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Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat 2022 The University of Texas MD Anderson Cancer Center

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and 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, …


A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye 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 …


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 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, Javier A. Mas Rosario 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, Sajid Bashir Soofi, Maureen Martinez, Noha H. Farag, William S. Hendley, Derek Ehrhardt, Imran Ahmed, Imtiaz Hussain, William Weldon, Ahmed M. Kassem 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 …


The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia 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

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and 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, Alex Lac 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 …


Factors Affecting The Antibacterial Activity Of Cefiderocol On Klebsiella Pneumoniae With Diverse Characteristics, Lana Jamal Rashed Daoud 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 …


Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner 2022 Clemson University

Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner

All Theses

Aspergillus fumigatus is a fungus found ubiquitously in the environment including in the air we breathe. Though not a threat to most people, immunodeficient or immunosuppressed individuals are at risk for developing severe infection, including the life-threatening condition of invasive aspergillosis. The hematopoietic cell specific GTPase protein Rac2 is associated with major roles in innate immune defense. Currently Rac2 has been demonstrated to be crucial for survival against a variety of infections. Here, we use a rac2 null mutant zebrafish line and morpholino approaches to elucidate roles of Rac2 in mounting the macrophage host defense response against A. fumigatus infection. …


Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert 2022 University of Arkansas, Fayetteville

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert

Animal Science Undergraduate Honors Theses

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 …


Aggregatibacter Actinomycetemcomitans Exploits And Modulates The Immune Response By Human Neutrophils For Survival In The Anaerobic Environment., Hazel Ozuna 2022 University of Louisville

Aggregatibacter Actinomycetemcomitans Exploits And Modulates The Immune Response By Human Neutrophils For Survival In The Anaerobic Environment., Hazel Ozuna

Electronic Theses and Dissertations

Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative facultative anaerobe and an opportunistic oral pathogen, strongly associated with localized periodontitis and other inflammatory diseases. Periodontitis is a chronic inflammation of the periodontium resulting from the inflammatory response of the host towards the dysbiotic microbial community present at the gingival crevice. The host immune response creates a hostile environment for microorganisms; therefore, it is important for Aa to be able to regulate the necessary genes to survive and thrive in such an environment. Aaexpresses several virulence factors such as a cytolethal distending toxin (Cdt), lipopolysaccharide (LPS) and leukotoxin A (LtxA), …


Increasing Human Papillomavirus Vaccination Intent And Knowledge Through An Educational Intervention, Angelica E. Musumeci 2022 University of Nevada, Las Vegas

Increasing Human Papillomavirus Vaccination Intent And Knowledge Through An Educational Intervention, Angelica E. Musumeci

UNLV Theses, Dissertations, Professional Papers, and Capstones

Human papillomavirus (HPV) is a widely discussed topic in healthcare as it affects patients of all genders and ages who partake in sexual activity. The most significant concern it poses to those at risk is HPV-related cancer. Fortunately, a vaccination exists that targets specific strains associated with these types of cancers. Despite evidence-based research supporting the vaccination’s efficacy and safety, lack of awareness and misinformation diminish the receipt of the vaccine and drive the lack of protection. Thus, educational interventions directed at parents and caregivers, which aims to improve their understanding of HPV and the vaccination’s benefits, is key to …


Genomic Tools And Models For Investigating The Role Of Germline Diversity In Mouse Antibody Repertoire Development., Justin T. Kos 2022 University of Louisville

Genomic Tools And Models For Investigating The Role Of Germline Diversity In Mouse Antibody Repertoire Development., Justin T. Kos

Electronic Theses and Dissertations

Given the diversity and complexity within immunoglobulin (IG) loci, effective mouse models first require characterization of intra-strain differences and construction of high-quality reference assemblies for IG loci in several representative strains. To understand light chain germline diversity across biomedically significant mouse strains, we profiled the expressed IGK and IGL repertoires of 18 commonly used laboratory mouse strains using AIRR-seq. Across strains, we observed germline IGKV sequences shared by three different IGK haplotypes and a more conserved IGLV germline repertoire among common laboratory strains. Pacific Biosciences (PacBio) Single-Molecule Real-Time (SMRT) sequencing was used to sequence and assemble bacterial artificial chromosomes (BAC) …


Physician's Attitudes On Pulmonary Rehabilitation Following Covid-19: A Brief Perspective From A Developing Country, Ivan Cherrez-Ojeda, Emanuel Vanegas, Miguel Felix, María José Farfán Bajaña, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho, Alanna Barrios-Ruiz, Jack Michel 2022 Universidad Espíritu Santo, Samborondón, Ecuador

Physician's Attitudes On Pulmonary Rehabilitation Following Covid-19: A Brief Perspective From A Developing Country, Ivan Cherrez-Ojeda, Emanuel Vanegas, Miguel Felix, María José Farfán Bajaña, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho, Alanna Barrios-Ruiz, Jack Michel

Department of Paediatrics and Child Health

Despite the uncertainty about the follow up of COVID-19 survivors, there is a growing body of evidence supporting specific interventions including pulmonary rehabilitation, which may lead to a reduced hospital stay and improved overall respiratory function. The aim of this short report was to assess the attitudes toward pulmonary rehabilitation following COVID-19 among Ecuadorian physicians. A cross-sectional study was conducted, in which a 5-question survey was used to assess the level of agreement to specific statements with a 5-point Likert scale. Out of the 282 participants, 48.2% (n=136) were male, with a mean of 12.6 (SD=11.3) years of experience. More …


Wc1 And Tcr Interactions For Γδ T Cell Activation, Alexandria Gillespie 2022 University of Massachusetts Amherst

Wc1 And Tcr Interactions For Γδ T Cell Activation, Alexandria Gillespie

Doctoral Dissertations

Major subpopulations of gamma delta T cells within ruminant and pigs are defined by expression of WC1, a hybrid pattern recognition receptor/co-receptor to the T cell receptor (TCR). It is known that when WC1 is knocked down cells fail to respond. Showing that WC1 plays an active role in the stimulation of bovine gamma delta T cells. Here we explored the spatio-temporal dynamics of WC1 and TCR interaction using imaging flow cytometry and stochastic optical reconstruction microscopy. We found that in quiescent gamma delta T cells both WC1 and TCR existed in separate protein domains (protein islands) but after activation …


Salicylic Acid And N-Hydroxypipecolic Acid At The Fulcrum Of The Plant Immunity-Growth Equilibrium, Alyssa Shields, Vanessa Shivnauth, Christian Danve M. Castroverde 2022 Wilfrid Laurier University

Salicylic Acid And N-Hydroxypipecolic Acid At The Fulcrum Of The Plant Immunity-Growth Equilibrium, Alyssa Shields, Vanessa Shivnauth, Christian Danve M. Castroverde

Biology Faculty Publications

Salicylic acid (SA) and N-hydroxypipecolic acid (NHP) are two central plant immune signals involved in both resistance at local sites of pathogen infection (basal resistance) and at distal uninfected sites after primary infection (systemic acquired resistance). Major discoveries and advances have led to deeper understanding of their biosynthesis and signaling during plant defense responses. In addition to their well-defined roles in immunity, recent research is emerging on their direct mechanistic impacts on plant growth and development. In this review, we will first provide an overview of how SA and NHP regulate local and systemic immune responses in plants. We …


Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef 2022 The American University in Cairo AUC

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …


The Role Of Ly49 Receptors In Maintaining Healthy Murine Pregnancy, Michelle Belmont 2022 Loyola University Chicago

The Role Of Ly49 Receptors In Maintaining Healthy Murine Pregnancy, Michelle Belmont

Master's Theses

Natural Killer (NK) cells are abundant in pregnancy and contribute to the health of the fetus. Uterine NK (uNK) cells provide less cytotoxic function than their conventional NK (cNK) cell counterparts. Various combinations of Killer Immunoglobulin Receptor (KIR)- Human Leukocyte Antigen (HLA) on maternal NK and fetally derived cells, respectively, can have different effects on the health of pregnancy in humans. Murine NK cells contain Ly49 receptors, an equivalent to KIRs. Therefore, Ly49 receptor interactions with fetally-derived MHC-I molecules can be a valuable model for studying the role of NK cells in pregnancy. The process of spiral artery remodeling can …


Phenotypic Analysis Of Murine Gut Associated Lymphocytes, Madison Flood 2022 Loyola University Chicago

Phenotypic Analysis Of Murine Gut Associated Lymphocytes, Madison Flood

Master's Theses

γδ T cells are important in the role of immune homeostasis, especially in relation to the gut. It has been shown that there is a higher proportion of γδ T cells in the intestines than in circulation. With this knowledge, our lab focused on understanding the mechanisms of these cells, specifically regarding immune tolerance. In our preliminary research, we identified a subset of γδ T cells that express Foxp3, a transcription factor essential for the functioning of regulatory T cells, in the neonatal (5 day old) intestine. We hypothesized that these Foxp3+ γδ T cells have immunosuppressive functions upon exposure …


Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian M. Gilbert, Jossie M. Santamaria, Gisela F. Erf 2022 University of Arkansas, Fayetteville

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian M. Gilbert, Jossie M. Santamaria, Gisela F. Erf

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Lipoteichoic acid (LTA) is a cell-wall polymer in Gram-positive bacteria that stimulates inflammation. Few studies have investigated in vivo immune response to LTA, and none of the in vivo studies have been performed in birds. For this project, the pulp (a skin derivative) of growing feathers (GF) of chickens was used to investigate the in vivo effects of intradermally injected LTA. In Study 1, GF of chickens were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 or 250 μg LTA/mL; 3 chickens/dose). Growing feathers were plucked before injection (0 h) and at 6, 24, 48, …


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