Other Immunology and Infectious Disease Commons^™

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

Mathematical Modelling Of Disease Outbreak, Favour Christian, Matthew Molloy

SURE Journal: Science Undergraduate Research Experience Journal

Establishing a model framework for more research necessitates a thorough understanding of the causes, distribution, prevalence, and evolution of infectious illnesses. The main mathematical concept used in this modelling simulation is ordinary differential equations (ODEs). The purpose of this study was to investigate the significance of the many criteria linked to a zombie virus spread. The zombie framework provides an accessible and relatively simple representation of the nature of infectious disease spread, allowing for tractable assumptions and the development of more complex situations.

The models are designed around a zombie outbreak in which the zombie virus is spread through a …

Low Prevalence Of Soil Transmitted Helminth Infection In Ugandan Children Hospitalized With Severe Malaria, Drew Capone, Nuzrath Jahan, Ruth Namazzi, Robert Opoka, Chandy John

Paediatrics and Child Health, East Africa

Co-infection by intestinal helminths and Plasmodium spp. may be common in endemic communities. Several studies have identified a relationship between helminth infection, Plasmodium spp. infection and malaria severity. However, the relationship is not well defined, and results are inconclusive. We analyzed stool samples from a cohort of children with severe malaria enrolled in two hospitals in Uganda from 2014-2017 and asymptomatic community children from the same household or neighborhood and enrolled at the same time, all 6 months to 48 months of age. We investigated if intestinal helminth infection modified risk of severe malaria. We extracted nucleic acids from stool …

Exploring Berberine As A Novel Therapeutic Agent Against Staphylococcus Aureus Infections: Targeting Inflammation And Antibiotic Resistance, Daniel Kopulos

NYMC Student Theses and Dissertations

Staphylococcus aureus is a versatile Gram-positive bacterium commonly found on human skin. While often harmless, it can cause various infections when the skin is compromised, ranging from minor issues to life-threatening conditions in immunocompromised individuals.

The bacterium’s ability to resist antibiotics, particularly methicillin, underscores its clinical challenge. Staphylococcus aureus can also acquire vancomycin resistance. It evades immune responses through multiple mechanisms, including capsule formation, interference with immune proteins like staphylococcal protein A, and secretion of toxins such as Panton-Valentine Leukocidin. Understanding these mechanisms is crucial for developing effective strategies against Staphylococcus aureus infections.

The immune response to Staphylococcus aureus infections …

Complement Propagates Visual System Pathology After Traumatic Brain Injury, Davis Marchant Borucki

MUSC Theses and Dissertations

Background: Traumatic brain injury is associated with the development of visual system disorders, including deficits in visual acuity. Visual deficits can present with delay and worsen over time, suggesting that ongoing neuroinflammatory changes contribute to their development and progression. Complement activation is strongly associated with the neuroinflammatory response after TBI and has been shown to contribute to neuronal and synaptic loss. However, the contributions of complement activation after TBI to vision loss remains unclear.

Methods: We employed an open skull controlled cortical impact model of traumatic brain injury in adult male mice to study how TBI affects vision. Animals were …

Establishment Of Bacteroides In The Gut And Its Role In The Cystic Fibrosis Gut-Lung Axis, Rebecca A. Valls

Dartmouth College Ph.D Dissertations

In the quest to understand the complex interplay between the gut microbiota and cystic fibrosis (CF), a disease characterized by chronic upper respiratory complications and an exacerbated proinflammatory response, our lab engaged in a collaborative study with Dartmouth-Hitchcock Medical Center (DHMC) to characterize the gut microbiota of pediatric CF patients. Initial analyses established a connection between gut microbial composition and respiratory health, particularly highlighting a scarcity of Bacteroides species compared to healthy controls. In following investigations, we utilized random forest models to understand how stool microbiota may influence clinical outcomes of these pediatric CF patients, including: age, upper respiratory infections, …

A One Health Approach To Enhancing Sars-Cov-2 Surveillance, Lauren C. Cybulska

Dissertations and Theses

Background

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease-2019 (COVID-19) in humans, can also infect domestic dogs (Canis lupus familiaris) and cats (Felis catus). Susceptibility and viral transmissibility in these species are concerns for public health due to the spillover risk to humans or other animals. This dissertation uses a One Health framework to explore key issues on this topic. We aim to identify gaps in understanding of SARS-CoV-2 in companion animals and investigate novel surveillance methods through human, animal, and environmental health perspectives.

Methods

Paper 1 provides an in-depth exploration of …

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

Biology and Medicine Through Mathematics Conference

No abstract provided.

The Physiological Significance Of Nitric Oxide Synthase In Staphylococci, Ryan M. Singh

Theses & Dissertations

Staphylococci, particularly Staphylococcus epidermidis, are common causes of implant-associated infections that may result in notable morbidity and mortality. One of the ways the innate immune system attempts to combat these invading pathogens is via the respiratory burst, in which free radical species such as nitric oxide (NO^•), toxic to bacterial respiration, are released in large quantities. Despite the toxicity of NO^•, some bacteria, including staphylococci, encode an endogenous bacterial nitric oxide synthase (bNOS), whose physiological role has been unclear until now. In this dissertation, we demonstrate that S. epidermidis is able to overcome the toxicity …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

An Exploration Of The Effectiveness Of Xanthorrhiza Simplicissima And Its Secondary Alkaloids As Antibiotics Against Staphylococcus Aureus With The Use Of Reserpine, Donald Bothe, Savita Chaurasia

Undergraduate Theses

Xanthorhiza simplicissima is a plant that is steeped in medical history. It has been used for hundreds of years by the Native Americans, and later by the Europeans, of Appalachia for its medicinal properties. One of the most useful medical applications of this plant are its antibiotic properties, as typified by its use as a tea that was consumed to treat mouth sores. These antibiotic properties can be attributed to some of its secondary alkaloids such as berberine, liriodenine, oxyacanthine, and magnoflorine. These compounds have been studied in other systems; however, oxyacanthine and magnoflorine have not been researched in tandem …

The Conceptual Foundations Of Innate Immunity: Taking Stock 30 Years Later, Thomas Pradeu, Bart P.H.J. Thomma, Stephen E. Girardin, Bruno Lemaitre

Presidential Fellows Articles and Research

While largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding of immunology. Innate immunity provides the first barrier to infection in vertebrates, and it is the sole mechanism of host defense in invertebrates and plants. Innate immunity also plays a critical role in maintaining homeostasis, shaping the microbiota, and in disease contexts such as cancer, neurodegeneration, metabolic syndromes, and aging. The emergence of the field of innate immunity has led to an expanded view of the immune system, which is no longer restricted to vertebrates and …

Staphylococcus Aureus Oleate Hydratase Produces Ligands That Activate Host Ppara, Christopher D. Radka, Matthew W. Frank, Tyler S. Simmons, Cydney N. Johnson, Jason W. Rosch, Charles O. Rock

Markey Cancer Center Faculty Publications

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10- hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived …

High Prevalence Of Trypanosoma Cruzi Infection In Raccoons (Procyon Lotor) And Associated Risk To Humans In Central Illinois, Esther Onuselogu

Masters Theses

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a neglected tropical disease and a growing health threat in the United States. Raccoons (Procyon lotor) often coexist with humans in urban and suburban areas and serve as reservoir hosts for T. cruzi. While T. cruzi is rare in humans and domestic animals in the U.S., it is common in wildlife species, particularly raccoons and Virginia opossums (Didelphis virginiana). This study aimed to assess the prevalence of T. cruzi infection in the raccoon population of Central Illinois and evaluate the risk of transmission to humans. …

The Differential Proteomic Response To Ischemic Stroke In Appalachian Subjects Treated With Mechanical Thrombectomy, Christopher J. Mclouth, Benton Maglinger, Jacqueline A. Frank, Kristin J. Hazelwood, Jordan P. Harp, Will Cranford, Shivani Pahwa, David Dornbos Iii, Amanda L. Trout, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

Introduction The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. Methods There were 81 subjects that met inclusion criteria for this …

Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak

Markey Cancer Center Faculty Publications

Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the …

Atm-/-Ung-/- Mice Present Reduced Levels Of Switched Immunoglobulin Isotypes Igg1 And Igg3, Lyric M. Haughton

Dissertations and Theses

B cells excise and recombine the immunoglobulin heavy chain gene locus during class switch recombination (CSR). CSR is mediated by activation induced cytidine deaminase (AID) and results in a new immunoglobulin isotype that B cells will secrete and present. AID produces mutations that convert cytosines to uracils within the intronic switch regions that precede and follow the target immunoglobulin isotype coding sequence. To resolve the mutations, B cells conduct either base excision repair (BER) or mismatch repair (MMR). Inactivating genetic mutations in BER or MMR reduce CSR. For example, a knock-out of uracil DNA glycosylase (UNG) causes a 50% reduction …

Molecular Investigation Of Tick-Borne Pathogens In Feral Swine (Sus Scrofa) From Seven Us States, Sofiane Aiche

Masters Theses

Feral swine (Sus scrofa) have been proposed as part of the lifecycles of multiple tickborne pathogens (TBP). This is a result of the increase in feral swine populations and increased tick populations and geographic ranges. Few surveys exist on the TBP relevant to human and wildlife of feral swine in the US. The aim of this study is to investigate the prevalence of 10 TBP: Anaplasma spp., Borrelia spp., Cytauxzoon felis, Hepatozoon spp., Babesia spp., Mycoplasma spp., Trypanosoma cruzi, Toxoplasma gondii, Yersinia pestis, and Rickettsia spp. A total of 87 feral swine blood samples …

Bridging The Gap: Assessing Cmv Dnaemia In Kidney Transplant Recipients With Previous Solid Organ Transplants, Goni Katz-Greenberg, Julie M Steinbrink, Krishna Shah, Jennifer S Byrns

Faculty, Staff and Students Publications

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive …