Comprehensive Investigation Into The Molecular Mechanisms Driving The Emergence Of Emm4 Group A Streptococcus, Chioma Odo, Samuel A Shelburne, Anthony R. Flores, Steven J Norris, Anna Konovalova, Blake Hanson

Dissertations and Theses (Open Access)

Abstract

Comprehensive Investigation into the Molecular Mechanisms Driving the Emergence of emm4 Group A Streptococcus

Chioma Modeline Odo, M.S.

Advisory Professor: Samuel A. Shelburne, MD, Ph.D.

The major gram-positive bacterium group A Streptococcus (GAS) is a model organism for studying microbial epidemics as it is well known to cause infections that occur in waves. GAS strains are grouped based on the composition of the N-terminal sequence of the M protein which is encoded by the emm gene. With the advent of large-scale whole genome sequencing, GAS clonal emergence events in emm1, emm3, and emm89 types have been identified …

Adaptive Immune Profiling Of Sin Nombre Hantavirus And Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Tonilynn M. Baranowski

Biomedical Sciences ETDs

Hantaviruses are causative agents of potentially fatal respiratory illness and/or organ failure in humans worldwide. In the United States, the predominant hantavirus species, Sin Nombre hantavirus (SNV), causes a severe disease pathology, called hantavirus cardiopulmonary syndrome (HCPS). Infection with SNV and subsequent clinical manifestations of HCPS lends itself to case fatality rates approaching 40%, even under supportive care. This is partially due to the lack of FDA-approved vaccines and antivirals, in addition to a deficit in our knowledge regarding the human immune response to SNV. Further investigation of the adaptive immune response may reveal key targets to mediate disease outcome. …

Role Of Acute Alcohol Exposure In Klebsiella Pneumoniae-Induced Pneumonia, Prantho Malakar Dipta

LSU Master's Theses

Klebsiella pneumoniae (KP), a Gram-negative bacterium, induces severe pneumonia associated with devastating pathological consequences in the lung, such as substantial parenchymal damage. K. pneumoniae is responsible for causing life-threatening lung infections in patients with alcoholics and diabetics. The need to look for new therapeutic approaches is due to the emergence of Klebsiella pneumoniae strains that are resistant to many drugs. The effects of acute alcohol consumption on the host’s innate immune response to KP during infection remain unclear. Age-matched C57BL/6 female mice were administered 6g/kg of 32% alcohol or same amount of PBS via oral gavage 30 minutes prior to …

Deep Sequence-Coupled Biopanning And Vaccine Development, Julianne Peabody

Biomedical Sciences ETDs

Virus-like particles (VLPs) are nanoparticles comprised of viral structural proteins. They physically resemble the virus from which they are derived but lack genomic material. They are non-infectious, non-replicating, and have a favorable safety profile. VLPs are highly immunogenic with a dense, repetitive structure that is strongly activating for B cells. VLPs can be utilized to develop vaccines and can be used either as direct immunogens or platforms for the display of heterologous antigens. The display of foreign peptides on VLPs can be used to elicit high-titer antibodies against the displayed peptide. A virus-like particle based on the RNA bacteriophage MS2 …

Anticoagulant Medications: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Katherine Cashen, Arun Saini, Leonardo R Brandão, Jennifer Le, Paul Monagle, Katie M Moynihan, Lindsay M Ryerson, Alison Gehred, Elizabeth Lyman, Jennifer A Muszynski, Peta M A Alexander, Heidi J Dalton

Faculty, Staff and Students Publications

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the medications used for anticoagulation for pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE (PEACE).

DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION: Included studies assessed anticoagulation used in pediatric ECMO.

DATA EXTRACTION: Two authors reviewed all citations independently, with a third reviewer adjudicating any conflicts. Eighteen references were used for data extraction as well as for creation of recommendations. Evidence tables were constructed using a standardized data extraction form.

DATA SYNTHESIS: …

Management Of Extracorporeal Membrane Oxygenation Anticoagulation In The Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Ariane Willems, Marc M Anders, Alejandro V Garcia, Adam M Vogel, Andrew R Yates, Jennifer A Muszynski, Peta M A Alexander, Katherine Steffen, Sitaram Emani, Alison Gehred, Elizabeth Lyman, Lakshmi Raman

Faculty, Staff and Students Publications

OBJECTIVES: To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference.

DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION: ECMO anticoagulation and hemostasis management in the perioperative period and during procedures.

DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. Evidence tables were constructed …

Priorities For Clinical Research In Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Jennifer A Muszynski, Melania M Bembea, Alison Gehred, Elizabeth Lyman, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Peta M A Alexander

Faculty, Staff and Students Publications

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus.

DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children.

DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third …

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative (Peace) Consensus Conference, Peta M A Alexander, Melania M Bembea, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed S Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Christopher Almond, Marc M Anders, Gail M Annich, Leonardo R Brandão, Wayne Chandler, Megan Delaney, Robert Digeronimo, Sitaram Emani, Samir K Gadepalli, Alejandro V Garcia, Bereketeab Haileselassie, Robert Hyslop, Martin C J Kneyber, Lisa Baumann Kreuziger, Jennifer Le, Laura Loftis, Ali B V Mcmichael, D Michael Mcmullan, Paul Monagle, Kathleen Nicol, Matthew L Paden, Jason Patregnani, John Priest, Leslie Raffini, Lindsay M Ryerson, Steven R Sloan, Jun Teruya, Andrew R Yates, Alison Gehred, Elizabeth Lyman, Jennifer A Muszynski

Faculty, Staff and Students Publications

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.

DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill children.

DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any …

Reversible Male Contraception By Targeted Inhibition Of Serine/Threonine Kinase 33, Angela F Ku, Kiran L Sharma, Hai Minh Ta, Courtney M Sutton, Kurt M Bohren, Yong Wang, Srinivas Chamakuri, Ruihong Chen, John M Hakenjos, Ravikumar Jimmidi, Katarzyna Kent, Feng Li, Jian-Yuan Li, Lang Ma, Chandrashekhar Madasu, Murugesan Palaniappan, Stephen S Palmer, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Yasmin M Vasquez, Jian Wang, Jennifer Wilkinson, Zhifeng Yu, Qiuji Ye, Damian W Young, Mingxing Teng, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that …

A Potential Of Watercress Nasturtium Officinale Bioactive Compounds In Inhibiting Infectious Myonecrosis Virus (Imnv) By Targeting Rna-Dependent Rna Polymerase (Rdrp) Virus From Several Countries: In Silico Approach, Qurrota A’Yunin, Fatchiyah Fatchiyah, Maftuch Maftuch, Feri Eko Hermanto, Muhammad Hermawan Widyananda, Narendra Santika Hartana, Muhaimin Rifa’I, Yoga Dwi Jatmiko

Karbala International Journal of Modern Science

Infectious myonecrosis virus (IMNV) disease causes mass mortality and decreased shrimp production. The RdRp region projects to the interior, where it may function in transcription. The focus of this study was to determine the effect of amino acid polymorphisms from several countries on the structure of RdRp and identify the potential of watercress in inhibiting IMNV by targeting the RdRp protein of IMNV through an in silico approach. The results showed that the structure of the IMNV RdRp protein from Indonesia was similar to Mexico, and the protein structure from India_QDN was identical to India_QIL. Ligand binding affinity values showed …

Mathematical Modeling Suggests Pathways Of Systemic Dissemination Of Mycobacterium Tuberculosis In Mice, Vitaly V. Ganusov

Biology and Medicine Through Mathematics Conference

No abstract provided.

Graphing The Curve: A Mathematical Expedition Into Social Distancing's Role In The South African Covid-19 Narrative, Chidozie Williams Chukwu

Biology and Medicine Through Mathematics Conference

No abstract provided.

New Insights Into T Lymphocyte-Mediated Immunity To Toxoplasma Gondii, Claire Marie Doherty

Biology ETDs

With nearly a third of the global population infected with the protozoan, Toxoplasma gondii, this parasite sits at a unique, immune-mediated interface of health and disease. In healthy individuals, Toxoplasma results in a chronic yet asymptomatic infection of the central nervous system. This quiescent infection is the result of parasite exploitation of host immune barriers, yet Toxoplasma can quickly become an opportunistic pathogen when immunity is disrupted by illness or immunosuppressive therapies. During the HIV-AIDS pandemic, it was observed that once latent Toxoplasma infections became the cause of severe, even fatal, disease in the absence of an intact T …

Inhibition Of Pro-Inflammatory Lipid Mediators By Yersinia Pestis., Amanda Brady

Electronic Theses and Dissertations

Yersinia pestis causes the human disease known as plague. A key manifestation of plague is a delayed inflammatory response. Because this delay in inflammation is required for virulence, I was interested in defining the molecular mechanisms used by Y. pestis to evade immune recognition. Eicosanoids are produced early during infection and necessary to initiate a rapid inflammatory response. Despite the importance of these lipids in mediating inflammation, the role of eicosanoids during plague has not been previously investigated. Using an intranasal mouse model infection, I determined the kinetics of eicosanoid synthesis during pneumonic plague. I further demonstrated that LTB_{4 …}

Porphyromonas Gingivalis Inactivates Anti-Viral Immunity At The Oral And Respiratory Epithelium., Carlos J. Rodriguez Hernandez

Electronic Theses and Dissertations

The host microbiome plays an important role in fine-tuning host immune responses in a manner that ultimately impacts outcomes in viral infection. Symbiotic relationships between commensal bacteria and host epithelial and immune cells prime interferon (IFN) signaling, modulating the nature and intensity of the immune response to viral infections at mucosal barrier surfaces. In this doctoral thesis, I explore how dysbiotic shifts in the oral microbial communities modulate antiviral responses at the oral and oro-respiratory mucosal barriers. I identified that in response to a viral challenge, gingival epithelial cells (GECs) preferentially induced type III IFNs (IFN-λ), a newly described family …

Regulation Of Cd4 T Cell Functions By Ncrna-Mediated Signaling Pathways During Chronic Viral Infections, Lam Nguyen

Electronic Theses and Dissertations

CD4 T cell homeostasis and competency are critical for the effectiveness of antiviral immunity. However, CD4 T cells derived from people living with HIV (PLWH) and individuals with chronic HCV infection often exhibit an inflammaging phenotype, evidenced by persistent inflammation, immune activation, exhaustion, senescence, and cellular apoptosis. Despite intensive investigations, the molecular mechanisms underlying CD4 T cell dysfunction in antiretroviral therapy (ART)-controlled PLWH and HCV-infected patients remain poorly understood. By investigating the roles of non-coding (nc)RNA transcripts in regulating the functions of CD4 T cells derived from PLWH and HCV-infected patients, we demonstrated that long non-coding (lnc)RNA - growth arrest-specific …

Antimicrobial Activity Of Cat Flea (Ctenocephalides Felis) Gut Proteins On Different Days After Blood Feeding, Dhruva K. Karnik

Honors College Theses

Cat fleas (Ctenocephalides felis) are a blood-feeding ectoparasitic insect and a common domestic pest found throughout the world. Because of their reliance on host blood, fleas are exposed to blood-borne pathogens; however, the flea gut lumen is a hostile environment for microbial colonization. For example, the gut epithelia differentially express immune genes in response to feeding. In the present study, we measured the antimicrobial activity of gut proteins from cat fleas at different days after feeding (2, 5, 7, and 14). Dissected flea guts were homogenized, passed through a syringe filter, and measured in a protein assay kit. …

Role Of Toll-Like Receptor 2 In Macrophage Recognition And Response To Borrelia Burgdorferi, Yukiye A. Koide

Master's Theses

Lyme disease is the most common vector-borne disease in the US and will experience an uptick as the insect host, the ixodid tick, gains habitat with climate change. The causative agent of Lyme disease, Borrelia burgdorferi, is recognized by Toll-like receptor 2 (TLR2), which initiates the innate immune response. Here, I used ELISA and SEAP detection assays to determine that knocking out TLR2 in THP-1 macrophages reduces the amount of NFkB activation, as well as IL-10 and IL-1β secretion. Then, I used fluorescence microscopy and Incucyte assays to quantify the amount of phagocytosis performed by wild-type and knock-out THP-1 cells. …

Large-Scale Phenotyping Of Patients With Long Covid Post-Hospitalization Reveals Mechanistic Subtypes Of Disease, Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin K Sidhu, Stephanie Ascough, Shona C Moore, Noura Mohamed, Jose Nunag, Clara King, Olivia C Leavy, Omer Elneima, Hamish J C Mcauley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria C Harris, Linzy Houchen-Wolloff, Neil J Greening, Nazir I Lone, Matthew Thorpe, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke S Howard, Daniel G Wootton, Jennifer K Quint, Thushan I De Silva, Antonia Ho, Christopher Chiu, Ewen M Harrison, William Greenhalf, J Kenneth Baillie, Malcolm G Semple, Lance Turtle, Rachael A Evans, Louise V Wain, Christopher Brightling, Ryan S Thwaites, Peter J M Openshaw, Phosp-Covid Collaborative Group, Isaric Investigators

Faculty, Staff and Student Publications

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers …

Effectiveness Of Cord Blood As A Strategy To Rule Out Conjugated Hyperbilirubinemia, Miray Kurtca, Sanjiv Harpavat, Sridevi Devaraj

Faculty, Staff and Students Publications

Early detection of biliary atresia is crucial for timely intervention and improved outcomes in infants with elevated conjugated bilirubin levels. This study aims to investigate the viability of cord blood gas analysis as a novel method for assessing conjugated bilirubin levels. Infants with high heel stick levels also showed elevated cord blood bilirubin levels, indicating that cord blood testing could replace the need for repeat heel stick tests, especially benefiting low birth weight infants. Ongoing research, including larger cohorts and alternative bilirubin measurement methods, will further validate this innovative screening approach. Infants with biliary atresia have high conjugated bilirubin levels …