH setting. To achieve this aim, an in vitro NASH model using fat-laden HepG2 cells was first used to validate …
The Psychology Of Science Denialism And Lessons For Public Health Authorities, 2023 King & Spalding
The Psychology Of Science Denialism And Lessons For Public Health Authorities, Brenna Moreno, Molly J. Walker Wilson
All Faculty Scholarship
As it wreaked tragedy on the world, the outbreak of COVID-19 helped expose a pandemic of a different kind, one steeped in distrust and contrarianism. This movement, termed science denialism, has been lurking and undermining public health efforts for decades. Specifically, it is “the employment of rhetorical arguments to give the appearance of legitimate debate where there is none, an approach that has the ultimate goal of rejecting a proposition on which a scientific consensus exists.” Unlike skepticism, which is “doubt as to the truth of something” and works to progress both science and society, denialism is characterized by individuals’ …
Tissue And Sex-Dependent Regulation Of Innate Immunity And Rna Editing In Mice, 2023 Missouri State University
Tissue And Sex-Dependent Regulation Of Innate Immunity And Rna Editing In Mice, Kelsey R. Kendrick
MSU Graduate Theses
Inflammation occurs as a result of insult or infection within the body. Individual cells respond to inflammation by upregulating genes that help mediate the immune response, such as ADAR1. ADAR1 helps regulate the immune response but also catalyzes a process called RNA editing. RNA editing alters the sequence of select mRNAs to alter the encoded proteins. The result is altered function of the encoded protein, which is often beneficial for the cell. Our goal was to determine how inflammation affects the function of ADAR1. Since we know that the effects of inflammation vary between different organs and sexes, we examined …
Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, 2023 Missouri State University
Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas
MSU Graduate Theses
The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …
Cluster Homolog Of Immunoglobulin-Like Receptor Genes In Chicken Immune Responses, 2023 West Virginia University, Western University of Health Sciences
Cluster Homolog Of Immunoglobulin-Like Receptor Genes In Chicken Immune Responses, Brandi A. Sparling
Graduate Theses, Dissertations, and Problem Reports
This dissertation explores the identity and role of immunoglobulin-like (Ig-like) receptors in chickens, with focus on their implications in disease and disease progression. These receptors, wisely expressed across immune cells, interact with the major histocompatibility complex (MHC) class I molecules to modulate immune responses in mammals. Due to the insufficient representation of chicken Ig-like receptors in online databases, this study systematically annotates the chicken Cluster Homolog of Immunoglobulin-like Receptors (CHIR) genes using advanced bioinformatic techniques, aligning with the release of the 7th edition of the chicken genome assembly that comprises builds for a broiler and layer chicken. The analysis identifies …
Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, 2022 The University of Western Ontario
Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury
Electronic Thesis and Dissertation Repository
While the role of autoimmune T cells has been extensively studied in anti-myelin
autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …
A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, 2022 University of Tennessee, Knoxville
A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye
Doctoral Dissertations
T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …
Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, 2022 The University of Texas MD Anderson Cancer Center
Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat
Dissertations & Theses (Open Access)
Doxorubicin (Dox) is one of the most effective chemotherapy agents that is used for the treatment of childhood cancer. Unfortunately Dox treatment can cause damage to the heart. Indeed, childhood cancer survivors are at a higher risk of developing a cardiovascular disease at an earlier age. The mechanisms by which Dox causes acute and late cardiotoxicity are not completely understood. One understudied area in Dox-induced cardiotoxicity is the contribution of inflammation and innate immune cells, in particular neutrophils. Recognizing that neutrophils have been implicated in a number of heart diseases, we evaluated the role of neutrophils in Dox-induced cardiotoxicity. Here, …
Comparison Of The Humoral Immune Response Following Both Bacterial Challenge And Rnai Of Major Factors On Proliferation Of Bartonella Quintana In The Human Louse, 2022 University of Massachusetts Amherst
Comparison Of The Humoral Immune Response Following Both Bacterial Challenge And Rnai Of Major Factors On Proliferation Of Bartonella Quintana In The Human Louse, Jake Zina
Masters Theses
Human body lice, Pediculus humanus humanus, and head lice, Pediculus humanus capitis, have been hematophagous ectoparasites of humans for thousands of years. Despite being ecotypes, only body lice are known to transmit bacterial diseases to humans, and it appears that lower humoral and cellular immune responses allow body lice to possess a higher vector competence. We previously observed that the transcription level of the defensin 1 gene was up-regulated only in head lice following oral challenge of Bartonella quintana, a causative agent of trench fever, and also that body lice excreted more viable B. quintana in their …
Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, 2022 University of Massachusetts Amherst
Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario
Doctoral Dissertations
Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …
Poliovirus Immunity Among Children Aged 6-11 And 36-48 Months In 14 Polio High-Risk Provinces Of Afghanistan: A Health-Facility-Based Study, 2022 Aga Khan University
Poliovirus Immunity Among Children Aged 6-11 And 36-48 Months In 14 Polio High-Risk Provinces Of Afghanistan: A Health-Facility-Based Study, Sajid Bashir Soofi, Maureen Martinez, Noha H. Farag, William S. Hendley, Derek Ehrhardt, Imran Ahmed, Imtiaz Hussain, William Weldon, Ahmed M. Kassem
Department of Paediatrics and Child Health
Afghanistan is one of two countries where wild poliovirus (WPV) type 1 remains endemic. We conducted a facility-based cross-sectional survey of antipoliovirus antibodies in children in 14 provinces of Afghanistan. The provinces were selected based on programmatic priorities for polio eradication. Children aged 6-11 and 36-48 months attending outpatient clinics were enrolled in the study. We collected venous blood, isolated serum, and conducted neutralization assays to detect poliovirus neutralizing antibodies. A total of 2086 children from the 14 provinces were enrolled. Among the enrolled children, 44.3% were girls; the median age in the 6-11-month group was 9.4 months, and in …
Elucidating The Mechanisms Underlying How Vmp1 Regulates Inflammatory Responses, 2022 Loyola University Chicago
Elucidating The Mechanisms Underlying How Vmp1 Regulates Inflammatory Responses, Stephanie Zack
Dissertations
autophagy, inflammation, mitochondria, NLRP3 inflammasome, SERCA, VMP1
Function Of Atm And Msh2 During Dna Repair And Recombination, 2022 The Graduate Center, City University of New York
Function Of Atm And Msh2 During Dna Repair And Recombination, Emily Sible
Dissertations, Theses, and Capstone Projects
Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm-/- mice …
Neural Stem Cells: Age-Dependent Outcomes During Viral Infections In The Central Nervous System, 2022 Duquesne University
Neural Stem Cells: Age-Dependent Outcomes During Viral Infections In The Central Nervous System, Manisha N. Chandwani
Electronic Theses and Dissertations
Viral infections in the central nervous system (CNS) are associated with neurodevelopmental and neurobehavioral deficits. The outcomes of viral infections can be driven by damage and death of neurons. Neural stem cells (NSCs) play key roles in neurodevelopment, repair, and physiological brain function. During a viral infection, NSC activity can disturbed by direct infection of NSCs by the virus or by anti-viral immune response. Here, we aimed to assess whether the anti-viral immune response can impact NSC activity during an immunocompetent response in the adult brain. We utilized a transgenic mouse model of Measles virus infection where only the CNS …
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, 2022 The Texas Medical Center Library
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia
Dissertations & Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …
Regulation Of Mhc Ii Trafficking And Expression By Host And Viral Factors, 2022 The University of Western Ontario
Regulation Of Mhc Ii Trafficking And Expression By Host And Viral Factors, Alex Lac
Electronic Thesis and Dissertation Repository
Antigen presentation by major histocompatibility complex class II (MHC II) to the adaptive immune system is crucial for mounting sterilizing immune responses. This central role has made antigen presentation a target for antagonism by many pathogens. Notably, infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decrease MHC II expression in several immune cells. The mechanisms responsible for this suppression are unknown but involves either redirecting MHC II molecules away from the cell surface or inhibiting MHC II expression. To understand how pathogens manipulate intracellular MHC II trafficking, we first investigated the role of the Golgi trafficking regulator, ERC1, in …
The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, 2022 The University of Western Ontario
The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams
Electronic Thesis and Dissertation Repository
B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …
Characterizing Endogenous Dicer Products To Unravel Novel Rnai Biogenesis Pathways, 2022 The University of Southern Mississippi
Characterizing Endogenous Dicer Products To Unravel Novel Rnai Biogenesis Pathways, Jacob Oche Peter
Dissertations
ABSTRACT
RNA interference (RNAi) is a pervasive gene regulatory mechanism in eukaryotes based on the action of multiple classes of small RNA (sRNA). Exploiting RNAi pathways in non-model systems have great potential for creating potent RNAi technologies. Here, we accessed RNAi-mediated control of gene expression in the two-spotted spider mite, Tetranychus urticae (T. urticae) using engineered dsRNA designed to modulate the host RNAi pathway and increase RNAi efficacy. Analysis of Dicer (Dcr) generated fragments revealed how exogenous RNAs access the host RNAi pathway in this animal, opening avenues for designing RNAi technology for their control. Further, some organisms …
Factors Affecting The Antibacterial Activity Of Cefiderocol On Klebsiella Pneumoniae With Diverse Characteristics, 2022 United Arab Emirates University
Factors Affecting The Antibacterial Activity Of Cefiderocol On Klebsiella Pneumoniae With Diverse Characteristics, Lana Jamal Rashed Daoud
Theses
Antimicrobial resistance (AMR) is a growing serious threat that poses a burden on the healthcare system. Spread of AMR bacteria limits treatment options; thus, new antimicrobial agents are required. Cefiderocol (CFDC) is a novel siderophore cephalosporin, approved by the FDA in 2019 for use in treating infections caused by multi-drug resistant (MDR) pathogens; but it is not yet in clinical use in the UAE. CFDC is equipped with stabilizers against β-lactamases as well as a siderophore side chain that allows it to penetrate the outer membrane of bacteria through the iron uptake pathways. The aim of this study is to …