Life Sciences Commons^™

Gut Dysbiosis Correlates With Covid-19 Severity, Ednita Escobar

CMC Senior Theses

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) impacts not only respiratory but also gut and oral microbiomes, influencing the manifestations of COVID-19. Each person’s unique microbiome consists of microorganisms such as bacteria, fungi, and viruses, some of which are symbiotic and others potentially harmful. Alterations in the gut microbiome, specifically, can affect the severity and symptoms of COVID-19. A review of studies indicate a pattern of gut dysbiosis in COVID-19 patients characterized by a decrease in beneficial microbiota and/or an increase in opportunistic pathogens. This gut imbalance correlates with disease severity, suggesting that the gut microbiome plays a significant role …

The Characterization Of Vig-1’S Expression Patterns In Ipnv-Infected, Or Dsrna-Treated, Rainbow Trout Cells, Samantha Lum

Theses and Dissertations (Comprehensive)

In Canada, annual trout production is valued at over $60M with approximately 10,000 tonnes of trout produced per year. Rainbow trout (Oncorhynchus mykiss) are one of the most commonly farmed fresh-water fish in Canada. The high-density farming practices involved in aquaculture increase rainbow trout susceptibility to aquatic viruses such as infectious pancreatic necrosis virus (IPNV). The innate antiviral immune response in rainbow trout is poorly characterized, and the functions of numerous interferon stimulated genes (ISG) in rainbow trout remain unclear. One such gene, virus-induced gene 1 (vig-1) has been poorly studied; however, the human orthologue for vig-1 …

Effect Of Macrophage Expressed Α7 Nicotinic Acetylcholine Receptor (Α7nachr) On Migration Of Macrophages During Inflammation, Kasey Keever

Electronic Theses and Dissertations

Sepsis is a life-threatening condition characterized by overwhelming inflammation, resulting in organ system damage, leading to a high mortality rate. Care in the clinical setting is supportive, and there are no approved sepsis-specific treatments. In septic mice, activation of the cholinergic anti-inflammatory pathway decreases cytokine secretion by leukocytes and improves survival. The cholinergic anti-inflammatory pathway is a reflex of the parasympathetic nervous system, converging on the α7 nicotinic acetylcholine (α7nAChR) at the surface of macrophages. Signaling through the receptor blocks NF-kB activation, thus cytokine secretion. Receptor activation has other effects on macrophages, including modulating their migration to …

Cellular Mechanism Of Pentagalloyl Gucose-Mediated Prevention And Reversal Of Abdominal Aortic Aneurysms, Greg Halsey

All Dissertations

Abdominal aortic aneurysm (AAA) has been the 15th leading cause of death in persons older than 55 for the past ten years in several Western countries, with rupture resulting in an almost 100% mortality rate. AAA is a focal dilation of the aorta characterized by progressive loss of elastin and vascular smooth muscle cells (SMCs), as well as persistent inflammatory response [1]. The only treatment for AAA is surgery; however, the mortality post-procedure is still 1-4%, with a 15-30% chance of morbidity [2].

Pentagalloyl glucose (PGG) treatment is effective in the reversal of AAA. While its stabilizing interactions with extracellular …

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman

All Dissertations

The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …

Development Of Novel Methods To Study Host-Microbe Interactions In The Larval Zebrafish Gastrointestinal Tract, Anh K. Trinh Nguyen

Dissertations & Theses (Open Access)

The dynamic nature and inaccessible location of the intestine pose significant challenges to the study of intestinal physiology and pathology. Zebrafish larvae, possessing optical transparency and genetic tractability, offer an accessible and clinically relevant model for investigating dynamic events in the intestine via time-lapse imaging. In the first part of this work, I discuss our efforts to optimize the parameters of a foodborne infection assay using paramecia as a vehicle. This method provides an effective, high-throughput alternative to infection via immersion or oral gavage, and replicates the most common route of transmission of gastrointestinal (GI) infection in humans. The foodborne …

Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson

Graduate Theses and Dissertations

Bats are an ecologically important taxon that can host zoonotic pathogens. Globally, many bat species are synanthropic and live closely with humans, often roosting in man-made structures. The spatial overlap between humans and bats creates opportunities for human-bat contact, which can lead to human exposure to bat-borne pathogens and conflicts that cause bat mortality. Despite this risk, little is known about the drivers and characteristics of these human-bat interactions in buildings and work is needed to understand this aspect of the wildlife-urban interface. In Chapter I, I present a literature review that identifies the geographic and taxonomic trends in reported …

Evaluation Of The Efficacy Of Synthetic Glycovaccines Against Both Murine Acute Chagas Disease And Cutaneous Leishmaniasis, Colin D. Knight

Open Access Theses & Dissertations

Chagas disease (CD) and cutaneous leishmaniasis (CL) are neglected tropical diseases caused by the protozoan trypanosomatids, Trypanosoma cruzi and Leishmania spp., respectively. There are approximately 6-8 million people infected with T. cruzi worldwide and ~300,000 people in the US. Between 700,000 and 1.2 million new cases of CL occur worldwide yearly. The approved chemotherapies for both diseases are partially effective and may cause serious adverse events, resulting in premature treatment interruption. Moreover, no effective vaccine for either disease is available. Therefore, developing a vaccine that would provide effective cross-protection against both diseases would provide a cost-effective alternative to the existing …

Exploration Of The Implementation Of An Integrated Electronic Laboratory Information Management System On Quality Diagnostics Service Indicators At A County Level Public Hospital In Western Kenya., Kelly Allen

Capstone Collection

Underinvestment in pathology and laboratory capacity caused by low visibility in research and in prioritization by public health leaders results in limited effective healthcare coverage and an estimated 1.1 million premature deaths annually in Low-and-Middle-Income Countries. Kenya’s public health laboratories provide a median 41% of the Essential Diagnostic List to their patients and in Kisumu County, as much as 44.2% of the population has little to no access to essential diagnostics. The government of Kisumu implemented the county Health Laboratory Strategic Plan 2018-2022 to address this public health challenge. Little information exists on the effectiveness of these initiatives and the …

Modified Vaccine Vectors To Understand Adjuvant Functions Of Listeria During Chronic Schistosomiasis, Stephanie K. Norwood

Biological Sciences Theses & Dissertations

Vaccination is one of the most effective strategies employed to prevent infectious diseases. Successful vaccination is dependent upon the induction of a specific, robust, and prolonged immune response. One of the major challenges faced by vaccine development is vaccine failure due to host-related factors that can modulate the immune system, which leads to non-responsiveness to vaccinations. The generation of new vaccine strategies is imperative to combat these effects. Live bacterial vectors are one approach used as they can elicit humoral immunity, cellular immunity, or both. Listeria monocytogenes is a Gram positive, intracellular pathogen that is an effective bacterial vaccine vector …

The Role Of The Mek1/2-Erk-Rsk Signalling Axis In Innate Immune Memory, Rachel Low

Electronic Thesis and Dissertation Repository

Macrophages are innate immune cells that change their cellular states in response to different stimuli. This process is referred to as “innate immune memory” which can render two polarizing states: hyporesponsive (tolerated) or hyperresponsive (trained) states. To date, epigenetic modifications were shown to play a key role in innate immune memory. However, the signalling that induces memory is poorly understood. In this study, I examined the effects of various inhibitors targeting key signalling molecules involved in the activation of macrophages by the Gram-negative cell wall component lipopolysaccharide. I found that prolonged inhibition of the MEK1/2-ERK-RSK signalling axis prevented tolerance and …

Endothelial Interleukin-17 Receptor D (Il17rd) Promotes Western Diet-Induced Aortic Myeloid Cell Infiltration, Shivangi Pande

Electronic Theses and Dissertations

The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor), belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent monocyte adhesion. We utilized primary human aortic endothelial cells and demonstrated that RNAi targeting of IL17RD suppressed transcript levels by 83% compared to non-targeted controls. Further, RNAi knockdown of IL17RD decreased the adhesion of THP-1 cells …

Genome-Scale Methylation Analysis In Blood And Tumor Identifies Immune Profile, Age Acceleration, And Dna Methylation Alterations Associated With Bladder Cancer Outcomes, Ji-Qing Chen

Dartmouth College Ph.D Dissertations

Bladder cancer patients receive frequent screening due to the high tumor recurrence rate (more than 60%). Nowadays, the conventional monitoring method relies on cystoscopy which is highly invasive and increases patient morbidity and burden to the health care system with frequent follow-up. As a result, it is urgent to explore novel markers related to the outcomes of bladder cancer. Immune profiles have been associated with cancer outcomes and may have the potential to be biomarkers for outcomes management. However, little work has been conducted to investigate the associations of immune cell profiles with bladder cancer outcomes. Here, I utilized the …

Parasites Versus Predation: The Role Of Chronic And Acute Parasite Exposure In Infection Risk And Anti-Predator Behavior, Delaney Farrell

All HCAS Student Capstones, Theses, and Dissertations

Parasites with complex, multi-host lifecycles often engage in host behavior manipulation to increase transmission between successive hosts. In intermediate fish hosts, previous research has measured increased frequency of conspicuous behaviors, decreased swimming performance, and reduced antipredator behavior, which would collectively increase the fish’s risk of predation. In ecosystems where this type of parasite increased trophic transmission (PITT) occurs, parasites can play a substantial role in food webs. In this study, I investigate how chronic versus acute exposure to the trematode Euhaplorchis sp. A. affects the antipredator behavior of the Gulf killifish Fundulus grandis. Using a fully crossed design, I …

Cytokine Profiles In Peruvian Pinnipeds And Their Relationships With Environmental Stressors, Mykenzee L. Munaco

All HCAS Student Capstones, Theses, and Dissertations

Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as environmental contaminants and El Niño-Southern Oscillation (ENSO) events. Cytokine concentrations can be indicative of an animal’s health and immune function by allowing for immunoresponse characterization as Th1 or Th2 dominant. Utilizing an archived pinniped plasma collection of samples from 2009-2019 (n=148), 13 cytokines were analyzed in PFS and SASL: GM-CSF, IFN-γ, KC-like, MCP-1, TNF-α, IL-2, IL-6, …

Cancer: The Burden Of Treatments Eased By Recent Developments In The Field: A Review Of The Literature, Zachary J. Seim

Culminating Experience Projects

Cancer is a very prevalent disease that has affected most of the population. Treatment options that have been used for decades are beginning to be outcompeted by newer developments in the field. Newer developments allow a more specific response to cancers that have proven to be very difficult for traditional treatment. Immune specific treatments also give the ability to specifically target areas affected by the cancer, to reduce potential risk of systemic damage and autoimmunity. Developing cancer treatments that are highly specific brings forth a new age of medicine, hoping to prolong the life expectancy of those affected with cancers, …

Evaluating The Role Of The Bovine Vaginal Microbiome In Neonatal And Maternal Health Outcomes, Riley D. Messman

Theses and Dissertations

The dam vaginal microbiota is the first major microbial inoculating community within the neonate. The composition of the dam vaginal microbiota has implications in calf commensal microbiota development. Alterations of the dam microbial community prior to parturition could alter inoculating communities and immune responses in both the dam and calf. Thus, authors aimed to elucidate the microbial community composition of the bovine dam vaginal and calf nasal microbiota post-partum after utilizing betadine lavages (BL). The dam vaginal and calf nasal microbial communities and immune responses were evaluated at 0-, 15-, 30- and 60-day post-partum. Microbiota composition of the dam haircoat, …

The Development Of Fetal Immunity From In Utero To Shortly After Birth And Complications That Can Arise From Improper Functioning, Marlee Curnutt

Culminating Experience Projects

The development of the immune system in humans is highly complex and requires precise timing which is still debated today. Research has shown IL-10 and T-regulatory cells play a significant role in the proper development of the immune system from in utero continuing into months after birth. These components and various cytokines continue to be guiding factors supplemented by the mother via placenta and breastfeeding. The dysregulation of immune development can have detrimental effects on the infant and may lead to autoimmune disorders. In this paper, we aim to further understand the development of the immune system from fetal to …

The Role Of Lkb1 Spliceoforms In Itreg-Th17 Plasticity And Their Interactions With Pkcθ And Sirt1 Downstream Of Il-6 Signaling, Deeksha Mohan

Doctoral Dissertations

Following activation, CD4 T cells undergo metabolic and transcriptional changes as they respond to external cues and differentiate into T helper (Th) cells. T cells exhibit plasticity between Th phenotypes in highly inflammatory environments, such as colitis, in which high levels of IL-6 promote plasticity between regulatory T (Treg) cells and Th17 cells. Protein Kinase C theta (PKCθ) is a T cell-specific serine/threonine kinase that promotes Th17 differentiation while negatively regulating Treg differentiation. Liver kinase B1 (LKB1), also a serine/threonine kinase and encoded by Stk11, is necessary for Treg survival and function. Stk11 can be alternatively spliced to produce a …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations & Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

Characterization Of The Immunoglobulin Lambda Chain Across Diverse Human Populations., William Gibson

Electronic Theses and Dissertations

The adaptive immune system relies on a diverse set of over one hundred immunoglobulin (IG) genes across three genomic loci that are variably combined to form antibodies (Ab). The IG Lambda locus is one of two loci which encodes the IG light chain. The complexity of the IGL locus severely limits the effective use of standard short-read sequencing, limiting our knowledge of population diversity in these loci. We leveraged single molecule real-time (SMRT) long-read sequencing in conjunction with IGL-targeted DNA capture to develop the method IG-Cap for accurate and high-throughput sequencing of the IGL locus. We benchmarked this method using …

Investigation Of Orthohantavirus Genetics In Rodent Reservoirs And Clinical Samples, Samuel M Goodfellow

Biomedical Sciences ETDs

Orthohantaviruses are negative-sense, single stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of ~36% and the highest cases occuring in the southwest region. The primary SNV host reservoir is thought to be the western deer mouse, Peromyscus maniculatus, however it has been shown that other rodents can carry different orthohantaviruses. We designed a pan-orthohantavirus detection tool to survey several small mammal populations throughout New …

Illuminating Underappreciated Mechanisms Of Receptor Regulation In Human Lymphocytes., Cassandra Woolley

Electronic Theses and Dissertations

A thorough understanding of receptor regulation is imperative to predict expression in varying contexts of disease or treatment. Lymphocyte surface receptors are often used as biomarkers and drug targets, making them particularly important for study. For receptors of debated functionality, such as the Fc receptor for IgM (FcMR), understanding regulation can also help to predict expression in vivo to supplement hypotheses of biological roles. Various mechanisms exist for altering receptor surface expression, including direct feedback mechanisms such as ligand-induced endocytosis and broader mechanisms such as transcriptional and translational control. In this dissertation, we explore selected underappreciated mechanisms of lymphocyte receptor …

Black Bear Population Health Monitoring In The Southeast, Kathleen Elizabeth Riese

Masters Theses

Recent growth of the American black bear (Ursus americanus) population in the southeast raises concerns about the potential spread of density-dependent diseases among bears, particularly sarcoptic mange. However, research on the health of bears in this area is limited. We analyzed samples from 169 bears in the region. We performed Knotts tests, skin scrapes, fecal floats; Canine adenovirus (CAV), canine parvovirus (CPV), canine distemper virus (CDV), and Toxoplasma gondii serology, Trypanosoma, Rickettsia rickettsii, and apicomplexan PCR, and identified ecto- and endoparasites found grossly or histologically. We found that 69% (63 of 91) had microfilaria; genetic analysis identified …

Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson

Electronic Thesis and Dissertation Repository

Macrophages are key mediators of efferocytosis – the phagocytic engulfment and removal of apoptotic cells. During engulfment, the coordinated activity of efferocytic receptors induces the remodeling of the actin cytoskeleton, which facilitates the envelopment of the cell by the plasma membrane. Mer receptor tyrosine kinase (MERTK) is a crucial efferocytic receptor, but its role during actin remodeling is not well understood. Previously, our lab showed that MERTK is an activator of β₂ integrins – which are comprised of receptors known to induce the actin polymerization that is required for engulfment. We hypothesized that MERTK is an indirect stimulator of …

Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil

USF Tampa Graduate Theses and Dissertations

Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …

Evaluation Of The Humoral Immune Responses To Plasmodium Vivax Circumsporozoite Protein (Csp)-Based Pre-Erythrocytic Vaccine Candidates, Jack Esquenazi

USF Tampa Graduate Theses and Dissertations

Malaria, caused by the apicomplexan Plasmodium spp. , is a major public health issue that impacts over one-third of the world’s population ,with Plasmodium vivax accounting for over 130 million clinical cases annually. The circumsporozoite protein (CSP) is the most abundant molecule on the surface of Plasmodium sporozoites and is considered a leading pre-erythrocytic stage vaccine candidate. CSP is essential for sporozoite maturation, migration, and invasion. Anti-CSP antibodies interrupt sporozoite migration and infection of hepatocytes thus reducing liver-stage burden. P. vivax CSP is composed of three subdomains: a highly polymorphic immunodominant central repeat region (CRR), conserved N-terminal ,and C-terminal subdomains. …

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …

Effects Of 11-Kt And Prolactin On Gene Expression, Parental Care Behaviour And Immune Response In Male Bluegill Sunfish., Adriano A P Da Cunha

Electronic Thesis and Dissertation Repository

Parental care is very critical for reproduction in species that provide it. Hormones such as prolactin and androgens play a crucial role in parenting and reproductive behaviours. In mammals and birds, prolactin’s role in parental care is well-established; it stimulates milk production and stimulates attachment to newborns by its release in the preoptic area of the hypothalamus (POA), among other functions. Androgens, on the other hand, are commonly associated with male secondary sex characteristics, territoriality, and aggressiveness in mammals and birds. There are similar reports of prolactin and androgen effects in fish, but there are fewer studies. I investigated if …

Mining Sars-Cov-2 Phylogenetic Trees To Estimate Circulating Infections And Patterns Of Migration, Erin V. Brintnell

Electronic Thesis and Dissertation Repository

The SARS-CoV-2 pandemic led to the formation of very large databases of genomic viral data. These databases contain information on transmission dynamics, emergence and evolution of SARS-CoV-2. However, extracting this information from sequences is difficult, as most methods of analyzing viral genomes were developed for smaller data sets. Therefore, my objective was to develop new fast estimators of the number of infections (I) and the rate of migration based on simple features of SARS-CoV-2 phylogenies.

I simulated pathogen evolution using a susceptible-exposed-infectious-recovered (SEIR) model of pathogen spread, reconstructing evolution using CoVizu. For simulations of I, I varied the total number …